Our Food

OurFood Database of Food and Related Sciences
Karl H. Wilm [email protected] July 6, 2013
Contents
1 Introduction Bibliography . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 7
Nutrition
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11 42 52 54 56 58 65 83 90 127 133 140 141 146 149 152 159 160 166 166 167 169 170 180 184 194 197
2 Food, what is it? 2.1 Plant sterols . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.2 Deep frying oil and shortenings . . . . . . . . . . . . . . . . . . . . . . . . 2.3 Palmoil . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.4 Toxicology of heated fat . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.5 Colon carcinogenicity of heated oil . . . . . . . . . . . . . . . . . . . . . . 2.6 Isomalt . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.7 Seafood . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.8 Functional Food . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.9 The FINE Study . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.10 Mood Food . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.11 Cocoa and chocolate directive 2000/36 EC . . . . . . . . . . . . . . . . . . 2.12 Sales names and denitions of cocoa, chocolate and their products . . . . 2.13 Vegetable fats allowed to be added to chocolate and related products . . . 2.14 Inuenza and probiotic bacteria . . . . . . . . . . . . . . . . . . . . . . . 2.15 Acrylamide . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.16 Surface browning as indicator of acrylamide formation . . . . . . . . . . . 2.17 Advanced glycation end products (AGEs) in grilled, fried or broiled meat and cheese products . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.18 Frozen Food Standards . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.19 Canned food . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.20 Dieting fads . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.21 Bromate in bottled water . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.22 Starch . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.23 Glycemic index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.24 Encapsulation of avours . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.25 Food pyramids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.26 Alternative food pyramids . . . . . . . . . . . . . . . . . . . . . . . . . . . ii
CONTENTS
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Bibliography . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 200 3 Obesity 3.1 Green Tea and weight reduction . . . . . . . . . . . . . . . . . . . . . . . 3.2 Yoghurt snacks and their impact on appetite control . . . . . . . . . . . . 3.3 Obesity may be inuenced by a B12 conjugate hormone developed for oral administration . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.4 Drugs to ght obesity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.5 New anti-obesity drug Contrave . . . . . . . . . . . . . . . . . . . . . . . Bibliography . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 Food Allergies 4.1 EC labelling legislation . . . . . . 4.2 Evaluation of the Allergic State . . 4.3 Developing Food allergies . . . . . 4.4 Treatment of Food Allergy . . . . 4.5 Food intolerance . . . . . . . . . . 4.6 Prevalence of food hypersensitivity 4.7 Detection of food allergens . . . . 4.8 Allergies and cross-reactivity . . . Bibliography . . . . . . . . . . . . . . . . 241 241 245 246 260 266 271 283 293 300 305 310 311 318 322 324 348 367 368 371 379 387 393 419 420 424 425 427 429 439 439 445 456 461 461 463
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5 Baby Food and Infant Formulas 5.1 How to feed a baby, recommendations of 5.2 Infant Formula Regulations . . . . . . . 5.3 Studies related to infant formulas . . . . Bibliography . . . . . . . . . . . . . . . . . . .
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6 Functional Foods and Novel Foods 6.1 Flavonoids, such as isoavones, anthocyanidins and avonols 6.2 Eect of phytoestrogens such as lignans on cancer risk . . . . 6.3 Health benets of avonoids from citrus fruits . . . . . . . . . 6.4 Soy as supplement in infant formulas . . . . . . . . . . . . . . 6.5 Special purpose value added soybeans . . . . . . . . . . . . . Bibliography . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7 Physiology 7.1 Diet pills and powders . . . . . . . . . . . . . . . . 7.2 Early Nutrition Programming Project EARNEST . 7.3 Resveratrol, the "anti-aging drug" . . . . . . . . . 7.4 Dietary bre and inammation . . . . . . . . . . . 7.5 Dietary natural agents and cancer . . . . . . . . . 7.6 Green tea reducing cancer risk . . . . . . . . . . .
Copyright 1998-2010 Karl H. Wilm. All rights reserved.
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iv 7.7 7.8 7.9 7.10 7.11 7.12
CONTENTS Green Tea and amyloidosis . . . . . . . . . . . . . . . . . . . . . . . . . . 469 Neurodegeneration and foods . . . . . . . . . . . . . . . . . . . . . . . . . 473 Cannabinoids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 485 The relation of foods and micronutrients to stroke . . . . . . . . . . . . . 498 Cardiovascular protection of red wine and white wine . . . . . . . . . . . 503 Recommended Dietary Allowance (RDA) and Dietary Reference Intakes (DRI) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 505 7.13 Actual dietary references set from US Food and Drug Administration FDA 507 7.14 Blood levels of Cholesterol . . . . . . . . . . . . . . . . . . . . . . . . . . 515 7.15 Mangosteen . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 524 7.16 Omega-3 polyunsaturated fatty acids in food . . . . . . . . . . . . . . . . 526 7.17 Methylmercury . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 541 7.18 Fatty acids with trans conguration . . . . . . . . . . . . . . . . . . . . . 548 7.19 Trans fat claims, FDA proposal . . . . . . . . . . . . . . . . . . . . . . . . 555 7.20 New discussion connecting high fructose syrup with obesity . . . . . . . . 567 7.21 Low-calories, low dietary energy density and physical activity . . . . . . . 582 7.22 Warning about high levels of multivitamins increasing the risk of prostate cancers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 589 7.23 Protective eect of green tea and soy intake in relation to breath cancer risk608 7.24 19.02.2008: Eect of low-fat, high-carbohydrate diet on radiological features of the breast . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 609 7.25 Complementary and Alternative Medicine . . . . . . . . . . . . . . . . . . 614 7.26 Homeopathy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 614 7.27 Flavonols in chocolate . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 620 7.28 Legumin and homologous proteins . . . . . . . . . . . . . . . . . . . . . . 627 7.29 Butter avour diacetyl in Popcorn linked to deadly lung disease . . . . . . 631 Bibliography . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 634
8 Fruits and Vegetables 8.1 Eect of fruit juices . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8.2 Fruit and vegetables in local diets . . . . . . . . . . . . . . . . . . . . . 8.3 Broccoli . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8.4 The European Prospective Investigation into Cancer (EPIC) 2009 . . . . 8.5 Antioxidant capacity of tomato and tomato-based products . . . . . . . 8.6 Triterpenoid compounds in fruits and plant in Bilberry and Lingonberry Bibliography . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9 Ingredients 9.1 No-eect-level . . . . . . . . . . . . 9.2 Additives in the European Food Law 9.3 Codex Alimentarius . . . . . . . . . 9.4 EU food additives regulations . . . . 9.5 European food colours legislation . .
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693 697 704 707 709 715 724 726 741 741 742 743 747 747
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CONTENTS Smoke avourings . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Measuring the antioxidant activity of phytochemicals . . . . . . . . . . . . Safety and bioavailability of Vanadium, EFSA and FSA assessment . . . . Enzymes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Ezyme Commission number (EC number) . . . . . . . . . . . . . . . . . . UniProt . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . SodiumBenzoate and certain colours increases hyperactivity in children . . Sugar, anti-social behaviour and ADHD . . . . . . . . . . . . . . . . . . . Sodium benzoate as source of benzene in soft drinks . . . . . . . . . . . . Benzene in foods without added benzoates . . . . . . . . . . . . . . . . . Natural cure for meats . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Nitrites and nitrates in cured meat fruit and vegetable may protect against heart attack . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9.18 Cherry fruits or cherry extract may prevent recurrent gout attacks . . . . Bibliography . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9.6 9.7 9.8 9.9 9.10 9.11 9.12 9.13 9.14 9.15 9.16 9.17
v 750 756 760 766 767 768 771 778 779 781 785 789 792 795
10 Food Supplements 809 10.1 Medicinal products . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 809 10.2 Energy drinks . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 816 10.3 Cherry juice and sports drinks . . . . . . . . . . . . . . . . . . . . . . . . 818 10.4 Diabetes and carotenoids . . . . . . . . . . . . . . . . . . . . . . . . . . . 819 10.5 Pros and cons related to supplements . . . . . . . . . . . . . . . . . . . . 831 10.6 Slimming ingredients, an unserious category? . . . . . . . . . . . . . . . . 833 10.7 Conjugated Linoleic Acid (CLA) as food supplement . . . . . . . . . . . . 837 10.8 Conjugated Linoleic Acid (CLA), a review . . . . . . . . . . . . . . . . . . 839 10.9 Memory Supplements without solid scientic support . . . . . . . . . . . . 840 10.10 The controversity of bre and colorectal cancer . . . . . . . . . . . . . . . 846 10.11 Zinc deciency . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 860 10.12 Bioactive compounds of tropical fruits to stabilise neurodegenerating diseases867 10.13 Prevention of prostate cancer . . . . . . . . . . . . . . . . . . . . . . . . . 869 10.14 Acai protection of neuronal damage . . . . . . . . . . . . . . . . . . . . . 871 10.15 Food marketing exagerate polyphenol rich fruits and juices health eects . 872 10.16 Blind trials . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 878 10.17 Argan oil, a nutraceutical? . . . . . . . . . . . . . . . . . . . . . . . . . . 889 Bibliography . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 892 11 Vitamins 11.1 Vitamins . . . . . . . . . . . . . . . . 11.2 Folic acid . . . . . . . . . . . . . . . . 11.3 Folic acid supplementation of bread or 11.4 Vitamin K . . . . . . . . . . . . . . . 11.5 Provitamin A Carotene . . . . . . . . 11.6 Vitamin B . . . . . . . . . . . . . . .
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921 921 923 923 928 931 933
vi 11.7 Bioavailability of vitamin C 11.8 Vitamin D . . . . . . . . . 11.9 Vitamin E . . . . . . . . . 11.10 Biochemical indicators . . . Bibliography . . . . . . . . . . . . from . . . . . . . . . . . . kiwifruit . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
CONTENTS . . . . . . . . . . . . . . . . . . . . . . . . . 936 936 953 954 958 971 971 971 973 994 1001 1012 1022 1030
12 Additives and E-Numbers 12.1 International Numbering System for Ingredients INS- Number . . . . . . . 12.2 EU food additives regulations . . . . . . . . . . . . . . . . . . . . . . . . . 12.3 Stability of natural food colours under production conditions . . . . . . . 12.4 Citric acid ester of mono- and di-glycerides replacing lecithin in chocolate applications. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12.5 Bulk sweeteners and intersity sweeteners . . . . . . . . . . . . . . . . . . . 12.6 Lack of association between saccharin, aspartame and other sweeteners and the risk of several common neoplasms. . . . . . . . . . . . . . . . . . . . . 12.7 Low-calorie sweeteners and obesity . . . . . . . . . . . . . . . . . . . . . . Bibliography . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
II
Dietary Habits
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13 Dieting and Dietary Habits 13.1 Vegetarian food with animal ingredients . . . . . . . . . . . . . . . . 13.2 Psychology of diet plans . . . . . . . . . . . . . . . . . . . . . . . . . 13.3 The cause of failure of diet plans and how to do it better . . . . . . 13.4 The separation diet of Dr. Howard Hay . . . . . . . . . . . . . . . . 13.5 Good diets . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13.6 The risks of bad diets . . . . . . . . . . . . . . . . . . . . . . . . . . 13.7 Evaluation of High-Protein Diets . . . . . . . . . . . . . . . . . . . . 13.8 Weight Reduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13.9 Physiology of hunger . . . . . . . . . . . . . . . . . . . . . . . . . . . 13.10 Appetite to specic foods . . . . . . . . . . . . . . . . . . . . . . . . 13.11 Well-fed . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13.12 Reductil, a suppressant of appetite . . . . . . . . . . . . . . . . . . . 13.13 Xenical, The ght against fat . . . . . . . . . . . . . . . . . . . . . . 13.14 Use of Xenical in case of low body weight (BMI below 30) . . . . . . 13.15 Food with reduced fat . . . . . . . . . . . . . . . . . . . . . . . . . . 13.16 Medical prescription of Xenical in case of BMI 30 to 40 . . . . . . . 13.17 Use of Xenical in case of BMI over 40 . . . . . . . . . . . . . . . . . 13.18 Xenical, the drug of the rich society . . . . . . . . . . . . . . . . . . 13.19 Dexfenuramin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13.20 Breakfast . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13.21 The Conference on Preventing Childhood Obesity, December 8, 2003
CONTENTS 13.22 Frequency of meals . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13.23 A classication and regression trees analysis on risk factors for childhood overweight (CART analysis) . . . . . . . . . . . . . . . . . . . . . . . . . 13.24 Salt intake and hypertension . . . . . . . . . . . . . . . . . . . . . . . . . 13.25 Salt reduction- Lower Sodium Intake Recommendations to Adults . . . . . 13.26 Mediterranean diet . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13.27 Other low-carbohydrate diets . . . . . . . . . . . . . . . . . . . . . . . . . 13.28 Non-communicable diseases caused by improper diet and sedentary lifestyle 13.29 The Jo-Jo eect reviewed . . . . . . . . . . . . . . . . . . . . . . . . . . . 13.30 Moslems . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13.31 Haram Food List of Dubai . . . . . . . . . . . . . . . . . . . . . . . . . . 13.32 Shubhah (Mushbooh) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13.33 Pork detection in meat products . . . . . . . . . . . . . . . . . . . . . . . 13.34 Ritual slaughter . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13.35 Ritual slaughter . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13.36 Mechanical slaughter . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13.37 United global halal standards . . . . . . . . . . . . . . . . . . . . . . . . . 13.38 What is behind a brand . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13.39 Castration of animals without anaesthesia . . . . . . . . . . . . . . . . . . Bibliography . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
vii 1075 1076 1080 1084 1091 1095 1101 1102 1110 1112 1118 1123 1126 1129 1130 1146 1148 1149 1154
14 Vegetarianism 1173 14.1 Food and ecology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1179 14.2 High consumption of red and processed meat linked breast cancer risk. . . 1180 Bibliography . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1183 15 Organic Food 15.1 New label: Organic food, holistic food, Biokost and 15.2 Organic foods compared to conventional produces 15.3 Introduction . . . . . . . . . . . . . . . . . . . . . 15.4 Organic Food in Europe . . . . . . . . . . . . . . . 15.5 The Proposal on Organic Food . . . . . . . . . . . 15.6 Organic farming . . . . . . . . . . . . . . . . . . . 15.7 Controls . . . . . . . . . . . . . . . . . . . . . . . 15.8 Principles applicable to all organic production . . . 15.9 Principles applicable to organic farming . . . . . . 15.10 Production of processed organic feed and food . . 15.11 General farm production rules . . . . . . . . . . . 15.12 Plant production rules . . . . . . . . . . . . . . . . 15.13 Livestock production rules . . . . . . . . . . . . . 15.14 Production rules for feed . . . . . . . . . . . . . . 15.15 General rules on the production of processed food 15.16 Label and advertising claims . . . . . . . . . . . .
Naturproduct . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
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1187 1187 1189 1197 1200 1200 1201 1202 1202 1202 1203 1204 1204 1205 1206 1207 1207
viii 15.17 15.18 15.19 15.20 15.21 15.22 15.23 15.24 15.25 15.26 15.27 15.28 15.29 15.30 15.31 15.32 15.33 15.34 15.35 15.36 15.37 15.38 15.39 15.40
CONTENTS
Certication . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1208 Imports from third countries . . . . . . . . . . . . . . . . . . . . . . . . . 1208 Aquaculture . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1208 International harmonization of organic food - Codex Alimentarius . . . . 1208 Global situation of organic farming . . . . . . . . . . . . . . . . . . . . . . 1212 NOP Standards (7 CFR Part 205) . . . . . . . . . . . . . . . . . . . . . . 1213 Other special food systems with organic claims . . . . . . . . . . . . . . . 1215 The International Federation of Organic Agriculture Movements (IFOAM) 1215 The IFOAM Principles of Organic Agriculture . . . . . . . . . . . . . . . 1216 Other special food systems with organic claims . . . . . . . . . . . . . . . 1218 AGL regulation for organic animal farming . . . . . . . . . . . . . . . . 1220 Labelling of organics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1221 Global situation of organic farming . . . . . . . . . . . . . . . . . . . . . . 1221 Social economic environment . . . . . . . . . . . . . . . . . . . . . . . . . 1222 Alternative Diets . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1223 Macrobiotics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1225 Water for agriculture . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1226 Environmental development . . . . . . . . . . . . . . . . . . . . . . . . . . 1227 Other Agricultural Systems . . . . . . . . . . . . . . . . . . . . . . . . . . 1230 Sustainable agriculture . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1245 Agroecosystem . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1246 Campylobacter in organic poultry . . . . . . . . . . . . . . . . . . . . . . 1247 Recover of natural antioxidants of industrial fruit and vegetable waste . . 1251 REPCO: Replacement of copper fungicides in organic production of grapevine and apple in Europe . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1253 15.41 Food and ecology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1254 15.42 Better cheese with corn silage feed milk than from fresh pasture milk . . 1261 15.43 New denition of organic food and nature food . . . . . . . . . . . . . . . 1271 Bibliography . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1283
III
Food Related Diseases

. . . . . . . . . . . . . . . . . . . . cereals . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1299
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16 Food-Borne Diseases 16.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . 16.2 Bacterial infections . . . . . . . . . . . . . . . . . . . . . 16.3 Cholera . . . . . . . . . . . . . . . . . . . . . . . . . . . 16.4 Staphylococcus aureus . . . . . . . . . . . . . . . . . . . 16.5 Moulds . . . . . . . . . . . . . . . . . . . . . . . . . . . 16.6 Prevention and reduction of mycotoxin contamination in 16.7 Disaster plans . . . . . . . . . . . . . . . . . . . . . . . 16.8 Review of pathogens heat-resistance . . . . . . . . . . . 16.9 Improved sanitation of large food systems . . . . . . . .
CONTENTS
ix
16.10 Antimicrobial Products . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1338 Bibliography . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1340 17 Moulds and Yeasts 17.1 Culture media for moulds and yeasts . 17.2 Determination of yeasts and moulds . 17.3 EFSA Qualied Presumption of Safety 17.4 Mould in Buildings . . . . . . . . . . . 17.5 Disease of the nails . . . . . . . . . . Bibliography . . . . . . . . . . . . . . . . . . 1345 1346 1356 1369 1375 1379 1379
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. . . . . . . . . . . . of Yeasts . . . . . . . . . . . . . . . . . .
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18 BSE 1387 18.1 The prion diseases still endemic in 2011 . . . . . . . . . . . . . . . . . . . 1387 Bibliography . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1416 19 Parasites and Protozoa 19.1 Free-living amoebae as human pathogens . . . . . . . . . . . . 19.2 Primary amoebic meningoencephalitis kills 10 in Pakistan . . . 19.3 Acanthamoeba . . . . . . . . . . . . . . . . . . . . . . . . . . . 19.4 Human genetic resistance against falciparum malariae . . . . . 19.5 Parasitic worms . . . . . . . . . . . . . . . . . . . . . . . . . . 19.6 Fishborn ukes . . . . . . . . . . . . . . . . . . . . . . . . . . . 19.7 Anisakis and Herring . . . . . . . . . . . . . . . . . . . . . . . 19.8 Climate change inuencing parasites and pathogen development Bibliography . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20 Anthrax 20.1 Introduction . . . . . . . . . . . . . 20.2 History of Anthrax . . . . . . . . . . 20.3 Bacillus anthracis Cohn 1872,177.Al 20.4 Culture of Bacillus anthracis . . . . 20.5 Pathogenesis of Bacillus anthracis . Bibliography . . . . . . . . . . . . . . . . . 1421 1423 1423 1426 1446 1446 1455 1463 1467 1476 1491 1491 1491 1492 1493 1496 1501
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21 Foot and Mouth Disease 1505 21.1 New strain of Asia 1 FMD of Central Asia and China . . . . . . . . . . . 1510 Bibliography . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1514 22 Livestock Diseases 1517 22.1 The new "Schmallenberg virus" aects European livestock (European Shamondalike orthobunyavirus) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1521 22.2 Fungal diseases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1527 22.3 Brucellosis in pigs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1528 22.4 Safe disposal of carcasses and manure . . . . . . . . . . . . . . . . . . . . 1529
Copyright 1998-2010 Karl H. Wilm. All rights reserved. OurFood Database of Food and Related Sciences
CONTENTS 22.5 Zoonoses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1530 Bibliography . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1556
23 Colony Collapse Disorder (CCD) 1571 23.1 Causes of Colony Collapse Disorder . . . . . . . . . . . . . . . . . . . . . 1571 Bibliography . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1582
IV
Bacteriology and Virology
1587
1589 1589 1600 1602 1605 1606 1615 1618 1618 1619 1635 1645 1671 1677 1678 1682 1687 1690 1691 1692 1694 1698 1702 1708 1708 1721 1725 1727 1727 1727 1729
24 General Bacteriology 24.1 General classication of bacteria related to food science . . . . . . . . . . 24.2 Classication of Aeromonas spp. . . . . . . . . . . . . . . . . . . . . . . . 24.3 Further classication of aeromonads . . . . . . . . . . . . . . . . . . . . . 24.4 The culture of aeromonads . . . . . . . . . . . . . . . . . . . . . . . . . . 24.5 Family of Campylobacteraceae . . . . . . . . . . . . . . . . . . . . . . . . 24.6 Helicobacter . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24.7 Transmission and sources of infection of Campylobacter . . . . . . . . . . 24.8 Avoid contamination of Campylobacter . . . . . . . . . . . . . . . . . . . 24.9 Isolation and identication . . . . . . . . . . . . . . . . . . . . . . . . . . 24.10 Internalisation of E.coli and Samonella in vegetable products . . . . . . . 24.11 Bacteriocins in food industry, veterinary use and importance for human health . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24.12 Chlamydia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24.13 Clostridium perfringens . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24.14 Diseases transmitted by water . . . . . . . . . . . . . . . . . . . . . . . . 24.15 Enterobacteriaceae, culture methods . . . . . . . . . . . . . . . . . . . . . 24.16 Fluorescence methods for detection of Escherichia coli . . . . . . . . . . . 24.17 Thin layer chromatography with immunologic analysis to detect E.coli 0157:H7 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24.18 Polymerase chain reaction (PCR) identifying microorganism . . . . . . . . 24.19 Impedance technologies for rapid detection and enumeration of bacteria . 24.20 Lactic acid bacteria LM . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24.21 Clostridium dicile Infection . . . . . . . . . . . . . . . . . . . . . . . . . 24.22 Corrosion caused by bacteria . . . . . . . . . . . . . . . . . . . . . . . . . 24.23 Biolms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24.24 The ten most dangerous diseases of the world . . . . . . . . . . . . . . . . 24.25 Methicillin-Resistant Staphylococcus aureus [MRSA] . . . . . . . . . . . . 24.26 Lantibiotics as natural food preservative and bacterial disease prevention . 24.27 Infectious diseases in the Amazon region . . . . . . . . . . . . . . . . . . . 24.28 Flagellates . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24.29 Leishmaniasis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24.30 Mycoses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
CONTENTS 24.31 Tetrahymena protozoan and Samonella and resistance to sanitizers 24.32 Meat "blown pack" spoilage . . . . . . . . . . . . . . . . . . . . . . 24.33 New predictive microbiology tools for Listeria monocitogenes . . . 24.34 Bacteriological methods . . . . . . . . . . . . . . . . . . . . . . . . Bibliography . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25 Virology 25.1 Diseases caused by viruses . . . . . . . . . . . . . . . . . . 25.2 Viral hepatitis . . . . . . . . . . . . . . . . . . . . . . . . 25.3 Viral infections . . . . . . . . . . . . . . . . . . . . . . . . 25.4 Inuenza viruses . . . . . . . . . . . . . . . . . . . . . . . 25.5 WHO Recommendations Regarding Avian Inuenza . . . 25.6 Avian Inuenza and food safety . . . . . . . . . . . . . . . 25.7 Still human death cases caused by H5N1 avian ue virus . 25.8 Avian inuenza and industry . . . . . . . . . . . . . . . . 25.9 Norovirus . . . . . . . . . . . . . . . . . . . . . . . . . . . 25.10 Reoviruses . . . . . . . . . . . . . . . . . . . . . . . . . . 25.11 Rotaviruses . . . . . . . . . . . . . . . . . . . . . . . . . . 25.12 Astroviruses . . . . . . . . . . . . . . . . . . . . . . . . . 25.13 Adenoviruses . . . . . . . . . . . . . . . . . . . . . . . . . 25.14 Parvoviruses . . . . . . . . . . . . . . . . . . . . . . . . . 25.15 SARS Severe Acute Respiratory Syndrome . . . . . . . . 25.16 Vaccine against H5N1 for humans . . . . . . . . . . . . . 25.17 Researches on HIV and antiretroviral drugs strategies, the 25.18 Hantavirus . . . . . . . . . . . . . . . . . . . . . . . . . . Bibliography . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
xi 1732 1734 1743 1763 1768
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1807 . . . . . 1807 . . . . . 1811 . . . . . 1813 . . . . . 1814 . . . . . 1829 . . . . . 1830 . . . . . 1832 . . . . . 1834 . . . . . 1851 . . . . . 1868 . . . . . 1870 . . . . . 1871 . . . . . 1871 . . . . . 1873 . . . . . 1873 . . . . . 1879 035 Study1882 . . . . . 1884 . . . . . 1886
Poisonous Chemicals in Food
1901
26 Dioxin 1903 Bibliography . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1924 27 Food Poisoning 27.1 Algal Toxins . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27.2 Algal blooms at eutrophic estuarine and water sheds . . . . . . . . . . . . 27.3 European regulatory limits for marine biotoxins not eective to protect consumer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27.4 Bacterial poisoning . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27.5 Ochratoxin and aatoxins in spices . . . . . . . . . . . . . . . . . . . . . . 27.6 Pesticides . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27.7 Organochlorine compounds . . . . . . . . . . . . . . . . . . . . . . . . . . 27.8 In utero exposure to pesticides . . . . . . . . . . . . . . . . . . . . . . . .
1931 1932 1936 1946 1952 1964 1970 1973 1975
xii 27.9 27.10 27.11 27.12 27.13
CONTENTS 1981 1981 1985 1995 2002 2004 2005 2006 2010 2012 2013 2013 2022 2023 2032 2034 2035 2036 2045 2046 2052 2053 2054 2056 2056 2056 2057 2061 2067 2077 2105 2132 2134 2136 2143
Changing ecology and toxic foods . . . . . . . . . . . . . . . . . . . . . . Origin of mercury in the Amazon region . . . . . . . . . . . . . . . . . . . Chemical contaminants . . . . . . . . . . . . . . . . . . . . . . . . . . . . Pesticide risk assessment . . . . . . . . . . . . . . . . . . . . . . . . . . . Toxicity of Roundup weed-killer and Monsanto NK 603 corn long-time study . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27.14 Inorganic Insecticides . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27.15 Miscellaneous compounds . . . . . . . . . . . . . . . . . . . . . . . . . . . 27.16 Other contaminants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27.17 Integrated Pest Management (IPM) . . . . . . . . . . . . . . . . . . . . . 27.18 Herbicides in rainfall . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27.19 Biopesticides . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27.20 Conventional pesticides . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27.21 Antimicrobial agents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27.22 Pesticides . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27.23 Agent Orange . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27.24 Pollutants in milk and dairy products . . . . . . . . . . . . . . . . . . . . 27.25 Use of DDT for indoor spraying . . . . . . . . . . . . . . . . . . . . . . . 27.26 Chlorpyrifos . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27.27 Plasticisers as possible cancer-causing agents . . . . . . . . . . . . . . . . 27.28 Growth stimulating hormones in beef . . . . . . . . . . . . . . . . . . . . 27.29 International trade of Pesticides . . . . . . . . . . . . . . . . . . . . . . . 27.30 List of the Rotterdam Convention on the Prior Informed Consent of banned or severely restricted chemicals . . . . . . . . . . . . . . . . . . . . . . . . 27.31 Annex III - Chemicals Subject To The Prior Informed Consent Procedure - Category Pesticide . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27.32 Category Severely hazardous . . . . . . . . . . . . . . . . . . . . . . . . . 27.33 Category Severely hazardous pesticide formulation . . . . . . . . . . . . . 27.34 Category Industrial . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27.35 Non dioxin-like polychlorinated biphenyls (PCB) in feed and food . . . . . 27.36 Tryptophan and eosinophilia-myalgia-syndrome (EMS) . . . . . . . . . . . 27.37 Veterinary medicine residues in eggs and poultry meat . . . . . . . . . . . Bibliography . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 28 Radioactivity and Food 28.1 Conversion of Becquerel to millisievert 28.2 Chernobyl contamination data . . . . 28.3 Irradiated foods in EU . . . . . . . . . Bibliography . . . . . . . . . . . . . . . . . .
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CONTENTS
xiii
VI
Food Industry
. . . . . . . . . . . . . . . bacteria . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
2151
. . . . . 2153 2154 2155 2164 2165 2170 2173 2173 2175 2176 2178 2178 2184 2186 2198 2204 2213 2216 2218 2219 2220 2227 2233 2234 2242 2245 2246 2253 2255 2255 2256 2257 2261 2262 2263 2267 2271 2273
29 Hygienemonitoring 29.1 ATP-Bioluminescence . . . . . . . . . . . . . . 29.2 Hygienemanagement in food industry . . . . . 29.3 Improving CIP technology . . . . . . . . . . . 29.4 Origin of Contamination of food with pathogen Bibliography . . . . . . . . . . . . . . . . . . . . . . .
30 Avoiding Food Scandals 30.1 The cause of food scandals . . . . . . . . . . . . . . . . . . . . . 30.2 The ComBase Database . . . . . . . . . . . . . . . . . . . . . . . 30.3 ComBase Predictor . . . . . . . . . . . . . . . . . . . . . . . . . 30.4 Sea water and irrigation water as cause of food born diseases . . 30.5 Animal product health threats . . . . . . . . . . . . . . . . . . . 30.6 Melamine in pet food and human consumption . . . . . . . . . . 30.7 Heparin scandal . . . . . . . . . . . . . . . . . . . . . . . . . . . 30.8 Tainted alcoholic beverages induce deadly methanol intoxication Bibliography . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
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31 HACCP and ISO 9000 31.1 Food chain steps . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31.2 The European Food Safety Authority (EFSA) . . . . . . . . . . . . . . . . 31.3 What to take care of in order to ensure food safety . . . . . . . . . . . . . 31.4 History of HACCP . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31.5 Hygiene regulations in Germany . . . . . . . . . . . . . . . . . . . . . . . 31.6 Production, improve the technical processing . . . . . . . . . . . . . . . . 31.7 Health condition or the sta which comes in contact with food . . . . . . 31.8 Canadian IPM without methyl bromide . . . . . . . . . . . . . . . . . . . 31.9 HACCP for supermarkets . . . . . . . . . . . . . . . . . . . . . . . . . . . 31.10 How to install an HACCP system for supermarkets . . . . . . . . . . . . . 31.11 Total Quality Management . . . . . . . . . . . . . . . . . . . . . . . . . . 31.12 Hyperlinked Management . . . . . . . . . . . . . . . . . . . . . . . . . . . 31.13 Introduction of the Hyperlinked Management . . . . . . . . . . . . . . . . 31.14 Hyperlinked Management Structure . . . . . . . . . . . . . . . . . . . . . 31.15 Software to handle Global Hyperlinked Management . . . . . . . . . . . . 31.16 HACCP and small businesses . . . . . . . . . . . . . . . . . . . . . . . . . 31.17 Regional Programmes for Food Security (RPFS) . . . . . . . . . . . . . . 31.18 Good Agricultural Practices (GAP) . . . . . . . . . . . . . . . . . . . . . 31.19 Certication of Uganda Tea by the Rainforest Alliance . . . . . . . . . . . 31.20 Multilateral trade negotiations on agriculture . . . . . . . . . . . . . . . . 31.21 ISO 15161:2001, Guidelines on the application of ISO 9001:2000 for the food and drink industry . . . . . . . . . . . . . . . . . . . . . . . . . . . .
xiv ISO 22000: 200x Food Safety Management Standard . . . Overview of the BRC/IoP Standard . . . . . . . . . . . . Content of the BRC/IoP Standard . . . . . . . . . . . . . Certication bodies . . . . . . . . . . . . . . . . . . . . . EN45011: The standard for the European Accreditation of involved in certication . . . . . . . . . . . . . . . . . . . 31.27 Detail of the Standards . . . . . . . . . . . . . . . . . . . 31.28 Auditing Standard ISO 19011 . . . . . . . . . . . . . . . . 31.29 Quality Control . . . . . . . . . . . . . . . . . . . . . . . 31.30 Demings Management-Program . . . . . . . . . . . . . . 31.31 Arman Feigenbaum . . . . . . . . . . . . . . . . . . . . . 31.32 Interoperability of Standards . . . . . . . . . . . . . . . . 31.33 The main producers of national standards . . . . . . . . . 31.34 International Standards . . . . . . . . . . . . . . . . . . . 31.35 International Organization for Standardisation . . . . . . 31.36 ISO 9001:2000 . . . . . . . . . . . . . . . . . . . . . . . . 31.37 Specications . . . . . . . . . . . . . . . . . . . . . . . . . 31.38 Control of non-conforming products . . . . . . . . . . . . 31.39 Economics of Quality . . . . . . . . . . . . . . . . . . . . 31.40 Pork quality and pH . . . . . . . . . . . . . . . . . . . . . 31.41 EMAS . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31.42 ISO 14001 . . . . . . . . . . . . . . . . . . . . . . . . . . 31.43 European food safety regulation activities in EU . . . . . 31.44 EC General Food Law Regulation 178/2002 . . . . . . . 31.45 Shelf life testing . . . . . . . . . . . . . . . . . . . . . . . Bibliography . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31.22 31.23 31.24 31.25 31.26 . . . . . . . . . . . . . . . . bodies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
CONTENTS . . . . . . . . . . . . . . . . . . . . who are . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2274 2275 2276 2277 2277 2278 2279 2280 2280 2281 2282 2282 2283 2283 2284 2287 2288 2288 2288 2289 2292 2292 2293 2295 2297 2303 2306 2307 2311 2314 2315 2315 2322 2325 2329 2330 2333 2343 2347 2348 2349
32 Packaging 32.1 The EU food packaging regulation EC1935/2004 . . . . . . 32.2 The war between glass and plastics . . . . . . . . . . . . . . 32.3 German regulations concerning recycling of packaging . . . 32.4 The Euro glass . . . . . . . . . . . . . . . . . . . . . . . . . 32.5 European regulations concerning packaging recycling . . . . 32.6 Types of plastic packaging . . . . . . . . . . . . . . . . . . 32.7 Phthalates in medical devices . . . . . . . . . . . . . . . . . 32.8 Carbon monoxide treated meat . . . . . . . . . . . . . . . . 32.9 Bioplastics . . . . . . . . . . . . . . . . . . . . . . . . . . . 32.10 Biodegradable Packaging . . . . . . . . . . . . . . . . . . . 32.11 Degradable plastics . . . . . . . . . . . . . . . . . . . . . . 32.12 Latex proteins from contact materials and food allergies . . 32.13 Polyhydroxibutirate (PHB), new biodegradable plastic from 32.14 Corkiness of wine . . . . . . . . . . . . . . . . . . . . . . . 32.15 Additives and plasticisers migration from PVC gasket seals
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xv
32.16 Bioplastic packaging materials . . . . . . . . . . . . . . . . . . . . . . . . 2353 32.17 Eects of edible coatings to extended shelf life of ready to eat foods . . . 2357 Bibliography . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2361 33 Dehydrated Foods 2373 33.1 Improving spray-dried emulsions . . . . . . . . . . . . . . . . . . . . . . . 2380 Bibliography . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2382 34 Food Advertising 34.1 Promotional material in television programming . . . . . . . . . . . . . . 34.2 Television advertising of food and drink products to children in UK . . . . 34.3 Junk food adds in USA . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34.4 International code needed to protect children from Internet and TV marketing Excesses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34.5 Pavlovian conditioning and food advertising . . . . . . . . . . . . . . . . . 34.6 Debate over advertising childrens products . . . . . . . . . . . . . . . . . 34.7 Food labelling . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34.8 Common nutrition labelling scheme . . . . . . . . . . . . . . . . . . . . . 34.9 Mislabelling Misdescription of foods . . . . . . . . . . . . . . . . . . . . . 34.10 Guidance on the use of marketing terms on food labels . . . . . . . . . . . 34.11 UK Advertising Standards Authority (ASA) . . . . . . . . . . . . . . . . . 34.12 U. S. Food labelling . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34.13 Misleading claims . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34.14 Examples of misleading packaging design . . . . . . . . . . . . . . . . . . 34.15 Universal Ethical Code for Scientists . . . . . . . . . . . . . . . . . . . . . 34.16 Little scientic evidence supporting corn oil health claim. . . . . . . . . . 34.17 Nutrient proling of food . . . . . . . . . . . . . . . . . . . . . . . . . . . 34.18 UK Trac Light and food . . . . . . . . . . . . . . . . . . . . . . . . . . . 34.19 Brand Community . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34.20 The aspartame controversy . . . . . . . . . . . . . . . . . . . . . . . . . . 34.21 Omega Eggs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34.22 Omega-3 fatty acids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34.23 Omega-6 fatty acids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34.24 Food crunchyness test . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34.25 Rising taxes on alcohol in UK . . . . . . . . . . . . . . . . . . . . . . . . . 34.26 Advertising strategies of food industry and retail services . . . . . . . . . Bibliography . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 35 Food Processing Innovations 35.1 Ingredients . . . . . . . . . . . . . . . . . . . . . . . 35.2 Beta-glucans and their eect on the immune system 35.3 Innovative ingredients . . . . . . . . . . . . . . . . . 35.4 Alternatives to controversial ingredients . . . . . . .
2385 2385 2387 2389 2395 2401 2401 2403 2404 2409 2411 2412 2418 2419 2422 2426 2427 2428 2432 2445 2447 2463 2466 2467 2470 2470 2471 2472 2491 2491 2492 2494 2499
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xvi 35.5 35.6 35.7
CONTENTS 2500 2509 2511 2517 2540 2549 2558 2583 2583 2583 2587 2591 2593 2594 2596 2597 2602 2610
Marine gelatin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Pectin, innovative use . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Asian longhorned beetle Anoplophora glabripennis invasion spreads in Germany . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 35.8 Renewable fuel . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 35.9 Antioxidant eect of grape seed extract . . . . . . . . . . . . . . . . . . . 35.10 Beet red production . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Bibliography . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 36 Nanofood 36.1 Denition . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 36.2 Standards and Nanotechnology . . . . . . . . . . . . . . . . . . . . . . . . 36.3 Nanoparticles and food safety . . . . . . . . . . . . . . . . . . . . . . . . . 36.4 Nanoparticles structure . . . . . . . . . . . . . . . . . . . . . . . . . . . . 36.5 Nanotechnology and food . . . . . . . . . . . . . . . . . . . . . . . . . . . 36.6 Nanotechnology regulations concerning foods and cosmetics . . . . . . . . 36.7 Health and environmental implications of nanomaterials . . . . . . . . . . 36.8 Plants uptake of nanomaterials, access to the food chain . . . . . . . . . . 36.9 Occupational safety and health (OSH) research focusing on nanomaterials Bibliography . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
VII
Food Safety
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2621
. . . . . . . . . . . . . 2623 2623 2624 2627 2628 2630 2631 2632 2634 2635 2636 2642 2643 2647 2651 2651 2652 2652
37 Bioterrorism 37.1 Food and Bioterrorism . . . . . . . . . . . . . . . . . . . . . 37.2 The Bioterrorism Security Act . . . . . . . . . . . . . . . . 37.3 Fort Detrick . . . . . . . . . . . . . . . . . . . . . . . . . . 37.4 Dangerous agents . . . . . . . . . . . . . . . . . . . . . . . 37.5 Emergency Preparedness . . . . . . . . . . . . . . . . . . . 37.6 Survival at home . . . . . . . . . . . . . . . . . . . . . . . . 37.7 The German preparedness recommendation . . . . . . . . . 37.8 The William Bell and Cham Dallas report on nuclear threat 37.9 Food terrorism and sabotage . . . . . . . . . . . . . . . . . 37.10 WHO Food Safety Response to Terrorist Threats . . . . . . 37.11 Surveillance, Preparedness and Response . . . . . . . . . . 37.12 World Health Organisation and food terrorism . . . . . . . Bibliography . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
38 Global Food Safety 38.1 Global food safety and global food trade . . . . . . . . . . . . . . . . . . . 38.2 Food and Agriculture Organization (FAO) . . . . . . . . . . . . . . . . . . 38.3 Convention on Biological Diversity . . . . . . . . . . . . . . . . . . . . . .
CONTENTS 38.4 FAO Anti-Hunger Program . . . . . . . . . . . . . . . . . . . 38.5 Famines . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 38.6 Activities of the Third World . . . . . . . . . . . . . . . . . . 38.7 Food sovereignty . . . . . . . . . . . . . . . . . . . . . . . . . 38.8 WTO and the conference in Cancun . . . . . . . . . . . . . . 38.9 The future of WTO . . . . . . . . . . . . . . . . . . . . . . . 38.10 North American Free Trade Agreement (NAFTA) . . . . . . 38.11 Misuses of NAFTA . . . . . . . . . . . . . . . . . . . . . . . . 38.12 Mercosur and the South American Free Trade Area (SAFTA) 38.13 The American Free Trade Area (AFTA) . . . . . . . . . . . . 38.14 Agriculture and plant protection . . . . . . . . . . . . . . . . 38.15 Monocultures . . . . . . . . . . . . . . . . . . . . . . . . . . . 38.16 Agroecology . . . . . . . . . . . . . . . . . . . . . . . . . . . 38.17 Integrated Production Systems . . . . . . . . . . . . . . . . . 38.18 Cuba agroecological example . . . . . . . . . . . . . . . . . . 38.19 Intelligent Pest Management (IPM Systems) . . . . . . . . . 38.20 Precision Farming Project . . . . . . . . . . . . . . . . . . . . Bibliography . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
xvii 2653 2654 2655 2656 2658 2658 2658 2659 2661 2661 2662 2662 2662 2663 2664 2664 2666 2669
39 Future of Global Nutrition 2671 39.1 Global corporations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2671 39.2 Instruments of economic regulation . . . . . . . . . . . . . . . . . . . . . . 2673 39.3 World Trade Organization ( WTO ) . . . . . . . . . . . . . . . . . . . . . 2673 39.4 Functions of WTO . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2673 39.5 Agreements and other organizations resulting from WTO . . . . . . . . . 2674 39.6 Codex Alimentarius Commission . . . . . . . . . . . . . . . . . . . . . . . 2681 39.7 Developing Countries and the WTO System . . . . . . . . . . . . . . . . . 2682 39.8 Export Dumping . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2682 39.9 The joint paper for Cancun . . . . . . . . . . . . . . . . . . . . . . . . . . 2686 39.10 Kyoto protocol . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2687 39.11 Oysters, climate change and increasing pollution of costal waters . . . . . 2697 39.12 Drought in USA and India demand action to avoid famine . . . . . . . . . 2705 39.13 Fungal bioabsorption of heavy metals in wastewater . . . . . . . . . . . . 2708 39.14 Deep sandstone aquifers of Middle East and North Africa with high carcinogenic radionuclides . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2718 39.15 Food waste . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2733 39.16 Climate change makes near-surface sh grow faster . . . . . . . . . . . . . 2743 39.17 No chance for DOHA no chance for climate control no chance to avoid nuclear war . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2747 39.18 GATS (General Agreement on Trade in Services) . . . . . . . . . . . . . . 2751 39.19 Origin of GATT and other Agreements . . . . . . . . . . . . . . . . . . . 2752 39.20 Agreement on Trade-Related Aspects of Intellectual Property Rights TRIPs 2753 39.21 TRIPSs and Software . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2753
xviii
CONTENTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2755 2757 2757 2759 2760 2761 2764 2770 2771 2778 2809
39.22 NAFTA and FTA . . . . . . . . . . . . . . . . . . . . . . . . . . . 39.23 Environment and trade . . . . . . . . . . . . . . . . . . . . . . . . 39.24 World Bank . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 39.25 IMF International Monetary Fund . . . . . . . . . . . . . . . . . . 39.26 OECD Organization for Economic Co-operation and Development 39.27 Excessive trade endangers species . . . . . . . . . . . . . . . . . . . 39.28 The Roadmap to Recovery of Marine Reserves . . . . . . . . . . . 39.29 Fermentation products . . . . . . . . . . . . . . . . . . . . . . . . . 39.30 Renewable fuel in the City of Portland . . . . . . . . . . . . . . . . 39.31 Sustainability of palm oil certication . . . . . . . . . . . . . . . . Bibliography . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
VIII
Agriculture and Ecology
2837
2839 2856 2857 2871 2883 2888 2889 2890 2891 2892 2900 2901 2905 2913 2924 2926 2927 2928 2955 2955 2956 2958 2965 2966 2970 2971
40 Phytopathology 40.1 Mediterranean fruit y . . . . . . . . . . . . . . . . . . . . . . . . . . . . 40.2 Ug99 fungus, other crop pests and drought are threatening food security of large population groups . . . . . . . . . . . . . . . . . . . . . . . . . . . . 40.3 Moulds of agricultural importance in coee production . . . . . . . . . . . 40.4 Ilarviruses, agronomically relevant viruses . . . . . . . . . . . . . . . . . . 40.5 Phenology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 40.6 Soybean diseases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 40.7 Extreme heat and drought in some regions of Europe . . . . . . . . . . . . 40.8 Genetic diversity within a species improves the ecosystem . . . . . . . . . 40.9 Insect Resistance Management . . . . . . . . . . . . . . . . . . . . . . . . 40.10 Cassava . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 40.11 Verticillium wilt diseases and their prevention . . . . . . . . . . . . . . . . 40.12 Biotrophic Phytopathogens . . . . . . . . . . . . . . . . . . . . . . . . . . 40.13 Leaf cutting ants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 40.14 Plastids in Plants, bacteria and Archaea . . . . . . . . . . . . . . . . . . . 40.15 Bacterial canker on kiwifruit . . . . . . . . . . . . . . . . . . . . . . . . . 40.16 Integrated Pest Management (IPM) . . . . . . . . . . . . . . . . . . . . . Bibliography . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 41 Ecology and Biofuels 41.1 Destruction of the rainforest . . . . . . . . . . . . . . . . . . . . . . . . 41.2 Controversial eect of biofuels on the environmental balance . . . . . . . 41.3 Food crops for fuel . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 41.4 Sequencing genes which express cellulose degrading enzymes of bacteria 41.5 Researches to improve biofuel production from cellulose . . . . . . . . . 41.6 Methane, a greenhouse gas . . . . . . . . . . . . . . . . . . . . . . . . . 41.7 The alternative to fossil fuel . . . . . . . . . . . . . . . . . . . . . . . . .
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CONTENTS 41.8 Particulate Matter . . . . . . . . . . . . . . . 41.9 Climate . . . . . . . . . . . . . . . . . . . . . 41.10 Rising food prices . . . . . . . . . . . . . . . 41.11 The IPSO report on declines in Ocean health 41.12 Decommissioning costs of nuclear waste . . . 41.13 Sick Building Syndrome . . . . . . . . . . . . 41.14 Coral bleeching . . . . . . . . . . . . . . . . Bibliography . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
xix 2972 2978 2985 2994 3001 3006 3015 3027
IX
Genetics
3049
3051 3069 3082 3083 3087 3090 3098 3101 3102 3110 3130 3130 3133 3139 3145 3156 3159 3169 3172 3186 3186 3189 3194 3197 3209 3218 3219
42 Genetic Modication of Food 42.1 Low-linolenic soyseeds . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 42.2 Hybrid rice . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 42.3 Genetically modied rice in Japan . . . . . . . . . . . . . . . . . . . . . . 42.4 Liberty herbicide and NAG (N-acetyl-L-glufosinate) . . . . . . . . . . . . 42.5 Transporter IRTI for assimilation of iron . . . . . . . . . . . . . . . . . . . 42.6 Cultivation of genetic modied seeds in Brazil . . . . . . . . . . . . . . . . 42.7 Human embrionic stem cells . . . . . . . . . . . . . . . . . . . . . . . . . . 42.8 Cloning of cells from frozen material . . . . . . . . . . . . . . . . . . . . . 42.9 Cloning of animals for better foods . . . . . . . . . . . . . . . . . . . . . . 42.10 Australian GM eld peas . . . . . . . . . . . . . . . . . . . . . . . . . . . 42.11 Lycopene from Fusarium sporotrichoides . . . . . . . . . . . . . . . . . . . 42.12 GM Maize . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 42.13 Unwanted gene ow from canola . . . . . . . . . . . . . . . . . . . . . . . 42.14 EU concept of coexistence . . . . . . . . . . . . . . . . . . . . . . . . . . . 42.15 USDA eld test permission for genetically engineered crop . . . . . . . . . 42.16 Recommendations from the Canadia Canola Council Canola to farmers . . 42.17 Genetic regulations in the EU . . . . . . . . . . . . . . . . . . . . . . . . . 42.18 GM corn in Europe . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 42.19 Genetic risk of type 2 diabetes mellitus . . . . . . . . . . . . . . . . . . . 42.20 Genetic factors of obesity . . . . . . . . . . . . . . . . . . . . . . . . . . . 42.21 Antibiotic resistance marker genes nptII in GM plants poses no risk to human, animal or environment . . . . . . . . . . . . . . . . . . . . . . . . 42.22 Pharmaceutical rice . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 42.23 Transgenes in Mexican maize at the preliminary stage of climate change . 42.24 Brown algae genetic code may explain origin of higher living beings . . . . 42.25 CRISPR, a RNA-based immune systems of bacteria . . . . . . . . . . . . Bibliography . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
43 Nutritional Genomics 3255 43.1 The beginning of nutritional genomics . . . . . . . . . . . . . . . . . . . . 3255

xx 43.2 Uses of food genomics . . . . . . . . . 43.3 metabolomics . . . . . . . . . . . . . . 43.4 Genomics, a clinical decision support . 43.5 The human gut microbiota . . . . . . 43.6 Modifying gut bacteria could inuence 43.7 Metagenomics of biolms . . . . . . . 43.8 The Human Microbiome Project . . . 43.9 The resistome . . . . . . . . . . . . . Bibliography . . . . . . . . . . . . . . . . . . Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . caloric intake . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
CONTENTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3256 3264 3267 3269 3272 3274 3276 3282 3283 3295
Chapter 1 Introduction
OurFood is a database containing information concerning food, related physiology, technology, analytical methods, bacteriology and topics of general interest.
1.0.1
The author
Karl H. Wilm diplome biochemist, graduated in the Faculty of Pharmacy of the University of Belm do Par, Brazil.
CHAPTER 1. INTRODUCTION
As member of the Council of Pharmacy of Porto Alegre the author became director of the section of bacteriology of the Biochemical Laboratory Dr. Friedel in Sao Leopoldo, Rio Grande do Sul Brazil, later chief chemist of the laboratory of food industry in Germany.
1.0.2
Disclaimer
OurFood was compiled with great care. However the author does not take any guarantee and denies any responsibility upon failures or damages caused by errors or misunderstanding of the contents.
1.0.3
General information Why a database on food ?
Health No physician denies the truth that the most frequent causes of illness are based on wrong behaviour related to food. More information about food is necessary to avoid unhealthy life-style and to cut cost of resulting medical care. You cannot avoid contaminants and other dangers of modern food, but you can reduce exposition maintaining good dietary habits. Industrialization OurFood is being increasingly industrialized. The organic food and alternative food are being commercialized. Due to a wide distribution the shelf life must be kept long. Vitamins and proteins lose their value.
1.0.4
Evolving food systems are dominated by nancial interests
[1] Impacts of conventional food systems Conventional food systems aim to maximize eciency in order to reduce costs and increase overall production. The industrial agriculture and its infrastructure coincides with the start of the industrial revolution. It enabled the conventional food systems to increase the availability of food for an ever growing global population. It is base on the use of chemical fertilisers and heavy industrial agriculture, however, turned it possible to utilise large areas of virgin forests. The climate the biodiversity and the ecology of large areas are endangered. Conventional food systems impoverish aected rural population. Organic food systems Organic food systems Organic farming was introduced by Lord Northbourne, base on theories of Rudolf Steiner It depends on reduced input of chemical pesticides and fertilisers, livestock is reared without antibiotics or growth hormones. Great supermarket chains took over the business with organic food, perverting the original meaning of organic farming to mass production and monocultures. It is now far from being a holistic, ecologically-balanced approach to farming. Biodynamic agriculture [1] The agricultural system of Rudolf Steiner now known as Biodynamic agriculture, contains the concept of "the farm as organism". Farms following the holistic idea of Steiner should keep distance to organic food made for supermarkets.
OurFood Database of Food and Related Sciences Copyright 1998-2010 Karl H. Wilm. All rights reserved.
3 They should label their products as "biodinamic food", building a strong separation with industrialised organic food.
1.0.5
Globalization of trade and industry
Globalization of multinational companies destroys the ecological isolated markets introducing the global business. Dumping prices from abroad destroy smaller industries killing jobs. The self-sucient demographic groups as seen in the Amazon rain forest will be destroyed by global thinking. Traditions and real target of life will be gone in a world which is being controlled by a hand full of mighty global players. Economic and ecological isolated units like the habitation in the Amazon jungle as self feeding unit will be a picture of the past.
Table 1.1: The great top 10 food giants (1998) Company Home based Turnover food USmm 50 31 23 23 22 21 18 18
Nestl Switzerland Phillip Morris USA ConAgra USA Unilever Netherlands PepsiCo USA Cargill USA Coca-Cola USA Diageo
4 Archer Daniels Midland Danone USA 16 14
The recent opening of the European Common Market adds further power to giant industries. Concentration on the retail sector has destroyed in Germany 60 000 full-time jobs. Mergers and acquisitions are the prime culprit. When a smaller company is being taken over, a number of duplicated functions are concentrated and jobs destroyed. [2] The retail sector is also getting global. Carrefour, a retail group with head in France reports the opening of 10 new business elds in Brazil, China, the Czech Republic, Korea, Malaysia, Mexico, Spain and Taiwan. The total number of stores of Carrefour come up to 345 in 20 dierent countries. [3] The concentration of the market proceeds and even increases in speed, seen at the European activity of the US giant Wal-Mart [4] buying at the end of 1998 the Interspar-SB warehouses. Wal-Mart is interested to buy the Carrefour group. Wal-Mart has already reached a turnover in 1997 of 200 billion Mark. It has a giant data-processing system which is only surpassed by the system of US Ministry of Defence in the Pentagon. Wal-Mart controls the behaviour of its clients utilizing data from the buying checks client charts and interviews of its employees. In this way Wal-Marts gets a picture of the behaviour of the client, the speed of turnover of the ware and regional dierent reactions of the market. Wal-Mart has an enormous knowledge concerning its customers.
Table 1.2: Retailers and their turnover 1999 Retailer Home based Total Branch in turnover bn US Dollar 156 Canada, Mexico, Brazil, Argentina, China, South Corea and Germany 46 45 40 37 36 Austria, Cherchenien, Slowakia, Poland, Hungary, Italy, West and East Europe, China,
Wal-Mart
USA
Metro Germany,Zwitzerland The Kroger Co USA Carrefour France Albertons USA Edeka Germany Rewe Germany
5 and France Royal Aholda Netherlands 35 Intermarch France 34 Tesco GB 32 The former head of the board of directors of the Daimler-Chrysler automobile group, Jrgen Schrempp expects a wide dissolution of nations as a result of growing international fusion of enterprises. To the magazine "Forbes" Schrempp stated: "We are going to come to a transatlantic union and then we should get ahead and nally build a world union without borders between countries [5]. As head of DASA(the aerospace division of Daimer-Benz), now EADS, Schremp acquired the Dutch aircraft manufacturer Focker in 1992 subsidizing the company with billions of Deutsche Mark. Only four years later, in 1996 Daimler-Benz decided to stop putting more money into Fokker that subsequently went bankrupt. Under the leadership of Schremp, Daimler-Benz made the disastrous acquisition of the Chrysler Corporation to become DaimlerChrysler. In May, 2007, facing tremendous losses, Daimler got rid of Chrysler and Schremp. This is an example how the visions of powerful leaders may score own goals. In 1971 Gudrun Tempel wrote that the world was becomming a small village governed by the head of global companies which have more power than a president or a minister of nance [6]. Unfortunately the great global companies do not bring wealth or better life to the country where they operate. Oranges are being marketed in Brazil mainly by four companies: The Brazilian Cutrale and Citrosuco,the French Coimbra and the US American Cargill producing 40% of world orange juice. Price of fruits and pay for workers are kept at extreme low levels without benets to the workers of this giant industry. Globalization does not bring a better live to the world. It destroys the basis of social organization. [7] As former Foreign Minister of Germany, Hans-Dieter Genscher[8] considers 1989, the year of the opening of the Wall of Berlin as a beam of the industrial as well as social globalization. According to his words it is now time to get together and ght the common threats of globalization which are: Mass poverty Ignorance and No access to education At the end of the cold war when the scare which was paralyzing humanity had been lifted, better transport and information ow was able to drive on development of technology and
business. According to Mr. Genscher, globalization has to be carried by the spirit of tolerance to avoid collision of cultures. Intolerance is often the product of ignorance. It is therefore important to furnish information about other cultures in our schools. As the availability of food resources depend on the political leadership of the countries where basic foods grow the political conguration of the world in the 21.century is for food trade and industry of crucial importance. Mr. Genscher says: "Russia will remain a part of the power of the world. China and India will play growing roles. Japan will remain strong. Brazil, despite its economical troubles will gain weight. Regional unions like MERCOSUR in Latin America. The Gulf Cooperation Council ASEAN in Southeast Asia and the European Union in Europe will built new economic blocks.The European Union is already of equal rank to USA."
Sustainability of the resources of our planet Globalization concentrates the power of global companies which develop enormous agricultural activities creating monocultures of biofuel crops. Jobs are lost and prices of staple foods rise. The only way to save the climate and the sustainability of the resources of our planet is to get back to economic, ecological and cultural isolated systems. The regions must produce for their own market which must become self supporting. This social revolution can take place like the fall of the Berlin Wall 1989 as a great part of the population of the DDR recognized the dusk of the communist system. The legion of the unemployed persons will recognize that global business destroys our society and will make a ban of global products. The Arab unrest splashes over to Europe, escalating in riots on the streets, of Greece, Spain , Italy and others. This will speed the process of change of the global society. Strong potentates will tumble like the Roman Empire and economic, ecological and cultural isolated systems will get free of the international speculative nancial system." You cannot avoid globalization. You cannot turn back time, but you can inform yourself through databases like OurFood. Free databases like OurFood provide information on how to avoid the menace of daily poisoning. That is why databases on food are important.
OurFood wishes you success on your researches.

BIBLIOGRAPHY
Bibliography
[1] Biodynamic farming and compost preparation. http://attra.ncat.org/attra-pub/ PDF/biodynam.pdf. [2] 60 000 jobs lost in German retail sector; Eurofood, 17 December1998 pg 5. [3] Carrefour sales up 10.4% in November; Eurofood, 17 December 1998. pg. 9. [4] Freese, Gunhild: Billig wie noch nie;Die Zeit, Nr.9; 25.2.99. [5] Schrempp erwartet Weltregierung; Bild am Sonntag; 45.Jahr;nr. 52 27.12.98. [6] Tempel, Gudrun: Als wrs der liebe Gott,Die Weltmacht der Konzerne;Bertelsmann Sachbuchverlag; Gtersloh-Wien, 1971. [7] UNICEF - Nachrichten 3 September 1998 Schuften fr den Whltisch. [8] Genscher, Hans-Dieter: Wer regiert unsere Welt 2000, Herr Genscher?: TV Hren und Sehen 27.2.99/5.03.99 S. 20.
Part I Nutrition
Chapter 2 Food, what is it?

2.0.6 Milk and dairy products
Milk and dairy products are an important source of proteins, calcium and vitamins.They are ideal baby food therefore is this product of great importance. The production of milk is worldwide concentrating in very few big companies. This increases quality through modern know how destroying, however, the small decentralized factories.
2.0.7
The very big international dairy food producers [1]

Table 2.1: The biggest milk producer of the World Sales Mio US Dollar 13.500 8.000 6.900 5.800 5.500 5.100 5.000 4.800 4.600 4.000
Seat of the Head 1 Nestl Ch 2 Kraft (Philip Morris) USA 3 Dairy Farmers of America USA 4 Danone F 5 Friesland Coberco Dairy Food NL 6 Besnier F 7 Snow Brand Milk Products J 8 Campina Melkunie/MKW NL 9 Bongrain F 10 Meji Milk Products J
Enterprise
2.0.8
Milk Calcium[2]
Milk is a natural source of calcium. Unfortunately young people drink less milk and more carbonated drinks increasing a possible undersupply of calcium. The decline in use of dairy products along with the increase of osteosporosis has boosted the fortication of food and beverages with o calcium all over the world [3]. Calcium sources are: 11
12 Calcium carbonater Calcium phosphate Calcium lactate Calcium gluconate Bone ash Oyster Eggshell calcium
CHAPTER 2. FOOD, WHAT IS IT?
But none of these sources have the same high bio availability as milk and their derivates.That is why milk should be carefully protected against pollution and diseases such as BSE.
2.0.9
Bio availability of calcium
One liter skim or full fat milk contains 1.200 mg calcium.About 30% of it is available to humans. The availability of calcium depends largely of it being soluble. Mineral water is a good source of calcium being present in soluble form.In dietary supplements the availability of calcium can be dier from case to case. The bio availability of calcium in vegetables is smaller as from milk. In milk calcium is linked with other components which avoid reactions as insoluble salts. Lactose and citrate of milk help resorption. Phytate and oxalate reduce resorption. Roughage and bres do not inuence bio availability. Even having a low bio availability fruits and vegetables represent an important factor in daily intake. A low calcium status causes the organism to absorb better as it does under normal conditions. Vitamin D and a normal intake of proteins promote a better bio availability. Human male reabsorb more calcium as women do. During Pregnancy and nursing calcium is reabsorb more easily. As one gets older calcium resorption diminishes. Diseases such as Morbus Chron and Colitis Ulcerosa slow down the resorption.
13 An undersupply of oestrogen causes low levels of calcium. Daily intake of calcium : Adults = 800 mg Infants =1.200 mg To keep bones strong magnesium as well as calcium and vitamin D are needed. The ratio of calcium and magnesium is important.Too much calcium and two little magnesium makes blood more apt to clot, leading to heart attack. The proper ratio is half as much magnesium as calcium.It is believed that old people get only one-fourth as much magnesium as calcium, specically if they take calcium supplements. An intake of 1.200 milligrams of calcium per day demands 600 mg of magnesium [2]. A separate supplement of 200 to 300 mg per day seems to be good.Dr. Seelig insists that the daily intake of magnesium should be about 500 milligrams [4].
Table 2.2: Content of calcium Food A glass of skim milk A cup of low fat Yogurt Kale Tofu milligram calcium 300 415 very rich in calcium high content of calcium
2.0.10
Daily calcium intake [5]
The Institute of Medicine released a report listing the requirements for daily calcium intake. How much calcium a person needs to maintain good health varies by age group. Recommendations from the report are shown in the following table. Age group Amount of calcium to consume daily, in milligrams (mg) 0-6 months 400 mg 6-12 months 600 mg 1-5 years 800 mg 6-10 years 1,200 mg 11-24 years 1,200-1,500 mg 19-50 years 1,000 mg 51-70+ years 1,500 mg In addition, pregnant and nursing women need between 1,200 and 1,500 mg of calcium daily.
14
2.0.11
Pollutants in milk and dairy products
Pesticides and aatoxins in milk have their origin in imported animal feed. The fat soluble pesticides like polychlorated hydrocarbons can contaminate easily milk, heavy metals are very seldom found in milk because they have low solubility. All eorts should be made to avoid contamination because milk is used to feed children, dairy products such as cheese or yoghurt are consumed in large scale. Contagious diseases like BSE should therefore be avoided through rigorous epidemiological measures. Pesticides such as insecticides, fungicides herbicides, hexachlorobenzene ( HCB ) and isomers of hexachloro cyclohexane ( HCH )are used in agriculture or are found on the elds. Even with low concentration of pesticides in animal feed the milk may be heavily aected because liposoluble pesticides usually store in the body of animals and can be detected in the milk in high level. Mycotoxines such as aatoxin B1 may be present in ground peanuts or cotton seeds.The cows changes the aatoxin B1 to aatoxin M1. This is why animal feed should be protected against deterioration. Contaminated or spoiled food should not be given to animals. Chlorated hydrocarbon such as Polychlorated biphenyl(PCB) were used in the past in transformers, refrigerators, in hydraulic oil and as all round chemicals. Its level in milk has decreased after the use of PCB has been reduced. Other chlorated hydrocarbons such as polychlorated dibenzodioxine ( PCDD ) and polychlorated dibenzofurane ( PCDF ) are also present in the human milk and in the milk of cows, but not as high as Chlorine hydrocarbons ( HCB, DDT and PCB ). Heavy metals such as lead, cadmium and mercury are of small importance because its concentration in milk is low.
2.0.12
Radioactive pollution of milk
In Europe the nuclear accident of Chernobyl hat caused an considerable increase of radioactivity in milk and milk products in 1986. The amount of radioactive material which was liberated into the atmosphere was several times the amount liberated by the Hiroschima bomb in 1945. Immediately after the accident due to west bounded winds there were the following radionuclides found in West Europe: Iodine-131, cesium-134 and cesium-137. There was a small amount of Strontium-90.Strontium,
15 which is even today very high in Brazil nuts of the Amazon region originated from nuclear bomb test in Nevada, USA in the forties. The radioactive pollution was carried through the Stratosphere and came down as fall-out in the rain forest. These incidents show how carefully radioactivity should be handled. In milk the nuclides are concentrated in the whey and remain there. That is why whey powder was highly contaminated causing headlines. The contamination with Strontium 90 in butter was low. In whey powder due to the concentration, radioactivity can increase from 200 Bq/liter to 7.200 Bq/kg. In 1986 500 tons of whey powder were discarded in in Germany having high radioactivity resulting from the concentration of cesium.In cheese the remaining cesium is very little. After some weeks only cesium -134 and cesium -137 was left. Low levels of radioactivity is told to increases the eciency of the DNA repair-system an increases the activity of the immune system[6]. This is not valid for radionuclide in food because they are deposited in bones and organs and with the time this material is being concentrated in the body. Damage of cells are than possible. Therefore radioactivity in food should be kept as low as possible.
2.0.13
Cheese
The dierent types of cheese are made from sour milk, separation of the whey and inoculating special bacteria or moulds creating the characteristic avor of each sort. The following bacteria and moulds are being used in dairies:
Table 2.3: Bacteria and moulds used in dairies Microorganism used in Lactic acid bacteria cottage cheese, fresh cheese Propionic acid bacteria Emmental cheese, Appenzeller cheese Some bacYellow- and red cultures Mnster cheese, Romadur cheese Pennicillium camemberti (white) Camembert cheese and brie Pennicillium roqueforti (blue/green) Roquefort, Gorgonzola teria, such as some kinds of lactic acid bacteria built toxic products such as biogenic amines in cheese. [7] Table 2.4: Biogenic amines in cheese, according Baum et col 1886, Lindner 1990.
16
Biogenic amines found as Tyramine Tyramine Tryptamine Tyramine Cadaverine Tyramine Putrescine Tyramine Phenylethylamine Histamine
mg/Kg 86 180 225 72 - 1.416 2.000 - 4.000 up to 2.300
Cheese Camembert Brie Emmentaler Cheddar Cheddar Roquefort
2.0.14
Whey
Traditionally, whey was a by-product with a negative value from cheese production. Sport nutrition and functional food market increase the demand of whey protein concentrates and isolates.
2.0.15
Whey protein concentrates
Food industry uses for baking and other uses whey protein powders with 30-40 per cent protein, high amounts of lactose and fat.
2.0.16
Whey protein concentrates
Reducing lactose with ultra-ltration processing the content of protein can be elevated up to 70-80 percent and an increased content of fat. subsectionWhey Protein isolates (WPIs) They contain 90- 96 per cent protein, minimal lactose and almost no fat, and are obtained using ion exchange columns or micro/nanoltration "cross ow micro ltered process" using high tech ceramic lters. Some vital peptides such as lactoferrin, alpha lactalbumin, immunoglobulins, beta lactoglobin have been removed from whey protein isolates using ion exchange. Nanoltration, however, retains valuable peptide fractions.
2.0.17
Biogenic amines
Biogenic amines are present in low concentrations in human, animals and plants. They have regulating functions, acting on the nervous system. Bacteria can produce biogenic amines decarboxilating amino acids in food. Biogenic amines can be produced by Bacillus, Clostridium, Hafnia, Klebsiella, Morganella morganii, Proteus, Lactobacillus such as Lactobacillus buchneri and Lactobacillus delbrueckii in cheese, Enterobacteriaceae and Enterococcus growing on sh, meat and their products. They are found also in fermented food, like cheese, camembert, wine, beer, sauerkraut and yeast extract.
17
The concentration of biogenic amines in spoiled food can be toxic. Biogenic amines of importance are: Histamine, tyramine, phenylethylamine, putrescine, cadaverine. Phenylethylamine is also found in chocolate and acts together with coeine and theobromine vitalizing. , and spermidine.
2.0.18
Dietary polyamines [8]
Polyamines, such as putrescine, spermine, and spermidine, are synthesized endogenously from ornithine with the enzymes ornithine decarboxylase and S-adenosylmethionine decarboxylase. Other source is food and absorption from the products of bacterial metabolism. Polyamines play an important role in regulating cell growth and proliferation. If cellular polyamine synthesis is inhibited, cell growth is stopped or severely retarded. The provision of exogenous polyamines restores the growth of these cells. Most eukaryotic cells have a polyamine transporter system on their cell membrane that facilitates the internalization of exogenous polyamines. This system is highly active in rapidly proliferating cells and is the target of some chemotherapeutics currently under development. Polyamines are also engaged in the stabilization of negative charges of DNA, RNA transcription, protein synthesis and the regulation of the immune response. Polyamines are found in breast milk and may be important in maturation of infant gut, and a possible supplementation of infant formulas with polyamines is being studied, say Larqu and colleagues 2007. Programmed cell death (apoptosis) include the activation of endogenous calcium and magnesium dependent endonucleases, leading to fragmentation of the chromosomal DNA which is destabilized in polyamine-depleted cells. [9]
2.0.19
Swedish Food Database contains selected data on polyamine [10]
The Swedish Food Database contains data on polyamine content of selected Swedish dairy products. According to Ali and colleagues 2011, these data suggest that fruits and cheese have the highest content of putrescine. Vegetables and meat products were high in spermidine and spermine, respectively. Highest levels of total polyamides were found in Swedish matured cheese, namely 52.3, 1.2, and 2.6 mg/kg for putrescine, spermidine, and spermine, respectively. Low fat milk had higher Putrescine and spermidine, 1.2 and 1.0 mg/kg, respectively, compared with other types of milk. The authors calculated the polyamine intake from food in adolescents using the database, and compared these results to a diet fullling the Swedish Nutrition Recommendations (SNO). The mean daily polyamine intake was found to be 316 micromol/day, and 541 micromol/day calculated according to SNO. Almost half of the polyamide intake came
18
from fruits The dierence between both results was caused by low vegetable intake by the adolescents. This was found by the authors to have caused the dierence between both results. The authors stress that the ideal diet according to Swedish nutrition recommendations presents higher results for polyamide than achieved Sweden and reported in Europe. [11]
2.0.20
Toxicology of histamine
An intake of maximum of 10 mg of histamine is tolerable An intake of 70 to 100 mg histamine causes median poisoning with headache, vomit, low blood pressure and rash. The incubation time is 30 minutes to one hour. The poisoning of histamine bearing sh is called scombroid poisoning An intake of 1.000 mg and higher causes severe poisoning, but seldom death Biogene amines cn be particularly dangerous in people taking monoamine oxidase (MAO) inhibitors, an older class of antidepressant pill, ecause they can potentially interact with the medication and cause dangerously high blood pressure.
2.0.21
Regulations
In Germany there is a maximum of 200 mg/kg histamine in sh established.In 10 samples the average should be under 100 mg/Kg. In Switzerland there are 100 mg histamine/Kg sh permitted and a maximum of 500 mg/Kg are established. In wine Switzerland has 10 mg/l a tolerable value of histamine in wine.
2.0.22
Tyramine
Tyramine rises blood pressure and causes headaches. It is formed in rockeford cheddar and cheese with white moulds. Tyrosine-decarboxylase is build by many bacteria such as Streptococcus of the serological group D ( Enterococcus), many Clostridium, some strains of Escherichia coli and many types of Proteus and some lactic acid bacteria like Lactobacillus, Leuconostoc and Pediococcus.
2.0.23
Pollutants in milk and dairy products [12]
In Bavaria,(south of Germany) the pollutants in milk and dairy products are being controlled over 25 years by the laboratory muva kempten (Veterinary medical analytical oce
19 of Kempten). This laboratory has monitored the organochlor-pesticides, PCB, halogenated solvents and heavy metals. The results of these analysis made it possible to nd the cause and to reduce the contamination. At the moment most of the former pollutants of organochlor-pesticides have fallen below detection level in milk from Bavaria. Only lindan is still increased. This is an example of handling the environment problems making long terms monitoring of food with the cooperation of the laboratory the agriculture and the industry. The muva kempten now checks organochlor-pesticides (OCP) polychlorated biphenyles (PCB) dioxines, halogenated solvents, mycotoxines, heavy metals, radionuclides, phtalates, nitroso compounds, polycyclic aromatic hydrocarbon substances, organophosphorand pyrethroid-pesticides using multi methods of preparation of the material, GC-PND and GS-MS. These methods enables the muva kempten to analyse all kind of food. One important concern of the laboratory is the contamination of food caused by migration of packing components into the food, such as styrol from polystyrol, dioxines from cardboard, plasticiser, heavy metals, nitrosamines from rubber, and (Bisphenyl-Adiglycidilether) Problems which come from coating of tin cans.
Organic migrations are detected by GC-MS and HPLC and AAS and inorganic ions migrations with AAS.About 70% of canned food were found to be contaminated with BADGE and BFDGE (Bisphenol-A-diglycidilether) according to the French magazine "test achat".Heavy contamination was found in cans containing sh and foods with high amount of acid like lemon, vinegar or tomatoes. The European Commission made has completed in early 1999 a study concerning the safety of BADGE. According to this Study there is no danger coming from BADGE. Therefore the Commission rose the maximum allowed amount of BADGE in foods from 20 microCopyright 1998-2010 Karl H. Wilm. All rights reserved. OurFood Database of Food and Related Sciences
20
gram in one kilogram up to 1 milligram in one kilogram food.This was intended only for tin cans coated with plastics. As there are no limits established for for coatings with clear varnish many countries use this high value also for varnished cans. The toxicology of BFDGE and the catabolic products of BADGE and BFDGE are still unknown.
2.0.24
Recommendations to reduce BADGE and BFDGE
"test achat" recommends to change from canned food to food in glass packaging. Discarding the immersion brine can further reduce BADGE and BFDGE. Contamination of cleaning and disinfection agents are also possible as contaminants of food. This has to be monitored. The cooperation between ocial supervision of food, agriculture and industry has brought good results in research and improvements since repressive rules of supervision had been changed to open discussion and mutual good will of all parts engaged in the long way from farming to the consumer.
2.0.25
Bisphenol A and phthalates in canned or packaged food [13]
Rudel et al. 2011 found that removing bisphenol A (BPA) and DEHP (bis(2-ethylhexyl)phthalate) from food packaging will signicantly decrease exposure for adults and children. Bisphenol A is widely used in the manufacture of polycarbonate and other plastic products and epoxy resin-based food can liners. The authors measured urinary BPA and phthalate metabolites after diet avoiding canned foods and foods in plastic packaging, compared with usual diet. The authors report that urine levels of BPA and DEHP metabolites decreased signicantly during a diet free of canned food and free of plastic packed foods. The authors call for the phase out of the use of bisphenol A and phthalate because of its implication in endocrine disruption.
2.0.26
Contaminants in baby food
In baby food were found for health dangerous phtalate DBP and DEHP. These contaminants were found in the milk used for these products. All eorts should be made to reduce or even to avoid the possibility of contamination of the milk on its origin.
2.0.27
More safety for food
The French President Jacques Chirac after the latest aairs of food poisoning has suggested the creation of an international board for food security. The board should contain
21 scientist of high reputation. Chirac spoke with US president Bill Clinton which assured the cooperation from US.
2.0.28
New bacterology tools for enhanced food safety
New DNA tools developed by the Agence Fransaise de Scurit Sanitaire des Aliments, together with other French food laboratories have demonstrated that dominant bacterial population of fresh milk was Lactobacillus lactis. This bacterium is commonly used as a starter culture in dairy. It is not harmful. After 24 hours of refrigeration at 4o C psychotroc bacteria such as Listeria spp and Aeromonas hydrophila emerge. These psichotroc bacteria are life threatening in cheese products. DNA using temporal gel electrophoresis TTGE and denaturing gradient gel electrophoresis (DGGE). Bacterial identication was facilitated by comparision with a bacterial reference database which had been established with DNA fragments of pure bacterial strains. The results contribute to the knowledge on the bacterial ora of raw milk samples and also describe the consequences of a simple process, milk refrigeration, on the quality of dairy products and its impact on health.[14]
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Calcium supplementation reduces severe preeclamptic complications [15]
J. Villar and colleagues in a study of the UN Development Programme found no change in preeclampsia rates in women supplemented with calcium, but did nd a decrease in the rate of severe preeclamptic complications.
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Small changes in nutritional patters may increase ischemic heart disease risk [16]
Il Suh and colleages found in a study published in 2001 that in China dietary fat intake increased from 15.9% of energy in 1982 to 21.1% in 1990; ischemic heart disease incidence and mortality also increased. Mortality from ischemic heart disease among Koreans has increased 5- to 6-fold during the past decade. the average fat intake of Koreans increased during the same period: from 14% of energy in 1986 to 19% of energy in 1997. This increased dietary intake may aect the incidence of ischemic heart disease. The authors of the study conclude that in a population with a relatively low fat intake, a moderate increase in total fat intake may be a risk factor for ischemic heart disease.
22
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Enzymes
Enzymes are active substances which are produced by living organismn which may act on chemical reactions in living cells or outside. Enzymes are proteines with low molecular active group with strong binding called prostetic group or with weak binding and easy to split o group called coenzyme Examples of enzymes are lipases (enzymes which split fats), proteases (enzymes which split proteines) Enzymes are used in industrial technology and in colorimetrical methodes for the determination of specic substances in foodstus.
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Vitamins
Vitamins, such as beta-carotene acting as an antioxidant and indirect source of vitamin A give can supplement foods turning color yellow to red (Lucarotin 10 CWD G/R from BASF, red provitamin A). Supplemented antioxidant drinks are also labeled as A-C-E drinks.
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Vitamin A deciency
Vitamin A deciency causes blindness in children and is a risk of severe infections disease, heart disease, skin cancer, prostate cancer, and arthritis. Plant foods may contain provitamin A pigments such as alfa-carotene, beta-carotene, and beta-cryptoxanthin that ore converted to vitamin A by the body. Globally, it is estimated that 140-250 million children under ve years of age are aected by vitamin A deciency. These children suer a dramatically increased risk of death, blindness and illness, especially from measles and diarrhoea. The WHO calls for a combination of breast feeding, dietary improvement, food fortication, and supplementation. [17]
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Harvest Plus and Maize biofortication [18]
While many micronutrients are available from fruits, vegetables, and animal products, most of the poor are unable to grow or buy these micronutrient-rich foods. Their diets are characterized by high intakes of staple food crops (such as maize, wheat, and rice) but low consumption of micronutrient-rich foods such as fruits, vegetables, and animal and sh products. By providing a regular daily dose of vitamins and minerals, biofortied staple crops do not need to provide the entire recommended daily allowance (RDA) of micronutrients, but they can be eective in reducing hidden hunger as part of a strategy that includes dietary diversication, supplementation, and commercial fortication, among others. HarvestPlus focuses on three critical micronutrients that are recognized by the World
23 Health Organization (WHO) as most limiting in diets: iron, zinc, and vitamin A. HarvestPlus envisions that in fteen years, millions of people suering from micronutrient malnutrition will be eating new biofortied crop varieties, such as orange sweet potato rich in vitamin A, orange maize and rice with increased zinc.
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Biofortication [19]
Biofortication is a method of breeding crops to increase their nutritional value of staple crops. This can be done either through conventional selective breeding, or through genetic engineering. Biofortication diers from ordinary fortication because it focuses on making plant foods more nutritious as the plants are growing, rather than having nutrients added to the foods when they are being processed.
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Selective breeding
Using this method, plant breeders search seed or germplasm banks for existing varieties of crops which are naturally high in nutrients. They then crossbreed these high-nutrient varieties with high-yielding varieties of crops, to provide a seed with high yields and increased nutritional value. This method is quicker, cheaper, and less controversial than genetically engineering crops. For example, HarvestPlus primarily use conventional breeding techniques to develop biofortied crops.
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Genetic modication
Golden rice is an example of a GM crop developed for its nutritional value. Golden rice contains genes from the soil bacterium Erwinia and either maize or daodil plants, and contains increased levels of beta-carotene which can be converted by the body into vitamin A. This can help alleviate symptoms of vitamin A deciency. Here are some studies concerning improvement of micronutrients in staple foods.
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Provitamin A biofortication of maize using crtRB1 alleles [20]
New breedings are focused on biofortication to improve the dietary vitamin A status in developing world. Yan and colleagues 2010, studying the genetic code of maize (Zea mays L.), report that the gene encoding beta-carotene hydroxylase 1 (crtRB1) associated with beta-carotene which may increase the concentration of provitamin A in maize kernel 18 times compared with standard maize. Alleles of crtRB1 are being introgressed via inexpensive PCR marker-assisted selection into tropical maize. The researchers avoided to introduce alien genes in maize. They use the natural variation of the crtRB1 gerne within the same plant increasing the production of provitamin A and reducing its transformation to other, not biologic active chemical structures. Davis and colleagues 2008 studying
24
the biologic activity of other carotenoids report that twice the molar amount of betacryptoxanthin was as ecacious as beta-carotene. [21]
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Biofortication of staple food crops [22]
Nestel and collegues 2010 highlights the progress which has been made to control micronutrient deciencies through supplementation and food fortication. The authors stress that biofortication is being supported by predictive cost-benet analyses, however additional public work is needed to induce producers and consumers to accept biofortied crops. Activities, such as the good seed systems, the development of markets and products, and demand creation may be helpful to achieve this goal. Good seeds is supported by Bill & Melinda Gates Foundation and the Rockefeller Foundation. It helps to create new varieties of seeds and make improved seeds much more accessible in Africa, especially to rural farmers. [23]
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Genes related to carotenogenesis and heat resistance in maize [24]
Li and colleagues 2008 studied the carotenoid expression in maize. The authors report that maize endosperm carotenoid accumulation requires PSY1 expression, but this was not related to PSY2 or PSY3. Better understanding of the timing of PSY1 transcript critical information allowed to choose breeding alleles. The authors also found that PSY1 is required for carotenogenesis in the dark and for heat stress tolerance. Leaf carotenogenesis was shown to require photoregulation of PSY2 plus nonphotoregulatiing PSY1 expression.
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Natural genetic variations used for biofortication of maize [25]
Harjes and colleagues 2008 describe the variation at the lycopene epsilon cyclase (lcyE) locus which alters the two branches of the pathway of the alpha-carotene versus betacarotene. Four natural lcyE polymorphisms could lead to a threefold dierence in provitamin A compounds. The best suited lcyE alleles may now be selected using inexpensive molecular markers developing maize with higher provitamin A levels
2.0.42
Vitamin A reduction of inammation [26]
Kurt Long from Harvard School of Public Health aand colleagues studied the eect of vitamin A (retinol) supplements on levels of the molecule, monocyte chemoattractant protein-1 (MCP-1), which is associated with a state of increased inammation and is also involved
25 in the pathogen-specic mucosal immune response. Children who received the vitamin A supplement were found to have reduced fecal concentrations of MCP-1 compared with children in the placebo group. The supplementation also reduced MCP-1 levels in children with infections, like the bacteria Escherichia coli or the human roundworm Ascaris lumbricoides. The authors conclude that vitamin A has an anti-inammatory eect in the gastrointestinal tract by reducing MCP-1 concentrations.
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Retinol
Retinol is the dietary form of vitamin A. It is fat soluble and is found mainly in sh liver oils, liver, egg yolks, butter, and cream. Retinol is ingested in a precursor form; animal sources are milk and eggs in form of retinyl esters. Green leafy and yellow vegetables such as spinach and carrots contain beta-carotene and other provitamin carotenoids, which are converted to retinal in the mucosal cells of the small intestine. Retinal is reduced to retinol, then esteried as retinyl palmitat. Most of the bodys vitamin A is stored in the liver as retinyl palmitate. It is released into the circulation as retinol Hydrolysis of retinyl esters results in retinol while pro-vitamin A carotenoids can be cleaved to produce retinal which can be reduced to retinol.
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Biologic equivalents
Biologic equivalents, for diets with dierent proportions of retinol and beta-carotene, are as follows: 1 USP U equals 1 IU; 1 IU equals 0.3 microg of retinol; 1 microg of beta-carotene equals 0.167 microg of retinol. Other provitamin carotenoids are half as active as beta-carotene, because they have only one un-substituted font beta end group.
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Beta-cryptoxanthin
Beta-cryptoxanthin can be found in many vegetables and fruits, mainly in papaya, mango, peaches, oranges, tangerines, bell peppers, corn and watermelon. Beta-cryptoxanthin is also found in some yellow coloured animal products such as egg yolk and butter, and is told to be the main source of provitamin A.
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Production of beta-cryptoxanthin [27]
According O. Serrato-Joya from the Department of Chemical and Biochemical Engineering at the Technological Institute of Celaya, Guanajuato, Mexico, beta-cryptoxanthin has been neglected because most of the information were focused on b-carotene alone. This was due to the lack of suitable analytical techniques, and alternative viable processes for production. O. Serrato-Joya and colleagues describe a process producing beta cryptoxanthin additives, as supplement in food formulation, thus assisting vitamin A deciency prevention. The process uses fermentation technology of Flavobacterium lutescens ITCB008, attaining 770 mg of beta-cryptoxanthin/kg biomass in dry weight in 28 hours with a purity of 95% of the total carotinoid content. This process oers higher yields in less time compared with similar carotinoids production techniques. O. Serrato-Joya and colleagues from the Technology Institute of Celaya, Guanajuato, Mexico, describe a process producing beta-cryptoxanthin additives, as supplement in food formulation, thus assisting vitamin A deciency prevention. The process uses fermentation technology of Flavobacterium lutescens ITCB008, attaining 770 mg of beta-cryptoxanthin/kg biomass in dry weight in 28 hours with a purity of 95% of the total carotinoid content. This process oers higher yields in less time compared with similar carotinoids production techniques.
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Omega-3 Polyunsaturated fatty acids
The eicosapentaen acid and docosahexaen acid are essential fatty acids.They are available only in form of fatty sh like mackerel, herring , salmon . An undersupply of omega-3 PUFA is therefore possible and the search for this essential fatty acids in plants and microorganism is being started. Microencapsulated omega-3 fatty acids are used in healthy diets and in prevention of cardiovascular diseases, supplement bakery products,pasta, breakfast cereals, ready-made meals, soups,dairy products and baby food. Microencapsulated omega-3 high unsaturated fatty acids have neutral taste, without smell and are protected from oxidation. Omega-3 polyunsaturated fatty acids help to prevent cardiovascular diseases, hypertonia, Diabetes mellitus. They also act against inammation and allergic diseases like psoriasis. Omega-3 PUFA are important for neurophysiological functions and brain and vision development of newborn.The role of omega-3 fatty acids in the prevention of depressions is being studied.
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Classication of omega-3 fatty acids
The classication of omega-3 PUFA regards: 1.- The number of C-atoms of the molecule, 2.- The number of unsaturated links, 3.- The position of the rst double link in relation to the methyl end of the fatty acid. The structure of omega-6 PUFA is given below as they are often seen in relation with omega-3 PUFA:
Most important omega-6 PUFA are: linoleic acid, gamalinolenic acid, dihomo-gamalinolenic acid, arachidonic acid. Structure of omega-3 PUFA:
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Most important omega-3 PUFA are: alfa- linolenic acid (C18:3), eicosanpentaen acid (C20:5) EPA, and docosahexaen acid (C22:6) DHA, Alfa linolenic acid can be changed to EPA only up to 15% in human physiology and only 4% can be change to DHA That is why about 50 g daily of rapeseed oil can substitute only 50 to 100 g fat sh in a week. The transformation rate depends on the type of the nutrition. A high intake of linoleic acid and saturated fatty acids in relation to alfa-linolenic acid can strongly reduce synthesis of omega-3 fatty acids. Alfa-Linolenic acid is available in green leaf vegetables,nuts, and some vegetable oils such as rapeseed oil, soya oil, wheat germ oil and walnut oil. Linseed is a good source of omega-3 fatty acids, being 40 to 60% alfa- linolenic from total oil. Linseed has therefore found its place in baking industry with 6 - 8% from dry weight in all types of bread.Linseed can also be used as animal feed to produce alfa- linolenic enriched foods like Eggs, butter, cheese and meat. Feeding animals with linseed or linseed oil an increase of alfa- linolenic fatty acid is achieved.Feeding them with sh oil or seaweeds enriched with omega-3 fatty acids leads to an increase of DHA.
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Eicosanpentaen acid (C20:5) EPA
Phytoplankton is the nutrition of sh of cold water and is the source of EPA and DHA (DHA = docosahexaen acid). Fish farming of eel, trout and salmon may produce a sh with reduced omega-3 fatty acids because of dierent nutrition. That is why sh from natural sources are of superior quality compared with sh from farms. Omega-3 fatty acids EPA and DHA are being produced microencapsulated using carbohydrates or protein basis such as maltodextrin, beta- cyclodextrin, egg white, gelatine or caseinate as covering lm. In this way they can be added to beverages like orange juice. Researches are being made to nd other sources of omega-3.PUFA using single cells such as Crypthecodinum cohnii ( Dinoagellata), Mortierella elongata (fungus), Schizochrytium (Microalgae). The DART Study[28] and the Lyon Diet Heart-Study [29] have demonstrated that omega-3 fatty acids have a protective activity against cardiac infarct using 200-400 g fat saltwater sh/week, or 3 times 0,5g/day sh oil and a diet rich in fruits and vegetables and little amount of meat and milk products. Beginning with 1800 with the industrial era the nutrition changed. Total fat, saturated fats and omega-6 fatty acids increased rapidly and starting at 1930 trans-fatty acids as a result from hydration increased the unhealthy side, meanwhile healthy omega-3 fatty acids decreased constantly beginning with 1900. According to DGE (Deutsche Gesellschaft fr Ernhrung ) the intake of fat for an adult should be reduced to 30 to 35%. essential fatty acids should be 3,5% of total energy and should be distributed between 3% omega-6 and 0,5% omega-3 fatty acids. The quotient between the two should be 5:1. The amount of omega-3 fatty acids should be approximately 1 g/day. European estimates indicate that only Portugal and Spain have an intake over 1 g/d. Germany has an undersupply of omega-3 fatty acids of only 1/3 of the necessary daily intake. Netherlands despite being known for herring shery has an intake of only 1/5 of the necessary daily amount. Target group for food enriched with omega-3 fatty acids should be early or newborn, pregnant women, nursing mothers and persons with cardiovascular diseases.
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WHO/FAO fat and fatty acids intake recommendations [30]
The Food and Agriculture Organization/ World Health Organization issued a recommendation on fats and oils intake in 1994. A new update and new recommendations followed. Three articles summarise the actual knowledge on fatty acids in human nutrition:
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Update of the 1994 WHO/FAO fat and fatty acids intake recommendations for children [31]
Uauy and Dangour 2009 summarize the highlights of the update of the WHO/FAO recommendations: During the rst 6 months of life, dietary total fat should contribute 40-60%E (% of total energy) to cover the energy needed for growth and the fat required for tissue deposition. From age 6 months to 3 years, fat intake should be reduced gradually, depending on the physical activity of the child, to approximately 30-35%energy, which is in line with the upper adult acceptable range. In industrialised countries a dietary fat intake of 30%energy is recommended to be adequate for normal growth and development of healthy children, provided that the diet supplies adequate energy and essential nutrients. The proposed ranges are slightly lower than the ranges of the report of 1994, aiming to control the obesity epidemic. For children over 2 years of age, saturated fat intake in the diet should be below 10%E with special attention to limit those with chain lengths of C12, C14 and C16. Polyunsaturated fatty acids should contribute 5-15%E whereby the ratio between omega 6 and omega 3 should lie between 5:1 and 10:1. The rest of the fat derived energy can come from mono-unsaturated fatty acids. Use of low priced hydrogenated fats to increase shelf life of complementary foods and other products is discouraged due to possible long-term adverse eects of this type of fat.
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Dietary fat and coronary heart disease
[32] Skea and Miller 2009 assessed the relation between dietary fat and risk of Coronary Heart Disease (CHD). The study presents evidence that diets low in SFA reduced total cholesterol and should therefore reduce the risk of CHD. Trans fatty acids were strongly and signicantly associated with CHD mortality and CHD events. Monounsaturated fatty acids were not signicantly associated with CHD mortality or events. Polyunsaturated fatty acids were strongly and signicantly associated with CHD mortality, but not with CHD events. n-3 LCPUFA or sh consumption were strongly associated with CHD mortality, but not with CHD events. The authors concluded that CHD risk is reduced when PUFA replaces SFA.
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Inconclusive evidence that dietary fat intake eects weight or diabetes [33]
Melanson and colleagues 2009 found that actual studies have failed to nd a consistent relationship between total fat and saturated fat intake and body weight or diabetes. They also found insucient evidence of any association between total fat intake and any type of fat, including trans fatty acids and conjugated linoleic acid, both found in dairy products, and risk of diabetes.
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Unilever suggestions to meet the fatty acid recommendations [34]
According to Unilever the current recommendations on essential fatty acid intake are around 4% of energy for linoleic acid (omega-6) and 0.25% for alpha linolenic acid (omega3). The new FAO/WHO recommendations could go up to 10% of energy for linoleic and 2% for alpha linolenic acid. Docosahexaenoic acid (DHA, an omega-3), now considered an essential fatty acid will also be included in these recommendations. Unilever stresses the diculty to meet these recommendations, because adding more of these fats and oil the calories count exceeds the energy recommendations The company suggests the production of ready to eat products in which some of the carbohydrates are replaced by the essential fatty acids, or replacing saturated fats with monounsaturated fatty acids in margarines, mayonnaise and dressings. To achieve the goals the company calls joint eorts between the food industry, governments, NGOs and other stakeholders for increased awareness of the consumer in relation to health issues using crisp and clear claims.
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Recommendations to eat more sh or take sh oil capsules should be avoided [35]
The National Health and Nutrition Examination Survey III, advices to increase intake of fatty sh and the actual intake of 100 mg/d of omega-3 sh oils up to 1000 mg (2 servings of oily sh) per week for prevention of chronic disease. Amounts of 250 mg/d to as high as 1000 mg/d are suggested for secondary prevention of coronary artery disease, and amounts of 2000-4000 mg/d are recommended for the management of elevated triglyceride levels. Jenkins, however, stresses that evidence for health benets from eating more servings of oily sh is not conclusive, and must should to be seen to increase worldwide depletion of sh stocks.
32
The authors recommend not to propagate increase of intake of long-chain omega-3 fatty acids through sh consumption until alternative sources of omega-3 fatty acids from plants, algae, or yeast become more available. Evidences of benets of sh oil for primary prevention of CVD cannot be supported for peoples eating a healthy lifestyle, eating a hearthealthy diet, exercising, and having a healthy body weight. Increasing demand of sh are depleting the sh population. Aquaculture increase the problem, because these shes are fed with sh meal. The American Heart Association (AHA), according to Dr. Penny M. Kris-Etherton, still stands by its recommendation to consume two servings of fatty sh sh per week to prevent cardiovascular diseases. The Prevenzione trial is cited to have 15% benet in the outcome of all-cause mortality, nonfatal miocardial infarction, or nonfatal stroke. documented benets that included a 45% reduction in sudden death. Heart and brain benets from omega-3 fatty-acid consumption reports include a decrease in age-related memory loss and Alzheimers disease. [36] However, the DART-2 showed that men with angina who were advised to consume sh oil had an increased risk of cardiac death.
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Very low intakes of saturated fats may increased risk of stroke [37]
Saturated fat intakes are known to rise blood cholesterol levels, increasing the risk of heart disease. A study of Yamagishi and colleagues 2010 suggests that other pathways as found in ischemic stroke may be implicated in ischemic stroke. The inverse association of saturated fats with overall stroke mortality was especially strong for intraparenchymal hemorrhage and ischemic stroke. The study also states that a reduction of intake of saturated fatty acids, together with increased polyunsaturated fatty acids (PUFA) resulted in an additional increase in stroke mortality. The authors speculate that in large vessels saturated fats can increase the risks of atherosclerotic plaques. However, in small vessels low saturated fatty acids levels may lead to angionecrosis, reduction of smooth muscles cells and increased fragility of vascular walls. The study is part of the ongoing Japan Collaborative Cohort Study for Evolution of Cancer Risk (JACC Study). The study included a follow up of 14.1 years, and included intraparenchymal and subarachnoid hemorrhages and ischemic stroke as well as heart diseases such as ischemic heart disease, cardiac arrest, and heart failure. The study says that an intake below 18 g of fatty acids/day increase the stroke risk by 20%, a diet with less than 11g/day increased the stroke risk by 66%.
33
Following this study the recommendations of the American Heart Association of a maximum of 16g per day of saturated fatty acids must be revised. The authors, however, say that on the other hand, an increase of saturated fatty acids in the diet might rise the risk on ischemic heart disease, and more studies are needed before public recommendations should be changed.
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Biodiesel byproduct as omega-3 EPA fortied food [38]
In three to four years foods omega-3 fatty acid EPA (eicosapentaenoic acid) fortied using byproduct of biodiesel will be on market depending on process optimization, yield of EPA and FDA approval. According to Zhiyou Wen and colleagues crude glycerol, one of the major byproducts of the biodiesel industry, added to yeast extract and submitted to the activity of the mould Pythium irregulare may resulte in biomass which is rich in omega-3 fatty acid EPA. To increase EPA content axseed oil and soybean oil was added to the mould culture. The mould elongated the shorter chains of linoleic acid and alpha-linolenic acid, into EPA and other longer chain fatty acids. The authors report a yield of glycerol-derived fungal biomass of 40 per cent carbohydrate, 15 per cent lipid, and 36 per cent protein. The authors conclude that biodiesel-derived crude glycerol may be used for the production of EPA fortied food or feed using the mould Pythium irregulare, however, yields are low, compared with other procedure using microalgae, such as diatom.
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The Korean Meta-analysis Study Group and the omega-3 sh oil controversyeKwakdoubl93407
A meta-analysis conducted by Kwak and the Korean Meta-analysis Study Group concluded in 2012 that omega-3 supplements (eicosapentaenoic acid and docosahexaenoic acid) do not prevent cardiovascular disease. A study of Kwak and colleagues included 14 randomized, double-blind, placebo-controlled trials, involving 20485 patients with a history of CVD. The authors found that supplementation with omega-3 fatty acids did not reduce the risk of overall cardiovascular events, all-cause mortality, sudden cardiac death, myocardial infarction, congestive heart failure, or transient ischemic attack and stroke. No signicant preventive eect was observed in in dierent subgroup analyses including concomitant medication use, duration of treatment, dosage of eicosapentaenoic acid or docosahexaenoic acid, or use of sh oil supplementation only as treatment. Kwak and colleagues concluded that omega-3 supplements were not benecial for secondary prevention of CVD.
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Comment on the Korean Meta-analysis [39]
Hu and Manson 2012 commented that the randomized trials used by the study of Kwak et al. were secondary prevention trials. These were high-risk participants, and many trials were short-term.and doses of omega-3 sh oil was to low (0,4 g and average 1,7 g daily). Hu and Mansosn also point to the fact that many of the participants were taking other medications, such as statins, aspirin, angiotensin-converting enzyme (ACE) inhibitors, beta-blockers, and medications that may have interfered with the ability to detect a moderate benet from omega-3s. Hu and Manson stress the importance of randomized trials of omega-3s to be done in primary-prevention trials, with average-risk populations. Such trials, like the ongoing Vitamin D and Omega-3 Trial (VITAL) [40] are being performe in a usual-risk population. Participants of the VITAL study receive vitamin D (2000 IU/d), marine omega-3 fatty acids (1 g/d, with 840 mg EPA and DHA). The Korean Meta-analysis Study excluded two open-label trials (the Gruppo Italiano per lo Studio della Sopravvivenza nellInfarto Miocardico [GISSI]-Prevenzione trial [41] and the Japan EPA Lipid Intervention Study [42]) found signicant benets of sh oil supplementation on CVD outcomes. Hu and Manson stress that regular consumption of sh should still be recommended. The American Heart Association recommends at least 2 servings per week of dark, fatty sh that are high in EPA/DHA such as salmon, mackerel, tuna, herring, and sardines. Fish replaces less healthful sources of protein, such as red meat or processed meats high in saturated fats. Vegetarians and vegans may increase intake of alpha-linolenic acid (ALA) or plant-derived sources of omega-3, using axseed, canola, and soybean oil.
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The mould Pythium irregulare is a plant pathogen [43]
Pythium irregulare root rot and blackleg of geranium is a mefenoxam insensitivity reemerging disease. The fungus is also commonly isolated from poinsettia, chrysanthemum, snapdragon, impatiens, and lavender. It is also known as downy mildew. Blight, damping o, root and other rots.
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Diet and Angina Randomized Trial (DART)and DART 2 Trial [44]
Burr and colleagues found in successive trials (DART) and (DART 2) conicting results examining the eect of an increased intake of fatty sh, or the use of sh oil supplements, in reducing mortality in men with heart disease. The Diet and Reinfarction Trial (DART) [45] reduced mortality by 29% in men recovering from acute myocardial infarction taking sh oil capsules or eating fatty sh.
35
The Diet and Angina Randomized Trial (DART 2) [46]found that eating fatty sh or taking sh oil capsules did not reduce mortality, and increased the risk of cardiac and sudden death in men with angina. Burr and colleagues suggest that dierent results of both trials are due to dierent actions of n-3 fatty acids in acute and chronic conditions, together with dierent eects of eating sh and taking sh oil capsules.
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Improved absorption of omega-3 fatty acids by pre-emulsication
Plummer and colleagues (2007) studying the absorption of omega-3 fatty acid, found that pre-emulsifying a blend of a standardized oil increases signicantly the postprandial plasma triacylglycerol (TAG) and the C18:3 (n-6), C18:3(n-3), C20:5(n-3) and C22:6 (n-3) polyunsaturated fatty acid (PUFA) levels. C16:0 and C18:0 saturated fatty acids, the C18:1 (n-9) monounsaturated fatty acid and the C18:2 PUFA were not signicantly changed, compared with a non-emulsied oil group. The authors conclude that the emulsication of an oil mixture prior to ingestion increases the absorption of longer chain more highly unsaturated fatty acids (especially eicosapentaenoic acid and docosahexaenoic acid) but does not aect absorption of shorter chain less saturated fatty acids, and suggest that pre-emulsication of sh oils may be a useful means of boosting absorption of these benecial fatty acids. This study may lead to improved sh oil supplementation.
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Riboavin
is used for food coloring. It has yellow color.Riboavin is vitamin B 12 and is therefore a safe color.
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Nutraceuticals
Nutraceuticals are compounds which normally occur in the body and have benecial eects on health. As they often do not occur in natural foods they have to be released by food authorities of each country or handled as drugs. SAMe ( S-adenosylmethionine ) enhances according to BASF well being. 5-m-THF (5-methyltetrahydrofolic acid )reduces according to BASF the risk of heart disease.These nutraceuticals were already launched in USA.
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Flavonoids and allergy [47]
Satomi Yano and colleagues from Kyushu University found that diet rich in plant avonoid such as apigenin (4, 5, 7,-trihydroxyavone) from herbs, fruits and vegetables can reduce serum IgE and inammatory cytokines such as RANTES (Regulated upon Activation Normal T cell Expressed and Secreted) and sTNFRI (tumor necrosis factor receptor I) and could protect and/or reduce the occurrence of asthma and other allergies associated with the immunoglobulin E (IgE). The authors found that apigenin-rich foods, such as celery and parsley are often associated with adverse food reactions. Therefore they used a diet supplemented with apigenin. This diet reduced immune and inammatory markers, such as IgE, IgG, IgM, IgA, and cytokine expression in mice signicantly. Other foods rich in apigenin are apples, beans, broccoli, cherries, grapes, leeks, onions, and tomatoes, as well as plant-derived beverages like tea and wine.
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Apigenin and prostate tumor [48]
Previous research into avonoids, and particularly apignenin, has focused on the potential anti-cancer properties of the compounds. Increased intake of fruits and vegetables may be associated with a reduced risk of prostate cancer. Apigenin, has shown remarkable anti-proliferative eects against various malignant cell lines like prostate cancer , slowing prostate tumour growth in mice. A study presented by Sanjeev Shukla relates evidence of the in vitro and in vivo growth inhibitory eects of apigenin on tumour cells.
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Algae[49]
There are up to 30000 types of algae which are being used in the production of drugs, cosmetics, thickening agent for soft cheese, puddings, ice cream and sauces, as animal feed, and fertilizer. Algae produce organic compounds and oxygen using carbonic dioxide and solar energy. Microscopic algae are responsible for the major part of the photosynthesis in the sea. Japan has a great consumption of algae such as:
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Ao-nori
,Awo-nori algae whose leaves are used as sushis(which are made of rice and other ingredients wrapped up in seaweed leaves),akes for salads, roasted as spice. They are rich on minerals, iron and vitamins. Porphyre tenera is an alga known as nori.
2.0.69
Kelp
or Green Nori is generally used as thickening agent, alga meal, as spice. It is rich on iron,potassium, magnesium and vitamins.
2.0.70
Green laver
,Sea lettuce(Ulva lactuca)is used as akes and grind for salads, snacks and cookies.It is rich on iron,proteins,minerals and vitamins. Alga composition: Humidity, as plant: 80 to 90% Humidity,dry : 10 to 20% Carbohydrates: 50% Minerals : 7 to 38% from dry weight Proteins : 8% in the Kombu-weed and 35% in the Nori-leaves Fat : 1 to 2% Algae are rich on cellulose being therefore partially not digested when used in human nutrition.[50]
2.0.71
Minerals found in algae
Iron, iodine, potassium, calcium, magnesium, sodium, phosphorus and zinc.
2.0.72
Trace elements found in algae
Aluminum, chromium, cobalt, manganese, nickel and titanium.
2.0.73
vitamins found in sea weeds
Vitamin A, B1, B2, B5, C, folic acid, niacin in fresh algae. The pro-vitamin A (beta-carotin) is present in very high concentration in the variety Dulce and 50.0000 i.U.in 100g of Nori. It is important as natural sources of alfa-tocopherols. Industry is making researches to substitue the synthetic provitamin A with natural pro-vitamin A from algae. The green seaweed Dunaliella salina is very rich in beta-carotin.
38
Arame ( Eisenia bicyclis)is rich in potassium, calcium, trace elements in particular iodine and vitamins. Dierent types of Laminarias which are brown algae and known as Kombu are very rich in iodine. Carrageen is used as thickening agent in numerous foods. It is being obtained from the seaweed Chondrus crispus Dulse(Palmaria palmata) is being used in the production of chips and other foods. It is rich in proteins, minerals, trace elements and vitamins. In human medicine is dulse used against anemia during pregnancy, against problems with the stomach and intestines and is known to act against worms Hijiki (Hizikia) has ten times the amount of calcium of milk. It is used against goitre because of its iodine. Table 2.5: Algae
Green algae,Chlorophyceae Ao-Nori, Awo-Nori Porphyra tenera Green Nori, Sea Grass Enteromorpha intestinalis Sea lettuce, green laver Ulva lactuca Thongweed, Buttonweed, Sea Haricots, Sea Spaghetti Himanthalia elongata Brown algae, Phaeophyceae Arame Hijiki, Hizikia Kombu Wakame Forest kelp, Cuvie, May-weed, Sea-rods
Eisenia bicyclis Laminaria japonica Undaria pinnatida Laminaria hyperborea
Red algae, Rhodophyceae Agar-Agar Thickening agent Dulse, Shell Dulse, Sea Grass Palmaria palmata Irisch Moos,Jelli Moss, Carrageen, Carrageen Moss Chondrus crispus Nori, Laver Porphyra laciniata Nori, Laver, Purple Laver, Sloke Porphyra umbilicalis Mannitol: Is a sugar which is being won from brown algae such as Kombu algae (Laminaria digitata with up to 16% of manitol). It has a sweetness equivalent of 60% of sugar. Kelp was used as fertilizer in the 12. century. In the 17. century kelp was used in the production of sodium hydroxide in manufacturing of glass. The potassium of kelp was
39 used to make gunpowder in World War I and II. Table 2.6: Composition of important Algae
Protein Fat Carbohydrates Vitamin C Calcium Iodine Iron Magnesium Manganese Sodium
Alaria Laminaria Laminaria Himanthalia Palmaria esculenta saccharina digitata elongata palmata 15% 9 11 9 18 1% 0,5 1 0,5 2 45% 60 45 60 48 300ppm 15 15 2.000 200 10.000ppm 9.000 13.000 9.000 5.000 170ppm 2.000 2.500 2.000 300 100ppm 30 60 30 200 9.000ppm 6.000 7.000 6.000 3.000 1ppm 10 8 8 100 4,5% 3 3 3 2 Alaria Laminaria Laminaria Himanthalia Palmaria esculenta saccharina digitata elongata palmata Table 2.7: Composition of important Algae
Protein Fat Carbohydrates Vitamin C Calcium Iodine Iron Magnesium Manganese Sodium Potassium
Chondrus Porphyra Ulva Enteromorpha crispus umbilicalis lactuca intestinalis 15% 20 20 14 2% 1 1 1 60% 60 44 45 20ppm 500 150 80 10.000ppm 5.000 7.000 8.500 200ppm 300 200 50 200ppm 200 1.000 150 7.000ppm 3.000 28.000 25.000 10ppm 40 300 8 2% 2 1 8 3% 0,7 0,5 Chondrus Porphyra Ulva Enteromorpha crispus umbilicalis lactuca intestinalis
40
2.0.74
Seaweed as a rich new source of heart-healthy food ingredients [51]
According to Hayes et al. 2011 algae are becoming important because of their conten of bioactive peptides, now obtained mainly from milk products, as ingredients in functional foods. Macroalgae provide up to 47% protein of the dry weight of macroalgae. Peptides derived from marcoalgae have hypotensive eects. Hypotensive peptides derived from marine and other sources have already been incorporated into functional foods.
2.0.75
Sushi [52]
Sushi is a traditional food of Japan which is known all over the world.The original meaning of Sushi was rice which had been turned souer using vinegar. Nowadays it stands for a special combination of Sushi-rice and other ingredients such as raw sh.
2.0.76 2.0.77
Classic Forms of Sushi Nigiri-Sushi
Raw sh or shrimps are coated with Wasabipaste and placed on top of small rice dumplings.NigriSushi is always served two at a time.
2.0.78
Maki-Sushi-roll
The lling is placed in the center of the roll and may contain two to ve ingredients coated with rice, wrapped in a layer of Nori. There are dierent forms of Maki-Sushi such as: Hosomaki are small Sushis. Futomaki are big ones. Gunkan-Maki have rice as bottom, Nori as wall and dierent ingredients on top of the rice. Ura-Maki-Inside Out is also known as California Roll which are nori leaves coated with rice and rolled so that the rice layer is outside and can be coated with sesame seeds or caviar. Temaki-Cornet are leaves of Nori foldet as cornet with rice and plenty of ingredients inside.
2.0.79
Sashimi
is Sushi without rice.All ingredients such as raw sh, vegetable, caviar and Nori leaves are placed on a Sushi board.
2.0.80
Chirashi
is a layer of warm Sushi-rice with seafood on top in a bowl served with Soysauce.
41
2.0.81
Margarine
As allergies are getting more frequent all possible allergens are controlled. In Leipzig (Germany) many families reported to have chosen margarine instead of butter. Children of these families suer more frequently from hay fever as children of families using butter in their nutrition. In those groups which had increased the intake of butter there were smaller levels of allergy - antibodies found. These results should be analysed very carefully because they are based merely on a limited number of statistical cases. The oversupply of our population with linolic acid from sunower oil, corn germ oil, Soy and thistle oil can cause problems. Linolic acid is an essential fatty acid. In small amounts it is indispensable for life. High levels of linolic acid act as basis for the synthesis of inammatory hormones. Together with the fact that a high level of linolic acid when burned can originate free radicals by unsucient supply of tocopherol, and the fact that polyunsaturated fats oxidize and turn rancid very easily her intake should be reduced. Olive oil and rapeseed oil should be preferred[2] As olive oil cannot supply the world demand of oil, only canola is left as ideal basis for the production of margarine. Excessive amounts of olive oil may cause inhibition of phagocitosis of the reticular endothelian system (RES)[53]. 12 persons were given 240 ml olive oil to drink in form of an emulsion with water in a period of 24 hours. Three hours after the last portion of oil 2,5 mg/ Kg albumin marked with iodine-125 were given intravenous. The level of marked albumin in blood was compared with the blood of control persons. The slow decrease of blood albumin of the test persons after intake of the high amount of olive oil compared with a rapid decrease in the blood of control persons has led to the theory of inhibition of the RES caused by excessive intake of olive oil. This shows that large amounts of fat are unhealthy.
2.0.82
High-oleic sunower seeds
New sunower seeds with more than 80% of oleic acid are distributed by the BME ( Bundesernhrungsministerium ) ministry of nutrition in Germany to test the possibility to use it as growing raw material.
42
This plant may become very important by growing need of oleic rich oil for human nutrition bearing in mind that high oleic olive oil is told to responsible for better health of the population of region of the Mediterranean Sea.[54]. Industry, traders, stores, and consumer should be aware that margarine containing rapeseed oil being better as made with sunower and soybean oil. Butter and other saturated animal fats must also be reduced because of their content of cholesterol and the arteriosclerotic risk. There are functional foods which are said to lower bad LDL cholesterol. Margarine with this property contains plant sterol esters. [55]. When eaten regularly this margarine can reduce the level of LDL cholesterol in blood by as much as 14%. The results of a Mayo Clinic study presented at the 81st Annual American Dietetic Association Meeting in Kansas City has conrmed this activity of plant sterol esters. Benecol is a margarine on market in Finland having plant sterol esters (sitostanol ester) as dietary ingredient. Benecol margarine and Benecol cheese spread was launched on the Netherlands market in 1999 by Johnson & Johnson with cholesterol lowering claim. Benecol cheese spread is based on the Benecol margarine. The health Ministry of Netherlands ordered to recall Benecol cheese spread as it is classied as Novel Food and must therefore undergo the approval procedure before entering the market.
2.1
Plant sterols
Plant sterols are naturally present in vegetable oils, in small amount in foods such as corn, wheat, rye, oats and olive oil and in wood in form of hydrated steroles called Stanoles. Plant sterol esters are formed by esterifying sitosterol with fatty acids becoming fat-soluble. Sitosterol is obtained as soybean extract. The average intake of plant sterols is 300-500 mg/day.Vegetarians have a daily intake of 800 mg. According to Westrate[56] there are 1,5 - 3 g/day necessary to lower blood cholesterol about 10%. Other studies such as the MRFIT- Study[57] and Meta-Study of law et al. came to the same result. Plant steroles reduce blood LDL cholesterol. The HDL cholesterol remains unchanged.
2.1. PLANT STEROLS
43
Plant steroles are similar in its chemical conguration to cholesterol. They reduce the cholesterol blood level preventing it to be absorbed in the intestines and is being excreted with the excrements. Less than 5% of phytosteroles are absorbed the prevailing part is eliminated with faecis carrying precipitated cholesterol. There is also a competitive action between plant steroles and cholesterol in the anity to the micelles as the plant steroles are more hydrophobic than cholesterol having therefore a higher anity to the micelles which they ll, leaving any place to cholesterol, blocking thus the way in the interior of the cells. Unilever wants to include Sterol derived from soybeans but must wait for the approval as novel food. Benecol does not need to wait for an approval because it had been already launched before Novel Food Regulation came into force.
2.1.1
Plant sterols contributed over one third of the LDL-cholesterol reduction [58]
High LDL-cholesterol levels are strongly associated to cardiovascular diseases. According to the guidelines of the National Cholesterol Education Program Adult Treatment Panel III (ATP III) the LDL-lowering eect of plant sterols/stanols esters, from soybean and tall pine-tree oils at dosages of 2-3 g/day lower LDL-C levels by 6 -15 percent with little or no change in HDL cholesterol or triglyceride levels. Whereas 2 g/day are recently considered as having maximal LDL lowering eect. Stanols are obtained hydrogenating plant sterols. The ecacy of both are similar. Because lipids are needed to solubilize stanol/sterol esters, they are usually available in commercial margarines. [59] According to a study leaded by David Jenkins the ATP III guidelines advocate eective combinations of cholesterol-lowering dietary components, resulting in large reductions in serum cholesterol. The authors assessed the contribution of the individual components of these diets. Plant sterols were selected because at 2 g/d, they have been reported to reduce low-density lipoprotein cholesterol (LDL-C) by 9% to 14%. The researchers found that plant sterols contributed over one third of the LDL-C reduction seen with the dietary portfolio after 1 year of following dietary advice.
44
2.1.2
Consumption of Food and Beverages with Added Plant Sterols [60]
Food products with added plant sterols are widely available in the EU, such as yellow fat spreads, dairy products and sauces including mayonnaises. Consuming plant sterols has been shown to help reduce blood cholesterol as part of a healthy diet. However, high doses can also reduce levels of carotenoids in the blood. These are a source of vitamin A and may help reduce the risk of certain chronic health disorders including some forms of cancer. Consumers should therefore restrict intake of such products to below the recommended maximum level of 3g per day.
2.1.3
EFSA Report on food and beverages with added sterols [61]
The report 2008 of the European Food Safety Authority on Food and beverages with added plant sterols highlights that while there seems to be little over-consumption of such products in the EU, a small subgroup appears to be consuming in excess of recommended amounts. It also reveals low consumer awareness of labelling and dietary guidelines for such products and of the need to consume sucient fruit and vegetables to ensure robust blood carotenoid levels.
2.1.4
Structure of plant sterols
Plant sterols are structurally related to cholesterol and can be divided into phytosterols and phytostanols, phytostanols being the saturated form of the phytosterols. Phytosterols and phytostanols both exist in free or esteried form. Phytostanols are less used in commercial products because the production is more expensive requiring hydrogenation and esterication while phytosterols require only esterication. Plant sterols fall into one of three categories: 4-desmethylsterols (no methyl groups); 4monomethylsterols (one methyl group) and 4,4-dimethylsterols (two methyl groups). The most common plant sterols are beta-sitosterol, campesterol and stigmasterol and structurally these are very similar to cholesterol, belonging to the class of 4-desmethylsterols.
2.1.5
Intake recommendations
It is clear that the manufacturers target a daily intake of between 1.5-3 g of phytosterol for an average person, covering the benecial range as noted by the Scientic Committee on Food (SCF, 2002a) [62]. In many cases the portion size provides about a third of the recommended daily phytosterol intake and the manufacturers suggest accordingly that the specic product should be consumed three times a day or other phytosterol-enriched products should be consumed to supplement the intake.
2.1. PLANT STEROLS
45
There is a growing concern that, as the number of enriched product categories increases, consumers might use several products simultaneously and receive higher doses of plant sterols than intended. The normal Western diet would contribute a daily supply of plant sterols in the range of 150-400 mg per person [62]. It should be noted that vegetarian diets are closer to the upper range. It has been found that plant sterols in the diet reduce the cholesterol absorption in humans and there is some evidence that levels of naturally occurring plant sterols might reduce blood cholesterol to a small degree. However, for an eective reduction higher doses are required. Scientic studies indicate that consumption of 1.5-3 g of plant sterols per day can signicantly reduce the level of low-density lipoprotein cholesterol in individuals if consumed as part of a healthy diet. It can be concluded that the estimated average intake of 300 mg of naturally occurring plant sterols in the diet constitutes only about 10-20% of the recommended intake of 1.5-3 g To take advantage of the cholesterol-lowering eect, an increasing number of food products with added plant sterols or plant sterol esters have become available on the EU market. Foods with added phytosterols or phytosterol esters require a novel food authorisation according to regulation 258/97/EC [63] since they were not used signicantly as food in the European Union before 15 May 1997. Foods with added phytostanols or phytostanol esters do not need a novel food authorisation since they were already used as food within the EU before the introduction of the novel food legislation.
2.1.6
Plant sterols inuence on carotene and other other essential fat-soluble micro nutrients [64]
Unfortunately, the consumption of high doses of plant sterols can also signicantly reduce the blood levels of carotenoids and, to a lesser extent, other essential fat-soluble micro nutrients. Although the consequences of a persistently decreased blood concentration of carotenoids on human health are largely unknown, there could be a concern during pregnancy, lactation or infancy when vitamin A requirements are greater than normal. As a prudent precaution it has thus been suggested that intakes of plant sterols should not exceed 3 g per day. [62]
2.1.7
Plant sterol intake and low-fat diet [65]
Chen and colleagues 2009 studied the eect of low-fat diet and plant sterols on plasma lipids, lipoproteins and carotenoids.
46
2.1.8
Eect of low-fat diet
Plasma total cholesterol (TC), high density lipoprotein (HDL) cholesterol, low density lipoprotein (LDL) cholesterol, Apo A1 and Apo B were lower with a fat reduction diet (26.4% fat and 7.7% of energy) compared with the typical American diet (33.5% fat and 13.2% of energy). TC/HDL cholesterol was found by the authors to remain inaltered.
2.1.9
Eect of plant sterol
Plant sterol intake (3.3 g/day) lowered TC, LDL cholesterol, Apo B and TC/HDLC by without aecting HDL cholesterol and Apo A1. The authors stress that the eect of phytosterol intake and low-fat diet lower independently plasma LDL cholesterol lipids and their eects are summed. The authors comment further that their ndings support foregoing studies in relation to the eect of phitosterols on plasma carotenoids.
2.1.10
Phytosterol and carotinoids [66]
Ntanios and colleagues 2002 studying side-eects associated with the consumption of PSenriched spreads had found a small reduction in plasma levels of the most lipophilic carotenoids such as -carotene, but no changes in plasma vitamins A and E levels.
2.1.11
Labelling of foods with added plant sterols [67]
The EC regulation 608/2004 imposes a statutory requirement for all products with added plant sterols to label the maximum daily dose of such compounds and include an advise pregnant or nursing women and children under 5 years of age to avoid consuming these products.
2.1.12
Resolution of the European Commission 200/500/EG. Phytosterine rich margarine
The Commission has allowed Unilever to put on market her new margarine containing a maximum of 8% of phytosterine corresponding 14% phytosterin ester. This fat spread is suitable for persons who want to lower their blood cholesterol. Contraindications: Patients which are taking drugs to lower cholesterol should include this fat spread in their nutrition under supervision of a doctor. Consuming this fat spread a signicant reduction of vitamin A takes place. People with a deciency of vitamin A (pregnant women, breast-feeding and children under 5 years) should be informed that the margarine is not suitable for these groups.
2.1. PLANT STEROLS
47
Consuming this margarine more fruits and vegetables should be included in the nutrition in order to compensate the reduction of vitamin A . Unilever has to monitor the groups of consumers in order to inform the European Commission whether the margarine reaches the target group and how much other groups are getting exposed to a high phytosterin level. Other companies trying to commercialize plant sterols are: Forbes Medi-tech and Novartis using phytosterols made from wood and Monsanto extracting sterols from corn bre oil and esterifying with ferulic acid as natural antioxidant Esters of sterols blocks cholesterol absorption inhibiting the transportation from the digestive tract to the liver. The amount of total and LDL cholesterol are lowered. [68] Table 2.8: Total sterols Oil/fat Total sterols gramm in 100 g oil/fat Palmkernel oil 0,08 Palm oil 0,04 Olive oil 0,11 Peanut oil 0,24 Rapeseed oil 0,62 Cotton oil 0,43 Corn oil 0,85 Soybean oil 0,34 Sunower oil 0,35 Linseed oil 0,43 [69] Table 2.9: Sterols % Oil/fat Palmkernel oil Palm oil Olive oil Peanut oil Rapeseed oil Cotton oil Corn oil Soybean oil Sunower oil cholesterol 1 4 1 brasicasterol 10 1 campesterol 12 21 3 12 27 8 20 19 11 stigmasterol 13 12 12 6 24 8 sitosterol 74 63 97 76 63 91 74 57 62*
48 Linseed oil 2 2 28 10
CHAPTER 2. FOOD, WHAT IS IT? 54* * and other components
2.1.13
The Mayo Clinic Study on Plant Sterol Esters,October 21.1998
A group of individuals who had borderline and mildly raised blood cholesterol were given three times a day 8 g of spread containing 1 g of plant sterol ester reducing 14% of LDL cholesterol after a period of 8 weeks. The HDL cholesterol levels (the good one) did not decrease.
2.1.14 2.1.15
Classication of the steroles Zoosteroles
: Are the steroles which are present in animals. Most important of them is the cholesterol.It is present in brain (2,5%),heart (2,0%), egg yolk (1,5%), mayonnaise (0,25%), butter (0,25%),meat (0,07%) and sh (0,05%).
2.1.16
Phytosteroles
: Are the steroles which are present in plants such as beta-sitosterol, stigmasterol and campesterol.
2.1. PLANT STEROLS
49
2.1.17
Mykosteroles
2.1.18
Ranation of oils and steroles
Ranation of oils and fats removes components with bad taste and smell, such as free fatty acids, products of oxidation, ketones, aldehydes and ketones, waxes,slime and phosphatides. It also removes environmental contaminants, herbicides,pesticides, fungicides, polycyclic hydrocarbon, heavy metals and products of the metabolism of of microorganism leaving traces which are tolerable.
50
Ranation of oils remove part of the steroles. Rened oils have 0,1 to 0,45% of steroles left. Vegetable oil cannot be a source of a daily intake of approximately 2 g/day.
2.1.19
Acid Value: AOAC pH-Metric Determination in Vegetable Oils without Titration [70]
Free fatty acids are measured as a quality control of vegetable oils during their production, trade, and use. It is expressed as acid value (AV). According to AOAC the acid value of edible oils can be determined without titration using a reagent containing a solution of water, isopropyl alcohol and triethanolaminea. The oil sample is mixed with the reagent in the pH-metric cell, free fatty acids from the sample are extracted into the reagent. The initial pH, called conditional pH1, is measured, a standard acid (HCl) is added,
2.1. PLANT STEROLS
51
and the nal pH, pH2, is measured. AV is calculated from the dierence between pH1 and pH2.
2.1.20
Texture of fats,oils and margarine
Fats and oils modify the structure, the stability the shelf life and the taste of food. It is therefore very important to determine the texture of fats and their blends.
2.1.21
Dilatation values
The fat Industry used to determine the texture of fats by measuring the dilatation of the product at dierent temperatures. The dilatation of fats goes straight on in solid form. As soon a part of the fatty acids melts the dilatation graphic suers a jump tha can be seen on a diagram and can be expressed as percentage of solids at dierent temperatures. 10, 20, 30 and 40o usually reported. The method was very work intensive and was therefore changed by NMR values using Brookfeld equipment.
2.1.22
NMR-values
As explained above, fats give a dierent response in solid or in melted form. This can be measured by Nuclear Mass Resonance ( NMR ) giving the percentage of solids in fats present in dierent temperatures. NMR- values dier about 4 points to the old not any more used method of dilatation. So if you nd in old literature dilatation values you can compare it with NMR-values subtracting 4%. NMR values are important to fat industry. They gives informations about melting response of the product at dierent stages of their using. Bakery, chocolate an all manufacturing factories depend on the texture of fat during processing in their equipments at dierent temperatures.
2.1.23
Texture analysis of fats oils and margarine
To have more informations about taste properties of fats oils and margarine and to express them in gures a conic shaped metal piece with a long stem was dropped under determined conditions on the margarine. The immersion of the cone expressed in centimeters gave an indication concerning the texture of the fat blend. This method was very imperfect and giving often false response.
52
To overcome these problems a texture analyzer such as TA.XT2i [71]have been developed. It consists of a conic sensor with an angle of 45o and a plate with the same angle where the fat is placed. The force which is necessary to deform the test material is by means of a graphic analysed giving so informations about the spreading properties of margarine and other fat spreads showing the force which is necessary to deform the product.
Spreading properties and hardness result from the relation of solids to liquid oil at 10o C (refrigerator) and 20o C (room temperature). Smoothness and stiness as well as other undesired properties of fat blends depend on the dimension and form of the fat crystals. A product is smooth when the crystals are small. Stiness and other failures result from great crystals. Texture analysis can express such failures in form from graphics.
2.2
Deep frying oil and shortenings
The fast food is mainly based on deep frying using oil or fat. The oil used is soybean oil rapeseed oil and cotton oil which may be hydrogenated. Palmoil
2.2. DEEP FRYING OIL AND SHORTENINGS and his fractions are also used in large scale.
53
2.2.1
Rened edible fats used in products like margarine and in infant formula may pose a health risk [72]
In a statement the German Federal Institute for Risk Assessment (BfR) rened edible fats used in products like margarine and in infant formula, may pose a health risk. During the rening of vegetable oil, such as palm oil, the ester-bound glycidol is formed. The BfR says that glycidol may be released during digestion. Glycidol is carcinogenic. The BfR adopts the hypothetical assumption that one kilogram of edible fat contains one milligram glycidol. The Institute says that infants who are fed exclusively industrially prepared infant milk formula would take in harmful levels of glycidol. As there is no alternative to infant milk formula with rened fats for infants who are not exclusively breastfed, the manufacturers of these products must do everything they can to reduce the levels of glycidol fatty acid esters as far as possible. The German association Stiftung Warentest analysed a vegetable fat creme which is labelled as a butter substitute. The association found palm oil glycidol-esters which may release the carcinogenic glycidol during digestion. [73]
2.2.2
Soybean oil
due to its high content of polyunsaturated fatty acids is not suitable for deep frying because it deteriorates very soon during frying. Soybean and cottonseed oil is therefore used in hydrogenated form to reduce the chemical reactions during long periods of heating.
2.2.3
Partially hydrogenated oil
Partially hydrogenated oil has high amounts of trans fatty acids 7.18. Partially hydrogenated soybean oil is used in North and South America because they are produced there and oer price advantage over imported palmoil. Palmoil and his fractions are widely used in Europe because soybeans as well as palmoil are imported. Soybean oil oers therefore no price advantage in Europe. Recent studies have shown that the trans fatty acids originated from hardening process increases the LDL cholesterol and lowers the HDL cholesterol in plasma. Moreover the trans fatty acids are suspected to interfere with the metabolism of essential fatty acids.
54
Danish retail margarine is now produced with trans-free hard fats. Industrial margarine such as used for backery has today under 5% of trans fatty acids. In near future "zero" will be the standard.(Peter Petersen, Aarhus Olie, Margarine-New Trends for a New Millenium Anuga Food Tec 2000, Cologne 13 April 2000.)
2.2.4
Margarine free of atherogenic trans-fatty acids [74]
Kim, Lumor and Akoh 2008, researchers from the University of Georgia developed alternatives to partially hydrogenated vegetable oils high in trans fatty acids used for the production of margarine and other foods. Structured lipids for formulating trans-free margarines were synthesized by lipase-catalyzed interesterication of the blends of canola oil, palm stearin, and palm kernel oil in weight ratios of 50:30:20 or 60:25:15. Both blends were trans-free and had similar hardness, adhesiveness, or cohesiveness to margarines which were produced from hydrogenated vegetable oils margarine fats high in trans-fratty acids. The authors claim that lipase-catalyzed interesterication of canola /palm stearin/ palm kernel oil is the is one of the most successful process in the production of trans-free margarines.
2.3
Palmoil
[75] Palm oil is one of the worlds most popular vegetable oils. Ninety per cent of the worlds palm-oil exports come from the oil-palm plantations of Malaysia and Indonesia. Most of these plantations are on the islands of Borneo and Sumatra. The very lowland forest that the oil-palm industry favours for conversion is the only remaining habitat of the orang-utan. Destructive oil-palm plantations will continue to spread, and the forests of Borneo and Sumatra will continue to be destroyed, unless the governments of Indonesia and Malaysia recognise the customary land rights of indigenous peoples and local communities. Solution: This report calls for an immediate end to all forest conversion to oil palm, and recognition of the customary land rights of local people. Boycotting palm oil is not the answer. There are also serious social and environmental problems associated with growing other vegetable oils, such as soy in Brazil. The UK is the second biggest importer of palm oil in Europe after the Netherlands. UK
2.3. PALMOIL
55
imported 914.000 tons in 2004, representing 23% of total palm oil import in the EU. The demand will further increase with the development of bio-fuel plants. As the promise of prots increases, the big players are beginning to get involved. The two largest external stakes in Greenergy Biofuels are held by Tesco and Cargill. Tesco will shift the product on its petrol forecourts, while Cargill - one of two giants that dominate the world food market - will supply the feedstock. Gone are the days when biofuels meant bearded hippies running their clapped-out vans on recycled chip fat. [76] Biofuels Corporation has just nished building a biodiesel plant at Seal Sands, near Middlesbrough, and supplies fuel throughout the UK, with an annual production capacity of 284 million litres of biodiesel, using as feedstock palm oil from Malaysia and other vegetable oils. Greenergy Biofuels, with its new plant at Immingham on Humberside, expects palm oil to be one of the main feedstocks. [76]
2.3.1
Palm oil health related concerns [77]
According to Enas tropical oils, such as coconut and palm oil are very rich in saturated fats. Their cholesterol-raising potential is similar to or higher than most animal fats. Liberal use of these oils should be discouraged. The American Medical Association expressed concern about the atherogenicity of coconut and/or palm oil in food products. Saturated fatty acids are found primarily in animal products and in tropical oils"(coconut, palm, and palm kernel oils). Persons attempting to limit saturated fatty acid intake should be aware of the high content of saturated fatty acids in tropical oils. [78] According to a meta-analysis by Clarke and colleagues, the ratio of total cholesterol to HDL cholesterol is important. The higher the ratio, the greater the risk. Palmitic acid increases that ratio more than other saturated fatty acids, including lauric acid and myristic acid, which are abundant in palm kernel oil and coconut oil, the other tropical oils. Palm oil increases the total:HDL cholesterol ratio more than the average U.S. dietary fat, though less than stick margarine, typical vegetable shortening (made with partially hydrogenated vegetable oil).[79] The World Health Organization has stated that there is convincing evidence that palmitic acid increases the risk of cardiovascular disease. [80]
56
A U.S. government regulation requires that, by January 1, 2006, food labels list a products content of trans fat, which comes from partially hydrogenated vegetable oil and is a major cause of heart disease. Many food processors are seeking to eliminate trans fat by switching to other oils. Palm oil is one such alternative. [81] The Center for Science in the Public Interest in a letter to the U.S. Department of Health and Human Services in June 1, 2005 expressed concerne that the use of palm oil may increase due to the Food and Drug Administrations (FDA) impending labeling requirement for trans fat. The group urged the FDA to encourage companies to reformulate foods without both partially hydrogenated oil and palm oil. [82]
2.4
Toxicology of heated fat
Oil and fat being heated in presence of oxygen form hydroperoxydes [83] Overheated fat causes irritation of the gastric system, enlarged liver retarding and even death of animals. This is intensied by an unsucient supply of vitamin E. Polymerization under high temperatures can also take place without oxygen. Chemical compound formed during deep frying are:Aldehydes, free fatty acids, alcohol, lactones, esters, ketone, aromatic compounds and epoxides. Peroxides of polyunsaturated fatty acids are the most toxic of all mentioned compounds. Enzymes bearing, SH-groups are inhabited by peroxides of polyunsaturated fatty acids. Peroxides of polyunsaturated fatty acids are also formed without strong heating. Atmospheric oxygen can originate peroxides when unsucient antioxidants like alfa-tocopherol is present. Vegetable fats and oils have sucient natural tocopherol to protect them from oxidation. Wrong food processing such as heating and long time storage reduces the natural antioxidant system.Strong heating and long storage of oils and fats during renation should be avoided. Sometimes processing of food destroys natural tocopherol Peroxides of linolic acid has proved to be toxic for the miocardium, it has breast tumor activity [83].
2.4.1
Vitamin E in edible oils
Edible oils are a source of tocopherol. Some of them have many unsaturated bounds which can form peroxides in human organism. These lipid peroxides which harm the cell membrane. Signal transduction and permeability of the cell membrane are disturbed.
2.4. TOXICOLOGY OF HEATED FAT
57
To avoid the formation of lipid peroxides natural antioxidants such as vitamin E are necessary summing up to 0,3 mg alfa tocopherol for 1 gram of double bound. The vitamin E which is available as antioxidant after deducting its own need are as follow:
2.4.2
Wheat germ oil
is rich on vitamin E (220mg/100g).After deduction of its own need there 170 mg/100 are available.Unfortunately it is very expensive and is therefore not used commonly in Kitchen.
2.4.3
Sunower oil
It has about 50 mg/100g tocopherol. After deduction of its own need there are about 19 mg/100g available.
2.4.4
Butter fat
It has about 2 mg Tocopherol in 100 g fat.Its own need demands more than that, so that a supplement of tocopherol of 0,2 mg/100g is necessary.
2.4.5
Maize oil
It has 30 mg tocopherol/100g and around 60% of polyunsaturated fatty acids . Its own need of antioxidants to avoid peroxidation exceeds by far its natural content of vitamin E. It needs therefore a supplementation of 5 mg/100 g for its own need. Be sure there is vitamin E added to maize oil otherwise it would increase the demand of tocopherol from other sources.
2.4.6
Lard
: It has about 10% polyunsaturated fatty acids and 0,3% vitamin E/100 g. The demand for its own antioxidant need is 6 mg/100g which has to be supplied from other sources.
2.4.7
Saower oil
It has 75 to 80% of polyunsaturated fatty acid and 35 mg tocopherol/100.Its own antioxidant need 13 mg/ 100 from other sources. Be sure there is vitamin E added to saor oil to avoid a negative balance of vitamin E.
Table 2.10: Biological activity of tocopherol isomers
58 Tocopherol isomer beta tocopherol Gamma tocopherol delta tocopherol [84] Table 2.11: Tocopherol Lange,Brown,Tufel,Schmidt isomers
CHAPTER 2. FOOD, WHAT IS IT? Biological activity of alpha tocopherol 30% 15% 1%
of
oils
and
fats(mg/Kg)
according
to
Oil or fat Total tocopherol Coconut oil 80 Maize oil 1020 Cottonseed oil 1100 Olive oil 200 Palmoil 460 Soybean oil 1140 Sunower oil 595 Wheatgerm oil 3800 Tallow 10 Lard 27 Butter 30
alpha tocopherol 36 126 760 150 80 560 -
beta -
gamma 47 894 340 240 660 35 -
delta 70 400 -
2.5
Colon carcinogenicity of heated oil
Corn germ oil heated at 210 C together with bubbles of air oxidize rapidly. This oil after cooling when fed to rats activated enzymes such as benzpyren hydroxylase in the mucous layer of their colon. Liver and enzymes of small intestine remained unchanged. Benzpyren hydroxylase triggered by heated corn germ oil could increase the transformation of procarcinogenic products in carcinogenic ones . Deep frying should not exceed the temperature of 180 C .Heating time should be short. Intermittent heating and cooling should be avoided because it leads to form polymerization of fat.
2.5. COLON CARCINOGENICITY OF HEATED OIL
59
2.5.1
Recommendations for Frying Oils, Third International Symposium on Deep-fat Frying. March 20-21,2000.
[85] The following recommendations for frying oils were adopted by the delegates: 1- Principle quality index for deep-fat frying should be sensory parameters of the food being fried. 2- Analysis of suspect frying fats and oils should utilize two tests to conrm abuse. Recommended analytic should be: Total Polar Materials (24%) Polymeric Materials (12%) 3- The use of rapid tests for monitoring oil quality are recommended. Rapid tests should exhibit the following characteristics: Correlate with internationally recognized standard methods Safe for use in food processing/preparation area Quantify with oil degradation 4- Previous work: There are no health concerns associated with consumption of frying fats and oils that have not been abused at normal frying conditions. (Note of the author of OurFood: There are health concerns with the consumption of frying fats related to transfatty acids, so fried food should be consumed with reserve. For further information search in "Physiology". 5- Encourage development 6- Encourage and support basic research 7- Use of lter materials to maintain oil quality.
2.5.2
Behavioural eects of trans-fatty acids linked to aggression [86]
According to Golomb et al 2012 some studies found omega-3 fatty acids to be associated with increased agreeableness and reduced impulsivity. Dietary trans fatty acids (dTFA) inhibit the production of omega-3 fatty acids, which experimentally have been shown to reduce aggression. Nutrient data were collected using a food frequency questionnaire, together with behavioural acts of aggression toward self, others, and objects assessing Overt Aggression Scale Modied, Life History of Aggression, Conict Tactics Scale, impatience and irritability. The authors found that eating more trans fats increased aggression and irritability. High trans-fat consumption increases heart disease and certain cancers and behavioural distress. Supporting the public health initiatives to limit trans-fat consumption.
60
Table 2.12: Classication of edible oil plants Group Legumen Soya Peanut Oil lupine Erucic acid plants Rape group Rape Brassica napus L. oleifera Rape of India Brassica napus L. dichotoma Sarson, Colza India Brassica napus. glauca Ravison,Colza Brassica campestris) Mustard group White mustard Other rape seed crops Rocket OIl radish Flax plants Linseed oil Mallow Cottonseed oil Other oil plants Oilseeds Maize Rice Wheat Sunower Saower Wine Palm tree Zea mays Oryza sativa Triticum ssp Helianthus annuus Carthamus tinctorius Vitis vinifera Gossypium hirsutum Linum usitatissimum Camelina sativa Eruca vesicaria sativa Raphanus sativus Sinapis alba Glycine max (L.) Merill Arachis hypogaea Lupinus albus Plant Name
2.5. COLON CARCINOGENICITY OF HEATED OIL Oil palm Elaeis guineensis Coco palm Cocos nucifera Olive tree Olea europaea Babassu palm Orbignia speciosa L. Table 2.13: Classication of animal oils and fats Group Land animals Oil or fat Lard tallow Mutton fat Goose fat Animal pigs bovine Mutton Goose Name Sus domesticus Bos taurus Ovis aries Anser domesticus
61
Marine animals Whale Seals Fish Herring Clupea harengus Sardine Sardinops caerulea Sardine of Peru Clupeapilchardus Atlantic menhaden Brevoortia tyrannus Mamals
2.5.3
Soya bean
The soya plant was known in china since antiquity. The cultivation of Soya started in USA in 1910 increasing rapidly in 1936 and by beginning of the II world war. About 90% of the world consumption is covered by USA and china. Brazil covers about 12%. Soya and peanut are plants of the family of the legumen.They form fruit leaves which fold forming husks.On the edge of the fruit leaves the seeds are attached In case of peanuts the husks are underground. That is why peanuts need a special soil with high content of sand which turns the soil soft this enables the husks to spread around. Soya beans are rich in oil, proteins and carbohydrates. The beans are processed in the country of destination. After winning oil and lecithin from the beans The soya cake is left over from the production of oil.It is used as valuable animal feed because of the high content of proteins and carbohydrates.Therefore the Soya beans are traded at the stock market, stored and transported in form of beans. Other oilseeds like palmoil, palmkernel oil or coco nut oil are processed in the countries of origin because the leftovers from the winning of oil are not valuable enough to pay the costs of transportation. Lecithin Lecithin of soya beans is a valuable ingredient of foods
62
and has many uses in pharmacy. Lecithin is a part of the cell wall of the nervous system. The spread of genetic modied seeds all over the earth is the reason why all eorts are being made to nd substitutes for soya lecithin. On market are already lecithin from rape oil. The amount being obtained from rape however cannot cover the needs of the international market. The purity of nature of soya plant should therefore be protected. The plants of the family of Leguminosae (Soya and peanuts) can undergo symbiosis with certain bacteria which can assimilate atmospheric nitrogen. This is the reason why the seeds of these plants are rich in proteins making the valuable for human and animal nutrition. Soya proteins are used in in backery,as substitute for meat and as fortier in sport medicine. In case of allergy against milk protein soya milk made of soya proteins can be used as substitute.
2.5.4
Calcium fortication of soymilk [87]
The protein of soymilk and other high protein drinks interacts with with calcium lactate and precipitates out. Not fortied soy milk have not more than 20 mg of calcium/100 ml. Producers are eager to fortify soymilk and rice drinks with 120 mg of calcium /100 ml to match it with milk. High protein content of soymilk and rice drinks, acidity of acidied milk products and tannins, and other polyphenols interact with calcium. Fortication with calcium to justify high calcium claim reduces shelf life of the product. Inorganic calcium phosphate and calcium carbonate have lower bioavailability than organic calcium lactate, calcium gluconate, calcium citrate. According to Sojaland, Schwerin-based company owned by Wild, the new capacity is intended to improve product taste. The soy foods started as health foods and are now located in the mainstream sector based on improvements to taste which do not have the typical beany taste. [88]
2.5.5
Health benets
The health benets from soy milk and other soy foods are such as for menopausal women, the products present an alternative to dairy for the lactose intolerant. Traditional dairies expand their range into soy with a variety of taste. Soy isoavones are involved in building bone mass, suppressing bone turnover and enhancement of calcium absorption.
2.5. COLON CARCINOGENICITY OF HEATED OIL
63
2.5.6
Tofu
Tofu is a cheese-like product of Soymilk which is curdled by a coagulant.It is known as soybean curd. Calcium sulfate (gypsum), Nigari ( a mixture of magnesium chloride, sodium chloride won from sea water), lemon juice or vinegar are used as coagulant. Calcium sulfate increases tofu content of calcium of . Nigari is told to produce a better tastes of the resulting tofu.
2.5.7
Rape oil
Rape plants are being cultivated in Europe (Germany, France, Netherlands and Scandinavia, Sweden).Canada is one of the main producer of rape. Argentina and Japan must also be mentioned. Rape seed has 30 to 50% of oil, up to 25% of proteins. In 1960 was noted that erucic acid which was present in the rape oil in about 50% had a necrotic toxic eect on the heart muscle and deposit of fat in the heart muscle. A selection of seeds made it possible to reduce erucic acid under 1% turning therefore rapeseed oil a valuable part of nutrition. Erucic free sorts of Brassica campestris and B. napus are cultivated as summer seed in Canada and Brassica napus as winter seed in Germany Rapeseed oil has aquire an importance as renewable energy as it can be used as substitute for diesel oil.
2.5.8
Erucic acid [89]
Erucic acid is a substance naturally found in some oils derived from plants, primarily in some varieties of mustard seed oil and rapeseed oil. Although there have been no conrmed cases of erucic acid toxicity in humans, high levels of erucic acid have been linked to the formation of fatty deposits in heart muscle in animals. Erucic acid is a 22-carbon monounsaturated fatty acid with a single double bond at the omega 9 position. Erucic acid constitutes about 30-60% of the total fatty acids of rapeseed, mustard seed and wallower seed and up to 80% of the total fatty acids of nasturtium seeds. Erucic acid has also been found in some marine animal oils. The Erucic Acid in Food Regulations 1977 (S.I. 1977 No. 691 [as amended]) limit the erucic acid content of foods to no more than 5% of the total fatty acid, in products with more than 5% fat (the latter restriction does not apply for foods aimed at infants or young
64 children).
In response to potential safety concerns associated with high dietary exposure to erucic acid (myocardial lipidosis and heart lesions in laboratory rats), eorts were made, using selective breeding, to transfer a low erucic acid trait into agronomically adapted cultivars of Brassica napus and B. campestris, which are used in the production of rapeseed oils. These varieties of rape were superseded by the canola varieties in the 1980s. Canola varieties have improved agronomic characteristics, such as increased yield and improved disease resistance. By denition, canola refers to B. napus and B. campestris lines containing less than 2 % of the total fatty acids as erucic acid. These canola varieties comprise almost the entire rapeseed crop produced in the world today. In 1997, the erucic acid content of 50% of the Australian canola crop was 0.3 % or less of the total fatty acids. The maximum reported erucic acid level was 1.6 % of the total fatty acids. The term canola has been registered and adopted in Canada to describe the oil (seeds, plants) obtained from the cultivars Brassica napus and Brassica campestris. In 1986, the denition of canola was amended to refer to B. napus and B. campestris (now Brassica rapa) lines containing <2% erucic acid in the oil and <30 micromol/g glucosinolates in the air-dried, oil-free meal. Throughout this document, the term "low erucic acid rapeseed" refers to low erucic acid, low glucosinolate rapeseed, or canola.
2.5.9
"Double zero" rapeseed varieties
indexRapeseed, double zero [89] In Europe, "double zero" rapeseed varieties are dened as those producing seed with a maximum glucosinolate content of 25 moles/g (seed weight) and with a moisture content of 9% (determined by method EN ISO 9167-1:1995) and, having erucic acid content of not more than 2% of the total fatty acid content (determined by method EN ISO 5508:1995).
2.5.10
Developments in Low Erucic Acid Rapeseed
After ten years of backcrossing and selection to transfer the low erucic acid trait into agronomically adapted cultivars, the rst low erucic acid varieties, B. napus and B. campestris were released in 1968 and 1971, respectively (Eskin et al., 1996). In Canada, the terms LEAR (low erucic acid rapeseed oil) and Canbra (Canadian Brassica) were used to identify rapeseed oil containing less than 5% erucic acid. Rapeseed meal is used exclusively as a high protein feed supplement for livestock and poultry.
2.6. ISOMALT
65
Prior to the late 1970s, the use of this oilseed processing by-product as an animal feed was limited by the presence of glucosinolates in the seed. Glucosinolates themselves are generally considered to be innocuous, however the hydrolysis products have negative eects on animal production. The low palatability and the adverse eects of glucosinolates due to their antithyroid activity led to the development of varieties of rapeseed which have combined low levels of both glucosinolates and erucic acid (also known as "double low" varieties). Low erucic acid rapeseed breeding programs in the 1980s and 1990s have produced cultivars with higher yields, increased oil and protein contents, earlier maturity, yellow seeds, reduced green seed and improved disease, insect and herbicide resistance (Eskin et al., 1996).
2.5.11
Sugar free products
Sugar free products are increasingly accepted by the consumer. They have sometimes better quality and taste compared with sugar products.Certain types are teeth friendly, low in calories and suitable for diabetic.
2.6
Isomalt
[90] Isomalt is a sugar replacer produced from sugar beet. His taste is not so sweet as sugar and it has no cooling eect which is often unwanted.It is low hygroscopic which makes candies stable without being wrapped one by one. Isomalt is a mixture of 6-O-alfa-D-glucopyranosol-D-sorbitol (1,6-GPS) and 1-O-alfa-Dglucopyranosol-D-mannitol-dihydrate (1,1-GPM). Increasing the 1,6-GPS part, which is water soluble part, isomalt increases the solubility kinetic soluble as maltitol and is comparable to xylitol.
2.6.1
Xylitol, Xilit, also called wood sugar or birch sugar, (2,3,4,5)tetrahyd pentanol, (C5H12O5) (E 967) [91] [92]
Xylitol is a ve-carbon sugar alcohol that is used as a sugar substitute. It can be extracted from birch, rasperries, plums, and corn and is primarily produced in China. It is roughly as sweet as sucrose, but contains less than 40% food energy. It is very popular in Finnland which is considered its "home country". It can have a mild laxative eect at high doses. It has no known toxicity. It is a popular sweetener for
66 the diabetic diet in some countries.
Xylitol belongs to the polyol family of sugar alcohols. It is as sweet as sucrose, xylitol is the sweetest of all the polyols, but is said to have no after-taste and is safe for diabetics. Xylitol is increasingly being used as a sugar substitute because it has one-third fewer calories, a cool mint avour, helps ght cavity-causing bacteria and does not involving insulin. The EU Scientic Committee for Food (SCF) authorised polyols for use in foods are sorbitol, xylitol, lactitol, mannitol, maltitiol and isomalt.
2.6.2
Production of xylitol
Xylitol is won from birch-wood bres under acids, high pressure and temperature, chemical catalysts followed by separation and purication steps. US Agricultural Research Service (ARS) chemist Badal Saha Timothy D. Leathers and collaborators developed a technology experimenting with yeasts like Aureobasidium, Pichia guilliermondii, Candida peltata and modied Escherichia coli bacteria, which can convert the hemicellulose sugars xylose and arabinose from corn ber leftovers of U.S. ethanol production or other sources into xylitol.
2.6.3
Xylitol reduces browning and degradation of preservative in beverages [93]
Carmen Campos and colleagues 2008 studying the interaction between aspartame, glucose and xylitol in aqueous model systems of pH 3.00 and containing potassium sorbate found that 0.050 to 0.500 per cent aspartame reduced the degradation of potassium sorbate from of system. Xylitol was used as humectant to minimized aspartame degradation and nonenzymatic browning development. According to Campos the preservative potassium sorbate suers an oxidative degradation in aqueous solutions and brown pigments develop, aecting the microbial stability and the sensory quality of the food. The authors stress that the presence of aspartame, xylitol or glucose and their mixtures produced a synergistic eect on sweetness intensity. The authors concluded that xylitol and the use of more than one sweetener would enhance sweetness of the product and minimize degradation of potassium sorbate and reduce browning development.
2.6. ISOMALT
67
2.6.4
Tomato ketchup, tomato and tomato pulp
Tomato ketchup has a growing acceptance all over the world.It was born in USA and soon became a place in fast food restaurants. Children like it because of the color and last but not least because of strong taste. In German 1,4 Kg of tomato Ketchup were eaten each year ( Weber, 1992) Tomato ketchup is produced from tomato pulp, salt, sugar and other monosaccharides, vinegar and spices.Onions garlic, thickening agents like carob seed, Guar seed, gum tragacanth and starch may be used. In Germany the Bundesverband der Deutschen Feinkostindustrie (The association of the German ne food industry) has established a guideline for tomato Ketchup. At least 24,1% of tomato pulp 28-30% dry matter also called double concentrated tomato pulp are to be used for tomato ketchup. High quality products have up to 37% of tomato pulp double concentrated. Tomato pulp is a basic part of tomato ketchup. It is therefore very intensively submitted to quality analysis. Taste, odor and color are important tests on receipt of tomato pulp. Some further quality criteria are given below[94]: Table 2.14: Analytic of good tomato pulp double concentrated, S.Hanewinkel-Meshkini and W.Hackmann 1989 EtOH 0,1 0,1 0,1 0,1 0,1 0,1 0,1 0,1 0,1 TA 16,9 17,3 16,6 18,5 19,5 19,4 19,6 16,9 17,4 CA CA/Ta 17,9 1,06 16,2 0,94 16,6 1,00 19,7 1,06 19,7 1,01 20,6 1,06 17,4 0,89 17,2 1,02 16,4 0,94 L-LA 0,8 0,9 0,5 1,1 0,6 0,5 0,3 0,6 0,1 D-LA 1,3 0,6 0,4 0,9 0,7 0,3 0,3 0,3 0,1 AA 0,4 0,5 0,6 0,4 0,6 0,3 0,9 0,5 0,5 SA 2,5 2,0 1,5 2,4 1,9 1,1 1,6 1,4 0,7
Table 2.15: Abbreviations used EtOH TA CA L-LA Ethanol Total acids as citric acid Citric acid L-lactic acid
68 D-LA AA SA
D-lactic acid acetic acid [94] Sum of L-lactic acid, D-lactic acid and acetic acid. All numbers are g/Kg Table 2.16: Analytic of spoiled and o avor tomato pulp double concentrated, S.Hanewinkel-Meshkini and W.Hackmann 1989 EtOH TA CA CA/Ta L-LA D-LA AA SA 4,39 15,0 9,3 0,62 5,7 3,6 2,2 11,6 0,87 24,2 18,6 0,77 4,6 3,7 4,2 12,5 2,28 24,4 16,0 0,66 8,1 4,0 3,1 15,2 0,68 18,1 10,4 0,57 3,5 5,4 2,8 11,7 0,1 17,4 8,3 0,48 4,7 3,4 2,7 10,7 4,57 17,6 13,6 0,77 3,8 3,3 1,4 8,5 7,5 17,3 12,2 0,71 3,6 2,1 1,3 7,0 1,76 16,8 7,7 0,46 7,5 3,1 4,6 15,2 1,2 15,4 7,7 0,50 6,8 2,6 4,0 13,4 0,10 19,1 12.4 0,65 4,9 4,3 2,2 11,4 2,42 18,8 13,2 0,70 3,5 2,6 2,2 8,3 2,77 18,0 11,2 0,62 4,5 3,4 3,4 11,3 1,26 18,2 12,6 0,69 3,6 3,3 1,4 8,3 2,40 18,2 10,2 0,56 4,9 3,4 4,0 12,3 10,4 15,8 12,3 0,78 1,0 0,9 1,3 3,2 0,96 17,3 7,8 0,45 3,3 2,7 3,0 9,0 1,26 17,6 7,0 0,40 2,9 6,5 1,6 11,1 Table 2.17: Summery of the analytical criteria, according to Hanewinkel-Meshkini and Hackmann: A tomato pulp is spoiled when one or more alterations are found Ethanol is present Relation citric acid/total acid the relation in spoiled pulp is between 0,4 and 0,9. Good pulp has a relation over 0,9 as citric acid is metabolized by spoiling bacteria. Sum of organic acids The Sum of L-lactic acid, D-lactic acid acetic acid over 3 g/Kg.These acids are formed during spoilage. Good tomato pulp has the following analytical data Alcohol content less than 0,1 g/kg Organic acids (total of L-D-lactic acids and acetic acid) under 3 g/Kg Citric/total acid relation of over 0,9
2.6. ISOMALT
69
All mentioned analytical data testing tomato pulp should be considered together because dierent acids are formed by dierent species of bacteria. Recently ergosterol is also used in quality control of tomato pulp, being a maximum of 3,0 mg/Kg allowed. Tomato pulp of the European Union is being produced mainly in Italy, Greece and Spain. Pulp of Turkey, and Uzbek (Russia ) are imported in small amount. The quality varies to its origin and producer. The products of northern Italy such as the region of Parma are of high quality. The main product of this region is the pulp which is concentrated and packed assepticaly without delay during harvest in these factories, thus giving yeasts, moulds and bacteria no chance of spoilage. In southern Italy, such as the region of Neapel and Salermo the main products are peeled and crushed tomatoes. The rest of this production is used to manufacture tomato pulp. As the capacity of the production line during harvest in these factories are insucient, the pulp is left in open barrels, unprotected, sometimes exposed to sun. Deterioration takes place. The Ubekistan tomato pulp is triple concentrated. Due to old technology the color and the taste are of very low quality. The biogenic acidsaatoxins and other contaminants are originated under these conditions. Color and taste are often a useful indicator of bad manufacturing practice such as described by Hanewinkel-Meshkini [95] At rst the Howard mould count ( HMC ) was used to monitor mould activity in tomato pulp. Moulds are a hazard in tomato pulp because of possible production of mycotoxines such as tenuazonic acid from the mould Alternaria alternata (tenuis), Alternaria tenuissima , Alternaria kikuchiana, Alternaria longipes (Roth et al 1990).
2.6.5
Jasmonic acid in ozone stressed tomato plants [96]
Ozone activates defence responses in plants according to Zadra and coleagues from the University of Perugia. The researchers fumigated tomato plants with ozone. The highest concentration of jasmonic acid in the leaves of these plants were noted 9 hours after the treatment. Jasmonic acid concentration in leaves of stressed plants increased 13-fold. The level of endogenous methyl-jasmonate was not altered during the experiment.
2.6.6
Bacteria deteriorating tomatoes
Penicillium Aspergillus Alternaria alternata

70 Alternaria solani Alternaria tenuis Alternaria tenuissima Alternaria tomato Colletotrichium coccodes Didymella lycopersici Fulvia fulva Phoma destructiva
Phytophthora infestans, a brown mould growing on tomatoes causing at rst graygreen, later brown dots.The esh remains hard. Pyrenochaeta lycopersici Fusarium oxysporum Mucor, causing o-avor Botrytis, grow on tomatoes causing small round dots surrounded by a small bright ring (Krug1991) Cooling tomatoes to 6C reduces deterioration signicantly. Tomatoes were at rst cultivated in South America. The name was "tumatl" meaning "bad taste" and were brought to Europe by the Spanish conquistadores. At rst used as decoration the plant was told later to have erotical activity and was therefore classied by the church as "plant of Satan". Only after World War II tomatoes became largely used as food in Germany, Tomatoes are now widely known as base for the production of tomato juice, baked, cooked or peeled tomatoes, as pulp in sauces, in pieces in salads, on pizzas and last but not least as tomato ketchup. Tomatoes are eaten more than other vegetables[97] Table 2.18: Vegetables eaten in Germany, Kg/person/year.(Globus Statistic of 1990/91 Tomatoes Onions Cucumber Carrots 15,3 6,0 5,7 5,5
2.6. ISOMALT
71
Mushrooms 2,5 Beans 1,9 Asparagus 1,3 Industry in Germany has intensied analytical supervision of tomato concentrate used in the production of tomato ketchup and related products. The eort of quality management triggered by certain publications of test magazines, the HACCP concept and ISO 9.000 resulted in increasing quality and security of tomato pulp used in the production of tomato ketchup and related products.
2.6.7
Pesticides in tomatoes
Pesticides can be present in tomatoes and related products. Of actual concern are: Lindan Procymidon Endosulfan Dicofol Vinclosolin Tetradifon Iprodion Farmers should use pesticides only in accordance to users instructions. All eorts should be undertaken to make tomatoes and relate products safe and keep a high quality standard all over the world. Developing countries should invest much work to garantee standards of the Codex Alimentarius.
2.6.8
Origine of tomato concentrate
Tomato concentrate is being produced in large scale in Italy in the region of Parma, Grece, Turkey,Spain and China in the Xinjang region.
72
2.6.9
Meat and poultry, growing market and environment
The production of meat from pigs in Germany has increased since 1960 about 60%. At the same time the number of animal owners has been 85% reduced. This causes a great concentration of animals in some places, creating an environmental problem with growing amount of liquid manure. Liquid manure is a good fertilizer when used in small amount.In case of intensive animal breeding it turns out to be an environmental factor because of growing quantities of ammonia. Ammonia is harmful to humans, animals and plants. Excessive ammonia can be transformed to nitrate by bacteria, washed out by rain and pollute the water. To handle this problem the DIL (Deutsches Institut fr Lebensmitteltechnik) made experiments to reduce ammonium and TOC Total Organic Carbon by means of cultivating algae, such as Chlorella and bacteria in presence of small amount of glucose. In these experiments ammonia had been 80% reduced and TOC up to 90%. The bacteria involved in these experiments were: Alcaligenes faecalis Alcaligenes sp Ochrobactrum anthropi Rhodococcus erythropolis[98] Because of growing environment pollution the concentration of Farming and industrialization should be a main concern of governments to allow only an organic growth dictating maximum limits of growth. Great projects can be distributed in dierent sectors in order to harmonize with nature.
2.6.10
Garlic
The treatment of hyperlipidemia is a signicant value in the prevention of diseases of the blood vascular system. As this treatment can take years it may develop intolerability to the drugs used. Garlic powder can be used to avoid these inconvenience. As it has been found by the Association of German Physicians (Fachverband Deutscher Allgemeinrzte) garlic preparations such as Sapec and Kwai reduces total cholesterol about 9% an triglycerides about 15% after several month of therapy.
2.6. ISOMALT
73
Much has been written about the activity of garlic in the treatment of hyperlipidemia. Holzgartner, Schmidt and Kuhn compared garlic preparations with benzabrate in a study with 98 patients with primary hyperlipoproteinemia with more than 250 mg/dl of cholesterol, and or triglycerides. The daily doses were 900 mg of garlic powder (standardizes as to 1,3 % alliin) and 600 mg of benzabrate. The study was divided in the following parts: Pre-phase with placebo during 6 weeks. Treatment period during 12 weeks together using garlic powder or benzabrate together with a low-fat "step - I diet to reduce blood fat ". (Total food fat under 30% of total calories. Relation between saturated and polyunsaturated fatty acids 1:1 . Daily intake of cholesterol under 300 mg. Reduced calories to reach normal body weight.)
2.6.11
Total cholesterol
The garlic treatment reduced the total cholesterol from 282 mg/dl to 210 mg/dl. The benzabrate treatment reduced cholesterol from 287 mg/dl to 208 mg/dl.
2.6.12
HDL-cholesterol
HDL-cholesterol had increased in both groups, in the garlic group from 34,3 mg/dl to 48,6 mg/dl and in the Benzabrate group from 35,5 mg/dl to 51,4 mg/dl.
2.6.13
LDL-cholesterol
LDL-Cholesterol was signicantly reduced in both groups, in the garlic group from 195,3 mg/dl to 130,2 mg/dl and in the Benzabrate group from 200,8 mg/dl to 130,0 mg/dl.
2.6.14
Triglycerides
Triglycerides were signicantly reduced in both groups, in the garlic group from 306,0 mg/dl to 207,5 mg/dl and in the Benzabrate group from 307,2 mg/dl to 168,6 mg/dl.
2.6.15
Reported garlic smell
The blood lipids decrease with and without resulting garlic body smell is signicant only in regard to triglycerides there is a better action when smell is noted. Hozgartner, Schmidt and Kuhn suggest therefore to adjust the dose from patient to patient so that there is no body smell left. The table below gives the results of the study:
74 Lipid fraction Total cholesterol HDL-cholesterol LDL-cholesterol Triglycerides
CHAPTER 2. FOOD, WHAT IS IT? with smell without smell decrease of 83 mg/dl decrease of 58 mg/dl increase of 18 mg/dl increase of 10 mg/dl decrease of 77 mg/dl decrease of 51 mg/dl decrease of 163 mg/dl decrease of 34 mg/dl
Garlic is therefore an ingredient of food used as spice which is proved to have blood lipid reducing action. Garlic seems to interfere in in the synthesis of cholesterol acting on the HMG-CoAreductase. Allicin [99]is the active part being originated from Alliin of garlic. Garlic is also told to have many antioxidants. According to Jean Carper [2] acting antiaging, revs up immune functions, reduces high blood cholesterol, acts as anticoagulant thinning blood, protects aging brains, inhibits cell changes leading to cancer, suppresses free radicals. Carper advises the intake of half a fresh clove to two or three a day. As supplements 600 to 900 mg of garlic powder per day has heart-protective eects. About one and a half cloves of garlic block the formation of carcinogenic nitrosamines in the stomach. The activity of garlic depends on the size of the glove and the soil in which it is grown. Garlic grown in selenium rich earth is particularly rich in trace mineral selenium which enhances the antiaging powers. Carper recommends not to exceed three raw garlic cloves a day. Raw garlic in high dose can be toxic. There is little danger in cooked garlic. Eating more than 20 grams a day of garlic is told to cause gastric bleeding [2].
2.6.16
Antioxidant properties of garlic unveiled [100]
Garlic is known for its strong aroma taste and its antioxidant properties of allicin to scavenge free radicals. The food researchers Vaidya, Ingold and Pratt, found that allicin has to decompose generating sulfenic acid, which is the link between garlic and its health benets. According to the authors, other plants of the same family of garlic, such as onions, leeks and shallots and garlic, also contain compounds similar to allicin, but do not have such strong antioxidant properties due to a slower rate of decomposition of the allicin analogs to the active sulfenic acid.
2.6. ISOMALT
75
2.6.17
Biological and chemical stability of allicin dier, suggesting other active compounds [101]
Toyohiko Ariga and colleagues 2008 assessed the instability of allicin in water, ethanol and vegetable oil. Allicin from crushed fresh garlic is known to have antibacterial activity. The authors determined the stability of allicin, in dierent solutions, looking at its antibacterial activity toward Escherichia coli. Allicin was found more stable in 20% alcohol than in water, and very unstable in vegetable oil. The authors suggest the existence of bioactive compounds other than allicin on account of the fact that, in the dierent extracts, the biological half-life of allicin was longer than the chemical one.
2.6.18
Enzyme alliinase increases healthy properties of garlic [102]
According to Galmarini and colleagues 2007 crushing garlic before cooking can reduce the loss of garlics healthful properties, such as the in-vitro antiaggregatory activity of human blood platelets. The authors suggest that cooking inactivates the enzyme alliinase which catalyses the formation of allicin (allyl 2-propenylthiosulnate), which then breaks down to form a variety of healthful organosulfur compound. Crushing or chopping garlic the alliinase can trigger the formation of allicin and its breakdown compounds before being inactivated by heat. The study of Vaidya 2009 supports Ariga 2008 and Galmarini 2007 which suggest that decomposition products of allicin are the active compounds of the health benets of garlic.
2.6.19
Selenium [103]
Selenium acts together with garlic. An undersupply of selenium reduces signicantly the benets of garlic. Germany is under supplied with selenium. Fruits, vegetables, and grains growing here are poor in selenium. Source of selenium Amount of selenium, microg/100g Bread of German grain 1 to 2 Bread of Canadian grain up to 60 Selenium is toxic in large amounts, but trace amounts of it, forming the active center of certain enzymes, are necessary for the function of all cells in (probably) all living organisms. In 1996, continuing research showed a positive correlation between selenium supplementation and cancer prevention in humans. Used widely in vitamins and food supplements, in small doses (typically 50 to 200 microg per day for adult humans. Some livestock feeds are fortied as well). [104]
76
2.6.20
Cancer prevention properties of selenium
Studies on this matter are Shamberger and Frost (1969) [105], Burguera (1990), [106], Clark (1996) [107], Patterson (1997) [108], Fleet (1997 [109], Knekt (1998) [110], Young (1999) [111], Schrauzer (2000) [112], Brooks (2001) [113], and Akbaraly et al (2005) [114].
2.6.21
Protection of the immune system [115]
Melinda A. Beck and colleagues, in a review, found that host nutritional status can inuence not only the host response to the pathogen, but can also inuence the genetic make-up of the viral genome. The researchers noted that selenium decient mice infected with a mild strain of inuenza developed severe lung infections. Viral mutations resulted in a more virulent phenotype in the infected mice. This could be linked to the development of emerging new infection diseases such as the severe acute respiratory syndrome (SARS) and the acquired immune deciency syndrome (AIDS).
2.6.22
Bladder cancer prevention properties of selenium [116]
This case-control study suggests an inverse association between serum selenium concentration and bladder cancer risk.
2.6.23
Impact of selenium on mood [117]
Margaret Rayman and colleagues in a study, found no evidence that selenium supplementation beneted mood or quality of life in elderly volunteers.
2.6.24
Selenium supplementation reduces oxidative stress of coronary diseases [118]
Fausta Natella and colleagues found that a supplementation of 110 micrograms of selenium per day as selenium yeast during 10 days prevented postprandial oxidative stress. Oxidatively modied LDL activates a series of cellular events in the arterial wall ultimately leading to plaque formation. Dietary lipid hydroperoxides that escape from the gastrointestinal barrier can be incorporated into plasma lipoproteins, leading to a modied form of LDL (LDL minus). Selenium supplementation inhibited after-meal increases in oxidatively modied LDL. Selenium induced a signicant decrease in preprandial plasma glutathione peroxidase (GPx) activity and inhibited the meal-induced increase in GPx activity. Selenium supplementation fully prevented the meal-induced increase in both LDL minus level and LDL suscepOurFood Database of Food and Related Sciences Copyright 1998-2010 Karl H. Wilm. All rights reserved.
2.6. ISOMALT tibility to oxidation.
77
Selenium supplementation also avoided the increase of post-prandial malondialdehyde (MDA), a major end product of lipid oxidation. Prior to supplementation MDA plasma levels had been increased by about 10 per cent. The European recommended daily intake (RDI) of selenium is 65 micrograms. Following EU levies imposed on wheat imports from the US where the soil is rich in selenium, the intake has fallen from 60 to 34 micrograms per day. Dietary source of selenium is oatmeal, cereals and bread, dependent on the selenium content of the soil where the ingredient grains are cultivated. Soil acidity and selenium complexion with iron or aluminium decrease the amount of selenium available to plants.
2.6.25
High-selenium wheat [119]
Average intake of selenium in the UK has fallen from 60 to 34 micrograms per day changing USA and Canadian wheat import to homegrown and EU wheat grown on low selenium soils. The European recommended daily intake (RDI) is 65 micrograms. The vast majority of the worlds population (including that of Australia, with a probable mean plasma/serum level around 89 microg/l. An intake of 200-300 microg/day selenium is being suggested to signicantly reduce cancer risk, and Moyad (2002), suggests that an intake of 200 microg/day Se and around 50 mg/day of vitamin E may be benecial, particularly for current or previous smoker. The results of the NPC trial suggest that males may have a higher Se requirement than females. Further studies may nd optimum adult Se intakes in the range 125-280 microg/day, with means of around 130 (F) and 250 (M). [119] Se deciency and sub-optimality are manifested in populations as increased rates of thyroid dysfunction, cancer, severe viral diseases, cardiovascular disease, and various inammatory conditions. The authors call for a supra-nutritional selenium intake to achieve an optimal cancer protection suggesting to increase the selenium content of wheat by biofortication of wheat with selenate. Before recommending large-scale fortication of the food supply with Se, it will be necessary to await the results of current SELECT and PRECISE intervention studies. [119]
2.6.26
SELECT [120]
The Selenium and Vitamin E Cancer Prevention Trial is currently investigating the eect of selenium and vitamin E supplementation on incidence of prostate cancer.
78
Data and additional analyses of the SELECT trial were published online December 9, 2008, in JAMA. Among the specic results highlighted, the ve-year rate of prostate cancer diagnosis in the four arms of the study was 4.43 percent in the placebo arm of the trial, 4.56 percent in the selenium arm, 4.93 percent in the vitamin E arm (the highest rate, but one that does not show a statistically signicant dierence from the placebo arm), and 4.56 percent in the selenium plus vitamin E arm.
2.6.27
Selenium and Vitamin E alone or in combination did not prevent prostate cancer in the SELECT study [121]
Selenium and vitamin E supplements, taken either alone or together, did not prevent prostate cancer. This study iwas found a small but not statistically signicant increase in the number of prostate cancer cases among the men in the trial taking only vitamin E and a small, but not statistically signicant increase in the number of cases of adult onset diabetes in men taking only selenium. Neither of these ndings proves an increased risk from the supplements and both may be due to chance. Data and additional analyses of the SELECT trial were published online December 9, 2008 [122], in JAMA. Among the specic results highlighted, the ve-year rate of prostate cancer diagnosis in the four arms of the study was 4.43 percent in the placebo arm of the trial, 4.56 percent in the selenium arm, 4.93 percent in the vitamin E arm (the highest rate, but one that does not show a statistically signicant dierence from the placebo arm), and 4.56 percent in the selenium plus vitamin E arm. SELECT participants received letters in October 2008 explaining the study review and telling them to stop taking their study supplements. The study was stopped.
2.6.28
The Physicians Health Study (PHS) II [123]
The Physicians Health Study (PHS) II, in a nal report from Gaziano and colleagues 2008 does not support vitamin E and C for cancer prevention. The authors conclude that in this trial of male physicians, neither vitamin E nor C supplementation reduced the risk of prostate or total cancer. The authors do not support supplementation with vitamin E nor vitamin C for the prevention of cancer in middle-aged and older men.
2.6.29
Use of Selenium and vitamin E not recommended for prostate cancer prevention [124]
Highlighting some controversies on selenium and vitamin E in the prevention of cancer Dr. Peter H.Gann says that physicians should not recommend selenium or vitamin E, or any other antioxidant supplements, to their patients for preventing prostate cancer.
2.6. ISOMALT
79
2.6.30
Selenium in soils varies signicantly
There are enormous geographical variations in the Se content of soil and food, and hence in Se intakes and concentrations in human blood and tissues. Thus, it is essential to use local data for monitoring and interpreting Sestatus. The 2000 US Recommended Dietary Allowance (RDA) is 55 microg/day. The 1987 Australian RDAs are 70 microg/day for women and 85 microg/day for men. [125] Combs calls for a regular adult intakes of at least 40 microg/d to support the maximal expression of the selenium enzymes, and perhaps as much as 300 microg/d to reduce risks of cancer. He writes that low selenium status is likely to contribute to morbidity and mortality due to infectious as well as chronic diseases, and increasing selenium intakes in all parts of the world can be expected to reduce cancer rates. [126] Research results continue to illustrate the importance of Se in human health, in particular its anti-inammatory, anti-cancer and anti-viral activities. It is evident, due mainly to its poor availability in many soils, that at least a billion people may be Se-decient. Furthermore, the vast majority of the worlds population would receive well below the level needed to maximise cancer prevention, which is likely to be within the range of 125280 microg/adult/day, depending on gender, pregnancy and exposure to oxidative stress. [126]
2.6.31
Selenium-enriched yeast (Se-yeast) [127]
In a review article Margaret P. Rayman states that selenium-enriched yeast (Se-yeast) is a common form of Se used to supplement the dietary intake of this important trace mineral. However, its availability within the European Union is under threat, owing to concerns expressed by the European Community (EC) Scientic Committee on Food that Se-yeast supplements are poorly characterised and could potentially cause the build up of Se in tissues to toxic levels. The author concludes that Se-yeast from reputable manufacturers is adequately characterised, of reproducible quality, and that there is no evidence of toxicity even at levels far above the EC tolerable upper intake level of 300 microg/d.
80
2.6.32
Deciency of Selenium intake in animals [128]
In most European countries, native Se content in grain and forages is very low. Regular use of such feeds can result in Se deciency, associated with severe disorders like myodystrophy (white muscle disease), exudative diathesis, impaired functions of liver and pancreas and a concomitant depression of production performance and reproductive ability (more information in Sharma et al., 2005 and Surai, 2002). Another situation is characterised by a marginal shortage of Se, which usually does not exert apparent clinical signs of Se deciency, but may cause delayed development of immunocompetence and hence raise susceptibility of animals to infectious diseases. Therefore, the insucient native Se contents of feedingstus and the severe consequences of decient Se supply give urge to supplement livestock routinely with extra Se.
2.6.33
Selenosis [128]
It is well established that both accidental and long-term overdose of Se result in intoxication of farm animals. In general, a single oral intake of Se dose in range of 1-5 mg kg-1 body weight (bw) may already lead to death. While high blood Se levels up to 25 mg L-1 are typical to acute selenosis, the chronic Se overdose usually results in blood Se concentrations of 1 to 4 mg L-1. It is generally accepted that animal selenosis may appear when dietary Se content exceeds 5 mg kg-1 feed. The acute Se toxicity is characterised by abnormal posture, unsteady walk, diarrhoea, abdominal pain, increased pulse and respiration rates, hypotension due to vasodilatation, foamy nasal discharge, prostration and typical garlic smelt of breath due to presence of volatile DMSe in expirated air (Gasmi et al., 1997). The primary targets of acute Se toxicity in animals appear to be the cardiovascular, gastrointestinal, central nervous and hematopoietic systems (Raisbeck, 2000). The signs of chronic selenosis in cattle include deformations, cracking and loosing of hooves, lameness, stiness of joints, dullness, lack of vitality, emaciation, loss of hair. Various forms of blind staggers can develop. In sows, the chronic selenosis is accompanied with reduced performance of reproductive system. Hooves of pigs show breaks similar to those in cattle. Other signs include loss of hair, reddened skin and neurological symptoms. The immune system may be also impaired (Raisbeck, 2000). In poultry, the intake of feeds containing Se above 5 mg kg-1 results in lower hatchability of eggs due to deformities of embryos. Mature birds seem to tolerate more Se than
2.6. ISOMALT
81
do pigs or cattle and do not exhibit signs of poisoning other than poor hatchability of their eggs. Experimental Se intoxication in growing chickens led to severe diarrhoea, dyspnoea and somnolence of birds (Salyi et al., 1993).
2.6.34
Production of selenium enriched yeast [129]
Selenium enriched yeast (Saccharomyces cerevisiae NCYC R397) is the product of industrial fermentation of Saccharomyces cerevisiae NCYC R397 in selenium enriched media. The aerobic fermentation takes place in a medium containing beet or cane molasses, nutritional salts, vitamins and a food grade selenium source leads to the nal product. Live yeast cells absorbs selenium and biochemically transforms it into L (+) selenomethionine and other seleno-related compounds. The inactivated and dried selenium enriched yeast is subsequently blended with non viable dehydrated yeast (Saccharomyces cerevisiae) to standardize the nal selenium content. The end product becomes inactivated whole cell yeast containing a minimum of 2000 ppm of total selenium and a maximum of 2% of residual inorganic selenium. At least 60% of the total organic selenium is in the form of selenomethionine (SeMet). Bibliographic data show that organic selenium as selenium enriched yeast is comparable if not better than inorganic selenium in providing for a higher blood and milk selenium concentration and GSH-px activity. The benecial eects obtained with selenium enriched yeast of Saccharomyces cerevisiae NCYC R397 compared with inorganic selenium as feed additive are the following: Higher bioavailability to animals (ruminants, pigs, and poultry) compared to inorganic sources of selenium (sodium selenite and sodium selenate). Increased activity of the enzyme glutathione peroxidase (GSH-Px) in blood. Increased milk, tissue and blood Se content. These trials show that selenium enriched yeast of Saccharomyces cerevisiae NCYC R397 can be used as an alternative to inorganic selenium (like sodium selenite (Na2 SeO3 ) and sodium selenate (Na2 SeO4 ) at a maximum content of selenium in the complete feedingstu of 0.5 ppm (Directive 70/524/EC)) currently authorised without time-limit. FDA approved the use of selenium enriched yeast in animal nutrition from September 3, 2003 as a source of selenium for beef and dairy cattle (with previous approval given in 17 July 2002 for use in feed for swine, turkeys, and chickens). The product included a
82 maximum of 2% of inorganic selenium.
In Canada, selenium enriched yeast (Saccharaomyces cerevisiae NCYC R397) is registered and approved for use in animal nutrition from March 2004 by the Canadian Food Inspection Agency (CFIA ).
2.6.35 2.6.36
Selenium enriched yeast and drip loss of meat [128] Less drip loss of meat (poultry, pigs)
A signicant reduction of drip loss by Sel-Plex selenium enriched yeast was seen in broiler study 2, whereas selenite was signicantly less eective than Sel-Plex selenium enriched yeast. In broiler study 3 Sel-Plex selenium enriched yeast did not inuence drip loss in comparison to the unsupplemented control group. Expressible moisture in muscle was signicantly increased by Sel-Plex selenium enriched yeast in broiler study 4. In broiler study 5 the drip loss was signicantly inuenced by Se level and Se source (Sel-Plex selenium enriched yeast and selenite), Sel-Plex selenium enriched yeast being more eective than selenite. But there was no unsupplemented control group. Pig studies 4 and 5 did not show any signicant eect of Sel-Plex selenium enriched yeast on drip loss.
2.6.37
Conclusion
A reduction of drip loss by Sel-Plex selenium enriched yeast could only be shown in two broiler studies; in both studies selenite was less eective. In a broiler study as in the two pig experiments Sel-Plex selenium enriched yeast did not exert any inuence on drip loss. The FEEDAP Panelcon cludes that the eects observed are not consistently demonstrated and, if so, the eect is likely due to Se itself and not to the Se source.
2.6.38
Selenium position statement of Australian Cancer Council [130]
The Cancer Council Australia in a position statement on selenium supports the National Health and Medical Research Council recommended dietary intake of 65 microg/day for men and 55 microg/day for women with an upper intake limit of 400 microg/day. Some studies suggest that selenium may be inversely associated with prostate cancer and colorectal cancer. The evidence of a protective role of selenium in other types of cancers is weak and inconsistent.
2.7. SEAFOOD
83
The Cancer Council Australia does not support the use of health claims on food labels that suggest selenium protects against the development of cancer.
2.6.39
Elevated serum selenium is associated with elevated serum lipids [131]
Selenium, known for its antioxidant properties may, however, aect several cardiometabolic risk factors, such as glucose homeostasis and lipid concentrations. Joachim Bleys and colleagues 2008 examined the relation of serum selenium concentrations with serum lipids. They found that elevated serum selenium was associated with elevated serum concentrations of total cholesterol, LDL cholesterol, HDL cholesterol, triacylglycerols, apo B, and apo A-I among US adults, a population with high selenium intake. The authors call for more experimental studies to determine cause and eect of the relations of elevated serum selenium and serum lipids.
2.7
2.7.1
Seafood
Hake
The term hake refers to sh in either of: families Gadidae (subfamily Phycinae) families Merlucciidae (both subfamilies Merlucciinae and Steindachneriinae). An old European source mentions a hake that was transplanted from the coast of Ireland to Cape Cod. [132] Meatver hake, whitin (Merluccius bilinearis): North America Pacic hake,Pacic whiting, North Pacic whiting, Merluccius productus Snook (Merluccius vulgaris) Hake, merluce (Merluccius merluccius) Merluccius merluccius, merluce Cape hake, stock sh (Merluccius capensis) Chilean hake, Peruvian hake (Merluccius gayi)
84
2.7.2
Tuna
Albacore is harvested by US vessels trolling with articial lures on or near the surface and with pole and line. These same vessels use bait to attract albacore wherein they are hooked with a jigging pole o the stern and landed individually. Barbless hooks are used in this shery. The absences of nets ensures the shery is "dolphin free". [133] Pacic albacore, Long nned albacore (Thunnus alalunga) Black n tuna (Thunnus atlanticus) Bigeye tuna (Thunnus obesus) Bluen tuna, Atlantic tuna, Californian bluen, horse mackerel (Thunnus thynnus) Others: Monksh, anglersh (Lophius piscatorius) It is a bone sh. Common sole, black sole, Dover sole (Solea vulgaris vulgaris) Sprat(Sprattus sprattus) Brown shrimp, common shrimp (Crangon crangon) Black tiger (Panaeus monodon) Deep-sea prawn (Pandalus borealis) Dublin Bay prawn, langoustine, Norway lobster (Nephrops norvegicus) Squid, cuttlesh (Sepia ocinalis) Whale, cetacean (Cetacea spec.)
2.7.3
Salmon
There are dierent grades of fat content. The low fat grade is being sold in Europe. The medium fat grade is used to produce smoked salmon and the grade of high fat content is sold in Asia. Since 1995 there is also the Omega-3-salmon available. Greatest producers of salmon are Canada and Norway. There is a great variety on market, depending on their origin: Atlantic salmon, graved salmon from Sweden, Irish salmon. The variety of Norwegian salmon is Salmo salar. More than one fourth of the Norwegian salmon is bred in cages in the fjords. This form of concentrated sh farming represents an environment problem. In order to avoid disease, boils, bacteria and moulds pesticides are used. To avoid sh louse the pesticide ivermictin is used. Virotic infections are under control with vaccination by means of feed. Ivermectin kill not only the sh louse but also the worms living in the sediments of the bottom of the Water and which is an important feed source free living sh. Overfeed and enormous amounts of excrements trigger the development of bacteria of putrefaction and toxic algae One of the best known sh in the history of shery was codOurFood Database of Food and Related Sciences Copyright 1998-2010 Karl H. Wilm. All rights reserved.
2.7. SEAFOOD sh (Gadus spec.).
85
Codsh had been an important basic nutrient. It was preserved through drying or salting.
2.7.4
Salmon an trout is endangered by a multi-host parasite [134]
The infectious pathogen, a rosette-like intracellular parasite Sphaerothecum destruens carried by invasive cyprinids threatens Stocks of Atlantic salmon along with varieties of domestic brown trout. In 2005 Dr. Gozlan warned that the parasite poses a severe threat to some freshwater sh species in Europe. The parasite causes high morbidity and mortality in North American salmonid species including Atlantic salmon, brown and rainbow trout. [135] According to DNA ndings conducted by the authors, the European strain of the parasite was found to present a degree of isolation toward the North American agent. It is found on healthy invasive shes which spread the agent to sympatric populations of native shes. Freshwater sh such as bream, carp and roach are endangered by the parasite. The authors call to develop more sensitive detection tools of the rosette agent to counter future outbreaks which may pose a risk for sheries and commercial aquaculture. Movement of sh for stocking purposes may further facilitate its spread. The decrease of the number of the sunbleak (Leucaspius delineatus) in parts of Europe is to be associated with the spread of a healthy carrier, the Asian topmouth gudgeon.
2.7.5
Codsh and the church in the Middle Ages
Dried and salted codsh is today still being consumed in large scale due to the activity of the Roman Catholic church. In the Middle Ages the Church imposed their believers days of fasting. Sexual act and meat was forbidden, however no restriction on "cold food" was known. Fish and whale living in cold water were therefore allowed. Whale was eaten on "slender days", on all Friday because this was the day in which Jesus was cruzied, the forty days of fasting and a couple of holy days leaving almost no days for the consumption of meat. Basques as leading nation on codsh at that time became wealthy. Codsh became a religious cult object as a symbol of religious life. That is the reason why in many Catholic countries dried salty codsh is being traditionally eaten on Good Friday.
86
2.7.6
Codsh as basic nutrient
Codsh had been an important source of proteins for the islands of the Caribbean Sea. A supply shortfall of salty codsh due to rotten political relationship between United States and England caused th death of starvation of 15.000 slaves in Jamaica during 1780 and 1785. With the industrial revolution a growing market for bottom dwelling sh arose in Great Britain. Codsh, haddock, plaice and later sh and chips developed as important food for workers in town and is today still a traditional food consisting of fried sh nuggets and French fries. In the 18th Century cod liver oil was used in Great Britain to cure rheumatism. In the 19th Century sh liver oil was used in case of tuberculosis, malnutrition and other diseases related with poverty. During the second world war liver oil was given to pregnant women, children under 5 years f age and persons over 40 as malnutrition was feared by the Ministry of Nutrition.Fish liver oil is not being used today because of its taste.
2.7.7
History of codsh shery
The Vikings were the rst population strongly united to codsh shery. Their boats sailed from Norway to Iceland, Greenland and the coast of Canada following shoals of Atlantic codsh (Gadhus morhua) which they salted preserving it. Due to its very low concentration of fat and its white esh is codsh the best raw product for salty and dried sh. Between 985 and 1011 the Viking Thorwald and his son Erik the Red sailing from Norway settled in Island, Greenland and the coast of Canada leaving places to dry the codsh. Later on Basques specialized on codsh, sailing as far as the banks of North America where the cold water of Greenland meet the Gulf Stream. In these regions the water was extremely rich on codsh. For long time the Basques could hide the secret of their shing grounds and became wealthy feeding the whole Mediterranean region with Atlantic salty codsh. Miguel de Cervantes cites codsh in Don Qixote (1605-1616) being called as pollack in Castila and salt codsh in Andalusia. As the Basques disposed of plenty of salt their codsh was very stable. That is why the Basques could make longer journeys as the Vikings. John Cabots in 1497 discovered the secret shing grounds of the Basques on his rst
2.7. SEAFOOD voyage to America. A second trip was of no return. No one knows what happened.
87
The resulting competition between nations ghting for the shing grounds and later on the introduction of the steam boats with ground nets nearly exterminated the codsh. The second world war a time to recover for codsh in the North Atlantic because of the intensive war activity. As soon as war was over big trawlers started shery on large scale. In 1822 a treaty between France, Germany, Netherlands, Denmark and Great Britain in Den Haag established for the rst time a tree miles of territorial waters valid for the North Sea. A treaty between England and Denmark in 1901 declared the sea around Island as international water with the exclusion of a three mile zone . Island was at that time a colony of Denmark and was to weak to make any opposition to that treaty. As reaction to intruders Island started a well organized coast gard to counter German and British trawlers which entered the three miles zone. A further eort to protect marine species was a close cooperation with the International Council for Exploration of the Seas (IREM) which controls the size of the sh population of endangered species. The British trawlers installed in the beginning of 1928 radio transmitters to warn their colleague with the message "Grandmother is not feeling good" whenever a coast gard boat had left the harbor. In 1944 Island became independent from Denmark and could now extend the territorial waters to four miles. In 1945 The USA under President Harry Truman proclaimed the claims at the mineral raw materials of the continental shelf in order to protect oil reserves. In addition these claims were also risen by all other Latin American countries giving support to the international recognition of territorial waters.
2.7.8
The rst codsh war
As the population of haddock and codsh decreased Island extended in 1958 their territorial waters to 12 miles. This started a real Codsh War between England and Island. Finally in February 1961 Great Britain recognized the twelve miles waters.
2.7.9
The second codsh war
In 1971 Island announced the extention of their waters up to 50 miles. The second codsh war began. The Island coast gard used to cut o the nets oh the trawlers. Fish was the
88
only wealth of Island which remained therefore unchanged in its position. Because of the intervention of the NATO Great Britain was forced to recognize the 50 miles zone.
2.7.10
The third codsh war
The population of codsh still decreased despite the 50 miles. Eighteen years old cod sh got extremely rare. Only fteen years old specimens were caught. Island announced therefore beginning with the 15. October 1975 the extention of their territorial waters to two hundred miles. It came to 53 ship collision. In February 1976 the European Community proclaimed the 200 miles territorial waters ending thus the third codsh war. Spain and Portugal were deeply aected by the 200 miles regulation because their waters do not bear good shes. Nevertheless the population of codsh decreased and many regulations were issued. In 1992 shing of codsh in North Atlantic was forbidden. A recovery of the population will take about 15 years. The European Union is going to reduce the catch quota of codsh in the Kattegat about 58%, haddock in the Irish Sea about 52% and sole in the North Sea about 25%. According to the commissioner of the EU Franz Fischler at 6.12.01 the situation is alarming and everything should be undertaken to avoid a complete extermination of some species due to overshing. From the number of ground shes in EU shing waters in the 70th only 10% are left in the late 2001. [136]
2.7.11
EU sh quota causes 40%-60% of sh being dumped [137]
European Union quotas strictly limit the amount of sh that vessels can bring back to port. Quota exceeding catch is being dumped. most of it dead. Fisher boats in the North Sea, catching a species or size of sh which is above their quota and have to throw it back, however less than 1 percent survives. The EU estimates that between 40% and 60% of sh caught by trawlers in this area is dumped back into the sea. According to Green Peace 186 million sh caught in UK waters in 2006, 117 million of them were thrown away dead as waste. According to Enever, Revill and Grant 2007, discards in the English Channel, Western Approaches, Celtic and Irish Seas are about 63% by number and 35% by weight of all sh caught. [138] World Wildlife Funds Helen McLachla calls for selective gear to avoid unwanted catch. Centre for Environment, Fisheries and Aquaculture Science (Cefas) looks after such selecOurFood Database of Food and Related Sciences Copyright 1998-2010 Karl H. Wilm. All rights reserved.
2.7. SEAFOOD
89
tive gears, analysing results of the Rhode Island design as a cod-conservation tool allowing to sh for haddock and not harming cod. [139]
2.7.12
US Navy may continue sonar training at California harmes marine animals [140]
US Navy sonar training goes on, despite harming marine mammals. Environmental groups, such as the Natural Resources Defense Council n (NRDC), brought a lawsuit against the US navy, alleging that military sonar harms or even kill 37 species of marine mammals, such as sea lions and blue whales, disturbing their ability to navigate and communicate. Sonar has been linked to substantial and irreparable harm to marine mammals, like mass strandings and hemorrhaging around the brain and ears, and symptoms akin to a severe case of "the bends", the illness that can kill scuba divers who surface quickly from deep water, indicating that sonar alters their dive patterns. NRDC is working nationally and internationally to establish strict regulations on sonar use so that whales and other marine mammals dont have to die for practice. The lawsuit involved 14 training exercises o the California coast that began in February 2007 and ends in January 2009. According to Chief Justice John Roberts, who prepared the judgement, the overall public interest favoured the Navy, which needs realistic training with active sonar to respond to the threat posed by enemy submarines. This outweighs environment interests. President George W. Bush interfered in the judicial process citing the national security necessity of the training and exempting the Navy from the environmental laws.
2.7.13
The military sonar and whale mortality
The NRDC reports that the military employs two types of active sonar: mid-frequency and low-frequency. Low-frequency sonar travels enormous distances in seawater. During testing o the California coast, noise from SURTASS LFA, the Navys main low-frequency system, was detected across the breadth of the North Pacic. By the Navys own estimates, even 300 miles from the source these sonic waves can retain an intensity of 140 decibels. This is a hundred times more intense than the level known to alter the behavior of large whales. Mid-frequency sonar is more widely used and has been associated with mortalities of whales.
2.7.14
Anisakiasis
Anisakis is a nematode (hairworm) which attack sh and live in their body.Anisakis simplex is common in the Seas of the North. The worm is being found in many shes such as herring, codsh, mackerel, pollack and sprat.
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Anisakis can live only in sea water. The worm is uncoloured almost transparent. It resists to 1% sulphuric acid for a period of 6 Days. Deep-freezing at -30o C kills immediately th worm. Frozen food is therefor safe of Anisaki.
2.7.15
Life cyclus of Anisakis
The parasite must go through hosts to complete its life cyclus. The male expelles eggs of 0,02 mm diameters.Larvas of 0,25 mm come out of the eggs after some days. To survive the larvas have to nd a host in the next weeks.
2.7.16
The rst host
As rst host the Anisakis invades small crabs such as Copepoda and Euphausiacea where the rst sloughing 4 to 6 mm takes place.
2.7.17
Infection of sh
A sh is infected by ingesting the rst host in form of small crabs. The larva of Anisakis remains unchanged in a capsule in the stomach and intestines of the sh. About 0,7% of the larva get into the muscles of the belly piece. Liver hard sh roe and other organs are seldom infected by the larva. However as the sh dies the larva abandons its capsule and migrates to the muscles. The sh should therefore opened and the innards schould be taken out as soon as possible to avoid migration of the Anisaki larva to the muscles. Sometimes when the sea is ru and the tripulation is seasick work is not done and the sh is left unprocessed waiting for better weather. In this case Anisakis larvae migrate to the muscles, being an unpleasent nding later on when it is consumed.
2.7.18
Sexual maturity
The Anisakis larva can only achieve sexual maturity in a mammal host such as whale, delphin or seal.
2.8
2.8.1
Functional Food
Mass market brands
The consumer is forced to look after packaged staple foods at fair price, which are found in the mass production segment with benets located at daily needs. Non-essential products such as bottled water, drinking yoghurts and chewing gum are good items to spare money.
2.8. FUNCTIONAL FOOD
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2.8.2
Health benets labelling in Canada, E.U., and U.S. Emphasise on scientic credibility [141]
Sanders and colleagues 2005 stress that successful and responsible global introduction of probiotic and prebiotic products requires labelling for health benets that meets consumer needs, adheres to regulatory standards and does not overextend scientic evidence. They also note that existing regulations emphasis on scientic credibility of health claims. The authors also analyse the value of dierent types of evidence of ecacy and examine the imitations of in vitro, animal and human studies used for ecacy substantiation for probiotics and prebiotics.
2.8.3
Health claims in the United States may be misleading to consumer [142] [143]
Hasler 2008 Health claims in the United States have been a topic of intense controversy since the mid-1980s. Health claims are based on a very high standard of scientic evidence and signicant scientic agreement. Hasler says that US health claims regulations had limited success and may be misleading to consumers.
2.8.4
Premarket authorization and substantiation of health claims on foods [144]
Labb and colleagues 2008 analyse the regulatory framework of health claims on foods in Canada and compare it with international approaches, and how risk-reduction claims for serious diseases are managed in the United States, European Union and Australia, stressing the need for premarket authorization and the requirement for a high level of certainty in substantiating claims.
2.8.5
Health claims in Europe: new legislation and PASSCLAIM for substantiation [145]
The EU regulation on nutrition and health claims from 2007 will be fully implemented by January 2010. It includes reduction of disease risk claims. A community list of permitted and rejected claims will be dened. To achieve this, the European Commission supported the project, "Process for the Assessment of Scientic Support for Claims on Foods" (PASSCLAIM), with the main purpose to dene a set of generally applicable criteria for the scientic substantiation of health claims on foods.
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2.8.6
Foodwatch says there is no dierence of the eect of Actimel compared with normal yoghurt [146] [147]
Foodwatch says that Danone makes a mountain out of a molehill suggesting that Actinimel protects from cold and boots health. Foodwatch believes that the company sells a common product using excessive advertising. [146] Alexa Meyer, from the Department of Nutritional Sciences, University of Vienna, Austria, comparing probiotic drinks and normal yoghurt, found no signicant dierence in the eect of Actimel and normal yoghurt with living bacteria. The nutritional researcher recommends to get enough sleep, wash hands often and eat a daily bowl of yoghurt. She says this would activate more active germ-ghting white blood cells,enhancing the immune system, probably due to the presence of Lactobacillus bulgarius, from any normal yoghurt, which has half the price of Actimel. [148] This is being supported by Bethold Koletzko from the University of Munich, Metabolic Diseases and Nutrition, Munich, Germany in case of diarrhoea advices parents to give their children yoghurt with living bacteria. It does not necessarily be Actinimel, but may also be other yoghurts. The Advertising Standards Authority (ASA) is an independent regulator for advertisements, sales promotion and direct marketing in the UK. According to Spiegel Online one TV spot from Actimel was blocked by the ASA in 2006 and one in 2008. [147] However, a measurable health benets linked to the presence of live Streptococcus thermophilus and Lactobacillus delbrueckii sp. Bulgaricus was reported by Koletzko and colleagues 2005 yoghurt. In this review Koletzko and colleagues say that it was clearly demonstrated that yoghurt containing viable bacteria improves lactose digestion and eliminates symptoms of lactose intolerance, and clearly full the current concept of probiotics. [149]
2.8.7
Scientic evidences of probiotic healt eects [150]
Despite controversies, there are many published research articles which say probiotics have positive health eects. Here some of them are presented:
2.8.8
Probiotics found to be benecial for health [150]
Parvez and colleagues 2006 state, in a review of probiotics that the benecial eect of lactic acid bacteria consumption include improved intestinal tract health; enhanced immune system, synthesis and enhanced bioavailability of nutrients; reduction of symptoms of lactose intolerance, reduced allergy in susceptible individuals; and reduction of risk of certain cancers. Modied gut pH, production of antimicrobial compounds, interfering with the binding and receptor sites of pathogens, stimulating immunomodulatory cells, and proOurFood Database of Food and Related Sciences Copyright 1998-2010 Karl H. Wilm. All rights reserved.
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ducing lactase are some of the mechanisms how it works. The authors concluded that probiotics are important as a part of a healthy diet for human and may become a safe, cost eective, approach against microbial infection.
2.8.9
German review of probiotic studies [151]
According de Vrese and Schrezenmeir 2008 the probiotics are dened in Gernay as viable microorganisms, sucient amounts of which reach the intestine in an active state and thus exert positive health eects. Such bacteria are Lactobacillus rhamnosus GG, L. reuteri, bidobacteria and certain strains of L. casei or the L. acidophilus-group, Escherichia coli strain Nissle 1917, certain enterococci (Enterococcus faecium SF68) and the probiotic yeast Saccharomyces boulardii. Health benets are the (transient) modulation of the intestinal microora of the host and the capacity to interact with the immune system directly or mediated by the autochthonous microora, are basic mechanisms. The authors list well-established probiotic eects: Help to cure rotavirus infections or antibiotic-associated diarrhoea. Reduce the cancer-promoting enzymes and putrefactive metabolites in the gut. Prevent unspecic intestinal complaints in healthy people. Produce benecial eects on inammatory diseases of the gastrointestinal tract, such as Helicobacter pylori infection. Normalize stool and stool consistency in subjects suering from obstipation or an irritable colon. Prevent or alleviate allergies and atopic diseases in infants. Prevent respiratory tract infections (common cold, inuenza) and other infectious diseases as well as treatment of urogenital infections.
2.8.10
Probiotics and dietetics practice [152]
Douglas and Sanders in a review of 2008 cite enhanced immune function, improved colonic integrity, decreased incidence and duration of intestinal infections, down-regulated allergic response, and improved digestion as benets of regular consumption of probiotics. The authors stress that Information on probiotic species, applications for specic strains, dosages and forms, safety, and shelf life is not suciently worked out to be used by most food and nutrition professionals. The authors present science and practice-based guidelines to enhance clinician and client understanding of probiotics and prebiotics.
2.8.11
Lactobacillus casei reduce the incindence of diarrhoea compared with traditional yoghurt [153]
Pedone and colleagues 2000 found that supplementation of healthy children with milk fermented by yoghurt cultures and Lactobacillus casei strain DN-114 001reduces incidence of acute diarrhoea compared with traditional yoghurt. The authors underline the additional benet of L. casei in acute diarrhoea in children compared with standard yoghurt.
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2.8.12
Lactobacillus casei DN-114 001 protects rats from rotavirus [154]
Gurin-Danan and colleagues 2001 found that food supplementation with milk fermented by Lactobacillus casei DN-114 001 protects suckling rats from Group A rotavirus diarrhoea, which is the leading cause of diarrhoea among children aged 3-36 mo worldwide. The authors infected rats with SA11 rotavirus at d 5 (RF group). The suckling rats which had been early supplemented with fermented milk by the DN-114 001 presented decreased clinical signs of diarrhoea, rotavirus infection prevention, and reduction of histologic lesions of the small intestine, leaving the number of mucin cells unchanged.
2.8.13
Fermented milk eect in young children in transition countries [155]
Branca and Rossi 2002, comparing the eects of a traditional yogurt, and a yoghurt with Lactobacillus casei. found that fermented dairy products change the equilibrium and metabolism of the intestinal microora and may have benecial eects to humans. The authors report that the number of enterococci in faecal samples increased with traditional yoghurt, and the markers of proteolytic fermentation, represented by branched-chain and long-chain fatty acids, decreased. Ingestion of milk fermented with yoghurt bacteria and Lactobacillus casei the lactobacilli count in faeces increased, and harmful enzyme activity of beta-glucuronidase and beta-glucosidase decreased, this eect being most accentuated in infants where these enzymes were initially unusually high.
2.8.14
Probiotics in treatment of antibiotic-associated diarrhea [156]
Kligler and Cohrssen 2008 point out that probiotics may prevent and treat antibioticassociated diarrhea and acute infectious diarrhea, be useful in the treatment of irritable bowel syndrome, and atopic dermatitis in children. Bacteria often used as probiotics are Lactobacillus sp., Bidobacterium sp., Streptococcus thermophilus, and Saccharomyces boulardii, in a dosages range from 5 to 10 billion living bacteria per day for children, and from 10 to 20 billion for adults. Probiotics taken orally should be resistant to acid and bile so that it can pass through the upper gastrointestinal tract and must be taken regularly to maintain colonization, otherwise they will be gone after 1 to 2 weeks.
2.8.15
Probiotics role in the health of children [157]
Kligler, Hanaway and Cohrssen 2007 stress that Probiotics are useful to reduce the risk of antibiotic-associated diarrhea and the duration of acute infectious diarrhea, are eective in preventing community-acquired diarrheal infections, reduce the risk of necrotizing enterocolitis in premature infants. Help in the prevention and treatment of atopic dermatitis were noted. The authors hypothesize that the exact strain used is less important, important is
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the administration of a high dosis of living bacteria , typically 5 to 10 billion per day or higher.
2.8.16
A probiotic eect is strictly restricted to one dened strain [158]
Seksik and colleagues 2008 reviewed the literature related to the use of probiotics ion the treatment of inammatory bowel disease (IBD). The authors concluded that a probiotic eect is strictly restricted to one dened strain and cannot be generalized from one to another. According to Seksik and colleagues, some probiotic drugs are useful in pouchitis (VSL3), and in the prevention of recurrence of ulcerative colitis (Escherichia coli Nissle 1917), however, ecacy of probiotic drugs in Crohns disease and dietary ecological treatments is still low.
2.8.17
Immunologic eects of probiotics
Deshpande, Rao and Patole 2007 reported in a review that the risk of necrotising enterocolitis, one of the most common gastrointestinal problems in premature babies, may be cut by 74 per cent by probiotic supplementation. [159] Carlo Caarelli and Sergio Bernasconi stressed that more research is needed, because each bacterial strain used as probiotics is believed to have specic immunomodulatory properties. Dierent probiotics, such as Lactobacillus acidophilus, L casei GG, L bulgaricus, Bidobacterium bidum, B breve, B infants, B lactis, Streptococcus thermophilus, and Saccharomyces boulardii. Present dierent imunologic eects and cannot be generalised. [160] Amanda Cox and colleagues 2007 studied the Lactobacillus fermentum VRI 003 (PCC)strain on its eect to boost the immune health of high performance athletes such as long distance runners. The authors found that the bacterium boosted T cells and activated the immune system, reducing the number of days and severity of respiratory illness of these athletes. [161]
2.8.18
Antiallergic eect of probiotics
Kamal Ivory and colleagues 2008 studied the antiallergic eect of Lactobacillus casei Shirota (LcS). The authors found that the bacterium modulated the immune response to grass pollen, and helped hay fever suerers. [162] Tamura and colleagues 2006 studied the antiallergic eect of Lactobacillus casei strain Shirota (LcS) in fermented milk on patients allergic to Japanese cedar pollen. The authors found that Lactobacillus casei strain Shirota (LcS) did not prevent Nasal and ocular allergic symptoms, but may delay the occurrence of allergic symptoms. [163]
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Xiao and colleagues 2006 studied the antiallergic eects of another bacterium, the Bidobacterium longum BB536 in the treatment of Japanese cedar pollinosis. The authors found a signicant decreases in rhinorrhea and nasal blockage in patients receiving the BB536 strain which was caused probably through the modulation of Th2-skewed immune response. [164]
2.8.19
Other eects of probiotics
Bekkali and colleagues 2008 studied the eect of a probiotic mixture on children aged 4-16 years with constipation. The probiotic mixture (Ecologic Relief) containing Bidobacteria (B.) bidum, B. infantis, B. longum, Lactobacilli (L.) casei, L. plantarum and L. rhamnosus was used. The authors found that a mixture of probiotics, has positive eects on symptoms of constipation and call for more studies on this matter. [165] Hickson and colleagues 2007 found that L casei, L bulgaricus, and S thermophilus can reduce the incidence of antibiotic associated diarrhoea and C dicile associated diarrhoea. The authors recommend such mixture for elderly patients [166]. These ndings are, however being challenged by Wilcox and Sandoe. They are concerned about the conclusion of Hickson that a probiotic yoghurt drink, given during and after antibiotic treatment, has the potential to decrease morbidity, healthcare costs, and mortality if used routinely in patients aged over 50. Wilcox and Sandoe say that the data are not widely applicable. [167]
2.8.20
Probiotics and allergy in Japan [168]
Kirin Group discovered Lactobacillus KW (Lactobacillus paracasei), a lactic acid bacteria which can reduce severness of symptoms of allergies such as hay fever added to foods. The Japanese Society of Allergology researchers found that this strain improved the Th1/Th2 balance. The results of Wang et al. suggest that the ingestion of LP-33-fortied fermented milk for 30 days can eectively and safely improve the quality of life of patients with allergic rhinitis.
2.8.21
Camel milk [169]
A team of inspectors of the European Union will verify food safety of production of camel milk in the United Arab Emirates UAE in order to allow the selling of camel milk to Europe. For this, the production must be increased. Arabian camels produce produce eight litres of milk whereas a cow produces up to 40 litres/day. To increase milk yield the UAE looks at Turkmeni dromedary camels which produce nearly 50 per cent more milk than the UAEs.
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Pakistan and Afghanistan camels have the highest yields of milk, up to 30 litres per day. The Bactrian camel, produces between 2.5-5 litres per day. The dromedary, one-humped camel, produces an average of 6-9 litres per day. Intensive breeding of cows has created animals that can produce 40 litres per day.
2.8.22
Camel milk marketed as healthy food
Tests have shown the milk has less than half the fat and 40 per cent of the cholesterol of cows milk - as well as three times the vitamin C. It can be digested by people who are intolerant to lactose, and can even ease food allergies. All this, Emirates Industry believes, gives it the scope to be marketed as a health food. Camels can endure 21 days without drinking water and may feed on low-quality fodder and still produce milk. These animals are therefore an option for food security in hot and dry areas...
2.8.23
Lactation of camels
Gestation of camels takes thirteen month. The mother must stay with the calf and raise it herself, otherwise it will stop producing milk, whereas a dairy cow can be separated from her calf when it is born and still gives milk for six to nine months. A mother camel can feed her calf and can be milked for twelve to eighteen months.
2.8.24
Water deprivation impact on camel milk [170]
Bekele et al. 2011 report that camels maintain milk volume during water deprivation for about 1 week, but they produced less milk during the second week. Osmolality increased during the rst 4 days of water deprivation, but remained at this level during another 12 days without watering. Milk lactose content did not increase. The authors stress that camels do not dilute their milk when dehydrated.
2.8.25
Camel brucellosis in Sudan [171]
Omer and colleagues 2010 assessed brucellosis in Sudan. Seroprevalence in camels milk and serum samples was 37.5% and 9% in abattoir workers. Brucella abortus biovar 6 was isolated from camels and cows, suggesting that camels were infected from cattle which is the primary host of Brucella abortus.
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2.8.26
Q fever in Iranian camels [172]
Rahimi et al. 2011 used polymerase chain reaction to determine the contamination of Coxiella burnetii as source of Q fever infection in dairy bovine, ovine, caprine, and camel herds in Iran. Using polymerase chain reaction in bulk milk samples, the authors found positive rections for Coxiella burnetii in 3.2% bovine milk samples, 5.7% sheep milk samples, 4.5% goat milk samples and 1.4% camel milk samples. The authors call for more studies on prevalence and epidemiology of Q fever in Iran. Coxiella burnetii shedding seems to occur frequently in milk taken from asymptomatic dairy cows. The number of Coxiella shed in milk is generally low. The phase I vaccine prevented abortion and greatly decreased the shedding of C. burnetii in milk. [173] Fretz et al 2007 report the results of a screening of Q-fever agent in bulk milk samples from cows, sheep and goats and in shell eggs produced in and imported into Switzerland. In this study 4.7 of the samples of bovine milk samples tested positive for Coxiella burnetii by nested PCR. Ovine and caprine bulk milk samples, and shell eggs were also found to be negative for C. burnetii. The authors concluded that Coxiella burnetii infection in cattle is frequent. [174] Goat exposure was associated with increased seroprevalence of Q fever counting up to 26.3% in veterinaries and farm workers in southern Taiwan, and 43.8% goats tested poitive for Coxiella burnetii. Chang et al. 2010 concluded that goats the most important risk of human contamination with Ccoxiella burnetii and health education could help to reduce Coxiella burnetii risk infection in southern Taiwan. [175]
2.8.27
Camelpox [176]
Camelpox is a contagious skin disease of camelids caused by camelpox virus (CMLV) and is characterized by mild local skin infection and less common severe systemic infections going ahead with morbidity, mortality, loss of weight and reduction in milk yield. The virus has close genetic relatedness to variola virus, the causative agent of smallpox, and carrying genes responsible for host immune evasion mechanisms say Bhanuprakash et al 2010.
2.8.28
GB virus C in Arabian camels [177]
GB virus C (GBV-C), formerly known as Hepatitis G virus (HGV), is known to infect humans, but is not known to cause human disease. Abu Odeh 2011 found 18.2% of dromedary Arabian camels in the United Arab Emirates positive for GBV-C , however, all camels milk samples tested negative. Sequence analysis of the 5-UTR using isolates from the 4 camels revealed the prevalence of the European/North American genotype 2.
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2.8.29
Composition of camel milk [178]
Konuspayeva et al.2009 describe the camel milk composition from dromedary and Bactrian species Asian values were higher in all the components, except ash, because of the predominance of the Bactrian camel in this region. Fat content of camel milk of East Africa was higher than milk from other areas of Africa and Western Asia. Camel milk from Kazakhstan hat higher content of fat and protein but reduced lactose compared to references from Central Asia. Tables of composition of camel milk may be found at: http://ipac.kacst.edu.sa/eDoc/2010/190507_1.pdf http://www.dairyforall.com/camel-milk-nutrients.php http://www.fao.org/docrep/003/X6528E/X6528E03.htm
2.8.30
NLEA: Nutrition Labeling and Education Act 1990. Functional Foods in USA
The NLEA act of the FDA contains the denition of model claims for functional foods:
Table 2.19: Model claims from FDA Nutrient-relation to disease Fat and heart disease Calcium and Osteosporosis Model claim Diets low in saturated fat and cholesterol may reduce the risk of heart disease Regular exercise and a healthy diet with enough calcium helps teen and young adult white and Asian women maintain good bone health and may reduce their high risk of osteosporosis Diet low in sodium may reduce the risk of blood pressure, a disease associated with many factors. Low-fat diets rich in ber-contain grain products, fruits, and vegetables may reduce the risk of some types of cancer, disease associated with many factors.
Sodium and hypertension
Dietary ber and heart disease
2.8.31
Dried plums reduces bone loss in rats [179]
Dried plums are a rich source of polyphenolic compounds with antioxidant and antiinammatory properties, improving bone density, microstructure and biomechanics in feCopyright 1998-2010 Karl H. Wilm. All rights reserved. OurFood Database of Food and Related Sciences
100 male animal models of osteopenia.
Brenda Smith and colleagues determine the amount of dried plums which are necessary to decrease bone loss, and looked its mechanism of action. Gonadal hormone decient male rats were used for the study. The authors found hat at doses of 15% of the diet or higher, the dried plum supplementation totally prevented the induced decrease in bone mineral density in the rats. At lower doses, modest protective results were found. The benecial eects of dried plums were attributed in part to a decrease in osteoclastogenesis via down-regulation of RANKL and stimulation of bone formation mediated by IGF-I.
2.8.32
Colas associated with low bone mineral density (BMD) in older women [180]
Katherine L. Tucker, in the Framingham Osteoporosis Study, found that cola intake was associated with signicantly lower BMD at each hip site, but not the spine, in women but not in men. Similar results were seen for diet cola and, although weaker, for decaeinated cola. No signicant relations between noncola carbonated beverage consumption and BMD were observed. Total phosphorus intake was not signicantly higher in daily cola consumers than in nonconsumers; however, the calcium-to-phosphorus ratios were lower. The authors concluded that intake of cola, but not of other carbonated soft drinks, is associated with low BMD in women.
2.8.33
Minerals
The active minerals in our body are : Calcium Chlorine Chromium Cobalt Copper Fluorine Iodine Iron Magnesium Manganese Molybdenum Phosphorus
2.8. FUNCTIONAL FOOD Potassium Selenium Sodium Sulfur Vanadium Zinc
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2.8.34 2.8.35
Phytochemical activity of fruits and vegetables Carotenoids
There are about 500 coloured components which are classied as carotenoids. Only six of them are found in appreciable amounts the human body. Alpha-carotene: is found in carrots, pumpkin, butternut squash. Beta-carotene: is found in apricots, broccoli, cantaloupe, carrots, kale, red pepper, sweet potatoes, pumpkin, spinach, butternut squash, orange. Lutein and Zeathanithin : They are found in broccoli, brussels sprout, kale, peas, spinach, courgette. Lutein is an antioxidant nutrient belonging to the family of carotenoids. It is a primary component of the macula pigment, functioning as a lter that prevents harmful UV to damage tissues in the retina of the eye. It protects the human eye cells from UV-induced damage and can help prevent cataracts. Ultraviolet-beta radiation (UVB) is thought to be the primary environmental culprit in causing skin cancer as well as initiating cataract disease. According to Dr. Joshua Bomser the lutein and zeaxanthin accumulate in the retina and in the lens of the eye, but it is unknown how they reach the eye in the rst place. They travel through the blood stream, but the lens doesnt have a blood supply. Further data suggest that xanthophylls are more potent than alpha-TC (tocopherol) for protecting human lens epithelial cells against UVB insult. [181] Zeaxanthin: is found in maize, egg yolk and fruits. Cryptoxanthin: is found in red pepper and orange. Lycopene: is found in tomato, watermelon, pink grapefruit.
2.8.36
Vitamin E
It is found in vegetable oils and cod liver oil.

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2.8.37
Vitamin C
It is found in citrus fruits, kiwi, strawberry, melon, tomato, green pepper, potato.
2.8.38
Flavonoids
They are a class over 4.000 phytochemicals that are responsible for ultra-violet protection within the plant and which may have a protective action against chronic diseases. Soybeans and their products are rich in isoavonoids. QuercetinindexQuercetin: are found in apple, onions, tea and red wine. Anthocyanins: are found in berries.
2.8.39
Glucosinolates
They are found in brassica vegetables. When the plant is damaged by cutting or chewing the glucosinolates break down into substances with biological activity giving the characteristic smell of watercress which is only released when the leaves are crushed or cut. Examples of Glucosinolates are sulphorophane from broccoli which is active against cancerous bowel cells, and sinigrin from brussels sprout making cancerous cells to die. It seems unlikely that the most benecial source of these compounds for the majority of the population will be from single-substance supplements, but rather from consumption of a wide variety of fruits and vegetables. Many of these phytochemicals are not destroyed by processing, but may actually become more readily available for digestion. Beta-carotene for example is more readily available from processed tomatoes and canned apricots then from fresh fruits. The decay of vitamin C in frozen peas and vegetables is slower as the decay after days by normal temperatures. A better understanding of the need to eat a wide variety of fruit and vegetables, both fresh and processed may turn out to be a more important message than eating a certain number of portions a day[182].
2.8.40
Denition of functional Food according to European consensus publication
The European consensus publication of ILS an European-coordinated concerted action FUFOSE [183] consider as context: A food can be regarded as "functional" if it is satisfactorily demonstrated to aect benecially one or more target functions in the body, beyond adequate nutritional eects, in a
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way which is relevant to either the state of well-being and health or the reduction of the risk of a disease. Benecial eects can be: 1- Maintenance or promotion of a state of well-being or health. 2- Reduction of the risk of a pathologic process or a disease.
A food can be made "functional"by: 1- applying any technological or biotechnological means to increase the concentration of, add, remove or modify a particular component as well as to: 2- improve its bioavailability. Promising range of functional foods are: Lycopenein tomatoes, fruits and vegetables containing vitamins and secondary phytocompounds like phytoestrogenic substances with cancer protective activity. Vitamin A, provitamin A, vitamin C and E blocking free radicals. Soluble and insoluble bers[184] in fruits and vegetables can be enriched in functional foods protecting specically against intestinal cancer. Insoluble bers in plant cell walls are associated with phenolic compounds which are natural antioxidants. Experiments have demonstrated that potatoes peels replacing wheat our in oatmeal cookies reduces peroxides values because of the content of phenolic acids such as chlorogenic acids (Arora and Camire, 1994)[184]. Skins and esh of grapes as waste of wine and grape juice are available as commercial product under the name of Vitis Fibre. Saura-Calixto 1998 compared Selenium this product with the activity of red wine skins and alpha-tocopherol. Although positive ndings were reported safety of these ingredients on regard to concentration of pesticides and other environment poisons should be carefully studied. Selenium as trace element in wheat germs, acting against free radicals can be enriched in corn akes. Zinc from vegetables and marine animals is an important part of our immune system. An undersupply of zinc makes susceptible to cold and cancer. Green tea and its extracts acting against free radicals can be incorporated in energy drinks and other beverages.
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An example of functional food is probiotic yoghurt with bacteria which can survive acidity of the digestive tract and settle in the small and large intestine.The special strains of these Lactobacillae help digestion or strengthen the immune system.
2.8.41
Microencapsulated probiotics
Microencapsulation technology is being used to protect probiotic bacteria from the acidity of the gastrointestinal tract. There is a poor survival of probiotic bacteria in many probiotic health-based products. Some methods of micro-encapsulation of probiotic bacteria include spray drying, extrusion, emulsion and phase separation have not been successful for industrial shelf-stable products. Other methods were tried using calcium-alginate gel capsules, carrageenan, gellan gum, gelatin and starch as excipients. The need to design and develop equipment that will generate presise and uniform micro or nano capsules in large quantities have been reported by Kallasapathy[185] ProbioStick is based on two probiotic strains Rosell-52 and Rosell-175. It is being evaluated to relieve some of the chronic stress-related disorders, nausea and abdominal pain, and its benets for suerers of irritable bowel syndrome Other studies on the benet of micro-encapsulated probiotics on irritable bowel syndrome used the bacterium Bidobacterium infantis 35624 . The study was conducted by Clinical Trials, US National Institutes of health. [186] Another hopeful part of functional food are the Omega-3 LCPs (Long Chain Polyunsaturated fatty acids)also called omega-3-fatty acids. These fatty acids are told to lower the level of blood cholesterol reduce incidence of peripheric heart vessel diseases, are essential for the development of the retina and brain of new born babies. Omega-3-fatty acids are already present in omega-3 enriched eggs.Further informations under the keyword omega. Omega-3-fatty acids are rened from marine oils produced by Roche Vitamins Europe and can be incorporated into a wide range of everyday foods, from bread,milk and margarine to mayonnaise Special substances of plants such as phytosterols can be enriched in functional foods and reduce the risk of heart and vessels diseases. Sterols are already being enriched in some special brands of margarine. Further informations under keyword sterol. A functional food may be "functional" for some specic groups and act as normal nuOurFood Database of Food and Related Sciences Copyright 1998-2010 Karl H. Wilm. All rights reserved.
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trition for the rest of the population. Specic groups which are aected may be school-age children, pregnant women, elderly, insulin-resistant people or disease-risked people. Research on health linkages between foods and botanical ingredients nd new ways to eective alternative ways to treat or to avoid diseases such as new researches on zeaxanthin and lutein to improve vision and prevent cataracts and macula degeneration. This study is being made by the US Department of Agriculture.[187] New studies are funded by USs National Institutes of Health concerning melatonin related to weight control, aging and contraception.
2.8.42
Cherry juice and sports drinks [188]
Tart cherries are known to be rich in antioxidant and anti-inammatory agents. Such anti-inammatory agents may be benecial for the management and prevention of inammatory diseases. Darshan S. Kelley and colleagues propose that the avonoids and anthocyanins in the cherries exert an anti-inammatory eect and may lessen the damage response to exercise. [189] In another study Declan Connolly tested the ecacy of a tart cherry cherry juice blend in preventing the symptoms of exercise-induced muscle damage. This study was published in the British Journal of Sports Medicine, demonstrating that the strength loss and pain were signicantly lower in the cherry juice trial versus placebo . Relaxed elbow angle and muscle tenderness were not dierent between trials. Connolly came to the conclusion that cherry juice decreased some of the symptoms of exercise-induced muscle damage. These results have important practical applications for athletes aected by strength loss and pain after damaging exercises.
2.8.43
Cherry juice and sports drinks [188]
Tart cherries are known to be rich in antioxidant and anti-inammatory agents. Such anti-inammatory agents may be benecial for the management and prevention of inammatory diseases. Darshan S. Kelley and colleagues propose that the avonoids and anthocyanins in the cherries exert an anti-inammatory eect and may lessen the damage response to exercise. [189]
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In another study Declan Connolly tested the ecacy of a tart cherry cherry juice blend in preventing the symptoms of exercise-induced muscle damage. This study was published in the British Journal of Sports Medicine, demonstrating that the strength loss and pain were signicantly lower in the cherry juice trial versus placebo. Relaxed elbow angle and muscle tenderness were not dierent between trials. Connolly came to the conclusion that cherry juice decreased some of the symptoms of exercise-induced muscle damage. These results have important practical applications for athletes aected by strength loss and pain after damaging exercises.
2.8.44
Anti-Inammatory Eects of Strawberries in Overweight/obese Individuals: Research Project, Agricultural Research Service, USDA Gov [190]
Adipose tissue is a major source of pro-inammatory molecules, such as interleukin-6, tumor necrosis factor-, and leptin which can contribute to chronic inammation in obese individuals. Strawberries contain high levels of antioxidants including ellagic acid, catechins, anthocyanins, and the avanols quercetin and kaempferol, all of which have displayed antiinammatory abilities. The specic hypothesis is that strawberries contain potent anti-inammatory antioxidants that can prevent the oxidization of LDL involved in the generation of atherosclerotic plaques, reduce the production of inammatory cytokines in obese individuals, and suppress the immune response.
2.8.45
Adipose tissue is a major source of pro-inammatory molecules, such as interleukin-6, tumor necrosis factor, and leptin which can contribute to chronic inammation in obese individuals. Strawberries contain high levels of antioxidants including ellagic acid, catechins, anthocyanins, and the avanols quercetin and kaempferol, all of which have displayed antiinammatory abilities. The specic hypothesis is that strawberries contain potent anti-inammatory antioxidants that can prevent the oxidization of LDL involved in the generation of atherosclerotic plaques, reduce the production of inammatory cytokines in obese individuals, and supOurFood Database of Food and Related Sciences Copyright 1998-2010 Karl H. Wilm. All rights reserved.
2.8. FUNCTIONAL FOOD press the immune response.
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2.8.46
Recent studies on ellagic acid [191]
Ellagic acid is a naturally occurring tannic acid derivative, a phenol antioxidant found in fruits and vegetables such as blackberries, raspberries, strawberries, cranberries, walnuts, pecans, pomegranates, wolfberry and other plant foods. Ellagic acid has antiproliferative and antioxidant properties in a number of in vitro and small-animal models. The antiproliferative properties of ellagic acid are due to its ability to directly inhibit the DNA binding of certain carcinogens, including nitrosamines and polycyclic aromatic hydrocarbons. Very little study of these proposed benets on humans has been reported. Despite the very preliminary state of evidence supporting health benets in humans FDA warns of exaggerated health claims on isolated plant compounds or plant extracts which might cure cancer or other serious ailments.
2.8.47
Ellagic acid from berries and fruits, such as pomegranate, reduce the risk of atherosclerosis [192]
Atherosclerosis starts with the formation of foam cells. Lipid uptake by scavenger receptors (SR) in macrophages starting chronic proinammatory cascades which are linked to atherosclerosis. According to Park et al. 2011 ellagic acid suppresses scavenger receptors SR-B1 induction and formation of such foam cells. In their study the authors found that Ellagic acid upregulated PPARgamma and ATP binding cassette transporter-1 in lipidladen macrophages, all responsible for cholesterol eux. Cholesterol eux in foam cells was increased by upregulation of PPARgamma and ATP binding cassette transporter-1. The expression and transcription of the nuclear receptor of liver X receptor-alpha were increased supporting the PPAR pathway. Park and colleagues concluded that ellagic acid reduced macrophage lipid uptake to block foam cell formation, and cholesterol eux in foam cells. The authors suggest that berries rich in ellagic acid may be useful in treatment of atherosclerosis.
2.8.48
Urolithin links ellagic acid and DBC compounds to inhibit Protein Kinase (CK2) Gozzaurcouand
Casein kinase 2 (CK2) is a pleiotropic protein kinase envolved in neoplasia and other diseases. Cozza et al.2011 report that ellagic acid and 3,8-dibromo-7-hydroxy-4-methylchromen2-one (DBC) are strong selective CK2 inhibitors, and urolithin moiety is proposed as a
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possible bridging scaold between both. Optimization of urolithin A by the authors identied 4-bromo-3,8-dihydroxy-benzo[c]chromen-6-one as a strong inhibitor of CK2 protein kinase which is active in cancer.
2.8.49
Ellagic acid protection of lung injury after intestinal ischemiareperfusion [193]
Byk et al 2011 studied the protective role of antioxidant treatment with ellagic acid (EA) on lung injury after intestinal ischemia-reperfusion (I/R) injury. They found that serum total antioxidant capacity (TAC) was increased, and total oxidative status (TOS), and oxidative stress index (OSI) and malondialdehyde (MDA) were decreased in a group of rats supplemented with elladic acid and submitted to intestinal ischemia, compared with the group with intestinal ischemia without elladic acid supplementation. The authors suggest that elladic acid treatment protects lung tissue against ischemia-reperfusion injury.
2.8.50
Ellagic acid protects brain and nerves of diabetic rats [194]
Uzar et al. 2011 assessed the eects of ellagic acid in brain and sciatic nerve tissues of diabetic rats. They report that ellagic acid had neuroprotective eects against oxidative damage in brain and sciatic nerves of diabetic rats.
2.8.51
Nanocarrier for ellagic acid [195]
Kakran describe a graphene oxide as a nanocarrier for loading and delivery of a poorly water soluble antioxidant and anticancer drug, ellagic acid. Their capabilities to kill human breast carcinoma cells (MCF7) and human colon adenocarcinoma cells (HT29) were not compromised by nano encapsuling. The cytotoxicity of ellagic acid loaded onto the functionalized graphene oxide was higher than that of free dissolved ellagic acid. The authors concluded that the described nanocarriers are suitable for ellagic drug delivery.
2.8.52
Antioxidant and apoptotic eects of pomegranate described [196]
Pomegranate is known for its antioxidant and anticancer eects. Dikmen et al 2011 describe the antioxidant potency of a methanolic pomegranate fruit peel extract and the relation with its antiproliferative and apoptotic eects of Abstract Pomegranate (Punica granatum L.) Dikmen and colleagues concluded that the extract of pommegranate peel reduces cell proliferation and induces apoptosis on MCF-7 cancer cells, and is an important antioxidant.
2.8.53
Calculating caeine content
Coee content is about 80 mg caeine/100 mL of coee, and 26 mg per 100 mL of tea. [197]
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One cup of coee contains about 85 mg of caeine, almost twice the caeine content of tea (45mg) [198]
2.8.54
Coee and pregnancy
The eect of consumption of caeine in coee and other beverages (energy drinks like Red Bull) on fertility, spontaneous abortion and premature birth, foetal malformations, foetal growth and birth weight takes Gil Esparza in Alimentaria No. 293, 109-112 to the conclusion to limit the intake of caeine to 200-300 mg/day. Such an intake was found to have no adverse eects on the foetus during pregnancy. Avoiding black coee may help to avoid cancer of the esophagus. Tannin, found in coee and tea, is a suspected carcinogen. The protein in milk, though, neutralizes tannin, rendering it non-absorbable by the body.
2.8.55
Coee may reduce risk of ovarian cancer
[199] Tworoger, Shelley S. and colleagues examined the associations between smoking, caeine, and alcohol intake and ovarian cancer risk. The authors found that neither current nor past smoking was associated with ovarian cancer risk overall; however, both were associated with mucinous tumors. Caeine from three or more cups of coee may reduce epithelial ovarian cancer risk. more pronounced in women who had never used hormones. No association between alcohol and ovarian cancer risk was found.
2.8.56
Caeine and gamma rhythm [200]
Dr. Martin Vreugdenhil says that caeine might enhance memory by blocking the calming eect of adenosine neurotransmitter. Adenosine increases during the day and rising age. It binds to the A1 receptor decreasing the activity of nerve cells. Binding to an A2a receptor it boosts activity. The authors have found that caeine boosts the gamma rhythms, due to a selective blocking of the A1 receptor. They conclude that a few cups of coee could increase gamma rhythm strength, contributing to the cognitive benecial eects of caeine warning, however, against drinking excessive amounts or very strong coee considering the sleep problems and eects on the heart and blood system caused by caeine They call for scientists to separate the benecial eects from the side eects.
2.8.57
Volatile compounds of coee aroma alleviate sleep deprivation stress and have antioxidant activities [201]
There are about 900 volatile compounds in the aroma of roasted coee beans. Han-Seok Seo and colleagues found that the volatiles in coee induce changes in the expression of messenger RNA (mRNA)and protein levels in the rat brain, resulting in antioxidant or stress relaxation activities. mRNA are messenger molecules that indicate when a gene is being expressed. There
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are 11 genes which are important to brain function. When the rats were exposed to the aroma of coee, the mRNA for nine of the genes was restored to near normal levels, and pushed to above normal levels for two: GIR which is involved in neuro-endocrine control, and NFGR, which controls oxidative stress. The authors concluded that it is not yet known if the results may be translated to humans, however, these results may explain why coee is preferred by humans when they need to stay awake. The volatiles of the coee aroma may help alleviate the stress of the sleep deprivation caused by sleep deprivation changing the mRNA and protein expression levels of the rat brain, and have antioxidant activities.
2.8.58
Antioxidant activity of caeine [202]
The antioxidant activity of caeine metabolites and colonic metabolites m-coumaric acid and dihydroferulic acid in coee was studied by Jos ngel Gmez-Ruiz and colleagues. The caeine metabolite 1-Methyluric acid was able to delay for more than 13 h human low-density lipoprotein LDL oxidation by copper and 2,2-azobis(2-amidinopropane) dihydrochloride. Dr. Francesca Bravi and colleagues found, in a meta-analysis, an inverse relation between coee drinking and liver cancer and the risk of other liver diseases, suggesting favourable eect of coee on liver function. These ndings justify moderate coee consume [203]
2.8.59
Coee and tea may reduce risk of a certain type of stroke [197]
Larsson and colleagues 2008 in a large, prospective, observational study using data from the Finnish Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study showed that smokers who consumed 8 or more cups of coee per day, and those who drank 2 or more cups of black tea daily had reduced cerebral infarction risk. The authors concluded that high consumption of coee and tea may reduce the risk of cerebral infarction among men but not to other types of stroke, such as intracerebral hemorrhages, subarachnoid hemorrhages, and unspecied strokes.
2.8.60
Coee consumption was inversely associated with mortality [204]
Freedman et al. 2012 report that coee consumption of 2 to 3 cups of coee daily reduce mortality by 10% in men and by 13% in women. This was valid for deaths due to heart disease, respiratory disease, stroke, injuries and accidents, diabetes, and infections, but not for deaths due to cancer.
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The authors stress that other studies which found coee to increase the risk of death, established association with increased low-density lipoprotein cholesterol levels and shortterm increases in blood pressure. However these studies were found to be inconsistent because of the structure of the studies and also tobacco smoking had not been considered. The study war carried out during 13 years and included 33,731 men and 18,784 women. As for cause-specic mortality, the researchers say they noted inverse associations for deaths resulting from heart disease, stroke, diabetes, respiratory disease, infections, injuries, and accidents, but there was no signicant association between coee consumption and deaths from cancer in women, However, a positive association of cancer in men who consumed at least 6 cups of coee each day was found.
2.8.61
The eect of adenosine A1 receptor modulation on brain rhythms and cognitive functions [205]
At the University of Birmingham further projects aime to assess mechanisms underlying the benecial cognitive eects of caeine and selective adenosine A1 receptor agonists in electrophysiological studies in vitro and in vivo, and in behavioural studies.
2.8.62
Caeine and reduction of Alzheimers disease [206]
Research carried out at the Faculty of Medicine, Lisbon, Portugal, and published in the European Journal of Neurology (2002, 9 (4): 377-382) found that consuming 200 mg of caeine a day may reduce the risk of developing Alzheimers disease. Experiments on mice had previously found caeine to be promising as a treatment of Alzheimers disease.
2.8.63
Study supports caeine protection of the blood brain barrier [207]
Chen and colleagues 2008 studied the way how chronic ingestion of caeine protects against high cholesterol diet-induced disruptions of the blood brain barrier (BBB). High levels of serum cholesterol and disruptions of the blood brain barrier may increase risk of Alzheimers disease. In this study rabbits were fed with a 2% cholesterol-enriched diet and 3 mg caeine daily for 12 weeks. Caeine reduced the biochemical indicators of disruption of the blood brain barrier. The authors concluded that chronic ingestion of caeine protects against high cholesterol diet-induced disruptions of the BBB. They suggest that caeine and drugs similar to caffeine might be useful in the treatment of Alzheimers disease. According to the authors
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caeine is a safe and readily available drug which stabilises the blood brain barrier and protects against neurological disorders.
2.8.64
Coee reduces risk of Parkinsons disease [208]
Payami et al 2010 report that the GRIN 2A gene controls the activity of coee reducing the risk of Parkinsons disease for some people. The researchers compared the amount of caeinated coee consumed during lifetime and the coexistence of the GRIN2A gene. Those who had high intake of coee, and the GRIN 2A gene presented the lowest risk of Parkinsons disease. This special gene is present in about 25% of the population. The authors explain further, that the GRIN 2A gene is associated with glutamate which kills brain aected by the Parkinsons disease patients adenosine may be involved in this process. Coee may interfere with this pathway. In Parkinsons disease the immune system attacks neurons in the substantia nigra, a part of the brain that helps control movement, resulting in involuntary shaking, slow movement, stiened muscle tone, and impaired balance. The cause is unclear, but researchers are looking for an interplay of genetics and environmental factors, such as caeine consumption and cigarette smoking reducing the risk of the disease. These ndings may help to identify patients which respond to drugs targeting the caeine pathway. More studies are needed and at present patients should not change their caeine consumption.
2.8.65
Genes associated with Parkinsons disease
The authors describe SNCA and MAPTgenes, associated with GAK and HLA region which have only a small impact on disease risk by itself, but additively, these genes can have a large impact, MAPT gene encodes a protein inside neurons and SNCA encodes alphasynuclein which regulates signaling both within and between neurons. The HLA genes encode proteins which identify cells as "foreign".A variant of the HLA-DRA gene is the GAK gene which is strongly associated with late-onset, sporadic cases and was seen more often in men In addition to nding an association between Parkinsons disease and a variant in HLA-DRA, the study conrmed previously reported associations with SNCA, MAPT and a gene called GAK. The variant in HLA-DRA was most strongly associated with, who are aected by sporadic Parkinsons disease more often than women. [209]
2.8.66
Caeine or nicotine do not reduce the risk of Parkinsons disease [210]
Trinh et al.2010 studying the eect on Parkinsons disease found that coee and tobacco, but not caeine or nicotine, are neuroprotective in y Parkinson disease models. The authors stress further that these eects can also be noted with Drosophila models of Alzheimers disease and polyglutamine disease. The authors explain that the mentioned
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neuroprotective eects require the activity of the transcription factor Nrf2 and Nrf2 activator in coee, cafestol, which may be used for therapeutic intervention in Parkinsons disease or other neurodegenerative diseases.
2.8.67
Caeine improving the time to exhaustion in exercise tests [211]
According to a study by Douglas G. Bell and Tom McLellan caeine improves the time to exhaustion in exercise tests, the eects of caeine were still apparent six hours after ingestion and heart rates were higher for the non-users throughtout the trials. Six hours after ingestion of caeine eects were still apparent. During trials non-users experienced higher heart rates. The authors concluded that both the duration and magnitude of the ergogenic eect that followed a 5 mg/kg dose of caeine were greater in the no-users compared with the users.
2.8.68
Caeine and diabetes mellitus 2 [212]
SoJung Lee in a study found that caeine ingestion was associated with a signicant reduction in insulin sensitivity by a similar magnitude in the lean, obese, and type 2 diabetic groups in comparison with placebo. After exercise training, caeine ingestion was still associated with a reduction in insulin sensitivity. The authors conclude that caeine consumption is associated with a substantial reduction in insulin-mediated glucose uptake independent of obesity, type 2 diabetes, and chronic exercise.
2.8.69
Coee and risk of nonfatal myocardial infarction and genotype F1
[213] Caeine is metabolised by the polymorphic cytochrome P450 1A2 (CYP1A2) enzyme. Individuals who are homozygous for the CYP1A2-1A allele (genotype F1A) are rapid caeine metabolisers, whereas carriers of the variant CYP1A2-1F (genotype F1) are slow caeine metabolisers. Marilyn C. and colleagues studied the activity of genotype CYP1A2 in residents of Costa Rica, in relation to the association between coee consumption and risk of acute nonfatal myocardial infarction. The authors concluded that intake of coee was associated with an increased risk of nonfatal myocardial infarction only among individuals with slow caeine metabolism (genotype
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F1), suggesting that caeine plays a role in this association.
2.8.70
Coee triggering myocardial infarction [214]
Dr. Anna Baylin and colleagues believe that coee in the presence of predisposing factors can induce a cascade of events that, through sympathetic nervous activation, can induce the onset of myocardial infarction.The ndings of their study indicate that coee intake may trigger myocardial infarction. The association is particularly strong among people with light/occasional intake of coee (one or less cup/day), with sedentary lifestyle, or with 3 or more risk factors for coronary heart disease.
2.8.71
Commentary on the researche of Baylin and colleagues
David S. Siscovick writes that there may be major dierences between Costa Rica where the research of Baylin and colleagues were made, and other countries in other factors such as the dietary consumption of saturated fatty acids from tropical oils. He says that the eect modication could occur with dierences in lifestyle, health status, or medical therapies. Siscovick concludes that the dierences in these potential eect modiers would need to be explored fully before assuming that the hazard would be similar in other settings. [215]
2.8.72
Optimal diets for prevention of coronary heart disease [216]
Frank B. Hu and Walter C. Willet (2002) to reduce the risk of coronary heart diseases, suggest diets using nonhydrogenated unsaturated fats as the predominant form of dietary fat, whole grains as the main form of carbohydrates, an abundance of fruits and vegetables, and adequate omega-3 fatty acids, together with regular physical activity, avoidance of smoking, and maintenance of a healthy body weight.
2.8.73
Western dietary pattern in women is linked to cardiovascular, cancer and all-cause mortality [217]
Christin Heidemann and colleagues 2008 found that women who eat a diet rich in vegetables, fruits, legumes, whole grains, sh and poultry may reduce their risk for death from cardiovascular disease and from all causes, according to the results of a prospective study. In contrast, women who follow a traditional "Western" diet of red and processed meat, rened grains, french fries, and sweets are at a higher risk of mortality from cardiovascular disease, cancer, and all causes.
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2.8.74
Clear labelling of caeine content in caeinated beverages [218]
Mc Cusker, Golberg and Cone analysed caeine content of some caeinated beverages. Surprisingly high levels of caeine were found in products without labelling it:
Caeinated energy drinks ranged up to 141.1 mg/serving. Carbonated sodas ranged from none detected to 48.2 mg/serving. Other beverages ranged up to 105.7 mg/serving. zzy sodas had caeine levels well inside the 65mg/serving recommended limit for cola drinks in the US. Most energy drinks had levels in the high 60s and 70s/serving. Coca-Cola fountain samples were up to 44.5 mg/serving. The European version of Red Bull contains 80mg caeine/250 ml can. Coee with milk, Xpresso, and other canned coes contain 135 mg/serving corresponding two cups of strong brewed coee. The authors say that due to health concerns arising from the consumption of caeine it seems appropriate that warning labels should accompany all caeinated beverages. They should display the caeine content on their labels to prevent those at risk from consuming too much caeine. High caeine intake is associated with delayed conception, spontaneous miscarriage and low birth weight, but not with birth defects. The current position (2008) of the American Dietetic Association is that pregnant women should avoid caeine intake above 300 mg per day. In its position paper"Nutrition and lifestyle for a healthy pregnancy outcome" The Association outlines references for healthy standards for the nutritionduring pregnancy.[219]
2.8.75
Caeine consumption during pregnancy, advice 2008 [220]
The CARE Study Group found in a study published in 2008 that caeine intake by pregnant women was linked to babies being born with a low birth weight, or even being miscarried. The Group recorded caeine intake in the four weeks before and throughout pregnancy. Individual caeine metabolism was calculated using a saliva sample test. The average caeine intake during pregnancy was 159 mg/day. This is below of the UK governments recommended limit of 300 mg/day. Of the caeine consumed, 62% came from tea, 14%
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from coee, 12% from cola, 8% from chocolate and 2% from soft drinks. Taking as the base pregnant women consuming less than 100 mg/day (the equivalent of one cup of coee), the risk of having a lower birth baby increased by 20% for intakes of 100-199 mg/day, by 50% for those taking between 200-299 mg/day, and by 40% for over 300 mg/day. Women who metabolised caeine more quickly presented a stronger link between caeine and a reduced birth weight, compared with those of a low caeine metabolism. The CARE Study Group concluded that caeine consumption during pregnancy was associated with an increased risk of foetal growth restriction and this association continued throughout pregnancy. The group calls for a reduction of caeine intake before conception and throughout pregnancy.
2.8.76 2.8.77
Energy drinks Health Eects of Energy Drinks on Children [221]
Seifert and colleagues 2011 report that 30% to 50% of adolescents and young adults consume energy drinks contain high and unregulated amounts of caeine. Serious adverse eects of these drinks have been reported in association with other health risks. In 2007 there were 5448 US cases of caeine overdoses of which 46% occurred in persons younger than 19 years. According to the authors the use of energy drinks in these young populations should be debated, as they provide no therapeutic benet, are associated with health risks, many of their ingredients are understudied and not regulated. Seifert and colleagues argue that such drinks present no therapeutic benet. The toxicity surveillance should be improved, sales and consumptions regulations should be established. Bigard et al. 2010 reports that the eect of energy drinks on physical and cognitive performances remains controversial. The toxicity of ingredients or ingestion in combination with alcohol may be the cause of related serious eects. Taurine-induced toxic encephalopathy has been cited in some studies, but the taurin content of energy drinks do not pose a health risk, but the eect of more then 3 gram taurin/day of energy drinks must be studied. Bigard stresses that consumption of energy drinks may increase the risk for caeine overdose and toxicity in children and teenagers. This group considers energy combined with alcohol a social way to meet people. Such combination was found to reduce subjective perceptions of some symptoms of alcohol intoxication. [222]
2.8.78
FSA new advice on caeine consumption during pregnancy [223]
The Agency had previously recommended a maximum daily intake of 300mg. However, the new research, published by the CARE Study Group Nov. 2008, suggests a limit of 200 mg per day will help to reduce this low risk even further. The FSA says that the new
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advice means that there is no need to cut out caeine completely, pregnant women should, however, be careful not to have too much and to reduce caeine as much as possible.
2.8.79
The European Union on caeinated drinks [224]
As far as caeine is concerned, the Scientic Committee for Food, in its opinion of 21 January 1999 on caeine and other substances used as ingredients in "energy drinks", concluded that, for adults, apart from pregnant women, the contribution of "energy drinks" to the total consumption of caeine did not appear to be a cause for concern, assuming that "energy drinks" replace other sources of caeine. However, for children, an increase in the daily intake of caeine to a certain level of consumption per day may bring about temporary changes in behaviour, such as increased excitability, irritability, nervousness or anxiety. In addition, for pregnant women, the Committees view is that moderation of caeine intake is advisable. These ndings make it necessary to provide labelling which gives the consumer clear information on the presence or otherwise of quinine or caeine in a foodstu and, in the case of caeine, to provide a warning message and an indication of the amount of caeine, where this is in excess of a specic level, in beverages which do not naturally contain caeine. Where a beverage which is intended for consumption without modication, or after reconstitution of the concentrated or dried product, contains caeine, from whatever source, in a proportion in excess of 150 mg/l, the following message must appear on the label in the same eld of vision as the name under which the product is sold: High caeine content . Excluded from this regulation are beverages based on coee, tea or coee or tea extract where the name under which the product is sold includes the term "coee" or "tea".
2.8.80
The EU Scientic Committee on Food and the European Food Safety Authority (EFSA) [225]
Germany, Australia, and New Zealand have reported adverse eects of energy drinks associated with liver damage, kidney failure, respiratory disorders, agitation, heart disfunctions and deaths. These incidents usually involved improper intake of energy drinks, such as drinking them with alcohol or in greater quantities than recommended. EU Scientic Committee on Food (SCF) has issued a statement on the safety of energy drinks and their stimulant ingredients in 1999, and supplemented this statement in 2003. This opinion says that the caeine content of energy drinks is not so high that intake of caeine as a result of moderate consumption of energy drinks would be detrimental to a healthy adult. However, energy drinks are not recommended to children and pregnant women. A daily intake of 300 mg is safe for pregnant women. Because of most recent
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research results, setting the safe limit at 200 mg has been considered. European Food Safety Authority (EFSA) gave in 2009 an opinion on taurine and glucuronolactone, stating that frequent intake of energy drinks is not a matter of safety concern. However, the EFSAs committee stressed the acute health concerns including accidents causing death that have been reported for young people that consume excessive amounts of energy drinks combined either with physical stress or as in most cases the use of alcohol. The committee considers it not probable that taurine and caeine carry a combined impact on the uid and sodium losses of the body. Glucuronolactone probably has no combined impact with the eects of caeine, taurine, alcohol or physical stress. Recommended though is that energy drinks not be used in combination with excessive use of alcohol or as drinks to quench thirst. [226] Drug interactions and dose-dependent eects remain largely unknown, although the current study reports that the ingredients 5-hydroxy tryptophan, vinpocetine, yohimbine, and ginseng have the potential for drug interactions that could result in adverse eects. Such combination is found in JetFuel. [227]
2.8.81
Energy drinks labelled as nutritional supplements in USA [228]
Energy drinks are categorized as nutritional supplements in order to avoid the limit of 71 mg caeine per 12 uid ounces set by the FDA for soda, but also evade pharmaceutical safety testing and labelling in USA. Actually these drinks contain 75 to 400 mg caeine per container, and guarana, kola nut, yerba mate, and cocoa adds a lot more not yet included in the .declaration of the label. USA has the the most lax regulatory requirements on energy drinks compared with any other country. These drinks vary from 50 mg to 505 mg per unit. Reissig et al. 2009 state that the absence of regulatory opened to doors to aggressive marketing of energy drinks targeted toward young males, for psychoactive, performance-enhancing and stimulant drug eects, resulting in increasing cases of caeine intoxication and caeine dependence and withdrawal in children and adolescents. According to the authors, there are signs that combined use of caeine and alcohol may increase the rate of alcohol-related injury and provide a gateway to other forms of drug dependence. [229]
2.8.82
Aggressive marketing of energy drinks [230]
Howland et al. 20011 report that marketing promotes mixing caeinated "energy" drinks with alcoholic beverages, such as Red Bull with vodka. Young drinkers are brought to expect that these drinks might reduce the eects of alcohol and enhance alertness, leading to
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increased risk in trac. Tests performed by the authors performed demonstrate that alcohol signicantly impaired driving and sustained attention/reaction time. No improvement of driving performance was obtained with the addition of caeine. The authors concluded that energy drinks or caeine alone does not inuence the eects of alcohol related to driving.
2.8.83
Health Canadas New Recommendations [231]
For children age 12 and under, Health Canada recommends a maximum daily caeine intake of no more than 2.5 milligrams per kilogram of body weight. Based on average body weights of children, this means a daily caeine intake of no more than: 45 mg for children aged 4 - 6. 62.5 mg for children aged 7 - 9. 85 mg for children aged 10 - 12. For women of childbearing age, the recommendation is a maximum daily caeine intake of no more than 300 mg, or a little over two 8-oz (237 ml) cups of coee (Nawrot et al. 2003) [232]. For the rest of the general population of healthy adults, Health Canada advises a daily intake of no more than 400 mg. The organisation provides a list of foods and caeine contents. [233]
2.8.84
Health risks of energy drinks and energy shots [234]
Hebert, Stanbrook and MacDonald 2010 point to the health risk of energy drinks due to inadequate labelling requirements, a lack of awareness of caeines harmful eects and clever marketing aimed at children. Energy drinks contain 80 to 140 mg of caeine per 250 mL, the equivalent caeine in one cup of coee. New formulations with caeine concentrations as high as 500 mg per can are now being marketed. The authors stress that many countries are working on strict regulations. Red Bull is being sold only in pharmacies in Norway. It is prohibited in Denmark. Herbert and colleagues recommend all products with caeine levels exceeding 100 mg to have label and advertising with warnings comparable to those required for caeine tablets. There should be no advertising targeting children, and public education should focus on the health consequences of caeine in children.
2.8.85
Energy shots
Similar to energy drinks, energy shots contain caeine, vitamins, and herbs such as guarana, ginseng or ginkgo biloba, taurine, maltodextrin, inositol, carnitine, creatine or glucuronolactone. The central ingredient in most energy shots is caeine, the same stimulant found
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in coee or tea. The average 50 ml energy shot has about 80 mg of caeine ranging up to 200 mg per shot, and 200-1000 mg Taurin. This is approximately equivalent to a cup of coee.
2.8.86
Micro shots
These are shots with 1-5 teaspoons of liquid, such as Dynapep and FIXX Extreme with 400 mg caeine. [235]
2.8.87
Excessive energy shot intake [236]
According to the German Federal Institute for Risk Assessment (BfR) energy shots are a new kind of energy drinks that contain caeine and taurine. In advertisements, these are claimed to increase concentration and capacity or physical performance. They are marketed in smaller portions (25-75 ml) than the more common energy drinks yet contain a higher concentration of caeine and in some cases taurine per litre than energy drinks. The compositions of energy shots known to BfR vary signicantly and contain between 50200 mg caeine and 200-1000 mg taurine per portion. In contrast to energy drinks, these energy shots are labelled with the manufacturers suggested intake levels recommending one portion per day.
2.8.88
Health risks
BfR writes that health risks can result if the suggested intake level is exceeded considerably. The extent of potential health risks depends on the intake amounts (caeine and taurine) and the manner of intake (e.g. once, rapid intake over a short period of time, high amounts distributed over several single doses), on individual consumer sensitivity to the eects of caeine, the usual amount of caeine consumed daily, the amount of caeine consumed through other sources of caeine as well as potential parallel factors such as alcohol intake or strenuous physical/sports activity. According to BfR, there is a risk that energy shots are not used in accordance with the manufacturers advice for intended use. The Institute assumes that energy shots are sometimes consumed in place of energy drinks without quantitative limit. It should also be noted that consumers in night clubs may choose to increase their energy shot intake in an attempt to counteract fatigue or to reach a state of arousal. According to BfR, the desire to improve performance produces a risk of excessive energy shot intake. As consumers can be expected to disregard the advice for intended use, thus taking in high doses of caeine which could result in adverse eects, the Institute deems energy shots unsafe. The compositions of energy shots assessed here vary signicantly (caeine concentrations
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1.3-6 g/L, taurine concentrations 4-20 g/L). With respect to the manufacturers advice for intended use (1 portion/day), caeine intake ranges from 50-200 mg and taurine intake ranges from 200-1000 mg/day. The interaction of caeine with other constituents in energy drinks (e.g. taurine) or with ethanol in the alcoholic beverages consumed together with energy shots or with physical exertion (e.g. extended, physically strenuous dancing) or sports activities could amplify the adverse eects of caeine.
2.8.89
The use of caeine as pharmaceutical product [236]
- For the indication "to temporarily counteract symptoms of fatigue", single doses of 100 to 200 mg caeine are used, which can be repeated if necessary, but not more than twice within 24 hours (BGA, 1988; pharmaceutical product information of a caeine monopreparation, 2008). - With regard to "side eects", the information states that the appearance of side effects depends on the above named factors and that even low doses (this probably refers to 100 mg) can cause tachycardia, insomnia, apprehension and gastrointestinal disturbances, while doses over 200 mg can cause irritability, headaches and intensied physiological muscle tremors even in individuals with low sensitiv-ity (pharmaceutical product information of a caeine monopreparation, 2008). - In section "special warnings and special precautions for use" patients with hyperthyroidism (may increase) and patients with cirrhosis of the liver (caeine may accumulate) are advised to take caeine at a low dosage (about 100 mg) and only under medical supervision (pharmaceutical product information of a caeine monopreparation, 2008). - "Overdosing" contains the information that symptoms of poisoning can occur at 1g caffeine and more if the amount is taken in a short time span. It also states that fa-tal doses of caeine range from 3 g and 10 g (pharmaceutical product information of a caeine monopreparation, 2008).
2.8.90
Warning labels about excessive consumption of caeine and taurine rejected by the EU Commission [237]
In July 2010 the European Commission rejected the German motion to require energy drinks to carry warning labels because of concerns about excessive consumption of caeine and taurine. The Commission found no evidence of a specic risk associated with these substances that would require additional labelling. This disregards several international warnings.
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2.8.91
Energy drink consumption and alcohol intoxication [238]
Thombs and colleagues 2010 assessed the consumption of energy drink, alcohol intoxication and intention to drive a motor vehicle. The authors found that consuming alcohol mixed with energy drinks increased the risk 3-fold of leaving a bar highly intoxicated, as well as a 4-fold increased risk of intending to drive, compared to other drinkers who did not consume alcoholic beverages mixed with energy drinks. The authors concluded that energy drink consumption by young adults at bars is a marker for elevated involvement in nighttime risk-taking behaviour. The authors call for further research to develop sound regulatory policy on alcohol/energy drink sales practices of on-premise establishments.
2.8.92
Combination of alcohol and energy drinks like Red Bull [239]
Young adults increasingly use energy drinks in the hope to reduce the intensity of the depressant eects of alcohol. Objective motor coordination and visual reaction time is, however, not improved trac safety is thus endangered when alcohol is consumed together with energy drinks like Red Bull and GSK Lucozade Energy. A Brazilian study leaded by Sionaldo Eduardo Ferreira studied the eect of energy drinks on symptoms of alcohol intoxication. The study concludes that the ingestion of alcohol plus energy drink signicantly reduced subjects perception of headache, weakness, dry mouth, and impairment of motor coordination. However, the ingestion of the energy drink did not signicantly reduce the decits caused by alcohol on objective motor coordination and visual reaction time. The ingestion of the energy drink did not alter the breath alcohol concentration in either group. Energy drinkscannot reduce the harmful eects of alcohol on motor coordination, the person is drunk but does not feel as drunk as he really is. Energy drinks also dangerously increase the amount and the speed of ingestion -of alcoholic beverages. Earlier ndings demonstrate that even a small volume (250ml) of a specially formulated energy drink (Solstis, GlaxoSmithKline, Brentford UK, providing 75 mg caeine and 37.5 g glucose) can have a consistent eect on sleepiness, lane keeping and speed choice in trac. These ndings are important, and if supported by further research could have implications for future highway safety. This study, however, gives no information about a simultaneous consumption of energy drinks and alcohol intoxication as it highlights the eect on sleepiness in absence of alcohol.[240]
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2.8.93
Energy drinks as nutritional healthcare product [241]
The GSK company promotes its Lucozade glucose energy and sports drinks under the category of nutritional healthcare product giving them a touch of health and ttness.
2.8.94
New data suggest that energy drinks increase health risks [242]
Energy drinks contain caeine, taurine, inosite and glucuronolactone. Energy drinks with high popularity are Red Bull, Full Throttle, Amp and Rush. According to the Federal Institute for Risk Assessment (BfR) provides information on more recent human data on the possible health risks posed by the consumption of energy drinks. It draws attention to reports that cardiac dysrhythmia, seizures, kidney failure and fatalities occurred after consuming energy drinks. The question about the causal relationship is still open. The BfR calls attention to ndings which indicate that test persons no longer realistically assess their dwindling responsiveness caused by alcohol consumption under the inuence of energy drinks. The parallel consumption of alcohol and energy drinks can, therefore, lead to an individual misjudging his ability to perform. Caeine-containing lemonades which taurine, inosite and glucuronolactone have been added (energy drinks), are approved in Germany as follows: - caeine up to max. 320 mg/l, - taurine up to max. 4000 mg/l, - inosite up to max. 200 mg/l and - glucuronolactone up to max. 2400 mg/l The BfR recommends comprehensive information on product labels in addition to the currently prescribed labelling on a high caeine content: - adverse eects cannot be ruled out when larger amounts of these beverages are consumed in conjunction with intensive physical activity or with intake of alcoholic beverages; - beverages of this kind, particularly when consumed in larger amounts, are not recommended for children, pregnant women, lactating women or individuals who are sensitive to caeine.
2.8.95
Study says energy drinks may be harmful to people with hypertension, heart disease [243]
The study, leaded by James Kalus, Pharm.D. says that participants consuming two cans of energy drinks per day had their heart rate increased 7.8 percent the rst day and 11 percent the seventh day. Blood pressure increased at least 7 percent the rst and seventh days.
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The authors recommend that people who have hypertension or heart disease and are taking medication for them to avoid consuming energy drinks because of a potential risk to their health. Kalus stressed further that energy drinks should not be confused with sports drinks, which aim to replenish the carbohydrates and electrolytes that a body needs, and that both caeine and taurine from energy drinks have a direct impact on cardiac function.
2.8.96
Australia study says one can of energy drink can increase the risk of heart attack or stroke [244]
Scott Willoughby and colleagues 2008 say that one 250 ml can of the energy drink Red Bull is sucient to increase the risk of heart attack or stroke, even in young people. The study found that the drink caused the blood to become sticky, a precursor to cardiovascular problems such as stroke. After one hour after Red Bull ingestion, the blood systems were similar to patients with cardiovascular disease. It altered platelet aggregation and endothelial function in young healthy adults. One can contains 80 mg of caeine and 1000mg of taurine. Results showed that mean arterial pressure increased signicantly after one can of Red Bull but heart rate was unaected. Platelet reactivity was acutely increased by Red Bull while endothelial function deteriorated. Willoughby and colleagues stressed that although the incidence of sudden cardiac death is low, the drink could be dangerous for people with any sort of cardiovascular abnormality. They also said that the sugar-free version of Red Bull could increase the danger of blood clots and raise the risk of heart attack or stroke. Energy drinks with caeine and taurine are banned in Norway, Uruguay and Denmark because of health risks.
2.8.97
Nutritional information on the most popular drinks [245]
Kotke and Gehrke 2008 provided a table with nutritional information on the most popular drinks. The table was compiled to help renal dietitians to stay informed of the abundance of products and to guide chronic kidney disease (CKD) patients appropriately. The authors stress that a sports drink is a beverage designed to help athletes rehydrate and replenish sugar and other nutrients that can be depleted after strenuous training or competition. An energy drink is a beverage designed to give the consumer a burst of energy through a combination of ingredients including caeine, vitamins, minerals, and exotic herbal ingredients. Some CKD patients may need a sports drink if they are training for or performing in a strenuous sports-related event that depletes their electrolytes and sugar. Energy drinks, if approved by the renal dietitian, may be appropriate for patients who can tolerate them.
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Kotke and Gehrke say that most energy drinks contain herbal supplements such as guarana, yerba mate leaves, Pannax ginseng, gingko biloba, and milk thistle, which may interact with prescription medications and alter their eectiveness or interact in a harmful way.
2.8.98
Important coe groups [246]
There are four important coee groups: Robusta, Columbian Milds, Other Milds and Brazilian Naturals. Coee from the species Coea arabica are richer in avor than their Coea robusta conterparts. C. arabica has many dierent varietals, each with unique characteristics. Some well-known arabica coees include: Robusta grows at altitudes usually up to 800 meters in Indonesia, West Africa, Brazil and Vietnam representing around 30% of world production. Arabica grows at altitudes between 600 and 2000 meters in Latin America and East Africa representing 70% of world production.
2.8.99
Diterpenes, bad components of coee [247]
Urgert and colleagues analysed the coee diterpenes and their eects on the human serum. Cafestol and the related compound kahweol was present in unltered coee brews and raises serum concentrations of cholesterol, triacylglycerols, and alanine aminotransferase in humans and and aect liver function. Filtered coee is free of diterpenes. They are removed by the paper of the lter. Other materials used as lter should be tested on their ability to retain the diterpenes.
2.8.100
Caeine [248]
Caeine, depending upon the quantity consumed: increased alertness, anxiety, irritability, interference with sleep, and jitteriness and is a mild diuretic. The most notable behavioural eects of caeine occur after consumption of low to moderate doses (50-300 mg) and include increased alertness, energy, and ability to concentrate. Moderate caeine consumption rarely leads to health risks. Caeine was considered in one study as a potential drug of abuse and more recently was described as a model drug of abuse. Coee can be said to be habit-forming.
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2.8.101
Moderate consumption of coee reduces risk of Parkinson disease [249]
The association of caeine, particularly coee intake and Parkinson disease was evaluated in the Honolulu Heart Program between 1965 and 1968 concluding that those who consumed caeine had a signicantly lower incidence of PD than those who did not. For example, the adjusted incidence of PD decreased from 10.4:10,000 person-years in those who did not consume coee to 1.9:10,000 person years for those who consumed at least 28 ounces/day. This eect was dose-related with increased caeine consumption inversely correlated with the risk of developing PD. The data suggest that the mechanism is related to caeine intake and not to other nutrients contained in coee. The National Institute of Neurological Disorders and Stroke found that available studies evaluating caeine and PD prevention are overall positive, however they are limited, in that they are primarily retrospection/case-control in nature, or they do not assess caeine intake in a well controlled manner. Typically, caeine or coee intake is assessed as a categorical variable (1-2 cups/day of coee), hence there is also no denite dose or dose-range that has been evaluated. [250]
2.8.102
Coee and reduction of risk for type 2 diabetes [251]
Long-term coee consumption (7 or more cups of coee a day) were found by SalazarMartinez and colleagues to be associated with a statistically signicantly lower risk for type 2 diabetes. Total caeine intake from coee and other sources was associated with a statistically signicantly lower risk for diabetes in both men and women. Battram and colleagues found that acute alkaloid caeine (CAF) ingestion results in an impaired glucose tolerance, chronic coee (RCOF) ingestion decreases the risk of developing type 2 diabetes. The eect of RCOF compared with decaeinated coee DECAF was less pronounced.[252]
2.8.103
Coee, caeine and diabetes 2 risk [253]
Dam and Hu in 2005 found that higher coee consumption was consistently associated with a lower prevalence of postprandial hyperglycemia. They concluded that habitual coffee consumption is associated with a substantially lower risk of type 2 diabetes. Legrand and Scheen in 2007 reviewed studies on the relationship between type 2 diabetes and coee drinking, the most of them conrmed a protective eect against the disorder. Decaeinated coee had a stronger protective eect as compared to regular coee. The authors stress that the blood glucose reduction could not be attributed exclusively to caeine
2.9. THE FINE STUDY
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and other components, such as chlorogenic acid and/or various anti-oxidants may add to the eect. [254]
2.8.104
Caeine found to increase diabetes risk [255]
Dr James Lane and his colleagues in 2008 found that too much caeine can raise blood glucose levels and impede the transport of glucose from the blood into muscle and other cells. A moderate dose of 500 mg/day caeine their average daily blood glucose levels rose by 8% and at peaks up to 26%. The authors are uncertain about the mechanism of action of caeine but suggest that it might inhibit inhibit glucose uptake in adipocytes and skeletal muscle cells by antagonising adenosine receptors. Another way of action could be that caeine might act indirectly by pushing up levels of adrenalin. The authors suggest to quit drinking coee, or any other caeinated beverages to reduce blood glucose.
2.8.105
Coee and rectal cancer [256]
Consumption of caeinated coee, tea with caeine, or caeine was not associated with incidence of colon or rectal cancer, whereas regular consumption of decaeinated coee was associated with a reduced incidence of rectal cancer.
2.8.106
Coee and liver cancer [257]
Manami Inoue and colleagues found that drinking coee on a daily or almost daily basis resulted in a lower hepatocellular carcinoma HCC risk than those who almost never drank coee; risk decreased with the amount of coee consumed. The risk of liver cancer in almost never drinkers in this population was 547.2 cases per 100 000 people over 10 years, but it was 214.6 cases per 100 000 people with drinking coee on a daily basis. In the Japanese population, habitual coee drinking may be associated with reduced risk of HCC.
2.9
The FINE Study
[258] The FINE Study, a prospective European cohort study, investigated whether coee consumption is associated with 10-year cognitive decline in elderly men in the Finland, Italy and The Netherlands.
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The study found that caeine use or coee consumption is associated with better cognitive functioning. [259] [260] However, Johnson 2002 found cognitive performance induced by coee elderly women but not in elderly men. [261] The Study pointed out that Fredholm and colleagues (1999) suggest that caeine acts as an antagonist on the A2a adenosine receptors in the brain, which consequently stimulates cholinergic neurons. According to the researchers, its weak reinforcing properties are due to a unique and atypical mechanism of action caeine is a self-limiting drug and subjects do not gradually increase the dose, because tolerance development to both the reinforcing and aversive eects is limited. [198]. According to DallIgna and colleagues (2002) these neurons protect against beta-amyloid-induced neurotoxicity, a precursor of cognitive decline. [262] Coee is a major source of caeine and one cup of coee contains about 85 mg of caffeine, almost twice the caeine content of tea (45mg) . Research of Freedholm and colleagues with mice showed caeine from coee acts as an antagonist on the A2a adenosine receptors in the brain. [198] DallIgna and colleagues found that this stimulates the secretion of cholinergic neurotransmitters, preventing betaamyloid-induced neurotoxicity in cerebellar neurons. [262] Kopf and colleagues 1999 suggest that the A2a adenosine receptor has an eect on the memory part of the brain, the hippocampus. [263] Other important substances of coee, like magnesium and many phenolic acids, such as chlorogenic acid increase the antioxidant capacity in plasma, protecting neurons from oxidative damage are highlighted by Nardini and Christensen. [264] [265]
2.9.1
Conclusions of the FINE Study
Coee reduces cognitive decline in elderly men, with the least cognitive decline for men consuming three cups of coee per day.
2.9.2
Caeine and newborn infants
There is no blood-brain barrier to caeine in the adult or the fetal animal [266]. There is no placental barrier to caeine [267] [268] and unusually high levels of caeine have been reported in premature infants born to women who are heavy caeine consumers. [269]
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2.9.3
Caeine equivalents [246]
In general, each of the following contains approximately 200 mg of caeine: One 200 mg caeine pill (in some countries these are 100 mg, in the UK these are 50 mg) Two 8-uid ounce containers of regular coee (16 uid ounces (4.73 dl) total) Five 1-uid ounce shots of expresso from robusta beans (5 uid ounces (1,47 dl) total) Five 8-uid ounce cups of black tea (40 uid ounces (1.18 l) total) Five 12-uid ounce cans of soda (60 uid ounces total (1.77 l), although these can vary widely in content) Ten 8-uid ounce cups of green tea (80 uid ounces (2.36 l) total) One and a half pounds (0,68kg total) of milk chocolate. Fifty 8-uid ounce cups of decaeinated coee (400 uid ounces (11.82 l) total) 1 uid ounce (US and CA) = 29,56 ml 1 uid ounce (GB) = 28,41 ml Caeinated carbonated beverages contain from 20-70 mg of caeine. A cup of coee contains between 65 and 175 mg. A cup or glass of tea typically contains 40-70 mg. A chocolate bar contains about 30 mg.
2.9.4
Gunpowder tea
Gunpowder tea [270] is made up of leaves hand-rolled into tiny pellets resembling gunpowder. Rolling tea leaves into gunpowder tea renders the leaves less susceptible to physical damage and allows them to retain more of their avor and aroma.
2.9.5
Claims for functional foods
Claims for functional foods There are two main types of claims for functional foods. [183]: 1. Enhanced function claims: There are given interactions of a food component and specic functions in the body.There are no direct references to diseases given. Some examples of enhanced function claims are: Strengthening the immune functions Antioxidants, acting against oxidative stress
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CHAPTER 2. FOOD, WHAT IS IT? Restore or stabilize bacterial intestinal colonies such as the stimulation of Bidus bacteria (Bidobacterium longum Bioavailability of minerals by milk oligopeptides or inulin.
2. Diseases risk reduction claim: Not allowed by German Food Regulation.New regulations on European level are therefore needed to make these claims European wide accepted.Some examples of disease risk reduction claims are: Cardiovascular diseases Intestinal infections Diarrhoea,constipation Osteoporosis Non-insulin dependent diabetes or obesity
2.9.6
Denition of Probiotics
Since 1960 bacteria used in the therapy of people with pathological modied intestinal ora and prophylactic purpose were called probiotics. Probiotics are especially selected microorganisms showing a health-promoting eect on the host organism if consumed in a certain cell count, inuencing the microbiological composition of the gastro-intestinal tract. The specic activity must surpass the activity of usual food.
2.9.7
Probiotics found to be protective against cold and inuenza [271]
Probiotic bacteria strains were tested by Leyer from Danisco and colleagues 2009 for prophylaxis against cold and inuenza-like symptoms in healthy children aged 3 to 5 years. In this study randomly assigned groups received twice daily placebo, Lactobacillus acidophilus NCFM, and L acidophilus NCFM in combination with Bidobacterium animalis subsp lactis Bi-07. The authors found that compared with the placebo group, the groups receiving single and combination probiotics had healthier outcomes. The authors concluded that L acidophilus NCFM alone was eective. There was, however, a trend for a broader protective eect with the combination of L acidophilus NCFM and B lactis Bi-07. Daily dietary supplementation reduced fever, rhinorrhea and cough incidence, antibiotic prescription and number of missed school days.
2.9.8
Probiotic bacteria and irritable bowel syndrome(IBS)
The concept of small bowel bacterial overgrowth (SBBO) as an explanation for IBS symptoms and the use of a probiotic to help promote normal digestive function has been proposed. Certain strain of bacteria like Rosell-52 and Rosell-175 are available as a micro-encapsulated
2.9. THE FINE STUDY
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ProbioStick in thin tubes to be protected against the acidity of the stomach. They are being surveyed concerning the reduction in gastrointestinal symptoms, nausea and abdominal pain, related to stress disorders. Improvements of suerers of irritable bowel syndrome were reported by Dr. Laurent Diop There is a poor survival of probiotic bacteria in the human gastrointestinal tract. Several methods of micro-encapsulation of probiotic bacteria included spray drying, extrusion, emulsion and phase separation had not achieved satisfactory results. The most common reported method is the calcium-alginate gel capsule formation. Other excipients are kappa-carrageenan, gellan gum, gelatin and starch. The available equipment for microencapsulation must undergo further development in order to generate precise and uniform micro or nano capsules in large quantities for industrial application. [185] For micro-encapsulation to be applicable in probiotic yoghurt, the beads should not be sensed by the consumer. Small and uniform beads may allow the retention of a desirable mouth feeling as well as minimise cell death due to oxygen toxicity.[272] Other studies of the ecacy of encapsulated probiotic bacteria in irritable bowel syndrome (IBS)were performed by ClinicalTrials.gov, U.S. National Institutes of Health, using Bidobacterium Infantis 35624 under the ClinicalTrials.gov Identier: NCT00135031. [186]
2.9.9
Probiotics and prevention of diarrhoea [273]
A meta-analysis evaluated the evidence for the use of probiotics in the prevention of acute diarrhoea. Results suggest that probiotics signicantly reduced antibiotic-associated diarrhoea, reduced the risk of travellers diarrhoea, and that of acute diarrhoea of diverse causes, and reduces the associated risk of acute diarrhoea among children and adults. The protective eect did not vary signicantly among the probiotic strains Saccharomyces boulardii, Lactobacillus rhamnosus GG, Lactobacillus acidophilus, Lactobacillus bulgaricus, and other strains used alone or in combinations of two or more strains.
2.9.10
Probiotic bacteria can ameliorate stress induced gastrointestinal disorders [274]
According to Laurent Diop and colleagues, the stress induces various disorders with gastrointestinal, physical, and psychological symptoms, in this case probiotics can help regulate or modulate gastrointestinal functions. The authors found that the consumption of probiotics signicantly reduced stress-induced gastrointestinal symptoms such as abdominal pain and nausea/vomiting.
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For this study a proprietary blend of Lactobacillus acidophilus Rosell-52 and Bidobacterium longum Rosell-175 was used. The researchers concluded that this blend of probiotic strains can provide a benecial eect on the gastrointestinalsymptoms experienced by individuals aected by chronic stress.
2.9.11
Negative outcome probiotics in acute pancreatitis [275]
According to a press release of Gut Flora from 23.01.2007 in a study concerning the eects of probiotics in patien was given probiotics than in the group that was not. Earlier studies had shown that that the treatment reduce the rate of pancreas infection. In this study twenty-four died in the study group and nine died in the control group. It is not know what has caused the higher death rate, but the investigators advise colleagues not to use probiotic bacteria in the acute phase of this serious disease, at intensive-care patients,or the administration of probiotics through a feeding tube (directly into the intestine). The bacteria involved in the research were varieties of Lactobacillus, Enterococcus, or Bidobacterium, from the DutchWinclove Bio Industries
2.9.12
Denition of prebiotics
Prebiotics are ingredients which help the intestinal ora to develop. Inulin is an example of a prebiotic ingredient which helps Bidus to develop. The eective daily dosage of prebiotics like fructooligosaccharides (FOS) for humans is 3.0 g and and 0.7 g for xylooligosaccharides (XOSs). [276]
2.9.13
Denition of symbiotic
Symbiotic is the combination of probiotic ( the positive acting intestinal ora) and prebiotics (the ingredients which help intestinal ora).
2.9.14
Cholesterol-reducing claim
The USA Food and Drug administration has approved at 8.07.99 the claim that a a nutrition rich on bres and low fat reduces the risk of cardiac infarct.
2.9.15
Targets for functional foods according Roberfroid
Targets for functional food are[183]: Growth, development and dierentiation.

2.10. MOOD FOOD Insulin resistance and other substrate specic problems. Defense against oxidative reactions Modications of the cardiovascular system
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In functional food there should be included also Mood Food. Depressions and changes of mood can be inuenced by neurotransmitter enriched food. Unfortunately European Functional Foods market is dominated by digestive products. US market addresses a wide range of health conditions such as arthritis, cholesterol, blood pressure lowering,insomnia, immune booster and vision enhancer. They are called "Health Food"[187]. German regulations forbid to point out prophylactic,relieve or healing activities of food.
2.10
Mood Food
Giesela Krahl in her book "Mood Food"[277] explains the relationship between food and mood. Mood food utilizes the knowledge of physiology and pharmacology to create good mood. Changes of mood and sudden bad feeling are not always a disease of body or soul and food is not medicine, but according to Krahl there is a relation between them. A deep depression will not be solved by a meal of bananas, however bananas are a good choice because they interfere in the physiology of serotonin and help to lower the grip of depression. After explaining the fundamentals of this relationship in her book Krahl gives excellent formulas and suggestions of ne food to trigger high feeling. Color, taste, smell and composition of meals can act positively on our feeling. Some substances which interfere with the mood[277]:
2.10.1
Serotonin
Serotoninis a neurotransmitter which regulates our feeling and our mood. High serotonin levels are responsible for a balanced feeling and contentment. Low levels of serotonin may produce fear, anxiety, and depression. Serotonin is made by our body using tryptophan. Sugar and carbohydrates trigger the production of insulin which helps tryptophane to get
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to the brain where serotonin can be built out of this raw material. Sugar acts more quickly on the mood as carbohydrate rich food such as pasta and rice do. The good mood of candies last however less time as carbohydrate rich food do.
Tryptophan is an essential amino acid which cannot be prepared by the body itself. It must assimilated with food. The synthesis of serotonin needs tryptophan and carbohydrates in higher concentration as fat and proteins. Dr. Astrid Lindhorst is studying neurotransmitters of the Hypothalamus, a part of the limbic system.[278] The limbic system makes the connection between consciousness, emotions and motivations at one side and the activity of the internal organs on the other side. Dr. Lindhorst studies the production of neurotransmitters under stress situations. The neurotransmitter of importance on this study are serotonin (5-hydroxytryptamin also
2.10. MOOD FOOD called 5-HT) and 5 hydroxyindolacetic acid(5HIAA)
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Serotonin is used in pharmacy in antidepressants. Foods rich in carbohydrates such as pastas and rice as well as sugar rises the blood level of serotonin acting as happy food. The neurotransmitter are extracted with microdialysis and measured with HPLC. Catecholamineare responsible for vigilance, attention, activity. The group of catecholamines also embraces the neurotransmitter adrenalin ,noradrenalin and dopamine. These substances carry messages keeping ones awake and active. They aect attention, sexual activity, aggressiveness and regulate the appetite.
2.10.2
Formation of catecholamine
Tyrosine can be made by the body. Phenylalanine must be obtained from food, it is an essential aminoacid. Phenylalanine triggers the motivation, the memory and learning. Phenylalanine produces in the brain a neuroregulator which is very near in its structure to the doping drugs amphetamines which peps up. To form catecholamine the body needs tyrosine, phenylalanine dierent minerals and vitamins. Tyrosine is an aminoacid which the body can buildup by himself.Phenylalanine however must be present in food.
2.10.3
Phenylalanine
Is psychoactive substance which boosts the motivation, makes thinking active and makes learning better. In brain phenylalanine produces a neuroregulator which is very near to amphetamines used by drug addicts and acts antidepressive.
2.10.4
Acetylcholine
Acetylcholine is a messenger substance which is found in the brain an in the neurovegetative system and changes informations between nerve cells and muscle cells.It also has a function on thinking, learning. It is being formed starting from choline.
2.10.5
Endorphine, enkephalin, neuropeptides and similar substances
Endorphin,enkephalin and neuropeptides are messenger substances of the brain which are similar to opiates regulating fear, rage, euphoria, sexual drive, and the perception of pain.
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These substances are made by the body himself starting from serotonin and acetylcholine during long physical activities such as marathon, music playing and daydreams.
2.10.6
Sources of neurotransmitters
Our body is not capable to produce by himself the whole amount of hormones and neurotransmitters which are needed. Our brain must be continuously fed with special substances which are present in food. These compounds are responsible for good function of the brain. Our food bears a never ending number of compounds which are necessary to the function of life.This however does not mean that bananas , soy bean, vegetables or yoghurt should be sold in health stores and pharmacies as powerful medicine. We cannot live without food. Industry however should not advertise food as concentrated drugs which can perform miracles in short time. Food act on long time basis. Food should be varied to cover all our needs.Eating continuously one brand of yoghurt will not cover all aspects of our life. Some foods together with some functions are listed below. This shows that a variety of ingredients are needed of our meal are necessary to cover all our needs.
Table 2.20: Sources of Neurotransmitters in food which may act on mood Neurotransmitter Serotonin Source Pasta, rice, potatoes, cereals (wholemeal), bread, nuts, almonds, dates, gs, bananas, pineapple and chestnuts. Tyrosine and Phenylalanine milk and milk products, Eggs, potatoes, rice, soy, noodle, poultry, meat and sh, in aspartame and chocolate. Choline and acetylcholine lecithin from soy,beer yeasts, soy, seeds, nuts,wheat germs, vegetables, cereals (wholemeal), liver, eggs and cheese. Endorphin, enkephalin, neuropeptides everything rich in carbohydrates like cereals, pasta, honey,bananas, dried fruits, food rich in fat like nuts, cream, butter, cocoa and cheese.Chocolate and gum bears are therefore eaten during depressions. Table 2.21: Active compounds in food Active compound Source activity
2.10. MOOD FOOD Lecithin Soy beans, egg yolk, liver, milk Omega-3-fatty acid Mackerel, herring, tuna, margarine Iron Meat, eggs, crustaceans, cereals, carrots Phenylalanin Milk, eggs, potatoes, rice, soy beans, noodles Zink Cereals, almonds, oysters, carrots,oranges Acetycholine Egg yolk, liver, cereals, vegetables Vitamin B1 Avocados, bananas, nuts Suldes Garlic, onions Nucleic acids Germinating cereals, vegetables folic acid Green leaf vegetables, cheese, meat Magnesium Dried fruits, dates, wheat germs Pectin Apples, quinces Vitamin B Milk, egg yolk, mushroom, poultry Concentration Concentration Learning Learning Memory Memory Memory Creativity Creativity Creativity Anti-stress Anti-stress Anti-stress
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2.10.7
Taurine
Taurine is present in mussel, crustaceae such as shrimps and oysters and is produced in the liver. It stimulate the production of fat-killing hormones. Oestrogen (female hormone) can inhibit the production of taurine. This is why women easily built a depot of fat as male. Taurine participates also in the production of bile acids.
2.10.8
Methionine
Methionine is an essential amino acid and is part of adrenalin which is responsible of the release of great amounts of energy. Methionine is present in sh, egg yolk, meat, poultry, liver, soy beans, cheese and lentils.
2.10.9
Choline
Choline is part of external layers of nerve cells and brain cells. Choline controls the exchange of molecules through the membrane of the cells and helps to burn fat. Low levels of choline result in fat deposit in liver.
2.10.10
Magnesium
It is present in green salad, seeds, nuts, vegetables, cereals, and banana. Magnesium acts on the fat burning system. Many over weight people have an undersupply of magnesium. These compounds act all together. In order to have them all at once a well-balanced nutrition of natural origin are necessary together with sucient physical activity.
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2.10.11
Spices which may act on mood
Spices which may act on mood[277]:
2.10. MOOD FOOD Spices Anise Basil Savory Curry Dill Ginger Fennel seed Garlic Caraway Majoram
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Melissa Nutmeg Clove Paprika Pepper and chilly Pepper mince Rosemary Sage Thyme Vanilla
Cinnamon Onions
Activity Nomenclature calming, relaxing Pimpinella anisum reduces fear , nervous sleepless Ocimum basilicum acts on the intellect and sexual feeling Satureja hortensis can change mood Several spices acts calming and relaxing Anethum graveolens is a stimulating tonic spice Zingiber ocinale acts calming for the stomach of babies as well Foeniculum vulgare for the mood of adults acts stimulating,lowers blood pressure Allium sativum acts stimulating Carum carvi wars up body and soul and is known Origanum majorana as antiaphrodisiac,reducing sexual desire, therefore good for nuns and monks acts calming and relaxing Melissa ocinalis acts stimulating, known as aphrodisiac. Myristica fragans acts seducing because of its strong Jambosa caryophyllus and exotic smell. warming and stimulating, Capsicum annuum love desire stimulates sexual desire Piper nigrum stimulates the mind and concentration, Mentha piperita activating memory, and clears thinking acts on the brain strength Rosmarinus ocinalis memory and nerves improves the concentration Salvia pratensis and learning calms and ,relaxing Thymus vulgaris builds up, aphrodisiac, strong activity Vanilla panifolia on emotions, security, soft love and memories of the youth Warm, velvet,security, Cassia vera in India used to increase love. increase concentration Allium cepa.
2.10.12
Chocolate, the new EU Directive 2000/36
The new EU Directive replacing the Directive 73/241/EEC sets the labeling standards for cocoa and chocolate products as follow:
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2.10.13
Milk chocolate
At least 25% of total dry cocoa solids, 14% dry milk solids, 2,5% dry non-fat cocoa solids, 3,5% milk fat.
2.10.14
Chocolate
At least 35% total dry cocoa solids, 18% cocoa butter, 14% dry non-fat cocoa solids.
2.10.15
Family milk chocolate
At least 20% total dry cocoa solids, 20% dry milk solids, 2,5% dry non-fat cocoa solids, 5% milk fat, 25% total fat.
2.10.16
Cocoa Butter Equivalents (CBE)
Vegetable fats, other than cocoa butter may be added to chocolate not exceeding 5% of the nished product.Addition of fats other than cocoa butter must be cited on the label. Vegetable fats which are allowed to be added to chocolate are: Illipe,palm oil, sal, shea, kokum gurgi and mango kernel. The addition of fats other than cocoa butter to chocolate and their products has risen many discussions. According to Mr. Kattenberg from ADM Cocoa liqueed chocolate containing cocoa butter when tempered correctly the resulting product should have a good shelf life. It seems that new technologies of the chocolate industry made the addition of vegetable fats other than cocoa butter unnecessary to prevent blooming. These Fats seem to benet lled chocolate, ice cream and biscuit products.
2.11
Cocoa and chocolate directive 2000/36 EC
The addition of certain vegetable fats other than cocoa butter to chocolate products, up to a maximum of 5 %, should be permitted in all Member States; those vegetable fats should be cocoa butter equivalents. Labelling, presentation and advertising in particular a listing of ingredients of cocoa and chocolate products must comply with Directive 79/112/EEC in order to provide consumers with correct information. The labelling of the cocoa and chocolate products must indicate the total dry cocoa solids content by including the words: "cocoa solids:... % minimum".
2.12. SALES NAMES AND DEFINITIONS OF COCOA, CHOCOLATE AND THEIR PRODUCTS 141 The sales names "chocolate", "milk chocolate" and "couverture chocolate" may be supplemented by information or descriptions relating to quality criteria provided that the products contain:
2.11.1
- Chocolate
in the case of chocolate, not less than 43 % total dry cocoa solids, including not less than 26 % of cocoa butter,
2.11.2
- Milk chocolate
in the case of milk chocolate, not less than 30 % total dry cocoa solids and not less than 18 % dry milk solids obtained by partly or wholly dehydrating whole milk, semi- or fullskimmed milk, cream, or from partly or wholly dehydrated cream, butter or milk fat, including not less than 4,5 % milk fat,
2.11.3
-Couverture chocolate
in the case of couverture chocolate, not less than 16 % of dry non-fat cocoa solids.
2.12
2.12.1
Sales names and denitions of cocoa, chocolate and their products

1. Cocoa butter
designates the fat obtained from cocoa beans or parts of cocoa beans with the following characteristics: - free fatty acid content (expressed as oleic acid): not more than 1,75 % - unsaponiable matter (determined using petroleum ether): not more than 0,5 %, except in the case of press cocoa butter, where it shall not be more than 0,35 %
2.12.2
2.(a) Cocoa powder, cocoa
designate the product obtained by converting into powder cocoa beans which have been cleaned, shelled and roasted, and which contains not less than 20 % cocoa butter, calculated according to the weight of the dry matter, and not more than 9 % water;
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2.12.3
(b) Fat-reduced cocoa, fat- reduced cocoa powder
designate cocoa powder containing less than 20 % cocoa butter, calculated according to the weight of the dry matter;
2.12.4
(c) Powdered chocolate, chocolate in powder
designate the product consisting of a mixture of cocoa powder and sugars, containing not less than 32 % cocoa powder;
2.12.5
(d) Drinkind chocolate, sweetened cocoa, sweetened cocoa powder
designate the product consisting of a mixture of cocoa powder and sugars, containing not less than 25 % cocoa powder; these names shall be accompanied by the term "fat-reduced" in the case where the product is fat-reduced as dened at (b).
2.12.6
3. Chocolate
(a) designates the product obtained from cocoa products and sugars which, subject to (b), contains not less than 35 % total dry cocoa solids, including not less than 18 % cocoa butter and not less than 14 % of dry non-fat cocoa solids; (b) however, where this name is supplemented by the words:
2.12.7 2.12.8
- "Chocolate Vermicelli" - "akes"
the product presented in the form of granules or akes must contain not less than 32 % total dry cocoa solids, including not less than 12 % cocoa butter and not less than 14 % of dry non-fat cocoa solids;
2.12.9
- "couverture"
the product must contain not less than 35 % total dry cocoa solids, including not less than 31 % cocoa butter and not less than 2,5 % of dry non-fat cocoa solids;
2.12.10
- "Gianduja"
(or one of the derivatives of the word "gianduja") nut chocolate: the product must be obtained rstly from chocolate having a minimum total dry cocoa solids content of 32 % including a minimum dry non-fat cocoa solids content of 8 %, and secondly from nely ground hazelnuts in such quantities that 100 g of the product contain not less than 20 g
2.12. SALES NAMES AND DEFINITIONS OF COCOA, CHOCOLATE AND THEIR PRODUCTS 143 and not more than 40 g of hazelnuts. The following may be added: milk and/or dry milk solids obtained by evaporation, in such proportion that the nished product does not contain more than 5 % dry milk solids; almonds, hazelnuts and other nut varieties, either whole or broken, in such quantities that, together with the ground hazelnuts, they do not exceed 60 % of the total weight of the product.
2.12.11
4. Milk chocolate
(a) designates the product obtained from cocoa products, sugars and milk or milk products, which, subject to (b)contains: - not less than 25 % total dry cocoa solids, - not less than 14 % dry milk solids obtained by partly or wholly dehydrating whole milk, semi- or full-skimmed milk, cream, or from partly or wholly dehydrated cream, butter or milk fat, - not less than 2,5 % dry non-fat cocoa solids, - not less than 3,5 % milk fat, - not less than 25 % total fat (cocoa butter and milk fat). (b) However, where this name is supplemented by the words:
2.12.12 2.12.13
- "Milk Chocolate Vermicelli" -"akes"
the product presented in the form of granules or akes must contain not less than 20 % total dry cocoa solids, not less than 12 % dry milk solids obtained by partly or wholly dehydrating whole milk, semi- or full-skimmed milk, cream, or from partly or wholly dehydrated cream, butter or milk fat, and not less than 12 % total fat (cocoa butter and milk fat),
2.12.14
- Couverture
the product must have a minimum total fat (cocoa butter and milk fat) content of 31 %,
2.12.15
- "Gianduja"
(or one of the derivatives of the word "gianduja")

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2.12.16
- Nut milk chocolate
the product must be obtained rstly from milk chocolate having a minimum content of 10 % of dry milk solids, obtained by partly or wholly dehydrating whole milk, semi- or full-skimmed milk, cream or from partly or wholly dehydrated cream, butter or milk fat and secondly from nely ground hazelnuts, in such quantities that 100 g of the product contain not less than 15 g and not more than 40 g of hazelnuts. Almonds, hazelnuts and other nut varieties may also be added, either whole or broken, in such quantities that, together with the ground hazelnuts, they do not exceed 6% of the total weight of the product. (c) Where in this name the word "milk" is replaced by: - "cream": the product must have a minimum milk fat content of 5,5 %, - "skimmed milk" the product must have a milk fat content not greater than 1 %. (d) The United Kingdom and Ireland may authorise the use in their territory of the name "milk chocolate" to designate the product referred to in point 5, on condition that the term is accompanied in both cases by an indication of the amount of dry milk solids laid down for each of the two products, in the form "milk solids: ...% minimum.
2.12.17
5. Family milk chocolate
designates the product obtained from cocoa products, sugars and milk or milk products and which contains: - not less than 20 % total dry cocoa solids, - not less than 20 % dry milk solids obtained by partly or wholly dehydrating whole milk, semi- or fullskimmed milk, cream, or from partly or wholly dehydrated cream, butter or milk fat, - not less than 2,5 % dry non-fat cocoa solids, - not less than 5 % milk fat, - not less than 25 % total fat (cocoa butter and milk fat).
2.12.18
Detection and quantication of cocoa-butter equivalents (CBEs) in milk chocolate to nd chocolate fraud [279]
The Institute for Reference Materials and Measurements (IRMM) recommends the use of the Joint Research Centre (JRC) method to determine the amount of vegetable fats other than cocoa butter in chocolate products, which is limited to 5% by the Chocolate Directive 2000/36/EC. The JRC developed two methods to determine foreign fats in dark chocolate and another method to test milk chocolate. The development of this method took more time because the chemical composition and physical properties of vegetable fat resembles those of cocoa butter very closely and the milk fats in milk chocolate interfere with vegetable fats.
2.12. SALES NAMES AND DEFINITIONS OF COCOA, CHOCOLATE AND THEIR PRODUCTS 145
2.12.19
6. White chocolate
designates the product obtained from cocoa butter, milk or milk products and sugars which contains not less than 20 % cocoa butter and not less than 14 % dry milk solids obtained by partly or wholly dehydrating whole milk, semi- or full-skimmed milk, cream, or from partly or wholly dehydrated cream, butter or milk fat, of which not less than 3,5 % is milk fat.
2.12.20
7. Filled chocolate, chocolate with ... lling, chocolate with ...centre
designate the lled product, the outer part of which consists of one of the products dened in 3, 4, 5 and 6. The designations do not apply to products, the inside of which consists of bakery products, pastry, biscuit or edible ice. The outer chocolate portion of products bearing one of these names shall constitute not less than 25 % of the total weight of the product.
2.12.21
Chocolate a la taza
designates the product obtained from cocoa products, sugars, and our or starch from wheat, rice or maize, which contains not less than 35 % total dry cocoa solids, including not less than 18 % cocoa butter and not less than 14 % dry non-fat cocoa solids, and not more than 8 % our or starch.
2.12.22
9. Chocolate familiar a la taza
designates the product obtained from cocoa products, sugars, and our or starch from wheat, rice or maize, which contains not less than 30 % total dry cocoa solids, including not less than 18 % cocoa butter and not less than 12 % dry non-fat cocoa solids, and not more than 18 % our or starch.
2.12.23
10. A chocolate or a praline
designates the product in single-mouthful size, consisting of: - lled chocolate, or - a single chocolate or a combination or a mixture of chocolate within the meaning of the denitions given in 3, 4, 5 or 6 and other edible substances, provided that chocolate constitutes not less than 25 % of the total weight of the product. The directive 200/36/EC prohibits the addition of animal fats and their preparations not deriving solely from milk to chocolate and related products.
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2.13
Vegetable fats allowed to be added to chocolate and related products
According to the Directive 2000/36 EEC the vegetable fats which are allowed up to an extend of 5 %, must comply with the following criteria: (a) they are non-lauric vegetable fats, which are rich in symmetrical monounsaturated triglycerides of the type Palmitic-Oleic-Palmitic, Palmitic-Oleic-Stearic, and Stearic-OleicStearic; (b) they are miscible in any proportion with cocoa butter, and are compatible with its physical properties (melting point and crystallisation temperature, melting rate, need for tempering phase); (c) they are obtained only by the processes of rening and/or fractionation, which excludes enzymatic modication of the triglyceride structure. The following vegetable fats, obtained from the plants listed below, may be used:
Table 2.22: Vegetable fats allowed in chocolate and related products Usual name of vegetable fat 1. Illipe, Borneo tallow or Tengkawang 2. Palm-oil 3. 4. 5. 6. Sal Shea Kokum gurki Mango kernel Scientic name of the plants Shorea spp Elaeis guineesis Elaeis olifera Shorea robusta Butyrospermum parkii Garcinia indica Mangifera indica
2.13.1 2.13.2
Codex Standard for chocolate and chocolate products (CODEX STAN 87-1981, Rev. 1 - 2003) Chocolate as functional food
Developments on the confectionery and chocolate sector leads to sugar-free products such as isomalt with addition of green tea, zinc, calcium antioxidants in form of vitamins A, C and E, dietary bres such as inulin and oligofructose with claims that the active ingredients help protect cells, reinforce the natural defence of the body or stimulate intestinal microora. Interest is also risen on chewy confectionery with acacia gum, inclusion of polyunsaturated fatty acids in dairy ingredients to reduce the risk of cardiovascular diseases. Industry is also looking forward to incorporate phosphatidyl choline and phosphatidyl serine to increase
2.13. VEGETABLE FATS ALLOWED TO BE ADDED TO CHOCOLATE AND RELATED PRODUCTS mind function.
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These claims are dangerous to public health as they suggest that confectioneries and chocolate are healthy, well balanced foods. The high content of saturated fatty acids from cocoa butter, the high caloric content without sucient dietary bres and to much monosaccharides stand for unbalanced foods which should be consumed reluctantly. Chocollings, snacks and energy bars should not replace the 10 oclock breakfast The small amount of active ingredients are a help for sales and do not improve health of the consumer.
2.13.3
Catechines in chocolate
Chocolate with high content of cacao is rich in catechines which are members of the group of avonoids. The content of catechines in chocolate is related to the amount of the percentage of cacao of the product. Bitter chocolate contains 53,3 mg catechines / 100 g. Milk chocolate contain 15,9 mg/100 g [280]
2.13.4
Dark chocolate as prevention therapy of cardiovascular disease [281]
According to Zomer et al. 2012, studies reported reduction of cardiovascular diseases risk, however such studies were short term trials. Zomer and colleagues, therefore, using statistical modeling techniques estimated the long term eectiveness and the cost eectiveness of daily dark chocolate consumption in a population with metabolic syndrome at high risk of cardiovascular disease was assessed during the Australian Diabetes, Obesity and Lifestyle study. The authors report that daily consumption of dark chocolate (polyphenol content equivalent to 100 g of dark chocolate) can reduce cardiovascular events by 85 per 10 000 population treated over 10 years. A prevention strategy using dark chocolate would cost $40 is seen by the author as an. eective cardiovascular protection, based on avanols which stimulate the production of nitric oxide which causes blood vessels to dilate lowering blood pressure. Dark chocolate also decreases total and low density lipoprotein cholesterol levels and increasing high density lipoprotein cholesterol levels improving coronary health.
2.13.5
Metabolic syndrome
The metabolic syndrome is an accumulation of risk factors increasing the risk of developing cardiovascular disease and diabetes. Lifestyle changes such as dietary modications and behavioural adaptations constitute rst line treatment in the prevention of diseases associated with the metabolic syndrome. Experts recommend to increase the intake of vegetables, fruit, whole grains, nuts tea and dark chocolate which are rich in polyphenolic
148
antioxidants reducing blood pressure, inammation and thrombotic processes. Associated behavioural causes of metabolic syndrome are stress, central obesity, sedentary lifestyle, aging, coronary disease, lipodystrophy, Schizophrenia and other psychiatric illnesses and rheumatic diseases.
2.13.6
Dietary Sodium and Risk of Stroke [282]
Gardener et al 2012, provide further data linked to vascular disease by direct relationship with hypertension and their association with stroke risk. The study supports the American Heart Association recommendation to limiting sodium intake to 1500 mg/day for ideal cardiovascular health.
2.13.7
Food supplements
Food supplement may be useful in case of stress, depressions, signs of overfatigue, diseases and convalescence.In supermarkets the following articles are sold as food supplements: Beer yeasts, gelee royale, wheat germs, sh oil capsules, energy drinks, Ginseg, multi vitamin capsules, Valerian capsules and others.Remember, they do not work wonders their function is a complement to other main factors.
2.13.8
Organic food
Organic food is being regarded as free from pesticides, chemicals and additives. It should be better for environment as usual food and helps to preserve nature. It should be free of GMO. To reduce the number of bacteria in organic food Antibac is used as a natural keeping and preserving compound consisting of natural fruit acids. It works by blocking the vital processes linked with the anabolism of the microbes.The pH value of water is lowered and stabilised, creating an environment which is unsuitable for a number of pathogen microorganisms. Harmless lacto bacillus are not aected. According to the Reiner Group, which produces Antibac, cut surfaces and breaks on vegetables and other products are sealed and the enzymes are inactivated. Discolouration is reduced and texture of the product is being maintained.
2.13.9
Gelatine
Gelatine is made from bones skin and useless parts from cattle, pigs and nowadays from sh (for non-mammalian special products), through partial hydrolysis of the collagen present in these animal parts which are collected in slaughterhouses, meat-cutting facilities and hide-processing plants. Gelatine contains important aminoacids: Glycine..........27%
2.14. INFLUENZA AND PROBIOTIC BACTERIA Proline..........16% Hydroxyproline...14%
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2.13.10
Gelatine as dietary supplement
According to the report of the experts of food chemistry in Germany, gelatine and hydrolysed gelatine have no special physiological properties and have no positive eect on cartilage or joints. Amino acids resulting from the hydrolysis of gelatine are also available from other foods. The claim " joint lubrication" does not correspond to truth. The hydrolysis is made with acids or with alkaline. As BSE cases are getting more frequent in Europe, with main incidence in UK and Portugal gelatine has turned out to be a possible source of infection of CJD disease in all kind of foods which were prepared with gelatin and also drugs using gelatin as coverings for capsules pills and so on. Gelatin was used in human nutrition for many centuries. as a good source of seven out of eight essential aminoacids and was a natural ingredient which was better tolerated as the new chemical modied starches and thickening agents. In the last two decades prot thinking of industry and business has made this natural food to become a menace to public health.
2.14
Inuenza and probiotic bacteria
The Second European Inuenza Conference in Malta 11-14 September 2005 presented the ndings of researches related to probiotic bacteria and inuenza. Most probiotic bacteria are promoted for improving gut health. The ndings presented at the Conference demonstrate the benets of probiotic bacteria not only to gut health, but also improve the immune system. According to ndings presented at the European Inuenza Conference, the probiotic bacteria are thought to activate certain defence cells in the immune system, particularly the T cell. This mechanism is supported by the new trial led by Dr. Michael de Vrese at the Federal Researche Centre of Nutrition and Food in Kiel. He observed higher levels of cytotoxic plus T suppressor cells (CD8+) and T helper cells (CD4+) in a subsample of the probiotic group after just two weeks of supplementation. The bacteria which were included in this study include Lactobacillus gasseri PA 16/8, Bidobacterium longum SP 07/3, and B. bidum MF 20/5 [283]
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2.14.1
Vaccinations
Vaccinations are key in managing seasonal inuenza. In a pandemic vaccines matching the new virus strain can only be developed once it has been isolated at the start of the global outbreak. The WHO estimates that it may take up to six month to develop and market a vaccine that matches the circulating pandemic strain 5. The stockpiling of antivirals has therefore been recommended by the WHO as part of its Pandemic Preparedness Plan.
2.14.2
Antivirals
Antivirals are required that are eective against both inuenze A and B, however in a pandemic situuation ecacy against only inuenza A will be required. M2 inhibitors, amantadine and rimantadine, and the neuraminidase inhibitors, oseltamivir and zanamivir are available drugs against inuenza. Neuranimidase inhibitors present advantages over M2 inhibitors and are the treatment of choice for seasonal and pandemic inuenza.
2.14.3
Safety and ecacy of the anti-inuenza drug oseltamivir (Tamiu) questioned [284]
The World Health Organization in 2002 recommended governments to stockpile oseltamivir and zanamivir (Relenza, GlaxoSmithKline) - neuraminidase inhibitor drugs as treatment in the event of an inuenza pandemic. Billions of dollars were spent, now doubts on its safety and ecacy arises. Jeerson et al 2012 published at the Cochrane Library a review of unpublished data unveiling inconsistencies. Previously unpublished material from15 studies on oseltamivir and 10 studies on zanamivir were used in this study, however, 42 studies could not be reviewed because of insucient information. The researchers sought manufacturer explanations of discrepancies in the data. GlaxoSmithKline (GSK) disclosed individual patient data and responded to queries, but Roche did not provide complete clinical study reports. Roche failed to provide transparency of their data. In a foregoing study of 2009, Jeerson and his group of researchers concluded that neuraminidase inhibitors are not eective. Neuraminidase inhibitors might be regarded as optional for reducing the symptoms of seasonal inuenza. Paucity of good data has undermined previous ndings for oseltamivirs prevention of complications from inuenza. [285]
2.14. INFLUENZA AND PROBIOTIC BACTERIA
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2.14.4
Identifying and minimising data bias, consequences of oseltamivir studies [286]
Toby Lasserson and David Tovey commented in an Editorial of 18 Jan 2012 the issue of The Cochrane Library Jeerson et al 2012 Neuraminidase inhibitors for preventing and treating inuenza in healthy adults and children (review). The review of unpublished data on oseltamivir unveiled inconsistencies. Previously unpublished material from15 studies on oseltamivir and 10 studies on zanamivir were used in this study, however, 42 studies could not be reviewed because of insucient information.
2.14.5
The Jeerson et al 2012 review of oseltamivir studies
The Jeerson study could not access the entire set of documents. The available data conrmed that oseltamivir shortened the time to alleviation of symptoms by around 21 hours compared with placebo. Many uncertainties, however, remain unresolved and question the mechanism of action of these drugs, in particular that of oseltamivir. Further, the study doubts the hypothesis that oseltamivir does not aect antibody production. The editorial of Lasserson and Tovey stresses that the study of Jeerson et al demonstrates that systematic reviews can be biased when only restricted research data are included. Bias is known in scientic publications, and is an inclination to present or hold a partial perspective at the expense of other also valid alternatives. A common bias in scientic publications is that positive results are more likely to be published and published sooner, than those with negative results. To avoid misleading results it should be made sure that systematic reviews avoid bias.
2.14.6
The eects on other studies
The Jeerson et al review rises question which other review need to be re-evaluated, what measures should be taken to correct errors, and how to include data obtained from regulatory agencies? The Cochraine Library awaits the maturation of trial registration repositories and better disclosure of data. The Cochrane Collaboration is supporting a new research project that aims to identify when and how exploration of regulatory and licensing agency data is needed. Systematic reviews should adopt the methods developed by Jeerson et al 2012. To improve the methodology of systematic reviews the Cochraine Editorial Unit presented methodological expectations. [287] http://www.editorial-unit.cochrane.org/meci
2.14.7
Chicken soup and therapy of colds
Scientists of the University of NebrasKa Medical Center found that chicken soup contains several ingredients that aect the immune system of the body.
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It helps to stop the movement of neutrophils that eat bacteria and cellular debris which are released in great numbers by viral infection like colds. Neutrophil activity can stimulate the release of mucous which may be the cause of the coughs and stuy nose caused by upper respiratory infections such as colds. Vitamins and other agents in the ingredients could possibly have a biological action.
2.14.8
Eect of global transport on local fauna
Killer shrimp Dikerogammarus villosus coming from Romania endanger the ecological system of the Rhine. Their origin is the Black Sea and are hidden in the system of cooling water of great container ships. Dikerogammarus feeds itself from ies, worms and other shrimps. It is being feared that Dikerogammarus will nd its way to the great seas in North America menacing there the biological system. This is an example of eects of excessive global transportation endangering local micro fauna.
2.15
Acrylamide
Acrylamide, a potential carcinogen is likely to be formed in a wide rage of foods, specically starchy foods which are fried or baked.such as potato chips roasted asparagus, banana chips, toasted English muns, tacco shells, pretzels The natural occurring amino acid asparagine coupled with a carbonyl source such as reducing sugar like dextrose is a precursor to acrylamide in foods. Trace amounts of acrylamide can be formed by boiling, signicant formation generally requires a processing temperature of 1200 C or higher. Most acrylamide is accumulated during the nal stages of baking, grilling or frying processes as the moisture content of the food falls and the surface temperature rises, with the exception of coee where levels fall considerably at later stages of the roasting process. Acrylamide seems to be stable in the majority of the aected foods in the majority of the aected foods, with the exception of ground coee where the acrylamide level declines during storage over months The limiting precursor in cereals is asparagine while fructose and glucose are more important in potatoes. Other important factors are pH and water content. According to UN scientists meeting in Rome in February 2005 the major contributing foods to total exposure for most countries were: Potato chips (60 - 30 per cent )
2.15. ACRYLAMIDE Potato crisps ( 6 - 46 per cent ) Coee (13 - 39 per cent ) Pastry and sweet biscuits (10 - 20 per cent ) Bread and toasts (10 - 30 per cent ) Other foods (Less than 10 per cent of exposure)
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2.15.1
Acrylamide linked to breast cancer [288]
Pelle Thonning Olesen and colleagues 2008 found a positive association between an increased acrylamide haemoglobin level and the development of breast cancer. Acrylamide had been found to to cause cancer in laboratory rats, in carbohydrate-rich foods. Tobacco smoking also generates substantial amounts of acrylamide. Despite being a carcinogen in the laboratory, many epidemiological studies have reported that actual exposition to acrylamide in food is too low to be of concern. Pelle Thonning Olesen concludes in his publication that all previous epidemiological studies have been based on food frequency questionnaires, and that the risk of breast cancer doubles with a tenfold increase in the acrylamide-haemoglobin level. There is a stronger association for oestrogen receptor positive breast cancer. The authors say that it is uncertain whether breast cancer is instead related to other chemical compounds formed along with acrylamide during the heating of foods and that some of the acrylamide may come from sources other than food.
2.15.2
The Netherlands Cohort Study on diet and cancer [289]
Janneke Hogervorst and colleagues 2007 increased risks of postmenopausal endometrial and ovarian cancer with increasing dietary acrylamide intake, particularly among neversmokers. Risk of breast cancer was not associated with acrylamide intake.
2.15.3
The HEATOX Study [290]
The HEATOX risk characterization concludes that the evidence of acrylamide posing a cancer risk for humans has been strengthened, and that acrylamide is not the only genotoxic compound formed when heating food. Furan, HMF and other compounds have been investigated. A database of more than 8 carcinogens based on their chemical structure, has been compiled to aid future research. Acrylamide reduction methods for industry and for home are highlighted.
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2.15.4
How to reduce acrylamide in baked and fried foods
Use low temperatures for frying or backing (under 170 C.) Change your eating habits: Try to like white ships and French fries. Refuse golden brown ones as they were overheated and bear high amount of acrylamide Do not toast your bread as the high temperature and low moisture of bread soars up acrylamide. If you are really concerned with your health eat your toast without heating it. Just change your habit and you will enjoy it. Avoid any kind of corn akes, crispbread,cookies chocolate, cocoa, coee, tortillas as in some brands high amount of acrylamide were found[291][292] Prefer cooked food as the water avoids overheating of potatoes and cereal products. Cover all dishes when using microwave. Avoid excessive loss of humidity of the surface of the food The storage of potatoes inuence the acrylamide being formed during processing. Potatoes should be fresh. They should be free of green parts and free of sprouts. They should not had been kept in refrigerator Use margarine instead of oil or cooking fat. Margarine cannot be heated as high as oil avoiding overheat during frying Use cooked potatoes to make fried potatoes. If you have to use raw potatoes you can leave them in water for two hours before frying.The reducing sugars are then diminished in the surface which is most like to develop acrylamide. If you use raw fresh potatoes for your french fries leave them after cutting for one hour in water. Pizzas are low in acrylamide but do not let the edge get brown or dried Dont let bread and cake get a brown, hard and dry surface because this is a sign that acrylamide could have been formed. Bread rolls and muns are likely to bear more acrylamide than voluminous breads and cakes. The most eective reduction of acrylamide has been achieved by using the enzyme asparaginase to selectively remove asparagine prior to heating. This process is, however limited to specic products manufactured from liquidised or slurried materials. Variety selection and plant breeding, controlling growth and storage factors aecting sugar concentration in potatoes, pre-treatment of potato pieces by soaking or blanching and prolonged yeast fermentation time in breadmaking is being studied as possible acrylamide reduction.
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2.15.5
Calcium chloride preventing acrylamide formation [293]
Gokmen and Senyuva found that the formation of acrylamide was reduced by 95% in fried potatoes when dipped for 60 minutes in calcium chloride at room temperature before frying at 170o C . According to the authors the Schi base of asparagines, intermediate of acrylamide, was prevented. Colour and texture of French fries and crisps were not aected.
2.15.6
Calcium chloride was found to be the best choice to reduce acreylamide in potato crisps [294]
Shiyi Ou and colleagues 2007 tested the food additives ferulic acid, catechin, calcium chloride, sodium bisulte, and l-cysteine on inhibition of acrylamide formation. They found that acrylamide formation in fried potato crisps was signicantly reduced immersing the potato slices in solutions of l-cysteine and solution of CaCl2. Immerging the potato slices in a solution of 5 g/l of CaCl2 was the best choice because of its low price and the acceptable mouth feel of fried crisps. Industrial blanching at 85o C reduced the formation of acrylamide by 85% when potato slices were immersed in the solution.
2.15.7
L-cysteine and Calcium chloride are promising additives to reduce acrylamide potato chips [295]
Frederic Mestdagh and colleagues 2008 found L-cysteine to reduce the acrylamide content in the most eective way, with a reduction of about 92 per cent. L-lysine and glycine were found less eective additives in the study. Organic acids like citric, acetic, and L-lactic acid reduced the acrylamide content but not as much as L-cysteine or calcium chloride. The acrylamide lowering eect of the organic acids was related to a low pH. Dipping potatoes in a solution of Calcium chloride was found to inhibit the formation of acrylamide by up to 95% during frying according to the study of Gkmen and Senyuva 2007. [296] The inhibition of acrylamide formation of ferulic acid, catechin, calcium chloride, sodium bisulte and l-cysteine were tested by Shiyi Ou and colleagues 2007 and found l-cysteine the most ecient agent but CaCl2 is most potential. They suggest the immersion of potato slices in CaCl2 solution at 5 g/L to reduced acrylamide formation by more than 85% in fried crisps. [294]
2.15.8
Reports and statements on acrylamide [297]
Acrylamide (CH2=CHCONH2) is neurotoxic and carcinogenic in laboratory animals. JECFA (FAO/WHO Joint expert Committee on Food Additives)cautioned in April 2005 that there
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are uncertainties in its conclusion as the toxicological database is incomplete and recommended that (FAO/WHO, 2005): acrylamide be re-evaluated when results of ongoing carcinogenicity and long-term neurotoxicity studies become available. work should be continued on using physiologically based pharmacokinetic (PBPK) modelling to better link human biomarker data with exposure assessments and toxicological eects in experimental animals. appropriate eorts to reduce acrylamide concentrations in food should continue. The CIAA Confdration des Industries Agro-Alimentaires issued in 2005 guidelines related to successful procedures on reducing acrylamide formation during manufacturing processes.
2.15.9
References
EC (European Commission), 2002. Opinion of the Scientic Committee on Food (SCF) on new ndings regarding the presence of acrylamide in food. Available at http://europa.eu.int/comm/food/
EFSA (European Food Safety Authority), 2005. Draft Opinion of the Scientic Committee on a harmonised approach for risk assessment of compounds which are both genotoxic and carcinogenic (in consultation process). Available at http://www.efsa.eu.int/science/sc_commitee/sc_co
FAO/WHO (Food and Agricultural Organisation/World Health Organisation), 2005. Summary and conclusions of the sixty-forth meeting of the Joint FAO/WHO Expert Committee on Food Additives (JECFA), pp. 7-17. Available at http://www.who.int/ipcs/food/jecfa/summaries/en/
2.15.10
Citric acid and glycine and reduction of acrylamide formation [298]
Professor Don Mottram from the School of Food Biosciences at the University of Reading leaded a study focused on how to suppress the formation of acrylamide without detrimentally aecting avour formation using citric acid and glycine. The scientists noted that citric acid limited the generation of volatiles, particularly the alkylpyrazines which are responsible for avour. Glycine increased the total volatile yield by promoting the formation of certain alkylpyrazines, namely, 2,3-dimethylpyrazine, trimethylpyrazine, 2-ethyl-3,5-dimethylpyrazine, tetramethylpyrazine, and 2,5-diethyl-3-methylpyrazine. However, the formation of other pyrazines and Strecker aldehydes was suppressed. To minimise the impact on avour but still achieve the desired reduction in acrylamide levels, the reseachers propose that the opposing eects of the treatment with citric acid
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limiting the generation of volatile avour compounds, in particular the alkylpyrazines, and glycine, which promotes the formation of certain alkylpyrazines but does not suppress the formation of certain Strecker aldehydes. The combination of the two compounds in 0.39% w/w for each, does not suppress the formation of certain Strecker aldehydes on total volatile yield and may be used to best advantage in reducing acrylamide.
2.15.11
Formation of acrylamide from wheat gluten [299]
The scientic team from the Institute of Food Technology at Hohenheim University, Stuttgart, revealed dierent acrylamide formation mechanisms describing pyrolytic acrylamide formations in puried wheat gluten and gluten-supplemented wheat bread rolls. The gluten was dry heated at temperatures ranging from 160 to 240o C for 8 to 12 min and analysed for acrylamide and cinnamic amide. Under these conditions acrylamide could be detected up to 3997 g/kg gluten dry weight. Cinnamic amide was detected and unambiguously identied in the gluten samples, thus conrming the proposed formation of acrylamide from proteins. The manner in which acrylamide was formed makes the German teams study interesting . After gluten was added to bread roll dough, protein pyrolysis to form acrylamide in the complex food matrix was assessed. In this study the contents of asparagine and reducing sugars were diminished by adding wheat gluten. In contrast to the expectation with respect to the well-established common formation mechanism of acrylamide, it increased from 53.4 to 63.9 g/kg (+20 per cent), which was in good correlation with the higher proportion of gluten. Cinnamic amide could be found in crusts of bread rolls. The scientists claim that their research provides evidence of pyrolytic formation of acrylamide from wheat gluten.
2.15.12
Acrylamide formation in foods high in fat and low in carbohydrates [300]
Capuano and colleagues 2010 report that carbonyl compounds derived from lipid oxidation in high-fat and low water foodstus induce the formation of acrylamide even in sugar-free, where carbonyls come from lipids. The authors found that lipid oxidation positively inuenced the formation of acrylamide. Catechins Acrylamide formation is being reduced by catechins which trap carbohydrates and/or prevent lipid oxidation, say the authors. The Lipid oxidation theory is being backed by the fact that sunower systems were more prone to produce acrylamide than model systems containing palm oil which is less susceptible to oxidation.
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Higher water content of foods produced less acrylamide compared with dry foods. Evaporative cooling may increase the eect of catechin and lipid oxidation was retarded. The authors concluded that lipid oxidation is an important factor for acrylamide formation in low-carbohydrate dry foods.
2.15.13
CIAA Acrylamide Toolbox [301] [302]
The CIAA Acrylamide "Toolbox" provides descriptions of the intervention steps being evaluated by food manufacturers. In some cases the procedures are already being used by food processors, are undergoing testing or are the result of laboratory studies. The CIAA stresses that some of the tools and parameters of this guide will also be helpful within the context of domestic food preparation and in catering establishments, where stringent control of cooking conditions may be more dicult. The latest update in December 2007, includes the feasibility of the enzyme asparaginase in production of biscuits on an industrial scale. The asparginase enzyme products on market are Preventase from DSM obtained from Aspergillus niger and Acrylaway from Novozyme from Aspergillus oryzae they transform asparagine in aspartic acid which cannot form acrylamide. Nutritional value, browning and crispness remain are not aected. Biscuits are being tested, promising a 70 percent of reduction of acrylamide. Pedreschi and colleagues 2007 report that blanching potato strips at 75o C for 10 min followed by soaking in an 10,000 ASNU/l asparaginase solution at 40 degrees Celsius for 20 minute reduced acrylamide formation after frying by 60 per cent. [303]
2.15.14
Glycidamide
The update of December 2007 stresses that epoxidation of acrylamide by fatty acid hydroperoxides, which are formed during lipid peroxidation, could be another pathway for the interactions of acrylamide with food constituents. Glycidamide is the genotoxic metabolite of acrylamide. Download the CIAA Acrylamide TOOLBOX Rev 11 December 2007 at: http://www.ciaa.eu/documents/brochures/toolbox%20rev11%20nov%202007nal.pdf
2.15.15
Soaking Frech fries in standing water reduces formation of acrylamide [304]
Rachel S Burch and colleagues 2008 investigated simple measures which could be used to reduce acrylamide formation in industrial and home-cooked French fries. The authors found that washing for 30 seconds under running tap water and then soaking in standing
2.16. SURFACE BROWNING AS INDICATOR OF ACRYLAMIDE FORMATION 159 water for 30 min or 2 hours raw French fries before cooking led to reductions in acrylamide of up to 48 per cent and the colour was lighter compared with untreated French fries. The authors stress that standing water removes sugars from the potato and extracts less starch from the surface of the potato than running water. Lower acrylamide levels were found when starch is not removed.
2.16
Surface browning as indicator of acrylamide formation
The work of Jackson and Al-Taher focuses on the eects of cooking conditions (e.g. time/temperature) on acrylamide formation in consumer-prepared foods, the use of surface colour (browning) as an indicator of acrylamide levels in some foods, and methods for reducing acrylamide levels in home-prepared foods. They found that acrylamide levels in cooked food depended greatly on the cooking conditions and the degree of "doneness", as measured by the level of surface browning. Analysis of the surface colour by colorimetry indicated that some components of surface colour ("a" and "L" values) correlated highly with acrylamide levels. This indicates that the degree of surface browning could be used as an indicator of acrylamide formation during cooking. [305]
2.16.1
Predictive model for acrylamide [306]
Enda Cummins, a researcher at University College Dublin, developed and presented an acrylamide predictive computer model for industrial and home at the Foodsim 2006 in June 15-17 at the University of Naples, Italy. This model was developed for the production and consumption of chips and crisps in Ireland. For other foods and outside of Ireland the model must be adjusted to take account of the specic amino acids and sugars of each food. According to Cummins the use of potato cultivars with low sugar levels, blanching, lowering cooking time and temperature reduces acrylamide signicantly. Extended frying times above six minutes and above 180o C should be avoided. Soaking and washing were found to be less ecient. The initial selection of cultivars and in the initial levels of glucose and fructose was found by Cummins to be most eective way to reduce the formation ofd acrylamide in processed potato foods.
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2.16.2
Predictive results
His model predicts a mean acrylamide level of 317 micrograms per kilogram in fried potatoes, 720 micrograms per kilogram in crisps, and 1073 micrograms per kilogram in home made french fries (industrial washing and blanching processes are not considered in home cooking). Male consumption patterns of french fries and crisps result in 0.27 micrograms of acrylamide per kilogram of body weight per day, and females slightly less, being far below of the World Health Organisation recommended daily intake (RDI) is one microgram per kilogram of body weight per day.
2.16.3
Researches with green tea and bomboo extract to reduce acrylamide formation in foods [307] [308]
Yu Zhang and Ying Zhang investigated the antioxidant-rich extracts of bamboo leaves (AOB) and extract of green tea (EGT). They found that when both were added in levels of 0,1 micrograms, the reduction rates of formation of acrylamide of 74,4 per cent for the use of AOB and 74,3 per cent for the use of EGT were achieved. The researchers tested the addition the extracts at 180 degrees Celsius in an oven under low-moisture conditions. The active components of the extracts reducing the acrylamide formation were homoorientin for AOB and epigallocatechin gallate for EGT. The antioxidants of bamboo leaves had beenstudied before by Zhang. The authors obtained 74,1% and 76,1% reduction of acrylamide in potato crisps and French fries with AOB addition of 0,1% and 0,01% (w/w), respectively and an immersion time of 60 s. According to the authors acrylamide formation in potato-based foods could be reduced signicantly with the Extract of antioxidants of bamboo leaves and original crispness and avour of potato products may stay unaltered. The authors call for more research on natural antioxidants to reduce the formation of acrylamide.
2.17
Advanced glycation end products (AGEs) in grilled, fried or broiled meat and cheese products
[309] Helen Vlassara and colleagues (2007) found new toxins in grilled meat and cheese. Advanced glycation end products AGEs are a group of compounds formed from the nonenzymatic reaction of reducing sugars with the free amino groups of proteins in grilled, fried or broiled animal products and sterilised or pasteurised meat products and are responsible for desirable tastes and smells of these foods.
2.17. ADVANCED GLYCATION END PRODUCTS (AGES) IN GRILLED, FRIED OR BROILED MEAT AND CHEESE PRODUCTS 161 These compounds are linked with inammation, insulin resistance, diabetes, vascular and kidney disease, and Alzheimers. According to the authors the kidney function of older people slows down and it might be the cause why the capacity to remove AGEs from the body is reduced. People aged 65 and older were found to have higher AGE levels in their blood as people younger than age 45. AGEs accumulates in the tissues, take over the bodys own built-in defences, pushing them toward a state of inammation leading to disease or early ageing. N-carboxymethyl-lysine (CML) and methylglyoxal (MG) derivatives are found in blood and are used to measure the body content of AGEs. They correlate with indicators of inammation and oxidative stress According to the authors, indicators of both AGEs and oxidative stress are directly inuenced by the intake of dietary AGEs, independent of age or energy intake. The researchers call for reduced consumption of these oxidants to prevent age-related diseases, especially in an ageing population. The authors advice to avoid excessive intake of fried, broiled, and grilled foods and call for new methods of cooking to reduce AGE intake, particularly steaming, boiling or making stews, keeping the heat down and maintaining the water content in food.
2.17.1
AGEs and diabetes [310]
Wautier and Guillausseau in a review in 2001 focuses on the consequences of hyperglycemia on the formation of advanced glycation end-products (AGEs), and on the role of AGEs and of their specic receptors (RAGE) in the functional and anatomical alterations of the vascular wall. The data of this review emphasize the role of AGEs and of the interaction of AGE modied proteins with diabetic mesangial cells in glomerulosclerosis development. (scarring of the kidneys tiny blood vessels, the glomeruli, the functional units in the kidney that lter urine from the blood). The authors come to the conclusion that AGEs and RAGE play a central role in the development of chronic complications of diabetes.
2.17.2
Flavonoids and reduction of colorectal cancer risk [311]
Flavonoids such as isoavones, anthocyanidins, avones, avonols, avan-3-ols, and avanones were assessed in a case-control study concerning colon cancer cases. A signicant risk reductions were calculated by lead author Marta Rossi . The highest intake of avonols was associated with a 46 per cent reduction in the risk of colorectal cancer, compared to people in the lowest intake group. No signicant benet of avan-3-ols, avanones, and total avonoids was observed. According to Marta Rossi and colleagues, avonoids may have an important role in exCopyright 1998-2010 Karl H. Wilm. All rights reserved. OurFood Database of Food and Related Sciences
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plaining the protective eects of vegetables, fruit, and, possibly, tea against cancer. The estimates did not substantially dier for colon and rectal cancers, as well as in strata of sex, age, and body mass index. The ndings of this large study provide support for an inverse association of selected classes of avonoids with colorectal cancer risk. Several limitations of this study make further studies necessary. Other studies add further support of the ve-a-day message for a healthy, balanced diet rich in fruit and vegetables. Blueberries, for instance, are a rich source of anthocyanidins, mainly delphinidin, cyaniding, petunidin, peonidin and malvidin, could stop the growth of liver cancer cells. [312]
2.17.3
Blueberries [312]
Blueberries and muscadine grapes are a source of polyphenols antioxidants such as phenolic acids, tannins, avonols and anthocyanins and pterostilbene which reduces cholesterol. Three cultivars of blueberries ("Briteblue", "Tifblue" and "Powderblue") and four cultivars of muscadine grapes ("Carlos", "Ison", "Noble", and "Supreme") were assessed in a study lead by Weiguang Yi from the University of Georgia. The inhibition of the blueberry and muscadine grapes extracts on liver cancer cell growth were studied using HepG2 cell cultures. The greatest inhibitory eects were observed from the anthocyanin fractions. The main anthocyanidins present were delphinidin, cyaniding, petunidin, peonidin and malvidin.
The avonol and tannin fractions showed intermediate activities. The authors concluded that blueberries and muscadine grapes may contribute to reduction in liver cancer risk, proposing that incorporating blueberries into the diet could potentially reduce liver cancer risk.
2.17.4
Dynamic high pressure (DHP) technology for juices [313]
Alternative methods to heat pasteurisation of juices such as pulsed electric elds (PEF), pulsed magnetic elds, pulsed light, carbon dioxide, irradiation and high pressure have been proposed for the cold pasteurization. PEF is based on the electromechanical instability of the cell membrane. It is not in use due to high costs of these systems. High hydrostatic pressure (HHP) requires a pressure of 350 Mpa for 30 min to achieve a 5 log reduction. This technology is not in use because treatment must be done in charges
2.17. ADVANCED GLYCATION END PRODUCTS (AGES) IN GRILLED, FRIED OR BROILED MEAT AND CHEESE PRODUCTS 163 and is very costly on an industrial scale. Dynamic high pressure (DHP) technology uses a pump to force a liquid under high pressure and high velocity through a very narrow and adjustable concentric orice, bringing physical changes in the treated products due to the creation of a sudden pressure drop, very high exit ow velocity and evaporation. Tahiri, Makhlouf, Paquin and Fliss researched the inactivation of bacteria using DHP. They came to the conclusion that DHP can become an alternative for cold pasteurization of fruit juices.
2.17.5
Non-Thermal preservation processes
Non-thermal processes are food preservation methods which do not use signicant temperature increases. Ionizing radiation, pulsed-electrical eld pasteurization and ultra highpressure processing (UHF) are currently in use. High intensity pulsed electric eld (PEF) processing involves the application of pulses of high voltage (typically 20 - 80 kV/cm) to foods placed between 2 electrodes. PEF treatment is conducted at ambient, sub-ambient, or slightly above ambient temperature for less than 1 s, and energy loss due to heating of foods is minimized. For food quality attributes, PEF technology is considered superior to traditional heat treatment of foods because it avoids or greatly reduces the detrimental changes of the sensory and physical properties of foods (Quass 1997). Although some studies have concluded that PEF preserves the nutritional components of the food, eects of PEF on the chemical and nutritional aspects of foods must be better understood before it is used in food processing. Processing of apple and orange juices, of milk, liquid eggs and soups have been tested. Technical drawbacks or limitations of the PEF technology are: The availability of commercial units. The presence of bubbles, which may lead to non-uniform treatment. Limited application, which is restricted to food products that can withstand high electric elds. The particle size of the liquid food in both static and ow treatment modes. The lack of methods to accurately measure treatment delivery. [314]
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2.17.6
Cloudy apple juice healthier than clear one [315]
Apple juice is treated with enzyme to remove the pectin and starch content in order to avoid cloudiness of the product. 75% of the polyphenol content.of clear apple juice was found by Oszmianski and colleagues to be only 25% of that of cloudy apple juice. According to the authors of the study the suppression of enzymatic browning conditions and the lack of clarication prevent the loss of polyphenols in cloudy apple juice. The authors found 250 milligrams of polyphenols per litre in clear juice from Idared apple variety and 1044 milligrams per litre in cloudy juice made from the Champion apple variety. The authors come to the conclusion that health benets are expected mainly in the case of cloudy apple juice consumption resulting from the high content of procyanidins.
2.17.7
Industrial processed (clear) apple juice and chronic nonspecic diarrhoea (CNSD) [316]
According to Hoekstra and colleagues clear and cloudy apple juice dier in their bre and non-absorbable monosaccharide and oligosaccharide contents. They found that clear apple juice signicantly promoted diarrhoea and suggest that fructose, the increased availability of non-absorbable monosaccharides and oligosaccharides as a result of the enzymatic processing of apple pulp is the cause of apple juice induced CNSD in children.Cloudy apple juice did not inuence stool frequency and consistency. In case of toddler diarrhoea Hoekstra recommends that fruit juices, in particular clear apple juice, and other squashes should be limited to restore appetite at meal times.
2.17.8
Red grapefruits inuencing serum lipid and antioxidant levels and cancer-preventive eect [317]
Shela Gorinstein and colleagues found that fresh red grapefruit contains higher quantities of bioactive compounds and has signicantly higher antioxidant potential than blond grapefruit. Diet supplemented with fresh red grapefruit positively inuences serum lipid levels of all fractions, especially serum triglycerides and also serum antioxidant activity. They concluded that the addition of fresh red grapefruit to generally accepted diets could be benecial for hyperlipidemic, especially hypertriglyceridemic, patients suering from coronary atherosclerosis. Kun Gao and colleagues found that naringenin , a citrus avonoid, stimulates DNA repair following oxidative damage in LNCaP human prostate cancer cells. They conclude that the cancer-preventive eects of citrus fruits demonstrated in epidemiological studies may be due in part to stimulation of DNA repair by naringin, which by
2.17. ADVANCED GLYCATION END PRODUCTS (AGES) IN GRILLED, FRIED OR BROILED MEAT AND CHEESE PRODUCTS 165 stimulating base excision repair processes may prevent mutagenic changes in prostate cancer cells. [318]
2.17.9
Inulin and avonoids from grapefruit [319]
Zenon Zdunczyk and colleagues found that avonoid extract from grapefruit used as a single dietary supplement did not display a benecial inuence on cecal metabolism, increased pH, hydration of digesta, and lowered bacterial activity and SCFA concentration. The authors suggest that the simultaneous intake of inulin and polyphenols could reduce the detrimental eects of the latter on cecal fermentation. The authors conclude that simultaneous intake of inulin and polyphenols can decrease the detrimental eects of the latter on cecal fermentations.
2.17.10 2.17.11
Arteriosclerosis prevention Diet rich in green and yellow vegetables [320]
Michael R. Adams and colleagues from the University of California in Los Angeles determined the eects of a diet rich in green and yellow vegetables on the development of atherosclerosis. The results of this study indicate that a diet rich in green and yellow vegetables inhibits the development of atherosclerosis and may lead to the reduction in the risk of coronary heart disease through antioxidant and anti-inammatory pathways. Vegetables contain a variety of micronutrients, such as carotenoids, vitamin C, vitamin E, and selenium that are potent antioxidants, and broccoli as a source of sulforaphane , an anti-inammation compound.
2.17.12
Reduction of risk of hypertension with vegetable protein and cereal bre [321]
The World Health Organisation (WHO) advices since 1991 to have ve meals rich in fruit and vegetables to lower incidences of heart disease and some cancers. According to Alvaro Alonso and colleagues bre and protein intake can be associated with lower levels of blood pressure, but results from prospective cohorts are scarce, and none of them have been conducted outside the US. In a new study the scientists found that risk reduction was more important among men, obese and older individuals. Total or animal protein, total bre as well as bre from other sources dierent from cereal were not associated with the risk of HT.
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The authors suggest that the relationship between bre and insulin resistance could, in turn, aect blood pressure, or that vegetable protein could result in higher serum concentrations of certain amino acids such as L-arginine, L-tryptophan, and tyrosine could reduce hypertension. Vegetable protein intake was inversely related to blood pressure. This nding is consistent with recommendations that a diet high in vegetable products be part of healthy lifestyle for prevention of high blood pressure and related diseases [322]
2.17.13
Denition of high blood pressure
Hypertension = blood pressure higher than 140/90 mm Hg, Prehypertension = blood pressure 120/80 mmHg to 139/89 mmHg.
2.18
Frozen Food Standards
The growth of frozen food is largely due to the performance of frozen potatoes (chips and potato products) which is the largest sector in volume terms, growing 6.9% year-after-year. Purchasing diagnostics reveal that frozen potatoes growth is driven by households buying more of the category in 2003. Other sectors in growth are ready meals and snacks. Ready meals are growing in volume 5.5% year-after-year, driven by retailer own brands and Heinz. Growth comes from price reduction and an increase in the amount bought per occasion. Healthy meals is a fast growing sector within this category although it remains a small player within ready meals. Frozen snacks has seen strong growth (18.8% year-after-year volume) led by Tesco and Asda own label ranges. McCains Micro range has also attained good growth in this category. The traditional sectors such as frozen sh, green vegetables, red meat and pizza, are all in volume decline as consumers buy less.
2.19
Canned food
The process of canning was pioneered in the 1790s when a French confectioner, Nicolas Appert, discovered that the application of heat to food in sealed glass bottles preserved the food from deterioration. In about 1806 Apperts principles were successfully trialed by
2.20. DIETING FADS
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the French Navy on a wide range of foods including meat, vegetables, fruit and even milk. Based on Apperts methods of food preservation the packaging of food in sealed airtight tin-plated wrought-iron cans was rst patented by an Englishman, Peter Durand, in 1810. Canned foods were greatly favoured by early explorers. Beginning in 1814 canned foods were sent to distant British colonies. The very earliest cans were "tinned iron canisters", which were very heavy and needed a hammer and chisel to open them! They were also made one at a time, by hand. Today very light materials are employed with Ring-Pullo system which need no tools to open them.
2.20
Dieting fads
Dieting and health trends with low-calorie and nutrient enriched products enjoying greater popularity. Meal replacement drinks, healthy snack bars and bakery products enriched with vitamins and calcium are considered as healthy. On the other hand, food deemed to be unhealthy, such as ice cream, savoury snacks, and cakes and pastries, has seen declining consumption. It also revealed the growing awareness of prebiotics, a market still in development stage. But while today the European prebiotic market is restricted to a handful of companies (three companies hold 70 per cent of the market share), new entrants are expected as awareness grows and consumers become increasingly interested in gut health. Closely related to probiotics, prebiotics are carbohydrates thought to stimulate the growth and activity of certain benecial bacteria in the gut. Ingredients that have so far been identied as having such activity include inulin, fructooligosaccharides, resistant starch and the sweetener tagatose.
2.20.1
Probiotics in animal breed
Some bacteria resent good activities in the animal gut. This will be used in animal feed for pork, poultry cattle and pet feed. Spores of Bacillu licheniformis and Bacillus subtilis cause a better digestion and help to control pathogenic bacteria. With these probiotics improved body weight of 9% and a better food conversion of 5% were found.
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2.20.2
Probiotics in crops
10 to 60% of nitrogen accumulated in maize, rice, sugar cane and grass are of atmospheric provenience. In the many plants the assimilation is done by symbitic activities of nitrogen bacteria such as Azospirillum spp. and Gluconacetobacter. Using Azospirillumm spp an increase of 30 percent of yield and a reduction of 40 percent of nitrogen fertilizer could be achieved in sugar cane, maize and oath. Closely related to probiotics, prebiotics are carbohydrates thought to stimulate the growth and activity of certain benecial bacteria in the gut. Ingredients that have so far been identied as having such activity include inulin, fructooligosaccharides, resistant starch and the sweetener tagatose.
2.20.3
Metabolic changes induced by probiotic bacteria [323]
Jeremy K. Nicholson and colleagues 2008 using nutrimetabonomics researche tools found that probiotic strains could alter intestinal bacteria populations, and that this signicantly inuenced major metabolic pathways. Nestl strains of Lactobacillus paracasei and Lactobacillus rhamnosus were given to mice whose intestinal microora had previously been changed to human gut microbes. The researchers found that the supplementation with the probiotics led to changes in host intestinal microora and this lead to changes in the metabolism of liver, blood, urine, and faeces, aecting energy, lipid and amino acid. The energy recovery from the diet was modied, with subsequent eects on circulating lipids in theplasma and metabolism of glucose in the liver and bile acids, which are important key in the metabolism of fatty acids. Stressing the dierent metabolic eects of the two probiotics in the host, the authors suggest the possibility of giving probiotic combinations according to a persons individual metabolic prole. Nutrimetabonomics was developed by Sunil Kochhar and colleagues at the Nestl Research Center (Switzerland) and Imperial College London to correlate metabolic phenotypes with a behavioral phenotype such as an anity for rich, creamy chocolate. The Method is an ospring of metabonomics, a discipline that uses metabolic proles of bodily uids such as blood plasma and urine to understand drug toxicity, pharmacological responsiveness, and other biological events. This method is applied to examine the eects that diet has on metabolism. [324]
2.21. BROMATE IN BOTTLED WATER
169
2.20.4
Probiotics in farming:
Probiotics in animal breed: Some bacteria resent good activities in the animal gut. This will be used in animal feed for pork, poultry cattle and pet feed. Spores of Bacillu licheniformis and Bacillus subtilis cause a better digestion and help to control pathogenic bacteria. With these probiotics improved body weight of 9% and a better food conversion of 5% were found.
2.21
Bromate in bottled water
Bottled water was found in 2006 in US to exceed by far the maximum permissible amount of 0.01 g/L of bromate. Kurokawa and colleagues reported in 1986 that bromate ion is capable of causing kidney carcinomas in rats. US Environmental Protection Agency (EPA) classies bromate ion as an increased risk of cancer. Its MCL is 0,01 g/l (10 ppb) for bottled drinking water. [325] [326] [327] Bromate ion in drinking water is a disinfection byproduct. It is formed by the oxidation of bromide ion when ozone is used for disinfection. Bromide ion is present in the majority of raw waters and changes to bromate during disinfection by ozone The speed of reaction increases in presence of calcium chloride. Reduction of bromate formation in drinking water when using ozonation as disinfection can be achieved by: 1. Keeping pH 6.5 or below during ozonation. 2. Adding ammonia before ozonation. 3. Keeping dissolved ozone as low as possible.
2.21.1
Indulgent food
Ice cream, candies and biscuits are often seen as an indulge of healthy way of life rewarding for good results or conpensating for a loss. Food industry grouped recently Chilled dairy desserts, cheese, ice cream, chocolate, cakes and biscuits as indulgent food category. Consumer trends indicate that, despite health concerns, full-fat ice cream and cookies, and other indulgence foods are not loosing their popularity.
170
2.21.2
Chocolate as beauty treatment [328]
Emma Little, a beauty therapist, introduced the chocolate beauty skin treatment. The treatment is a facial mask consisting of cacao butter, shea butter and high content of antioxidants rich melted chocolate. Their customers say that the skin is soft and smooth claiming it to be an eect of the cacao butter and the antioxidants of chocolate.
2.22
Starch
All starches have amylose-to-amylopectin ratios. As the amylopectin level increases, the thickening potential increases. Waxy corn starch containing 100% amylopectin generally forms weaker gel systems, but is an excellent starch base for speciality starches. Starches that contain 50% to 80% amylose molecules form very rigid gel systems. The size of the starch granules is another important characteristic which is responsible for the physical properties of starch. [329] [330] Table 2.23: Amylose/Amylopectine Relation of Starches Starch Source % Amylose % Amylopectine Granule size Average size Range (microm) ((microm) 2 - 13 4 - 22 5 - 25 3 - 28 3 - 27 3 - 34 4 - 40 9 - 40 15 - 50 10 - 70 5.5 9.8 14.3 14 16 6.5, 19.5 18.5 23 33 36
Waxi rice High amylose corn Corn,native Corn,waxi Cassava Waxi sorghum Wheat Sweet potato Arrow root Sago Potato
0 70 28 5 20 0 26 18 21 26 20
100 30 72 95 70 100 74 82 79 74 80
2.22.1
Labelling of modied starches
Modied starches must be labelled as such, using either the number or the name given in the table below. In order to keep the label clean, special starches are being developed with native starch
2.22. STARCH
171
labelling. They have the same texture, viscosity and mouthfeeling of chemically modied ones.
2.22.2
Starch, physical modication
Physical modications inuence pre-cooking or pre-gelatinization and cold water-swelling (which create good dispersibility). There are also modications that produce resistant starch.
2.22.3
Cross-linking
Cross-linking increases starchs stability during processing conditions such as heat, acids and mechanical shear. Cross-linking avoid viscosity loss and such conditions. It reinforces hydrogen bonding of starch chain-to-starch chain with a covalent chemical bond.
2.22.4
Chemical modication of starch
The chemical modication of starch is regulated and limited by food regulations. Acetic anydride or hydroxypropyl groups substitute the hydrogen atom of the hydroxyl groups of carbon 2, 3 and 6 resulting a steric conguration which avoids the starch chains to hydrate with water. Hydrogen bonding with another starch chain cannot take place. Such modied starches have a lower cook temperature, increased clarity and water holding capacity. Retrogradation is decreased resulting in increased cold storage stability and longer shelflife.
2.22.5
Frozen foods
Production of frozen foods which are suitable to be thawen and heated in microwave devices use waxy cite which is cross-linked and substituted.
2.22.6
Conventional breeding techniques
Conventional breeding techniques have created genetic mutants with the result of waxy and high-amylose starches. By cross-breeding and through cultivation the ability to form a phosphate ester is enhanced. Waxy-based corn starch is popular in the U.S.
2.22.7
Micro encapsulation
Microencapsulation is a technique which provides a protective lm on avours, vitamins, and other components which are susceptible to evaporation, oxidation or heat damaging. Etheric oils, avourings vitamins and other highly damageable ingredients are spray-dried together with starch providing a protective outer shell. Evaporation and oxidation is thus
172 diminished improving handling and storage.
Esteried starches are generally used for encapsulation. These + have a lipophylic group in their molecule giving them emulsifying properties. Emulsifying starches are also used in beverages which avoid dairy components because of religious or health concerns. These starches can replace sodium caseinate and emulsify lipophilic vitamins in these preparations. Resistant starches: The nutritional value of resistant starch are used in low-carb products to lowers the glycemic index. Resistant starches are produced from high-amylose starches, partially depolymerizing it and then allowing the smaller amylose chains of starch to reassociate and retrograde into a strong crystalline structure that melts at a high temperature. They have white colour, bland taste and low moisture binding ability. The crystalline structure makes resistant starch resist human digestion. Waxy maize starch containing 100% of amylopectin is highly branched and its derivative will be a good substitute for gum Arabic which is also high branched being similar in its functionality. Sometimes a combination of starches and gums such as xanthan gum can reduce slimy mouthfeel which is a characteristic of some gums and some starches.
Table 2.24: E-Numer INS-Number 1400 1401 1402 1403 1404 1405 1410 1411 1412 141 1414 CAS Nr 009004-53-9 065996-63-6 977075-42-5 065996-62-5 Mainterm Dextrins, white and yellow Acid treated starch Alkaline modied starch Bleached starch Oxidized starch Enzyme treated starch Monostarch phosphate Distarch glycerol Distarch phosphate 3Phosphated distarch phosphate Acetylated distarch phosphate
E1404 E1410 E1412 E1413 E1414
058944-89-1 977088-75-7 977043-58-5 068130-14-3
2.22. STARCH E1420 E1422 E1440 E1442 E1450 E1451 1420 1421 1422 1423 1440 1442 1443 1450 Acetylated starch, mono starch acetate Acetylated starch, mono starch acetate Acetylated distarch adipate 053123-84-5 009049-76-7 053124-00-8 059419-60-2 066829-29-6 Acetylated distarch glycerol Hydroxypropyl starch Hydroxypropyl distarch phosphate Hydroxypropyl distarch glycerol Starch sodium octenyl succinate Acetylated oxidised starch
173
Normal native starches consist of a mixture of 15-30% amylose and 70-85% Amylopectin.
2.22.8
Amylose
Amylose is composed of 250 to 2000 units and is responsible for the gelling property of starch. It is an unbranched helix chain. is a linear polymer of glucose linked with mainly (1-4) bonds. It can be made of several thousands glucose units. [331] The alfa(1-4) bonds promote the formation of a helix structure. The number of repeated glucose subunits (n) can be many thousands. Amylose starch is less readily digested than amylopectine. However it takes up less space so is preferred for storage in plants; it is how about 80% of the starch in plants is stored. The digestive enzyme amylase works on the ends of the starch molecule, breaking it down into sugars. [331]
2.22.9
Amylopectine
Amylopectin. It is a branching molecule anhydroglucose with many branch points. The molecular weight may reach as high as 80 000 000 and does not form a helical coil. Glucose units are linked in a linear way with alfa(1-4) bonds. Branching takes place with alfa(1-6) bonds occurring every 24 to 30 glucose units. Its counterpart in animals is the glycogen (the principal storage form of glucose in animal cells) which has the same composition and structure, but with more extensive branching that occurs every 8 to 12 glucose units. [331]
2.22.10
Starch derivatives
Starch can be hydrolyzed into simpler carbohydrates by acids, enzymes or a combination of the two. MaltodextrinIt is a bland-tasting ller and thickener. Corn syrup It is used as sweetener and thickener.
174
Dextrose It is glucose obtained by complete hydrolysis of starch. High fructose corn syrupIt is the most used sweetener in beverages. It is mainly fructose resulting from dextrose solution under hydrolysis with the enzyme glucose isomerase
2.22.11
Reformulating Fruit Yoghurt
There are many yoghurt with fruit products on market. Their content of added carbohydrates range from 11 to 13% of a mixture of sugar and glucose-fructose syrup. This mixture is an outcome of the corn syrup industry and sweetens the yoghurt. It manages shelf life of the Fruit Mix, its capability to be pumped over long distances and the way to handle it reduces costs. The growing concern about obesity needs to have a look on it. The idea of having a serving of fruits with the yoghurt suggests a healthy product. On account of adding up to 13% of the mix of sugar, glucose-fructose, highly triggering the insulin mechanism, the diary business starts researches for an urgent reformulation of the Fruit-Yoghurt. Actual ingredients of fruit yoghurt is a mixture of 50% fruit and 50% Sugar-Glucosefructose from hydrolysed corn or sometimes wheat. An alternative to the high fructose corn syrup content of fruit yoghurt a paste of banana paste, cantaloup melon and other sweet tropical fruits could replace the syrup. These pastes give the necessary rheologic stability to the fruit mixture and a natural sweetness. The modern equipment and sanitising programs allow it to handle the product without spoilage. Meanwhile some eorts are being done by some supermarket chains such as Lidl Stores selling fruit yoghurt with sugar but without added glucose-fructose syrup. A small step, but a one in the right direction. Other like PLUS and ALDI Stores, also strong in the European Market, have much work to phase out glucose-fructose syrup in fruit yoghurt. Meanwhile the consumer should watch the ingredient list and avoid those products labelling added glucose-fructose syrup which may lead to obesity and diabetes.
2.22.12
New fruit sweetener with low glycemic [332]
A natural fruit concentrate produced in Spain by Wild Deprovesa from various fruits contains a wide range of sugars with a balanced ratio of the carbohydrates fructose, glucose
2.22. STARCH
175
and sucrose in the fruit concentrate - as it occurs naturally in fruit concentrate blends has a glycemic index of 34. That is the lowest index compared to other natural fruit sweeteners. According to the producer some of the energy is available immediately, while the body also receives energy on a more sustained basis, being perfect for sport drinks and suitable for use in near water beverages, herbal or tea drinks with all-natural ingredients or beverages with a low glycemic index, in dairy products, bakery and confectionery as well as ice cream products. This new sweetener may help dairy industry to reformulate the fruit yoghurt, soft drinks and other products using corn or wheat syrup leading to a clean label. Fruit Up beverages using the product can be marketed as "sweetened with fruit". But remember: sweet foods and sweet drinks are loaded with calories. Sweet beverages are can lead to obesity and diabetes because of the high amount of liquids which are consumed in hot periods. Yoshida found that pure fruit juices reduce the risk of diabetes, but cautions, that even too much fruit juice can cause an excess of calories and sugar. It is therefore wise to reduce these beverages. [333]
2.22.13
Sugar-sweetened beverages increase coronary heart disease in women [334]
Teresa Fung and colleagues 2009 wrote that studies linked full-calorie sugar-sweetened beverages with greater weight gain and an increased risk of type 2 diabetes. The authors found in a recent study that women drinking two or more servings of sweetened beverages per day may increase their risk of heart disease by 35 per cent. Data from 88,520 women aged between 34 and 59 participating in the Nurses Health Study were evaluated. In this study the authors note that articially sweetened beverages did not increase the risk of coronary heart disease.
2.22.14
Fructose increasing coronary heart disease
According to Dr.Fung fructose increases triacylglycerol synthesis in the liver which, in elevated concentrations, increases coronary heart disease risk. Fructose also increases blood uric acid concentrations which reduces endothelial nitric oxide being a link between soft drink consumption and risk of coronary heart disease.
2.22.15
Other natural sweeteners on market
Fruit juice concentrates from pear, pineapple and peach. Granulated fruit sweeteners are made from grape juice concentrate and rice syrup.
176 Date sugar Honey Barley malt Brown rice syrup Maple syrup Stevia (Stevia rebaudiana) Simple sugars: Glucose, fructose , galactose.
2.22.16
Stevioside and rebaudiana A (Rebiana) from Stevia rebaudiana Bertoni
Stevia is grown by small farmers in Paraguay and Brazil. Its culture is very dicult and does not suit global agriculture practices. That is why great agricorporations did not started extensive stevia plantations. The dried leaves of Stevia rebaudiana Bertoni, contain the sweet-tasting stevioside 3-8%, rebaudioside A approximately 1%, D, and E, and dulcosides A about 0.27%. Rebaudioside D and E, together with dulcoside B are minor components counting for 0.03 to 0.04% of the dried leaves. Stevioside is a glycoside with a glucosyl and sophorosyl residue attached to the aglycon steviol.The structure of rebaudioside A is the same as that of stevioside except that the sophorosyl residue is replaced by a glucosyl-(1-3)-sophorosyl residue. Stevioside and rebaudioside A are therefore in focus of safety and stability studies.
2.22.17
Sweetening power
The sweetening powers of stevioside is 100, rebaudioside A 130, and the dulcosides 30 times that of sucrose. The food industry is eager to introduce stevioside and rebaudioside A in its products because it is a natural, and overall a low priced sweetener.
2.22.18
Natural Stevia a strong sweetener is also source of antioxidants [335]
Stevia is derived from the plant stevia rebaudiana, which grows in South America. It is told to have 300 times the sweetness of sugar. The ingredient is not approved for use in food yet in Europe, but the EFSA is carrying out a safety assessment of stevia. Petition to approve stevia by the FDA to uses in food is being expected. Srijani Ghanta and colleagues 2007, found the extract from stevia leaves to be rich in antioxidant polyphenols such as quercitrin, apigenin, and kaempferol, and could protect DNA from oxidative damadge. Its ecacy is better than that of quercetin.
2.22. STARCH
177
The authors conclude that Stevia rebaudiana may be useful as a potential source of natural antioxidants.
2.22.19
The Kobylewskil and Eckhert study rises new safety concerns about rebiana from stevia [336]
Kobylewskil and Eckhert 2008, in a study prepared for the CSPI, concluded that the FDA should ensure that the genetic toxicity studies that produced either positive or conicting results be repeated. The authors added that studies that look at potential DNA adducts related to the potential reactive metabolites (C-13 carbonium ion or the epoxide) of steviol would be a strong addition to the genotoxicity data. Finally, the FDA should require carcinogenicity and toxicology studies in rats and in mice before accepting rebaudioside A as a GRAS substance or approving it as a food additive. The toxicologists emphasized the need for more genotoxicity tests, because of the evidence that derivatives of stevia that are closely related to rebiana damage DNA and chromosomes. Coca-Cola and Pepsi are planning to introduce new drinks made with rebiana, an extract of stevia leaves that is 200 times sweeter than sugar. But according to the study of Kobylewskil and Eckhert, several, though not all, laboratory tests show that the sweetener causes mutations and DNA damage, which raises the prospect that it causes cancer. The CSPI asks the FDA for additional tests before accepting rebiana as Generally Regarded as Safe, or GRAS. Rebiana is shorthand for rebaudioside A, a component of stevia. It is obtained from the leaves of a shrub native to Brazil and Paraguay. [337] Stevia is legal in foods in Japan and several other countries, but the United States, Canada, and the European Union bar stevia in foods because of older tests that suggested it might interfere with reproduction. New tests sponsored by Cargill did not nd such problems. [337]
2.22.20
Rebiana sweetener in USA accepted by FDA [338]
The US Food and Drug Administration (FDA) concluded in a notication in December 2008, that it has no objection to rebiana, (Reb A) at 95 percent purity or above, having GRAS (generally recognized as safe) status as a general purpose sweetener for food and drink, not just as a supplement. This decision followed the application of Coca-Cola partnered with Cargill under their brand called Truvia, and PepsiCo under the PureVia brand. Applications for dairy, bakery and confectionary products, including boiled sweets and chewing gum are expected to follow. PureCircle, a Malaysian company, which will supply rebiana, (Reb A) at 95 percent puCopyright 1998-2010 Karl H. Wilm. All rights reserved. OurFood Database of Food and Related Sciences
178
rity ingredient to PepsiC, Coca-Cola and Cargil. China is the worlds largest exporter of stevioside. [339]
2.22.21
Rebiana had been banned until December 2008 [340]
In 1999, last revised in 2004, FDA stated: "Another product, stevia, is derived from a South American shrub. Though it can impart a sweet taste to foods, it cannot be sold as a sweetener because FDA considers it an unapproved food additive."The safety of stevia has been questioned by published studies," says Martha Peiperl, a consumer safety ocer in FDAs Oce of Premarket Approval. "And no one has ever provided FDA with adequate evidence that the substance is safe." Under provisions of 1994 legislation, however, stevia can be sold as a "dietary supplement," though it cannot be promoted as a sweetener." FDA Import Alert last revised 24/4/2008 considered stevia leaves, and food containing stevia as unsafe food additive. [341]
2.22.22
CSPI says it is too soon to allow stevia in the diet sodas and juice drinks [342]
In a Statement of the CSPI, the Executive Director Michael F. Jacobson berates the FDA for declaring a sweetener extracted from the herb Stevia, is "generally recognized as safe," or GRAS. CSPI argues that rebaudioside A is inadequately tested in terms of cancer and caused mutations in some laboratory tests.
2.22.23
Rebiana still banned in the EU and other countries [343]
Rebiana is still banned in the European Union, in Singapore and Hong Kong [344]. Stevioside is isolated and puried from Stevia rebaudiana Bertoni leaves. The leaves naturally contain a complex mixture of eight sweet diterpene glycosides, including stevioside, steviolbioside, rebaudiosides (A,B,C,D,E) and dulcoside A. However, for the majority of toxicological studies, a precise composition of the extract that has been tested has not been adequately dened. In particular, studies on preparations of stevioside of higher than 95% purity are limited in number.
2.22.24
The data of the WHO 2006 [345]
Data compiled in the safety evaluation released by the World Health Organization in 2006 suggest that EU and Hong Kong policies may be obsolete.
2.22. STARCH
179
2.22.25
Acute renal failure induced by steviol, breakdown product of stevioside [346]
Toskulkao and colleagues 1997 investigated the acute toxicity of stevioside and steviol (a product of enzymatic hydrolysis of stevioside). Stevioside and steviol at a dose as high as 15 g/kg BW was not lethal to mice and rats. Hamsters did not die with Stevioside doses as high as 15 g/kg BW, however, their LD50 values of steviol were 5.20 and 6.10 g/kg BW for males and females, respectively. Severe degeneration of the proximal tubular cells of hamster kidneys, with acute renal failure induced by steviol were noted by the authors.
2.22.26
Stevioside and steviol are not mutagenic but toxic at high concentration [347]
Klongpanichpak and colleague 1997 found that stevioside and steviol showed no mutagenic eect on both tester Salmonella typhimurium TA 98 and TA 100 strains either in the presence or absence of metabolic activating system. The authors stress, however, that high concentration of stevioside and steviol showed some toxic which decreased in the presence of the metabolic activating system.
2.22.27
No genetic risc from stevioside and steviol [348]
According to Brusik 2008 the mutagenic activity of steviol and some of its derivatives, exhibited in strain TM677, related by some authors, was not reproduced in the same bacteria having normal DNA repair processes. Neither stevioside nor stevio-induced clastogenic effects at extremely high dose levels in vivo were found. The author concludes that neither stevioside nor steviol do not pose a risk of genetic damage following human consumption.
2.22.28
Stability of stevioside and rebaudioside A in carbonated acidic beverages [349] [349]
Chang and Cook 1983, observing the stability of pure stevioside and rebaudioside A in carbonated phosphoric and citric acidied beverages during long-term storage, reported some degradation of both sweeteners after 2 months of storage at 370C, but no signicant changes at room temperature or below following 5 months of storage of stevioside, or 3 months of storage of rebaudioside A. Exposure to 1 week of sunlight did not aect stevioside but resulted in approximately 20% loss of rebaudioside A. Heating at 60 0C for 6 days resulted in 0-6% loss of the sweeteners.
180
2.22.29
Degradation of stevioside and rebaudioside A is acidpromoted, not by sunlight [350]
Clos, DuBois and Prakash 2008, working for Coca-Cola Company and Cargill, performed stability tests with Rebiana, traded as Truvia, the common name of rebaudioside A. They reported no signicant photodegradation in acidic beverages exposed to light, containing rebaudioside A or steviosid. Degradation of the sweeteners were acid-promoted. The authors challenge the Chang and Cook 1983 article which had suggested that rebaudioside A is unstable to sunlight exposure, while the structurally homologous stevioside is stable, however found rebaudioside and stevioside light stable, and degradation of the sweeteners were acid-promoted.
2.22.30
The position of the European Union [343]
The European Commission in an opinion on Stevia Rebaudiana Bertoni plants and leaves from 1999, responding to a request for authorisation to market as a novel food for the plants and dried leaves of Stevia rebaudiana Bertoni concluded that there are no satisfactory data to support the safe use of these products as ingredients of food or as sucrose substitute for diabetics and obese individuals. No appropriate data were presented to enable the safety of the commercial plant product to be evaluated. Stevia was therefore banned in the EU.
2.23
Glycemic index
The glycemic index (GI) is a ranking of carbohydrates on a scale from 0 to 100 according to the extent to which they raise blood sugar levels after eating. Foods with a high GI are those which are rapidly digested and absorbed and result in marked uctuations in blood sugar levels. Low-GI foods, by virtue of their slow digestion and absorption, produce gradual rises in blood sugar and insulin levels. [351] Low GI carbohydrates, producing small uctuations in our blood glucose and insulin levels, reduces the risk of heart disease and diabetes and helps to control weight. According to the Glycemic Index low GI foods are breakfast cereals based on oats, barleyand bran, breads with wholegrains, stone-ground our, sour dough all other types of fruit and vegetables except potatoes, Basmati or Doongara rice, pasta, noodles, quinoa, salad vegetables with a vinaigrette dressing Foods containing little or no carbohydrate (such as meat, sh, eggs, avocado, wine, beer, spirits, most vegetables) cannot have a GI value. If the food has no carbohydrates, it has no GI. [351]
2.23. GLYCEMIC INDEX
181
2.23.1
Labelling of Glycemic Index
Some foods on the Australian market already show their GI rating on the nutrition information panel. Terms such as complex carbohydrates and sugars, which commonly appear on food labels, are now recognised as having little nutritional or physiological signicance. The WHO/FAO recommend that these terms be removed and replaced with the total carbohydrate content of the food and its GI value. [351]
2.23.2
Glycemic Index Databank
The Human Nutrition Unit at the University of Sydney hosts the GI Databank and tests foods on its Glycemic index. The Databank can be accessed at the Glycemic Index.com homepage. [351]
2.23.3
International Table of Glycemic Index
Jennie Brand Miller is the senior author of International The International Tables of Glycemic Index published by the American Journal of Clinical Nutrition in 1995 and 2002. The GI has proven to be a more useful nutritional concept than is the chemical classication of carbohydrate (as simple or complex, as sugars or starches, or as available or unavailable), permitting new insights into the relation between the physiologic eects of carbohydrate-rich foods and health. Two similar foods may have dierent ingredients or may have been processed with a dierent method, resulting in signicant dierences in the rate of carbohydrate digestion and hence the GI value. [352]
2.23.4
Glycemic load
The glycemic load of a food is determined by multiplying its glycemic index by its available carbohydrate content per serving. [353]
2.23.5
Glycemic index reducing risk of cardiovascular diseases and obesity [354]
A randomized, controlled trial conducted by Prof Jennie Brand-Miller, Joanna McMillanPrice and colleagues from the University of Sydney compared the eects on weight loss and cardiovascular risk of low-glycemic index (GI) and high-protein diets. Four diets of varying GL on weight loss and reducing cardiovascular disease risk in young overweight or obese adults. Brand Miller and colleagues concluded that both high-protein and low-GI regimens increase body fat loss, but cardiovascular risk reduction is optimized by a high-carbohydrate, lowGI diet. The researchers conclude further that dietary glycemic load and not just overall energy intake, inuences weight loss and postprandial glycemia. Diets based on low GI wholegrain products maximise cardiovascular risk reduction, particular if protein intake is
182 high.
Peter Clifton, however disagrees with the conclusions of the study of Brand-Miller and colleagues. [355]
2.23.6
Reduction of Glycemic Load
Reducing glycemic load may be especially important to achieve weight loss among individuals with high insulin secretion. Regardless of insulin secretion, a low-glycemic load diet has benecial eects on high-density lipoprotein cholesterol and triglyceride concentrations but not on low-density lipoprotein cholesterol concentration. [356]
2.23.7
Glycemic index and pregnancy
Robert G Moses and colleagues compared the eects of low-GI and conventional dietary strategies on pregnancy outcomes in healthy women. Glycemic index may be of particular relevance during pregnacy because maternal glucose is the main energy substrate for intrauterine growth. The authors found that birth weight and ponderal index may predict chronic disease in later life. A low-GI diet may, therefore, favourably inuence long-term outcomes. [357]
2.23.8
High Glycemic Index may lead to high oxidative stress
According to Hu and colleagues 2006 acute hyperglycemia may increase in vivo free radical production increasing the risk of many diseases. Chronic consumption of high-GI foods may lead to chronically high oxidative stress. A low-GI diet, not a low-carbohydrate diet, appears to be benecial in reducing oxidative stress. [358]
2.23.9
Carbohydrates and obesity
According to Glenn Gaesser, diets high in carbohydrates are almost universally associated with slimmer bodies. They found that consuming high levels of high-glycemic foods is not associated with higher body weights. 0n this contest, Several large studies in the United States revealed that high-glycemic diets were linked to better weight control. With few exceptions, high glycemic load is associated with lower BMI. Carbohydrates had been labelled as "good" for low, or "bad" for high glycemic index (GI), a measure of how much it raises blood sugar. High GI foods are such as white bread, white rice, breakfast cereals and concentrated sugar. Low GI foods include most vegetables, fruits, beans and unprocessed grains. Low GI foods help to reduce the risk of diabetes and related conditions. The author,
2.23. GLYCEMIC INDEX
183
however, found that the relationship between carbohydrate intake and body mass index (BMI) is controversial.
2.23.10
Denition related to Glycemic Index used in labelling and claims
The Glycemic (Net) Carbohydrate Denition Committee of the American Association of Cereal Chemists (AACC) International has approved denitions related to glycemic carbohydrates such as: Available carbohydrate, Glycemic response, Glycemic carbohydrate Glycemic impact The denitions may be found at http://www.aaccnet.org/news/06glycemicdenitions.a However, Gaesser urges caution in the use of GI labels and claims, not before more research is done on this matter. He stresses that whole-grain intake is generally inversely associated with BMI, and rened grain intake is not. A low-fat dietary strategy, with carbohydrates rich on cereal ber, may be benecial for health and weight control.
2.23.11
High glycemic index foods are a universal mechanism for disease progression [359]
Alan W. Barclay and colleagues 2008 evaluated the association between Glycemic index (GI), glycemic load (GL) and chronic disease risk. According to the authors high blood glucose leads to a higher risk of type 2 diabetes and heart disease, gallbladder disease and some types of cancer, such as breast cancer. High blood glucose releases high amounts of insulin together with insulin like growth factor one (IGF-1). Insulin-like growth factor 1 (IGF-1) is an insulin similar hormone which plays an important role in childhood growth and anabolic eects in adults. The authors stresses that both hormones increase cell growth and decrease cell death, and increase the risk of developing cancer. Low GI food diets like whole grain bread musli are being suggested instead of white bread, corn akes high in sugar candies and cookies. The authors stress that higher postprandial glycemia is a universal mechanism for disease progression.
184
2.23.12
GI ranking [360] [361]

GI range 55 or less Examples most fruit and vegetables (except potatoes, watermelon and sweet corn), wholegrains, pasta, beans, lentils sucrose, croissant, basmati rice, brown rice corn akes, baked potato, some white rices (e.g. jasmine), white bread, candy bar
Classication Low GI
Medium GI High GI
56 - 69 70 or more
2.24
Encapsulation of avours
Beta-cyclodextrin has become a viable avour carrier and protectant for food applications. Embuscado and Gottneid studied encapsulation of avour. In their researches orange oil was encapsulated as a model avour via spray-drying using beta-cyclodextrin, gum arabic and a starch n-octenylsuccinate with a starch hydrolyzate. They compared it with orange oil which had been adsorbed respectively to lactose and a starch hydrolyzate.at room temperature and at 45 C for up to 12 months. While the absorbed oil oxidized rapidly, while , the rate of degradation was reduced to dierent extents by encapsulation with the starch octenylsuccinate and gum arabic. Beta-cyclodextrin provided outstanding protection to the orange oil. [362]
2.24.1
Interactions of Milk Proteins and Volatile Flavour Compounds [363]
Low-fat/low-sugar food market poses avouring challenges. Protein or carbohydrates take the place of fat but, according to Janina Khn many proteins are able to bind several avour compounds tightly and inuence the perceived aroma prole signicantly. Instead of focusing on model systems using one protein and one aroma compound in a solution, Khn calls for research on complex systems of several food matrix components and avour mixtures and their physicochemical interaction. Khn suggests the use of solid-phase microextraction (SPME) and nuclear magnetic resonance (NMR) as fast, solvent-free, and very sensitive techniques to study binding mechanisms and binding topology. The review is focused on the binding of volatile avour compounds by milk proteins in aqueous solutions.
2.24. ENCAPSULATION OF FLAVOURS
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2.24.2
Sugar beet pectine as wall material for microencapsulation of oil [364]
Sugar beet pectin and glucose syrup is being proposed by Dr. Stephan Drusch as an alternative to milk proteins and gum Arabic for the spray-drying technique of microencapsulation of lipophilic functional food ingredients, like omega-3 polyunsaturated fatty acids. Emulsions up to 50 per cent oil and 2.2 per cent sugar beet pectin with median oil droplet sizes less than two micrometres, however, there may be a maximum limit on the amount of oil that can be encapsulated. Microencapsulation eciency is being controlled by physicochemical parameters like particle morphology, particle size and extractable fat, and tests on the oxidative stability of the microcapsules over time as well as avour retention for aroma compounds are going on.
2.24.3
Peanut butter [365]
Peanut butter contains a minimum of 90% peanuts, with no articial sweeteners, colors or preservatives. Some brands add about 7% natural sweeteners and 1% salt for taste, plus a stabilizer to keep the peanut butter fresh and the oil from separating. "Old-fashioned" or "natural" peanut butter does not have the stabilizer so the oil will separate and should be stirred back in before using. Regular peanut butter contain less than 1% partially hydrogenated oil, avoiding oil from separating out of the peanut butter and increases the shelf life of the peanut butter. The amount of trans fat in regular peanut butter is less than 1%. Under the proposed FDA labeling guidelines for trans fats, the peanut butter labels will list 0 trans fats. However, natural peanut butters do not contain partially hydrogenated oils. Oil separates, simply stir it back in before using. For that, natural peanut butter mixer were developed. [366] "Peanut butter spreads", contain only 60% peanuts, but are nutritionally equivalent to peanut butter (although they may contain more sugar or salt). But today there also are real peanut butters on the market which are 25% reduced-fat and still contain at least 90% peanuts. [365]
2.24.4
Peanut butter and diabetes 2 [367]
Examining the relationship between nut consumption and risk of type 2 diabetes Jiang and colleagues found in a Prospective cohort study of women that nut consumption was inversely associated with risk of type 2 diabetes. The authors suggest potential benets of higher nut and peanut butter consumption in
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lowering risk of type 2 diabetes in women. To avoid increasing caloric intake, regular nut consumption can be recommended as a replacement for consumption of rened grain products or red or processed meats.
2.24.5
Glucosinolate from broccoli and reduction of cancer risk [368]
According to several studies related to biological activities of broccoli claim that isothiocyanates and indoles, released from glucosinolates by the enzyme myrosinase reduce the risk of cancer. The glucosinolates are a class of organic compounds that contain sulfur and nitrogen and are derived from glucose and an amino acid. Many studies found that broccoli is rich on glucosinolates and other bioactive phytochemicals such as avonols, hydroxycinnamic acid esters, carotenoids, folates and vitamin C. Interactions amongst these compounds may result in cancer protection and alter their biological eect. Cooking is also likely to aect bioactivity. Because the use of glucosinolate-containing crops as primary food source for animals was shown to have negative eects, food crops have been developed that contain very low amounts of glucosinolates (e.g double zero canola variety). Extracts of plants high in glucosinolates can serve as natural pesticides. Low contents of glucosinolates were found to have health benets.
2.24.6
Eect of cooking improves the cancer protecting eect of bloccoli [369]
Glucosinolate, their degradation products and other phytochemicals with biological activity may contribute to health benets of crucifer vegetables such as broccoli. The authors studied the eects of extracts of broccoli derived from broccoli that had been heat treated to dierent extents on Caco-2 cancer cells exposed to glucosinolates and their degradation products after microwave cooking. The authors found that thermal degradation products increased the protecting eect of broccoli on account of the degradation products formed during the cooking process.
2.24.7
Isothiocianate from broccoli is inhibith Helicobacter pylori and blocks gastric tumor [370]
Fahey and colleagues 2002 found that sulforaphane ((-)-1-isothiocyanato-(4R)-(methylsulnyl)butane), an isothiocyanate abundant as its glucosinolate precursor in certain varieties of broccoli and broccoli sprouts, is a potent bacteriostatic agent against stomach infectious with Helicobacter pylori. Sulforaphane was also found to block benzo[a]pyrene-evoked forestomach
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tumors in mice. The authors concluded that sulforaphane inhibiting Helicobacter infections and blocking gastric tumor formation act synergistically and provide a diet-based protection against gastric cancer in humans.
2.24.8
Increase intake of variety of plant components to ght prostate cancer [371]
John Erdman and colleagues found in a study on implanted Dunning R3327-H prostate tumours in rats that the combination of tomato and broccoli was more eective at slowing tumour growth that either tomato or broccoli alone. The authors believe that dierent bioactive compounds, such as lycopene in tomatoes and glucosinolates in broccoli in each food work on dierent anti-cancer pathways the public health. This supports the older recommendations to increase the intake of a variety of plant components. The authors call for future human prevention trials based on dietary interventions and highlight that it is very doable for a man to eat a cup and a half of broccoli per day or put broccoli on a pizza with half a cup of tomato concentrate. Based on this study, Erdman concludes that tomatoes are better than lycopene supplement, and that chopping and heating makes the cancer-ghting constituents of tomatoes and broccoli more bioavailable. Cooked tomatoes had been found healthier than fresh ones.
2.24.9
Sulforaphane, the powerful cancer-ghting agent in broccoli [372]
Sulforaphane is a chemopreventive phytochemical. It is found in broccoli and to a lesser extent in other cruciferous vegetables. Sulforaphane can be released from its parent compound glucoraphanin by bacteria in the lower gut and absorbed into the body. This increases broccolis cancer-preventive power according to a study of Jeery, Miller and Lai 2010. Overcooking broccoli destroys the plant enzyme which turn sulforaphane free. In this study the authors demonstrated that microbiota in our digestive tract can turn glucoraphanin into sulforaphane. Three to ve servings a week is enough to have an anti-cancer eect. Sulforaphane also has anti-inammatory properties, responsible to chronic diseases associated with obesity and ageing. To boost heath eects of broccoli the authors suggest to feed the desirable bacteria with prebiotics like ber, or combine broccoli with a yogurt sauce that contains the hydrolyzing bacteria.
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2.24.10
Inamatory pathway NF-kappaB [373]
Prasad and colleagues 20101 stress that lifestyle risk factors such as tobacco, alcohol, highfat diet, radiation, and infections increase risk of cancer. Lifestyle risk factors have been found to activate NF- kappaB and NF- kappaB-regulated genes, mediating inammation and tumor cells. Diet consisting of fruits and vegetables spices and nuts, rich in avones, avanones, avonols, isoavones, anthocyanins, and chalcones can prevent cancer can suppress the proinammatory cell signaling pathways of cancer.
2.24.11
Neuroprotective activity of antioxidant nutraceuticals [374]
Natural neuroprotective antioxidant compounds directly scavenge free radicals or increase endogenous cellular antioxidant defenses, such as the nuclear factor erythroid-derived 2related factor 2 (Nrf2) transcription factor pathway, modulation of signal transduction cascades or eects on gene expression. Kelsey and colleagues 2010 cites such neuroprotective antioxidants. According to Greco and Fiskum 2010 oxidative stress promotes Ca(2+)-dependent opening of the mitochondrial inner membrane permeability transition pore (PTP). This causes bioenergetic failure and subsequent cell death. To avoid such oxidative stress the activation of the Nrf2/ARE pathway of antioxidant gene expression by sulforaphane was found to confers resistance of brain mitochondria to redox-regulated PTP opening. [375] Sharma and colleagues 2010 stresses the downregulation of Bcl-2, COX-2 and IL-1beta upon treatment with sulforaphane, explaining the anti-proliferative, anti-inammatory, anti-oxidant and anti-cancer activities od sulforaphane. [376] Kalpana and colleagues 2010 found sulforaphane to be very successful in combating the oxidative stress mediated mitochondrial dysfunction in experimental lung carcinogenesis induced by benzo(a)pyrene. [377]
2.24.12
Bladder cancer induced by tobacco smoke [378]
A human bladder carcinogen present on tobacco smoke is 4-aminobiphenyl (ABP). Ding and colleagues 2010 demonstrated that sulforaphane inhibits ABP-induced DNA damage in bladder cells. Dings and colleagues 2010 write that sulforaphane activates NF-E2 related factor-2 (Nrf2), which is kown as a chemopreventive target and activates the Nrf2-regulated cytoprotective signaling pathway. The authors also report that sulforaphane-enriched broccoli sprout extracts strongly inhibits N-butyl-N-(4-hydroxybutyl)nitrosamine-induced bladder cancer development, supOurFood Database of Food and Related Sciences Copyright 1998-2010 Karl H. Wilm. All rights reserved.
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porting epidemiologic observation that consumption of broccoli is inversely associated with bladder cancer risk and mortality.
2.24.13
Chronic inammation, a major mediator of tumor [379]
Gupta and colleagues 2010 write that as 35% of all cancers can be prevented by dietary changes. The study focuses on nutraceuticals, such as allicin, apigenin, berberine, butein, caeic acid, capsaicin, catechin gallate, celastrol, curcumin, epigallocatechin gallate, setin, avopiridol, gambogic acid, genistein, plumbagin, quercetin, resveratrol, sanguinarine, silibinin, sulforaphane, taxol, gamma-tocotrienol, and zerumbone, derived from spices, legumes, fruits, nuts, and vegetables. They reduce the risk of cancer modulating inammatory pathways and thus aect the survival, proliferation, invasion, angiogenesis, and metastasis of the tumor.
2.24.14
The chemopreventive activity of broccoli may be higher than found by animal studies [380]
Abdull Razis and colleagues 2010 studied the ability of the stereoisomers R- and Ssulforaphane to modulate the cell enzyme systems. They found that R-sulforaphane elevated glutathione S-transferase (GST alpha, GST my) and quinone reductase in liver and in lung, in comparision S-sulforaphane presented lower eect or even no eect at all. The authors concluded that R-sulforaphane was the more active isomer of both. Animal studies using S-sulforaphane present results which are too low for human diet which provides mainly the high active R- racemic form.
2.24.15
Eect of broccoli and tomatoes Eect in humans remain still unclear
Dr Julie Sharp of Cancer Research UK commenting the study of Professor John Erdman said that both broccoli and tomatoes may contain chemicals with anticancer properties, their eects in humans, however, are still unclear in face of conicting results from other studies with people using these vegetables.
2.24.16
The role of tomato products and lycopene in the prevention of prostate cancer [381]
Etminan and colleagues 2004 determined whether intake of tomato products reduces the risk of prostate cancer using a meta-analysis. The researchers concluded that tomato products may play a role in the prevention of prostate cancer. However, this eect is modest and restricted to high amounts of tomato intake.
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Further research is needed to determine the type and quantity of tomato products with respect to their role in preventing prostate cancer.
2.24.17
Tomato powder reduce prostata cancer risk in animals [382]
Valeri Mossine and colleagues 2008 report that enhanced protective eect of tomatoes against prostate cancer comes by rehydrating tomato powder into tomato concentrate. Rats which were fed with tomato concentrate plus FruHis, a complex carbohydrate developed 10 per cent prostate tumors, compared with 30 percent of animals receiving tomato powder alone, 25 percent receiving tomato concentrate alone and 60 percent in the control group. The authors write that processing of edible plants (heating, grinding, mixing, drying, etc.) may have an eect on the nutritional value of the product, largely due to changes that occur in organic carbohydrates. The authors conclude that the interaction of FruHis carbohydrate and lycopene which develops during the dehydration process of tomato powder is responsible for the benecial activity of tomato powder. This study gives the tomato soups, prepared with powder from the bag, a new healthy anti-cancer image.
2.24.18
Lycopene may be benecial treating benign prostate hyperplasia (BPH) [383]
A possibly benecial role of lycopene in patients diagnosed with benign prostate hyperplasia (BPH), who are at increased risk of developing prostata carcinome was assesed by Silke Schwarz and colleagues 2008 using 15 mg lycopene for 6 month. The researchers found that lycopene decreased the level of serum prostate-specic antigen (PSA) levels, the prostate did not enlarge in the lycopene group. Symptoms of the disease were signicantly improved. he authors concluded that , lycopene inhibited progression of BPH.
2.24.19
The World Cancer Research Funds (WCRF) study [384]
The report "Food, Nutrition, Physical Activity, and the Prevention of Cancer" is based on publications published since 1960. Its core message is a group of 10 recommendations on how to prevent cancer:
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2.24.20
Whole grains
Wholegrain cereals, roots, tubers, and plantains are recommended in the diet. Consuming relative high amounts of vegetables, fruits, pulses (legumes), nuts, seeds, herbs, and spices were recommended.
2.24.21
Red and processed meat
Red and processed meat causes colorectal cancer up to 30 percent compared with low red meat eaters.The report suggests an average intake of no more than 300g each week of red meat. Fish is recommended to be included in diet. Egg consumption should be limited. According to WCRF red meat contains haem, a substance derived from red blood cells which causes a reaction in the gut that converts the amino acid glycine into a toxic substance which can damage DNA and can give rise to mutations in genes which may ultimately be necessary for cancer to occur. [385]
2.24.22
Healthy diet should displace ham and bacon in lunchbox says World Cancer Research Fund relation to cancer [386]
The World Cancer Research Fund (WCRF) stresses that processed meats such as ham and salami in the diet of children may increase their risk of developing cancer later in life. This advice is based on scientic evidence that eating processed meat, such as those preserved by smoking, curing, salting or by the addition of preservatives, increases bowel cancer risk. Eating less than 70 g of processed meat a week bowel cancer could drop by 3,700 cases. This includes ham, bacon, pastrami and salami, as well as hot dogs and some sausages. Hamburgers and minced meats only count as processed meat if they have been preserved with salt or chemical additives. For the same reason WCRF also calls to limit red meat consumption to 500 g (cooked weight) per week. A healthy eating pattern from the time they start school should include poultry, sh, low-fat cheese, houmous or small amounts of lean meat, salad, fruits and vegetables. The WCRF says that cancer is largely preventable and helps people make choices to reduce their chances of developing the disease. This includes research into how cancer risk is related to diet, physical activity, and weight management, and education programmes that highlight the fact that about a third of cancers could be prevented through changes to lifestyle.
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2.24.23
Report Food, Nutrition, Physical Activity, and the Prevention of Cancer [387]
Report published by WCRF studies actual eects of food, nutrition, physical activity, and body composition on risk of cancer, and gives recommendations to reduce the incidence of diseases.
2.24.24
FSA ecommendations on processed meat [388]
The Food Standards Agency, commenting the recommendations of the WCRF agrees that some evidences link bowel cancer to red and processed meats, however, this does not mean that occasional ham sandwich in the lunchbox increases the risk. The FSA highlights the importance of a balanced diet with limited amount of foods high in fat, saturated fat, sugar and salt. According to the FSA, processed meats, such as ham and salami, can form part of a balanced diet, however these foods often contain high levels of fat, particularly saturated fat and salt. They should not be eaten too often.
2.24.25
Fat and trans-fatty acids
Total dietary fats and trans-fatty acids should be limited. Salt intake should be limited to no more than 5 to 6 g/day for adults. Intake of sugar should be limited.
2.24.26
Overweight
The body weight should be maintained as low as possible in order to avoid cancer.
2.24.27
Alcohol
The report provides evidences that alcohol may cause cancer.
2.24.28
Dietary supplements
Dietary supplements are not recommended for cancer prevention. Some studies suggest an increased risk of prostate cancer caused by high doses of calcium and zinc. Some ndings suggest moderate protection from vitamin E for smokers, but there was no advantage found in non-smokers. Selenium may be protective. [389]
2.24.29
Special foods
Foods rich in folate such as tomatoes, broccoli, cabbage, and Brussels sprouts,may reduce the risk for cancer, and diets rich in calcium may reduce the risk of colorectal cancer.
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2.24.30
Salt and sugar
Salt should be reduced to 5 or 6g/day for adults. Sugar schould be reduced as much as possible.
2.24.31
Water
Water should be chosen as a drink instead of fruit juices, soft drinks, and hot drinks to prevent overweight/obesity and dental damage. Individuals (particularly older people) should consume between 1.5 and 2 litres of water each day to prevent constipation.
2.24.32
Dairy
Low-fat dairy products should be chosen in preference to high-fat versions.
2.24.33
Prediction of drinking water needs [390]
The US is engaged in operations all over the world. Transporting water to troops accounts for about one-third of costs of war activities. To make these activities less expensive Cheuvront and colleagues 2009 from The Institute of Medicine (IOM) developed sweating rate prediction models that calculate hourly and daily water needs based on metabolic rate, clothing and environment. It improves the Shapiro equation, which often over-predicts uid needs.
2.24.34
The Shapiro equation (OSE): OSE
It was developed by the US army in 1982. It is expressed as (msw (g m2 h -1) = 27.9 Ereq (Emax)0.455 , where: - Ereq is evaporative heat loss required to maintain proper body temperature - Emax is the evaporative potential of the environment - msw represents sweat loss - g m-2 is grams of sweat multiplied by the bodys surface area - = multiplied by
2.24.35
The new sweat equations
The authors published two new equations which are 58 and 65% more accurate with minimal error.
2.24.36
The corrected OSE
The corrected OSE is : (OSE,C): msw = 147 exp (0.0012 OSE)

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2.24.37
The new equation PW
The new equation is: (PW): msw = 147+1.527(Ereq) - 0.87 (Emax) The authors stress that the two new equations provide for more accurate sweat predictions over a broader range of conditions with applications to public health, military, occupational and sports medicine settings. Cheuvront and colleagues try to develop a public online application program calculating the sweat loss using individual variables such as height and weight, how hard and long they would be active, temperature, humidity, sunlight, wind and tness levels.
2.24.38
Breastfeeding
Mothers are advised to breastfeed exclusively for six months and to continue with complementarybreastfeeding after that. As well as convincing evidence that this protects the mother against breast cancer, there is also probable evidence that it protects the child against obesity in later life. UKs Food and Drink Federation, commenting the report says that a balanced diet coupled with moderate amounts of exercise is the key to a healthy lifestyle. The American Meat Institute (AMI) refers to conicting research ndings so that denitive conclusions and precise recommendations about specic foods should not be made. The World Cancer Researche Fund responds to this allegation saying that their study is base on sound evidences [385].
2.25
[391]
Food pyramids
2.25.1
USDA Food Pyramid and MyPyramid
The U.S. Department of Agriculture created the Food Guide Pyramid and replaced it recently by a new version called MyPyramid. It should be based on the Dietary Guidelines for Americans. [392] According to the Harvard School of Public Health the MyPyramid continues to recommend foods that arent essential to good health, and may even be detrimental in the quantities included in MyPyramid. [391]
2.25. FOOD PYRAMIDS Dietary Guidelines, 2005 [393]
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Dietary Guidelines for Americans 2005, according to the Harvard School of Public Health (HSPH) is still being inuenced by the food industry. The HSPH cites some points which being considered as not correct: [391]. - The guidelines suggest to consume half of grains as rened starch. HSPH consider this as not healthy, since rened starches behave like sugar. - The guidelines do not distinguish between the dierent type of fat contained in red meat, poultry, sh, and beans (including soy products). It does not recommend to change red meat for a combination of sh, poultry, beans, and nuts, says HSPH. - The recommendation to drink three glasses of low-fat milk or eat three servings of other dairy products per day would bring 300 calories per day encouraging obesity according to HSPH.
Dietary Guidelines for Americans, 2010 [394] The Dietary Guidelines for Americans include recommendations for healthy eating and informations about nutrients and food components. The Guidelines are reviewed every 5 years. They contain advice for people 2 years and older about how good dietary habits can promote health and reduce risk for major chronic diseases. The 2010 Dietary Guidelines released on January 2011 recommend to balance intake of calories with physical activity and consume more vegetables, fruits, low-fat dairy products, seafood., beans and peas, and nuts and seeds. Kitchen salt, solid fats, added sugars, and rened grains should be reduced. Advices to persons with chronic diseases due to the poor diet and physical inactivity resulting in overweight and obesity of the US population were included in the new version of the Guidelines. Two new chapters were included in the new Guideline: "The Total Diet: Combining Nutrients, Consuming Food" and "Translating and Integrating the Evidence: A Call to Action." According to the Guidelines Poor diet and physical inactivity are the most important factors contributing to an epidemic of overweight and obesity. In USA 72 percent of men and 64 percent of women are overweight or obese [395]. Poor diet and physical inactivity are the major causes of morbidity and mortality. Daily sodium intake in general population should be less than 2300 mg and less than 1500 mg for people older than50 years and those with hypertension, diabetes, or chronic kidney disease.
196 The Healthy Eating Pyramid [391]
It is founded on: - Daily exercise and weight control. - Whole Grain Foods (at most meals) such as oatmeal, whole-wheat bread, and brown rice. - Plant oils such as olive, canola, soy, corn, sunower, peanut, and other vegetable oils. However, fatty sh such as salmon are also welcome. - Vegetables (in abundance) and Fruits (2 to 3 times). - Fish, Poultry, and Eggs (0 to 2 times). - Nuts and Legumes (1 to 3 times). - Dairy or Calcium Supplement (1 to 2 times). If you dont like dairy products, calcium supplements may be the roght answer. - Red Meat and Butter (Use Sparingly): Both contain lots of saturated fat. HSPH recommends to change red meat with sh or chicken, and butter with olive oil. - White Rice, White Bread, Potatoes, White Pasta, Soda, and Sweets (Use Sparingly). - Multiple Vitamin: HSPH recommends a daily multivitamine, multimineral supplement as a nutritional back-up. - Alcohol (in moderation). Modied MyPyramid for Older People [396] Lichtenstein and colleagues 2008 presented My Modied Food Guide Pyramid for Older Adults based on their rst issue of 1999. It is targets individuals aged 70 years and older, is intended to complement and not substitute MyPyramid graphic. Core claims are whole grains and variety within the grains group; variety and nutrient density, with specic emphasis on dierent forms particularly suited to older adults needs in the vegetables and fruits groups, fresh or frozen; low-fat and non-fat forms of dairy products including reduced lactose alternatives in the milk group; low saturated fat and trans fat choices in the oils group; and low saturated fat and vegetable choices in the meat and beans group, nutrient-and bre-rich foods within each group and food sources of nutrients. The foundation of the pyramid for adults stresses good hydration with sucient uid intake. Regular physical activity which are appropriate to the age are illustrated. The potential need of calcium, and vitamins D and B-12 supplements is located at the top of the pyramid. The potential overnutrition of older adults is a new concern highlighted in this study which considers the changes in body composition and metabolic rate of older people. See the MyPyramid fore Older People at http://images.medscape.com/pi/editorial/news/artmmn567940.g1.gif USDA MyPyramid graphic and further informations USDA MyPyramid graphic and detailed informations are found under: http://www.mypyramid.gov/ MyPyramid for Preschoolars: http://www.mypyramid.gov/preschoolers/index.html
2.26. ALTERNATIVE FOOD PYRAMIDS
197
MyPyramid for Kids (6-11yrs): http://www.mypyramid.gov/kids/index.html MyPyramid for Pregnancy and Breatfeeding: http://www.mypyramid.gov/mypyramidmoms/index.htm MyPyramid for Professionals: http://www.mypyramid.gov/professionals/index.html Dietary Guidelines The Dietary Guidelines for Americans, 2005, gives science-based advice on food and physical activity choices for health. http://www.dietaryguidelines.gov/ The Dietary Guidelines describe a healthy diet as one that - Emphasizes fruits, vegetables, whole grains, and fat-free or low-fat milk and milk products; - Includes lean meats, poultry, sh, beans, eggs, and nuts; and - Is low in saturated fats, trans fats, cholesterol, salt (sodium), and added sugars.
2.26
2.26.1
Alternative food pyramids

Oldways Preservation and Exchange Trust
The Asian, Latin, Mediterranean, and vegetarian pyramids are also good, evidence-based guides for healthy eating. [397]
2.26.2
Genetic dependence to nicotine [398]
Scientists from an EU-supported consortium have discovered that a mutation in a human gene confers nicotine dependence. They have shown that a particular variant of a nicotinereceptor gene impacts smoking behaviour and hence confers a 30% increase in risk of lung cancer and a 20% increase in risk of peripheral artery disease (PAD), a common and debilitating constriction of the arteries to the legs. Roughly half of the people of European descent carry at least one copy of this genetic variant, which does not inuence smoking initiation, but makes it more dicult to quit. The results stem out from the European project GENADDICT (Genomics, mechanisms and treatment of addiction) The mutation which contributes to nicotine addiction is located on chromosome 15q24 and aects one nicotine-acetylcholine receptor in the brain. A study of 11,000 Icelandic smokers participating in the research showed that the mutation is more common in heavier smokers than in smokers overall and in the general population. It was also correlated with likelihood of clinical diagnosis of nicotine dependence. Comparisons between current and past smokers showed that people carrying this variant tend to smoke more and are less likely to quit smoking. Interestingly, the variant is less common among smokers who smoked less than 10 cigarettes per day than it is among non-smokers, supporting the notion that the mutation does not inuence smoking initiation, but rather confers risk of nicotine dependence among those who start.
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Through understanding the genetics of addiction the GENADDICT research may give new insight into its biological basis, and into the dysfunction of the addicted brain. It is likely to boost the development of new treatments and strategies against this serious disease.
2.26.3
Nicotine dependence
Recent articles report that genetic mutations on chromosomes 8, 15 and 19 make addiction to smoke more critical, and they are more prone to lung cancer compared to persons without this mutation. Also chromosome 11 is known to intensify the addiction, but chromosome 9 contains a gene which make it less dicult to stop smoking. The researchers say that some genes are responsible for the synthesis of enzymes which may be active in metabolising nicotine. Nicotine activates the nicotine receptors in the brain which releases the "feel good" hormones dopamine and serotonine.
2.26.4
Genes associated with smoking behaviour [399]
The Tobacco and Genetics Consortium together with the European Network of Genetic and Genomic Epidemiology and the Oxford-GlaxoSmithKline identied three loci associated with number of cigarettes smoked per day. These loci were the 15q25 single-nucleotide polymorphism (SNP) in the nicotinic receptor gene CHRNA3, two 10q25 SNPs, and one 9q13 SNP in EGLN2. Other genes were found which facilitate smoking initiation, and other genes which are. The good news are that one loci located on chromosome 9 was signicantly associated with smoking cessation.
2.26.5
Smoking behaviour and genetics [400]
Thorgeirsson and colleagues report that variants in the genomic regions at 15q25, 19q13, 8p11, and rs6474412-T are related to number of cigarettes smoked per day. Two loci are genes encoding nicotine-metabolizing enzymes (CYP2A6 and CYP2B6) and nicotinic acetylcholine receptor subunits (CHRNB3 and CHRNA6), already known to be related to smoking and nicotine dependence. The genes at 8p11 and 19q13 are linked with lung cancer
2.26.6
Gene locus on 15q25 associated with smoking quantity [401]
Liu and colleagues 2010 conrmed an eect on smoking quantity at a locus on 15q25 that includes CHRNA5, CHRNA3 and CHRNB4, three genes encoding neuronal nicotinic acetylcholine receptor subunits.
2.26. ALTERNATIVE FOOD PYRAMIDS
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2.26.7
Genetics as culprit to failure to quit smoking? [402]
Chapman and MacKenzie 2010 argue that the volume of research and eort devoted to professionally and pharmacologically mediated cessation is in inverse proportion to that examining how most ex-smokers actually quit. The authors say that nal results of nicotine replacement therapy or other drugs is dramatically overestimated. Many of these studies are funded by pharmaceutical companies. Up to three-quarters of ex-smokers have quit without assistance, and unaided cessation is by far the most common method used by most successful ex-smokers. Recidivism is normal if eorts are not serious attempts. The increasing medicalisation of smoking cessation implies professionally mediation. The author call on health authorities emphasise the positive message that the most successful method used by most ex-smokers is unassisted cessation. Nicotine replacement therapy may help, but is not used in most cases of successful cessations.
2.26.8
Small hint to quit smoking
The most stringent factor needed to stop smoking is a strong will to do it. The rst 4 days of cessation are dicult. You have to avoid any trouble. Take a vacation or some days o for the start. You will feel sick and nervous. Remember that after this period you will feel better each day. You will be proud of your mental strength and you will be able to handle other weaknesses much easier. Do not blame genetics. Pharmaceutical companies, like Oxford-GlaxoSmithKline, pose to much emphasis on studies related to nicotine replacement and genetics. It is your strength which you have to rely on.
2.26.9
Maternal smoking or even using nicotine patches or gum causes long-term cardiovascular harm for the child [403]
Xiao at al. 2011 reported that nicotine given to rats during pregnancy cause anomalous vascular reactivity and increased blood pressure in adult male rat ospring compared with rat population fed without nicotine. Nicotine causes the formation of reactive oxygen species (ROS), in the walls of blood vessels in the foetus. ROS cause permanent changes in the behaviour the blood vessel. This faulty programming is then carried throughout the individuals life and may lead to high blood pressure and cardiovascular diseases. In a commentary accompanying this paper, Lim and Sobeyn say that if applicable to humans a new cardiovascular risk factor which is predened before birth. The authors also stress that nicotine replacement therapy results in nicotine crossing the placenta causing a foetal programming of vascular oxidative stress in the ospring with vascular dysfunction
200
mediated by reactive oxygen species in association with decreased superoxide dismutase activity and increased Nox2-NADPH oxidase expression in the vascular wall in adulthood. [404] Nicotine replacement therapy is considered to be a safer alternative for women to smoking during pregnancy. Bruin, Gerstein and Holloway in a review of 2010 stress that according to studies on animals, there are long-term eects associated with maternal cigarette smoking on the ospring, such as impaired fertility, type 2 diabetes, obesity, hypertension, neurobehavioural defects, and respiratory dysfunction.[405]
2.26.10
Benets of smoking-cessation
The study of Jha et al. 2013 analysed data of the U.S. National Health Interview Survey related to smoking and smoking-cessation histories from 113,752 women and 88,496 men 25 years of age or older and determined the causes of deaths by end of 2006. The mortality among smokers was due to neoplastic, vascular, respiratory, and other diseases related to smoking. The death rate among smokers was about three times that among those who had never smoked. Life expectancy was shortened by more than 10 years among the current smokers, as compared with those who had never smoked. Cessation before the age of 40 years reduces the risk of death associated with continued smoking by about 90% [406] The risk of death from smoking is increasing impressingly in women For women who were current smokers, the relative risks of death from lung cancer increased from 2.7 in the 1960s to 25.7 in the 2010s while the relative risks for male smokers increased from 12.2 in the 1960s to 24,9 in the 2010s, according to a study of Thun et al. 2013. Male and female current smokers also had similar relative risks for death from chronic obstructive pulmonary disease (COPD), ischemic heart disease, any type of stroke and all causes combined, compared to non-smokers. Mortality from COPD among male smokers continued to increase Smoking cessation at any age dramatically reduced death rates. [407] Schoeder 2013 stresses that it is never too late to quit smoking. Clinicians in general should do more to stimulate quit attempts. The health hazard of smoking is being underestinmated. Schroeder writes that more women die of lung cancer than of breast cancer and cigarette smoking remains the the most important health hazard. [408]
Bibliography
[1] Lebensmittel Zeitung 9.7.98.
BIBLIOGRAPHY
201
[2] Carper,Jean: Stop aging now, The ultimate plan for staying young and reversing the aging process;HarperCollins Publishers,Inc.East 53rd Street, New York,Ny: 1995. [3] Milk Calcium: A natural choice; Ingredients and Analysis; Food Engineering International; September 1998 Pg 19. [4] Seeling,M.S.: Interrelationship of magnesium and estrogen in cardiovascular and bone disorders, eclampsia, migraine and premenstrual syndrome. Journal of the American College of Nutrition 1993;12(4): 442-58. [5] http://www.iom.edu/?id=12704. Institute of Medicine: Dietary Reference Intakes for Calcium, Phosphorus, Magnesium, Vitamin D, and Fluoride. [6] Feinendegen,L.E.; Feldmann,A.; Mnch,E.;Paschke,M.: Strahlenschutz Radioaktivitt und Gesundheit; im Auftrag des Bayrischen Staatsministerium fr Landesentwicklung und Umweltfragen.1986 Pg 66. [7] Lebensmittelfhrer: Inhalte, Zustze, Rckstnde/Vollmer, Gnter, Stuttgart; New York: Thieme (Wissenschaft fr den Alltag). [8] Larqu E, Sabater-Molina M, and Zamora S:. Biological signicance of dietary polyamines. Nutrition, 23(1):8795, 2007. http://www.ncbi.nlm.nih.gov/pubmed/ 17113752. [9] Lund University. Cell proliferation group: The role of the polyamines in cell cycle control and programmed cell death. 2011. http://www.djur.cob.lu.se/Cellprolif/ Research/research_area_1.html. [10] Ali MA, Poortvliet E, Stroemberg R, and Yngve A:. Polyamines in foods: development of a food database. Food Nutr Res, 14(55), 1 2011. http://www.ncbi.nlm. nih.gov/pubmed/21249159. [11] Ali MA, Poortvliet E, Stroemberg R, and Yngve A:. Polyamines: total daily intake in adolescents compared to the intake estimated from the swedish nutrition recommendations objectied (sno). Food Nutr Res, 14(55), 1 2011. http: //www.ncbi.nlm.nih.gov/pmc/articles/PMC3022765/?tool=pubmed. [12] Westermair,Dr. Thomas: Neue Aufgaben in der Schadstountersuchung? ;ZFL 49 (1998)Nr. 7/8 S.28. [13] Rudel RA, Gray JM, Engel CL, Rawsthorne TW, Dodson RE, and Ackerman JM. Food packaging and bisphenol a and bis(2-ethylhexyl) phthalate exposure: Findings from a dietary intervention. Environ Health Perspect, 3 2011. http://ehp03.niehs. nih.gov/article/info:doi/10.1289/ehp.10031700. [14] Unit Composition et Hygine des Produits Laitiers; Applied and Environmental Microbiology, 70.9:5644-5655.
202
[15] http://www.ncbi.nlm.nih.gov/pubmed/16522392. Villar J, Abdel-Aleem H, Merialdi M, Mathai M, Ali M, Zavaleta N, Purwar M, Hofmeyr J, Nguyen T, Campdonico L, Landoulsi S, Carroli G, Lindheimer M (2006): World Health Organization randomized trial of calcium supplementation among low calcium intake pregnant women. Am J Obstet Gynecol 194 (3): 639-49. [16] http://www.ajcn.org/cgi/content/full/73/4/722. Il Suh, Kyung Won Oh, Kang Hee Lee, Bruce M Psaty, Chung Mo Nam, Suk Il Kim, Hyung Gon Kang, Seung Yun Cho and Won Heum Shim: Moderate dietary fat consumption as a risk factor for ischemic heart disease in a population with a low fat intake: a case-control study in Korean men; American Journal of Clinical Nutrition, Vol. 73, No. 4, 722-727, April 2001. [17] http://www.who.int/vaccines/en/vitamina.shtml. WHO: Vitamin A supplementation. [18] http://www.harvestplus.org/content/about-harvestplus. HarvestPlus: Nutrients. What is hidden hunger? [19] http://en.wikipedia.org/wiki/Biofortification. Wikipedia: Biofortication. [20] http://www.ncbi.nlm.nih.gov/pubmed/20305664. Yan J, Kandianis CB, Harjes CE, Bai L, Kim EH, Yang X, Skinner DJ, Fu Z, Mitchell S, Li Q, Fernandez MG, Zaharieva M, Babu R, Fu Y, Palacios N, Li J, Dellapenna D, Brutnell T, Buckler ES, Warburton ML, Rocheford T: Rare genetic variation at Zea mays crtRB1 increases beta-carotene in maize grain. Nat Genet. 2010 Apr;42(4):322-7. [21] http://www.ncbi.nlm.nih.gov/pubmed/18616269. Davis CR, Howe JA, Rocheford TR, Tanumihardjo SA: The xanthophyll composition of biofortied maize (Zea mays Sp.) does not inuence the bioecacy of provitamin a carotenoids in Mongolian gerbils (Meriones unguiculatus). J Agric Food Chem. 2008 Aug 13;56(15):6745-50. Epub 2008 Jul 11. [22] http://www.ncbi.nlm.nih.gov/pubmed/16549478. Nestel P, Bouis HE, Meenakshi JV, Pfeier W: Biofortication of staple food crops. J Nutr. 2006 Apr;136(4):1064-7. [23] http://www.gatesfoundation.org/agriculturaldevelopment/pages/ connecting-poor-farmers-to-good-seeds-feature.aspx. Bill & Melinda Gates Foundation: Good Seeds, Better Lives for Poor Farmers. [24] http://www.plantphysiol.org/cgi/content/full/147/3/1334. Li F, Vallabhaneni R, Yu J, Rocheford T, Wurtzel ET: The maize phytoene synthase gene family: overlapping roles for carotenogenesis in endosperm, photomorphogenesis, and thermal stress tolerance. Plant Physiol. 2008 Jul;147(3):1334-46.
BIBLIOGRAPHY
203
[25] http://www.ncbi.nlm.nih.gov/pubmed/18202289. Harjes CE, Rocheford TR, Bai L, Brutnell TP, Kandianis CB, Sowinski SG, Stapleton AE, Vallabhaneni R, Williams M, Wurtzel ET, Yan J, Buckler ES: Natural genetic variation in lycopene epsilon cyclase tapped for maize biofortication. Science. 2008 Jan 18;319(5861):330-3. [26] http://jn.nutrition.org/cgi/content/abstract/136/10/2600. Kurt Z. Long, Jose Ignacio Santos, Teresa Estrada Garcia, Meredith Haas, Mathew Firestone, Jui Bhagwat, Herbert L. DuPont, Ellen Hertzmark, Jorge L. Rosado, and Nanda N. Nanthakumar: Vitamin A Supplementation Reduces the Monocyte Chemoattractant Protein-1 Intestinal Immune Response of Mexican Children J. Nutr. 2006 136: 26002605. [27] http://www.merck.com/mrkshared/mmanual/section1/chapter3/3b.jsp. Merck Manual: Vitamin A Deciency. The
[28] Burr,M.L.; Gilbert, J.F.; Holliday,R.M.; Elwood,P.C.; Fehily,A.M.; Rogers,S.; Sweetnam,P.M.; Deadham,N.M.; : Eects of changes in fat, sh, and bre intakes on the death and myocardial reinfarction: Diet and reinfarction trial (DART),Lancet ii, (1989), 757-761. [29] DeLorgeril,M.; Renaud,S.; Mamelle,N.; Salen,P.; Martin,J.L.; Monjaud,L.; Guidollet,J.; Touboul,P.; Delaye,J.: Mediterranean alpha-linolenic acid-rich diet in secondary prevention of coronary heart disease. Lancet 343, (1994)1454-1459. [30] http://www.fao.org/ag/agn/nutrition/docs/Fats%20and%20Fatty%20Acids% 20Summary.pdf. FAO: Fats and Fatty Acids. [31] http://content.karger.com/produktedb/produkte.asp?typ=fulltext&file= 000228997. Uauy R, Dangour AD: Fat and fatty acid requirements and recommendations for infants of 0-2 years and children of 2-18 years. Ann Nutr Metab. 2009;55(1-3):76-96. [32] http://content.karger.com/produktedb/produkte.asp?typ=fulltext&file= 000229002. Skea CM, Miller J: Dietary fat and coronary heart disease: summary of evidence from prospective cohort and randomised controlled trials. Ann Nutr Metab. 2009;55(1-3):173-201. [33] http://content.karger.com/produktedb/produkte.asp?typ=fulltext&file= 000229004. Melanson EL, Astrup A, Donahoo WT: The relationship between dietary fat and fatty acid intake and body weight, diabetes, and the metabolic syndrome. Ann Nutr Metab. 2009;55(1-3):229-43. [34] http://www.foodnavigator.com/On-your-radar/Healthier-products/ Unilever-expects-products-to-help-meet-essential-fatty-acid-advice. Unilever expects products to help meet essential fatty acid advice. Food Navigator. 28 May 2010.
204
[35] http://www.cmaj.ca/cgi/content/full/180/6/633. Jenkins,David J.A.; Sievenpiper, John L.; Pauly, Daniel; Sumaila Rashid, Ussif; Kendall, Cyril W.C.; Mowat, Farley M.: Are dietary recommendations for the use of sh oils sustainable? CMAJ 2009; 180:633-637. [36] http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(99) 90191-5/fulltext. Jialal, I.; Devaraj, S.; Huet, B.A.;Traber, Maret: GISSIPrevenzione Trial. The Lancet, Volume 354, Issue 9189, Page 1554, 30 October 1999 doi:10.1016/S0140-6736(99)90191-5. [37] http://www.ajcn.org/cgi/content/abstract/ajcn.2009.29146v1. Yamagishi K, Iso H, Yatsuya H, Tanabe N, Date C, Kikuchi S, Yamamoto A, Inaba Y, Tamakoshi A; for the JACC Study Group: Dietary intake of saturated fatty acids and mortality from cardiovascular disease in Japanese: the Japan Collaborative Cohort Study for Evaluation of Cancer Risk Study? Am J Clin Nutr. 2010 Aug 4. Doi:10.3945/ajcn.2009.29146. [38] http://pubs.acs.org/doi/abs/10.1021/jf803922w. Athalye, Sneha K.; Garcia, Rafael A; Wen, Zhiyou: Use of Biodiesel-Derived Crude Glycerol for Producing Eicosapentaenoic Acid (EPA) by the Fungus Pythium irregulare. Journal of Agricultural and Food Chemistry 6 March 2009, doi: 10.1021/jf803922w. [39] Hu FB and Manson JE. Omega-3 fatty acids and secondary prevention of cardiovascular diseaseis it just a sh tale?: Comment on "ecacy of omega-3 fatty acid supplements (eicosapentaenoic acid and docosahexaenoic acid) in the secondary prevention of cardiovascular disease.". Arch Intern Med, 172(9):694 696, 2012. http://archinte.jamanetwork.com/article.aspx?doi=10.1001/ archinternmed.2012.463. [40] Manson JE, Bassuk SS, Lee IM, Cook NR, Albert MA, Gordon D, Zaharris E, Macfadyen JG, Danielson E, Lin J, Zhang SM, and Buring JE. The vitamin d and omega-3 trial (vital): rationale and design of a large randomized controlled trial of vitamin d and marine omega-3 fatty acid supplements for the primary prevention of cancer and cardiovascular disease. Contemp Clin Trials, 33(1):159171, 2012. http://www.ncbi.nlm.nih.gov/pubmed/21986389. [41] Gissi-prevenzione investigators (gruppo italiano per lo studio della sopravvivenza nellinfarto miocardico).dietary supplementation with n-3 polyunsaturated fatty acids and vitamin e after myocardial infarction: results of the gissi-prevenzione trial. Lancet, 357(9256):642, 2001. http://www.ncbi.nlm.nih.gov/pubmed/10465168. [42] YokoyamaM, OrigasaH, MatsuzakiM, and et al. Eects of eicosapentaenoic acid on major coronary events in hypercholesterolaemic patients (jelis): a randomised open-label, blinded endpoint analysis. Lancet, 369(9567):10901098, 2007. http: //www.ncbi.nlm.nih.gov/pubmed/17398308.
BIBLIOGRAPHY
205
[43] http://www.agriculture.state.pa.us/agriculture/cwp/view.asp?q=128033. Pensilvania Department of Agriculture: Mefenoxam-insensitive Pythium Irregulare Root Rot and Blackleg of Geranium. [44] http://www.ncbi.nlm.nih.gov/pubmed/16456725. Burr ML, Dunstan FD, George CH.: Is sh oil good or bad for heart disease? Two trials with apparently conicting results. J Membr Biol. 2005 Jul;206(2):155-63. [45] http://www.ncbi.nlm.nih.gov/pubmed/2571009. Burr ML, Fehily AM, Gilbert JF, Rogers S, Holliday RM, Sweetnam PM, Elwood PC & Deadman NM (1989): Eects of changes in fat, sh, and bre intakes on death and myocardial reinfarction: diet and reinfarction trial (DART). Lancet 2, 757-761. [46] http://www.ncbi.nlm.nih.gov/pubmed/12571649. Burr ML, Asheld-Watt PAL, Dunstan FDJ, Fehily AM, Breay P, Ashton T, Zotos PC, Haboubi NAA & Elwood PC (2003): Lack of benet of dietary advice to men with angina: results of a controlled trial. Eur. J. Clin. Nutr. 57, 193-200. [47] Satomi Yano, Daisuke Umeda, Norihide Maeda, Yoshinori Fujimura, Koji Yamada, and Hirofumi Tachibana: Dietary Apigenin Suppresses IgE and Inammatory Cytokines Production in C57BL/6N Mice; Journal of Agricultural and Food Chemistry (Vol. 54, pp. 5203-5207)(Article) DOI: 10.1021/jf0607361. [48] Sanjeev Shukla, Anil Mishra, Pingfu Fu, Gregory T. MacLennan, Martin I. Resnick, and Sanjay Gupta: Up-regulation of insulin-like growth factor binding protein-3 by apigenin leads to growth inhibition and apoptosis of 22Rv1 xenograft in athymic nude mice; The FASEB Journal Express Article doi:10.1096/fj.05-3740fje. [49] Klingel, Brigitta:Gesund und schlank mit der Algenkche, Sdwest. [50] Koie, Marianne; Kristiansen, Aase: Der grosse Kosmos Strandfhrer; Kosmos-Verlag pg 276. [51] Fitzgerald C, Gallagher E, Tasdemir D, and Hayes M. Heart health peptides from macroalgae and their potential use in functional foods. J Agric Food Chem, 59(13):68296836, 7 2011. http://www.ncbi.nlm.nih.gov/pubmed/21574559. [52] Furtmayr,Andreas: Sushi; GU Ratgeber. [53] Linder,Ernst: Toxikologie der Nahrungsmittel; 4. Auage; Stuttgart; New York; Thieme,1990 pg 53. [54] Versuch mit Sonnenblumen mit hohem lsuregehalt;vwd/25.08.99/jc/mi. [55] Consumer Healthcare: Mayo Clinic Study an Plant Stanol Ester Spread (Benecol) Presented at American Dietetic Assotiation Meeting;Advance/Kansas City, Oct. 20/PrNewswire.
206
[56] Westrate,J.A., Meijer,G.W.(1998) Plant sterol-enriched margarines and reduction of plasma total and LDL-cholesterol concentrations in normocholesterinemic and mildly hypercholesteremic subjects. Eur. J. Clin Nutr. 52, 334-344. [57] Martin et al.:Serumcholesterol,blood pressure and mortality (1996), Lancet II:933936. [58] http://www.ncbi.nlm.nih.gov/pubmed/18078870. Jenkins, D.J.A; Kendall, C.W.C.; Nguyen, T.H.; Marchie, A.; Faulkner, D.A.; Ireland, C.; Josse, A.R.; Vidgen, E.; Trautwein, E.A.; Lapsley, K.G.; Holmes, C.; Josse, R.G.; Leiter, L.A.; Connelly, P.W.; Singer, W.: Eect of plant sterols in combination with other cholesterollowering foods. Metabolism (Elsevier) January 2008, Volume 57, Issue 1, Pages 130139. [59] http://www.nhlbi.nih.gov/guidelines/cholesterol/atp3full.pdf. National Cholesterol Education Program (NCEP) Third Report of the Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (ATP III Final Report). [60] http://www.efsa.europa.eu/EFSA/efsa_locale-1178620753812_ 1178690353765.htm. EFSA: Consumption of Food and Beverages with Added Plant Sterols. 4.03.2008. [61] http://www.efsa.europa.eu/EFSA/Scientific_Document/datex_report_ phytosterols,0.pdf. EFSA: Consumption of Food and Beverages with Added Plant Sterols in the European Union. Issued on 20 February 2008. [62] http://ec.europa.eu/food/fs/sc/scf/out143_en.pdf. SCF (Scientic Committee on Food) (2002a). General view on the long-term eects of the intake of elevated levels of phytosterols from multiple dietary sources with particular attention to the eects on beta-carotene. Opinion adopted by the Scientic Committee on Food on 26 September, 2002. [63] http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=CELEX: 31997R0258:EN:HTML. Regulation (EC) No 258/97 of the European Parliament and of the Council of 27 January 1997 concerning novel foods and novel food ingredients. [64] http://www.lipidworld.com/content/3/1/5/abstract. Berger, A., Jones, P.J.H. and Abumweis, S.S. (2004). Plant sterols: factors aecting their ecacy and safety as functional food ingredients. Lipids Health Dis. 3:5. [65] http://www.ncbi.nlm.nih.gov/pubmed/19145455. Chen SC, Judd JT, Kramer M, Meijer GW, Clevidence BA, Baer DJ.: Phytosterol intake and dietary fat reduction are independent and additive in their ability to reduce plasma LDL cholesterol. Lipids. 2009 Mar;44(3):273-81.
BIBLIOGRAPHY
207
[66] http://jn.nutrition.org/cgi/content/full/132/12/3650. Ntanios FY, Homma Y, Ushiro S.: A spread enriched with plant sterol-esters lowers blood cholesterol and lipoproteins without aecting vitamins A and E in normal and hypercholesterolemic Japanese men and women. J Nutr. 2002 Dec;132(12):3650-5. [67] http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=OJ:L:2004:097: 0044:0045:EN:PDF. Commission Regulation (EC) No 608/2004 of 31 March 2004 concerning the labelling of foods and food ingredients with added phytosterols, phytosterol esters, phytostanols and/or phytostanol esters. [68] Schormller,J.: Handbuch der Lebensmittelchemie, Band IV, Fette und lipoide; Springer-Verlag 1969. pg 777. [69] Schormller,J.: Handbuch der Lebensmittelchemie, lipoide;Springer-Verlag 1969. pg 791. Band IV, Fette und
[70] http://www.aoac.org/pubs/PVMs/phmetric.htm. AOAC Publications: pH-Metric Determination of the Acid Value of Vegetable Oils without Titration. [71] Sensorische Eigenschaften objektiv beurteilen;7-8/99 dei 41; page 48. [72] http://www.bfr.bund.de/cm/245/initial_evaluation_of_the_assessment_ of_levels_of_glycidol_fatty_acid_esters.pdf. Initial evaluation of the assessment of levels of glycidol fatty acid esters de-tected in rened vegetable fats. BfR Opinion No. 007/2009, 10 March 2009. [73] http://www.test.de/themen/essen-trinken/schnelltest/ -Pflanzencreme-Flair/1794115/1794115/. Panzencreme Flair:Duerfte nicht verkauft werden. Stiftung Warentest. Test 8, 2009. [74] http://pubs.acs.org/cgi-bin/abstract.cgi/jafcau/asap/abs/jf801412v. html. Kim, Byung Hee; Lumor, Stephen E.; Akoh, Casimir C.: trans-Free Margarines Prepared with Canola Oil/Palm Stearin/Palm Kernel Oil-Based Structured Lipids. Journal of Agricultural and Food Chemistry. Published online ahead of print, ASAP Article, doi: 10.1021/jf801412v. [75] http://www.sumatranorangutan.org/site_mawas/UK/NEWS/pag_no_DB/OTHER_ news_2006.htm. Sumatra Orangutan Society: The oil for ape scandal, How palm oil is threatening the orangutan. Author Helen Buckland. [76] http://www.newstatesman.com/200608070031. The Australian Orangoutan Project: Frankenstein fuels by Mark Lynas, New Statesman, 7th August 2006. [77] Enas EA: Cooking oils, cholesterol and CAD: facts and myths. CADI Research Foundation, Woodridge, IL 60517, USA. Indian Heart J. 1996 Jul-Aug;48(4):423-7.
208
[78] http://www.ncbi.nlm.nih.gov/pubmed/2296125. Saturated fatty acids in vegetable oils. Council on Scientic Aairs. JAMA 1990 Feb 2;263(5):693-5. PMID: 2296125 (PubMed - indexed for MEDLINE). [79] Clarke R, Frost C, Collins R, et al. Dietary lipids and blood cholesterol: quantitative metaanalysis of metabolic ward studies. Brit Med J. 1997;314:112-7. [80] World Health Organization. Diet, Nutrition and the Prevention of Chronic Diseases. WHO Tech. Rep. Series 916. Geneva. 2003. P. 88. [81] http://www.cspinet.org/palmoilreport/index.html. Center for Science in the Public Interest: Cruel Oil. [82] http://www.cspinet.org/new/pdf/hhs_obesity_letter.pdf. Center for Science in the Public Interest: Letter to Secretary Michael Leavitt. Department of Health and Human Services. [83] Linder,Ernst: Toxikologie der Nahrungsmittel;4. Auage; Stuttgart; New York; Thieme, 1990 pg 155. [84] Schormller: Handbuch der Lebensmittelchemie, Fette und Lipoide, Band IV, Springer Verlag,1969, page 809. [85] GDCH. Recommendations for frying oils, third international symposium on deepfat frying march 20-21,2000,hagen/wesphalia,germany. 3 2000. http:www.gdch.de/ dgf/recomm.htm. [86] Golomb BA, Evans MA, White HL, and Dimsdale JE. Trans fat consumption and aggression. PLoS One, 7(3):e32175, 2012. http://www.ncbi.nlm.nih.gov/pmc/ articles/PMC3293881/?tool=pubmed. [87] http://www.tri-calcium-citrate.com/var/184/1416-Calcium%20-%20for% 20Soy%20.pdf. Gadot Biochemical Industries: Soy milk and soy product fortication with calcium. [88] http://www.wildflavours.com/index.cfm?fuseaction=home.viewPage&page_ id=EDC1224C-CF1C-2465-1B93161219B35494. Sojaland Schwerin. [89] http://www.olis.oecd.org/olis/2001doc.nsf/c5ce8ffa41835d64c125685d005300b0/ 19f31700dc91b614c1256b19003bd79d/FILE/JT00118009.PDF. OECD Environmental Health and Safety Publications Series on the Safety of Novel Foods and Feeds, Consensus Document on Key Nutritients and Key Toxicants in Low Erucic Acid Rapeseed (Canola). [90] Sss und trozdem gesund;7-8/99 dei 39; page 38.
BIBLIOGRAPHY
209
[91] http://en.wikipedia.org/wiki/Xylitol. Wikipedia, the free enzyclopedia: Xylitol. [92] http://www.ars.usda.gov/is/AR/archive/jul00/xylit0700.htm. USDA, Agricultural Research Service: Making Xylitol Sweetener From Corn. [93] Gliemmo, M.F.; Calvino, A.M.; Tamasi, O.; Gerschenson, L.N.; Campos, C.A.: Interactions between aspartame, glucose and xylitol in aqueous systems containing potassium sorbate. LWT - Food Science and Technology (Elsevier). Volume 41, Issue 4, Pages 611-619, doi: 10.1016/j.lwt.2007.05.004. [94] Hanewinkel-Meshkini,S. and Hackmann, W.Chemisches Untersuchungsamt der Stadt Bielefeld: Beitrag zur Beurteilung von Tomatenmark; Deutsche LebensmittelRundschau 85. Jahrgang, Heft 11, 1989. [95] Beckmann,Johannes: Verdorben bis ins Mark;Stern Nr 49/1969 II 21. [96] http://pubs.acs.org/cgi-bin/abstract.cgi/jafcau/2006/54/i25/abs/ jf062249r.html. Zadra, Claudia; Borgogni, Andrea; Cesare Marucchini: Quantication of Jasmonic Acid by SPME in Tomato Plants Stressed by Ozone; J. Agric. Food Chem.; 2006; 54(25) pp 9317 - 9321; (Article) DOI: 10.1021/jf062249r. [97] Karpf,Walter: Rote Karte fr die Tomate ?:HRZU Nr. 12,1991. [98] Nagel,Dr.rer.nat. M.: Verminderung von Sticksto- und Kohlensto- Verbindungen in Glle durch Algen und andere Mikroorganismen;Jahresbericht 1996 Deutsches Institut fr Lebensmittel. [99] Holzgartner,H.; Schmidt,U.; Kuhn,U.: Wirksamkeit und Vertrglichkeit eines Knoblauchpulver Prparates im Vergleich mit Bezabrat; Arzneimittel-Forschung Drug Research 42 (II), 12, 1473-1477 (1992). [100] http://www3.interscience.wiley.com/cgi-bin/fulltext/121541722/ HTMLSTART. Vaidya V, Ingold KU, Pratt DA.:Garlic: source of the ultimate antioxidants - sulfenic acids. Angew Chem Int Ed Engl. 2009;48(1):157-60. [101] http://pubs.acs.org/doi/abs/10.1021/jf8000907. Fujisawa, Hiroyuki; Suma, Kaoru; Origuch, Kana i; Kumagai, Hitomi; Seki, Taiichiro; Ariga, Toyohiko: Bioological and Chemical Stability of Garlic-Derived AllicinJ. Agric. Food Chem., 2008, 56 (11), pp 4229-4235. Doi: 10.1021/jf8000907. [102] http://pubs.acs.org/doi/abs/10.1021/jf062587s. Cavagnaro, Pablo F.; Camargo, Alejandra; Galmarini, Claudio R.; Simon, Philipp W.: Eect of Cooking on Garlic (Allium sativum L.) Antiplatelet Activity and Thiosulnates Content. J. Agric. Food Chem., 2007, 55 (4), pp 1280-1288 Publication Date (Web): January 27, 2007 (Article) Doi: 10.1021/jf062587s.
210
[103] Spurenelement Selen,Aktueller Stand der wissenschaftlichen Erkenntnisse; Der Lebensmittelbrief,9. Jahrgang, Mrz/April 1998 ; pp 90. [104] http://en.wikipedia.org/wiki/Selenium. Wikipedia, The Free Enzyclopedia: Selenium. [105] Shamberger, R.J. and D.V. Frost. 1969. Possible protective eect of selenium against human cancer. Can. Med. Assoc. J. 100:682. [106] Burguera JL, Burguera L, Gallignani M, Alarcon OM, Burguera JA: Blood serum selenium in the province of Merida, Venezuela, related to sex, cancer incidence and soil selenium content. J Trace Elem Electrolytes Health Dis. 1990 Jun;4(2):73-7. [107] http://www.journalclub.org/vo12/a39.html. Clark L, Combs G, Turnbull B, Slate E, Chalker D, Chow J, et al.Eects of selenium supplementation for cancer prevention in patients with carcinoma of the skin; JAMA. 276:1957-63. December 25, 1996. [108] http://cebp.aacrjournals.org/content/6/1/63.long. Patterson BH, Levander OA: Naturally occurring selenium compounds in cancer chemoprevention trials: a workshop summary. Cancer Epidemiol Biomarkers Prev. 1997 Jan;6(1):63-9. [109] http://www.ncbi.nlm.nih.gov/pubmed/9279064. Fleet JC: Dietary selenium repletion may reduce cancer incidence in people at high risk who live in areas with low soil selenium. Nutr Rev. 1997 Jul; 55(7):277-9. [110] http://www.ncbi.nlm.nih.gov/pubmed/9829869. Knekt P, Marniemi J, Teppo L, Heliovaara M, Aromaa A: Is low selenium status a risk factor for lung cancer? Am J Epidemiol. 1998 Nov 15;148(10):975-82. [111] http://www.ncbi.nlm.nih.gov/pubmed/10335455. Young KJ, Lee PN: Intervention studies on cancer. Eur J Cancer Prev. 1999 Apr;8(2):91-103. [112] http://jn.nutrition.org/cgi/content/abstract/130/7/1653. Gerhard N. Schrauzer: Selenomethionine: A Review of Its Nutritional Signicance, Metabolism and Toxicity Journal of Nutrition. 2000;130:1653-1656. [113] http://med.stanford.edu/profiles/frdActionServlet?choiceId= showPublication&pubid=39140&fid=6178. Brooks JD, Metter EJ, Chan DW, Sokoll LJ, Landis P, Nelson WG, Muller D, Andres R and Carter HB. Plasma selenium level before diagnosis and the risk of prostate cancer development. J Urol 2001; 166(6): 2034-2038. [114] http://www.clinchem.org/cgi/content/abstract/51/11/2117. N.Tasnime Akbaraly, Josiane Arnaud, Isabelle Hininger-Favier, Veronique Gourlet, Anne-Marie Roussel and Claudine Berr: Selenium and Mortality in the Elderly: Results from
BIBLIOGRAPHY
211
the EVA Study. Clinical Chemistry 51: 2117-2123, 2005. First published August 25, 2005; 10.1373/clinchem.2005.055301. [115] Melinda A. Beck, Jean Handy and Orville A. Levander: Host nutritional status: the neglected virulence factor. Trends in Microbiology, 2004, Vol. 12, pp. 417-423 doi:10.1016/j.tim.2004.07.007. [116] Eliane Kellen, Maurice Zeegers, Frank Buntinx: Selenium is inversely associated with bladder cancer risk: A report from the Belgian case-control study on bladder cancer. International Journal of Urology Volume 13 Page 1180 - September 2006 doi:10.1111/j.1442-2042.2006.01526.x Volume 13 Issue 9. [117] Margaret Rayman, Alexander Thompson, Margaret Warren-Perry, Rachel Galassini, Janet Catterick, Emma Hall, David Lawrence and Judith Bliss: Impact of Selenium on Mood and Quality of Life: A Randomized, Controlled Trial Biological Psychriatry Pages 147-154 doi:10.1016/j.biopsych.2005.06.019. [118] http://www.nmcd-journal.com/article/PIIS0939475306001220/abstract. Natella, Fausta; Fidale, Michela; Tubaro, Franco; Ursini, Fulvio; Scaccin, Cristina: Selenium supplementation prevents the increase in atherogenic electronegative LDL (LDL minus) in the postprandial phase. Nutrition, Metabolism and Cardiovascular Diseases. published online 15 Febuary 2007. doi: 10.1016/j.numecd.2006.05.002. [119] http://www.acnem.org/journal/22-3_december_2003/selenium_wheat.htm. Graham Lyons, James Stangoulis, Robin Graham: Nutriprevention of Disease with High-Selenium Wheat; Journal of the Australasian College of Nutritional & Environmental Medicine, Vol. 22, No. 3, December 2003, pages 3-9. [120] http://www.crab.org/select/. SELECT Men Fighting to Prevent Prostate Cancer. [121] http://cme.nci.nih.gov/newscenter/pressreleases/SELECTJAMAresults2008. SELECT: Review of Prostate Cancer Prevention Study Shows No Benet for Use of Selenium and Vitamin E Supplements. National Cancer Institute. December 09, 2008. [122] http://jama.ama-assn.org/cgi/content/full/301/1/39?ijkey= 8f686985e45995c36480e114c9d9d9e5729fb768. Lippman SM Klein EA, Goodman PJ; et al. 2008: Eect of Selenium and Vitamin E on Risk of Prostate Cancer and Other Cancers. The Selenium and Vitamin E Cancer Prevention Trial (SELECT). JAMA. 2009;301(1). 09, December 2009. Doi:10.1001/jama.2008.864. [123] http://jama.ama-assn.org/cgi/content/abstract/301/1/52. Gaziano JM, Glynn RJ, Christen WG; et al. Vitamins E and C in the prevention of prostate and total cancer in men: the Physicians Health Study II randomized controlled trial. JAMA. 2009;301(1):52-62. Doi:10.1001/jama.2008.862.
212
[124] http://jama.ama-assn.org/cgi/content/full/2008.863. Gann, Peter H.: Randomized Trials of Antioxidant Supplementation for Cancer Prevention First Bias, Now Chance, Next Cause. JAMA. 2009;301(1):102-103. Published online December 9, 2008 (doi:10.1001/jama.2008.863). [125] http://www.mja.com.au/public/issues/180_08_190404/dan10064_fm.html# i1083242. Lynne A Daniels: Selenium: does selenium status have health outcomes beyond overt deciency; The Medical Journal of Australia; MJA 2004; 180 (8): 373-37. [126] http://www.ncbi.nlm.nih.gov/pubmed/11348568. Combs GF. Selenium in global food systems. Brit J Nutr 2001; 85: 517-547. [127] http://www.enlink.org/pt/re/nestle/abstract.00002375-200410000-00002. htm;jsessionid=F6qbndGl1631n3F2FwRxs2d6yXx5JdhWH69nfD3httQntG81hTKv!336912420!949856144!8091!-1?article=3&basedoc=00002375-200401000-00004&nav=forward arelli, C. and Lanzarini, G.) Elsevier London. pp. 1-16. Rayman, Margaret P.: The use of high-selenium yeast to raise selenium status: how does it measure up?. Review article British Journal of Nutrition. 92(4):557-573, October 2004. [128] http://www.efsa.europa.eu/en/science/feedap/feedap_opinions/1478.html. European Food Safety Authority: Opinion of the Scientic Panel FEEDAP on the safety and ecacy of the product Sel-Plex 2000 as a feed additive according to Regulation (EC) No 1831/2003. Publication Date: 8 May 2006. [129] http://www.efsa.europa.eu/en/science/feedap/an_applications/ summaries/1137.html. European Food Safety Authority: Summary of the dossier: Selenium enriched yeast (Saccharomyces cerevisiae NCYC R397 or S. cerevisiae CNCM I3399) (ALKOSEL/SELSAF). For all species. Publication Date: 14 September 2005 Last updated: 6 June 2006. [130] http://www.cancer.org.au/documents/Pos_St_Selenium_OCT05.pdf. Selenium position statement of Australia Cancer Council. [131] http://www.ajcn.org/cgi/content/abstract/88/2/416. Bleys, Joachim; NavasAcien, Ana; Stranges, Saverio; Menke, Andy; Miller, Edgar R. 3rd; Guallar. Eliseo: Serum selenium and serum lipids in US adults. American Journal of Clinical Nutrition, Vol. 88, No. 2, 416-423, August 2008. [132] http://en.wikipedia.org/wiki/Hake. Wikipedia, The Free Enzyclopedia: Hake. [133] http://www.msc.org/html/content_1228.htm. AAFA Pacic Albacore Tuna. [134] http://www.ncbi.nlm.nih.gov/pubmed/19477179. Gozlana,Rodolphe E.; Whippsb, Christopher M.; Andreouc, Demetra;Arkushe. Kristen D.: Identication of a rosette-like agent as Sphaerothecum destruens, a multi-host sh pathogenstar, open. International Journal of Parasitology, DOI: 10.1016/j.ijpara.2009.04.012.
BIBLIOGRAPHY
213
[135] http://www.ncbi.nlm.nih.gov/pubmed/15973399. Gozlan, R.E.; St-Hilaire, S.; Feist, S.W.; Martin, P.; Kent, M.L.: Biodiversity: disease threat to European sh. Nature. 2005 Jun 23;435(7045):1046. [136] Lebensmittel Zeitung, 6. Dezember 2001. [137] http://news.bbc.co.uk/2/hi/uk_news/7102241.stm. BBC: Fish dumping will ruin industry. 20.11.2007. [138] R Enever, A Revill and A Grant (2007), Discarding around the UK-New information and analyses: 1) English Channel, Western Approaches, Celtic & Irish Sea (ICES subarea VII), Fisheries Research, Volume 86, Issues 2-3, September 2007. p.143-152. [139] http://www.cefas.co.uk/news-and-events/news-releases/ news-releases-2007/cefas-sees-discards-hope-in-usa-gear-design.aspx. Cefas sees discards hope in USA gear design. [140] http://www.newsdaily.com/stories/tre4ab51l-us-usa-navy-whales/. Daily: U.S. top court rules for Navy in whales-sonar case 12-11.2008. News
[141] http://www.ncbi.nlm.nih.gov/pubmed/15338247. Sanders ME, Tompkins T, Heimbach JT, Kolida S.: Weight of evidence needed to substantiate a health eect for probiotics and prebiotics: regulatory considerations in Canada, E.U., and U.S. Eur J Nutr. 2005 Aug;44(5):303-10. Epub 2004 Sep 2. [142] http://www.cfsan.fda.gov/~dms/lab-qhc.html. FDA: Qualied Health Claims. [143] http://www.ncbi.nlm.nih.gov/pubmed/18492860. Hasler, C.M.: Health claims in the United States: an aid to the public or a source of confusion? J Nutr. 2008 Jun;138(6):1216S-20S. [144] http://www.ncbi.nlm.nih.gov/pubmed/18492861. Labb, M.R.; Dumais, L.; Chao E.; Junkins, B. : Health claims on foods in Canada. J Nutr. 2008 Jun;138(6):1221S-7S. [145] http://www.ncbi.nlm.nih.gov/pubmed/18492859. Asp, Nils-Georg; Bryngelsson, Susanne: Health claims in Europe: new legislation and PASSCLAIM for substantiation. J Nutr. 2008 Jun;138(6):1210S-5S. [146] http://www.abgespeist.de/actimel/index_ger.html. Foodwatch: Abgespeist: Actimel von Danone. Activer Etikettenschwindel. 17.12.2008. Danone actimel compactinfo 20081217. [147] http://www.spiegel.de/wirtschaft/0,1518,druck-597184,00.html. Amann, Susanne: Marketing-Erfolg. Mit Joghurt Millionen scheeln. Spiegel Online 22.12.2008.
214
[148] http://www.ncbi.nlm.nih.gov/pubmed/16508257. Meyer AL, Micksche M, Herbacek I, Elmadfa I.: Daily intake of probiotic as well as conventional yogurt has a stimulating eect on cellular immunity in young healthy women. Ann Nutr Metab. 2006;50(3):282-9. Epub 2006 Feb 23. [149] http://www.ncbi.nlm.nih.gov/pubmed/16022746. Guarner, F.; Perdigon, G.; Corthier, G.; Salminen, S.; Koletzko, B.; Morelli, L.: Should yoghurt cultures be considered probiotic? Br J Nutr. 2005 Jun;93(6):783-6. Review. [150] http://www.ncbi.nlm.nih.gov/pubmed/16696665. Parvez. S.; Malik, K.A, Ah Kang, S.; Kim, H.Y.: Probiotics and their fermented food products are benecial for health. J Appl Microbiol. 2006 Jun;100(6):1171-85. [151] http://www.ncbi.nlm.nih.gov/pubmed/18461293. de Vrese, M.; Schrezenmeir, J.: Probiotics, prebiotics, and synbiotics. Adv Biochem Eng Biotechnol. 2008;111:1-66. [152] http://www.ncbi.nlm.nih.gov/pubmed/18313433 ibitemFAO/WHO evaluation probiotics guidelinesFAO/WHO. Guidelines for the evaluation of probiotics in food. Joint FAO/WHO Working Group. Report on Drafting Guidelines for the Evaluation of Probiotics in Food London, Ontario, Canada, 2002. FAO Food and Nutrition Paper 85. ftp://ftp.fao.org/docrep/fao/009/a0512e/a0512e00.pdf. Douglas, L.C.; Sanders, M.E.: Probiotics and prebiotics in dietetics practice. J Am Diet Assoc. 2008 Mar;108(3):510-21. [153] http://www.ncbi.nlm.nih.gov/pubmed/11220983. Pedone CA, Arnaud CC, Postaire ER, Bouley CF, Reinert P. Multicentric study of the eect of milk fermented by Lactobacillus casei on the incidence of diarrhoea. Int J Clin Pract. 2000 Nov;54(9):568-71. [154] http://www.ncbi.nlm.nih.gov/pubmed/11208946. Gurin-Danan C, Meslin JC, Chambard A, Charpilienne A, Relano P, Bouley C, Cohen J, Andrieux C.: Food supplementation with milk fermented by Lactobacillus casei DN-114 001 protects suckling rats from rotavirus-associated diarrhea. J Nutr. 2001 Jan;131(1):111-7. [155] http://www.ncbi.nlm.nih.gov/pubmed/12556942. Branca F, Rossi L. The role of fermented milk in complementary feeding of young children: lessons from transition countries. Eur J Clin Nutr. 2002 Dec;56 Suppl 4:S16-20. [156] Kligler B, Cohrssen A: Probiotics. November 1, 2008 Vol. 78 No. 9 Am Fam Physician. 2008;78(9):1073-1078. [157] http://www.ncbi.nlm.nih.gov/pubmed/18061785. Kligler B, Hanaway P, Cohrssen A.: Probiotics in children. Pediatr Clin North Am. 2007 Dec;54(6):94967; xi.Review.
BIBLIOGRAPHY
215
[158] http://www3.interscience.wiley.com/journal/117952031/abstract. Seksik, Philippe; Dray, Xavier; Sokol, Harry; Marteau Philippe: Is there any place for alimentary probiotics, prebiotics or synbiotics, for patients with inammatory bowel disease? Volume 52 Issue 8, Pages 906-912. Special Issue: Nutrition and Inammatory Bowel Disease Published Online: 2 Apr 2008. [159] http://www.ncbi.nlm.nih.gov/pubmed/17499603. Deshpande, Girish; Rao, Shripada; Patole, Sanjay: Probiotics for prevention of necrotising enterocolitis in preterm neonates with very low birthweight: a systematic review of randomised controlled trials. Lancet. 2007 May 12;369(9573):1614-20. Review. doi:10.1016/S01406736(07)60748-X. [160] Caarelli, Carlo; Bernasconi, Sergio: Preventing necrotising enterocolitis with probiotics. The Lancet, Volume 369, Issue 9573, 12 May 2007-18 May 2007, Pages 1578-1580. [161] http://bjsm.bmj.com/cgi/content/abstract/bjsm.2007.044628v1. Cox, Amanda J.; Pyne, David B.; Saunders, Philo U.; Fricker, Peter Allen: Oral administration of the probiotic Lactobacillus fermentum VRI-003 and mucosal immunity in endurance athletes. Br J Sports Med. Published Online First: 13 February 2008. doi:10.1136/bjsm.2007.044628. [162] http://www.ncbi.nlm.nih.gov/pubmed/18510694. Ivory, K.; Chambers, S.J.; Pin, C.; Prieto, E.: Arqus, J.L.; Nicoletti, C.: Oral delivery of Lactobacillus casei Shirota modies allergen-induced immune responses in allergic rhinitis. Volume 38 Issue 8, Pages 1282-1289. doi: 10.1111/j.1365-2222.2008.03025.x) Published Online: 28 May 2008. [163] http://www.ncbi.nlm.nih.gov/pubmed/17199093. Tamura M, Shikina T, Morihana T, Hayama M, Kajimoto O, Sakamoto A, Kajimoto Y, Watanabe O, Nonaka C, Shida K, Nanno M.: Eects of probiotics on allergic rhinitis induced by Japanese cedar pollen: randomized double-blind, placebo-controlled clinical trial. Int Arch Allergy Immunol. 2007;143(1):75-82. Epub 2006 Dec 29. [164] http://www.ncbi.nlm.nih.gov/pubmed/17083353. Xiao JZ, Kondo S, Yanagisawa N, Takahashi N, Odamaki T, Iwabuchi N, Miyaji K, Iwatsuki K, Togashi H, Enomoto K, Enomoto T.: Probiotics in the treatment of Japanese cedar pollinosis: a doubleblind placebo-controlled trial. Clin Exp Allergy. 2006 Nov;36(11):1425-35. [165] http://www.nutritionj.com/content/6/1/17. Bekkali, Noor-L-Houda; Bongers, Marloes E.J.; Van den Berg, Maartje M.; Liem, Olivia; Benninga, Marc A: The role of a probiotics mixture in the treatment of childhood constipation: a pilot study. Nutrition Journal 2007, 6:17doi:10.1186/1475-2891-6-17.
216
[166] Hickson, Mary; DSouza, Aloysius L.; Muthu, Nirmala; Rogers, Thomas R.; Want, Susan; Rajkumar, Chakravarthi; Bulpitt, Christopher J.: Use of probiotic Lactobacillus preparation to prevent diarrhoea associated with antibiotics: randomised double blind placebo controlled trial. BMJ 2007;335:80 (14 July), doi:10.1136/bmj.39231.599815.55 (published 29 June 2007). [167] http://www.bmj.com/cgi/content/extract/335/7612/171. Wilcox, Mark H.; Sandoe, Jonathan A.: Letters. Probiotics and diarrhoea. Data are not widely applicable. BMJ 2007;335:171 (28 July), doi:10.1136/bmj.39283.396285.1F. [168] http://ai.jsaweb.jp/fulltext/054040515/054040515?_index.html. Naoki Shimojo, Shuichi Suzuki, Eduardo Campos and Yoichi Kohno: Eects of Probiotics on the Immune System and Allergic Diseases; Allergology International 2005; 54: 515520 doi:10.2332/allergolint.54.515. [169] Uae set to import camels. the national 2.05.2011. http://www.thenational.ae/ news/uae-news/uae-set-to-import-camels. [170] Bekele T, Lundeheim N, and Dahlborn K. Milk production and feeding behavior in the camel (camelus dromedarius) during 4 watering regimens. J Dairy Sci, 94(3):13107, 3 2011. http://www.ncbi.nlm.nih.gov/pubmed/21338796. [171] Omer MM, Musa MT, Bakhiet MR, and Perrett L. Brucellosis in camels, cattle and humans: associations and evaluation of serological tests used for diagnosis of the disease in certain nomadic localities in sudan. Rev Sci Tech, 29(3):6639, 12 2010. http://www.ncbi.nlm.nih.gov/pubmed/21309464. [172] Rahimi E, Ameri M, Karim G, and Doosti A. Prevalence of coxiella burnetii in bulk milk samples from dairy bovine, ovine, caprine, and camel herds in iran as determined by polymerase chain reaction. Foodborne Pathog Dis, 8(2):30710, 2 2011. http://www.ncbi.nlm.nih.gov/pubmed/21091216. [173] Rodolakis A. Q fever in dairy animals. Ann N Y Acad Sci, 1166:903, 5 2009. http://www.ncbi.nlm.nih.gov/pubmed/19538267. [174] Fretz R, Schaeren W, Tanner M, and Baumgartner A. Screening of various foodstus for occurrence of coxiella burnetii in switzerland. Int J Food Microbiol, 116(3):4148, 5 2007. http://www.ncbi.nlm.nih.gov/pubmed/17434220. [175] Chang CC, Lin PS, Hou MY, Lin CC, Hung MN, Wu TM, Shu PY, Shih WY, Lin JH, Chen WC, Wu HS, and Lin LJ. Identication of risk factors of coxiella burnetii (q fever) infection in veterinary-associated populations in southern taiwan. Zoonoses Public Health, 57(7-8):e95101, 12 2010. http://www.ncbi.nlm.nih.gov/pubmed/ 19968850.
BIBLIOGRAPHY
217
[176] Bhanuprakash V, Prabhu M, Venkatesan G, Balamurugan V, Hosamani M, Pathak KM, and Singh RK. Camelpox: epidemiology, diagnosis and control measures. Expert Rev Anti Infect Ther, 8(10):1187201, 10 2010. http://www.ncbi.nlm.nih.gov/ pubmed/20954883. [177] Abu Odeh RO. Detection and genotyping of gb virus-c in dromedary camels in the united arab emirates. Vet Microbiol, 147(3-4):22630, 1 2011. http://www.ncbi. nlm.nih.gov/pubmed/20674194. [178] Konuspayeva G, Faye B, and Loiseau G. The composition of camel milk: A metaanalysis of the literature data. journal of food composition and analysis. 22 (2009):95 101, 2009. http://ipac.kacst.edu.sa/eDoc/2010/190507_1.pdf. [179] M. Franklin, S.Y. Bu, M.R. Lerner, E.A. Lancaster, D. Bellmer, D. Marlow, S.A. Lightfoot, B.H. Arjmandi, D.J. Brackett, E.A. Lucas, and B.J. Smith: Dried plum prevents bone loss in a male osteoporosis model via IGF-I and the RANK pathway. Bone, published online ahead of print, doi: doi:10.1016/j.bone.2006.05.024. [180] http://www.ajcn.org/cgi/content/abstract/84/4/936. Katherine L Tucker, Kyoko Morita, Ning Qiao, Marian T Hannan, L Adrienne Cupples, and Douglas P Kiel Colas, but not other carbonated beverages, are associated with low bone mineral density in older women: The Framingham Osteoporosis Study Am J Clin Nutr 2006 84: 936-942. [181] Chureeporn Chitchumroonchokchai, Joshua A. Bomser, Jayme E. Glamm, and Mark L. Failla: Xanthophylls and alpha-Tocopherol Decrease UVB-Induced Lipid Peroxidation and Stress Signaling in Human Lens Epithelial Cells; J. Nutr. 2004 134: 3225-3232. [182] Belsten,Jo; Institute of Food Research UK:The protective factors of fruit and vegetables; Food Technology International, issue 2001, page 10. [183] Roberfroid, Marcel B.: Functional Foods; Ingredients Health and Nutrition; January 1999. [184] Camire, Mary Ellen: Focus on bre; Ingredients Health and Nutrition; January 1999; S.27. [185] Kailasapathy, Kalla: Microencapsulation of Probiotic Bacteria: Technology and Potential Applications; Curr.Issues Intwestinal. Microbiol. (2002)3(2):39-48. [186] http://www.clinicaltrials.gov/ct/show/NCT00135031. ClinicalTrials.gov, US National Institutes of Health: Ecacy of an Encapsulated Probiotic Bidobacterium Infantis 35624 in Irritable Bowel Syndrome. [187] Sloan, Dr.Elisabeth: The next generation of American health foods; Ingredients,Health and Nutrition; Turret RAI plc; Volume one: Isue Four;Jan.1999.
218
[188] DAJ Connolly, Malachy Mc Hugh, and Olga Padilla-Zakour: The ecacy of a tart cherry juice blend in preventing the symptoms of muscle damage; Br. J. Sports Med., Jun 2006; doi:10.1136/bjsm.2005.025429. [189] Darshan S. Kelley, Reuven Rasooly, Robert A. Jacob, Adel A. Kader, and Bruce E. Mackey : Consumption of Bing Sweet Cherries Lowers Circulating Concentrations of Inammation Markers in Healthy Men and Women; J. Nutr. 2006 136: 981-986. [190] http://www.ars.usda.gov/research/projects/projects.htm?ACCN_NO=409033. Research Project: Anti-Inammatory Eects of Strawberries in Overweight/obese Individuals Project Number: 5306-51530-013-04 Start Date: Jul 01, 2005 End Date: Jun 30, 2007. [191] Ellagic acid. wikipedia. http://en.wikipedia.org/wiki/Ellagic_acid. [192] Park SH, Kim JL, Lee ES, Han SY, Gong JH, Kang MK, and Kang YH. Dietary ellagic acid attenuates oxidized ldl uptake and stimulates cholesterol eux in murine macrophages. J Nutr, 141(11):19317, 11 2011. http://www.ncbi.nlm.nih.gov/ pubmed/21940512. [193] Byk A, Onder A, Kapan M, Gms M, Firat U, Basarali MK, and Alp H. Ellagic acid ameliorates lung injury after intestinal ischemia-reperfusion. Pharmacogn Mag, 7(27):224228, 7 2011. http://www.ncbi.nlm.nih.gov/pmc/articles/ PMC3173897/?tool=pubmed. [194] Uzar E, Alp H, Cevik MU, Frat U, Evliyaoglu O, Tufek A, and Altun Y. Ellagic acid attenuates oxidative stress on brain and sciatic nerve and improves histopathology of brain in streptozotocin-induced diabetic rats. Neurol Sci, 2011. http://www.ncbi. nlm.nih.gov/pubmed/21922312. [195] Kakran M, Sahoo NG, Bao H, Pan Y, and Li L. Functionalized graphene oxide as nanocarrier for loading and delivery of ellagic acid. Curr Med Chem, 8 2011. http://www.ncbi.nlm.nih.gov/pubmed/21864287. [196] Dikmen M, Ozturk N, and Ozturk Y. The antioxidant potency of punica granatum l. fruit peel reduces cell proliferation and induces apoptosis on breast cancer. J Med Food, 8 2011. http://www.ncbi.nlm.nih.gov/pubmed/21861726. [197] http://stroke.ahajournals.org/cgi/content/abstract/39/6/1681. Larsson, Susanna C.; Mnnist, Satu; Virtanen, Mikko J.; Kontto, Jukka; Albanes, Demetrius; Virtamo, Jarmo: Coee and Tea Consumption and Risk of Stroke Subtypes in Male Smokers. Stroke. 2008;39:1681-1687; published online before print March 27 2008, doi:10.1161/STROKEAHA.107.504183.
BIBLIOGRAPHY
219
[198] http://pharmrev.aspetjournals.org/cgi/content/full/51/1/83. Fredholm, Bertil B.; Bttig, Karl; Holmn, Janet; Nehlig, Astrid and Zvartau, Edwin E.: Actions of Caeine in the Brain with Special Reference to Factors That Contribute to Its Widespread Use. Pharmacol Rev 51, 83-133. (1999). [199] http://www3.interscience.wiley.com/cgi-bin/abstract/117888868/ ABSTRACT?CRETRY=1&SRETRY=0. Tworoger, Shelley S.; Gertig, Dorota M.; Gates, Margaret A.; Hecht, Jonathan L.; Hankinson, Susan E.: Caeine, Alcohol, Smoking, and the Risk of Incident Epithelial Ovarian Cancer. Cancer. Published online ahead of print, 22 January 2008, doi: 10.1002/cncr.23275. [200] http://www.foodnavigator.com/news/ng.asp?n=69088-caffeine-memory-coffee. Stephen Daniells: Caeine could protect against memory loss. [201] http://pubs.acs.org/cgi-bin/abstract.cgi/jafcau/2008/56/i12/abs/ jf8001137.html. Seo, Han-Seok; Hirano, Misato; Shibato, Junko; Rakwal, Randeep; Hwang, In Kyeong; Masuo, Yoshinori: Eects of Coee Bean Aroma on the Rat Brain Stressed by Sleep Deprivation: A Selected Transcript- and 2D Gel-Based Proteome Analysis. J.Agric.Food Chem. 56(12),4665-4673, 2008. doi:10.1021/jf8001137. Web Release Date: June 3,. [202] http://pubs.acs.org/cgi-bin/abstract.cgi/jafcau/asap/abs/jf0710985. html. Gmez-Ruiz, Jos ngel; Leake,David S.; Ames, Jennifer M.: In Vitro Antioxidant Activity of Coee Compounds and Their Metabolites. J.Agric. Food Chem. ASAP Article 27.07.2007. [203] http://www3.interscience.wiley.com/cgi-bin/abstract/114281048/ ABSTRACT. Bravi, Francesca; Bosetti Cristina; Tavani, Alessandra; Bagnardi, Vincenzo; Gallus, Silvano; Negri, Eva; Franceschi, Silvia; La Vecchia, Carlo: Coee drinking and hepatocellular carcinoma risk: A meta-analysis. Hepatology, August 2007, 46 (2): 430-435). [204] Freedman ND, Park Y, Abnet CC, Hollenbeck AR, and Sinha R. Association of coee drinking with total and cause-specic mortality. N Engl J Med, 366:1891 1904, 5 2012. http://www.nejm.org/doi/full/10.1056/NEJMoa1112010. [205] http://www.neuroscience.bham.ac.uk/neurophysiology/teaching/ postgraduate/. University of Birmingham, Division of Neuroscience: The effect of adenosine A1 receptor modulation on brain rhythms and cognitive functions. [206] http://www3.interscience.wiley.com/journal/118961114/abstract. Maia, L.; de Mendonsa, A.: Does caeine intake protect from Alzheimers disease? European Journal of Neurology. 2002,9(4) 377. doi:10.1046/j.1468-1331.2002.00421.x. [207] http://www.ncbi.nlm.nih.gov/pubmed/18387175 http://news.bbc.co.uk/ 2/hi/health/7326839.stm. Chen X, Gawryluk JW, Wagener JF, Ghribi O,
220
CHAPTER 2. FOOD, WHAT IS IT? Geiger JD.: Caeine blocks disruption of blood brain barrier in a rabbit model of Alzheimers disease. J Neuroinammation. 2008 Apr 3;5:12. PMID: 18387175.
[208] Hamza TH, Zabetian CP, Tenesa A, Laederach A, Montimurro J, Yearout D, Kay DM, Doheny KF, Paschall J, Pugh E, Kusel VI, Collura R, Roberts J, Grith A, Samii A, Scott WK, Nutt J, Factor SA, and Payami H. Common genetic variation in the hla region is associated with late-onset sporadic parkinsons disease. Nat Genet, 42(9):7815, 9 2010. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2930111/ ?tool=pubmed. [209] Researchers explore gene-caeine interaction in parkinsons disease. national institute of neurological disorders and stroke. 9 2010. http://www.ninds.nih.gov/news_ and_events/news_articles/parkinsons_caffeine_GRIN2A.htm. [210] Trinh K, Andrews L, Krause J, Hanak T, Lee D, Gelb M, and Pallanck L. Decaeinated coee and nicotine-free tobacco provide neuroprotection in drosophila models of parkinsons disease through an nrf2-dependent mechanism. J Neurosci, 30(16):552532, 4 2010. http://www.jneurosci.org/content/30/16/5525.long. [211] http://www.bbcenter.sk/main.php?node=16681. Douglas G. Bell and Tom M. McLellan: Exercise endurance 1, 3, and 6 h after caeine ingestion in caeine users and nonusers; Defence R&D Canada-Toronto, Toronto, Ontario, Canada M3M 3B9 Journal Of Applied Physiology 10/2002 Vol. 93, Issue 4, 1227-1234, October 2002. [212] SoJung Lee, PHD, Robert Hudson, MD, PHD, Katherine Kilpatrick, MD, Terry E. Graham, PHD and Robert Ross, PHD: Caeine Ingestion Is Associated With Reductions in Glucose Uptake Independent of Obesity and Type 2 Diabetes Before and After Exercise Training; Diabetes Care 28:566-572, 2005. [213] http://jama.ama-assn.org/cgi/content/short/295/10/1135. Marilyn C. Cornelis, BSc; Ahmed El-Sohemy, PhD; Edmond K. Kabagambe, PhD; Hannia Campos: Coee, CYP1A2 Genotype, and Risk of Myocardial Infarction, PhD; JAMA, 2006;295:1135-1141.
[214] http://www.epidem.com/pt/re/epidemiology/abstract. 00001648-200609000-00007.htm;jsessionid=FTLM8mTwXJctMfHh0xdYV83SP51yDdnMZML9QzDXL 949856145!8091!-1?index=1&database=ppvovft&results=1&count=10&searchid=2&nav=search. Baylin, Ana; Hernandez-Diaz, Sonia; Kabagambe, Edmond K.; Siles, Xinia; Campos, Hannia: Transient Exposure to Coee as a Trigger of a First Nonfatal Myocardial Infarction. Epidemiology. 17(5):506-511, September 2006.
[215] http://www.epidem.com/pt/re/epidemiology/fulltext. 00001648-200609000-00004.htm;jsessionid=FTRBC5nLQnVR1B6vwxTNWpMPjnNmytVv1yzhB91Zd 949856145!8091!-1?index=1&database=ppvovft&results=1&count=10&searchid=2&nav=search. Siscovick, David S.: Triggers of Clinical Coronary Heart Disease (Commentary) Epidemiology: Volume 17(5) September 2006 pp 495-497.
BIBLIOGRAPHY
221
[216] http://jama.ama-assn.org/cgi/content/abstract/288/20/2569. Hu, Frank B.; Willett, Walter C.: Optimal Diets for Prevention of Coronary Heart Disease JAMA. 2002;288:2569-2578. No.20, November 27, 2002. [217] http://www.ncbi.nlm.nih.gov/pubmed/18574045. Heidemann C, Schulze MB, Franco OH, van Dam RM, Mantzoros CS, Hu FB: Dietary patterns and risk of mortality from cardiovascular disease, cancer, and all causes in a prospective cohort of women. Circulation. 2008 Jul 15;118(3):230-7. Epub 2008 Jun 23. [218] McCusker, Rachel R; Goldberg, Bruce A; Cone, Edward J: Caeine Content of Energy Drinks, Carbonated Sodas, and Other Beverages; Journal of Analytical Toxicology, Volume 30, Number 2, March 2006, pp. 112-114(3). [219] http://www.eatright.org/ada/files/PIIS0002822308000679NP.pdf. Nutrition and lifestyle for a healthy pregnancy outcome; J AM Diet Assoc 2008;108:553-561. Doi:10.1016/j.jada.2008.01.030. [220] http://www.bmj.com/cgi/content/full/337/nov03_2/a2332. Konje, Justin C.; Cade, Janet E. And the CARE Study Group: Maternal caeine intake during pregnancy and risk of fetal growth restriction: a large prospective observational study. BMJ. 2008 Nov 3;337:a2332. doi: 10.1136/bmj.a2332. [221] Seifert SM, SchaechterJL, Hershorin ER, and Lipshultz SE. Health eects of energy drinks on children, adolescents, and young adults. Pediatrics, 127:511528, 2011. http://pediatrics.aappublications.org/cgi/content/abstract/peds. 2009-3592v1. [222] Bigard AX. Risks of energy drinks in youths. Arch Pediatr, 17(11):162531, 11 2010. http://www.ncbi.nlm.nih.gov/pubmed/20926266. [223] http://www.food.gov.uk/news/newsarchive/2008/nov/caffeinenov08. Pregnant women advised to limit caeine consumption. 03.11.2008. FSA
[224] http://europa.eu.int/smartapi/cgi/sga_doc?smartapi!celexapi!prod!CELEXnumdoc&lg=E European Union: Commission Directive 2002/67/EC of 18 July 2002 on the labelling of foodstus containing quinine, and of foodstus containing caeine. [225] EU Scientic Committee on Food. SCF. Opinion on additional information on "energy" drinks. 05.03.2003. 3 2003. http://ec.europa.eu/food/fs/sc/scf/out169_ en.pdf. [226] Efsa adopts opinion on two ingredients commonly used in some energy drinks. 12.02.2009. 2 2009. http://www.efsa.europa.eu/en/press/news/ans090212.htm. [227] Supplement news: German american technologies jetfuel - product review. http: //www.supplementnews.org/German_American_Technologies/JetFuel.
222
[228] Consumer Reports Health.org. Does the government regulate supplements? http://www.consumerreports.org/health/free-highlights/ manage-your-health/supplements_questions.htm?AFFID=HNARSIC5. [229] Reissig CJ, Strain EC, and Griths RR. Caeinated energy drinks-a growing problem. Drug Alcohol Depend, 99(1-3):110, 1 2009. http://www.ncbi.nlm.nih.gov/ pmc/articles/PMC2735818/?tool=pubmed. [230] Howland J, Rohsenow DJ, Arnedt JT, Bliss CA, Hunt SK, Calise TV, Heeren T, Winter M, Littleeld C, and Gottlieb DJ. The acute eects of caeinated versus non-caeinated alcoholic beverage on driving performance and attention/reaction time. Addiction, 106(2):33541, 2 2011. http://onlinelibrary.wiley.com/doi/ 10.1111/j.1360-0443.2010.03219.x/abstract. [231] Health Canada. Healthy living: Caeine. 3 2010. http://www.hc-sc.gc.ca/hl-vs/ iyh-vsv/food-aliment/caffeine-eng.php. [232] Nawrot P, Jordan S, Eastwood J, Rotstein J, Hugenholtz A, and Feeley M. Eects of caeine on human health. Food Addit Contam, 20(1):130, 1 2003. http://www. ncbi.nlm.nih.gov/pubmed/12519715. [233] Health Canada. Sources of caeine. 3 2010. http://www.hc-sc.gc.ca/fn-an/ securit/addit/caf/food-caf-aliments-eng.php. [234] http://www.cmaj.ca/cgi/rapidpdf/cmaj.100953v1.pdf. Hebert P, Stanbrook M, MacDonald N: Caeinating children and youth. CMAJ 2010. July 26. DOI:10.1503/cmaj.100953. [235] http://www.getyourfixx.com/. Fixxtreme: Micro shots. [236] http://www.bfr.bund.de/cm/245/health_risks_of_excessive_energy_shot_ intake.pdf. Health risks of excessive energy shot intake. BfR Opinion No. 001/2010, 2 December 2009.
[237] http://www.nutraingredients.com/Regulation/EC-Energy-drinks-don-t-need-warning-l Nutraingredients: EC: Energy drinks dont need warning labels. 20.07.2010. [238] http://www.ncbi.nlm.nih.gov/pubmed/19954894. Thombs DL, OMara RJ, Tsukamoto M, Rossheim ME, Weiler RM, Merves ML, Goldberger: BA: Event-level analyses of energy drink consumption and alcohol intoxication in bar patrons. Addict Behav. 2010 Apr;35(4):325-30. Epub 2009 Nov 24. [239] http://www.blackwell-synergy.com/doi/abs/10.1111/j.1530-0277.2006. 00070.x. Sionaldo Eduardo Ferreira, Marco Tlio de Mello, Sabine Pompia, Maria Lucia Oliveira de Souza-Formigoni: Eects of Energy Drink Ingestion on Alcohol Intoxication; Alcoholism: Clinical and Experimental Research Vol. 30 Issue 4 Page 598 April 2006 doi:10.1111/j.1530-0277.2006.00070.x.
BIBLIOGRAPHY
223
[240] http://ppc.uiowa.edu/Driving-Assessment/2001/Summaries/Driving% 20Assessment%20Papers/12_Parkes_Andrew.htm. A.M. Parkes, B.F. Sexton, S. Burton, H.L. Hu, J.A. Shaw and B.P. Daggy: AN EVALUATION OF THE EFFECTS OF A FUNCTIONAL ENERGY DRINK ON POST-LUNCH AND EARLY EVENING DRIVING PERFORMANCE. [241] http://www.gsk.com/products/consumer_healthcare/dw_lucozade.htm. sumer Healthcare Lukozade. Con-
[242] http://www.bfr.bund.de/cm/245/new_human_data_on_the_assessment_of_ energy_drinks.pdf. German Federal Risk Institute: New Human Data on the Assessment of Energy Drinks BfR Information No. 016/2008, 13 March 2008. [243] http://www.americanheart.org/presenter.jhtml?identifier=3050874. American Heart Association: Energy drinks may pose risks for people with high blood pressure, heart disease. AHA News 11/06/2007. [244] http://www.reutershealth.com/archive/2008/08/15/eline/links/ 20080815elin007.html. DeSciscio, Paolo; Prabhu, Anisha; Worthley, Matthew; Roberts-Thomson, Ross; Sanders, Prashanthan; Willoughby, Scott: Acute Eects of Red Bull on Platelet and Endothelial Function. Heart, Lung and Circulation. Volume 17, Supplement 3, 2008, Pages S23-S24 Doi:10.1016/j.hlc.2008.05.055. [245] Kotke, Kelly; Gehrke, Kim: Sports and Energy Drinks. Journal of Renal Nutrition. Volume 18, Issue 2, March 2008, Pages e1-e8. doi:10.1053/j.jrn.2007.10.034. [246] http://en.wikipedia.org/wiki/Coffee_varieties. Wikipedia, The Free Enzyclopedia: Coe varieties. [247] Urgert R, Essed N, van der Weg G, Kosmeijer-Schuil TG, and Katan MB: Separate eects of the coee diterpenes cafestol and kahweol on serum lipids and liver aminotransferases; Am. J. Clinical Nutrition, Feb 1997; 65: 519 - 524. [248] http://www.emedicine.com/neuro/topic666.htm. Suleman A, Lorenzo N: Caffeine; eMedicine. [249] http://jama.ama-assn.org/cgi/content/abstract/283/20/2674. Webster Ross G, Abbott R D, Petrovitch H, Morens D, Grandinetti A, Ko-Hui Tung, Tanner C M, Masaki K H, Blanchette P L, Curb J D, Popper J S, White L R.:Association of Coee and Caeine Intake With the Risk of Parkinson Disease; JAMA 2000;283:2674-9. [250] http://www.ninds.nih.gov/funding/research/parkinsonsweb/drug_ summaries/caffeine.htm. National Institute of Neurological Disorders and Stroke: Caeine Information Summary; Clinical Trial/Epidemiological Evidence in Human PD.
224
[251] Salazar-Martinez E, Willett, W C, Ascherio A, Manson Jo A, Leitzmann MF, Stampfer M J, and Hu F B:Coe Consumption and Risk for Type 2 Diabetes Melitus. Ann Intern Med. Jan 2004; 140:1-8. [252] Battram D S, Arthur R, Weekes A, and Graham T E: The Glucose Intolerance Induced by Caeinated Coee Ingestion Is Less Pronounced than That Due to Alkaloid Caeine in Men J. Nutr., May 1, 2006; 136(5): 1276 - 1280. [253] http://www.ncbi.nlm.nih.gov/pubmed/15998896?dopt=AbstractPlus. van Dam, R.M.; Hu, F.H.: Coee consumption and risk of type 2 diabetes: a systematic review. JAMA 2005 Jul 6;294(1):97-104. [254] http://www.rmlg.ulg.ac.be/index.php?page=resume?num_id= 1634&SessionID=874e2f808d08726e285591bac21d65d9&langue=FR. Legrand, D.; Scheen A.J.: La consommation rgulire de caf rduirait le risque de diabte de type 2 Rev Med Liege,62(9),554-559, 2007. [255] http://care.diabetesjournals.org/cgi/content/extract/31/2/221. Lane, James D.; Feinglos, Mark N.; Surwit, Richard S.: Caeine Increases Ambulatory Glucose and Postprandial Responses in Coee Drinkers With Type 2 Diabetes. Diabetes Care 31:221-222, 2008. DOI: 10.2337/dc07-1112. [256] http://jncicancerspectrum.oxfordjournals.org/cgi/content/abstract/ jnci;97/4/282?fulltext=Coffee&searchid=QID_NOT_SET. Michels KB, Willet WC, Fuchs CS, and Giovannucci E: Coee, Tea, and Caeine Consumption and incidence of Colon and Rectal Cancer, J Natl Cancer Inst 2005; 97:282-292. [257] http://jncicancerspectrum.oxfordjournals.org/cgi/content/abstract/ jnci;97/4/293?fulltext=Coffee&searchid=QID_NOT_SET. Inoue M, Yoshimi I, Sobue T, Tsugane S: Inuence of Coee Drinking on Subsequent Risk of Hepatocellular Carcinoma: a Prospective Study in Japan; Journal of the National Cancer Institute, Vol. 97, No. 4, 293-300, February 16, 2005 DOI: 10.1093/jnci/dji040. [258] http://www.nature.com/ejcn/journal/v61/n2/full/1602495a.html. van Gelder, MB.: Coee consumption is inversely associated with cognitive decline in elderly European men: the FINE Study. European Journal of Clinical Nutrition (2007) 61, 226-232. doi:10.1038/sj.ejcn.1602495; published online 16 August 2006. [259] http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?holding=npg&cmd= Retrieve&db=PubMed&listuids=8920174&dopt=Abstract. Riedel WJ, Jolles J (1996). Cognition enhancers in age-related cognitive decline. Drugs Aging 8, 245-274. [260] http://dx.doi.org/10.1007/BF02246949. Jarvis MJ. Does caeine intake enhance absolute levels of cognitive performance? Psychopharmacology (Berlin) 110, 45-52. (1993).
BIBLIOGRAPHY
225
[261] Johnson-Kozlow M, Kritz-Silverstein D, Barrett-Connor E, Morton D (2002). Coee consumption and cognitive function among older adults. Am J Epidemiol 156, 842850. [262] http://dx.doi.org/10.1038/sj.bjp.0705185. DallIgna OP, Porciuncula LO, Souza DO, Cunha RA, Lara DR (2003). Neuroprotection by caeine and adenosine A2A receptor blockade of beta-amyloid neurotoxicity. Br J Pharmacol 138, 12071209. [263] http://dx.doi.org/10.1007/s002130051109. Kopf SR, Melani A, Pedata F, Pepeu G (1999). Adenosine and memory storage: eect of A(1) and A(2) receptor antagonists. Psychopharmacology (Berlin) 146, 214-219. [264] http://dx.doi.org/10.1021/jf0257547. Nardini M, Cirillo E, Natella F, Scaccini C (2002). Absorption of phenolic acids in humans after coee consumption. J Agric Food Chem 50, 5735-5741. [265] http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?holding=npg&cmd= Retrieve&db=PubMed&listuids=10681270&dopt=Abstract. Christen, Y.: Oxidative stress and Alzheimer disease. Am J Clin Nutr 71, 621S-629S.(2000). [266] Lachance MP, Marlowe C and Waddell WJ Autoradiographic disposition of (1methyl-14C)- and (2-14C)caeine in mice. Toxicol Appl Pharmacol 71: 237-241 (1983). [267] Ikeda GJ, Sapienza PP, McGinnis ML, Bragg LE, Walsh JJ and Collins TF : Blood levels of caeine and results of fetal examination after oral administration of caeine to pregnant rats. J Appl Toxicol 2: 307-314 (1982). [268] Kimmel, C.A.; Kimmel, G.L., White, C.G.; Grafton, T.F.; Young, J.F. and Nelson, C.J. : Blood ow changes and conceptual development in pregnant rats in response to caeine. Fundam Appl Toxicol 4: 240-247 (1984). [269] Khanna N.N. and Somani S.M. Maternal coee drinking and unusually high concentrations of caeine in the newborn. J Toxicol Clin Toxicol 22: 473-483 (1984). [270] http://en.wikipedia.org/wiki/Gunpowder_tea. Wikipedia: Gunpowder tea. [271] http://www.ncbi.nlm.nih.gov/pubmed/19651563. Leyer GJ, Li S, Mubasher ME, Reifer C, Ouwehand AC: Probiotic Eects on Cold and Inuenza-Like Symptom Incidence and Duration in Children. Pediatrics.2009; 124: 172-179. [272] Talwalkar, A. and Kailasapathy, K. (2003): Eect of microencapsulation on oxygen toxicity in probiotic bacteria; The Australian Journal of dairy Technology 58(1), 36-39.
226
[273] Sunil Sazawal, Girish Hiremath, Usha Dhingra, Pooja Malik, Saikat Deb and Robert E Black: Ecacy of probiotics in prevention of acute diarrhoea: a meta-analysis of masked, randomised, placebo-controlled trials; The Lancet Infectious Diseases 2006; 6:374-382 DOI:10.1016/S1473-3099(06)70495-9. [274] Diop, Laurent; Guillou, Sonia; Durand, Henri: Probiotic food supplement reduces stress-induced gastrointestinal symptoms in volunteers: a double-blind, placebocontrolled, randomized trial. Nutrition Research (Elsevier). Volume 28, Issue 1, January 2008, Pages 1-5 . Doi:101016/j.nutres.2007.10.001. [275] http://www.gutflora.org/hs-news.php?id=159. Gut Flora: Experimental treatment for acute pancreatitis leads to unexpectedly high death rate. Negative outcome probiotics in acute pancreatitis Press release- 23/01/2008. [276] Food Technology: Food Tech, 1994, Vol. 48, pp. 61-65). [277] Krahl,Gisela:Mood Food das Kochbuch fr Lust und Laune;Deutscher Taschenbuch Verlag, Mnchen; 1998. [278] Erlenspiel,Johannes: HPLC mit elektrochemischer Detektion zur Bestimmung von Neurotransmittern; GIT Laborfachzeitschrift 43.Jahrgang 1/99, Seite 26. [279] http://irmm.jrc.ec.europa.eu/html/activities/cocoa_butter_ calculation_toolbox/. Foreign fats in chocolate-Cocoa butter calculation (CoCal) toolboxes. [280] aid Presseinfo Nr. 26 (2000) pg 5. [281] Zomer E, Owen A, Magliano DJ, Liew D, and Reid CM. The eectiveness and cost eectiveness of dark chocolate consumption as prevention therapy in people at high risk of cardiovascular disease: best case scenario analysis using a markov model. BMJ, 344:e3657, 5 2012. http://www.bmj.com/cgi/pmidlookup?view=long&pmid= 22653982. [282] Gardener H, Rundek T, Wright CB, Elkind MS, and Sacco RL. Dietary sodium and risk of stroke in the northern manhattan study. stroke. 2012 apr 12. http: //www.ncbi.nlm.nih.gov/pubmed/22499576. [283] de Vrese, Michael: Clinical Nutrition vol 24, issue 4, pp481-91. [284] Jeerson T, Jones MA, Doshi P, Del Mar CB, Heneghan CJ, Hama R, and Thompson MJ. Neuraminidase inhibitors for preventing and treating inuenza in healthy adults and children (review). The Cochrane Library, 1, 1 2012. http://www. thecochranelibrary.com/details/file/1440293/CD008965.html.
BIBLIOGRAPHY
227
[285] Jeerson T, Jones M, Doshi P, and Del Mar C. Neuraminidase inhibitors for preventing and treating inuenza in healthy adults: systematic review and meta-analysis. BMJ, 339:b5106, 12 2009. http://www.bmj.com/content/339/bmj.b5106?view= long&pmid=19995812. [286] Lasserson T and Tovey D. Neuraminidase inhibitors for inuenza: methods change, principles dont (editorial). the cochrane library 2012 (18 january). 1 2012. http://www.thecochranelibrary.com/details/editorial/1442857/ Neuraminidase-inhibitors-for-influenza-methods-change-principles-dont. html. [287] Cochrane editorial unit: Methodological expectations of cochrane intervention reviews (mecir). http://www.editorial-unit.cochrane.org/meci. [288] http://www3.interscience.wiley.com/journal/117881842/abstract. Olesen, Pelle Thonning; Olsen, Anja; Frandsen, Henrik; Frederiksen, Kirsten; Overvad, Kim;Tjonneland, Anne: Epidemiology: Acrylamide exposure and incidence of breast cancer among menopausal women in the Danish Diet, Cancer and Health Study. International Journal of Cancer. Published online January 8 2008. Doi:10.1002/ijc.23359. [289] http://cebp.aacrjournals.org/cgi/content/abstract/16/11/ 2304?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&fulltext= acrylamide&searchid=1&FIRSTINDEX=0&resourcetype=HWCIT. Hogervorst, Janneke G.; Schouten, Leo J.; Konings, Erik J.; Goldbohm, R. Alexandra; van den Brandt, Piet A. : A Prospective Study of Dietary Acrylamide Intake and the Risk of Endometrial, Ovarian, and Breast Cancer. Cancer Epidemiology Biomarkers & Prevention 16, 2304-2313, November 1, 2007. doi: 10.1158/1055-9965.EPI-07-0581. [290] http://www.slv.se/templates/SLV_NewsPage.aspx?id=14750&epslanguage= EN-GB. Press release: HEATOX project completed - brings new pieces to the Acrylamide Puzzle. Newsarchieves 26.11.2007. [291] www.cfsan.fda.gov/-dms/acrydata : Exploratory Data on Acrylamide in Food.Center for Food Safety and Applied Nutrition. December 4, 2002. [292] www.munlv.nrw.de/sites/arbeitsbereiche/verbraucherschutz: Acrylamid in Lebensmitteln. [293] Gokmen, Vural; Senyuva, Hamide Z.: Acrylamide formation is prevented by divalent cations during the Maillard reaction; Food Chemistry; doi: 10.1016/j.foodchem.2006.08.011. [294] Ou, Shiyi; Lin, Oilin; Zhang, Yuping; Huang, Caihuan; Sun, Xi; Fu, Liang: Reduction of acrylamide formation by selected agents in fried potato crisps
228
CHAPTER 2. FOOD, WHAT IS IT? on industrial scale. Innovative Food Science & Emerging Technologies doi: 10.1016/j.ifset.2007.06.008.
[295] http://dx.doi.org/10.1016/j.foodchem.2007.07.013. Mestdagh, F.; Maertens, J.; Cucu, T.; Delporte, K.; Van Peteghem, C.; De Meulenaer, B.: Impact of additives to lower the formation of acrylamide in a potato model system through pH reduction and other mechanism. Food Chemistry s 1 March 2008, Volume 107, Issue 1, Pages 26-31. [296] http://dx.doi.org/ 10.1016/j.foodchem.2006.08.011. Gkmen, Vural; enyuva, Hamide Z.: Acrylamide formation is prevented by divalent cations during the Maillard reaction. Food Chemistry. Vol 103 issue 1 2007 pages 196-203. [297] http://www.efsa.europa.eu/science/contam/contam_statements/902_it. html. EFSA: Statement of the CONTAM Panel to a summary report on Acrylamide in food of the 64th meeting of the joint FAO/WHO expert committee on food additives. Adopted on 19 April 2005. [298] http://pubs.acs.org/cgi-bin/abstract.cgi/jafcau/asap/abs/jf060328x. html. Mei Yin Low, Georgios Koutsidis, Jane K. Parker, J. Stephen Elmore, Andrew T. Dodson, and Donald S. Mottram: Eect of Citric Acid and Glycine Addition on Acrylamide and Flavor in a Potato Model System; J. Agric. Food Chem. Web Release Date: 06-Jul-2006. [299] Achim Claus, Georg M. Weisz, Andreas Schieber, Reinhold Carle: Pyrolytic acrylamide formation from puried wheat gluten and gluten-supplemented wheat bread rolls. Molecular Nutrition & Food Researche, Volume 50, Isue 1 Pages 67-93 Published Online 30 Nov. 2005. [300] http://dx.doi.org/ 10.1016/j.foodres.2010.01.013. Capuano, E.; Oliviero, T.; Acar, O.C.; Gokmen, V.; Fogliano V.: Lipid oxidation promotes acrylamide formation in fat-rich model systems. Food Research International. Doi:10.1016/j.foodres.2010.01.013. [301] http://www.ciaa.eu/documents/brochures/toolbox%20rev11%20nov% 202007final.pdf. The Confederation of Food and Drinks Industries: CIAA Acrylamide Toolbox Rev 11.
The
[302] http://ec.europa.eu/food/food/chemicalsafety/contaminants/ciaa_ acrylamide_toolbox.pdf. CIAA Toolbox has been updated since 16 October 2006. [303] http://ec.europa.eu/food/food/chemicalsafety/contaminants/acrylamide_ en.htm. Food Safety-From Farm to Fork: Food Contaminants-Acrylamide.
BIBLIOGRAPHY
229
[304] http://www3.interscience.wiley.com/cgi-bin/abstract/117923641/ ABSTRACT?CRETRY=1&SRETRY=0. Burch, Rachel S.; Trzesicka, Agnieszka; Clarke, Matthew; Elmore, J. Stephen; Webber, Nina: The eects of low-temperature potato storage and washing and soaking pre-treatments on the acrylamide content of French fries. Journal of the Science of Food and Agriculture. Published online ahead of print, doi: 10.1002/jsfa.3179. [305] http://www.ncbi.nlm.nih.gov/pubmed/16438318. Jackson LS, Al-Taher F: Eects of consumer food preparation on acrylamide formation. Adv Exp Med Biol 2005 ; 561:447-65. [306] Cummins, E. Butler , F., Gormley R. and Brunton N. (2006). Simulation of the dietary exposure to acrylamide from French fries for Irish consumers. International conference paper, Foodsim2006, 15-17 June 2006, Naples , Italy pp 137-142. [307] Zhang, Yu; Zhang, Ying: Eect of natural antioxidants on kinetic behavior of acrylamide formation and elimination in low-moisture asparagine-glucose model system.Journal of Food Engineering (Elsevier), Ahead of print, 2 August 2007, doi: 10.1016/j.jfoodeng.2007.07.013. [308] http://pubs.acs.org/cgi-bin/abstract.cgi/jafcau/2007/55/i02/abs/ jf062568i.html. Zhang, Yu; Chen, Jie; Zhang, Xiaoling; Wu, Xiaoqin; Zhang, Ying: Addition of Antioxidant of Bamboo Leaves (AOB) Eectively Reduces Acrylamide Formation in Potato Crisps and French Fries. J. Agric. Food Chem.; 2007; 55(2) pp 523-528; (Article) DOI 10.1021/jf062568i. [309] http://www.ncbi.nlm.nih.gov/pubmed/17452738. Uribarri, Jaime; Cai, Weijing; Peppa, Melpomeni; Goodman, Susan; Ferrucci, Luigi; Striker, Gary and Vlassara, Helen: Circulating Glycotoxins and Dietary Advanced Glycation Endproducts: Two Links to Inammatory Response, Oxidative Stress, and Aging J. Gerontol. A Biol. Sci. Med. Sci. 2007 62: 427-433. [310] http://www.ncbi.nlm.nih.gov/pubmed/11694852. Wautier, J.L. And Guillausseau P.J.: Advanced glycation endproducts, their receptors and diabetic Angiopathy. Diabetes Metab (Paris) 2001, 27, 535-542. [311] http://cebp.aacrjournals.org/cgi/content/abstract/15/8/1555. Marta Rossi, Eva Negri, Renato Talamini, Cristina Bosetti, Maria Parpinel, Patrizia Gnagnarella, Silvia Franceschi, Luigino Dal Maso, Maurizio Montella, Attilio Giacosa, and Carlo La Vecchia: Flavonoids and Colorectal Cancer in Italy Cancer Epidemiol Biomarkers Prev 2006 15: 1555-1558. [312] Weiguang Yi, Casimir C. Akoh, Joan Fischer and Gerard Krewer: Eects of phenolic compounds in blueberries and muscadine grapes on HepG2 cell viability and apoptosis. Food Research International Volume 39, Issue 5 June 2006, pages 628-638.
230
[313] Tahiri, Imane; Makhlouf, Joseph; Paquin, Paul and Fliss, Ismail: Inactivation of food spoilage bacteria and Escherichia coli O157:H7 in phosphate buer and orange juice using dynamic high pressure. Food Research International Volume 39, Issue 1, January 2006, Pages 98-105. [314] http://www.fda.gov/Food/ScienceResearch/ResearchAreas/ SafePracticesforFoodProcesses/ucm101662.htm. U. S. Food and Drug Administration Center for Food Safety and Applied Nutrition:Kinetics of Microbial Inactivation for Alternative Food Processing Technologies Pulsed Electric Fields, June 2, 2000. [315] http://www3.interscience.wiley.com/cgi-bin/abstract/113494176/ ABSTRACT?CRETRY=1&SRETRY=0. Oszmianski J.; Wolniak, M.; Wojdylo, A. and Wawer, I.: Comparative study of polyphenolic content and antiradical activity of cloudy and clear apple juices; Journal of the Science of Food and Agriculture doi: 10.1002/jsfa.2707. [316] http://adc.bmjjournals.com/cgi/content/full/79/1/2. Hoekstra, J.H.: Toddler diarrhoea: more a nutritional disorder than a disease Arch. Dis. Child., July 1, 1998; 79(1): 2 - 5. [317] http://pubs.acs.org/cgibin/abstract.cgi/jafcau/2006/54/i05/abs/ jf058171g.html DOI: 10.1021/jf058171g. Shela Gorinstein, Abraham Caspi, Imanuel Libman, Henry Tzvi Lerner, Dejian Huang, Hanna Leontowicz, Maria Leontowicz, Zev Tashma, Elena Katrich, Shengbao Feng, and Simon Trakhtenberg: Red Grapefruit Positively Inuences Serum Triglyceride Level in Patients Suering from Coronary Atherosclerosis: Studies in Vitro and in Humans J. Agric. Food Chem.; 2006; 54(5) pp 1887- 1892. [318] Kun Gao, Susanne M. Henning, Yantao Niu, Arthur A. Youssean, Navindra P. Seeram, Anlong Xu and David Heber: The citrus avonoid naringenin stimulates DNA repair in prostate cancer cells; The Journal of Nutritional Biochemistry, Vol. 17, pp. 89-95 doi:10.1016/j.jnutbio.2005.05.009. [319] Zenon Zduczyk, Jerzy Jukiewicz and Isabel Estrella: Cecal parameters of rats fed diets containing grapefruit polyphenols and inulin as single supplements or in a combination; Nutrition (doi: 10.1016/j.nut.2006.05.010). [320] Adams, Michael R.; Golden, Deborah L.; Chen, Haiying; Register, Thomas C. and Gugger, Eric T.: A Diet Rich in Green and Yellow Vegetables Inhibits Atherosclerosis in Mice; J. Nutr. 2006 136: 1886-1889. [321] http://www.unav.es/preventiva/ultimas_publis/arcmed_d05002171.pdf. Alvaro Alonso, MD, MPH, PhD; Juan J. Beunza, MD; Maira Bes-Rastrollo, PharmD; Raquel M. Pajares, BS; Miguel Angel Martinez-Gonzalez, MD, MPH, PhD: Vegetable
BIBLIOGRAPHY
231
protein and ber from cereal are inversely associated with the risk of hypertension in a Spanish cohort: Elsevier Editorial System(tm) for Archives of Medical Research Manuscript Draft Manuscript Number: ARCMED-D-05-00217R1. [322] http://archinte.ama-assn.org/cgi/content/abstract/166/1/79. Paul Elliott; Jeremiah Stamler; Alan R. Dyer; Lawrence Appel; Barbara Dennis; Hugo Kesteloot; Hirotsugu Ueshima; Akira Okayama; Queenie Chan; Daniel B. Garside; Beifan Zhou: Association Between Protein Intake and Blood Pressure: The INTERMAP Study Arch Intern Med. 2006;166:79-87. [323] http://www.nature.com/msb/journal/v4/n1/full/msb4100190.html. J Martin, Yulan Wang, Norbert Sprenger, Ivan K S Yap, Torbjrn Lundstedt, Per Lek, Serge Rezzi, Ziad Ramadan, Peter van Bladeren, Laurent B Fay, Sunil Kochhar, John C Lindon, Elaine Holmes, Jeremy K Nicholson: Probiotic modulation of symbiotic gut microbial-host metabolic interactions in a humanized microbiome mouse model. Molecular Systems Biology. 4 Article number: 157. Published on-line ahead of print 15 January 2008. doi:10.1038/msb4100190. [324] http://pubs.acs.org/subscribe/journals/jprobs/6/i11/pdf/ 1107chocolate.pdf. Perkel Jerey M.: A molecular picture of chocoholics. Journal of Proteome Research, Vol. 6 No.111, 2007. [325] Kurokawa, Y.; Aoki, S.;Matsushima, Y.: Takamura, N.;Imazawa, T.; Hayashi, Y.: Dose-Response Studies on the Carcinogenicity of Potassium Bromate in F344 Rats After Long-Term Oral Administration, 1986, J. Natl. Cancer Inst. 77:977-982. [326] http://www.mazzei.net/publications/ozone/Paper11_ioawc99b.pdf. RICE, R.G.; OVERBECK P.K: Ozone Treatment of Small Water Systems. 24.08.1999. [327] http://www.epa.gov/safewater/mcl.html#mcls. EPA: List of Drinking Water Contaminants & MCLs. [328] http://tvscripts.edt.reuters.com/2008-03-19/232df844.html. Women nd a way to indulge their passion for chocolate this Easter without gaining an ounce. [329] FAO Corporate Document Repository: The Global Cassava Development Strategy: An Overview of Cassava in Sub-Sahara African. [330] http://www.fao.org/ag/ags/agsi/starch41.htm. Satin, Morton: Functional Properties of Starches; FAO Agro-Industries and Post-Harvest Management Service. [331] http://en.wikipedia.org/wiki/Amylopectine. Wikipedia, The free enzyklopedia: Amylopectin. [332] http://www.wild.de/wild/opencms/en/ingredient_solutions/hottest_WILD_ ingredients/fruit_up.html. Fruit Up - The Natural Fruit Sweetener with the Low Glycemic Index Information from Wild.
232
[333] Yoshida M, McKeown NM, Rogers G, Meigs JB, Saltzman E, DAgostino R, Jacques PF.: Surrogate markers of insulin resistance are associated with consumption of sugar-sweetened drinks and fruit juice in midlle and older-aged adults. The Journal of Nutrition, September 2007, 137: 2121-2127. [334] http://www.ajcn.org/cgi/content/abstract/89/4/1037. Fung, Teresa T.; Malik, Vasanti; Rexrode, Kathryn M.; Manson, JoAnn E.; Willett, Walter C. Hu, Frank B.: Sweetened beverage consumption and risk of coronary heart disease in women. American Journal of Clinical Nutrition. April 2009, Volume 89, Pages 1037-1042, doi:10.3945/ajcn.2008.27140. [335] http://pubs.acs.org/cgi-bin/abstract.cgi/jafcau/asap/abs/jf071892q. html. Ghanta, Srijani; Banerjee, Anindita; Poddar, Avijit; Chattopadhyay, Sharmila: Oxidative DNA Damage Preventive Activity and Antioxidant Potential of Stevia rebaudiana (Bertoni) Bertoni, a Natural Sweetener. Journal of Agricultural and Food Chemistry Published online ahead of print, ASAP Article,Received June 26, 2007, doi: 10.1021/jf071892q. [336] http://cspinet.org/new/pdf/stevia-report_final-8-14-08.pdf. Kobylewski1, Sarah; Eckhert, Curtis D.: Toxicology of Rebaudioside A: A Review. University of Kalifornien, Los Angeles. August 2008. [337] http://www.cspinet.org/new/200808281.html. CSPI: Lab Tests Point to Problems with Trendy New Stevia Sweetener. CSPI Urges More Testing Before Stevia Extract is Used in Food, Drinks. 28.08.2008. [338] http://en.wikipedia.org/wiki/Stevia. Wikipedia: Stevia. [339] http://www.ianrpubs.unl.edu/epublic/pages/publicationD.jsp? publicationId=609. Jones, Georgia: Stevia (HTML). NebGuide: University of Nebraska-Lincoln Institute of Agriculture and Natural Resources. September 2006. Retrieved on 2007-05-04. [340] http://www.fda.gov/FDAC/features/1999/699_sugar.html. FDA: Sugar Substitutes: Americans Opt for Sweetness and Lite. FDA Consumer magazine. NovemberDecember 1999. [341] http://www.fda.gov/ora/fiars/ora_import_ia4506.html. FDA Import Alert: IA #45-06, Revised 2/2/96, Attachment revised 4/24/08. [342] http://www.cspinet.org/new/200812181.html. CSPI: FDA Issues Midnight Goahead for Potentially Harmful Stevia Sweetener Statement of CSPI Executive Director Michael F. Jacobson. [343] http://www.food.gov.uk/multimedia/pdfs/stevioside.pdf. European Commission: Scientic Committee on Food CS/NF/STEV/3 Final 17 June 1999: Opinion on Stevia Rebaudiana Bertoni plants and leaves.
BIBLIOGRAPHY
233
[344] http://www.legco.gov.hk/yr01-02/english/sec/library/0102fs04e.pdf. Simon, L.I.: Fact Sheet: Stevioside. Legislative Council Secretariat Research and Library Services Division 27 March 2002. [345] http://whqlibdoc.who.int/publications/2006/9241660546_eng.pdf. Benford, D.J.; DiNovi, M., Schlatter, J. (2006). Safety Evaluation of Certain Food Additives: Steviol Glycosides (PDF - 18 MB). WHO Food Additives Series (World Health Organization Joint FAO/WHO Expert Committee on Food Additives (JECFA)) 54: 140. [346] http://cat.inist.fr/?aModele=afficheN&cpsidt=2715813. Toskulkao, C.; Chaturat, L.; Temcharoen, P.; Glinsukon, T.: Acute toxicity of stevioside, a natural sweetener, and its metabolite, steviol, in several animal species. Drug and chemical toxicology 1997, vol. 20, nr 1-2, pp. 31-44. [347] http://www.ncbi.nlm.nih.gov/pubmed/9347659. Klongpanichpak S, Temcharoen P, Toskulkao C, Apibal S, Glinsukon T.: Lack of mutagenicity of stevioside and steviol in Salmonella typhimurium TA 98 and TA 100. J Med Assoc Thai. 1997 Sep;80 Suppl 1:S121-8. [348] http://www.ncbi.nlm.nih.gov/pubmed/18556105. Brusick D.J.: A critical review of the genetic toxicity of steviol and steviol glycosides. Food Chem Toxicol. 2008 Jul;46 Suppl 7:S83-91. Epub 2008 May 16. [349] http://pubs.acs.org/cgi-bin/abstract.cgi/jafcau/1983/31/i02/f-pdf/f_ jf00116a056.pdf. Chang, Shin S.; Cook, Joanne M.: Stability studies of stevioside and rebaudioside A in carbonated beverages. Journal of Agricultural and Food Chemistry. 1983; 31(2) Pages 409 - 412; Doi: 10.1021/jf00116a056. [350] Clos, J.F.; DuBois, G.E.; Prakash, I.: Photostability of Rebaudioside A and Stevioside in Beverages Journal of Agricultural and Food Chemistry Published online ahead of print, ASAP Article, doi: 10.1021/jf801343e. [351] http://www.glycemicindex.com/. The Glycimic Index and the GI Database. [352] http://www.ajcn.org/cgi/content/full/76/1/5. Foster-Powell, Kaye; Holt, Susanna H.A. and Brand-Miller, Janette C.: International table of glycemic index and glycemic load values: 2002 American Journal of Clinical Nutrition, Vol. 76, No. 1, 5-56, 2002. [353] http://www.ajcn.org/cgi/content/full/77/4/994. Mendosa, Rick:Letter to the Editor. Glycemic load values American Journal of Clinical Nutrition, Vol. 77, No. 4, 994, April 2003. [354] http://archinte.ama-assn.org/cgi/content/short/166/14/1466. McMillanPrice, Joanna; Petocz, Peter; Atkinson, Fiona; ONeill, Katleen; Samman, Samir;
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CHAPTER 2. FOOD, WHAT IS IT? Steinbeck, Katherine; Caterson, Ian; Brand-Miller, Jennie: Comparison of 4 diets of varying glycemic load on weight loss and cardiovascular risk reduction in overweight and obese young adults: a randomised controlled trial. Arch Intern Med. 2006;166:1466-1475.
[355] http://archinte.ama-assn.org/cgi/content/extract/167/2/206. Clifton, Peter: Glycemic Load and Cardiovascular Risk Archives of Internal Medicine. 2007;167:206. [356] http://jama.ama-assn.org/cgi/content/abstract/297/19/2092. Ebbeling,Clara B.; Leidig,Michael M.; Feldman, Henry A.; Lovesky, Margaret M.; Ludwig, David S. : Eects of a Low-Glycemic Load vs Low-Fat Diet in Obese Young Adults JAMA.2007;297:2092-2102. [357] http://www.ajcn.org/cgi/content/abstract/84/4/807. Moses, Robert G., Luebcke, Megan; Davis, Warren, S.; Coleman, Keith J.; Tapsell, Linda C.; Petocz, Peter and Brand-Miller, Jennie C.: Eect of a low-glycemic-index diet during pregnancy on obstetric outcomes. Am. J. Clin. Nutr. 2006;84:807-812. [358] http://www.ajcn.org/cgi/content/abstract/84/1/70. Hu, Youqing;Block, Gladys; Norkus, Edward P.; Morrow, Jason D.; Dietrich, Marion and Hudes, Mark: Relations of glycemic index and glycemic load with plasma oxidative stress markers. American Journal of Clinical Nutrition, Vol. 84, No. 1, 70-76, July 2006. [359] http://www.ajcn.org/cgi/content/abstract/87/3/627. Barclay, Alan W.; Petocz, Peter; McMillan-Price, Joanna; Flood, Victoria M.; Prvan, Tania; Mitchell, Paul; Brand-Miller, Jennie C.: Glycemic index, glycemic load, and chronic disease risk,a meta-analysis of observational studies. Am. J. Clinical Nutrition, Mar 2008; 87: 627 - 637. [360] http://www.glycemicindex.com/. University of Sydney: Glycemic Index and GI Database. [361] http://en.wikipedia.org/wiki/Glycemic_index. Wikipedia: Glycemic index. [362] http://www.aaccnet.org/meetings/99mtg/abstracts/acabc59.htm. A. XU, Z. H. Qi, M. E. Embuscado, and D. Gottneid. Cerestar USA, Inc., Hammond, IN 46320: Comparative study of orange oil encapsulation using dierent carriers; 1999 AACCAnnual Meeting Oct. 31-Nov.3. [363] Khn, Janina; Considine, Thrse; and Singh, Harjinder: Interactions of Milk Proteins and Volatile Flavour Compounds: Implications in the Development of Protein Foods Journal of Food Science Volume 71 Page R72- June/July 2006 doi:10.1111/j.1750-3841.2006.00051.x Volume 71 Issue 5.
BIBLIOGRAPHY
235
[364] Stephan Drusch: Sugar beet pectin: A novel emulsifying wall component for microencapsulation of lipophilic food ingredients by spray-drying. Food hydrocolloids (doi: 10.1016/j.foodhyd.2006.08.007). [365] http://www.peanutbutterlovers.com/nutrition/index.html. Peanut advisory board: Peanut butter lovers.com.; Nutrition; Trans Fats. [366] http://onlinestore.smucker.com/natural.cfm. Peanut butter mixer. [367] http://jama.ama-assn.org/cgi/content/abstract/288/20/2554?lookupType= volpage&vol=288&fp=2554&view=short. Jiang, Rui; Manson, JoAnn E.; Stampfer, Meir J.; Liu, Simin; Willett, Walter C.; Hu, Frank B.:Nut and Peanut Butter Consumption and Risk of Type 2 Diabetes in Women JAMA.2002;288:2554-2560.No. 20, November 27, 2002. [368] http://en.wikipedia.org/wiki/Glucosinolates. Wikipedia: Glucosinolate. [369] http://www.ncbi.nlm.nih.gov/pubmed/18806090. Furniss, C.S.; Bennett, R.N.; Bacon, J.R.; LeGall, G.; Mithen, R.F.: Polyamine metabolism and transforming growth factor-beta signaling are aected in Caco-2 cells by dierentially cooked broccoli extracts. J Nutr. 2008 Oct;138(10):1840-5. [370] http://www.ncbi.nlm.nih.gov/pubmed/12032331. Fahey JW, Haristoy X, Dolan PM, Kensler TW, Scholtus I, Stephenson KK, Talalay P, Lozniewski A.: Sulforaphane inhibits extracellular, intracellular, and antibiotic-resistant strains of Helicobacter pylori and prevents benzo[a]pyrene-induced stomach tumors. Proc Natl Acad Sci U S A. 2002 May 28;99(11):7610-5. [371] Canene-Adams, K.; Lindshield, B. L.; Jeery, E. H. and Erdman, J.W.: Combinations of tomato and broccoli enhance antitumor activity in Dunning R3327-H prostate adenocarcinomas; Cancer Research January 15, 2007, Volume 67, Pages 836-843. doi: 10.1158/0008-5472.CAN-06-3462. [372] http://pubs.rsc.org/en/Content/ArticleLanding/2010/FO/c0fo00110d. Lai R-H, Miller MJ, Jeery E: Glucoraphanin hydrolysis by microbiota in the rat cecum results in sulforaphane absorption. Food & Function, 2010; 1, 161-166. Doi: 10.1039/C0FO00110D. [373] http://www.ncbi.nlm.nih.gov/pubmed/20635307. Prasad S, Phromnoi K, Yadav VR, Chaturvedi MM, Aggarwal BB: Targeting inammatory pathways by avonoids for prevention and treatment of cancer. Planta Med. 2010 Aug;76(11):1044-63. Epub 2010 Jul 15. [374] http://www.ncbi.nlm.nih.gov/pubmed/21060289. Kelsey NA, Wilkins HM, Linseman DA: Nutraceutical antioxidants as novel neuroprotective agents. Molecules. 2010 Nov 3;15(11):7792-814.
236
[375] http://www.ncbi.nlm.nih.gov/pubmed/21061051. Greco T, Fiskum G: Brain mitochondria from rats treated with sulforaphane are resistant to redox-regulated permeability transition. J Bioenerg Biomembr. 2010 Nov 9. [376] http://www.ncbi.nlm.nih.gov/pubmed/20956097. Sharma C, Sadrieh L, Priyani A, Ahmed M, Hassan AH, Hussain A: Anti-carcinogenic eects of sulforaphane in association with its apoptosis-inducing and anti-inammatory properties in human cervical cancer cells. Cancer Epidemiol. 2010 Oct 16. [377] http://www.ncbi.nlm.nih.gov/pubmed/20833254. Kalpana Deepa Priya D, Gayathri R, Gunassekaran GR, Sakthisekaran D: Protective role of sulforaphane against oxidative stress mediated mitochondrial dysfunction induced by benzo(a)pyrene in female Swiss albino mice. Pulm Pharmacol Ther. 2010 Sep 15. [378] http://www.ncbi.nlm.nih.gov/pubmed/20810543. Ding Y, Paonessa JD, Randall KL, Argoti D, Chen L, Vouros P, Zhang Y: Sulforaphane inhibits 4aminobiphenyl-induced DNA damage in bladder cells and tissues. Carcinogenesis. 2010 Nov;31(11):1999-2003. [379] http://www.ncbi.nlm.nih.gov/pubmed/20737283. Gupta SC, Kim JH, Prasad S, Aggarwal BB: Regulation of survival, proliferation, invasion, angiogenesis, and metastasis of tumor cells through modulation of inammatory pathways by nutraceuticals. Cancer Metastasis Rev. 2010 Sep;29(3):405-34. [380] http://www.ncbi.nlm.nih.gov/pubmed/20726001. Abdull Razis AF, Iori R, Ioannides C: The natural chemopreventive phytochemical R-sulforaphane is a far more potent inducer of the carcinogen-detoxifying enzyme systems in rat liver and lung than the S-isomer. Int J Cancer. 2010 Aug 19. [381] http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&dopt= Citation&list_uids=15006906. Etminan, M.; Takkouche, B.; Caamano-Isorna F.: The role of tomato products and lycopene in the prevention of prostate cancer: a meta-analysis of observational studies. Cancer Epidemiol Biomarkers Prev. 2004 Mar;13(3):340-5. [382] Mossine, Valeri et al.: Interaction of Tomato Lycopene and Ketosamine Against Rat Prostate Tumorigenesis. Cancer Research. June 68 (11). [383] http://jn.nutrition.org/cgi/content/abstract/138/1/49. Silke Schwarz, Ute C. Obermller-Jevic, Eva Hellmis, Winfried Koch, Gnther Jacobi, and Hans-Konrad Biesalski: Lycopene Inhibits Disease Progression in Patients with Benign Prostate Hyperplasia. J. Nutr. 2008 138: 49-53. [384] http://www.dietandcancerreport.org/er/. World Cancer Research Funds: Food, Nutrition, Physical Activity, and the Prevention of Cancer. Second Report. 2007.
BIBLIOGRAPHY
237
[385] http://www.aicr.org/site/News2?abbr=pr_&page=NewsArticle&id=12920. Statement From the American Institute for Cancer Research (AICR) on Meat Institute Press Release. The American Institute for Cancer research. [386] http://www.wcrf-uk.org/audience/media/press_release.php?recid=71. World Cancer Research Fund: Parents urged to take ham o menu. 17 August 2009. [387] http://www.dietandcancerreport.org/downloads/Second_Expert_Report.pdf. World Cancer Research Fund and American Institute for Cancer Research: Food, Nutrition, Physical Activity, and the Prevention of Cancer: A Global Perspective. [388] http://www.food.gov.uk/news/newsarchive/2009/aug/lunch. Food Standards Agency: Parents urged to take ham o menu. 17 August 2009. [389] http://www.hsph.harvard.edu/cancer/cancers/prostate/riskfactors/ expert_lifestyle.htm. Giovannucci, Edward: Lifestyle changes to reduce the risk of prostate cancer. Harvard Center for Cancer Prevention. [390] http://jap.physiology.org/cgi/content/abstract/00089.2009v1. Gonzalez, Richard R.; Cheuvront, Samuel N.; Montain, Scott J.; Goodman, Daniel A.; Blanchard, Laurie A.; Larry G. Berglund, Michael N. Sawka: Expanded prediction equations of human sweat loss and water needs. Journal of Applied Physiology, 2009; DOI: 10.1152/japplphysiol.00089.2009. [391] http://www.hsph.harvard.edu/nutritionsource/pyramids.html. School of Public Health: Food Pyramids. Harvard
[392] http://www.mypyramid.gov/. USDA: Steps to a Healthier You. My Pyramid. [393] http://www.health.gov/dietaryguidelines/dga2005/document/default.htm. US Department of Health and Human Services: Dietary Guidelines for Americans 2005. [394] U.S. Department of Agriculture. U.S. Department of Health and Human Services. Dietary guidelines for americans, 2010 (released 1/31/11). http://www.cnpp.usda. gov/Publications/DietaryGuidelines/2010/PolicyDoc/PolicyDoc.pdf. [395] Flegal KM, Carroll MD, Ogden CL, and Curtin LR. Prevalence and trends in obesity among u.s. adults, 1999-2008. JAMA, 303(3):235241, 2010. http://www.ncbi.nlm. nih.gov/pubmed/20071471. [396] http://jn.nutrition.org/cgi/content/abstract/138/1/5. Lichtenstein, AH, Rasmussen, H,Yu, WW, Epstein, S, Russell, RM.: Modied MyPyramid for Older Adults. Journal of Nutrition. 2008 (January); 138 (1). [397] http://www.oldwayspt.org/. Oldways: The Asian, Latin, Mediterranean, and vegetarian pyramids.
238
[398] http://ec.europa.eu/research/index.cfm?pg=newsalert&lg=en&year= 2008&na=na-030408. European Commission: Smoking genes? European scientists discover the rst case of a genetic dependence to nicotine. News Alert Brussels, 3 April 2008. [399] http://www.ncbi.nlm.nih.gov/pubmed/20418890. The Tobacco and Genetics Consortium: Genome-wide meta-analyses identify multiple loci associated with smoking behavior. Nature Genetics Published online: 25 April 2010. Doi:10.1038/ng.571. [400] http://www.ncbi.nlm.nih.gov/pubmed/20418888. Thorgeirsson et al.: Sequence variants at CHRNB3-CHRNA6 and CYP2A6 aect smoking behavior. Nature Genetics. 25 April 2010. Doi:10.1038/ng.573. [401] http://www.ncbi.nlm.nih.gov/pubmed/20418889. Liu et al: Meta-analysis and imputation renes the association of 15q25 with smoking quantity. Nature Genetics. 25 April 2010. Doi:10.1038/ng.572. [402] http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed. 1000216. Chapman, Simon; MacKenzie, Ross: The Global Research Neglect of Unassisted Smoking Cessation: Causes and Consequences. PLoS Med 7(2), February 9, 2010: e1000216. doi:10.1371/journal.pmed.1000216. [403] Xiao D, Huang X, Yang S, and Zhang Lia. Antenatal nicotine induces heightened oxidative stress and vascular dysfunction in rat ospring. Br J Pharmacol, 7 2011. http://www.ncbi.nlm.nih.gov/pubmed/21777225. [404] Lim R and Sobey CG. Maternal nicotine exposure and fetal programming of vascular oxidative stress in adult ospring. Br J Pharmacol, 2011. http://www.ncbi.nlm. nih.gov/pubmed/21585345. [405] Bruin JE, Gerstein HC, and Holloway AC. Long-term consequences of fetal and neonatal nicotine exposure: a critical review. Toxicol Sci, 116(2):36474, 8 2010. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2905398/?tool=pubmed. [406] Jha P, Ramasundarahettige C, Landsman V, Rostron B, Thun M, Anderson RN, McAfee T, and Peto R. 21st-century hazards of smoking and benets of cessation in the united states. N Engl J Med, 368(4):34150, 1 2013. http://www.nejm.org/ doi/full/10.1056/NEJMsa1211128. [407] Thun MJ, Carter BD, Feskanich D, Freedman ND, Prentice R, Lopez AD, Hartge P, and Gapstur SM. 50-year trends in smoking-related mortality in the united states. N Engl J Med, 368(64):35164, 1 2013. http://www.nejm.org/doi/full/10.1056/ NEJMsa1211127.
BIBLIOGRAPHY
239
[408] Schroeder SA. New evidence that cigarette smoking remains the most important health hazard. N Engl J Med, 368(4):38990, 1 2013. http://www.nejm.org/doi/ full/10.1056/NEJMe1213751.
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Chapter 3 Obesity
3.1
3.1.1
Green Tea and weight reduction

Nestl and CocaCola advertising weight control ENVIGA [1]
Servane Rudelle and colleagues 2007 studied the eect on weight control of a beverage containing Epigallocathechin gallate EGCG, green tea and caeine. The authors found an increase in 24-hour energy expenditure of 100 kcal/d on account of this beverage. The weight gain of the American population is slightly less than 1 kg/yr, which represents a median excess energy of 15 kcal/d, and because energy is stored with 50% eciency, a negative energy balance of 100 kcal/d would be sucient to prevent weight gain in most of the U.S. population The authors conclude that consuming this type of beverage regularly together with exercise, may be helpful in weight control. Based on this study Nestl and CocaCola launched its ENVIGA product with the advertising adds: Benets: "burn more calories" "drink negative". [2]
The Center for Science in the Public Interest CSPI Says "Calorie Burning" and Weight Loss Claims Illegal [3] The Federal Trade Commission (FTC) should take enforcement action against Coca-Cola and Nestl for their unlawful deceptive advertising for Enviga, their green-tea-avored diet soda, according to a complaint lled with the agency on May 2007 by the nonprot Center for Science in the Public Interest (CSPI). At issue is the companies claim that Enviga burns more calories than the ve calories per can it delivers, which, CSPI says, strongly implies weight loss. 241
242 Obesity control reducing energy density of foods [4]
CHAPTER 3. OBESITY
Julia Ello-Martin and colleagues 2007 assessed as reduction diet the reduction of fat in comparison to the reduction of fat together with higher intake of fruits and vegetables during 1 year. For both groups no goals for energy or fat intake were assigned; the participants could eat ad libitum. The low fat and high intake of fruits and vegetables group, had a lower dietary energy density,a higher weight loss (7,9 kg/1 y), and less hunger than did the low fat group (6,4 kg/1y) with variation of +- 0,9 kg for both. The authors concluded that the reduction of dietary energy density, combining increased fruit and vegetable intakes with decreased fat intake, is an eective strategy for managing body weight. Commentary of OurFood Reducing fat in dairy products, convenience foods and fried products such as french fryies sh sticks, croissants, forget about oily dressings and sugar-glucose energy bars to sweeten your calories, adding fruits and vegetables to your menu is the right way. Instead of roasting lean beef or chicken breast in your pan using plenty of oil, you can cook it using water and zero oil. Gourmet add some wine instead of water. If you add a tomato salad on vinegar you meet the Juilia Ello-Martin specications. Gradual reduction of fat in foods for children increases acceptance of lower energy intake [5] Children obesity is liked to high energy intake. Olsen et al 2011 suggests that gradually reducing the amount of fat in foods for children may reduce energy consumption without reducing taste preference or liking. The authors found that reducing fat content of familiar foods, such as macaroni and cheese, pudding, chocolate milk and regular milk. Children aged between four and six, were given such foods in high-fat and in low-fat versions. The study reports that liking and consumption by weight did not dier between highfat and low-fat meals and the total energy intake was 59% lower for the low-fat meals. Reducing fat content is therefore being suggested by the authors to lower energy consumption of children. To increase the acceptance of lower fat in familiar traditional foods, the reduction should be processed gradually. Reducing the use of fats and oils in the kitchen, and choosing low-fat ready to eat foods at the grocery may do a lot to avoid overweight and coronary diseases. Low-fat receipts and how to avoid fat spreads and oily sauces my be found at http://www.ourfoodnews.com/Healthy_Recipes
3.1. GREEN TEA AND WEIGHT REDUCTION
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3.1.2
Eat less at breakfast to reduce total daily intake [6]
Feeding experiments demonstrated that high breakfast energy leads to greater overall intake. Instead of comparing people which eat much with people which eat less for breakfast, the study of Schusdziarr an colleagues focused on individuals. The researchers looked at the eect of high caloric breakfast days compared with days of low food intake or even skipping breakfast at all. The result of the study of Schusdziarra and colleagues opposes the general opinion that breakfast should be copious. A high caloric breakfast is a remnant of days when the society depended on physical activity, which cannot be sustained in the actual sedentary society. Increasing breakfast energy was associated with greater overall intake, and reduced breakfast energy intake is associated with lower total daily intake, and may be a good weight control strategy. Television viewing and eating behaviour of children [7] Television viewing was associated with a cluster of unhealthy eating behaviors in US adolescents Television viewing was inversely related to intake of fruit and vegetables and positively related to intake of candy and fast food and skipping breakfast School-age: Brug et al 2012 inform that the ENERGY-Project was a survey among 10-12 year old children conducted in seven European countries. 25.8% and 5.4% of boys, and 21.8% and 4.1% of girls were overweight (including obese) and obese (according to International Obesity Task Force criteria), respectively. Anti-obesity strategies are urgently needed in Greece, Hungary, Slovenia and Spain which present the high rates of obese children. [8] Preschool-age:Van Stralen et al 2012 determined overweight indices in European preschoolers (4-7 years). Analyses of six European determined a prevalence of overweight and obesity of 8% to 30% and 1% to 13%, respectively, with highest rates in Spain and Greece. Positive associations between sedentary behaviours and overweight indices were found. Children of parents with high body mass index or low socioeconomic status were at increased risk of overweight/obesity. [9] Childhood overweight (in 4- to 6-year-old children) is inuenced by physical activity, sedentary behaviour and eating behaviour. Gender and ethnicity were not associated with sedentary behaviour Preschoolers were more physically active as well as sedentary on weekdays. Watching television was associated with a higher consumption of snacks and sweet beverages. De Craemer et al. 2012 recommend strategies aiming to inuence energy balance-related behaviours in preschoolers focused on both genders, all ethnic groups and social status. The authors recommend to reduce sedentary behaviour during the week,
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increase physical activity at weekend, reduce television viewing and limit consumption of snacks and sweet beverages. [10] Breakfast and religiosity [11] Consumption of fruits, vegetables and sweets, physical inactivity, tooth brushing, ghting and bullying others in both genders were not related to religiosity, however, an inverse association to health-risk behaviour such as smoking, drunkenness, cannabis use, having breakfast, soft drinks consumption was determined in a study of Pitel et al.2012. Three meals a day and better lifestyle may reduce body weight [12] Obesity in children aged 12.8 0.9 years was found at Turkey schools was found by Dndar and Oz 2012 to be 10.3%. The authors stress that the percentage of obese children who skipped breakfast was found to be higher than that in the group that consumed 3 meals a day regularly, and practicing less sport, watching TV over 3 hour a day were more prone to obesity than those who spent less time at screen. The authors advise parents to monitor the lifestyle of their children. Obesity in Arabian countries is a problem of serious health concern [13] According to an article in Kuwait Times May 2012, obesity level of people living in Kuwait has reached 42 percent, 65 percent do not practice any form of physical activity and 53 percent of young people spend over three hours in front of the television. Healthcare professionals warn of diseases that accompany obesity such as diabetes, heart disease and stroke. They recommend daily exercise, reduction of calories consumption and renouncing to unhealthy fast food. Bad eating habits such as burger, fries pizza or shawarma sandwich are increasing. Fatty foods, hydrogenated fats and dishes that have no nutritional value are in abundance here. Healthy nutrition should be include in the curriculum of schools. There should be more education and information given to the whole family; especially mothers. Exercise must be supported by healthy eating habits. Long-term consumption of green tea [14] According to Yung-hsi and colleagues 200, long-term consumption of green tea may decrease the incidence of obesity and, perhaps, green tea components such as EGCG may be useful for treating obesity. The authors point out, however, that oolong tea was found to reduce obesity in mice, despite having much less EGCG that green tea does. The authors calls for studies with puried components to identify the active components of tea.
3.2. YOGHURT SNACKS AND THEIR IMPACT ON APPETITE CONTROL Oolong tea [15]
245
According to Han and colleagues 1999 oolong tea has anti-obesity eects in high-fat diettreated mice which might result from an enhancing eect of caeine isolated from oolong tea The auithors suggest that oolong tea may be eective in treatment of obesity and fatty liver caused by a high-fat diet. Eect of tea catechins on obesity [16] Murase and colleagues 2002 studied the eects of long-term feeding with tea catechins, which are naturally occurring polyphenolic compounds widely consumed in Asian countries, on the development of obesity in mice. They found that the anti-obesity eects of tea catechins might be caused by the stimulation of the hepatic lipid metabolism They suggest that long-term consumption of tea catechins may help to suppress diet-induced obesity, and it may reduce the risk of coronary diseases.
3.2
Yoghurt snacks and their impact on appetite control
[17] Douglas et al. 2012 report that having afternoon snacks inuence appetite-control and eating initiation in women. Regardless of protein content, snacks reduced hunger and delayed the demand for dinner by up to 120 minutes compared to persons having no snacks. High protein snacks, such as Greek yoghurt containing 24 g protein, induce higher fullness, longer satiety and led to the latest request time of dinner compared to low protein snacks. Remarkably, people consuming snacks before dinner eat less and do not compensate the 160 kcal of the snack eaten in this study. In men yoghurt snacks had the greatest suppressive eect on appetite. Hunger rating was lower after the intake of yoghurt than cheese, milk and water. Postprandial responses of hormones did not dier, however alanine and isoleucine concentrations were higher after the intake of yoghurt than cheese and milk. Dougkas et al. 2012 concluded that dairy snacks reduced appetite and lunch intake, with yoghurt presenting the best results. [18] Fibre-enriched drinking yoghurt more satiating than the other snacks [19] Almiron-Roig et al. 2009 caution that recommending small portions of low energy foods for weight management can result in rapid return of hunger or an increase in the next meal size. To avoid this, the authors recommend to increase the satiating capacities of low energy foods. They report that bre-enriched drinking yoghurt oered a higher satiety compared to a regular yoghurt, banana, crackers and water in decreasing order of their eect.
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Low-energy-density foods with soluble bre present high satiating eect [20] According to Perrigue yoghurt beverages and liquid orange juice signicantly suppressed appetite and promoted satiety relatively to not-liquid ones. Yoghurt beverages had greater satiating power and reduced energy intakes at lunch compared to orange juice. The addition of soluble bre, such as inulin, made the satiating power of low-energy-density yoghurt comparable to that of high-energy-density yoghurt. Deterioration in nutrient quality of Australian yoghurts [21] Walker et al. 2010 deplore the deterioration in nutrient quality of dairy snacks such as yoghurt, fromage frais or dairy desserts in Melbourne, Australia. Between 2005 and 2008 the median packet size rose signicantly. In yoghurts, energy and total fat content increased while protein decreased. Sugar content of "reduced-fat" yoghurts increased turning its energy content similar to many "full-fat" yoghurts. Sugar was found in levels up to 29 g/100 g of yoghurt. The proportion of "full-fat" products rose from 36% to 46%. Walker concluded that yoghurts and dairy desserts are becoming "less healthy", high in saturated fat, salt and sugar content. Reduction of abdominal fat in humans [22] Long-term feeding of tea catechins suppressed body fat accumulation in high-fat dietinduced obesity in mice, and that their eects might be attributed, at least in part, to the activation of hepatic lipid metabolism. Consecutive intake of tea catechins (588 mg/day) reduced body fat, especially abdominal fat in humans. These results demonstrate that intake of tea catechins is benecial for body fat accumulation.
3.3
Obesity may be inuenced by a B12 conjugate hormone developed for oral administration
[23] The hPYY(336) has been identied to achieve weight-loss having a role in regulating appetite and energy. PYY hormone concentration in blood serum are lower in obese people during fasting and after eating, compared with lean persons. Fazen et al 2011 used recent developments of the insulin oral delivery system as transport vehicle for PYY hormone. Added to chewing gums or oral tablets taken after a meal the B12-hPYY(336) conjugates described by the authors may suppress hunger for three to four hours to bridge the time gap between the meals. Synthesis of hPYY hormone [24] Kitagawa et al 1990 described the synthesis of the peptide synthetic hPYY was as active as synthetic porcine PYY in terms of the eects on systemic arterial blood pressure, and
3.3. OBESITY MAY BE INFLUENCED BY A B12 CONJUGATE HORMONE DEVELOPED FOR ORAL ADMINISTRATION splanchnic blood ow. Vitamin B12 cotransport system for nPYY hormone [25]
247
In a 1998 review Russell-Jones describes an uptake system to overcome the hurdle of the oral administration of proteins and peptides to avoid troublesome injection. The oral route causes degradation of these products by enzymes of the digestive tract, and intestine walls provide a poor uptake by the body. In this system vitamin B12 is used to cotransport peptides and proteins through the intestine to the circulation. This technology may also be used to transport nanoparticles loaded with peptides or proteins to protect them from digestive enzymes. Recent developments of vitamin B12 cotransport of bioactive substances [26] Petrus, Fairchild and Doyle describe further advances on researches focused on oral peptide/protein delivery by the dietary uptake pathway for vitamin B(12), which included the delivery of erythropoietin, granulocyte-colony-stimulating factor, luteinizing-hormonereleasing hormone, and insulin. Epigallocathechin gallate (EGCG) and fat-reduction eect [27] Wolfram and colleagues 2005 examined the antiobesity eect of tea epigallocatechin gallate (EGCG), in mice fed with high-fat diet. They found that food intake was not aected but faeces energy content was slightly increased by EGCG, indicating a reduced food digestibility and thus reduced long-term energy absorption, and conclude that d ietary EGCG attenuated diet-induced body fat accretion in mice. EGCG apparently promoted fat oxidation, but its fat-reducing eect could be entirely explained by its eect in reducing diet digestibility. TEAVIGO [28] Wolfram and colleagues 2005, in a study from DSM Nutritional Products Ltd found that epigallocatechin gallate (EGCG), in a pure form, present in the commercial product TEAVIGO inhibited adipocyte dierentiation in vitro, and concluded that supplementation with EGCG, abolishes diet-induced obesity, and should be considered as a valuable natural treatment option for obesity. Antimitogenic eect of green tea epigallocatechin gallate [29] Pei-Fang Hung and colleagues 2005 investigated the pathways of EGCGs modulation of the mitogenesis(cell- division) of preadipocytes. They found that EGCG inhibited preadipocyte 3T3-L1 proliferation.
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The authors demonstrate the ERK- and Cdk2-dependent antimitogenic eects of EGCG, and that EGCG was more eective than epicatechin, epicatechin gallate, and epigallocatechin in changing the mitogenic signals. The signal of EGCG in reducing growth of 3T3-L1 preadipocytes diered from that of 3T3 broblasts. Hung and colleagues conclude that reduction of obesity caused by EGCG may be linked to the inhibition of fat-cells division.
3.3.1
Gut bacteria implicated in obesity and metalolic disorders [30]
According to Zupancic et al. 26 species of bacteria in the human gut microbiota are linked to obesity and related metabolic syndrome. The scientists used deep pyrosequencing of bar-coded PCR amplicons from the V1-V3 region of the 16S rRNA gene to identify bacteria entangled in this process. The metabolic syndrome include insulin resistance, high blood sugar levels, increased blood pressure, high cholesterol, diabetes, cardiovascular disease and stroke. Controlling such gut bacteria may become interesting to reduce the impact of obesity and metabolic syndrome and chronic diseasses using medication, diet or lifestyle changes, say the authors. In this study it was found that patients with metabolic syndrome with elevated serum markers associated with inammation presented low levels of bacteria groups known to have anti-inammatory properties. All persons have one of three dierent communities of interacting gut bacteria, which, however, are not associated with obesity or metabolic syndrome. Only the 26 species of bacteria with the 16SrNA gene were found to be linked to obesity and metabolic complications. In this study it also was found that people with regular contact with livestock, such as farmers and their wives, had bacterial communities dominated by genus Prevotella such as Prevotella copri generally found in cattle and sheep and in type 2 diabetes which is associated with compositional changes in the intestinal microbiota mostly apparent at phylum and class levels. [31] Such dysbiosis or microbial imbalance on or within the body may cause obesity and its metabolic complications. Dysbiosis is also associated associated with dierent illnesses, such as inammatory bowel disease [32] and chronic fatigue syndrome [33].
3.3.2
EGCG inhibits proliferation of fat-cels and induces autodestruction of fat-cells [34]
Green tea catechins have been shown to promote loss of body fat and to inhibit growth of many cancer cell types by inducing apoptosis. Ji Lin and colleagues 2005 studied the
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inuence of epigallocatechin gallate (EGCG) on adipocytes to inhibit adipogenesis and induce apoptosis using mouse 3T3-L1 preadipocytes and mature adipocytes. The researchers found that EGCG had no eect on either viability or apoptosis of preconuent preadipocytes. EGCG also did not aect viability of mature adipocytes; however, EGCG increased apoptosis in mature adipocytes and inhibited lipid accumulation in maturing preadipocytes. The authors concluded that EGCG can act directly to inhibit dierentiation of preadipocytes and to induce apoptosis of mature adipocytes and, thus, could be an important adjunct in the treatment of obesity.
EGCG downregulates the fat hormone Resistin expression by reducing the amounts of phospho-ERK1/2 proteins [35] Resistin is a hormone discovered in 2001 and is a response of leucocytes to inammation and participates in the inammatory response, and this may be the link to insulin resistnce. According to Hang-Seng Liu and colleagues 2006 resistin is an adipocyte-specic secretory hormone that can cause insulin resistance and decrease adipocyte dierentiation, and epigallocatechin gallate (EGCG) of green tea, have been reported to act against obesity and diabetes. The study suggest that EGCG may modulate the distribution of resistin protein between the intracellular and extracellular compartments. EGCG reduced the amounts of phospho-extracellular signal-related kinase-1/2 proteins (phospho-ERK1/2 proteins). The researchers conclude that EGCG downregulates Resistin expression via a pathway that is dependent on the ERK pathway.
Resistin controversy [36] Most all ndings (many times elucidated under the same experimental conditions) reported by groups opposing the resistin link theory are the exact opposite from what those groups who support the theopry have observed. The idea that resistin links obesity to type 2 diabetes mellitus is now under even more scrutiny as recent investigations have conrmed a rather vast expression of resistin in many tissues rather than those only characteristic of obesity such as adipocytes. With nearly as many scientists against this theory as those scientists who seem to support it, the likelihood that resistin will ever be viewed as the key node linking obesity to type 2 diabetes mellitus in the near future is very low. The very extent to which these two views oppose each other raises questions about the synchrony and methodology used in these respective groups which resulted in polar opposite results.
250 Insucient data of EGCG human trials [37]
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Wolgang, Wang an Thielecke 2006 write that studies conducted with human subjects report reduced body weight and body fat, as well as increased fat oxidation and thermogenesis related to green tea. However, according to the authors, there is still a need for welldesigned and controlled clinical studies to validate the studies. According to Wolfgang and colleagues specic eects of EGCG of green tea on obesity should be investigated in human trials. Tea-catechins together with swimming reduces obesity gain by 20 percent [3] The eects of long-term intake of tea catechins in combination with regular exercise on the development of obesity in mice was investigated by Murase and colleagues 2006. TeaCatechins intake in combination with swimming exercise suppressed high fat diet-induced body-weight gain by 18 and 22%, respectively, compared to Exercise and tea-Catechins intake on their own. These results indicate that intake of tea Catechins, together with regular exercise helps to reduce diet-induced obesity. This eect might be attributed, at least in part, to the activation of whole-body energy metabolism.
3.3.3
Hope for diabetes, obesity, and cancer treatment using the hedgehog signalling pathway
The signalling pathway, acting downstream of the hedgehog protein enables muscle cells and brown fat cells to absorb sugars without relying on insulin. Substances that selectively activate the signalling pathway could thus be utilized in the treatment of diabetes and obesity. [38] Diabetes, obesity and cancer rely on dysregulated intracellular signalling with altered metabolic state. Teperino et al 23012 identied a cilium-dependent Smo-Ca2+Ampk axis that triggers rapid Warburg-like metabolic reprogramming. The Smo modulators can uncouple the Smo-Ampk axis from signaling and identify cyclopamine capable to regulate hedgehog signalling. Hedgehog was initially identied as an important protein for embryonic development. Hedgehog also inuences replication, migration and specialisation of cells and may be important in cancer physiology. It also inhibits the formation of "bad" white adipose tissue. Hedgehog may therefore targeted to ght cancer, diabetes and adiposity. An hedgehog inhibitor, Vismodegib, for treatment of cancer presented serious side eects, such as weight loss and muscle cramps. The authors explain these cramps and suggest and present a solution using the new hedgehog signalling pathway that is independent of the activation of transcription factors and genes known thus far. Cells control their primary energy metabolism, including the glucose, fatty acid and amino acid metabolisms, via this
3.3. OBESITY MAY BE INFLUENCED BY A B12 CONJUGATE HORMONE DEVELOPED FOR ORAL ADMINISTRATION pathway.
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The authors write that Smo plays an important role. Smo is a cell membrane protein which controls the known signalling pathway through transcription factors, as well as the new pathway via a much faster AMP-kinase enzyme and calcium dependent pathway. Smo is activated if hedgehog binds to a specialised receptor in the cell membrane. Calcium ows through the membrane channels into the cell and activates calcium-dependent enzymes that in turn activate the AMP-kinase. The cell can rapidly absorb large quantities of glucose using the AMP-kinase and other enzymes, rebalancing anabolism and catabolism. The new hedgehog signalling pathway prompts does not use mitochondria, but the less ecient lactic acid fermentation, a process with which cancer cells use to acquire their energy without oxygen, the Warburg eect. Activation of the hedgehog and Smo-calcium/AMP-kinase signalling pathways of the AMPkinase and increased catabolism explains weight loss and the inux of calcium into muscle cells leads to instant contraction triggering the cramps of the patients. The scientists nd that cells dramatically increase the glucose quantity they can absorb, without relying on insulin. Mice that had previously been treated with the classic hedgehog inhibitor cyclopamine had correspondingly lower blood glucose than untreated animals. Cyclopamine increases the glucose absorption, but only in the brown adipose tissue and various types of muscle tissue, increasing body temperature. A substance which activate the Smo-calcium/AMP-kinase hedgehog signalling pathway may become a treatment of obesit and diabettes type-1 and type-2.
3.3.4
The PTEN gene may oer a way to treat diabetes [39]
The PTEN gene is the cause of increased sensitivity to the hormone insulin. Aparna Pal et al.2012 write that the PTEN gene may become a target for drugs to ght insulin resistance, the cause of type 2 diabetes. The PTEN gene encodes for an enzyme that is part of the insulin signalling pathway in the body. It is known to have a role in controlling the bodys metabolism, and to play a part in cell growth. The authors write that epidemiologic and genetic evidence links type 2 diabetes, obesity, and cancer. The Cowden syndrome is an inherited genetic condition caused by faults in the PTEN gene causing an increased risk of breast cancer, thyroid cancer and womb cancer. PTEN is a gene that is heavily involved in processes for both cell growth and metabolism. Those with Cowden syndrome had signicantly higher insulin sensitivity caused by increased activity in the insulin signalling pathway. The body mass index of those with Cowden syndrome appeared greater than the controls. Cowden syndrome goes along with obesity, while normally insulin sensitivity goes with being lean. Mutations that inactivate the PTEN gene result in increased cancer risk and obesity,
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but also increase insulin sensitivity which is very likely to protect against type 2 diabetes. Epidemiologic and genetic evidence links type 2 diabetes, obesity, and cancer. The tumorsuppressor phosphatase and tensin homologue (PTEN ) has roles in both cellular growth and metabolic signaling. Germline PTEN mutations cause a cancer-predisposition syndrome, providing an opportunity to study the eect of PTEN haploinsuciency in humans. Research of the enzyme fatty acid synthase (FAS) may reduce obesity and diabetes [40] Another research by Lodhi et al 2012 target the enzyme fatty acid synthase (FAS) which is needed to transform carbohydrates in fat. The authors silenced the FAS enzyme in mice which became more sensitive to insulin and were less likely to get fat even being on a highfat diet. The animals with depleted FAS metabolised more of the fat and released it as heat. Mice have white fat and brown fat in their tissues. White fat stores excess calories and contributes to obesity. Brown fat helps burn calories and protects against obesity, explain the authors. When the FAS enzyme was blocked the white fat was transformed into a kind of brown fat, having the genetic signature of brown fat cells and acted like brown fat cells. The mice became resistant to obesity. switching between white fat and brown fat. The researchers will use this strategy for treating people with diabetes and obesity by activating brown fat cells. The FAS pathway involves a family of proteins known as the PPARs (peroxisome proliferatoractivated receptors). PPARs are important in lipid metabolism. One of them, PPARalpha, helps burn fat, but the related protein, PPAR-gamma manufactures fat and helps store it. In mice without FAS in their fat cells, activity of PPAR-alpha (the fat burner) was increased, while PPAR-gamma (the fat builder) activity decreased. A protein called PexRAP (Peroxisomal Reductase Activating PPAR-gamma) turned out to be a downstream mediator of the eects of FAS and a key regulator of the PPAR-gamma, fat-storing pathway. Blocking PexRAP in fat cells in mice interfered with the manufacture and buildup of fat and glucose metabolism was also improved. PexRAP is downstream and their control might cause fewer side eects as expected with interfering in the activity of FAS. The enzyme PKC-delta may target diabetes and related ailments [41] Kahn et al 2011 compared the genome of two mice, the B6 prone to develop both obesity and diabetes, and the 129 mouse is quite protected from both which diered at an area of chromosome 14, important for insulin sensitivity. The PKC-delta gene was a prominent dierence between both mice. The levels of the PKC-delta enzyme were about two times as high in the liver and other tissues in the B6 as in the 129 mouse. When both types were put on high-fat diets, levels of the enzyme stayed the same in the 129 mouse but rose to three times higher in the B6 mouse.
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Levels of the PKC-delta enzyme in human liver are heightened in people who are obese or have diabetes. They often get fatty liver. Drugs that target this enzyme could help to treat diabetes and fatty liver disease. Calorie load responsible for activation of the food reward system and obesity [42] According to Andrews and Horvath 2008 food palatability acts on the dopaminergic reward system to override homeostatic control. The authors support the study of Ivan Araujo and colleagues 2008 which lifts questions on the dopamin theory. The study of Araujo and colleagues used trpm5/ mice which have no capacity for sweet taste. They found that these mice developed preference for a sugar solution based only on the caloric content and dopamin was secreted, but not when clear water was ingested. Dopamin was not secreted when the sugar solution was sucralose sweetener solution lacking calories. The authors concluded that calorie-rich nutrients can directly inuence brain reward circuits that control food intake independently of palatability or functional taste transduction. [43] A better control of obesity could therefore be attained reducing calories content of foods, being the taste of foods independent of the craving. This speaks for an urgent reduction of fat, sugar and caloric load in diet to avoid overweight. Intensive sweet taste is linked to the neurophysiology of obesity [44] According to Kovacs and Hajnal 2008 the increased palatability of modern diet contributes to eating beyond caloric need, adding to obesity. The authors studied the way how palatability is coded in taste-evoked neural activity comparing the response of brain neurons of obese and lean rat strains triggered by dierent concentrations of sugar and other ingredients. Neurons of the pontine parabrachial nucleus which relays information from the surface of the tongue were the subject of this study. They found that the neurons of lean rats responded to sucrose very early, while the reaction in obese rats demanded high concentrations of sugar. Increased consumption of sweet food could numb the reward centre of the brain reducing the intensity of the signals which results in a weaker perception of taste through the pontine parabrachial nucleus (PbN). The eect of other food ingredients such as salt, water, citric acid, quinine-HCI, monosodium glutamate did not dier between obese and lean rats. The authors stress that fat and sugar and other sweeteners such as fructose syrups and
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high intensity sweeteners, which are increasingly used in processed foods, over-stimulate taste receptors and food reward neurons making them less sensitive. The authors concluded that central gustatory processing for sucrose is altered in strains of obese rat and further support the notion that palatability is encoded in the across neuron pattern. These ndings suggests that there may be a link between taste preference and body weight aecting food intake. Roussin and Di Lorenzo in an editorial in 2008 [45] point out that the results of the study of Kovacs and Hajnal 2008 are consistent with observations that obese humans tend to be less responsive to mildly sweet stimuli and prefer sweeter stimuli when compared with the nonobese, such as noted by Bartoshuk et al. 2006. Bartoshuk added that genetic variation as well as taste pathology contribute to these results. [46] Roussin and Lorenzo [45], in its editorial, reviews studies related to the perception of sweet taste stressing that obesity may alter the taste processing of sweet stimuli at the parabrachial nucleus of the pons (PbN) which is the home to third-order gustatory neurons and inuences the motivational and pleasure aspects of taste via dopaminergic mesolimbic pathways. Sweet taste does not increase caloric intake, says study [47] Cicerale, Riddell and Keast 2012 report that taste is important to choose food, however perceived sweetness intensity alone does not inuence decisively food behaviours related to sugar consumption and dietary intake in adults. The authors studied the behaviour of 85 adults which tasted a sugar solution and rated the percepted sweetness. The study found no correlation between perceived sweetness and total caloric intake, food behaviours relating to sugar consumption dietary intake and micronutrients. Applied methodology The study was based on the general labeled magnitude scale (gLMS) to measure the perceived sweetness intensity. Applying one-way analysis of variance (ANOVA) no dierence between sweetness and importance of adding or not sugar to tea or coee was found; the same results apply for avoiding sugar-sweetened or zzy drinks. Independent t-test analysis found no association between sweetness intensity and confectionery intake, selected fruit and vegetable intake. The authors report that persons produced similar results rating tastes and sounds using gLMS compared with magnitude matching, suggesting that the gLMS is valid for taste comparisons across nontasters, medium tasters, and supertasters.
3.3. OBESITY MAY BE INFLUENCED BY A B12 CONJUGATE HORMONE DEVELOPED FOR ORAL ADMINISTRATION The General Labeled Magnitude Scale (gLMS) [48]
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Bartoshuk et al 2004 developed the General Labeled Magnitude Scale based on the LabeledMagnitude Scale of 1993. The gLMS is a continuous scale using "strongest imaginable of any kind" as the top rating too overcome ceiling eects. The authors explain that labeled scales use adjective/adverb intensity descriptors such as "very strong" rose odour, compared with a "very strong" headache, compressing or expanding the descriptor to t the domain of interest. Magnitude matching Magnitude matching asks a person to rate the intensities of taste stimuli and stimuli of another sensory system, such as the loudness of a tone, on a similar scale to overcome dierent perception intensities among subjects. Other studies linking food taste and nutritional behaviour The sensation of taste can be categorized into ve basic tastes: sweet, bitter, sour, salty, and umami. Fat identied as sixth human taste, discovery relevant for obesity management [49] After discovering "umami" taste, scientists postulate that fat as a "sixth taste" with CD36 receptor as responding signal to fat stimulus. CD 36 is located on the tongue and makes obese people to prefer foods with higher fat content, crave high fat foods more frequently and consume more fat than lean individuals. Pepino et al. 2011 found that CD36 genes vary among dierent rs1761667 genotypes (6 AA, 7 AG and 8 GG), inuencing the perception of fat. The homozygous A-allele (AA) lowers the expression of CD36. Subjects with the AA-allele had 8 fold higher detection thresholds for fat than subjects homozygous for the G-allele (GG). Heterozygous (AG) presented intermediate results. Detection threshold (sensitivity to fat) is increased by hydrolysis of triacylglycerols. Oleic acid was earlier detected than not hydrolysed fat. despite its higher viscosity. The authors concluded that taste rather than texture is the primary detection mechanism of taste of fat, having implications in the regulation of food intake and obesity management. Bitter taste: Bitter taste is linked to a reduction of fruits and vegetables intake in people reacting to natural bitter compounds. 6-n-propylthiouracil (PROP) a thionamide, tastes very bitter by some people, but tasteless by others depending on genetic makeup. Wooding et al. 2004 suggests that natural selection modied alleles at the PTC locus , resulting in humans."taster" and "nontaster" [50]
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Saltiness: Saltiness is a taste produced by sodium, potassium or lithium. Sourness: Sourness is a response to acidity. the taste receptor PKD2L1 is involved in this response. Umami: The amino acid glutamic acid is responsible for umami. Some nucleotides like inosinic acid and guanylic acid enhancing the taste.
Reduction of energy intake is more eective than exercise [51] [52] Swinburn and Eggers 2004 compares obesity with a train driving downhill. According to the authors movement inertia, mechanical dysfunction, psychological dysfunction, cyclical dieting, and socioeconomic disadvantage are factors promoting weight gain, moulding an "obesogenic" environment. The social, personal, cognitive, physiological factors which slow weight gain are weak compared with the obesogenic ones. In a recent study Swinburn and colleagues 2009 say that over-eating causes obesity of developed countries. Physical activity cannot compensate the excess calories. American adults increased the average weight by four kilograms, and children eight kilograms during the past three decades. According to the study adults increased weight despite having increased physical activity. Changes in physical activity of children had no impact on growing children obesity. To regain average weigt of people in the 70s, children should reduce 350 calories a day (one can of soda and a small portion of French fries or walk for an extra two-and-a-half hours a day) and adults 500 calories (one Big Mac burger or walking two hours a day). Reducing intake is there a feasible solution compared with a daily two hours extra walk. The authors call for a stronger emphasis on the energy intake side than on the physical activity side.
Obesity is associated with a favourable prognosis in many patients with established cardiovascular disease [53] Artham et al. 2008 st6ress that obesity is a global epidemic. It is known as a risk of cardiovascular diseases such as heart failure, coronary heart disease, hypertension, type 2 diabetes mellitus, dyslipidemia, certain cancers, and chronic kidney disease. The authors found, however, that, once these conditions develop, obese patients with hypertension, heart failure, and coronary heart disease have a favourable prognosis. The authors point out that greater eorts on primary prevention of obesity must be done in the eld of dietary therapy and regular physical activity.
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3.3.5
The Dutch Obesity Intervention in Teenagers Program and reduction of sugary beverages [54]
The program was designed to increase awareness of obesity and change the behaviours of school children appears reduced the intake of sugary beverages and also improved body composition in girls alone, but did not seem to aect other behaviours. The program included lessons in biology, physical education and lifestyle changes over eight months. Reduction of sugary beverages were 287 millilitres per day less for boys and 249 millilitres per day less for girls and 12 months later 233 millilitres per day less for boys and 271 millilitres per day less for girls, compared with children of schools not participating with the program. Skinfold measures showed benecial eects of the program as a result of reduced intake of sugary beverages. Other behavioural measure such as consumption of snacks or in walking or biking to school were not altered by the program. The authors stress that reducing intake of sugar-containing beverages should therefore be considered a good behavioural target for future interventions aimed at the prevention of overweight among adolescents. Reduction of consumption of sugar-containing beverages in both boys and girls should be focused in future interventions.
3.3.6
Cochrane strategy to prevent obesity in children [55]
The Cochrane database presented a strategy of prevention of childhood obesity to reduce the impact of resulting acute and chronic diseases, general health, development and wellbeing. The review intended to prevent obesity in children focuses on Body Mass Index (BMI) and aims to nd strategies to obtain best results under specic conditions. The studies classied children in three subgroups with intervention eects of -0.26kg/m(2) for the group of 0-5 years, -0.15kg/m(2) for the group of 6-12 years, and -0.09kg/m(2) for the group of 13-18 years. Child obesity prevention programmes presented benecial eects on BMI, particularly in the group of six to 12 years. The following policies and strategies are being suggested by Waters et al, authors of the study:in 2011: Improve lessons on healthy eating, increase physical activity and body image, increase sessions for physical activity at school, improve nutritional quality of the food supply in schools,and support teachers and parents to implement health promotion strategies to be more active, eat more nutritious foods and spend less time on screen based activities. The authors stress the need of more studies in very young children and adolescents to improve obesity prevention in children.
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3.3.7
Policy and action to counter global obesity epidemics [56]
Obesity, dened as a body-mass index of more than 30 kg/m2 in adults, increases worldwide. To help governments and other relevant institutions in choosing the best activities to counter the obesity epidemic, Gortmaker et al 2011 assessed quantitative models to calculate the eect of behaviours, interventions, and obesity reduction policies. The authors found cost-eective policies that governments should prioritise to counter the obesity epidemics. To do so, governments, international organisations, the private sector, and civil society need to contribute complementary actions in a coordinated approach. However only few governments show commitment to lead obesity prevention. Activities of the food industry should be independently assessed. The authors stress the need of policies to improve the food and built environments, crosscutting actions such as leadership, healthy public policies, and monitoring, increase funding for prevention programmes and obesity monitoring of the population. Integration of actions within health and non-health sectors, such as trade, agriculture, transport, urban planning, and development is being considered as fundamental by the authors. According to Rutter 2011, scientists prefer to stay within their own disciplinary boundaries. Clinicians promote clinical solutions, nutritionists support dietary ones, however, these parts must t together and aect one another. The system must function as a whole. Tackling obesity demands to coordinate the huge number of actions of individuals, organisations, and sectors, and integrate them in a corrective system. Rutter calls to develop the understanding of complex adaptive systems, build on the biomedical paradigm, and move beyond linear thinking to create new ways to tackle obesity or other problems, such as climate change. [57] Energy imbalance and bodyweight variation To predict the bodyweight time course the dynamic energy imbalances must be considered. Hall and colleagues 2011describe a mathematical model to simulates energy expenditure adaptations during weight loss, and a web-based simulator for prediction of weight change dynamics. The authors found that bodyweight response to a change of energy intake is slow, with half times of about 1 year, adults with greater adiposity have a larger expected weight loss for the same change of energy intake, and to reach their steady-state weight will take longer than it would for those with less initial body fat. Calculating the energy-balance dynamics of the US adult obesity epidemic Hall and colleagues found that a persistent average daily energy imbalance gap between intake and expenditure of about 30 kJ per day caused the average weight gain of the US population. However, energy intake rose to about 0,9 MJ per day in order to compensate the increased
259
expenditure associated with increased weight. This is needed to reverse the obesity epidemic. Dynamic physiological adaptations to weight change Health and nutrition organisations have created the believe that a reduction of food intake of 2 MJ per day will lead to a steady rate of weight loss of 0,5 kg per week. This is a static weight-loss rule which does not consider the dynamic physiological adaptations that occur with decreased bodyweight. It leads to drastically overestimated expectations for weight loss says Hall and colleagues. The dynamic simulation model of adult human metabolism, developed by Hall, predicts the time course of individual weight change in response to behavioural interventions. The authors suggest as a rule of thumb for an average overweight adult that every change of energy intake of 100 kJ (25 Cal) per day will lead to an eventual bodyweight change of about 1 kg with half of the weight change being achieved in about 1 year and 95% of the weight change in about 3 years. Reduction of fat level in fried sh [58] Three hydrocolloid coating materials were tested in reducing fat uptake in battered sh products. Camden and Chorleywood Food Research Association Group coatings such as alginate, pectin, gellan gum, methyl cellulose, and hydroxypropyl methyl cellulose. Fish llets were coated with alginate, pectin and gellan gum and then fried. All three coated battered sh llets with either water or one of the three hydrocolloids showed reduced fat level in the nal product. These ndings could help to reduce total lipid intake by the population as fried sh is an important constituent of the average population. The authors suggest that the reduction of fat was due to the waterbinding ability of the coatings. In fully fried products, the reduction in fat uptake was less marked, although an eect was still seen. It is likely that the longer frying times compromised the integrity of the coatings, emphasising the need to consider the requirements of both product and process when applying edible lms.
3.3.8
Green Paper "Promoting healthy diets and physical activity" [59]
Unhealthy diets and lack of physical activity are the leading causes of avoidable illness and premature death in Europe, and the rising prevalence of obesity across Europe is a major
260 public health concern. The obesity crisis [59]
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The Green Paper of the Commission of the European Communities entitled" Promoting healthy diets and physical activity: towards a European strategy for the prevention of overweight, obesity and chronic diseases" opens the discussion on the obesity crisis, focusing on the factor of food for the prevention of chronic diseases, overweight and obesity Improving the health of Europeans through better diets and greater physical activity is crucial to preventing a range of non-communicable diseases and improving quality of life for millions of people. According to the Confederation of Food and Drink Industry of the EU a greater understanding of all obesity-related factors is needed, calling for improved public health education on nutrition and healthy lifestyles. This would enable consumers to take responsibility for making healthy choices. It will be also be the basis for understanding and making use of product information provided by the industry. Strategies should include the determinants that aect food choice, factors that lead to insucient physical activity in every-day life, and not just food products themselves. [60] The Green Paper considers industry self-regulation the best way of dealing with the problem. According to the CIAA, however, a broader approach is needed to meet all factors involved, such as: It should be clear that each consumer is responsible for ensuring that his or her own lifestyle is a healthy one. Parents have a similar responsibility for their children. Increase of level of physical activity in children, adolescents and adults, in particular in the school environment. The European Vending Association (EVA) questions the scientic data of the Green Paper regarding the excessive intake of energy-dense snacks and sugar-sweetened soft drinks: EVA says the "notion of excessive intake" is vague and very subjective, and it is unclear how it impacts directly on the Body Mass Index. EVA calls for other factors such as energy out determining if intake is excessive or not.
3.4
Drugs to ght obesity
[61] The classic diets and fasting are seldom long lasting. The pharmaceutical industry is conscious of the growing market of drugs to reduce weight without changing once life
3.4. DRUGS TO FIGHT OBESITY
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habits. H. HAUNER [62] writes:"For the moment being there are no convincing drugs for treatment of overweight. The majority of authorized Drugs act on the neurotransmitter noradrenalin or serotonin. Suppressant of appetite like derivates of amphetamines should be used very seldom because of their side reactions (such as rise of heart beat frequency and rise of blood pressure, insomnia, pulmonary hypertension), their short time of activity and the danger of habit formation. A long-time eect every overweight therapy are disappointing. Only less than one third of patients can hold their weight after a diet."
3.4.1
Obesity drug treatment [63] [64]
Antiobesity treatment is recommended for selected patients in whom lifestyle modication is unsuccessful. In US there are only two antiobesity drugs licensed.
3.4.2
Orlistat
Orlistat is a gastrointestinal lipase inhibitor, reduces weight and decreases progression to diabetes in high-risk patients; adverse gastrointestinal eects are common. Orlistat works by inhibiting pancreatic lipase, an enzyme that breaks down triglyzerides in the intestine into absorbable free fatty acids. Fat is excreted undigested. Orlistat is a synthetic substance resulted from the research regarding lipstatin which had been found in bacteria which live in the soil of Mallorca, the Island in the Mediterranean Sea. Lipstatin was found to slow down the absorbtion of fat. This took the research of Roche to the discovery of orlistat. Xenical was liberated on the European market in august 1998. Amylin/Leptin synergistic eect and weight reduction [65] Tam, Lecoultre and Ravussin 2011 point to the fact that there are currently no treatment options for obesity. Many drugs were removed from the market due to signicant side eects, such as Sibutramine. Orlistat provide only modest weight loss. The promising combination of leptin/amylin in the form of pramlintide/metreleptin, for the treatment of obesity in a randomized clinical trial was stopped due to safety concerns. Pramlintide is an analog of the hormone amylin. These trials were based on the study of Roth et al.2008 which explained that body weight is regulated by the interactions between endocrine signals of long-term adiposity, such as leptin, a hypothalamic signal, and short-term satiety, such as amylin, a hindbrain signal. The authors report a synergistic eect of fat-specic weight loss when amylin and leptin is given to leptin-resistant diet-induced obese rats. [66]
262 Sibutramine
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Sibutramine has the generic name Merida in Europe and Reductil in US. It is a monoaminereuptake inhibitor which results in weight losses, but is associated with increases in blood pressure and pulse rate. Sibutramine acts by increasing serotonin and norepinephrine levels in brain. The serotonergic action, in particular, is thought to inuence appetite.
Rimonabant Rimonabant is the rst of the endocannabinoid receptor antagonists, reduces weight and improves waist circumference and concentrations of HDL cholesterol and triglyceride. It works by blocking the CB1 receptors in the brain. In Europe, it is indicated for use in conjunction with diet and exercise for patients with a body mass index greater than 30 kg/m2 or patients wih a BMI greater than 27 kg/w2 with associated risk factors, such as type 2 diabetes or dyslipidaemia. However, an increased incidence of mood-related disorders has been reported. Generic names are Acomplia in Europe, and Riobant, Slimona, Rimoslim in India. In United States, it is intended to be marketed under the name Zimulti. The FDA concluded in 2007 that Sano-Aventis failed to demonstrate the safety of rimonabant and voted against recommending the anti-obesity treatment for approval. The main concern was over suicidality, depression and other related side eects associated with use of the drug.
Anti-obesity drug Acomplia: German health insurance does not pay for acomplia and scientist warns for late-eects [67] The Lower House of the German Parliament (Bundestag) decided that German health insurance will not pay for Acomplia classifying the drug as lifestyler. Rimonabant is the active ingredient of Acomplia. The drug was banned in USA because of depression and suicide side eects, but is approved in France, Germany and UK. [68] Acomplia acts on the central nerve system, blocking certain receptors. This is of concern for the neurobiologist Andreas Zimmer from the University Bonn, Germany. He found that a special type of mice which received Acomplia had a reduced lifespan, presented epilepsy and a loss of nerve cells in the brain was found. The producer of the drug, Sano-Aventis, argues that eects in animals cannot be translated to human physiology. Zimmer says that the 2 an 3 years studies presented by SanoAventis were to short to show late-eects. The company expects revenues from Acomplia of up to 5 billion Dollar/year.
3.4. DRUGS TO FIGHT OBESITY Fluoxenti (Prozac)
263
It is an antidepressant which is also licensed for bulemia nervosa and is therefore sometimes classied as antiobesity drug. Other antiobesity drugs acting on the central melanocortin pathway, are far away from clinical use. A meta-analysis of trials by the international Cochrane Collaboration concluded in 2007 that in diabetic patients Fluoxetine, orlistat, and sibutramine can achieve statistically signicant weight loss over 12 to 57 weeks. The magnitude of weight loss is modest, however, and the long-term health benets remain unclear. The safety of sibutramine is uncertain. There is a paucity of data on other drugs for weight loss or control in persons with type 2 diabetes. [69] Raj S. Padwal and colleague criticise all antiobesity drug trials because they have been limited by their high attrition rates and lack of long-term morbidity and mortality data. The authors suggest that the assessment processes of new antiobesity drugs should include both surrogate endpoints such as weight loss, and clinical outcomes such as major obesity-related morbidity and mortality, to insure that the putative benets of such drugs outweigh their risks and costs. [70] Xenical, the antifat drug Xenical is a drug containing the substance orlistat . It can reduce bodyweight up to 10% without serious side eects. Xenical can help when used for a long period together with a change of life habits. Its activity takes place in the intestines. It reduces the absorption of fat up to 30 percent. Xenical is being produced by Homann la Roche, Grenzach, Swiss. Creatine may reduce risk of fatty liver disease [71] A large number of studies tried to tackle the obesity problem. Creatine ignites new hopes in treating lipid diseases. Supplementation of 1% (wt:v) of creatine monohydrate to the liquid high-fat diet with 71% calories derived from fat was found by Deminice et al.2011 to reduce fat accumulation in liver of rats. Pathologic increases of liver parameters such as cellular oxidative stress, immunity and other liver function linked parameter were improved, compared with rat under this diet but without supplementation of creatine. The authors suggest that high-fat diet decreased mRNA for PPARalfa as well as 2 of its targets, carnitine palmitoyltransferase and long-chain acylCoAa dehydrogenase. Creatine supplementation normalized these mRNA levels preventing the formation of fatty
264 liver.
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Vinegar medicinal uses, antiglycemic eect and weight reduction [72] Johnston and Gaas 2006 write that scientic investigations do not support the use of vinegar as an anti-infective agent, reduced risk for hypertension and cancer. Vinegar ingestion, however, reduces postprandial responses of blood glucose and insulin, and increased satiety. Ostman and colleagues 2005 point to thr potential of fermented and pickled products containing acetic acid. [73] Future investigations,however, are needed to explain how vinegar alters postprandial glycemia and to determine whether regular vinegar ingestion favourably inuences glycemic control. Johnston and Gaas calls for more studies to determine whether vinegar is a useful for the therapy of diabetes or prediabetes. Kondo and colleagues 2009 studied the eect of 0.3 or 1.5% acetic acid on the prevention of obesity in high-fat-fed mice. The administration inhibited the accumulation of body fat and hepatic lipids without changing food consumption or skeletal muscle weight. The authors suggest that weight reduction where due to the eect of the acetic acid increasing fatty oxidation and thermogenesis in the liver through PPAR-alpha. The acetic acid upregulated the expression genes for PPAR-alfa and fatty-acid-oxidation-related enzymes in the liver. [74]
3.4.3
Amphetamines
Amphetamines were used in war to keep soldiers awake during combat. Later amphetamines were found to act as appetite suppressant and being sold as such. Very soon the selling was canceled because of heart complaints, Angina-pectoris tremble and nervosity.
3.4.4
Phentermin and norephedrine
Phentermine is the active substance of Adipex N and norephedrine was used in Antidiapositum X 112 Fugoa N and Regenon. They are appetite suppressant. They have the same side reactions noted by amphetamines. Phentermin was prohibited in Germany because of the high blood pressure of the pulmonary artery. In Austria it is still being sold under the name Adipex.
3.4. DRUGS TO FIGHT OBESITY
265
3.4.5
Appetite suppressant drug phentermine linked to heart failure
Tobbia et al 2012 report the case of a 70-year-old woman which developed a life-threatening ventricular brillation following obesity treatment with phentermine. Recurrent ventricular brillation were caused by a coronary artery vasospasm. Discontinuing phentermine use the woman remained symptom free. [75] It is being supposed that the appetite suppressant drug containing phentermine caused the heart problem which almost killed the patient. It is prescribed in America for individuals who are at increased medical risk because of their weight. In Germany phentermine is not allowed because of possible heart valve disfunction. It is not clear how phentermine acts in weight reduction. Stroke cases, heart attack, dysrhythmia and cardiac arrest linked to phentermine are known. [76] Phentermine can produce side eects consistent with its catecholamine-releasing properties, such as tachycardia (increased heart rate) and elevated blood pressure, but the incidence and magnitude of these appear to be less than with the amphetamines. Because phentermine acts through sympathomimetic pathways, the drug may increase blood pressure and heart rate. It may also cause palpitations, restlessness, and insomnia. Additionally, phentermine has the potential to cause psychological dependence. After short-term use, tolerance begins and can be followed by rebound weight gain. [77] FDA approved drug with phentermine [78] The U.S. Food and Drug Administration on July 2012 approved Qsymia, a combination of two FDA-approved drugs, phentermine and topiramate. Qsymia is an appetite suppressant, which used in combination with a reduced-calorie diet and exercise, provides a treatment option for chronic weight management in Americans who are obese or are overweight and have at least one weight-related comorbid condition. The American unhealthy food high in fat and sugar together with little exercise is the main cause of obesity. Unhealthy Hamburgers, fatty steaks and high content of sugar of soft drinks. The Qsymia oral capsule containing phentermine acting as appetite suppressant and topiramate which has anti-epileptic eects and is used to treat obesity. Qsymia is also being developed to treat sleep apnoea syndrome and type 2 diabetes mellitus. [79]
3.4.6
Aminorex
Aminorex was used as active substance of the drug Menocil. Its selling was canceled because of irreparable high pressure at the pulmonary artery.
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3.4.7
Phenuramine
Phenuramine is an appetite suppressant which stimulates serotonin presenting the same side reactions described above as well as depressions.
3.4.8
Sesame seed and oil and control of high blood pressure
Researches at the Osaka University of Pharmaceutical Sciences and Taiwanese researchers have demonstrated vasodepressing properties which help to control high blood pressure. Sesamin, a supplement made from sesame exerts action on nitric oxide production and its ability to inhibit ET-1 production from endothelial cells. ET-1 constricts blood vessels.
3.5
New anti-obesity drug Contrave
A combination of the dopamine and norepinephrine reuptake antagonist bupropion and the opioid antagonist naltrexone were proposed to treat obesity. The dual mechanism of action is to stimulation of central melanocortin pathways, resulting in increased energy expenditure and reduced appetite. Contrave of Orixegen will be approved by FDA in a combination of 360 mg bupropion and 32 mg naltrexone in a single tablet. [80] The recommended daily dose of Contrave is two 8mg naltrexone/90 mg bupropion tablets taken twice daily (4 tablets total - 32 mg naltrexone, 450 mg bupropion). Upon initiation, the drug will be started with a quarter-dose (or one tablet) for one week and a pill will be added to the regimen each week until the full recommended dose is reached on Week 4. Treatment is designed to aect the hypothalamus to decrease food intake over extended period of time. [81] The US Food and Drug Administration Endocrinologic and Metabolic Drugs Advisory Committee gave a positive recommendation for the use of Contrave in the treatment of obesity and weight management. The nal approval is expected for Jan 31, 2011. Its use may produce a decrease in bodyweight of 5 percent. But this drug showed weight loss only when combined with lifestyle modication. The underlying causes of obesity must also be addressed such as promoting the modications of lifestyle, diet, and exercise. [82] Hypothalamic melanocortins, particularly alpha-MSH, are known to constitute the main brake to consumptive behaviour of food. Opiates are known to both suppress alpha-MSH and to stimulate hedonic food consumption, therefore the antagonism between melanocortins and opioids are promising to reduce obesity. Monoamines, opioids and cannabinoids are
3.5. NEW ANTI-OBESITY DRUG CONTRAVE
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known to be involved in appetite regulation acting on the hypothalamic appetite regulatory centre, more studies on this subject are being suggested by Reece 2010. [83] The Contrave Obesity Research I (COR-I) study assessed the eect of naltrexone and bupropion treatment on bodyweight in overweight and obese participants. The adverse event were nausea, headache, constipation, dizziness, vomiting, and dry mouth. A transient increase of around 1.5 mm Hg in mean systolic and diastolic blood pressure was followed by a reduction of around 1 mm Hg below baseline. No increase of depression or suicidality events compared with placebo were noted. [84] Nathan and colleagues 2008 stress that antiobesity drugs target the central neurochemical systems including the monoamine, opioid, and cannabinoid systems which also modify emotional behaviour and cognitive function, acting on the receptors within the fronto-striatal and limbic circuitry. Drugs targeting the m-opioid receptors, such as naltrexone and combination therapies targeting the opioid and monoamine systems, such as Contrav were reported to produce sedfation and tiredness. The authors recommend, therefore, to assess assess neuropsychiatric adverse events antiobesity drugs with such central mechanism of action. [85]
3.5.1
Serotonin-rich food like bananas and chocolate may increase obesity [86]
According to Grs et al.2013 serotonin-rich food like bananas and chocolate increases 5hydroxytryptamine (5-HT) in blood. Serotonin is oxidized to 5-HT oxidation products which behave as ligands of peroxisome proliferator-activated receptor (PPAR- ) controlling deposition in fat cells. In studies using human adipose cells the authors found that 5-HT increased lipid-binding proteins, glucose carriers, and enzymes of triacylglycerol synthesis (FABP4, CD36, GLUT1, and phosphoenolpyruvate carboxykinase). 5-HT increased fat storage and upregulation of PPAR- -responsive genes. The authors concluded that the amine oxidation of serotonin may promote PPAR- activation and excerts an peripheral eect on the deposition of fat at the adipose tissue.
3.5.2
Dierentiation of progenitor cells into energy-burning brown fat cells as anti-obesity therapy [87]
According to Tim J. Schulz and colleagues 2010, brown fat cells are specialized for energy expenditure and may be included in a strategy for body weight reduction. The authors found that progenitor cells in mouse white fat tissue and skeletal muscle (Sca-1(+)/CD45()/Mac1(-), referred to as Sca-1(+) can be transformed into brown fat cells. The authors report that fat cells, marked with Scal protein and exposed to BMP-7 protein, presented characteristics of brown fat cells. The dierentiation could be intensied
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by adding rosiglitazone, known as a diabetes drug. The molecular characteristics of tissueresident adipose progenitors were determined by the group around Schulz. The authors stress that diet and exercise are still the best approaches for losing weight in the general population. Therapy involving energy-burning brown fat cells may, however, help people with heavy body weight problems. TPL2 gene regulates obesity-associated inammation and insulin resistance [88] According to Pereld et al.2011 tumor progression locus 2 (TPL2), a kinase that integrates signals from Toll receptors, cytokine receptors, and inhibitor of K-B kinase-beta mediates obesity-associated inammation and insulin resistance. Mice fed with a low-fat diet or a high-fat diet to investigate the eect of TPL2 deletion on obesity, inammation, and insulin sensitivity. The authors found that TPL2 deletion does not alter body weight gain or adipose depot weight, but improves insulin sensitivity with enhanced glucose uptake in skeletal muscle and increased suppression of hepatic glucose output, diminished immune cell inltration reduced inammation in obese TPL2suppressed mice. The author concluded that TPL2 is a target which may improve the metabolic state associated with obesity. Blueberries reduce insulin resistance, adipocyte death and the resulting inammation [89] Supplementation of a high-fat diet with whole blueberry powder of Vaccinium ashei and Vaccinium corymbosum was found by DeFuria et al. 2009 to protects against adipose tissue inammation and insulin resistance but did not alter energy intake, metabolic rate, body weight, or adiposity. The authors report that the shift toward global upregulation of inammatory genes, increased M1-polarized ATMPhi (CD11c+), and increased oxidative stress was attenuated or nonexistent in mice fed with blueberries which were also protected from insulin resistance and hyperglycemia adipocyte death. These eects may result from anthocyanins of blueberries which alter mitogen-activated protein kinase and nuclear factor-kappaB stress signaling pathways. Oils reducing belly fat [90] According to Pereld 2011 abnormally high belly fat or abdominal adiposity has been linked to a range of health problems, including insulin resistance, diabetes, cardiovascular disease and other obesity-associated health disorders. The author found that oil of the seeds of the Sterculia foetida tree contains sterculic oil curbs a human enzyme associated with insulin resistance. Belly fat is a key to reducing the incidence of serious disease, and this oil could have a future as a nutritional supplement. Mice with high amount of abdominal fat, which were fed with sterculic oil, presented decreased liver fat and an improved glucose tollerance. The dose was comparable to providing 3 grams of sterculic oil to a 250 pound human.
3.5. NEW ANTI-OBESITY DRUG CONTRAVE
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Malvalic acid and sterculic acid are cyclopropene fatty acids. The structure of sterculic acid was proposed by Nunn as C19 H34 O2, by the method of urea complexes and suggested its structure as omega-(2n-octylcycloprop-1-enyl)-octanoic acid (I). [91]
Sterculic acid is present in sterculia oils and at 12% in kapok seed oil, cottonseed oil 1%and in the seeds of the tree Sterculia foetida 65-78%. The authors stress that these acids are highly reactive and are destroyed during rening and hydrogenation of the oils. [92] Saor oil improving glycemia, inammation, and blood lipids [93] Asp et al. 2011 reported that a daily dose of 8g of saower oil for 16 weeks may improve glycemia, inammation, and blood lipids in obese postmenopausal women who have Type 2 diabetes. No such eects were noted with conjugated linoleic acid. Perilipin role in obesity and thermogenesis [94] Miyoshi et Al. 2010 describe the function of perilipin A in adipocyte lipid droplets which is essential for lipid storage and lipolysis. Overexpression of perilipin diminished adipose tissue, elevates basal lipolysis, reduces catecholamine-stimulated lipolysis, and increased insulin resistance, lower body weight, fat mass, and adipocyte size were also attained. The expression of oxidative genes was increased and lipogenic genes decreased in brown adipose tissue of transgenic mice. Sawada and colleagues 2010 report that FSP27 has been shown to control gene expression of fat metabolic regulators. Overexpression of Perilipin A in 3T3-L1 adipocytes also reduced FSP27 expression and diminished lipid droplet size. The authors concluded that overexpression of Perilipin A in white adipocytes reduces lipid droplet size by decreasing FSP27 expression and thereby inducing a brown adipose tissue-like phenotype. The authors suggest to modulation the lipid droplet proteins in white adipocytes as a treatment of obesity and its related disorders. [95] Souza et al. 2007 reports that protein kinase A-mediated perilipin phosphorylation is essential for norepinephrine-dependent lipolysis and thermogenesis in brown adipose tissue . The authors report that in perilipin knockout mice an increased basal lipolysis attributable to the absence of perilipin causes a temperature increase of approximately 3.0
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degrees C, suggesting that. one or more norepinephrine-dependent mechanism of perilipin phosphorylation regulates the interscapular brown adipose tissue thermal response. [96] Low-calcium diet triggers calcium-sensing receptor (CaSR) pathway leading to obesity [97] Sensing of extracellular calcium by CasR is important in regulating calcium homeostasis,The CasR has a predominant role in controlling parathyroid gland function. CasR receptor also has functions in other tissues, including regulation of renal calcium excretion and calcitonin secretion by thyroidal C-cells, but sensing mechanisms for extracellular calcium in other tissues outside of the parathyroid gland, kidney, and thyroidal C-cells is unclear. He et al 2011 report that low-calcium intake is associated with increased risk of obesity. The calcium-sensing receptor (CaSR) plays an important role in modulating the expression of rate-limiting lipolysis enzymes in human adipocytes. Rats fed with a low-calcium diet had greater visceral fat mass, lower serum FFA and glycerol concentrations, and greater CaSR expression in white adipose tissue than did those fed with normal-calcium. The authors suggest that low-calcium diet aects the CaSR pathway with antilipolytic activity leading to obesity.[98] The calcium-sensing receptor (CaSR) was found by He et al. to maintaining constant blood Ca(2+) levels and has an inhibitory eect on lipolysis by mediating potential [Ca(2+)](i) and cAMP pathways. [99]
3.5.3
Obesity Paradox: Obesity increases chance of survival in case of stroke, heart failure miocardial infarction and bypass surgery [100]
Doehner et al. 2012 report that overweight or obese patients with acute stroke or transient ischemic attack have better survival rates and recovery of dependency or recurent stroke, than patients with normal body weight. The worst outcomes present underweight patients. The same applies for heart failure, acute myocardial infarction, and bypass surgery patients. Body mass index (BMI) The study found that mortality was highest among underweight patients (BMI < 18.5 kg/m2 C ) and declined with increasing BMI such as normal weight (BMI 18.5 to <25 kg/m2), overweight (BMI 25 to <30 kg/m2 C ), obese (BMI 30 to <35 kg/m2 C ), and very obese (BMI 35 kg/m2 C ). Survival curves for BMI subgroups demonstrate that mortality is highest in underweight patients compared with normal-weight patients. Mortality risk decreased in overweight
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and obese patients and was lowest for very obese. Experts call this phenomena the obesity paradox which has also been observed in diseases such as chronic kidney disease, chronic pulmonary disease, and chronic liver disease. The authors are not sure how obesity improves the outcome of stroke. They suggest extra pounds provide more reserves to ght o disease. A molecular explanation of the obesity paradox is conceivable. The authors explain that weight loss recommendations should apply only to primary prevention, it has to be dierentiated between healthy people and those patients who already have a disease. Recommendations may be completely dierent for one population compared to the other. Doehner and colleagues call to rethink the weight management recommendations after stroke of the US and the European guidelines which suggest that after a stroke people should lose weight. These recommendations are not supported by clinical trials. However, experts call for more studies on overweight in relation to stroke and specic heart diseases. Obesity is a risk factor for vascular disease but dierent studies describe the obesity paradox with decreased mortality in class I obese patients undergoing vascular surgery. Jackson et al. 2012 report that the obesity paradox exists for stroke and mortality after carotid endarterectomy. [101]
Bibliography
[1] http://www.enviga.com/_doc/nestle_clinical_study.pdf. Rudelle, Servane; Ferruzzi, Mario G.; Cristiani, Isabelle; Moulin, Juli; Mac, Katherine; Acheson, Kevin J. and Tappy, Luc: Eect of a thermogenic beverage on 24-hour energy metabolism in humans. Obesity. 2007;15:349 -355. [2] http://www.enviga.com/. Enviga, THE CALORIE BURNER. [3] http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd= Retrieve&dopt=AbstractPlus&list_uids=16247510&itool=iconabstr&query_ hl=2&itool=pubmed_docsum. Murase, T.; Haramizu, S.; Shimotoyodome, A.; Tokimitsu, I: Reduction of diet-induced obesity by a combination of tea-catechin intake and regular swimming. Int J Obes (Lond). 2006 Mar;30(3):561-8. PMID: 16247510. [4] http://www.ajcn.org/cgi/content/abstract/85/6/1465?maxtoshow= &HITS=10&hits=10&RESULTFORMAT=&fulltext=1586&searchid=1&FIRSTINDEX= 0&volume=85&issue=6&resourcetype=HWCIT. Ello-Martin, Julia A.; Roe, Liane S.; Ledikwe, Jenny H.; Beach, Amanda M. and Rolls, Barbara J.: Dietary energy
272
CHAPTER 3. OBESITY density in the treatment of obesity: a year-long trial comparing 2 weight-loss diets. Am. J. Clinical Nutrition, Jun 2007; 85: 1465 - 1477.
[5] Olsen A, van Belle C, Meyermann K, and Keller KL. Manipulating fat content of familiar foods at test-meals does not aect intake and liking of these foods among children. Appetite, 57(3):573577, 7 2011. http://www.ncbi.nlm.nih.gov/pubmed/ 21801772. [6] Schusdziarra V, Hausmann M, Wittke C, Mittermeier J, Kellner M, Naumann A, Wagenpfeil S, and Erdmann J. Impact of breakfast on daily energy intakean analysis of absolute versus relative breakfast calories. Nutr J, 17(10):5, 1 2011. http://www. ncbi.nlm.nih.gov/pmc/articles/PMC3034667/?tool=pubmed. [7] Lipsky LM and Iannotti RJ. Associations of television viewing with eating behaviors in the 2009 health behaviour in school-aged children study. Arch Pediatr Adolesc Med, 166(5):46572, 5 2012. http://www.ncbi.nlm.nih.gov/pubmed/22566548. [8] Brug J, van Stralen MM, Te Velde SJ, Chinapaw MJ, De Bourdeaudhuij I, Lien N, Bere E, Maskini V, Singh AS, Maes L, Moreno L, Jan N, Kovacs E, Lobstein T, and Manios Y. Dierences in weight status and energy-balance related behaviors among schoolchildren across europe: The energy-project. PLoS One, 7(4):e34742, 2012. http://www.ncbi.nlm.nih.gov/pubmed/22558098. [9] van Stralen MM, te Velde SJ, van Nassau F, Brug J, Grammatikaki E, Maes L, De Bourdeaudhuij I, Verbestel V, Galcheva S, , Iotova V, Koletzko BV, von Kries R, Bayer O, Kulaga Z, Serra-Majem L, Snchez-Villegas A, Ribas-Barba L, Manios Y, and Chinapaw MJ. Toybox-study group: Weight status of european preschool children and associations with family demographics and energy balance-related behaviours: a pooled analysis of six european studies. Obes Rev, Suppl 1:2941, 3 2012. http://www.ncbi.nlm.nih.gov/pubmed/22309063. [10] De Craemer M, De Decker E, De Bourdeaudhuij I, Vereecken C, Deforche B, Manios Y, and Cardon G. Toybox-study group: Correlates of energy balance-related behaviours in preschool children: a systematic review. Obes Rev, 13(Suppl 1):1328, 3 2012. http://www.ncbi.nlm.nih.gov/pubmed/22309062. [11] Pitel L, Geckova AM, Kolarcik P, Halama P, Reijneveld SA, and van Dijk JP. Gender dierences in the relationship between religiosity and health-related behaviour among adolescents. J Epidemiol Community Health, 5 2012. http://www.ncbi.nlm.nih. gov/pubmed/22569749. [12] Dndar C and Oz H. Obesity-related factors in turkish school children. ScienticWorldJournal, page 353485, 2012. http://www.ncbi.nlm.nih.gov/pmc/articles/ PMC3322393/?tool=pubmed.
BIBLIOGRAPHY
273
[13] Kuwait obesity a huge problem. kuwait times 13 may 2012. http://news. kuwaittimes.net/2012/05/13/kuwait-obesity-a-huge-problem/. [14] http://www.ajcn.org/cgi/content/full/72/5/1232. Yung-hsi Kao, Richard A Hiipakka and Shutsung Liao: Modulation of obesity by a green tea catechin : Letter to the Editor. American Journal of Clinical Nutrition, Vol. 72, No. 5, 1232-1233, November 2000. [15] http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db= pubmed&list_uids=10094584&dopt=Abstract. Han LK, Takaku T, Li J, Kimura Y, Okuda H. Anti-obesity action of oolong tea. Int J Obes Relat Metab Disord 1999;23:98-105. [16] http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd= Retrieve&dopt=AbstractPlus&list_uids=12439647&query_hl=2&itool= pubmed_docsum. Murase, T.; Nagasawa, A.; Suzuki, J.; Hase, T.; Tokimitsu, I.: Benecial eects of tea catechins on diet-induced obesity: stimulation of lipid catabolism in the liver. Int J Obes Relat Metab Disord. 2002 Nov;26(11):1459-64. PMID: 12439647. [17] Douglas SM, Ortinau LC, Hoertel HA, and Leidy HJ. Low, moderate, or high protein yogurt snacks on appetite control and subsequent eating in healthy women. Appetite, 60:117122, 2012. http://www.ncbi.nlm.nih.gov/pubmed/23022602. [18] Douglas A, Minihane AM, Givens DI, Reynolds CK, and Yaqoob P. Dierential eects of dairy snacks on appetite, but not overall energy intake. Br J Nutr, pages 112, 3 2012. http://www.ncbi.nlm.nih.gov/pubmed/22380537. [19] lmiron Roig E, Grathwohl D, Green H, and Erkner A. Impact of some isoenergetic snacks on satiety and next meal intake in healthy adults. J Hum Nutr Diet, 22(5):469 74, 10 2009. http://www.ncbi.nlm.nih.gov/pubmed/19743984. [20] Perrigue MM, Monsivais P, and Drewnowski A. Added soluble ber enhances the satiating power of low-energy-density liquid yogurts. J Am Diet Assoc, 109(11):1862 8, 11 2009. http://www.ncbi.nlm.nih.gov/pubmed/19857627. [21] Walker KZ, Woods J, Ross J, and Hechtman R. Yoghurt and dairy snacks presented for sale to an australian consumer: are they becoming less healthy? Public Health Nutr, 13(7):103641, 7 2010. http://www.ncbi.nlm.nih.gov/pubmed/20025831. [22] http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd= Retrieve&dopt=AbstractPlus&list_uids=15630269&itool=iconabstr&query_ hl=2&itool=pubmed_docsum. Tokimitzu, I: Eects of tea catechins on lipid metabolism and body fat accumulation.Biofactors. 2004;22(1-4):141-3.
274
CHAPTER 3. OBESITY
[23] Fazen CH, Valentin D, Fairchild TJ, and Doyle RP. Oral delivery of the appetite suppressing peptide hpyy(3-36) through the vitamin b(12) uptake pathway. J Med Chem, 11 2011. http://www.ncbi.nlm.nih.gov/pubmed/22054008. [24] Kitagawa K, Tomoyasu T, Futaki S, Akita T, Higashide S, Inoue K, and Tobe T. Solution synthesis of human peptide yy (hpyy). Chem Pharm Bull (Tokyo), 38(6):17314, 6 1990. http://www.ncbi.nlm.nih.gov/pubmed/2208387. [25] Russell-Jones GJ. Use of vitamin b12 conjugates to deliver protein drugs by the oral route. Crit Rev Ther Drug Carrier Syst, 15(6):55786, 1998. www.ncbi.nlm.nih. gov/pubmed/9883390. [26] Petrus AK, Fairchild TJ, and Doyle RP. Traveling the vitamin b12 pathway: oral delivery of protein and peptide drugs. Angew Chem Int Ed Engl, 48(6):10228, 2009. http://www.ncbi.nlm.nih.gov/pubmed/19072807. [27] http://www.nature.com/ijo/journal/v29/n6/abs/0802926a.html. Klaus, S.; Pltz, S.; Thne-Reineke. C. and Wolfram, S.: Epigallocatechin gallate attenuates diet-induced obesity in mice by decreasing energy absorption and increasing fat oxidation. International Journal of Obesity (2005) 29, 615-623. doi:10.1038/sj.ijo.0802926 Published online 1 March 2005. [28] http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd= Retrieve&dopt=AbstractPlus&list_uids=15735368&itool=iconabstr&query_ hl=2&itool=pubmed_docsum. Wolfram, Swen; Raederstor, Daniel; Wang, Yng; Teixeira, Sandra R.; Elste, Volker and Weber, Peter: TEAVIGO (epigallocatechin gallate) supplementation prevents obesity in rodents by reducing adipose tissue mass. Annals of Nutrition & Metabolism 2005;49:54-63 (DOI: 10.1159/000084178). [29] http://ajpcell.physiology.org/cgi/content/abstract/288/5/C1094. Hung, Pei-Fang; Wu,Bo-Tsung; Chen, Hui-Chian; Chen, Yen-Hang; Chen, Chia-Lin; Wu, Ming-Hua; Liu, Hsien-Chun Lee, Meng-Jung, and Kao, Yung-Hsi: Antimitogenic effect of green tea (-)-epigallocatechin gallate on 3T3-L1 preadipocytes depends on the ERK and Cdk2 pathways Am J Physiol Cell Physiol, May 1, 2005; 288(5): C1094 C1108. [30] Zupancic ML, Cantarel BL, Liu Z, Drabek EF, Ryan KA, Cirimotich S, Jones C, Knight R, Walters WA, Knights D, Mongodin EF, Horenstein RB, Mitchell BD, Steinle N, Snitker S, Shuldiner AR, and Fraser CM. Analysis of the gut microbiota in the old order amish and its relation to the metabolic syndrome. PLoS ONE, 7(8):e43052, 2012. http://www.plosone.org/article/info%3Adoi%2F10. 1371%2Fjournal.pone.0043052. [31] Larsen N, Vogensen FK, van den Berg FW, Nielsen DSV Andreasen ASV Pedersen BKV Al-Soud WAV Sorensen SJ, Hansen LH, and Jakobsen M. Gut microbiota
BIBLIOGRAPHY
275
in human adults with type 2 diabetes diers from non-diabetic adults. PLoS One, 5(2):e9085, 2 2010. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2816710/ ?tool=pubmed. [32] Marteau p. "bacterial ora in inammatory bowel disease". Digestive Diseases, 27:99 103, 2009. http://www.ncbi.nlm.nih.gov/pubmed/20203504. [33] Lakhan SE and Kirchgessner A. Gut inammation in chronic fatigue syndrome. Nutr Metab (Lond), 7:79, 10 2010. http://www.ncbi.nlm.nih.gov/pmc/articles/ PMC2964729/?tool=pubmed. [34] http://www.obesityresearch.org/cgi/content/abstract/13/6/982. Lin, Ji; Della-Fera, Mary Anne and Baile, Clifton A.: Green Tea Polyphenol Epigallocatechin Gallate Inhibits Adipogenesis and Induces Apoptosis in 3T3-L1 Adipocytes. Obesity Research 13:982-990 (2005). [35] http://ajpendo.physiology.org/cgi/content/abstract/290/2/E273. Liu, Hang-Seng; Chen, Yen-Hang; Hung, Pei-Fang and Y.-H. Kao, Yung-Hsi: Inhibitory eect of green tea (-)-epigallocatechin gallate on resistin gene expression in 3T3-L1 adipocytes depends on the ERK pathway Am J Physiol Endocrinol Metab, February 1, 2006; 290(2): E273 - E281. [36] http://en.wikipedia.org/wiki/Resistin. Wikipedia, the free encyclopedia: Resistin. [37] http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd= Retrieve&dopt=AbstractPlus&list_uids=16470636&itool=iconabstr&query_ hl=2&itool=pubmed_docsum. Wolfgang S., Wang, Y.Thielecke F.: Anti-obesity effects of green tea: from bedside to bench. Mol Nutr Food Res. 2006 Feb;50(2):176-87. Review. PMID: 16470636. [38] Raaele Teperino, Sabine Amann, Martina Bayer, Sean L. McGee, Andrea Loipetzberger, Timothy Connor, Carsten Jaeger, Bernd Kammerer, Lilli Winter, Gerhard Wiche, Kevin Dalgaard, Madhan Selvaraj, Michael Gaster, Robert S. Lee-Young, Mark A. Febbraio, Claude Knauf, Patrice D. Cani, Fritz Aberger, Josef M. Penninger, J. Andrew Pospisilik, and Harald EsterbauerCell. Hedgehog partial agonism drives warburg-like metabolism in muscle and brown fat. 151(2), 2012. http://www.mpg.de/6387693/cells_hedgehog-signalling-pathway. [39] Pal A, Barber TM, Van de Bunt M, Rudge SA, Zhang Q, Lachlan KL, Cooper NS, Linden H, Levy JC, Wakelam MJ, Walker L, Karpe F, and Gloyn AL. Ptenmutations as a cause of constitutive insulin sensitivity and obesity. New England Journal of Medicine, 367(11):1002, 2012. http://www.ncbi.nlm.nih.gov/pubmed/22970944. [40] Lodhi IJ, Yin L, Jensen-Urstad AP, Funai K, Coleman T, Baird JH, El Ramahi MK, Razani B, Song H, Fu-Hsu F, Turk J, and Semenkovich CF. Inhibiting adipose tissue
276
CHAPTER 3. OBESITY lipogenesis reprograms thermogenesis and ppar activation to decrease diet-induced obesity. Cell Metabolism, 2012. http://www.ncbi.nlm.nih.gov/pubmed/22863804.
[41] Bezy O, Tran TT, Pihlajamki J, Suzuki R, Emanuelli B, Winnay J, Mori MA, Haas J, Biddinger SB, Leitges M, Goldne AB, Patti ME, King GL, and Kahn CR. Pkcdelta regulates hepatic insulin sensitivity and hepatosteatosis in mice and humans. Journal of Clinical Investigation, 2011. http://www.ncbi.nlm.nih.gov/ pmc/articles/PMC3104767/. [42] http://www.neuron.org/content/article/abstract?uid= PIIS0896627308002171. Andrews, Zane B. Horvath; Tamas L.: Food Reward. Neuron, 2008, 57:6:806-808. Tasteless
[43] http://www.neuron.org/content/article/abstract?uid= PIIS0896627308001190. Araujo, Ivan; Oliviera-Maia, Albino; Sotnikova, Tatyana; Gainetdinov, Raul; Caron, Marc; Nicolelis, Miguel; Simon, Sidney: Food Reward in the absence of taste receptor signalling. Neuron. Vol 57, 930-941, 27 March 2008. Doi: 10.1016/j.neuron.2008.01.032. [44] http://jn.physiology.org/cgi/content/abstract/100/4/2145. Peter Kovacs and Andras Hajnal: Altered Pontine Taste Processing in a Rat Model of Obesity. J Neurophysiol 100: 2145-2157, 2008. First published June 11, 2008; doi:10.1152/jn.01359.2007. [45] A. T. Roussin and P. M. Di Lorenzo Oh, How Sweet It Is. Focus on ltered Pontine Processing in a Rat Model of Obesity J Neurophysiol, October 1. 2008; 100(4): 1697 - 1698. [46] http://www.ncbi.nlm.nih.gov/pubmed/16815797. Bartoshuk LM, Duy VB, Hayes JE, Moskowitz HR, Snyder DJ. Psychophysics of sweet and fat perception in obesity: problems, solutions and new perspectives. Philos Trans R Soc Lond B Biol Sci 361: 1137-1148, 2006. [47] Cicerale S, Riddell LJ, and Keast RS. The association between perceived sweetness intensity and dietary intake in young adults. J Food Sci, 77(1):H315, 1 2012. http: //www.ncbi.nlm.nih.gov/pubmed/22132685. [48] Bartoshuk LM, Duy VB, Green BG, Homan HJ, Ko CW, Lucchina LA, Marks LE, Snyder DJ, and Weienbach JM. Valid across-group comparisons with labeled scales: the glms versus magnitude matching. Physiol Behav, 82(1):10914, 204. http://www.ncbi.nlm.nih.gov/pubmed/15234598. [49] Pepino MY, Love-Gregory L, Klein S, and Abumrad NA. The fatty acid translocase gene, cd36, and lingual lipase inuence oral sensitivity to fat in obese subjects. J Lipid Res, 12 2011. http://www.ncbi.nlm.nih.gov/pubmed/22210925.
BIBLIOGRAPHY
277
[50] Wooding S, Kim UK, Bamshad MJ, Larsen J, Jorde LB, and Drayna D. Natural selection and molecular evolution in ptc, a bitter-taste receptor gene. Am J Hum Genet, 74(4):63746, 4 2004. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1181941. [51] http://www.bmj.com/cgi/reprint/329/7468/736. Swinburn, Boyd; Egger, Garry: The runaway weight gain train: too many accelerators, not enough brakes. BMJ 2004;329;736-739 doi:10.1136/bmj.329.7468.736. [52] http://www.ncbi.nlm.nih.gov/pubmed/19369382. Swinburn BA, Sacks G, Lo SK, Westerterp KR, Rush EC, Rosenbaum M, Luke A, Schoeller DA, Delany JP, Butte NF, Ravussin: Estimating the changes in energy ux that characterize the rise in obesity prevalence. E. Am J Clin Nutr. 2009 Apr 15. [. [53] http://www.postgradmed.com/index.php?free=pgm_07_2008?article=1788. Artham, S.M.; Lavie, C.J.; Milani, R,V.; Ventura, H.O.: The obesity paradox: impact of obesity on the prevalence and prognosis of cardiovascular diseases. Postgrad Med. 2008 Jul;120(2):34-41. [54] http://archpedi.ama-assn.org/cgi/content/abstract/163/4/309. Singh, Amika S.; Chin A Paw, Marijke J. M.; Brug, Johannes; van Mechelen, Willem: Dutch Obesity Intervention in Teenagers: Eectiveness of a School-Based Program on Body Composition and Behavior. Archives of Pediatrics and Adolescent Medicine, 2009; 163 (4): 309 DOI: 10.1001/archpediatrics.2009.2. [55] Waters E, de Silva-Sanigorski A, Hall BJ, Brown T, Campbell KJ, Gao Y, Armstrong R, Prosser L, and Summerbell CD. Interventions for preventing obesity in children. Cochrane Database Syst Rev, 12:CD001871, 12 2011. http://www.ncbi.nlm.nih. gov/pubmed/22161367. [56] Gortmaker SL, Swinburn BA, Carter R Levy D AND, Mabry PL, Finegood DT, Huang T, Marsh T, and Moodie ML. Changing the future of obesity: science, policy, and action. The Lancet, 378(9793):838847, 8 2011. http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2811% 2960815-5/abstract?elsca1=ETOC-LANCET&elsca2=email&elsca3=segment. [57] Rutter H. Where next for obesity? The Lancet, 378(9793):746747, 2011. http://www.thelancet.com/journals/lancet/article/PIIS0140-6736% 2811%2961272-5/fulltext. [58] http://www.foodnavigator.com/news/ng.asp?n=66244-ccfra-fat-thickeners. Ahmed ElAmin: Coatings reduce fat in battered sh production; Food Navigator.com Europe. [59] http://europa.eu.int/comm/health/ph_determinants/life_style/ nutrition/documents/nutrition_gp_en.pdf. Commission of the European Communities: GreenPaper Promoting healthy diets and physical activity: a
278
CHAPTER 3. OBESITY European dimension for the prevention of overweight, obesity and chronic diseases; Brussels, 08.12.2005 COM(2005) 637 nal.
[60] http://www.ciaa.be/documents/news_events/CIAA_comments_re_Comm_GP_on_ D&PA.pdf. CIAA Comments on the Commissions Green Paper: Promoting healthy diets and physical activity: towards a European strategy for the prevention of overweight, obesity and chronic diseases COM (2005) 637 nal. [61] Langbein, Kurt; Skalnik, Christian: Endlich schlank mit Xenical? 1. Auage 1998 Verlag Kiepenheuer und Witsch,Kln. [62] Biesalzki, Hans-Konrad: Ernhrungsmedizin; Stuttgart; New York;Thieme,1995 ppg 197. [63] http://en.wikipedia.org/wiki/Rimonabant. Wikipedia: Rimonabant. [64] http://en.wikipedia.org/wiki/Anti-obesity_drug. drug. Wikipedia: Anti-obesity
[65] Tam CS, Lecoultre V, and Ravussin E. Novel strategy for the use of leptin for obesity therapy. Expert Opin Biol Ther, 9 2011. http://www.ncbi.nlm.nih.gov/pubmed/ 21910668. [66] Roth JD, Roland BL, Cole RL, Trevaskis JL, Weyer C, Koda JE, Anderson CM, Parkes DG, and Baron AD. Leptin responsiveness restored by amylin agonism in dietinduced obesity: evidence from nonclinical and clinical studies. Proc Natl Acad Sci U S A, 105(20):725762, 5 2008. http://www.ncbi.nlm.nih.gov/pmc/articles/ PMC2438237/?tool=pubmed. [67] http://www.tagesschau.de/wirtschaft/meldung93178.html. ARD. Tagescschau.de: Entscheidung ber Schlankmacherpille. Kassen mssen nicht fr complia zahlen. 28.06.2008. [68] http://news.bbc.co.uk/2/hi/health/6907160.stm. BBC: Weight loss pill warning issued. A weight-loss drug used by thousands is unsafe for those also taking antidepressants, health watchdogs warn. 19.07.2007. [69] http://mrw.interscience.wiley.com/cochrane/clsysrev/articles/ CD004096/frame.html. Norris SL, Zhang X, Avenell A, Gregg E, Schmid CH, Lau J (2005). Pharmacotherapy for weight loss in adults with type 2 diabetes mellitus. Cochrane database of systematic reviews (Online) (1): CD004096. Doi: 10.1002/14651858.CD004096.pub2. [70] Padwal,Raj S.; Majumdar, Sumit R.: Drug treatments for obesity: orlistat, sibutramine, and rimonabant. The Lancet, Volume 369, Issue 9555, 6 January 2007-12 January 2007, Pages 71-77 doi: 10.1016/S0140-6736(07)60033-6.
BIBLIOGRAPHY
279
[71] Deminice R, da Silva RP, Lamarre SG, Brown C, Furey GN, McCarter SA, Jordao AA, Kelly KB, King-Jones K, Jacobs RL, Brosnan ME, and John T. Brosnan JT. Creatine supplementation prevents the accumulation of fat in the livers of rats fed a high-fat diet. J. Nutr, 141:17991804, 9 2011. http://jn.nutrition.org/content/ early/2011/08/31/jn.111.144857.abstract. [72] http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool= pubmed&pubmedid=16926800. Johnston, Carol S.; Gaas, Cindy A.: Medicinal Uses and Antiglycemic Eect. MedGenMed. 2006; 8(2): 61. Vinegar:
[73] http://www.nature.com/ejcn/journal/v59/n9/abs/1602197a.html. Ostman, E.; Granfeldt, Y.; Persson, L.; Bjrck, I.: Vinegar supplementation lowers glucose and insulin responses and increases satiety after a bread meal in healthy subjects Eur J Clin Nutr 59: 983-988; advance online publication, June 29, 2005; doi:10.1038/sj.ejcn.1602197. [74] http://pubs.acs.org/doi/abs/10.1021/jf900470c. Kondo, Tomoo; Kishi, Mikiya; Fushimi, Takashi; Kaga, Takayuki: Acetic Acid Upregulates the Expression of Genes for Fatty Acid Oxidation Enzymes in Liver To Suppress Body Fat Accumulation. Journal of Agricultural and Food Chemistry. Doi: 10.1021/jf900470c. [75] Tobbia P, Norris LA, and Klima LD. Ventricular brillation coinciding with phentermine initiation. BMJ Case Rep, page pii: bcr2012006410, 10 2012. http: //www.ncbi.nlm.nih.gov/pubmed/23076689. [76] Ein r tselhafter patient: Herzstillstand durch muskelkrampf. spiegel online 04.nov 2012. http://www.spiegel.de/gesundheit/diagnose/ herzstillstand-abnehm-pille-bringt-frau-in-lebensgefahr-a-864429. html. [77] Wikipedia: Phentermine. http://en.wikipedia.org/wiki/Phentermine. [78] Fda approves weight-management drug qsymia. fda july 17. 2012. http://www.fda. gov/NewsEvents/Newsroom/PressAnnouncements/ucm312468.htm. [79] Cameron F, Whiteside G, and McKeage K. Phentermine and topiramate extended release (qsymia tm): rst global approval. Drugs, 72(15):203342, 10 2012. http: //www.ncbi.nlm.nih.gov/pubmed/23039320. [80] http://www.journalofdst.org/Journal/pdf/September2008/ VOL-2-OBT2-KLONOFF.pdf. Klono DC, Greenway F: Drugs in the Pipeline for the Obesity Market. Journal of Diabetes Science and Technology. Volume 2, Issue 5, September 2008. [81] http://en.wikipedia.org/wiki/Bupropion/naltrexone. pion/naltrexone.
Wikipedia:
Bupro-
280
CHAPTER 3. OBESITY
[82] http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2810% 2962281-7/ fulltext?elsca1=TL-171210&elsca2=email&elsca3=segment. New obesity pill: new hopes, old fears. Editorial. The Lancet, Volume 376, Issue 9758, Page 2042, 18 December 2010 doi:10.1016/S0140-6736(10)62281-7. [83] http://www.ncbi.nlm.nih.gov/pubmed/20926200. Reece AS: Hypothalamic opioid-Melanocortin appetitive balance and addictive craving. Med Hypotheses. 2010 Oct 4. [84] http://www.ncbi.nlm.nih.gov/pubmed/20673995. Greenway FL, Fujioka K, Plodkowski RA, Mudaliar S, Guttadauria M, Erickson J, Kim DD, Dunayevich E; COR-I Study Group: Eect of naltrexone plus bupropion on weight loss in overweight and obese adults (COR-I): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2010 Aug 21;376(9741):595-605. [85] http://www.ncbi.nlm.nih.gov/pubmed/20626429. Nathan PJ, ONeill BV, Napolitano A, Bullmore ET: Neuropsychiatric Adverse Eects of Centrally Acting Antiobesity Drugs. CNS Neurosci Ther. 2010 Jul 7. [86] Grs S, Canteiro S, Mercader J, and Carpn C. Oxidation of high doses of serotonin favors lipid accumulation in mouse and human fat cells. Mol Nutr Food Res, 2 2013. http://www.ncbi.nlm.nih.gov/pubmed/23390020. [87] http://www.pnas.org/content/early/2010/12/16/1010929108. Schulz TJ, Huang TL, Tran TT, Zhang H, Townsend KL, Shadrach JL, Cerletti M, McDougall LE, Giorgadze N, Tchkonia T, Schrier D, Falb D, Kirkland JL, Wagers AJ, Tseng YH: Identication of inducible brown adipocyte progenitors residing in skeletal muscle and white fat. Proc Natl Acad Sci U S A. 2010 Dec 20. [88] Pereld JW 2nd, Lee Y, Shulman GI, Samuel VT, Jurczak MJ, Chang E, Xie C, Tsichlis PN, Obin MS, and Greenberg AS. Tumor progression locus 2 (tpl2) regulates obesity-associated inammation and insulin resistance. Diabetes, 60(40):116876, 4 2011. http://www.ncbi.nlm.nih.gov/pubmed/21346175. [89] DeFuria J, Bennett G, Strissel KJ, Pereld JW 2nd, Milbury PE, Greenberg AS, and Obin MS. Dietary blueberry attenuates whole-body insulin resistance in high fat-fed mice by reducing adipocyte death and its inammatory sequelae. J Nutr, 139(8):15106, 8 2009. http://jn.nutrition.org/content/139/8/1510.long. [90] Plant oil may hold key to reducing obesity-related medical issues, says james pereld of the university of missouri-columbia. Eurek Alert, 3, 3 2011. http: //www.eurekalert.org/pub_releases/2011-03/uom-pom032311.php. [91] Verma JP, Bhola Nath, and Aggarwal JS. Structure of sterculic acid. Nature, 175:8485, 1 1955. http://www.nature.com/nature/journal/v175/n4445/abs/ 175084a0.html.
BIBLIOGRAPHY
281
[92] Carbocyclic fatty acids in plants: Biochemical and molecular genetic characterization of cyclopropane fatty acid synthesis of sterculia foetida. PNAS, 99(10):71727177, 5 2002. http://www.pnas.org/content/99/10/7172.full.pdf. [93] Asp ML, Collene AL, Norris LE, Cole RM, Stout MB, Tang SY, Hsu JC, and Belury MA. Time-dependent eects of saower oil to improve glycemia, inammation and blood lipids in obese, post-menopausal women with type 2 diabetes: A randomized, double-masked, crossover study. Clin Nutr, 2 2011. http://www.ncbi.nlm.nih. gov/pubmed/21295383. [94] Miyoshi H, Souza SC, Endo M, Sawada T, Pereld JW 2nd, Shimizu C, Stancheva Z, Nagai S, Strissel KJ, Yoshioka N, Obin MS, Koike T, and Greenberg AS. Perilip overexpression in mice protects against diet-induced obesity. J Lipid Resin, 51(5):97582, 5 2010. http://www.ncbi.nlm.nih.gov/pubmed/19797618. [95] Sawada T, Miyoshi H, Shimada K, Suzuki A, Okamatsu-Ogura Y, Pereld JW 2nd, Kondo T, Nagai S, Shimizu C, Yoshioka N, Greenberg AS, Kimura K, and Koike T. Perilipin overexpression in white adipose tissue induces a brown fat-like phenotype. PLoS One, 5(11):e1406, 11 2010. http://www.plosone.org/article/info%3Adoi% 2F10.1371%2Fjournal.pone.0014006. [96] Souza SC, Christoolete MA, Ribeiro MO, Miyoshi H, Strissel KJ, Stancheva ZS, Rogers NH, DEon TM, Pereld JW 2nd, Imachi H, Obin MS, Bianco AC, and Greenberg AS. Perilipin regulates the thermogenic actions of norepinephrine in brown adipose tissue. J Lipid Res, 48(6):12739, 6 2007. http://www.jlr.org/content/ 48/6/1273.long. [97] Quarles LD. Extracellular calcium-sensing receptors in the parathyroid gland, kidney, and other tissues. Curr Opin Nephrol Hypertens, 12(4):34955, 7 2003. http://www. ncbi.nlm.nih.gov/pubmed/12815330. [98] He YH, Song Y, Liao XL, Wang L, Li G, Alima Li Y, and Sun CH. The calciumsensing receptor aects fat accumulation via eects on antilipolytic pathways in adipose tissue of rats fed low-calcium diets. J Nutr, 141(11):193846, 11 2011. http://www.ncbi.nlm.nih.gov/pubmed/21940515. [99] He Y, Zhang H, Teng J, Huang L, Li Y, and Sun C. Involvement of calcium-sensing receptor in inhibition of lipolysis through intracellular camp and calcium pathways in human adipocytes. Biochem Biophys Res Commun, 404(1):3939, 1 2011. http: //www.ncbi.nlm.nih.gov/pubmed/21130730. [100] Doehner W, Schenkel J, Anker SD, Springer J, and Audebert HJ. Overweight and obesity are associated with improved survival, functional outcome, and stroke recurrence after acute stroke or transient ischaemic attack: observations from the tempis trial. Eur Heart J, 10 2012. http://www.ncbi.nlm.nih.gov/pubmed/23076781.
282
CHAPTER 3. OBESITY
[101] Jackson RS, Black JH 3rd, Lum YW, Schneider EB, Freischlag JA, Perler BA, and Abularrage CJ. Class i obesity is paradoxically associated with decreased risk of postoperative stroke after carotid endarterectomy. J Vasc Surg, 55(5):130612, 5 2012. http://www.ncbi.nlm.nih.gov/pubmed/22542344.
Chapter 4 Food Allergies

Allergies can be a serious threat to life and can end as anaphylatic shock. The allergens in foods represent a hazard for those who suer from allergies. According to the European Federation of Allergy and Airways Diseases Patients Association an estimated 4 per cent of adults and 8 percent of children in the European Union suer from food Allergies. First signs of an allergic reaction to food - Running nose - Itchy skin rash - Tingling in the tongue, lips, or throat - Swelling in the throat or other parts of the body - Abdominal pain - Eczema - Dizziness - Diarrhoea or vomiting - Wheezing
4.0.4
Major serious food allergens
Cereals containing gluten (i.e. wheat, rye, barley, oats, spelt or their hybridised strains, and products thereof), sh, crustaceans, egg (globulin; albumin; Apovitellenin; livetin; ovalbumin; ovomucin; ovomucoid; ovovitellin; phosvitin), peanut, soybeans (soy protein, textured vegetable protein TPV, hydrolysed plant protein, hydrolysed soy protein, hydrolysed vegetable protein,), milk and dairy products including lactose (milk sugar), nuts i.g. almond (Amygdalus communis), hazelnut (Corylus avellana),walnut (Juglans regia), cashew (Anacardium occidentale),pecan nut(Carya illinoiesis), Brazil nut (Bertholletia excelsa), pistachio nut (Pistacia vera), macadamia nut, Queensland nut (Macadamia ternifolia), celery and other foods of the Umbelliferae family, mustard, sesame seed, sulphur dioxide and sulphites (at concentrations of more than 10 mg/kg or 10 mg/litre expressed as SO2 ) are the major serious food allergens. The most common food allergens are found in a wide variety of processed foods and may 283
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cause allergies or intolerances in consumers endangering their health. Food allergens are part of a wide group of adverse reactions to foods. In order to provide all consumers with better information and to protect the health of certain consumers all ingredients must now be included in the list of ingredients.
Table 4.1: Frequency of food allergies Foods Per cent Milk (cow) 42.0 Egg (hen) - Egg white 14.6 - Egg yolk 9.0 - Egg white and yolk 9.7 Fish 11.0 Citrus fruit 4.5 Legume 2.5 Horse meat 1.3 Meat 1.0 Vegetable 1.0 Onion 1.0 Nuts, chocolate and others 2.0 Allergens Cereals containing gluten ( i.e. wheat, rye, barley, oats, spelt, kamut or their hybridised strains) and products thereof.) (Coeliac disease) Crustaceans and products thereof. Eggs and products thereof. Fish and products thereof. Peanuts and products thereof. Soybeans and products thereof. Milk and products thereof (including lactose). Nuts i. e. Almond (Amygdalus communis L.), Hazelnut (Corylus avellana), Walnut (Juglans regia), Cashew (Anacardium occidentale), Pecan nut (Carya illinoiesis (Wangenh.) K. Koch), Brazil nut (Bertholletia excelsa), Pistachio nut (Pistacia vera), Macadamia nut and Queensland nut (Macadamia ternifolia) and products thereof. Celery and products thereof.
285 Mustard and products thereof: Mustard protein allergic individuals may react to the protein content of the mustard oil. Individuals sensitised to and by the skin sensitising component allyl isothiocyanate may react to oil in the absence of mustard proteins. Sesame seeds and products thereof. Sulphur dioxide and sulphites at concentrations of more than 10 mg/kg or 10 mg/litre expressed as SO2. Preservatives A small part of humans suer fron allergy to preservatives. Labels like "Free of preservatives" must be true as some persons suer heavy allergic responds to some preservatives. To avoid recourses due to cross over " No preservatives added" is being now labeled. This, however, does not solve the problem of allergic reactions.
4.0.5
Diagnostic criteria of food allergies need further standardisation [1]
Chafen and colleagues 2010 deplore the lacking of clear consensus regarding the prevalence, most eective diagnostic, management and prevention of food allergies. The term "food allergy" needs an universal denition. In this review cows milk, hens eggs, peanuts, tree nuts, sh, and shellsh foods were found responsible for 50% of all food allergies. The authors also stress that more than 1% to 2% but less than 10% of the population are aected by food allergies. Skin prick tests and serum food-specic IgE presented no statistical advantage compared with food challenge. No other valid testing methods exist. Despite being the most important tool in the therapy of food allergies, elimination diets are not suciently studied. The data on Immunotherapy are insucient and cannot be recommended. Standardized denitions of high risk and hydrolysed formula do not exist to protect infants from cows milk allergy. The authors call for uniformity in the criteria for what constitutes a food allergy and a set of evidence-based guidelines on which to make this diagnosis.
4.0.6
Diagnosis of food allergy [2]
Accurate diagnosis of cows milk allergy by determining the immunoglobulin E (IgE)mediated response may be more useful than skin or blood tests performed with whole extracts. Fiocchi et al 2011 stresses that diculties must be resoled to nd and validate markers and correlate them to disease and patient proles, meanwhile oral food challenge remains the reference standard for the diagnosis of this allergy.
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Foods with baked milk may improve tolerance to dairy foods in children [3] Increasing amounts of foods that contain baked milk in the diets of children suering with milk allergies may improve tolerance to milk and milk products. Sampson et al 2011 report that approximately 75 percent of children, aged 2 to 17 years, with milk allergy, were found to tolerate foods containing baked milk, such as muns, waes and cookies. The high temperatures used in baking cause the proteins in milk to break down. This is believed to reduce the allergenicity. After an initial mun food challenge of six to twelve months, the children were given cheese pizza which is less heated than muns and contains higher amount of unmodied milk protein. After three years of a diet containing cheese pizza At the end of the study period, 47 percent of the children could tolerate unheated milk products, such as skim milk, yoghurt and ice cream, compared to only 22 percent in a control group. The authors concluded that increased exposure to baked milk products helps to children outgrow milk allergies.
4.0.7
Milk and egg in baked food may help children to overcome allergy [4]
Huang and Nowak-Wegrzyn report that some children with milk allergies may reduce allergic reactions when small quantities of milk and egg are present in baked foods. These children became able to consume milk at the end of the study. The authors caution, however, that not all children can cope with such strategy, they present allergy reactions further on. In this study milk allergic children received a mun and a wae made with milk in the oven. Those who tolerated this trial received, during 6 years, milk products such as macaroni and cheese and pizza baked in the oven. A total of 44,3% of children which started the study become capable of eating milk unheated products as well. This compared to 21,7% of children which went to the clinic, and outgrew their allergies becoming capable of eating non-heated milk. The authors explain that severity of the allergy are likely due to the part of the milk protein, which is less resistant to heat. After baking these denaturated proteins may be tolerated by these children which are allergic to them in unheated form. Nowak-Wegrzyn said the study helps to explain why some allergic children which are more careless about what they eat have reduced problems, while other children who are much more careful still have severe reactions to traces of milk. The authors suggest oral challenge to extensively heated milk and egg into milk and egg should be considered in case of allergic cases. However giving baked foods to allergic chilOurFood Database of Food and Related Sciences Copyright 1998-2010 Karl H. Wilm. All rights reserved.
287 dren should only be started under clinical supervision, because some proteins such as those of wheat, appear to cause the same reaction when baked in the oven, the authors warned. Kim, Nowak-Wegrzyn and colleagues 2011 found that approximately 75% of children, allergic to milk, tolerate extensively heated baked milk muns. Children having a diet containing baked milk products, such as cheese topped pizzas were 16 times more likely to become unheated milk tolerant.than children who observed a strict milk-free diet, Median casein IgG(4) levels in the baked milk-tolerant group increased signicantly, but median milk IgE values remained unchanged. [5] Allergen avoidance remains the most important tool to reduce allergy reactions. Lieberman and Nowak-Wgrzyn 2012, however, stress that improvements vaccines using modied proteins of decreased allergenicity by purifying, cloning and modifying allergens in molecular biology have allowed researchers to purify, clone, and modify allergens opening new research elds related to allergies, such as various allergen-nonspecic immunomodulatory therapies. [6]
4.0.8
Environmental changes and allergy prevention [7]
The number of food allergy, eczema, atopic dermatitis, allergic rhinitis, asthma and respiratory allergic diseases and anaphylaxis are increasing. The developing immune system is highly vulnerable to modern environmental changes. Strategies to cope with the allergy epidemic is to identify factors associated with modern lifestyle during early development, improve hygienic conditions and restoring bacterial balance using probiotic and prebiotic supplements. Dietary supplements such as polyunsaturated fatty acids, antioxidants, folate, and vitamin D may provide immunomodulating activities, and the role of early introduction of allergenic foods for the promotion of tolerance. Environmental pollutants may also be implicated in undesirable development of the immune system of children. Guidelines for allergy prevention recommend to avoid smoking, breastfeeding, if not possible, hydrolysed formula should be used.
4.0.9
Allergy testing [8]
Sicherer and Wood 2012 recommend to test for allergen-specic immunoglobulin E (IgE) or skin prick tests (SPT). Newer enzymatic assays based on anti-IgE antibodies have supplanted the radioallergosorbent test (RAST). The serum sIgE test and the skin prick test SPT are sensitive and have similar diagnostic properties. The Skin prick tests (SPT) and the total serum IgE (Radio-Immuno-Sorbens-Test RIST test) detect specic immunoglobulin E ( sIgE). Allergen-specic IgE antibody testing (Radioallergosorbent RAST testing) screens for a type I hypersensitivity to a specic substance or substances in response to acute or chronic allergy-like symptoms.
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Food allergy consensus on treatment of allergic diseases [9] According to Burks et al. 2012, leading allergy organizations have joined to elaborate consensus documents called International Consensus ON (ICON) on treatment of allergic diseases. The authors stress that more than 170 foods are allergenic, but only a small number cause the majority of reactions, varying between geographic regions. Identication and strict avoidance of the food which causes the allergy is still the recommended treatment, because medication treat only symptoms of the disease. Ovomucoid-specic IgE concentrations predicting egg allergy [10] Ovomucoid-specic IgE antibodies as predictors of whether children could tolerate heattreated egg were assessed by Ando and colleagues 20008. They found that the quantitative measurements of specic IgE antibodies to both egg white and ovomucoid and the evaluation against the suggested positive and negative decision points for specic IgE may be useful in the diagnosis of egg allergy. The positive decision point was 7.4 kU(A)/L, and the negative decision point, was 0.6 kU(A)/L for raw egg white. For heated egg white the positive decision point was 10.8 kU(A)/L, and the negative decision point was 1.2 kU(A)/L. Guidelines of the Dutch College of General Practitioners [11] Brand 2011 reports that the diagnosis of food allergy includes detailed history and reproducible symptoms and double-blind oral food challenges. Pattern must elicited from the history to conrm food allergy. Measuring specic immunoglobulin E in serum is not a help in the diagnosis of food allergy because asymptomatic sensitisation is common, says the author. The 2011 revised version of the practice guideline on food hypersensitivity in infants of the Dutch College of General Practitioners also states that the examination of serum specic IgE levels should not be used in the diagnosis of food allergy, and a double-blind placebo-controlled food challenge is recommended. [12] Quantication of Ara h 2-specic IgE for peanut allergy and soy bean allergy diagnosis [13] Nicolaou and Custovic 2011 write that the quantication of Ara h 2-specic IgE may accurately discriminate peanut allergy from tolerance may be more useful to predicting the presence and severity of clinical allergy than skin or blood tests based on whole extracts, however, until this is conrmed by further studies oral food challenge remains the gold standard for accurate diagnosis. The authors report that dierent pollen and dietary exposures produce regional dierent results, for peanut-allergy sensitisation to Ara h 1-3 in the USA, to Ara h 9 in Spain and to Ara h 8 in Sweden. Soybean allergy sensitisation to Gly m 5 or Gly m 6 allergens may increase the risk to severe allergic reactions.
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Ballmer-Weber and Homann-Sommergruber 2011 report that celeriac, carrot and tomato are the most prevalent allergenic vegetables, whereas fruit allergy is mainly induced by apple, peach and kiwi. In kiwifruit allergy Act d 1 and Act d 3 were identied as potential marker allergens for severe symptoms. For celeriac allergy, however, such markers are still missing. The authors stress that the diagnosis of fruit and vegetable allergy in birch pollen-sensitized patients should not be excluded on a negative IgE testing to extracts, because Bet v 1-related allergens are often under-represented in extracts. [14]
4.0.10
Mediterranean type of diet reduces asthma in children [15]
According to the PANACEA study the adherence to the Mediterranean type of diet is associated with lower prevalence of asthma symptoms, among 10 to 12 years old children: Greater adherence to the Mediterranean diet was inversely associated with ever had wheeze, exercise wheeze, ever had diagnosed asthma. No signicant associations were found between asthma symptoms and consumption of fruits, vegetables, legumes, cereals, dairy, salty snacks, or margarine/butter consumption, while increased sh and meat intake was associated with less asthma symptoms. The authors suggest an inverse relationship between level of adherence to the Mediterranean diet and prevalence of asthma in school-aged children.
4.0.11
Food allergies and asthma [16]
Wang and Liu 2011 report that children with food allergies together with asthma are more likely to have near-fatal or fatal allergic reactions to food and more likely to have severe asthma. The authors stress that a causal link has not been determined, however, both condition together should increase the awareness of the severity of these ailments.
4.0.12
Food-induced anaphylaxis is the leading single cause of emergency treatment [17]
According to Jrvinen 2011 peanut, tree nuts, and shellsh are the most commonly implicated foods in anaphylaxis, although milk is a common trigger in children, and asthma increases the risk of severe reactions. The authors stress that schools and restaurants have inadequate management plans and symptom and lack in sta education. Markers to predict risk of anaphylaxis and news therapies should be developed.
4.0.13
Costs of food allergies [18]
According to Patel et al. 2011, 4% to 6% of children and 1% to 2% of adults in the United States are suering of food allergies. Direct medical costs and indirect costs of food-induced
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allergic reactions and anaphylaxis in the United States amount to half a billion dollars in 2007. Ambulatory visits accounted for more than half of the costs.
4.0.14
Food allergy training for restaurant sta must be improved [19]
Deaths caused by food-induced anaphylactic reactions are increasing, with most caused by food purchased outside the home. Bailey et al. 2011 report gaps in restaurant stas knowledge of allergy. The authors stress the necessity to improve food allergy training practice for restaurant sta.
4.0.15
No proof of food allergenicity of genetically modied plants [20]
Goodman and Tetteh 2011 reviewing studies related to a possible allergenicity of genetic modied organisms found no documented proof of an adverse eect resulting from foods produced from GM plants. The authors suggest improvements for the allergenicity assessment of GMO plants.
4.0.16
Food allergens and Good Manufacturing Practice
According to the Institute of Food Science and Technology (IFST) the "greatest care must be taken by food manufacturers to formulate foods so as to avoid, whenever possible, inclusion of unnecessary major allergens as ingredients. Food makers must organise raw material supplies, production schedules and cleaning procedures so as to prevent cross-contact of products by "foreign" allergens. Training of all personnel should be focused on the understanding of necessary measures and the reasons for them. Food manufacturers should comply with the relevant labelling legislation providing appropriate warning, to potential purchasers, of the presence of a major allergen in a product. An appropriate system for recall of any product found to contain a major allergen not indicated on the label should be in place ".
4.0.17
The cause of increasing number of allergies is unclear [21]
Many allergies and immune system diseases have quadrupled in the last decade. Researchers suspect suspect modern living, including the sterile homes, changes in diet, air pollution, obesity and increasingly sedentary lifestyles to be responsible for the increase of the ailments.
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4.0.18
Particulate Emission From Natural Gas Burning stove tops and water heaters [22]
According to Minutolo and colleagues 2008, burning natural gas in home appliances such as stove tops and water heaters ultrane airborne particles with diameters in the 1 nm to 10 nm size range are formed. In home-heating burners these particles, formed in the ame region are oxidized in the post-oxidation region, presenting no hazard. However, domestic stove tops and water boilers do not have a post-oxidation region. The emit, therefore, a high number of hazardous particles. Soot particles with size larger than 10 nm are not formed. Small particles are the most dangerous [23] Because of the size of the particle, they can penetrate the deepest part of the lungs. Larger particles are generally ltered in the nose and throat and do not cause problems, but particulate matter smaller than about 10 micrometers can settle in the bronchi and lungs and cause health problems. Similarly, particles smaller than 2.5 micrometers tend to penetrate into the gas-exchange regions of the lung, and very small particles (< 100 nanometers) may pass through the lungs to aect other organs. Particles smaller than 100 nanometers can pass through cell membranes and migrate into other organs, including the brain. It has been suggested that particulate matter can cause similar brain damage as that found in Alzheimer patients. Particles emitted from modern diesel engines are typically in the size range of 100 nanometers. In addition, these soot particles also carry carcinogenic components like benzopyrenes adsorbed on their surface. Long-term exposure to ne particulate [24] Pope and colleagues 2002 found that particles smaller than 2.5 micrometers leads to high plaque deposits in arteries, causing vascular inammation and atherosclerosis. Fine particulate and sulfur oxide-related pollution were associated with all-cause, lung cancer, and cardiopulmonary mortality. The authors concluded that long-term exposure to combustion-related ne particulate air pollution is an important environmental risk factor for cardiopulmonary and lung cancer mortality. The authors stress that the legislative limits for engines are unsuitable to protect against particulate matter. Toxicology of particulate matter [25] According to Valavanides and colleagues 2008 the inammatory injury, oxidative damage, and other biological eect are stronger for ne and ultrane particles, such those from exhaust particles from automobiles because they can penetrate deeper into the airways of
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the respiratory tract. These particles pollute urban areas. The authors call for studies on the cytotoxic and carcinogenic mechanisms of particulate matters in the lungs. They stress the importance to understand the formation of particulate matter by internal combustion engines and other sources.
4.0.19
The Hygiene hypothesis [26]
According to Fernando Martinez the hygiene hypothesis, as originally proposed, postulated an inverse relation between the incidence of infectious diseases in early life and the subsequent development of allergies and asthma. Researchers say that microbial burden in general, and not any single acute infectious illness, is the main source of "danger" signals which modulate the immune response in early life. This may interact with genetic variations and result in an inherited susceptibility to asthma and allergies. Some are feeding high-risk children gradually larger amounts of allergy-inducing foods, hoping to train the immune system not to overreact. Others are testing benign bacteria or parts of bacteria. Still others have patients with MS, colitis and related ailments swallow harmless parasitic worms to try to calm their bodies misdirected defences. Robert Summers and colleagues 2004 postulated that helminth parasites mostly have been eliminated in industrialized parts of the world, where the incidence of inammatory bowel disease became the highest. Therefore the authors experimented with whipworms, proposing that helminths protect the bowel by downregulating inammatory responses. They call on the symbiotic eect of helmnths and humans on developing and maintaining the immune system. [27] Although hay fever, eczema, asthma and food allergies seem quite dierent, they are all "allergic diseases" because they are caused by the immune system responding to substances that are ordinarily benign, such as pollen or peanuts. Autoimmune diseases also result from the bodys defence mechanisms malfunctioning. But in these diseases, which include lupus, MS, Type 1 diabetes and inammatory bowel disease, the immune system attacks parts of the body such as nerves, the pancreas or digestive tract. According to Jean-Francois Bach the immune systems are much less busy, resulting in much more strong responses to much weaker stimuli, triggering allergies and autoimmune diseases. The researcher stresses that children raised with pets or older siblings are less likely to develop allergies, possibly because they are exposed to more microbes and parasites. Children reared on farms were one-tenth as likely to develop diseases such as asthma and hay fever. This was strongly supported by Erika von Mutius of the Ludwig-Maximilians University in Munich. [28] The lack of exposure to potential threats early in life leaves the immune system with
4.1. EC LABELLING LEGISLATION
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fewer command-and-control cells known as regulatory T cells, making the system more likely to overreact or run wild, says William Parker of the Duke University. Ropbert Wood of the Johns Hopkins School of medicine is against the "hygiene hypothesis" because it does not explain asthma which is common in poor population which is exposed to cockroaches and rodents. Other researchers blame processed foods or change in the balance of certain vitamins, such as vitamins C and E and sh oil. This is being supported by Thomas Platts-Mills But many researchers believe the hygiene hypothesis is the strongest, and is in connection with a genetic predisposition. William Cookson says to develop allergies or autoimmune diseases both environmental factors and genetic susceptibility are needed. Some researches following the hypothesis that challenge is necessary to develop a correct response, try to give increasing amounts of milk, egg and peanut to children suering from these allergies . At start tiny doses are given, trying to train the immune system, the studies are leaded by Wesley Burks. Other researches give patients microscopic parasitic worms to try to tamp down the immune system. Multiple sclerosis patients who had intestinal parasites were found to be in better conditions than those who did not. Professor John O. Fleming and colleagues will therefore undertake experiments with pig worms on MS patients. [29]
4.1
[30]
EC labelling legislation
Labelling According to labelling Directive 2000/13, a full list of ingredient was considered not to be compulsory when the compound ingredient constitutes less than 25% of the nished product. Many of allergenic ingredients were so hidden. The Directive 2003/89/EC amended Directive 2000/13. The mandatory inclusion on food labels of the most common food allergen ingredients and their derivate is contained in this directive which came into force in 2005. A similar law goes into eect in the US on 1 January 20 due to the US Food Allergen and Consumer Protection Act (FALCPA). Food makers have to list in lain, common language, the presence of any of the eight major food allergens- milk, egg, peanut, tree nut, sh, shellsh, wheat and soy a products label. When cross-over of food allergens is not possible to be completely avoided, the warning " May contain traces of..." should be included in the label.
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The EU directives regarding the indication of ingredients in food and Food allergens are: Directive 2003/89 Directive regarding the indication of ingredients in food. [31] Directive 2005/26 Ingredients provisionally excluded from Directive 2003/89/EC. [32] Directive 2006/142 Directive listing ingredients which must appear on food labels. [33] Directive 2007/68 Listing ingredients exempt from labelling rules in 2003/89/EC. [34]
4.1.1
Directive 2003/89 EC [31]
New labelling rules in European Directive (2003/89/EC) ensure that all consumers are given comprehensive ingredient listing information and make it easier for people with food allergies to identify ingredients they need to avoid. The new rules came into force on 25 November 2004 establishing a list of 12 food allergens, which have to be indicated by reference to the source allergen whenever they, or ingredients made from them, are used at any level in pre-packed foods, including alcoholic drinks. The list consists of cereals containing gluten, crustaceans, eggs, sh, peanuts, nuts, soybeans, milk, celery, mustard, sesame, and sulphur dioxide at levels above 10mg/kg or 10 mg/litre expressed as SO2 . The new rules also removed the "25%" rule in the previous legislation, which meant that individual ingredients making up a compound ingredient did not have to be listed if the compound ingredient made up less than 25% of the nished products. So, apart from a few exceptions, all ingredients now have to be indicated on the label, even when they make up only a small proportion of the product.
4.1.2
Mustard seed oil (allyl isothiocyanate) not exempted from labelling as allergen [35]
Mustard and products thereof are included in the list of the Annex IIIa of the Directive 2003/89/EC [31].
Manufacturing process of mustard seed oil Mustard seed from Brassica juncea are ground, tap water is added and the slurry is incubated at 50o C for 30 minutes. The allyl isothiocyanate is released from its precursor by the enzyme myrosinase. The oil is obtained by steam distillation under reduced pressure. The mustard seed oil is separated from water by centrifugation and dried with sodium sulphate and ltered.
4.1. EC LABELLING LEGISLATION Allergic reactions of mustard
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Mustard is known to trigger allergic reactions or intolerances in sensitive individuals and was therefore included in this list and must be labelled.. International Flavours & Fragrances (IFF) requested the European Commission exempt mustard seed oil from labelling European Food Safety Authority to evaluate the scientic data and came to the following conclusion:
4.1.3
Arguments of IFF regarding safety of mustard seed oil
IFF claims that mustard seed oil is not likely to trigger adverse reactions on the basis of two arguments: 1) the typical low levels of mustard seed oil in foods, and 2) the in vitro demonstration that proteins are not present in amounts higher than 1.5 microg/g in ve samples of mustard seed oil analysed with an ELISA test developed by the applicant. According to the Panel IFF did not take into account the known toxicity of allyl isothiocyanate and its role in causing allergic contact dermatitis, or the possibility that proteins not detectable with the ELISA test could cause an IgE-mediated reaction (Lerbaek et al., 2004; Kohl and Frosch, 1990). The main volatile component of mustard seed oil is allyl isothiocyanate (97-100%). which has been classied as toxic by inhalation, in contact with the skin and if swallowed, and irritating to eyes, respiratory system and skin Allergic reactions to mustard, including severe anaphylactic reactions, are well documented in clinical and laboratory studies. Mustard allergy may account for 1-7% of all food allergies with regional variations. Mustard allergens are resistant to heat and to enzymatic degradation, and therefore are not markedly aected by food processing. The major mustard allergens identied are Sin a 1, belonging to the 2S albumin family, and Bra j 1, also from the 2S albumin family, with a MW. A new major allergen in mustard seeds has been recently isolated and identied, an 11S globulin called Sin a 2 with a MW of 51 kDa (Palomares et al., 2005), but not all mustard allergens and their occurrence in dierent species are known. [36] [37] In addition, allyl isothiocyanate is a major skin-sensitizing agent (non IgE-mediated mechanism). Mustard protein allergic individuals may react to the protein content of the oil. Individuals sensitised to the skin-sensitising component allyl isothiocyanate may react to oil even in the absence of mustard proteins (Lerbaek, 2004).
296 Conclusions
Taking account of the potential allergen content and well documented clinical allergic reactions in individuals sensitive to mustard (NDA, 2004a), it is appropriate for the Panel to assess the likelihood that mustard seed oil may cause an allergic reaction in mustardallergic individuals. Mustard seed oil (allyl isothiocyanate) will therefore not be exempted from labelling as allergen. Directive 2005/26 EC [38] Some ingredients derived from the listed allergenic foods are so highly processed that they are no longer capable of triggering an adverse reaction. A list of products that are temporarily exempt (til 25 November 2007) from the labelling requirements of 2003/89/EC was published as Commission Directive 2005/26/EC
4.1.4
May contain...warning [30]
Manufacturers often use phrases such as "may contain nut traces" to show that there could be traces of nut in a food product, either in the ingredients, or because it has entered the product accidentally during the production process. It is not a legal requirement to say on the label that a food might contain traces of nut, but many manufacturers label their products in this way. Some members of the public have expressed concern that "may contain" labelling is used too much and could undermine valid warnings on products and restrict peoples choice unnecessarily.
4.1.5
Food allergen labelling regulation in Japan [39]
Akiyama, Imai and Ebisawa 2011 describe the history of the food-labelling system for specic allergenic ingredients (i.e., egg, milk, wheat, buckwheat, and peanut) which became required by law in Japan on April 1, 2002. Foods containing walnut and soy bean must be labelled with subspecic allergenic ingredients, shrimp/prawn and crab has also become mandatory. Ocial guidelines of 2006 determine that any food containing allergen proteins at greater than 10mg/kg must be labelled under the Law.
4.1.6
EuroPrevall
EuroPrevall is an EU-funded multidisciplinary project aiming to improve quality of life for food allergenic people. The partner organisations of the project will: 1- Characterise the pattern and prevalence of food allergies across Europe in infants, children and adults.
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2- Develop methods to improve the quality of food allergic diagnosis, reducing the need for food challenge tests. 3- Determin the impact of food allergies on the quality of life and its economic cost for food allergic people and their families, workplace and employers, and healthcare. The EuroPrevall researche project [40] EuroPrevall is a multi-disciplinary research project looking at the prevalence cost and basis of food allergy in Europe to estimate the currently unknown prevalence of food allergy and exposure to known or suspected risk factors for food allergy across Europe. A protocol for the sampling strategy, the use of questionnaires, and collection of blood samples for immunological analyses is presented bei Kummeling and colleagues 2009. Basic information on adverse reactions to foods in groups aged 7-10 years and 20-54 years were collected, together with a questionnaire on potential risks and exposures. Blood sample were taken to allow serological analysis. Subjects reporting adverse reactions to foods and sensitized to the same food(s) were called in for a full clinical evaluation that included a double blind placebo controlled food challenge. The authors hope that data of these studies will improve disease prevention, diagnosis and management. The EuroPrevall-INCO project for China, India and Russia [41] To assess global variations in the prevalence of food allergies the EuroPrevall-INCO project has been developed to evaluate the prevalence of food allergies in China, India and Russia using the methodology of the EuroPrevall protocol applied in the EU, and compare the data with dierent European countries. The authors hope that these Asian data added to Europe ndings will improve knowledge about the development of food allergy.
4.1.7
The Avon Longitudinal Study of Parents and Children [42]
The Avon Longitudinal Study of Parents and Children was conceived to assess the sensitization within a large birth cohort, the associations between sensitization to dierent allergens and determine whether small groups of allergen may be responsible for atopy, an allergic hypersensitivity aecting parts of the body not in direct contact with the allergen. Roberts and colleagues performed skin allergy tests at 7 years of age with positive sensitization found with grass pollens (8.5%), house dust mite (Dermatophagoides pteronyssinus 7.8%, Dermatophagoides farinae 3.6%), cat (4.9%), dog (2.7%), horse (1.4%), rabbit (1.4%), peanut (1.4%) and mixed tree nuts (1.0%). The authors concluded that aeroallergens are the most important ones, and peanuts and tree nuts are most frequent food allergens. Strong associations within and between dierent allergen classes such as pollens, animals, foods, peanut and tree nuts were noted.
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4.1.8
Strict avoidance of allergenic foods beyond 4-6 month is being challenged [43]
Shaker and Woodmansee 2009 stresses that 4 to 6% of US children have an allergic reaction to at least one food, being inuenced by a combination of genetic inuences, characteristics of food antigen processing, and timing of food introduction. The authors point out that early introduction of allergenic foods is being under trial because strict avoidance of allergenic foods beyond 4-6 months may not be eective. Current management of food allergy is summarized by the authors to depend on accurate diagnosis, appropriate counseling regarding strict allergen avoidance, emergency preparedness, instruction on the use of self-injectable epinephrine, and ongoing surveillance for the possible development of tolerance. Kim and Sicherer 2010 writes that strict allergen avoidance has been considered to be the best strategy to prevent food allergy. It was found, however, that children with milk and egg allergy tolerate extensively heated forms of these foods, oral exposure can lead to desensitization, and delaying introduction of highly allergenic foods to infants and young children does not prevent the development of food allergy, and may even increase risks. Biomarkers are being identied to select those patients who can prot from an early exposure to allergens. The authors stress that, depending on the specic case, strict avoidance is inevitable. [44]
4.1.9
Egg allergy [45]
Benhamou and colleagues 2009 write that egg allergy in children below the age of three are the most frequent of allergies. Ovomucoid is the major allergen of egg, and egg white proteins allergy may occur without clinical symptoms. The diagnosis of egg allergy comprises IgE tests and standardized food challenges. Treatment of egg allergy includes strict avoidance of eggs and their products, also tolerance induction protocols, in particular with egg proteins with reduced allergenic properties in specic cases, are promising. Food colour allergy [46] Patent Blue V, also called Food Blue 5 or Sulphan Blue, is a dark bluish synthetic dye used as a food coloring. As a food additive, it has E number E131. It is not widely used, but can be found in certain jelly sweets. Patent Blue V is banned as a food colour in Australia, USA, and Norway. In medicine, Patent Blue V is used in lymphangiography as a dye to colour lymph vessels. It is also used in dental disclosing tablets as a stain to show dental plaque on teeth. It may cause allergic reactions, with symptoms ranging from itching and nettle rash to nausea, hypotension, and in rare cases anaphylactic shock; it is not recommended for children.
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4.1.10
Vegetables and allergies [47]
It was suggested that vitamin E and zinc intake during pregnancy might reduce the risk of wheeze and/or asthma in the ospring. Miyake and colleagues 2010 examining such associations found that higher maternal intake of green and yellow vegetables, citrus fruit, and beta-carotene during pregnancy was signicantly associated with a reduced risk of eczema, but not wheeze, and vitamin E consumption during pregnancy reduced the risk of infantile wheeze, but not eczema. The authors, however, found no protection against wheeze nor eczema generated by higher maternal intake of total vegetables, vegetables other than green and yellow vegetables, total fruit, apples, alpha-carotene, vitamin C, or zinc.
4.1.11
Document No.00P-1322 International Dairy Foods Association [48]
International Dairy Foods Association IDFA helped develop new guidelines for clear labeling of allergenic ingredients on food labels and supports the implementation of these guidelines, encourages disclousure of allergenic ingredients in clear and simple language, and is dedicated to assisting dairy processors in preventing cross contamination. IDFA urges all members to review their policies and verify that they are operating within the new allergen guidelines. Further it ist being recommended that member companies follow these recommendations: 1- Review formulations to identify the presence, if any, of the 8 major allergens. 2- Contact ingredient suppliers to determine if ingredients they supply contain any allergen, including components of avours, colors, incidental additives and processing aides, which may not be required to list specic ingredients. 3- Review their current labels to ensure that if any allergen are present they are included in the ingredient declaration in terms that are easily understood by consumers. The dairy industry is currently using the following labeling guidelines, which are among the options listed in the Allergy Labeling Guidelines issued by the Allergen Issues Alliance. - Use of parenthetical statement following the ingredient name or class of names that identies the presence of an allergic ingredient. For example, caseinate (derived from milk); and - Use of a commonly understood name that identies the presence of the allergen such as "natural walnut avour." 4- Advisory statement should not be used as a substitute for Good Manufacturing Practices (GMP). Only use advisory label statements such as "may contain..." when all four of the criteria established in the Allergen Guidelines are met. These criteria are:
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- The presence of a major food allergen is documented throughout visual examination or analytical testing of the processing line, equipment, ingredient or product, or other means. - A major food allergen is present in some, but not all, of the product. - The presence of a major food allergen is potentially hazardous. - The risk of presence of a major food allergen is unavoidable even when current GMPs are followed.
4.1.12
Food allergy diagnosis
Food allergy is diagnosed by a process of elimination. The rst step is a detailed patient history to establish a pattern of reactions to foods in order to decide if the facts match with a food allergy. Other causes such as food intolerance or other health problems, should at this point be excluded. The diagnosis is usually based on the symptom and dietary histories and subsequently conrmed via more specic investigations including skin prick tests, blood chemistry, and response to dietary restriction.
4.2
4.2.1
Evaluation of the Allergic State

Test Diets
These are oral food challenge tests. Skin prick tests These tests are performed if history, diet diary or elimination diet suggests a specic food allergy to be present. A drop of allergen extract is placed on the skin of the lower arm, and the skin scratched with a needle. A positive reaction is shown by the rapid development of a localised reddening and swelling. The only conclusive demonstration of food allergy (gold standard) is the result of a doubleblind placebo-controlled food challenge, which must be performed in hospital with resuscitation facilities available because even extremely small doses can lead to a life-threatening reaction. The sensitivity of in vitro immunoassays compared with prick/puncture skin tests has been reported to range from 50-90% with an average of about 70%. Skin testing, therefore, continues to be the preferred method for the diagnosis of IgE-mediated sensitivity.
4.2. EVALUATION OF THE ALLERGIC STATE Total serum IgE (Radio-Immuno-Sorbens-Test RIST test)
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RIST Test evaluates only the total amount of IgE antibody. The RAST test is much more complicated but gives the answer to what allergen the patient is sensitive. Allergen-specic IgE antibody testing (Radioallergosorbent RAST testing The allergen-specic IgE antigen testing is done to screen for a type I hypersensitivity to a specic substance or substances in response to acute or chronic allergy-like symptoms in patients. The specic serum IgE Testing incorporates the use of microwell plastic strips, which have been coated with allergen proteins. Serum or plasma is exposed to the microwell and the bound IgE antibody is detected using an enzyme labelled anti-human IgE antibody. Peroxide substrate detects the levels of enzyme present, which is directly proportional to the level of specic IgE bound to the specic allergen. Food Sensitivity Panel The measure of high levels of IgG, IgA and IgM antibodies in serum for specic food antigens is a dependable diagnosis of specic forms of food sensitivity. Testing about 96 dierent types of food indicates not only gastrointestinal diseases,but also neuromuscular and cardiovascular events, as well as cross reactivity of food antigens with tissue antigens as an initiating process in some autoimmune diseases. Available are following test by ALLETESS Medical Laboratory of the serum of a patient [49]: - IgG/IgA to Gliadin - IgG/IgA to Gluten - IgG/IgA to Casein - IgG/IgA to lactalbumin - IgG/IgA to Ovalbumin - IgG/IgA to beta-lactalbumin - Reticulin Antibodies - Tissue Transglutaminase (tTG)(Specic to Endomysium) Antibody IgA Related tests Complete blood count (CBC), white blood cell dierential count, eosinophil count, basophil count are blood tests for an indirect indication of an ongoing allergic process with special attention to the eosinophils and basophils. Elevation of their number suggest an allergy, but they may also be elevated for other reasons.[50]
Table 4.2: Gell and Coombs Classication of Immune Reactions
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CHAPTER 4. FOOD ALLERGIES Skin reaction and cellular inltrate Allergy skin test eosinophils Arthus reaction) (PMNs) TB skin test mononuclear cells time of Onset 1-20 min 7-10 hrs ?-10 hrs 1-3 days
Reaction Type I Type II Type III Type IV
Description Anaphylaxis Cytotoxic Immune complexes Delayed-type hypersensitivity (DTH)
Antibody IgE IgG/IgM IgG(IgM) -
4.2.2
Treating the allergic state
At present there is no cure for food allergy, The only option is to avoid eating the problem food. Food allergic young people between 16 to 24 years are more likely to experience a severe allergic reaction leading to death. The following measures can be taken: 1. Avoidance of all allergens if possible 2. Desensitisation (induce IgG) 3. Drug: Antihistamines and decongestants Corticosteroids Cromolyn sodium Ephedrine and isoproterenol
4.2.3
Incidence of most common food allergies
A relative small group of foods or food products are responsible for most cases of food allergies.[51] Milk allergies Two out of a hundred babies under 12 month are allergic to cows milk. It is the most common food allergen in childhood but nine out of ten milk allergic children are no longer allergic by the age of three. It is unusual for adults to be milk allergic, but a small number of children have an anaphylactic reaction to milk and remain allergic into adulthood. Because the proteins in milk are similar in sheep, goats and cows, people who are usually allergic to cows milk are usually allergic to other milks and dietary calcium must be sourced from non-dairy foods.
4.2. EVALUATION OF THE ALLERGIC STATE
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Foods with baked milk may improve tolerance to dairy foods in children [52] Increasing amounts of foods that contain baked milk in the diets of children suering with milk allergies may improve tolerance to milk and milk products. Sampson et al 2011 report that approximately 75 percent of children, aged 2 to 17 years, with milk allergy, were found to tolerate foods containing baked milk, such as muns, waes and cookies. The high temperatures used in baking cause the proteins in milk to break down. This is believed to reduce the allergenicity. After an initial mun food challenge of six to twelve months, the children were given cheese pizza which is less heated than muns and contains higher amount of unmodied milk protein. After three years of a diet containing cheese pizza At the end of the study period, 47 percent of the children could tolerate unheated milk products, such as skim milk, yoghurt and ice cream, compared to only 22 percent in a control group. The authors concluded that increased exposure to baked milk products helps to children outgrow milk allergies. Egg allergies Allergy to eggs also occurs in young children rather than adults. Most egg allergies disappear with time but whilst allergic to hens eggs individuals are also allergic to other eggs. Shellsh allergies Shellsh allergies are unusual in children, but reactions to sh are found in both children and adults. Severe reactions are more frequently found with these foods, including anaphylaxis. Cooking does not destroy the proteins responsible for the allergy, but some people may be allergic to the cooked food whilst they are able to eat raw sh. Those who are allergic to cod are also allergic to hake, carp, pike and whiting. The protein that causes shellsh allergy are usually found in the esh whilst the proteins responsible for allergy in foods such as shrimps are in the muscle and the shells. Fruits and vegetable allergies Generally they are mild. The proteins causing allergy in fruits and vegetables are similar to pollen proteins. Four out of ten individuals who are allergic to tree and weed pollens are also allergic to some fruits, and people who are allergic to birch pollen are likely to be allergic to apples. Many of fruit and vegetable proteins are destroyed by cooking. The cooked food may be safe to eat. However, Kiwi fruit allergy , and peach and Rosaceae fruit allergies are severe
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and life-threatening. Their proteins are resistant to cooking and are found in fermented products such as wine and beer.
4.2.4
Food related anaphylaxis incidences [53]
Vetander et al. 2012 reviewed medical records of a paediatric emergency department, in Stockholm County/Sweden, related to incidence of anaphylaxis. Of 383 cases of anaphylaxis, 371 were caused by reactions to foods, standing for 92% of all cases, leaded by cashew, and peanut. Milk and egg allergy was also frequent in children younger than three years, being as common as peanut and tree nuts incidence, Food-induced anaphylaxis were more frequent in children with pollen-allergy. Exposure pollen increases the risk of anaphylaxis to foods.
4.2.5
Tannic acid may reduce allergenicity [54]
To reduce allergenicity of peanut products, such as peanut butter Chung and Reed 2012 suggest the addition of tannic acid at a concetration of 1 mg/ml. This was found to reduce substantially unbound levels of the major peanut allergens Ara h 1 and Ara h 2. The insoluble complexes of tanic acid with the allergenic proteins remained stable at pH 2 and ph 8 simulating digestic tract conditions. The authors note that the binding of tannic acid with the allergens is very strong. Allergens will therefore not be absorbed. Tannic acid is, therefore, being suggested to be used in low-allergen peanut products or the be given in case of accidental ingestion of peanuts. Further clinical/animal studies are needed to conrm the actual data.
4.2.6
Bioinformatics approach to test for peanut allergy [55]
To present an alternative to the double-blind, placebo-controlled food challenge for the diagnosis of food allergy-related disorders, Lin et al. 2012 developed a laboratory test using peptide microarray immunoassays and bioinformatic methods. Specic IgE and IgG(4) covering the amino acid sequences of Ara h 1, Ara h 2, and Ara h 3 are measured and data are analysed using bioinformatic methods. Peanut allergy produced greater IgE binding and broader epitope diversity compared to peanut-tolerant persons, however, IgG(4) was similar in both groups. Four peptide biomarkers may be used to predict with high accuracy the outcome of double-blind, placebo-controlled food challenges which may cause life-threatening allergic reactions.
4.3. DEVELOPING FOOD ALLERGIES
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4.2.7
Peanuts allergies
Peanuts are not nuts but legumes like soya, peas and beans. Peanuts are one of most allergenic foods and cause severe reactions. This allergy persists throughout life. Traces found in processed oils or on cooking or serving utensils can be sucient to trigger anaphylaxis. Reduction of allergenicity of peanuts by roasting and autoclaving [56] Cabanillas et al 2012 report a remarcable reduction of IgE-binding capacity of peanut allergens of roasted peanuts, submitted to autoclaving at 2.56 atm, for 30 min. Antibodies against peanut allergens (Ara h 1, Ara h 2 and Ara h 3), digestion experiments, and circular dichroism spectroscopy analysis were performed by the authors. Obtained data suggest that the heat and pressure treatment increases the protein unfolding and digestibility. The authors concluded that the described treatment of peanuts may improve food safety.
4.2.8
Tree nuts allergies
They are also called as true nuts and almond, Brazil nut, cashew nut, hazelnut, macadamia, pecan, pistachio, Queensland and walnut. Cashew nut allergenic reaction are not altered during food processing [57] Dr Shridhar Sathe and colleagues 2008 studied the allergenic proteins of cashew nut (Anacardium occidentale L.). They found that the three cashew nut allergens Ana o 1, Ana o 2 and Ana o 3 were good marker proteins for the detection of cashew in foods such as snacks, bakery products, deserts and sauces. Searching for appropriate detection methodology of traces of cashew nuts in these foods, the authors found that specic mouse monoclonal antibodies responded for the three cashew nut allergens even after normal food processing, like sterilisation, pasteurisation, microwaving and gamma irradiation. Ana o 2 was found by the authors to be the most stable, and was also the major allergen of cashew. Ana o 2 is therefore being suggested as best marker protein for cashew detection. [58]
4.3
Developing Food allergies
Our body has a host of defensive mechanisms to prevent food from making contact with our immune system. Even so some people have a tendency to react to particular foods and develop food allergies. This tendency is present from birth and may be aected by environmental factors such as childhood infections.
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Food tolerance is poorly developed in infancy and children become more susceptible to developing food allergies than adults. Children who are introduced to cows under the age of 6 month are more likely to develop milk protein allergy. Some babies are sensitised to peanuts, milk and eggs at or around birth. It is possible that they were exposed to these allergens in the womb or during breath feeding.[51]
4.3.1
Peanut, vaccination and atopic allergic disease revision
The UK Department of Health advice issued by the Committee on Toxicity in Chemicals in Food, Consumer Products and the Environment (COT) issued in 1998 a precautionary advice that pregnant or breast-feeding women with a family history of atopy, may wish to avoid eating peanuts during pregnancy and lactation as this could increase the chances of peanut sensitisation in children. Atopy or atopic syndrome is an allergic hypersensitivity aecting parts of the body not in direct contact with the allergen. There appears to be a strong hereditary component linked to genes such as 5q31-33 with a cluster of cytokine genes. The individual components, such as asthma, eczema or hay fever, are all caused at least in part by type I I hypersensitivity reactions. [59] [60] Consumption of peanut during pregnacy Dr. Tara Dean and Dr. Carina Venter assessed the compliance with this recommendation and its impact upon peanut sensitization. In this study children sensitized to peanuts were found, but their mothers had not consumed peanuts during pregnacy. The scientists conclude therefore that maternal consumption of peanuts during pregnancy was not associated with peanut sensitization in the infant. The majority of mothers avoided peanut consumption during pregnancy. The authors found that either the government advice is misunderstood by mothers, or that those who communicate the advice have not fully explained who it is targeted at, and stress the necessity of a review of the 1998 COT document. The authors call for clear, consistent factual advice and information about the real risks associated with peanut consumption during pregnancy/lactation and peanut allergy in the developing child, and specically to whom these risks apply. [61] UKs House of Lords report on allergy 2007 says peanuts abstinence during pregnancy is not necessary [62] [63] Despite highlighting that the increase in peanut allergy has been extraordinary, with a 117.3 per cent increase in the prevalence of peanut allergy from 2001 to 2005 the report recommended to withdraw government guidance advising some pregnant women and young
4.3. DEVELOPING FOOD ALLERGIES
307
children to avoid peanuts, alleging that abstinence from peanuts during pregnancy and early life may actually increase the risk of developing peanut allergy. The report refers to Israel, where peanuts are commonly used in infants weaning foods with a low incidence of peanut allergy.
Peanuts and peanut products consumption during pregnancy increases risk on childhood asthma development [64] The study of Saskia Willers and colleagues 2008 present new arguments against the House of Lords report 2007 which speaks in favour of peanut consumption. Willers found a strong association between daily versus rare nut product consumption during pregnancy and symptoms of asthma in children. The authors concluded that daily consumption of peanuts and their products increased the asthma outcomes for about 50 per cent compared to rare consumption, but no association was found for vegetable, sh, egg, milk or milk products during pregnancy with asthma. The authors stress that the study deals with asthma and not specically with peanut allergy and call for caution on this respect.
4.3.2
In utero exposure to vitamine folate may increases asthma risk inherited transgenerationally [65]
Asthma, a complex heritable disease, aects notably developed countries. Changes in DNA methylation resulting in aberrant gene transcription may enhance their risk. Hollingsworth and colleagues 2008 report that a study using mice found maternal diet supplemented with methyl donors (vitamine folate) to enhance the severity of allergic airway disease. Using a methyl-rich supplemented diet the authors found that 82 gene-associated loci were dierentially methylated during gestation, increasing allergic reactions. Important genes which were downregulated were Runt-related transcription factor 3 (Runx3), and Runx3 mRNA, which reduce the outcomes of allergic airway disease in progeny exposed in utero to a high-methylation diet. Treatment with a demethylating agent caused the opposite eect. The authors concluded that dietary factors can modify the heritable risk of asthma through epigenetic mechanisms during fetal development in mice. Rachel Miller, commenting the study of Hollingsworth and colleagues 2008 stresses that greater airway allergic inammation and IgE production in F1 and, to some extent, F2 progeny were noted using high-methylation diet during gestation, but not during lactation or adulthood, suggesting that asthma-related phenotypes across multiple generations via epigenetic mechanisms is acquired during gestation. [66]
308
4.3.3
Atopy and vaccination
Analysing prevalences of allergic sensitization and atopic disease in relation to vaccination coverage. Grber and colleagues (2003) found that children with a higher vaccination coverage seemed to be transiently better protected against development of atopy in the rst years of life. [67] Grber reassured in 2005 that common childhood vaccines are unlikely to promote atopic disease. He wrote that possible future development of atopic symptoms is most likely not causally related to vaccination but a coincidence. However, according to Grber, vaccines specically designed to down-regulate Th-2 type immunity have to be further elucidated if they are safe and eective in preventing the development of atopic disease. He concludes that eective protection against potentially life threatening or disabling infectious diseases should be oered to every child-atopic or not. [68] According to Nakajima and colleagues in 2007 all few eects, which were seen in their study concerning vaccination and atopic disease, were small and age-dependent. The study supports numerous previous studies of no eect of vaccines on asthma. The authors conclude that the fear of their child developing atopic disease should not deter parents from immunising their children, especially when weighed against the benets. [69]
4.3.4
Western lifestyle and allergies
Contact with new drugs, cosmetics, exotic fruits and spices can be one cause of growing number of food allergies in the industrial countries. Results of studies suggest that a western lifestyle is associated with allergic diseases in childhood.[70] For 1995-1996, the International Study of Asthma and Allergies in Childhood (ISAAC) found prevalence of self-reported asthma symptoms in children aged 13-14 years at 2.6 to 4.4 per cent in Albania, Roumania, Georgia, Greece and Russian Federation. In United Kingdom and Ireland these rates reached 32 percent, suggesting that western lifestyle is associated with allergic diseases in childhood.
Table 4.3: Asthma Prevalence Land Prevalence UK 36% Australia 33% New Zealand 32% Ireland 28% USA 24% South Africa 16%
4.3. DEVELOPING FOOD ALLERGIES Japan 13% China <5% (Source ISAAC Study) Indonesia <5% India <5%
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4.3.5
Gut microora and immune system
Changes in gut microora caused by widespread use of antibiotics and todays high fat, lowbre diet could be responsible for a major increase in allergies in recent years. Gary Hunagle is an associated professor of internal medicine and of microbiology and immunology at the University of Michigan. He says that researches indicates that microora lining the walls of the gastrointestinal tract are a major underlying factor responsible for the immune systems ability to ignore inhaled allergens. Changes in the microora in the gut upsets the immune systems balance between tolerance and sesitization. To test this hypothesis, Balb/C laboratory mice were given a ve-day course of antibiotics, killing their gut bacteria. A single oral introduction of Candida albicans stimulated an increase of growth of this yeast in the gut of the mice. This is a common side-eect of antibiotics. An increased airway hypersensitivity to ovalbumin (egg whites) inserted via nasal cavities was noted. Hunagle says that dierences in host genetics and the type of allergens does not matter as the response had been identical in all studies. It conrms that microora are the key to maintain a balanced immune response. Changing the composition of microora in the gut predisposes animals to allergic airway diseases. Allergic sensitization can also occur outside lungs [71]. However, an article by Sunia Foliaki, from the International Study of Asthma and Allergies in Childhood (ISAAC) published in the International Journal of Epidemiology in 2004 says that ndings are generally not consistent with the hypothesis that antibiotic use increases the risk of asthma, rhinitis, or eczema. If there is a casual association of antibiotic use with asthma risk, it does not appear to explain the international dierences in asthma prevalence. It has been hypothesized that antibiotic use early in life may increase the subsequent risk of asthma. Foliaki conducted an ecological analysis of the relationship between antibiotics sales and the prevalence of symptoms of asthma, allergic rhinoconjunctivitis and atopic eczema in 99 centres from 28 countries[72]. The ndings of Hunagle gives a new dimension to the relationship between gut microora and immunology trying to explain the dierent occurrence of East and West asthma.
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4.3.6
Allergens
Allergens are macromolecules (usually proteins) which are involved in sensitising and eliciting allergic reactions. The International Union of Immunological Societies (IUIS) published in 1986 the characterisation and nomenclature of allergen which was revised (Ocial list of allergens I.U.I.S. Allergen Nomenclature Sub-Committee 2003.03.02) http://www.allergen.org/Archive/Meetings/2003/List 20030302.pdf and List of allergens as of September 12, 2005 http://www.allergen.org/list.htm standardisation allergen preparations guidelines.
4.4
Treatment of Food Allergy
Food allergy is a very individual problem. Treatment of food allergy involves changes in the lifestyle.
4.4.1
Elimination diet
Food allergy is best treated by avoiding the foods that cause it. Special diets are the most often used treatment for food allergies. If the patient is allergic to only one or two foods, elimination of these foods may be the only treatment. The best thing is to ban the foods which cause the problem from the kitchen. Ready to eat meals from the supermarket must be carefully screened to avoid the oending ingredients. New food labelling directives gives a better chance to avoid specic allergen. Rotation diet Rotation diets are necessary when a patient has multiple food allergies. The foods causing the allergy must be eliminated and all other foods should be eaten in intervals of four to ve days. This reduces the exposure to many other foods to which the person has also unknown subclinical allergies. This will avoid future intolerance to these foods. The ideal rotation interval can vary from person to person and from food to food, but should never be less than four days. No food should be eaten in extremely large quantities. Rice should not make up half of the food of the day. New and unusual foods should be included in the diet, to avoid eating one food in large quantities. Medication Mild allergies may be controlled by nonprescription antihistamines. More severe cases need epinephrine and antihistamine medication and a medical bracelet
4.5. FOOD INTOLERANCE
311
Severe cases need an allergy kit that contains everything necessary for an epinephrine shot. All child caregivers should know how to recognise the signs of a severe allergic reaction and how to give an epinephrine shot.
4.5
Food intolerance
Food intolerance do not involve the immune system. It includes reactions to histamines and other amines found in the foods, and lactose intolerance, where individuals lack the enzyme necessary to break down lactose in the gut. Such adverse reactions to food do not involve the immune system and are also called non-allergic food hypersensitivity reactions. They are also called pseudoallergy. Food, additives and drugs are the main responsibilities for pseudoallergies. Substances which may trigger a pseudoallergy are: Food colours, preservatives such as benzoic acid and sulte, acetysalicyl acid and other not steroidal antiphlogystica. Salicilates contained in foods may cause pseudoallergies. Foods high in salicilates are: Berry fruits, oranges, apricots (Prunus armeniaca), pineapple (Ananas comosus), cucumber (Cucumis sativa), olives (Olea europaea), grapes and wine. The treatment of pseudoallergies is similar to that of allergic diseases (antihistamine drugs, steroids, B2 agonists, epinephrine). Biogenic amines such as histamine, cadaverine and putrescine can be present in foodstus or be formed during their storage by microbial decarboxylation of the corresponding amino acids, mainly during fermentation processes. Elevated concentrations of these compounds also indicate bad hygienic conditions during the fermentation process. Foods produced with the help of bacteria have therefore often a high level of biogenic amines. These foods are yeast extract, some types of cheese, sauerkraut, red wine and spoiled foods containing meat or certain shes. Scombroid poisoning occur when the spiny-nned sh of the family of Scombridae undergoes improper storage resulting scombroid toxin. Susceptible sh include albacore, amberjack, anchovy, Australian salmon, bluesh, bonito, kahawai, herring, mackerel, mahi-mahi, needlesh, sauri, sardine, skipjack, wahoo and yellown tuna. Aected sh have a metallic or peppery taste. Biogenic amines are responsible for a pseudoallergy reactions such as headache, skin irritation or changes in blood pressure.
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4.5.1
Milk allergy [73]
Milk allergy is an immunologically mediated adverse reaction to one or more milk proteins. In some children the ingestion of milk can trigger the body into launching an inappropriate immune response to the proteins in milk resulting in an allergic reaction. Currently the only treatment for milk allergies is total avoidance of milk proteins. Initially if the infants are breastfed, the lactating mothers are given an elimination diet. If symptoms are not relieved or if the infants are bottle-fed, milk substitute formulas are used to provide the infant with a complete source of nutrition. Milk substitutes include soy milk, rice milk, and hypoallergenic formulas based on hydrolysed protein or free amino acids. Milk allergy is the most common food allergy. It aects somewhere between 2% and 3% of infants in developed countries, but approximately 85-90% of children lose clinical reactivity to milk once they surpass 3 years of age.
4.5.2
Lactose intolerance [74] [75]
Lactose intolerance is marked by a relative or absolute absence of the enzyme lactase in the small intestine which prevents metabolism of lactose. It is a clinical syndrome with symptoms including abdominal pain, diarrhoea, nausea, atulence, and/or bloating after ingesting lactose-containing substances. Lactose is not absorbed in the gut, and can draw uids into the intestine by osmosis, which produces diarrhoea, and the carbohydrate can be metabolised by certain intestinal bacteria that produce carbon dioxide, methane and hydrogen as waste products, thereby leading to atulence. Dierences between primary, secondary, congenital, and developmental lactase deciency are discussed in a review from the American Academy of Pediatrics (AAP). Treatment consists of use of lactase-treated dairy products or oral lactase supplementation, limitation of lactose-containing foods, or dairy elimination. The American Academy of Pediatrics supports use of dairy foods as an important source of calcium for bone mineral health and of other nutrients such as protein, and riboavin that facilitate growth in children and adolescents. If dairy products are eliminated, other dietary sources of calcium or calcium supplements need to be provided. According to AAP pediatricians and other pediatric care providers should maintain awareness of the benets and controversies related to the consumption of dietary milk products and milk-based infant formula. A lactose tolerance test, a hydrogen breath test, or a stool acidity test is required for a clinical diagnosis.
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Most adults in the world are lactose-intolerant: the majority of humans stop producing signicant amounts of lactase sometime between the ages of two and ve. A relatively recent genetic change caused some populations, including many northern Europeans, to continue producing lactase into adulthood; these lactose-tolerant populations are in the minority. Lactose intolerance is an autosomal recessive trait, while lactase-persistence is the dominant allele. Important lactose intolerant ethnic groups are gathered in the south of Africa, China and Hispanics ranging from 100 to 65% of cases. Meanwhile in UK, Germany and other states of northern Europe have only 2% of persons suering from intolerance to lactose. Yoghurts containing live cultures are well tolerated by people with lactose intolerance because the bacteria partially digest the lactose into glucose and galactose. Aged cheeses, such as Cheddar and Swiss, have lower lactose contents than other cheeses.
4.5.3
New lactic acid bacteria and a Streptococcus strain mix reduce milk allergenicity [76]
Kleber and her colleagues from the Germanys University of Hohenheim report that over70% of beta-lg antigenicity content in the sweet whey and 90% in skim milk were reduced using a wide range of lactic acid bacteria (Lactobacillus) independently or in mixture 1:1 with Streptococcus thermophilus subspecies salivarius incubated at 40o C for 24 hrs. The research is important because 80 per cent of all cases of milk allergies is caused by the whey protein beta-lactoglobulin (beta-lg) which is not present in human milk. Antigenicity refers to the capacity to induce an immune response. In this study only the antigenity of beta-lg was tested and not the allergenicity. The enzymes are reported to be more or less specic with some better at reducing the beta-lg content in milk and/ or whey. The research has industrial relevance regarding new fermented milk products with reduced antigenic properties
4.5.4
Lactose intolerance [77] [78]
Lactose intolerance is caused by a shortage of the enzyme lactase, which is produced by the cells that line the small intestine. Lactase breaks down milk sugar into two simpler forms of sugar called glucose and galactose, which are then absorbed into the bloodstream. Lactose intolerance occurs in about 25% of people in Europe; 50-80% of people of Hispanic origin, people from south India, black people, and Ashkenazi Jews; and almost 100% of
314
people in Asia and American Indians.Lactose intolerance is a problem caused by the digestive system.
Cowmilk intolerance Symptoms are often the same of lactose intolerace. Cows milk is an allergic reaction triggered by the immune system. Symptoms of lactose intolerance Common symptoms, which range from mild to severe, include nausea, cramps, bloating, gas, and diarrhea. Symptoms begin about 30 minutes to 2 hours after eating or drinking foods containing lactose. The severity of symptoms depends on many factors, including the amount of lactose a person can tolerate and a persons age, ethnicity, and digestion rate. Diagnosis There are sophisticated tests for the diagnosis of lactase malabsorption,like the Lactose Tolerance Test, the Hydrogen Breath Test and the Stool Acidity Test. However, the diagnosis can be made easily on the basis of clinical history. Improvement in symptoms after eliminating such foods and worsening when they are reintroduced conrms the diagnosis.
4.5.5
Classication of lactase deciency and dietary measures
No treatment can improve the bodys ability to produce lactase, but symptoms can be controlled through diet. Primary lactase deciency Lactase concentration after birth and declines after weaning. In primary lactase deciency lactase concentrations declines at the age of weaning. It is associated with a recessive inherited trait, dierent between Europeans and Africans.
4.5.6
Treatment
In primary lactase deciency the development of symptoms depends on how much lactose needs to be ingested before the available lactase is saturated. Thus, most people with primary lactase deciency can ingest up to 240 ml of milk (12 g of lactose) without developing symptoms. It may help to divide daily milk intake into several small portions and to take it with
315
other foods. Yoghurt, curds, and cheeses are better tolerated, because lactose is partially hydrolysed by bacteria during their preparation and gastric emptying is slower as these products have a thicker consistency. People with lactose intolerance should be encouraged to gradually increase their intake of milk- this causes changes in the intestine that permit higher milk intake. Milk-cereal mixtures delay the entry of lactose into the intestine, permitting better absorption. Since these are cheap and easily prepared at home, their use should be promoted. Secondary lactase deciency It results from injury to the small bowel mucosal brush border secondary to viral or nonviral intestinal infection, common in developing countries. Treatment is directed at the underlying cause. Cogenital lactase deciency It is characterized by minimal or absent lactase immediately after birth. It is a rare disorder. Developmental lactase deciency It occurs in premature infants, because lactase levels do not increase until the third trimester of a womans pregnancy. The deciecy, however, rapidly improves as the intestinal mucosa matures.
4.5.7
Lactase enzyme tablets
For those who react to very small amounts of lactose or have trouble limiting their intake of foods that contain it, the lactase enzyme is available without a prescription to help people digest foods that contain lactose. The tablets are taken with the rst bite of dairy food. Lactase enzyme is also available as a liquid. Adding a few drops of the enzyme makes lactose more digestible for people with lactose intolerance. Young children and infants with lactase deciency should not consume lactose-containing formulas or foods until they are able to tolerate lactose digestion. Most older children and adults do not have to avoid lactose completely, but people dier in the amounts and types of foods they can handle.
4.5.8
Children with infective diarrhoea [78]
Short periods of lactose intolerance are common after episodes of infective diarrhoea and may prolong the diarrhoeal illness. a meta-analysis has shown that most children with acute diarrhoea can safely continue to receive breast or undiluted animal milk Milk-cereal
316
mixtures given at frequent intervals (nearly 2 g/kg/day of lactose or 40 ml/kg/day of milk) were well tolerated by most children with persistent diarrhoea. Non-responders will benet from reducing lactose intake below their current threshold of tolerance, followed by long term steps directed at improving adaptation of the intestine. Recent research shows that yogurt with active cultures may be a good source of calcium for many people with lactose intolerance. Even though yogurt is fairly high in lactose, the bacterial cultures used to make it produce some of the lactase enzyme required for proper digestion. [77]
4.5.9
Calcium RDI [79]
The Institute of Medicine released a report listing the requirements for daily calcium intake. How much calcium a person needs to maintain good health varies by age group. Recommendations from the report are shown in the following table. Age group Amount of calcium to consume daily, in milligrams (mg)
0-6 months 400 mg 6-12 months 600 mg 1-5 years 800 mg 6-10 years 1,200 mg 11-24 years 1,200-1,500 mg 19-50 years 1,000 mg 51-70+ years 1,500 mg In addition, pregnant and nursing women need between 1,200 and 1,500 mg of calcium daily Calcium sources. Many non-dairy foods are high in calcium, including dark green vegetables such as broccoli, or sh with soft, edible bones, such as salmon and sardines.
[80] Table 4.4: Calcium and Lactose in Common Foods Vegetables Calcium mg Soymilk, fotied, 1 cup 200-300 Lactose g 0 Dairy products Calcium mg Yoghurt,plain,low-fat 415 Lactose g 5
4.5. FOOD INTOLERANCE 1 cup Milk,reduced fat 1 cup Swiss cheese,1 oz.
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Sardines,with edible bones, 3 oz. Salmon,canned, with edible bones, 3 oz. Broccoli, raw, 1 cup Orange, 1 medium Pinto beans, 1/2 cup Tuna,canned,3 oz. Lettuce greens,1/2 cup
270
295
11
205
270
90 50 40 10 10 0 0 0 0
Ice cream,1/2 cup Cottage cheese 1/2 cup
85 75
6 2-3
Yoghurt with active cultures may be a good source of calcium for many people with lactose intolerance. Even though yoghurt is fairly high in lactose, the bacterial cultures used to make it produce some of the lactase enzyme required for proper digestion. Clearly, many foods can provide the calcium and other nutrients the body needs, even when intake of milk and dairy products is limited. However, factors other than calcium and lactose content should be kept in mind when planning a diet. Some vegetables that are high in calcium (Swiss chard, spinach, and rhubarb, for example) are not listed in the chart because the body cannot use the calcium they contain because these foods also contain substances called oxalates, which stop calcium absorption. Calcium is absorbed and used only when there is enough vitamin D in the body. A balanced diet should provide an adequate supply of vitamin D from sources such as eggs and liver. Sunlight also helps the body naturally absorb vitamin D, and with enough exposure to the sun, food sources may not be necessary.
4.5.10
Hidden lactose
Although milk and foods made from milk are the only natural sources of lactose, it is often added to prepared foods. People with very low tolerance for lactose should know about the many food products that may contain even small amounts of lactose, such as: Bread and other baked goods, processed breakfast cereals, instant potatoes, soups, and breakfast drinks, margarine, lunch meats (other than kosher), salad dressings, candies and other snacks, mixes for pancakes, biscuits, and cookies, powdered meal-replacement supplements. Some products labeled non-dairy, such as powdered coee creamer and whipped toppings,
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may actually include ingredients that are derived from milk and therefore contain lactose such as whey, curds, milk by-products, dry milk solids, and non-fat dry milk powder. They contain lactose.
4.6
Prevalence of food hypersensitivity
About 5 per cent of the general population have some type of food allergy. Some bowl disorders seem to trigger food hypersensitivity. In case of Irritable Bowel Syndrome 65 percent of patients may be aected by food allergy.
4.6.1
IBS Irritable Bowel Syndrome
Irritable bowel syndrome is the most common functional disorder of the gastrointestinal tract, characterised by abdominal pain, bloating and irregular bowel function with constipation or diarrhoea. IBS is believed to aect more than 58 million people wordwide, and more women suer from it than men. It is untreatable and intervention involves management of symptoms. It is not life threatening but it is a long-term condition that involves abdominal discomfort. IBS patients had higher IgG4 titers to wheat (Pi< 0.001), beef (<0.001), pork (<0.001), and lamb(P=0.009), and soy beans (P=0.012) as compared with healthy controls. The IgG4 titers to potatoes, rice, sh, chicken, yeast, tomato or shrimp were not signicantly dierent to titers found in healthy people. Probiotic bacteria has been widely researched for its impact on gut health but few strains have enough evidence to claim a benet on IBS symptoms showing promise in normalising bowel movements. The probiotic bacteria Lp299v (Lactobacillus plantarum 299v) is the rst probiotic targeting IBS symptoms. It helps to reduce intestinal discomfort and other symptoms. International regulations mean that probiotic products cannot carry explicit disease prevention or treatment claims. Probiotics are, however, marketed with "friendly" or "good" bacteria that can redress the balance of ora in the gut and help the user to feel "better" , other address the improvement of the immune system.[81]
4.6.2
Probiotics and allergy
Lactobacillus reuteri ATCC 55730 is a probiotic (health-promoting) lactic acid bacterium widely used as a dietary supplement to improve gastrointestinal, immune and oral health. Dietary supplementation with the probiotic L. reuteri ATCC 55730 induces signicant
4.6. PREVALENCE OF FOOD HYPERSENSITIVITY
319
colonization of the stomach, duodenum, and ileum of healthy humans, and this is associated with signicant alterations of the immune response in the gastrointestinal mucosa. [82] [83] Probiotic bacteria taken by mothers may reduce the likelihood of eczema, also an allergic disease. Children who were exposed to probiotics around the time of birth were 40 per cent less likely to develop atopic eczema at four years of age than children in a placebo group. However exposure to probiotics did not have any protective eect over asthma in this study. Child care infants fed a formula supplemented with L reuteri or B lactis had fewer and shorter episodes of diarrhea, with no eect on respiratory illnesses. These eects were more prominent with L reuteri, which was also the only supplement to improve additional morbidity parameters. [84] Dr Steve Allen is investigating the impact of probiotics on allergies giving Lactobcillus reuteri supplements to mothers for four weeks prior to birth of their babies and these babies are now being given probiotics for their rst year. Analysis of breast milk taken from the mothers a couple of days after giving birth showed increased levels of the anti-inammatory cytokine (cell signal substance) IL-10 and reduced levels of TGF-beta-2. The cytokine IL-10 is central to regulation of the immune system and has anti-inammatory properties. However the origine of TGF-B2 in breast milk is uncertain because it is produced by many cell types and there is the possibility of an association with a subclinical mastitis. [85] Milk ker and soymilk ker may help to prevent food allergies Je-Ruei Liu and colleagues evaluated the eect of oral consumption of milk ker and soymilk ker on in vivo IgE and IgG1 production induced by ovalbumin (OVA) in mice. They found that both foods suppressed the IgE and IgG1 responses and altered the intestinal microora. The intestinal populations of Bidobacterium spp. and Lactobacillus spp. were increased and Clostridium spp., decreased. Disorder of the intestinal microora is told to be closely related to food allergy development, According to the authors, milk ker and soymilk ker may, therefore, help to prevente food allergy and enhancement of mucosal resistance to gastrointestinal pathogen infection.
4.6.3
Soybean lecithin and allergy [86]
The protein fraction of soybeans are allergenic. The vast majority of this protein is removed in the soy lecithine manufacturing process. The remaining trace levels of soy proteins in lecithine are not sucient to produce allergic reactions in the majority of soy-allergic perCopyright 1998-2010 Karl H. Wilm. All rights reserved. OurFood Database of Food and Related Sciences
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sons. Some of the more sensitive persons, however should avoid soy-lecithine when used as ingredient in food.Source labelling of soy-lecithine is provided in the Food Allergen Labeling and Consumer Protection Act of 2004. Dr. Hee and Dr. Taylor from the University of Nebraska advocate that no conceivable allergenic risk would occur from the use of shared equipment for products that contain soybean lecithin and products that do not. The transfered amount of soy protein will be verylow. An "allergen-cleanout" is according to these authors not necessary.
4.6.4
NOAEL for Soy prodructs established in Europe [87]
In a study performed in Switzerland, Denmark and Italy Barbara K. Ballmer-Weber and colleagues 2007 reported that the no observed adverse eect level (NOAEL) in Europe should be two milligrams for soy and 1 milligram for soy protein. According to the authors 1% of patients with soy allergy would react subjectively and objectively with 0.21 and 37.2 mg of soy protein, respectively. this should be considered in food-labelling directives.
4.6.5
Reductiion of allergic eect of soy products [88]
Juana Frias and colleagues 2007 studied the reduction of the immunoreactivity and improvement of amino acid content after fermentation of soybean our. The highest reduction in IgE immunoreactivity was obtained with Lactobacillus plantarum fermenting milled soybean our in liquid state, and most of the total amino acids increased. Cracked soybean in solid state fermentation with Bacillus subtilis presented high reduction in immunoreactivity, alanine and threonine improved. Less eective were fermentations with Aspergillus oryzae and Rhizopus oryzae. The authors concluded that fermentation can decrease soy immunoreactivity, and nutritious hypoallergenic soy products may be developed using this technology.
4.6.6
The biochemistry of allergies
The immune system produces immunoglobulins which act as defence against viral, microbial and fungal infections. One particular for of immunoglobulins are immunoglobulin E (IgE) which respond to parasitic infections such as malaria agents. Some of this group of immunoglobulins are a response to contact with pollen, dust and food causing allergic reactions such as hay fever. The normal function of the body produces IgG and IgA in response to food proteins.
4.6. PREVALENCE OF FOOD HYPERSENSITIVITY
321
The immune reaction of certain predisposed individuals result in the so-called Th2 response which leads to the secretion of IgE immunoglobulins. This response happens normally only in case of parasitic infectins such as malaria but also happens in case of hypersensitivity to food allergens. This is called Th2 response. Allergies develop in two stages: Stage 1 - Sensitisation Sensitisation occurs when an antigen comes in contact with cells called progenitor Blymphocytes. These cells break down the antigen in peptide fragments which are bound in special molecules called hystocompatibility complex class II complex. This complex is transported to the surface of the B-lymphocyte cell. The T-cell receptors of CD4 of another cell type, called T helper cell recognises the foreign peptide on the surface of the B-lymphocytes, triggering the secretion of specic antibodies, the IgE immunoglobulins. Stage 2 - Elicitation During the elicitation of an allergic reaction, the IgE becomes associated with specic IgE receptors on the surface of basophile or mast cells. These cells are packed full of inammatory mediators such as histamine. The cell-bound IgE is crosslinked by the agent in case of a re-exposure. The mast cell is then caused to release the inammatory mediators which trigger the allergic symptoms usually within minutes following exposure, resulting in asthma, vomiting, eczema and hives (nettle rash).
Table 4.5: Allergens Food Milk Eggs Fish Shell-sh and Seafood Peanut Soya Tree nuts Mustard, Sesame seeds Allergen Casein, beta-lactoglobulin, alfa-lactalbumin Ovomucoid, ovalbumin Parvalbumin Tropomyosin 7S seedstorage globulin, 11S seed storage globulins, 2S albumin 7S seedstorage globulin, 11S seed storage globulins, Bet v 1 homologue, inactive papain-related thiol protease 2S albumin, 7S storage globulins, 11S seed storage globulins Non specic lipid transfer proteins, Bet v 1 homologue 2S albumin
322 Cereals wheat Fresh fruit and vegetables Kiwi, peach,celery
CHAPTER 4. FOOD ALLERGIES Seed storage prolamins, alfa-amylase, trypsin inhibitors, Glycosylated peroxidase Homologues of the major birch pollen allergen Bet v1 Cysteineprotease, LTP
4.7
Detection of food allergens
Food manufacturers must comply with directives calling for mandatory declaration of major allergens on labels. Special kits for the detection of some of these allergens are being developed to help food manufacturers to screen their raw ware and their production lines for unforeseen cross-over of traces of ingredients. Many kits on the market only detect egg white and do not indicate the presence of egg yolk. Biotrace Tecra Egg Via Kit detects both. Other kits avilable using simple extraction methods and sensitive specic immunoassay techniques and " on-site" tests highly eective in the food industry as part of a HACCP programme: [89] - Wheat gluten - Milk proteins (caseins/caseinates; whey protein and albumin; lactoglobulin) - Peanut and sesame tests are directed towards their major components. The antibodies are specic and can be used in a wide rage of food matrices, including chocolate-based foods, which can sometimes cause problems. - Soya protein - Sesame protein - Tree nuts
4.7.1
ELISA Systems Kits to Detect Food Allergens
The following rapid Elisa (enzyme-linked immunosorbent assay) kits are available:[90] - Almond (Prunus dulcis): It belongs to the tree nuts group. Almonds are a common cause to food allergy. - Beta-lactalbumin and casein: Non-dairy products should be tested to ensure raw and nished products have not been contaminated with milk proteins. Either beta-lactalbumin or casein can be tested. - Crustacean: Trompomyosin is a major protein in Crustaceans. It is the major shrimp allergen and presents evidences of cross-reactivity among crustaceans and molluscs. - Egg: It tests only egg white. - Hazelnut (Corylus avelana): Detects heat stable protein component of hazelnut.
4.7. DETECTION OF FOOD ALLERGENS
323
- Peanut: The proteins Ara h1 and Ara h2 of peanuts are focused. Ara h2 is heat stable - Sesame (Sesamum indicum): Allergy to sesame seeds is increasing. In Israel sesame is a major cause of food allergy. Anaphylaxis has been reported after ingestion of meat and sesame seed oil. - Soy: The incidence of allergy to soybean proteins is quite low in comparison to other major food proteins. However, the increasing consumption of soybean products makes this test necessary.
4.7.2
Celery allergens [91]
Celery (Apium graveolens), together with peanuts, is a potent allergenic vegetable. Three celery allergens are known: Api g 1, Api g 4, and Api g 5. Gadermaier et al. 2010 identifed a new lipid transfer protein (nsLTP).from celery stalks consisting of a single isoallergen designated as Api g 2.0101 with a typical alfa-helical fold and high thermal stability and gastrointestinal digestion. Thermal denaturation did not aect the IgE binding of Api g 2. Therefore, patients with Api g 2 allergy may develop serious reactions responding to cooked celery stalks Api g 2-specic IgE antibodies cross-reacted with peach and mugwort pollen nsLTPs. The authors suggest to include the recombinant Api g 2 in the current panel of allergens for molecule-based diagnosis in celery allergy. According to Harrer et al. 2010 the data on plant food allergies at the molecular level, the allergen structure,and stability, together with immunological methods at the level of IgE and T-cell reactivity can be integrated in computational algorithms to predict allergenicity of novel foods. Lipid-transfer proteins are important food allergens, being used in herbs and spice mixes. Over fty allergenic non-specic lipid transfer protein (nsLTPs) are already know. All these data can be used in molecule-based diagnosis and future development of specic immunotherapy in plant food allergy. [92] Faeste et al. 2010 developed a detection method for celery in food, using a sandwich celery ELISA using polyclonal anticelery antibodies, however, it may only be used for screening foods because of its cross-reactivity with potato and carrot proteins. It is based on the detection of nanoLC-ion-trap MS/MS proteins which are present in celery, potatoes and carrots. The authors also describe a novel patatin (Sola t 1)-like protein in celery and a avin adenine dinucleotide binding domain-containing protein (Api g 5)-like protein in carrot. The authors suggest that further development of the MS-based screening method may be used to detect celery allergens in foods. Such a method is not yet available but it is needed to comply with the mandatory labelling of celery proteins in preprocessed foods.[93]
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4.7.3
Microarrays for the determination of antibodies and cell activation tests [94]
Ferrer et al. 2009 stresses the importance microarray technique to determine specic IgE against multiple allergens and allows the determination of IgG and IgM against the same allergens.. Microarray procedures are being developed not only for the determination of antibodies but also for cell activation tests and determination of cross-reactions. Microarray technique can help to improve the safety and ecacy of immunotherapy and increase knowledge on the physiopathology of allergic diseases. Diagnosis of IgE-mediated allergies was improved with the development of ow-assisted analysis of allergen-specic activated basophils and component-resolved diagnosis (CRD). De Knop et al. 2010 reviewed the component-resolved allergy diagnosis by microarray, which allows an analysis of individual sensitization proles with multiplexed puried and recombinant allergens which may facilitate the formulation of diagnostic algorithms. The authors, however, stresses that this method needs further assessment and it should be considered part of a complementary diagnostic and should not be used as nal tool. [95]
4.8
4.8.1
Allergies and cross-reactivity

Milk allergy
There are at least 30 antigenic proteins in milk. Casein is the most commonly used milk protein in the food industry; lactalbumin, lactoglobulin, bovine albumin, and gama globulin are other protein groups within the milk. Digested fractions of milk proteins may induce the production of IgE, IgA, and IgG antibodies and may trigger complex, variable immune responses. Skin tests with whole milk proteins are, therefore, misleading because secondary antigens of digested proteins are not detected. Accurate diagnosis is important in case of an immediate symptomatic hypersensitivity to cows milk protein because a milk-free diet with substitute formula should be established. Many children who are allergic to cows milk protein also show sensitivity to soy- based products. There are infant formulas in which the milk and soy proteins are degraded so the immune system does not recognise the allergen and the product can be consumed safely.
4.8.2
alfa-lactalbumin
alfa-lactalbumin and beta-lactalbumin are the major cows milk allergens. The presence of cows milk is widespread due also to its unlabelled inclusion as an ingredient, or to errors in
4.8. ALLERGIES AND CROSS-REACTIVITY
325
cooking, processing and preparation, especially in restaurants. For this reason, individuals with milk allergies should avoid processed foods as much as they can and try to consume foods prepared at home; only food items with all the ingredients listed on the label should be consumed. Hot dog, salad mayonnaise, dressings, and meat products are often produced using caseinates as emulsier. Caseinates replaces egg yolk in these products which resist deep freezing. The same products produced with egg yolk are extremely sensitive to freezing. A hot dog may contain caseinate.
4.8.3
Kiwi fruits allergies
Birch pollen and Kiwi allergy Fruit allergy is frequently associated with birch pollen. Kiwi allergy is a new manifestation of birch pollen-associated food allergy and is mediated by cross-reacting antigens in the kiwi fruit. Kiwi allergy can be expected in patients with birch pollen allergy exhibiting high levels of IgE to birch pollen. [96] Fahlbusch and associated scientists at the Institute of Clinical Immunology, at the University of Jena, Germany found that the major allergen for kiwi allergy is the 30 kDa protein and additionally that the cross-rection between kiwi and birch pollen allergy is mainly due to carbohydrate moieties. [97]
4.8.4
Birch pollen associated Allergies
Basophil activation is associated with the expression of CD63. In birch-pollen-associated food allergy to celery, carrot and apple, Bet v 1, Api g 1, Dau c 1 and Mal d 1 are major allergens.
4.8.5
Basophil Activation Test (BAT) and birch pollen associated allergies
: Recombinant allergens have not yet been used in the CD63-based basophil activation test (BAT). However, the BAT using recombinant allergens provides a valuable new in vitro method for the detection of sensitization to foods. In the presented study Erdmann determined specic IgE by the CAP method and basophil activation by owcytometry upon double staining with anti-IgE/anti-CD63 monoclonal antibodies after incubating with puried recombinant Bet v 1, Bet v 2, Api g 1, Dau c 1 and Mal d. According to Erdmann double-blind placebo-controlled food challenges remain the gold
326
standard to conrm food allergy, however, the CD63-based BAT with recombinant allergens may supplement routine tests for allergy diagnosis.[98] The basophil activation test (using either CD203c or CD63 as activation marker) has become a robust and reliable test for in vitro investigations of immediate allergy, complementary to other existing in vitro tests. Inter-laboratory standardization in clinical decision-making is necessary. Each allergen has to be assessed one by one to determine its optimal concentration as well as the denition of the threshold for positivity (using ROC analysis).[99]
4.8.6
Green and yellow cultivars of Kiwi and allergy
The green-eshed kiwi Actinidia deliciosa cv Hayward and the yellow-eshed cultivar Actinidia chinensis cv Hort 16A are grown commercially. According to ndings of Bublin and associated scientists of the Department of Pathophysiology, Medical University of Vienna, Austria. the IgE immunoblotting showed marked dierences in the allergen compositions of green and gold kiwifruit extracts. Phytocystatin which is a novel plant food allergen, and a thaumatin-like protein were allergens common for both cultivars. In the extract of gold kiwifruits two allergens with homologies to chitinases were found. Actinid was detected exclusively in green kiwifruits. Green and gold kiwifruit extracts were shown to be highly cross-reactive as determined by the authors using IgE ELISA inhibition. The authors conclude that the gold kiwifruit should be considered as new allergen source for patients allergic to green kiwifruits because of the presence of common allergens and the IgE cross-reactivity to green kiwifruit.[100]
4.8.7
Fescue meadow pollen and kiwi
Fescue meadow pollen cross-sensitise to kiwi fruits. This was found by Gavrovic-Jankulovic and associated scientists at the Department of Biochemistry from the University of Belgrade using the sera from polysensitized patients with specic IgE to grass pollen and kiwi fruit. According to their ndings a 24 kDa kiwi glycoprotein represent potential major allergen, which share common epitopes with Fes p 4 and 36kDa meadow fescue allergen. [101]
4.8.8
Rye, timothy and mugwort pollen and kiwi allergy
The cross-reactivity to birch, rye, timothy, and mugwort pollen (Artemisia vulgaris) with kiwi was studied by Rudescko and associated scientists at the the Institute of Clinical Immunology, at the University of Jena, Germany.
327
They found that an extract of kiwi was able to bind immunoglobulin E from kiwi-allergic patients in the immunoblots and EIA. Immunoblots results revealed a broad spectrum of IgE specicities; 12 allergens were identied within a range of 15 to 94 kDa, 10 of which cross-reacted with birch, timothy, rye, and mugwort pollen, while two (25 and 30 kDa) were not inhibited homologously by pollen. EIA additionally revealed kiwi-specic allergens. Three proteins of the kiwi extract (25, 30, and 43 kDa) were considered to contain a carbohydrate miety. Prolin seems to be relevant in cross-reactivity of kiwi allergens. [102]
4.8.9
People who are allergic to birch pollen may react hypersensitively to soy products too [103]
People who are allergic to birch pollen react also to peanuts, hazelnuts, apples, strawberries, carrots, celery and pulses. Certain proteins in these foods are so similar in structure to the protein in birch pollen that triggers the allergy that the body manifests such cross allergy. According to Professor Dr. Dr. Andreas Hensel, President of the Federal Institute for Risk Assessment (BfR).BfR stresses that such cross allergy with soy products are possible. The trigger of the cross allergy to soy is a protein (the PR-10 stress protein Gly m 4), which is found in soybeans and is similar in structure to the birch pollen allergen Bet v 1. The activity of the soy protein Gly m 4 can be dampened through heating to high temperatures or the protein itself can be destroyed. Allergy suerers can, therefore, eat most products with soy ingredients which were heated during processing without suering any health disorders. BfR does not believe that it makes sense for the packaging of soy products to carry additional warnings for allergy suerers. Not all soy products contain the protein Gly m4 that triggers the allergy. At the present time, no ocial detection method is available. Furthermore, besides soy numerous other foods such as peanuts could trigger severe cross allergy in people with a birch pollen allergy. They include apples, hazelnuts, and celery. Warnings on soy products would not, therefore, protect people who are allergic to birch pollen from a cross allergy.
Table 4.6: Food Allergens Food Allergen IUIS Nomeclature Chemical Structure
328 Milk beta-lactoglobulin alfa-lactalbumin Caseine Serum albumin Immunoglobulins ovomucoid Ovalbumin Conalbumin Lysozyme Ovomucin Apovitellenin I Apovitellenin IV Livetin Alfa-livetin Beta-livetin Gama-livetin Phosvitin Allergen M Antigen-I Antigen-II Sa-I Sa-II Sa-III
Chicken egg
Gal d 1 Gal d 2 Gal d 3
Glycoprotein Glycoprotein Glycoprotein Glycoprotein
Serum albumin
Cod Common shrimp
Glycophosphoprotein Gad C 1 Glycoprotein Glycoprotein Glycoprotein Pen i-1 Pen a 1 Pen s 1 Met A 1 Par f 1 Trompomyosin tRNA Trompomyosin Trompomyosin Trompomyosin Trompomyosin Glycoprotein Glycoprotein Glycoprotein
Peanuts
Arachin Conarachin Ara h 1 Ara h 2 Aglutinin Peanut 1 Concanavalin-A-reactive glycoprotein wheat germ-lectin-reactive material Glycinin
Glycoprotein Glycoprotein Glycoprotein Protein
Soybean
4.8. ALLERGIES AND CROSS-REACTIVITY Beta-conglycinin 2S-Globulin Kunitz Soybean Trypsin inhibitor Wheat Tri v BD 47 Tri v BD 17 Tri v BD 15 0.28 alfa-amylase- inhibitor Alfa-amylase-inhibitor WTAI-CM 16 Alfa-amylase (BMAI-1) BTAI-CMb RP16KD Prolin Polygalacturonase 2A (PG2A) Beta-fructofuranosidase Superoxide dismutase (SOD) pectinesterase (PE) Prs a 1 Glycoprotein
329
Protein Protein Protein Protein
Barley Rice Tomato
Avocado Mustard
Sin a 1 Bra j IE Kiwi 24kDa kiwi glycoprotein 43-kDa Actinidin Act c 1 Strawberry 20/18-kDa Banana Class I chitinases with hevein-like domain 33kDa 37 kDa Appel Skin-allergen Mal d 1 Food Allergen IUIS Nomeclature
Hevein-like domain peptides 2s-albumin 2s albumin Glycoprotein
homologues to Bet v 1
Protein similar to Bet v I (birch) Chemical Structure
4.8.10
A potentially allergenic protein in transgenic Starlink maize [104]
Starlink maize was developed inserting the Cry9C-gene turning it resistant to plague insects. Starlink had been approved for use in feed and industrial uses, not for human consumption due to Cry9-protein potentials to cause allergic reactions. In September 2000 taco-shells in retail-stores contained meal from StarLink corn were found, triggering
330
a recall. Aventis had to buy back all harvested Starlink maize as well as Starlink sowing seed. In July 2001 EPA expert panel concluded that Starlink maize could result in allergy and decided that it should not be used for human consumption (www.epa.gov/scipoly/sap/). As contamination of maize for food purposes with fodder maize can not be avoided, cultivation of Starlink was no longer allowed. Although traces of Starlink can still be expected in the food chain, it has never been detected in products on EU-markets.
4.8.11
Commercial enzymes of no concern with regard to food allergy [105]
Carsten Bindslev-Jensen and colleagues studied the possible allergenicity of a wide variety of enzyme classes and origins, including enzymes produced by genetically modied organisms using prick test, histamine release and oral challenges. Some positive skin prick test result or a positive histamine release were not supported by oral challenges using exaggerated dosages of the enzymes, and the ndings were seen without clinical relevance. No allergenic ndings of clinical relevance were related and the authors concluded that ingestion of food enzymes in general is not considered to be a concern with regard to food allergy.
4.8.12
A Campaign calls to stop the use of processing aids during bread production [106]
Current legislation allows manufacturers to use substances known as processing aids during bread production without declaring so on the label. The "Real Bread Campaign" says that these ingredients include enzymes such as xylanase, transglutaminase, hemicellulase, phospholipase and fungal alpha-amylase some of which are known allergens or may be produced using substances of animal or GM origin.
4.8.13
Enzymes being used in bread production:
Bakery enzymes are used to extend the shelf-life of baked goods, maintain bread volume, crumb softness, crust crispiness and improves browning. Such enzymes are: Amylases which convert starch to sugar and produce dextrins. Oxidases strengthen and bleach the dough. Proteases and hemicellulases reduce gluten elasticity. Hemicellulases improve gluten strength.
331
The Campaign stresses that the only essential ingredients of basic leavened bread are our, water and yeast, to which a small amount of salt may be added, The campaign calls on bread producers to to stop the use of processing aids during bread production or include a declaration of any and all added enzymes and other processing aids used.
4.8.14
Authorisation procedure for food additives, food enzymes and food avourings
The EU regulation 1331/2008 demands that enzymes used as processing aids must be approved prior to their use. Approval was not required before December 2008 [107].
4.8.15
Lactococcus lactis IL-10-secreting strain reduces anaphylaxis and allergy responses [108] [109]
Christophe Frossard and Philippe Eigenmann from the University Hospital of Geneva in a study published in March 2007 found that Lactococcus lactis, bioengineered to deliver murine IL-10, can decrease food-induced anaphylaxis. According to the authors, this may provide an option to prevent IgE-type sensitization to common food allergens. The antiinammatory interleukin-10 (IL-10) is a potential regulator for food tolerance. The researchers administered the transfected Lactococcus lactis to mice and induced oral sensitization with beta-lactoglobulin in the presence of cholera toxin. Anaphylaxis and blood levels of antigen-specic immunoglobulin E (IgE) were found to be signicantly reduced in mice which had received the L. lactis strain.
4.8.16
Premature and low birth weight babies may develop less allergies in later life when they are exposed to allergens early [110]
Liem and colleagues (2007) in a Canadian study, found that immaturity of the gastrointestinal tract or immune response of prematurity and low birth weight does not change the risk for development of IgE-mediated food allergies allergy in childhood. The researchers disagree with previous studies indicating that at an age less than 3 years the immature gastrointestinal tracts result in an increased uptake of food antigens, increasing the risk for sensitization but in this study they found that food allergy was associated with a maternal history of asthma and food allergy. The authors write that a development of immunologic tolerance of the immature immune system to orally ingested allergens may take place, preventing sensitivation. They call for more studies to nd out how early exposure to food antigens, such as preCopyright 1998-2010 Karl H. Wilm. All rights reserved. OurFood Database of Food and Related Sciences
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and probiotics traces of peanuts, may protect premature children by increasing immune tolerance to those antigens.
4.8.17
The PARSIFAL study: Unpasteurised farm milk protecting from allergies [111] [112]
The PARSIFAL study - Prevention of Allergy Risk factors for Sensitisation in Children related to Farming and Anthroposophic Lifestyle -looked at farm children from rural and suburban communities in Austria, Germany, the Netherlands, Sweden and Switzerland. Waser and colleagues report that consumption of farm milk, whether boiled or not, was associated with a reduction in the occurrence of asthma by 26%, hay fever by 33%, and food allergy by 58%. No eect was observed for eczema. Other farm-produced products were not related to any allergy-related health outcome. It is not know what components of the raw milk may be responsible for such eects, but it could be linked to the pathogenic and non-pathogenic microbe levels in the milk, a kind of action observed with probiotic bacteria which may reduce the risk of certain allergies. The authors, however, warn that raw milk may contain pathogens such as salmonella or enterohaemorrhagic E coli and they do not recommend to drink unheated milk. The authors call for more studies on the omega-3 fatty acids prole in addition to the microbial content of the farm milk.
4.8.18
D-apha tocopherols, phytosterols and phytosterol esters derived from soybean oil not of allergen concern [113] [114]
Soy is a common dietary constituent and allergic reactions to soy proteins are well described. Soy allergy prevalence studies are lacking, estimated prevalences are about 0.5% in the general population with about 3-6% of allergic children being allergic to soy proteins. Clinical reactions are similar to those observed with other major food allergens, such as milk, egg or peanut and include systemic anaphylaxis. The ADM and Cargill asked for an exemption of allergy warning for natural mixed tocopherols (vitamin E, E306) and a range of D-alpha tocopherols acetate and succinate derived from vegetable oil (soybean oil). Natural mixed tocopherols are mainly used as antioxidants in fatty foods at a concentration of about 50 mg/kg (referring to the fat fraction of the specic food). Natural mixed tocopherols are also used as dietary supplements. The application covers phytosterol esters produced from vegetable oil (soybean oil). PhyOurFood Database of Food and Related Sciences Copyright 1998-2010 Karl H. Wilm. All rights reserved.
333
tosterol esters are currently commercially available in selected foods in several EU countries. The EU regulations limit exposure to a maximum of 3 grams per day of phytosterols through labelling requirements and maximum concentrations in certain food categories in order to avoid intakes above the recommended limits from multiple sources of intake. Plant sterols under consideration are derived from soybean oil deodorised distillates. Considering the information provided by the applicant regarding the starting material, the subsequent production process, and the demonstration of low residual protein content, the Panel of the European Food Safety Authority considers that it is unlikely that natural mixed tocopherol/D-alpha tocopherols from soybean sources and vegetable oils derived phytosterols and phytosterol esters from soybean sources will trigger a severe allergic reaction in susceptible individuals. The mixed tocopherols from soybean will therefore exempted from labelling of allergy warning.
4.8.19
Celiac disease [115]
Celiac disease, coeliac disease or sprue, is a condition in which genetically predisposed people have an autoimmune reaction to gluten proteins found in all wheat types and closely related cereals such as barley and rye. These autoantibodies destroy of the villi in the small intestine, which results in malabsorption of nutrients. This autoimune reaction is caused by a response to gliadin, a gluten protein found in wheat (and similar proteins of the tribe Triticeae which includes other cultivars such as barley and rye). Upon exposure to gliadin, the enzyme tissue transglutaminase modies the protein, and the immune system cross-reacts with the bowel tissue, causing an inammatory reaction that leads to attening of the lining of the small intestine, which interferes with the absorption of nutrients. The only eective treatment is a lifelong gluten-free diet.
4.8.20
Oats may improve vitamin and minerals nutritional prole of gluten-free diet [116]
Oats may enhance levels of vitamin B1, magnesium, zink and antioxidants of gluten-free diets, according to Kemppainen and colleagues 2010. In this study 100g of kilned and unkilned oats a day were included in the diet of adult celiac patients. Kilning is a heat and moisture treatment to balance moisture, but mainly to stabilize the groat. Oat groats are high in fat (lipids) and once exposed from their protective hull, enzymatic (lipase) activity begins to break down the fat into free fatty acids, ultimately causing an o avor or rancidity. Oats will begin to show signs of enzymatic rancidity within 4 days of being dehulled and not stabilized.
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The researchers report that kilned oats increased intake of vitamin B1 and magnesium, while the unkilned oats increased intakes of magnesium and zinc. Oats may be acceptable for patients with celiac disease and can improve the nutritional quality of the diet. However, concerns of potential contamination of commercial oats with gluten containing cereals.
4.8.21
Oat may prodive a source of antioxidant in glute-free diets [117]
Lovik and colleagues 2010 write that gluten-free oats help to meet the bre recommendations of glute-free diets. It also increased billirubin levels, which act as antioxidants. Low serum bilirubin levels are linked to endothelial dysfunction and increased atherosclerosis. This could signicantly improve heart health of coeliac diseased.
4.8.22
Wheat-based glucose syrups including dextrose not of allergen concern [118]
Since wheat is relevant both as a source of epitopes known to induce coeliac disease and as a source of allergens triggering wheat allergy, it is appropriate to investigate wheat products, namely wheat starch hydrolysates, for their potential to induce coeliac disease or trigger wheat allergy. The Association des Amidonneries de Cereales de lUnion Europeenne AAC provides information on wheat starch hydrolysates, particularly concerning the potential eects of wheat-based glucose syrups including dextrose in coeliac disease and wheat allergy. The history of safe use of wheat-based glucose syrups including dextrose is claimed based on the safe use of wheat starch-based gluten-free diet in coeliac disease. Wheat-based glucose syrups including dextrose may contain low levels of proteins and peptides. It is not known at which levels of intake glucose syrups including dextrose would cause allergic reactions in wheat-allergic individuals. Nevertheless, taking into account all the scientic information provided and in particular the levels of wheat proteins reported in glucose syrups including dextrose, the Panel considers that it is not very likely that this product will trigger a severe allergic reaction in susceptible individuals. For coeliac disease, assessment of the evidence provided including a new clinical study indicates that wheat-based glucose syrup is unlikely to cause an adverse reaction in individuals with coeliac disease provided that the (provisional) value of gluten considered by Codex Alimentarius for foods rendered gluten-free is not exceeded.
335
The Codex Standard for Gluten-Free Foods (Codex Stan 118-1983) species that the nitrogen content of food ingredients derived from gluten containing cereals may not exceed 0.05 g per 100 g on a dry basis (or 0.31 % protein/ds, Nx6.25), when they are used in a gluten-free food. [119]
4.8.23
Labelling of gluten-free foods [120]
Wheat (i.e. all Triticum species, such as durum wheat, spelt, and kamut), rye and barley, have been identied as grains that are scientically reported to contain gluten. The gluten present in those grains can cause adverse health eects to persons intolerant to gluten and therefore should be avoided by them. Dierent people with intolerance to gluten may tolerate variable small amounts of gluten within a restricted range. In order to enable individuals to nd on the market a variety of foodstus appropriate for their needs and for their level of sensitivity, a choice of products should be possible with dierent low levels of gluten within such a restricted range. EU gluten labelling regulation [120] Under the new European Union regulation (EC) No 41/2009 of 20 January 2009 , two claims are allowed: Gluten-free A maximum of 20 parts per million of gluten are allowed. These products are intended for those who are extremely sensitive to gluten. Very low gluten This declaration is allowed for products which have up to 100 ppm of gluten. Foods with this label can be used by persons which are less sensitive to gluten. Codex Alimentarius [121] The claims of gluten specied in EC 41/2009 were also adopted in the Codex Standard Codex Stan 118-1979, in the version of 2008.
4.8.24
Codex analytical method for guten in foods is untrustworthy testing fermented or heated foods [122]
Coeliac diseased persons must follow a life-long gluten-free diet. Food producers have a great responsibility to guarantee gluten level of products labelled as gluten-free not to exceed the 20 ppm threshold. The specic technique for gluten analysis in foods, adopted
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by the Codex Alimentarius Commission, the R5 antibody-based sandwich ELISA, combined with the cocktail-extraction solution of 60% ethanol/water, was found to produce values which do not represent the real content of gluten in fermented foods. Thompson T and Mndez 2008 write that criticism of the Codex method is that it overestimates barley hordein and is unable to accurately quantify hydrolysed gluten. [123] The Codex technique requires at least two epitopes in the protein. Fermenting or heating food products long protein molecules are divided in smaller parts, the peptides which have only one epitope instead of two of the original protein. Mena et al 2012 report the development of new competitive R5 ELISA which uses the extracting solution called UPEX (universal prolamin and glutelin extractant solution). The authors claim that the new assay produces better results than the sandwich R5 ELISA for detecting gliadins quantitatively in hydrolysed foods, and may be used forcomplete gluten analysis in any kind of food.
4.8.25
Gluten proteomic-based detection methods [124]
Haraszi et al. 2011 evaluated the available methodologies are suitable to meet the requirements of food labeling standards for individual gluten source declaration to meet the Codex Alimentarius [121] and European Union (EU) legislation and the European Commission issued Regulation No. 41/2009 [120]. The authors dene a basis for further development of gluten proteomic-based detection methods.
4.8.26
The Association of European Coeliac Societies [125]
The Association of European Coeliac Societies (AOECS) was founded in 1988. This Association reviews problems of international importance, coordinates international activities and matters of common interest of the members and favours the exchange of information among the members for the benet of Europeans aected by the coeliac condition or dermatitis herpetiformis.
4.8.27
Population screening test [126]
Early diagnosis and strict maintenance of a gluten-free diet will signicantly reduce the risk of problems associated with coeliac disease stresses, says the Association of European Coeliac Societies (AOECS) According to the Association population screening is the only way to identify the majority of CD patients. A combination of serology and HLA-typing is the only denitive way to screen for coeliac disease; a combined diagnosis accounting for symptomatic, silent and latent CD patients aims for a 100% specicity and sensitivity.
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European Commission, therefore, designated 9.5M EUR towards research and innovation for the diagnosis, monitoring and management of Coeliac Disease (CD).
4.8.28
The diagnosis system CD-MEDICS [126]
The CD-MEDICS Integrated Project-Coeliac Disease Management Monitoring and Diagnosis using Biosensors and an Integrated Chip System developes a lab-on-a-chip device. In this system a drop of blood on a card is subjected the a microstructured uidic network of reagents. The special surface of the card captures biological components being looked for and are detected by a sensor. This enables a fast diagnosis of population screening, based on the combination of serology and Human Leukocyte Antigen-typing (HLA-typing).
4.8.29
Other Tests made easy [127]
Biosensor devices also can precisely measure blood glucose using biosensor for detecting blood glucose and other biological molecules using hollow structures called single-wall carbon nanotubes anchored to gold-coated "nanocubes." The device resembles a tiny cubeshaped tetherball anchored to electronic circuitry by a nanotube. Timothy Fisher, from the Purdue University develops such devices using nanotechnology, similar to the European Project to monitore Coeliac Disease. According to Fischer, the sensing portion of the system, the nanocubes, extend out from the rest of the device and can more easily come into contact with target molecules enhancing sensitivity. Contrary to other sensors the nano-tetherball biosensor can detect wide range of concentrations whereas other sensors work only in narrow rages of specic concentrations. The researchers grow nanotubes on a porous anodic alumina template. Paladium nanocubes, coated with gold,are also formed. They are then connected with biotin-streptavidin combination which is already being used to analyse biological samples. Replacing the biotin with glucose oxidase the sensor became sensitive to glucose concentrations. The enzyme causes an electrochemical reaction in the presence of glucose and oxygen, generating an electrical signal, explain the authors.
4.8.30
New classication of gluten- related disorders [128]
According to Sapone et al. 2010, an increasing number of consumers look for gluten free food products, following the current awareness about gluten reactions. The authors describe the three main forms of gluten reactions: Allergic (wheat allergy), autoimmune (coeliac disease, dermatitis herpetiformis, and gluten ataxia), and possibly immunemediated (gluten sensitivity). New nomenclature and classications are being suggested by Sapones group.
338
In April 2010 Sapone et al. described the the dierence between both reactions to gliadin, the immune-mediated enteropathy, coeliac disease, and gluten sensitivity, classifying them as distinct clinical condition. Contrary to gluten sensitivity, coeliac disease is an autoimmune process, and gliadin induces the activation of IL-17-producing T cells and that IL-17 triggers the responses of the mucosa. Mucosal expression of IL-17A was signicantly increased in coeliac disease but not in gluten sensitivity patients. [129]
4.8.31
Serological diagnosis of coeliac disease [130]
According to Armstrong, Don-Wauchope and Verdu 2011, immunoglobulin A tissue transglutaminase is the single most ecient serological test for the diagnosis of coeliac disease. Immunoglobulin A tissue transglutaminase levels correlate with the degree of intestinal damage, however, serological testing requires consideration of the full clinical scenario. Antigliadin serological tests are no longer recommended.
4.8.32
Coeliac disease, low immunotoxic foods [131]
Coeliac disease widespread in the western world, Eastern Europe and Asia at rates of 1% and 1.44% of north Indians. Armstrong, Hegade and Robins 2012 write that genes related to coeliac disease also overlap with other autoimmune diseases. Human leukocyte antigen genotyping increases sensitivity in detecting coeliac disease in atypical cases. The authors also describe proinammatory pitfalls of vitamin A supplementation in active coeliac disease.
4.8.33
Genetic testing for Coeliac disease
The combination of a tTG antibody more than 100U/ml and symptomatic response to a gluten-free diet (GFD) avoids the need for a diagnostic biopsy. Antibodies against deamidated gliadin peptides (-DGP) have a high sensitivity and specicity for coeliac disease. Coeliac disease is extremely unlikely to aect persons who test negative for both HLADQ2 and HLA-DQ8. Susceptibility for coeliac disease was found to be linked to HLA-DQ2 and HLA-G I. Protection of the disease is linked to NLRP3, however, NLRP1 predisposes to the development of the disease.
4.8.34
Testing oat cultivar for gluten-free diet [132]
Comino et al. 2011 examined dierences in monoclonal antibodies moAb G12 against the main immunotoxic 33-mer peptide (A1 and G12). The oat cultivars presented dierent reactivity and one cultivar had no detectable reactivity. The immunogenicity was determined with isolated peripheral blood mononuclear T cells from patients with CD. A direct correlation of the reactivity with G12 and the immunogenicity of the cereal cultivar was
339
conrmed. The authors suggest to use moAbG12 antibody reaction to nd immunologically safe oat cultivars for a gluten-free diet.
4.8.35
Identifying hordein fractions in barley to create hordeinfree barley [133]
Tanner et al. 2010 identied the immunotoxicity of hordeins from experimental barley lines using peripheral hordein-specic blood T-cells from coeliac volunteers under oral barley challenge The authors found that D- and C-hordeins were the most immunotoxic of all prolamin fractions, and barley lines lacking B- and C-hordeins had a 5-fold reduced hordein-content, and a 20-fold reduced immunotoxicity as found in wild-type barley. Fresh activated T-cells may be used to identify low B- and C-hordeins barley to create of hordein-free barley.
4.8.36
Germinating enzyme pretreatment of coeliac-safe food products [134]
Gluten-free diet excludes food products containing wheat, rye and barley. In a study of Stenman et al. 2010 the immunotoxicity of rye secalin in vitro in intestinal epithelial cell models was found to be comparable to wheat gliadin. This conrms the need to exclude rye from the coeliac patients diet. Pretreatment of rye with germinating barley enzymes provided the most ecient degradation of secalin and gliadin peptides, reducing all toxic reactions induced by secalin. The authors suggest further studies to use such enzymes as medical treatment of coeliac disease, or to use it for the production of coeliac-safe food products.
4.8.37
Transgenic wheat plants with low toxicity [135]
Gil-Humanes et al. 2010 down-regulated the expression of gliadins in transgenic bread wheat using a set of RNAi hairpin constructs expressed in the endosperm, obtaining wheat lines with very low levels of toxicity.
4.8.38
Gluten, a complex protein composite harmful to coeliac patients
Gluten describes a composite of the proteins called prolamins and glutelins found in wheat, barley rye, oats and their crossbred varieties. Prolamins are dened as the fraction that can be extracted using 4070 percent of ethanol, and this fraction is called gliadin, hordein, secalin or avenin, respectively, depending on the grain variety.
340
The coeliac immune reacts strongly to the 2-gliadin fragment, which is 33 amino acids long and a principal contributor to gluten immunotoxicity. The 33-mer is highly resistant to breakdown by digestive enzymes and is, therefore, a suitable molecule for use as an analytical marker.
4.8.39
Hidden Gluten
The only eective treatment for coeliac disease is a lifelong gluten-free diet, This is very dicult, as gluten is being use in pharmaceuticals, sausages, sauces and desserts, and occurs as cross contamination taking place during milling, storage and production. For coeliac patients it is being suggested to keep the ingestion of gluten below 50 mg per day. [136]
4.8.40
Suitability of quinoa (Chenopodium quinoa Willd.) as gluten-free food requires further investigations [137]
Quinoa has low concentrations of prolamins, and has been recommended as part of a glutenfree diet. Zevallos et al 2012 reports that of fteen tested quinoa cultivars 4 cultivars had quantiable concentrations of celiac-toxic epitopes, but they were below the maximum permitted for a gluten-free food. The cultivars Ayacuchana and Pasankalla produced celia-toxic reactions similar to gliadin. According to the authors more studies are needed, because of the importance of quinoa in the coeliac diet.
4.8.41
Infant feeding and coeliac disease [138]
Shamir 2012 stresses that it is not clear whether breastfeeding and the age of introduction of gliadin prevent celiac disease or merely delay its onset. A PREVENTCD cohort started in 2010 and studies the relationship of breastfeeding, age at introduction of gluten and coeliac disease. The Complete results will be available when all children reach the age of 3 years. Based on all available data until 2009, the ESPGHAN Committee on Nutrition recommendations are still valid: Gluten should be introduced to the diet of infants when the infant is still being breastfed and not before 4 months or after 7 months of age.
4.8.42
Enzymes may reduce toxicity of grain protein [139]
The prolamin peptides in wheat gluten and in the homologous storage proteins of barley and rye are harmful to coeliac patients. Osorio et al 2012 studied the capacity of cereal grains to synthesize and store the enzymes prolyl endopeptidase from Flavobacterium meningosepticum and the barley cysteine endoprotease B2. The combination of these enzymes may detoxifying immunogenic gluten peptides and may be useful in the treatment of coeliac disease suggest the authors.
341
4.8.43
Gluten Analysis
Actual detection methods for gluten in food are based on specic antibody such as enzyme linked immunosorbent assays (ELISA) or lateral ow assays, polymerase chain reaction methods and mass spectrometry. Gluten is a complex mixture of proteins found in a variety of foods. This makes quantication and selection of reference material dicult. In 1985, the Prolamin Working Group (PWG) establish a gluten/gliadin standard which is used for calibration, despite doubts on its suitability. ELISA is the recommended method for the detection of gluten in food. Dierent test kits do not necessarily give similar results because of dierent specicities of the polyclonal and monoclonal antibodies used, dierent extraction methods and dierent materials for the calibration of the assays. Bugyi et al.2012 developed an incurred food matrix with a potential use as a reference material to compare commercially available ELISA kits. [140] The Skerritt antibody, developed in the 80ers, is a monoclonal antibody raised against wheat gliadin and reacts to the heat stable subfraction called -gliadins, which makes the Skerritt antibody suitable for gluten analysis in processed foods. However, the -gliadins dier among cereals species, and the Skerritt antibody only has a weak response to hordein. This causes considerable variiation in results. The R5 antibody, developed by Professor Mendez, was raised against rye secalin, but showed strong cross reactivity to wheat gliadin. However, it also detects proteins from soy and lupin that are not harmful prolamins. The epitope of secalin is the QQPFP pentapeptide. [141] The G12 antibody [142] The G12 antibody specically recognizes the 33-mer of the gliadin protein present in gluten, described by Shan et al. in 2002. The G12 antibody was raised against this 33-mer peptide using knowledge gained from this publication, and recognizes the hexapeptide sequence QPQLPY and similar peptides found in barley, rye and oats, the primary initiator of the inammatory response to gluten in Celiac Sprue patients. The 33-mer peptide react with tissue transglutaminase, the major autoantigen in Celiac Sprue. The peptide could be detoxied by exposure to a bacterial prolyl endopeptidase, suggesting a strategy for oral peptidase supplement therapy for Celiac Sprue. G12 does not give any false positive signals with soy maize or rice. Halbmayr-Jech et al 2012 describe a a sandwich ELISA using a monoclonal antibody called G12. The assay calibration was performed using material from the Prolamin Working Group. [143]
342 Gluten fragment detection [144]
The suitability to detect partially hydrolyzed prolamins in food using a competitive ELISA for prolamin quantication based on the R5 antibody was studied by Haas-Lauterbach et al. 2012 using a new calibrator consisting of a peptic-tryptic digest of wheat, rye, and barley prolamine. The limit of detection (LOD), and the limit of quantication (LOQ) of the assay were 1.36 and 5.0 mg prolamin/kg food, respectively. The new method provided higher results for prolamine in beer and hydrolysed wheat as compared to sandwich ELISA, which measures only intact prolamins.
Mass spectrometric analysis [145] Diaz-Amigo and Popping 2012 suggest to use mass spectrometric analysis which dierentiates between gluten derived peptides of wheat, barley, rye, and oat of processed foods. This could improve comparability of data across ELISA kits an other methods.
Omega-Gliadin-like D-Type Glutenin and an alpha-Gliadin from Wheat in diagnosis of wheat-dependent allergies [146] Mameri et al.2012 report that the serum from patients with cutaneous hypersensitivity to hydrolyzed wheat proteins react with the -gliadin-like D-type glutenin and -gliadin. The authors suggest that both proteins may be used to diagnosis of these diseases.
4.8.44
Helicobacter pylori and coeliac disease [147]
Helicobacter pylori is associated with with non-autoimmune chronic gastritis. Rostami Nejad et al. 2011 report that Helicobacter pylori is the causative agent in the majority of cases of peptic ulcer disease and other maladies up to gastric cancer. In developing countries and Iran 90% of the population is infected with the bacteria.
4.8.45
Coeliac disease is undistinguishable from Helicobacter pylori infections, despite lack of association of both diseases
Infections with Helicobacter pylori frequently cause upper gastro intestinal (GI) symptoms and 10% of cases come along with coeliac serology. The authors point out that coeliac disease presents atypical symptoms undistinguishable from Helocibacter pylori which presents high prevalence of gluten sensitivity. Rostami and her group suggest that duodenal biopsies and pertinent laboratory tests should be performed in patients presenting with upper GI symptoms such as dyspepsia to exclude Helicobacter pylori infection in case of coeliac disease.
343
4.8.46
Trace elements Cu and Zn are increased in case of Helicobacter pylori infection compared to coeliac disease and healthy serum [148]
Bozkurt et al 2011 write that serum zinc and copper levels were signicantly increased in Helicobacter pylori and positive coeliac disease patients as compared to Helicobacter negative patients and healthy controls, and were more altered in severe inammations compared to milder infections in patients with Helicobacter pylori associated coeliac disease. Serum trace element measurements may thus be used in the evaluation of treatment success, suggest the authors. Lahner, Persechino and Annibale, in a Meta-analyses in 2011, found that Helicobacter pylori infection is associated with reduced serum levels of ascorbic acid and cobalamin. [149]
4.8.47
Biochemical markers in coeliac disease [150]
Accomando and colleagues 2010 reviewed the laboratory ndings, histology passing and genetics. The gluten is the main environmental factor targeting a complex genetic background. HLA genes and also not HLA related genes are supposed to increase the risk to the disease. Serological markers may monitor the disease and a safe and eective gluten free diet. Special interest is given to histology, where intra epithelial cell inltration by several lymphocyte subsets may increase further knowledge of the pathogenesis of the disease.
4.8.48
Coeliac disease and neurological manifestations without gut symptoms [151]
According to Hadjivassiliou and colleagues 20101 there are many manifestations of the autoimmune disease to ingested gluten, among which the best known is coeliac disease. The authors reviewed the neurological manifestations which leaded to the concept of extraintestinal presentations of gluten sensitivity without enteropathy.
4.8.49
Many cases of coeliac disease remain undetected [152]
Rubio-Tapia and colleagues 2010 stressed that nearly 1% of the population suer from coeliac disease, and many remain undetected. The number of cases increases. Mortality risk may be increased if not diagnosed. The genetic pathway and the overlap with type 1 diabetes mellitus are explained. The authors point out that diagnostic using novel deamidated gliadin peptides antibodies produce better results than native gliadin-based tests. In a review of 2008 Leeds, Hopper and Sanders report that in spite of the development of more sensitive and specic serological markers diagnosis should always be conrmed with a duodenal biopsy. Strict, lifelong gluten-free diet is essential, however, alternatives to
344
the gluten-free diet are about to go into clinical studies. The authors also point to the controversy on complications of coeliac disease, such as neurological eects,which are not widely accepted. [153]
4.8.50
Amount of gluten permitted in gluten-free products is being discussed [154]
A life-long gluten-free diet is challenged in cases such as silent and latent patients is under discussion, and tolerance to gluten may be acquired later in life, but must be accompanied by a strict follow-up. The amount of gluten permitted in gluten-free products is being discussed, however, the daily amount of gluten that can be safely consumed is not dened. Oath are seen to be tolerated by most patients with coeliac disease.
4.8.51
Coeliac disease is not only a childhood disease, it also aects elderly [155]
Rashtak and Murray 2009 stress that coeliac disease can aect people of any age. The authors assessed the prevalence, clinical features, diagnosis, and consequences of celiac disease in the elderly and adjusted particular nutritional and nonnutritional to the needs of this group.
4.8.52
Similar presentation of coeliac disease in elderly and young adult patients [156]
Mukherjee and colleagues 2010 compared coeliac disease eect in the elderly to that of a population of young adults with coeliac disease. Diarrhoea was the main presenting symptom in both groups. Autoimmune disease prevalence, the degree of villous atrophy and prevalence of bone disease was similar in young adults and in the elderly, but thyroid disease and neuropathy were more common in the older group.
4.8.53
Neurological disorders as sole manifestation of gluten sensitivity [157]
Neurological disorders occur with a frequency of up to 10% in patients presenting symptoms of coeliac disease, and may also be the only symptom of gluten sensitivity. Hadjivassiliou and colleagues 2008 identied a neuronal transglutaminase isozyme which is the target of the immune response in patients with such neurological dysfunction. The authors found that anti-transglutaminase 2 IgA is linked with gastrointestinal disease, an anti-transglutaminase 6 IgG and IgA response is prevalent in gluten ataxia, independent of intestinal involvement. The authors suggest that antibodies against transglutaminase 6 can serve as a marker in addition to human leukocyte antigen type and anti-gliadin and anti-transglutaminase 2
345
antibodies may identify patients with gluten sensitivity who are at risk of neurological disease.
4.8.54
Transglutaminase TG2 is involved in the mechanism of coeliac disease [158]
De Vivo and colleagues in a review 2009 discuss the role of transglutaminases in neurodegenerative diseases. The authors point out that transglutaminase TG2 is involved in the molecular mechanisms of celiac disease, and is also engaged in human neurodegenerative diseases such as Alzheimers disease, Parkinsons disease, supranuclear palsy, Huntingtons disease polyglutamine diseases and others.
4.8.55
Early introduction of a gluten-free diet [159]
Armstrong, Robins and Howdle 2009 stress the high risk of siblings of coeliac patients. Negative coeliac serology of these siblings can, however, are an armation that they are very unlikely to develop the disease. Developments in serological antibody testing turns screening programmes in the community possible, however, early introduction of a glutenfree diet remains the best action to reduce the risk of coeliac related complications. The authors point out that altering the toxicity of cereal proteins opens promising alternatives for the future.
4.8.56
Zinc supplementation not essential for patients on glutenfree diet [160]
Rawal and colleagues 2010 evaluated the plasma levels of zinc in decient patients with coeliac disease. The researchers found that plasma levels of zinc were similar between patients which received gluten free diet without zinc supplementation and a group of patient which received gluten free diet with zinc supplementation. Plasma zinc levels rose in both groups and did not depend on supplementation. The authors concluded that zinc levels rise with gluten free diet and do not depend on supplementation.
4.8.57
New liquid chromatography-mass spectrometry (LC-MS) to detect wheat gluten peptides [161]
Sealey-Voyksner and colleagues 2010 presented a new specic and sensitive non-immunological liquid chromatography-mass spectrometry (LC-MS) based assay to detect and quantify trace levels of six wheat gluten peptides in food and consumer products. At present, immunochemistry is the leading analytical method for gluten detection in food. Consequently, enzyme-linked immunosorbent assays (ELISAs), such as the sandwich or competitive type assays, are the only commercially available methods. The news LC-MS method detects and quanties select target peptides in food over a range from 10pg/mg to 100ng/mg.
346
4.8.58
The diagnostic accuracy of IgG anti-DGP assays are comparable to IgA anti-tTG assays [162]
Vermeersch and colleagues 2010 report that the detection of IgG antibodies against deamidated gliadin peptides (DGP) assays is more sensitive and more specic for celiac disease than detection of IgG antibodies against native gliadin. The authors compared these assays and found that the diagnostic accuracy of the IgG anti-DGP assays was comparable to the diagnostic accuracy of the IgA anti-tTG assays. The sensitivity of the IgG antiDGP assays was signicantly better than sensitivity of the IgG anti-tTG assays and the specicity was better than the IgA and IgG anti-gliadin assays.
4.8.59
tTG antibodies considered the best serological test for CD screening [163]
Volta and colleagues 2010 compare the performance of DGP antibodies with that of tTG antibodies. In coeliac disease, deamidation of gliadin peptides is induced by tissue transglutaminase (tTG). Serological tests based on the detection of antibodies to deamidated gliadin peptides (DGP) have been developed. although both tests represent a very good tool for identifying coeliac patients, tTG antibodies display a higher predictive value than DGP antibodies, and must still be considered the best serological test for CD screening. Volta and colleagues, in another recent study,recommend the combined search for IgA tTGA and IgG DGP-AGA to provide the best diagnostic accuracy for coeliac disease, reducing the number of tests and improving cost-ecacy. [164]
4.8.60
Serological testing with tissue transglutaminase (TTG) associated with increased risk of osteosporosis [165]
Duerksen and Leslie 2010 write that low bone density and osteoporosis is associated with celiac disease. The authors stress that serological testing with tissue transglutaminase (TTG) and immunoglobulin A endomysial (EMA) antibodies is highly specic for celiac disease, while antigliadin antibody (AGA) testing is less specic. Higher prevalence of osteosporosis and lower bone density in TTG/EMA seropositive women compared with seronegative women were found by the authors. Isolated AGA seropositivity showed no signicant association with any bone density measurements.
4.8.61
Immunology of celiac disease and diagnostic in adults [166]
Arranz and Garrote point out that it is widely accepted that coeliac disease is based on adaptive immunity after T CD4(+)lymphocyte stimulation by tissue transglutaminemodied gluten peptides and HLA-DQ2/DQ8 restriction, which produce proinammatory
347
cytokines. Gluten also activates innate immunity and epithelial cytotoxicity mediated by intraepithelial lymphocytes. The authors stress that perception of serological and immunogenetic markers increased the knowledge of coeliac disease and led to a reevaluation of diagnostic of the disease in adults with minimal or atypical disease expression.
4.8.62
Mass screening for celiac disease [167]
Hershcovici and colleagues 2010 state that coeliac disease is frequently diagnosed after a long delay-period resulting in increased morbidity and mortality. Mass screening for coeliac disease of the young-adult general population to improved life quality and is a costeectiveness strategy is being suggested. Rising awareness of health-care professionals is also being mentioned as an alternative to mass screening, say the authors.
4.8.63
Blue toes related to coeliac disease [168]
Kearby and colleagues report a case of pernio or chilblains a rare condition, presenting blue toes exposed to cold or humid environments. Pernio is associated with variety of systemic conditions such as cryoglobulinemia and celiac disease. In the present case diagnosis of coeliac disease was conrmed. Medication and a gluten free diet was successfu
4.8.64
Chromium (VI) in leather clothing and shoes problematic for allergy suerers! [169]
BfR recommends strictly limiting levels in leather goods. Studies by the regulatory authorities of the federal states reveal that many leather goods like gloves, shoes or watch straps which come into direct contact with the skin contain high levels of chromium (VI). Hexavalent chromium is a strong allergen and it can lead to allergic skin reactions like contact eczema in sensitised individuals. Clinical picture of Chromium VI allergy The typical clinical picture is allergic contact eczema on the areas of the skin which come into contact with chromium (VI). Clothing which has direct skin contact should not, therefore, contain any chromium (VI). Even the lowest levels of chromium (VI) in leather are sucient to trigger an allergic reaction in hypersensitive individuals. At a level of 5 mg per kg leather half of the sensitised individuals already manifested allergic skin reactions like for instance contact eczema. The only eective protection for them against skin disorders is to avoid any contact with products containing chromium (VI).
348 Regulation
At the present time the chromium content of leather goods has not been regulated by law apart from industrial safety provisions. In 2006 a DIN standard stipulated that the chromium (VI) levels in work gloves must be below the detection limit of three milligrams chromium (VI) per kilogram leather. In more than 50% of leather goods such as gloves and shoes and other ware which is worn close to the skin like watch straps, chromium IV was found up to 10 mg/kg. Tanning processing of hides Normally, chromium (III) sulphate is used as the tanning agent. Chromium (VI) either appears as an impurity in the tanning substance or it is formed through oxidation from chromium (III) in the ensuing processing stages. There are methods available which can considerably reduce the chromium levels in the leather or even completely remove the chromium (VI). Chromium-free tanning methods are another option. Chromium free leather processing or mandatory declaration The BfR believes that leather goods that come into contact with skin should not, if possible, contain any chromium (VI). At the very least, the levels should be reduced as far as possible. At the present time, the analytical detection limit is approximately 3 mg per kg leather. The studies by the regulatory authorities and the standard for work gloves prove that this limit can be complied with by using the corresponding technologies. On the other hand, mandatory declaration could help allergy suerers to consciously avoid purchasing products containing chromium (VI).
Bibliography
[1] http://jama.ama-assn.org/cgi/content/abstract/303/18/1848. Chafen JJ, Newberry SJ, Riedl MA, Bravata DM, Maglione M, Suttorp MJ, Sundaram V, Paige NM, Towgh A, Hulley BJ, Shekelle PG.Diagnosing and managing common food allergies: a systematic review. JAMA. 2010 May 12;303(18):1848-56. [2] Fiocchi A, Bouygue GR, Albarini M, and Restani P. Molecular diagnosis of cows milk allergy. Curr Opin Allergy Clin Immunol, 4 2011. http://www.ncbi.nlm.nih. gov/pubmed/2150532. [3] Kim JS, Nowak-Wegrzyn A, Sicherer SH, Noone S, Moshier EL, and Sampson HA. Dietary baked milk accelerates the resolution of cows milk allergy in children. Journal of Allergy and Clinical Immunology, 2011. http://www.jacionline.org/ article/S0091-6749%2811%2900674-9/fulltext.
BIBLIOGRAPHY
349
[4] Huang F and Nowak-Wgrzyn A. Extensively heated milk and egg as oral immunotherapy. Curr Opin Allergy Clin Immunol, 12(3):28392, 6 2012. http: //www.ncbi.nlm.nih.gov/pubmed/22508193. [5] Kim JS, Nowak-Wgrzyn A, Sicherer SH, Noone S, Moshier EL, and Sampson HA. Dietary baked milk accelerates the resolution of cows milk allergy in children. J Allergy Clin Immunol, 128(1):125131.e2., 7 2011. http://www.ncbi.nlm.nih.gov/ pubmed/21601913. [6] Lieberman JA and Nowak-Wgrzyn A. Vaccines and immunomodulatory therapies for food allergy. Curr Allergy Asthma Rep, 12(1):5563, 2 2012. http://www.ncbi. nlm.nih.gov/pubmed/22090174. [7] Prescott S and Nowak-Wgrzyn A. Strategies to prevent or reduce allergic disease. Ann Nutr Metab, 59(Suppl 1):2842, 2011. http://content.karger.com/ produktedb/produkte.asp?DOI=000334150&typ=pdf. [8] Sicherer SH and Wood RA. American academy of pediatrics section on allergy and immunology. allergy testing in childhood: using allergen-specic ige tests. Pediatrics, 129(1):1937, 1 2012. http://pediatrics.aappublications.org/content/129/ 1/193.full.pdf. [9] Burks AW, Tang M, Sicherer S, Muraro A, Eigenmann PA, Ebisawa M, Fiocchi A, Chiang W, Beyer K, Wood R, Hourihane J, Jones SM, Lack G, and Sampson HA: ICON. Icon food allergies. J Allergy Clin Immunol, 129(4):90620, 4 2012. http: //www.ncbi.nlm.nih.gov/pubmed/22365653. [10] Ando H, Movrare R, Kondo Y, Tsuge I, Tanaka A, Borres MP, and Urisu A. Utility of ovomucoid-specic ige concentrations in predicting symptomatic egg allergy. J Allergy Clin Immunol, 122(3):5838, 9 2008. http://www.ncbi.nlm.nih.gov/ pubmed/18692888. [11] Brand PL. Dutch college of general practitioners practice guideline can be more rm - the food allergy test does not exist. Ned Tijdschr Geneeskd, 155(18):A3104, 2011. http://www.ncbi.nlm.nih.gov/pubmed/21466732. [12] Luning-Koster MN, Lucassen PL, Boukes FS, and Goudswaard AN. Summary of the dutch college of general practitioners practice guideline on food hypersensitivity. Ned Tijdschr Geneeskd, 155(18):A3063, 2011. http://www.ncbi.nlm.nih.gov/pubmed/ 21466730. [13] Nicolaou N and Custovic A. Molecular diagnosis of peanut and legume allergy. Curr Opin Allergy Clin Immunol, 4 2011. http://www.ncbi.nlm.nih.gov/pubmed/ 21464707.
350
[14] Ballmer-Weber BK and Homann-Sommergruber K. Molecular diagnosis of fruit and vegetable allergy. Curr Opin Allergy Clin Immunol, 4 2011. http://www.ncbi. nlm.nih.gov/pubmed/21460714. [15] Arvaniti F, Priftis KN, Papadimitriou A, Papadopoulos M, Roma E, Kapsokefalou M, Anthracopoulos MB, and Panagiotakos DB. Adherence to the mediterranean type of diet is associated with lower prevalence of asthma symptoms, among 10 to 12 years old children: the panacea study. Pediatr Allergy Immunol, 22(3):283289, 5 2011. http://www.ncbi.nlm.nih.gov/pubmed/21457335. [16] Wang J and Liu AH. Food allergies and asthma. Curr Opin Allergy Clin Immunol, 4 2011. http://www.ncbi.nlm.nih.gov/pubmed/21467928. [17] Jrvinen KM. Food-induced anaphylaxis. Curr Opin Allergy Clin Immunol, 4 2011. http://www.ncbi.nlm.nih.gov/pubmed/21467923. [18] Patel DA, Holdford DA, Edwards E, and Carroll NV. Estimating the economic burden of food-induced allergic reactions and anaphylaxis in the united states. J Allergy Clin Immunol, 4 2011. http://www.ncbi.nlm.nih.gov/pubmed/21489610. [19] Bailey S, Albardiaz R, Frew AJ, and Smith H. Restaurant stas knowledge of anaphylaxis and dietary care of people with allergies. Clin Exp Allergy, 41(5):7137, 5 2011. http://www.ncbi.nlm.nih.gov/pubmed/21488998. [20] Goodman RE and Tetteh AO. Suggested improvements for the allergenicity assessment of genetically modied plants used in foods. Curr Allergy Asthma Rep, 4 2011. http://www.ncbi.nlm.nih.gov/pubmed/21487714. [21] http://www.washingtonpost.com/wp-dyn/content/article/2008/03/03/ AR2008030303200_pf.html. Stain, Rob: Immune Systems Increasingly On Attack. Washington Post 04.03.2008. [22] http://www.liebertonline.com/doi/abs/10.1089/ees.2007.0188. Minutolo, Patrizia; DAnna, Andrea; Commodo, Mario; Pagliara, Rocco; Toniato, Guiseppe; Accordini, Claudio: Emission of Ultrane Particles from Natural Gas Domestic Burners. Environmental Engineering Science, 2008; 25 (10): 1357 DOI: 10.1089/ees.2007.0188. [23] http://en.wikipedia.org/wiki/Particulate. Wikipedia: Particulate matter. [24] http://jama.ama-assn.org/cgi/content/full/287/9/1132. Pope, C.A. 3rd; Burnett, R.T.; Thun, M.J.; Calle, E.E.; Krewski, D.; Ito, K; Thurston, G.D.: Lung Cancer, Cardiopulmonary Mortality, and Long-term Exposure to Fine Particulate Air Pollution. JAMA. 2002;287(9):1132-1141. Doi:10.1001/jama.287.9.1132.
BIBLIOGRAPHY
351
[25] http://www.ncbi.nlm.nih.gov/pubmed/19034792. Valavanidis A, Fiotakis K, Vlachogianni T.: Airborne particulate matter and human health: toxicological assessment and importance of size and composition of particles for oxidative damage and carcinogenic mechanisms. J Environ Sci Health C Environ Carcinog Ecotoxicol Rev. 2008 Oct-Dec;26(4):339-62. [26] http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2002071. Martinez, Fernando D.: The coming-of-age of the hygiene hypothesis. Respir Res. 2001; 2(3): 129-132. Published online 2001 April 2. doi: 10.1186/rr48. [27] http://www.nature.com/ncpgasthep/journal/v2/n2/full/ncpgasthep0087. html. Summers, Robert W.; Elliott, David E.; Weinstock, Joel V.: Is there a role for helminths in the therapy of inammatory bowel disease? Nature Clinical Practice Gastroenterology & Hepatology (2005) 2, 62-63 Doi:10.1038/ncpgasthep0087 Received 2 September 2004 Accepted 14 December 2004. [28] http://www.uni-muenchen.de/einrichtungen/zuv/uebersicht/komm_presse/ verteiler/presseinformationen/2006/nf-11-06.html. von Mutius, Erika. Ludwig-Maximilians Universitt Mnchen: EU-Projekt sucht genetische Faktoren und Umwelteinsse. LMU-Forscherin als Co-Koordinatorin von Asthma-Studie Mnchen, 09.05.2006. [29] http://main.nationalmssociety.org/site/PageServer?pagename=HOM_RES_ research_fleminghttp://main.nationalmssociety.org/site/PageServer? pagename=HOM_RES_research_fleming. Fleming, John O.: Helminth-induced immunomodulation therapy (HINT) in relapsing-remitting MS A novel, pilot clinical trial testing whether ingestion of worm eggs has the potential to alter the immune attack in MS. National Miltiple Sclerosis Society. [30] http://www.food.gov.uk/safereating/allergyintol/. Agency: Allergy and intolerance; Advisory labelling. UK Food Standards
[31] http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=OJ:L:2003:308: 0015:0018:EL:PDF. Directive 2003/89/EC of the European Parliament and of the Council of 10 November 2003 amending Directive 2000/13/EC as regards indication of the ingredients present in foodstus. [32] http://europa.eu.int/eur-lex/lex/LexUriServ/LexUriServ.do?uri=OJ:L: 2005:075:0033:0034:EN:PDF. Commission Directive 2005/26/EC of 21 March 2005 establishing a list of food ingredients or substances provisionally excluded from Annex IIIa of Directive 2000/13/EC. [33] http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=OJ:L:2006:368: 0110:0111:EN:PDF. Commission Directive 2006/142/EC of 22 December 2006 amending Annex IIIa of Directive 2000/13/EC of the European Parliament and of
352
CHAPTER 4. FOOD ALLERGIES the Council listing the ingredients which must under all circumstances appear on the labelling of foodstus.
[34] http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=OJ:L:2007:310: 0011:0014:EN:PDF. Commission Directive 2007/68/EC of 27 November 2007 amending Annex IIIa to Directive 2000/13/EC of the European Parliament and of the Council as regards certain food ingredients . [35] http://www.efsa.europa.eu/en/science/nda/nda_opinions/food_allergy/ nda_op_ej481_mustardseedoil.html. Opinion of the Scientic Panel NDA related to a notication from IFF on mustard seed oil pursuant to Article 6, paragraph 11 of Directive 2000/13/EC. [36] http://www.efsa.europa.eu/en/science/nda/nda_opinions/food_allergy/ 341.html. NDA (Scientic Panel on Dietetic Products, Nutrition and Allergies) (2004a). Opinion of the Scientic Panel on Dietetic Products, Nutrition and Allergies on a request from the Commission relating to the evaluation of allergenic foods for labelling purposes. The EFSA Journal 32, 1-197. [37] http://www.efsa.europa.eu/en/science/nda/nda_opinions/food_allergy/ 764.html. NDA (Scientic Panel on Dietetic Products, Nutrition and Allergies) (2004b). Opinion of the NDA Panel related to a notication from IFF on mustard seed oil pursuant to Article 6 paragraph 11 of Directive 2000/13/EC. The EFSA Journal 157, 1-6. [38] http://europa.eu.int/eur-lex/lex/LexUriServ/LexUriServ.do?uri=OJ:L: 2005:075:0033:0034:EN:PDF. Commission Directive 2005/26/EC of 21 March 2005 establishing a list of food ingredients or substances provisionally excluded from Annex IIIa of Directive 2000/13/EC of the European Parliament and of the Council. [39] Akiyama H, Imai T, and Ebisawa M. Japan food allergen labeling regulation-history and evaluation. Adv Food Nutr Res, 62:13971, 2011. http://www.ncbi.nlm.nih. gov/pubmed/21504823. [40] http://www.ncbi.nlm.nih.gov/pubmed/19385958. Kummeling I, Mills EN, Clausen M, Dubakiene R, Prez CF, Fernndez-Rivas M, Knulst AC, Kowalski ML, Lidholm J, Le TM, Metzler C, Mustakov T, Popov T, Potts J, van Ree R, Sakellariou A, Tndury B, Tzannis K, Burney P: The EuroPrevall surveys on the prevalence of food allergies in children and adults: background and study methodology. Allergy.2009 Oct;64(10):1493-7. Epub 2009 Apr 6. [41] http://www.ncbi.nlm.nih.gov/pubmed/19889114. Wong GW, Mahesh PA, Ogorodova L, Leung TF, Fedorova O, Holla AD, Fernandez-Rivas M, Clare Mills EN, Kummeling I, van Ree R, Yazdanbakhsh M, Burney P: The EuroPrevall-INCO surveys on the prevalence of food allergies in children from China, India and Russia: the study methodology. Allergy. 2009 Nov 4.
BIBLIOGRAPHY
353
[42] http://www3.interscience.wiley.com/journal/118705101/abstract. Roberts, G; Peckitt,C; Northstone,K; Strachan, D; Lack, G; Henderson, J; Goldin, J. and the ALSPAC Study Team: Relationship between aeroallergen and food allergen sensitization in childhood. Clinical & Experimental Allergy Volume 35 Issue 7, Pages 933-940. Published Online: 6 Jul 2005. [43] http://www.ncbi.nlm.nih.gov/pubmed/19629009. Shaker M, Woodmansee D: An update on food allergy. Curr Opin Pediatr. 2009 Oct;21(5):667-74. [44] http://www.ncbi.nlm.nih.gov/pubmed/20164762. Kim JS, Sicherer S: Should avoidance of foods be strict in prevention and treatment of food allergy? Curr Opin Allergy Clin Immunol. 2010 Feb 16. [45] http://www.ncbi.nlm.nih.gov/pubmed/19912153. Benhamou AH, Caubet JC, Eigenmann PA, Nowak-Wgrzyn A, Marcos CP, Reche M, Urisu A: State of the art and new horizons in the diagnosis and management of egg allergy. Allergy. 2009 Nov 12. [46] http://en.wikipedia.org/wiki/Patent_blue_V. Wikipedia: Patent Blue V. [47] http://www.ncbi.nlm.nih.gov/pubmed/20102358. Miyake Y, Sasaki S, Tanaka K, Hirota Y. Consumption of vegetables, fruit, and antioxidants during pregnancy and wheeze and eczema in infants. Allergy 2010 Jan 22. Doi: 10.1111/j.13989995.2009.02267.x. [48] International Dairy Foods Association (IDFA): Document No 00P-1322 Public Meeting on Labelling of Food Allergens. Docket July 25,2001. [49] http://www.foodallergy.com/services/test.html. Alletess Medical Laboratory: Our Services; Allergy Tests. [50] http://www.labtestonline.org/. Lab Tests Online A pubilc resource on clinical lab testing: Allergies. [51] http://www.europrevall.org.asp?id=52. EuroPrevall: Project Summery. [52] Kim JS, Nowak-Wgrzyn A, Sicherer SH, Noone S, Moshier EL, and Sampson HA. Dietary baked milk accelerates the resolution of cows milk allergy in children. Journal of Allergy and Clinical Immunology, 2011. http://www.jacionline.org/ article/S0091-6749%2811%2900674-9/fulltext. [53] Vetander M, Helander D, Flodstrm C, Ostblom E, Alfvn T, Ly DH, Hedlin G, Lilja G, Nilsson C, and Wickman M. Anaphylaxis and reactions to foods in children - a population-based case study of emergency department visits. Clin Exp Allergy, 42(4):56877, 4 2012. http://www.ncbi.nlm.nih.gov/pubmed/22417215.
354
[54] Chung S-Y and Reed S. Removing peanut allergens by tannic acid. Food Chemistry, 3 2012. http://dx.doi.org/10.1016/j.foodchem.2012.03.057. [55] Lin J, Bruni FM, Fu Z, Maloney J, Bardina L, Boner AL, Gimenez G, and Sampson HA. A bioinformatics approach to identify patients with symptomatic peanut allergy using peptide microarraundery immunoassay. J Allergy Clin Immunol, 3 2012. http: //www.ncbi.nlm.nih.gov/pubmed/22444503. [56] Cabanillas B, Pedrosa MM, Rodrguez J, Muzquiz M, Maleki SJ, Cuadrado C, Burbano C, and Crespo JF. Inuence of enzymatic hydrolysis on the allergenicity of roasted peanut protein extract. Int Arch Allergy Immunol, 157(1), 2012. http://www.ncbi.nlm.nih.gov/pubmed/21912172. [57] http://www.ncbi.nlm.nih.gov/pubmed/18795784. Venkatachalam M, Monaghan EK, Kshirsagar HH, Robotham JM, ODonnell SE, Gerber MS, Roux KH, Sathe SK.: Eects of processing on immunoreactivity of cashew nut (Anacardium occidentale L.) seed our proteins. J Agric Food Chem. 2008 Oct 8;56(19):8998-9005. Epub 2008 Sep 17. [58] http://www.ncbi.nlm.nih.gov/pubmed/14555856. Wang F, Robotham JM, Teuber SS, Sathe SK, Roux KH.: Ana o 2, a major cashew (Anacardium occidentale L.) nut allergen of the legumin family. Int Arch Allergy Immunol. 2003 Sep;132(1):27-39. [59] http://en.wikipedia.org/wiki/Atopy. Wikipedia, the free enzyclopedia: Atopy. [60] http://www.blackwell-synergy.com/doi/abs/10.1034/j.1398-9995.2001. t01-1-00001.x. Johansson SGO et al. A revised nomenclature for allergy. An EAACI position statement from the EAACI nomenclature task force. Allergy 2001; 56: 813-824 doi:10.1034/j.1398-9995.2001.t01-1-00001.x. [61] http://www.blackwell-synergy.com/doi/abs/10.1111/j.1365-277X.2007. 00751.x. Dean, T.; Venter, C.; Pereira, B.; Grundy, J.; Clayton, C. B.; Higgins, B.; (2007): Government advice on peanut avoidance during pregnancy-is it followed correctly and what is the impact on sensitization? Journal of Human Nutrition and Dietetics 20 (2), 95-99. doi:10.1111/j.1365-277X.2007.00751.x. [62] http://www.publications.parliament.uk/pa/ld200607/ldselect/ldsctech/ 166/166i.pdf. UK House of Lords : Science and Technology Committee, 6th Report of Session 2006-07. Allergy. Volume I Report. [63] http://www.parliament.uk/parliamentary_committees/lords_press_ notices/pn260907st.cfm. House of Lords Press Release: The Committee make a specic recommendation that current Government guidance, which advises some pregnant women and young children to avoid peanuts, should be immediately withdrawn Wednesday 26 September 2007.
BIBLIOGRAPHY
355
[64] http://ajrccm.atsjournals.org/cgi/content/abstract/178/2/124. Willers,Saskia M.; Wijga, Alet H.;Brunekreef, Bert; Kerkhof, Marjan; Gerritsen, Jorrit; Hoekstra, Maarten O.; de Jongste, Johan C.; Smit, Henriette A.: Maternal Food Consumption during Pregnancy and the Longitudinal Development of Childhood Asthma. American Journal of Respiratory and Critical Care Medicine. Volume 178, Pages 124-131. [65] http://www.ncbi.nlm.nih.gov/pubmed/18802477. Hollingsworth JW, Maruoka S, Boon K, Garantziotis S, Li Z, Tomfohr J, Bailey N, Potts EN, Whitehead G, Brass DM, Schwartz DA.In utero supplementation with methyl donors enhances allergic airway disease in mice. J Clin Invest. 2008 Oct;118(10):3462-9. [66] http://www.jci.org/articles/view/37171. Miller, Rachel L.: Prenatal maternal diet aects asthma risk in ospring. J. Clin. Invest. 118(10): 3265-3268 (2008). doi:10.1172/JCI37171. [67] http://pediatrics.aappublications.org/cgi/content/full/111/3/e282. Grber, Christoph. Illi, Sabina; Lau, Susanne; Nickel Renate; Forster Johannes; Kamin, Wolfgang; Bauer, Carl-Peter; Wahn,Volker; Wahn, Ulrich; MAS-90 Study Group: Transient suppression of atopy in early childhood is associated with high vaccination coverage. Pediatrics Vol. 111 No. 3 March 2003, pp. e282-e288. [68] http://adc.bmj.com/cgi/content/full/90/6/553. Grber, Christoph: Childhood immunisations and the development of atopic disease. Archives of Disease in Childhood 2005;90:553-555. [69] http://thorax.bmj.com/cgi/content/abstract/62/3/270. Nakajima, K.; Dharmage, S. C.; Carlin, J.B.; Wharton, C.L.; Jenkins, M.A.; Giles, G.G.; Abramson, M.J.; Haydn Walters, E. and Hopper J.L.: Is childhood immunisation associated with atopic disease from age 7 to 32 years? Thorax, March 1, 2007; 62(3): 270 - 275. [70] Kasper, Heinrich: Ernhrungsmedizin und Ditetik, Urban und Schwarzenberg 8. Auage pg 154. [71] Hunagle, Gary: Microora of the Gastrointestinal tract and immune systems response to allergens; Infection and Immunity (73, pp30-38) 2005. [72] Foliaki, Sunia and coll.: Antibiotic sales and the prevalence of symptoms of asthma, rhinitis and eczema: The International Study of Asthma and Allergies in Childhood (ISAAC); International Journal of Epidemiology, Volume 33, Number 3, pp.558-563. [73] http://en.wikipedia.org/wiki/Milk_allergy. Wikipedia, the free encyclopedia: Milk allergy. [74] http://pediatrics.aappublications.org/cgi/content/abstract/118/3/1279. Melvin B. Heyman: Lactose Intolerance in Infants, Children, and Adolescents Pediatrics 2006; 118: 1279-1286.doi:10.1542/peds.2006-1721.
356
[75] http://en.wikipedia.org/wiki/Lactose_intolerance. Wikipedia, the free encyclopedia: Lactose intolerance. [76] http://www.sciencedirect.com/science?_ob=PublicationURL&_tockey= %23TOC%236596%232006%23999929996%23629079%23FLA%23&_cdi=6596&_ pubType=J&_auth=y&_acct=C000050221&_version=1&_urlVersion=0&_userid= 10&md5=4b1846d04c4d340cda45db358b240113. Kleber,Nicole; Ulrike Weyrich, Ulrike and Jrg Hinrichs: Screening for lactic acid bacteria with potential to reduce antigenic response of beta -lactoglobulin in bovine skim milk and sweet whey; Innovative Food Science & Emerging Technologies Volume 7, Issue 3, Pages 233-238. [77] http://digestive.niddk.nih.gov/ddiseases/pubs/lactoseintolerance/. National Digestive Diseases Information Clearinghouse (NDDIC): Lactose intolerance. [78] http://www.bmj.com/cgi/content/full/334/7608/1331. Bhatnagar, Shinjini; Aggarwal, Rakesh: Lactose intolerance is common and can be diagnosed clinically and treated with simple dietary measures.BMJ 2007;334:1331-1332 (30 June), doi:10.1136/bmj.39252.524375.80. [79] http://www.iom.edu/?id=12704. Institute of Medicine: Dietary Reference Intakes for Calcium, Phosphorus, Magnesium, Vitamin D, and Fluoride. [80] Adapted from Manual of Clinical Dietetics. 6th ed. American Dietetic Association, 2000; and Soy Dairy Alternatives. Available at: www.soyfoods.org. [81] Quigley, Eamonn M.M. Gastroenterology vol 128, issue 3 pp541-51. [82] Casas IA, Dobrogosz WJ: Validation of the Probiotic Concept: Lactobacillus reuteri Confers Broad-spectrum Protection against Disease in Humans and Animals. Microbial Ecology in Health and Disease 2000;12(4):247-85. [83] http://www.pubmedcentral.nih.gov/pubmed/14766603. Nana Valeur, Peter Engel, Noris Carbajal, Eamonn Connolly, and Karin Ladefoged: Colonization and Immunomodulation by Lactobacillus reuteri ATCC 55730 in the Human Gastrointestinal Tract. Appl Environ Microbiol. 2004 February; 70(2): 1176- 1181. [84] http://www.ncbi.nlm.nih.gov/pubmed/15629974. Weizman Z, Asli G, Alsheikh A.: Eect of a probiotic infant formula on infections in child care centers: comparison of two probiotic agents: Pediatrics 2005 Jan;115(1):5-9. [85] http://www.biogaia.se/public/documents/Conf_abstracts_posters/ jakobsson_breastmilk.pdf. Jakobsson Ted,Abrahamsson Thomas, Bjrkstn Bengt, Fredriksson Mats, Bttcher F Malin: The eect of oral supplementation of Lactobacillus reuteri, on the immunologic composition of breast milk;Abstract of oral presentation at the 38. Congress of the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN), 1-4 June, Porto, Portugal, 2005.
BIBLIOGRAPHY
357
[86] http://www.farrp.org/articles/feolecithin.pdf. Hee, Ssusan L.; Taylor, Steve L.: Expert Opinion: Soybean Lecithin, September 24, 2004, University of Nebraska, Institute of Agriculture and Natural Resources, Food Allergy Research and Resouce Program. [87] http://journals.elsevierhealth.com/periodicals/ymai/issues/contents#. Ballmer-Weber, Barbara K.; Holzhauser, Thomas; Scibilia, Joseph; Mittag, Diana; Zisa, Guliana; Ortolani, Claudio; Oesterballe, Morten; Poulsen, Lars K.; Vieths, Stefan; Bindslev-Jensen, Carsten: Clinical characteristics of soybean allergy in Europe: A double-blind, placebo-controlled food challenge study, The Journal of Allergy and Clinical Immunology. 12 April 2007.pages 1489-1496. [88] http://pubs.acs.org/cgi-bin/abstract.cgi/jafcau/2008/56/i01/abs/ jf072177j.html. Frias, Juana; Song, Young Soo; Martnez-Villaluenga, Cristina; De Mejia, Elvira Gonzalez; Vidal-Valverde, Concepcion: Immunoreactivity and Amino Acid Content of Fermented Soybean Products. Journal of Agricultural and Food Chemistry. Volume 56, Issue 1, Pages 99-105, 2007. doi: 10.1021/jf072177j. [89] http://www.tepnel.com/. Tepnel, News and events. [90] http://www.elisas.com.au/prod05.htm. ELISA Systems: Rapid test kits to detect food allergens. [91] Gadermaier G, Egger M, Girbl T, Erler A, Harrer A, Vejvar E, Liso M, Richter K, Zuidmeer L, Mari A, and Ferreira F. Molecular characterization of api g 2, a novel allergenic member of the lipid-transfer protein 1 family from celery stalks. Mol Nutr Food Res, 12 2010. http://www.ncbi.nlm.nih.gov/pubmed/21174327. [92] Harrer A, Egger M, Gadermaier G, Erler A, Hauser M, Ferreira F, and Himly M. Characterization of plant food allergens: an overview on physicochemical and immunological techniques. Mol Nutr Food Res, 54(1):93112, 1 2010. http: //www.ncbi.nlm.nih.gov/pubmed/19960453. [93] Faeste CK, Jonscher KR, Sit L, Klawitter J, Lvberg KE, and Moen LH. Differentiating cross-reacting allergens in the immunological analysis of celery (apium graveolens) by mass spectrometry. J AOAC Int, 93(2):45161, Mar-Apr 2010. http://www.ncbi.nlm.nih.gov/pubmed/20480890. [94] Ferrer M, Sanz ML, Sastre J, Bartra J, del Cuvillo A, Montoro J, Juregui I, Mullol J Dvila I, and Valero A. Molecular diagnosis in allergology: application of the microarray technique. J Investig Allergol Clin Immunol, 19(Suppl 1):1924, 2009. http://www.ncbi.nlm.nih.gov/pubmed/19476050. [95] De Knop KJ, Bridts CH, Verweij MM, Hagendorens MM, De Clerck LS, Stevens WJ, and Ebo DG. Component-resolved allergy diagnosis by microarray: potential,
358
CHAPTER 4. FOOD ALLERGIES pitfalls, and prospects. Adv Clin Chem, 50:87101, 2010. http://www.ncbi.nlm. nih.gov/pubmed/20521442.
[96] Gall H, Kalveram, KJ, Forck G, Sterry W: Department of Dermatology, University of Ulm, Germany: Kiwi fruit allergy: a new birch pollen food allergy; J Allergy Clin Immunol 1994 Jul;94(1):70-6. PMID: 8027500 (PubMed - indexed for MEDLINE). [97] http://foodallergens.ifr.ac.uk/clinical.lasso?selected-food=30. [98] Erdmann S.M., Sachs B., Schmidt A., Merk H.F., Scheiner O., Moll-Slodowy S., Sauer I., Kwiecien R., Maderegger B., Homann-Sommergruber K.: In vitro Analysis of Birch-Pollen-Associated Food Allergy by Use of Recombinant Allergens in the Basophil Activation Test; International Archives of Allergy and Immunology 2005;136:230-238. [99] Boumiza, Radhia; Debard, Anne-Lise; Monneret, Guillaume: The basophil activation test by ow cytometry: recent developments in clinical studies, standardization and emerging perspectives; Clinical and Molecular Allergy 2005, 3:9. [100] Bublin M, Mari A, Ebner C, Knulst A, Scheiner O. Homann-Sommergruber K, Breiteneder H, Radauer C: IgE sensitisation proles toward green and gold kiwifruits dier among patients to kiwifruit from 3 European countries; J Allergy Clin Immunol 2004 Nov. 114(5):1169-75 PMID: 15536427 (PubMed - ed for MEDLINE). [101] Gavrovic-Jankulovic M, Cirkovic T., BurazerL. Vuckovic O, Jankov RM: IgE cross reactivity between meadow fescue pollen and kiwi fruit in patients sera with sensitivity to both extracts.; J Investig Allergol Clin Immunol 2002;12(4):279-86. PMID: 12926188(PubMed-indexed for MEDLINE). [102] Rudeschko O, Fahlbusch B, Steurich F, Schlenvoigt G, Jager L: Kiwi allergens and their cross-reactivity with birch, rye, timothy, and mugwort pollen; Institute of Clinical Immunology, Friedrich-Schiller-University, Jena, Germany: J Investig Allergol Clin Immunol. 1998 Mar-Apr;8(2):78-84. PMID: 9615299 (PubMed - indexed for MEDLINE). [103] http://www.bfr.bund.de/cms5w/sixcms/detail.php/9553. Federal Institute for Risk Assessment: People who are allergic to birch pollen may react hypersensitively to soy products too. 09/2007, 28.06.2007.
[104] http://www.voedingscentrum.nl/NR/rdonlyres/52365DEB-A391-45C3-859A-82025BA5CC6F/ 0/factsheetmaispdf.pdf#search=%22Fact%20Sheet%20Maize%20Christopher% 20Preston%20NAG%22. Fact sheet maize. [105] Carsten Bindslev-Jensen, Per Stahl Skov, Erwin L. Roggen, Peter Hvass and Ditte Sidelmann Brinch: Investigation on possible allergenicity of 19 dierent commercial enzymes used in the food industry Pages 1909-1915 doi:10.1016/jfct.2006.06.012.
BIBLIOGRAPHY [106] http://www.sustainweb.org/realbread/what_is_real_bread/. Campaign: Bread labelling transpoarency.
359 Real Bread
[107] http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=OJ:L:2008:354: 0001:0006:EN:PDF. Regulation (EC) No 1331/2008 of the European Parliament and of the Council of 16 December 2008 establishing a common authorisation procedure for food additives, food enzymes and food avourings. [108] Frossard, Christophe P.; Steidler, Lothar; Eigenmann, Philippe: Oral administration of an IL-10-secreting Lactococcus lactis strain prevents food-induced IgE sensitization. Journal of Allergy and Clinical Immunology (Elsevier) doi: 10.1016/j.jaci.2006.12.615. [109] http://download.journals.elsevierhealth.com/pdfs/journals/0091-6749/ PIIS0091674904040850.pdf. Eigenmann, Philippe; Frossard, Christophe P: IL-10 transfected lactoccocus lactis prevent food allergy in a mouse model of food-induced anaphylaxis. Journal of Allergy and Clinical Immunology February 2005 (Vol. 115, Issue 2 (Supplement), Page S205). [110] http://journals.elsevierhealth.com/periodicals/ymai/issues/contents#. Liem, Joel J.: Kozyrskyj, Anita L.; Huq Shamima I. and Becker, Allan B.: The risk of developing food allergy in premature or low-birth-weight children. Journal of Allergy and Clinical Immunology May 2007, Volume 119, Issue 5, Pages 1203-1209 doi:10.1016/j.jaci.2006.12.671. [111] http://www.blackwell-synergy.com/doi/abs/10.1111/j.1365-2222.2006. 02640.x. Waser, M.;. Michels, K..B.;.Bieli,. Floistrup, C. H.; Pershagen, G.; von Mutius, E.; Ege, M; Riedler, J.; Schram-Bijkerk, D.;. Brunekreef, B.; van Hage, M.; Lauener, R.; Braun-Fahrlander, C.: the PARSIFAL Study team: Inverse association of farm milk consumption with asthma and allergy in rural and suburban populations across Europe Clinical and Experimental Allergy Clinical and Experimental Allergy May 2007, Volume 37, Pages 661-670 doi:10.1111/j.1365-2222.2006.02640.x. [112] http://www.blackwell-synergy.com/doi/abs/10.1111/j.1365-2222.2007. 02715.x. Perkin, M.R.Unpasteurised milk: health or hazard ? Clinical and Experimental Allergy Editorial May 2007, Volume 37, Pages 627-630 doi:10.1111/j.13652222.2007.02715.x. [113] http://www.efsa.europa.eu/en/science/nda/nda_opinions/food_allergy/ ej485_tocopherols.html. EFSA: Opinion of the NDA Panel related to a notication from Cognis, ADM and Cargill on natural mixed tocopherols (E306), natural D-alpha tocopherol, natural D-alpha tocopherol acetate and natural D-alpha tocopherol succinate from soybean sources pursuant to Article 6, paragraph 11 of Directive 2000/13/EC. 6.6.2007.
360
[114] http://www.efsa.europa.eu/en/science/nda/nda_opinions/food_allergy/ ej486_phytosterols.html. EFSA: Opinion of the NDA Panel related to a notication from Cognis, ADM and Cargill on vegetable oils-derived phytosterols and phytosterol esters from soybean sources pursuant to Article 6 paragraph 11 of Directive 2000/13/EC. 6.6.2007. [115] http://en.wikipedia.org/wiki/Celiac_disease. Wikipedia: Coeliac disease. [116] http://www.ncbi.nlm.nih.gov/pubmed/19756027. Kemppainen TA, Heikkinen MT, Ristikankare MK, Kosma VM, Julkunen RJ.: Nutrient intakes during diets including unkilned and large amounts of oats in celiac disease. Eur J Clin Nutr. 2010 Jan;64(1):62-67. Doi:10.1038/ejcn.2009.113. [117] Lovika, Astrid; Gjoenb, ; Morkridc, Lars; Guttormsend, Vigdis; Uelande, Thor ,Lundinaf, Knut E.A.: Oats in a strictly gluten-free diet is associated with decreased gluten intake and increased serum bilirubin. Volume 4, Issue 6, Pages e315-e320 (December 2009). European Society for Clinical Nutrition and Metabolism. [118] http://www.efsa.europa.eu/en/science/nda/nda_opinions/food_allergy/ ej488_glucose_syrups.html. EFSA: Opinion of the NDA Panel related to a notication from AAC on wheat-based glucose syrups including dextrose pursuant to Article 6, paragraph 11 of Directive 2000/13/EC. 6.6.2007. [119] http://www.codexalimentarius.net/download/standards/291/CXS_118e.pdf. Codex Stan 118 Standard for Gulte-Free Foods 1983. [120] http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=OJ:L:2009:016: 0003:0005:EN:PDF. European Commission Regulation 41/2009 of 20 January 2009 concerning the composition and labelling of foodstus suitable for people intolerant to gluten. [121] http://www.codexalimentarius.net/download/standards/291/cxs_118e.pdf. Codex Stan 118-1979: Codex Standard for Special Dietary Use for Persons Intolerant to Gluten. Adopted in 1979; amended 1983; revised 2008. [122] Mena MC, Lombarda M, Hernando A, Mndez E, and Albar JP. Comprehensive analysis of gluten in processed foods using a new extraction method and a competitive elisa based on the r5 antibody. Talanta, 91:3340, 3 2012. http://www.ncbi.nlm. nih.gov/pubmed/22365676. [123] Thompson T and Mndez E. Commercial assays to assess gluten content of glutenfree foods: why they are not created equal. J Am Diet Assoc, 10:16827, 10 2008. http://www.ncbi.nlm.nih.gov/pubmed/18926134. [124] Haraszi R, Chassaigne H, Maquet A, and Ulberth F. Analytical methods for detection of gluten in foodmethod developments in support of food labeling legislation. J
BIBLIOGRAPHY
361
AOAC Int, 94(4):100625, Jul-Aug 2011. http://www.ncbi.nlm.nih.gov/pubmed/ 21919334. [125] http://www.aoecs.org/. The Association of European Coeliac Societies (AOECS). [126] http://www.etseq.urv.es/cdmedics/. AOECS Research News: Coeliac Disease - Management, Monitoring and Diagnosis using Biosensors and an Integrated Chip System (CD-MEDICS). [127] http://news.uns.purdue.edu/x/2009a/090122FisherBiosensor.html. Purdue University News: Nano-tetherball Biosensor Precisely Detects Glucose. 22.01.2009. [128] Sapone A, Bai J, Ciacci C, Dolinsek J, Green PHR, Hadjivassiliou M, Kaukinen K, Rostami K, Sander DS, Schumann M, Ullrich R, Villalta D, Volta U, Catassi C, and Fasano A. Spectrum of gluten-related disorders: consensus on new nomenclature and classication. Int Arch Allergy Immunol, 152(1):7580, 2010. http://www. biomedcentral.com/1741-7015/10/13/abstract. [129] Sapone A, Lammers KM, Mazzarella G, Mikhailenko I, Carten M, Casolaro V, and Fasano. Dierential mucosal il-17 expression in two gliadin-induced disorders: gluten sensitivity and the autoimmune enteropathy coeliac disease. Int Arch Allergy Immunol, 152(1):7580, 4 2010. http://www.ncbi.nlm.nih.gov/pmc/articles/ PMC2956008/?tool=pubmed. [130] Armstrong D, Don-Wauchope AC, and Verdu EF. Testing for gluten-related disorders in clinical practice: the role of serology in managing the spectrum of gluten sensitivity. Can J Gastroenterol, 25(4):1937, 4 2011. http://www.ncbi.nlm.nih.gov/pubmed/ 21523259. [131] Armstrong MJ, Hegade VS, and Robins G. Advances in coeliac disease. Curr Opin Gastroenterol, 28(2):10412, 3 2012. http://www.ncbi.nlm.nih.gov/pubmed/ 22123644. [132] Comino I, Real A, de Lorenzo L, Cornell H, Lpez-Casado MA, Barro F, Lorite P, Torres MI, Cebolla A, and Sousa C. Diversity in oat potential immunogenicity: basis for the selection of oat varieties with no toxicity in coeliac disease. Gut, 60(7):915 22, 7 2011. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3112367/?tool= pubmed. [133] Tanner GJ, Howitt CA, Forrester RI, Campbell PM, Tye-Din JA, and Anderson RP. Dissecting the t-cell response to hordeins in coeliac disease can develop barley with reduced immunotoxicity. Aliment Pharmacol Ther, 32(9):118491, 11 2010. http://www.ncbi.nlm.nih.gov/pubmed/21039679.
362
[134] Stenman SM, Lindfors K, Venlinen JI, Hautala A, Mnnist PT, Garcia-Horsman JA, Kaukovirta-Norja A, Auriola S, Mauriala T, Mki M, and Kaukinen K. Degradation of coeliac disease-inducing rye secalin by germinating cereal enzymes: diminishing toxic eects in intestinal epithelial cells. Clin Exp Immunol, 161(2):2429, 8 2010. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2909406/?tool=pubmed. [135] Gil-Humanes J, Pistn F, Tollefsen S, Sollid LM, and Barro F. Eective shutdown in the expression of celiac disease-related wheat gliadin t-cell epitopes by rna interference. Proc Natl Acad Sci U S A, 107(39):170238, 9 2010. http: //www.ncbi.nlm.nih.gov/pubmed/20829492. [136] Sapone A, Bai JC, Ciacci C, Dolinsek J, Green PH, Hadjivassiliou M, Kaukinen K, Rostami K, Sanders DS, Schumann M, Ullrich R, Villalta D, Volta U, Catassi C, and Fasano A. Spectrum of gluten-related disorders: consensus on new nomenclature and classication. BMC Med, 10:13, 2 2012. http://www.ncbi.nlm.nih.gov/pmc/ articles/PMC3292448/?tool=pubmed. [137] Zevallos VF, Ellis HJ, Suligoj T, Herencia LI, and Ciclitira PJ. Variable activation of immune response by quinoa (chenopodium quinoa willd.) prolamins in celiac disease. Am J Clin Nutr, 96(2):33744, 8 2012. http://www.ncbi.nlm.nih.gov/pubmed/ 22760575. [138] Shamir R. Can feeding practices during infancy change the risk for celiac disease? Isr Med Assoc J, 14(1):502, 1 2012. http://www.ima.org.il/imaj/dynamic/web/ ArtFromPubmed.asp?year=2012&month=01&page=50. [139] Osorio C, Wen N, Gemini R, Zemetra R, von Wettstein D, and Rustgi S. Targeted modication of wheat grain protein to reduce the content of celiac causing epitopes. Funct Integr Genomics, 6 2012. http://www.ncbi.nlm.nih.gov/pubmed/22732824. [140] Bugyi Z, Trk K, Hajas L, Adonyi Z, Poms RE, Popping B, Diaz-Amigo C, Kerbach S, and Tmskzi S. Development of incurred reference material for improving conditions of gluten quantication. J AOAC Int, 95(2):3827, Mar-Apr 2012. http://www.ncbi.nlm.nih.gov/pubmed/22649923. [141] Gluten. romer labs. http://www.romerlabs.com/en/knowledge/gluten. [142] Shan L, Molberg O, Parrot I, Hausch F, Filiz F, Gray GM, Sollid LM, and Khosla C. Structural basis for gluten intolerance in celiac sprue. Science, 27(297(5590)):22759, 9 2002. http://www.ncbi.nlm.nih.gov/pubmed/12351792. [143] Halbmayr-Jech E, Hammer E, Fielder R, Coutts J, Rogers A, and Cornish M. Characterization of g12 sandwich elisa, a next-generation immunoassay for gluten toxicity. J AOAC Int, 95(2):3726, Mar-Apr 2012. http://www.ncbi.nlm.nih.gov/pubmed/ 22649921.
BIBLIOGRAPHY
363
[144] Haas-Lauterbach S, Immer U, Richter M, and Koehler P. Gluten fragment detection with a competitive. J AOAC Int, 95(2):37781, Mar-Apr 2012. http://www.ncbi. nlm.nih.gov/pubmed/22649922. [145] Diaz-Amigo C and Popping B. Gluten and gluten-free: issues and considerations of labeling regulations, detection methods, and assay validation. J AOAC Int, 95(2):33748, Mar-Apr 2012. http://www.ncbi.nlm.nih.gov/pubmed/22649917. [146] Mameri H, Bouchez I, Pecquet C, Raison-Peyron N, Choudat D, Chabane H, Kerre S, Denery-Papini S, Gohon Y, Briozzo P, and Sngaro J Laurire M. A recombinant -gliadin-like d-type glutenin and an -gliadin from wheat (triticum aestivum): Two immunoglobulin e binding proteins, useful for the diagnosis of wheat-dependent allergies. J Agric Food Chem, 8 2012. http://www.ncbi.nlm.nih.gov/pubmed/ 22809016. [147] Rostami Nejad M, Rostami K, Yamaoka Y, Mashayekhi R, Molaei M, Dabiri H, Al Dulaimi D, Mirsattari D, Zojaji H, Norouzinia M, and Zali MR. Clinical and histological presentation of helicobacter pylori and gluten related gastroenteropathy. Arch Iran Med, 14(2):1158, 3 2011. http://www.ncbi.nlm.nih.gov/pmc/ articles/PMC3126917/?tool=pubmed. [148] Bozkurt F, Gulsun1 S, Ustun C, Geyik MF, and Hosoglu S. The role of trace elements in helicobacter pylori infected patients. Kuwait Medical Journal, 43(4):287290, 2011. http://www.kma.org.kw/KMJ/journals/December%202011.pdf. [149] Lahner E, Persechino S, and Annibale B. Micronutrients (other than iron) and helicobacter pylori infection: A systematic review. Helicobacter, 17:115, 2011. http: //onlinelibrary.wiley.com/doi/10.1111/j.1523-5378.2011.00892.x/pdf. [150] http://www.ncbi.nlm.nih.gov/pubmed/20036949. Accomando S, Pellitteri V, Corsello G: Biochemical markers in Celiac disease. Front Biosci (Schol Ed). 2010 Jan 1;2:313-7. [151] http://www.ncbi.nlm.nih.gov/pubmed/20170845. Hadjivassiliou M, Sanders DS, Grnewald RA, Woodroofe N, Boscolo S, Aeschlimann D: Gluten sensitivity: from gut to brain. Lancet Neurol. 2010 Mar;9(3):318-330. [152] http://www.ncbi.nlm.nih.gov/pubmed/20040864. Rubio-Tapia A, Murray JA: Celiac disease. Curr Opin Gastroenterol. 2010 Mar;26(2):116-22. [153] http://www.ncbi.nlm.nih.gov/pubmed/19073695. Leeds JS, Hopper AD, Sanders DS: Coeliac disease. Br Med Bull. 2008;88(1):157-70. [154] http://www.ncbi.nlm.nih.gov/pubmed/18403932. Troncone R, Auricchio R, Granata V: Issues related to gluten-free diet in coeliac disease. Curr Opin Clin Nutr Metab Care. 2008 May;11(3):329-33.
364
[155] http://www.ncbi.nlm.nih.gov/pubmed/19699406. Rashtak S, Murray JA: Celiac disease in the elderly. Gastroenterol Clin North Am. 2009 Sep;38(3):433-46. [156] http://www.ncbi.nlm.nih.gov/pubmed/20165980. Mukherjee R, Egbuna I, Brar P, Hernandez L, McMahon DJ, Shane EJ, Bhagat G, Green PH: Celiac Disease: Similar Presentations in the Elderly and Young Adults. Dig Dis Sci. 2010 Feb 18. [157] http://www.ncbi.nlm.nih.gov/pubmed/18825674. Hadjivassiliou M, Aeschlimann P, Strigun A, Sanders DS, Woodroofe N, Aeschlimann D: Autoantibodies in gluten ataxia recognize a novel neuronal transglutaminase. Ann Neurol. 2008 Sep;64(3):33243. [158] http://www.ncbi.nlm.nih.gov/pubmed/19929789. De Vivo G, Di Lorenzo R, Ricotta M, Gentile V : Role of the transglutaminase enzymes in the nervous system and their possible involvement in neurodegenerative diseases. Curr Med Chem. 2009;16(36):4767-73. [159] http://www.ncbi.nlm.nih.gov/pubmed/19528877. Armstrong MJ, Robins GG, Howdle PD: Recent advances in coeliac disease. Curr Opin Gastroenterol. 2009 Mar;25(2):100-9. [160] http://www.ncbi.nlm.nih.gov/pubmed/20176568. Rawal P, Thapa BR, Prasad R, Prasad KK, Nain CK, Singh K: Zinc supplementation to patients with celiac diseaseis it required? J Trop Pediatr. 2010 Feb 21. [161] http://www.ncbi.nlm.nih.gov/pubmed/20181349. Sealey-Voyksner JA, Khosla C, Voyksner RD, Jorgenson JW: Novel aspects of quantitation of immunogenic wheat gluten peptides by liquid chromatography-mass spectrometry/mass spectrometry. J Chromatogr A. 2010 Feb 1. [162] http://www.ncbi.nlm.nih.gov/pubmed/20171961. Vermeersch P, Geboes K, Marien G, Homan I, Hiele M, Bossuyt X: Diagnostic performance of IgG antideamidated gliadin peptide antibody assays is comparable to IgA anti-tTG in celiac disease. 2010 Feb 18.Clin Chim Acta. [163] http://www.ncbi.nlm.nih.gov/pubmed/20136587. Volta U, Fabbri A, Parisi C, Piscaglia M, Caio G, Tovoli F, Fiorini E: Old and new serological tests for celiac disease screening. Expert Rev Gastroenterol Hepatol. 2010 Feb;4(1):31-5. [164] http://www.ncbi.nlm.nih.gov/pubmed/20042872. Volta U, Granito A, Parisi C, Fabbri A, Fiorini E, Piscaglia M, Tovoli F, Grasso V, Muratori P, Pappas G, De Giorgio R: Deamidated gliadin Peptide antibodies as a routine test for celiac disease: a prospective analysis. J Clin Gastroenterol. 2010 Mar;44(3):186-90 amidated gliadin Peptide antibodies as a routine test for celiac disease: a prospective analysis.
BIBLIOGRAPHY
365
[165] http://www.ncbi.nlm.nih.gov/pubmed/20151068. Duerksen DR, Leslie WD: Positive celiac disease serology and reduced bone mineral density in adult women. Can J Gastroenterol. 2010 Feb;24(2):103-7. [166] http://www.ncbi.nlm.nih.gov/pubmed/20129704. Arranz E, Garrote JA: Immunology of celiac disease. Gastroenterol Hepatol. 2010 Feb 1. [167] http://www.ncbi.nlm.nih.gov/pubmed/20096017. Hershcovici T, Leshno M, Goldin E, Shamir R, Israeli E: Cost eectiveness of mass screening for celiac disease is determined by time-delay to diagnosis and quality of life on a gluten free diet. Aliment Pharmacol Ther. 2010 Jan 19. [168] http://www.ncbi.nlm.nih.gov/pubmed/20089550. Kearby R, Bowyer S, Scharrer J, Sharathkumar A: Case Report: Six-Year-old Girl With Recurrent Episodes of Blue Toes. Clin Pediatr (Phila). 2010 Jan 28. [169] Chromium (vi) in leather clothing and shoes problematic for allergy suerers!, 2007. http://www.bfr.bund.de/cms5w/sixcms/detail.php/9575.
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Chapter 5 Baby Food and Infant Formulas

5.0.65 Infant nutrition
[1] Infant nutrition consists of two phases: 1. Diet solely of breast milk or breast milk substitutes (rst 4-6 months) 2. Diet with breast milk or breast milk substitutes supplemented with weaning food (at the earliest from 5 months, at the latest from 7 months. If a mother is unable to or does not breastfeed, breast milk substitutes can be given to healthy, full-term infants: a - Infant formula can replace breast milk from birth onwards and like breast milk is suitable as the sole source of food for the rst four to six months. After that infant formula plus weaning food can be given throughout the rst year of life. In Germany and in the European Union there are four types of infant formula: - based on cows milk protein with lactose as the sole carbohydrate. - based on cows milk protein with other carbohydrates besides lactose - based on soy bean protein isolate (N.B.: this food is only lactose-free in Germany) - based on partially hydrolysed (cleaved) protein (name HA). This initial food is intended for non-breast fed infants from families with a history of allergies. b - Follow-on formula can replace breast milk at the earliest from the fth month onwards. It is not suitable from birth onwards as it is not adapted to the needs of the very young infant. There is no compelling reason to switch from infant formula to follow-on formula. c - Weaning food is the name for all dietary foods intended specically for infants (and small children) which should supplement the diet with breast milk or breast substitute products at the earliest from the 5th month and at the latest from the 7th month onwards. It is recommended that weaning food be selected which corresponds to the Ernhrungsplan des Forschungsinstituts fr Kinderernhrung in Dortmund (Nutrition Plan of the Research 367
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CHAPTER 5. BABY FOOD AND INFANT FORMULAS
Institute for Childrens Nutrition in Dortmund) and to use them in the stipulated sequence. Both for infant bottle formula and weaning food products there are especially sti statutory provisions concerning the composition, the use of additives (colouring agents, avourings, preservatives are banned), the bacteriological requirements and the limit values for residues and contaminants which are uniform throughout the European Union
5.1
How to feed a baby, recommendations of UK FSA
[2] The UK Food Standards Agency promulgates the following advices on how to feed a baby.
5.1.1
Breastfeeding
According to the advice of the Agency breastfeeding is best for babies. It should continue exclusive breastfeeding for six months, the longer the better. Continue to give breast milk or formula milk until it is at least a year old. A change to follow-on milk isnt necessary at any stage.
5.1.2
Infant formula
Infant formula is the only alternative to breast milk. Cows milk is not suitable as a drink until a baby is a year old because it contains too much salt and protein, and not enough iron and other nutrients, to meet your babys needs. Starting on solid foods The amount of solid foods may be gradually increased, beginning from the sixth month so that by twelve months, solid foods become the main part of your babys diet, with breast or formula milk making up the balance. FSA says that commercial baby foods can be useful but should not replace family foods altogether. It is cheaper than buying baby foods, youll know what the ingredients are, and your baby will get used to eating like the rest of the family. Meat and sh-free babyfood for vegetarians The FSA recommends to make sure to give two servings a day of pulses (such as red lentils, beans or chickpeas), or tofu to make sure they get all the energy and nutrients they need. The vitamin C in fruit and vegetables helps the absorption of iron, fruit and vegetables at mealtimes should therefore not be forgotten at babys meal.
5.1. HOW TO FEED A BABY, RECOMMENDATIONS OF UK FSA Avoid the following foods: The FSA recommends to avoid Salt
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Babies up to 6 months old should have less than 1g salt a day. From 7 months to a year old they should have a maximum of 1g salt a day. Sugar Avoid adding sugar to the food or drinks you give your baby. If you give your baby stewed sour fruit, such as rhubarb, you could sweeten it with mashed banana, breast or formula milk. Honey Honey can contain a type of bacteria that may produce infant botulism. Honey should therefore be avoided for babies under one year, after that age the intestine matures and the bacteria cant grow. Other foods to avoid up to six months Because of possible allergies babies under six years old should not be fed with: Wheat-based foods containing gluten This includes bread, wheat our, breakfast cereals and rusks. Nuts and seeds This includes peanuts, peanut butter and other nut spreads. Peanuts can be given from six months old onwards, if you always crush or ake them. Eggs Fish and shellsh Hydrolysed protein infant formulas might be prescribed a GP if a baby has an allergy to cows milk. Soya-based infant formulas They should only be fed on the advice a GP or health visitor. Babies who are allergic to cows milk may also be allergic to soya.
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5.1.3
Goats milk infant formulas and follow-on formulas based on goats milk protein
are not suitable for babies, and have not been approved for use in Europe. Since the levels of lactose are similar in both milks, formulas derived from goats milk are also unsuitable for babies that are lactose-intolerant. Pasteurised goats and sheeps milk can be used once a baby is a year old. Start using full-fat milks in cooked foods, and full-fat milk products, such as yoghurt after the age of six month.
5.1.4
Water
The FSA says that water is the best alternative drink to milk, but fully breastfed babies dont need any water until they start eating solid food. For babies under six months old, take water from the mains tap in the kitchen and boil it.
5.1.5
Fruit juice
FSA comments that Fruit juices, such as orange juice, are a good source of vitamin C, particularly for vegetarian diet or breastfed babies, however fruit juice should not be given to babies under six month. However, vitamin C might help our bodies absorb iron from a meal, so you may be advised to give diluted fruit juice with your childs meals after six months, In this case, give very dilute juice (one part juice with ten parts cooled, boiled water) in a feeding cup and at mealtimes only.
5.1.6
Introducing sh in diet of low-aged children protects of asthma [3]
According to Kiefte-de Jong et al. 2012, children born in Rotterdam, the Netherlands, who ate sh for the rst time between the ages of 6 and 12 months but had no dietary sh intake at 14 months were less likely to have asthma symptoms, such as wheezing and shortness of breath, as preschoolers. The protective eect of sh was not seen when they rst ate sh when they were younger than 6 months or eating no sh in their rst year of life. Diets high in sh, vegetables, and fruit have been found to protect pregnant women and school-aged children from asthma. The authors concluded that early life exposure to n-3 polyunsaturated fatty acids (n-3 PUFA) protects against developing asthma, and there is a specic window of opportunity between the age of 6 and 12 months which causes the protection eect of sh against asthma. The study was part of the Generation R Study, a multiethnic prospective birth cohort in Rotterdam.
5.2. INFANT FORMULA REGULATIONS
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5.2
Infant Formula Regulations
For US laws, Regulations, and Guidance please refer to the US FDA/CFSAN Infant Formula Homepage under Program Area: Infant Formula http://www.cfsan.fda.gov/
5.2.1
The new European baby food regulation
[4] [5] The new regulations of the Commission Directive 2006/141/EC amending Directive 1999/21/EC on baby food is focused on the nutritional value of the formula to satisfy the nutritional requirements of the infant. FSA says the rules will help parents and carers to clearly tell the dierence between infant formula, which can be used for the rst six months, and follow-on formula, which is only to be used after six months. It also hopes to make sure labelling and advertising is in line with the principles laid out in the European code, on infant formula and follow-on formula and amending Directive 1999/21/EC. Baby Milk Action say advertisements for formula are putting mothers o breastfeeding, and campaign for a complete ban. Baby Milk Action is a non-prot organisation which aims to save lives and to end the avoidable suering caused by inappropriate infant feeding. [6] A marketing code was introduced in 1981 to regulate the marketing of breastmilk substitutes. Companies continue to violate its provisions. The Infant and Dietetic Foods Association (IDFA) wants to delay by two years the regulation to come into force applying for a judicial review [7]. UK infant and follow-up formula may keep current labels [8] According to a notice of FSA the UK High Court has ruled that manufacturers may continue to produce (and retailers may continue to sell) infant and follow-on formula bearing the current labels until 1 January 2010. After this time, they will have to ensure that products are labelled in accordance with the new labelling rules in the 2007 regulations. The judgement does not aect the rules relating to advertising of infant and follow-on formula, which apply immediately. The implementation of new European legislation on infant and follow-on formula. inCopyright 1998-2010 Karl H. Wilm. All rights reserved. OurFood Database of Food and Related Sciences
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fant and follow-on formula legislation was announced by the Department of Health and the Food Standards Agency in November. It is designed to introduce stricter controls on labelling and advertising of all types of formulae to ensure that breastfeeding is not undermined by the marketing and promotion of such products. Codex Alimentarius: Draft Revised Standard for Infant Formula and Formulas for Special Medical Purposes Intended for Infants [9] [10] [11] The Codex in its ALINORM 05/28/26(2004) - 06/29/26(2005) and 07/30/26 Rev(2006) lays down the standard for the composition of infant formulas. Highlights of this standard are: Denition of infant formula Infant formula means a breast-milk substitute specially manufactured to satisfy, by itself, the nutritional requirements of infants during the rst months of life up to the introduction of appropriate complementary feeding. Infant formula is so processed by physical means only and so packaged as to prevent spoilage and contamination under all normal conditions of handling, storage and distribution in the country where the product is sold. The term infant means a person not more than 12 months of age. Essential Composition Infant formula is a product based on milk of cows or other animals and/or other ingredients which have been proven to be suitable for infant feeding. The nutritional safety and adequacy of infant formula shall be scientically demonstrated to support growth and development of infants. All ingredients and food additives used shall be gluten-free. Essential and semi-essential amino acids in breast milk For an equal energy value the formula must contain an available quantity of each essential and semi-essential amino acid at least equal to that contained in the reference protein (breast-milk as dened in Annex 1. Infant formula prepared ready for consumption in accordance with instructions of the manufacturer shall contain per 100 ml not less than 60 kcal (250 kJ) and not more than 70 kcal (295 kJ) of energy. Isolated amino acids may be added to Infant Formula only to improve its nutritional value for infants. Essential and semi-essential amino acids may be added to improve protein quality, only in amounts necessary for that purpose. Only L-forms of amino acids shall be used. Nutrients of infant formula Nutrients in 100 g/ml are given in table 3.1.3 of the Standard.
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Optional Ingredients In addition to the compositional requirements listed under 3.1, other ingredients may be added in order to provide substances ordinarily found in human milk and to ensure that the formulation is suitable as the sole source of nutrition for the infant. Only L(+) producing lactic acid cultures may be used. Vitamin Compounds and Mineral Salts Vitamins and minerals added should be selected from the Advisory Lists of Mineral Salts and Vitamin Compounds for Use in Foods for Infants and Children (CAC/GL 10-1979). [12] Specic Prohibition The product and its components shall not contain commercially hydrogenated oils and fats and shall not have been treated by ionizing radiation. Food Additives In this standard part 4. the permitted food additives are grouped as thickening agents, emulsiers, pH adjusting Agents, Antioxidants and packaging gas (propellants). Contaminants The standard sets a maximum level of lead of 0.02 mg/kg (in the ready-to-use product) Hygiene The product should comply with the appropriate sections of the following codes: Recommended International Code of Practice - General Principles of Food Hygiene (CAC/RCP 1 1969, Rev. 3 - 1997), [13] Recommended International Code of Hygienic Practice for Foods for Infants and Children (CAC/RCP 21-1979). [14] Principles for the Establishment and Application of Microbiological Criteria for Foods (CAC/GL 21-1997) [15] Fill of Container In the case of products in ready-to-eat form, the ll of container shall be: Not less than 80% v/v for products weighing less than 150 g (5 oz.) Not less than 85% v/v for products in the weight range 150-250 g (5-8 oz.) Not less than 90% v/v for products weighing more than 250 g (8 oz.) Labelling Labelling should comply with Guideline: Codex General Standard for the Labelling of Prepacked Foods (CODEX STAN 11985 (Rev. 1-1991), [16]
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Codex Guidelines on Nutrition Labelling (CAC/GL 2-1985 (Rev.1-1993) [17] Guidelines for Use of Nutrition and Health Claims [18] Labelling should contain:
5.2.2
The Name of the Food
The name of the product shall be either "Infant Formula" or any appropriate designation indicating the true nature of the product, in accordance with national usage. The sources of protein in the product shall be clearly shown on the label. If cows milk is the only source of protein, the product may be labelled "Infant Formula Based on Cows Milk". A product which contains neither milk or any milk derivative shall be labelled "contains no milk or milk products" or an equivalent phrase. Products containing not less than 0.5 mg Iron (Fe)/ 100 kilocalories shall be labelled "Infant Formula with added Iron". Or Products containing less than 0.5 mg Iron (Fe)/ 100 kcal shall be labelled with a statement to the eect that when the product is given to infants over the age of four months, their total iron requirements must be met from other additional sources.
5.2.3
Periconceptional supplementation of micronutritients
Iron supplementation for infants and development of brain [19] Lozo and colleagues 2003 suggest that unsupplemented infants responded less positively to the physical and social environment and blame it to iron deciency on the developing brain. The authors recommend iron supplementation in the rst year of life. Supplementation of vitamin A or iron alone did not improve growth, but multimicronutrient does [20] Usha Ramakrishnan and colleagues 2004 in a meta-analyses of randomized controlled intervention trials assessing the eects of vitamin A, iron, and multimicronutrient interventions on the growth of children under 18 years old found that suplementation of vitamin A or iron alone did not improve child growth. Multimicronutrient, however, improved children growth.
5.2. INFANT FORMULA REGULATIONS Combined iron and zinc supplementation of infants [21]
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Emorn Wasantwisut and colleagues 2006 found in a study that iron supplementation improved hemoglobin, iron status, and ponderal growth, whereas zinc supplementation improved zinc status. The authors concluded that for infants, combined iron and zinc supplementation is preferable to iron or zinc supplementation alone.
5.2.4
Undernutrition during gestation and infancy leads to gene changes linked to disease resistance [22]
A study of Khulan et al. 2012 supports the hypothesis that undernutrition during gestation and infancy predisposes to ill health in later life. The researchers suggest that micronutrient supplementation might be a cause of methylation of foetal genes which control the immune system. Such changes were found by the authors in the DNA of cord blood and in a 9 months after birth. The authors stress that children born in Gambia during the wet season were at higher risk of infections than children born in the dry season. During the wet season less food is available as compared to the dry season. The reduced supply of micronutrients during the wet season may weaken the immune system due to a methylation of genes linked to disease resistance. The link of nutrition and methylation of genes during and after gestation was demonstrated by supplementation of micronutrients of pregnants compared to a group without supplementation. Of micronutrients. The authors suggest that periconceptional nutrition in humans is an important determinant of newborn whole genome methylation patterns but may also inuence postnatal development. Intrauterine exposures mediated by maternal diet may also aect risk of cardiovascular disease, obesity, and type 2 diabetes. Cooper et at 2012 studied the DNA methylation at 12 dierentially methylated regions (DMRs) was analysed in cord blood samples of pre- and periconceptional micronutrient supplementation which included folate, zinc, and vitamins A, B, C, and D. [23]
5.2.5
Prenatal dietary supplementation trials on the impact on risk of diseases such as CVD [24]
Trials investigating the eect of maternal supplementation of protein-energy, multiplemicronutrient and Ca on CVD risk in ospring were assessed by Hawkesworth 2009. Lower systolic blood pressure at 2 years of age in Nepal were reported. However no blood pressure reduction was found in the protein-energy trial in Guatemala trial, where only a reduction of fasting glucose and body composition was reported. No association between supplementation and CVD.
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In The Gambia no association has been found between prenatal protein-energy supplementation and markers of CVD risk including body composition, blood pressure and fasting glucose and insulin in childhood and adolescence. [25] The author concluded that four trials presented little evidence of an eect of maternal Ca supplementation on ospring blood pressure has been demonstrated in four trials, except reduced risk of high systolic blood pressure in one trial.
5.2.6
Bioavailability of zinc gluconate salts compared with zinc from yeasts
Zinc is, after iron, the most important trace elements in the body,being related to a healthy immune system, inuence memory, muscle strength and endurance in adults. According to Thomas Tompkins and colleagues compared the bioavailability of zinc gluconate and zinc from yeasts in two studies presented in 2007. The rst study found zinc yeast to have signicantly less loss in the faeces, accounting for a gain in net zinc balance, while, in comparison, zinc gluconate supplementation resulted in net loss of zinc through the faeces. [26] In the second study Tomkins and colleagues wrote that zinc-enriched yeast was 3.7 times more bioavailable than the zinc gluconate and that copper-enriched yeast was 1.4 times more bioavailable than the Cu gluconate. Lallemand Health Ingredients is waiting for the approval from EFSA for the mineral enriched yeast supplement. [27]
5.2.7
Food choice has little inuence on iron status
[28] Dietary intake was not signicantly correlated with hemoglobin concentrations according to a study by Inger hlund and colleagues. The authors found in this study that the consumption of meat products had a positive eect on serum ferritin concentrations and mean corpuscular volume in boys. In healthy, well-nourished children with a low prevalence of iron deciency, the mothers but not the fathers hemoglobin was signicantly associated with that of her child, but the authors could not explain its reason.
5.2.8
Infant social-emotional behaviour and iron deciency
[29] Lozo and colleagues 2008 assessed the dose-response relationships between severity of iron
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deciency (ID) and infant social-emotional behaviour. The authors found a linear eects of poorer iron status for shyness (increasing, maternal rating), orientation-engagement, and soothability (decreasing, examiner ratings). The authors stress that iron deciency without anemia is not detected by common screening procedures and is more widespread than the other form, and social-emotional behaviour can profoundly inuence the care-giving environment, with repercussions for overall development.
5.2.9
Does iron-fortied formula slow development in children?
[30] Infant formulas are fortied in USA with 12 mg/L of iron to prevent iron-deciency anaemia whereas Europe generally uses a lower amount; in the UK, the limit for iron in cows milk based infant formula is 1.5mg/100 kcal and 2,0 mg/100 kCal. [31] According to Betsy Lozo and colleagues iron-fortied baby formula may pose a developmental risk to children who do not need iron supplementation. The authors found that ten years after receiving formula containing 12 mg/L of iron as infants, children had lower scores across a battery of developmental tests compared with children given formula containing 2.3 mg/L of iron. The authors, however call for more studies on this subject before any change is warranted.
5.2.10
Infant motor development and iron
[32] According to Shar and colleagues 2008 poorer motor function in iron decient infants with and without anemia were found, Whereas non anemic iron deciency were classied by the authors as particularly concerning, since it is not detected by common screening procedures and is more widespread than the anemic form. List of Ingredients A complete list of ingredients shall be declared on the label in descending order of proportion. Declaration of Nutritive Value It should contain: The amount of energy, expressed in kilocalories (kcal) and/or kilojoules (kJ), and the number of grammes of protein, carbohydrate and fat per 100 grammes or per 100 millilitres of the food as sold as well as per 100 millilitres of the food ready for use, when prepared according to the instructions on the label. The total quantity of each vitamin, mineral, choline as listed in paragraph 3.1.2 and any other ingredient as listed in paragraph 3.2 of this Standard per 100 grammes or
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CHAPTER 5. BABY FOOD AND INFANT FORMULAS per 100 millilitres of the food as sold as well as per 100 millilitres of the food ready for use, when prepared according to the instructions on the label.
In addition, the declaration of nutrients in a) and b) per 100 kilocalories (or per 100 kilojoules) is permitted.
5.2.11
Other labelling requirements
The date of minimum durability (preceded by the words "best before") and storage instructions. Information for use. Labels should not discourage breastfeeding. Label should contain the statement "Breastmilk is the best food for your baby" or a similar statement as to the superiority of breastfeeding or breastmilk. Label should contain a statement that the product should only be used on advice of a independent health worker as to the need for its use and the proper method of use. The label shall have no pictures of infants and women nor any other picture or text which idealizes the use of infant formula. The terms "humanized", "maternalized" or other similar terms shall not be used. Information shall appear on the label to the eect that infants should receive supplemental foods in addition to the formula, from an age that is appropriate for their specic growth and development needs, as advised by an independent health worker, and in any case from the age over six months. The products shall be labelled in such a way as to avoid any risk of confusion between infant formula, follow-up formula, and formula for special medical purposes. No nutrition and health claims shall be made regarding the dietary properties of the product. Basic informations of the Codex guidelines for infant formulas The Codex guidelines for infant formulas was based on the recommendations on the compositional requirements for a global infant formula standard from Koletzko et al (2005) from the European Society for Pediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) which had formed an International Expert Group (IEG) collecting data for the guidelines. [33] One important conclusion of the IEG was that infant formulae should only contain components in such amounts that serve a nutritional purpose or provide another benet. The inclusion of unnecessary components, or unnecessary amounts of components, may put a
5.3. STUDIES RELATED TO INFANT FORMULAS burden on metabolic and other physiologic functions of the infant. [33]
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Carlo Agostoni and Magnus Domellf in an editoral in 2005 presented a list of recommended concentrations of nutrients in infant formulae 1977-2005 which helped to ll a data gap. [34] Reduction of severity of diarrhoea with fermented infant formulae [35] Carlo Agostini and colleagues in an analysis found only limited published data on the eects of fermented infant and follow-up formulae. In these products the lactic acid producing bacteria are heat inactivated after the fermentation. Only 2 studies mentioned that some fermented infant formulae may reduce the occurrence or severity of infectious diarrhoea in infants. The authors recommend further studies on the eects of fermented infant formulae on infectious diarrhoea and other relevant outcomes Available data do not allow general conclusion on this matter.
5.2.12
Swedish study recommends reduction of saturated fats in infancy
[36] Inger hlund and colleagues in a study of Swedish infants between 6 and 12 month old, published in 2008, found that total fat intake complied with the Nordic recommendations, but polyunsaturated fatty acids of 5.6% was to low and saturated fatty acids with 15,1% of total energy was too high. The authors found that high polyunsaturated fatty acids intake was associated with lower total serum cholesterol, lower low-density-lipoprotein cholesterol and apolipoprotein B in girls but not in boys. The authors stress that higher polyunsaturated fatty acids and lower saturated fatty acids intakes may reduce total cholesterol and lower low-density-lipoprotein cholesterol LDL-C early in life. The authors recommend to focus on fat quality rather than on quantity to lower serum lipid concentrations in early childhood.
5.3
5.3.1
Studies related to infant formulas

The Euro-Growth Study on infant food
[37] The Euro-Growth Study of milk feeding (Freeman, vant Hof, Haschke 2000) found that at the age of I month, 52% of the infants were exclusively breast fed and 26% were exclusively formula fed. At the age of 9 months, 18% of infants were fed only cows milk.
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At the ages of 3, 4, and 5 months, 50%, 67%, and 95% of infants were fed solid foods, respectively. The study found high rates of breast-feeding initiation are found in Umea, Sweden, and in Athens, Greece; and low rates in Dublin, Ireland, in Toulouse, France, and in Glasgow, United Kingdom. The authors concluded that the use of cows milk as the main milk drink before the age of 12 months is still common in certain European centres.
5.3.2
Leptin in infant formulas to prevent late obesity
[38] Claire C. Stocker and colleagues (2007) report that supplementing infant rats diets with the hormone leptin resulted in adult animals that did not fat or develop diabetes, even when fed a high-fat diet. The researchers concluded that leptin levels during pregnancy and lactation can aect the development of energy balance regulatory systems in their ospring. Stocker points out that the absence of leptin is known to disrupt the development of energy balance regulatory mechanisms. Adding leptin to infant formulas could turn baby foods more similar to the composition of mother milk similar which contains leptin. Breastfeeding may often not be possible because of health situation of the mother or for comodity reasons. Thus well balanced infant formulas replicating the healthy prole of breast milk as far as possible are essential for the st months of life. This article started a discussion on leptin. Leptin in new UK baby food [39] In UK new infant formula with leptin will be lauched in late 2007 with the intention to protect from obesity and diabetes into adulthood. Leptin is present in milk but not in infant formulas. Adding leptin could restore natural composition of baby food.
5.3.3
Leptin
[40] Leptin is a hormone that plays a key role in regulating energy intake and energy expenditure, including the regulation (decrease)of appetite and metabolism.Leptin is produced by adipose tissue and interacts with six types of receptor (LepRa-LepRf). LepRb is the only receptor isoform that contains active intracellular signaling domains. This receptor is present in a number of hypothalamic nuclei, where it exerts its eects. Importantly, leptin binds to the Ventral Medial nucleus of the hypothalamjus, known as the satiety center. Binding of leptin to this nucleus signals to the brain that the body has had enough to eat - a sensation of satiety.
5.3. STUDIES RELATED TO INFANT FORMULAS
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5.3.4
Leptin-sensitizing agents to treat obesity
[41] Leptin is an appetite-suppressing hormone secreted by fat tissue. It was proposed to treat obesity, however, obese persons were found to develop leptin resistance. Umut Ozcan and colleagues 2009 found that elevated leptin secretion increased the stress on a part of the brain, the endoplasmic reticulum, which assembles proteins and folds them into their appropriate congurations. Under stress the endoplasmic reticulum produces unfolded protein in the hypothalamus of obese mice resulting in results in severe leptin resistance and obesity. The stress triggers the production of unfolded proteins, that tries to relieve the stress by increasing the level of molecular "chaperones," which assist in protein folding, and by blocking more proteins from coming in. The authors suggest a new treatment of obesity with chemical chaperones, 4-phenyl butyric acid (PBA), and tauroursodeoxycholic acid (TUDCA), which were found to decrease endoplasmic reticulum stress and act as leptin-sensitizing agents.
5.3.5
Ways to tackle overweight
[42] Absorption of fat molecules Xenical (orlistat), Roches (Basel, Switzerland) drug that blocks the breakdown and absorption of about 30% of dietary fats. Studies on a fatty acid transporter (FATP4) which blocks the uptake of fatty acids which result from the digestion of fat may replace Xenical. Thermogenesis Thyreoid hormones stimulating thermogenesis to burn o excessive caused loss of bone calcium. Increasing the expression of uncoupling proteins (UCPs) to create heat and thus reduce risk of obesity and agonists of the beta3-adrenergic receptor which also targets the energy output, are being studied. Feeling of satiety Peptides produced by the gastrointestinal system and pancreas such as cholecystokinin (CCK), and others include neuromedin B, gastrin-releasing peptide, and enterostatin naturally regulate peripheral feelings of satiety and the amount of food consumed. Centrally acting appetite suppressants in weight-reducing drugs such as Redux (dexfenuramine) and fenuramine in combination with phentermine (acts as a noradrenaline
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reuptake inhibitor) in the fen-phen diet drug were approved by FDA in 1996 and withdrawn in the same year because of link to heart valve damage. [43] Dexfenuramine boosted serotonin levels by stimulating its release and inhibited its reuptake. The American Home Products (AHP) company is being sued for withholding and concealing informations on the safety of the drug. The company still researches on serotonergic control systems, however, it concentrates on mice studies targeting the 5-HT2c subtype of receptor 5-HT. Leptin, a fat-regulating hormone Jerey Friedman and his team (2002) discovered the "ob" gene, which underlies the gross obesity in the ob/ob strain of mice. Injecting leptin back into the ob/ob mice appetites were reduced and the excess weight was lost. [44] Je Flier, an obesity researcher at Harvards Beth Israel Deaconess stressed the fact that high levels of endogenous leptin in obese people had been found, suggesting that sensitivity to leptin is lost and cannot be restored by further elevation of the compound. The company Amgen is still working on new formulations on the product. It has been used successfully to treat a handful of severely obese children who have an inherited deciency in the hormone. Researchers now suspect that obese people appear to be resistant to leptin because the hormone is not transported into the brain. Leptin is produced by fat cells, circulating in the blood to the hypothalamus where it works through a number of nuclei and pathways to reset the bodys weight controller. As fat levels increase, leptin levels rise, triggering a reduction of food intake and increasing metabolism. Leptin inhibits the release of neuropeptide Y (NPY), a small protein that increases appetite. Leptin eects Leptin is related to the alfa-melanocyte-stimulating hormone (alfa-MSH), which is actually a fragment of the precursor protein POMC.alfa-MSH acts through the MCR-4 receptor to reduce appetite. Leptin increases the production of the SOCS-3 (suppressor of cytokine signaling-3) protein, which terminates its activity at the leptin receptor. The SOCS-3 a regulator of the leptin signaling pathways in healthy individuals, it is overactive in obese patients. Researchers of Johns Hopkins University discovered that malonyl coenzyme A inhibits NPY independently of leptin, decreasing appetite in mice and might lead to eight loss in humans.
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Ciliary neurotrophic factor (CNTF) George Yancopoulos of Regeneron tested Axokine (ciliary neurotrophic factor, CNTF) as a treatment of a disease noted that the drug used the same signaling pathway as leptin with the eect of weight reduction. There are hope that the drug has better eects compared with leptin, but it must be injected, because it is not stable by oral intake. Fatty acid synthase inhibitors (cerulenin and compound C75) [45] Francis P. Kuhajda and colleagues (2000) identied a link between anabolic energy metabolism and appetite control. According to the authors treating mice with fatty acid synthase (FAS) inhibitors (cerulenin and a synthetic compound C75) inhibited feeding and caused a dramatic weight loss. C75 inhibited expression of the prophagic signal neuropeptide Y in the hypothalamus and acted in a leptin-independent manner that appears to be mediated by malonyl-coenzyme A. They conclude that FAS may become important in feeding regulation. Fatty acid synthase (FAS) and carnitine palmitoyltransferase-1 [46] Gabriele V. Ronnett and colleaugues (2006) say that fatty acid synthase (FAS) catalyzes the synthesis of long-chain fatty acids, whereas the breakdown of fatty acids by betaoxidation is regulated by carnitine palmitoyltransferase-1, the rate-limiting enzyme for the entry of fatty acids into the mitochondria for oxidation. Studies indicate that inhibition of FAS or stimulation of carnitine palmitoyltransferase1 using cerulenin or synthetic FAS inhibitors reduces food intake with resulting weight loss. compounds also increase energy consumption. The authors say that at least part of C75s eects is mediated by modulation of adenosine monophosphate-activated protein kinase, a member of an energy-sensing kinase family, and conclude that these eects could be useful in obesity therapy. Leptin and melanocortin activity on the hypothalamus [47] Shimizu and colleagues (2007) note that the brain hypothalamus coordinates extra-hypothalamic regions to maintain energy homeostasis through the regulation of food intake and energy expenditure. According to these authors leptin and pro-opiomelanocortin (POMC)-derived alfa-melanocyte-stimulating hormone are key anorectic molecules, and the leptin receptor and POMC gene are both expressed in the hypothalamic arcuate nucleus. Data support the concept of a leptin-independent melanocortin signaling system in the regulation of energy homeostasis. The position of the charity Weight Concern [48] According to Dr. Ian Campbell, medical director of the charity Weight Concern leptin has proved to be a great disappointment, and most of us have plenty and true deciencies are rare. Obese people tend to have higher than normal levels.
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5.3.6
Hydrolysed protein infant formulas
Short- and long-term eects of feeding hydrolysed protein infant formulas [49] Rzehak and colleagues 2009 analysed dierences of body mass index (BMI) of infants fed with partially hydrolysed whey (pHF-W), extensively hydrolysed whey (eHF-W), extensively hydrolysed casein (eHF-C), or cow-milk formula (CMF) and infants exclusively breastfed. The authors report no dierences in BMI in all groups, except the extensively hydrolysed casein (eHF-C) group,which presented a lower weight gain in the rst year of life, but not later with no long-term consequences of dierent formulas on BMI. Protein hydrolysate formulas, feeding behaviour and growth of infants [50] Mennella and colleagues 2011 assessed dierences in feeding behaviour and growth of infants of ages 0.5 to 7.5 months, fed with an extensively protein hydrolysate formula compared with infants fed with cow-milk formula. Anthropometric Z-scores were calculated using the World Health Organization growth standards. [51] Infants fed with protein hydrolysate formula presented lower weight-for-length z scores, slower weight gain velocity, and consumed less formula to satiation than infants fed with cow-milk formula. The authors call for more studies on longer-term eects of hydrolysed protein diets focusing on later development of obesity, diabetes, other diseases, long-term consequences of the early growth dierences associated with infant formulas, and how it diers from breastfeeding. Soybased infant formulas could reduce severity of diarrhea in infants [52] Acccording to Andres and colleagues 2007, rotavirus infections cause acute gastroenteritis in children and are responsible forve percent of all child deaths globally. Infection aects almost all children within their rst 5 years of life. Soy-based infant formula, containing high levels of isoavones were found to have antiviral activity on numerous viruses. The authors found that genistin was responsible for the inhibition of rotavirus activity of the isoavones from soy. The authors suggest that the modulation of isoavone composition and concentration of infant formulas may reduce the severity of rotavirus infection in human and production animals.
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Infant formula made from soy protein is no substitute for cows milk products [53] Soya formula for infants should only be administered on doctors advice According to the German Federal Institute for Risk assessment (BfA) If a mother is unable to breastfeed her baby, she can fall back on infant formula from the drug store or supermarket. However, soybeans contain high concentrations of isoavones genistein and daidzein. Besides isoavones, soy formula may also contain phytate. The natural plant component can inuence the intake of minerals and trace elements. Furthermore, soybeans may also contain higher amounts of the plant component, phytate. Professor Dr. Dr. Andreas Hensel, President of the Federal Institute for Risk Assessment (BfR), comments, "Infant formula and follow-up formula made from soy protein should only be administered on medical grounds and then only under medical supervision." The Health Committee of New Zealand recommends that the current mandatory label on soy-based infant formula should be amended to read: "Breastmilk is best for babies. Soy-based formulas have a high phytoestrogen content, which may pose a risk for the longterm reproductive health of infants. Before you decide to use this product, consult your doctor or nurse for advice." [54]
5.3.7
Infant botulism
[55] Botulism in infants 6 weeks to 1 year of age was rst recognized as a distinct clinical entity in 1976. This form of botulism results from growth and toxin production by C. botulinum within the intestinal tract of infants rather than from ingestion of a food with preformed toxin. It is usually caused by C. botulinum types A or B, but a few cases have been caused by other types.botulism has been diagnosed in most U.S. states and in every populated continent except Africa. Honey, a known source of C. botulinum spores, has been implicated in some cases of infant botulism. In studies of honey, up to 13% of the test samples contained low numbers of C. botulinum spores.Heat treatment is not sucient to destroy C. botulinum spores, but the high sugar content of the honey prevents the spores from germinating. Normal adults are not at risk of botulism from eating honey; however, the gastrointestinal tracts of young infants (under one year of age) may promote spore germination. For this reason, the FDA, the Centers for Disease Control and Prevention (CDC), and the American Academy of Pediatrics recommend not feeding honey to infants under one year old.
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5.3.8
German BFR concerned about 3-MCPD in rened oil and derived products
[56] According to the Federal Institute for Risk Assessment (BfR) the substance 3-monochloropropane1,2-diol (3-MCPD) may be formed when fat-containing foods that also contain salt are exposed to high temperatures during production. It has been detected in numerous heated foods, for instance in dark brown toast, infant formula and follow-up formula. During the production of fats and oils, 3-MCPD fatty acid esters may be formed from 3-monochloropropane-1,2-diol when the fats and oils are heated to high temperatures. The BfR recommends that concerted action be taken to lower the levels of 3-MCPD esters in infant formula and follow-up formula, contain varying amounts of dried powder and water. The Institute recommends that mothers who are unable to breastfeed their infants and give them infant formula should continue to do so. Infants who are not breastfed there is no alternative to formula and follow-up formula. Mothers should not switch to cow, goat or horse milk either as they do not contain some of the essential nutrients that infants need. Detected levels of 3-MCPD fatty acid esters The BfR found that the amounts of 3-MCPD fatty acid esters detected in edible oils and fats were in the four to ve digit microgram range. The highest level of 11,206 micrograms per kilogram (microg/kg) was found in deep-frying fat. In the infant formula and follow-up formula examined the highest level identied was 4,196 microg/kg in the fat content. For this food it amounts to around 25 percent of the dried powder. The BfR stresses that it is unknown whether 3-MCPD fatty acid esters have the same toxic properties as free 3-MCPD. No data are available but it cannot be ruled out that free 3-MCPD is formed from most of the fatty acid esters during digestion. According to the BfR men who consume 100 g of vegetable margarine with the highest detected level of 3-MCPD fatty acid esters daily would exceed the TDI ve-fold, assuming that 3-MCPD fatty acid esters are fully converted into free 3-MCPD. Following tis assumption, intakes of formula and follow-up formula, infants would exceed the TDI three to twenty-fold. Risk for infants and consumers According to the BFR there are many uncertanties of a risk assessment. However, assuming that toxicological eects of 3-MCPD on animals can be translated to humans or that there is large scale conversion of 3-MCPD fatty acid esters into 3-monochloropropane-1,2diol, then the expected long-term exceeding of the TDI is not acceptable in the opinion of BfR particularly as children and adults ingest 3-MCPD from other sources, too. Any short-term exceeding of the TDI value would, by contrast, not present a safety concern.
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Bibliography
[1] http://www.bfr.bund.de/cd/1463. BFR: Infant Nutrition. [2] http://www.eatwell.gov.uk/agesandstages/baby/weaning/. FSA: Eat well, be well: Weaning your baby. [3] Kiefte de Jong JC, de Vries JH, Franco OH, Jaddoe VWV, Hofman A, Raat H, de Jongste JC, and Moll HA. Fish consumption in infancy and asthma-like symptoms at preschool age. peds, 0875, 2012. http://pediatrics.aappublications.org/ citmgr?gca=pediatrics;peds.2012-0875v1. [4] http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=OJ:L:1999:091: 0029:0036:EN:PDF. COMMISSION DIRECTIVE 1999/21/EC of 25 March 1999 on dietary foods for special medical purposes. [5] http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=OJ:L:2006:401: 0001:0033:EN:PDF. European infant formula and follow-on formula Regulation Commission Directive 2006/141/EC of 22 December 2006 on infant formulae and follow-on formulae and amending Directive 1999/21/EC Text with EEA relevance. [6] http://www.babymilkaction.org/press/press10aug07.html. Baby Milk Action: New UK formula labels lack correct information - calls for better warnings and instructions. [7] http://www.idfa.org.uk/publications/IDFA_position_statement.pdf. IDFA Newsroom: IDFAs action to protect the continued supply of baby milk formula. [8] http://www.food.gov.uk/news/newsarchive/2008/feb/infantjr. dards Agency: Judicial review of infant formula regulations. Food Stan-
[9] http://www.codexalimentarius.net/download/report/627/al28_26e.pdf. The 26. Session of the Codex Committee on Nutrition and Foods for Special Dietary Uses. ALINORM 05/28/26. [10] http://www.codexalimentarius.net/download/report/646/al29_26e.pdf. The 27.Session of the Codex Committee on Nutrition and Foods for Special Dietary Uses. 21 - 25 November 2005 ALINORM 06/29/26. [11] http://www.codexalimentarius.net/download/report/669/al30_26e.pdf. The 28.Session of the Codex Committee on Nutrition and Foods for Special Dietary Uses. 30 October - 3 November 2006. ALINORM 07/30/26-Rev. [12] http://www.codexalimentarius.net/download/standards/300/CXG_010e.pdf. Advisory Lists of Mineral Salts and Vitamin Compounds for Use in Foods for Infants and Children (CAC/GL 10-1979.
388
[13] http://www.codexalimentarius.net/download/standards/23/cxp_001e.pdf. Recommended International Code of Practice - General Principles of Food Hygiene (CAC/RCP 1 1969, Rev. 3 - 1997). [14] http://www.codexalimentarius.net/download/standards/297/CXP_021e.pdf. Recommended International Code of Hygienic Practice for Foods for Infants and Children (CAC/RCP 21-1979). [15] http://www.codexalimentarius.net/download/standards/394/CXG_021e.pdf. Principles for the Establishment and Application of Microbiological Criteria for Foods (CAC/GL 21-1997). [16] http://www.codexalimentarius.net/download/standards/292/CXS_146e.pdf. Codex General Standard for the Labelling of Prepackaged Foods (CODEX STAN 1-1985 (Rev. 1-1991). [17] http://www.codexalimentarius.net/download/standards/34/CXG_002e.pdf. Codex Guidelines on Nutrition Labelling (CAC/GL 2-1985 (Rev.1-1993). [18] http://www.codexalimentarius.net/download/standards/351/CXG_023e.pdf. Guidelines for Use of Nutrition and Health Claims. [19] http://pediatrics.aappublications.org/cgi/content/abstract/112/4/846. Lozo, Betsy; De Andraca, Isidora; Castillo, Marcela; Smith, Julia B.; Walter, Tomas; Pino, Paulina: Behavioral and Developmental Eects of Preventing Iron-Deciency Anemia in Healthy Full-Term Infants. Pediatrics Vol. 112 No. 4 October 2003, pp. 846-854. [20] http://jn.nutrition.org/cgi/content/abstract/136/9/2427. Olney, Deanna K.; Pollitt, Ernesto; Kariger, Patricia K.; Khalfan, Sabra S.; Ali, Nadra S.; Tielsch, James M.; Sazawal, Sunil; Black, Robert; Allen, Lindsay H.; Stoltzfus, Rebecca J.: Combined Iron and Folic Acid Supplementation with or without Zinc Reduces Time to Walking Unassisted among Zanzibari Infants 5- to 11-mo old. J. Nutr., September 1, 2006; 136(9): 2427 - 2434. [21] http://jn.nutrition.org/cgi/content/abstract/136/9/2405. Wasantwisut, Emorn; Winichagoon, Pattanee; Chitchumroonchokchai, Chureeporn; Yamborisut, Uruwan; Boonpraderm, Atitada; Pongcharoen, Tippawan; Sranacharoenpong, Kitti; Russameesopaphorn, Wanphen: Iron and Zinc Supplementation Improved Iron and Zinc Status, but Not Physical Growth, of Apparently Healthy, Breast-Fed Infants in Rural Communities of Northeast Thailand J. Nutr., September 1, 2006; 136(9): 2405 - 2411. [22] Khulan B, Cooper WN, Skinner BM, Bauer J, Owens S, Prentice AM, Belteki G, Consta ncia M, Dunger D, and Aara NA. Periconceptional maternal micronutrient supplementation is associated with widespread gender related changes in the
BIBLIOGRAPHY
389
epigenome: a study of a unique resource in the gambia. Hum Mol Genet, 2 2012. http://www.ncbi.nlm.nih.gov/pubmed/22307237. [23] Cooper WN, Khulan B, Owens S, Elks CE, Seidel V, Prentice AM, Belteki G, Ong KK, Aara NA, Consta ncia M, and Dunger DB. Dna methylation proling at imprinted loci after periconceptional micronutrient supplementation in humans: results of a pilot randomized controlled trial. FASEB J, 1 2012. http://www.ncbi.nlm.nih. gov/pubmed/22267336. [24] Hawkesworth S. Conference on "multidisciplinary approaches to nutritional problems". postgraduate symposium. exploiting dietary supplementation trials to assess the impact of the prenatal environment on cvd risk. Proc Nutr Soc, 68(1):7888, 2 2009. http://www.ncbi.nlm.nih.gov/pubmed/19012806. [25] Hawkesworth S, Walker CG, Sawo Y, Fulford AJ, Jarjou LM, Goldberg GR, Prentice A, Prentice AM, and Moore SE. Nutritional supplementation during pregnancy and ospring cardiovascular disease risk in the gambia. Am J Clin Nutr, 94, 12 2011. [26] http://www.ncbi.nlm.nih.gov/pubmed/17873352. Tompkins, Thomas A.; Renard, Nadine E.; Kiuchi, Akira: Clinical Evaluation of the Bioavailability of Zinc-enriched Yeast and Zinc Gluconate in Healthy Volunteers. Biological Trace Element Researche , Humana Press, (Humana Press). Volume 120, Numbers 1-3 / December 2007 pp 28-35 (8)doi: 10.1007/s12011-007-0072-2. [27] http://www.springerlink.com/content/n138537440760645/. Vinson, Joe A.; Tompkins, Thomas A. Agbor, Gabriel A.: Comparative Bioavailability of Mineralenriched Gluconates and Yeast in Rat Liver After Depletion-Repletion Feeding. Biological Trace Element Researche , Humana Press. Volume 118, Number 2 / September, 2007 104-110 (7). [28] http://www.ajcn.org/cgi/content/abstract/87/4/839. hlund, Inger; Lind, Torbjrn; Hrnell, Agneta; Hernell, Olle: Predictors of iron status in well-nourished 4y-old children. American Journal of Clinical Nutrition, Vol. 87, No. 4, 839-845, April 2008. [29] http://www.ncbi.nlm.nih.gov/pubmed/18410777? Lozo, B.; Clark, K.M.; Jing, Y.; Armony-Sivan R.; Angelilli, M.L.; Jacobson, S.W.: Dose-response relationships between iron deciency with or without anemia and infant social-emotional behavior. 2008 May;152(5):696-702, 702.31-3. Epub 2007 Nov 19. [30] http://www.medpagetoday.com/MeetingCoverage/PAS/tb/9334. Lozo, Betsy; Castillo, Marcela; Smith, Julia B.: Poorer developmental outcome at 10 years with 12 mg/L iron-fortied formula in infancy PAS Meeting 2008; Abstract 5340.2.
390
[31] http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=CONSLEG: 1991L0321:19960319:EN:PDF. EU Commission: Commission Directive of 14 May 1991 on infant formulae and follow-on formulae (91/321/EEC). [32] http://www.ncbi.nlm.nih.gov/pubmed/18272298? Shar T.; Angulo-Barroso, R.; Jing Y.; Angelilli, M.L.; Jacobson, S.W.; Lozo, B.: Iron deciency and infant motor development. Early Hum Dev, 2008 Feb 11. [33] http://jpgn.org/pt/re/jpgn/pdfhandler.00005176-200511000-00006.pdf. Koletzko, Berthold; Baker, Susan; Cleghorn, Geo; Fagundes Neto, Ulysses; Gopalan, Sarath; Hernell, Olle; Hock, Quak Seng; Jirapinyo, Pipop; Lonnerdal, Bo;Pencharz, Paul; Pzyrembel, Hildegard; Ramirez-Mayans, Jaime; Shamir, Raanan; Turck, Dominique; Yamashiro, Yuichiro and Zong-Yi, Ding: Global Standard for the Composition of Infant Formula: Recommendations of an ESPGHAN Coordinated International Expert Group. J Pediatr Gastroenterol Nutr 2005; 41: 58-599. [34] http://jpgn.org/pt/re/jpgn/pdfhandler.00005176-200511000-00005.pdf. Domellf, Magnus; Agostoni, Carlo: Infant Formulae: From ESPGAN Recommendations Towards ESPGHAN-coordinated Global Standards. Journal of Pediatric Gastroenterology and Nutrition 41:580-583 November 2005. [35] http://www.jpgn.org/pt/re/jpgn/abstract.00005176-200703000-00022.htm. Agostoni,Carlo, Goulet, Olivier; Kolacek, Sanja; Koletzko, Berthold; Moreno, Luis; Puntis, John; Rigo, Jacques; Shamir, Raanan; Szajewska, Hania; Turck, Dominique; ESPGHAN Committee on Nutrition: Fermented Infant Formulae Without Live Bacteria. J Peditr Gastroenterol Nutr March 2007, 44(3) 392-397. [36] http://www.nature.com/ejcn/journal/v62/n9/abs/1602824a.html. hlund, I.; Hrnell, A.; Lind, T.; Hernell, O.: Dietary fat in infancy should be more focused on quality than on quantity: European Journal of Clinical Nutrition (2008) 62, 10581064; doi:10.1038/sj.ejcn.1602824. [37] http://www.ncbi.nlm.nih.gov/pubmed/10896092. Freeman, V.; vant Hof, M.; Haschke, F.: Patterns of milk and food intake in infants from birth to age 36 months: the Euro-growth study. J Pediatr Gastroenterol Nutr. 2000; 31 Suppl 1:S76-85. [38] http://ajpregu.physiology.org/cgi/content/abstract/292/5/R1810. Stocker, Claire J.; Wargent, Ed; ODowd, Jackeline; Cornick,Claire; Speakman, John R.; Arch, Jonathan R.S.; Cawthorne, Michael A.: Prevention of diet-induced obesity and impaired glucose tolerance in rats following administration of leptin to their mothers. American Journal of Physiology - Regulatory, Integrative and Comparative Physiology doi: 10.1152/ajpregu.00676.2006. [39] http://www.soci.org/SCI/general/2007/html/ge610.jsp. The Society of Chemical Industry. New formula for t future. Baby food oering lifetime protection against
BIBLIOGRAPHY
391
obesity could be in the supermarket soon, Lisa Melton. Chemistry & Industry magazine. [40] http://en.wikipedia.org/wiki/Leptin. Wikipedia: Leptin. [41] http://www.cell.com/cell-metabolism/abstract/S1550-4131(08)00389-6. Lale Ozcan, Ayse Seda Ergin, Allen Lu, Jason Chung, Sumit Sarkar, Duyu Nie, Martin G. Myers, Umut Ozcan: Endoplasmic Reticulum Stress Plays a Central Role in Development of Leptin Resistance. Cell Metabolism, Volume 9, Issue 1, 35-51, 7 January 2009. [42] http://www.nature.com/nbt/journal/v19/n1/full/nbt0101_25.html. Alan Dove: Biotech weighs up the options in obesity.Nature Biotechnology 19, 25 - 28 (2001) doi:10.1038/83465. [43] http://www.fda.gov/cder/news/mmwr.pdf. CDC: Cardiac Valvulopathy Associated with Exposure to Fenuramine or Dexfenuramine: U.S. Department of Health and Human Services Interim Public Health Recommendations, November 1997. November 14, 1997 / Vol. 46 / No. 45. [44] Zhang,Yiying; Proenca, Ricardo; Maei, Margherita; Barone, Marisa; Leopold, Lori and. Friedman, Jerey M.: Positional cloning of the mouse obese gene and its human homologue. Nature 372, 425 - 432 (01 December 2002); doi:10.1038/372425a0. [45] http://www.sciencemag.org/cgi/content/abstract/288/5475/2379. Loftus, Thomas M.; Joworski, Donna M.; Frehywot Gojeb L; Townsend, Craig A.; Ronnett, Gabriele V.; Lane, Daniel M.; Kuhajda, Francis P.: Reduced Food Intake and Body Weight in Mice Treated with Fatty Acid Synthase Inhibitors. Science 30 June 2000: Vol. 288. no. 5475, pp. 2379 - 2381 DOI: 10.1126/science.288.5475.2379. [46] http://www.obesityresearch.org/cgi/content/abstract/14/5/201S. Ronnett, Gabriele V.; Kleman, Amy M. ; Kim, Eun-Kyoung; Landree Leslie E. and Tu, Yajun: Fatty Acid Metabolism, the Central Nervous System, and Feeding. Obesity 14:201S -207S (2006). [47] http://joe.endocrinology-journals.org/cgi/content/abstract/193/1/1. Shimizu, Hiroyuki; Inoue, Kinji and Mori, Masatomo: The leptin-dependent and -independent melanocortin signaling system: regulation of feeding and energy expenditure. J. Endocrinol.2007 193, 1-9 DOI: 10.1677/JOE-06-0144. [48] http://news.bbc.co.uk/1/hi/health/6575767.stm. BBC News: Fat-ghting baby milk criticised. Sunday, 22 April 2007, 23:11 GMT 00:11 UK. [49] Rzehak P, Sausenthaler S, Koletzko S, Reinhardt D, von Berg A, Krmer U, Berdel D, Bollrath C, Grbl A, Bauer CP, Wichmann HE, Heinrich J, and German Infant
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CHAPTER 5. BABY FOOD AND INFANT FORMULAS Nutritional Intervention Study Group:. Short- and long-term eects of feeding hydrolysed protein infant formulas on growth at < or = 6 y of age. results from the german infant nutritional intervention study. Am J Clin Nutr., 89:184656, 6 2009. http://www.ajcn.org/content/89/6/1846.long.
[50] Mennella JA, Ventura AK, and Beauchamp GK. Dierential growth patterns among healthy infants fed protein hydrolysate or cow-milk formulas. Pediatrics, 127:1108, 1 2011. http://www.ncbi.nlm.nih.gov/pubmed/21187303. [51] WHO. The who child growth standards. standards/en/. http://www.who.int/childgrowth/
[52] http://jn.nutrition.org/cgi/content/abstract/137/9/2068. Andres, Aline; Donovan, Sharon M.; Kuhlenschmidt, Theresa B.; Kuhlenschmidt, Mark S.: Isoavones at Concentrations Present in Soy Infant Formula Inhibit Rotavirus Infection in Vitro J. Nutr. 2007 137: 2068-2073. [53] http://www.bfr.bund.de/cd/10333. BfR: Infant formula made from soy protein is no substitute for cows milk products. 19.11.2007. [54] http://www.soyonlineservice.co.nz/downloads/NZHC_Petition_Report.pdf. Report of the New Zealand House of Representatives Health Committee on Petition 2005/123 of Valerie Ann James and 214 others. Heard on 17 October 2007. [55] http://www.cfsan.fda.gov. FDA : Clostridium botulinum. Bacteriological Analytical Manual Online. Chapter 17. [56] http://www.bfr.bund.de/cd/10581. BFR: Frequently Asked Questions about 3monochloropropane-1,2-diol (3-MCPD).
Chapter 6 Functional Foods and Novel Foods

6.0.9 6.0.10 Novel Food, Nutraceuticals,Functional Foods, Fast Food, Snacks, Finger Food Novel Foods
are foods which can be assigned to special types of foods such as genetic modied foods,genetic modied organism and their products, new molecular structures or new technological procedures.Foods which are regulated by the Novel Food Regulation of the European Community have to pass a complicated license procedure.
6.0.11
Functional foods
are foods which have a positive action upon the health of the consumer. The origin of functional food lies im Japan. Increasing sales of probiotic yoghurt and dairies have boosted the hope of massive prots with functional foods health ingredients, isoavones, Aloe vera, probiotic bacteria and dietary bre. It is called " up trading " of the product. Up trading is the rise of quality to achieve better prices.
6.0.12
Functional Food, Nutrition, Nutriceuticals
All these words are used by marketing to boost selling. It is true that bre can be useful to reduce blood cholesterol or calcium can help to reduce the risk of osteoporosis and vitamins can strengthen the immune system. The truth is that it does not work. The consumer is taken to believe that everything is all right when he takes a calcium enriched drink, sometimes with 4 or 5 added synthetic vitamins.
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CHAPTER 6. FUNCTIONAL FOODS AND NOVEL FOODS
These foods cannot substitute natural nutrition rich in vegetables, fruits and fat reduced meals and whole-meal bread which was the nutrition at the beginning of the 20 th century. The German Nutrition Society (DGE) says that for an average population there is no need of supplements, functional foods or whatsoever when enough vegetables, fruits, sh and whole-meal bread are eaten and low fat nutrition is observed. Publicity around one-sided modied foods give the consumer a wrong feeling of safety. He things that " he nally can feel well all round " drinking some special stu of functional drinks which now come on market and does not need to get classic foods which bear all these ingredients together with thousands of other components. Jos Lutzenberger a Brazilian Nobel-Price bearer and Franz-Theo Gottwald in their book Ernhrung in der Wissensgesellschaft, CAMPUS EXPO 2000 Hannover in their vision about world nutrition say that the global distribution of food and growing modication of food by mighty companies destroy the natural resources of the world. Many products which are on market and claim to be functional food have only calcium added claiming for health. The supply of Calcium can easily achieved drinking milk or eating yoghurt. Hannu Salovaara, professor of grain technology at the University of Helsinki says:"It is not new knowledge that foods may also have a healthy activity. In the discussion about Functional Food does one sells only old wine in new tubes?".
6.0.13
Marine omega-3 phospholipids are best for the brain, says study [1]
Omega-3 fatty acids occur as triglycerids, as diglyceride with a phosphate group (phospholipids) or as sphingomyelin, which is derived from sphingosine instead of glycerol. Most phospholipids contain a diglyceride, a phosphate group, and a simple organic molecule such as choline; one exception to this rule is sphingomyelin, which is derived from sphingosine instead of glycerol. A review by Berge et al. 2012 explains that marine omega-3 phospholipids (n-3 PLs) are phospholipids containing n-3 long-chain polyunsaturated fatty acids (PUFAs) derived from marine organisms. They dier from vegetable phospholipids which do not contain long-chain n-3 PUFAs. Clinical studies were mainly focused on n-3 FAs bound to triglyceridess or ethyl esters. Only recently, health benets of marine n-3 phospholipids were studied. There are three main classes of phospholipids: glycerophospholipids (Fatty acids esterbound to backbone), ether glycerolipids and sphingophospholipids. Glycerophospholipids are the most common subgroup. The most predominant phospholipids in marine sources such as salmon, tuna, rainbow trout and mackerel, is phosphatidylcholine, whereas phosOurFood Database of Food and Related Sciences Copyright 1998-2010 Karl H. Wilm. All rights reserved.
395 phatidylethanolamine is shown to be the second most abundant. Phosphatidylinositol, phosphatidylserine, lysophosphatidylcholine, and sphingomyelin are found in smaller amounts. Marine omega-3 phospholipids (n-3 Pls) have nutritional properties with an amazing bioavailiability compared to other forms of omega-3 fatty acids (n-3 FAs). The paper notes that n-3 fatty acids were mainly studied as triglycerides (TGs) or omega-3 ethyl esters, and little attention was given to omega-3 phospholipids (Pls). Berge and colleagues stress the increasing availability of omega n-3 phospholipids which come from sources like krill and sh by-products. Krill oil is extracted from the Antarctic crustacean krill (Euphausia superba), a shrimp-like zooplankton, rich in phospholipid-bound n-3 PUFAs, in particular EPA and DHA. One by-product of the sh industry is sh roe, eggs and the ovaries full of eggs of seafood. The authors underline that the n-3 phospholipids of sh oil are delivered to brain tissues more eciently than fatty acids in the triglyceride form. Krill oil has healing eects in case of fatty liver and reduces plasma cholesterol levels and reduces inammation and arthritis symptoms. The review suggests the use of that marine n-3 phospholipids as functional food used as emulsiers, as n-3 fatty acids supplement and as benecial nutritional supplements of phospholipids with their eects. Bioavailiability of omega-3 fatty acids from krill oil [2] Bioavailability of omega-3 fatty acids depends on their chemical form. Superior bioavailability was found by Schuchardt et al. 2011 for phospholipid bound omega-3 FA in krill oil. The authors compared the bioavailability of krill oil with the uptake of two sh oils: Re-esteried triacylglycerides (rTAG), and ethyl-esters (EE). The highest incorporation of EPA+DHA into plasma phospholipids was presented by krill oil with 80%, compared to sh oil rTAG 60% and EE 48%. Also a high content of free EPA and DHA in krill oil was found. which might have a signicant inuence on the availability of EPA+DHA from krill oil, as no free EPA and DHA were determined in the other two sh oils. This may have an inuence on the excellent bioavailability of krill oil. No dierences between Krill oil and sh oil regarding eects on metabolic markers and inammation [3] Ulven et al. 2011 compared the eect of krill oil and sh oil on serum lipids and markers of oxidative stress and inammation. Both oils increased signicantly plasma EPA, DHA, and DPA content, but no signicant dierences in changes in any of the serum lipids or the markers of oxidative stress and inammation between the group supplemented with krill oil and the group receiving sh oil were found. The authors concluded that both oils were comparable as a dietary sources of n-3 PUFAs, even with a lower content of EPA+DHA in krill oil which was only 68,2% of that in sh oil.
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6.0.14
The evolution of the nal target of nutrition
The nal target of nutrition moved between survival, through hunger satisfaction, food safety with deep concern of the consumer and recently a new wave of foods to promote health and healthy living.New concepts like Functional Food,Nutraceuticals , Fortied Foods, Dietary Supplements are created by the industry trying to open new market segments[4]. This has created a great confusion among the consumer resulting in runs after melatonin, abuse of vitamins and sometimes a loss of condence to retailed foods. Functional Food is not yet well dened. It is intended to close the gap between food and drugs. Scientic evidence supports the hypothesis that, by modulating specic target functions in the body, diet can have benecial physiological and psychological eects that go beyond the widely accepted nutritional eects. Nutritive and nonnutrition components in food have the potential to modulate target functions in the body which are relevant to well-being and health and/or reduction of disease risk [4].
6.0.15
Regulation of functional food
Functional food is not yet regulated by food legislations.The idea behind Functional Food is to make food suited to avoid undernourishment with some special ingredients or to prevent against diseases such as cancer or heart attack. The main concern of industry and retailers is to nd new ways to increase their turnovers. This is why functional food is being on number one in sales promotions. It should always be kept in mind that normal nutrition is the best guarantee for health. Eat more fruits and vegetables and you get enough bres and plant sterols. Eat more dairy products and you have no trouble with undersupply of calcium, eat sh and less beef and you get enough iodine. Functional foods addresses always certain groups of persons which have specic problems as they cover only one or best of all few specic dietary needs. They cannot substitute natural healthy foods.
6.0.16
Denition of functional food
Functional food is currently dened as food of the normal daily intake enriched with substances or organism which have health supporting activity.
397 They do not help in case of acute diseases, they act on long terms against health risks such coronary diseases or cancer. Sometimes it is unknown at what dose the protective activity takes place, and sometimes the concentration of the active substance in food is not known[5]
6.0.17
Scientic requirements for health claims related to antioxidants, oxidative damage and cardiovascular health [6]
The Panel on Dietetic Products, Nutrition and Allergies (NDA) of the European Food Safety Authority (EFSA) published a draft guidance on scientic requirements for health claims related to antioxidants, oxidative damage and cardiovascular health. The guidance cites the type of evidence for a health claim. The panel takes position to several claims such as: Benecial physiological eects: Reference to general, non-specic benets of the nutrient or food for overall good health or health-related well-being may only be made if accompanied by a specic health claim. Claims on antioxidant properties of food: These claims are based on the scavenging of free radicals in vitro, however, the physiological eect in humans is not established yet. Claims on antioxidant status and antioxidant defence: Claims referring to antioxidant status and antioxidant defence have been proposed. The references provided for the scientic substantiation of these claims included in vivo human studies which assessed changes in the overall antioxidant capacity of plasma using methods such as the total reactive antioxidant potential (TRAP), the trolox-equivalent antioxidant capacity (TEAC), the ferric reducing antioxidant potential (FRAP), the oxygen radical absorbance capacity (ORAC) or the ferrous oxidation-xylenol orange (FOX) assays. It is not established that changes in the overall antioxidant capacity of plasma exert a benecial physiological eect in humans as required by Regulation (EC) No 1924/2006. Claims on the protection of cells from premature ageing: For these claims, no denition has been provided of "premature aging" or of "healthy aging" in relation to the antioxidant properties of foods, and therefore the claimed eect is considered to be general and non-specic, and thus does not comply with the criteria laid down in Regulation (EC) No 1924/2006. Oxidative damage, including photo-oxidative (UV-induced) damage Claims on the protection of body cells and molecules (i.e. DNA, proteins and lipids) from oxidative damage, including photo-oxidative (UV-induced) damage: The antioxidant properties of foods (measured in vitro), and changes in the overall antioxidant capacity of plasma (measured in vivo as, for example, TRAP, TEAC, FRAP,
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ORAC or FOX), do not predict a role of the food/constituent in the protection of body cells and molecules such as DNA, proteins and lipids from oxidative damage in vivo, and therefore are not suitable outcome measures for the scientic substantiation of the claimed eect. Oxidative damage to lipids: The guide proposes Direct measurements of oxidative damage to lipids (i.e. lipid peroxidation) could be obtained in vivo by measuring changes in F2-isoprostanes in 24-h urine samples, which is a better matrix than plasma for this measurement, using gas-chromatography techniques with various detection modes, of which mass spectrometry is preferred. F2-isoprostanes can also be measured using immunoassays. However, lack of specicity owing to possible cross reactions with other prostanoids needs to be taken into account. Measurements of oxidative damage to lipids (i.e. lipid peroxidation) could also be obtained in vivo by measuring oxidised LDL particles in blood using immunological methods (i.e. antibodies) with appropriate specicity. Phosphatidylcholine hydroperoxides (PCOOH) measured in blood or tissue by high-performance liquid chromatography (HPLC) is also an acceptable. Oxidative damage to DNA: Analyses of 8-hydroxy-2-deoxy-guanosin (8-OHdG) in blood (e.g. lymphocytes), tissue (e.g. skin) and urine have been used to assess oxidative damage to DNA. Free 8-OHdG results from oxidative damage and excision-repair; it may also result from oxidation of free bases or nucleotides, from oxidation of other nucleic acids, and from artefacts during sample work up. Urinary 8-OHdG does not directly reect DNA oxidation within cells, but could be used in combination with direct measurements of oxidative damage to DNA if appropriate techniques are used for analysis (e.g. HPLC). Cardiovascular health: Claims referring to cardiovascular health in general need to be accompanied by a specic claim (e.g. claims addressed in sections 5.1 to 5.5 of this guidance). For a health claim on the normal function of the heart, evidence from human studies on specic outcomes (e.g. coronary events) can be used for substantiation. Claims related to changes in the blood lipid prole: This Claim requires identication of the particular markers which should be considered for the evaluation (e.g. LDL-cholesterol, HDL-cholesterol and triglycerides). Claims related to blood LDL-cholesterol concentration: Claims for a benecial eect of the absence (or reduced content) of a food constituent in a food or category of food on LDL-cholesterol concentration have been proposed. Substantiation may be based on evidence for an independent role of the food constituent in increasing LDL-cholesterol concentration. Claims related to blood HDL-cholesterol concentration: Evidence for a sustained eect with continuous consumption of the food/constituent over longer periods of time (e.g. eight weeks) should also be provided.
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Claims on the reduction of blood pressure: The scientic evidence for the substantiation of health claims on the maintenance of normal blood pressure can be obtained from human intervention studies showing a short-term (e.g. three to four week) reduction in systolic blood pressure, or a reduction in diastolic blood pressure if accompanied by a reduction in systolic blood pressure as compared to a food/constituent which is neutral with respect to the claimed eect, or exceptionally to no treatment. Claims on endothelial function: Endothelial function per se is not suciently dened for a scientic evaluation, because endothelium-derived active factors play a role in the maintenance of several functions of the vascular system. These include vasomotion, smooth muscle proliferation, thrombosis, inammation, coagulation, brinolysis and oxidation, which can be assessed by indirect methods. Claims on reduced platelet aggregation: Decreasing platelet aggregation in subjects with platelet activation during sustained exposure to the food/constituent (e.g. four weeks) would be a benecial physiological eect. Claims on homocysteine: Scientic substantiation of this claim may come from the well established role of a food in contributing to the remethylation or degradation of homocysteine (e.g. some vitamins), or can be obtained from human intervention studies. Disease risk reduction claims: Reduction in blood LDL-cholesterol concentration, therefore, is considered benecial in the context of a reduction of disease risk claim for CHD, and reduction in (systolic) blood pressure is considered benecial in the context of a reduction of disease risk claim for CHD and stroke. Therefore, human studies on the risk of CHD are required for the substantiation of these claims in order to validate the association between these variables and the risk of disease in the context of a particular nutritional intervention. The guidance will be an invaluable source for those wishing to make a health claim for their products, since they can focus resources on studies that will be most acceptable to the regulatory authorities.
6.0.18
FOSHU: Functional Foods in Japan
In the seventies there were Japanese researches on food which discovered special activities of some components. These substances were later on used in pharmacology. That is how functional food had its origin. In Japan three functions of food were reported.: 1- Nutritional value: The primary function is to help the body to keep alive. 2- Taste: The secondary function of food is to satisfy the feeling of taste and smell 3- Activity on the physiological system: The third function of food is to strengthen and
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modulate the physiological system. This activity is to be claimed as functional food. In Japan functional foods are grouped under FOSHU (Foods for Special Dietary Uses). The products with functional claims must be authorized by the Japanese food administration. There are only few products which are FOSHU authorized. A great variety of foods with functional claims are not authorized as the produce say that costs to make necessary tests are to expensive, the time it takes to make these test is to long and therefore unfriendly to innovations, the higher concentration of the functional ingredient increases the price and alters the taste. Health claims are scientic and not understandable for an average consumer. Therefore not authorized functional foods are tolerated by Japanese authorities. The development of functional foods must be considered critically as it misleads the consumer. A broad activity of commercials takes the consumer to by a specic food in the hope to be fed all round with all other components he can only get with a well-balanced nutrition.
6.0.19
Foods with Health Claims Foods for Specied Health Uses in Japan
Foods with Health Claims Foods for Specied Health Uses (FOSHU) and Foods with Nutrient Function Claims have been regulated by the Ministry of Health, Labor and Welfare since 2001, updated in 2005. FOSHU foods are the only type of foods that can carry some kind of a health claim in Japan. They have only a small market because of high costs for their approval which includes human clinical trials. Therefore functional foods and dietary supplements are marketed without labelled health claims. This situation caused that unregulated functional foods were put on market, such as conventional food and beverages fortied with health ingredient to promote both general and specic health conditions without label health claims. [7]
Table 6.1: Unregulated functional foods in Japan Ingredient Alpha lipoic acid (ALA) CoQ10 Healt claim status Health food Health food
401 Collage Ceramide Pracenta Hyaluronic acid Isoavones Carnitine Essential fatty acids (EPA, DHA, DPA) Tocotorienol Astaxanthin Creatine Green tea drink Soymilk Health food health food Health food Health food Health food Health food Health food Health food Health food Health food Healt Food Health food
Kirin, seasonal allergy Kibu soy peptide, energy boost Kagome lactic acid bacteria, gastrointestinal health Olio linolenic acid, Healt claim
Plant lactic acid drink
Health food
Pucera cookies Ingredient
Health food status
The other is regulated functional foods, known as FOSHU (Foods for Specic Health Uses). FOSHU is the government approved foods that carries specic health claims on product labels, ranging from gastrointestinal health to lowering cholesterol.
Table 6.2: Regulated Foods for Specic Health Uses (FOSHU) in Japan Healt claim Ingredient Gastrointestinal health Oligosaccharides / Prebiotics Dietary ber Lactic acid bacteria, probiotics Lower cholesterol Soy protein/ soy globulin Soy phospholipds (CSPHP) Low molecule alginic acid Plant sterol/stanol esters Lower hipertension Gama-aminobutiric acid GABA Vinegar acid status FOSHU FOSHU
FOSHU FOSHU FOSHU FOSHU FOSHU FOSHU
402
CHAPTER 6. FUNCTIONAL FOODS AND NOVEL FOODS Lactololi-peptide Eucommia leaf glycoside Wakame peptide, Undarine pinnatida Marine peptide, sardine peptide
FOSHU FOSHU
Lower blood glucose Wheat albumin Guava Polyphenoles Indigestible dextrin Lower serum triglycerides Diacylglycerol Plant sterol Medium chain fatty acid Globin protein enzyme disintegrated Green tea catechin EPA and DHA acid Better mineral absorption Calcium,citric acid, malic acid (CCM) Casein phospho peptide (CPP) Heme-iron Improve dental health Xylitol,phosphate-hydro calcium, funoran Phospho acid olygosaccharides calcium Recaldent (CPP-ACP) Improve bone health Soy isoavones Fructo Oligosccharides Vitamin K2 Milk Basic Protein Ingredient FOSHU FOSHU FOSHU MBP status FOSHU FOSHU FOSHU FOSHU FOSHU FOSHU FOSHU FOSHU FOSHU FOSHU FOSHU FOSHU FOSHU FOSHU FOSHU
Healt claim
6.0.20
Probiotics [?]
According to FAO/WHO Guidelines for the evaluation of probiotics in food 2002 probiotics are live microorganisms which when administered in adequate amounts confer a health benet on the host.
403
6.0.21
Probiotic health claims are often confusing and controversial [8]
Morrow and Kollef 2008 state that probiotics are not marketed as pharmaceuticals and no rigorous scientic documentation of their ecacy are needed for placing them on market. Many probiotic health-claims are based on confusing and controversial studies. The authors write that new understanding of the mechanisms of action of probiotics may lead to a more logical framework of future trials.
6.0.22 6.0.23
Controversity about probiotic drink Actimel from Danone [9] The marketing of Actimel [10]
According to Spiegel Online Danone spent 50 Million Euro from January to October 2008 as marketing budget for Actimel in Germany counting for a volume of sales of about one Billion Euro worldwide per year. Actimel helps to strengthen the bodys defence mechanisms, exceeded e1 billion in sales.
6.0.24
Flourishing global market of probiotics [11]
Khan and Ansari in a monograph of 2007 stresses the growing interest in self-care and the recognition of the link between diet and health of the consumer, providing a ourishing market for functional foods and probiotic products which represent a wealth of marketing opportunities. The authors provide a summary of research on the health benets of probiotics and information regarding the global market of probiotics.
6.0.25
Functional foods with unclear benets suer the impact of nancial crisis [12]
According to UK Financial Times the so-called "functional foods" movement with exotic products such as avour and vitamin enhanced waters may be severely hit by the nancial crisis leaving less money to be spent by the consumer.
6.0.26
Nutritional cosmetics [13]
A yoghurt with ingredients like borage oil, vitamin E and green tea antioxidants It is supposed to "nourish" the skin, while claiming that it "nourish your skin from within" entering the eld of nutritional cosmetics. Experts say that beauty brands are out of place at the food department of a supermarket. A pharmacy distribution suits better for products with undened claims.
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6.0.27
Confusing range of fruit drinks, with and without milk [14]
Special marketing pressure is exerted on drinks for children. A confusing constellation of claims like GM free, no preservatives added no whole soy milk, but soy protein isolate is used to avoid bitter taste, vitamins and calcium are added. Fruit avoured waters and ice cream drinking yoghurts and even chewing gum with special health claims are being marketed by global food companies. Other drinks call on the negative calorie eect (thermogenesis) of epigallocatechin gallate EGCG found in green tea extract which is supposed to speed up the metabolism and increase energy expenditure when taken together with caeine. These drinks burn 60 to 100 calories, says the producer. A cup of green tea and a cup of coee during the day have the same eect heralded by the producer of sophisticated drinks. [15] [16]
6.0.28
Functional properties of feijoa extract [17]
The functional properties of aqueous extracts of blueberry, strawberry, green kiwifruit and feijoa towards the growth of probiotic and pathogenic bacteria were found by Hap and Gutierrez 2012 to have growth-stimulating eects on the probiotic bacteria, except with Bidobacterium longum. Pathogen were inhibited. Feijoa extract was most eective against Listeria monocytogenes and Bacillus cereus. The authors highlight the importance of aqueous extracts of these fruits as functional ingredients in food. These extracts may become interesting to control the growth of pathogens and stimulate the growth of probiotic bacteria during production and storage.
Feijoa, guayabo, goiaba The feijoa (Feijoa sellowiana Berg, new name Acca sellowiana (O.Berg) Burret) is native to extreme southern Brazil, northern Argentina, western Paraguay and Uruguay where it is common wild in the mountains. It is closely related to guava. In Uruguay, it is called, in Spanish, guayabo del pais. It has been nicknamed "pineapple guava", "Brazilian guava" and "g guava". The term "guavasteen" has been adopted in Hawaii. The fruit is rich in water-soluble iodine compounds. The percentage varies with locality and from year to year but the usual range is 1.65 to 3.90 mg/kg of fresh fruit. Most types are high in pectin, so that 3 lbs (1.4 kg) of jelly can be made from 1 lb (.45 kg) of fruit. Ascorbic acids content varies between 28 to 35 mg/100 g edible portion. [18]
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6.0.29
Stability of green tea extract in biscuits increases with reduction of pH of the dough [19]
Sharma and Zhou 2011 describe the inclusion of green tea extract in biscuits as a mean to increase tea catechins in pastries. Catechins proved to be stable in dough but decreased during baking, and increased as the concentration of green tea extract was increased in the biscuit dough. The stability of catechins could be improved by reducing the pH of the dough using less alkaline baking powder, sodium bicarbonate, and ammonium bicarbonate.
6.0.30
Herbal ingredients
Herbal ingredients have been used as food avoring for hundreds of years. Many herbs are used in pharmacy and are regarded as natural remedies looking for new market segments functional foods rediscovered the value of these herbs when used as ingredient of food. Consumer are increasingly looking for self-medication using drugs on herbal extract basis available in supermarkets and practicing disease prevention through diet. Possible functional ingredients are: Vitamins Minerals Essential fatty acids, such as omega 3 and omega 6 fats and oils Amino acids Aloe vera to nourish and hydrate the body Echinachea to support the bodys immune system
6.0.31
Fibre
A new bre is Psyllium which grows in India is told to be very eective to lower cholesterol. Other polysaccharides with bre activities are beta-gulcane, pectin, guar gum, inulin, chitosane,cyclodextrine. Oligosaccharides Green tea extract has powerful anti-oxidant properties Tocotrienols Alpha lipoic acid Sugar alcohols Gingko biloba claimed to relieve stress and aid mental alertness.
6.0.32
Oligofructose and body weight reduction strategy
Oligofructose is a carbohydrate-based dietary ber extracted from chicory roots (Cichorium intybus var. sativum) Fresh chicory root contains, by dry weight, 68% inulin, 14% sucrose, 5% cellulose, 6% protein, 4% ash, and 3% other compounds It is being proposed as a sugar and fat substitute to reduce energy intake of obese people.
406
Verhoef, Meyer and Westerterp 2011 report that taking oligofructose 8 grams twice daily during 13 days, reduces the energy consumption by 10%, concentrations of the satiety hormones PYY and GLP-I were increased, feelings of hunger and satiety remained unaltered. [20] In an earlier study, oligofructose (8 g ingested twice daily = 16 g/day in total) were found by Cani et al. 2006 to increases satiety, reduces hunger and food consumption. The authors proposed oligofructose supplements to treat obesity. [21] Parnell and Reimer 2009 report that 21g oligofructose supplementation per day reduces body weight and improve glucose regulation The supplementation reduced the hunger inducing hormone ghrelin, and increases the peptide YY (PYY), a hormone which reduces appetite, resulting in weight loss. [22]
6.0.33
Inulin [23]
According to Roberfroid 2005, inulin is a generic term to cover all beta 1-2 bond linear fructans. Chicory inulin is a linear beta 1-2 fructan, its partial enzymatic hydrolysis product is oligofructose. The beta-conguration of the anomeric C2 in their fructose monomers makes inulin resistant to digestion by intestinal enzymes. According to Shepherd and Gibson 2006, dietary fructose induces abdominal symptoms, known as irritable bovel syndrome in patients with fructose malabsorption. The authors explain that free fructose can be present in foods like fruits and honey; as a constituent of sugar or as fructans. About 3040% of people in Central Europe suer from fructose malabsorption. Inulin is a fructan and may lead to increased atulence and loose stools in those with fructose malabsorption. Therefore the authors recommend to keep the consumption of fructan less than 0.5 grams/serving for people which suer from fructose malabsorption. [24] Fructans, Oligofructose and short-chained carbohydrates were measured by Muir and colleagues in vegetables and fruits [25] [26] and in grains and cereals. [27]
6.0.34 6.0.35
Isoavones Phytoestrogens [28] [29]
Dietary phytoestrogens are plant-derived nonsteroidal compounds with weak estrogen-like activity. Most phytoestrogens in foods are inactive which are transformed into a steroidal structure similar to estrogens by enzymes of the gastrointestinal duct. Phytoestrogens are subdivided into 4 main classes: isoavones, lignans, cumestrans and phytosterols, of which the isoavones and the lignans are the 2 the most important.
407 Isoavones are the most common form, of the phytoestrogens. Important isoavones are genistein and daidzein, which are formed from the precursors genistin and daidzin and are found, among other sources, in soy products, soybeans, chickpeas, and red clover. Lignans The ligan metabolites, enterolactone and enterodiol, are formed from the precursors matairesinol and secoisolariciresinol. Lignans are derived from rye grains, linseeds, carrots, tea, spinach, broccoli, and other vegetables. Coumesterol is the predominant estrogenic phytoestrogen in the cumestran group and is mainly found in beans, peas, clover, spinach, and sprouts. Phytosterols [30] are derived from the intestinal absorption of vegetable oils, margarines, spreads, grains, and certain fruits and vegetables. Phytosterols include betasitosterol, campesterol, and stigmasterol could aect levels of endogenous hormones through alterations in bile acid metabolism and estrogen reabsorption or by acting as substrates for synthesis of steroid hormones.
6.0.36
Phytoestrogens exposure and reproductive consequences [31]
Phytoestrogens have been promoted as healthy dietary supplements and foods, such as soybean-derived foods, rich in the isoavones genistein and daidzein. These isoavones are also found in soy-based infant formulas. Phytoestrogen groups: Isoavones (genistein, daidzein, glycitein, formononetin), avones (luteolin), coumestans (coumestrol), stilbenes (resveratrol) and lignans (secoisolariciresinol, matairesinol, pinoresinol, lariciresinol). Isoavones are found at high concentrations in soybean products whereas lignans are found in ax seed, coumestans are found in clover, and stilbenes are found in cocoa- and grape-containing products, particularly red wine. Jeerson, Patisaul and Williams 2012 write that many studies provide evidence that phytoestrogen exposure can impact the reproductive health, depending on the dose, route of exposure, and the timing of exposure beginning in the early prenatal period. The authors caution that more phytoestrogens are recognized or developed as therapeutic compounds, and are placed on the food market as supplements. The researchers call for careful study of their the eects on the reproductive system, as negative eects are known.
6.0.37
Soy isoavones supplement
Soy foods are well balanced and are ingredients of a wide rage of products. Daniel Doerge and Daniel Sheehan oppose the decision of the FDA to approve a health claim that soya reduces the risk of heart disease.
408
According to Doerges and Sheehan the isoavones of soya (genistein, daidzein and glycitein) have similar eects to the female hormone oestrogen. Soy oestrogen can lead to health problems in animals including altering sexual development of foetuses and causing thyroid disorders. Although soy is thought to protect against breast cancer, some studies show that some substances may increase the chances of breast cancer which uses oestrogen-type hormones for growth. The claims of soy isoavones supplement are to compensate the declining oestrogen levels and thus relieve menopausal symptoms, such as hot ashes, as well as decrease the risk of heart disease and osteoporosis, without promoting breast cancer. However, exactly what eect concentrated isoavones have remains unclear. That is why normal soy food or soy powder is benecial but isolated soy oestrogen supplements are being looked upon with scepticism.
6.0.38
Isolated Isoavones not without risk [32]
The Federal Institute for Risk Assessment (BfA) stresses that soy and red clover contain isoavones. These phytoestrogens }indexPhytoestrogenscan have a hormone-like eect. There are reports that Asian women who follow a traditional diet and regularly consume soy products scarcely suer at all from menopausal complaints. The Bfa, however, reminds that a distinction must be made between whether bioactive compounds are ingested naturally from food or in isolated, fortied form via food supplements. In Germany for some time now food supplements with isolated isoavones have been available on the market as an alternative to the pre-scribed hormone replacement therapy for menopausal complaints. The products are claimed to be ecacious natural products on menopausal complaints as well as other advantageous health eects on the heart, bones and breasts without any side eects. Adverse eects of soy/red clover-containing products do not refer to uniform sets of symptoms and point to allergic reactions and/or other causes, perhaps to the basic symptoms of the menopausal complaints of the persons concerned. The adverse eects are linked to various food supplements including ones which contain or contained other possible causal substances besides isoavones, like nicotinic acid - a source of niacin. The health assessment of isoavone-containing food supplements, made by the German Federal Institute for Risk Assessment (BfR) found that the assumed positive eects of isolated isoavones on menopausal complaints Toxicological studies showed that high does of isoavones, impair the functioning of the thyroid gland and can change mammary gland tissue. It cannot be ruled out that these estrogen-like eects could promote the development of breast cancer.
409 At the present time, the claimed favourable eects of isolated isoavones must be deemed to be not suciently scientically substantiated. The BfR advises against the long-term intake of these products given the unproven positive eects and the serious health consequences for meno-pausal women which cannot be ruled out. BfR concludes that the safety of products containing isolated isoavones on a soy or red clover basis has not been suciently proven. In addition, BfR concludes that there are health risks with low probability from food supplements of this kind for women during and after menopause.
6.0.39
Phytoestrogens in foods of animal origin [33]
Gunter Kuhnle and colleagues 2008 assessed the phytoestrogens content of foods of animal origin. The study focused on the isoavones biochanin A, daidzein, formononetin, genistein, and glycitein; the lignans secoisolariciresinol and matairesinol; coumestrol; equol; enterolactone; and enterodiol in 115 foods of animal origin. The authors detected phytoestrogens in all foods analyzed; the average content was 20 microg/100 g of wet weight (isoavones, 6 microg/100 g; lignans, 6 microg/100 g; equol, 3 microg/100 g; and enterolignans, 6 microg/100 g). In infant soy formula, 19 221 microg/100 g phytoestrogens were detected (compared to 59 microg/100 g in non-soy formula). According to the study phytoestrogens in animal products are low when compared to foods containing soy, but the range is similar to that of many commonly consumed vegetables.
6.0.40
The controversy of phytoestrogens
The authors point out that, despite their potentially benecial eects, dietary phytoestrogens may be involved in the occurrence of chronic diseases. Studies cite hormone-dependent cancers, cardiovascular diseases, osteoporosis, menopausal symptoms, male infertility, obesity and type-2 diabetes. the compounds were found to be biologically active even at low levels in humans with the gene variants of the estrogen receptor (ESR1 and NR1, sex-hormone binding globulin (SHBG), and probably aromatase (CYP19). [34] [35] [36]
6.0.41
New analysing technique
Kuhnle and colleagues present a modied technique to analyse phytoestrogens in food samples and publish their content in foods of animal origin. The authors stress that actual data limited to isoavones and ligans in fruit, vegetables, nuts, and seeds and very little concerning animal foods, may lead to an underestimation and misclassication of dietary exposure. They emphasize, therefore the need for chromatographic analytical systems using as many labeled standards as possible and urges not to rely only on single focused analytical methods based on immunouorescence.
410
They conclude that reliable information on the phytoestrogen content in animal foods is required to assess dietary exposure and disease risk in epidemiological studies.
6.0.42 6.0.43
Soy foods and reduced fertility The soy genistein may damage human sperm [37]
Isoavones that exert an oestrogen-like eect like genistein, daidzein, and glycitein from soy, are dietary oestrogens that are a natural alternative to hormone replacement therapy and are supposed to slow prostate and breast cancer. Lynn Fraser and colleagues 2005 reported that even tiny doses of these natural compounds can cause human sperm to lose fertility. Fraser says that genistein combined with other environmental oestrogens, such as 8-prenylnaringenin (found in hops),and nonylphenol that is found in industrial products like paints, pesticides and cleaning products, the damage to fertility increases. The combination of these chemicals get eective at capacitation, the stage when a sperm acquires the ability to fertilise an egg. The chemicals cause the release of the enzymes that enable the sperm to penetrate the coverings of the egg. When the release happens before the sperm nds the egg cell, it looses the capability to penetrate the egg. Fraser says that the premature capacitation is stimulated by both genistein and nonylphenol which trigger the production of the messenger AMP which is more likely to aect sperm when they reached the female tract where they would be preparing to fertilise eggs. Maternal exposure to the compounds is therefore probably more important than paternal exposure.
6.0.44
Soy products were found to reduce the concentration of sperm particularly in overweight or obese persons [38]
A study by Jorge Chavarro and colleagues 2008 found that high consumption of soy isoavones could aect fertility. Soy foods like tofu, tempeh, soy milk and other non-daily alternatives, energy bars, and vegetarian products using soy as a meat analogue were included in the study. Half a serving is said to be equivalent to one cup of soy milk or one portion of tofu, tempeh, or soy burgers every other day. High intake of aan average of half a portion of soy foods per day reduced the sperm concentrations of 41m less per ml. The normal sperm concentration range is 80-120m per ml.
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6.0.45
High sperm count and overweight
The eect on sperm concentrations seemed to be more pronounced in men who already had higher or normal sperm counts. Overweight people presented a more pronounced eect, because higher body fat produces more oestrogen than slimmer men. Chavarro and colleagues concluded that men should avoid eating too much soy if they are planning a family. The authors stress, however that Asian populations consuming high amounts of soy foods presented no reduced fertility or other health problems.
6.0.46
Genetic susceptibility to estrogen from soy products [39]
Although the importance of estrogens in male reproduction is indisputable, little attention has been paid to the role of estrogen receptor (ER) gene mutations in male infertility. The authors found an association between higher TA repeat number (genotype A) and lower sperm production. In line with this observation, normospermic subjects with genotype A had a signicantly lower mean sperm concentration with respect to men bearing genotype B with shorter TA alleles and a lower total sperm count. The authors concluded that specic allelic combinations of the ERalpha, which confer a stronger estrogen eect, may negatively inuence human spermatogenesis.
6.0.47
No cardiovascular benet from soy isoavones [40]
Garrido and colleagues followed the suggestion that isoavones protect the cardiovascular system, in part by improving lipid prole. They examined the eect of 12-weeks soy isoavone supplementation on lipoprotein status and platelet thromboxane A2 receptor density. Blood pressure, body mass index, subcutaneous fat, insulin, serum lipoprotein, sex hormones and sex hormone-binding globulin did not dier among experimental group and placebo group. However, platelet thromboxane A2 receptor density declined signicantly in the experimental group, remaining mostly unchanged in the placebo group. The change in platelet thromboxane A2 receptors correlated negatively with isoavones serum concentration. The authors concluded that there were no cardiovascular benet from soy isoavones. The benecial eects of isoavones in menopausal women could be more related to platelet function than to improving classical cardiovascular risk factors.
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6.0.48
Phytoestrogens protect against lung cancer [41]
Margaret R. Spitz and colleagues assessed the role of phytoestrogens and reduction of risk of lung cancer. They found that total phytosterols, isoavones, lignans, and phytoestrogens were each associated with reductions in risk of lung cancer ranging from 21% for phytosterols; to 46% for total phytoestrogens from food sources onlyfor men abut only total phytoestrogens from food sources were eective against lung cancer in women. There were also signicant joint eects found between hormone therapy use and phytoestrogen intake, such as the lignans enterolactone and enterodiol in women. The authors concluded that their data provide further support for the limited but growing epidemiologic evidence that phytoestrogens are associated with a decrease in risk of lung cancer, however, more studies on this subject are needed.
6.0.49
Other bioactive food ingredients are
Phosphatidylserine and Garlic.
6.0.50
Aloe vera
Aloe vera (Linn) was taxonomically renamed by Miller in 1768 as Aloe barbadensis (Miller). Both names relate to the same plant. There are about 300 species of Aloe, but only Aloe vera and Aloe arborescens bear compounds with health related eects. The most important of these is the mucopolysaccharid acemannan. [42] Aloe latex and aloe gel can be derived from Aloe vera.
6.0.51
Aloe latex (or aloe juice)
It is the bitter yellow exudate from the outer skin of the leaves. Its active compounds are the anthraquinone glycosides aloin A and B. Aloe latex is laxative.
6.0.52
Aloe gel
: It is often sold as powder. It is the colourless gel contained in the inner part of the fresh leaves. Important polysaccharides are pectins, cellulose, hemicellulose, glucomannan, acemannan and mannose derivatives. The most important of these compound is acemannan. Aloe gel is often commercialised as powdered concentrate.
6.0.53
Eects in burn wound healing [43]
Maenthaisong and colleagues 2007 say that aloe vera might be an eective interventions used in burn wound healing for rst to second degree burns, and call for more studies.
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6.0.54
Cautions against specic eects [44]
Aterton in 1998 calls for caution against complementary treatments like chronic venous leg ulcers with oral or topical application of Aloe vera that may aid healing.
6.0.55
Aloe vera gel
It is a preparation of leaf pulp from the parenchymal tissue of the plant Aloe vera (Liliaceae). Aloe vera gel contains carbohydrate polymers, such as glucomannans or pectic acid, and various vitamins and essential amino acids, as well as other organic and inorganic compounds. This agent has been used internally or externally for sunburn, skin problems, insect bites, ulcers, arthritis, constipation, and as an immune system enhancer.
6.0.56
Antitumor activity [45]
Aloe-emodin: It is a compound of the family of anthraquinones, with anti-inamatory andf anticancer eects. Aloe-emodin (1,8-dihydroy-3-[hydroxymethyl]-anthraquione) puried from Aloe vera leaves has been reported to have antitumor activity. The authors found that aloe-emodin delayed the number of cells entering and exiting DNA synthesis (S) phase in cells indicating that aloe-emodin may inhibit S phase progression. The cancer growth inhibition by aloe-emodin was due to apoptosis. The authors suggest that aloe-emodin represents a novel antitumor chemotherapeutic drug. [46] Maxey C. M. Chung and colleagues 2007 found that Aloe-emodin induced anticancer effects in HepG2 cells via multiple pathways by aecting dierent protein targets and was able to decrease cell migration via up-regulation of the metastasis inhibitor, nm23. [47] Giorgio Palu and colleagues report that Here we show that aloe-emodin selectively inhibits human neuroectodermal tumor cell growth in tissue cultures and in animal models. Neuroblastoma, pPNET, and Ewings sarcoma cells were found highly susceptible to aloe-emotin, The authors write, however, that human malignant cells from epithelial and blood-derived tumors, as well as human hemopoietic progenitors and normal broblasts, were not sensitive to this compound. [48]
6.0.57
Toxicology [49]
Boudreau and Beland 2006 report that ingestion of Aloe vera is associated with diarrhea, electrolyte imbalance, kidney dysfunction, and conventional drug interactions; and contact dermatitis, erythema, and phototoxicity with topical applications. The authors reviewed the botany, physical and chemical properties, and biological activities of the Aloe vera plant. The toxic eects are related to aloin.
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6.0.58
Alantoin in aloe latex, exudate from outer skin of aloe
It is used in beverages because of its taste and laxative eects. The EU directive 88/388 sets maximum limits of 0,1 mg/kg in foods and beverages, and 50 mg/kg in alcoholic beverages. Incomplete separation of the leaf skin may cause aloin or other hydroxyanthracene derivatives to be present in Aloe vera gel. [50]
6.0.59
Aloe vera and diabetes [51]
According to Vogler and Ernst 1999 the clinical eectiveness of oral or topical aloe vera as adjunct for lowering blood glucose in diabetic patients as well as for reducing blood lipid levels in patients with hyperlipidaemia is not suciently dened at present. Aloe vera leaf pulp extract devoid of the gel has hypoglycaemic eect non-insulin dependent diabetes mellitus. Okyar and colleagues 2001 report that Aloe vera leaf pulp extract showed hypoglycaemic activity on type 1 diabetic and type 2 diabetic rats. However, Aloe vera leaf gel extract showed hyperglycaemic activity on type 2 diabetic rats. The authors concluded that the pulps of Aloe vera leaves devoid of the gel could be useful in the treatment of type 2 diabetes. [52] Tanaka and colleagues 2006 evaluated the anti-hyperglycemic eect of Aloe vera gel in mice. The authors isolated a ve active compounds from lophenol, cycloartanol and their derivates. There were no dierences between the ve phytosterols, which reduced fasting blood glucose levels up to 64% compared with the control group. They concluded that Aloe vera gel and phytosterols derived from Aloe vera gel could be useful for the treatment of type 2 diabetes mellitus. [53] Beppu and colleagues 2006 performed experimental trials to determine antidiabetic effects of Aloe vera. The authors found that The dietary administration of 10 KDa fraction powder to mice exerted an antioxidant activity in the pancreas and blood, which could protect islets of Langerhans from destruction. They also stress that the 10 KDa fraction powder alleviates the burden of insulin secretion as it has an inhibitory action on glucose absorption in the jejunum of rats. [54] Perez and colleagues 2007 report that Aloe vera gel could be eective for the control of insulin resistance, which precedes type 2 diabetes mellitus. [55]
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6.0.60
Analysis of components of Aloe vera [56]
According to A.Bozi and coleagues 2007 glucose, malic acid, and the polysaccharide acemannan, are the three main natural components of aloe vera gel. Maltodextrin remains a common adulterant of aloe vera gel powders.
6.0.61
Organic acid analysis to assess freshness of Aloe vera products
The authors found that lactic acid is a negative quality characteristic of aloe raw materials, indicating improper processing or incorrect storage. Fumaric acid, succinic acid, and pyruvates may be produced by enzymes. During fermentation and enzymatic degradation acemannan is degraded to acetic acid. Malic acid is the only organic acid contained in fresh aloe vera gel. Commercial aloe gel powders have citric and added for preservation and avour.
6.0.62
Sugars
Acemanan in aloe vera gel powders should be the major polysaccharide. Bozi and colleagues measured the amount of mannose after acid hydrolysis gave a direct and rapid measurement acemannan in the gel powder.
6.0.63
Ginseng extract
A new ginseng extract called Cold-fx was developed by a spin-o company of the University of Alberta, CV Technologies. I contains 80 per cent poly-furanosyl-pyranosyl-saccharides and 10 percent protein from the ginseng roots. The North American ginseng (Panax quiquefolium) is used as raw material. A publication of the Canadian Medical Association Journal (173, issue 9) claims that the extract is a safe,eective prophylactic treatment for upper respiratory tract infections. It may boost production of natural killer cell activity, thought to decrease susceptibility to frequent colds. Further studies on its ecacy and safety to children and immunocompromised populations were recommended. The composition of the Asian or Korean ginseng (Panax Ginseng C.A. Meyer) should also be analysed to nd new ways to boost the human immune system to counter pandemics of inuenza like an avian inuenza outbreak. Ronald Turner from the University of Virginia School of Medicine in the same journal warned of the many pitfalls faced by clinical studies of natural remedies for viral infections. Since the proposed mechanism of action of ginseng on colds is unclear, and the
416
active compounds have not been identied, even though the extract was standardized " it is possible that there is lot-to-lot variability for important phytochemical components that are not measured". Peptides Lactic acid bacteria Isoprenoids Lecithin St. Johns wort whose claim is emotional balance. Dietary bre as they prevent constipation. Polyunsaturated fats to help to lower cholesterol Carnitine[57] Carnitine was discovered in 1905 and is also called vitamin BT . It is trimethylbetaine (beta-OH-gama-trimethylamino butyric acid). Long chain fatty acids are bind to carnitine which makes them able to cross the membrane of the mitochondrions and are there exposed to a beta-oxidation, it has a transmethylation and tyrosine eect. Carnitine has also a role in the oxidation but not in the transport of medium-chain fatty acids.[58] Carnitine triggers the appetite and increases and bodyweight, the reason why it is being added to animal feed.
6.0.64
Biosynthesis of carnitine
The biosynthesis of carnitine which starts from lysine and methionine needs additional L-ascorbic acid and takes place in the liver. In case of an undersupply of vitamine C there will be very soon a drop of carnitine in the muscles resulting in weariness and weakness.[59] Vitamine C is a cofactor of two dioxygenases reaction of the carnitine synthesis which needs also alpha-chetoglutarate. Guinea pigs with scurvy have low concentrations of carnitine in their blood. A low level of vitamine C reduces the availability of energy and the lipid metabolism due to a drop of carnitine.
6.0.65
Food as source of carnitine
Parallel to biosynthesis of carnitine in the liver food acts as an additional source. Vegetarians have a daily intake of 2 mg carnitine and mixed food bring 32 mg daily intake.
Table 6.3: Carnitine in Food Carnitine mg in 100g mutton 210 beef 70 Food
417 pork 30 tomato 2.9 pear 2.7 pea 1.2 potato 0 carrot 0 Fifteen days of parenteral feeding leads to a drop of carnitine which cannot be compensated by biosynthesis. A carnitine substitution of 10 mg/day normalizes the concentration of carnitine in the serum and the beta-oxidation of long-chain fatty acids. Hemodialysis drops carnitine about 50%. Feeding carnitine reduces the amount of free fatty acids in the serum as it is forwarded to the beta-oxidation. Hepatocirrhosis low carnitine is due to a diminished biosynthesis and reduced intake of food.
6.0.66
Carnitine and sport
Carnitine is being used as supplement in the nutrition of athletes to increase performance. A positive eect has not been conrmed.[60] It is considered as a non drug-doping substance but it is not on the "red list". Folate Psyllium to help to reduce cholesterol levels Magnesium Functional foods should taste good, be well prepared, and oer real benets such as gastrointestinal function, antioxidant activity, micronutrients, positive activity on fetal and early life development. On global market the functional foods will be sold under "Hard claims" [61] which are claims related to activities against diseases. " Soft claims " are used to describe preventive health claims.
6.0.67
Food supplements
Food supplements are dened in a leaet of the German Institute for consumer Health and Veterinary Medicine (Bundesinstitut fr Gesundheitlichen Verbraucherschutz und Veterinrmedizin (BgVV) Food supplements are foods having one or more nutritional substances in concentrated form (mainly vitamins, minerals and trace elements), presenting a for food unusual form (pills or capsules etc.) Food supplements should be labeled as "Food supplement" together with the suggested daily intake.Food supplements are ruled by Food laws, in Germany by the LMBG ( Lebensmittel- und Bedarfsgegenstndegesetz. they do not need a special release. Exception are dietary supplements , they do need a registration and a release.
418
6.0.68
Denition of Dietary Supplements according FDA
http://vm.cfsan.fda.gov/list.html. Dietary supplement is any product taken by mouth, that contains a so called dietary ingredientnd its label states that it is a dietary supplement. Dietary supplements may be presented in form of pills, tablets, capsules, liquids or powders.
6.0.69
Denition of Dietary Ingredients
Dietary ingredients are present in dietary supplements. They may include vitamins,minerals, herbs, and aminoacids as well as substances such as enzymes, organ tissues, metabolites extracts or concentrates. The producer of food supplements is responsible for health safety of his products. He has to avoid deceiving informations and disease related statements ( 17 and 18 LMBG). Substances with pharmacological activities are not food supplements. They are ruled under pharmacy laws. The BgVV says that well-balanced adequate nutrition is sucient to feed the daily nutrients.An increase of wellness through food supplements is according to BgVV doubtful. An exception is iodine and folic acid.For these two elements there is an undersupply in Germany. It is therefore advisable to use iodine salt in kitchen, community provisioning, production of bread, backery products and meat derivates.
6.0.70
Folic acid
Is important in the prevention of neural tube defects in the early pregnancy and reduces plasma homocystein which can lead to atherosclerotic damage.
6.0.71
Cancer, the medicine op, a statement of Dr. Lothar Weissbach,president of the German Cancer Society
Dr. med. Lothar Weissbach is president of the German Cancer Society. He is an authority in research and treatment of human cancer. He works in the "Krankenhaus am Urban" Berlin. In an interview with Hans Halter published in"Der Spiegel"[62] made the following statement: "Early identication of cancer is very expensive, but not very eective.The interactive work between dierent specialists doctors is unsucient and reduces the chances of the patients. The genetherapy will come but it will be necessary that more patients are willing to participate in clinical studies.Experts await the begin of the genetherapy for 2.003 or
6.1. FLAVONOIDS, SUCH AS ISOFLAVONES, ANTHOCYANIDINS AND FLAVONOLS
419
2005. One hundred years ago there were 43.000 death per year in Germany, on end of 1999 there were 218.000 death of the same cause. This come from a growing age of the population. Cancer is a disease of high age (this is not correct in related to breast and lung cancer, see WHO statistics:-comment of OurFood.com-). Pancreas cancer und lung cancer cannot be treated. Prognosis is bad. It is true that in ten years cancer will be at place number one in the death causes in Germany. We are not prepared for this. Main concern are death cases from lung cancer, bowel cancer and breast cancer which has increased about 20% after introduction of early detection checks. We have to learn that we can cure only a small part of cancer diseases. The knowledge gets through that we have to detect cancer earlier and -better as that- we have to avoid cancer." Better understanding of food physiology, better care of our environment and self discipline regarding smoking and alcohol consume can be a precious contribution to reduce risk of cancer.
6.0.72
Breast cancer and high fat diet
High fat diet may increase breast cancer risc according to the London School of Hygiene and Tropical Medicine. The fat is not causal agent but instead causes depletion of an undiscovered essential agent that is normaly protective against breast cancer Omportant factors engaged in the origine of breast cancer are: 1.- Deciency, inadequate intake or depletion via a high fat diet. 2 - Age 3.-Estrogen.
6.0.73 6.0.74
Supplemented Foods Isoavonoids
: Isoavonoids are phytochemicals which are free radical scavangers and can be extracted from soy beans. Supplementing foods with isoavonoids can help to reinforce the positive action of nature.
6.1
Flavonoids, such as isoavones, anthocyanidins and avonols
Phytoestrogens are substances which are estrogen-like. They are sometimes called endocrine disrupters. Some hypothesis say that exogenous substances with estrogenic or otherhormonally active properties may adversely aect human health.[63]
420
Endocrine disruptors can be industrial contaminants, such as pesticides and plasticizers, and others are natural phytoestrogens found in plants such as soy and in herbal supplements. They may cause male wild-life animals in water contaminated by detergent, polychlorinated biphenyls (PCBs) and herbicide to express female characteristics and other modications. Human development can also be feminized by exposure to estrogenic chemicals, aect breast growth and lactation, and could have a role in uterine diseases such as broids and endometriosis. Endocrine-disrupting chemicals mostly exhibit estrogenic eects, but a few are anti-estrogenic or anti-androgenic,resulting in reduced fertility in breeding cattle. [64] They are found in plants. Important phytoestrogens are ligans, isoavones and coumetans.
6.2
6.2.1
Eect of phytoestrogens such as lignans on cancer risk

Lignans
They are found in ax seed (300 mg/100g), sesame seed (290 mg/100g), brassica vegetables (0,2-2 mg/100 g), red wine (0,09 mg/100 g). Several hundred individual lignans have been discovered. Research, however, is focussed on lignans from axseed (Linum usitatissimum) and only few studies were made on lignans from Norwegian spruce bark (Picea abies). When part of the human diet, some lignans are metabolised to form mammalian lignans known as enterediol and enterolactone by intestinal bacteria. Lignans that can be metabolised to form mammalian lignans are pinoresinol, lariciresinol, secoisolariciresinol, matairesinol, hydroxymatairesinol, syringaresinol and sesamin. [65] Phytoestrogens may play a role in hormone-related diseases such as cancer, but epidemiological and clinical data are conicting. The mammalian lignans enterolactone and enterodiol are produced by the microora in the colon of humans and animals from precursors in foods such as lignans. They have been suggested to have potential anticancer eects. Lilian U. Thompson and colleagues in 2005 determined the production of mammalian lignans from precursors in food bars containing unground whole axseed and sesame seed. The authors demonstrated that precursors from unground whole axseed and sesame seed
6.2. EFFECT OF PHYTOESTROGENS SUCH AS LIGNANS ON CANCER RISK 421 are converted by the bacterial ora in the colon to mammalian lignans. [66]
6.2.2
Sesame seed is not protective and negatively interferes with tamoxifen in inducing regression of established MCF-7 tumor size [67]
Flaxseed enhances the tumor growth-inhibitory eect of tamoxifen, but sesame seed was found by Sandra M.Sacco and colleagues to have no eect on tumor and tend to negate the tumor-inhibitory eect of tamoxifen, reducing apoptosis. The authors concluded in a 2008 study that sesame seed is not protective and negatively interferes with tamoxifen in inducing regression of established MCF-7 tumor size.
6.2.3
The Waagening lignan study January 2008: Enteroligans do not protect against colorectal cancer [68]
Peter C.H. Hollaman and colleagues say that high plasma enterodiol or enterolactone concentrations do not reduce risk of colorectal cancer. Enterolignans are biphenolic compounds that possess several biologic activities whereby they may inuence carcinogenesis. Enterodiol and enterolactone are a product of the activity of the microora of the colon metabolising lignans from plants such as ax seed, whole grain cereals, berries, vegetables and fruits. The authors stressed that plasma enterodiol and colorectal increased the risk of colorectal cancer among current smokers. The results contradict the study published in 2006.
6.2.4
The Waagening lignan study June 2006: Enteroligans protect against colorectal cancer [69]
Peter C.H. Hollaman and colleagues reported in June 2006 a substantial reduction in colorectal adenoma risk among subjects with high plasma concentrations of enterolignans, in particular, enterodiol. The authors write that ndings could be important in the prevention of colorectal adenomas.
6.2.5
Enterolactone reduces the proliferation of prostate cancer cells in vitro [70]
According to Marc J. McCann and colleagues 2008 ecological data suggest that a longterm diet high in plant material rich in biologically active compounds, such as the lignans, can signicantly inuence the development of prostate cancer. The authors performed an in vitro study which suggests that the antiproliferative activity of enterolactone of the LNCaP human prostate cancer cell line in vitro is a consequence of altered expression of
422
cell cycle associated genes. According to the authors this study provides evidence for the antiproliferative properties of a pure lignan in prostate cancer.
6.2.6
Dietary axseed reduces tumor growth in patients with breast cancer [71]
Lilian U. Thompson and colleagues found in 2005 that dietary axseed, the richest source of mammalian lignan precursors, increased the apoptosis of cancer cells, increased urinary lignan excretion and reduced tumor biological markers in postmenopausal patients with newly diagnosed breast cancer. The authors concluded that dietary axseed has the potential to reduce tumor growth in patients with breast cancer.
6.2.7
Flaxseed, soy protein isolates and their action on breast cancer cells [72]
Previous study of Lilian U. Thompson and colleagues had found that axseed (FS) reduced while soy protein isolate (SPI) stimulated MCF-7 breast tumor growth in ovariectomized mice. In 2007 the authors found that combining SPI and FS resulted in a negation of SPI-induced tumor growth. Uterus weight was signicantly increased by the SPI + FS group, while SPI alone induced an intermediate eect. The authors concluded that although the SPI + FS and SPI groups exerted stimulatory eects on uterus weight, other histological parameters need to be measured to determine the overall safety of these breast cancer treatments on the uterus.
6.2.8
Flaxseed and soy protein isolates and their eect on breast cancer [73]
In several epidemiological studies, a phytoestrogen-rich diet containing lignans and isoavones is associated with reduced breast cancer risk, but experimental ndings are controversial. In 2006 Lilian U. Thompson and colleagues found that in mouse, ligans of axseed reduced breast cancer growth, while isoavones from soy protein enhanced it. The combination of soy protein with axseed reduced the tumor growth. The authors concluded that dietary axseed did not stimulate the growth of estrogen responsive MCF-7 cancers in mice, while long-term consumption of soy protein did, and axseed reduced the tumor growth stimulating eect of soy protein. Flaxseed is therefore being suggested to attenuate tumor growth.
6.2. EFFECT OF PHYTOESTROGENS SUCH AS LIGNANS ON CANCER RISK 423
6.2.9
The combination of axseed with soy reduce the growth stimulatory eect on established breast cancer [74]
Concern over the safety of soy and its isoavones are growing. Soy genistein was found to increase the risk of postmenopausal breast cancer. According to Lilian U. Thompson and colleagues in july 2007 wrote that axseed with enterodiol and enterolactone, was found to negate the tumor stimulatory eects of soy protein or genistein alone. The authors, analysing the ndings of their study, concluded that soy should be consumed together with lignan-rich foods to avoid an increased risk of postmenopausal breast cancer.
6.2.10
Isoavones
Isoavones are polyphenolic compounds produced almost exclusively by the members of the Fabaceae/ Leguminosae (bean) family. Important isoavones are genistein, daidzein, glycitein and formononetin. Soy products contain the highest amounts of isoavone, followed by legumes, meat products and other processed foods, cereals and breads, nuts and oilseeds, vegetables, alcoholic beverages, fruits, and non alcoholic beverages. [75]
6.2.11
Coumetans
A known coumestan is the coumestrol. Coumestans are estrogen-like substances (phytoestrogens) made by some plants. Coumestans may have anticancer eects according to the U.S. National Cancer Institute. A new coumestan, tephcalostan has been isolated from the whole plant of Tephrosia calophylla BEDD. together with two known avonoids. [76]
6.2.12
Flavonoids, lignans and reduction of risk of breath cancer [77]
Bryan Fink and colleagues investigated the association of dietary avonoid intake with reduced risk of breast cancer in a population-based sample of US women. The authors found a decrease in breast cancer risk associated with avonoid intake, most pronounced for avonols, avones, avan-3-ols, and lignans in postmenopausal women. The authors conclude that women consuming sucient levels of avonoids may benet from their potential chemopreventive eects. Flavonoids antioxidants may thus reduce mortality among postmenopausal in breast cancer patients [78] Brian Fink from the University of North Carolina states, write in another publication, that his team found that the breath-cancer mortality in postmenopausal women may be
424
reduced in association with high levels of dietary avones and isoavones. No reduction of risk was found in premenopausal women.
6.2.13
Flavonoids and avanones reduce oral and paryngeal cancer [79]
Rossi and colleagues 2007 in a study found that the intake of avonoids was inversely related to the risk of various common neoplasms, but scanty data exist on oral and pharyngeal cancer. The authors applied data on food and beverage content of six major classes of avonoids, for avanones, for avonols, and for total avonoids. In this study no signicant association emerged for isoavones, anthocyanidins, avan-3-ols, and avones. The inverse relations with total avonoids and avanones was signicant, whereas that with avonols were nonsignicant.
6.3
6.3.1
Health benets of avonoids from citrus fruits

Enzymatic modication of the citrus avonoid hesperidin improves bioavailability in humans [80]
Hesperidin is the predominant polyphenol from citrus fruits and juices, but it has reduced bioavailability due to the rutinoside moiety attached to the avonoid. In a study by Nielsen and colleagues 2006 the rhamnose group was removed to yield the corresponding avonoid glucoside improving the bioavailability of the aglycone hesperetin. The authors concluded that the bioavailability of hesperidin was modulated by enzymatic conversion to hesperetin-7-glucoside, thus changing the absorption site from the colon to the small intestine.
6.3.2
Hesperidin and naringin from orange and grape fruits can lead to reductions in cholesterol levels in lab animals [81]
Shela Gorinstein and colleagues 2007 compared the inuence of hesperidin and naringin, the main avonones of plasma antioxidant activity increasing avonones.
6.3.3
Flavanones from citrus fruits may help to treat neurovegetative diseases [82]
According to Sam-Long Hwang and Gow-Chin Yen 2007 the citrus avanones hesperidin, hesperetin, and neohesperidin from cirus fruits, have neuroprotective eects against H2 O2 induced cytotoxicity in PC12 cells. The avanones protect against oxidative stress, playing
6.4. SOY AS SUPPLEMENT IN INFANT FORMULAS
425
thus a neuroprotective role. Citrusfruits fruits have potential as functional foods for neuroprotectione. The authors suggest the use of these avanones in the intervention for neurodegenerative diseases such as Alzheimers disease,
6.4
Soy as supplement in infant formulas
Soy as a supplement or replacement for maternal breast milk or cows milk in infant formulas is becoming increasingly important. Antioxidant eects of isoavones from soy, such as genistein, daidzein, and glycitein had been seen as some of good merits of soy. However, according to ongoing discussions phytoestrogens in soy infant formulas may have an adversely aect human growth, development, or reproduction. Genistein beside its antioxidant eect is also a phytoestrogen which may be hazardous to human development or reproduction. Concerns about oestrogen eects of genistein in human body are being discussed. [83] A summary of the bibliography related to soy and Genistein in the management of menopauserelated symptoms is given by Nelson HD. [84]. The outcomes of a discussion, leaded by US Center for the Evaluation of Risks to Human Reproduction (CERHR) of the National Institute of Environmental Health Services (NIEHS) and National Toxicology Program in March 2006, were: When given orally, there was no threat from the reproductive and developmental eects of soy, supporting the safety of soy isoavone dietary supplements. The eects of genistein in relation to heart disease or cancer risk, were not explored by the panelists. One member of the pannel, however called for greater caution on this matter. Soy Isoavones are known for acting similarly to natural estrogens as well as performing protective functions within our bodies. When estrogen levels are low, Isoavones and other phyto-estrogens bring the body to state of equilibrium. This balanced state reduces the eect of estrogen on our bodies cells and therefore reduces the risk of estrogen linked cancers.
6.4.1
Long exposure to soy diet may reduce male fertility [85]
Nef and colleagues 2010 assessed the eects of isoavone phytoestrogens in soybean eects on the development and function of the male reproductive system. Feeding soy-rich diet to
426
mice the authors found that behaviour and fertility of adult mice were normal, however, sperm counts were 25 per cent lower, and 21 per cent smaller litter sizes, than found in mice fed a soy-free diet. Also reduced transcripts coding for androgen-response genes in Sertoli cells and Gapd-s, involved in sperm glycolysis and mobility were noted. The authors concluded that dietary soy may decrease male fertility.
6.4.2
Soy-based formula infant feeding should be avoided [86]
In a review 2009 Nef and collegues write that some indications that phyto-oestrogens, alone or in combination with other endocrine disruptors, may alter reproductive hormones, spermatogenesis, sperm capacitation and fertility. The authors call for more studies suggest perinatal phyto-oestrogen exposure to be reconsidered, in especial infants feeding on soybased formula should be avoided. The authors in another review of 2009 acknowledge that phytoestrogens of soy favourably alter glycemic control, improve weight and fat loss, lower triglycerides, low density lipoprotein (LDL) cholesterol and total cholesterol, however, more studies are needed to identify which soy component is responsible for specic eects, which are the mechanisms engaged, and what are possible negative eects of the phytoestrogens of soy. [87]
6.4.3
Soy phytoestrogen present no apparent estrogenic eects [88]
In this study the risks of phytoestrogens as potential endocrine-disrupting chemicals (EDC) were compared with those posed by estradiol and other EDC. Kwack and colleagues 2009 estimated the soy products intake of Koreans to be 135.2 g/d which is an equivalent of 0.51 mg/kg body weight (bw)/d of phytoestrogens and compared it with Amercan diet low in soy products. Estimated daily intakes (EDI) and estrogenic potencies (EP) the margins of safety (MOS) were used. Estradiol presents an MOS value of 0.05 for estradiol (MOS value <1, considered to exert a positive estrogenic eect); thus, MOS values of 1.89 for Japanese, 1.96 for Koreans, and 5.55 for Americans. The authors concluded that consumption of soybeanbased foods exerted no apparent estrogenic eects, as all MOS values were all higher than 1, but poses a relatively higher health risk for humans than synthetic EDC such as dieldrin 27, nonylphenol 250, butyl benzyl phthalate 321, bisphenol A 1000, biochanin A 2203, and coumesterol 2898.
6.4.4
Functions of Genistein
Genistein as antioxidant reduces the risk for arteriosclerosis minimizing peroxidation and prevets thus LDL cholesterol being absorbed by aarterial walls.
6.5. SPECIAL PURPOSE VALUE ADDED SOYBEANS
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Genistein blocks the enzime tyrosinereducing the risk of cancer. Breat and prostata cancer are also being said to be reduced by genistein.
6.4.5
Functions of daidzein
Daidzein has little estrogen activity but is very eective as antioxidant. It was linked to reduction of risk of mammary tumors and reduction of risk of osteoporosis.
6.4.6
Functions of glycitein
Glycitein has the greatest estrogenic activity levels of all the Isoavones when measured in vivo. It is the most easily absorbed Isoavone.
6.5
Special purpose value added soybeans
[89] Scientists are searching the loci controlling the accumulation of specic soybean isoavones. Reducing unwanted isoavones while enhancing benecial isoavones could be a keybreeding target. Manipulation of isoavone contents and proles will result in the creation of special purpose value added soybeans. Future research needs to focus on the production of a cultivar that consistently produces 5-6 mg/g of total isoavone, with a white hilum and non-GMO herbicide resistance for the international soy protein isolate market.
6.5.1
Benecial health claims for soy [90]
Phytoestrogen supplements have become popular as alternatives for hormone replacement therapy based on their potential as prevention of hormonedependent diseases. Isoavonoids found in legumes, such as soybeans, are converted by intestinal bacteria to metabolites with increased or decreased estrogenic activity. Microbial biotransformation plays a central role in regulating the biological activity of isoavonoid phytoestrogens. They can convert them to potent estrogens or break them to nonestrogenic metabolites. Microbial activities are also involved in prolonging enterohepatic circulation of isoavonoids by decongugation of the liver isoavonoid metabolites. These activities result in delay in excretion, consequently prolonging the period of exposure of target tissues, such as reproductive organs. Detection of the specic bacteria from the human intestinal tract that are involved in the metabolism of phytoestrogens has
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been the subject of this study. Specic bacteria involved in biotransformation of three natural isoavonoids, biochanin A, formononetin and glycitein, to their primary more estrogenic metabolites (genistein, daidzein, and 6,7,4-trihydroxyisoavone) by demethylation, which also enhances their absorption, have been found. One of the reasons for the lack of benecial eect of phytoestrogens has been their conversion by bacteria to nonestrogenic metabolites. FDA has granted the petition for a claim that the use of soy protein is safe, however, it still does not have a ruling on isoavonoids for consumers. In addition to advancing the study of phytoestrogen metabolism, the data obtained provide background information that FDA can use when evaluating data on the benecial or detrimental eects of phytoestrogens for regulatory purposes.
6.5.2
Catechin
Catechin in chocolate
6.5.3
Pine bark
Pine bark of Finland is according to the producer of Vitabak rich on bioavonids. The content of bioavonids of the bark rises as one gets in north direction. Composition of 1 g bark Flavonoids 33,4 mg Calcium 680 mg Iron 270 mg Magnesium 250 mg Zinc 89 mg and 61% of bres. The University of Kuopio has started a research about LDL-Cholesterol reducing properties of Vitabark. 14 g of bark powder were given daily in form of bread to a special group. After one week blood cholesterol lowered about 17%. Many bioavonoids have a very bitter taste and are therefore generaly taken as supplements in time-release tablets or in capsules that will not dissolve radily in mouth. Bioavonoids are water-soluble substances associated with materials that often appear in fruits and vegetables as companions to vitamin C.According to Dr. Z. Zloch of Charles University in Czechoslovakia the antioxidant activity of bioavonoids seems to result from their unique chemical structure; they act as reducing agents which are transported to the site where vitamin C is to be stored in the cell.
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There is an increased uptake of vitamin C into the liver, kidney and adrenal gland when bioavonoids were administrated with vitamin C. There is also an increased protection of the vitamin C against oxidation because the bioavonoids convert the ascorbic acid to a less active form as dehydroascorbate. Decrease in blood cholesterol in animals treated with vitamin C together with bioavonoids was also noted by Dr. Zloch. The decrease was not so high when vitamin C was used without bioavonoids[91].
6.5.4
Maritime pine
The Maritime Pine, Pinus pinaster, is a pine native to the western Mediterranean region. Often the old generic name Pinus maritima is used for the French maritime pine. Both names refer to the same tree. The bark is a source of proanthocyanidins, also known as procyanidin oligomeric proanthocyanidin (OPC), pycnogenol, leukocyanidin and leucoanthocyanin, they are avanols.
Bibliography
[1] Burri L, Hoem N, Banni S, and Berge K. Marine omega-3 phospholipids: Metabolism and biological activities. Int J Mol Sci, 13(11):1540119, 11 2012. http://www.mdpi. com/1422-0067/13/11/15401/pdf. [2] Schuchardt JP, Schneider I, Meyer H, Neubronner J, von Schacky C, and Hahn A. Incorporation of epa and dha into plasma phospholipids in response to dierent omega3 fatty acid formulations-a comparative bioavailability study of sh oil vs. krill oil. Lipids Health Dis, 10:145, 8 2011. http://www.ncbi.nlm.nih.gov/pmc/articles/ PMC3168413/. [3] Ulven SM, Kirkhus B, Lamglait A, Basu S, Elind E, Haider T, Berge K, Vik H, and Pedersen JI. Metabolic eects of krill oil are essentially similar to those of sh oil but at lower dose of epa and dha, in healthy volunteers. Lipids, 46(1):3746, 1 2011. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3024511/. [4] Roberfroid, Marcel B.: Functional Foods; Ingredients Health and Nutrition; January 1999. [5] Kneucker,Dieter: Gesund essen mit Functional FoodLabor Praxis Nr.1; Januar 1999; 23.Jahrgang; S.4. [6] Guidance on the scientic requirements for health claims related to antioxidants, oxidative damage and cardiovascular health efsa panel on dietetic products, nutrition and allergies (nda). http://www.efsa.europa.eu/en/efsajournal/doc/2474.pdf.
430
[7] http://www.ffnmag.com/asp/articleDisplay.asp?strArticleId=530&strSite= FFNSite. Kaori Nakajima: Japans long, tough road to health claims regulations; Fuctional foods and Nutracuticals, August 2004. [8] http://www.ncbi.nlm.nih.gov/pubmed/18598379. Morrow, L.E.; Kollef, M.H.: Probiotics in the intensive care unit: why controversies and confusion abound. Crit Care. 2008;12(3):160. Epub 2008 Jun 24. [9] http://www.spiegel.de/wirtschaft/0,1518,druck-597184,00.html. Amann, Susanne: Marketing-Erfolg. Mit Joghurt Millionen scheeln. Spiegel Online 22.12.2008. [10] http://www.danone.com/en/brands/business/fresh-dairy-products.html. Danone: Healthy growth boosts agship products. [11] http://www.ncbi.nlm.nih.gov/pubmed/17337434. Khan SH, Ansari FA.: Probiotics-the friendly bacteria with market potential in global market. Pak J Pharm Sci. 2007 Jan;20(1):76-82. [12] http://www.ft.com/cms/s/0/7faa94c8-f193-11dd-8790-0000779fd2ac.html. UK Financial Times: Taste for Danones Essensis yoghurt dwindles. By Jenny Wiggins in London. February 3 2009 02:00. [13] http://www.fitsugar.com/129566. FitSugar: Essensis: Healthy From the Inside Out. 02.07.2007. [14] http://www.soya.be/adez.php. Soya, Information about Soy and Soya products.: AdeZ Fruit Juice and Soya. [15] http://www.thecoca-colacompany.com/presscenter/nr_20061011_americas_ enviga.html. New Enviga and Trade; Proven to burn Calories: Sparkling Green Tea Creates a Brand New Category That Combines Great Taste and Negative Calories. [16] http://www.cspinet.org/new/200702121.html. CSPI: Enviga Study Casts Doubt on Calorie Burning & Weight-Loss Claims. Companies Own Study Shows Many People May Expend Less Energy-Not More-After Drinking New Beverage. 12 February 2007. [17] Hap S and Gutierrez NA. Functional properties of some new zealand fruit extracts towards selected probiotic and pathogenic bacteria. Benef Microbes, pages 110, 9 2012. http://www.ncbi.nlm.nih.gov/pubmed/22968373. [18] Morton, j. 1987. feijoa. p. 367370. in: Fruits of warm climates. julia f. morton, miami, . feijoa: Feijoa sellowiana berg. http://www.hort.purdue.edu/newcrop/morton/ feijoa.html.
BIBLIOGRAPHY
431
[19] Sharm A and Zhou W:. A stability study of green tea catechins during the biscuit making process. Food Chemistry, 126(2):568573, 5 2011. http://dx.doi.org/10. 1016/j.foodchem.2010.11.044. [20] Verhoef SP, Meyer D, and Westerterp KR. Eects of oligofructose on appetite prole, glucagon-like peptide 1 and peptide yy3-36 concentrations and energy intake. Br J Nutr, pages 16, 6 2011. http://www.ncbi.nlm.nih.gov/pubmed/21679485. [21] Cani PD, Joly E, Horsmans Y, and Delzenne NM. Oligofructose promotes satiety in healthy human: a pilot study. Eur J Clin Nutr, 60(5):56772, 5 2006. http: //www.ncbi.nlm.nih.gov/pubmed/16340949. [22] Parnell JA and Reimer RA. Weight loss during oligofructose supplementation is associated with decreased ghrelin and increased peptide yy in overweight and obese adults. Am J Clin Nutr, 89(6):17519, 6 2009. http://www.ajcn.org/content/89/6/1751. long. [23] Roberfroid MB. Introducing inulin-type fructans. Br J Nutr, 93(Supl 1):S1325, 4 2005. http://www.ncbi.nlm.nih.gov/pubmed/15877886. [24] Shepherd SJ and Gibson PR. Fructose malabsorption and symptoms of irritable bowel syndrome: guidelines for eective dietary management. Journal of the American Dietetic Association, 106(10):16319, 2006. http://sacfs.asn.au/download/ SueShepherd_sarticle.pdf. [25] Muir JG, Shepherd SJ, Rosella O, Rose R, Barrett JS, and Gibson PR. Fructan and free fructose content of common australian vegetables and fruit. J Agric Food Chem, 55(16):661927, 8 2007. http://www.ncbi.nlm.nih.gov/pubmed/17625872. [26] Muir JG, Rose R, Rosella O, Liels K, Barrett JS, Shepherd SJ, and Gibson PR. Measurement of short-chain carbohydrates in common australian vegetables and fruits by high-performance liquid chromatography (hplc). J Agric Food Chem, 57(2):55465, 1 2009. http://www.ncbi.nlm.nih.gov/pubmed/19123815. [27] Biesiekierski JR, Rosella O, Rose R, Liels K, Barrett JS, Shepherd SJ, Gibson PR, and Muir JG. Quantication of fructans, galacto-oligosacharides and other short-chain carbohydrates in processed grains and cereals. J Hum Nutr Diet, 24(2):15476, 4 2011. http://www.ncbi.nlm.nih.gov/pubmed/21332832. [28] http://jama.ama-assn.org/cgi/external_ref?access_num=10.1016/ S1470-2045(02)00777-5&link_type=DOI. Phyto-oestrogens and cancer. Lancet Oncol. 2002; 3:364-373. [29] http://jama.ama-assn.org/cgi/ijlink?linkType=ABST&journalCode= jcem&resid=83/7/2223. Tham DM, Gardner CD, Haskell WL. Clinical review 97: potential health benets of dietary phytoestrogens: a review of the clinical, epidemiological and mechanistic evidence. J Clin Endocrinol Metab. 1998;83:2223-2235.
432
[30] http://jama.ama-assn.org/cgi/external_ref?access_num=10.1016/ S0163-7827(02)00006-1&link_type=DOI. Moreau RA, Whitaker BD, Hicks KB. Phytosterols, phytostanols, and their conjugates in foods: structural diversity, quantitative analysis, and health-promoting uses. Prog Lipid Res. 2002;41:457-500. [31] Jeerson WN, Patisaul HB, and Williams C. Reproductive consequences of developmental phytoestrogen exposure. Reproduction, 1 2012. http://www.ncbi.nlm.nih. gov/pubmed/22223686. [32] http://www.bfr.bund.de/cm/245/isolated_isoflavones_are_not_without_ risk.pdf. Federal Institute for Risk Assessment: Isolated isoavones are not without risk. 29 October 2007. [33] http://pubs.acs.org/doi/full/10.1021/jf801344x?cookieSet=1. Kuhnle, Gunter G. C.; DellAquila, Caterina; Aspinall, Sue M.; Runswick, Shirley A.; Mulligan, Angela A.; Bingham, Sheila A.: Phytoestrogen Content of Foods of Animal Origin: Dairy Products, Eggs, Meat, Fish, and Seafood. J. Agric. Food Chem., 2008, 56 (21), pp 10099-10104. Publication Date (Web): October 16, 2008. Doi: 10.1021/jf801344x. [34] http://cebp.aacrjournals.org/cgi/content/full/14/1/213. Low, Y.-L.; Taylor, J. I.; Grace, P. B.; Dowsett, M.; Scollen, S.; Dunning, A.M.; Mulligan, A.A.; Welch, A.A.; Luben, R.N.; Khaw, K.T.; Day, N.E.; Wareham, N.J.; Bingham, S.A. Phytoestrogen exposure correlation with plasma estradiol in postmenopausal women in European prospective investigation of cancer and nutrition-Norfolk may involve diet-gene interactions Cancer Epidemiol., Biomarkers Prev. 2005 14 1 213 220. [35] http://cebp.aacrjournals.org/cgi/content/full/16/5/1009. Low, Y.L.; Dunning, A. M.; Dowsett, M.; Folkerd, E.; Doody, D.; Taylor, J.; Bhaniani, A.; Luben, R.; Khaw, K.T.; Wareham, N.J.; Bingham, S.A. Phytoestrogen exposure is associated with circulating sex hormone levels in postmenopausal women and interact with ESR1 and NR1I2 gene variants Cancer Epidemiol., Biomarkers Prev. 2007 16 5 1009 1016. [36] http://cancerres.aacrjournals.org/cgi/content/full/66/18/8980. Low, Y.L.; Dunning, A. M.; Dowsett, M.; Luben, R.N.; Khaw, K.T.; Wareham, N.J.; Bingham, S.A. Implications of gene-environment interaction in studies of gene variants in breast cancer: An example of dietary isoavones and the D356N polymorphism in the sex hormone-binding globulin gene Cancer Res. 2006 66 18 8980 8983. [37] http://humrep.oxfordjournals.org/cgi/content/full/21/5/1184. Fraser, Lynn R.; Beyret, Ergin; Milligan, Stuart R.; Adeoya-Osiguwa, Susan A.: Eects of estrogenic xenobiotics on human and mouse spermatozoa. Human Reproduction 2006 21(5):1184-1193; doi:10.1093/humrep/dei486. [38] http://humrep.oxfordjournals.org/cgi/content/abstract/den243v1. Jorge E. Chavarro, Thomas L. Toth , Sonita M. Sadio , and Russ Hauser. Soy food and
BIBLIOGRAPHY
433
isoavone intake in relation to semen quality parameters among men from an infertility clinic. Human Reproduction, July 24, 2008 DOI: 10.1093/humrep/den243. [39] http://humrep.oxfordjournals.org/cgi/content/abstract/21/4/994. Guarducci, Elena; Nuti, Francesca; Becherini, Lucia; Rotondi, Mario; Balercia, Giancarlo; Forti, Gianni; Krausz, Csilla: Estrogen receptor alpha promoter polymorphism: stronger estrogen action is coupled with lower sperm count. Human Reproduction 2006 21(4):994-1001; doi:10.1093/humrep/dei439. [40] http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db= pubmed&dopt=Abstract&list_uids==16414215. Garrido A, De la Maza MP, Hirsch S, Valladares L: Soy isoavones aect platelet thromboxane A2 receptor density but not plasma lipids in menopausal women. Elsevier Maturitas. 2006 Jun 20;54(3):270-6. Epub 2006 Jan 18. [41] http://jama.ama-assn.org/cgi/content/full/294/12/1493. Schabath, Matthew, B.; Hernandez, Ladia M.; Wu, Xifeng; Pillow, Patricia C.; Spitz, Margaret R.: Dietary Phytoestrogens and Lung Cancer Risk JAMA.2005;294:No. 12, September 28, 2005. 1493-1504. [42] http://www.ncbi.nlm.nih.gov/pubmed/15531292. Talmadge JE, Chavez J, Jacobs L, Munger C, Chinnah T, Williamson D, Yates K. 2004 Fractionation of Aloe vera L. inner gel, purication and molecular proling of activity. IASC Aloe Special Issue. International Immunopharmacology. 14(4): 1757-1773. [43] http://www.ncbi.nlm.nih.gov/pubmed/17499928. Maenthaisong R.; Chaiyakunapruk N.; Niruntraporn S.; Kongkaew C.: The ecacy of aloe vera used for burn wound healing: a systematic review. Burns. 2007 Sep;33(6):713-8. Epub 2007 May 17. [44] http://www.ncbi.nlm.nih.gov/pubmed/9776900. Aterton, P.; Aloe vera: magic or medicine? Nurs Stand. 1998 Jul 1-7;12(41):49-52. [45] http://www.cancer.gov/templates/drugdictionary.aspx?expand=A. Cancer Institute: Dictionary of Cancer Terms: Aloe-emodin. National
[46] http://cat.inist.fr/?aModele=afficheN&cpsidt=16266603. Mildred AcevedoDuncan, Christopher Russell, Sapna Patel, Rekha Patel: Aloe-emodin modulates PKC isozymes, inhibits proliferantion, and induces apoptosis in U-373MG glioma cells. International Immunopharmacology Volume 4, Issue 14, (20 December 2004) Pages 1775-1784. [47] http://www3.interscience.wiley.com/journal/114182354/abstract?CRETRY= 1&SRETRY=0. Dong Lu, Guo; Shen, Han-Ming; Nam Ong, Choon; Chung, Maxey C. M.: Anticancer eects of aloe-emodin on HepG2 cells: Cellular and proteomic studies. Proteomics Clinical Applications: Volume 1 Issue 4. Pages 410-419 Published Online: 13 Mar 2007.
434
[48] http://www.ge.infm.it/biofisica/Adobe/Diaspro/Aloe%20pecere00.PDF. Teresa Pecere, M. Vittoria Gazzola, Carla Mucignat, Cristina Parolin, Francesca Dalla Vecchia, Andrea Cavaggioni, Giuseppe Basso, Alberto Diaspro, Benedetto Salvato, Modesto Carli, and Giorgio Palu: Aloe-emodin is a New Type of Anticancer Agent with Selective Activity against Neuroectodermal Tumors1. [49] http://www.ncbi.nlm.nih.gov/pubmed/16690538. Boudreau MD, Beland FA: An evaluation of the biological and toxicological properties of Aloe barbadensis (miller), Aloe vera. J Environ Sci Health C Environ Carcinog Ecotoxicol Rev, 2006 Apr;24(1):103-54. [50] http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=CELEX: 31988L0388:EN:HTML. Council Directive 88/388/EEC of 22 June 1988 on the approximation of the laws of the Member States relating to avourings for use in foodstus and to source materials for their production. [51] http://www.ncbi.nlm.nih.gov/pubmed/10885091. Vogler BK, Ernst E. Aloe vera: a systematic review of its clinical eectiveness. Br J Gen Pract. 1999 Oct;49(447):8238. [52] http://www.ncbi.nlm.nih.gov/pubmed/11268118. Okyar, A.; Can, A.; Akey, N.; Baktir, G.; Stlplinar N.: Eect of Aloe vera leaves on blood glucose level in type I and type II diabetic rat models. Phytother Res. 2001 Mar;15(2):157-61. [53] http://www.ncbi.nlm.nih.gov/pubmed/16819181. Tanaka M, Misawa E, Ito Y, Habara N, Nomaguchi K, Yamada M, Toida T, Hayasawa H, Takase M, Inagaki M, Higuchi R.: Identication of ve phytosterols from Aloe vera gel as anti-diabetic compounds. Biol Pharm Bull. 2006 Jul;29(7):1418-22. [54] http://www.ncbi.nlm.nih.gov/pubmed/16406411. Beppu H, Shimpo K, Chihara T, Kaneko T, Tamai I, Yamaji S, Ozaki S, Kuzuya H, Sonoda S. : Antidiabetic eects of dietary administration of Aloe arborescens Miller components on multiple lowdose streptozotocin-induced diabetes in mice: investigation on hypoglycemic action and systemic absorption dynamics of aloe components. J Ethnopharmacol. 2006 Feb 20;103(3):468-77. Epub 2006 Jan 6. [55] http://www.ncbi.nlm.nih.gov/pubmed/18186589. Prez YY, Jimnez-Ferrer E, Zamilpa A, Hernndez-Valencia M, Alarcn-Aguilar FJ, Tortoriello J, Romn-Ramos R.: Eect of a polyphenol-rich extract from Aloe vera gel on experimentally induced insulin resistance in mice. Am J Chin Med. 2007;35(6):1037-46. [56] http://www.aseanfood.info/Articles/11018276.pdf. Bozzi, A.; Perrin, C.; Austin, S.; Arce Vera, F.: Quality and authenticity of commercial aloe vera gel powders. Food Chemistry. Volume 103,Issue 1, 2007, Pages 22-30. doi:10.1016/j.foodchem.2006.05.061.
BIBLIOGRAPHY
435
[57] Kasper, Heinrich: Ernhrungsmedizin und Ditetik; Urban and Schwarzenberg 8. Auage, 1996 Pg 20. [58] o.V.: A role of carnitine in medium-chain fatty acid metabolism? Nutr. Rev. 49 (1991) 243-245. [59] Biesalski, Hans-Konrad: Ernhrungsmedizin Thieme, 1995 pg 130. [60] Scheck, A.: L-Carnitin: Sinn und Unsinn der Substituition einer krpereigenen Substanz.; Ernhrungs-Umschau 41 (1994) 9 - 15.l. [61] Juretko, Axel: Facts ber Functional Food Wissenschaftliche Informationstagung in Berlin; Lebensmitteltechnik 3/1999 S. 29. [62] Halter,Hans: Die rzte haben versagt Der President der Deutschen Krebsgesellschaft Lothar Weissbach ber die Mngel der Frherkennung, die Versumnisse der Mediziner und die Zukunft der Tumortherapie; Der Spiegel 12/2000, page 230. [63] Juberg, Daland R.: An Evaluation of Endocrine Modulators: Implications for Human Health. Ecotoxicology and Environmental Safety. Volume 45, Issue 2, February 2000, Pages 93-105. Doi:10.1006/eesa.1999.1851. [64] McLachlan, John A.; Weatherhead, Erica Simpson; Melvenia Martin: Endocrine disrupters and female reproductive health. Best Practice & Research Clinical Endocrinology & Metabolism. Volume 20, issue1, March 2006, Pages 63-75. Doi: 10.1016/j.beem.2005.09.003. [65] http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&cmd=Retrieve&dopt= AbstractPlus&list_uids=16898863. Thompson LU, Boucher BA, Liu Z, Cotterchio M, Kreiger N. Phytoestrogen content of foods consumed in Canada, including isoavones, lignans, and coumestan. Nutr Cancer 2006; (cited 2007 1 Mar);54(2):184201. [66] http://www.informaworld.com/smpp/content?content=10.1207/ s15327914nc5202_6. Coulman, Karen D. Liu, Zhen; Hum, Winston Quan Michaelides, John; Thompson, Lilian U.: Whole sesame seed is as rich a source of mammalian lignan precursors as whole axseed. Nutr Cancer. 2005;52(2):156-65. [67] http://www.menopausejournal.com/pt/re/menopause/ abstract.00042192-200815010-00029.htm;jsessionid= HcBZwK2SWyrzYSL0zzB2MvLF7XZVqJhrJLY33x7QS1jJnXhWldy5!1122534142!181195628!8091!1. Sacco, Sandra M.; Chen, Jianmin; Power, Krista A.; Ward, Wendy E.; Thompson, Lilian U.: Lignan-rich sesame seed negates the tumor-inhibitory eect of tamoxifen but maintains bone health in a postmenopausal athymic mouse model with estrogen-responsive breast tumors. Menopause. 2008 Jan-Feb;15(1):171-9.
436
[68] http://aje.oxfordjournals.org/cgi/content/abstract/kwm349v1. Kuijsten, Anneleen; Hollman, Peter C. H.; Boshuizen, Hendriek C.; Buijsman, Michel N. C. P.; van t Veer, Pieter; Kok, Frans J.; Arts, Ilja C. W.; Bueno-de-Mesquita, H. Bas: Plasma Enterolignan Concentrations and Colorectal Cancer Risk in a Nested CaseControl Study. American Journal of Epidemiology. Published on-line ahead of print 12 January 2008, doi:10.1093/aje/kwm349. [69] http://cebp.aacrjournals.org/cgi/content/abstract/15/6/1132. Kuijsten, Anneleen; Arts, Ilja C.W.; Hollman, Peter C.H.; vant Veer, Pieter; Kampman Ellen: Plasma Enterolignans Are Associated with Lower Colorectal Adenoma Risk. Cancer Epidemiol Biomarkers Prev 2006 15: 1132-1136 doi: 10.1158/1055-9965.EPI-05-0991. [70] http://www3.interscience.wiley.com/journal/117954792/abstract?CRETRY= 1&SRETRY=0. McCann, Mark J.; Gill, Chris I. R.; Linton, Trevor; Berrar, D.; McGlynn, Hugh; Rowland, Ian R.: Enterolactone restricts the proliferation of the LNCaP human prostate cancer cell line in vitro. Molecular Nutrition & Food Research Published online ahead of print, 8 April 2008, doi: 10.1002/mnfr.200700052. [71] http://clincancerres.aacrjournals.org/cgi/content/abstract/11/10/3828. Thompson, Lilian U.; Chen, Jian Min; Li,; Strasser-Weippl, Kathrin; Goss, Paul E.: Dietary axseed alters tumor biological markers in postmenopausal breast cancer. Clin Cancer Res 2005 May 15;11(10):3828-35. [72] http://www.informaworld.com/smpp/content~content=a783547576~db= all~order=page. Power, Krista A.; Ward, Wendy E.; Chen, Jian Min,; Saarinen, Niina M.; Thompson, Lilian U.: Flaxseed and soy protein isolate, alone and in combination, dier in their eect on bone mass, biomechanical strength, and uterus in ovariectomized nude mice with MCF-7 human breast tumor xenografts. J Toxicol Environ Health A. 2007 Nov;70(22):1888-96. DOI: 10.1080/15287390701549179. [73] http://www3.interscience.wiley.com/cgi-bin/abstract/112550811/ABSTRACT. Saarinen, Niina M.; Power Krista; Chen, Jianmin; Thompson, Lilian U.: Flaxseed attenuates the tumor growth stimulating eect of soy protein in ovariectomized athymic mice with MCF-7 human breast cancer xenografts. Int J Cancer 2006 Aug 15;119(4):925-31. [74] http://www3.interscience.wiley.com/cgi-bin/abstract/114281170/ ABSTRACT?CRETRY=1&SRETRY=0. Power Krista A.; Thompson, Lilian U.: Can the combination of axseed and its lignans with soy and its isoavones reduce the growth stimulatory eect of soy and its isoavones on established breast cancer? Mol Nutr Food Res. 2007 Jul;51(7):845-56. Review. DOI: 10.1002/mnfr.200600218. [75] http://www.springerlink.com/content/c1wx00ufqkwl/?p= e92cfdd557f64fa18e33b29ba2eb81de&pi=77. Horn-Ross, P.L.; Barnes, S.; Lee, M.; Coward, L.; Mandel, J.E.; Koo J.; John, E.M.; Smith, M.: Assessing phytoestrogen
BIBLIOGRAPHY
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exposure in epidemiologic studies: development of a database (United States). Cancer Causes Control 2000 Apr;11(4):289-98. [76] http://www.jstage.jst.go.jp/article/cpb/51/2/51_194/_article/-char/en. Pennaka Hari Kishore, Mopuru Vijaya Bhaskar Reddy, Duvvuru Gunasekar, Madugula Marthanda Murthy, Cristelle Caux and Bernard Bodo, A New Coumestan from Tephrosia calophylla, Chem. Pharm. Bull., Vol.51, 194-196 (2003). doi:10.1248/cpb.51.194. [77] http://aje.oxfordjournals.org/cgi/content/abstract/165/5/514. Fink, Brian N.; Steck, Susan E.; Wol, Mary S.; Britton, Julie A.; Kabat, Georey C.; Schroeder, Jane C.; Teitelbaum, Susan L.; Neugut, Alfred I.; Gammon, Marilie D. : Dietary Flavonoid Intake and Breast Cancer Risk among Women on Long Island. Am. J. Epidemiol. March 2007 165: 514-523; doi:10.1093/aje/kwk033. [78] http://cebp.aacrjournals.org/cgi/content/abstract/16/11/2285. Fink, B.N.; Steck, S.E.; Wol, M.S.; Britton, J.A.; Kabat, G.C.; Gaudet, M.M.; Abrahamson, P.E.; Bell, P.; Schroeder, J.C.; Teitelbaum, S.L.; Neugut, A.I.; Gammon: M.D. Dietary Flavonoid Intake and Breast Cancer Survival among Women on Long Island. Cancer Epidemiology, Biomarkers & Prevention. November 2007, Volume 16, Number 11, Pages 2285-2292. [79] http://cebp.aacrjournals.org/cgi/content/abstract/16/8/1621. Rossi,M.; Garavello, W.; Talamini, R.; Negri, E.; Bosetti, C.; Dal Maso, L.; Lagiou, P.; Tavani, A.; Polesel, J.; Barzan, L.: Flavonoids and the Risk of Oral and Pharyngeal Cancer: A Case-Control Study from Italy. Cancer Epidemiol. Biomarkers Prev., August 1, 2007; 16(8): 1621 - 1625.doi: 10.1158/1055-9965.EPI-07-0168. [80] http://jn.nutrition.org/cgi/content/abstract/136/2/404. Nielsen, Inge Lise F.; Chee, Winnie S.S.; Poulsen, Lea; Oord-Cavin, Elizabeth; Rasmussen,Salka E.; Frederiksen, Hanne; Enslen, Marc ; Barron, Dennis; Horcajada, Marie-Noelle; Williamson, Gary: Bioavailability Is Improved by Enzymatic Modication of the Citrus Flavonoid Hesperidin in Humans: A Randomized, Double-Blind, Crossover Trial. J. Nutr. 2006 136: 404-408. [81] http://www3.interscience.wiley.com/cgi-bin/abstract/114178333/ ABSTRACT?CRETRY=1&SRETRY=0. Gorinstein, Shela; Leontowicz, Hanna; Leontowicz, Maria ; Krzeminski, Ryszard; Gralak, Mikolaj; Jastrzebski, Zenon; Park, Yong-Seo; Jung, Soon-Teck; Kang, Seong-Gook; Trakhtenberg Simon: Eect of hesperidin and naringin on the plasma lipid prole and plasma antioxidant activity in rats fed a cholesterol-containing diet. Journal of the Science of Food and Agriculture, Vol 87, issue 7. Pages 1257-1262. Published Online: 26 Mar 2007. doi: 10.1002/jsfa.2834.
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[82] http://pubs.acs.org/cgi-bin/abstract.cgi/jafcau/asap/abs/jf072826r. html. Hwang, Sam-Long; Yen, Gow-Chin: Neuroprotective Eects of the Citrus Flavanones against H2O2-Induced Cytotoxicity in PC12 Cells. Journal of Agricultural and Food Chemistry. Published on-line ahead of print, doi: 10.1021/jf072826r Received September 23, 2007. [83] Farmakalidis E, Hathcock JN, Murphy PA. Oestrogenic potency of genistin and daidzin in mice. Food Chem Toxicol 1985 Aug;23(8):741-5. [84] Nelson HD, Haney E, Humphrey L, Miller J, Nedrow A, Nicolaidis C, Vesco K, Walker M, Bougatsos C, Nygren P. Management of Menopause-Related Symptoms. Evidence Report/Technology Assessment No. 120. (Prepared by the Oregon Evidence-based Practice Center, under Contract No. 290-02-0024.) AHRQ Publication No. 05-E016-2. Rockville, MD: Agency for Healthcare Research and Quality. March 2005. [85] http://www.ncbi.nlm.nih.gov/pubmed/20171261. Cederroth CR, Zimmermann C, Beny JL, Schaad O, Combepine C, Descombes P, Doerge DR, Pralong FP, Vassalli JD, Nef S: Potential detrimental eects of a phytoestrogen-rich diet on male fertility in mice. Mol Cell Endocrinol. 2010 Feb 18. [86] http://www.ncbi.nlm.nih.gov/pubmed/19919579. Cederroth CR, Auger J, Zimmermann C, Eustache F, Nef S: Soy, phyto-oestrogens and male reproductive function: a review Int J Androl. 2009 Nov 16. [87] http://www.ncbi.nlm.nih.gov/pubmed/19433245. Cederroth CR, Nef S: Soy, phytoestrogens and metabolism: A review. Mol Cell Endocrinol. 2009 May 25;304(1-2):3042. [88] http://www.ncbi.nlm.nih.gov/pubmed/20077194. Kwack SJ, Kim KB, Kim HS, Yoon KS, Lee BM: Risk assessment of soybean-based phytoestrogens. J Toxicol Environ Health A. 2009;72(21-22):1254-61. [89] http://www.ahrq.gov/downloads/pub/evidence/pdf/menopause/menopaus.pdf. K. Meksem, V. N Njiti, W. J Banz, M. J Iqbal, My. M Kassem, D. L Hyten, J. Yuang, T. A Winters, and D. A Lightfoot: Genomic regions that underlie soybean seed isoavone content; J Biomed Biotechnol. 2001; 1(1): 38-44. doi: 10.11551/S1110724301000110. [90] http://www.fda.gov/nctr/science/05-06_Research_Plans/pdf/ FY2005-2006ResDoc.pdf. Rai, Fatemeh:Importance of Human Intestinal Microora in Conversion of Phytoestrogens to Estrogenic Compounds (E0700701); Fy 200y 2006 Researche Accoplishments and Plans, National Center for Toxicological Researche. [91] Zloch, Z. International J.Vit. Res. 39: 269 (1969).
Chapter 7 Physiology
Research and intensive supervision of food has widened the knowledge about the physiology of nutrition. The activity of newspaper, broadcasting and television searching for sensational news have mobilized the food industry in order to optimize their products. The interest of the industry on nutrition physiology developed a great know how in the sector of laboratory analysing methods, in processing technologies, in packaging material and in storage. All these eorts resulted in better quality and safety. The consumer, however needs more information. Many basic rules for healthy nutrition are not known and misleading information are spread by commercials seeking sales increase resulting sometimes in extreme reactions of certain groups of consumers.
7.1
Diet pills and powders
Many pills and powders are sold in super market in health stores and in pharmacies. They promise wonders for much money without success [1]:
7.1.1
L-carnitin
Bodybuilder were the rst to use L-carnitin as fat-burner. L-carnitin works only with long time persistent muscle training, together with fat reduced food. L.carnitin under these condition can act as a biocarrier in the energy system of the mitochondria of the muscle cells. Without physical activity fat is not burned. Even carnitin cannot change that. Oxygen must burn the fatty acids and the resulting energy must be used. L-carnitin can be obtained by the body through synthesis using methionine and lysin in liver and kidneys. Carnitin is present in bovine and in sheep meat. That is the etymology of carnitin (Carnelatin=meat). 439
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Vegetarians could get an undersupply of carnitin. However there are no signs of over weight because vegetarians eat less fat. The use of pills containing carnitin is therefore unnecessary.
7.1.2
Tyrosine
Tyrosine is an hormone of the thyroid gland. It is supposed to stimulate burning of food components. Tyrosine is sometimes prescribed by physician to compensate an insucient function of the thyroid gland gland. In normal persons the use of tyrosine can lead to hyperfunctioning of the thyroid gland gland causing insomnia, restlessness, heart throbbing, tachycardia, trembling, fear and overexcitability as well as intensive sweat. Instead of using tyrosine normal persons should have more activity.
7.1.3
Genistein
Genistein is a phytoestrogen (plant hormone) found in soybeans being of great importance in human and in animal nutrition. The fertility of sheep and birds were found to be reduced by high amount of genistein. It may be a natural defence of plants against natural enemies. Genistein has reduced anity to estrogen receptors and thus a reduced activity compared with estrogen. As the use of soy beans in nutrition is increasing high levels of genistein in blood stream is to be expected. Importance has the nutrition in Asia which has 50 times in normal nutrition and 400 times more genistein in baby food with soy bean diet than European baby food and normal nutrition respectively. It is however interesting that there have been no reports on negative activities with such nutrition. A certain protection against women Breast cancer is brought into combination with an interference of genistein in the hormone household interfering in the menstrual cycle of Asiatic women. [2]
7.1.4
Genistein stimulates the enzyme which regulates the vascular tone and reduces hipertension [3]
Hongwei Si and Dongmin Liu studied the eect of genistein, an isoavone from soy. They found that dietary supplementation of this phytoestrogen may increase levels of endothelial nitric oxide synthase (eNOS)wich is an enzyme linked to higher endothelial-derived nitric oxide (NO) which regulates the vascular tone and atherogenesis, improving vascular health in hipertensive rats. Hypertension, blood pressure higher than 140 and 90 mmHg, is a major risk factor for cardiovascular disease Nitric oxide NO is a messenger molecule by which the endothelium of blood vessels communicates with the vessels muscles to relax. Blood pressure and the risk of infarction and strokes are reduced.
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The authors concluded that genistein improves hypertension by excerting direct genomic eects on the vascular wall leading to increased synthesis of enzyme eNOS improving vascular health and reducing hypertension.
7.1.5
Healthy lifestyle and increase of dietary potassium may reduce stroke risk [4]
Dairy foods, fruits and vegetables are rich in Potassium which is now being associated with a reduction of stroke risk, according to a meta-analysis of studies conducted by Larsson, Orsini and Wolk 2011, which included total of 8695 stroke cases. For every1000-mg/day increase in potassium intake, the risk of stroke decreased by 11%. The authors stress that the protective action of potassium is limited to ischemic strokes, the leading type of stroke, which is caused by an interruption of blood current to the brain. No association was found with hemorrhagic stroke which results from ruptured vessels in the brain. These data support foregoing studies which suggested that potassium plays an active role in reducing ischemic strokes incidence. [5] A healthy lifestyle, such as lowering the blood pressure, reducing salt intake, controlling body weight and keeping alcohol consumption, together with increased potassium rich foods intake are a good strategy to reduce the risk of stroke, say the authors. Healthy diet rich in nutrients like vitamin C, folate, magnesium, Vitamin B2, iron, vitamin A carotenoids, dietary bre, and also calcium, may increase the stroke reducing eect of potassium. [6]
7.1.6
New animal model to evaluate drug ecacy of genistein [7]
Raymond Bergan and colleagues found that genistein inhibits prostata cancer cell detachment and cell invasion in vitro by blocking activation of p38 MAP kinases molecules. The authors developed and animal model to evaluate the antimetastatic drug ecacy of genistein. Usind this model genistein was found to decreased metastases by 96%, but did not alter tumor growth. Dietary concentrations of genistein can inhibit prostata cancer cell metastasis. Studies of antimetastatic ecacy in man are warranted and are under way.
7.1.7
Natural dietary approaches to menopause disorders
The natural hormone replacement therapy concepts came about as a result of population studies in Asia. The outcomes of these studies were that many menopausal disorders of Western civilisation (1 to 5 mg/day of soy isoavones) were absent in the East due to
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large amount of soybean products (daily soy isoavone intake of estimated 50 mg/day) associated with a low fat intake. Entering menopause a diet is being recommended being moderate in protein and complex carbohydrates, with 15 to 20 % of the calories coming from fat. Saturated fat from animal products should be low, unsaturated fats should come from cold water sh (salmon, tuna, mackerel and herring). A good portion of the diet should come from soybean products, such as tofu. To keep bowel bacteria in balance Lactobacillus acidophilus should be included in the program.
7.1.8
Isoavone intake amounts
The US National Guideline Clearinghouse (NGC) suggests the following isoavone intake amounts: [8] Optimal cholesterol reduction seems to require approximately 50 mg/day of isoavones; this amount would be found in approximately 25 g/day of soy protein. For eects of arterial compliance amounts of 40-80 mg/day isoavones are needed. For antioxidant eect on lipids 10 mg/day may be eective. For bone health a minimum of 50 mg/day of isoavones are needed. For hot ashes and vasomotor symptoms 40-80 mg/day of isoavones were used in studies.
7.1.9
More evidence that soy isoavones and proteins reduce cholesterol levels [9]
In eleven studies selected for a meta-analysis Kyoko Taku and colleagues 2007 found that soy isoavones signicantly reduced serum total and LDL cholesterol but did not change HDL cholesterol and triacylglycerol. The authors concluded that soy protein containing enriched or depleted isoavones also signicantly improved lipid proles. Reductions in LDL cholesterol were larger in hypercholesterolemic than in normocholesterolemic subjects, but no signicant linear correlations were observed between reductions and the starting values.
7.1.10
Added sugars, in special fructose, may be aecting cholesterol levels [10]
Welsh and colleagues 2010 assessed the association between consumption of added sugars and blood lipid levels in adults. Carbohydrates have been associated with dyslipidemia, a
7.1. DIET PILLS AND POWDERS lipid prole known to increase cardiovascular disease risk.
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The authors found that High Density Lipoprotein (HDL), which lower blood cholesterol, decreases with higher sugar intake. The harmful blood levels, such as Low Density Lipoprotein (LDL) and the ratios of triglycerides to HDL-Cholesterol increased with high added sugar intake. The researchers say that fructose is the main component of added sugars. It is probably responsible for the increase of liver production of fat, triglycerides and Low Density Lipoproteins (LDL). The authors call for dietary guidelines that target a reduction in consumption of added sugar. The UK Food Standards Agency is active in promoting awareness on the necessity to cut sugar recommending that food manufacturers reduce saturated fat in foods such as biscuits, cakes, buns, chocolates and added sugar in soft drinks. [11] Reducing saturated fat, sugar and salt content industrial food may have a signicant eect on growing obesity and coronary diseases.
7.1.11
Antinutritional factors of soy and faba beans [12]
Antinutritional factors of soy and faba beans are trypsin inhibitors, glysinin, B-conglysinin, oligosacarides, saponines, and lectines. These factors are reduced during crushing and processing of the soy beans. According to El-Shemy and colleagues 2000, antinutritional factors such as trypsin inhibitors, phytic acid, and tannins were detected in soy bean and faba bean seeds They report that phytic acid content and trypsin inhibitor activity were higher in soy bean seeds than in faba bean seeds. The authors found that removing the cortex a high concentration of antinutritional factors such as tannins could be removed turning soy bean and faba bean suitable for human diet or industrial products.
7.1.12
Iodine and algae
Algae (Fucus vesiculosus)are sometimes used to increase the supply of iodine. and are sometimes added to diet pills and diet powders. Iodine is needed for the synthesis of thyroid gland hormones which regulate the energy household. Iodine can be obtained from marine sh, iodised kitchen salt, and food prepared with iodinated salt. The daily intake of 180 to 200 mcg is recommended. Increasing the intake over this value no further activity on the fat burning machine is takes place.
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7.1.13
Appetite depressant
Ephedrine, Norephedrine, Fenuramine can cause heart throbbing, restlessness, insomnia, and hypertension. They can cause addiction.
7.1.14
Laxatives
Long time use of laxatives leads to an important loss of potassium ions which on its turn increases the intestinal inactivity. Laxatives increase the problems. More physical activity and enough water during meals can solve it.
7.1.15
Cynarine
The bitter constituent and enzyme of chicory can promote the production of biliary acids which act on the digestion of fatty acids. Cynarine does not destroy fat as often is being told. Physical training is better than cynarine.
7.1.16
Bromelain and papain
These enzymes are found in tropical fruits such as pineapple, papaya and mango. They help the digestion of food increasing the absorption. In this way these enzymes do not reduce or destroy fat. As a matter of fact the assimilation of the food is optimized. This has nothing to do with weight reduction.
7.1.17
Herbal metabolism boosters
Some herbal metabolism boosters can temporarily cause weight drop. However, they do not eliminate excess of fat. Most of them contain stimulants which increase the central nervous system and decrease appetite. They are mild diuretics . They can cause unpleasant side eects such as dizziness, nausea, and frequent urination. As soon the administration of these drugs is ended the weight returns to its original height.
7.1.18
How to avoid diet pills
Instead of appetite depressant chew longer during meals. Eat slowly. Drink a glass of water before meals and eat a great portion of salad before the main dish.
7.2. EARLY NUTRITION PROGRAMMING PROJECT EARNEST
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Instead of laxatives eat bre rich food, drink enough water and make physical training Instead of dehydration pills use less salt in the kitchen. Eat more vegetables and fruit juices, rice containing much potassium Instead of enzymes eat protein and vitamins rich foods. The body can produce sufcient enzymes from proteins and vitamins which exist in nature. Instead of carnitin reduce the fat in your meals.
7.1.19
Breath feeding and intelligence [13]
Several studies suggest a positive association between breastfeeding and intellectual development in childhood. Mortensen and colleagues noted in a study published in 2003, that test scores suggested a dose-response relationship for breastfeeding during the rst nine months of life and adult intelligence. The researchers found a signicant positive association between duration of breastfeeding and intelligence. They conclude that duration of breastfeeding may correlate with maternal intelligence and with the quality of mother-child interaction, and that nutrients in breastmilk may have long-term positive eects on cognitive and intellectual development.
7.2
Early Nutrition Programming Project EARNEST
[14] The Early Nutrition Programming Project EARNEST is an European collaborative investigation into the long-term consequences of early nutrition by metabolic programming and will work until 2010 being coordinated by Professor Koletzko of the Childrens Hospital, University of Munich, Germany. It investigates early nutrition programming to enable a better understanding of the extent to which nutritional inuences in early life can programme a persons development and metabolism in adulthood, and studies the consumer attitudes to early nutrition programming and their economic importance. Important questions are targeted such as benecial eects of maternal diet on visual, motor and cognitive development, and cardiovascular risk factors, including obesity propensity and type II diabetes for the child. Also on the agenda is the safety of prenatal docosahexaenoic acid (DHA) supply with regard to growth, infection rates, and occurrence of other potential adverse eects, the relation between prenatal (maternal) and postnatal (infant) dietary factors and how they predict early disease markers and risk factors for chronic diseases, including chryptorchism,
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early growth patterns, psychomotor developmental milestones, atopic diseases and cognitive development. One point is the importance of promotion of breastfeeding, together with the development of the right composition of infant formula and the appropriate complementary food. The Program also wants to determine when are the critical windows during early development when maternal nutrition programmes can inuence one or more of the following chronic degenerative diseases; obesity, cardiovascular disease, metabolic syndrome, diabetes, renal disease, immune function and cancer. A possible genotype dependence of these outcomes is to be elucidated.
7.2.1
Lifestyle, environmental factors and cancer
According to a series of articles by Parkin et al 2011 published as a supplement of the British Journal of cancer, one third of all cancers are caused by tobacco, unhealthy diet, alcohol, and obesity. About 40% of all cancers are caused by things we mostly have the power to change say the authors. [15] In a foreword Professor Sir Richard Peto writes that tobacco still remains the most important avoidable cause of cancer, responsible for almost 20% of all cases of cancer. The authors determined the proportion of cancers that could be attributed to smoking tobacco, drinking alcohol, lack of fruit and vegetables, lack of ber, eating red and processed meat, too much salt, being overweight or obese, lack of physical exercise, ionizing radiation, ultraviolet radiation, occupational exposure such as asbestos, infections such as human papillomavirus (HPV), and postmenopausal hormone replacement therapy and lack of breast-feeding. A diet rich in fruits vegetables and bres proved to be an important protection against cancer in men. In women overweight was a greater cancer risk than alcohol. Parkin, however, stresses that a healthy lifestyle is still no guarantee to reduce the risk of getting cancer. There are too many factors involved, but it is what one can do to improve its health. Smoking, obesity, excessive sun exposure, are such a factor. Sir Richard Peto points out that controlling the 4 lifestyle factors that contribute most to cancers, that is tobacco, alcohol, diet, and obesity, may substantially reduce the burden of other noncommunicable diseases, particularly cardiovascular, diabetic, renal, and hepatic disease. After all, the advice from the Department of Health from 2005 [16] is still valid. It aims to improve the nutritional balance of the average diet as follows: 1. increase the average consumption of a variety of fruit and vegetables to at least ve portions per day (currently 2.8 portions per day); 2. increase the average intake of dietary bre to 18 grams per day (currently 13.8 grams per day);
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3. reduce the average intake of salt to 6 grams per day by 2010 (currently 9.5 grams per day); 4. reduce the average intake of saturated fat to 11% of food energy (currently 13.3%); 5. maintain the current trend in the average total intake of fat at 35% of food energy (currently 35.3%); and 6. reduce the average intake of added sugar to 11% of food energy (currently 12.7%).
7.2.2
Combined analysis of European Databases
EARNEST also assesses the combined analyses of the Danish National Birth Cohort (DNBC) and Norwegian Mother and Child Cohort (NMCC) databases.
7.2.3
Analysis of the information sources used by parents
The aim is to determine the information sources used by parents to acquire knowledge about matters related to infant care and nutrition in selected EU countries, and evaluate the accuracy of available information on early nutritional programming.
7.2.4
Improved dietetic producs and commercial application
The knowledge generated by EARNEST has great potential for application in new and improved dietetic products and thus for creation of wealth and employment in Europe, and studies the modication of infant formulae for commercial application. Such as innovative approaches to inulin-type oligosaccharides and a recombinant human protein, both of which are natural constituents of breast milk.
7.2.5
Height, predictors of C-peptide and cancer risk in men [17]
Giovannucci and colleagues in a study, found that excessive energy intake tends to increase circulating levels of insulin and free insulin-like growth factor-1 (IGF-I), which may increase risk of some cancers that are common in Western countries. Greater body mass index, lower physical activity, and a Western dietary pattern were independentpredictors of higher plasma C-peptide levels. A C-peptide score, based on these variables, was positively related to risk of Western-related cancers, but not to other cancer types. Height was also only related to Western-related cancers. The authors concluded that maximal growth in the pre-adult period and hyperinsulinaemia during adulthood may largely underlie the excess risk of some cancers that are common in Western populations. A substantial proportion of these cancers may be modiable in adulthood, through alterations in body weight, sedentary behaviour, and dietary patterns that stimulate hyperinsulinaemia. The risk for Western cancers could be cut by about 50% if the entire population had an adult height and C-peptide score comparable to those values seen in the lowest decile of the population.
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7.2.6
Dietary bre
Dietary bre are a variety of carbohydrates which are not hydrolysed by the digestive system of the small intestine. They comprise polysaccharides which are not starch, Oligosaccharides and lignin. They are found in vegetables, fruits, wheat bran, oat bran, sugar beet pulp, Guar gum, locust bean gum, gum arabic, Psyllium, carrageenan,gum tragacanth (Astragalus spec., alginic acid, xanthan gum, dextran, lactulose, karaya gum ( Sterculia urens) ) Dietary bre have great nutritional values for intestinal bacteria in the colon. Dietary bre have inuence in the metabolism of the carbohydrates, lipids and minerals they act protective against colon cancer.
7.2.7
Recommended daily intake of dietary bre
It schould be at least 30 g/day. European and other industrial countries daily intake of dietary bre is around 20 g/day. The intake of food rich in dietary bre should therefore be increased. Recommended composition of the dietary bre - 20 g macromolecular dietary bre of polysaccharides of not starch type. 5 g of them should be insoluble. - 15 g of resistant starch - 3-4 g oligofructose
7.2.8
Mango dietary bre
Interest in dietary bre has been increasing with scientic studies linking increased intake to reduced risks of cancers such as colorectal, and cardiovascular disease. According to the Columbia University showed the average intake in the US was about 12.5 grams a day, instead of 32 grams recommended by the US National Fibre Council. According to Nely Vergara-Valencia from the Centro de Desarrollo de Productos Bioticos del IPN Mango dietary bre might be an alternative for development of products with balanced dietary bre components and low glycaemic response, aimed to people with special carbohydrate/energy requirements. Unripe mangoes have promising chemical composition, soluble and insoluble bre content, antioxidant activity and of extractable polyphenols. The concentrated extract of mango was tested in cookies and bread with a better balance of soluble and insoluble dietary bre compared to control bakery products. The new products had higher total dietary bre that respective controls, and the products maintained signicant antioxidant capacity associated to their extractable polyphenols.
449
7.2.9
Discarded mango peel is a valuable source of antioxidants and dietary bre [18]
Mango peel from mango products processing is being discarded whilst being a valuable source of antioxidants. Prasada Rao and colleagues 2007 studied the improvement in the nutraceutical properties of the biscuits with added mango peel powder. The wheat our incorporated with mango peel powder showed an increase in water absorption, and the biscuits incorporated with 10 per cent mango peel presented a high content of total and soluble dietary ber, increased polyphenols and carotenoid content, and improved antioxidant properties. The authors concluded that mango avoured biscuits produced with wheat our and mango peel powder are dietary bre enriched.
7.2.10
Dietary ber from cerals prevent gain in body weight and waist circumference
[19] Huaidong Du and colleagues 2009 found that a 10-g/d higher total ber intake correlated with -39 g/y for weight change and -0.08 cm/y for waist circumference change for 10-g/d higher total bre, A 10-g/d higher ber intake from cereals was associated with -77 g/y weight change and -0.10 cm/y waist circumference change for bre from cereals, but no weight change with fruit and vegetable ber, compared with total dietary ber and cereal bre. The authors stress that higher intake of bre, particularly that of cereals may prevent body-weight and waist circumference gain.
7.2.11
Dietary bres, resistant starch and phenolic compounds in pasta and backery. Banana our increases undigestible carbohydrate content of pasta [20]
Maribel Ovando-Martinez and colleagues 2008 point out that unripe banana, with a high proportion of undigestible compounds, such as resistant starch and non-starch polysaccharides, might be used as our to increase resistant starch and antioxidant phenolics contents of pasta (spaghetti) of high quality. The resulting spaghetti had an increased indigestible fraction and antioxidant capacity, and low rate of carbohydrate enzymatic hydrolysis with low-glycaemic index,compared with traditional products. According to the authors the high antioxidant properties of unripe banana is due to its condensed tannins or proanthocyanidins. The authors stress that this would also create a new use for the excess of production and large quantities of bananas which are otherwise lost.
450
7.2.12
USDA Database for Proanthocyanidins 2004 [21]
Proanthocyanidins, also known as procyanidin oligomeric proanthocyanidin (OPC), pycnogenol, leukocyanidin and leucoanthocyanin, they are avanols. Proanthocyanidins are polymers of avan-3-ols, also referred to as "Condensed Tannins", with astringent avour. Their free radical scavenging properties may reduce the risk of cardiovascular diseases, cancer, blood clotting and certain types of trimeric PAs may protect against urinary tract infections. USDA provides a database for proanthocyanidins for epidemiologists and health researchers to estimate the intakes and to investigate relationships between intakes and reduction in the risks of various diseases. The database contains values for 205 food items for proanthocyanidins listed as monomers, dimers, trimers, 4-6 mers (tetramers, pentamers and hexamers), 7-10 mers (heptamers, octamers, nonamers and decamers) and Polymers (DP>10).
7.2.13
Synergistic eect of polyphenols from skin and seed from grape inhibit platlet aggregation [22]
Polyphenols composed of more than one phenol unit or building block per molecule. Polyphenols are generally divided into hydrolyzable tannins (gallic acid esters of glucose and other sugars) and phenylpropanoids, such as lignins, avonoids, and condensed tannins. (See chemical formulas at http://en.wikipedia.org/wiki/Polyphenolics) Reed and colleagues 2002 found that combining extracts of grape seed and grape skin, rich in grape polyphenolics, individually shown to inhibit platelet aggregation, might enhance their individual antiplatelet eects. Feeding the extracts individually did not aect platelet aggregation, whereas feeding them in combination in combination as found in in red wine, grape juice exhibit a greater antiplatelet eect than when present individually.
7.2.14
Apple polyphenols extand lifespan of fruit ies by 10 per cent [23]
Polyphenols include plant antioxidants such as avonoids, phenolic acids, proanthocyanidins and resveratrol. Chen et al. 2011 report that oxidative stress may be involved in the ageing process and some other diseases. Antioxidants of fruits and vegetables such as tomatoes, broccoli, blueberries, and apples may help to reduce the eects of the free radicals extending the life span in animals such as fruit ies. The authors found that apple polyphenols increased the average lifespan of fruit ies and improved their motility like walking, climbing and moving Polyphenols of apples also reduced the level of age related markers up-regulation of genes SOD1, SOD2, and CAT and down-regulation of MTH in old ies. The authors write that apple polyphenols interact with interaction with gene expressions of superoxide dismutase (SOD), catalase (CAT), methuselah (MTH), Rpn11, and cytochrome c oxidase (CcO) subunits III and Vib.
451
The authors concluded that the antiaging activity of apple polyphenols is linked to its interaction with genes SOD, CAT, MTH, and Rpn11. Several foregoing studies had referred to benecial eects of certain polyphenols. In 2003 Huxley and Neil wrote that high dietary intake of avonols from a small number of fruits and vegetables, tea and red wine may reduce the risk of coronary heart disease [24]. Cutler et al. 2008 found that avonoids of certain plant foods may reduce the risk of lung cancer among current and past women smokers, probably due to the antioxidant, antiestrogenic and antiproliferative properties of these compounds [25]. The eect of polyphenols on blood sugar was studied by Hanhineva and colleagues 2010. The authors point out that quercetin and other avonoids inhibit carbohydrate-digesting enzymes and polyphenols reduce the absorption of glucose. Other possible mechanisms cited by the authors are stimulation of insulin secretion, modulation of glucose release from the liver, activation of insulin receptors and glucose uptake in the insulin-sensitive tissues, and modulation of intracellular signalling pathways and gene expression. The authors call for more studies and human trials on the eect of polyphenols on type 2 diabetes [26]. Berries such chokeberries, cranberries, blueberries, and strawberries were found in dierent studies to be rich in anthocyanins, micronutrients and bre. These compounds reduce cardiovascular risks, LDL oxidation, lipid peroxidation and improve the total plasma antioxidant capacity, the dyslipidemia, and the glucose metabolism. Basu, Rhone and lyons 2010 write that these benecial eects may derive from an upregulation of endothelial nitric oxide synthase, decreased activities of carbohydrate digestive enzymes, decreased oxidative stress, and inhibition of inammatory gene expression and foam cell formation [27].
7.2.15
Anticancer and urinary antibacterial properties of cranberry fruit [28]
Catherine C. Neto reviewed the existing research on the anticancer properties of fruit of cranberry (Vaccinium macrocarpon). The author found that polyphenolic extracts rich in proanthocyanidins inhibit the growth and proliferation of breast, colon, prostate, lung, and other tumors, as do avonols, proanthocyanidin oligomers, and triterpenoids isolated from the fruit. The unique combination of phytochemicals found in cranberry fruit may produce synergistic health benets. The proanthocyanidins of cranberry also prevent urinary tract infections, inhibiting the adhesion of Escherichia coli bacteria. Also inhibition of the adhesion of Helicobacter pylori to human gastric mucus was noted, reducing the risk of gastric cancer.
452
7.2.16
Grape seed procianidins reduces liver cancer risk [29]
Quesada and colleagues 2007 found that procianidins inhibit the metallothionein gene expression in the liver by 70 per cent. Inhibition of the metalothionein genes expression was found dose dependent to grape seed procyanidins extract used in the study. The authors stress that metallothione in genes are direct targets of procyanidins action, both in vivo and in vitro, in hepatic cells. The authors elucidate the mechanisms how procyanidin achieves the benecial eects. Metallothionein plays an important role in transcription factor regulation. Increased expression of metallothioneins were found in some cancers of the breast, colon, kidney, liver, lung, nasopharynx, ovary, prostate, mouth, salivary gland, testes, thyroid and urinary bladder. Lower levels of metallothioneins were found in hepatocellular carcinoma and liver adenocarcinoma. [30]
7.2.17
Grape seed extracts protect from cardiovascular diseases [31]
Woodward and colleagues 2004 stress that the French have a lower incidence of cardiovascular disease than Americans. Researchers say this is an eect of grape polyphenolic of red wine consumed by French. The authors, however do not recommend red wine, neither red grape juice, because of the pro-oxidant and pro-inammatory eect of alcohol in wine and the high sugar content of the juice which might harm diabetic or promote obesity. The authors recommend therefore polyphenolic extracts of grapes as an alternative to wine or purple grape juice. Blood pressure (BP) lowering eect of polyphenols of nonalcoholic red wine Chiva-Blanch et al 2012 evaluated the eects of red wine fractions (alcoholic and nonalcoholic) on Blood-pressure and plasma nitric oxide (NO). [32] A group of participants of the study was submitted to a diet containing red wine with 30g alcohol/d being compared to a group consuming the equivalent amount of dealcoholized red wine, and a group receiving gin with 30g alcohol/d. The authors report that the polyphenols found in red wine reduces the blood-pressure, however, alcohol appears to weaken their antihypertensive eect. Daily consumption of nonalcoholic red wine may be promissing in prevention of mild to moderate hypertension, which may be associated with a 14% decrease in coronary heart disease and 20% reduction in stroke risk. The beverage industry has technologies to de-alcoholize wine. There should be a great market of the product, comparable to de-alcoholized beer.
453
7.2.18
Grape seed extract have anti ageing eect and are potent antioxidants [33]
John Shi and colleagues 2003 point out that grape seeds contain 5-8 per cent of polyphenols, proanthocyanidins including avonoids, such as gallic acid, the monomeric avan-3ols catechin, epicatechin, gallocatechin, epigallocatechin, and epicatechin 3-0-gallate, and procyanidin dimers, trimers, and more highly polymerized procyanidins. The antioxidant eect of Proanthocyanidins is 20 times greater than vitamin E and 50 times greater than vitamin C. The most abundant phenolic compounds isolated from grape seed are catechins, epicatechin, procyanidin, and some dimers and trimers.
7.2.19
Seeds and marcs from the mao plant are a good source of proanthocyanidins [34]
Puangpronpitag and colleagues 2008 analysed the seeds and marcs of Antidesma thwaitesianum Mll. Arg. or mao which, a waste product of the production of juice and wine in Thailand. The authors looked on the polyphenolic content and their radical scavenging activities of the polyphenols and proanthocyanidins. The researchers found that the protective eect of seeds and marcs of mao on lipid peroxidation is as strong as grape seed proanthocyanidin extract, and stress that mao waste products may be a good source of polyphenolics.
7.2.20
Marjoram volatile oil and grape seed extract are strong antioxidants [35]
El-Ashmawy and colleagues 2007 studied the antioxidant eect of Marjoram volatile oil (Origanum majorana L., Lamiaceae) and grape seed extract (Vitis vinifera L., Vitaceae), when simultaneously administratedwith ethanol. They found that the ethanol toxicity induced signicant alterations in the histological structures of the testis, liver and brain, an increase in lipid peroxidation and decrease in the level of glutathione in the testis, liver and brain. The co-administration of marjoram volatile oil and grape seed extract reduced signicantly the eects of ethanol toxicity on male fertility, liver and brain tissues. The authors concluded that the extracts of both plants are indicated to control oxidative damages.
7.2.21
Glutathione (GSH)
Glutathione is a tripeptide that is produced naturally all the time by the body. It is a combination of three simple building blocks of protein or amino acids, L-cysteine, glycine and L-glutamic acid. It contains an unusual peptide linkage between the amine group of cysteine and the carboxyl group of the glutamate side chain. Glutathione, an antioxidant, helps protect cells from reactive oxygen species such as free radicals and peroxides.
454
7.2.22
Gastrointestinal protective eect of dietary spices [36]
Prakash and Srinivasan report that spices, such as black pepper, piperine, red pepper, capsaicin, and ginger enhance the activities of antioxidant enzymes - superoxide dismutase, catalase, glutathione reductase, and glutathione-S-transferase - in both gastric and intestinal mucosa. They have a gastrointestinal protective eect and alleviate the diminished activities of antioxidant enzymes in gastric and intestinal mucosa induced by alcohol.
7.2.23
Anti-cancer drugs acts inhibiting the uptake of glutamine, precursor of glutathione [37]
Tamoxifen and raloxifen are selective estrogen receptor modulators (SERMs), drugs used in the treatment of breast cancer. Tumor cells are known for their high requirement of glutamine (Gln) that serves multiple functions within the cells, including nutritional and energy source, as well as one of the precursors for the synthesis of natural antioxidant glutathione (GSH). The authors found that one of the mechanisms for their anti-neoplastic properties may also cause adverse side eects inhibiting the glutamine uptake in a dose-dependent manner through inhibition of ASCT2 glutamine transporter resulting in oxidative stress which causes the death of the cancer cells.
7.2.24
Glutaminase 2 regulates energy metabolism and antioxidant function of cells [38]
The tumor suppressor p53 gene regulates cellular energy metabolism and antioxidant defense mechanisms. Hu and colleagues 2010 found the glutaminase 2 (GLS2) mediates these two functions of the p53 protein. GLS2 regulates cellular energy metabolism by increasing production of glutamate and alpha-ketoglutarate, and antioxidant defence function in cells are rugulated by increasing reduced glutathione (GSH) levels and decreasing reactive oxygen species (ROS) levels. The authors note that GLS2 expression is lost or greatly decreased in hepatocellular carcinomas. Its overexpression reduces cancer proliferation.
7.2.25
Proanthocyanidins of grape seed prevent skin cancer [39]
Meeran and Kativar report that dietary grape seed proanthocyanidins prevent photocarcinogenesis in mice. The authors stress that grape seed proanthocyanidins possess chemotherapeutic potential against human epidermoid carcinoma cells in vitro. They call for more studies to verify the chemotherapeutic eect of grape seed proanthocyanidins in skin cancers.
455
7.2.26
Polyphenols of red grape skin and grape seed extracts prevent cardiovascular diseases [40]
Hanne Frederiksen report that polyphenols in red grape skin and seed extract had positive eect on the development of atherosclerosis. In their study the authors found that grape skin and seed extract had no signicant eects in females rabbits but was associated with transient less hypercholesterolemic response to semisynthetic diet. The development of aortic atherosclerosis in males was retarded.
7.2.27
Non-nutrient dietary constituents may present useful bioactive eects [41]
Rosemary Carpenter and colleagues 2006 determined the concentration of compound that inhibited cell growth by 50% (IC50) of a range of phytochemicals and plant extracts and to investigate their antioxidant and genoprotective eects. The authors found that resveratrol presented the highest IC50 value of 13.7 g/mL, and Echinacea the lowest at 9,400 g/mL. Oxidative stress was strongly reduced by olive leaf extract and bearberry, grapeseed polyphenols and bearberry strongly protected against H2O2- and DNA damage. The authors concluded that non-nutrient dietary constituents may present important bioactive eects. Extracts of bearberry, grapeseed polyphenols, and olive leaf extract, protect against oxidative stress.
7.2.28
Resveratrol from grapes, a potent antioxidant, is nontoxic, says study [42]
Williams and colleagues 2009 found that trans-resveratrol, a polyphenolic compound found in grapes and other foods was found to be non-mutagenic in a bacterial assays, but produced disruption or breakages of chromosomes. In bone marrow test in rats, Resvida, a high pure resveratrol, however, was found to be non-genotoxic, and did not cause adverse reproductive eects in rats. Physiologic tests found resveratrol to be readily absorbed, metabolized and excreted. The authors concluded that Resvida is well tolerated and non-toxic.
7.2.29
Resveratrol fraud, scandal of scientic publications [43]
The preparations for the international Resveratrol 2012 conference scheduled for later this year became dicult on account of the controversy over the research fraud allegations against Dr Dipak Das, a member of the scientic committee of the conference. The investigations against Dr Dipak Das are going on since 2008. A report of the U.S. Oce of Research Integrity unveiled a series of manipulations of pictures using image processing software. These pictures were the basis of his study supporting health benets of resveratrol. The investigation involved a scientic paper of Dr.Das published by the University of Connecticut School of Medicines Cardiovascular Research Center (CRC) in
456 2008. [44]
According to the University of Connecticut Das fabricated and falsied data in dozens of published papers on resveratrol, saying that the bioavonoid of red wine improved cardiovascular health. The university dismisses Das and returned $890 000 of the federal research funding awarded to Dr. Das. Resveratrol became headline after results of the rst international resveratrol meeting in Denmark in 2010 were published PLoS One with Dr. Das as coauthor. The position paper of the meeting states that animal data are promising in prevention of various cancer types, coronary heart diseases and diabetes and there is a strong need for human clinical trials. Meanwhile, more than 4000 papers on resveratrol were published. [45] All publications on resveratrol reported at the 2010 meeting were published in Annals of the New York Academy of Sciences. January 2011 [46]
7.3
Resveratrol, the "anti-aging drug"
[47] The "anti-ageing" drugs are being developed by a Glaxo subsidiary called Sirtris Pharmaceutical in the US, and are thought to mimic the eects of the red wine component resveratrol as well as activate a key anti-ageing protein called SIRT1. However, a controversy arose over whether resveratrol directly activates SIRT1 as well as the anti-ageing eects of certain dietary restrictions. Minghan Wang and colleagues 2009 reports that ndings related to SIRT1 activation might be an experimental artifact. Resveratrol activates SIRT1 only when a uorescent molecule used to gauge its activity was present. [48] Dai and clloegues 2010, most of them former employees of Sirtris Phamaceuticals, claim that drugs designed to combat age-related diseases work as advertised. [49]
7.3.1
Sirtris Pharmaceuticals [50] [51]
Christoph Westphal co-founded Sirtris Pharmaceuticals in 2004 with David Sinclair and served as Chief Executive Ocer until April 2010. Dr. Westphal also founded the Longwood Founders Fund, and is currently the President of SR One, the corporate venture capital arm of GlaxoSmithKline (GSK) that invests globally in emerging life science companies. Michelle Dipp, senior vice president of Glaxos Center of Excellence for External Drug Discovery. and Christoph Westphal started online sales of resveratrol charging $540 for a
7.3. RESVERATROL, THE "ANTI-AGING DRUG"
457
one-year supply, alleging that revenues from sales are to cover the costs of a 10 years project regarding life extending properties of resveratrol. The project planed to control 10.000 subjects. Half of them receiving resveratrol as supplement, the other half a placebo.Selling resveratrol as supplement no clinical trials are needed such as those demanded by FDA for drugs to get permission to begin sales. Resveratrol supplements is being sold online for years using the most sometimes strange and unfounded claims.
7.3.2
Sirtuins extending human life span [51]
Scientists found that yeast, maggots, ies and mice lived longer and healthier when some special proteins, the sirtuins, were induced. Less cases of diabetes occurred and individuals were slimmer than the control group. The sirtuine- proteins were found to curb specic genes engaged in ageing processes, and resveratrol and a couple of other substances regulating sirtuins were identied. The Sirtris company activated the promotion of reservatrol. The farmaceutical company GlaxoSmithKline (GSK) bought Sirtris for $ 729 million in June 2008. Westphal founded then the Healthy Lifespan Institute initiating the resveratrol study. According to Spiegel Online, Dr. Westphal started the selling of reservatrol disregarding the traditional procedure of pharmacological studies which call for laboratory testing the active agent in 10 to 15 years, followed by trials on animals and nally on humans. This makes sure that only safe chemicals or botanicals are sold to consumers, the activity must be proved and side eects known. Healthy Lifespan Institute did not follow such scientic rules to market the resveratrol product. There are doubts on any eect of resveratrol on sirtuins. There are no evidences that resveratrol extends the life span of humans, says Ulrich Mahlknecht. The Healthy Lifespan Institute stopped selling resveratrol in August 2010.
7.3.3
Classication of sirtuins [52]
Sirtuins are classed according to their sequence of amino acids. They were initially found in yeasts and named sir2. In mammals, seven genes were detected and named SIRT1 to SIRT7 their expression of enzymes act as on cellular regulation.
458
From Wikipedia based on North/Verdin diagram. Sirtuin activity is inhibited by nicotinamide, which binds to a specic receptor site, so it is thought that drugs that interfere with this binding should increase sirtuin activity. Development of new agents that would specically block the nicotinamide-binding site could provide an avenue for development of newer agents to treat degenerative diseases such as cancer, Alzheimers, diabetes, atherosclerosis, and gout.
7.3.4
Alzheimers
SIRT1 deacetylates and coactivates the retinoic acid receptor beta that upregulates the expression of alpha-secretase (ADAM10). Alpha-secretase in turn suppresses beta-amyloid production. Furthermore, ADAM10 activation by SIRT1 also induces the Notch signaling pathway, which is known to repair neuronal damage in the brain.
7.3.5
Diabetes
Sirtuins have been proposed as a chemotherpeutic target for type II diabetes mellitus.
7.3.6
Aging
Cell culture research into the behaviour of the human sirtuin SIRT1 shows that it behaves like the yeast sirtuin Sir2: SIRT2 assists in the repair of DNA and regulates genes that undergo altered expression with age. Adding resveratrol to the diet of mice inhibit gene expression proles associated with muscle aging and age-related cardiac dysfunction. Preliminary studies with resveratrol, a possible SIRT1 activator, have led some scientists to speculate that resveratrol may extend lifespan. However, this hypothesis has not yet been borne out in experiments with mammals.
7.3. RESVERATROL, THE "ANTI-AGING DRUG"
459
7.3.7
No increase of life span of mice starting supplementation with resveratrol when started mid-life [53]
Rafael de Cabo and colleagues 2008 report that in elderly mice Resveratrol reduced signs of aging including reduced albuminuria, decreased inammation and apoptosis in the vascular endothelium, increased aortic elasticity, greater motor coordination, reduced cataract formation, and preserved bone mineral density. However, when supplementation started at mid-life the mice did not live longer as control mice. The authors concluded that resveratrol caused benecial eects in mice but did not increase life span when started mid-life.
7.3.8
Sirtuin Sir2/Sirt1 is connected to metabolism and inammation [54]
Tang and Chua 2010 describe the activities of Sir2/Sirt1, related to longevity in several animal models, regulating energy metabolism, such as peroxisome proliferator-activated receptor-gamma (PPARgamma), and its transcriptional coactivator, PPARgammacoactivator1alpha (PGC-1alpha). This may explain the activity of Sirt1 within the metabolic changes of a caloric restriction (CR) diet. Sirt1 is also associated with other metabolic regulators like AMP-activated kinase (AMPK). The authors stress that interfering in the activity of Sirt1 in animal, ageing-associated disorders, such as neurodegenerative diseases could be improved.
7.3.9
Sirtuins and metabolic homeostasis [55]
Yu and Auwerx 2009 stress that all sirtuins are linked to cellular energy levels. They require nicotinamide adenine dinucleotide (NAD(+)) for their deacetylase or ADP-ribosyl transferase activity. Specically SIRT1 modulates many aspects of glucose and lipid homeostasis, SIRT2, SIRT3, and SIRT4 are also implicated in other metabolic pathways.
7.3.10
Sirtuins, metabolic and degenerative diseases [56]
Dransfeld and colleagues 2010 write that sirtuins are associated with stress response, apoptosis and energy metabolism, degenerative diseases, the pathogenesis of cancer, and regulation of cellular life span. Specically SIRT3 shows strong eects on stress response, apoptosis, cell cycle and energy metabolism, mimicking eects of caloric restriction. SIRT3 was found by the authors to increase cellular respiration by 80% when compared to 30% by SIRT1.
460
7.3.11
The sirtuin activator SRT1 720 does not extend lifespan in nematodes [57]
Zarze and colleagues 2010 report that resveratrol and SRT1720 have been shown to act as sirtuin activators improving type 2 diabetes in mice. Studies using nematodes found that resveratrol extends lifespan in nematode models by more than 3%, but SRT1 720 did not have any eect on lifespan extension. The authors suggest that relevant eects of resveratrol are not found in STR 720.
7.3.12
Mitochondrial sirtuin are metabolic sensors controling enzymes [58]
According to Huang and colleagues 2010 sirtuins are important proteins in aging, stress resistance and metabolic regulation. The authors describe biochemical properties of three sirtuins SIRT3, 4 and 5, which are located within the mitochondrial matrix. Large fraction of mitochondrial proteins are acetylated which is modulated by nutritional status. The authors concluded that mitochondrial sirtuins, such as SIRT3, 4 and 5, are metabolic sensors modulating the activity of enzymes via protein deacetylation or mono-ADP-ribosylation. In a review of 2010 Aljada Dong and Mousa write that sirtuins are NAD+-dependent histone/protein deacetylases regulating various normal and abnormal cellular and metabolic processes, including tumorigenesis, neurodegeneration, and processes associated with type 2 diabetes and obesity, Alzheimers disease, and longevity. The authors describes the mechanisms regulating sirtuin activity, and how to interfere in the mechanism of related diseases. [59]
7.3.13
Apple fruit skin powder may add nutritional value of muns [60]
Vasantha and colleagues 2008 used blanched, dehydrated, and ground apple fuit skin to improve the nutritional value of muns. The apple skin powder used by the authors contained 41% total dietary bre and high content of antioxidants. The authors stressed that apple fruit skin, a by-product of apple processing, is a rich source of dietary bre and phenolics such as quercetin glycosides, catechins, chlorogenic acid, phloridzin, and cyanidin galactoside. Using apple skin powder in bakery may turn apple skin from by-product to a valious nutritional enhancer.
7.3.14
Pectin
Pectin can: - Bind and help the excretion of steroid compounds reducing thus blood level of LDLOurFood Database of Food and Related Sciences Copyright 1998-2010 Karl H. Wilm. All rights reserved.
7.4. DIETARY FIBRE AND INFLAMMATION
461
cholesterol[61]. - It increases viscosity and reduces the availability of nutritional energy. - It reduces the peak of glucose after meals. - It binds water and increases volume of faecis. - Pectin has anionic groups which can be used as a transport medium of special drugs which should act in colon. On the other side it should always taken under consideration if medication should be taken during meals or between meals as the in some cases important parts of the drug may be absorbed by pectin and other dietary bre. -Pectin can cause modication ofthe mucosa. Increase of the weight of ileum and colon of mice was found by Schmehl[62]. Low esteried pectin had great activity. Even with no limits established by food law the use of pectin should be kept in a reasonable level as the high viscosity may reduce resorption of important food components.
7.4
Dietary bre and inammation
[63] C-reactive protein (CRP) is produced in the liver and is a known marker for inammation. Increased levels of CRP are a good predictor for the onset of both type-2 diabetes and cardiovascular disease. Yunsheng Ma and colleagues suggest that a diet high in bre may play a role in reducing inammation and, thus, the risk of cardiovascular disease and diabetes, and that dietary bre is protective against high CRP. 20 to 35 grams of bre per day, including both soluble and insoluble bre are being recommended. It was suggested that dietary bre could reduce the oxidation of fats and that soluble bre act as prebiotics improving gut health diminishing inammatory conditions.
7.5
7.5.1
Dietary natural agents and cancer

Lupeol from fruits and vegetables [64]
Lupeol, a triterpene present in fruits and vegetables is being studied as dietary natural agent to slow tumour progression in prostate cancer. Lupeol treatment resulted in signicant inhibition of cell viability in a dose-dependent manner and caused apoptotic death of prostate cancer cells. Among all death receptor targets examined, Lupeol specically caused a signicant increase in the expression of Fas receptor. The small interfering RNA-mediated silencing of the Fas gene and inhibition of caspase-6,
462
caspase-8, and caspase-9 by their specic inhibitors conrmed that Lupeol specically activates the Fas receptor-mediated apoptotic pathway in androgen-sensitive prostate cancer cells. The treatment of cells with a combination of anti-Fas monoclonal antibody and Lupeol resulted in higher cell death compared with the additive eect of the two compounds alone, suggesting a synergistic eect. Because early clinical prostate cancer growth is an androgen-dependent response, the results of the present study suggest that Lupeol may have a potential to be an eective agent against prostate cancer.
7.5.2
Green tea
Green tea polyphenols, a mixture of various polyphenols inhibit the growth and progression of prostate cancer in TRAMP mice. Epidemiologic reports support that green tea may reduce prostate cancer risk in humans. During the course of prostate cancer development and progression the eectiveness of green tea is not yet certain in humans. However, based on the study, it is suggested that green tea in general and polyphenols present therein may prove to be a useful supplement in the prevention or slower progress of prostate cancer in humans. [65] The IGF-I/IGFBP-3 signalling pathway is a prime pathway for green tea polyphenol mediated inhibition of prostate cancer that limits the progression of cancer through inhibition of angiogenesis and metastasis.
7.5.3
Chemopreventive and chemotherapeutic activity of C3G compound from blackberry [66]
Min Ding an colleagues say that epidemiological data suggest that consumption of fruits and vegetables has been associated with a lower incidence of cancer. Cyanidin-3-glucoside (C3G), a compound found in blackberry and other food products, was shown to possess chemopreventive and chemotherapeutic activity in the present study. They conclude that a puried compound of anthocyanin inhibits tumor promoter-induced carcinogenesis and tumor metastasis in vivo.
7.5.4
Antioxidant-rich foods and essential fatty acids slows down brain decay [67]
Willis, Shukitt-Hale and Joseph 2009 report that increased oxidative stress and modications in brain lipid composition cause damage and dysfunction of the ageing brain. The authors stress that inclusion of antioxidant-rich foods and essential fatty acids in the diet can slow the age-related progression of cognitive and behavioural decline.
7.6. GREEN TEA REDUCING CANCER RISK
463
7.5.5
Moderate consume of walnuts protects brain from ageing [68]
James A. Joseph and colleagues 2009 found that adding a moderate, 7 to 9 walnuts/day to an otherwise healthy diet improves motor and behavioural skills middle-aged individuals. Polyphenols, other antioxidants and essential fatty acids are the content of walnut which cause the benecial neurological eects. However, higher doses of walnut impaired performance in the rodent study. The authors concluded that walnuts, eaten in moderation protect the neural tissue from ageing.
7.5.6
Blackberry improves cognitive function in aged rats [69]
Joseph and colleagues 2009 write that polyphenols from fruits and vegetables increasing antioxidant and/or anti-inammatory levels, or by direct eects on signalling, in the brain retard and even reverse age-related decrements in motor and cognitive performance. The authors report that increased dietary intake of 2% blackberry-supplemented diet improved balance and co-ordination working, or short-term, memory performance in aged rats.
7.5.7
Genistein [70]
Studies in vitro suggest that osteopontin (OPN), an extracellular matrix protein secreted by macrophages inltrating prostate tumours, and by tumour cells, may have a role in the transition from clinically insignicant tumours to metastatic prostate cancer. Studies are consistent with the possibility that dietary genistein may delay the progression from benign to malignant tumours by inhibiting OPN expression. Our earlier studies in Transgenic Mouse Prostate adenocarcinoma (TRAMP) mice showed that genistein, an isoavone found in soybeans, lowered the incidence of advanced PC. This suggested that lower intake of dietary soy may be one possible cause for higher incidence of advanced prostate carcinome in Western men. [71]
7.6
Green tea reducing cancer risk
Green tea is supposed to reduced risks of breast, lung, prostate and ovarian cancer. Black tea does not present cancer protective eect. The meta-analysis of Can-Lan Sun and colleges from the Cancer Center of the University of Minnesota indicates a lower risk for breast cancer with green tea consumption. Available data suggest a possible late-stage, promotional eect of black tea on breast carcinogenesis. [72]
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Administration of green tea to SKH-1 mice, via the drinking uid, was found to significantly reduce the incidence and volume of ultraviolet B (UVB) radiation-induced skin tumors in a study by leading author Q Liu. [73] Epigallocatechin Gallate is an anti-oxidant polyphenol avonoid isolated from green tea. Its possible benet as a nutritional chemopreventive agent for cancer, atherosclerosis, and neurodegenerative diseases is generating increased scientic interest. The protection from breast cancer by tea is related specically to the catechin content, specically epillocatechin. According to Joshua D. Lambert and Chung S. Yang a typical cup of brewed green tea contains, by dry weight, 30-40% catechins including epicatechin, epigallocatechin, epicatechin3-gallate, and epigallocatechin-3-gallate. Through fermentation, a large percentage of the catechins are converted to oligomeric theaavins and polymeric thearubigins in black tea. The resulting brewed black tea contains 3-10% catechins, 2-6% theaavins and >20% thearubigins. [74] The catechins have been demonstrated to undergo considerable biotransformation and to have low bioavailability. The theaavins are even less bioavailable. This poor availability confounds attempts to correlate in vitro ndings with cancer prevention in animal models. Cell line studies typically require concentrations of compound in the 5-100-micro mol/L range. Such concentrations are typically not observed systemically. [74]
7.6.1
Adding milk to tea does not reduce bioaccessibility of catechins [75]
van der Burg-Koorevaar, Miret and Duchateau 2011 tested the eect of skimmd milk and full-fat milk on the polyphenols of English black tea and Indian black tea. The authors found that milk proteins formed polyphenolprotein complexes resulting in decrease of total catechin (TCAT) recovery, however the bioaccessibility of polyphenols remainde unchanged compared with tea without milk. The authors concluded that digestion degrades the polyphenolprotein complexes and the healthy eects of tea remain unchanged with or without added milk.
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7.6.2
Japan Public Health Center-based Prospective Study Group: Green tea polyphenols may increase stomach cancer in men but reduces the risk in women [76]
Shizuka Sasazuki and colleagues 2008 investigated the eect of the tea polyphenols on the risk of gastric cancer in a nested case-control study. The authors found an increased risk of gastric cancer for men, when a high plasma level of (-)-epigallocatechin was measure. For women, a high plasma level of (-)-epicatechin3-gallate (ECG) of 9.3 ng/mL and up, decreased risk of gastric cancer by 73 per cent compared with ECG not detectable cases. The eect of ECG plasma levels below 9.3 ng/ml was not signicant. The authors suggest that cigarette smoking to play a role as an eect modier observed between men and women.
7.6.3
Dietary supplementation with green tea extract, epigallocatechin gallate EGCG as a contribution to anti-diabetic nutritional strategies [77]
Swen Wolfram and colleagues in a study found that dietary supplementation of epigallocatechin gallate (high purity green tea leaf extract] resulted in improved oral glucose tolerance, blood glucoses levels, lower free fatty acid plasma concentrations, as well as increasing plasma insulin concentrations in mice and rats. The researchers wrote that EGCG downregulated genes involved in gluconeogenesis, as well as genes involved in the synthesis of fatty acids, triacylgycerol, and cholesterol. The authors conclude that EGCG benecially modies glucose and lipid metabolism in H4IIE cells and markedly enhances glucose tolerance in diabetic rodents. Dietary supplementation with EGCG could potentially contribute to nutritional strategies for the prevention and treatment of type 2 diabetes mellitus if the ndings can be translated to humans.
7.6.4
Green tea does not reduce iron absorption [?]
Ariel et al. 2012 found that iron Fe2+ absorption was not reduced by green tea, compared to a group with a diet without tea. The authors, however, noted that the expression of salivary proteins decreased. Reduced were amylase, chitinase, deoxyribonuclease, cysteine-rich secretory protein 1, and parotid secretory protein. The authors concluded that the iron absorption inhibitory effects of tea is balanced by a modied protein composition of the saliva of the rats with
466 green tea in their diet.
7.6.5
Dierent response to anti-diabetic drug rosiglitazone in lean and obese humans [78]
Lefebvre and colleagues 2010 stress that obese patients have chronic, low-grade inammation that predisposes to type 2 diabetes and results, in part, from dysregulated visceral white adipose tissue (WAT) functions. The authors describe the PARgama signaling pathway operates dierently in the visceral WAT of lean and obese. PPARgama in visceral, but not subcutaneous WAT from obese mice displayed increased sensitivity to activation by its agonist, an anti-diabetic drug rosiglitazone which acts as an insulin sensitizer, by binding to the PPAR receptors in fat cells and making the cells more responsive to insulin. The authors explain the selective proteasomal degradation of RXRalfa initiated by UCH-L1 upregulation which modulates the relative anity of PPARgama heterodimers for SMRT and their responsiveness to PPARgama agonists, activating the PPARgama-controlled gene network in visceral WAT of obese animals and humans.
7.6.6
Plasma glucose concentration at 1 hour during the oral glucose tolerance test to predict the risk for type 2 diabetes [79]
Muhammad A. Abdul-Ghani and colleagues 2008 assessed the ecacy of 1-h plasma glucose concentration and the metabolic syndrome in predicting future risk of type 2 diabetes. The authors suggest the use of the plasma glucose concentration at 1 hour during the oral glucose tolerance test to predict the risk of type 2 diabetes. A plasma glucose higher than 155 mg/dl, and the Adult Treatment Panel ATP III criteria for the metabolic syndrome was found useful to classify nondiabetic patients into three risk groups: low, intermediate, and high risk.
7.6.7
Macrophage cells in fat tissue may explain the link between obesity and diabetes [80]
Wentworth and colleagues 2010 found that the presence of macrophage cells in fat tissue are closely related to insulin resistance in human obesity. Macrophage cells are special white blood cells which are produced by the bone marrow as a response to an infection. In obese people, macrophages move into the fat tissue where they cause inammation and release cytokines, Certain cytokines cause cells to become resistant to the eects of
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the hormone insulin, leading to diabetes and heart disease. The authors write that complications of obesity such as insulin resistance and diabetes, cardiovascular disease associated with hardening of the arteries, and liver problems are the result of the inammation. Developing drugs which control the macrohage release of cytokines may reduce the risk of these diseases, say the authors. The authors also report that weight reduction caused the macrophages in the fat tissue to disappear reducing the risk of developing insulin resistance and diabetes.
7.6.8
Vegetables but not fruits protect against type 2 diabetes [81]
Raquel Villegas and colleagues 2008 examined associations between fruits and vegetables intake and the incidence of type 2 diabetes. They found that vegetables in general and as individual groups were inversely associated with type 2 diabetes. Fruit intake did not reduce the risk of diabetes. In this study consumption of about 430 grams vegetables per day, was associated with a 28per cent lower risk of diabetes compared with low consumption of about 129 grams per day. The authors suggest that the hight content in bre, antioxidants, magnesium and a low glycemic index in vegetables were responsible for the decreased risk of type 2 diabetes, but could not entirely explain it, other compounds such as phytates, lignans, isoavones, vitamin E and C, but not beta-carotene might have an additive or synergetic eect. The authors concluded that vegetables, but not fruit consumption may protect against the development of type 2 diabetes.
7.6.9
Bamboo leaves extract
The active compounds, include avone, phenolic acid, lactone, polyose, amino acid, and microelements of bamboo extract and are, according to Carol Cheow from Cactus Botanics, linked to protection of blood vessels, the liver, improving sleep quality, protection against cancer, and anti-age, having positive impacts on the health and longevity of human beings.
7.6.10
Bamboo shoots, fruit, vegetables and honey are rich in xylooligosaccharides which have benecial eect on gut health [82]
Chung and colleagues evaluated the eects of xylooligosaccharides on the intestinal microbiota, gastrointestinal function, and nutritional parameters of elderly people. In the study
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4 grams of xylooligosaccharides for three weeks signicantly increased the population of bidobacteria, increased the faecal moisture content, and decreased the faecal pH value due to increased production of short chain fatty acids such as butyrate and proprionate. In this study the supplementation of xylooligosaccharides was found more eective than prebiotics like inulin and fructooligosaccharides in promoting the intestinal health.
7.6.11
Eective daily dosage of oligosaccharide for humans [83]
Fructooligosaccharides (FOS) = 3.0 g Xylooligosaccharides = 0.7 g
7.6.12
Compound to increase the capacity of learning [84]
Interfering in the function of the brain to improve learning and memory has a long histrory of trials an errors. None of chemicals used proved to be without side eect. Greely and colleagues 2008 point to the fact that on university campuses around the world, prescription drugs such as Adderall and Ritalin are dealt between the students to get higher grades. The authors stress that such transactions are not legal and are punished in U.S.A. by prison. Thaler 2009 comments the article of Greely et al 2008 Nature 456: 702-705. The author analyses the possibility of humane societal appreciation of mind-altering drugs, such as cognitive enhancing drugs. The author hypotheses the use of ever-smaller amounts of psychoactive drugs reducing the harm and proting from benign eects. The authors ignites again the discussion of cognitive enhancing drugs for healthy individuals, and turns the attention to gene-environment interaction regarding the cognitive ability. [85]
7.6.13
Notropics and cognitive enhancers [86]
Nootropics, also referred to as smart drugs, memory enhancers, and cognitive enhancers, are drugs, supplements, nutraceuticals, and functional foods that are purported to improve mental functions such as cognition, memory, intelligence, motivation, attention, and concentration. Nootropics are thought to work by altering the availability of the brains supply of neurochemicals (neurotransmitters, enzymes, and hormones), by improving the brains oxygen supply, or by stimulating nerve growth. However the ecacy of nootropic substances, in most cases, has not been conclusively determined.
7.7. GREEN TEA AND AMYLOIDOSIS
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7.6.14
Dierenciating between nootropic and cognitive enhance
A nootropic is a cognitive enhancer that is neuroprotective or extremely nontoxic. A cognitive enhancer is a substance that enhances concentration and memory, such as the amphetamines. These drug may have serious side-eects. The nutrients in food can inuence our memory, learning, concentration, and decisionmaking, therefore the lack of them has a negative eect on the brain. So far, the studies have been able to link brain function to vitamin B1 and B12, omega-3, caeine, antioxidants, protein, and iron. A varied diet with plenty of fruits and vegetables is thus the best way to enhance learning and memory.
7.6.15
Dietary supplements are not subjected to US premarketing regulatory clearance
Goldman 2001 points to the fact that many herbal products are of uncertain composition which may be unsafe. Herbal medicines are regulated as dietary supplements, which do not need a premarketing regulatory clearance required for drugs. The burden of proof is on the U.S. Food and Drug Administration to show a dietary supplement is unsafe, unlike for drugs. [87]
7.6.16
Polyphenolics in fruits and vegetables enhance cognitive function [88]
Shukitt-Hale, Cheng and Joseph 2009 found that dietary intake of a 2% blackberrysupplemented diet reversed age-related decits in behavioural and neuronal function in rats. This study suports previous investigations of the authors demonstrating improved motor and cognitive performance in aged rats after supplementation with other berry fruits. The authors write that the positive eects of the polyphenols may result from an antioxidant and/or anti-inammatory activity, or by directly interfering on signal transmission in the brain.
7.7
Green Tea and amyloidosis
[89] A 2012 study of the Medical Clinic Heidelberg/Germany looked at the eect of green tea on Transthyretin-related hereditary amyloidosis, a heart disease. The disease is characterized by the deposition of amyloidogenic variants of the transthyretin protein, especially in the peripheral nervous system, causing a progressive sensory and motor polyneuropathy. In the absence of a liver transplant, amyloidosis is invariably fatal, usually within a decade. Green tea (Camellia sinensis) is known to have several benecial health eect. About one third of the dry substance of green tea are catechins of the group of polyphenols. The
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main cathichin of green tea is (-)-epigallocatechin gallate (EGCG), with Epigallocatechin3-Gallat being the active form which is biologically active in a concentration of about 140 - 190 mg EGCG/litre green tea. Kristen et al 2012 of the Heidelberger study report that EGCG reduce the deposition of amyloid in Morbus Alzheimer animal model. In vitro EGCG dissolved amyloid deposition, which are known to impair brain cells of Alzheimer patients. Heart muscles were strengthened in vitro. In this study the patients had a daily intake of 500700 mg EGCG either by drinking 1.52 L of green tea/day per day (10g/L Green tea brewed 35 min at 1000 C , and containing about 340mg EGCG/L; or by the intake of 300 mg green tea extract with 75 mg EGCG/capsule). The data of the single-center observational Heidelberger report on the eects of green tea consumption in patients with amyloidotic transthyretin (ATTR) cardiomyopathy suggest an inhibitory eect of green tea or green tea extract on the progression of the disease. The authors call for a randomized placebo-controlled investigation to conrm these results. [90] The report of one patient, with amyloidosis, W. Hunstein, in 2006, describes markedly improved myocardial deformation conditions and quality of life drinking 2 litres of green tea/day, presumably because of its contents of EGCG (epigallocatechin gallate) and other phenols. This report had triggered the Heidelberg study of 2012. [91] Dr. Hunstein, in a letter to the Amyloid Center Heidelberg writes that EGCG is unstable and is quickly oxidized upon contact with oxygen in the air. EGCG is poorly absorbed. This may be improved black pepper extract or omega-3 sh oil. However, Dr. Hunstein urges to increase research to nd a pharmaceutical form of EGCG. Only with parenteral administration can 20- to 25-fold higher plasma levels be reached compared to that which may be attained via oral intake with all the tricks, as described by Shammas et al. (Blood, 2006) for cytotoxic eects, e.g. as those required for human plasmocytoma cells in animal experiments. [92]
Cathechins interactions with human genes [93] According to the Comparative Toxicogenomics Database catechins increase the expression of human gene such as PTGS2 (is a dioxygenase), IL1B (forms cyclooxygenase-2 (PTGS2/COX2)), CAT (is a catale and is decreased by cathechins), CYP1A1 (is a active in the metabolism of xenobiotics), SOD (Superoxide dismutase), BAX (Bcl-2associated X protein promotes cell apoptosis), CASP3 (Caspase 3, also active in cell apoptosis), MAPK1 and 3 (Mitogen-activated protein kinase 1and 3 are extracellular enzymes involved in cell processes), and S100B (S100 calcium binding protein B is a pro-inammatory enzyme).
7.7. GREEN TEA AND AMYLOIDOSIS EGCG antiadrenal cancer properties [94]
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According to Wu et al. 2009, Epigallocatechin-3-gallate (EGCG) of green tea has anticancer properties. The authors investigate the anticancer eect and molecular mechanisms of EGCG inducing growth inhibition on human adrenal NCI-H295 cancer cells. The authors suggest that EGCG as a drug candidate for the treatment of human adrenal cancer. Conversion of toxic amyloid proteins into nontoxic agregates [95] Protein misfolding and formation of -sheet-rich amyloid brils or aggregates is related to cellular toxicity and decay in various human disorders including Alzheimers and Parkinsons disease. Bieschke et al. 2010 demonstrated that the polyphenol (-)-epi-gallocatechine gallate (EGCG) inhibits -synuclein and amyloid- brillogenesis, and converts large, mature -synuclein and amyloid- brils into smaller, amorphous nontoxic protein aggregates. Teaavins of black tea [96] Grelle et al. 2011 report that theaavins (TF1, TF2a, TF2b, and TF3), of fermented black tea, are potent inhibitors of amyloid- (A ) and -synuclein (S) brillogenesis, causative agents of Alzheimers disease and Parkinsons disease. The eect of theaavins on amyloid proteins were compared with EGCG and congo red, all of them bind to the amino acids 12-23 and 24-36 of amyloid proteins. EGCG and theaavins promote the assembly of A and S into nontoxic, spherical aggregates. The nontoxic forms of amyloid cannot act as a seeling for further toxic amyloid forms. TF3 was more stable under oxidizing conditions compared to EGCG. The authors concluded that theaavins are promising agents which remove toxic amyloid deposits.
7.7.1
Green tea and cognitive function [97]
According to Kuriyama from the Tohoku University Graduate School of Medicine, Japan, considerable experimental and animal evidence shows that green tea may possess potent activities of neuroprotection, neurorescue, and amyloid precursor protein processing that may lead to cognitive enhancement, no human data are available. That is why Kuriyama analysed the consumption of green tea, black tea, oolong tea and coee) Green tea is a rich source of catechins, compounds suggested to play a benecial role in weight loss, cardiovascular and oral health, such as epigallocatechin gallate which is said to be brain permeable . Its protection of the brain is proposed to be due to mechanisms other than its antioxidant and iron-chelating properties. Modulation of cell survival and cell cycle genes and promotion of neurite overgrowth activity are cited as possible mechanism. This may be the reason why Kuriyama found that drinking more than two cups of green
472
tea a day could cut the risk of dementia by half in elderly Japanese subjects. Kuriyama concluded that a higher consumption of green tea is associated with a lower prevalence of cognitive impairment in humans. Kuriyama found only a weak or null relation between consumption of black or oolong tea or coee and cognitive impairment. The authors, however point out the limitations of the study noting that healthier and more active individuals might have more opportunities to consume green tea which might promote higher cognitive function.
7.7.2
Green tea catechin Polyphenols reduces oxidative stress in sleep-disordered breathing [98]
Obstructive sleep apnea is a breathing problems during sleep where soft tissue in the rear of the throat collapses and closes during sleep increasing risk of oxidative stress and changes in the brain tissue in areas involved in learning and memory. This sleep-disordered breathing is characterised by intermittent hypoxia which impairs spatial learning and increases NADPH oxidase activity and oxidative stress in rodents. [99] Isabel C. Burckhardt and colleagues 2008 studied the eect of oral supplements of green tea-derived polyphenols to reduce the neural susceptibility to intermittent hypoxia during sleep in rodents. The authors write that green tea catechin polyphenols (GTPs) may attenuate intermittent hypoxia-induced neurobehavioral decits by reducing intermittent hypoxia-induced NADPH oxidase expression, lipid peroxidation, and inammation. Following the results of their study the authors conclude that oral GTP attenuates intermittent hypoxia-induced spatial learning decits and mitigates intermittent hypoxiainduced oxidative stress through multiple benecial eects on oxidant pathways. The authors suggest further studies on the therapeutic role of green tea catechin polyphenols in sleep-disordered breathing to reduce oxidative processes underlying neurocognitive decits associated with these sleep disorders.
7.7.3
Habitual snoring are also associated with impair of neurocognitive functions [100]
Michael S. Urschitz and colleagues found in 2003 that habitual snoring (i.e., snoring frequently or always) was associated with poor academic performance in these primary school children. This was only partially related to intermittent hypoxia. Urschitz concluded that
7.8. NEURODEGENERATION AND FOODS
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primary snoring and/or upper airway resistance syndrome rather than obstructive sleep apnea-hypopnea syndrome were the cause cognitive impairments. The authors stress that habitual snoring (i.e., snoring frequently or always) without intermittent hypoxia, up to now largely considered benign, may impair neurocognitive functioning in children and, thereby, their performance at school. The ndings of Urschitz and colleagues extend the possible potential benets of green tea polyphenols also to habitual snoring.
7.8
7.8.1
Neurodegeneration and foods

Cycad plants used traditionally for food and medicine on Guam cause of ALS [101]
For a long time the search was going on to explain the chemical trigger of neurodegeneration by food. Spencer, Fry and Kisby present the fascinating story which started examining the toxin of the cycad plants used for food on Guam. The toxin (cycasin: methylazoxymethanol (MAM)- -d-glucoside) was the cause of a complex neurodegenerative disease, a combinations of amyotrophic lateral sclerosis (ALS), parkinsonism (P), and/or a dementia (D) akin to Alzheimers disease (AD). How food may cause neurodegeneration Spencer and colleagues explain that modication of the lifestyle at Guam the disease complex among the aected families (ALS was replaced by P-D and then by D) and and in two genetically distinct ALS-PDC-aected populations (Kii-Japan, West Papua-Indonesia) which used the plant as medicine. MAM forms DNA lesions that perturb mouse brain development and induce malignant tumors in peripheral organs. These lesions are normally repaired by O(6)-methylguanine methyltransferase (MGMT). The brains of young adult MGMT-decient mice given a single dose of MAM show DNA lesion-linked changes in cell-signalling pathways associated with miRNA-1, which is implicated in colon, liver, and prostate cancers, and in neurological disease, notably AD. MAM is metabolised to formaldehyde, a human carcinogen. Formaldehyde modulate MAM-associated genes miR-17-5p and miR-18d, which regulate genes involved in tumour suppression, DNA repair, amyloid deposition, and neurotransmission. The toxic contents of cycad derived foods explain the microRNA status of the Guam population, both to ALS, AD, and parkinsonism initiation and progression. Cycad plants have been reported to x nitrogen in association with a cyanobacterium
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living in the roots. These blue-green algae produce a neurotoxin called amino acid betamethylamino-L-alanine BMAA that is found in the seeds of cycads. BMAA is stored in the kesh of ying foxes wich consume cycad fruits. The Chamorro used to eat the esh of these animals acquiring the toxin despite detoxifying the fruits for the production of four for baking. [102] The role of micro RNAs [103] microRNAs (miRNAs) are small non-coding RNAs that mediate post-transcriptional gene silencing and promote mRNA degradation. Feng 2012 stress the link between dysregulation of microRNAs and human brain disorders such as neurodevelopmental and neurodegenerative diseases. The microRNA212/132 family contains miR132 and miR212 involved in tissue development and in the formation and plasticity of neuronal connections. Tognini and Pizzorusso 2012 underline their importance in pathological processes. [104] Numerous miRNAs are particularly important in neural development and function. They are involved in synaptic plasticity and brain diseases. According to Ruberti et al 2012 recent applications of miRNA antisense oligonucleotides, miRNA gene knockout and miRNA sponges in neuronal cells and miRNA-based therapies for neurological pathologies related to alterations in miRNA present signicant improvements of neurodegeneration treatment. [105] The miRNAs play a role regulating early brain development and in mediating synaptic plasticity later in life. Pathology of neurological disorders may be caused by altered expression or functioning of miRNAs. Olde Loohuis et al 2012 assesses the consequences of miRNA dysregulation. [106] Toxic environmental factors associated with sporadic ALS [107] Gagliardi et al 2012 report that recent ndings suggest a link of environmental poisons to sporadic amyotrophic lateral sclerosis (ALS). The avin-containing monooxygenases (FMOs) and paraoxonase (PONs) genes encode enzymes involved in detoxication and are associated with ALS. According to the authors FMO5 expression was generally higher in spinal cord and brain of ALS subjects compared with healthy persons. However, the PON2 gene was downregulated in ALS patients. FMO and PON are involved in the detoxication processes during ALS disease suggesting that environmental toxin exposure may play a role in the aetiology of the disease. Poisons in food, environment and oxidative stress should not be neglected in research of neurodegerneration diseases.
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7.8.2
Smoking increases risk of Amyotrophic Lateral Sclerosis (ALS) via formaldehyde exposure say EPIC data [108]
Gallo and colleagues, analysing data of EPIC, report that smokers and those who smoked more than 33 years have an almost two-fold risk of dying from ALS, while the risk of former smokers is 50%, compared to never smokers. The authors highlight the role of cigarette smoking in the aetiology of ALS and write that the exposure to formaldehyde from the smoke triggers the lipid peroxidation causing the disease.
7.8.3
Bioindicators of ALS disease [109]
Parkin-like proteins and iron and zinc bindings were found by Mendoa et al. 2012 in cerebrospinal uid (CSF) of ALS patients diering from cerebrospinal uid of healthy subjects. The authors explain that parkin is a ligase involved in ubiquitin-proteasome pathway. Mutations in the parkin gene are a cause of recessive familial Parkinsons disease, and iron and zinc are involved with many important metabolic processes and are related to neurodegenerative disease. Parkin-like proteins and high levels of iron and zinc ions are an bioindicator of ALS disease.
7.8.4
Pesticides and agricultural chemicals, manganese copper and lead may increase risk of Parkinson Disease [110]
Exposure to pesticides and agricultural chemicals in rural areas was reported to trigger Parkinson Disease. Willis and colleagues 2010 in a new study, analysed the environmental risk factors in urban areas. They found that manganese and copper emissions may be some of the triggers of the disease in susceptible individuals. Data from 1988 to 1998 of the Toxic Release Inventory of the Environmental Protection Agency were used. No strong correlation between industrial lead output and the incidence of Parkinson Disease was found. This, however, may be due to other sources, such as lead paint, lead in the water, or other sources. The authors suggest that all these environmental contaminants may have a neurotoxic eect in the same area of the brain aected in Parkinson Disease, interfering with the ability to eliminate toxic radicals. The metals may also induce or accelerate the formation of protein clumps during neurodegeneration. The authors concluded that urban Parkinson Disease incidence is greater in counties with high reported industrial release of copper or manganese. Environmental exposure to metals may increase risk of Parkinson Disease in urban areas. However, research should concentrate on overall metal pollution levels rather than focusing on any particular industry.
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7.8.5
Three major competing hypotheses exist to explain the cause of the Alzheimer disease (AD) [111]
The cholinergic hypothesis, proposes that the disease is caused by reduced synthesis of the neurotransmitter acetylcholine. However, treating acetylcholine deciency is not eective. Other cholinergic eects have also been proposed, for example, initiation of large-scale aggregation of amyloid leading to generalised neuroinammation. The amyloid hypothesis says that amyloid beta deposits are the fundamental cause of the disease. The gene for the amyloid beta precursor (APP) is located on chromosome 21, and people with trisomy 21 (Down Syndrome) who thus have an extra gene copy almost universally exhibit AD by 40 years of age. Also APOE4, the major genetic risk factor for AD, leads to excess amyloid buildup in the brain before AD symptoms arise. The tau hypothesis says that the hyperphosphorylated tau protein begins to pair with other threads of tau. Eventually, they form neurobrillary tangles inside nerve cell bodies. When this occurs, the microtubules disintegrate, collapsing the neurons transport system ending in the death of the nerve cells. However, epidemiological studies have proposed relationships between certain modiable factors, such as diet, cardiovascular risk, pharmaceutical products, or intellectual activities among others, and a populations likelihood of developing AD. Only further research, including clinical trials, will reveal whether, in fact, these factors can help to prevent AD. The components of a Mediterranean diet, which include fruit and vegetables, bread, wheat and other cereals, olive oil, sh, and red wine, may all individually or together reduce the risk and course of Alzheimers disease. Several vitamins such as B12, B3, C or folic acid have been found in some studies to be related to a reduced risk of AD but other studies indicate that they do not have any signicant eect on the onset or course of the disease and may have important secondary eects. Curcumin from the curry spice turmeric has shown some eectiveness in preventing brain damage in mouse models. There is still no conclusive therapy for the disease. Much research is being done on this disease.
7.8.6
Visininlike protein 1 (VILIP-1) in cerebrospinal uid for early diagnosis of Alzheimers disease [112]
Tarawneh et al.2012 report that visininlike protein 1 (VILIP-1) in cerebrospinal uid may be used as an indicator of ongoing injury to brain cells in patients with Alzheimers disease. In very mild cases of the disease prediction of the rate of cognitive decline over roughly 3 years could be made. Levels of VILIP-1 may thus become useful as a marker of neuronal injury, and are being considered by the authors to better than biomarkers such as tau,
477
p-tau, and amyloid beta 1-42 (A -42) in predicting rate of decline. This must, however be conrmed with more data. Cognitive decline progressed more rapidly in individuals with VILIP-1 560 pg/mL than individuals with lower values. The authors concluded that VILIP-1 is similar to tau and tau/A 42 and may become become useful to nd neurodegeneration in early Alzheimers disease. In an earlier study, the authors pointed to the need of cerebrospinal uid markers that can detect Alzheimers disease pathology before signs of the disease show up and start medication early. In this study the authors found VILIP-1 and VILIP-1/A 42 to be useful in early diagnosis of Alzheimers disease before cognitive abnormalities arise, similar to tau and tau/A 42. [113]
7.8.7
Alzheimers disease may be infectious. Contagious material may spread protein misfolding [114]
According to Soto et al. 2011the misfolding of amyloid- (A ) peptides and their accumulation in the brain triggers the Alzheimers disease, The researchers look now for the mechanisms responsible for the initiation of A accumulation. The authors report that A deposition can be induced by injection of AD brain extracts into animals. The disease spreads to other brain sections, even distant from injection point. The study suggests that Alzheimers disease underlies a prion-like mechanism of disease transmission through propagation of protein misfolding, spreading by infectious particles, similar to other neurological diseases such as mad cow disease and Creutzfeldt-Jakob disease in humans. Following such theory blood transfusions may thus be an Alzheimers disease transporter. Krohn et al. 2011 stress that the intracerebral clearance of amyloid- (A ) peptides A via the blood-brain barrier is reduced by approximately 30% in Alzheimers patients. The authors demonstrated that transporter ABCC1 is implicated in cerebral A clearance and accumulation. Its deciency increases cerebral A levels, without inuencing the production of A protein. The activation of ABCC1 reduced A accumulation in brains of rats. Krohn and colleagues suggest to develop drugs which activate ABCC1 transporters to inuence the disease development. [115] Polymenidou and Cleveland 2011 stress that the accumulation of misfolded proteins in several neurodegenerative diseases, such as Alzheimer, Parkinson, and Huntington diseases, is similar to the eect of infectious prion proteins. Such a prion-like mechanism has also been demonstrated in relation to the misfolded proteins, SOD1 and TDP-43 in amyotrophic lateral sclerosis (ALS). [116]
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7.8.8
Omega-6 arachidonic fatty acid may increase risk of Alzheimers disease [117]
Rene O Sanchez-Mejial and colleagues 2008 suggest that raised levels of the omega-6 fatty acid arachidonic acid may be linked to Alzheimers disease, according to the study in a mouse model. Fatty acids, such as arachidonic acid are part of the phospholipids that form the protecting membranous barrier from the nerve cells. The researchers found an increase in arachidonic acid and related metabolites in the brain of Alzmeimer mice. Arachidonic acid is released in the brain from phospholipids by enzymes of the phospholipase A2 (GIVA-PLA2) which were found to be elevated in the memory centre located in the hippocampus of diseased mice. Reduction, or removal of the PLA2 enzyme in Alzheimers mice by genetic engineering prevented memory deciency and other behavioural abnormalities in these mice. The authors believe that arachidonic acid cause is likely to cause excitation and neurons dysfunction. Normal function of the neurons may be restored by lowering the levels of arachidonic acid. The study suggests that reducing dietary omega-6 fatty acids from intake of poultry, cereals, eggs, nuts, vegetable oils and evening primrose oil, and developing medication to reduce the PLA 2 enzime activity may benet treatment and prevention of Alzheimers disease.
7.8.9
Dietary pattern to reduce Alzheimer disease risk [118]
Gu and colleagues 2010 found a dietary pattern which is strongly protective against the development of Alzheimer disease. This diet is high in omega-3 polyunsaturated fatty acids, omega-6 polyunsaturated fatty acids, vitamin E and folate but low in saturated fatty acids and vitamin B12, so as found in salad dressing, nuts, sh, tomatoes, poultry, fruit and green leafy vegetables, and low of high fat dairy, red meat and butter. Folate and vitamin B12 are known to reduce blood levels of homocysteine which is associated with dementia. The dietary pattern provides low ingestion of saturated fatty acids and higher ingestion of polyunsaturated fatty acids, vitamin E, and folate, this reduces the risk of Alzheimer disease. The authors stress the importance of the combination of the components of the diet. Focusing on an isolated increase or reduction of just one component is not sucient to build the protective eect.
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7.8.10
Glutaminyl cyclase [119]
Dr Hans-Ulrich Demuth of the company Probiodrug. Steen Roner from the University of Leipzig and colleagues 2008 studied the enzyme glutaminyl cyclase which is responsible for the production of the protein that cause blockages in the brain of Alzheimers patients. The researchers want to shut o production of the glutaminyl cyclase enzyme to stop the production of these proteins. The authors added an enzyme inhibitor to the food of diseased mice which started to produce up to 80 per cent less build-up of Alzheimer-causing proteins in their brains.
7.8.11
Gamma-secretase modulators [120]
A new class of drugs, gamma-secretase modulators (GSM) is told to reduce harmful long proteins and promote levels of shorter protein elements protecting against the disease.
7.8.12
Reduction of risk of age-related neurodegenerative pathologies [121]
Beta-amyloid deleterious role in the Alzheimers disease: Bastianetto and colleagues found that green and black tea extracts and avan-3-ols were neuroprotective active against toxicity induced by beta-amyloid-derived peptides.
7.8.13
Strong activity
Strong active avan-3-ol were found to be gallic acid, epicatechin gallate (ECG) and epigallocatechin gallate (EGCG) being the strongest of them.
7.8.14
Epigallocatechin ineective
Bastianetto and colleagues found epicatechin and epigallocatechin ineective in the same range of concentrations. According to this study the catechin gallates (through the galloyl moiety) contribute to the neuroprotective eects of both green and black teas, reducing age-related neurodegenerative diseases, such as Alzheimer disease. The content of catechins of green tea is about 70 mg per 100 mL. Black tea contains only about 15 mg per 100 mL. Green tea should therefore be given preference.
7.8.15
Increased intake of folate by diet and supplements may decrease risk of Alzheimers disease.
[122] Luchsinger and colleagues studied the role of higher intake of folate, vitamins B6 (pyridoxCopyright 1998-2010 Karl H. Wilm. All rights reserved. OurFood Database of Food and Related Sciences
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ine hydrochloride) and B12 (cyanocobalamin) in decreasing the risk of Alzheimer disease (AD) through the lowering of homocysteine levels. The authors concluded that higher folate intake from both dietary and supplements decrease the risk of Alzheimerss disease about 50%, and that the eect of folate was independent of other risk factors and levels of s B6 and B12 . The authors point out that dietary folate nor supplements alone were signicantly linked to Alzheimers disease risk; only the two in combination appeared to produce an eect, and that vitamin B12 and B6 levels were not associated with Alzheimers disease risk. Lower homocysteine levels were found in the group of higher folate intake. Homocystein is involved in the accumulation of amyloid proteins in the brains causing Alzheimer disease. The authors call for clinical studies before the decision to increase folate intake to prevent Alzheimers disease can be made. The results of the ongoing "B-Vitamin Treatment Trialists Collaboration" addressing the link between B-vitamins, homocysteine levels, and cognitive function should be waited for.
7.8.16
Hypothesis says that vitamin D may reduce risk of dementia [123]
Wiliam B. Grant hypothesises that vitamin D can reduce the risk of developing dementia based on observational evidences that vitamin D deciency, associated with increased risk for cardiovascular diseases, diabetes mellitus, depression, dental caries, osteoporosis, and periodontal disease, may also be a risk factor for dementia. The laboratory evidence included ndings of neuroprotection and inammation reduction related to vitamin D. The author calls for observational studies of incidence of dementia with respect to prediagnostic serum 25(OH)D or vitamin D supplementation.
7.8.17
Vitamin E supplementation in Alzheimers Disease may prevent loss of cognition in some individuals, in others it may be detrimental. [124]
Ana Lloret and colleagues 2009 studying vitamin E prevention of oxidative stress and loss of cognition in Alzheimers Disease found that some individuals responded to a supplementation of 800 IU of vitamin E per day for six month. The blood oxidized glutathione (GSSG) levels were lower after the treatment and scores on the cognitive tests were maintained. No prevention of oxidative stress, however, was found at other individuals which presented a detrimental eect of cognitive functions.
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The authors recommend, therefore, that supplementation of Alzheimers Disease patients with vitamin E should be monitored by determining the oxidative stress indicator GSSG in each patient.
7.8.18
Vitamin E reduces the risk of dementia and Alzheimer Disease [125]
Devore and colleagues 2010 studied the intake of vitamin E, vitamin C, beta carotene, and avonoids relative to long-term risk of dementia and Alzheimer disease. The authors, using data of the Rotterdam Study [126], found that persons with highest intake of vitamin E (18.5 mg per day, just over the recommended daily intake of 15 mg.) were 25% less likely to develop dementia and Alzheimer disease. Dietary intake levels of vitamin C, beta carotene, and avonoids were not associated with dementia risk or Alzheimer disease. The authors concluded that high intake of foods rich in vitamin E may reduce the risk of dementia and Alzheimer disease. This underlines the importance of a nutrition rich in fruit, vegetables and vitamin E of wheat germ, nuts such as almonds and hazelnuts, vegetable oils such as sunower and safower oils, and some green vegetables, such as spinach and broccoli. High doses of vitamin E from supplements increase risk of bleeding, adults should consume no more than 1,000 mg of vitamin E per day. Foods, however, cannot provide such high levels of vitamin E.
7.8.19
Alzheimers Disease Cooperative Study: Antioxidants and coenzyme CoQ did not result in benecial eects in Alzheimers Disease [127]
The antioxidant combination of vitamin E, vitamin C, and alpha-lipoic acid (ALA) did not alter cerebrospinal uid (CSF) biomarkers related to beta-amyloid-42 (A 42), tau, or P-tau181 in a 16-week study of patients with mild to moderate Alzheimers disease (AD), in a study of Galasko et al. 2012. Several studies had supported the antioxidant treatment in Alzheimers disease. However, the study of Galasko and colleagues did not nd the expected benecial antioxidant eects in central nervous system in diseased patients receiving 800 IU/d of vitamin E (tocopherol) plus 500 mg/d of vitamin C plus 900 mg/d ALA (E/C/ALA); 400 mg of CoQ 3 times a day for 16 weeks. Although a decrease in oxidative stress in the brain, as seen on a reduced level in CSF F2-isoprostane, an accelerated cognitive decline on the Mini-Mental State Examination (MMSE) was found, suggesting that a supplementation with E/C/ALA could adversely aect cognition in AD. The coenzyme CoQ did not improve indices of oxidative stress or neurodegeneration.
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The authors concluded that E/C/ALA antioxidants, despite reducing the oxidative stress in the brain, were associated with a faster cognitive decline.
7.8.20
Omega 3 fatty acids increase the protein SorLA/LR11 which reduces the expression of Alzheimers disease
[128] According to Greg M.Cole and colleagues found in a study that omega-3 docosahexaenoic acid (DHA) could increase the production of LR11, a protein key to the clearance of enzymes in the brain that make the beta amyloid plaques that cause Alzheimers disease.
7.8.21
Curcumin reducing Alzheimers risk [129]
Inammation in Alzheimers disease is characterized by increased cytokines and activated microglia. Long-term use of nonsteroidal anti-inammatory drugs are used the reduce the risk of Alzheimers disease. The authors found curcumin promising to reduce excessive use of nonsteroidal anti-inammatory drugs which can cause gastrointestinal, liver, and renal toxicity. Curcumin signicantly lowered oxidized proteins and interleukin-1 Beta, a proinammatory cytokine elevated in the brains of these mice. The authors concluded that curcumin spice may be promising for the prevention of Alzheimers disease. Curcumin is a polyphenolic compound derived from the plant Curcuma Long Lin. It has been antioxidant and anti-inammatory eects and reduces beta-amyloid aggregation in models of Alzheimers disease in mice. Ringman et al 2012 report that curcumin is well tolerated by humans and may become useful to treat the disease. [130]
7.8.22
Supplements of oligomeric proanthocyanidins (OPCs) may improved memory in animals and may become a treatment of dementia and Alzheimers disease [131]
Mice with age-related decits in learning and memory were fed with oligomeric proanthocyanidins (oligomers) (OPCs) on memory impairment. During the study Yokosawa and colleagues found that administration of oligomers improved spatial and object recognition impairment in mice due to an increase in the densities of axons, dendrites and synapses. Oligomers led to a neuroprotective role in the brains of the animals caused by an increase in the phosphorylation of vascular endothelial growth factor receptor (VEGFR)-2, more accentuated in the hypothalamus and choroid plexus than in other brain regions. Aging
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may lead to an increased risk of dementia and Alzheimers disease. These compounds may become interesting for the food industry.
7.8.23
A diet rich in omega 3 fatty acids reduces amyloid burden in an aged Alzheimer mouse [132]
According to Greg M. Cole and colleagues in 2005 increased intake of the omega-3 (n-3) polyunsaturated fatty acid (PUFA) docosahexaenoic acid (DHA) is associated with reduced risk of Alzheimers disease. DHA levels are lower in serum and brains of Alzheimers disease patients, which could result from low dietary intake and/or PUFA oxidation. In a mouse study the authors found that DHA-enriched diets signicantly reduced total beta-amiloid by >70% when compared with low-DHA or control chow diets. They concluded that dietary could be protective against beta -amyloid production, accumulation, and potential downstream toxicity. LR11 increase beta-amyloid production and may be a signicant genetic cause of late-onset Alzheimers disease. The authors concluded that DHA increases SOR/LR11 levels and may play an important role in preventing late-onset Alzheimers disease.
7.8.24
Can commercial green tea extract ward of Alzheimer and other diseases? [133]
Antioxidants of green tea may reduce oxidative stress induced by a build up of beta-amyloid protein deposits and brain cell damage and death induced by Alzheimers disease. Haque and colleagues 2008 report that green tea extracts in the form of Mitsui Norins commercial Polyphenon E composed of 63% of epigallocatechin-3-gallate, 11% of epicatechin, 6% of (-)-epigallocatechin and 6% of (-)-epicatechin-gallate prevents cognitive impairment in rats. A solution of 0.5 per cent of the green tea extract was fed to rats. Haque says that humans with a body weight of 50 kg must drink 3 litres/day of such solution to have a similar dose of antioxidants used in the study. However, one litre could be sucient if other antioxidant rich foods such as high in vitamins A, B, C and E as well as polyphenols were in the every days diet. The authors concluded that long-term administration of this commercial green tea extract prevents cognitive decits caused by oxidative stress, beta-amyloid-induced in rats. The authors stress that it is not known if same positive eects may result in humans. The food industry eager to present new functional qualities which may be hailed in marketing strategies, is increasingly focused on green tea as ice tea, energy bars, dairy products and backery products. Microencapsulation is being used to hide the bitter note of comCopyright 1998-2010 Karl H. Wilm. All rights reserved. OurFood Database of Food and Related Sciences
484 mercial green tea extracts.
In his study Hague and colleagues point to the fact that a high amount of 15 to 25 gram/day for a normal person of such commercial extracts are needed to produce the Alzheimer protective eects. Adding traces of such extracts to all kind of foods, drinks and confectioneries will decisively improve the performance of the product on market but its health benets may be challenged. The consumer should be aware that these functional products cannot replace drinking green tea , having a diet rich in vegetables and fruits, reducing intake of lean calories and fat.
7.8.25
The role of tea in wound healing, cardiovascular-related diseases and cancer [134]
Restricted oxygen supply (hypoxia) such as found in altitude sickness when oxygen supply to tissue or the whole body is restricted apoptosis takes place meaning that cells die. According to Hae Jeong Park, it is an important factor in wound healing, cardiovascularrelated disease and certain cancers. EGCG was found to have a benecial eect against hypoxia-induced apoptosis for human haematoma cells. According to Park EGCG probably prevents the expression of a certain enzyme called caspase 3, which plays a important role in programmed cell death.
7.8.26
FDA report on possible anti-cancer eect of green tea [135]
The origin, risk factors, diagnosis, and treatment for each type of cancer are unique. Since each form of cancer is a unique disease based on organ site, risk factors, treatment options, and mortality risk, each form of cancer must be individually evaluated in a health claim petition. As a result, the agency considered whether the studies supported the potential substance - disease relationship for any type of cancer. Two studies do not show that drinking green tea reduces the risk of breast cancer in women, but one weaker, more limited study suggests that drinking green tea may reduce this risk. According to FDA it is, therefore, highly unlikely that green tea reduces the risk of breast cancer and concludes that existing evidence does not support qualied health claims for green tea consumption and a reduced risk of any other type of cancer.
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7.8.27
Polyphenolic extracts of green tea, chokeberry and honeysuckle fruits reduce digestibility and absorption of nutrients [136]
Polyphenols are compounds present in teas and fruits. They are eective to scavenge free radicals and reduce the risk of a variety of diseases. Frejnagel and Wroblewska assessed the eects of high doses of polyphenol extracts (0,4%) from green tea chokeberry and honeysuckle fruits on nutrient absorption in male Wistar rats. Absorption from the small intestine of nutrients like zinc (Zn) and copper (Cu) was heavily and digestibility slightly decreased. However no harmful outcomes resulted from the consumption of polyphenol-rich extracts,concluded the authors.
7.9
Cannabinoids
[137] Cannabinoids are the active components of Cannabis sativa Linnaeus (marijuana) and their derivatives. Cannabinoids received renewed interest in pharmacology in recent years due to their diverse activities such as cell growth inhibition, anti-inammatory eects and tumour regression. Results of studies suggest that WIN-55,212-2 or other non-habit-forming cannabinoid receptor antagonists could be developed as novel therapeutic agents for the treatment of prostate cancer.
7.9.1
Cannabis, neurodegenerative diseases and cancer [138]
The endocannabinoid system, including endogenous ligands (endocannabinoids ECs), their receptors, synthesizing and degrading enzymes, as well as transporter molecules, has been detected from the earliest stages of embryonic development and throughout preand postnatal development. ECs are bioactive lipids, which comprise amides, esters and ethers of long chain polyunsaturated fatty acids. Anandamide (N-arachidonoylethanolamine; AEA) and 2-arachidonoylglycerol (2-AG) are the best studied ECs, and act as agonists of cannabinoid receptors. Thus, AEA and 2-AG mimic several pharmacological eects of the exogenous cannabinoid delta9-tetrahydrocannabinol (Delta(9)-THC), the psychoactive principle of cannabis sativa preparations like hashish and marijuana. Recently, however, several lines of evidence have suggested that the EC system may play
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an important role in early neuronal development as well as a widespread role in neurodegeneration disorders. The G protein-coupled receptors (GPCRs) Many of the eects of cannabinoids and ECs are mediated by two G protein-coupled receptors (GPCRs), CB1 and CB2. Both CB1 and CB2 couple primarily to inhibitory G proteins and are subject to the same pharmacological inuences as other GPCRs. The play a role in the EC pathway from neurodevelopment to neurodegenerative disorders, like Alzheimers disease, Parkinsons disease, Huntingtons disease, and multiple sclerosis. Ligands [139] In biochemistry and pharmacology, a ligand is a substance, that forms a complex with a biomolecule to serve a biological purpose. It is a signal triggering molecule, binding to a site on a target protein. Ligand binding to a receptor protein alters its chemical conformation. The conformational state of a receptor protein determines its functional state. Ligands include substrates, inhibitors, activators, and neurotransmitters. Endocannabinoids The human body creates cannabinoid-like chemicals within our own bodies, known as endocannabinoids. Endocannabinoids and cannabinoid receptors are involved many biochemical activities, such as helping to control brain and nerve activity, energy metabolism, heart function, the immune system and reproduction. A disfunction of their interaction with other biological systems leads, among others, to neurodegenerative diseases. Cannabis and cancer At the moment, there simply isnt enough evidence to prove that cannabinoids works to treat cancer in patients, although research is ongoing. And there is certainly no evidence that "street" cannabis can treat cancer. [140] McKallip et al. 2005 tested the impact of the exposure to Delta-9-tetrahydrocannabinol (Delta9-THC), the major psychoactive component in marijuana. Their ndings suggest that marijuana exposure either recreationally or medicinally may increase the susceptibility to and/or incidence of breast cancer as well as other cancers. [141] According to Bowles et al. 2012 Cannabis smoke may be carcinogenic but it has been dicult to conclusively link cannabis use and cancer development epidemiologically, and cannabinoids have shown some promise as anti-cancer therapies. Cannabinoids can palliate some cancer symptoms but it is unclear how eective they are compared to or combined
7.9. CANNABINOIDS with conventional therapies. [142]
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The main active ingredient of cannabis, (9) -tetrahydrocannabinol ( (9) -THC), produces its eects through activation of CB(1) and CB(2) receptors. CB(1) receptors are found in the central nervous system, and CB(2) receptors are concentrated in cells of the immune system. The two best characterized endocannabinoids identied to date are anandamide (AEA) and 2-arachidonoylglycerol (2-AG). Activation of the endocannabinoid system impacts breast, prostate and bone cancers by means of complex mechanisms. The authors stress that pro- and anti-apoptotic eects of cannabinoids have been reported. [143]
7.9.2
Cannabis sativa and amyotrophic lateral sclerosis (ALS) [144]
Reports suggested a neuroprotective eect of the Cannabis sativa plant. The cannabis resin, Delta(9)-tetrahydrocannabinol (Delta(9)-THC) acts on a G-protein coupled receptor in the brain. Endogenous cannabinoid compounds regulate the neuronal excitability. Researchers are hopeful that endocannabinoid-based therapies may reduce excitotoxic and oxidative cell damage as well as neuroinammation. Primary theories of the causes of amyotrophic lateral sclerosis (ALS) are susceptibility to excitotoxicity, oxidative damage and the regulation of glutamate activity. Signicant increases of glutamate in plasma and other post-mortem ndings are reported in ALS patients. Neurotoxicity of glutamate is, therefore, being suggested. Also loss of function of EAAT2 expressed exclusively by glia, in the motor cortex and spinal cord of 6070% of sporadic ALS patients are being considered. An increased cohort of CB2-positive microglia/macrophages are also reported. The involvement of the endocannabinoid system in the progression of disease in ALS mice and the benets associated with the administration of cannabinoid agonists by several studies. AEA and 2-AG accumulate in the lumbar spinal cord of ALS mice during disease progression and are presumed to be part of an endogenous defence mechanism. According to Basavarajappa et al. 2009, the endocannabinoids (ECs) Anandamide (Narachidonoylethanolamine; AEA) and 2-arachidonoylglycerol (2-AG) act as agonists of cannabinoid receptors. AEA and 2-AG present similar eects of the exogenous cannabinoid delta9-tetrahydrocannabinol (Delta(9)-THC) of cannabis sativa. This EC system is important factor during early neuronal development, however it may also present a role in neurodegeneration disorders. Many of the eects of cannabinoids and ECs are mediated by two G protein-coupled receptors (GPCRs), CB1 and CB2, which couple primarily to inhibitory G proteins. [145] The G-proteins are known as cannabinoid receptors of type 1 (CB1) and type 2(CB).
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CB1 receptors are expressed in neurons and regulate neurotransmitter release and synaptic streng. CB2 receptors are produced by glial cells and microglia. These cells are activated and over-express in neurological disorders. According to Carter et al. 2010, the sensitivity of cannabinoid CB1 receptor controlling both glutamate and GABA transmission was upregulated in ALS mice. This demonstrates the involvement of CB1 cannabinoid in the aethiology of ALS. Cannabinoid CB1 receptors should be included in therapeutic researches. [146] Bilsland et al. 2006 reports that synthetic cannabinoid, WINSS,212-2, signicantly delays disease progression. Genetic ablation of the Faah enzyme, which results in raised levels of the endocannabinoid anandamide, prevented the appearance of disease signs in mice However, the synthetic cannabiboid and the Faah ablation had no eect on life span. Ablation of the CB1 receptor signicantly extended life span and prevented the appearance of disease signs in mice. The authors concluded that cannabinoids are neuroprotective in ALS mediated by non-CB1 receptor mechanism. [147] Dronabinol, a synthetic THC [148] A synthetic THC called dronabinol is marketed as Marinol in Germany. Dronabinol was rescheduled in 1994 from annex I to annex II of the Narcotics Law in order to ease research; in 1998 dronabinol was rescheduled from annex II to annex III and since then has been available by prescription, whereas delta(9)-THC is still listed in annex I. Faulty RNA editing and abnormal activation of specic glutamate receptors as well as failure of glutamate transport resulting in glutamate excitotoxicity; however, the excitotoxicity theory is challenged by the inability of anti-glutamate drugs to have major diseasemodifying eects clinically. According to Martin and Chang 2012, motoneuron excitability is strongly modulated by synaptic inhibition mediated by presynaptic glycinergic and GABAergic innervations and postsynaptic glycine receptors (GlyR) and GABA(A) receptors. Abnormal synaptic inhibition resulting from dysfunction of interneurons and motoneuron GlyRs are suggested as target for a medication of ALS. [149] Microglia and glia cells: Microglia are a type of glial cell that are the resident macrophages of the brain and spinal cord, and thus act as the rst and main form of active immune defense in the central nervous system (CNS). Microglia constitute 20% of the total glial cell population within the brain. Microglia (and astrocytes) are distributed in large nonoverlapping regions throughout the brain and spinal cord. Microglia are constantly scavenging the CNS for plaques,damaged neurons, and infectious agents. [150] Cytotoxicity: In addition to being able to destroy infectious organisms through cell to cell contact via phagocytosis, microglia can also release a variety of cytotoxic substances,
7.9. CANNABINOIDS
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such as H2O2 and NO, Proteases and cytokines which directly damage cells and lead to neuronal cell death. Microglia can also injure neurons through NMDA receptor-mediated processes by secreting glutamate and aspartate. Chronic inammatory response can result in large scale neural damage as the microglia ravage the brain in an attempt to destroy the invading infection. [150] The sensitivity of cannabinoid CB1 receptors controlling both glutamate and GABA transmission was remarkably potentiated in ALS mice. Cannabinoid CB1 receptors may therefore become a target for medication of ALS, write Rossi et al. 2010. [151] An agonist is a chemical that binds to a receptor of a cell and triggers a response by that cell. Agonists often mimic the action of a naturally occurring substance. Whereas an agonist causes an action, an antagonist blocks the action of the agonist and an inverse agonist causes an action opposite to that of the agonist. [152] Excitotoxicity: Excitotoxicity is the pathological process by which nerve cells are damaged and killed by excessive stimulation by neurotransmitters such as glutamate and similar substances. This occurs when receptors for the excitatory neurotransmitter glutamate (glutamate receptors) such as the NMDA receptor and AMPA receptor are overactivated. [153] Cannabinoids as treatment ALS [144] Pathologic changes in endocannabinoid levels and CB2 expression are induced by the inammatory environment. Activation of CB2 by up-regulated endocannabinoids may reduce microglial activation. This, however, is insucient to prevent the subsequent inammatory damage to neurons, which may also suer from the loss of protection conferred by the down-regulated CB1. Sativex, an oromucosal spray delivering delta(9)-THC and cannabidiol, was found useful in treatment of symptoms of neuropathic pain and disturbed sleep. In animal models, Sativex was found to attenuate cannabinoid-mediated inammation, stimulate remyelination, and recover behavioural and symptomatic recovery in animal models. The extensive cell loss and inammatory environment of the ALS disease leaves the question whether the disease is caused by the pathological process, or it is a symptom of it, and endocannabinoids may either protect cells from the disease process, or treat the symptoms of the disease. CB1 activation has been shown to be eective in limiting cell death following excitotoxic lesions, while CB2 is involved in dampening inammatory immune cell response to disease. These two targets may therefore work together to provide both neuroprotection to acute injury and immune suppression during. Synthesis or degradation enzymes may also become a promising research target.
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Treatment with delta(9)-THC was eective if administered either before or after onset of signs in ALS mice. Bilsland et al. (2006) found a signicant delay in disease progression when another cannabinoid agonist WIN55,212-2. Bisland stresses that endocannabinoids are neuroprotective in ALS. Microglia from ALS mice possess increased cytotoxic potential. CB2 activation can increase microglial migration and proliferation. These results suggest that CB2-mediated processes may modify disease progression in ALS. [147] Carter and Rosen 2001 proposed marijuana as treatment of amyotrophic lateral sclerosis (ALS), due to the properties of the plant, such as analgesia, muscle relaxation, bronchodilation, saliva reduction, appetite stimulation, sleep induction, strong antioxidative and neuroprotective eects, which may prolong neuronal cell survival. [154] de Lago et al. 2012 assessed the result of the treatment with WIN55,512-2, a potent CB(1) and CB(2) agonist, to ameliorate tremor and spasticity in a murine model of multiple sclerosis. The authors focused on anti-glutamatergic and anti-inammatory eects of this cannabinoid agonist. The treatment reduced neurological disability and improving motor coordination of Experimental Allergic Encephalomyelitis (EAE) mice, however levels of glutamate and GABA remained similar to control animals. The eect of the treament activated CB(1) but not CB(2) receptors. The treatment of EAE mice with the cannabinoid agonist WIN55,512-2 reduced their neurological disability and the progression of the disease. This eect was exerted through the activation of CB(1) receptors, reducing the inammatory events linked to the pathogenesis of this disease. [155] Only moderate reduction of ALS symptoms with the use of Cannabis [156] According to Amtmann et al. 2004, reports of ALS patients using Cannabis (marijuana) indicate that cannabis may be moderately eective at reducing symptoms of appetite loss, depression, pain, spasticity, and drooling. However Cannabis was ineective in reducing diculties with speech and swallowing, and sexual dysfunction. No ALS survival improvement with vitamin E [157] Oxidative stress may be involved in the pathogenesis of amyotrophic lateral sclerosis (ALS). Desnuelle et al. 2001 found, however, that alpha-tocopherol did not improve survival and motor function in ALS. Graf et al. 2005 report that megadosis of 5 000 mg of vitamin E was not ecacious in slowing disease progression in ALS as an add-on therapy to riluzol. Larger or longer studies might be needed. [158] Greater carotenoids intake reduces ALS risk [159] Oxidative stress may be implied in the pathogenesis of amyotrophic lateral sclerosis (ALS). Foods high in carotenoids and vitamin C may, therefore help prevent or delay onset of ALS.
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Fitzgerald et al. 2012 report that high total major carotenoids intake reduces the risk of ALS. High dietary intakes of -carotene and lutein were inversely associated with ALS risk.
7.9.3
Black Tea and post-stress recovery
Andrew Steptoe and colleagues in a study concerning black tea, found that 6 weeks of tea consumption leads to lower post-stress cortisol and greater subjective relaxation, together with reduced platelet activation. Black tea may have health benets in part by aiding stress recovery. Speeding the recovery following acute stress may reduce risk of chronic illnesses such as coronary heart disease. 50 minutes after a stress situation, lower cortisol levels, a lower blood platelet activation, and a greater degree of relaxation in the recovery period were found in a tea drinking group, compared with a not drinking tea group. Because of the complex composition of tea comprising catechins, polyphenols, avonoids and amino acids, no compound, either independently or acting in synergistic could be identied to be responsible for these positive eects,
7.9.4
Green Tea has better health benets than black tea
Green tea contains between 30 and 40 per cent of water-extractable polyphenols, while black tea contains between 3 and 10 per cent. Epigallocatechin gallate (EGCG), epigallocatechin, epicatechin gallate, and epicatechin are being found in fresh tea leaves and are subject of numerous researches.
7.9.5
Green tea and rheumatoid arthritis [160]
Salah-uddin Ahmed and colleagues in a study evaluated the ecacy of Epigallocatechin3-gallate (EGCG), a polyphenol extracted from green tea on in multiple myeloma (MM). The authors found that the tea extract may suppress the inammatory products in the connective tissue of people with rheumatoid arthritis due to its ability to modulate growth factor-mediated cell proliferation. EGCG induced both dose- and time-dependent growth arrest and subsequent apoptotic cell death in MM cell lines also led to signicant apoptosis in human myeloma cells grown as tumors in SCID mice. EGCG activates distinct pathways of growth arrest and apoptosis in MM cells by inducing the expression of death-associated protein kinase 2 rising hope for therapies using the specic antimyeloma activity of EGCG.
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Synovial broblasts - cells that form a lining of the tissue surrounding the capsule of the joints - from patients with rheumatoid arthritis , under the inuence of pro-inammatory cytokine interleukin-1 beta (IL-1beta), produced molecules of interleukin-6 (IL-6) and cyclooxygenase-2 (COX-2) which is linked to joint destruction during rheumatoid arthritis. With EGCG the production of IL-6 and COX-2 was not observed.
7.9.6
Catechin reduces the risk of medication induced gastrointestinal ulcers [161]
The protective eect against medication induced gastric ulcers by catechin, theaavin, malvidin, cyanidin and apigenin were studied by Cheng et al. 2013 in vitro using human intestinal-407 cells and rat primary gastric cells treated with nonsteroidal anti-inammatory drugs (NSAIDs), such as ketoprofen and in vivo in rats. The authors report that catechin signicantly decreased the levels of lipid peroxidation and reactive oxygen species, and increased the activity of intracellular antioxidant enzymes glutathione peroxidase, glutathione reductase and total sulfhydryl groups in vitro. In vivo catechin inhibited oxidative damage in the intestinal mucosa. The authors found nuclear factor erythroid 2-related factor 2 and total heme oxygenase-1 protein expression in human intestinal cells increased. Catechin may thus have a protective eect on gastrointestinal ulcers.
Dietary polyphenols in fruits, vegetables tea and coee health protective activities [162] The direct antioxidant activity of dietary polyphenols in vivo is limited because of their low concentrations in vivo, except in the gastrointestinal tract where they are present in high concentrations. The indirect antioxidant activity is thought to arise primarily via the activation of nuclear factor-erythroid-2-related factor 2 which stimulates the activities of antioxidant enzymes such as glutathione peroxidase (GPx), glutathione S-transferase, catalase, NAD(P)H: quinone oxidoreductase-1 (NQO1), and/or phase II enzymes. Indirect antioxidants are ecient antioxidants because they upregulate the antioxidant enzymes or cytoprotective proteins which protect cells. In vitro polyphenols are found to have a pro-oxidant eect which activates the antioxidant enzymes and protective proteins in cultured cells and animal models because of the adaptation of cells and tissues to mild/moderate oxidative stress. Professor Miao-Lin Hu 2011 points to some unsolved questions related to the importance of the direct and the indirect antioxidant activities of dietary polyphenols in vivo, the importance of the eect of polyphenols as anticancer agent and last, but not least, the importance of the in vivo pro-oxidant eects of dietary polyphenols observed in vitro.
7.9. CANNABINOIDS Fresh fruit and vegetables protecting the gastrointestinal mucosa [163]
493
Apple extracts decreased xanthine-xanthine oxidase or indomethacin induced injury to gastric epithelial cells. The main phenolic components of apple extract, catechin and chlorogenic acid were found to prevent oxidative injury to gastric cells. Apple extract increased the intracellular antioxidant activity, prevented its decrease induced by xanthinexanthine oxidase, counteracted xanthine-xanthine oxidase induced lipid peroxidation, and decreased indomethacin injury in rat gastric mucosa. Graziani et al 2005 proposes that a diet rich in apple antioxidants might prevent gastric diseases with reactive oxygen species as origin. Strawberry reduces alcohol damage of gastric mucosa [164] Strawberry extracts were found to protect against severe gastric damage caused by alcohol. Antioxidant enzyme activities increased signicantly after strawberry extract intake and a concomitantly decrease in gastric lipid peroxidation was found. Alvarez-Suarez et al 2011 concluded that strawberry extracts protects against ethanol-induced damage to gastric mucosa was caused by. A diet rich in strawberries might be useful to prevent gastric diseases caused by reactive oxygen species. This protective mechanism may be caused by the activation of antioxidant enzymes. The antioxidant status preventing oxidative stress-induced ageing with involvement of the Nrf2 and MAPK signaling pathway [165] Shih and Yen 2007 found that increasing age was associated with serious oxidative injury demonstrated by increase of oxidation products in liver. The activities of antioxidant enzymes (AOEs) decrease and oxidative stress increase with increasing age. Nuclear factorerythroid 2 p45-related factor 2 (Nrf2) decreases with increasing age. Mitogen-activated protein kinase cascade (MAPK) exerts a regulatory role in signaling transduction. The authors suggest that age-related declines of the expression of Nrf2 regulation by the MAPK family are involved in the decline of the antioxidant defence in high age.
7.9.7 7.9.8
Findings on the biochemistry of sleep Adenosine triphosphate (ATP) and Phosphorylated AMPactivated protein kinase (P-AMPK) participate in the biochemistry of sleep [166]
Dworak and colleagues 2010, experimenting with rats, reported that ATP levels increase in the initial hours of spontaneous sleep in wake-active but not in sleep-active brain regions. The surge is dependent on sleep when neuronal activity is reduced, but is not related to time of day.
494
Phosphorylated AMP-activated protein kinase (P-AMPK), which has a cellular energy sensing and regulation, reacts inversely to ATP. The authors concluded that ATP level in brain and P-AMPK levels give insights to the biochemistry of sleep.
7.9.9
Adenosine key factor of sleep control [167]
Elmenhorst and colleagues 2009 report that adenosine acts via the A(1) adenosine receptor (A(1)AR). It is a key factor in the control of sleep. The authors suggest that cerebral A(1)ARs are involved in eects of sleep deprivation and the regulation of sleep maintaining the responsiveness to increased adenosine levels, and the eect of sleep deprivation and is in line with a sleep-induced homoeostatic reorganization at the synaptic level.
7.9.10
Sleep deprivation and its eect on neurotransmitter receptor [168]
Longordo and colleagues 2009 describe alterations in neurotransmitter receptor function in diverse neuronal cell types caused by sleep deprivation, focusing on sleep deprivation procedures that control for side-eects such as stress. The authors call for more studies on the eect of sleep deprivation on neurotransmitter receptor to increase knowledge of the detrimental eects of sleep loss.
7.9.11
Shift work eect on IL-6 and TNF-alpha immune system [169]
van Mark and colleagues 2010 write that short-term sleep deprivation lead to overstimulation of proinammatory immune mechanisms and moderates metabolic changes, such as lymphocyte count or level of IL-6 or TNF-alpha serum concentration. This increase cardiovascular disease risk. The authors report, however, that chronic sleep did not always lead to an activation of these indicators of immune system activation, between shift workers and day workers. The authors concluded that the eect of chronic sleep restriction may be compensated by a long-term immune regulation which protects against an overstimulation of proinammatory immune mechanisms and moderates metabolic changes.
7.9.12
Epilocathechin-3 gallate and multiple myeloma [170]
Masahiro Kisaki and colleaugue (2005) found that epigallocatechin-3-gallate from green tea has potential as a novel therapeutic agent for patients with B-cell malignancies including multiple myeloma via induction of apoptosis mediated by modication of the redox system, and enhances. As2O3-induced apoptosis in human multiple myeloma cells.
7.9. CANNABINOIDS
495
7.9.13
Green Tea reduces colorectal cancer risk in women [171]
Tea and its constituents have shown anticarcinogenic activities in in vitro and animal studies. Epidemiologic studies, however, have been inconsistent. Green tea contains between 30 and 40 per cent of water-extractable polyphenols, such as epigallocatechin gallate, epigallocatechin, epicatechin gallate, and epicatechin, while black tea contains between 3 and 10 per cent. Gong Yang assessed green tea consumption and colorectal cancer risk and rectal cancers. The researchers found an inverse dose-response relationship between the amount of tea consumed and duration in years of lifetime tea consumption This study suggests that regular consumption of green tea may reduce colorectal cancer risk in women.
7.9.14
Benets of Mediterranean diet [172] [173] [174]
Studies published in 2006 suggest that Mediterranean diet, rich in fruit, vegetables and olive and sparing in red meat and dairy products has been associated with a lower risk for several diseases and risk factors, including cancer, obesity, high cholesterol, high blood pressure and problems with processing glucose that may lead to diabetes, coronary heart disease, reduction of the risk of Alzheimer disease. According to the studies, the diet should contain turmeric and omega-3 fatty acids.
7.9.15
Increased risk of colorectal cancer recurrence associated with The high calorie, low bre dietary pattern [175]
Jerey Meyerhardt and colleagues from the Dana-Farber Cancer Institute, studied the association of dietary pattern and risk of cancer recurrence in stage III colon cancer patients. They found that a diet characterized by higher intakes of red and processed meats, sweets and desserts, French fries, and rened grains increases the risk of cancer recurrence and decreases survival. The authors say that eighty per cent of colorectal cancers may be preventable by dietary changes. The researchers compared dietary pattern characterized by high intakes of fruits and vegetables, poultry, and sh with the Western pattern, characterized by high intakes of meat, fat, rened grains, and dessert. The researchers found that a diet with a higher correspondence to the Western dietary pattern after cancer diagnosis were at a signicant increase in the risk of cancer recurrence or death. The top 20 per cent of people with the greatest Western-style diet were 3.3 times more likely to have cancer recurrence or death that those with least Western-style diet.
496
7.9.16
The European Prospective Investigation into Cancer and Nutrition (1993-2000) [176]
A study by E. Kesse and colleagues concerning the data of the European Prospective Investigation into Cancer and Nutrition (1993-2000), linked people with a "Western" diet pattern to a signicantly increased risk of the cancer. The study made a comparison between four dietary patterns: "Healthy": (Vegetables, fruit, yogurt, sea products, and olive oil). This diet was found to have the lowest recurrence risk of all other diets. "Western": (Potatoes, pizzas and pies, sandwiches, sweets, cakes, cheese, cereal products, processed meat, eggs, and butter). An increased risk of adenoma with high scores of a higher risk of colorectal tumors was observed. "Drinkers": (Sandwiches, snacks, processed meat, and alcoholic beverages). High risc of found. "Meat eaters": (Meat, poultry, and margarine). It was positively associated with colorectal cancer risk.
7.9.17
Western diet and high fructose diet blamed as "toxic environment" [177]
Robert Lustig from the University of California blames the "toxic environment" of Western diets to cause hormonal imbalances that encourage overeating by its increased energy density, high-fat content, high glycemic index, increased fructose composition, decreased ber, and decreased dairy content. Lustig blames in particular, too much fructose and not enough ber as the cornerstones of the obesity and diabetes epidemic.
7.9.18
The association of fatty diet of the Wester-style diet further explained by new study [178]
A study of Erdelyi and colleagues 2009 says that increased intake of red meat, processed meat and alcohol can increase risk of colorectal cancer, whereas greater consumption of dietary ber, milk and calcium might decrease risk. According to this study Western diet induces oxidative stress and alters immune responses in the colon of mice long before tumors occur. The researchers found 41 genes, related to metabolic processes such as lipid metabolism and glutathione metabolism, to be expressed dierently between the Western diet and control animals. Genes collectively associated with immune and inammatory responses were found to be increased. The authors also reported an increase of the number of macrophages, which are associated with inammation in the colon. Several proteins such as myeloperoxidase and MCP-1 and oxidative stress genes associated with inammation were also found
7.9. CANNABINOIDS to be increased.
497
The authors concluded that Western-style diet interferes with networks of related biological response pathways involving colonic lipid metabolism, oxidative stress, and the immune response.
7.9.19
No dierence in the acute eects on vascular reactivity between conventional fast-food and "healthy fast-food" [179]
Tanja K Rudolph and colleagues 2007, in a study from the University Hospital HamburgEppendorf, Germany looked for the acute eects of conventional and alternative fast-food meals on vascular function investigating the ow-mediated endothelium-dependent dilatation (FMD) and cardiovascular disease risk markers before and after a conventional beef burger meal and healthier choices. The researchers found that a conventional beef burger meal with French fries, ketchup and soda, did not dier signicantly in their acute eects on vascular reactivity. compared with a vegetarian burger with French fries, ketchup and soda and the vegetarian burger with salad, fruit, yogurt, and orange juice The authors attribute the postprandial decline in FMD in part to a postprandial increase in baseline arterial diameter. Fast-food remains unhealthy. Addingvegetables and orange juice does not present the variety of Mediterranean diet, according to the ndings of the Melbourne Collaborative Cohort Study: Viral infections due to undercooked red meat may cause colorectal cancer [180] Harald zur Hausen a German cancerologist writes that colorectal cancer has a high increasing incidence worldwide, notably in countries with the highest consumption of red meat such as China, Japan and Korea. In Japan and in Korea undercooked beef is consumed frequently, which correlates with the high incidence of the disease. Carcinogenic chemicals which are formed during the cooking process of meat may not be the sole cause of the disease because similar compounds are found even in higher concentrations, during the preparation of sh or poultry without increasing the incidence of colorectal cancer. The author concluded that data point to the possibility that one or more thermoresistant oncogenic bovine viruses (e.g., polyoma-, papilloma- or possibly single-stranded DNA viruses) contaminating beef preparations may cause chronic infections in the colorectal tract. Carcinogenic chemical carcinogens formed during cooking procedures increase synergistically the eect of such infections.
498
This study may be a warning to avoid steak tartar, which had been very popular in Europe before enterobacteria epidemics increased public awareness of the risk of raw meat.
7.9.20
Table grape reduced salt-sensitive hypertension [181]
According to Seymor and colleagues 2008 eating grapes reduce salt-sensitive hypertension in elderly people. In this strudy a high salt diet with grape powder lowered blood pressure and improved cardiac function, compared with a high salt diet without grape powder supplement.The grape powder diet reduced systemic inammation; reduced cardiac hypertrophy, brosis, and oxidative damage; and increased cardiac glutathione. The authors concluded that intake of phytochemical such as table grape powder reduce salt-sensitive hypertension and diastolic dysfunction.
7.10
The relation of foods and micronutrients to stroke
Micronutrients and stroke According to Larson 2012 diets high in magnesium and potassium may reduce the risk of stroke. High intake of sodium increases the rosk of stroke. However, the role of specic fatty acids, dietary cholesterol, and combinations of vitamins in the aetiology of stroke is unclear. [182] Long-chain omega-3 PUFAs Long-chain omega-3 PUFAs were found to be inversely associated with risk of stroke, but dietary cholesterol is positively associated with risk. Total fat, saturated fat, monounsaturated fat, polyunsaturated fat, -linolenic acid, and omega-6 PUFA intakes were not associated with stroke. [183] However, low consumption of sh and sh oil in most developed countries (0.1-0.5 g/d) result in low intake of long-chain n-3 PUFA, EPA and DHA. The conversion of dietary intake of the precursor n-3 fatty acid, alpha-linolenic acid present in plant oils such as rape-seed and soybean oil, to EPA and DHA seems to be insucient as only 8% are converted to EPA and less than 0,1% to DHA in adult men. In women 9% of plant oils are converted to DHA, and may even be higher as a result of the actions of oestrogen on Delta6-desaturase, during prgnancy. [184] Mozaarian and Wu 2012 explain that DHA [22:6(n-3)] requires direct dietary consumption, with little synthesis from or retroconversion to docosapentaenoic acid DPA [22:5(n-3)], DPA or EPA [20:5(n-3)]. Whereas EPA is also largely derived from direct consumption, EPA can also be synthesized in small amounts from plant (n-3) precursors, especially stearidonic acid. In contrast, DPA appears principally derived from endogenous elongation from
7.10. THE RELATION OF FOODS AND MICRONUTRIENTS TO STROKE
499
EPA, and DPA can also undergo retroconversion back to EPA. The authors concluded that EPA and DHA have both shared and complementary benets, and increasing consumption of either would be advantageous compared to little or no consumption. [185]
Animal proteins and stroke Intake of total and animal protein, but not vegetable protein, was inversely associated with risk of total stroke and cerebral infarction in women with hypertension. [186] Associated researches, however, note that consumption of fresh red meat and processed red meat as well as total red meat is associated with increased risk of total stroke and ischemic stroke, but are not associated with hemorrhagic stroke. [187]
Dairy foods and risk of stroke Consumption of low-fat dairy foods was inversely associated with risk of total stroke and cerebral infarction. Consumption of total dairy, full-fat dairy, milk, sour milk/yoghurt, cheese, and cream/crme fraiche was not associated with stroke risk. [188]
7.10.1
Prehypertension in young adulthood increases risk of atherosclerosis [189]
Prehypertension is dened as systolic blood pressure (BP) 120 to 139 mm Hg or diastolic BP 80 to 89 mm Hg. Recently, attention is driven to the fact that prehypertension, blood pressure levels lower than those usually considered abnormal might still be harmful. The eect of prehypertension on risk for heart attacks and strokes is not entirely clear. However, studies found that hypertension increases coronary artery calcium which is associated with heart attacks and strokes. Coronary calcium can be detected by computed tomography scan. In a study, using data of the Coronary Artery Risk Development in Young Adults (CARDIA), Mark J. Pletcher and colleagues 2008 found that prehypertension during young adulthood is common and is associated with coronary atherosclerosis 20 years later. The authors recommend to keep systolic pressure below 120 mm Hg before age 35 years to avoid ailments in advanced age. Pletcher points to the national guidelines, which say that people with prehypertension should work on diet, exercise, and lifestyle modications in order to prevent hypertension.
500
7.10.2
Processed meat, but not fresh red meat consumption increases risk of stroke [190]
Larsson, Virtamo and Wolk 2011, using data of The Cohort of Swedish Men study, found that consumption of processed meat, but not of fresh red meat, was positively associated with risk of stroke and cerebral infarction. The authors excluded confounder such as body mass index, aspirin use, history of diabetes and hypertension, alcohol consumption, and family history of heart disease, as well as subjects smoking history and level of physical activity. Another outcome of this study is that meats which are believed as healthy, such as low-fat deli turkey, ham, and bologna, may increase the risk for stroke if intake is high enough. The authors suggest that sodium and nitrites in processed meats might contribute to an increase of stroke, because no association between fresh red meat and stroke could be found in the study. Heme iron or cholesterol in processed meat are therefore not to be blamed for dierence of the stroke incidence between processed and fresh red meat. This study adds further evidence of negative eects of kitchen salt and nitrites. Robert Eckel, MD, commenting the study, noted that it is dicult blame the salt or the nitrite in processed meat for the increased risk of stroke, because the study relied on a survey and assessed association, not cause and eect. The group with the highest intake of processed meat had also a healthier diet overall, including more fruit, vegetables, and whole grains.
7.10.3
Guidelines for the primary prevention of stroke [191]
This guideline provides an overview of the evidence on established and emerging risk factors for stroke to provide evidence-based recommendations for the reduction of risk of a rst stroke. Modiable stroke risk factors include hypertension, exposure to cigarette smoke, diabetes, atrial brillation and certain other cardiac conditions, dyslipidemia, carotid artery stenosis, sickle cell disease, postmenopausal hormone therapy, poor diet, physical inactivity, and obesity and body fat distribution. Potentially modiable risk factors include the metabolic syndrome, excessive alcohol consumption, drug abuse, use of oral contraceptives, sleep-disordered breathing, migraine, hyperhomocysteinemia, elevated lipoprotein(a), hypercoagulability, inammation, and infection. Data on the use of aspirin for primary stroke prevention are reviewed. The Guidelines concluded that a variety of specic factors may increase the risk of a rst stroke and strategies for reducing that risk are provided. The Guidelines state further, that diet with reduced sodium that is rich in fruits and vegetables, such as a DASH-style diet, will reduce stroke risk. The Dietary Guidelines for Americans recommends a sodium intake of less than 2.3 g/d (100 mmol/d) for the general population, and a potassium intake of
7.10. THE RELATION OF FOODS AND MICRONUTRIENTS TO STROKE at least 4.7 g/d (120 mmol/d).
501
7.10.4
Soy sauce use to reduce salt content of food preparations [192]
Goh et al 2011 report that soy sauce may help to replace 33% up to 50% of the salt content of foods without reducing the palatability. The authors noted that percentage of salt reduction achievable may be higher in a population which already use soy sauce as avouring. This method may be used in industrial formulations as well in home made foods, say scientists from the National University of Singapore in collaboration with soy sauce manufacturer Kikkoman. Another study by Kremer, Mojet and Shimojo 2009 attained salt reduction of 50% in salad dressings, 17% in tomato soup and 29% in stir-fried pork, without decrease in consumer acceptance. With increased popularity of Asian foods the reduction of salt in traditional Wester European formulations becomes possible. [193]
7.10.5
The umami taste of soy sauce [194]
The fermentation of soy bean soy sauce production, gives a distinct delicious taste used as an umami seasoning. Umami is one of the ve basic tastes together with sweet, sour, bitter, and salty. Umami is a Japanese word meaning "pleasant savoury taste". According to Lioe, Selamat and Yasuda 2010 the Japanese and Indonesian soy sauces are rich in umami components with molecular weights lower than 500 Da. Free amino acids, add to the taste in combination with salt and small peptides, which, however, are less active as avour.
7.10.6
Modifying the food aroma may increase perception of sweetness without changing the sugar content [195]
Taste and olfaction are the most important sensory inputs which leads to whether a food is liked or not. Ortho- and retronasal olfaction are important to the perception of avour. Tieman et al. 2012 used targeted metabolomics and natural variation in avour-associated sugars, acids, and aroma volatiles to evaluate the chemistry of tomato fruits. Using these data, the authors created a predictive and testable model of liking. An amazing fact found by the authors is that aroma volatiles are linked to perceived sweetness independent of sugar concentration. Changing the food aroma my increase perception of sweetness without adding sugar.
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7.10.7
Dietary bre recent studies on colorectal cancer
Denis Burkitt proposed in 1971 the link between colorectal cancer and dietary bre. Inconsistent results of studies could not back this theory. A new study of Elizabeth Jacobs from the Arizona Cancer Center, however considered the sex of the participants and found a signicant benet of bre for men, but not for women. This may explain the discrepant results of the Wheat Bran Fibre Trial and the Polyp Prevention Trial. The Wheat Bran Fibre Trial assessed the eect of a high wheat bran bre supplement against a low wheat bran bre supplement men and women, randomly assigned to the supplements. The Polyp Prevention Trial studied the eect of a low-fat, high bre diet, rich in fruit and vegetables on the recurrence of pre-cancerous polyps in the colon and rectum. Both studies reported that the high-bre diets had no eect of the recurrence of colorectal polyps. The Arizona researchers from the Arizona Cancer Center re-evaluating the data of both studies observed statistically signicant reduced odds of recurrence for men, but no significant association for women. [196] The recently published results of the Womens Health Initiative (WHI) trial also reported no link between a diet low in fat, and high in fruit, vegetables and whole-grain intake. This study was restricted to women and appears to agree with the results from Arizona. Poor compliance with the dietary intervention in the WHI trial do, however, raise questions about the validity of these results. [197] Limitations of the two studies (Wheat Bran Fibre Trial and the Polyp Prevention Trial): 1.- Both had very short follow-up periods of only two to four years The latency period of the cancer is between 10 and 20 years, 2.- The use of polyps as a marker for actual cancer was criticized as questionable by Dr. Arasaradnam from Northern General Hospital in Sheeld in 2004. [198]
7.10.8
Concorde grape
Vitis labrusca (Fox grape) is a specic grape native in the northeast of the United States. It is the source of many grape cultivars, including concord grapes. The characteristic "foxy" musk of V. labrusca is inherited by the Concorde grape. A study performed by lead author Barbara Shukitt-Hale the Human Nutrition Research Center on Aging at Tufts University relate improved results on behavioural tests and enOurFood Database of Food and Related Sciences Copyright 1998-2010 Karl H. Wilm. All rights reserved.
7.11. CARDIOVASCULAR PROTECTION OF RED WINE AND WHITE WINE 503 hanced motor performance on rats fed with Concorde grape juice, which is rich in polyphenoles. The study suggests that the eects of Concorde grape juice may be more eective than any one single Hopes are rising that component of grape juice may reverse brain aging. [199] Concord grapes may have many health benets such as reducing hypertension and the negative eects of second-hand smoking, but these results are tentative. [200]
7.11
Cardiovascular protection of red wine and white wine
[201] M. Falchi and colleagues found that the esh of grapes are equally cardioprotective as skin, and antioxidant potential of skin and esh of grapes are comparable with each other despite of the fact that esh does not possess any anthocyanin activities. Recent studies have documented that grapes and grape juices are equally cardioprotective as red wine. despite vastly diering polyphenol content. Several studies have linked regular consumption of red wine to reduced risk of heart disease. The skin of red grapes is a rich source of red coloured anthocianine. Red grapes are usually crushed whole, meaning the anthocyanines are transferred to resulting wine and juice, on the contrary, most white wine or white grape juices are prepared by discarding the grape skin, nourishing the belief that red wines and red grape juice are healthier than white. M. Falchi fed three groups of rats with water only (control), grape skin extract, or grape esh extract. The increase of malondialdehyde (MDA), a reactive carbonyl compound related to oxidative stress, was measured under ischemic and myocardial infarction conditions. No dierence was observed between the esh and skin extracts, both groups had signicantly reduced heart attack size compared with water control group. Quantication of the polyphenol content conrmed that, while the skins had anthocyanin concentrations of about 128 milligrams per 100 grams, the esh contained no such compounds. However, the radical scavenging abilities of both the esh and skin extracts were found to be the same. The esh of the grapes did contain polyphenols but not of the anthocyanin type of grape skin. Furthermore caeic acid, caftaric acid, and coutaric acid have been reported which are also present in white grape varieties.
504
7.11.1
Red wine and reduction of atherosclerosis
Tony Hayek and colleagues studied the eect of consuming red wine, or its major polyphenol constituents catechin or quercetin, on the development of atherosclerotic lesions, in relation to the susceptibility of plasma LDL to oxidation and to aggregation in mice. They found that the inhibition of LDL oxidation by polyphenols could be related, at least in part, to a direct eect of the polyphenols on the LDL, since both quercetin and catechin were found to bind to the LDL particle via the formation of an ether bond. The authors conclude that dietary consumption of red wine or its polyphenolic avonoids quercetin and, to a lesser extent, catechin leads to attenuation in the development of the atherosclerotic lesion, and this eect is associated with reduced susceptibility of their LDL to oxidation and aggregation.
7.11.2
Concentrated red grape juice reduces risk of cardiovascular disease [202]
The aim of the study was to study the eects of dietary supplementation with concentrated red grape juice, a source of polyphenols, on lipoprotein prole, antioxidant capacity, LDL oxidation, and inammatory biomarkers. The authors concluded that dietary supplementation with concentrated red grape juice improves the lipoprotein prole, reduces plasma concentrations of inammatory biomarkers and oxidized LDL, and may favor a reduction in cardiovascular disease risk.
7.11.3
Importance of polyphenols in meals [203]
Polyphenols were found to prevent cardiovascular disease, but their mechanisms of action are not understood. Gorelik and colleagues investigated the impact of red wine polyphenols on postprandial cytotoxic lipid peroxidation products urine malondialdehyde (MDA) levels in humans, resulting from fat digestion. MDA is known as a risk of cardiovascular disease and other illnesses. The authors found that red wine polyphenols exert a benecial eect by the novel new function, absorption inhibition of the lipotoxin MDA. These ndings explain the potentially harmful eects of oxidized fats found in foods and the important benet of dietary polyphenols in the meal.
7.11.4
Nutrition claims in the Philippines
The US company Procter & Gambler has launched on the Philippines market a concentrated orange powder "NutriDelight". This orange juice in form of a dehydrated powder is
7.12. RECOMMENDED DIETARY ALLOWANCE (RDA) AND DIETARY REFERENCE INTAKES (DRI)
505
enriched with vitamin A, iron and iodine. This product is claimed to " let children grow stronger, taller, and smarter. According to P&G director Durk Jager the undersupply of these three elements is one of the most outstanding problem of worldwide nutrition. The "Nutridelight" according to Jager has been developed in cooperation with Health departments and UNICEF and was tested in Tanzania. This product may have importance in the nutrition of a wide population in case of undersupply during catastrophes where international associations try to feed people of a limited region to overcome a short period of calamity. It not suitable for the nutrition at normal times. The population which has no money to buy a balanced natural nutrition will certainly have not the possibility to achieve orange juice powder enriched with food supplements from Procter & Gambler. Health authorities should try to get the population educated in a way to get a well balanced nutrition with local fruits,vegetables, sh and meat. Getting back to the elementary balanced nutrition helps although the local industry, shery and agriculture bringing jobs and the most important of all: It gives thousand and thousand all other components which are necessary to our nutrition avoiding synthetic food from pills and pharmacy.
7.12
7.12.1
Recommended Dietary Allowance (RDA) and Dietary Reference Intakes (DRI)

History of RDA [204]
The RDA was developed during World War II by lydia J. Roberts, Hazel K. Stiebeling and Helen S. Mitchel under the auspices of the National Research Council. The National Research Council determined that a set of dietary standards were needed, especially given the possibility that rations would be needed during the war. The standards would be used for nutrition recommendations for the armed forces, for civilians, and for overseas population who might need food relief. Roberts, Stiebeling, and Mitchell surveyed all available data, created a tentative set of allowances, and submitted them to experts for review. The nal set of allowances were accepted in 1941. The allowances were meant to provide superior nutrition for civilians and military personnel, so they included a "margin of safety." The RDA was established by the Food and Nutrition Board of the (US) National Academy of Sciences. In 1997 at the suggestion of the Institute of Medicine of the National Academy RDA became one part of a broader set of dietary guidelines called the Dietary Reference Intake used by both the United States and Canada.
506
7.12.2
RDA inclusion in DRI family [205]
The Recommended Dietary Allowances (RDAs) had been valid from 1941 until 1989, the RDAs to evaluate and plan menus that would meet the nutrient requirements of groups as well as other applications such as interpreting food consumption records of populations, establishing standards for food assistance programs, establishing guidelines for nutrition labelling, to name a few. The RDAs were created to prevent nutrient deciencies. They were not intended to evaluate the diets of individuals.
7.12.3
Dietary Reference Intakes (DRIs) family
In 1997, the Food and Nutrition Board of the National Academy of Sciences created the Dietary Reference Intakes (DRIs) after a extensive revision of the RDAs. The new family of nutrient reference values is organized in four types of DRI reference values: 1. Estimated Average Requirement (EAR) A daily nutrient intake value that is estimated to meet the requirement of half of the healthy individuals in a life stage and gender group. EAR is used to assess dietary adequacy and as the basis for the RDA. 2. Recommended Dietary Allowance (RDA)The average daily dietary intake level that is sucient to meet the nutrient requirement of nearly all (97 to 98%) healthy individuals in a particular life stage and gender group. 3. Adequate Intake (AI) a recommended intake value based on observed or experimentally determined approximations or estimates of nutrient intake by a group (or groups) of healthy people, that are assumed to be adequate. AI is used when an RDA cannot be determined. 4. Tolerable Upper Intake Level (UL) The highest level of daily nutrient intake that is likely to pose no risk of adverse health eects for almost all individuals in the general population. As intake increase above the UL, the potential risk of adverse eects increases. These dietary reference values were intended to prevent nutrient deciencies and to reduce the risk of chronic diseases such as osteoporosis, cancer, and cardiovascular disease.
7.12.4
Critical Issues in the Application of Dietary Reference Intakes [206] [207]
Dr. George Beaton, University of Toronto, examining application of the Dietary Reference Intakes (DRI) among individuals and groups comes to the conclusion that the RDA lacks an acceptable scientic basis and suggests that dietary advice for both groups should be achieved through critical DRI reference values.
7.13. ACTUAL DIETARY REFERENCES SET FROM US FOOD AND DRUG ADMINISTRATION FDA
507
According to Beaton, tradition and the DRI reports themselves have created an erroneous impression that the Recommended Dietary Allowance (RDA) is intended for use with individuals, while the Estimated Average Requirement (EAR) is to be used with populations. He concludes that the median requirement and Tolerable Upper Limit (UL) are the critical reference values for both individuals and populations. The RDA is both unneeded and lacking a sound scientic basis.
7.12.5
Defending RDA [208]
According to Murphy, Barr, and Yates, Dietary each DRI category has specic uses in dietary assessment and/or planning for groups or individuals. For example, the RDA is "intended to be used as a goal for daily intake by individuals as this value estimates an intake level that has a high probability of meeting the requirement of a randomly chosen individual." The DRI paradigm is being used as a model for nutrient standards worldwide. The authors argue in favour of keeping the present thinking about it the uses of nutrients. Beaton replied that we now live in an era of increasing demand for evidence-based nutrition and stresses the necessity of revising previous thinking and approaches as it becomes apparent that they lack evidence of validity.
7.13
7.13.1
Actual dietary references set from US Food and Drug Administration FDA
DVs (Daily Values)
The use of Dvs on the food label started in 1994, following the US Nutrition Labelling and Education Act of 1990. [209] It is made up of two sets of references, DRVs and RDIs. But, according to Paula Kurtzweil from FDA, these two sets are "behind the scenes" in food labelling; only the Daily Value term will appear on the label to make label reading less confusing.[209] The labelling act from 1990 requires nutrition label information to be conveyed in a way that enables the public to observe and comprehend the information readily and to understand its relative signicance in the context of a total daily diet. [209] According to Christine Lewis from FDAs Oce of Food Labelling, the DV does that in two ways: First, it serves as a basis for declaring on the label the percent of the Daily Value for each nutrient that a serving of the food provides. [209] For example, the Daily Value for fat, based on a 2,000-calorie diet, is 65 grams (g). A
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food that has 13 g of fat per serving would state on the label that the "percent Daily Value" for fat is 20 percent. Second, it provides a basis for thresholds that dene descriptive words for nutrient content, called descriptors, such as "high bre" and "low fat." For example, the descriptor "high bre" can be used if a serving of food provides 20 percent or more of the Daily Value for bre - that is, 5 g or more. [209]
7.13.2
WHO strategies to monitor and evaluate population sodium consumption [210]
According to the WHO high blood pressure is responsible for 13% of deaths globally. The risk of death from high blood pressure in low- and middle-income countries (LMIC) is more than double that of high-income countries. The total dietary salt consumed is an important determinant of blood pressure levels and of hypertension risk. This relationship is direct and progressive with no apparent threshold, and salt reduction in individuals is an important intervention in reducing blood pressure, increasing the ecacy of pharmacological therapies, and reducing the global risk of cardiovascular disease. The 2005 edition of Dietary Guidelines for Americans recommends a sodium intake of no more than 2300 mg/day, with "specic populations" (i.e. people with hypertension, people of African ancestry and people 40 years of age or older) being advised to limit intake to 1500 mg/day. Average sodium intake in 2009 was estimated at 3466 mg/day, far in excess of even the highest recommendation. According to data collected in 2005 and 2006, only 9.6% of US adults met the current guideline. Table 7.1: Salt recommendations Current daily intake in Europe [211] Recommendations WHO recommendation [212] SACN recommendation [213] Salt grams/day 8 - 11 Sodium grams/day 3-5
<5 5-6
< 2,5 2 - 2,5
7.13.3
URLs (Daily Reference Values)
A set of dietary references that applies to fat, saturated fat, cholesterol, carbohydrate, protein, bre, sodium, and potassium.
7.13.4
RDIs (Reference Daily Intakes)
a set of dietary references based on the Recommended Dietary Allowances for essential vitamins and minerals and, in selected groups, protein. The name "RDI" replaces the term "U.S. RDA."
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7.13.5
RDAs (Recommended Dietary Allowances)
a set of estimated nutrient allowances established by the National Academy of Sciences. It is updated periodically to reect current scientic knowledge.
7.13.6
References on dietary references and dietary supplements
For more informations on US FDA dietary references, please go to their homepage of http://www.fda.gov/fdac/special/foodlabel/dvs.html For more informations on dietary supplements please go to http://vm.cfsan.fda.gov/dms/supplmnt.html
7.13.7
Vitamins and essential elements
The WHO (World health Organization of the United Nations) has recommended the Daily Allowance(RDA) of vitamins and minerals given in the table below. Linus Pauling and a group of his followers claim higher doses. The table draws a comparison between WHO and other recommended doses. The recommendations of WHO should be followed as the doses marked ***are likely to be considered as overdose when used for long time. You may nd the table of RDA useful to compare with the labeling of your food complements. Table 7.2: Recommended Daily Allowance(RDA) of vitamins and minerals Vitamin or mineral Vitamin C (ascorbic acid) Vitamin E (d-alfa tocopherol) Beta carotene Vitamin B1 (thiamine) Vitamin B2 (riboavin) Vitamin B3 (niacinamide) Vitamin B6 (pyridoxine) Pantothenic acid Folic acid Biotin Vitamin D Vitamin K Selenium Chrome picolinate RDA 60 mg 10 I.U. 1,0-1,4 mg 1,2-1,7 mg 18 mg 2,2 mg 4-7 mg 100-200g 200-300 I.U. 70-120g minimum 500 400 0 mg 10 10 10 10 50 400 0 0 0 100g 200g daily 2000 600 15 50 50 50 50 100 1.000 300 200 0 150 200 maximum 10.000 1.000 15 100 100 100 50 200 5.000 300 400 120 200 400
510 Zinc Calcium Magnesium Iodine 150g Bioavonoid Garlic Concentrated sh oil Glutathione Glutamine Coenzyme Q10 Ginkgo biloba Egb 761 Iron 0-18 mg Copper 2-3 mg Manganese 2,5-5,0 mg Molybdenum 0,15-0,5 mg Fluor Vitamin or mineral RDA 15 mg 500 mg 200mg 150 0 0 0 0 0 0 0 0 0 0 0 0mg minimum
CHAPTER 7. PHYSIOLOGY 15 30 1.000 1.500 400 600 150 300 200mg 1.000 600 mg 900 1.000 mg 2000 50 mg 100 2.000 mg 8.000 30 mg 240 120 mg 120 0 5 2 3 2,5 5,0 0,15 0,5 0 0 daily maximum
7.13.8
Vitamin B6 overdose
Heavy overdose of vitamin B6 (pyridoxine can cause alterations of mobility, psychological alterations and reactions like those of Contergan in new born. The Committee on Toxicity of Chemicals in Food Consumer Products and the Environment (COT) gives the advice not to exceed daily 10 mg. Supplier of vitamin B6 are meat, sh, eggs, cereals and some vegetables. Some food complements contain dose up to 100 mg. COT tries to establish a voluntary limit of vitamin B6 in food complements between manufacturers and include more informations on the label. The commission has great concern with possible about damages of the nervous System in case of over dose[214].
7.13.9 7.13.10
Other components of nutrition The nutritional value of fats
Oils and fats have high nutritional value as they are rich in energy and act as transport medium of liposoluble vitamins. Some fatty acids cannot be synthetize by human body, they are called essential fatty acids (arachidonic acid, linoleic acid and linolenic and linolenic acid) . They are important parts of the synthesis of the hormone prostaglandin and are part of the structure of cell membrane [215]. The intake of fat, however is to high. Adults should reduce the intake of fat There is a connection between the amount of fat consumed and arterial diseases, as well as duodenal cancer and mammal cancer. It is advisable to reduce fat an to chose fat with high amount of polyunsaturated fatty
7.13. ACTUAL DIETARY REFERENCES SET FROM US FOOD AND DRUG ADMINISTRATION FDA acids.
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7.13.11
Daily intake of fat
The European population has a daily intake of 130 to 150 gram/person/day. This should be reduced to 60 gram with maximum of 90 gram.
7.13.12
Recommended composition of fats
According to the DGE (Deutsche Gesellschaft fr Ernhrung) and WHO the intake of fat should be constituted by on third of saturated fatty acids, one third of monounsaturated fatty acids and one third of polyunsaturated fatty acids. (This rule is called "The one third rule". The amount of saturated fatty acids in nutrition is to high. The main source of saturated fatty acids is found in meat, sausages milk product, cakes and biscuits. This should be reduced.
7.13.13
Total fat intake
It should not be over 30% of total energy by people with light manual work, and not over 35% of total energy by people for people with heavy manual work.
7.13.14
Long chain saturated fatty acids
It should not be over 10% of total energy.
7.13.15
Polyunsaturated fatty acids
: should be about 7% of total energy and up to 10% when the amount of saturated fatty acids lies over 10%.
7.13.16
Relation between linoleic acid (n-6) and linolenic acid (n-3)
: the relation should be 5:1.
7.13.17
Monounsaturated fatty acids
: can ll up to the total amount of total energy.

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7.13.18
Trans-fatty acids
: should be less than 1% of total energy [216]
7.13.19
Recommended intake of Cholesterol
The European daily intake is 500 to 800 mg/person/day. This should be reduced to a maximum of 300 mg/day. Every health organization supports the theory of an excess of animal food rich in cholesterol and saturated fatty acids being the main cause of high levels of blood fats and arteriosclerosis. Saturated fatty acids rise the blood cholesterol, accelerating the formation of arteriosclerosis. Polyunsaturated fatty acids may help to reduce blood cholesterol.
7.13.20
The TRANSFACT Study says natural trans fatty acids not as detrimental to health as industrial once [217]
Jean-Michel Chardigny and colleagues comparing the eect of trans fatty acids (TFAs) from industrial with those of natural source found that TFAs from natural sources significantly increased HDL cholesterol increases in LDL-cholesterol concentrations in women but not in men. Large HDL and LDL concentrations were modied by TFAs from natural sources but not by those from industrially produced sources. The authors concluded that TFAs from industrially produced and from natural sources have dierent eects on CVD risk factors in women. The HDL cholesterol-lowering property of TFAs seems to be specic to industrial
7.13.21
The position of the European Dairy Association (EDA) [218]
These nding were eusively belauded by the the European Dairy Association (EDA) as it came in support of the trans fatty acids of dairy. Based on the results of TRANSFACT the participants of the European Dairy Associations TFA Policy Conference in Brussels, 13 February 2008 concluded that there is no evidence on negative health eects from dairy TFA and EDA stated that dairy TFA should therefore not be taken into consideration for labelling or nutrient proling for claims.
7.13.22
The Willett and Mozaarian position [219]
According to Willett and Mozaarian 2008 to reduce the intake of industrial TFA is ideally being done by replacing them with cis unsaturated fatty acids. The Danish government
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and the New York City have shown that the legislation to limit the use of partially hydrogenated vegetables oils in foods is feasible and eective. Multiple committees concluded that TFA intake should be as low as possible, and continued eorts to eliminate the consumption of partially hydrogenated vegetable oils are strongly warranted. The authors stress that despite small dierences between the metabolic eects of industrial and ruminant TFA, there is no compelling evidence to exclude natural TFA from the total TFA on food labels.
7.13.23
Reduced success of the Trans-Fat-Free Americas Initiative [220]
The pan-America Trans-Fat-Free initiative asked 12 representatives from food industries in Latin America and the Caribbean to voluntarily eliminate industrially produced transfatty acids of their products. A year later only few data on reformulations of the product were made available to the initiative. Reported diculties to phase out trans-fatty were availability of oil substitutes, cost, and consumers sensory acceptance. Because of reduced success of voluntary initiative the authors suggest that the trans-fatty acids and saturated fat in food should be regulated and strictly monitored in the Americas.
7.13.24
Mechanism of atherosclerosis caused by trans fats [221]
Chen and colleagues 2010 report that a diet rich in trans fats cause atherosclerosis by reducing the responsiveness of a protein, the transforming growth factor (TGF)-beta. The authors found that the suppression of the responsiveness of TGF-beta in aortic endothelium and other tissues was caused by dietary trans fats, mediated by deposition of cholesterol into the cellular membranes in vascular tissue. This may also be the cause of other trans fat-related diseases and disorders, such as cancer and immunity. In this study high trans fat diet increased the expression of VCAM-1, a marker of early lesions of atherosclerosis, reduced the expression of TGF-beta type I and II receptors and decreased the levels of phosphorylated Smad2, important TGF-beta response indicator. These markers returned to normal levels when diet was shifted to low trans fats. The authors concluded that transforming growth factor (TGF)-beta protects against atherosclerosis.
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7.13.25
Trans fatty acids consumption linked to unique cardiometabolic imprint via diabetes pathway [222]
TFA consumption produces a unique cardiometabolic imprint via pathways linked to the insulin resistance syndrome. Consumption of trans fatty acids (TFA) is linked to harmful changes in serum lipids, systemic inammation, endothelial function visceral adiposity, diabetes, increased risk of myocardial infarction, coronary heart disease death, and sudden death. In face of the adverse health eects of TFA and the feasibility of replacing partially hydrogenated oils containing TFA, Mozzafarian and Willet 2012 see no reason to continue the preparation and the production of foods with high TFA levels. The authors call for consumer education regarding the sources and hazards of TFA and use of alternatives to partially hydrogenated oils by restaurants and the food industry.
Consunmption of trans fatty acids in India [223] Trans fatty acids causes severe cardiovascular problems, insulin resistance, infertility in women, compromised fetal development and cognitive decline. Despite strict regulations for limiting or removing the TFA content from food supply across the world, there are only limited data on TFA contents in foods and their consumption in India where the number of diabetes and cardiovascular diseases is at rise. Bhardwaj, Passi and Misra call for removal of TFA from the food supply in India.
Punjab has an alarming high consume of trans fatty acids[224] According to Dixit and Das 2012 in India the butter and butter oil present TFA limit exceeded by 4.2- to 9.5-fold whereas hydrogenated vegetable oil (HVO) samples exceeded the limit by 9.8-fold, when compared to Denmark limit of 2%. The intake of TFA by Indian population was found to be probably less than WHO recommendation of 1% TFA [225]. However, Punjab with a highest consumption of hydrogenated vegetable oils has an intake of TFA 1.09-fold higher than the WHO recommendation, which is alarming and may be one of the factors for high cardiovascular disease mortality rate that needs further elucidation. The authors stress the need to prescribe TFA limit for edible oil, butter, and butter oil in India and to adopt trategies to decrease the consumption of hydrogenated vegetable oils or modify the industrial hydrogenating process to reduce trans fatty acids.
7.14. BLOOD LEVELS OF CHOLESTEROL
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7.14
Blood levels of Cholesterol
HDL cholesterol should be at least 45 mg/dl for females and 35 mg/dl for male. The maximum of cholesterol for adults allowed is 200 mg. Values of cholesterol between 200 and 250 mg/dl have to be controlled. They can be tolerated if the bad LDL is low and the good HDL is high and there are no secondary risks (high arterial pressure, smoke, diabetes, excessive body weight, no sports are made and continuous stress). The higher secondary risks are more cholesterol values have to be reduced. According Lancet 1996 every third person with more then 40 years, smoking, with high arterial pressure and cholesterol over 230 mg/dl of blood will suer an infarct. In Germany 261000 persons die of infarct each year. Values of cholesterol over 250 md/dl are always coronary risks. Everyone should know his values of blood cholesterol. Values over 200 mg/dl should be reason enough to change the way of life, the nutrition and the physical constitution. With a modication of nutrition indicated by a dietician blood cholesterol may be reduced by 20%. (250 mg/dl may be brought down to 200 mg/dl without medication.) It is therefore important to stop smoking, to have a healthy nutrition and practice sports. According to the WHO healthy nutrition should have 45 to 55% complex carbohydrates, 30% of oils and fats having more than half of her fatty acids unsaturated. (Some say 10% saturated, 10% monounsaturated and 10% polyunsaturated fatty acids.) The intake of cholesterol should be under 300 mg/day and less than 5 gram of salt /day. This means nutrition rich in pasta, sh, olive oil, vegetables and fruits. The daily sport should be 30 minutes biking or walking. Infarct risk and diabetes II can so be reduced signicantly. It is important to consider the fat intake not in percentage of calories but as grams of fat.[226]
7.14.1
Salt and salted foods have dierent eects regarding CVD and cancer [227]
Takachi and colleagues 2009 assessed the eect of salt and salted foods. Cooking and table salt was found to increase the risk of cardiovascular disease (CVD) but not cancer. Salt preserved foods, such as salted sh roe, however, were associated with a higher risk of total cancer. The authors concluded that increased intake of table salt may boost the risk of heart disease, while increased consumption of salted foods may increase the risk of cancer, probably resulting from carcinogens called N-nitroso compounds which may be formed from nitrate or nitrite preservatives.
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7.14.2
Report 2008 on global tobacco control eorts [228]
According to Dr Margaret Chan, Director-General of WHO virtually every country needs to do more to reduce tobacco consumption. The WHO Report of the Global Tobacco Epidemic presented six strategies to reverse this growing menace. No country fully implements all of the MPOWER policies and 80% of countries dont fully implement even one policy. While tobacco control measures are sometimes controversial, they save lives and governments need to step up and do the right thing. The six MPOWER strategies are: Monitor tobacco use and prevention policies Protect people from tobacco smoke Oer help to quit tobacco use Warn about the dangers of tobacco Enforce bans on tobacco advertising, promotion and sponsorship Raise taxes on tobacco According to the report tobacco epidemic is shifting to the developing world.
7.14.3
Blood LDL cholesterol should be treated in order to level with
LDL cholesterol > 160 mg/dl (4,14 mmol/l) LDL cholesterol > 130 mg/dl (3,36 mmol/l) with two or more secondary risks and HDL cholesterol > 35 mg/dl=0,91 mmol/l Secondary risks are: Arterial hypertension, smoke, overweight, Diabetes mellitus, peripheral arteriosclerosis and cerebral sclerosis Arterial hypertension: Blood pressure up to 140/90 mmHg is considered as normal. Blood pressure from 140/90 mmHg up to 160/95 should be put under medical supervision. Blood pressure higher than 160/95 is considered as hypertension which needs medication. LDL cholesterol > 100 mg/dl (2,6 mmol/l) in case of manifested coronary diseases LDL cholesterol > 110 mg/dl (2,8 mmol/l) in children and juveniles
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7.14.4
Traditional blood cholesterol values
Isolated values of total blood cholesterol does not give safe informations for therapy control. Below values are cited as being traditional:
Table 7.3: Blood values of cholesterol traditional considered as normal Adults < 30 years total cholesterol < 180 mg/dl (4,66 mmol/l) Adults > 65 years total cholesterol < 240 mg/dl (6,21 mmol/l) Children total cholesterol < 160 mg/dl (4,14 mmol/l) Diet necessary total Cholesterol < 200 mg/dl (5,17 mmol/l) LDL/HDL quotient < 5,0
7.14.5
Dietary measures to lower blood cholesterol
The following measures lower the blood cholesterol in great number of cases. Reduction of calories Reduction of fat in nutrition Change of nutrition related the composition of fatty acids, substituting saturated fatty acids Reduction of cholesterol in nutrition. An interesting way to reduce cholesterol in nutrition is made with the introduction of a low-cholesterol egg. These eggs are produced in Malaysia and also in Germany feeding chicken with monounsaturated fatty acids, maize and palm oil. They have 100 to 160 mg cholesterol which is 25 to 50% below normal [229].
7.14.6
The omega-3 egg
In Germany there are being made eorts to produce eggs with high level of omega-3 fatty acids. Hens are being fed with a special type of grains. This gets eggs rich on polyunsaturated fatty acids of the omega-3 type. The daily intake of omega-3 fatty acids should be 0,5% of total calories (with a diet of 2.200 kcal/day = approximately 1 g omega 3 fatty acids)(information from EIVIt Fischer Weppler GmbH PB 100572 76486 Baden-Baden). Rise of amount of bres in nutrition Reduction of the amount of meat in nutrition
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Reduction of Broca Index below 1,0. Broca Index Body weight in Kg = Body length in cm-100 Body Mass Index < 25 Body Mass Index = Body weight in Kg : (Body height in meters)2 Before medication is used a 6 month cholesterol lowering diet should be tried.
7.14.7 7.14.8
An immediate medication together with a diet is needed when LDL-cholesterol > 350 mg/dl= 9,1 mmol/l. New AAP policy on heart health in children recommendations [230]
According to the American Academy of Pediatrics cholesterol-reducing medications should be considered for children who are more than eight years old and who have high LDL concentrations. Younger patients with elevated cholesterol readings should focus on weight reduction and increased activity while receiving nutritional counseling. According to the new policy diets with reduced-fat dairy products, such as two percent milk should be considered for overweight children as young as one year of age. Some critics on this policy came from Stephen Daniells, science editor of Foodnavigator. He argues that diet is better than controlling cholesterol in kids with statins. Changing eating habits and lifestyle of obese kids should consider plant sterols at a daily amount of 1,5 to 3 grams/day, oatmeal and beta-glucan from oats, soy,rich in omega-3 rich oils, and even garlic , says Daniells. [231]
7.14.9
Nutrition and blood pressure [232]
Savica, Bellinghieri and Kopple 2010 resumed the eect of nutrition on blood pressure and pointed to excessive energy intake, obesity, high sodium chloride and high alcohol intake as primary causes of hypertension. Obesity is physiologically associated with increased reninangiotensin-aldosterone and sympathetic nervous systems, possibly other mineralcorticoid activity, insulin resistance, salt-sensitive hypertension and reduced kidney function. To reduce blood pressure high intakes of potassium, polyunsaturated fatty acids, and protein, along with exercise and possibly vitamin D are recommended. Other foods, such as amino acids, tea, green coee bean extract, dark chocolate, and foods high in nitrates, the Dietary Approaches to Stop Hypertension (DASH) diet, which is high in fruits, vegetables, whole grains, poultry, sh, nuts and low-fat dairy products, and the DASH low-sodium diet .have been suggested by some studies to reduce blood pressure. Other authors suggest a healthy lifestyle to reduce mild hypertension, notably: Vegetarian
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Diet which contains more potassium, complex carbohydrates, polyunsaturated fat, bre, calcium, magnesium, vitamin C and vitamin A. Sugar may be related to hypertension increasing the production of adrenaline which promotes contraction of the blood vessels. Drastically salt-reduced, low-calorie "rice diet." A number of common vegetables and spices have been suggested to reduce hypertension, such as celery, garlic, onion, tomato, broccoli, carrot, saron
7.14.10
Controversy about Statins [233]
Some scientists take a skeptical view of the need for many people to require statin treatment. Given the wide indications for which statins are prescribed, and the declining benet in groups at lower baseline risk of cardiovascular events, the evidence base for expanded statin use has been questioned by some researchers. Some groups claim that statins are not as benecial or safe as suggested.
7.14.11
Researchers recommend statin supplement to unhealthy fast food to reduce heart disease [234]
Francis and colleagues 2010 found that a daily consumption of statin, with the exception of pravastatin, reduced the risk of cardiovascular disease caused by fatty hamburger with cheese and a small milkshake. The authors stress that cardiovascular harm caused by unhealthy fatty diet may be reduced giving statin as supplement to their meals. The authors suggest that fast food chains oer statin in addition to free condiments such as salt, sugar and spices. However, statins may not be a substitute for a healthy lifestyle, varied diet low in saturated fats, regular exercise, weight loss, and smoking cessation.
7.14.12
Fried food, particularly fast-food are high in oxycholesterol [235]
Zhen-Yu Chen and colleaugues 2009 found that oxycholesterol boosts total cholesterol levels and promotes atherosclerosis more than non-oxidized cholesterol. It also damages cells and DNA. The authors stress that fried and processed food, particularly fast-food, contains high amounts of oxycholesterol. They recommend to avoiding these foods and eating a diet that is rich in antioxidants, such as fresh fruits and vegetables, beans, and certain herbs and spices. whole grains, seeds, and nuts. A diet high in oxycholesterol rose blood cholesterol in Hamsters to 22 percent and developed greater deposition of cholesterol (atherosclerotic plaques) in the lining of their arteries and a tendency to develop larger deposits of cholesterol compared with hamsters which were on non-oxidized cholesterol diet. The deposition of oxycholesterol also reduced
520
the elasticity of arteries,reducing the ability to transport more blood when needed. It is not known if Statin is eective against oxycholesterol.
7.14.13
Oxycholesterol or oxyphytosterol formation during processing and storage of foods [236]
Sterol oxidation products derived from cholesterol and phytosterol are formed during the processing and storage of foods. Bang and colleagues 2008 report that a diet with both oxysterols increase 4beta-hydroxycholesterol and total oxycholesterol in the liver, but the oxycholesterol-fed mice had a lower level of cerebral 24S-hydroxycholesterol and a higher level of the serum triacylglycerols than the control and oxyphytosterol groups. The authors concluded that both oxysterols in food are accumulated in the body, but diered in their biological eect.
7.14.14
Oxyphytosterol [237]
Phytosterols may undergo oxidative processes similar to the cholesterol oxidation. Consumption of phytosterols could therefore add to oxyphytosterols from foods or biologic formation from phytosterols, presenting a concern in terms of food quality and health, similar to oxycholesterol. Hovenkamp and colleagues 2008, however, stress that some data suggest that oxyphytosterols, depending on the type of oxidation product, have benecial properties.
7.14.15
Oxysterols [238]
The oxysterol:cholesterol ratio in atherosclerotic plaque play an active role in plaque development. Oxysterols in plaque are derived both non-enzymatically, either from the diet and/or from in vivo oxidation, or are formed enzymatically during cholesterol breakdown, like the 27-hydroxycholesterol. Brown and Jessup 1999 accentuate that in vitro, oxysterols interferes in the biology of cellular cholesterol homeostasis, reduces vascular reactivity and are cytotoxic and/or induce cell death. Injection of oxysterols into animals causes acute heart toxicity, however, studies concerning oxysterol in diet have yielded contrary results related to heart diseases. The authors comment that there is no direct evidence yet in humans that oxysterols contribute to atherogenesis. However, several studies found that oxysterol levels are elevated in human low-density lipoprotein (LDL) subfractions and raised plasma levels of a specic oxysterol (7beta-hydroxycholesterol) may be associated with an increased risk of atherosclerosis.
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7.14.16
Approval of products in EU: Regulation (EC) No 258/97 concerning novel foods and novel food ingredients
Before any new food product can be introduced on the European market it must be rigorously assessed for safety. In the UK the assessment of novel foods is carried out by an independent committee of scientists appointed by the Food Standards Agency, the Advisory Committee on Novel Foods and Processes (ACNFP).
7.14.17
Lower hurdles for novel foods? [239]
Industry on both sides of the Atlantic are calling to reduce the hurdles for the approval of new foods and new supplements. In Europe such a movement was spurred on by a recent decision by the UKs Food Standards Agency (FSA) to refer Cargills vegetarian glucosamine hydrochloride ingredient to further review by EFSA prior to granting novel food status. This matter should, however, be analysed very carefully, according to a comment of Stephen Daniells, from Food Navigator. Novel food and supplements are approved to be marketed in USA by the FDA and in Europe by the EFSA following the Novel Foods Regulation EC 258/97. [240] This ingredient was widely used as dietary supplement since 2004, and has been approved in USA under the less strict way of its self-armed GRAS (Generally Recognized As Safe) for certain food and beverage applications, which Cargill proclaimed in March 2007. It may be used in a variety of specic mainstream foods and beverages. Cargill stresses that glucosamine added to orange juice helps to protect cartilage and joints from the stresses of normal daily activities. [241] The UK Food Standards Agency, alleging that it is unknown how the ingredient aects glucose metabolism, asked the EFSA to review it considering diabetic concerns. The industry, leaded by the Confederation of Food and Drink Industries of the EU (CIAA) and he Alliance for a Competitive European Industry (ACEI) intensied lobbying for laxer regulations pointing to America to boost innovations. European Commission would be well advised not to ease regulations, adopt the US GRAS system, or charging fees for processing dossiers so as it is being done there. There is an unhealthy movement in the USA going on. It puts economic development in front of safety. This is most painfully noted in the case of strategy to avoid climate change last month at the APEC Conference in Australia and in the President Bushs Climate Conference in Washington denying clearly any activity which could hinder the economy. This works in opposition to the Kyoto Protocol, backed by European Countries. Failure of the next climate conference at Bali in December will endanger staple food supply of Africa and Asia. Prices will increase on account of the competition of biofuel versus food.
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The FDA nds itself amidst the interests of the industry and does weaken in relation to safety, such as the approval of GRAS.
7.14.18
The Contergan story and food safety [242]
A sad anniversary of Thalidomide is being commemorated in Germany. It was sold under the generic name Contergan, by the German pharmaceutical company Grnetal. Approximately 10,000 children were born with severe malformities, because their mothers had taken thalidomide during pregnancy. Phthalimidoglutarimide was obtained by heating the peptide phthaloylisoglutamine. High doses did not kill rodents, rabbits, cats or dogs, nor show any other side eects. The Grnenthal research team began to describe thalidomide as "nontoxic", with no teratogenicity tests (tests on pregnant animals), no clinical trial plans, and no scientic rationale. European food regulators and the European Commission should stick to food safety policy and never forget the lesson of Contergan where low hurdles and prot caused horrible malfomities.
7.14.19
UK novel foods committee
The Advisory Committee on Novel Foods and Processes (ACNFP ) is an independent group of experts who advise the Agency on any matters relating to novel foods and novel processes. Varied fruit juices have been subjected to approval, some of them enriched with plant sterols.
7.14.20
Pomegranate juice reverse proatherogenic eects of disturbed arterial ow [243]
According to F. de Nigris and colleagues, atherosclerosis is enhanced in arterial segments exposed to disturbed ow. Perturbed shear stress increases the expression of oxidationsensitive responsive genes (such as ELK-1 and p-JUN) in the endothelium. Evidence suggests that polyphenolic antioxidants contained in the juice derived from the pomegranate can contribute to the reduction of oxidative stress and atherogenesis. In their study, the authors conclude that the proatherogenic eects induced by perturbed shear stress can be reversed by chronic administration of pomegranate juice.
7.14.21
Heart UK and Coronary Heart Diseases [244]
Heart UK, the Cholesterol Charity specialises in patients who inherit high cholesterol, with particular concern for those who remain undiagnosed with the condition called Familial Hypercholesterolaemia (FH), or inherited high cholesterol (IHC)
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The Charity maintains relationships with companies whose product is benecial to a healthy diet particularly within the eld of high cholesterol, approving those products like pomegranate juice and others with evidence to support their heart health benets. [244] Supplementary juice product made from blackcurrants and blueberries, rich in antioxidants and vitamin C are being investigated on their eects on cardiovascular diseases. The Heart UK Charity stresses that diet is central to the treatment of hyperlipidaemia. Lipid-lowering drugs are generally only prescribed when treatment goals are not met through dietary change alone. For those who do require drug therapy, following a pattern of healthy eating is strongly encouraged.
7.14.22
The OPTILIP study concerning ischemic heart disease [245]
Sanders and colleagues measured the eect of low dietary ratio of n-6 to n-3 polyunsaturated fatty acids (n-6:n-3) (3:1)on high risk factors of ischemic heart disease. The risk factors are known to be elevated brinogen, activated factor XII (FXIIa), and factor VII coagulant activity (FVIIc). The authors concluded that decreasing the n-6:n-3 to 3:1 by increasing the intake of EPA and DHA lowers fasting and postprandial plasma triacylglycerol concentrations in older persons but does not inuence hemostatic risk factors.
7.14.23
Wild blueberries as protective factor against strokes [246]
Dorothy Klimis-Zacas and colleagues investigated the eects of wild blueberries (Vaccinium angustifolium) on functional and structural molecules in the walls of the aorta of rats. The study was focused on glycosaminoglycans (GAGs), which are carbohydrate molecules in the blood vessel walls that are directly or indirectly involved in a variety of functions, including lipoprotein metabolism, blood coagulation, and organization of the extracellular matrix. The increased intake of polyphenols may provide protection against coronary heart disease and stroke. Blueberries (Vaccinium angustifolium) are one of the richest sources of antioxidants among fruits and vegetables. Phenolic compounds from berry extracts inhibit human low density lipoprotein and liposome oxidation. Glycosaminoglycans (GAGs) and proteoglycans (PGs) are structural components of aortas interacting with compounds such as enzymes, cytokines, growth factors, proteins and
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lipoproteins and their subsequent role in degenerative diseases. The presence of three GAG populations were studied: Hyaluronan (HA), heparan sulfate (HS) and galactosaminoglycans (GalAGs). The study demonstrated that increased galactosaminoglycans (GalAGs) content, together with a lower concentration of oversulfated disaccharides in both HS and GalAG populations in the aortas of rats fed with a supplement of Blueberries was found to be a protective factor. The authors conclude that a diet rich in blueberries results in structural alterations in rat aortic tissue GAGs, aect cellular signal transduction pathways and biological function of GAG molecules within the vascular environment.
7.15
Mangosteen
Mangosteen (Garcinia mangostana)is a fruit of south east Asia. It is rich in mangostin, one of a family of active compounds known as xanthones. Mangosteen inhibits the oxidation of LDL-cholesterol and the activity of PGE2, COX-1, and COX-2 (prostaglandin E2 and cyclooxygenases-1 and -2) - key factors involved in inammatory conditions. Mangostin is a natural organic compound isolated from various parts of the mangosteen tree. It is a yellow crystalline solid. Mangostin and a variety of other xanthones from mangosteen have been investigated for biological properties including anti-bacterial, antiinammatory, and anticancer activities. [247] The extract of the mangosteen plant has a strong inhibitory eect on Propionibacterium acnes and Staphylococcus epidermidis. Therefore, it could become a possible alternative treatment for acne according to Chomnawang. It also provides in-vitro antibacterial activity against staphylococcus aureus [248] [249] The active substances of the crude extract of the fruit hull of mangosteen were identied as alpha-mangostin and gamma-mangostin. The structures of alpha-mangostin and gamma-mangostin is free from nitrogen atom. It does not resemble to the common structures of histamine and serotonin receptor antagonists. These compounds may therefore become novel types of lead compounds for histamine and serotonin receptor antagonists, helping to ght allergies and inammation. [250]
7.15.1
Other components of Garcinia mangostana [251]
Three new xanthones, mangostenol (1), mangostenone A (2), and mangostenone B (3), were isolated from the green fruit hulls of Garcinia mangostana, along with the known
7.15. MANGOSTEEN
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xanthones, trapezifolixanthone, tovophyllin B (4), alpha- and beta-mangostins, garcinone B, mangostinone, mangostanol, and the avonoid epicatechin. [252] Four new compounds of Garcinia mangostana were isolated byYang YL and col: Three minor xanthones, garcimangosone A (1), garcimangosone B (2), and garcimangosone C (3), and a benzophenone glucoside, garcimangosone D (4).
7.15.2
Mangostin inhibition of the oxidative modication of lipoprotein LDL [253]
The oxidation of low density lipoprotein (LDL) may play an important role in atherosclerosis. Mangostin, isolated from Garcinia mangostana was found to act as a free radical scavenger to protect the LDL from oxidative damage in vitro system.
7.15.3
Cancer chemoprevention of mangostin [254]
Researches with crude methanolic extract from the pericarp of Garcinia mangostana using human breast cancer (SKBR3) cell line as a model system suggestes that the methanolic extract from the pericarp of Garcinia mangostana had strong antiproliferation, potent antioxidation and induction of apoptosis. According to Moongkarndi the results of the study indicates that this substance can show dierent activities and has potential for cancer chemoprevention which were dose dependent as well as exposure time dependent.
7.15.4
Ischemic heart disease, epidemiological studies [255] [256] [257] [258] [259] [260]
Epidemiologic studies Western countries linked dietary factors such as total fat, saturated fatty acids (SFAs), polyunsaturated fatty acids (PUFAs), n-3 series fatty acids, and cholesterol with the incidence of ischemic heart disease. The most relevant studies were the Western Electric Study, the Zutphen Study, the Honolulu Heart Program, the Puerto Rico Heart Health Program, the Ireland-Boston DietHeart Study, and the Seven Countries Study. A total fat intakes of 35-40% of energy had been found in Western countries. Recommended dietary fat allowance in Western countries: Fat intake should be less than 30% of energy come from fat to prevent fat-related diseases.
7.15.5
Eect of dietary fatty acids on atherogenesis [261]
According to many studies saturated fat from foods, such as meat products, hard cheese, cream and palm oil, increase serum cholesterol.
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Studying the eect of dietary fatty acids on atherogenesis lead researcher, Dr. David CelermajerStephen, J. Nicholls and colleagues found that consumption of a saturated fat reduces the anti-inammatory potential of HDL and impairs arterial endothelial function. In contrast, the anti-inammatory activity of HDL improves after consumption of polyunsaturated fat. They found mechanisms by which dierent dietary fatty acids may inuence key atherogenic processes due to anti-inammatory properties of high-density lipoproteins (HDL) and vascular function. Raised levels Intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule1 (VCAM-1) were found to be a response of the immune system which results in inammation of the vascular endothelian. A saturated fat meal made HDL-cholesterol to be less eective at inhibiting the expression of both ICAM-1 and VCAM-1 and polyunsaturated meal caused HDL to have increased inhibitory activity compared HDL from fasting plasma. Labelling of the content of saturated fat and trans fatty acids could help to reduce the risk of hear disease by choosing products with reduced content of saturated fatty acids.
7.16
Omega-3 polyunsaturated fatty acids in food
Omega-3 polyunsaturated fatty acids are important for health of dierent organs. Omega-3 fatty acids are linked to prevention of cardiovascular diseases, some psychiatric, dermatological or rheumatological disorders. Best available alpha-linolenic-acid (ALA) source for humans are rapeseed oil (canola oil), and walnut oil. There is an increasing recognition of the health benets of polyunsaturated fatty acids (PUFA). The ratio n-6/n-3 fatty acids in the human diet which should have a value of 5 is being largely exceeded. Experts suggest, therefore, to include sh meals, or n-3 PUFA rich oils, or linseed in animal diets.
7.16.1
Broiler diet to reduce unhealthy n-3 and n6 fatty acids in meat [262]
Shin et al 2012 report the reduction of n-6 fatty acids in broiler chicken meat adding to their diet sh oil and dierent vegetable oils, such as soybean oil, olive oil, eicosapentaenoic acid (C20:5; EPA; n-3) and axseed oil, eicosapentaenoic acid (C20:5; EPA; n-3) of axseed oil. The authors also determined the delta6- and delta9-desaturase mRNA gene expression levels. Fatty acid desaturases introduce a double bond in a specic position of long-chain fatty acids. Three desaturases, Delta9, Delta6, and Delta5, are present in humans. Delta-9 catalyzes synthesis of monounsaturated fatty acids. Delta-6 and Delta5 desaturases are required for the synthesis of highly unsaturated fatty acids, which are esteried into phosOurFood Database of Food and Related Sciences Copyright 1998-2010 Karl H. Wilm. All rights reserved.
7.16. OMEGA-3 POLYUNSATURATED FATTY ACIDS IN FOOD pholipids an vital part of cell membrane. [263]
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Chicken fed with diet containing n-3 fatty acids presented reduced content of unfavourable linoleic acid (C18:2; n-6) and arachidonic acid (C20:4; n-6) in their meat compared with chickens fed animal and vegetable oil and soybean oil and olive oil diets. DHA was more active in reducing unfavourable fatty acids compared with EPA which suppressed the expression of favourable delta6- and delta9-desaturases. Best eect was found by the authors with the combination of sh oil and olive oil which is a blend of EPA and DHA. The authors suggest the addition of a mixed EPA and DHA to a broiler chicken diet to reduce arachidonic acid accumulation in meat of broiler chicken with functional quality. Alpha-linolenic-acid (ALA) enriched diets of farm animals [264] Bourre 2005 assessed the eect of diet on the fatty acid EPA and DHA composition of farm animals. The study focused on sh oil mainly from mackerel, salmon, sardine and herring, linseed and rapeseed. Monogastric farm animals such as birds, rabbits and pigs presented better preservation of the dietary omega-3 fatty acids, then polygastrics such as beef, mutton and goat due to their hydrogenating intestinal bacteria which transform EPA and DHA to unfavourable products. Birds, in contrst, present a good preservation of dietary omega-3 fatty acids in eggs. The enrichment in eggs is proportional to the amount of omega-3 fatty acids in the diet of hens. Fish farming Fish feeds high in ALA are only eective in vegetarian sh like carp. carp which a is eective only if they are, like carp, vegetarians, as they have the enzymes required to transform ALA into EPA and DHA; in contrast, it is probably less eective for carnivorous sh (75% of the sh used for human), which have little of these enzymes: their feed must contain marine animals, mainly sh or sh oil. To avoid shelve live reduction related to rancidity or colour change vitamin E may be added to the diet. Short-term diet enriched with PUFA oil, such as linseed oil has a rapid eect on meat. There is no need to feed animals with special diets to have the wanted functional eect on meat. [265] Diet with dairy fat blends high in ALA are suggested for optimal DHA level in brains of rats [266] Du et al. 2012 assessed the eect of various fat blends in neonatal nutrition to increase the docosahexaenoic acid (DHA) in the neonatal brain. The authors tested a palm oil blend-based diet with 1.5% ALA or 1.5% ALA and 0.12% DHA with 0.4% arachidonic acid. An anhydrous dairy fat blend provided 1.5% or 2.3% ALA. The best result presented the 1.5% ALA dairy fat and is a promising strategy to obtain
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optimal DHA levels in the brain of postweaning rats and may be interesting for human applications. Fish oil reduces sequelae of rheumatoid arthritis [267] According to Miles et al. 2012 n-6 polyunsaturated fatty acid (PUFA) arachidonic acid (ARA) is the precursor of inammatory eicosanoids which are involved in rheumatoid arthritis, a chronic inammatory autoimmune disease of the joints and bones. Rheumatoid arthritis is associated with increased cardiovascular mortality. Rontoyanni et al. 2012 stress the potential double eect of dietary intake of EPA and DHA reducing cardiovascular diseases and rheumatloid arthritis. The authors explain that n-3 fatty acids of sh oil reduce blood pressure, dyslipidemia, thrombosis and inammation,which are factors of cardiovascular diseases and rheumatoid arthritis. [268] The role of omega-3 in inammation resolution [269] Mittal et al.2010 postulate that resolution of inammation is caused by families of endogenous lipid mediators from omega-3 polyunsaturated fatty acids which help to remove proinammatory mediators generated from arachidonic acid. These chemical mediator families are Resolvins and Protectins. They control the duration and magnitude of inammation, together with the resolution signals, the Lipoxins. Omega-3 PUFAs are endogenous precursors of the chemical mediators Resolvins and Protectins which are active in the resolution phase of inammations. Both families of compounds may explain anti-inamatory properties of EPA and DHA. Bioactive mediators derived from omega-3 eicosapentaenoic acid (EPA) have strong antiinammatory actions. Isobe et al.2012 report the identication of two new metabolites of EPA, 18R- and 18S-RvE3. The resolvins E1 and E2 are biosynthesized by neutrophils via the 5-lipoxygenase pathway, but the 18R- and 18S-RvE3 metabolites are biosynthesized by eosinophils via the 12/15-lipoxygenase pathway. Both 18R- and 18S-RvE3 inhibited neutrophil chemotaxis in vitro at low concentrations. The authors concluded that RvE3 contributes to the anti-inammatory activity of EPA. [270] Pro-inammatory cytokine interleukin 1 in coronary diseases and in autoimmune inammation [271] Artemis and Simopoulos 2002 explain the activity of the cytokine "interleukin 1 (IL-1)" in coronary heart disease, major depression, ageing and cancer. Inammatory diseases, arthritis, Crohns disease, ulcerative colitis and lupus erythematosis are autoimmune diseases where also interleukin is present in high levels together with the proinammatory leukotriene LTB4 produced by omega-6 fatty acids. Interleukin 1 maintains the interactions between immune and inammatory. TNF- and IL-1 and IL-6 are the most important cytokines which are benecial response to infections when produced in appropriate amounts,
7.16. OMEGA-3 POLYUNSATURATED FATTY ACIDS IN FOOD
529
but overproduction can result in a pathological condition. Omega-3 has anti-inammatory eects suppressing LTB4 and reduces the overproduction of interleukin 1 (IL-1) and tumour necrosis factor (TNF). Omega-3 fatty acids suppress the expression of IL-1 mRNA gene explaining the benecial eects of omega-3 fatty acids in chronic inammatory disease. Gene expression alteration by omega-3 lipids [272] The EPA-rich oil altered the expression of fatty acid metabolism genes in THP-1 cells. Other omega3-PUFAs resulted in a similar gene expression response for a subset of genes involved in lipid metabolism and inammation. EPA-rich oil activated human peroxisome proliferator-activated receptor (PPAR) and PPAR / . Gillies et al 2012 concluded that the regulation of gene expression by EPA-rich oil is consistent with treating aspects of dyslipidemia and inammation. Alpha-linolenic acid (ALA) improve the symptoms of dry eye syndrome [273] Erdinest et al. 2012 reports that alpha-linolenic acid (ALA) inhibits the pro-inammatory cytokines with a signicant reduction of I-B in vitro, and may be promising in treating dry eye syndrome. The anti-inammatory eects of ALA are mediated through NF-B signal transduction. The authors suggest that ALA may act as an anti-inammatory agent in ocular surface inammation, similar to the eect of f corticosteroids.
7.16.2
Depression and lower levels of omega-3 fatty acids [274]
In order to examine whether depression was associated with lower levels of omega-3 FAs in serum phospholipids cancer patients were divided in three groups: major depression group a minor depression group and a nondepression group. There were no dierences between the major depression group and nondepression group in any FAs. The minor depression group had higher mean levels of docosahexaenoic acid. These results suggested that serum FAs are associated with minor, but not major, depression in lung cancer patients.
7.16.3
Omega-3 fatty acids of sh oil prevents fat accumulation in liver of mice [275]
Hirako et al. 2011 report that low-dose sh oil ingestion reduced hepatic lipid accumulation in mice, increased fatty acid oxidation-related hepatic gene expressions, and reduced the hepatic mRNA levels of fatty acid synthase (FAS), compared with animals fed fed with saower oil. Fatty acid synthase (FAS) is an enzyme known to catalyse fatty acid synthesis. Increased fatty acid oxidation-related hepatic gene expressions were higher in sh oil fed groups.
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The authors suggest that low-dose sh oil diets improve lipid metabolism by acting on lipid metabolism-related genes in the liver and increasing fecal cholesterol excretion, and that these benets may come from the high content of omega-3 fatty acids of sh oil.
7.16.4
Omega-3 fats and prostate cancer [276]
The Omega-6 poly-unsaturated fatty acid, Arachidonic acid, has been shown to enhance the proliferation of malignant prostate epithelial cells and increase the risk of advanced prostate cancer. Invasion of the human bone marrow takes place. This invasion is mediated by the arachidonic acid metabolite prostaglandin E2 . Mick Brown and colleagues found, however, when Omega-3 poly-unsaturated fatty acids eicosapentaenoic acid and docosahexaenoic acid at a ratio of 1 : 2 Omega-3: Omega-6 were present the spread of cancer cells was stopped.
7.16.5
Omega fatty acids of sh oil may increase risk of prostate cancer [277]
Brasky et al 2011 suggest that high levels of omega-3 fatty acids reduce heart diseases, but may harm the prostate. The authors report that high levels of omega-3 fatty acid (docosahexaenoic acid, or DHA), rises the risk of developing aggressive, high-grade prostate cancer by two and a half times compared to men with low DHA intake. Data of serum concentrations of omega-3, omega-6, and trans-fatty acids of the Prostate Cancer Prevention Trial were collected between 1994 and 2003. Trans-fatty acids from partially hydrogenated vegetable oils, linked to inammation and heart disease, were associated with 50% reduced risk of high-grade prostate cancer. Both types did not raise the risk of low-grade prostate cancer. They also found that omega-6 fatty acid, common in most vegetable oils, was not linked to a raised risk of either high-grade or low-grade prostate cancer. The ndings of Brasky and colleagues are confusing as chronic inammation are known to increase the risk of several cancers, and the omega-3 fatty acids of sh and sh oil supplements have anti-inammatory eects, and mega-6 fats in vegetable oil and trans-fats found in fast foods, may promote inammation. The authors say that these ndings demonstrate the complexity of the association of nutrition and chronic diseases, such as inammation and prostate cancer. Anyhow, the benecial eects of eating sh to prevent heart disease outweigh any harm related to prostate cancer risk, say the authors, and experts recommend 450 milligrams of omega-3 DHA per day as part of a healthy diet.
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7.16.6
Nutrients suggested for prostate cancer prevention [278]
In a study of 2010 by Kristal et al dietary calcium was positively associated with lowgrade cancer but inversely associated with high-grade cancer. Diet or supplements, such as lycopene, long-chain n-3 fatty acids, vitamin D, vitamin E, and selenium, were not signicantly associated with cancer risk. The authors stress further that high intake of n-6 fatty acids may increase prostate cancer risk.
7.16.7
N-3 polyunsaturated fatty acids and reduction of mortality due to myocardial infarction [279]
A meta-analysis of Heiner Bucher and colleagues suggests that dietary and nondietary intake of n-3 polyunsaturated fatty acids reduces overall mortality, mortality due to myocardial infarction, and sudden death in patients with coronary heart disease.
7.16.8
Lack of benet of dietary advice concerning fruits and oily sh [280]
In this study 3114 patients with angina were distributed in four groups: 1. advised to eat two portions of oily sh each week, or to take three sh oil capsules daily; 2. advised to eat more fruit, vegetables and oats; 3. given both the above types of advice; 4. and given no specic dietary advice. A study of Burr and colleagues found that the advice to eat more fruit resulted in no detectable eect on mortality. Men advised to eat oily sh, and particularly those supplied with sh oil capsules, had a higher risk of cardiac death. The result is unexplained, but caused a high repercussion in non-medical press like "Der Spiegel" denying any protection again cancer and are of no help against depression. [281]
7.16.9
Health benets of oats and oats-based products [282]
Mark B. Andon and James W. Anderson assessed the literature of the last 10 years concerning oats and oats-based products. They found that all concluded that consumption of oats and oat-based products signicantly reduces total cholesterol and low-density lipoprotein cholesterol concentrations without adverse eects on high-density lipoprotein cholesterol
532
or triglyceride concentrations, extending it to other health benets, such as reduce the risk for increased blood pressure, weight gain, and type-2 diabetes, reduce LDL cholesterol as part of a weight-loss programme, and turn LDL cholesterol less susceptible to oxidation, and that Beta-glucan from oats may be responsible for decreases to LDL-C levels. The authors concluded that the consumption of oats and oat-based products should be encouraged as part of an overall lifestyle medicine approach for the prevention of cardiovascular disease.
7.16.10
The Collaboration Review [283]
Despite the consistency of eects seen in trials of wholegrain oats, the positive ndings should be interpreted cautiously. Many of the trials identied were short term, of poor quality and had insucient power. Most of the trials were funded by companies with commercial interests in wholegrains. There is a need for well-designed, adequately powered, longer term randomised controlled studies in this area. In particular there is a need for randomised controlled trials on wholegrain foods and diets other than oats. The authors point to a lack of studies on other wholegrains or wholegrain diets.
7.16.11
Long chain and shorter chain omega 3 fats discredited [284]
Hooper and colleague in a meta-analysis of randomised control trials and cohort studies concluded that long chain and shorter chain omega 3 fats do not have a clear eect on total mortality, combined cardiovascular events, or cancer. Trial results were inconsistent and showed no strong evidence of reduced mortality or cardiovascular events in participants taking additional omega 3 fats. It is not clear whether long chain or short chain omega 3 fats (together or separately) reduce or increase total mortality, cardiovascular events, cancer, or strokes. The ndings do not rule out an important eect of omega-3 fats on total mortality, as robust trials at low risk of bias reported few deaths. There is no evidence that the source (dietary or supplemental) and dose of omega-3 fats aected the eectiveness of long chain omega-3 fats. Hooper looked for an explanation why the study by Burr et al contradict the other large studies by not suggesting a benet of omega-3. The authors examined the harmful cumulative eects of methylmercury in the long Burry trial, the fact that a specic angina patient group was chosen, and if oily sh could have a dierent eect as sh oil supplements, but no explanation was found. It is therefore not clear why the results of Burr et al dier from the other large studies on sh based omega- 3. The authors conclude that the eect of omega 3 fats on cardiovascular disease is smaller than previously thought, or that its
533
benecial eect is limited to a specic group not represented in the study by Burr et al. The authors add as nal recommendation that UK guidelines encourage the general public to eat more oily sh, and higher amounts are advised after myocardial infarction (supported by trials after myocardial infarction). This advice should continue at present but the evidence should be reviewed regularly. It is probably not appropriate to recommend a high intake of omega 3 fats for people who have angina but have not had a myocardial infarction.
7.16.12
Health recommendations conict concerning oily sh and omega-3 fat supplements [285]
In an editorial in 2006 Brunner states that for the general public some omega-3 fat is good for health. Long chain omega 3 fatty acids are structural components of neuronal and other cell membranes, and they modulate the production of eicosanoids and inammatory cytokines. Whether omega-3 fat prevents cognitive impairment and dementia is currently being tested in trials. Extreme nutritional deciency of these fats results in a neuropathy that can be reversed with rapeseed oil or other vegetable oils containing alfa-linolenic acid (18:3 omega 3). Alfa-Linolenic acid is a precursor of long chain omega-3, but endogenous conversion to eicosapentaenoic acid (20:5 omega-3) and docosahexaenoic acid (22:6 omega3) is limited and inecient.
7.16.13
Fish consumption reduces the stroke incidence in women says Swedish study [286]
Larsson, Virtamo and Wolk 2010 examined data of 34.670 women in the Swedish Mammography Cohort. Over 14 years 1680 incident cases of stroke, including 1310 cerebral infarctions, 233 hemorrhagic strokes, and 137 unspecied strokes were registered. The authors found that women who ate more than three servings of sh per week had a 16% lower risk of total stroke than women who ate less than one serving a week, However, cerebral infarction or hemorrhagic stroke were not reduced by diet rich in sh. Fatty sh like salmon, whitesh, char, herring and mackerel were not signicantly associated with risk of stroke. In Sweden salmon and herring are eaten salty. This might cancel the health benets of the omega 3 PUFAs. Claims of benets of moderate consumption of fatty sh should therefore still remain valid, say the authors. These results suggest that the consumption of sh, especially of lean sh, may reduce risk of stroke in women. Fish is source of omega 3 PUFAs selenium and taurin. Selenium acts as antioxidant and taurin reduces blood pressure and lowers the level of triglycerides in serum.
534
7.16.14
Benets of omega fatty acids supplementation outweighs any likely hazard of sh oils [287]
Hooper et al. address the risks and benets of omega-3 fats mentioning contaminants such as methylmercury, dioxins and dioxin like polychlorinated biphenyls (PCBs). Michael J. James and colleagues analysed the anti-inammatory eects of sh oil advising patients to take 15mls sh oil daily on juice (equivalent to 14 standard capsules daily) Third party analysis showed dioxins and indicator PCBs, which can be reduced by molecular distillation during processing of sh oil, to be below the level of detection and mercury present at 0.006mg/kg. Analysing mercury levels in both urine and blood in patients who had taken sh oil 15ml/day for at least 3 years low levels within the normal reference range and in most cases at or below the limit of detection were found. In evaluating the risks of sh oil one needs to consider the hazards of treatments it displaces. This collateral damage clearly outweighs any likely hazards associated with sh oil use.
7.16.15
Very high levels of marine-derived n-3 fatty acids reduce heart disease risk [288]
Akira Sekikawa and colleagues 2008 report that Japanese born and living in Japan had two-fold higher blood omega- 3 levels and lower atherosclerotic events compared with a population of white and Japanese living in the US which presented low levels of blood omega-3 and high coronary diseases. According to the authors marine-derived n-3 fatty acids at low levels are cardioprotective through their antiarrhythmic eect. The authors concluded that the diet in Japan rich in sh, with men consuming an average of 100 grams every day, result in high levels of omega-3 fatty acids which may help to prevent the buildup of cholesterol in the arteries. The authors stress that increasing sh intake to two times a week for healthy people is currently recommended in the U.S. The study shows that much higher intake of sh observed in the Japanese may have strong anti-atherogenic eect, which are lifestyle and not genetic dierences related.
7.16.16
High yields of DHA (docosahexaenoic acid) from microalgae [289]
With the introduction of Advanced BioNutritions DHA from microalgae rather than from sh meal and oil, there is the added benet of the sh fed with these microalgae to bee a completely renewable and contaminant-free resource which can be certied as organic. The fermentation process for the production of plant DHA uses the microalgae Crypthecodinium cohnii as well as some other microalgae.
535
DHA and ARA are used infant formulas. The best source of DHA, an omega-3 fatty acid, has traditionally been sh oil. DHA from microalgae avoids mercury contamination of sh oil. Other vegetarian sources such as ax oil are considerably less bioavailable. Other publications on this matter are: Clarke R, Frost C, Collins R, et al. Dietary lipids and blood cholesterol: quantitative metaanalysis of metabolic ward studies. Brit Med J. 1997;314:112-7. Mensink RP, Zock PL, Kester ADM, et al.: Eects of dietary fatty acids and carbohydrates on the ratio of serum total to HDL cholesterol and on serum lipids and apolipoproteins: a meta-analysis of 60 controlled studies. Am J Clin Nutr. 2003;77:1146-55.
7.16.17
Supercritical CO2 extraction for omega-3 fatty acids: Fish oil fractioning [290]
Ana Paula Antunes Corra and colleagues 2008 veried the possibility of using supercritical CO2 to concentrate polyunsaturated omega-3 fatty acids in the form of natural sh oil. The authors found that 7.8 MPa and 301.15 K were the best oil fractioning conditions. Eicosapentaenoic acid (EPA) could not be fractionalized.
7.16.18
Omega-3 fatty acids supplements obtained by supercritical extraction [291]
Espinosa and colleagues 2008 studied the thermodynamics, the simulation and the optimization of supercritical extraction of sh oil fatty acid ethyl esters with ethane as alternative solvent to carbon dioxide for the production of pharmaceutical grade concentrates of eicosapentaenoic acid (EPA) and docohexaenoic acid (DHA) esters, which are the most valuable omega-3 polyunsaturated fatty acid esters. The study included ethane-ester interaction parameters. The authors found a higher solubility of fatty acid ethyl esters in ethane, as well as a slightly better selectivity to EPA and DHA.
7.16.19
Supercritical fractioning of sh oil to improve the EPA/DHA ratio [292]
Perretti and colleagues 2007 used supercritical fractionation of sh oil fatty acid ethyl esters to obtain a lipid fraction enriched in Omega-3 fatty acids and modied EPA/DHA ratio. The authors found supercritical uid fractionation to be useful to change the composition of lipids. The use of proper fractionation temperatures and pressures along the column inuenced the solvent-to-feed ratio to obtain fractions with suitable EPA/DHA ratio for market requirements.
536
7.16.20
Omega-3 fatty acids levels in fresh beef from feedlots [293]
A feedlot or feedyard is a type of concentrated animal feeding operation (also known as factory farming) which is used for fattening livestock, notably beef cattle, prior to slaughter. Aside from ethical and environmental concerns, feedlots have come under criticism for human health reasons. The tissues of feedlot-raised cattle have far more saturated fat than that of grass-fed cattle, some sources say up to 500 percent more. Feedlot-raised beef may after long periods on feed have reduced healthy omega-3 fatty acids because of the corn-and-grain diets of the cattle. Maddock and colleagues assessed the eects of ax addition and ax processing on feedlot performance and carcass characteristics. The researchers found that feeding 8% ax to feedlot heifers increased gain and eciency, and processing ax increased available energy and resulted in increased eciency of gain and increased levels of n-3 fatty acids in fresh beef. [294]
7.16.21
Importance of n-3 fatty acids in health and disease [295]
William E. Connor in a supplement in 2000 states that n-3 Fatty acids favorably affect atherosclerosis, coronary heart disease, inammatory disease, and perhaps even behavioural disorders.
7.16.22
Omega-3 fatty acids and biomarkers of inammation and endothelian activation in women
[296] Lopez-Garcia and colleagues found in 2004 that the intake of alfa-linolenic acid was inversely related to plasma concentrations of C-reactive protein (CRP), and E-selectin. (n-3) fatty acids (eicosapentaenoic and docosahexaenoic) were inversely related to soluble intracellular adhesion molecule (sICAM-1) and soluble vascular adhesion molecule (sVCAM-1). Total (n-3) fatty acids had an inverse relation with CRP, E-selectin, sICAM-1, and sVCAM1. The researchers conclude that dietary (n-3) fatty acids are associated with levels of these biomarkers reecting lower levels of inammation and endothelial activation, which might explain in part the eect of these fatty acids in preventing cardiovascular disease.
7.16.23
The eects of diet on inammation [297]
Giugliano in a review in 2006, states that the incidence of coronary heart disease may be reduced with a diet comprising adequate omega-3 fatty acids intake, reduction of saturated and trans-fats, and consumption of a diet high in fruits, vegetables, nuts, and whole grains
537
and low in rened grains. Prudent dietary patterns may reduce inammation associated with the metabolic syndrome.
7.16.24
Omega-3 fatty acids and serum C-reactive protein [298]
The intake of n-3 polyunsaturated fatty acids or sh is inversely associated with serum C-reactive protein (CRP) concentrations. K. Niu and colleagues, studying in 2006 the eect of high intake of of omega-3 fatty acids from a diet rich in marine products, found that greater intake of n-3 PUFAs was independently related to a lower prevalence of high C- reactive protein concentrations in an older Japanese population with a diet rich in marine products, suggesting that even very high intakes of n-3 PUFAs may lower serum C- reactive protein concentrations.
7.16.25
n-3 Fatty acids and cardiovascular disease [299]
Jan L. Bleslow in 2006 writes that sh oil containing the n-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) is associated with decreased cardiovascular death, whereas consumption of the vegetable oil-derived n-3 fatty acid alfa-linolenic acid is not as eective. At doses >3 g/d, EPA plus DHA can improve cardiovascular disease risk factors, including decreasing plasma triacylglycerols, blood pressure, platelet aggregation, and inammation, while improving vascular reactivity. The American Heart Association recommends that everyone eat oily sh twice per week and that those with coronary heart disease eat 1 g/d of EPA plus DHA from oily sh or supplements.
7.16.26
Conjugated linoleic acid CLA, the cause of insulin resistance and fatty liver [300]
Conjugated linoleic acid (CLA), known as "trans-10, cis-12 CLA", is found in partially hydrogenated vegetable oils and some dietary supplements. CLA is found to be related to non-alcoholic fatty liver disease causing diabetes and obesity. Darshan S. Kelley and colleagues found that DHA (docosahexaenoic acid), and EPA (eicosapentaenoic acid) from sh oils may reduce the eects of CLA. Fish-oil, together with CLAsupplements, prevented harmful side eects of CLA in animals. DHA (docosahexaenoic acid), and EPA (eicosapentaenoic acid) occur in dierent amounts and ratios in fatty or oily sh and other sea food. The authors determined which one of these fatty acids is the active part of sh oils. They found that DHA protects against both CLA-induced insulin resistance and CLA-induced non-alcoholic fatty-liver disease. EPA
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oered only partial protection against CLA-induced fatty liver disease and no protection against insulin resistance.
7.16.27
Adinopectine hormone is associated with diabetes
Adinopectine is an hormone produced by fat cells. Low levels of this hormone is associated with insulin resistance, leading to diabetes. CLA depletes the adipose tissue where adiponectin is made. DHA can restore adipose tissue, and adiponectin levels may return to normal levels. This mechanism explains how DHA protects against insulin resistance, say the authors.
7.16.28
Fatty acids from sh or sh-oil supplements, but not alpha-linolenic acid, benet cardiovascular disease outcomes [301]
Wang and colleagues 2006 systematic reviewed the literature of the eect of dietary n3 fatty acids (eicosapentaenoic acid and docosahexaenoic acid) from sh compared with alpha-linolenic acid on cardiovascular disease outcomes and adverse events. The authors report that most cohort studies found that increased consumption of n-3 from sh or sh-oil supplements, but not of alpha-linolenic acid, reduces the rates of all-cause mortality, cardiac and sudden death, and possibly stroke. The evidence for the benets of sh oil is stronger in secondary- than in primary-prevention settings.
7.16.29
Fish consumption and cognitive decline [302]
In a prospective cohort study Morris and colleagues examined whether intakes of sh and the omega -3 fatty acids protect against age-related cognitive decline. The results of the study were a 10% and 13% slower decline among persons who consumed 1 sh meal per week and 2 or more sh meals per week, respectively, compared with the cognitive decline of persons who consumed sh less than weekly. The authors concluded that sh consumption may be associated with slower cognitive decline with age. Further study is needed to determine whether fat composition is the relevant dietary constituent, as there were little evidence that the omega-3 polyunsaturated fatty acids were associated with cognitive change.
7.16.30
Balancing benets and risks of seafood study 2006 [303]
The 2006 study "Seafood Choices: Balancing Benets and Risks" sponsored by the National Oceanic and Atmospheric Administrations (NOAA) Marine Fisheries Service and
7.16. OMEGA-3 POLYUNSATURATED FATTY ACIDS IN FOOD the FDA, supports public health guidelines.
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According to this study the contamination coming from seafood counts only for only 9 per cent of the PCBs in the diet. The rest come from meat and dairy. According to this study, which was conducted by the US National Academies of Science, Institutes of Medicine, the levels of dioxins and polychlorinated biphenyls are low, and potential cardiovascular and other eects are outweighed by potential benets of sh intake. The ndings of the study is backed up by the results of the study of Dariush Mozaarian and Eric B. Rimm [304]
7.16.31
Fish intake, the risks and the benets [304]
Searching reports published through April 2006, Dariush Mozaarian, and Eric B. Rimm found evidences that modest consumption of sh (eg, 1-2 servings/wk), especially species higher in the n-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), reduces risk of coronary death by 36% and total mortality by 17% and may favourably aect other clinical outcomes. Intake of 250 mg/d of EPA and DHA appears sucient for primary prevention. Women of childbearing age and nursing mothers should consume 2 seafood servings/wk, limiting intake of selected species. A variety of seafood should be consumed; individuals with very high consumption (>5 servings/wk) should limit intake of species highest in mercury levels. Levels of dioxins and polychlorinated biphenyls in sh are low, and potential carcinogenic and other eects are outweighed by potential benets of sh intake. the benets of sh intake exceed the potential risks. For women of childbearing age, benets of modest sh intake, excepting a few selected species, also outweigh risks.
7.16.32
Recommendations of the National Heart Foundation [305]
Reduce saturated fat (SF) (and -fatty acids) to reduce CVD risk. Replace SF and transfatty acids with polyunsaturated fatty acids (PUFAs), and monunsaturated fatty acids (MUFAs). Identify food sources of dierent fats i.e. SF (and trans fats), mono and poly. Promote consumption of at least 2 sh meals per week.
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7.16.33
The Northern Osteosporosis and Obesity Study (NO2 Study) linking omega-3 fatty with increased bone build up in young men
Magnus Hgstrm and colleagues in a Sweden study known as the Northern Osteosporosis and Obesity Study (NO2 Study) measured fatty acids in the serum phospholipids fraction in healthy men and their association with bone mineral density and bone accrual. They found that n-3 fatty acids, especially docosahexaenoic acid (DHA, 22:6n-3), are positively associated with bone mineral accrual and with peak bone mineral density in young men around the age of 16 to 22 years. In an earlier study higher ratio of n-6 to n-3 fatty acids was negatively associated with bone build up in elderly men and women. [306] Chaim Vanek and William Connor suggested that the healt benet of n-3 fatty acids on bone health might result from aecting expression of the role of peroxisome proliferatorsactivated receptor gama (PPAR-gama). Overexpression of this protein is linked to lower bone mass, therefore eicosapentaenoic acid EPA and docosahexaenoic acid DHA may protect bone mass. The authors call for more research on this matter. [307]
7.16.34
The essential fatty acids
The essential polyunsaturated fatty acids (PUFAs) comprise 2 main classes: n-6 and n-3 fatty acids. The most common source of n-6 fatty acids is linoleic acid is found in vegetable oils. Arachidonic acid n-6 fatty acid, is obtained largely by synthesis from linoleic acid in the body. The n-3 fatty acids eicosapentaenoic acid and docosahexaenoic acid are found in sh and sh oils. The benecial health eects of these two n-3 fatty acids were rst described in the Greenland Eskimos, who consumed a high-seafood diet and had low rates of coronary heart disease, asthma, type 1 diabetes mellitus, and multiple sclerosis. These positive health attributes of n-3 fatty acids include reduction of risc of cancer, inammatory bowel disease, rheumatoid arthritis, and psoriasis. [295] Signicant benets of dietary supplementation with sh oils were found in several inammatory and autoimmune diseases in humans, including rheumatoid arthritis, Crohns disease, ulcerative colitis, psoriasis, lupus erythematosus, multiple sclerosis and migraine headaches. [308]
7.16.35
Psoriasis
Psoriasis is a disease of the skin showing sharply dened red patches covered with silvery scales in the regions of the elbows and knees, genitals, perianal region, in the scalp and
7.17. METHYLMERCURY
541
rarely in the eyelids. Treatment with preparations of Anacardium, Carica, Cassia, Thespesia, or topical application of Dithranol (Cignolin or Anthralin) is used together with sunlight, articial UV light, steroids, coal tar, salicylic acid, and synthetic Vitamin D analogues. Psoriasis was considered to be an epidermal disease. Recently it was found that drugs like cyclosporin which suppress the activity of T-cells (white blood cells)and the immune system, reduced the severity of psoriasis. This underlines the importance of T-cells in the etiology of the disease. [309] Australian regulations for mercury in sh [310] The Australia New Zealand Food Standards Code prescribes maximum level for mercury of 1.0 mg mercury/kg for swordsh, southern bluen tuna, barramundi, ling, orange roughy, rays and shark. and a level of 0.5 mg/kg for all other species of sh, crustacea and molluscs. The U.S. Environmental Protection Agency (EPA) has issued two major reports on mercury the Mercury Study Report to Congress (1997) and the Utility Hazardous Air Pollutant Report to Congress (1998). In those reports, fossil-fuel power plants, especially coal-red utility boilers, were identied as the source category that generates the greatest Hg emissions, releasing approximately 40 tons annually in the United States.
7.17
Methylmercury
[311] The major pathway for human exposure to methylmercury is consumption of contaminated sh. Dietary methylmercury is almost completely absorbed into the blood and is distributed to all tissues including the brain; it also readily passes through the placenta to the foetus and foetal brain.
7.17.1
Major Health Eects of Methylmercury
Epidemics of mercury poisoning following high-dose exposures to methylmercury in Japan and Iraq demonstrated that neurotoxicity is the health eect of greatest concern, such as eects on the foetal nervous system, mental retardation, cerebral palsy, deafness, blindness, and dysarthria in utero and in sensory and motor impairment in adults. The studies in the Seychelles Islands, New Zealand, and the Faroe Islands were designed to evaluate childhood development and neurotoxicity in relation to foetal exposures to methylmercury in sh-consuming populations. No adverse eects were reported from the Seychelles Islands study, but children in the Faroe Islands exhibited subtle developmental dose-related decits at 7 years of age. These eects include abnormalities in memory, attention, and language. In the New Zealand prospective study, children at 4 and 6 years of age exhibited deciencies in a number of neuropsychological tests.
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Other studies were conducted in the Amazon; Ecuador; French Guiana; Madeira; Mancora, Peru; northern Quebec; and Germany. Eects of methylmercury on the nervous system were reported in all but the Peruvian population. The EPATissue Residue Criterion is 0.3 mg methylmercury/kg sh. This is the concentration in sh tissue that should not be exceeded based on a total sh and shellsh consumption-weighted rate of 0.0175 kg sh/day. The risks posed by pollutants such a methylmercury, and polychlorinated biphenols (PCBs) is outweighed by the benets of sh consumption, like omega-3, protein,mineral content, and essential vitamins such as vitamin D where a 150 g serve of sh will supply around 3 micrograms of vitamin D. EPA is proposed to function by increasing blood ow in the body, to aect hormones and the immune system, and is involved in the membrane of ion channels in the brain, making it easier for them to change shape and transit electrical signals.
7.17.2
Mercury in seafood [312]
Seafood is the most important source of human exposure to mercury which may spread globally when released from environmental stores due to human activities or through natural processes. In form of methylmercury it accumulate in the food chain where sh and marine mammals are the most prominent examples. Balshaw and colleagues 2007 report mercury concentration in marine animal to be one-million times that of the surrounding water body, exceeding 1 microg g(-1). Other seafood, however, have mercury content which ranges from 0.1 to 0.2 microg g(-1), usually below 0.5 microg g(-1). The primary source of human exposure to environmental mercury is through seafood consumption.
7.17.3
Highest concentrations of methylmercury in predator sh from Tapajs compared with other rivers [313]
Kehrig and colleaugues 2008 assessed the mercury assimilation by a predator sh (Cichla spp.) of three Amazon rivers (Negro, Madeira, Tapajs) and two hydroelectric reservoirs (Balbina, Tucuru). The authors found methylmercury concentrations varying from 0.04 to 1.43microgg(-1) w.w., growing accordingly to the sh body weight. The authors report that methylmercury concentrations was highest in one of the two reservoirs and in Rio Tapajs. The researchers associate this with gold mining and deforestation of these sites.
7.17.4
Mercury concentration higher in predator sh from river Madeira compared with those of Rio Negro [314]
Drea and Barbosa 2007 comparing mercury bioaccumulation in sh found that herbivorous sh of the Amazon rivers Madiera and Rio Negro had lower concentrations of mercury
7.17. METHYLMERCURY
543
compared with predator sh. Mercury concentration of herbivorous sh from both rivers were found not to dier (2 - 182 ngHg/g), despite the dierence of the mercury content of these rivers. Predator sh, at the top of the food chain such as Hoplias malabaricus and Cichla spp presented concentrations of 80 to 747 ngH/g. Predator sh from the river Madeira showed higher mercury concentrations than those of the Rio Negro. The authors stress that the Rio Madeira has been greatly impacted by agriculture, alluvial gold extraction, and a hydroelectric reservoir, whereas the Rio Negro is much less aected by these activities.
7.17.5
Mercury in sh from Alaska [315]
Jewett and Duy 2007 reviewed data of methylmercury concentrations in sh. It is the most toxic form of mercury. The authors found that most sh had muscle Hg concentrations of smaller or =1 mg kg(-1) (wet wt.), which is within the USFDAs Action Level and Alaskas guideline for safe concentrations of MeHg in sh. Pacic salmon (Oncorhynchus spp.) was found to have less than or equal to 0.1 mg kg(-1)) Hg concentrations. Pacic halibut (Hippoglossus stenolepis) has a mercury content less than 0.3 mg kg(-1) Hg. The authors stress, however, that Northern pike (Esox lucius), a predator sh, has the highest Hg values, which often exceedes guidelines for food consumption.
7.17.6
Mercury concentration in sh from Victoria Lake [316]
Campbell and colleagues 2003 found total mercury concentrations in sh of the Victoria Lake usually below permissible World Health Organization (WHO) concentrations. However, Nile perch was found to have up to 200 ng/g concentrations of total mercury, but is not being considered relevant because this sh is rarely caught. The total mercury concentrations of water were below Canadian drinking water guidelines but were higher then water of Great Lakes. Sediment and soil total mercury concentration are comparable to those in northern latitudes and lower than data of the Amazon basin. It is believed that important total mercury sources of the region are biomass burning and soil erosion, whereas gold mining in Tanzania is of less concern. The authors recommends regular monitoring and risk assessment in the catchments of Lake Victoria Still to insure human safety and protect the nature of the Lake.
7.17.7
The Pregnancy Outcome and Community Health (POUCH) Study
A diet high in ocean sh poses risk of premature birth. [317] A study leaded by Fei Xuein and published in 2006, reinforced previous ndings suggesting that sh consumption is a major source of mercury exposure for pregnant women. The
544
greatest sh source for mercury exposure appeared to be canned sh, both because it was consumed more and, per meal, it was among the sh categories associated with the highest levels of mercury in maternal hair. The observed relationship between elevated mercury levels and increased risk of very preterm delivery is a new nding and requires caution in interpretation. Major strengths of the present study include the large number of pregnant women participating, the prospective design, and the use of hair as an index of methylmercury exposure. Hair levels of total mercury represent a longer window of exposure than those of blood levels. Mercury levels in hair ranged from 0.01 to 2.50 ppm (mean = 0.29 ppm, median = 0.23 ppm). The study is the rst to report an association between delivery at less than 35 weeks gestation and maternal hair mercury levels at or above 0.55 ppm.
7.17.8
The Seychelles Islands study nds no threat coming from diet high in ocean sh [318]
Philip W. Davidson and colleagues in a ten-year study of over 700 children in the Seychelles Islands found that the mean maternal hair total mercury level was 6.8 ppm and the mean child hair total mercury level at age 66 months was 6.5 ppm. No adverse outcomes at 66 months were associated with either prenatal or postnatal MeHg exposure. The authors concluded that consumption of a diet high in ocean sh appears to pose no threat to developmental outcomes through 66 months of age. The Seychelles Islands study is signicant as the studied population eats 12 sh meals a week, There is no home made mercury pollution.
7.17.9
Omega-3 fatty acid function of brain neurons [319]
Docosahexaenoic acid (22:6n-3), one of the main structural lipids in the mammalian brain, plays crucial roles in the development and function of brain neurons. The function of DHA in neurogenesis and learning was examined in a study conducted by Kawakita, Hashimoto and Shido Ohese. The researchers demonstrated that docosahexaenoic acid eectively promotes neurogenesis both in vitro and in vivo, suggesting that it has the new property of modulating hippocampal functionregulated by neurogenesis. Maintaining brain DHA concentrations may be an important part of prevention of neurodegeneration with ageing.
7.17.10
Fish oil reduces pro-arrhytmic eects of saturated fats [320]
According to Pepe and McLennan sh oil modies cardiac membrane phospholipid fatty acid composition to confer increased eciency of oxygen utilization and antiarrhythmic
7.17. METHYLMERCURY
545
eects. Studying the eect on rats the researchers found that sh oil rich in EPA and DHA. at a dose as low as 3% of total fat dietary supplement eectively reversed the high oxygen requirements, reduced the coronary release of creatine kinase and reduced the proarrhythmic eects of a continued consumption of (9%) saturated fatty acids-rich diet in rats. The studies on omega-3 fatty acids started with Dr. Jrn Dyerberg Hans Olaf Bang and Aase Brondum Nielsen studying the blood lipids of the Inuit Eskimos of the north-west coast of Greenland in 1970. Despite their high fat diet the Inuits had a low rate of 5,3 per cent from cardiovascular disease, compared with 40 per cent found in USA. The researcher s found low blood lipids levels and high levels of eicosapentaenoic acid (EPA) acid and docosahexaenoic acid (DHA) in the Inuit blood serum. [321] [322] EPA and DHA ratio of 3:2 is indicated, but not essential because the fatty acids can be interconverted by the body. Overshing the oceans will limit the resources of omega fatty acids from sh. Algae culture and genetic engineering of plants may overcome the shortage of EPA and DHA. Improvements in blood lipid levels, a reduced tendency of thrombosis, blood pressure and heart rate improvements, and improved vascular function. Survivors of myocardial infarction fatty sh (300 g/week, or 0.35g n-3 polyunsaturated fatty acids daily) reduced overall mortality by 29% and mortality from coronary heart disease by a third. A reduced intake of saturated fat with a proportional increased intake of polyunsaturated fat and a high bre diet were ineective. [323]
7.17.11
Summary of current dietary recommendations concerning lipids [324]
Alice H Lichtenstein in a research paper summarizes the actual dietary recommendations as follows: Dierent types of dietary protein or individual amino acids have little eect on lipoprotein patterns. Saturated fatty acids increase LDL and HDL cholesterol, whereas trans fatty acids increase LDL but not HDL cholesterol. Unsaturated fatty acids decrease LDL and HDL cholesterol, polyunsaturated more so than monounsaturated. Dietary carbohydrate tends to increase plasma triglyceride when it displaces fat, accompanied by a decrease in HDL cholesterol concentrations.
546
Short-term data favour substituting protein and fat for carbohydrate, whereas long-term data have failed to show a benet for weight loss. During an active weight loss period lowcarbohydrate diets more favourably aect triglyceride and HDL and less favourably aect LDL cholesterol concentrations. The author calls for more research on macronutrients.
7.17.12
Fish advisories in United States [325]
Each state sets its own criteria and decides which bodies of water to monitor. Fish advisories are voluntary state recommendations and are not governed by federal regulations. Frequently, when a sh advisory is issued it is because of pollutants that have lingered in the environment for long periods, sometimes decades, even though they are no longer used or their use has been signicantly curtailed. These pollutants include PCBs, chlordane, DDT, mercury and dioxin. EPA has made considerable progress toward reducing the occurrence of these contaminants in the environment: EPA issued rst-ever regulations to control mercury emissions from the power sector by 70 percent, the Clean Air Mercury Rule. Production of PCBs for use ceased in 1977; chlordane was banned in 1988; DDT was banned in 1972; and known and quantiable industrial emissions of dioxin in the United States are estimated to have been reduced by approximately 90 percent from 1987 levels.
7.17.13
General Dietary Advice [325]
FDA recommends that consumers eat a balanced diet, choosing a variety of foods including fruits and vegetables, foods that are low in trans fat and saturated fat, as well as foods rich in high bre grains and nutrients. Fish and shellsh can be an important part of this diet.
7.17.14
WHO guidelines for mercury in sh [326]
The World Health Organizations guidelines maintain that the lowest level that could possibly be harmful to humans is 5 parts per million (ppm).This level is based on scientic results from the 1960s that placed the level at which risk begins at 50 ppm for most people; WHO then applied a safety factor of 10, deciding that a level of 5 or less is safe for even the most vulnerable populations. EPA has recommended that a person ingest no more than 30 micrograms of mercury per day. Based on estimates of U.S. sh consumption, FDA recommended that only commercial sh with less than 1 ppm of mercury be sold. Later on the EPA recommended to Congress that the tolerable daily intake of mercury be dropped to just one-fth the current allowable level, to about 6 micrograms per day.
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The FDA supports statements that it is safe to eat sh and shellsh twice a week and that one should always eat a variety of species. Morrissey stresses that pregnant women should stick with current FDA recommendations of about 12 ounces (340 grams) per week. Do not eat shark, swordsh, King Mackerel, Tilesh. The rest of the population should be eating sh four to seven times per week.
7.17.15
US FDA List of Mercury Levels in Commercial Fish and Shellsh
Recent US FDA data of mercury levels in sh and shellsh are available at: http:// www.cfsan.fda.gov/~frf/sea-mehg.html and Mercury Concentrations in Fish: FDA Monitoring Program (1990-2004) http://www.cfsan.fda.gov/~frf/seamehg2.html
7.17.16
EPA and FDA sh consumption advice for pregnant women and young children [327]
EPA and FDA advice not eat: Shark, Swordsh, King Mackerel, Tilesh. They contain high levels of mercury. EPA and FDA recommend to eat up to 12 ounces (2 average meals) a week of a variety of sh and shellsh that are lower in mercury. Five of the most commonly eaten sh that are low in mercury are shrimp, canned light tuna, salmon, pollock, and catsh. EPA and FDA says to be carefully with albacore ("white") tuna which has more mercury than canned light tuna. No more than 6 ounces (one average meal) of albacore tuna sh from local lakes, rivers, and coastal areas. per week should be eaten and no other sh during that week.
7.17.17
EWG recommendation in addition to FDA [328]
Recommendation of the Environmental Working Group (EWG) and the U.S. Public Interest Research Group (U.S. PIRG) published in Brain Food: What Women Should Know About Mercury Contamination of Fish: Pregnant women, nursing mothers and all women of childbearing age, should not eat tuna steaks, sea bass, oysters from the Gulf Coast, marlin, halibut, pike, walleye, white croaker, and largemouth bass. These are in addition to FDAs recommendation to entirely avoid shark, swordsh, king mackerel and tilesh. These women should eat no more than one meal per month combined of canned tuna, mahi-mahi, blue mussel, Eastern oyster, cod, pollock, salmon from the Great Lakes, blue crab from the Gulf of Mexico, wild channel catsh and lake whitesh.
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The following sh are safer choices for avoiding mercury exposure: farmed trout or catsh, shrimp, sh sticks, ounder, wild Pacic salmon, croaker, haddock, and blue crab from the mid-Atlantic.
7.17.18
Mercury Levels in High-End Consumers of Fish [329]
Jane M. Hightower and Dan Moore tested mercury levels in blood and hair of frequent sh eaters. They found mercury levels ranging from 2.0 to 89.5 g/L for the 89 subjects. The mean for 66 women was 15 g/L, and for 23 men was 13 g/L. (Environmental Protection Agency (U.S. EPA) and the National Academy of Sciences recommend keeping the whole blood mercury level < 5.0 g/L or the hair level < 1.0 g/g . This corresponds to a reference dose (RfD) of 0.1 g/kg body weight per day.) The authors concluded that high blood levels of mercury could be reduced by abstaining from eating sh for more than 21 weeks. Mercury levels in tested women averaged in this study 10 times the levels recommended by the U.S. Environmental Protection Agency and the National Academy of Sciences. Levels in men were close behind, while some of the children tested were found to have levels 40 times those recommended. Nearly 90% of those tested were above the recommended levels.
7.17.19
Environment and power plants [330]
Concern over mercury contamination has led government agencies to warn consumers not to eat bass, trout and other sport sh caught in over a thousand lakes and streams across 40 U.S. states. Coal-burning power plants are the single largest source of mercury pollution, and the only major source the government does not regulate. Mercury is an extremely volatile metal that can be transported great distances after spewed into the atmosphere. Once it reaches an aquatic environment, mercury is transformed into methylmercury, a potent neurotoxin, which accumulates in top predator sh and the people and wildlife who eat them. When ingested by pregnant women, methylmercury readily crosses placenta and targets the developing brain and central nervous system. Even relative tiny amounts can produce serious developmental delays in walking, talking hearing and writing. Infants can also be exposed to high levels of methylmercury during breastfeeding. Mercury emissions from the power sector was reduced by 70 percent, following the EPA Clean Air Mercury Rule of 2005. [331]
7.18
Fatty acids with trans conguration
Most of the unsaturated fatty acids in nature have a cis conguration. The trans conguration results mainly during chemical hydrogenation of polyunsaturated fatty acids.
7.18. FATTY ACIDS WITH TRANS CONFIGURATION
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In February 1995 the rst part of the Euromic-Study was published in The Lancet. This part of the study was mainly concerned with trans fatty acids and diseases of the coronary vessels. The second part of the study was related to intake of TFA and cancer. Approximately 2 to 3% of the fat of the milk and derivates have a cis conguration being elaidinic acid ( C18:1 trans) responsible for most of the trans fatty acids of milk. In some cases the amount of trans fatty acids in milk and derivates can be as high as 5%.
7.18.1
Trans Fatty acids and Alzheimers disease [332]
Grimm et al.2012 report that trans fatty acids accumulate in the membrane of cells. In this study the intake of trans fatty acids was found to increase the production of amyloid beta (A ) peptides which are the main components of senile plaques of Alzheimers disease. Trans fatty acids increase amyloidogenic and decrease nonamyloidogenic processing of APP increasing therefore amyloid beta (A ) peptides production and their oligomerization and aggregation. The data of this in vitro study suggests that the intake of trans fatty acids may increase the risk of Alzheimers disease or speed up its onset. Other negative health eects of trans fatty acids in food products The trans conguration was found to be linked to negative health eects. The food industry in Europe is replacing these fats using fractionated palm oil in their formulations. Danaei et al 2011 analysing data of 2005, listed the preventable causes of death in USA as tobacco smoking, high blood pressure. overweight/obesity and physical inactivity. High dietary salt, low dietary omega-3 fatty acids, and high dietary trans fatty acids were the dietary risks with the largest estimated mortality eects. [333] Mozaarian et al 2009 called for consumer education regarding the sources and hazards of TFA, combined with voluntary or legislated adoption by restaurants and food manufacturers of alternatives to partially hydrogenated oils, to reduce coronary events. [334]
7.18.2
Dairy trans fatty acids should be included in labelling or nutrient proling for claims says EDA [335]
During a conference of the European Dairy Association (EDA) on 12th February 2008 in Brussels the speakers concluded that there is no scientic evidence on negative health effects from TFA of natural origin found in dairy and ruminant meat. EDA therefore stated
550
that dairy TFA should not be taken into consideration for labelling or nutrient proling for claims. The association stresses that consumption of dairy products should rather be promoted for their signicant contribution to the nutrient supply such as high quality protein and several key minerals and vitamins. EDA underlines in a position paper that science indicates that: There are compositional and physiological dierences between ruminant TFA and industrially produced TFA from vegetable origin. Scientic literature showing negative health implications of TFA is based on data dealing with industrially produced TFA. Data looking into the health eects of ruminant TFA have not shown any negative eects. Intake of ruminant TFA from dairy products has no signicant nutritional relevance in relation to contribution to total energy intake and overall dietary consumption. Therefore, EDA is of the opinion that: Ruminant TFA are dierent from industrially produced TFA. Care should be taken to deliver the right message to the consumer. Dairy TFA should not be considered for nutrient proling or labelling. Dairy ts into a healthy diet. [336]
7.18.3
The action of the margarine industry
The International Federation of Margarine Association (IFMA) and the IMACE (Association of Margarine Industry of the EC Countries)indexAssociation of the Margarine Industry of the EC Countries (IMACE) recommended to lower the amount of TFA (Trans Fatty Acids) in margarine to a maximum of 5% of fat. Margarine to be used as spread or cooking should have less than 1%.[337] The trans fatty acids can be reduced during rening by reducing the temperature of the process. This however means a longer time the oil or fat has to spend in the system an therefore higher operation costs. The increased costs should be accepted in change of a healthy product. The deodorization of vegetable oils during rening using temperatures over 230o C results more than 3% of trans fatty acids. Using temperatures under 230o C a maximum of 0,5% trans fatty acids are formed. This can be tolerated.
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A real great amount of trans fatty acids are formed by partial hydrogenation of soy oil. A melting point of 36 to 37o C of soya oil very commonly used in the production of margarine as well as deep frying fat and products for bakery results in up to 50% of trans fatty acids. Trans fatty acids are therefore hidden in cakes, cookies, creams and margarine and all kind of fried product. In USA partially hydrogenated oil is used almost everywhere. The trans fatty acids represents therefore a great menace to health because they act as saturated fatty acids and may cause arteriosclerosis. Trans fatty acids can be avoided during industrial processing of oil using entirely hydrogenated oil. If all double and triple bindings of the molecule of the fatty acids are saturated the trans stereoisometric conguration ceases to exist and there is no negative physiological activity left. To obtain the same consistence of partially hydrogenated oil it is necessary to add more liquid oil and esteried the whole compound. This implies in higher production cost. All eorts to get healthy products should however be made, including the acceptance of a small increase of price of the nal product in order to get margarine, fats, creams and bakery products having less than 5% of their fatty acids in trans conguration.
7.18.4
Trans-fatty acids and their isomers in dierent food sources [338]
Micha and colleagues 2010 looked at food sources of individual plasma phospholipid trans fatty acid isomers which are known to increases the risk of coronary artery disease. TFAS were associated with foods made with partially hydrogenated vegetable oils. The authors found TFAS and their isomers in biscuits, chips and/or popcorn, fried foods. Bakery foods were associated with t-18:2 isomers,animal foods, including red measts and butter and high-fat dairy with t-16:1n-7, Margarine was associated with t-16:1n-9 isomers. The authors stress the importance to consider the isomer forms of trans fatty acids in studies and their dierent food sources. Isomers of trans fatty acids dier in their health eects.
7.18.5
Reduction of trans-fatty acids may contribute to the prevention of prostate cancer [339]
According to Jorge Chavarro and colleagues 2008 blood levels of trans isomers of oleic and linoleic acids are associated with an increased risk of non-aggressive prostate tumours. Trans fatty acids are also known to raise serum levels of LDL-cholesterol, reduce levels of HDL-cholesterol, can promote can cause endothelial dysfunction, and inuence other risk factors for cardiovascular diseases.
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This study backs food scientists and heath professionals and NGOs like CSPI which call for a worldwide ban of trans-fatty acids so as already in force in Europe. Partial hydration of edible oil can be avoided using fractions of palmoil. U.S., however has great plantations of soy, therefore the oil industry does not import palmoil which is more expensive. Deep-frying oil and margarine are still high on unhealthy trans-fatty acids.
7.18.6
Snacks, fast foods and restaurant meals should phase out unhealthy fats [340]
Marie-Pierre St-Onge and colleagues 2007 in a study found that replacing low-fat and highfat snacks with snacks rich in polyunsaturated fatty acids (PUFAs) and low in saturated and trans fatty acids improves cardiovascular health. The authors found in their study that the reduction of LDL- and total cholesterol concentrations were greater with the low-fat and the high-PUFA diets than with the high-fat diet The high-PUFA diet tended to reduce triacylglycerol concentrations, and this change was greater than that with the low-fat and high-fat diets. In addition the PUFA diet was the only one that tended to reduce triacylglyerol concentrations. However this that low fat diets may lead to reduction in high density lipoprotein (HDL /good cholesterol), and increase triacylglycerol concentrations. Some high fat foods such as nuts and avocados are therefore considered as healthy. The authors concluded that snack type aects cardiovascular health. Consuming snack chips rich in PUFA and low in saturated or trans fatty acids instead of high-saturated fatty acid and trans fatty acid or low-fat snacks leads to improvements in lipid proles concordant with reductions in cardiovascular disease risk. According to the authors the consumption of snacks above balanced meals should not be promoted as healthy, but this research adds to the evidences that snacks, fast food and restaurant meals should be reformulated to reduce unhealthy trans fatty acids and to increase polyunsaturated fatty acids. Organisations like the Center for Science in the Public Interest (CSPI) are working hard on this issue.
7.18.7
Replacing saturated fats [341]
Reviewing studies related to the eects of saturated fats on heart health, Micha and Mozzafarian 2010 found that replacing saturated fatty acids (SFA) with polyunsaturated fat modestly lowers coronary heart disease risk. Replacing SFA with carbohydrate has no benet and replacing SFA with monounsaturated fat has uncertain eects. Results of studies found mixed and unclear eects of SFA on vascular function, insulin resistance, diabetes, and stroke.
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The authors highlight the need of more studies, and warns from public health programs on reducing SFA consumption without considering the replacement nutrient or other foodbased risk factors for heart diseases.
7.18.8
Poly unsaturated fats should replace saturated fats and not be reduced in human nutrition [342]
Mozaarian, Micha and Wallace 2010 report that studies recommend to reduced saturated fat (SFA) consumption to reduce the risk of coronary heart disease (CHD), and some even recommend to lower or limit polyunsaturated fat (PUFA) consumption. The authors reviewing studies found that PUFAS consumption of 14.9% energy presented a CHD risk reduction of 10%, compared with groups consuming 5.0% PUFAS. The overall pooled risk reduction was 19%, corresponding to 10% reduced CHD risk for each 5% energy of increased PUFAS. The authors concluded that polyunsaturated fatty acids should therefore be used as replacement of saturated fats and PUFAS should not be reduced as they proved to reduce coronary heart disease.
7.18.9
Fats and margarine for bakery
Fats and margarine for bakery must have special stability, structure and melting point. Therefore special hydrogenated oils and fats are needed.
Table 7.4: Example of fat for aky pastry Palm oil, hydrogenated melting point 45/46o C 40% o Soybean oil, hydrogenated melting point 36/38 C 35% Rapeseed oil, liquid melting point 5o C 25% This fat blend has a content of trans-fatty acids of 20 to 25%. Melting points of fats found in nature Coconut fat melting point 24-28o C Palm oil melting point 37-39o C Palmkernel oil melting point 26-30o C These melting points are to low for the production of pastry margarine. To avoid hydrogenated oils and fats for bakery it is possible to fractionate fats leaving it at specic temperature to permit the hard components (stearin) to crystallize. Filtration separates the low melting components (olein). Industry still uses hydration instead of fractionated fats because of the the higher prices of fractionated fats. For the sake of health the higher price should be accepted by the
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consumer in order to get healthy food. Bakery products bear a lot of hidden fats and are a great source of trans fatty acids with arteriosclerotic and carcinogenic activity.
7.18.10
Bakery margarine, pop-corn and waels high on transfatty acids [343]
The researcher Gerhard Jahreis from the university of Jena, Germany, analysing more than 800 foods, found up to 20 percent to have trans fatty acids varying from low to very high. He calls for clear labelling of trans fatty acids on foods. Denmark sti regulations on trans fatty acids give a limit of maximal 2 percent. Germany does not have any such binding limits on foods. Jahreis found that meanwhile tube margarine had low trans levels,backers margarine, especially margarine for pu pastry, used in croissants, however, had extreme high content of trans fatty acids. He stresses that other foods like microwave-popcorn and waes also vary strongly in the level of the coronary diseases risking fatty acids. Feeding on snacks, like cookies, chips and others, the daily intake of trans fats may easily reach of 10g, where 2 g are considered as safe.
7.18.11
Madeira cake prepared with extra virgin olive oil/margarine mixture [344]
Madeira cake is a sponge cake with a rm yet light texture and is traditionally avoured with lemon. The Madeira Cake is sometimes mistakenly thought to originate from the Madeira Islands; however, that is not the case as it was instead named after the wine, popular in England at the time. [345] It is made with equal parts of butter, sugar, plain our, grated zest of orange and lemon, lemon juice, baking powder and candied peel. The industry replaces butter with margarine and uses emulsiers such as mono and diglycerides to replace most of the eggs. Butyric acid gives the butter aroma and riboavin gives the egg yolk colouring. Paraskevopoulou and colleagues 2010, trying to improve healthiness of this formulation, replaced some of the margarine with extra virgin olive oil. This supposedly reduces trans fatty acids of margarine used in the formulation. The authors report that olive oil in the formulation increased batter density and cake volume while decreased the weight loss during baking. The cake prepared with this olive oil/margarine mixture was highly appreciated by the consumers. [344]
7.19. TRANS FAT CLAIMS, FDA PROPOSAL
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7.18.12
Oxidative stress induced by trans fatty acids [346]
High consumption of trans fat has been associated with high oxidative stress in humans, which could increase the risk of the development or acceleration of several diseases, such as atherosclerosis, cancer, and type 2 diabetes. Jahreis and colleagues monitored several urinary and blood biomarkers of oxidative stress induced by a diet of 6g/day of trans fatty acids:
7.18.13
Free radical-induced lipid peroxidation
high concentration of urinary 8-iso-PGF2alfa were found.
7.18.14
Cyclooxygenase-mediated inammatory response
The concentrations of 15-keto-dihydro-PGF2alfa was not aected by the diet.
7.18.15
Oxiddative DNA damage
measured as urinary 7,8-dihydro-8-oxo-2-deoxy-guanosine was not aected by the diet. The authors conclude that prolonged diet of >5.0 g/d of trans fats could be relevant to the development of disease, as seen on an increase in urinary 8-iso-PG conguration being consumed about 30 to 40 gram a day make the total blood cholesterol and LDL cholesterol to rise. HDL cholesterol is reduced by trans fatty acids. In countries with high consume of partially hardened soya oil like USA there is an increase of heart diseases like heart infarct. Industrial manufactured oils and fats cannot avoid completely trans fatty acids. By using proper technologies the content of trans fatty acids however can be reduced to a tolerable amount of maximum 5%. A daily intake of 4 to 6 gram of trans fatty acids are told to be harmless. All eort should be made by the industry to reduce the amount of trans fatty acids.
7.19
Trans fat claims, FDA proposal
[347] In its November 1999 proposal, FDA proposed a denition for the nutrient content claim "trans fat free" and proposed limits on the amounts of trans fat wherever saturated fat limits are placed on nutrient content claims, health claims, or disclosure and disqualifying levels. With regard to the specic denitions, FDA proposed that "trans fat free" and "saturated fat free" should be dened as less than 0.5 g trans fat and less than 0.5 g saturated fat per reference amount and per labelled serving; "low saturated fat" as 1 g or less of
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saturated fat and less than 0.5 g of trans fat per reference amount and not more than 15 percent of calories from saturated fat and trans fat combined; "reduced saturated fat" as at least 25 percent less saturated fat and at least 25 percent less saturated fat and trans fat combined; "lean" as 4.5 g or less of saturated fat and trans fat combined; and "extra lean" as less than 2 g of saturated fat and trans fat combined. In addition, cholesterol claims were allowed only on foods containing 2 g or less of saturated fat and trans fat combined, and disqualifying and disclosure levels were set at 4 g or less of saturated fat and trans fat combined. FDA did not propose to dene "low trans fat."
7.19.1
Quantitative declaration of trans fat in the Nutrition Facts panel [347]
The Food and Drug Administration (FDA) amended its regulations on nutrition labelling to require that trans fatty acids be declared in the nutrition label of conventional foods and dietary supplements on a separate line immediately under the line for the declaration of saturated fatty acids. FDA is revised Sec. 101.9(c) by adding paragraph Sec. 101.9(c)(2)(ii) to require the quantitative declaration of trans fat in the Nutrition Facts panel. This new paragraph requires the listing of trans fat on a separate line under the statement for saturated fat. As is the case for all subcomponents of total fat, it is to be indented and separated by a hairline, with the amount expressed as grams per serving to the nearest 0.5 g increment below 5 g and to the nearest gram increment above 5 g. If the serving contains less than 0.5 g, the content must be expressed as 0, except when the statement "Not a signicant source of trans fat" is used. In addition, the agency is clarifying that the word "trans" may be italicized to indicate its Latin origin.
7.19.2
Not a signicant source of... [347]
Section 101.9(c) requires that information on mandatory nutrients, such as saturated fat and trans fat, be included in all nutrition labelling unless otherwise excepted from such labelling as provided for in specied paragraphs. Special provisions within Sec. 101.9(c) allow for shortened formats that provide manufacturers exibility to omit noncore nutrients (i.e., mandatory nutrients other than calories, total fat, sodium, total carbohydrate, and protein) that are present in insignicant amounts from the list of nutrients and group them in a summary statement at the bottom of the label that states -Not a signicant source of-(see 58 FR 2079 at 2083, Comment 8, January 6, 1993). These special provisions are found in Sec. 101.9(c)(1)(ii) for calories from fat, Sec. 101.9(c)(2)(i) for saturated fat, Sec. 101.9(c)(3) for cholesterol, Sec. 101.9(c)(6)(i) for dietary bre, Sec. 101.9(c)(6)(ii) for sugars, and Sec. 101.9(c)(8)(iii) for vitamin A, vitamin C, calcium, or iron. For consistency with the labelling scheme for these other noncore mandatory nutrients, new Sec. 101.9(c)(2)(ii) provides that if the trans fat content is not
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required and, as a result, not declared, the statement -Not a signicant source of trans fatmust be placed at the bottom of the table of nutrient values.
7.19.3
Physiology of saturated fatty acids
Saturated fatty acids rise the blood level of LDL cholesterol.
7.19.4
Claim to lower risk of heart disease with soy products [348]
U.S. Food and Drug Administration has approved to label foods containing at least 6,25 grams of soy protein per serving touting a link between eating soy and lower risk of heart disease. 6,25 grams of soy proteins are one-fourth of the 25 grams of soy protein daily which are supposed to be needed to show a signicant cholesterol-lowering eect. The claim was requested by Protein Technologies International, a subsidiary of DuPont Co, which is a manufacturer of isolated soybean protein. Foods which may be qualied for this claim are soy beverages, tofu, soy-based meat alternatives and some baked goods.
7.19.5
Tofu found to be a risk of brain decay in elderely persons [349]
Cell culture studies suggest that phytoestrogens, abundant in soy products such as tempe and tofu, could protect against cognitive decline. However, the Honolulu Asia Aging Study reported an increased risk for loss of memory and dementia with high tofu intake. [350] Phytoestrogens may protect the brains of younger and middle-aged people from damage, however, increase the risk of dementia in old persons. [351] Eef Hogervorst and colleagues 2008 found that high tofu consumption was associated with worse memory while high tempe consumption (a fermented whole soybean product) was independently related to better memory, particularly in participants over 68 years of age. Fruit consumption also had an independent positive association. The authors say that tofu is rich in phytoestrogens which tended to promote unhealthy growth among cells in the ageing brain. High doses of estrogens may release free radicals damaging nerve cells. It is also possible that toxic eects of formaldehyde which is sometimes used in Indonesia as a preservative, might have inuenced the results of the Honolulu Study. Hogervorst, however, stresses that moderated consume of tofu does not pose heath
558 risks.
According to the authors tempe contains high levels of phytoestrogens, however, it also presents high folate levels which may exert protective eects. Vitamin B9 from tempe is responsible for brain protection of old persons.
7.19.6
Soy protein may reduce cholesterol levels, and promote weight loss [352]
Cope, Erdman and Allison reviewed studies related to weight reduction induced by soy protein, They concluded that the weight loss was equivalent when using soy protein, dairy milk meal replacements, beef or pork at equal calorie levels. Suggestion were found that soy protein may decrease short-term appetite and calorie intake. There were limited data of some evidence of soy isoavones to improve the blood glucose and insuline levels, stopping fat tissue built up and enhancing fat breakdown. The cholesterol-lowering benets of soy, and reduction of bone loss in women was also supported by the review. The authors concluded that soy foods are as good as other protein sources for promoting weight loss and there is a suggestive body of evidence that soyfoods may confer additional benets, but results must be carefully interpreted and additional evidence is needed before making rm conclusions concerning soyfoods and weight loss.
7.19.7
Black soy bean useful in weight reduction and improvement of LDL/HDL ratio in serum [353]
Shin Joung Rho and colleagues 2007 found that a diet of black soy bean peptide (Rhynchosia volubilis Lour.) given to mice reduced total cholesterol concentration and lowdenslipoprotein/high-density lipoprotein ratio in serum, lowered the level of hepatic triglycerides, and excretion of faeces was higher compared with a casein diet. The authors concluded that black soy peptide can be a potent nutraceutical component for anti-obesity and hypolipidaemic benets.
7.19.8
Omega-3 fatty acids claims
The major source of omega-3 fatty acids is dietary intake of sh, sh oil, vegetable oils (principally canola and soybean), some nuts such as walnuts, and, dietary supplements.
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7.19.9
The Oxfor-Durham Study concerning Omega-3 fatty acids and DCD
Alexandra J. Richardson and colleagues studied the eect of dietary supplementation with omega-3 and omega-6 fatty acids on children with developmental coordination disorder (DCD). This disorder aects 5% of school-aged children. They present decits in motor function associated with diculties in learning, behaviour, and psychosocial adjustment. The authors found signicant improvements in reading, spelling, and behaviour, however, no eect of treatment on motor skills was apparent. They concluded that fatty acid supplementation may oer a safe ecacious treatment option for educational and behavioural problems among children with DCD. The British company Dairy Crest relying on these results claimed that her omega enriched milk could enhance childrens ability to concentrate and learn. The Britains Advertising Standards Authority requested to stop this claim alleging that children would have to drink more than ve litres of that milk every day to get the same amount of omega-3, being thus misleading. [354] Britains Joint Health Claims Initiative (JHCI) has approved a generic health claim that foods containing omega-3 benet heart health, but not learning ability or concentration. The JHCI oers pre-market advice and a code of practice for the food industry, enforcers and consumers, to ensure that health claims on foods are both scientically truthful and legally acceptable.[354] UKs Food Standards Agency, concerning omega fatty acids said that there is insucient quality evidence to reach rm conclusions on the eect of nutrition and dietary changes on learning, education or performance for all schoolchildren. The Agency maintains their advice to a diet lower in fat, sate and sugar but high in fruits, vegetables and complex carbohydrates, in addition to being physically active.
7.19.10
Omega-3 fatty acids and brain function [355]
Omega-3 fatty acids were proposed as having an important role in mental health, because up to 60% of the adult brain is composed of lipids (dry weight). Thirty ve percent of the lipids are phospholipids comprised of unsaturated fatty acid such as docosahexaenoic acid (an omega-3 fatty acid) and arachidonic acid (an omega-6 fatty acid) acids.
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7.19.11
Omega 3 and psychiatric disorders [355]
Disorders of mental health are becoming increasingly common in the US. It is estimated that in a given year, 22%, or one in ve American adults, suers from a diagnosable mental health disorder.[356] These disorders, including major depression, bipolar disorder, schizophrenia, and obsessive-compulsive disorder, account for four of the ten leading causes of disability in the US and other developed countries. Many people suer from more than one mental disorder at a given time.[357] Schachter, and colleagues co authors of the Oxford-Durham study write that overall, other than for the topics of schizophrenia and depression, few ecacy or safety studies were identied. Only with respect to the supplemental treatment of schizophrenia is the evidence even somewhat suggestive of omega-3 fatty acids potential as short-term intervention. Additional research might reveal the short-term or long-term therapeutic value of omega-3 fatty acids. One study demonstrating a signicant clinical eect related to 1 g/d E-EPA given over 12 weeks to 17 patients with depressive symptoms cannot be taken to support the view of the utility of this exposure as a supplemental treatment for depressive symptomatology or disorders. Nothing can yet be concluded concerning the clinical utility of omega-3 fatty acids as supplemental treatment for any other psychiatric disorder or condition, or as a primary treatment for all psychiatric disorders or conditions examined in the review. Primary treatment studies were rare. Much more research is needed before the possible utility of (foods or supplements containing) omega-3 fatty acids as primary prevention for psychiatric disorders or conditions can be ascertained. Studies of omega-3 fatty acids primary protective potential in mental health could be "piggybacked" onto longitudinal studies of their impact on general health and development.
7.19.12
UK parliamentary inquiry on the eect of nutrition on behaviour [358]
A report by the Associate Parliamentary Food and Health Forum, calls for more research and funding into the role of essential fatty acids on the mind. The forum does not recommend fatty acid fortication of foods, but recognizes functional eects of certain essential fatty acids such as Arachidonic Acid (AA) and Docosahexaenoic Acid (DHA), which form
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an important part of the cellular structure of the brain and in maintaining its normal functions. The forum stresses that deciency of omega-3 EFAs is associated with certain mental and behavioural disorders, such as ADHD, depression, dementia, dyspraxia, greater impulsivity and aggressive behaviour, but the association is still only partly understood.
7.19.13
Behaviour [359]
Bernard Gesch of Natural Justice leads a study on the eect of nutritional diet in young oenders institutes on behaviour and mental health of prisoners. The study is being funded by Welcome Trust
7.19.14
Learning and behavioural diculties [360]
The parliamentary forum recommended that the UKs Committee on Nutrition to look upon the optimum intake of omega-3 polyunsaturated fatty acids (PUFAs) in dierent stages of life, especially for pregnant women and children. Deciency of omega-3 can lead to a decreased ability to focus attention, which is vital for sequencing letters and numbers, skilled movements, and detecting facial and emotional expressions such as tone of voice and gestures.
7.19.15
The Durham Research [361]
The Durham Research 2004 studied the treatment eect on Conners Attention-decit Hyperactivity Disorder (ADHD). Dramatic results were seen within just 3 months of the trial. The children in the active group supplementing with fatty acids saw signicant improvements in reading, spelling and behaviour, compared to the placebo group where no overall improvement was made. During the 3-6 month period when the placebo group crossed over to fatty acid supplementation, considerable improvements were shown in the same areas, with an average reading gain of 13.5 months and an average spelling gain at over 6 months. The Sustain statement, however, points out that there is no published research evidence showing that omega-3 can help to improve a normal childs behaviour or school performance. The research done so far has been with children who have specic learning and behavioural diculties. However, this has not prevented the supplement companies from beneting massively from association with the research. An investigation of Sustain of sh-oil supplemented foods on market such as omega-3 milk although it uses the omega-3 research as a marketing hook - neglects to note that a
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child would need to drink two and a half litres of it to get the same dose as used in trials. The same situation is present in products such as omega-3 enriched yoghurts, omega-3 eggs, omega-3 orange juice and omega-3 margarine. Sustain questions that they provide any real benet.
7.19.16
Depression
According to the forum there is a high prevalence of depression, including childhood depression and there is some evidence that omega-3 fatty acid supplements may be helpful in the treatment of depression. The inquiry,however, does not recommend universal fatty acid supplementation or fortication until recommended daily intakes for adults and children have been established. Sustain has carried out work specically on the issue of food and mental health for over three years through its Food and Mental Health Project. The principle of nutrient interaction states that even though every nutrient has a specic function, no nutrient works alone, anything that it does, it does with the assistance of a series of other processes, only made possible by the presence of other nutrients. Sustain says it is deceptive to consider nutrients as independent entities. Whatever benet omega-3 provides, it must be considered in the context of the entire diet. Certain minerals are necessary for the successful incorporation of omega-3 into the body and the presence of other fatty acids may interfere, research or supplementation programmes that ignore this key factor risk providing inaccurate perceptions of the eect of omega-3 rich foods on the body. Sustain advocates two or three sh meals per week, and calls for policies that help and encourage every individual to eat a balanced, healthy diet, incorporating all of the necessary nutrients for brain health.
7.19.17
FSA Systematic review of the eect of nutrition, diet and dietary change on learning, education and performance of school children carried out by the University of Teeside [362]
The UKs Food Standards Agency has published the results of a systematic review of the eect of nutrition, diet and dietary change on learning, education and performance of school children aged 4 - 18 years, covering already published studies. The Government and those involved in education are committed to improving learning and raising standards in schools, as well as meeting the needs of individual pupils.
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There is widespread belief that nutrition and diet may have a part to play in this process; however, there is a degree of uncertainty as to what interventions or supplements work. Much of the available evidence is confusing and contradictory. In essence those charged with supporting and delivering education are seeking clear guidance for both individuals and groups of children, so as to be able to identify what probably works, what might work and what probably does not work. The authors conclude that there is insucient evidence to identify any eect of nutrition, diet and dietary change on learning, education or performance of school aged children from the developed world. Further research is required in settings of relevance to the UK and must be of high quality, representative of all populations, undertaken for longer durations and use universal standardised measures of educational attainment. However, challenges in terms of interpreting the results of such studies within the context of confounders such as family and community context, poverty, disease and the rate of individual maturation and neurodevelopment will remain. Whilst the importance of diet in educational attainment remains under investigation, the evidence for promotion of lower fat, salt and sugar diets, high in fruits, vegetables and complex carbohydrates, as well as promotion of physical activity remains unequivocal in terms of health outcomes for all school children.
7.19.18
Omega-3 fatty acids from diet or supplements and depression [363]
Omega-3 fatty acid supplementation have been linked with behavioural improvements of children with learning diculties, behavioural problems or Attention Decit Hyperactivity Disorder (ADHD). According to the phospholipid hypothesis the decreased omega-3 fatty acid intake could be responsible for the disease. According to the US Department of Health and Human Services 3% of children and 12% of adolescents may suer from clinical depression. Professor Haim Belmaker and colleagues treated for one month children aged between 6 and 12 with a combination of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), an omega-3 supplement commonly available at drugstores. The researchers found signicant depression reductions in the omega-3 treated group, concluding that Omega-3 fatty acids may have therapeutic benets in childhood depression. Cognitive function seems to benet from DHA which is involved in the membrane of
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ion channels in the brain, making it easier for them to change shape and transit electrical signals. EPA may inuence brain function directly increasing blood ow in the body, affecting hormones and the immune system. Belmaker and colleagues concluded that omega-3 fatty acids may have therapeutic benets in childhood depression.
7.19.19
Omega-3 Polyunsaturated Essential Fatty Acid Status as a Predictor of Future Suicide Risk [364]
Low levels of docosahexaenoic acid, a polyunsaturated fatty acid, and elevated ratios of omega-6/omega-3 fatty acids are associated with major depression and, possibly, suicidal behaviour. M. Elizabeth Sublette and colleagues found in a study that a low docosahexaenoic acid percentage and low omega-3 proportions of lipid prole predicted risk of suicidal behaviour among depressed patients over the 2-year period. If conrmed, this nding would have implications for the neurobiology of suicide and reduction of suicide risk.
7.19.20
Omega-3 Fatty Acids and Mood Disorders [365]
In an overview of epidemiological and treatment studies concerning decits in dietarybased omega-3 polyunsaturated fatty acids, resulting mood disorders and their therapy with omega-3 fatty acids supplementation Gordon and colleaugues found that according to the dierent authors reviewed eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA), is likely to provide the greatest benet. More studies studies clarifying the ecacy of omega-3 supplementation for unipolar and bipolar depressive disorders are needed.
7.19.21
Mood gene D4DR [366][367]
The gene, called D4DR (fourth dopamine receptor gene) and located on the 11th chromosome, is said to be responsible for 10 percent of peoples novelty-seeking or adventurous behaviour. The D4DR gene was discovered in the United States in 1991. Its functioning is expressed in the limbic part of the brain - the section involved in emotions - and binds with high anity to clozapine, a drug used to treat schizophrenia. Doctors at Soroka Hospital and the Beersheva Mental Health Center and at Jerusalems Herzog Memorial-Ezrat Nashim Hospital, who tested 124 healthy Israelis, made the discovery. Doctors from the U.S. National Cancer Institute also pinpointed the gene on 300 people of various ethnic groups at the University of Maryland. People who score low on the novelty-seeking test tend to be exploratory, ckle, excitable,
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quick tempered, and extravagant, while those who score high are more stoic, loyal, reective, frugal, rigid, and even-tempered. An U.S. team, which included Dr. Jonathan Benjamin of Soroka, backed up the Israeli ndings.
7.19.22
Changing nutritional habits regarding omega fatty acids [368]
Nutritional habits have changed from whole grains, beans and other seeds, and seafood high in omega -3 fatty acids to prepared foods containing corn oil, saower oil, cottonseed oil, peanut oil, soybean oil and red meat, which are high in omega-6. EM Berrry says omega-6 fatty acids are essential for normal growth, development and health, and so extreme care is necessary before deciding that they are harmful. The relation n-6 : n-3 changed from 3:1 towards 1:20 n-6 function cannot be considered in isolation but needs to be seen as part of the complex of nutrient interactions with n-3 fatty acids (which compete for the same enzymatic pathways) and antioxidants. Insulin sensitivity might be the common factor relating disease to fatty acid metabolism both within and between the fatty acid pathways. High linoleate to arachidonate concentrations have been observed in insulin resistance, diabetic complications and some tumours, but these are multifactorial processes that include many lifestyle determinants and it is therefore wrong to condemn only n-6 fatty acids in their etiology.
7.19.23
Omega-6 and prostate cancer [369]
New research, leaded by Professor William Aronson found that changing the ration of omega-3 to omega-6 in the typical Western diet mightreduce prostate cancer tumor growth rates and prostate specic antigen PSA levels. PSA is a marker for the risk of prostate cancer. Omega-3 fatty acids( eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)) and the omega-6 acid ( arachidonic acid) compete to be converted by cyclooxgenase enzymes (COX-1 and COX-2) into prostaglandins, which can become either pro-inammatory and increase tumour growth, or anti-inammatory and reduce growth. Aronson and colleagues found that levels of the pro-inammatory prostaglandin (PGE-2) were 83 per cent lower in tumours in the omega-3 group than in mice on the predominantly omega-6 fatty acid diet. According to this study higher levels omega-3 fatty acids may lead to development of
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more anti-inammatory prostaglandins. The authors conclude that eating a healthier ratio of these two types of fatty acids may make a dierence in reducing prostate cancer growth.
7.19.24
Oral contraceptive residues in drinking water are associated with prostate cancer [370]
Estrogen exposure increases the risk for prostate cancer. Margel and Fleshner 2011 suggest that the estrogenic compounds of oral contraceptives are excreted in the urine and end thus in the environment and water resources. The drinking water supply and local food are thereby over long time a source of estrogen residues. The authors used data of the International Agency for Research on Cancer of rates of prostate cancer in 2007, and data from the United Nations World Contraceptive Use. These data show that the use of contraceptives demonstrate that intrauterine devices, condoms and other vaginal barriers are not associated with an increased risk for prostate cancer. However, oral contraceptive use was associated with a signicantly increased incidence of prostate cancer and death from prostate cancer. The authors stressed that these ndings are observational and do not indicate a cause-andeect relation between oral contraceptive use and prostate cancer, however people should be aware of a a potential harmful eect of the use of estrogen-disruptive compounds. The authors will test estrogen levels in water supplies, and will verify if there is a dierence in estrogen content cancerous prostate tissue and healthy prostate tissue. The authors call for more research on the potential harmful eects of oral contraceptives and other endocrine-disruptive compounds in synergism with other biologic active compounds in the environment,
7.19.25
The role of fat and cardiovascular diseases [371]
The Womens Health Initiative Randomized Controlled Dietary Modication Trial leaded by Barbara Howard found that dietary changes like eating less fat and more vegetables has no eect on the risk of cardiovascular disease. This study is inconsistent with earlier studies which associate dietary fat intake and a lowered risk of cardiovascular disease, focusing on wholegrain, sh oil and omega-3 fatty acids. The authors, however, nd it possible that a diet specically lower in saturated and trans fat combined with increased intakes of vegetables, fruits, and grains might have led to a decrease in cardiovascular disease risk. According to Cheryl Anderson and Lawrence Appel The Womens Health Initiative study had not considered current dietary guidelines to cut CVD risk, such as less salt and more
7.20. NEW DISCUSSION CONNECTING HIGH FRUCTOSE SYRUP WITH OBESITY
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potassium, the DASH (Dietary Approach to Stop Hypertension) diet, and weight loss. Current policies towards fruit, vegetables and wholegrain would probably be unaected. The study, however, may indicate that saturated fat levels should be lowered from 10 per cent to seven per cent of total energy intake. The possibility that the eect might have been greater in men or if the diet had been initiated at younger ages cannot be ruled out. [372]
7.20
New discussion connecting high fructose syrup with obesity
[373] High fructose corn syrup (HFCS) was introduced in the 1970s. Food industry, particularly the soft drink industry, uses fructose syrup in excess. Removing fructose from soft beverages could help to reduce obesity, as a possible mechanism is suggested which may explain the link between rising obesity and sweetened beverages. Three important studies report that high fructose corn syrup is an important factor in the rising obesity epidemic: According to Hella S. Jrgens and colleagues (2005), from the Department of Pharmacology, German Institute of Human Nutrition, Potsdam-Rehbruecke, exposure to fructose water increased adiposity, whereas increased fat mass after consumption of soft drinks or diet soft drinks did not reach statistical signicance. Total intake of energy was unaltered, because mice proportionally reduced their caloric intake from chow. The researchers found that fructose also produced a hepatic lipid accumulation with a characteristic pericentral pattern. Jrgens conclude that a high intake of fructose selectively enhances adipogenesis, possibly through a shift of substrate use to lipogenesis. Swiss researcher Kim-Anne Le and colleagues report in December 2006 that moderate fructose supplementation over 4 weeks increases plasma triacylglycerol and glucose concentrations without causing ectopic lipid deposition or insulin resistance in healthy humans. [374] In February 27, 2007 Juan Carlos Laguna and colleagues wrote that liquid fructose changes the metabolism of fat in the liver by impacting a specic nuclear receptor called PPARalpha, leading to a reduction in the livers ability to degrade the sugar. According to the authors, this would partly explain the link between increased consumption of fructose and widening epidemics of obesity and metabolic syndrome. In their article the authors conclude that hypertriglyceridemia and the retention of fat in liver induced by fructose ingestion result from a reduction in the hepatic catabolism of fatty acids driven by a state of leptin resistance. According to this research, the fructose increased fat synthesis in the liver and also acted
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on the PPAR-alpha receptor( which controls the oxidation of fatty acids) to reduce the degradation of the fructose, and reduces the activity of the hormone leptin which is engaged in the metabolism of faty acids in liver. [375]
7.20.1
Fruit-avoured drinks with sugar sweetened may increase risk of type 2 diabetes [376]
Julie Palmer and colleagues 2008 found that the the risk of type 2 diabetes mellitus increased by 24 percent in African American women, who consume at least two soft drinks a day, compared to those who drank one product a month, and 33 percent with fruit drinks. Orange and grapefruit juices and diet soft drinks were not linked to diabetes. Fruit drinks and fruit avoured soft drinks are increasingly being promoted as healthy despite added sugar which increases obesity and diabetes risk, according to the study of Palmer and colleagues. The researchers found that fruit drinks were associated with healthy behavioural patterns like physical activity, cereal bre intake, and eating a low-glycemic index diet, and soft drink consumption with unhealthy behaviours. The authors refer to the literature which indicates a positive association between greater intakes of sugar sweetened beverages and weight gain and obesity in both children and adults, because of their high content of calories and are consumed as an addition to usual food intake. The researchers claimed that the use of sweeteners such as high-fructose corn syrup (HFCS)were likely to have a particularly strong impact on weight gain, due in part to the possible aects it has on insulin secretion and leptin release. Whereas the metabolic eect of natural glucose and fructose from orange and grapefruit juice diert from that of HFCS. The authors concluded that regular consumption of sugar-sweetened soft drinks and fruit drinks is associated with an increased risk of type 2 diabetes mellitus in African American women.
7.20.2
High fructose corn syrup in soft drinks and processed foods raises blood pressure [377]
According to Johnson and Perez-Pozo 2009 the average of U.S. consumption of fructose is 50 to 70 grams, but some people are getting as much as 150 grams a day. The data of the study performed by the researchers conrm the belief that fructose raises blood pressure by increasing uric acid levels, but more studies on this matter are necessary. Johnson stresses that ingesting a certain amount of fructose, one can raise blood pressure to the level of hypertension. Mariana Morris and colleagues 2009 found that the timing as well as the amount of fructose thats consumed aected blood pressure. The study was done on mice. The mice that consumed fructose continuously or at night had an increase in blood pressure, with a spike at night, when they were awake. Gain of body weight was increased. Mice that
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consumed fructose in the daylight hours, the blood Pressure was high during the day and low at night. This suggests that the timing of fructose intake is important in cardiovascular diseases. This study suggests that consuming junk foods and sweetened soft drinks at night increases body weight and rises blood pressure. [378] Although healthy levels exist in natural foods, such as in fruits, excessive amounts can rise blood pressure and lead to heart diseases. The American Heart Association says women should eat no more than 100 calories of added processed sugar per day, or six teaspoons (25 grams), while most men should keep it to just 150 calories or nine teaspoons (37.5 grams). On average Americans consume 22 teaspoons (90 grams) or 355 calories of added sugar each day. [379]
7.20.3
High-fructose corn syrup in foods and drinks increase obesity and other health risks [380] [381]
According to a study of Miriam B. Vos and colleagues 2008, commented by George A. Bray, the intake of fructose has increased in the US diets. The study of Vos and colleagues was part of the third National Health and Examination Survey (NHANES III). According to the authors fructose intake was estimated in 1977-1978 as 37 g/day (8% of total intake) and raise up to 54.7g/day (range, 38.4-72.8) and accounted for 10.2% of total caloric intake in 2008, and less than 20% of the fructose is consumed in natural form from fruits and vegetables. Fructose is not accompanied by comparable amounts of bre or other nutrients that promote healthy weight. The author stress that fructose is found in sugar, high-fructose corn syrup (HFCS), and fruits. Fruit juice and soft drinks have a higher concentration of fructose as found in whole fruit. Fructose intake from sugar or HFCS-sweetened beverages provides no other nutrients, whereas intake of fruit containing fructose provides a variety of natural, benecial nutrients. Soft drink and fruit juice consumption has largely replaced milk intake, increasing dietary sugar and reducing protein, calcium and vitamin. Fructose increases caloric intake, increases levels of serum uric acid, heart disease risk and gout in men. The study also points out that total fructose intake in normal-weight and overweight children was a signicant predictor of smaller low-density lipoprotein (LDL) cholesterol particle size, which in turn has been linked to an increased risk for cardiovascular disease. To avert the negative eects of fructose the authors recommend to consume a wholefoods diet consisting of fruits, vegetables, and healthy proteins and to avoid foods with added sugars. Bray and colleagues 2008 point to the fact that fructose from sugar or High Fructose Corn Syrup-sweetened beverages are lean calories which lack other nutrients, they lack other nutrients, such as fruits where sugar and fructose are accompanied with other
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nutrients. Another problem cited by the authors is that sweet soft drinks are consumed by youngsters instead of milk creating a shortage on calcium and vitamin D essential for bone building. The authors also write that the body does not perceive calories in sweetened beverages in the same way as it does with other foods and do not produce satiety as other solid foods do, leading to an increased intake of calories. [381]
7.20.4
High fructose corn syrup and sugar increase obesity risk [382]
Studies from Barry M. Popkin and George A. Bray suggested that high fructose corn syrup (HFCS) was a cause of obesity, particularly in infants. Many food manufacturers producers replace it with sugar, failing to meet the key problem which is the high calories content of their products. Popkin and colleagues 2004 report that by 2004, HFCS provided 17% of total energy intake, whereas soft drinks and fruit drinks provided the most. The authors stressed that sweetened tea and desserts also represented major contributors of calories from added sugar. They concluded that intake of calories from high fructose corn syrup and sugars should be examined, but also emphasize that the trends in added caloric sweeteners should not be omitted in such researches. Included are high caloric fruit juices, sodas and sport drinks supplemented with calcium to look healthy and liquid yoghurts sweetened with plenty of sugar [383].
7.20.5
HFCS and sugar 2007 position of the American Society for Nutrition [384]
Fulgoni III comments the annual American Society for Nutrition Public Information Committee symposium for 2007 on High Fructose Corn Syrup (HFCS) which presented data indicating that HFCS is very similar, few metabolic dierences to sucrose, being about 55% fructose and 45% glucose. It was concluded that High Fructose Corn Syrup does contribute to added sugars and calories. Weight reduction strategies should focus on calories from carbohydrates from beverages and other foods, regardless of High Fructose Corn Syrup content.
7.20.6
High sugar-sweetened beverage consumption is associated with higher serum uric acid levels and blood pressure [385]
Sugar-sweetened beverage consumption, including fruit drinks, sports drinks, soda, and sweetened coee or tea, is a signicant source of dietary fructose and is associated with higher serum uric acid levels and blood pressure in adolescents aged 12 to 18 years Nguyen and colleagues in a study of 2009 found in this group serum uric acid increased by 0.18
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mg/dL and systolic blood pressure z-score increased by 0.17 from the lowest to the highest category of sugar-sweetened beverage consumption which may lead to adverse heath outcomes, warn the authors.
7.20.7
High-fructose corn syrup-obesity hypothesis as sole cause is not supported [386]
White 2009 addressed misconceptions about high-fructose corn syrup (HFCS). He found that high-fructose corn syrup is not meaningfully dierent in composition or metabolism from other fructose-glucose sweeteners like sucrose, honey, and fruit juice concentrates. White concluded that the popular hypothesis that HFCS is uniquely responsible for obesity is not supported.
7.20.8
Fructose and sugar-swetened beverages provide higher endocrine activity than glucose [387]
Stanhope and Havel 2008 report that consumption of fructose-sweetened beverages substantially increases postprandial triacylglycerol concentrations compared with glucosesweetened beverages. Apolipoprotein B concentrations were also increased while consuming fructose, but not with glucose. It was found in this study that beverages sweetened with high-fructose corn syrup and sucrose increase postprandial blood levels compared with fructose alone. The authors call for more studies on increased consumption of fructosesweetened beverages which come along with obesity, metabolic syndrome, and type 2 diabetes.
7.20.9
Fructose and sugar linked with insucient secretion of insulin and leptin and suppression of ghrelin [388]
Melanson and colleagues 2008 assessed high-fructose corn syrup and excess weight gain reported in some acute feeding studies. According to the authors fructose is being suggested to be linked with insucient secretion of insulin and leptin and suppression of ghrelin compared with pure glucose, however such dierences are not apparent compared with sugar. Appetite and energy intake do not dier also. Intake reduction of both sweeteners must become the primary target in tackling the obesity problem.
7.20.10
Public and private regulations of sugar-sweetened beverage sales in schools [389]
Mello, Pomeranz and Morgan 2007 report that most US states adopted laws that regulate the availability of sugar-sweetened beverages in school settings. Consumer and parent groups, as well as the beverage industry responded with strong reactions. This shows how
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much work is needed to convince parents to accept regulations which try to implement healthy nutrition patterns for youngsters. The Food and Nutrition Board issued in 2007 a Nutrition Standards for Foods in Schools. Leading the Way Toward Healthier Youth. The standards include beverages, yogurts (including drinkable yogurt), puddings, soups, cheeses, snack chips, energy bars, confectionery and similar foods [390]. The American Beverage Association & The Alliance for a Healthier Generation beverage industry announced the adoption of the voluntary School Beverage Guidelines, which call for the curtailment of sugar-sweetened beverage sales in schools, aiming to avoid ocial regulations which might be more stringent than their own guidelines [391].
7.20.11
Only 15% of sweetened beverages are consumed at school, overall intake must be targeted [392]
Wang, Bleich and Gortmaker 2008 found that 55% to 70% of all sugar-sweetened beverage calories were consumed in the home environment, and 7% to 15% occurred in schools. Measures to restrict sugar-sweetened beverage sales in schools are therefore insucient. The authors stress that consumption increase in all ages, varying between 10% to 15% of total calories from sugar-sweetened beverages and 100% fruit juice . The authors urge to develop awareness of pediatricians to help children and parents to reduce excessive intake of calories and obesity.
7.20.12
Researchers say 235 kcal/ may be reduced if sweet beverages are replaced with water [393]
Gortmaker and colleagues 2009 estimate that replacing all sugar-sweetened beverages with water could result in an average reduction of 235 kcal/d.
7.20.13
Caloric sweetened inuence weight gain [394]
Light and colleagues in a study published in 2009 report that rats drinking caloric sweetened solutions failed to completely compensate for liquid calories ingested by reducing their consumption of solid food resulting in greater total energy intake compared to water control. However, there was no signicant dierence in total energy intake between the sucrose, fructose or high fructose corn syrup. However, high fructose corn syrup induced greater nal body weights and fat mass compared to water or glucose groups which may be related to a faster body weight gain due to high fructose corn syrup. The authors also noted that rats drinking high fructose corn syrup presented a prolonged estrus.
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7.20.14
Fructose-sweetened beverages [395]
Havel and colleagues assessed the eect of a diet containing 25% glucose- or fructosesweetened beverages for 10 weeks. They report that both groups gained about 1.5 kg, and visceral fat was increased in the fructose group, but not in the glucose group. Visceral fat is linked to an increased risk of both type 2 diabetes and heart disease. Also an increase of LDL-cholesterol levels was found, and insulin sensitivity decreased compared with the glucose group. The authors concluded that fructose promotes disorders of the lipid physiology, increased risk of both type 2 diabetes and heart disease and increases visceral fat in overweight persons. Intake of fructose and glucose, particularly the High Fructose Corn Syrup HFCS and sugar should be reduced. The consumer must read the list of ingredients. HFCS is almost everywhere present such as fruit yoghurt. Get simple yoghurt and mix it at home with your favourite fruits. Do not use sugar. You will learn to appreciate natural avour of food without over-sweetness or over-saltiness.
7.20.15
The Corn Reners Association CRA position [396]
The Corn Reners Association (CRA), claims in a release from April 6, 2006, that that HFCS is not the unique factor responsible for obesity. http://www.hfcsfacts.com/ High fructose corn syrup (HFCS), according to Kathleen J Melanson is similar to sugar in the production of leptin, insulin and ghrelin and regulation of the bodys calorie control mechanisms. (Experimental Biology conference on April 1-5, 2006, San Francisco.) Martine Perrigue et al compared the level of fullness (satiety) after consuming HFCS-, sucrose- and aspartame-sweetened beverages with milk and a no-beverage control. The study found that all four caloric beverages suppressed hunger ratings and increased satiety ratings relative to the no beverage control. However, there were no signicant dierences in satiety proles among the sucrose- and HFCS-sweetened beverages, diet cola, and 1% milk. [397]
7.20.16
High-fructose corn syrup may cause diabetes [398]
High-fructose corn syrup is being used to sweeten soda, fruit nectars, ice tea, sport drinks, backed goods, and even fruit yoghurt. Its fabulous popularity among manufacturers is based on the fact that it is supposed to be more economical, sweeter and more easy to blend into beverages than table sugar. According to a study presented by Chi-Tang Ho and colleagues of Rutgers University, carbonated sodas containing high-fructose corn syrup presented high levels of reactive carbonyls which are blamed to increase the risk of diabetes. These carbonyls are not found
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in table sugar whose fructose and glucose components are "bound" and chemically stable. The authors suggest to add tea extract to these products because the epigallocatechin gallate of tea was found to reduce reactive carbonyls, or replace the syrup with regular table sugar. The study has not been published and the full methodology and data have not been presented yet. Lona Sandon from the University of Texas Southwestern Medical Center at Dallas, said the Rutgers study is still inconclusive, but recommends that kids get zero sugary drinks a day, particularly overweight or obese children. Dr. Barbara B. Kahn, from Beth Israel Deaconess Medical Center in Boston, says Hos study needs to be validated by other studies. Kahn recommends to avoid most high-calorie beverages as part of a program to prevent obesity. The consumer can avoid beverages and foods containing high-fructose corn syrup looking for GLUCOSE-FRUCTOSE SYRUP in the ingredients list at the label. Watch your fruit yoghurt as many fruit compositions used for the yoghurt are based on glucose fructose syrup made from corn or wheat.
7.20.17
High fat build-up from fructose consumption compared with other types of sugars, such as glucose and sucrose [399]
Elizabeth Parks and colleagues 2008 compared the formation of fat (lipogenesis) following consumption of pure glucose, or combinations of glucose and fructose. They found a surprising speed with which humans make body fat from fructose. Dr. Parks explained that fructose, glucose and sucrose can be made into triglycerides, a form of body fat; however, once the process of fat synthesis from fructose has started, its hard to slow it down. The authors report that lipogenesis increased from 7.8 per cent for the glucose beverage to 15.9 per cent after a 50:50 glucose/fructose beverage and 16.9 per cent after a beverage containing 25:75 glucose/fructose, and blood triglyceride levels were between 11 and 29 per cent higher after consumption of the 50:50 and 25:75 beverage, compared to the 100 per cent glucose drink. Dr. Parks explained that sugar is either stored as glycogen, burnt for energy or turn the glucose into triglycerides. Fructose bypasses the liver and oods the metabolic pathways, that is why fructose very quickly gets made into fat in the body.
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The authors stress,however, that obesity and the rise of type-2 diabetes are not caused by one ingredient alone. The sum of calories of fat, proteins and carbohydrate is to high compared with the activity level of Western diet.
7.20.18
Fructose-sweetened beverages rises blood levels of triglycerides in obese people [400]
Karen L. Te and colleagues, in a study from 2009, found that drinking fructose-sweetened beverages increased triglyceride levels up to 200 per cent in obese people in comparison to glucose-sweetened beverages. Fructose containing beverages were also associated with less insulin secretion and blunted diurnal leptin prole. The increase of triglycerides was more accentuated in persons with insulin resistance increasing therefore an adverse metabolic prole. Increased levels of triglycerides are linked to heart diseases and obesity. The authors call for more studies on the eect of fructose and the link between pure fructose and high fructose corn syrup which consists of consists of 55 per cent fructose and 42 per cent glucose, according to the Corn Reners Association [401] . This study backs the theory that the body processes fructose in a dierent form as it does with other sugars. The consume of sweet soft drinks and foods high in fructose corn syrup and sugar, such as fruit yoghurt, candies and energy bars should be reduced or completely avoided because of their content of fructose and high calories. Changing once nutritional preferences to mineral water, or tap water, and consuming fruits and vegetables the taste of natural products is rediscovered.
7.20.19
Reduced consume of high-fructose corn syrup
The consume of high-fructose corn syrup in 2011 was the lowest amount since 1997. The average American ate 131 calories worth of corn sweeteners a day this year, down 16 percent from 2007, according to the USDA. [402] Use of corn for high fructose corn syrup, glucose, and dextrose increases at less than half the rate of population growth, limited by consumer dietary concerns and changes in tastes and preferences. Other food uses of corn are also projected to rise more slowly than the increase in population. [403] Sweeteners are dened as the sum of rened sugar, sugar in imported products, and high fructose corn syrup (HFCS). Sugar in imported products (accounting for 6.1 percent of sweetener demand in 2010/11) grows at 1 percent per year. A general decline in HFCS use since 2002 has moderated in recent years as the decrease in carbonated soft drink consumption has slowed. As a result, HFCS use levels out for several years at the start of the projection period. HFCS use is projected to rise somewhat over the latter part of the decade as sweetener demand increases and relative prices between HFCS and sugar
576 become more stable.
Decreasing consume of high-fructose corn syrup may be caused by critics for its badtasting and health concerns. Soft drinks are the major driver of high-fructose corn syrup use, because it is a lot cheaper than sugar which is 25 percent more expensive than fructose. An alternative to sweet soft drinks are juices, tea and bottled water. [404] Obesity and low satiety response Page et al 2013 report that people who ate high amounts of fructose have a lower satiety response compared to glucose consume. The authors suggest that fructose may be responsible for obesity. High-fructose corn syrup is sweeter than glucose and improves the appearance and texture of baked goods, sodas, energy drinks, and sports drinks, juice drinks, processed meats, sauces and other foods. [405] Type 2 diabetes and HFCS Goran et al 2012 report the relationships between availability of high fructose corn syrup (HFCS) and prevalence of type 2 diabetes. Diabetes prevalence was 20% higher in countries with higher availability of HFCS compared to countries with low availability. Countries with high consume of high fructose corn syrup are predicted to have a higher prevalence of type 2 diabetes independent of obesity, conclude the authors. [406] Cardiovascular risk of high fructose corn syrup (HFCS) Stanhope et al. 2011 compared the eects of consuming glucose, fructose, or high-fructose corn syrup (HFCS). The authors found that consumption of HFCS-sweetened beverages for 2 weeks at 25% energy requirements increased risk factors for cardiovascular disease comparable to fructose. Both sweeteners presented a much higher risk compared to glucose. [407]
7.20.20
Regularity of meals is an important cause of obesity [?]
Jodkowska et al. 2011 stresses that, the growing global epidemic of obesity among children, adolescents and adults is generally considered to be caused by inappropriate nutritional behaviour and too low level of physical activity. Nutritional behaviour include the content of the meal, the size of the portion of the product and the frequency of their consumption, the number, regularity and duration of the meals during the day, their preparation and their consumption, family meals. Watching television and using computers reduces energy expenditure. Overweight adolescents consumed substantially fewer unhealthy products, such as sweets and crisps and sweet drinks than teenagers with the normal body mass. Overweight
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teenagers ate substantially less often during all three basic meals and eat less often breakfast than their peers of normal weight. Overweight teenagers snacked less and consumed less high caloric snacks than normal weight teenagers. These observations may indicate that overweight young people are suciently aware of which products are good or bad for their health. The regularity of meals of meals is an important cause of obesity. Obese children skipped the main meals, mostly breakfast, more often than their peers with normal weight. These results indicate that educational activities on meals regularity may not be getting through to the young peoples awareness. Some young people consume their rst meal of the day only after returning from school. Such a lifestyle promotes the development of obesity. A healthy nutreitional behaviour should include eating no less than four meals during the day, at intervals of not more than 4 hours; and where possible, at about the same time of day, recommended number is 5 daily meals. The authors suggest that relying on low energy diet alone does not ensure the maintenance of normal body weight. Irregularity of meals and breakfast skipping play an important role in developing obesity. Future studies should be focused on portion size, food preparation and meal time. Nutritional health education should be placed concentrated on the importance of eating meals regularly and not just on the quality of the products consumed and their energy value. According to Stefaiska et al. 2012 nearly half of all examined children consumed 4 meals a day, with low consumption of porridge, whole meal bread, milk, curd cheese, shes, leguminous plants and raw fruits, but more often consumed meat and its preserves. The majority children and teenagers reported unhealthy excessive intake of sweets. Education targeting these incorrect dietary habits are urgently needed to prevent dietary obesity and realted diseases. [408]
Frequency of shared family mealtimes improves nutritional health [409] Hammons and Fiese 2011 found that children and adolescents who shared family meals 3 or more times per week are more likely to develop a normal body weight and have healthier dietary and eating patterns compared to those sharing fewer than 3 family meals together. Educational and public health initiatives are being suggested by the authors to promoting shared family mealtimes. The authors also call on clinicians to advise their patients to introduce 3 or more shared family mealtimes per week aiming health benets such as reductiuon of overweight, reducing consumption of unhealthy foods, and avoiding disordered eating.
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Socio economic status of parents should be considered in food education [410] Gatica et al. 2012 used data of the Pelotas Birth Cohort Study (Brazil) to identify food intake proles of children during their rst four years of life and linked them to the dierent socioeconomic levels of their parents. Higher breast milk intake, consumed more coee, bread/cookies compared to cows milk was seen among poorer children and higher milk, chocolate powdered milk drink, fruits, yogurt and soft drinks consumption was seen among more auent children aged 48 months. The authors stress that food prole in early life is associated with social status of their parents, such as maternal schooling, socioeconomic position and child care and behavioral characteristics like breast-feeding duration, bottlefeeding and pacier use. A study by Romulus-Nieuwelink found that energy intake from complementary foods of infants of 8 month of age were 20% higher than recommended (93.3 24.4 versus 77.3 kcal/kg/day of PAHO/WHO recommendations), due to a high intake of complementary foods and addition of cows milk to breast milk. In the high socio-economic status groups vegetables and fruit were more often consumed and less fats and sugar, compared to lower socio-economic status groups. This may have an inuence on metabolic programming and later obesity. [411]
High caloric diets as primary cause of the obesity epidemic [412] Klurfeld et al. 2012 argue that a link between obesity and fructose consumption is epidemiologic and does not establish cause and eect. The authors point to the fact that the causes of obesity include overconsumption of calories from all sources, such as high fat carbohydrates consumption and increased intake of fructose. This is worsened by decreased physical activity. Studies using pure fructose lead to wrong conclusions and distract from the high caloric diets as primary cause of the obesity epidemic. Data from USDA say sugar consumption rose 8.8 percent between 2007 and 2011. Even with the increase in sugar use, total sweetener production, particularly high fructose corn syrup, remains down 14 percent from a 1999 peak, consumer just shifted from fructose syrup to sugar. This increases the need of consumer education to reduce total caloric intake. [404]
Other names for sugar and derivates used in ingredients lists Food industry uses dierent names for sweeteners, however, all of them increase the daily calorie count: Dextrose, maltose, malt syrup, invert sugar, evaporated cane juice, crystaline fructose, glucose, high Maltose corn syrup, high fructose corn syrup, raw sugar and cane crystals.
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7.20.21
Soft drinks high in sugar are associated with ischemic stroke in women
Women who often drink soft drinks high in sugar almost every day are more likely to have a ischemic stroke than women who rarely drink sodas and other sweetened beverages. A study of Eshak et al. 2012 found that women who rarely had a soft drink 1.7% experienced an ischemic stroke, and 3% of women who had a soft drink a day had an ischemic stroke. [413] There was no link between soft drink consumption and stroke risk in men. The authors hypothesize that men present earlier signs of cardiovascular disease leading to a reduced soft drink consume. The authors believe that women may be more prone to the disease caused by the the eect of the beverage on their metabolism. The authors concluded that soft drink intake was linked with increased risk of total stroke, specically ischemic stroke for women. Soft drink intake was not associated with risk of ischemic heart disease or hemorrhagic stroke for either sex. However, soft drink intake is associated with higher risk of ischemic stroke for women. Dierent studies link sugary drinks to numerous untoward health eects, including heart attacks, obesity, diabetes and hipertension. Soft drinks are a carbonyl stress burden Carbonated soft drinks contain methylglyoxal, which is strongly associated with human carbonyl stress. Nakayama et al 2009 studied the eects of carbonated drink intake on human carbonyl stress caused by methylglyoxal. The authors report high levels of plasma methylglyoxal, glucose, insulin and uric acid at 30 min after intake of samples containing high glucose and high methylglyoxal, returning to basal levels by 120 minutes. Low-calorie carbonated samples containing little methylglyoxal did not increase plasma methylglyoxal. Nakayama and colleagues stress that soft drinks high in glucose aside are a carbonyl burden to the metabolism of the consumer. [414] Carbonyl stress and metabollism of methylglyoxal [415] According to Li et al. 2012 methylglyoxal (MG) induces cell death of brain microvascular endothelial cells by glycation of occludin. Reactive carbonyl species are linked to occludin glycation in cerebral microvessels and in microvascular endothelial cells that contribute to barrier dysfunction, a process that was prevented by glutathione-dependent metabolism of methylglyoxal. Methylglyoxal is a metabolite of glycolysis which is increased in patients with diabetes. Liu et al. 2012 methylglyoxal reduces the formation of new endothelial cells in blood vesCopyright 1998-2010 Karl H. Wilm. All rights reserved. OurFood Database of Food and Related Sciences
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sels. which may explain the hindrances of repair mechanism of vessels in diabetic patients. [416]
Methylglyoxal in manuka honey may impair healing of diabetic ulcers [417] The concentration of methylglyoxal in manuka honeys is up to 100-fold higher than in conventional honeys. Methylglyoxal is a potent protein-glycating agent and an important precursor of advanced glycation end products, both are linked with impaired diabetic wound healing. Majtan 2011 writes that methylglyoxal in manuka honey may delay wound healing in diabetic patients.
7.20.22
Leptin prole [418]
Leptin is a hormone which plays a key role in regulating energy intake and energy expenditure, including appetite and metabolism. Next to a biomarker for body fat, serum leptin levels also reect individual energy balance. Although leptin is a circulating signal that reduces appetite, in general, obese people have an unusually high circulating concentration of leptin. These people are said to be resistant to the eects of leptin, in much the same way that people with type 2 diabetes are resistant to the eects of insulin. The high sustained concentrations of leptin from the enlarged adipos stores result in leptin desensitization. The pathway of leptin control in obese people might be awed at some point so the body doesnt adequately receive the satiety feeling subsequently to eating. More research on how fructose acts on the pathway of leptin are needed for a better understanding the causes of obesity.
7.20.23
100 per cent fruit juice instead of sugar drinks reduce risk of diabetes [419]
Yoshida and colleagues found that sugar-sweetened drink consumption caused fasting insulin to rise, but was not associated with fasting glucose. Fruit juice consumption was inversely associated with fasting glucose. Fasting insulin was not aected. The authors conclude that in healthy adults, sugar-sweetened drink consumption could be a factor of insulin resistance. The authors caution, however that too much fruit juice can cause an excess of calories and sugar. They call for more studies on this subject.
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7.20.24
Insucient data to conclude that high-sugar diet results in lower nutrient intake [420]
Rennie and Livingston (2007) in a systematic computerised literature search determined the associations between dietary added sugar intake and micronutrient intake. Dietary added sugars are getting in headlines as they might compromise intakes of micronutrients. However, in this study, the authors found no clear evidence of micronutrient dilution such as vitamins or minerals, or a threshold for a quantitative amount of added sugar intake. The authors conclude, that there are insucient data and inconsistency between studies which require further research to determine which food products high in added sugars might adversely aect micronutrient intakes by displacing other food items from the diet.
7.20.25
Special foods "suitable for diabetics" are superuous [421]
According to Professor Dr. Dr. Andreas Hensel, President of the German BfR the classic strict diet with no sugar and instructions to keep an exact tally of bread units (BE) for diabetics are not necessary. New scientic ndings reveal that, in case of diabetes, there is no need to impose a strict control of sugar in the diet or to switch to foods with sugar substitutes, for instance fructose. Instead, diabetics should follow the nutrition recommendations for the population at large. The Federal Institute for Risk Assessment BfR recommends the daily consumption of fruit and vegetables because of their content of antioxidants and high level of roughage. Special diabetic foods with sugar substitutes such as fructose, are not needed. There is no need for special guidelines for diabetic foods. Extended, uniform nutrition labelling on packaged foods, instead, should make it easier for diabetics to make their selection. The BfR stresses that diabetes is not just a "sugar disease". Besides normal blood sugar levels, optimised blood fat levels, normal blood pressure and normal body weight must be observed in the treatment of diabetes. They can best be achieved by a diet that is rich in roughage and vitamins. Fruit, vegetables, salad, pulses and wholemeal products should feature in the daily diet of diabetics. Fatty sausage and cheese varieties, chocolate, cakes and crisps should be avoided. Diabetics should preferably drink low fat dairy products and use oil instead of butter for cooking. Their diet should be low in table salt. Alcohol should be consumed in moderation, for instance one to two glasses of wine a day, says the BfR. Professor Hensel says that special foods presented and labelled as "suitable for diabetics" are not necessary. This is particularly true as labelling fails to full its purpose. There are many other foods which are suitable for diabetics but which are not labelled as such. The German Diabetic Association DDG says that foods labelled as " suitable for diabetics" or "diabetics-product" are superuous and harmful. Such labelling may induce diabetics
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to believe they may eat these foods unboundedly. Many of the are built on saturated fats which increase obesity problems. [422]
7.20.26
German Regulation on Dietetic Foods [423]
The German diet regulation from 2005, with an update in January 2008 rules, among others, foods for persons with glucose metabolic disorders (Diabetics). Foods may be labelled as "Suitable for diabetics" when: 1 - Fat and alcohol level is not higher that traditional foods. 2 - Glucose,invertsugar, dissacharides, maltodextrin and glucose syrup is not used, small amouts are are allowed when used in blends with sweeteners or as carrier of other ingredients. On their place fructose and articial sweeteners are used.
7.20.27
The BfR recommends uniform nutrition labelling
The BfR calls for an extended, uniform nutrition labelling with not only of caloric value, proteins, carbohydrates and fat but also of total sugar content, saturated fatty acids, roughage, sodium and table salt on packaged foods would make it easier for diabetics and all consumers to select suitable products.
7.21
7.21.1
Low-calories, low dietary energy density and physical activity

PREMIER: Lifestyle Interventions for Blood Pressure Control [424]
The PREMIER study compared the eectiveness of advice of the Comprehensive Intervention and the DASH Intervention. Both multicomponent lifestyle interventions aimed to control blood pressure.
7.21.2
Comprehensive Intervention
Reduced sodium intake, increased physical activity, weight loss, and moderate alcohol ingestion are associated with a modest reduction of both systolic and diastolic blood pressure in with high normal and Stage 1 hypertension.
7.21.3
The DASH Intervention
The Dietary Approaches to Stop Hypertension (DASH) study found that a diet rich in fruits, vegetables, low-fat dairy products, and decreased saturated fat, total fat, and cholesterol reduced both diastolic and systolic blood pressure in similar baseline blood pressure groups.
7.21. LOW-CALORIES, LOW DIETARY ENERGY DENSITY AND PHYSICAL ACTIVITY
583
7.21.4
DASH-style diet is associated with a marked decrease in kidney stone risk [425]
Foods very high in oxalate such as spinach and almonds are generally avoided to reduce the risk of kidney stones. Taylor and colleagues 2009, analysing the results of the DASH-diet and the Health Professionals Follow-up Study, however, could not support the common practice of dietary oxalate restriction in calcium stone formers if such advice results in lower intake of fruits, vegetables, and whole grains. The DASH diet is high in fruits and vegetables, moderate in low-fat dairy products, and low in animal protein. According to the authors this diet is a kidney stone prevention strategy. The authors found that consumption of fruits and vegetables increases urinary citrate which inhibits calcium stone formation, and a diet with normal to high calcium content but low in animal protein and sodium reduces the risk of calcium oxalate stone by 51%. The study was based on a DASH score, where high scores were given to high consumption of fruits, vegetables, nuts and legumes, low-fat dairy products, and whole grains, and low consumption of sodium, sweetened beverages, and red and processed meats. High DASH scores resulted in higher intakes of calcium, potassium, magnesium, oxalate, and vitamin C, and low sodium intakes. This was associated with reduced risk of kidney stones even in participants with lower calcium intake.
7.21.5
Rising kidney stones disease is related to obesity and unhealthy lifestyle Scaleskidston8635
Scales et al 2012 assessed the prevalence of stone disease and associated factors. The authors found that kidney stones aect 10.6% men and 7.1% women and 11.2% obese compared with 6.1% of normal-weight individuals. One in 11 people are aected by kidney stones and as obesity rates rise, the cases of kidney stones double. Diet and lifestyle factors play an important role in the formation of kidney stones. The authors stress that people should maintain a healthy lifestyle and body weight. Prevention of kidney stones should include control of body weight. Brian Matlaga, in a related editorial, underlines the importance of prevention of kidney stones disease as 10% of the US population are aected by the disease. [426]
7.21.6
Urinary stone risk factors [427]
Johri et al 2010 resume kidney stone risk factors. Involved are environmental and lifestyle factors such as hot environment workplace or professions which have to minimize uid intake to avoid toilet use.
584
7.21.7
Dietary habits reducing kidney stone formation
The risk of stone formation decreased with increasing frequency of use of caeinated and decaeinated coee, tea, beer, and wine. High dietary intake of potassium or magnesium reduces stone formation. Potassium increases urinary citrate excretion, and inhibit the formation of crystals. Urinary citrate inhibits the crystallization of calcium salts. Low levels of urinary citrate excretion increases calcium oxalate stone risk. A diet high in meatis often associated with a low urinary citrate excretion. Vegetarians tend to have higher levels of citrate excretion.
7.21.8
Dietary habits increasing kidney stone risk
The risk increases with rising use of apple juice and grapefruit juice. Excesses in calcium intake, both high and low, increases stone risk. High vitamin D supplementation together with high absorption of calcium increases the risk of stone formation. Also vitamin C excess could favour calcium oxalate stone formation, but this is found to be rare. Chronic laxative abuse, antacid excess or betel nut chewing, tropical holidays, regular strenuous exercise increase urinary stone formation. Other factors are low uid intake, high intake of animal protein, high dietary sodium, excessive intake of rened sugars, foods rich in oxalate, high intake of grapefruit juice, apple juice and soft cola drinks.
Table 7.5: Frequency of kidney stones according to Johri et al 2010 Calcium oxalate Calcium phosphate Uric acid Struvite (infection stones) Cystine and others 59% 10% 17% 12% 2%
7.21.9
Dietary recommendations to minimize the formation of kidney stones, according to Paterson 2010 [428]
- Increasing uid intake of citrate-rich foods (especially citrate-rich uids such as lemonade and orange juice), with the objective of increasing urine output of >2liters per day - Attempt to maintain a calcium (Ca) intake of 1000 - 1200 mg per day - Limiting sodium (Na) intake < 2300 mg per day - Limiting vitamin C intake <000 mg per day - Limiting animal protein intake to no more than two meals daily, with less than 170-230 g per day. - Limiting consumption of foods containing high amounts of oxalate (such as spinach, strawberries, nuts, rhubarb, wheat germ, dark chocolate, cocoa, brewed tea)
585
7.21.10
Probiotics to reduce risk of oxalate kidney stones [429]
Plant foods, such as nuts, fruits, vegetables, grains, and legumes are rich in oxalate. Liebman and Al-Walsh 2011 stress that almost all absorbed oxalic acid is excreted in the urine and is therefore a risk faktor of kidney stones. The absorption of oxalate range from 2 to 15% for dierent foods, and seems to be decreased by concomitant food ingestion due to interactions between oxalate and other food components resulting in insoluble forms of the oxalic acid which is not absorbed by the intestinal tract. Another food related fact is the possible degradation of oxalate by oxalate-degrading bacteria within the gastrointestinal tract. Oral ingestion of probiotics such as oxalate-degrading strains were studied, but further research is necessary.
7.21.11
Uric acid stone disease [430]
Uric acid stone formation are on the rise, inuenced by diet, body habitus, and social reasons. Uric acid stone disease is strongly linked to errors purine metabolic pathway and its enzymes. Diets rich in meat increase the risk of uric acid stones disease. The high purine load and acid-ash content of animal protein results in high uric acid and low urinary pH. Dietary measures may prevent uric acid stone formation. [431]
7.21.12
Outcomes from the PREMIER study [432]
The PREMIER writing group, leaded by Apel wrote in 2003 that both behavioral interventions signicantly reduced weight, improved tness, and lowered sodium intake. The established plus DASH intervention also increased fruit, vegetable, and dairy intake. Individuals with above-optimal BP, including stage 1 hypertension, can make multiple lifestyle changes that lower BP and reduce their cardiovascular disease risk. Both behavioral interventions signicantly reduced weight, improved tness, and lowered sodium intake. The established plus DASH intervention also increased fruit, vegetable, and dairy intake. Across the groups, gradients in blood pressure and hypertensive status were evident.
7.21.13
Multiethnic Study of Atherosclerosis (MESA) says that healthy diet lowers the risk of cardiovascular disease (CVD) associated with kidney malfunction [433]
Jennifer A Nettleton and colleagues 2008 assessed the associations between urinary albumin excretion and dietary patterns and intake of plant and animal foods. Foods were grouped in plant food intake (fruit, fruit juice, vegetables, nuts, legumes, whole grains and rened grains), animal food intake (red meat, processed meat, poultry, sh, high-fat dairy, and low-fat dairy), and nondairy animal food intake, and the urinary albumin-to-creatinine ratio was determined.
586
The authors found that a high intake of low-fat dairy foods and a dietary pattern rich in whole grains, fruit, and low-fat dairy foods were both associated with lower urinary albumin-to-creatinine ratio, a high ratio indicates poor kidney function. Kidney malfunction may lead to coronary vascular diseases. In contrast, collectively, nondairy animal food intake was positively associated with urinary albumin-to-creatinine ratio. Low-fat dairy foods are also highlighted by the Dietary Approaches to Stop Hypertension (DASH) intervention which found that a diet rich in fruits, vegetables, low-fat dairy products, and decreased saturated fat, total fat, and cholesterol reduced both diastolic and systolic blood pressure in similar baseline blood pressure groups. Low-fat dairy foods are also highlighted by the Dietary Approaches to Stop Hypertension (DASH) intervention which found that a diet rich in fruits, vegetables, low-fat dairy products, and decreased saturated fat, total fat, and cholesterol reduced both diastolic and systolic blood pressure in similar baseline blood pressure groups.
7.21.14
Dietary Energy Density Reduction [434]
Jenny Ledikwe and colleagues 2007 found that participants of the PREMIER study maintained weight loss after dieting adhering to a low calorie, low energy density diet, even when large amounts of low calorie, low energy density foods were consumed. Both large and modest energy density reductions were associated with weight loss and improved diet quality. The researchers found that the energy density of the diet was decisive. Participants on a low energy density diet reported the same weight loss as those on low calorie high physical activity diets. However, the low energy density group reported consuming the largest increase in the weight of food consumed as well as increased intakes of fruit, vegetables, bre, vitamins and minerals. Even a modest reduction in energy density accomplished reduced body weight. The authors therefore concluded that a reduction in dietary energy density was a healthy weight management strategy.
7.21.15
Low Energy density may reduce physical activity necessary to maintain weight [435]
Tiany L. Cox and colleagues 2007 determined the role of physical activity and energy intake on weight maintenance among former EatRight Weight Management Program participants. The authors found that 80% of participants maintained their body weight and 20% had gained weight. Maintainers consumed 384 fewer kcal/d on average. Maintainers had a lower energy density dietary pattern (1.58 vs. 2.01 kcal/g,). There was no signicant dierence in physical activity min/d reported by maintainers and gainers. even for people who did not exercise regularly .Adopting a lower calorie, low energy density dietary pattern
587
may reduce the amount of physical activity that is truly necessary for weight maintenance. This is a new hope for those who cannot maintain a certain level of their daily exercise
7.21.16
EatRight model [436]
EatRight model encourages the intake of foods that have fewer calories by volume such as fruits, vegetables and whole grains, while limiting consumption of foods that are caloriedense such as meats, cheeses, sugars and fats, and includes increasing physical activity and behavioural intervention to reduce or remove barriers to lifestyle change.
7.21.17 7.21.18
Antioxidants in human nutrition Formation of radicals
Free radicals are told to start cancinogenic reactions in vivo. Oxygen is the main source of free radicals such as Singulett-O2, superoxydation and the hydroxilradical. In small amounts the radicals are used in many biochemical reactions. The amount of free radicals being however to high the benet of the radicals turn out to be dangerous to the physiology of the cell ending in Arteriosclerosis and cancer. The organism protects itself from free radicals with the building of an own free radical defence system helped by external antioxidant vitamins. Table 7.6: Antioxidant vitamins and their protective function Antioxidant vitamins Carotenoids (provitamin A) Tocopherols (vitamin E ) Protective function against free radicals Singulett-O2 quencher. Act as radical receiver in lipid layers together with vitamin C mainly to protect polyunsaturated fatty acids. Tocopherols also protects beta-carotene and vitamin A from autoxidation in cells. Act as radical receiver in the cytoplasm together with vitamin E. It also regenerates tocopherol from tocopheryl radicals which were originated during the antioxidant function.
Vitamin C
588
CHAPTER 7. PHYSIOLOGY Aspirin can triple the rate of excretion of vitamin C
Selenium, Zinc, copper, manganese As elements being found as traces in enzyme system of the cells. An undersupply of these elements reduces the eciency of vitamins, therefore they are here included Magnesium[437] Magnesium is a light metal which can burn in presence of oxygen, being used as torch but also in metal alloys in aeronautic.It is present in minerals, seawater and mineral water, in plants as chlorophyll and wheat bran 590 mg/100g, slim cocoa powder 500 mg/100g, sunower seed kernel 20 mg/1000g, sesame seed 350 mg/100g, cashew nut 270 mg/100g peanuts 163 mg/100g, oat akes instant 140 mg/100g dried gs 70 mg/100g, Edam cheese 45% 59 mg/ 100g cooked spinach 50 mg/100g, wholemeal bread 92 mg/100g white bread 19 mg/100g. A balanced diet supplies sucient magnesium It is an important biological element for animals and humans. It is a physiological antagonist of calcium. Values of serum are 0,65-1,03 mmol/l Magnesium is very important for many enzymatic reactions (it activates all reactions where ATP is present. Important for undisturbed building of bones, It acts relaxing. It is being told that magnesium improves the connections of the synapsis of nerve cells having therefore anti stress function, however there is no scientic evidence for it. According to D. Htze, C. Kpper and A. Zittermann[438] research has been done relating a permanent eect of the "stress hormones" catecholamine and cortisol. The result of this research was that there is a loss of magnesium. Other ndings say there is an improving of the stress situation with supplementation of magnesium working in very laud places. An undersupply of Magnesium may be an additional factor of the origin of arteriosclerosis[439] Undersupply of Magnesium electrolyte syndrome
7.22. WARNING ABOUT HIGH LEVELS OF MULTIVITAMINS INCREASING THE RISK OF PROSTATE CANCERS 589 caused by undersupply of magnesium due to unbalanced diet, infusion therapy, chronic diarrhea, special diets, excessive alcoholism. laxatives, inammation of the pancreas, diseases of the intestinal tract. faulty absorption syndrome, magnesium loss through urine with diuretica therapy. chemotherapy, Diabetes mellitus Syndromes of undersupply of magnesium are: Loss of appetite, nausea, vomiting,lack of drive, weakness. Course tremor, cramps, cramp in the leg during the night. Tetanic contractions. Selenium Aside of its function in enzymes selenium is known acting by itself as an antioxidant and probably protecting from cancer. All other inorganic elements have not been found with antioxidant properties.
7.21.19
The study of Finland
: Over 5.000 men and women over a period of 14 years in Finland were given a nutrition with high levels of vitamin E They had a signicantly lower cardiovascular death rate than the group with lower intake of vitamin E. In women vitamin E had a synergistic activity with beta-Carotene and vitamin C.
7.22
Warning about high levels of multivitamins increasing the risk of prostate cancers
[440] Karla Lawson in the National Institutes of Health-AARP Diet and Health Study found that regular multivitamin use has no eect on prostate cancer. High levels of multivitamins along with other supplements have increased the risk of advanced and fatal prostate cancer by 32%. The risc was strongest in men with a family history of the disease, or amongst men taking additional micronutrient supplements, including beta-carotin, selenium, or zinc. A new nested study published 2007 in The American Journal of Clinical Nutrition reported that an increased selenium intake in combination with a daily multivitamin may reduce the risk of prostate cancer by about 40 per cent. Goran Bjelakovic and Christian Gluud comment the study of Lawson and explain " that reactive oxygen species in moderate concentrations are essential mediators of reactions by which the body gets rid of unwanted cells. Thus, if administration of antioxidant supplements decreases free radicals, it may interfere with essential defensive mechanisms for ridding the organism of damaged cells, including those that are precancerous and cancerous.
590
Our diets typically contain safe levels of vitamins, but high-level antioxidant supplements could potentially upset an important physiologic balance." The author conclude that Lawson and colleagues add to the growing evidence that questions the benecial value of antioxidant vitamin pills in generally well-nourished populations and underscore the possibility that antioxidant supplements could have unintended consequences for our health. [441] Liz Baker, from the British charity Cancer Research UK commented the research saying that its still not entirely clear what factors can aect a mans risk of developing prostate cancer. And there is conicting evidence on the pros and cons of vitamin supplements. She refers to the benets of vitamins that naturally occur in our food, and encourages consumers to eat a diet rich in bre, vegetables and fruit, and low in red and processed meat. [442] The results were challenged by Daniel Fabricant of the Natural Products Association (NPA). [443]
7.22.1
Consumption Blueberries, mixed grapes and kiwi fruit during meals increase antioxidant activity [444]
Prior and colleagues 2007 found that the consumption of berries and fruits such as blueberries, mixed grape and kiwifruit, increased plasma Anti Oxidant Capacity (AOC) measured as Oxygen Radical Absorbance Capacity in the postprandial state. High caloric meals rich in carbohydrates, protein and fat containing no antioxidants was associated with a decline in plasma AOC. Antioxidants are cleared from blood in 2 - 4 hours after intake. Consumption of antioxidants such as berries and fruits during each meal is therefore recommended in order to prevent periods of postprandial oxidative stress. Oxidative stress has been linked to an increased risk of various diseases including cancer, Alzheimers, and cardiovascular disease. In this study dried plums and plum juice had no antioxidant activity. Consumption of blueberries during meals increased hydrophilic AOC and the lipophilic AOC. Mixed grape consumption with the meal was associated with a increase in hydrophilic AOC, but not lipophilic AOC. Cherries, eaten with the meal increased the lipophilic, but not the hydrophilic, AOC. The authors call for more studies on this matter.
7.22. WARNING ABOUT HIGH LEVELS OF MULTIVITAMINS INCREASING THE RISK OF PROSTATE CANCERS 591
7.22.2
The VITAL study [445]
Chris Slatore and colleagues of the University of Washington School of Medicine in Seattle presented the VITamins And Lifestyle (VITAL) study. No statistically signicant relationships between dierent types of supplements and lung cancer were found in this study. A study of more than 75.000 adults found that taking supplemental multivitamins, vitamin C and E and folate do not decrease the risk of lung cancer. The study, which also did not nd any increased lung cancer risk from the supplements, is one of the most detailed, prospective observational studies to look at the eect of vitamin supplements instead of vitamins from foods on lung cancer risk. This conrms foregoing studies which suggest that vitamin supplementation might not be as healthy as believed.:
7.22.3
The CARET study 1996 [446]
In 1996, a large study known as the CARET study which was looking into the eects of the dietary supplements beta-carotene and retinol (vitamin A), was halted after the supplements were found to increase lung cancer risk, particularly among smokers. That study, and others, encouraged researchers to look more deeply into the relationship between supplements and lung cancer, Dr. Slatore said.
7.22.4
Beta-Carotene, vitamin E or vitamin A increasing risk of death American Medical Society February 2007 [446]
Supplements have been getting a lot of attention this year. In February, the Journal of the American Medical Association published an overview of studies that found that supplements of beta-carotene, vitamin E, or vitamin A slightly increases a persons risk of death.
7.22.5
The recommendation of the National Cancer Institute related to supplements [446]
The recommendations of the NCI are: "The results of the Physicians Health Study showed no benet or harm to nonsmokers who took beta carotene every other day for 12 years. The results from CARET and the ATBC Study do not provide information about the eects of beta carotene supplements on non-smokers. NCI does not make recommendations as to whether Americans should take supplements. For those who wish to reduce their risk of cancer, NCI advises that it is prudent to adopt a low-fat diet containing plenty of fruits, vegetables, and grains." In a comment from Daniel Fabricant from the Natural Products Association the ndings
592
reported at the American Thoracic Society 2007 International Conference, on Monday, May 21, suggesting that taking supplemental multivitamins, vitamin C and E and folate do not decrease the risk of lung cancer were questioned. [447]
7.22.6
The role of vitamins, folate and vegetables in the prevention of gene promoter methylation of smokers lung cancer [448]
Stidley and colleagues 2010 report that early detection of lung cancer is possible by monitoring gene promoter hypermethylation events in sputum. The authors found that available multivitamins, folate and green vegetables signicantly protected against promoter methylation of lung cells of smokers, monitored in sputum. The authors call for more studies on the ability of diet and dietary supplements to aect reprogramming of the epigenome. to prevent lung cancer.
7.22.7
Diet and obstructive lung diseases [449]
Obstructive lung disease is a category of respiratory disease characterized by airway obstruction. It includes asthma, Bronchitis, chronic obstructive pulmonary disease and cystic brosis. Romieu and Trenga, in a review of 2001, report that antioxidant vitamins, particularly vitamin C and, to a lesser extent, vitamin E are useful to reduce severity of the obstructive lung disease by decreasing oxidant stress to the lung. Antioxidant vitamins could also play an important role in childhood asthma and data also suggest that omega-3 fatty may protect against airway hyperreactivity and lung function decrements, and cigarette smokers, may be more likely to benet from dietary supplementation. Daily intake of vitamin C at levels slightly exceeding the current Recommended Dietary Allowance (60 mg/day among nonsmokers and 100 mg/day among smokers) may have a protective eect, and should should be recommended for populations chronically exposed to photooxidant air pollutants (such as ozone), cigarette smoking, or vigorous exercise Over a long period of 20-30 years it may be signicant in retarding lung decay. Bioavailability of vitamin C when given in a single dose is 200 mg. Guidelines from the US National Cancer Institute recommend consumption of ve servings of fruit and vegetables daily. The author stress that even a small increase in fruit servings could have a benecial eect in children. Magnesium infusion may help in case of cute treatment of asthma, but is timely limited, say the authors. The author gives suggestions for further studies on lung health and stresses the necessity to convince the population to increase the consumption of fresh fruits and vegetables, to stop smoking cigarettes, and to minimize their environmental and occupational exposure
7.22. WARNING ABOUT HIGH LEVELS OF MULTIVITAMINS INCREASING THE RISK OF PROSTATE CANCERS 593 to air pollutants.
7.22.8
Antioxidants to treat Chronic obstructive pulmonary disease [449]
Chronic obstructive pulmonary disease (COPD) is associated with a high incidence mortality and cigarette smoke speeds the progression of the disease. Various antioxidants, thiol antioxidants, specic spin traps and mucolytic agents, and dietary polyphenols (curcumin, resveratrol, and green tea catechins/quercetin) are used to increase intracellular thiol status along with induction of GSH biosynthesis leading to detoxication of free radicals and oxidants as well as inhibition of ongoing inammatory responses. The author concludes that therapeutic administration of multiple antioxidants and mucolytics will be eective in management of COPD, however, the choice of antioxidant therapy must be adapted for a particular clinical phenotype of the disease.
7.22.9
The American study
: 1.900 men in the USA with hypercholesterolemie from type IIa (according Frederickson) had shown over a period of 14 years an inverse relation between the total carotenoids in serum and cardiovascular diseases.
7.22.10
The EUR0MIC-Study
: The EUROMIC Study has veried the risk of trans-fatty acidsin food. This study has demonstrated an inverse correlation between the level of beta-carotene and heart attack.
7.22.11
Basel Study
: This study monitored 4.000 employees of a chemical industry during 7 years. The study shows an inverse correlation between the serum level of beta-carotene and lungand stomach carcinoma. To obtain high levels of carotenoids, vitamin E and vitamin C, a nutrition rich in bres and reduced in fat, typical for vegetables was used in these studies. The prophylactic eect of this nutrition cannot be considered apart from the eect of the vitamins lowering thus the importance of the foregoing.
7.22.12
The ATBC Study of Finland
: Over 29.000 men in Finland between 50 and 69 years were given 20 mg beta-carotene and 50 mg vitamin E for 6 years.
594
The group of beta-carotene had an unexpected increase of 18 % of lung carcinoma and 8% higher mortality compared with the placebo group. Only the prostate gland carcinoma had 34% decreased and a very low decrease of colon carcinoma.
7.22.13
ATBC study and the Follow-up study [450]
According to Albanes and colleagues 1996 the adverse eects of beta-carotene increased with modest alcohol intake and in those at least 20 cigarettes daily. [451] According to leppl participants taking vitamin E had fewer cases of prostate cancer and fewer deaths from prostate cancer. Death from hemorrhagic stroke was increased in men taking alpha-tocopherol supplements; the increase occurred primarily among men with hypertension, but prevents cerebral infarction. Beta-Carotene supplementation increases the risk of intracerebral hemorrhage in male smokers. [452]
7.22.14
The Postintervention Follow-up study [453]
Taking the vitamin supplements were stopped in April 1993 and followed the participants until April 1999 In the follow-up period, the participants taking beta-carotene experienced 7 percent higher overall mortality than men on the placebo. In the beta-carotene group, the higher mortality during the trial was due to cardiovascular disease and lung cancer. In contrast, the higher mortality during the post-intervention period was due to cardiovascular disease alone.
7.22.15
The conclusion of the post-trial follow-up period [453]
The adverse eects from beta-carotene and the benecial eects from supplementation with alpha-tocopherol (vitamin E) largely disappeared during the post-trial follow-up period. There were no additional benecial late eects on cancer or mortality observed after the trial ended. The study supports the recommendation that beta-carotene supplementation should be avoided by smokers. The possible preventive eects of alpha-tocopherol on prostate cancer require conrmation in other ongoing trials.
7.22.16
Calcium supplements and excessive consumption of dairy products may increase the risk of prostate cancer in smokers, according to a study related to the ATBC study. [454]
Calcium is reported to be the biggest seller supplement claiming that high dietary intakes of calcium and dairy products to reduce prostate cancer risk. Mitrou and colleagues 2007 in a study concerning dietary intakes of calcium and dairy products in relation to risk of prostate cancer in the Alpha-Tocopherol, Beta-Carotene
7.22. WARNING ABOUT HIGH LEVELS OF MULTIVITAMINS INCREASING THE RISK OF PROSTATE CANCERS 595 (ATBC) Cancer Prevention Study in smokers, found that calcium intake of more than 2,000 mg/day was associated with a marked increase in prostate cancer risk. Total dairy intake was also positively associated with risk of prostate cancer, but eliminating calcium from the data no risk of prostate cancer was found being calcium the pro-cancer agent of dairy products. According to the authors intake of calcium or some related component contained in dairy foods is associated with increased prostate cancer risk.
7.22.17
The CARET Study
Approximately 14.000 smokers and employed persons in asbestos industries were given 30 mg beta-carotene and 25.ooo i.U. vitamin A during 6 years. The rate of lung cancer rate was 28% higher and the death rate 17% higher than the placebo group.
7.22.18
The Physician Health Study
Over 12 years 22.000 male physicians in USA were given 50 mg/day beta-carotene. There was no signicant change in cancer, heart disease rate or mortality.
7.22.19
The Linxian Study
: Linxian is a northern Chinese region which has worldwide the highest rate of Oesophagus cancer and a very low intake of retinol, beta-carotene, vitamin E, vitamin C and riboavin. In this study 29.000 men and women in the age of 40 to 69 years were supplemented with 30 mg vitamin E, 15 mg beta-carotene, 30 microgram selenium. Death rate of Oesophagus cancer was reduced about 13%, stomach cancer about 21% and death of general origin about 9% compared with a placebo group.
7.22.20
The Nurses Health Study
: 87.000 healthy US nurses were supplemented with 100 mg vitamin E /day during 8 Years. Death rate due to heart diseases was reduced to37% compared withe the placebo group.
7.22.21
The Health Professional Study
: 40.000 healthy US physicians were supplemented with 100 mg vitamin E /day during 4 Years. Death rate due to heart diseases was reduced to 43% compared withe the placebo group.
596
7.22.22
Association of BMI, waist circumference, and waist-tohip ratio with the risk of death [455]
In 2008 Pischon and colleagues examined the distribution of body fat and the prediction of death rate. They found that the lowest risks of death related to BMI were observed at a BMI of 25.3 for men and 24.3 for women. Waist circumference and waist-to-hip ratio were strongly associated with the risk of death. Relative risks among men and women of waist circumference were 2.05 for men and 1.78 for women and waist-to-hip ratio, the relative risks were 1.68 for men, and 1.51 for women. BMI remained signicantly associated with the risk of death in models that included waist circumference or waist-to-hip ratio. The authors concluded that general adiposity and abdominal adiposity are associated with the risk of death. The study supports the use of waist circumference or waist-to-hip ratio in addition to BMI to assess the risk of death.
7.22.23
Reduced physical activity is linked to both body mass index and waist circumference says EPIC-PANACEA data [456]
Data from the EPIC-PANACEA (European Prospective Investigation into Cancer-Physical Activity, Nutrition, Alcohol, Cessation of Smoking, Eating out of home And obesity) were used by Besson and colleagues to study the relation of physical activity, body mass index and waist circumference. The authors found that physical activity is inversely associated with both BMI and waist circumference across nine European countries. The association causally could not be found, but the results are based on large and diverse data.
7.22.24
Obesity is associated with ovarian cancer according to EPIC data [457]
Lahmann and colleagues 2009 report that according to data from the Prospective Investigation into Cancer and Nutrition (EPIC) cohort factors including general and central adiposity and height, are associated with ovarian cancer risk. The authors found that body mass index 30 kg/m2 was associated with excess ovarian cancer risk, compared with BMI >25 kg/m2 . Neither height, weight gain, nor BMI-adjusted measures of fat distribution assessed by waist circumference, waist-hip ratio (WHR), or hip circumference, were associated with overall risk, however, WHR was related to mucinous tumours. The authors concluded that obesity is a risk factor for epithelial ovarian cancer. Weight reduction may thus help to reduce the risk in postmenopausal women.
7.22.25
Specic dietary and other lifestyle behaviours may inuence weight gain [458]
Mozaarian et al. 2011 report a weight gain of 3.35 lb during a four-year period of participants of the study. Weight change was most directly associated with the intake of potato chips, potatoes, sugar-sweetened beverages, unprocessed red meats, and processed meats, and inversely associated with the intake of vegetables, whole grains, fruits, nuts, and yoghurt. Lifestyle factors, such as physical activity; alcohol use, smoking; former smokers, sleep (more weight gain with less than 6 or more than 8 hours of sleep), and television watching were independently associated with weight gain. These factors may inuence the "eat less and exercise more" strategy. SectionNeurodegenerating diseases and food toxicity
7.22.26
The Swedish Mammography Cohort and the Cohort of Swedish Men [459]
Susanna C. Larsson and colleagues prospectively investigated the association between consumption of fruits and vegetables and the incidence of gastric cancer among women of the Swedish Mammography Cohort and men of the Cohort of Swedish Men, found that consumption of green leafy vegetables and root vegetables was inversely associated with risk of gastric cancer. The authors concluded that frequent consumption of vegetables (three or more servings a week) of green leafy vegetables, like spinach, lettuce, and green salad reduced the risk of stomach cancer by 46% and roots vegetables by 57% compared with a group who ate less than half a serving every week. No relation between fruit consumption and stomach cancer was found. From all these studies it is to be noted: 1. No help to reduce cancer incidence is expected with high dose of antioxidant vitamins in high risk groups such as heavy smoker when cancer already had started before begin of the supplementation. 2. Very high, not physiological dose of beta-carotene can start prooxidative reactions in relation to the tension of oxygen in cells. The studies were made with high dose of beta-carotene which are not obtained with normal food. 3. Vitamin E can act as antioxidant only in presence of sucient concentration of vitamin C. Vitamin C bears the danger to build Fe++ ions when high iron levels are present.
598
4. In some regions were not sucient supply of vitamins are present a supplementation with low dose of antioxidant vitamins can act positively 5. With a nutrition rich in vegetables and fruits and reduced amount of lipids there is no need to supplement with vitamins because ideal blood levels are normally achieved
7.22.27
RDI of vitamin C
The recommended daily intake of the vitamin C in Europe is 60 mg. In the US, men are recommended to consume 90 mg per day, and women 75 mg per day. To provide data for the RDA of vitamin C, Mark Levine and colleagues conducted an in-hospital depletion-repletion study. They found that bioavailability was complete for 200 mg of vitamin C as a single dose. No vitamin C was excreted in urine of six of seven volunteers until the 100-mg dose. At single doses of 500 mg and higher, bioavailability declined and the absorbed amount was excreted. Oxalate and urate excretion were elevated at 1000 mg of vitamin C daily compared to lower doses. Based on these data and Institute of Medicine criteria, the current RDA of 60 mg daily should be increased to 200 mg daily, which can be obtained from fruits and vegetables. Safe doses of vitamin C are less than 1000 mg daily, and vitamin C daily doses above 400 mg have no evident value. [460]
7.22.28
Antiinammatory eects of vitamin C [461]
Blood levels of C-reactive protein (CRP) and tissue plasminogen activator (t-PA), known as markers linked to inammation were found inversely associated with Plasma vitamin C, fruit intake, and dietary vitamin C. Goya Wannamethee and colleagues from the RoyalFree and University College Medical School, London concluded that vitamin C has antiinammatory eects and is associated with lower endothelial dysfunction in men with no history of cardiovascular disease or diabetes. The authors found that the high blood levels of vitamin C were associated with a 45 per cent reduced risk of inammation (with respect to CRP levels), and high fruit intake was related to a 25 per cent reduced risk of inammation. Plasma (but not dietary) vitamin C also showed inverse associations with both brinogen concentrations and blood viscosity. No associations were seen with von Willebrand factor or factor VIII.
7.22.29
Critics on the Wannamethee study [462]
Previous clinical trials (with diabetics, smokers and healthy men) had not reported an anti-inammatory eect from vitamin C supplementation. In contrast, intravenous vitamin C trials did report an improvement in endothelial function.
Ishwarlal Jialal and Uma Singh from the University of California Davis Medical Center, writes in an editorial that in respect to the antiinammatory eects of vitamin C, the article of Wannamethee does not allow the drawing of any valid conclusions. Much further research in a dose-response structure is required to ascertain whether oral vitamin C supplementation is antiinammatory and whether it improves endothelial dysfunction. Until such studies have been conducted, it is safe to adhere to the guidelines of national organizations to consume e 5 or more daily servings of fruit and vegetables. Other shortcomings of the article of Wannamethee are cited in this editorial: The study was only focused on elderly white men and thus could not be generalized for other groups. The use of t-PA as a measure of endothelial inammation is being questioned. Previous clinical trials (with diabetics, smokers and healthy men) had not reported an anti-inammatory eect from vitamin C supplementation. Intravenous vitamin C trials did report an improvement in endothelial function. The authors call for more research in a dose-response to ascertain whether oral vitamin C supplementation is anti-inammatory and whether it improves endothelial dysfunction.
7.22.30
Anti-inammatory molecular mechanism of action of Lutein unveiled [463]
According to Mohamed Ra and Yassaman Shafaie lutein is an oxycarotenoid primarily found in dark-green leafy vegetables such as spinach and kale and moderate amounts were found in corn, egg yolks, and fruits like oranges and kiwi. Lutein reduces the risk of age related macular degeneration. It also reduces chronic inammation caused by an overexpression or lack of control of the normal protective mechanism and this may lead to inammatory diseases such as of the heart. The author investigated in 2005 the in vitro anti-inammatory eect of lutein using LPSstimulated mouse macrophage cell line (RAW 264.7). In this study LPS was found to stimulate the production of nitric oxide (NO) which is detrimental eects to the host. The authors write that the addition of lutein reduced NO production signicantly by decreasing the expression of the inducible NO synthase (iNOS) enzyme at the mRNA level and protein levels.
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7.22.31
Supplementation carotinoids and antioxidants reduces risk of age-related macular degeneration [464]
According to AMD Alliance Internationa age-related macular degeneration (AMD) is the leading cause of vision loss for people over the age of 50 in the Western world, aecting approximately 25-30 million people. [465] Vincenzo Parisi, and colleagues say that the daily antioxidant and carotenoid supplements of 180 mg vitamin C, 30 mg vitamin E, 22.5 mg zinc, 1 mg copper, 10 mg lutein, 1 mg zeaxanthin, and 4 mg astaxanthin was found to improve the function of the central retina among 27 people with non-advanced AMD. Other studies had found that leafy green vegetables, corn, egg yolks, squash, broccoli and peas, rich in lutein and zeaxanthin reduce the risk of AMD by absorbing blue light that could damage the macula.
7.22.32
High sh oil diet rich in EPA and DHA deduces risk of age-related macular degeneration [466]
Tuo and colleagues 2009 report that high n-3 fatty acid enriched EPA and DHA diet slowed progression of age-related macular degeneration in mice. Also reversion of some retinal lesions were found. The authors suggest that the arachidonic acid metabolism decreased pro-inammatory derivatives (prostaglandin E2 and leukotriene B4) and increased antiinammatory derivative (prostaglandin D2). Their results support other ndings in human studies on the eect of omega-3 fatty acids on age-related macular degeneration.
7.22.33 7.22.34
Eggs and CVD The Djouss and Gaziano study [467]
In general, a reduction in dietary cholesterol is recommended to prevent cardiovascular disease (CVD). Djouss and Gaziano 2008 studied the eect of egg consumption regarding to the risk of all-cause mortality and CVD mortality on account of its content of cholesterol of its egg-yolk. In this 20 years study the authors found eating more than 1 egg a day was related to all-cause mortality stronger association was noted among diabetic subjects. However infrequent egg consumption does not seem to inuence the risk of CVD or stroke.
7.22.35
Comment on the study of Djouss and Gaziano [468]
According to Robert H Eckel concerns about egg consumption and atherosclerotic risk have to do with the cholesterol content of eggs. Eckel stresses that cholesterol absorption has been shown to be higher in patients with type 1 diabetes but not in patients with type 2 diabetes,and suggests that most of the subjects with diabetes in the study had type 2, not type 1, diabetes, explaining the higher mortality of diabetes subjects. Eckel also points out that the all-causes were not specically analysed and coronary cases were omitted. Also other factors healthy factors such as age, smoking, physically activity, breakfast cereal eating habits, were not included in the study. Eckel advices to discard the egg yolk and use only the egg white. Eating whole eggs should be less than 3-4 d/week, and patients with diabetes should be prudent with eggs.
7.22.36
The Blue Mountains Eye Study [469]
Paul Mitchell and colleagues found that higher dietary lutein and zeaxanthin intake reduced the risk of long-term incident AMD. This study conrmed the Age-Related Eye Disease Study nding of protective inuences from zinc against AMD. Higher beta-carotene intake was associated with an increased risk of AMD. Energy-adjusted intakes of alfa-carotene; beta-carotene; beta-cryptoxanthin; lutein and zeaxanthin; lycopene; vitamins A, C, and E; and iron and zinc were at focus in this study.
7.22.37
EU panel says synthetic zeaxanthin as an ingredient in food supplements is not safe [470]
The EU Panel on Dietetic Products, Nutrition and Allergies found that the safety could not be established for synthetic zeaxanthin as an ingredient in food supplements for a level of up to 20 mg/person/day. According to the Panel, in European countries, the average intake level of zeaxanthin via food was estimated to be between 0.2 and 0.9 mg/day and for people with a high intake of zeaxanthin-rich vegetables and fruits this could result in a level of 1.8 mg/day. The proposed use levels of up to 20 mg/person/day of synthetic zeaxanthin as an ingredient in food supplements would lead to intake levels up to 100 times higher than the average intake from natural sources. These intake levels are within the range of the group ADI 0-2 mg/kg body weight for lutein and synthetic zeaxanthin as established by JECFA. However, in the opinion of the Panel, the toxicological data on synthetic zeaxanthin are not sucient to derive an acceptable daily intake.
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7.22.38
Zeaxanthin and eye diseases [471]
Zeaxanthin is one of the two carotenoids contained within the retina of the eye. Within the central macula, zeaxanthin is the dominant component, whereas in the peripheral retina, lutein predominates. As a food additive, zeaxanthin is a food colour wtith E number E161h. Zeaxanthin is one of the most common carotenoid alcohols found in nature. It is the pigment that gives corn, saron, and many other plants their characteristic colour. Zeaxanthin breaks down to form picrocrocin and safranal, which are responsible for the taste and aroma of saron. Sources of zeaxanthin and lutein are eggs, spinach and other green vegetables. Low plasma concentrations of lutein and zeaxanthin may increase the risk of developing age-related macula degeneration (AMD). Some studies say that supplemental lutein and/or zeaxanthin could reduce the risk of AMD [472] and cataract.
7.22.39
No support for prevention of AMD by omega-3 fratty acids
[473] Chong and colleagues 2008 in a systematic review and meta-analysis the evidence on dietary omega-3 fatty acid and sh intake in the primary prevention of age-related macular degeneration (AMD found that ndings of this meta-analysis suggests that consumption of sh and foods rich in omega-3 fatty acids may be associated with a lower risk of AMD, however, there is insucient evidence from the current literature to support their routine consumption for AMD prevention.
7.22.40
Intake of omega- 3 fatty acids from sh may reduce the risk of age-related macular degeneration (AMD) [474]
According to the European EUREYE study age-related macular degeneration (AMD) is the single most common cause of adult blind registration in many developed countries, including Europe. AMD occurs predominantly in the older population, especially in those aged over 70 years. There are two main types of AMD: neovascular "wet" AMD, and geographic atrophy "dry" AMD. AMD is considered to represent the severe form of a constellation of morphological changes in the retina that occur in the ageing eye. Longitudinal studies have shown that, in around one in ve people, these features are a risk for the development of AMD. The EUREYE study included possible causes such as dietary risks, smoking, solar radiation and antioxidant vitamins.
Cristina Augood and colleagues 2008 writing for EUREYE report that eating once a week oily sh rich in DHA (docosahexaenoic acid) and EPA (eicosapentaenoic acid) the risk of neovascular AMD (NV-AMD) was halved. According to the authors vitamin D might be a protective agent for AMD through its anti-inammatory properties. There was no independent association between dietary vitamin D and NV-AMD when either EPA or DHA were included in the model. [475]
7.22.41
No relation between alcohol consumption and AMD [476]
Boekhoorn and colleagues in the Rotterdam study 2008 found no relationship between overall or specic alcohol consumption and risk of aging macula disorder (AMD), a synonym for age-related macular degeneration. The authors concluded that alcohol consumption is not a risk factor for AMD.
7.22.42
Antioxidant carotenoids,lutein and zeaxanthin in coronary artery disease [477]
Some epidemiological studies claimed that supplementation with beta-carotene have no heart protective eect. Other authors turned, therefore, their attention to other carotinoids like lutein and zeaxanthin: James H.Dwye and colleagues found in 2001 in the Los Angeles Atherosclerosis Study that the protective eects of the oxygenated carotenoid lutein against early atherosclerosis. Their ndings in vitro, and mouse model support the hypothesis that increased dietary intake of lutein is protective against the development of early atherosclerosis. [477] Lidebjer and colleagues in a 2006 studied plasma levels of oxygenated carotenoids (lutein, zeaxanthin, beta-cryptoxanthin) and hydrocarbon carotenoids (alfa-carotene, beta-carotene, lycopene) in patients with coronary artery disease and relate the ndings to clinical, metabolic and immune parameters. The authors found that lower plasma levels of oxygenated carotenoids, in particular lutein+zeaxanthin, compared to controls were associated with cardiovascular disease. Low levels of oxygenated carotenoids were also associated other cardiovascular risk factors such as smoking, high body mass index, low high density lipoprotein cholesterol and, to a minor degree, inammatory activity. Plasma levels of lutein+zeaxanthin were independently associated with the proportions of natural killer cells which , but not with other lymphocytes, in blood, indicating that certain carotinoids may play a role in the immunology of heart diseases. Natural killer cells are part of the human immune response system. Dietary sources of lutein and zeaxanthin include corn, egg yolk, broccoli, green beans, cabbage, lettuce and kiwi fruit. [478]
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7.22.43
Lutein and zeaxanthin found to increase, and alfa and beta carotene reduce myocardial infarction [479]
Hannia Campos and colleagues in a study of 2005 concluded that Adipose tissue betacarotene showed a signicant inverse relation with myocardial infarction risk; Intake of fruits and vegetables that are rich in beta-carotene was also inversely associated with the risk of myocardial infarction. The authors suggest that beta-carotene protects against myocardial infarction or it is a marker of some protective factor in foods containing betacarotene. In contrast, lutein and zeaxanthin in adipose tissue increased the myocardial infarction risk. Other carotenoids or tocopherols in the diet or adipose tissue showed no eect on myocardial infarction. Daan Kromhout and colleaugues in 2008 found that dietary intakes of alfa-carotene and beta-carotene reduced the risk of cardiovascular diseases mortality in elderly men. However, other carotenoids, tocopherols, or vitamin C do not have an eect on cardiovascular diseases death. [480]
7.22.44
Low plasma carotenoids are associated with all-cause mortality in elderly men [481]
Results of the Epidemiology of Vascular Ageing (EVA) study show that Low total plasma carotenoid level was signicantly associated with all-cause mortality in men but not in women. Akbaraly, Favier and Berr 2008 explain that high intakes of fruits and vegetables were associated with lower mortality due to their carotenoids which have antioxidant properties. A low plasma carotenoid level was also associated with cancer in men. The authors suggest that total plasma carotenoid levels could be a health indicator in elderly populations.
7.22.45
Dierent forms of vitamin E
There are eight forms of vitamin E: Tocopherols: alpha, beta, gamma, delta. Alpha-tocopherol is found in supplements and in the European diet, and gamma-tocopherol is found in the American diet. Tocotrienols: alpha, beta, gamma, delta. They are found in palmoil, cereal grains and rice bran.
7.22.46
Tocotrienols stopping the spread of cancer cellsm [482] [483]
Yoshiyuki Mizushina from the Kobe-Gakuin University, leading author studied the eects of all eight forms of vitamin E on the inhibition of mammalian DNA polymerase, the enOurFood Database of Food and Related Sciences Copyright 1998-2010 Karl H. Wilm. All rights reserved.
7.22. WARNING ABOUT HIGH LEVELS OF MULTIVITAMINS INCREASING THE RISK OF PROSTATE CANCERS 605 zyme that assists DNA replication. He found that tocotrienols could stop the spread of cancer cells. The four tocopherols did not inuence the activities of mammalian polymerases and had no eect on the spread of cancer cells. Alpha- and delta-tocotrienols inhibited polymerase lambda activity, and inhibited the spread of cancer cells, and angiogenesis (the growth of new blood vessels) is inhibited and the spread of the cancer to other parts of the body is hindered reducing risk of metastasis. Other Study by Chandon Sen, Savita Khanna and Sashwati Roy [483] support identical claims for tocotrienols, including neuroprotection, reduction of cholesterol, as an antioxidant, and other anti-cancer studies.
7.22.47
The American Cancer Societys Cancer Prevention Study II Nutrition Cohort: Vegetable and fruit consume do not reduce risk of endometrial cancer [484]
According to Marjorie L. McCullough and colleagues lower risk of endometrial cancer was associated with greater vegetable consumption but not fruit consumption, and an inverse association with fruits and vegetables combined have been suggested. In context of the American Cancer Societys Cancer Prevention Study II Nutrition Cohort the authors found that neither fruit consumption nor vegetable consumption was associated with risk. Only among women who had never used hormone replacement therapy was the risk of endometrial cancer lower or vegetable consumption. The authors concluded that an association between vegetable or fruit consumption and endometrial cancer cannot be supported.
7.22.48
The Multiethnic Cohort Study: Flavonols and Pancreatic Cancer Risk [485]
Ute Nthlings and colleagues assessed the eect of avonols on pancreatic cancer risk, estimating the intakes of three avonols quercetin, kaempferol, and myricetin. Total avonols was associated with a reduced pancreatic cancer risk, kaempferol was associated with the largest risk reduction. Total avonols, quercetin, kaempferol, and myricetin were all associated with a signicant inverse trend among current smokers but not never or former smokers. The authors concluded that avonols have a preventive eect on pancreatic cancer, and stressed that current smokers do prot from that.
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7.22.49
Diet and the Risk of Barretts Esophagus [486]
Ai Kubo and colleagues assessed the dietary patterns of patients with Barretts Esophagus. They found that a diet high in fruits, vegetables, and nonfried sh was inversely associated with Barretts esophagus. A diet high in fast food and meat produced an adverse eect on the risk of the disease. The authors concluded that there is a strong associations between a diet rich in fruits and vegetables and the risk of Barretts esophagus. This backs the WHO recommendations to eat 400 g of fruit and vegetable a day.
7.22.50
Vitamins C, E, and beta-carotene from fruits and vegetables but not from supplements reduce risk of Barretts esophagus [487]
Ai Kubo and colleagues 2008 evaluated the associations among antioxidants, fruit and vegetable intake, and the risk of Barretts esophagus, a potential precursor to esophageal adenocarcinoma. The authors found that dietary antioxidants, fruits, and vegetables are inversely associated with the risk of Barrets esophagus, while no association was observed for supplement intake. Kubo and colleagues suggest that fruits and vegetables themselves or a not yet identied compound of fruits and vegetables may reduce the risc of esophageal cancer.
7.22.51
Vegetable phenols
Vegetable polyphenols are due to historical background known as "tannin" when they are able to tan animal skin to leather. Substances of the group of the vegetable phenols act antioxidant similar to antioxidant vitamins. These substances are:
7.22.52 7.22.53
Chlorogenic acid Quercentin reduces susceptibility to inuenza infection [488]
Quercetin is an antioxidant found in red onions, the skins of apples, grapes, blueberries, broccoli, tea and red wine. Quercentin is known for its chronic disease-ghting benets and reduction in blood pressure. Davis and colleagues 2008, found that quercentin may boost the immune systems and protect against u. According to the authors exercise stress is associated with increased risk of infections of the upper respiratory tract. The researchers used the inuenza virus A/Puerto Rico/8/34 (H1N1) to infect mice after stressful exercise. The authors report
7.22. WARNING ABOUT HIGH LEVELS OF MULTIVITAMINS INCREASING THE RISK OF PROSTATE CANCERS 607 that gavage of quercetin (12.5 mg/kg) 7 days before viral challenge reduced morbidity, mortality, and symptom severity of respiratory infections after stressful exercise.
7.22.54
Quercentin extraction methods [489]
Hu Wei and collegues 2003 improved the extraction of quercentin. The authors report that pre-dispersed solvent extraction (PDSE) was used to extract quercentin from its diluted solution. Compared with traditional extraction techniques under the same condition, a higher extraction productivity can be obtained by this method. The stability of colloidal liquid aphrons plays an important role in this process. Furthermore, the authors improved the analytical method by using ultraviolet spectrometer to determine the concentration of quercentin.
7.22.55
Flavonoids
Anthocyanesare the most important avonoids.Anthocyanes are found mainly in red grape peel, in red beet and bilberry. Flavonoids are found in nature having phenylchroman as basic element. Its characteristic molecular formula is C6 - C3 - C6 . Important avonoids are: quercentins: Scientists of the University of California have found that quercentins are present in yellow and red onions, red grapes and broccoli. Quercentins are anticancer agents suppressing malignant cells before they form tumors an were used against capillary fragility, easy bruising and small pin-point hemorrhages Quercentin is obtained by steam distillation of quercentins bark and epicatechin, in the rinds and barks of wild fruits and the rhododendron, forsythia, hydrangea, pansies and eucalyptus Antocyanes Catechines(Flavanoles). Flavonole Flavone Flavanole: (= 3-Hydroxyavone) Flavanonole: (= 3-Hydroxy-2,3-dihydroavone) Flavanoneor catechin: (= 2,3-Dihydroavone) Anthocyanide Isoavone
7.22.56
Activity of polyphenols
These substances interrupt the radical chain reaction in lipids of the cell membrane avoiding the formation of oxidized LDL which starts ateriosclerotic diseases. They have reducing properties. Flavonoids may also act as antimutagenic and anticarcinogenic. Some activities of avonoids in human are studied but are not conrmed yet:
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Inhibition of enzymes with carcinogenic activity. Inhibition of proteolytic enzymes. Polyphenoles of these groups are found in many fruits and vegetables. That is why more fruits and vegetables and less meat, fat and alcoholics should be consumed. Tea is the main source of catechins. According to the Rotterdam-Study the consumption of tea protects against heavy aorta ateriosclerosis in particular in women.[490] Important varieties and their content of polyphenoles are: Camellia sinensis var. assamica:
High content of catechins and coein
High activity of Phenoloxidase activity resulting in dark brown colour of black tea Camellia sinensis var. sinensis:
Lower content of catechins and caeine as noted in assamica Lower activity of Phenoloxidase activity which makes it suitabler for the production of green tea
7.23
Protective eect of green tea and soy intake in relation to breath cancer risk
There is substantial in vitro and in vivo evidence implicating tea polyphenols as chemopreventive agents against various cancers. However, epidemic data collected by researchers of the Department of Preventive Medicine, University of Southern California, Keck School of Medicine, Los Angeles are not supportive of a protective role of tea, mainly black tea, in the aetiology of breast cancer. The case study showed that both green tea and soy intake had signicant, independent protective eects on breast cancer risk The results of this case study point to an important roleof both green tea and soy intake in relation to breast cancer risk. [491]
7.24. 19.02.2008: EFFECT OF LOW-FAT, HIGH-CARBOHYDRATE DIET ON RADIOLOGICAL FEATURES OF THE BREAST
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7.24
7.24.1
19.02.2008: Eect of low-fat, high-carbohydrate diet on radiological features of the breast

The Canadian Diet and Breast Cancer Prevention Study Group Trial [492]
Boyd and colleagues 1997 assessed the eect of low-fat, high-carbohydrate diet on radiologic densities of the breast. Fat is radiolucent and appears dark on mammography, while stromal and epithelial tissue has greater optical density and appears light. Extensive areas of radiologically dense breast tissue seen on mammography are associated with an increased risk of breast cancer. In this trial the authors found that a low-fat (21% of calories), high-carbohydrate diet (61%) reduced the area of mammographic density. Control group received a diet of 32% of calories of fat and 50% from carbohydrates. Longer observation of a larger number of subjects will be required to determine whether these eects are associated with changes in risk of breast cancer.
7.24.2
Macronutrient intake and change in mammographic density at menopause [493]
Boyd and colleagues 1999 assessed the reduction in breast density eect of specic macronutrients in women. The authors found that reduction in total or saturated fat intake or cholesterol intake was signicantly associated with decreased dense area, whereas reduction in dietary cholesterol intake was the most eective. The authors suggest that the observation of an eect of diet at menopause on breast density may be an indication that exposures at this time have an enhanced eect on subsequent risk.
7.24.3
Fat and vitamines do not aect mammographic density [494]
Sala and colleagues investigated the eect of food and nutrient intake on mammographic patterns. Mammographic parenchymal patterns are related to breast cancer risk and are also thought to be aected by diet. The authors found that high intake of total protein and carbohydrate doubled the breast cancer risk. Total meat intake increased high risk patters among post-menopausal women. There was no excess risk for fat intake, and no association between intake of vitamins and mammographic parenchymal patterns was found.
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The authors, analysing the results of their study, suggest that certain macronutrients and foods such as protein, carbohydrate and meat intake inuence the risk of breast cancer through their eects on breast tissue morphology, whereas fat and vitamins do not aect mammographic density. It seems that parenchymal pattern acts as an informative biomarker of the eect of some macronutrient and foodstus intake on breast cancer risk.
7.24.4
Eect of a low-fat, high-carbohydrate dietary intervention on change in mammographic density over menopause [495]
Boyd and colleagues 2008 had previously found that a low-fat dietary intervention for 2 years in women with extensive mammographic density decreased mammographic density to a greater extent than in the control group. Post-hoc analysis indicated that this eect was strongest in women who became postmenopausal during the follow-up period. [492] A new study to conrm these data included women who were premenopausal at entry and became postmenopausal during follow-up. Total breast and non dense area increased more in the control group compared to the intervention group. However dense area decreased to a similar degree in both groups. Menopause reduced density to a similar extent in the low-fat diet and control groups. If a low-fat diet reduces breast cancer risk, the eect is unlikely to be through changes in mammographic density at menopause.
7.24.5 7.24.6
Other Dietary factors of increased risk of breath cancer Phyto-oestrogens and breast cancer [496]
David Ingram and colleagues assess the association between phyto-oestrogen intake (as measured by urinary excretion) and the risk of breast cancer. In this study the isoavonic phyto-oestrogens daidzein, genistein, and equol, and the lignans enterodiol, enterolactone, and matairesinol were controlled. There is a substantial reduction in breast-cancer risk among women with a high intake (as measured by excretion) of phyto-oestrogens-particularly the isoavonic phyto-oestrogen equol and the lignan enterolactone. The other phytoestrogens did not reduce the risk signicantly. These ndings could be important in the prevention of breast cancer.
7.24.7
Lifelong vegetarianism and risk of breast cancer [497]
Isabel dos Santos Silva and colleagues 2002 investigated the role of lifelong vegetarianism on the aetiology of female breast cancer. Their ndings suggest that lifelong vegetarianism with high intake of vegetables and pulses may be associated with a reduction in the risk of breast cancer. A lifelong meat abstention may also play a role.
611
The authors concluded that a diet rich in vegetables and pulses, such as found in South Asian diets, may be protective against breath cancer.
7.24.8
Phyto-oestrogen intake and breast cancer risk in South Asian women in England: ndings from a populationbased case-control study. [498]
In 2004 Isabel dos Santos Silva and colleagues investigated the phyto-oestrogens association with breast cancer risk in South Asian women from the Indian subcontinent, whose diet is rich in pulses and vegetables but poor in soy foods. According to their ndings high phyto-oestrogen intake may protect against breast cancer, but the authors call for further research in this matter.
7.24.9
Excess water consumption can harm [499]
The general advice is to consume eight glasses of water a day (2 - 2.5 litres), which is approximately equal to the amount lost through normal bodily functions. One litre as an absolute minimum to avoid kidney damage During times of excess perspiration (such as heavy exercise). Tea and coee also count as water intake.
7.24.10
Climatic Heat Stress and Children sport activities [500]
Outdoor sports and physical activity in the heat are safe for most healthy children and adolescents given adequate preparation, modications, and monitoring, says the American Academy of Pediatrics (AAP). The paper describes risk factors for heat illness in youth and possible modications of sports activities to reduce this risk. However, thermoregulatory ability, cardiovascular capacity, and tolerance for physical activity are not relatively impaired in youth compared to adults exercising in the heat, provided hydration is adequate. The 2011 policy statement says that heat illness is entirely preventable if coaches and other adults take some precautions to protect the young athletes. Most healthy children and athletes can safely participate in outdoor sports and activities in a wide range of warm to hot weather, but adults sometimes create situations that are potentially dangerous. The risk for heat stress illness during sports is increased by factors such as insucient recovery between rounds of exercise, inappropriate clothing that retain excessive heat, closely scheduled competition, or inappropriate protective equipment. Coaches should make decisions to improve safety for a team or event as a whole. Individual participants may require more or less concern based on their health status and conditioning such as overweight and obesity, recent recovery from diarrhoea or viral illness,
612
chronic physical conditions, poor physical tness, insucient sleep or rest, and lack of acclimatization to warm temperatures and/or high humidity when the season of hot weather begins. Therefore the AAP does not give precise recommendations regarding whether games or practices should be cancelled if temperatures reach a certain level and revokes the policy statement issued in 2000. [501]
7.24.11
Some useful recommendations
- Drinking uids should be encouraged at regular intervals. - Participants should be gradually introduced and permitted to adapt to the climate. - Physical activity should be modied as necessary by reducing duration and/or intensity, increasing the frequency and duration of breaks and moving them to the shade if possible, and cancelling the activity if weather is severe. - Between the sessions youth should be given at least 2 hours of recovery time. - Children or adolescents who are currently or who were recently ill, and those with other risk factors, should be permitted only limited or postponed participation. - Participants should be closely monitored for signs and symptoms of developing heatrelated illness. This statement and a series of nutrition-related policy statements of the AAP are available online. [502]
7.24.12
Hydration and detox diets
Hydration and detox diets promote excess water consumption. According to Sarah Palmer from Daily Mail a low plasma sodium level with brain damage or death may occur when too much water is consumed. Several adverse outcome are known. Some hydrating diets, like detox diets recommend drinking ve to six litres of water and eating only fruit and vegetables with no salt for a number of days. This may work for a short period, but salt levels, after some time, will fall below a harmful levels. Most prominent detox advocate is Dr Nish Joshi. [503] [503] [504] Dr. Andrew Wadge from UK FSA says that instead of being tempted by the latest "detox" diet or supplements one should drink a glass or two of water (tap is ne, cheaper and more sustainable than bottled), get a little exercise - maybe a walk in the park - and third, enjoy some nice homecooked food. Theres a lot of nonsense talked about "detoxing" and most people seem to forget that we are born with a built-in detox mechanism. Its called the liver. [505]
7.24.13
"Detox" is a food claim [506]
According to UK Food Standards Agency, the term "Detox" refers to a function in the body and would be a health claim. As detox could refer to a range of functions, whether this is a health claim that should be listed in the Community Register of authorised claims
613
or is a claim referring to general, non-specic benets of the nutrient or food for overall good health or health-related well- being, may depend on the nature of the product.
7.24.14
Saower and cinnamon tea as Detox herbal tea [507]
A herbal tea of saower and cinnamon is being produced as a Detox herbal tea by the Bhutanese Menjong Sorig Pharmaceuticals, backed by the Institute of Traditional Medicinal Services from the Health Ministry of Bhutan. Bhutanese traditional medicine: According to the company, Bhutan has integrated the traditional medical system, known as gso-ba rig-pa, in the modern healthcare system, achieving better results in public health. The traditional medicine aims to understand the Universe, man, and his sicknesses and is an holistic approach in the treatment of human beings. It not only considers in treating the disease and its causes but also considers the interdependency of man and nature and has spiritual component included in the treatment. [508]
7.24.15
No evidence that Detox products are better than a glass of tap water [509]
Detox diet is a marketing term used to describe diets that are purported to detoxify the body, by removal of toxins or other contaminants. Proponents claim they improve health, energy, resistance to disease, mental state, digestion, despite a lack of supporting evidence, as well as aiding in weight loss. Many scientists, dietitians, and doctors, however, regard detox diets as less eective than drinking a glass of water, and view detox diets as generally harmless (unless nutritional deciency results) but a waste of money. [510] The charitable trust Sense About Science group say that products promoted as "detox" agents, highlighting a signicant lack of evidence and a misleading use of scientic terminology. They assessed 15 products products of bottled water, vitamins, shampoo, detox patches and body brushes. In this study the group found no evidence that products widely promoted to help the body "detox" work, many detox claims were "meaningless". The authors stress that if they were to have any action upon the body at all, the same could be achieved by drinking plenty of water, having a healthy balanced diet and plenty of sleep. The Advertising Standards Authority said it would investigate such claims on a caseby-case basis if a complaint was made.
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7.25
Complementary and Alternative Medicine
[511] The National Center for Complementary and Alternative Medicine (NCCAM) of the National Institutes of Health (NIH) denes CAM as a group of diverse medical and health care systems, practices, and products that are not presently considered to be part of conventional medicine. Conventional medicine is medicine as practiced by holders of M.D. (medical doctor) or D.O. (doctor of osteopathy) degrees and by their allied health professionals, such as physical therapists, psychologists, and registered nurses.
7.25.1
Report of the the Task Force on Complementary and Alternative Medicine [512]
Kathi J. Kemper, MD, MPH, and colleagues from the Task Force on Complementary and Alternative Medicine and the Provisional Section on Complementary, Holistic, and Integrative Medicine. Released a report aiming to dene terms; to review the epidemiology; to list frequently used CAM modalities; to discuss medicolegal, ethical, and research implications; to describe education and training for CAM providers; to oer resources for additional learning regarding CAM; and to suggest communication strategies that clinicians may nd helpful when discussing CAM with patients and families. The terms holistic medicine or integrative medicine is being increasingly substituted for CAM. In their report Kemper and colleagues describe a model of holistic care which includes: Biochemical components: Included are items such as medications, dietary supplements, vitamins, minerals, herbal remedies. Lifestyle: The lifestyle includes nutrition, exercise/rest, environmental therapies such as heat, ice, music, vibration, and light, mind-body therapies (behavior management, meditation, hypnosis, biofeedback, counseling). Biomechanical components: Included are massage and bodywork, chiropractic and osteopathic adjustment, and surgery.
7.25.2
Bioenergetic therapies
Bioenergetic therapies may include acupuncture, radiation therapy, magnets, Reiki, healing touch, qi gong, therapeutic touch, prayer, homeopathy.
7.26
Homeopathy
was developed by Samuel Hahnemann in 1790 It is based on the theory that an ill person can be treated using a substance that can produce, in a healthy person, symptoms similar to those of the illness. According to Hahnemann, serial dilution, with shaking between each dilution, removes the toxic eects of the substance, while the essential qualities are retained by the diluent (water, sugar, or alcohol).
7.26. HOMEOPATHY
615
7.26.1
UK regulation on homeopathics [513]
The National Rules for Homoeopathic Products 2006 No. 1952 came into force that permit homeopathic products to make medical claims but exempt them from providing any scientic evidence that they are eective. According to the Sense About Science Group, the regulation of medicines moves away from science and from clear, meaningful information for the public. The UKs licensing body, the Medicine and Healthcare products Regulatory Agency (MHRA), with the introduction of the new rules for homeopathy, accepts homeopathic provings as evidence of ecacy. A proving is the method homeopaths use to determine the symptoms a substance causes (with a view to treating diseases with similar symptoms). Provings are not carried out on the nished product and are nothing to do with ecacy, says the group. [514]
7.26.2
FDA Regulation [515]
The Homeopathic Pharmacopeia of the United States includes standards for source, composition and preparation of homeopathic drugs. In 1938 a recognition of any product listed in the Homeopathic Pharmacopeia was included in the Food, Drug, and Cosmetic Act. FDA regulates homeopathic drugs in separate from other drugs. New drugs application to FDA are not compulsory. All homeopathic products are exempt from good manufacturing practice requirements related to expiration dating and from nished product testing for identity and strength. FDA found no toxicity or poison-control reason for safety and quality controls because homeopathic products contain little or no active ingredients.
7.26.3
Current Procedural Terminology (CPT) [516]
The Current Procedural Terminology code (CPT) accurately describes medical, surgical, and diagnostic services and is designed to communicate uniform information about medical services and procedures among physicians, coders, patients, accreditation organizations, and payers for administrative, nancial, and analytical purposes. Despite the publics increasing use of CAM therapies and willingness to pay out-of-pocket for these services, health insurers have had diculty including them in their plans because of variation in credentialing, diculties with accounting, and because there are so few Current Procedural Terminology (CPT) codes that cover these services.
7.26.4
The White House and Complementary and Alternative Medicine [517]
In 2000, the US President and Congress assembled and mandated the White House Commission on Complementary and Alternative Medicine Policy to make administrative and legislative recommendations to maximize the benets of CAM for Americans.
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Until recently, the primary response of Federal, state, and local health care regulatory agencies to this phenomenon was to restrict access to and delivery of CAM services to protect the public from unproven and potentially dangerous treatments. Since the early 1990s, however, scientic evidence has begun to emerge suggesting that some CAM approaches and products, when used appropriately, can be benecial for treating illness and promoting health. As this evidence is collected and disseminated to the wider health care community and the public, it should provide a reliable basis for making policy decisions that will facilitate the publics access to safe and eective CAM approaches and products.
7.26.5
FDA regulating Complementary and Alternative Medicine [518]
Complementary and Alternative Medicine related issues are regulated by the FDA through The Dietary Supplements Health and Education Act of 1994 (DSHEA), classifying them as dietary supplements. The law denes dietary supplements in part as products taken by mouth that contain a "dietary ingredient". Dietary ingredients include vitamins, minerals, amino acids, and herbs or botanicals, as well as other substances that can be used to supplement the diet. Generally, manufacturers do not need to register their products with FDA nor get FDA approval before producing or selling dietary supplements. Manufacturers must make sure that product label information is truthful and not misleading. FDAs post-marketing responsibilities include monitoring safety, e.g. voluntary dietary supplement adverse event reporting, and product information, such as labeling, claims, package inserts, and accompanying literature. The Federal Trade Commission regulates dietary supplement advertising. The DSHEA regulates informational materials, the labeling of dietary supplements. Claims to prevent, treat, or cure a specic disease are expressly prohibited, unless approved by the FDA. [519]
7.26.6
Synergistic eect of vegetable components reduce premenopausal breast cancer risk [520]
Freudenheim and colleagues 1996 studied the role of diet, including the intake of non-food supplements, and premenopausal breast cancer risk. According to the authors intake of vitamins C and E and folic acid taken as supplements did not reduce the breast cancer risk. The authors concluded that intake of vegetables appears to decrease premenopausal breast
7.26. HOMEOPATHY
617
cancer risk. This eect may be related, in part, to beta-carotene and lutein + zeaxanthin in vegetables. n The researchers stress that no single dietary factor explains the eect, and components found together in vegetables may have a synergistic eect on breast cancer risk.
7.26.7
Raw and cooked vegetables, fruits, selected micronutrients, and breast cancer risk: a case-control study in Germany [521]
Adzersen and colleagues 2003 published a case-control study of breast cancer in Heidelberg, Germany. The report that intake of raw vegetables, total vegetables, and whole-grain products was inversely associated with breast cancer risk. High intake of vitamin C, folate equivalents, b-carotene, zinc, and copper also reduced the risk, however, fruits, cooked vegetables, bre, calcium, manganese, or iron did not have such eect. The authors concluded that in this population of German women, components of raw vegetables and some micronutrients appear to decrease breast cancer risk.
7.26.8
Alfa-carotene and beta-carotenereduces risk of gastric cancer [522]
Cristina Pearson and colleagues 2008 studied the eect of carotenoids, retinol and tocopherol on gastric cancer among Japanese with known Helicobacter pylori infection. The authors found evidences that alfa- and beta-carotene reduces the risk of gastric cancer in men but not in women, where relatively higher plasma levels compared to men had been found. Lutein/zeaxanthin, lycopene, retinol, alfa- or gama-tocopherol had no eect on gastric cancer, according to the authors. They conclude that very low plasma levels of alfa-carotene and beta -carotene are signs of a higher risk of gastric cancer.
7.26.9
More evidences of anticancer eects of green tea [523]
Shaun K. Rodriguez et col. suggest a novel mechanism for green tea catechin, epigallocatechin3-gallate anticancer eects where epigallocatechin gallate can abrogate vascular endothelial growth factor signalling by interfering with the formation of a receptor complex, resulting in attenuated mitogenic and angiogenic signalling. Bitter chocolate has high levels of catechins ( 53,3 mg/100g chocolate) . Specic polyphenols are measured with aid of HPLC or capyllary electrophoresis. In order to act reducing it is necessary have at least one of the following structures: 1.- 3 , 4 -Dihydrofunction at the B ring. This makes the turnover of a proton building thus an aryloxy-radical. 2.- OH- A group in position 5 and 7 at the A ring. 3.- A doublebound in 2-3 position in conjugation with the 4-Oxo-function and the 3-OH
618
group at the ring C turning possible the delocalization of the electrons of the B ring. Quercentine has all three structures turning out to be an excelent antioxydant in water solution.
7.26.10
Green tea extract may protect from nonalcoholic fatty liver disease [524]
According to Richard S. Bruno and colleagues green tea extract inhibits intestinal lipid absorption and may regulate hepatic lipid accumulation and protects against hepatic lipid accumulation during the development of nonacoholic fatty liver disease in an obese mouse
7.26. HOMEOPATHY
619
model by limiting hepatic lipid accumulation and injury without aecting hepatic antioxidant status and adiponectin-mediated lipid metabolism. The polyphenols such as epigallocatechin gallate, epigallocatechin, epicatechin gallate, and epicatechin account for the health benets of green tea. They are reduced tenfold in black tea by oxidation during the fermentation process. The authors conclude that green tea extract may be used as a potential dietary strategy for preventing nonalcoholic fatty liver disease, and it may be helpful as a dietary therapy under conditions of preexisting hepatic steatosis. They suggest also to evaluate the extent to which green tea extract can prevent the transition toward more debilitating forms of nonalcoholic fatty liver disease.
7.26.11
The Singapore Chinese Health Study and black tea and Parkinson [525]
Woon-Puay Koh and colleagues 2007 write that according to data from the 1993-2005 Singapore Chinese Health Study smoking as well as total caeine intake were inversely related to Parkinsons disease risk. Black tea showed an inverse association with Parkinsons disease risk that was not confounded by total caeine intake or tobacco smoking, which on their own also reduced the risk of the disease. Ingredients of black tea other than caeine appear to be responsible for the beverages inverse association with Parkinsons disease. Diet and green tea drinking was unrelated to Parkinsons disease risk. Green tea contains between 30 and 40 per cent of water-extractable polyphenols, black tea only 3 to 10 per cent. Oolong tea is semi-fermented tea and is somewhere between green and blacktea. Ann Walker from the Tea Advisory Panel explains the positive eect of black tea with the fact that when brewing black tea the catechins undergo oxidation resulting in the generation of more complex varieties, called thearubigins and theaavins. [526]
7.26.12
Green tea extract may extend shelf life of mutton under Indian climatic conditions [527]
Kumudavally and colleagues 2008 evaluated the use of green tea to extend the shelf life of fresh mutton, at ambient storage conditions of Indian climate condition around 25 2o C and aproximately 855% RH). According to the authors the ethanolic extract of green tea signicantly inhibit spoilage microora, including certain pathogens of acidulant treated mutton (pH 3.8). Free fatty
620
acids, the biogenic amine index remained almost unchanged and the mutton was acceptable for up to 4 days. The control sample began to spoil between 20 and 24 hours. Very high free fatty acids and biogenic amine index values were found. The authors concluded that green tea extract could extend the shelf life of fresh mutton for up to 4 days inhibiting sensorial spoilage.
7.26.13
Green tea reduces periodontal disease [528]
Kushivama and colleagues 2009 report that routine intake of green tea may promote healthy teeth and gums. Three indicators of periodontal disease were examined in this study: periodontal pocket depth, clinical attachment loss of gum tissue, and bleeding on probing of the gum tissue. Periodontal disease is a chronic inammatory disease that aects the gums and bone supporting the teeth, cardiovascular disease and diabetes may also be associated. Symptoms of periodontal disease were reduced by the antioxidant catechin of green tea. In this study the authors suggest that green tea interferes with the bodys inammatory response to periodontal bacteria, promoting periodontal health.
7.27
Flavonols in chocolate
[529] A 15 years follow up study made by Brian Buijsse and colleges indicate that cocoacontaining foods improve endothelial function and reduce blood pressure. In a cohort of elderly men Brian Buijsse and colleges found that cocoa intake is inversely associated with blood pressure and 15-year cardiovascular and all-cause mortality, conrming previous studies which have linked avanols (Flavan-3-ols) to improved cardiovascular health. The cocoa-containing foods from this study included chocolate confectionery, cocoa sandwich lling, cocoa desserts, cocoa drinks, and dietary supplements. The men who consumed the most cocoa (more than 2.3 grams per day) had lower systolic diastolic blood pressures (3.7 mmHg and 2.1 mmHg, respectively) than those who consumed the least cocoa (less than 0.36 grams per day). Several previous studies have shown that avonol consumption increased blood vessel vasodilation, and improve endothelial function. However, Cathy Ross, of the British HeartFoundation, said that here is some evidence that when eaten in small quantities, dark chocolate might have some benecial eects on blood vessels and lowering blood pressure, but as yet no study has investigated the longterms clinical eects.
7.27. FLAVONOLS IN CHOCOLATE
621
People would have to eat about 100 grams of dark chocolate a day with 500 calories and 30 % of fat to get an eective amount of avanols. According to Cathy Ross there are much betterways of improving heart health like products with increased avonol content. [530]
7.27.1
Dark chocolate reduces liver blood pressure [531]
The cocoa avonoids, which are present in dark chocolate, are strong antioxidants. De Gottardi and colleagues 2010 found dark chocolate to exert benecial eects on patients with liver cirrhosis reducing the damage to the blood vessels. The researchers compared the eect of a diet containing dark chocolate with a diet containing white chocolate. Both meals caused a highly signicant increase in portal blood ow which was lower in patients receiving the dark chocolate, compared with the white chocolate diet. A smaller post-prandial hepatic vein pressure gradient HVPG reduces the risk of blood vessel ruptures. The authors concluded that meals containing dark chocolate reduces post-prandial increase in portal pressure in liver patients, caused by a reduction of the oxidant stress of the hepatic endothelial cells. This results in vasorelaxation and consequent reduction of the blood pressure in the liver.
7.27.2
Dark chocolate reduces inammation [532]
According to Dr Romina di Giuseppe and colleagues of the Moli-sani Project dark chocolate contains high concentrations of avonoids and has antiinammatory properties reducing serum C-reactive protein (CRP). The authors report that consuming of up to 1 serving (20 g) of dark chocolate every 3 d signicantly reduced serum CRP concentrations compared with nonconsumers or higher consumers. The authors suggest that regular consumption of small doses of dark chocolate reduces inammation. They stress further that lower CRP corresponds to a shift from medium risk of cardiovascular disease to low risk. However, eating less than 20g three times a week the benecial eect tends to disappear, eating more, the eect of additional lipids an calories surpasses the benecial eect of the avonoids on blood pressure, inammation and cardiovascular protection.
7.27.3
Dark chocolate increases plasma epicatechin levels, DNA resistance to oxidative stress, however has no eect on total antioxidant activity [533]
Spadafranca and colleagues 2009 found that dark chocolate contained 860 mg polyphenols, of which 58 mg epicatechin compared with white chocolate which contained only 5 mg polyphenols, with undetectable epicatechin. When 45 g dark chocolate were added to
622
the diet of healthy people the resulting increase of plasma epicatichin levels improved the resistance to damage of mononuclear blood cells DNA, but had no eect on the plasma total antioxidant activity. The authors report that after 22 hours neither plasma epicatichin nor improved DNA resistance to oxidative stress were detected. No changes were detected with white chocolate. The authors concluded that dark chocolate may transiently improve DNA resistance to oxidative stress, because of the content of avonoids.
7.27.4
Cocoa Products may reduce Blood Pressure, but more studies should answer open questions [534]
A meta-analysis performed by Desch and colleagues 2009 conrms the blood pressurelowering capacity of avanol-rich cocoa products due to their high content of plant-derived avanols. This study adds further data to previous studies and found -4.5 mm Hg for systolic blood pressure and -2.5 mm Hg for diastolic blood pressure. The authors, however, report a signicant statistical heterogeneity across studies which rise questions about the appropriate dose and the long-term side eect. The authors stress that these questions should be answered by more studies before recommending cocoa products as treatment in hypertension.
7.27.5
The neuroprotective eects of cocoa [535]
Nehling 2012, in a review of studies, stresses that cocoa powder and chocolate contain numerous avonoids, such as epicatechin which stimulate brain perfusion. These antioxidants may help to avoid brain cells from dying, may help to create new blood vessels, nerve cells, and may improve the neuron morphology engaged in learning memory and cognition. The author points out that chocolate releases endomorphines which improves the mood during emotional stress. However, the age is unknown at which regular consume of chocolate is indicated to reduce risk Alzheimers disease or cognitive decline. Flavonoid-rich foods such as green tea, blueberry, and cocoa interact with the ERK and PI3-kinase/Akt signaling pathways, at the level of receptors or kinases, increasing the expression of neuroprotective and neuromodulatory proteins, write Williams and Spencer 2012. The number and the strenghth of neuron synapses are increased. Increased brain blood ow improves the cognition and neurogenesis in the hippocampus. The progression of Alzheimers disease AD-like pathology and related neurodegenerative disorders, are delayed by avonoids which inhibit neuronal cell death triggered by oxidative stress and neuroinammation or disrupt amyloid aggregation and eects on amyloid precursor protein processing through the inhibition of -secretase (BACE-1) and/or activation of -secretase (ADAM10). [536]
623
7.27.6
Liver cancer protective eect of cocoa phenolic extracts [537]
The protective eect of cocoa phenolic extracts on AML12 and MLP29 liver cells were studied by Arlorio and colleagues 2009. They found that phenolic-rich extracts of both unroasted and roasted cocoa inhibits drug-triggered liver cytotoxicity by inducing autophagy. This was shown by enhanced Beclin 1 expression and accumulation of monodansylcadaverine in autolysosomes. Based on their ndings, the authors suggest that cocoa be added to the list of natural chemopreventive agents, and their possible use in the hepatopathy prevention should be further eroded.
7.27.7
Chocolate high in sugar improved bioavailiability of catechin and epicatechin more than dark chocolate [538]
Neilson and colleagues 2010 compared the nutritional eect of dark chocolate with high sucrose chocolate and milk chocolate in diets of rats. Plasma levels of catechin and epicatechin were monitored measuring their metabolites O-glucuronides and O-Me-O-glucuronides. High sucrose chocolate provided the highest concentrations of these metabolites, the lowest values were found for milk chocolate and intermediate concentrations for dark chocolate. Previous studies found that chocolate-milk-containing beverages performed better than milk chocolate. The authors concluded that the physical state of the product may signicantly modulate the bioavailiability of cocoa avanols (catechin and epicatechin) and milk beverages do not reduce the benec eect of cocoa. These ndings should be analysed carefully in face of studies with favourable results for dark chocolate. Confectioneries high in sugar increase obesity risk in children, a consumer group heavily targeted by marketing strategies.
7.27.8
No explanation was found for the appeal to people of chocolate [539]
Rabinerson and Melamed assessed the immense power of appeal to people of chocolate, leading to craving and addiction especially among women. The authors writes that texture and aroma, the presence of possible psycho-pharmacologic ingredients, and hormonal changes during the menstrual cycle, may induce womens attraction to chocolate. However, no explanation for the success of chocolate was ultimately found by the authors.
7.27.9
The CES-D scale [540]
The Center for Epidemiologic Studies Depression Scale (CES-D) is one of the most common screening tests for helping an individual to determine his or her depression quotient.
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7.27.10
Most of the healthy avonoids are lost during industrial processing of cocoa
[541] Alkalization is used in the cocoa processing to make it easier to mix, digest and to correct its colour. Andres-Lacueva and colleagues 2008 found a loss of avonoids between 60 and 86 percent during the alkalinization process. The authors concluded that the alkalinization treatment of cocoa can aect the antioxidant properties and the polyphenol biovailability of natural cocoa powder products. They call for a compromise between colour and phenolic content, especially for cocoa powder products derived from alkalised cocoa powder.
7.27.11
The Malaysian cocoa beans antioxidants study 2007 [542]
Amin Ismail and colleagues 2007 investigated the antioxidant capacity and total phenolic content of cocoa beans from Malaysia, Ghana, Ivory Coast and Sulawesi. They analysed the water extract to measure the antioxidant activity based on beta-carotene bleaching assay, while the ethanolic extract was used to measure the scavenging and ferric reducing activities. The researchers reported that Ghanaian cocoa beans had the highest antioxidant and scavenging activities, followed by Ivory Coast, Malaysian and Sulawesian. Malaysian and Sulawesian beans were found in this study to have the highest ferric reducing activity, compared to the other beans. The highest phenolic content was found in Malaysian beans, followed by Sulawesian, Ghanaian and Ivory Coast. The authors concluded that antioxidant capacity and phenolic content of Malaysian cocoa beans were comparable to Ghanaian, Ivory Coast, and Sulawesian beans.
7.27.12
Ghana cocoa hybrids nutrition and polyphenols study [543]
The yields of cocoa (Theobroma cacao L.) in Ghana is decreasing. New hybrids to be introduced in the near future were developed to improve yields, resist to diseases and improve pest resistance. Gregory Tucker and colleagues 2008 studied the nutritients and polyphenols in these hybrids. The authors found that the hybrid beans had signicantly higher antioxidant capacities found in the hybrids Amazon/Trinitario hybrids, two dierent Amazon/Amazon hybrids, and Amazon/Amelonado hybrids than in the traditional beans for most of the hybrids under scrutiny.
625
The authors concluded that these hybrid varieties were either similar to, or higher in polyphenols compared with traditional beans, the introduction of these new varieties will not impact detrimentally on nutritional components of the beans. Polyphenols from cocoa bean, such as dierent catechins, as well as procyanins, anthocyanins, and avone and avonol glycosides are linked to health issues such as cardiovascular health, diabetes and skin health. These researches are therefore supported by the chocolate industry such as Nestl, Barry Callebaut and Mars eager to improve the health image of chocolate strongly associated with high saturated fats, high sugar and high calories prole. [544]
7.27.13
New study of Buitrago-Lopez and colleagues on chocolate reopens health discussion [545]
A review of studies related to the eect of consumption of chocolate by Buitrago-Lopez and colleagues 2011 found that eating chocolate reduces the risk of cardiovascular disease by 37% and stroke by 29% compared with individuals who ate the least amount of chocolate. Included in this study were cardiometabolic disorders, including cardiovascular disease (coronary heart disease and stroke), diabetes, and metabolic syndrome. No association between chocolate consumption and the risk of heart failure, and no association on the incidence of diabetes in women were found. The harmful eects of overconsumption are highlighted but the reviewed studies agreed on a potential benecial association of chocolate consumption with a lower risk of cardiometabolic disorders. The authors suggest that the benecial eects are mediated by the high content of polyphenols present in cocoa products and the increasing bioavailability of nitric oxide, which subsequently might lead to improvements in endothelial function, reductions in platelet function, and additional benecial eects on blood pressure, insulin resistance, and blood lipids. The authors stress that their review and meta-analysis supports the results of foregoing studies, demonstrating a relationship between chocolate and cocoa consumption and cardiometabolic disorders.
7.27.14
Weakness of the chocolate study of Buitrago-Lopez and colleagues
A weakness of this review is that overall chocolate consumption was reported, with investigators not dierentiating between dark, milk, or white chocolate. Chocolate in any form was included, such as chocolate bars, chocolate drinks, and chocolate snacks, such as confectionary, biscuits, desserts, and nutritional supplements. Further studies are urgently needed to clear whether an increased consumption of chocoCopyright 1998-2010 Karl H. Wilm. All rights reserved. OurFood Database of Food and Related Sciences
626
late and derived products is healthy at all. Many of these products have a high content of sugar, corn syrup, increase carbohydrate craving leading to an increase of saturated fats from the cocoa fat (palmitic and stearic acids). Instead of directing the public attention to onesided diets, healthy diets focused on increased consumption of fruits and vegetables, eating mostly whole grain food, reducing saturated fats and trans fats and reducing intake of salty and sugary foods, should be the answer to a growing overweight epidemic and increasing coronary diseases. Onesided studies which do not consider the ingredients of chocolate products are focused by Foodwatch which writes that the milk chocolate snack "Milch-Schnitte" from Ferrero contains up to 60% of unhealthy fat and sugar. Instead of this chocolate snack for your 10am break, an apple may do more for your arteries. [546]
7.27.15
More frequent consumption of chocolate lowers body mass index BMI [547]
Golomb, Koperski and White 2012 report that chocolate reduces blood pressure (BP), insulin sensitivity, cholesterol level and lowers BMI due to the antioxidant activity of phytonutrients catechins. Body mass index (BMI) is part of the metabolic syndrome (MetS) picture, and other MetS elements relate favorably to moderate chocolate consumption. In this study participants consumed chocolate a mean 2.0 times per week and exercised for at least 20 minutes 3.6 times per week. Frequency of chocolate consumption was associated with greater intake of calories and saturated fats and higher CES-D scores (Center for Epidemiological Studies Depression scale); these all related positively to BMI. Chocolate consumption frequency was not associated with greater activity, but it was associated with lower BMI, however, no advantageous association was found with the amount of chocolate consumed (medium chocolate serving of 1 oz [28 g], The authors remind that chocolate products are frequently high in sugar and fat, they are often assumed to contribute to an increased BMI, and this may still be true in some cases. The authors concluded that frequent chocolate intake is linked to lower BMI suggesting that diet composition, as well as calorie number, may inuence BMI due to benets of chocolate to other elements of metabolic syndrome (MetS).
7.27.16
Almond supplementation benets smokers
According to Ning and colleagues smoking increases the risk of several chronic diseases associated with elevated oxidative stress status. The researchers assessed almonds as a source of antioxidant nutrients and the reduction of oxidative stress biomarkers from smokers. In a clinical trial the diet of smokers were supplemented with 84 g almonds. Oxidative stress
7.28. LEGUMIN AND HOMOLOGOUS PROTEINS indicators were found decreased after the almond supplementation.
627
The authors concluded that almond intake can enhance antioxidant defences and diminish biomarkers of oxidative stress in smokers. However, after almond supplementation, the concentration of of urinary 8-hydroxy-deoxyguanosine (8-OHdG), an indicator of oxidative stress, remained signicantly greater in smokers than in nonsmokers by 98% suggesting that the best protection against smoke related diseases is to stop smoking.
7.28
7.28.1
Legumin and homologous proteins

Legumin in maize [548]
Legumin is a member of a family of storage proteins (11S globulins) found in the Leguminaceae and other higher plants. It is a histidine- and glutamine-rich polypeptide of 50-55 kDa with a peptide bond joining the C-terminus of the alfa-subunit (always asparagine) and the N-terminus of the betasubunit (almost always glycine) Yamagata and colleagues found that a legumin does exist in maize, that it is uncleaved, that it appears to be localized to small protein bodies essentially identical to those found in legumes, and that it is more abundant in wild type (W64A), than in sweet corn or opaque-2 maize. The authors discuss the phylogenetic relations between maize legumin and 7S globulin (vicilins).
7.28.2
Convicilin in Pisum and faba beans [549]
Boulter and colleagues found in Pisum and faba beans two major families of storage proteins, legumin and vicilin. Legumins are hexameric proteins comprising of 6M gama 60 000 subunits. Vicilins are a less well-dened group of proteins consisting largely ofM gama 50 000 subunits. Boulter found a third storage protein, convicilin, a vicilin-type protein with vicilin immunological determinants. According to Boulter proteins homologous to legumin have been found in Arachis, Glycine,Vigna unguiculata, Lupinus, Cicer, Lens and Lathyrus. Equivalent vicilin-type proteins occur in Phaseolus vulgaris, Glycine, Arachis and Vigna unguiculata.
7.28.3
Legumin type protein in almond [550]
According to Shridhar and colleagues the almond major storage protein, amandin,Amandin is a legumin type protein. Amandin is composed of two major types of polypeptides linked via disulde bonds. Amandin is a storage protein Amandin is not a glycoprotein.
628
Amandin-1, amandin-2, and amandin-3 are antigenically related and have similar biochemical properties. Shiddhar found that methionine is the rst essential limiting amino acid in amandin followed by lysine and threonine.
7.28.4
Western Blot Legumin protein [551]
The classical three-step procedure of Western Blot (blocking, primary antibody-binding and secondary antibody-binding) takes about 4.5 hrs . GenScript developed the One-Step Western which performs Western blot or Dot blot to detect any protein including Legumin protein and related proteins within an hour. After the proteins are transferred from a gel to the membrane, the membrane is incubated in Pretreatment Solution for 5 minutes and in WB solution with primary antibody added for 40 min, the membrane is washed three times for 5 min each and the blots are develop using either Chemiluminescent substrate or TMB.
7.28.5
Prickly pear cactus pads may control diabetes in Mexico [552]
Nopalesare made from the young stem segments of prickly pear cactus, peeled to remove the spines. Opuntia cus indica and other cactuses are cultivated in Mexico. Nopales are very rich in insoluble and especially soluble dietary bre. They are also rich in vitamins and minerals. Nopales reduces the glycemic eect of a mixed meal according to Bacardi-Gascon and colleagues 2007 who studied the eect of the cactus pear nopales on blood sugar levels when eaten with regular Mexican fodder like burritos and quesadillas. Bacardi-Gascon and colleagues concluded that Mexican patients could use nopales as a culturally based choice for the management of diabetes. [553] Caterpillars of the Cactoblastis cactorum (Berg), known as the Prickly Pear Moth feed on the pads (cladodes) of cactus and may endanger yields. [554]
7.28.6
Cocoa extract and vitamin E counteract overproduction of free radicals [555]
P.Rozan and colleagues studied the eect of a cocoa polyphenolic extract and vitamin E on free radicals produced by leucocytes assessing cognitive impairments in rats which had been exposed to heat of 40o C /2hours. They found that the extract as well as vitamin E counteract the overproduction of free radicals under these conditions.
7.28. LEGUMIN AND HOMOLOGOUS PROTEINS
629
7.28.7
Industrial processing of cocoa discards epicatechin in commercial cocoa [556]
Norman Hollenberg and colleagues studied the Kuna people in Panama, descendants of the Inca Empire, which have a diet low in protein, very low in fat, however, is rich is rich in fruit and vegetables. They drink not less than 5 cups of cocoa a day. Their cocoa is processed very gently and is rich in avanoids, also found in red wine, tea, and onions. Hollenberg found that in the island-dwelling Kuna who drink much cocoa, the renal excretion of nitric oxide metabolites, nitrate and nitrite, is extremely high when compared to city-dwelling Kuna who drink little or no cocoa. The researcher believe elevated levels of nitric oxide in the blood helps relax the blood vessels and improves blood ow. Hollenberg found that all of the commercially-available cocoas are avanoid-poor because of the industrial processing which removes epicatechin because it is bitter. According to the researchers a vasodilator action of avanoid-rich cocoa include the kidneys, the extremity, and the cerebral circulation. In healthy humans, endothelial function fades with increasing age. Endothelial dysfunction is a hallmark of diabetes mellitus. As avanoid-poor cocoa with essentially similar levels of theobromine and other constituents has not replicated the eect of avanoid-rich cocoa, Hollenber nds it very likely that the avanols are involved. According to Hollenberg epicatechin can reduce the risk of ve of the major health problems: stroke, heart failure, cancer, diabetes and age-related high blood pressure which are found to be less than 10% in the Kuna people.
7.28.8
Pseudin-2 from frog to control diabetes type 2 [557]
A nocturnal frog (Pseudis paradoxa) that dwells in the ponds and lagoons of the Amazon secretes on its skin a protein that protects the frog from infection. A copy of this peptide called pseudin-2 is suggested to boost insulin production in people with Type 2 diabetes. The joint team from the University of Ulster in Northern Ireland and United Arab Emirates University say that pseudin-2 could join a new class of medicines, called incretin mimetics, that help diabetics to control their condition when dietary changes or other medicines have failed.
7.28.9
Incretin mimetics [558]
Intestinal peptides regulate postprandial insulin secretion resulting in a higher insulin response to an oral glucose load compared with an intravenous administration of an equivCopyright 1998-2010 Karl H. Wilm. All rights reserved. OurFood Database of Food and Related Sciences
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alent amount of glucose.This is the " incretin eect" leaded by the incretin hormones, gastric inhibitory polypeptide (GIP, renamed glucose-dependent insulinotropic peptide) and glucagon like peptide-1 (GLP-1). These hormones are synthesized and secreted by cells lining the intestinal tract, and stimulate insulin secretion. A class of substances with the incretin eect are called "incretin mimetics" and include Liraglutide and Exenatide, polypeptide hormones, similar to the human GLP-1, but it is not subjected to rapid degradation by dipeptidyl peptidase.
7.28.10
Copper may reverse cardiac hypertrophy caused by high blood pressure [559] [560]
A study on mice with unhealthy enlarged hearts found that the condition reversed itself with supplementation of copper. The researchers hope this could also humans be applied in humans using 3 mg dosis/ day.The current recommended daily intake for humans, however, is only 0.9 mg/day. Although high, the dose was nevertheless below safe upper limits for copperthat were fed the equivalent of three times the amount of copper recommended for human health. According to the list of copper-rich foods of the US Agricultural Research Service (ARS) some foods rich in copper are: [561] Food mg Cu/100g Mollusk, oyster 2,50 Bakin chocolate, bitter 2,00 Mushroms 0,40 Crustaceans, crab, canned 1,18 Tomato concentrate 0,40 Barley, pearled,raw 3,70 Beans, white, canned 0,50 Beans, white, raw 0,80
7.28.11
Fat-free uid milk promotes a greater positive protein balance than does soy protein [562]
Hartman and colleagues 2007 found that Acute consumption of fat-free uid milk after resistance exercise promotes better results on training-induced lean mass accretion. They compared drinks immediately and again 1 h after exercise: Fat-free milk with a drink of fat-free soy protein that was isoenergetic, isonitrogenous, and macronutrient ratio matched to Milk and a third drink of maltodextrin that was isoenergetic with Milk and Soy.
7.29. BUTTER FLAVOUR DIACETYL IN POPCORN LINKED TO DEADLY LUNG DISEASE 631 Greater increases in the Milk group than in both the Soy and control groups were found in Type I and type II muscle ber area and DXA-measured fat- and bone-free mass. The authors concluded that chronic postexercise consumption of milk promotes greater hypertrophy during the early stages of resistance training in novice weightlifters when compared with isoenergetic soy or carbohydrate consumption. Staple foods, like fat-free milk provide better results than many costly protein hydrolysates.
7.29
Butter avour diacetyl in Popcorn linked to deadly lung disease
Hundreds of US workers acquired a deadly lung disease called Bronchiolitis obliterans linked to the inhalation of the a volatile butter-avouring ingredients diacetyl used as popcorn avouring. A transplant is the only cure. [563] The health eects of eating diacetyl in butter-avoured popcorn, or breathing the fumes from the microwave, as well from Margarine, pastries and confectioneries is unknown. Diacetyl is considered as "generally recognized as safe" but no studied were made. US popcorn processors banned the chemical from their formulations to avoid further heavy payments of lawsuits to their sick workers. Strict safety guidelines for industry were issued by the Labour Department. Two bills to ban the use of diacetyl were introduced in the California Assembly. [564] The US labour department OSHA developed a guidance concerning the safety procedures for individuals working around butter avouring. [565]
7.29.1
Study supports that diacetyl may damage lungs [566]
Daniel Morgan and colleagues 2008 evaluated the respiratory toxicity of diacetyl in mice. The authors report that depending on the route and duration of exposure, diacetyl causes signicant epithelial injury, peribronchial lymphocytic inammation, or brohistiocytic lesions in the terminal bronchioles, a condition that can lead to the lung disease bronchiolitis obliterans syndrome (BOS), a thickening and scarring of the lungs. The authors concluded that workplace exposure to diacetyl contributes to the development of BOS in humans. US popcorn Pop Weaver and ConAgra announced to eliminate diacetyl in butter avours of popcorn.
632
7.29.2
EU Regulation [567] [568] [567]
The Committee of Experts on Flavouring Substances of the Council of Europe (CEFS) declared diacetyl as safe for human consumption in 1999 but failed to include inhalation of the chemical in the assessment. The European Food Safety Agency will re-evaluate the chemical. In 2005 the EU Commission declared that diketones (for example acetyacetone) are like dialcohols and hydroxyketones in that they are in vitro and in vivo genotoxic chemical substances and banned it as nutrition additives. As diacetyl is a diketone (in fact the simplest) it may eventually be subject to this EU regulation.
7.29.3
Flavourings regulation in Europe
- Council Directive 88/388/EEC of 22 June 1988 on the approximation of the laws of the Member States relating to avourings for use in foodstus and to source materials for their production. http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=CELEX:31988L0388:EN:HTML - 88/389/EEC: Council Decision of 22 June 1988 on the establishment, by the Commission, of an inventory of the source materials and substances used in the preparation of avourings. http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=CELEX:31988D0389:EN:HTML
7.29.4 7.29.5
European avour regulation inconsitent Strawbery foods and drinks with no or little strawbery [569]
The Food Magazine pictures and describes 24 products from outstanding brands which appear to contain strawberries, but get their avour from cheap avourings, with no or little fruit in it. The magazine calls the consumer to read the small print. See the Faking the Flavour article and the pictures of the commented foods at: http://www.foodcomm.org.uk/latest_avou The Food Commission says that avourings are used to improve the appeal of low-nutrient or high fat, sugar, salt foods, replacing genuine, nutritious ingredients, having a negative impact on health. It is well documented that the whole fruit with its vitamins, antioxidants and bioavonoids make food healthy. The avourings simulate healthy ingredients which are not present or their content is kept at a minimum.
7.29. BUTTER FLAVOUR DIACETYL IN POPCORN LINKED TO DEADLY LUNG DISEASE 633
7.29.6
The Food Commission comment on EU avour regulation and their loopholes [570]
The Food Commission stresses that describing a product containing little or no real fruit at all as strawberry avour and plastering the packet with pictures of strawberries is misleading and deceptive. Unfortunately, this is legal and the practice is widespread. The European directive 1999/217 [567] and their amendments regulating avours and labelling needs therefore urgently to be revised. According to the group the repeated exposure to avourings may negatively aect consumers reaction to the taste of fresh, unprocessed foods. The Food Commission also says that avourings should be identied on labels to protect consumer with associated health problems.
7.29.7
Codex Alimentarius
Codex Alimentarius Standards: General Requirements for natural Flavourings http://www.codexalimentarius.net/download/standards/358/CXG_029e.pdf
7.29.8
United States
Title 21 - Food and Drugs. Food Additives Permitted For Direct Addition to Food for Human Consumption. Subpart F Flavoring agents and related Substances Sec. 172.515 Synthetic avoring substances and adjuvants. http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfCFR/CFRSearch.cfm Title 21 - Food and Drugs. Food Additives Permitted For Direct Addition to Food for Human Consumption. Subpart F Flavoring agents and related Substances Sec. 172.510 Natural avoring substances and natural substances used in conjunction with avors. http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=172.510
7.29.9
Camphor in avourings and other food ingredients [571]
According to an opinion of the Panel of the EFSA dietary exposure to camphor arises from the consumption of foods avoured by using either herbs (e.g. basil, coriander, marjoram, rosemary, sage), their essential oils or the chemically dened avouring substance d-camphor. Camphor is easily absorbed in the gastrointestinal tract and oxidised to 5- and 3-hydroxycamphor, followed by conjugation and excretion. Camphor is not mutagenic, and there is no evidence of reproductive and developmental toxicity after oral administration to rats and rabbits.
634
A TDI could not be derived. A chronic exposure of 15 mg/day equivalent to 250 g/kg body weight (bw)/day was calculated. The Panel considered that there would be no safety concern regarding chronic toxicity. The acute exposure estimates for children and adults are about 60-120 times and 150360 times, respectively, lower than the probable lowest lethal oral bolus dose of 50 mg/kg bw. The acute exposure estimates for children and adults are about 2-5 times and 6-14 times, respectively, lower than the dose of 2 mg/kg bw below which no acute eects have been reported in human case studies. The Panel suggests that maximum limits should be set to ensure that exposure to camphor does not exceed 2 mg/kg bw on a single day in any age group.
Bibliography
[1] Hamm, Prof. Dr. Michael: Schlank und gesund ohne Dit, Mosaik Verlaag Mnchen, 1997. [2] Greim, Heidrun:Panzenhormone und ihre Wirkung auf den Menschen ;GIT LaborFachzeitschrift 10/200, page 1164. [3] http://jn.nutrition.org/cgi/content/abstract/138/2/297? maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&andorexacttitle= and&andorexacttitleabs=and&andorexactfulltext=and&searchid= 1&FIRSTINDEX=0&sortspec=relevance&volume=138&firstpage= 297&resourcetype=HWCIT. Si, Hongwei; Liu, Dongmin: Genistein, a Soy Phytoestrogen, Upregulates the Expression of Human Endothelial Nitric Oxide Synthase and Lowers Blood Pressure in Spontaneously Hypertensive Rats. Journal of Nutrition February 2008, Volume 138, Pages 297-304. [4] Larsson SC, Orsini N, and Wolk A. Dietary potassium intake and risk of stroke: a dose-response meta-analysis of prospective studies. troke, 42(10):274650, 10 2011. http://www.ncbi.nlm.nih.gov/pubmed/21799170. [5] McCabe RD and Young DB. Potassium inhibits cultured vascular smooth muscle cell proliferation. Am J Hypertens, 7(4Pt 1):34650, 4 1994. http://www.ncbi.nlm. nih.gov/pubmed/8031550. [6] Weng LC, Yeh WT, Bai CH, Chen HJ, Chuang SY, Chang HY, Lin BF, Chen KJ, and Pan WH. Is ischemic stroke risk related to folate status or other nutrients correlated with folate intake? stroke. pages 31528, 12 2008. http://stroke.ahajournals. org/content/39/12/3152.long. [7] http://cancerres.aacrjournals.org/cgi/content/abstract/68/6/2024. Lakshman, Minalini; Xu, Li; Ananthanarayanan, Vijayalakshmi; Cooper, Joshua; Takimoto, Chris H.; Helenowski, Irene; Pelling, Jilland; Bergan, Raymond: Dietary
BIBLIOGRAPHY
635
Genistein Inhibits Metastasis of Human Prostate Cancer in Mice. Cancer Research 2008;68(6):2024-32. Doi: 10.1158/0008-5472.CAN-07-1246. [8] http://www.guideline.gov/summary/summary.aspx?doc_id=2567&nbr= 001793&string=Isoflavone. National Guideline Clearinghouse: The role of isoavones in menopausal health: consensus opinion of The North American Menopause Society; Menopause 2000 Jul-Aug;215-29. [9] http://www.ncbi.nlm.nih.gov/pubmed/17413118. Taku, Kyoko; Umegaki, Keizo; Sato, Yoko; Taki, Yuko; Endoh, Kaori and Watanabe, Shaw: Nutritional Epidemiology and Public Health: Soy isoavones lower serum total and LDL cholesterol in humans: a meta-analysis of 11 randomized controlled trials Am. J. Clinical Nutrition, Apr 2007; 85: 1148-1156. [10] http://www.ncbi.nlm.nih.gov/pubmed/20407058. Welsh JA, Sharma A, Abramson JL, Vaccarino V, Gillespie C, Vos MB: Caloric sweetener consumption and dyslipidemia among US adults. JAMA. 2010 Apr 21;303(15):1490-7. [11] http://www.food.gov.uk/news/newsarchive/2010/mar/reducesat. saturated fat and sugar in sweet foods. EFSA 26 March 2010. Reducing
[12] http://cat.inist.fr/?aModele=afficheN&cpsidt=1530586. El-Shemy, H.; Abdel-Rahim, E.; Shaban, O.; Ragab, A.; Carnovale, E.; Fujita, K.: Comparison of nutritional and antinutritional factors in soybean and fababean seeds with or without cortex. Soil Science and Plant Nutrition. 2000, vol. 46, nr 2, pp. 515-524 (1 p.1/2). [13] http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd= Retrieve&dopt=AbstractPlus&list_uids=12703283&query_hl=8&itool= pubmed_docsum. Mortensen, EL; Michaelsen KF; Sanders SA; Reinisch JM: Breath feeding and intelligence Ugeskr Laeger, 2003 Mar 24; 165(13):1361-6 PMID: 12703283 PubMed - indexed for MEDLINE. [14] http://earnest.web.med.uni-muenchen.de/index2.htm. gramming Project EARNEST. Early Nutrition Pro-
[15] Parkin DM, Boyd L, Darby SC, Mesher D, Sasieni P, Walker LC, and Peto R. The fraction of cancer attributable to lifestyle and environmental factors in the uk in 2010. Br J Cancer, 105(Suppl 2):SiS81, 2011. http://www.nature.com/bjc/journal/ v105/n2s/index.html. [16] Choosing a better diet: A food and health action plan. uk department of health. http://www.dh.gov.uk/en/Publicationsandstatistics/Publications/ PublicationsPolicyAndGuidance/DH_4105356.
636
[17] http://ije.oxfordjournals.org/cgi/content/abstract/33/1/217. Giovannucci E, Rimm EB, Liu Y, Willett WC. Height, predictors of C-peptide and cancer risk in men. Int J Epidemiol 2004;33:217-25. [18] Ajila, C.M.; Leelavathi, K.; Prasada Rao, U.J.S.: Improvement of dietary ber content and antioxidant properties in soft dough biscuits with the incorporation of mango peel powder. Journal of Cereal Science. Published online ahead of print 22 November 2007, doi: 10.1016/j.jcs.2007.10.001. [19] http://www.ncbi.nlm.nih.gov/pubmed/20016015. Du H, van der A DL, Boshuizen HC, Forouhi NG, Wareham NJ, Halkjaer J, Tjonneland A, Overvad K, Jakobsen MU, Boeing H, Buijsse B, Masala G, Palli D, Sorensen TI, Saris WH, Feskens EJ.: Dietary ber and subsequent changes in body weight and waist circumference in European men and women. Am J Clin Nutr. 2009 Dec 16. [20] http://www.respyn.uanl.mx/especiales/2007/ee-12-2007/documentos/ CNCA-2007-10.pdf. Ovando-Martinez, Maribel; Syago-Ayerdi, Sonia; AgamaAcevedo, Edith; Goni, Isabel; Bello-Prez, Luis A. : Unripe banana our as an ingredient to increase the undigestible carbohydrates of pasta. Food Chemistry. Doi:10.1016/j.foodchem.2008.07.035. [21] http://www.nal.usda.gov/fnic/foodcomp/Data/PA/PA.pdf. USDA Nutrient Data Laboratory: USDA Database for the Proanthocyanidin Content of Selected Foods - 2004. [22] http://lib.bioinfo.pl/pmid:12468593. Shanmuganayagam D, Beahm M R, Osman H E, Krueger C G, Reed J D and Folts J D,Grape seed and grape skin extracts elicit a greater antiplatelet eect when used in combination than when used individually in dogs and humans, J. Nutr. (2002), 132: pp. 3,592-3,598. [23] Peng C, Chan HY, Huang Y, Yu H, and Chen ZY. Apple polyphenols extend the mean lifespan of drosophila melanogaster. J Agric Food Chem, 59(5):2097106, 3 2011. http://pubs.acs.org/doi/abs/10.1021/jf1046267. [24] Huxley RR and Neil HA. The relation between dietary avonol intake and coronary heart disease mortality: a meta-analysis of prospective cohort studies. Eur J Clin Nutr, 57(8):9048, 8 2003. http://www.ncbi.nlm.nih.gov/pubmed/12879084. [25] Cutler GJ, Nettleton JA, Ross JA, Harnack LJ, Jacobs DR Jr, Scraord CG, Barraj LM, Mink PJ, and Robien K. Dietary avonoid intake and risk of cancer in postmenopausal women: the iowa womens health study. Int J Cancer, 123(3):66471, 8 2008. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2572165/?tool=pubmed. [26] Hanhineva K, Trrnen R, Bondia-Pons I, Pekkinen J, Kolehmainen M, Mykknen H, and Poutanen K. Impact of dietary polyphenols on carbohydrate metabolism. Int
BIBLIOGRAPHY
637
J Mol Sci, 11(4):1365402, 3 2010. http://www.ncbi.nlm.nih.gov/pmc/articles/ PMC2871121/. [27] Basu A, Rhone M, and Lyons TJ. Berries: emerging impact on cardiovascular health. Nutr Rev, 68(3):16877, 3 2010. http://www.ncbi.nlm.nih.gov/pubmed/20384847. [28] http://jn.nutrition.org/cgi/content/full/137/1/186S. Neto, Catherine C. : Supplement: International Research Conference on Food, Nutrition, and Cancer. Cranberry and Its Phytochemicals: A Review of In Vitro Anticancer Studies. The American Society for Nutrition J. Nutr. 137:186S-193S, January 2007. [29] http://www.ncbi.nlm.nih.gov/pubmed/18850154. Quesada, I.M.; Del Bas, J.M.; Blad, C.; Ardvol, A.; Blay, M.; Salvad, M.J.; Pujadas, G.; Fernndez-Larrea, J.; Arola, L.: Grape seed procyanidins inhibit the expression of metallothione in genes in human HepG2 cells. Genes Nutr. 2007 Oct;2(1):105-9. [30] http://en.wikipedia.org/wiki/Metallothionein. Wikipedia: Metallothionein. [31] http://www.touchcardiology.com/files/article_pdfs/5242.pdf. Woodward, Derrick L.; Shanmuganayagam, Dhanansa yan; Folts, John D.: Grape Extracts and Risk Factors for Cardiovascular Disease. US Cardiology 2004. [32] Chiva-Blanch G, Urpi-Sarda M, Ros E, Arranz S, Valderas-Martinez P, Casas R, Sacanella E, Llorach R, Lamuela-Raventos RM, Andres-Lacueva C, and Estruch R. Dealcoholized red wine decreases systolic and diastolic blood pressure and increases plasma nitric oxide. Circ Res, 9 2012. http://circres.ahajournals.org/content/ early/2012/09/06/CIRCRESAHA.112.275636.abstract. [33] http://www.liebertonline.com/doi/abs/10.1089/109662003772519831. Shi, John; Yu, Jianmel; Pohorly, Joseph E.; Kakuda, Yukio: Polyphenolics in Grape Seeds - Biochemistry and Functionality. Journal of Medicinal Food. December 2003, 6(4): 291-299. [34] http://www3.interscience.wiley.com/journal/121451875/abstract?CRETRY= 1&SRETRY=0. Puangpronpitag, D.; Areejitranusorn, P.; Boonsiri, P.; Suttajit, M.; Yongvanit, P.: Antioxidant Activities of Polyphenolic Compounds Isolated from Antidesma thwaitesianum Mll. Arg. Seeds and Marcs. Journal of Food Science Published Online: 13 Oct 2008. [35] http://www3.interscience.wiley.com/journal/118500575/abstract. ElAshmawy, Ibrahim M.; Saleh, Amal; Salama, Osama M.: Eects of Marjoram Volatile Oil and Grape Seed Extract on Ethanol Toxicity in Male Rats. Basic & Clinical Pharmacology & Toxicology. Volume 101 Issue 5, Pages 320 - 327 Published Online: 3 Sep 2007.
638
[36] http://www.ncbi.nlm.nih.gov/pubmed/20383223. Prakash UN, Srinivasan K: Gastrointestinal protective eect of dietary spices during ethanol-induced oxidant stress in experimental rats. Appl Physiol Nutr Metab. 2010 Apr,35(2):134-41. [37] http://www.ncbi.nlm.nih.gov/pubmed/20383709. Todorova VK, Kaufmann Y, Luo S, Suzanne Klimberg V: Tamoxifen and raloxifene suppress the proliferation of estrogen receptor-negative cells through inhibition of glutamine uptake. Cancer Chemother Pharmacol. 2010 Apr 11. [38] http://www.ncbi.nlm.nih.gov/pubmed/20378837. Hu W, Zhang C, Wu R, Sun Y, Levine A, Feng Z: Glutaminase 2, a novel p53 target gene regulating energy metabolism and antioxidant function. Proc Natl Acad Sci U S A. 2010 Apr 8. [39] http://www.ncbi.nlm.nih.gov/pubmed/17437483. Meeran, Syed M.; Katiyar, Santosh K.: Grape seed proanthocyanidins promote apoptosis in human epidermoid carcinoma A431 cells through alterations in Cdki-Cdk-cyclin cascade, and caspase-3 activation via loss of mitochondrial membrane potential. Experimental Dermatology. 2007, Vol. 16, No. 5: 405. [40] http://www3.interscience.wiley.com/journal/114211524/abstract. Frederiksen, Hanne; Mortensen, Alicja; Schroder, Malene; Frandsen, Henrik; Bysted, Anette; Knuthsen, Pia; Rasmussen, Salka E.: Eects of red grape skin and seed extract supplementation on atherosclerosis in Watanabe heritable hyperlipidemic rabbits. Molecular Nutrition & Food Research. 2007, Vol. 51, No. 5: 564. [41] http://www.liebertonline.com/doi/abs/10.1089/jmf.2006.9.187. Carpenter, Rosemary; OCallaghan, Yvonne C.; OGrady, Michael N.; Kerry, Joseph P.; OBrien, Nora M.: Modulatory Eects of Resveratrol, Citroavan-3-ol, and Plant-Derived Extracts on Oxidative Stress in U937 Cells. Journal of Medicinal Food. Jun 2006, Vol. 9, No. 2: 187-195. [42] http://www.ncbi.nlm.nih.gov/pubmed/19505523. Williams LD, Burdock GA, Edwards JA, Beck M, Bausch J.: Safety studies conducted on high-purity transresveratrol in experimental animals. Food Chem Toxicol. 2009 Sep;47(9):2170-82. Epub 2009 Jun 6.
[43] Resveratrol scientists react to das fraud scandal: "research will continue" the heartwire 13 jan 2012. http://thunderfeeds.com/reader/news/ resveratrol-scientists-react-to-das-fraud-scandal-research-will-continue-thehear [44] Red-wine researcher charged with photo-editing fraud the heartwire. 1 2012. http: //www.theheart.org/article/1339923/print.do. [45] Vang O, Ahmad N, Baile CA, Baur JA, Brown K, Csiszar A, Das DK, Delmas D, Gottfried C, Lin HY, Ma QY, Mukhopadhyay P, Nalini N, Pezzuto JM, Richard T, Shukla Y, Surh YJ, Szekeres T, Szkudelski T, Walle T, and Wu JM. What is new for
BIBLIOGRAPHY
639
an old molecule? systematic review and recommendations on the use of resveratrol. PLoS One, 6(6):e19881, 2011. http://www.plosone.org/article/info%3Adoi/10. 1371/journal.pone.0019881. [46] Resveratrol and health. Annals of the New York Academy of Sciences, 1215:1 170, 1 2011. http://onlinelibrary.wiley.com/doi/10.1111/nyas.2011.1215. issue-1/issuetoc. [47] http://www.nature.com/news/2010/100816/full/news.2010.412.html. GlaxoSmithKline strikes back over anti-ageing pills. Drugs do work as thought, says pharmaceutical giant. Ewen Callaway. Nature. 16.08.2010. Doi:10.1038/news.2010.412. [48] http://onlinelibrary.wiley.com/doi/10.1111/j.1747-0285.2009.00901.x/ full. Beher D, Wu J, Cumine S, Kim KW, Lu SC, Atangan L, Wang M: Resveratrol is not a direct activator of SIRT1 enzyme activity. Chem Biol Drug Des. 2009 Dec;74(6):619-24. [49] http://www.jbc.org/content/early/2010/08/11/jbc.M110.133892.long. Dai H, Kustigian L, Carney D, Case A, Considine T, Hubbard BP, Perni RB, Riera TV, Szczepankiewicz B, Vlasuk GP, Stein RL. SIRT1 activation by small molecules - kinetic and biophysical evidence for direct interaction of enzyme and activator. J Biol Chem. 2010 Aug 11. [50] http://en.wikipedia.org/wiki/Christoph_Westphal. Westphahl. Wikipedia: Christoph
[51] http://www.spiegel.de/wissenschaft/medizin/0,1518,722026,00.html. Vermeintliche Jungbrunnen-Pillen. Geschaeft mit dem Leben. October 2010. [52] http://en.wikipedia.org/wiki/Sirtuin. Wikipedia: Sirtuin. [53] http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2538685/?tool=pubmed. Pearson KJ, Baur JA, Lewis KN, Peshkin L, Price NL, Labinskyy N, Swindell WR, Kamara D, Minor RK, Perez E, Jamieson HA, Zhang Y, Dunn SR, Sharma K, Pleshko N, Woollett LA, Csiszar A, Ikeno Y, Le Couteur D, Elliott PJ, Becker KG, Navas P, Ingram DK, Wolf NS, Ungvari Z, Sinclair DA, de Cabo R: Resveratrol delays age-related deterioration and mimics transcriptional aspects of dietary restriction without extending life span. Cell Metab. 2008 Aug;8(2):157-68. Epub 2008 Jul 3. [54] http://www.ncbi.nlm.nih.gov/pubmed/19912989. Tang BL, Chua CE: Is systemic activation of Sirt1 benecial for ageing-associated metabolic disorders? Biochem Biophys Res Commun. 2010 Jan 1;391(1):6-10. Epub 2009 Nov 11. [55] http://www.ncbi.nlm.nih.gov/pubmed/19751409. Yu J, Auwerx J: The role of sirtuins in the control of metabolic homeostasis. Ann N Y Acad Sci. 2009 Sep;1173 Suppl 1:E10-9.
640
[56] http://www.ncbi.nlm.nih.gov/pubmed/20198340. Dransfeld CL, Alborzinia H, Wl S, Mahlknecht U: SIRT3 SNPs validation in 640 individuals, functional analyses and new insights into SIRT3 stability. Int J Oncol. 2010 Apr;36(4):955-60. [57] http://www.ncbi.nlm.nih.gov/pubmed/20925017. Zarse K, Schmeisser S, Birringer M, Falk E, Schmoll D, Ristow M: Dierential Eects of Resveratrol and SRT1720 on Lifespan of Adult Caenorhabditis elegans. Horm Metab Res. 2010. [58] http://www.ncbi.nlm.nih.gov/pubmed/20060508. Huang JY, Hirschey MD, Shimazu T, Ho L, Verdin E: Mitochondrial sirtuins. Biochim Biophys Acta. 2010 Aug;1804(8):1645-51. Epub 2010 Jan 7. [59] http://www.ncbi.nlm.nih.gov/pubmed/20872319. Aljada A, Dong L, Mousa SA: Sirtuin-targeting drugs: Mechanisms of action and potential therapeutic applications. Curr Opin Investig Drugs. 2010 Oct;11(10):1158-68. [60] Rupasinghe, H.P. Vasantha; Wang, Laixin; Huber, Gwendolyn M.; Pitts, Nancy L.: Eect of baking on dietary bre and phenolics of muns incorporated with apple skin powder Food Chemistry. Volume 107, Issue 3, 1 April 2008, Pages 1217-1224. Pages 1217-1224. doi:10.1016/j.foodchem.2007.09.057. [61] Reiser,S.: Metabolic eects of dietary pectins related to human health. Food Technol. 41(2)(1987)91-99. [62] Schmehl, K;Dongowski, GNyska,A;Pster, C.: Einuss von Pectin unterschiedlichen Veresterungsgrades auf die Darmschleimhaut von Ratten. Z.Ernhrungswiss.36(1997)34-35. [63] http://www.ajcn.org/cgi/content/abstract/83/4/760. Yunsheng Ma, Jennifer A Grith, Lisa Chasan-Taber, Barbara C Olendzki, Elizabeth Jackson, Edward J Stanek, III, Wenjun Li, Sherry L Pagoto, Andrea R Hafner and Ira S Ockene : Association between dietary ber and serum C-reactive protein Ma et al. Am J Clin Nutr.2006; 83: 760-766. [64] Mohammad Saleem, Mee-Hyang Kweon, Jung-Mi Yun, Vaqar Mustafa Adhami, Naghma Khan, Deeba N. Syed, and Hasan Mukhtar: A Novel Dietary Triterpene Lupeol Induces Fas-Mediated Apoptotic Death of Androgen-Sensitive Prostate Cancer Cells and Inhibits Tumor Growth in a Xenograft Model; Cancer Researche. 2005 65: 11203-11213. [65] S. Gupta, K. Hastak, N. Ahmad, J. S. Lewin, and H. Mukhtar: Hasan Mukhtar: Inhibitiuon of prostate carcinogenesis in TRAMP mice by oral infusion of green tea polyphenols; PNAS, August 28, 2001, 98(18): 10350-10355.
BIBLIOGRAPHY
641
[66] Min Ding, Rentian Feng, Shiow Y. Wang, Linda Bowman, Yongju Lu, Yong Qian, Vincent Castranova, Bing-Hua Jiang, and Xianglin Shi: Cyanidin-3glucoside, a Natural Product Derived from Blackberry, Exhibits Chemopreventive and Chemotherapeutic Activity J. Biol. Chem., Jun 2006; 281: 17359 - 17368 ; doi:10.1074/jbc.M600861200. [67] http://www.ncbi.nlm.nih.gov/pubmed/19339395. Willis, L.M.; Shukitt-Hale, B.; Joseph, J.A.: Modulation of cognition and behavior in aged animals: role for antioxidant- and essential fatty acid-rich plant foods. Am J Clin Nutr. 2009 May;89(5):1602S-1606S. [68] http://www.ncbi.nlm.nih.gov/pubmed/18778529. Willis, Lauren M.; ShukittHale, Barbara; Cheng, Vivian; Joseph, James A.: Dose-dependent eects of walnuts on motor and cognitive function in aged rats. British Journal of Nutrition , Volume 101, Issue 08, April 2009, pp 1140-1144 doi:10.1017/S0007114508059369. [69] http://www.ncbi.nlm.nih.gov/pubmed/19356316. Shukitt-Hale B, Cheng V, Joseph JA.: Eects of blackberries on motor and cognitive function in aged rats. Nutr Neurosci. 2009 Jun;12(3):135-40. [70] R. Mentor-Marcel, C. A. Lamartiniere, I.-E. Eltoum, N. M. Greenberg, and A. Elgavish Genistein in the Diet Reduces the Incidence of Poorly Dierentiated Prostatic Adenocarcinoma in Transgenic Mice (TRAMP);Cancer Res., September 1, 2001; 61(18): 6777 - 6782. [71] R. Mentor-Marcel, C. A. Lamartiniere, I. A. Eltoum, N. M. Greenberg, and A. Elgavish: Dietary Genistein Improves Survival and Reduces Expression of Osteopontin in the Prostate of Transgenic Mice with Prostatic Adenocarcinoma (TRAMP) J. Nutr., May 1, 2005; 135(5): 989 - 995. [72] Can-Lan Sun, Jian-Min Yuan, Woon-Puay Koh, and Mimi C. Yu: Green tea, black tea and breast cancer risk: a meta-analysis of epidemiological studies. Carcinogenesis Advance Access published online on November 25, 2005 Carcinogenesis, doi:10.1093/carcin/bgi276. [73] Q Liu, Y Wang, KA Crist, ZY Wang, YR Lou, MT Huang, AH Conney and M You: Eect of green tea on p53 mutation distribution in ultraviolet B radiation-induced mouse skin tumors. Carcinogenesis, Vol 19, Number 7, 1257-1262,. [74] Joshua D. Lambert and Chung S. Yang: Supplement: Proceedings of the Third International Scientic Symposium on Tea and Human Health; Mechanisms of Cancer Prevention by Tea Constituents; The American Society for Nutritional Sciences; J. Nutr. 133:3262S-3267S, October 2003.
642
[75] van der Burg-Koorevaar MC, Miret S, and Duchateau GS. Eect of milk and brewing method on black tea catechin bioaccessibility. J Agric Food Chem, 6 2011. http: //www.ncbi.nlm.nih.gov/pubmed/21692489. [76] http://cebp.aacrjournals.org/cgi/content/abstract/17/2/343. Sasazuki, Shizuka; Inoue, Manami; Miura, Tsutomu; Iwasaki, Motoki; Tsugane, Shoichiro: Plasma Tea Polyphenols and Gastric Cancer Risk: A Case-Control Study Nested in a Large Population-Based Prospective Study in Japan. Cancer Epidemiology, Biomarkers & Prevention. 1st February 2008, Volume 17, Number 2, Pages 343-351, doi: 10.1158/1055-9965.EPI-07-0428. [77] Swen Wolfram, Daniel Raederstor, Mareike Preller, Ying Wang, Sandra R. Teixeira, Christoph Riegger, and Peter Weber Epigallocatechin Gallate Supplementation Alleviates Diabetes in Rodents J. Nutr. 2006 136: 2512-2518. [78] http://www.jci.org/articles/view/38606. Lefebvre, Bruno; Benomar, Yacir; Gudin, Aurore; Langlois, Audrey; Hennuyer, Nathalie; Dumont, Julie; Bouchaert, Emmanuel; Dacquet, Catherine; Pnicaud, Luc; Casteilla, Louis; Pattou, Francois; Ktorza, Alain; Staels, Bart ; Lefebvre, Philippe: Proteasomal degradation of retinoid X receptor alfa reprograms transcriptional activity of PPARgama in obese mice and humans. Journal of Clinical Investigation, 2010. [79] http://care.diabetesjournals.org/cgi/content/abstract/31/8/1650. Abdul-Ghani, Muhammad A.; Abdul-Ghani, Tamam; Ali, Nibal; DeFronzo, Ralph A.: One-Hour Plasma Glucose Concentration and the Metabolic Syndrome Identify Subjects at High Risk for Future Type 2 Diabetes. Diabetes Care 2008 31: 1650-1655. [80] http://diabetes.diabetesjournals.org/content/59/7/1648. Wentworth JM, Naselli G, Brown WA, Doyle L, Phipson B, Smyth GK, Wabitsch M, OBrien PE, Harrison LC: Pro-Inammatory CD11c+CD206+ Adipose Tissue Macrophages Are Associated With Insulin Resistance in Human Obesity. Diabetes, 2010; 59 (7): 1648 Doi: 10.2337/db09-0287. [81] http://jn.nutrition.org/cgi/content/abstract/138/3/574. Villegas, Raquel; Shu, Xiao Ou; Gao, Yu-Tang; Yang, Gong; Elasy, Tom; Li, Honglan; Zheng, Wei: Vegetable but not fruit consumption reduces the risk of type 2 diabetes in Chinese women. Journal of Nutrition. Volume 138, Pages 574-580 March 2008. [82] Chung, Yun-Chin; Hsu, Cheng-Kuang; Ko, Chih-Yuan; Chan Yin-Ching: Dietary intake of xylooligosaccharides improves the intestinal microbiota, fecal moisture, and pH value in the elderly Nutrition Research (Elsevier) Volume 27, Pages 756-761. doi: 10.1016/j.nutres.2007.09.09.014. [83] Health Eects of Oligosaccharides, Food Technology, Oct. 1994, p. 61-65.
BIBLIOGRAPHY
643
[84] http://www.nature.com/nature/journal/v456/n7223/full/456702a.html. Greely H, Sahakian B, Harris J, Kessler RC, Gazzaniga M, Campbell P, Farah MJ.: Towards responsible use of cognitive-enhancing drugs by the healthy.Nature. 2008 Dec 11;456(7223):702-5. [85] http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2702330/?tool=pubmed. Thaler DS: Improving introspection to inform free will regarding the choice by healthy individuals to use or not use cognitive enhancing drugs. Harm Reduct J. 2009 Jun 16;6:10. [86] http://en.wikipedia.org/wiki/Nootropic. Wikipedia: Nootropics. [87] http://www.ncbi.nlm.nih.gov/pubmed/11601931. Goldman P: Herbal medicines today and the roots of modern pharmacology. Ann Intern Med. 2001 Oct 16;135(8 Pt 1):594-600. [88] http://www.ncbi.nlm.nih.gov/pubmed/19356316. Shukitt-Hale B, Cheng V, Joseph J (2009): Eects of blackberries on motor and cognitive function in aged rats. Nutritional Neuroscience 12 (3): 135-140. doi:10.1179/147683009X423292. [89] Grner tee und amyloidose. universittsklinikum heidelberg. http://www. klinikum.uni-heidelberg.de/Gruener-Tee-und-Amyloidose.110556.0.html. [90] Kristen AV, Lehrke S, Buss S, Mereles D, Steen H, Ehlermann P, Hardt S, Giannitsis E, Schreiner R, Haberkorn U, Schnabel PA, Linke RP, Rcken C, Wanker EE, Dengler TJ, Altland K, and Katus HA. Green tea halts progression of cardiac transthyretin amyloidosis: an observational report. Clin Res Cardiol, 101(10):80513, 10 2012. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3445797/. [91] Hunstein W. Epigallocathechin-3-gallate in al amyloidosis: a new therapeutic option? Blood, 110(6):2216, 9 2007. http://bloodjournal.hematologylibrary.org/ content/110/6/2216.long. [92] Hunstein W. Letter to the amyloid center heidelberg. 22 july 2011. http://www. hunstein-egcg.de/amyloid-center.html. [93] Catechin on comparative toxicogenomic database. http://ctdbase.org/detail. go?type=chem&acc=D002392. [94] Wu PP, Kuo SC, Huang WW, Yang JS, Lai KC, Chen HJ, Lin KL, Chiu YJ, Huang LJ, and Chung JG. (-)-epigallocatechin gallate induced apoptosis in human adrenal cancer nci-h295 cells through caspase-dependent and caspase-independent pathway. Anticancer Res, 29(4):143542, 4 2009. http://ar.iiarjournals.org/content/ 29/4/1435.long.
644
[95] Bieschke J, Russ J, Friedrich RP, Ehrnhoefer DE, Wobst H, Neugebauer K, and Wanker EE. Egcg remodels mature alpha-synuclein and amyloid-beta brils and reduces cellular toxicity. Proc Natl Acad Sci U S A, 107(17):77105, 4 2010. http: //www.ncbi.nlm.nih.gov/pmc/articles/PMC2867908/. [96] Grelle G, Otto A, Lorenz M, Frank RF, Wanker EE, and Bieschke J. Black tea theaavins inhibit formation of toxic amyloid- and -synuclein brils. Biochemistry, 50(49):1062436, 12 2011. http://www.ncbi.nlm.nih.gov/pubmed/22054421. [97] Shinichi Kuriyama, Atsushi Hozawa, Kaori Ohmori, Taichi Shimazu, Toshifumi Matsui, Satoru Ebihara, Shuichi Awata, Ryoichi Nagatomi, Hiroyuki Arai, and Ichiro Tsuji: Green tea consumption and cognitive function: a cross-sectional study from the Tsurugaya Project; The American Journal of Clinical Nutrition (Vol. 83, pp. 355-361). [98] http://ajrccm.atsjournals.org/cgi/content/abstract/177/10/1135. Burckhardt, Isabel C.; Gozal, David; Dayyat, Ehab; Cheng, Yu; Li, Richard C.; Goldbart, Aviv D.; Row, Barry W.: Green Tea Catechin Polyphenols Attenuate Behavioral and Oxidative Responses to Intermittent Hypoxia. American Journal of Respiratory and Critical Care Medicine Vol 177. pp. 1135-1141, (2008) doi: 10.1164/rccm.200701110OC. [99] http://en.wikipedia.org/wiki/Sleep_apnea. Wikipedia: Sleep apnea. [100] http://ajrccm.atsjournals.org/cgi/content/full/168/4/464. Urschitz, Michael S.; Guenther, Anke; Eggebrecht, Esther; Wol, Judith; Urschitz-Duprat, Pilar M.; Schlaud, Martin; Poets, Christian F.: Snoring, intermittent hypoxia and academic performance in primary school children. American Journal of Respiratory and Critical Care Medicine. Aug 15, 2003. FindArticles.com. 17 May. 2008. [101] Spencer P, Fry RC, and Kisby GE. Unraveling 50-year-old clues linking neurodegeneration and cancer to cycad toxins: Are micrornas common mediators? Front Genet, 192, 3 2012. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3460211/. [102] Analysis, occurrence, and toxicity of -methylaminoalanine (bmaa) a risk for the consumer? temanord 2007:561. http://www.slv.se/upload/ dokument/rapporter/kemiska/Analysis,_occurrence,_and_toxicity_of_ %C3%9F-methylaminoalanine_(BMAA).pdf. [103] Feng W and Feng Y. Micrornas in neural cell development and brain diseases. Sci China Life Sci, 54(12):110312, 12 2011. http://www.ncbi.nlm.nih.gov/pubmed/ 22227902/. [104] Tognini P and Pizzorusso T. Microrna212/132 family: molecular transducer of neuronal function and plasticity. Int J Biochem Cell Biol, 44(1):610, 1 2012. http://www.ncbi.nlm.nih.gov/pubmed/22062950.
BIBLIOGRAPHY
645
[105] Ruberti F, Barbato C, and Cogoni C. Targeting micrornas in neurons: tools and perspectives. Exp Neurol, 235(2):41926, 6 2012. http://www.ncbi.nlm.nih.gov/ pubmed/22085592. [106] Olde Loohuis NF, Kos A, Martens GJ, Van Bokhoven H, Nadif Kasri N, and Aschra A. Microrna networks direct neuronal development and plasticity. Cell Mol Life Sci, 69(1):89102, 1 2012. http://www.ncbi.nlm.nih.gov/pmc/articles/ PMC3249201/. [107] Gagliardi S, Abel K, Bianchi M, Milani P, Bernuzzi S, Corato M, Ceroni M, Cashman JR, and Cereda C. Regulation of fmo and pon detoxication systems in als human tissues. Neurotox Res, 10 2012. http://www.ncbi.nlm.nih.gov/pubmed/23073612. [108] http://www.ncbi.nlm.nih.gov/pubmed/19399866. Gallo V, Bueno-De-Mesquita HB, Vermeulen R, Andersen PM, Kyrozis A, Linseisen J, Kaaks R, Allen NE, Roddam AW, Boshuizen HC, Peeters PH, Palli D, Mattiello A, Sieri S, Tumino R, Jimnez-Martn JM, Daz MJ, Suarez LR, Trichopoulou A, Agudo A, Arriola L, Barricante-Gurrea A, Bingham S, Khaw KT, Manjer J, Lindkvist B, Overvad K, Bach FW, Tjonneland A, Olsen A, Bergmann MM, Boeing H, Clavel-Chapelon F, Lund E, Hallmans G, Middleton L, Vineis P, Riboli E.: Smoking and risk for amyotrophic lateral sclerosis: analysis of the EPIC cohort. Ann Neurol. 2009 Apr;65(4):378-85. [109] Mendoa DM, Pizzati L, Mostacada K, de S Martins SC, Higashi R, Ayres S L, Moura Neto V, Chimelli L, and Martinez AM. Neuroproteomics: an insight into als. Neurol Res, 34(10):93743, 2012. http://www.ncbi.nlm.nih.gov/pubmed/ 23146297. [110] http://www.ncbi.nlm.nih.gov/pubmed/20959505. Willis AW, Evano BA, Lian M, Galarza A, Wegrzyn A, Schootman M, Racette BA: Metal Emissions and Urban Incident Parkinson Disease: A Community Health Study of Medicare Beneciaries by Using Geographic Information Systems. Am J Epidemiol. 2010 Oct 19. [111] http://en.wikipedia.org/wiki/Alzheimer. Wikipedia: Alzheimers disease. [112] Tarawneh R, Lee JM, Ladenson JH, Morris JC, and Holtzman DM. Csf vilip-1 predicts rates of cognitive decline in early alzheimer disease. Neurology, 78(10):709 19, 3 2012. http://www.ncbi.nlm.nih.gov/pubmed/22357717. [113] Tarawneh R, DAngelo G, Macy E, Xiong C, Carter D, Cairns NJ, Fagan AM, Head D, Mintun MA, Ladenson JH, Lee JM, Morris JC, and Holtzman DM. Visinin-like protein-1: diagnostic and prognostic biomarker in alzheimer disease. 2011 Aug;7, 70(2):27485, 8 2011. http://www.ncbi.nlm.nih.gov/pubmed/21823155. [114] Morales R, Duran-Aniotz C, Castilla J, and Estrada LD ANDSoto C. De novo induction of amyloid- deposition in vivo. Molecular Psychiatry, 10 2011. http: //www.nature.com/mp/journal/vaop/ncurrent/full/mp2011120a.html.
646
[115] Krohn M, Lange C, Hofrichter J, Scheer K, Stenzel J, Steen J, Schumacher T, Brning T, Plath AS, Alfen F, Schmidt A, Winter F, Rateitschak K, Wree A, Gsponer J, Walker LC, and Pahnke J. Cerebral amyloid- proteostasis is regulated by the membrane transport protein abcc1 in mice. J Clin Invest, 121(10):392431, 10 2011. http://www.jci.org/articles/view/57867. [116] Polymenidou M and Cleveland DW. The seeds of neurodegeneration: prion-like spreading in als. Cell, 147(3):498508, 10 2011. http://www.ncbi.nlm.nih.gov/ pubmed/22036560. [117] http://www.nature.com/neuro/journal/vaop/ncurrent/pdf/nn.2213.pdf. Sanchez-Mejial, Rene O.; Newman, John W.; Tohl, Sandy; Yu1, Gui-Qiu; Zhou1, Yungui; Halabisky1, Brian; Cisse1, Moustapha; Scearce-Levie1, Kimberly; Cheng1, Irene H.; Gan1, Li; Palop1, Jorge J.; Bonventre, Joseph V.; Mucke1, Lennart: Phospholipase A2 reduction ameliorates cognitive decits in a mouse model of Alzheimers disease. Nature Neuroscience. Received 24 July; published online 19 October 2008; doi:10.1038/nn.2213. [118] http://archneur.ama-assn.org/cgi/content/full/2010.84. Gu Y, Nieves JW, Stern Y, Luchsinger JA, Scarmeas N: Food Combination and Alzheimer Disease Risk. Arch Neurol. 2010 Apr 12. [119] http://www.ncbi.nlm.nih.gov/pubmed/18836460. Schilling S, Zeitschel U, Homann T, Heiser U, Francke M, Kehlen A, Holzer M, Hutter-Paier B, Prokesch M, Windisch M, Jagla W, Schlenzig D, Lindner C, Rudolph T, Reuter G, Cynis H, Montag D, Demuth HU, Rossner S.: Glutaminyl cyclase inhibition attenuates pyroglutamate Abeta and Alzheimers disease-like pathology. Nat Med. 2008 Oct;14(10):110611. Epub 2008 Sep 28. [120] http://www.ncbi.nlm.nih.gov/pubmed/18220933. Imbimbo B.P.: Therapeutic potential of gamma-secretase inhibitors and modulators. Curr Top Med Chem. 2008;8(1):54-61. [121] Stphane Bastianetto, Zhi-Xing Yao, Vassilios Papadopoulos, Rmi Quirion Neuroprotective eects of green and black teas and their catechin gallate esters against beta-amyloid-induced toxicity; European Journal of Neuroscience Volume 23 Page 55 - January 2006 doi:10.1111/j.1460-9568.2005.04532.x Volume 23 Issue 1. [122] http://archneur.ama-assn.org/cgi/content/abstract/64/1/86. Luchsinger, Jos A.; Tang, Ming-Xin; Miller, Joshua; Green, Ralph; Mayeux, Richard: Relation of Higher Folate Intake to Lower Risk of Alzheimer Disease in the Elderly; Arch Neurol. 2007; January 2007, Volume 64:86-92. [123] http://www.ncbi.nlm.nih.gov/pubmed/19494440. Grant, B. William: Hypothesis: Does Vitamin D Reduce the Risk of Dementia? Pages 151-159 J Alzheimers Dis. 2009 May;17(1):151-9.
BIBLIOGRAPHY
647
[124] http://www.ncbi.nlm.nih.gov/pubmed/19494439. Lloret A, Bada MC, Mora NJ, Pallard FV, Alonso MD, Vina J.: Vitamin E paradox in Alzheimers disease: it does not prevent loss of cognition and may even be detrimental. J Alzheimers Dis. 2009 May;17(1):143-9. [125] http://www.ncbi.nlm.nih.gov/pubmed/20625087. Devore EE, Grodstein F, van Rooij FJ, Hofman A, Stampfer MJ, Witteman JC, Breteler MM: Dietary Antioxidants and Long-term Risk of Dementia. Arch Neurol. 2010 Jul;67(7):819-25. [126] http://en.wikipedia.org/wiki/Rotterdam_Study. Wikipedia: The Rotterdam Study. [127] Galasko DR, Peskind E, Clark CM, Quinn JF, Ringman JM, Jicha GA, Cotman C, Cottrell B, Montine TJ, Thomas RG, and Aisen P for the Alzheimers Disease Cooperative Study. Antioxidants for alzheimer disease: A randomized clinical trial with cerebrospinal uid biomarker measures. Arch Neurol, 3 2012. http://www. ncbi.nlm.nih.gov/pubmed/22431837. [128] http://www.jneurosci.org/cgi/content/abstract/27/52/14299. Qiu-Lan Ma, Bruce Teter, Oliver J. Ubeda, Takashi Morihara, Dilsher Dhoot, Michael D. Nyby, Michael L. Tuck, Sally A. Frautschy, Greg M. Cole: Omega-3 Fatty Acid Docosahexaenoic Acid Increases SorLA/LR11, a Sorting Protein with Reduced Expression in Sporadic Alzheimers Disease (AD): Relevance to AD Prevention. The Journal of Neuroscience. 26 December 2007, Volume 27, Issue 52, Pages 14299-14307, doi:10.1523/JNEUROSCI.3593-07.2007. [129] http://www.jneurosci.org/cgi/content/short/21/21/8370. Lim, Giselle P.; Chu, Teresa; Yang, Fusheng; Beech, Walter; Frautschy, Sally A.; Cole, Greg M.: The Curry Spice Curcumin Reduces Oxidative Damage and Amyloid Pathology in an Alzheimer Transgenic Mouse. J. Neurosci., Nov 2001; 21: 8370 - 8377. [130] Ringman JM, Frautschy SA, Teng E, Begum AN, Bardens J, Beigi M, Gylys K, Badmaev V, Heath D, Apostolova LG, Porter V, Vanek Z, Marshall GA, Hellemann G, Sugar C, Masterman D, Montine TJ, Cummings JL, and Cole GM. Oral curcumin for alzheimers disease: tolerability and ecacy in a 24-week randomized, double blind, placebo-controlled study. Alzheimers Res Ther, 4(5):43, 10 2012. http:// www.ncbi.nlm.nih.gov/pubmed/23107780. [131] http://journals.cambridge.org/action/displayAbstract?fromPage= online&aid=6363920. Lee, Young A.; Cho, Eun Ju; Yokozawa, Takako: Oligomeric proanthocyanidins improve memory and enhance phosphorylation of vascular endothelial growth factor receptor-2 in senescence-accelerated mouse prone/8. British Journal of Nutrition Published online ahead of print, 13 Oct 2009. Doi:10.1017/S0007114509992005.
648
[132] http://www.jneurosci.org/cgi/content/short/25/12/3032. Lim, Giselle P.; Calon, Frdric; Morihara, Takashi; Yang, Fusheng; Teter, Bruce; Ubeda, Oliver; Salem, Jr, Norman; Frautschy, Sally A.; Greg M. Cole: A Diet Enriched with the Omega-3 Fatty Acid Docosahexaenoic Acid Reduces Amyloid Burden in an Aged Alzheimer Mouse Model The Journal of Neuroscience, March 23, 2005, 25(12):30323040; doi:10.1523/JNEUROSCI.4225-04.2005. [133] http://www.ncbi.nlm.nih.gov/pubmed/18280729. Haque, Abdul M,; Hashimoto M, Katakura M, Hara Y, Shido O.: Green tea catechins prevent cognitive decits caused by A-beta-1-40 in rats. Journal of Nutritional Biochemistry. J Nutr Biochem. 2008 Sep;19(9):619-26. Epub 2008 Feb 15. [134] http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=16445947&dopt=Abstract. Park HJ, Shin DH,Chung WJ, Leem K, Yoon SH, Hong Ms, Chung JH, Bae JH, Hwang JS: Epigallocatechin gallate reduces hypoxia-induced apoptosis in human hepatoma cells; Life Science 2006 Jan 26. [135] http://www.cfsan.fda.gov/~dms/qhc-gtea.html. CFSAN/Oce of Nutritional Products, Labeling, and Dietary Supplements: Letter Responding to Health Claim Petition dated January 27, 2004: Green Tea and Reduced Risk of Cancer Health Claim (Docket number 2004Q-0083) June 30, 2005. [136] http://www.ncbi.nlm.nih.gov/pubmed/20150725. Frejnagel S, Wroblewska M: Comparative Eect of Green Tea, Chokeberry and Honeysuckle Polyphenols on Nutrients and Mineral Absorption and Digestibility in Rats. Ann Nutr Metab. 2010 Feb 11;56(3):163-169. [137] Sami Sarfaraz, Farrukh Afaq, Vaqar M. Adhami, and Hasan Mukhtar Cannabinoid Receptor as a Novel Target for the Treatment of Prostate Cancer Cancer Researche. 2005 65: 1635-1641. [138] Basavarajappa BS, Nixon RA, and Arancio O. Endocannabinoid system: emerging role from neurodevelopment to neurodegeneration. Mini Rev Med Chem, 9(4):44862, 4 2009. http://www.ncbi.nlm.nih.gov/pubmed/19356123. [139] Ligand (biochemistry). %28biochemistry%29. http://en.wikipedia.org/wiki/Ligand_
[140] Scienceblog cancer research. http://scienceblog.cancerresearchuk.org/2012/ 07/25/cannabis-cannabinoids-and-cancer-the-evidence-so-far/. [141] McKallip RJ, Nagarkatti M, and Nagarkatti PS. Delta-9-tetrahydrocannabinol enhances breast cancer growth and metastasis by suppression of the antitumor immune response. J Immunol, 174:32819, 3 2005. http://www.jimmunol.org/content/ 174/6/3281.long.
BIBLIOGRAPHY
649
[142] Bowles DW, OBryant CL, Camidge DR, and Jimeno A. The intersection between cannabis and cancer in the united states. Crit Rev Oncol Hematol, 83:110, 7 2012. http://www.croh-online.com/article/S1040-8428%2811%2900231-9/ fulltext. [143] Guindon J and Hohmann AG. The endocannabinoid system and cancer: therapeutic implication. Br J Pharmacol, 163(7):144763, 8 2011. http://www.ncbi.nlm.nih. gov/pmc/articles/PMC3165955/. [144] Scotter EL, Abood ME, and Glass M. The endocannabinoid system as a target for the treatment of neurodegenerative disease. Br J Pharmacol, 160(3):48098, 6 2010. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2931550/. [145] Basavarajappa BS, Nixon RA, and Arancio O. Endocannabinoid system: emerging role from neurodevelopment to neurodegeneration. Mini Rev Med Chem, 9(4):44862, 4 2009. http://www.ncbi.nlm.nih.gov/pubmed/19356123. [146] Carter GT, Abood ME, Aggarwal SK, and Weiss MD. Cannabis and amyotrophic lateral sclerosis: hypothetical and practical applications, and a call for clinical trials. Am J Hosp Palliat Care, 27(5):34756, 8 2010. http://www.ncbi.nlm.nih.gov/ pubmed/20439484. [147] Bilsland LG, Dick JR, Pryce G, Petrosino S, Di Marzo V, Baker D, and Greensmith L. Increasing cannabinoid levels by pharmacological and genetic manipulation delay disease progression in sod1 mice. FASEB J, 20(7):10035, 5 2006. http://www. fasebj.org/content/20/7/1003.long. [148] Medical cannabis. wikipedia. http://en.wikipedia.org/wiki/Medical_cannabis. [149] Martin LJ and Chang Q. Inhibitory synaptic regulation of motoneurons: a new target of disease mechanisms in amyotrophic lateral sclerosis. Mol Neurobiol, 45(1):3042, 2 2012. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3530198/. [150] Microglia. wikipedia. http://en.wikipedia.org/wiki/Microglia. [151] Rossi S, De Chiara V, Musella A, Cozzolino M, Bernardi G, Maccarrone M, Mercuri NB, Carr MT, and Centonze D. Abnormal sensitivity of cannabinoid cb1 receptors in the striatum of mice with experimental amyotrophic lateral sclerosis. Amyotroph Lateral Scler, 11(1-2):8390, 2010. http://www.ncbi.nlm.nih.gov/pubmed/19452308. [152] Agonist. wikipedia. http://en.wikipedia.org/wiki/Agonist. [153] Excitotoxicity. wikipedia. http://en.wikipedia.org/wiki/Excitotoxicity. [154] Carter GT and Rosen BS. Marijuana in the management of amyotrophic lateral sclerosis. Am J Hosp Palliat Care, 18(4):26470, 7-8 2001. http://www.ncbi.nlm. nih.gov/pubmed/11467101.
650
[155] de Lago E, Moreno-Martet M, Cabranes A, Ramos JA, and Fernndez-Ruiz J. Cannabinoids ameliorate disease progression in a model of multiple sclerosis in mice, acting preferentially through cb1 receptor-mediated anti-inammatory eects. Neuropharmacology, 62(7):2299308, 6 2012. http://www.ncbi.nlm.nih.gov/pubmed/ 22342378. [156] Amtmann D, Weydt P, Johnson KL, Jensen MP, and Carter GT. Survey of cannabis use in patients with amyotrophic lateral sclerosis. Am J Hosp Palliat Care, 21(2):95 104, 3-4 2004. http://www.ncbi.nlm.nih.gov/pubmed/15055508. [157] Desnuelle C, Dib M, Garrel C, and Favier A. A double-blind, placebo-controlled randomized clinical trial of alpha-tocopherol (vitamin e) in the treatment of amyotrophic lateral sclerosis. als riluzole-tocopherol study group. amyotroph lateral scler other motor neuron disord. 2(1):918, 3 2001. http://www.ncbi.nlm.nih.gov/ pubmed/11465936. [158] Graf M, Ecker D, Horowski R, Kramer B, Riederer P, Gerlach M, Hager C, Ludolph AC, Becker G, Osterhage J, Jost WH, Schrank B, Stein C, Kostopulos P, Lubik S, Wekwerth K, Dengler R, Troeger M, Wuerz A, Hoge A, Schrader C, Schimke N, Kramp K, Petri S, Zierz S, Eger K, Neudecker S, Traufeller K, Sievert M, Neundrfer B, Hecht M, and German vitamin E/ALS Study Group. High dose vitamin e therapy in amyotrophic lateral sclerosis as add-on therapy to riluzole: results of a placebocontrolled double-blind study. J Neural Transm, 112(5):64960, 5 2005. http:// www.ncbi.nlm.nih.gov/pubmed/15517433. [159] Fitzgerald KC, OReilly EJ, Fondell E, Falcone GJ, McCullough ML, Park Y, Kolonel LN, and Ascherio A. Intakes of vitamin c and carotenoids and risk of amyotrophic lateral sclerosis: Pooled results from 5 cohort studies. Ann Neurol, 11 2012. http: //www.ncbi.nlm.nih.gov/pubmed/23362045. [160] http://www.ncbi.nlm.nih.gov/pubmed/16809610. Shammas M.A.; Neri, P.: Koley H.; Batchu, R.B.; Bertheau, R.C.; Munshi, V.; Prabhala, R.; Fulciniti, M.; Tai, Y.T.; Treon, S.P.; Goyal, R. K.; Anderson, K.C.; Munshi, N. C.: Specic killing of multiple myeloma cells by (-)-epigallocatechin-3-gallate extracted from green tea: biologic activity and therapeutic implications. Blood. 6006Oct 15;108(8):2804 10. Epub 2006 Jun 29. [161] Cheng YT, Wu CH, Ho CY, and Yen GC. Catechin protects against ketoprofeninduced oxidative damage of the gastric mucosa by up-regulating nrf2 in vitro and in vivo. J Nutr Biochem, 24(2):47583, 2 2013. http://www.ncbi.nlm.nih.gov/ pubmed/22704780. [162] Hu ML. Dietary polyphenols as antioxidants and anticancer agents: more questions than answers. Chang Gung Med J, 34(5):44960, Sep-Oct 2011. http://memo.cgu. edu.tw/cgmj/3405/340501.pdf.
BIBLIOGRAPHY
651
[163] Graziani G, DArgenio G, Tuccillo C, Loguercio C, Ritieni A, Morisco F, Del Vecchio Blanco C, Fogliano V, and Romano M. Apple polyphenol extracts prevent damage to human gastric epithelial cells in vitro and to rat gastric mucosa in vivo. Gut, 54(2):193200, 2 2005. http://www.ncbi.nlm.nih.gov/pmc/articles/ PMC1774853/. [164] Alvarez-Suarez JM, Dekanski D, Risti S, Radonji NV, Petronijevi ND, Giampieri F, Astol P, Gonzlez-Params AM, Santos-Buelga C, Tulipani S, Quiles JL, Mezzetti B, and Battino M. Strawberry polyphenols attenuate ethanol-induced gastric lesions in rats by activation of antioxidant enzymes and attenuation of mda increase. PLoS One, 6(10), 2011. http://www.ncbi.nlm.nih.gov/pmc/articles/ PMC3189224/. [165] Shih PH and Yen GC. Dierential expressions of antioxidant status in aging rats: the role of transcriptional factor nrf2 and mapk signaling pathway. Biogerontology, 8(2):7180, 4 2007. http://www.ncbi.nlm.nih.gov/pubmed/16850181. [166] http://www.ncbi.nlm.nih.gov/pubmed/20592221. Dworak M, McCarley RW, Kim T, Kalinchuk AV, Basheer R: Sleep and brain energy levels: ATP changes during sleep. J Neurosci. 2010 Jun 30;30(26):9007-16. [167] http://www.ncbi.nlm.nih.gov/pubmed/19146833. Elmenhorst D, Basheer R, McCarley RW, Bauer A: Sleep deprivation increases A(1) adenosine receptor density in the rat brain. Brain Res. 2009 Mar 3;1258:53-8. [168] http://www.ncbi.nlm.nih.gov/pubmed/19492440. Longordo F, Kopp C, Lthi A: Consequences of sleep deprivation on neurotransmitter receptor expression and function. Eur J Neurosci. 2009 May;29(9):1810-9. [169] http://www.ncbi.nlm.nih.gov/pubmed/20602750. van Mark A, Weiler SW, Schroder M, Otto A, Jauch-Chara K, Groneberg DA, Spallek M, Kessel R, Kalsdorf B: The impact of shift work induced chronic circadian disruption on IL-6 and TNF-alpha immune responses. J Occup Med Toxicol. 2010 Jul 5;5(1):18. [170] http://clincancerres.aacrjournals.org/cgi/content/full/11/16/6040. Nakazato, Tomonori; Ito, Keisuke; Ikeda, Yasuo and Kizaki, Masahiro: Green Tea Component, Catechin, Induces Apoptosis of Human Malignant B Cells via Production of Reactive Oxygen Species. Clinical Cancer Research 2005 Aug 15;11(16):6040-9. [171] http://cebp.aacrjournals.org/cgi/content/abstract/16/6/1219. Yang, Gong; Shu, Xiao-Ou; Li, Honglan; Chow, Wong-Ho; Ji, Bu-Tian; Zhang, Xianglan; Gao, Yu-Tng and Zheng, Wei: Prospective Cohort Study of Green Tea Consumption and Colorectal Cancer Risk in Women. Cancer Epidemiology Biomarkers and Prevention. Volume 16, Pages 1219-1223, doi: 10.1158/1055-9965.EPI-07-0097.
652
[172] http://archneur.ama-assn.org/cgi/content/full/63.12.noc60109 http://www.eurekalert.org/pub_releases/2006-10/jaaj-mda100506.php. Nikolaos Scarmeas, Yaakow Stern, Richard Mayeux, Jos A. Luchsinger: Mediterranean diet, Alzheimer Disease and Vascular Mediation. Arch Neurol. 2006;63:(doi:10.1001/archneur.63.12.noc60109). [173] http://www.j-alz.com/issues/10/vol10-1.html. Laura Zhang, Milan Fiala, John Cashman, James Sayre, Araceli Espinosa, Michelle Mahanian, Justin Zaghi, Vladimir Badmaev, Michael C. Graves, George Bernard, Mark Rosenthal: Curcuminoids enhance amyloid-Beta uptake by macrophages of Alzheimers disease patients. Journal of Alzheimers Disease, Volume 10, Number 1, September 2006, pages 1-7. [174] http://archneur.ama-assn.org/cgi/content/abstract/63/10/1402. Yvonne Freund-Levi; Maria Eriksdotter-Jnhagen; Tommy Cederholm; Hans Basun; Gerd Faxn-Irving; Anita Garlind; Inger Vedin; Bengt Vessby; Lars-Olof Wahlund; Jan Palmblad: Omega-3 Fatty Acid Treatment in 174 Patients With Mild to Moderate Alzheimer Disease: OmegAD Study: A Randomized Double-blind Trial Arch Neurol. 2006;63:1402-1408. [175] http://jama.ama-assn.org/cgi/content/abstract/298/7/754. Jerey A. Meyerhardt; Donna Niedzwiecki; Donna Hollis; Leonard B. Saltz; Frank B. Hu; Robert J. Mayer; Heidi Nelson; Renaud Whittom; Alexander Hantel; James Thomas; Charles S. Fuchs: Association of Dietary Patterns With Cancer Recurrence and Survival in Patients With Stage III Colon Cancer JAMA. 2007;298:754-764. [176] http://aje.oxfordjournals.org/cgi/content/abstract/164/11/1085. E Kesse, F Clavel-Chapelon, and MC Boutron-Ruault : Dietary Patterns and Risk of Colorectal Tumors: A Cohort of French Women of the National Education System (E3N). Am. J. Epidemiol. 2006 164: 1085-1093; doi:10.1093/aje/kwj324. [177] http://pub.ucsf.edu/newsservices/releases/200608105/. University of San Francisco: Childhood obesity caused by toxic environment of Western diets, study says. News:11 August 2006. [178] http://jn.nutrition.org/cgi/content/abstract/139/11/2072. Erdelyi, Ildiko; Levenkova, Natasha; Lin, Elaine Y.; Pinto, John T.; Lipkin, Martin; Quimby, Fred W.; Holt Peter R.: Western-Style Diets Induce Oxidative Stress and Dysregulate Immune Responses in the Colon in a Mouse Model of Sporadic Colon Cancer. Journal of Nutrition, 2009; 139 (11): 2072 DOI: 10.3945/jn.108.104125. [179] http://www.ajcn.org/cgi/content/abstract/86/2/334. Rudolph, Tanja K.; Ruempler, Kaike; Schwedhelm, Edzard; Tan-Andresen, Jing; Riederer, Ulrich; Bger, Rainer H.; Maas, Renke: Acute eects of various fast-food meals on vascular function and cardiovascular disease risk markers: the Hamburg Burger Trial. Am J Clin Nutr 2007 86: 334-340.
BIBLIOGRAPHY
653
[180] zur Hausen H. Red meat consumption and cancer: reasons to suspect involvement of bovine infectious factors in colorectal cancer. Int J Cancer, 130(11):247583, 6 2012. http://www.ncbi.nlm.nih.gov/pubmed/22212999. [181] http://www.ncbi.nlm.nih.gov/pubmed/18948553. Seymour, E. M.; Singer, Andrew A. M.; Bennink, Maurice R.; Parikh, Rushi V.; Kirakosyan, Ara;Kaufman, Peter B.; Bolling, Steven F.: Chronic Intake of a Phytochemical-Enriched Diet Reduces Cardiac Fibrosis and Diastolic Dysfunction Caused by Prolonged Salt-Sensitive Hypertension. The Journals of Gerontology Series A: Biological Sciences and Medical Sciences 63:1034-1042 (2008). [182] Larsson SC. Dietary fats and other nutrients on stroke. Curr Opin Lipidol, 11 2012. http://www.ncbi.nlm.nih.gov/pubmed/23123763. [183] Larsson SC, Virtamo J, and Wolk A. Dietary fats and dietary cholesterol and risk of stroke in women. Atherosclerosis, 221(1):2826, 3 2012. http://www.ncbi.nlm. nih.gov/pubmed/22265275. [184] Williams CM and Burdge G. Long-chain n-3 pufa: plant v. marine sources. Proc Nutr Soc, 65(1):4250, 2 2006. http://www.ncbi.nlm.nih.gov/pubmed/16441943. [185] Mozaarian D and Wu JH. (n-3) fatty acids and cardiovascular health: are eects of epa and dha shared or complementary? J Nutr, 142(3):614S625S, 3 2012. http: //www.ncbi.nlm.nih.gov/pubmed/22279134. [186] Larsson SC, Virtamo J, and Wolk A. Dietary protein intake and risk of stroke in women. Atherosclerosis, 224(1):24751, 9 2012. http://www.ncbi.nlm.nih.gov/ pubmed/22854187. [187] Kaluza J, Wolk A, and Larsson SC. Red meat consumption and risk of stroke: a meta-analysis of prospective studies. Stroke, 43(10):255660, 10 2012. http://www. ncbi.nlm.nih.gov/pubmed/22851546. [188] Larsson SC, Virtamo J, and Wolk A. Dairy consumption and risk of stroke in swedish women and men. Stroke, 43(7):177580, 7 2012. http://www.ncbi.nlm.nih.gov/ pubmed/22517598. [189] http://www.annals.org/cgi/content/abstract/149/2/91. Pletcher, Mark J.; Bibbins-Domingo, Kirsten; Lewis, Cora E.; Wei, Gina S.; Sidney, Steve J.; Carr, Jerey; Vittingho, Eric; McCulloch, Charles E.; Hulley, Stephen B.: Prehypertension during young adulthood and coronary calcium later in life. Ann Intern Med. 2008;149:91-99. [190] Larsson SC, Virtamo J, and Wolk A. Red meat consumption and risk of stroke in swedish men. Am J Clin Nutr., 94:417421, 2011. http://www.ajcn.org/content/ 94/2/417.abstract.
654
[191] Goldstein LB, Bushnell CD, Adams RJ, Appel LJ, Braun LT, Chaturvedi S, Creager MA, Culebras A, Eckel RH, Hart RG, Hinchey JA, Howard VJ, Jauch EC, Levine SR, Meschia JF, Moore WS, Nixon JV, Pearson TA, American Heart Association Stroke Counci, Council on Cardiovascular Nursing, Council on Epidemiology, Prevention, Council for High Blood Pressure Research, Council on Peripheral Vascular Disease ANDand Interdisciplinary Council on Quality of Care, and Outcomes Research. Guidelines for the primary prevention of stroke: a guideline for healthcare professionals from the american heart association/american stroke association. Stroke, 42(2):51784, 2 2011. http://stroke.ahajournals.org/content/42/2/517.long. [192] Goh FXW, Itohiya Y, Shimojo R, Sato T, Hasegawa K, and Leong LP. Using naturally brewed soy sauce to reduce salt in selected foods. journal of sensory studies. 26(6):429435, 12 2011. http://onlinelibrary.wiley.com/doi/10.1111/j. 1745-459X.2011.00357.x/abstract. [193] Kremer S, Mojet J, and Shimojo R. Salt reduction in foods using naturally brewed soy sauce. J Food Sci, 74(6):S25562, 8 2009. http://www.ncbi.nlm.nih.gov/ pubmed/19723231. [194] Lioe HN, Selamat J, and Yasuda M. Soy sauce and its umami taste: a link from the past to current situation. J Food Sci, 75(3):R716, 4 2010. http://www.ncbi.nlm. nih.gov/pubmed/20492309. [195] Tieman D, Bliss P, McIntyre LM, Blandon-Ubeda A, Bies D, Odabasi AZ, Rodrguez GR, van der Knaap E, Taylor MG, Goulet C, Mageroy MH, Snyder DJ, Colquhoun T, Moskowitz H, Clark DG, Sims C, Bartoshuk L, and Klee HJ. The chemical interactions underlying tomato avor preferences. Curr Biol, 5 2012. http://www. ncbi.nlm.nih.gov/pubmed/22633806. [196] Elizabeth T Jacobs, Elaine Lanza, David S Alberts, Chiu-Hsieh Hsu, Ruiyun Jiana, Arthur Schatzkin, Patricia A Thompson and Mara Elena Martnez: Fiber, sex, and colorectal adenoma: results of a pooled analysis; American Journal of Clinical Nutrition (Vol. 83, pp. 343-349). [197] http://jama.ama-assn.org/cgi/content/abstract/295/6/643. Shirley A. A. Beresford, PhD and col.: Low-Fat Dietary Pattern and Risk of Colorectal Cancer; The Womens Health Initiative Randomized Controlled Dietary Modication Trial; The Journal of the American Medical Assotiation Vol. 295 No. 6, February 8, 2006. [198] http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool= pubmed&pubmedid=14684595. R P Arasaradnam, S A Riley and B M Corfe: Diet and colorectal cancer: bre back on the menu? Gut 2004;53:155-156. [199] , Journal Nutrition (Vol. 22, pp. 295-302).
BIBLIOGRAPHY
655
[200] http://en.wikipedia.org/wiki/Concord_grape. Wikipedia, the free enzychlopedia: Concorde grape. [201] M. Falchi, A.Bertelli, R. Lo Scalzo, M. Morassut, R. Morelli, Samarjit Das, Jianhua Cui, and Dipak K. Das.Comparison of Cardioprotective Abilities between the Flesh and Skin of Grapes.: J. Agric. Food Chem.; 2006; ASAP Web Release Date: 04-Aug2006; (Article) DOI: 10.1021/jf061048k. [202] http://www.ajcn.org/cgi/content/abstract/84/1/252. Patricia Castilla, Roco Echarri, Alberto Dvalos, Francisca Cerrato, Henar Ortega, Jos Luis Teruel, Milagros Fernndez Lucas, Diego Gmez-Coronado, Joaqun Ortuno and Miguel A Lasuncin: Concentrated red grape juice exerts antioxidant, hypolipidemic, and antiinammatory eects in both hemodialysis patients and healthy subjects; American Journal of Clinical Nutrition, Vol. 84, No. 1, 252-262, July 2006. [203] http://www.fasebj.org/cgi/content/abstract/22/1/41. Gorelik, S., Ligumsky, M., Kohen, R., Kanner, J. A novel function of red wine polyphenols in humans: prevention of absorption of cytotoxic lipid peroxidation products. The FASEB Journal. 2008, Volume 22, Pages 41-46; doi: 10.1096/fj.07-9041com. [204] http://en.wikipedia.org/wiki/Recommended_Dietary_Allowance. The free encyclopaedia: Recommended Dietary Allowance. Wikipedia,
[205] http://ific.org/publications/other/driupdateom.cfm?renderforprint=1. International Food Information Council: Dietary Reference Intakes: an update. August 2002. [206] http://www.ilsi.org/Publications/NutritionReviews/. Nutrition Reviews Series Examines Critical Issues in the Application of Dietary Reference Intakes. [207] George H. Beaton: When is an Individual an Individual Versus a Member of a Group? An Issue in the Application of the Dietary Reference Intakes. International Life Sciences Institute; Nutrition Reviews. 2006;64(5):211-225. DOI: 10.1301/nr.2006.may.211-225. [208] Suzanne P. Murphy, Susan I. Barr, and Allison A. Yates: The Recommended Dietary Allowance (RDA) Should Not Be Abandoned: An Individual Is Both an Individual and a Member of a Group. Nutrition Reviews. 2006;64(7):313-318. [209] http://www.fda.gov/fdac/special/foodlabel/dvs.html. Paula Kurtzweil: Daily Values Encourage Healthy Diet. US Food and Drug Administration. [210] Who 2011: Strategies to monitor and evaluate population sodium consumption and sources of sodium in the diet: report of a joint technical meeting convened by who and the government of canada. world health organization. http://whqlibdoc.who. int/publications/2011/9789241501699_eng.pdf.
656
[211] Opinion of the scientic panel on dietetic products, nutrition and allergies on a request from the commission related to the tolerable upper intake level of sodium. efsa 2005. 2005. http://www.efsa.europa.eu/en/scdocs/doc/s209.pdf. [212] Global strategy on diet, physical activity and health. population sodium reduction strategies. http://www.who.int/dietphysicalactivity/reducingsaltintake_ EN.pdf. [213] Scientic advisory committee on nutrition: Salt and health. http://www.sacn.gov. uk/pdfs/sacn_03_14.pdf. [214] EU Food Law,January 1997 pg 27. [215] Bayrhuber,Horst; Kull,Ulrich; Linder Biologie, Lehrbuch fr die Oberstufe;20.Ausgabe,1989 ;J.B.Metzlersche Verlagsbuchhandlung,Stuttgart,S.166. [216] Wolfram,G.: Bedarfsermittlung fr wirksame Stoe, Ableitung von Referenzwerten/Verzehrsempfehlungen; Funktionelle Lebensmittel- Lebensmittel der Zukunft, Erwartungen, Wirkungen, Risiken; Band 25 der Schriftenreihe Lebensmittechemie, Lebensmittelqualitt. (Hrsg) Lebensmittelchemische Gesellschaft-Fachgruppe in der GDCH.Behrs Verlag, page 64 and 66. [217] http://www.ajcn.org/cgi/content/full/87/3/558. Chardigny, Jean-Michel; Destaillats, Frdric; Malpuech-Brugere, Corinne; Moulin, Julie; Bauman, Dale E; Lock, Adam L.; Barbano, Dave M.: Mensink, Ronald P.; Bezelgues, Jean-Baptiste; Chaumont, Patrice; Combe, Nicole; Cristiani, Isabelle; Jore, Florent; German, J. Bruce; Dionisi, Fabiola; Boirie, Yves; Sbdio, Jean-Louis: Do Trans Fatty Acid from Industrially-Produced Sources and from Natural Sources Have the Same eect on Cardiovascular Diseases Risk Factors in Healthy Subjects? Results of the trans Fatty Acids Collaboration (TRANSFACT) Study. American Journal of Clinical Nutrition Volume 87, Number 3, Mach 2008, Pages 558-566. [218] http://www.euromilk.org/upload/docs/EDA/PR%20TFA%20Policy% 20Conference.pdf. EDA: Major outcome of the European Dairy Associations TFA Policy Conference: No scientic evidence on negative health eects from dairy TFA. [219] http://www.ajcn.org/cgi/content/full/87/3/515. Walter Willett and Dariush Mozaarian: Ruminant or industrial sources of trans fatty acids: public health issue or food label skirmish? American Journal of Clinical Nutrition March 2008, Volume 87, Number 3, Pages 515-516. [220] Monge-Rojas R, Coln-Ramos U, Jacoby E, and Mozaarian D. Voluntary reduction of trans-fatty acids in latin america and the caribbean: current situation. Rev Panam Salud Publica, 29(2):1269, 2 2011. http://www.scielosp.org/scielo.php? script=sci_arttext&pid=S1020-49892011000200008&lng=en&nrm=iso&tlng=en.
BIBLIOGRAPHY
657
[221] http://www.ncbi.nlm.nih.gov/pubmed/21036587. Chen CL, Tetri LH, Neuschwander-Tetri BA, Huang SS, Huang JS: A mechanism by which dietary trans fats cause atherosclerosis. J Nutr Biochem. 2010 Oct 30. [222] Mozaarian D and Willett WC. Trans fatty acids and cardiovascular risk: a unique cardiometabolic imprint? Curr Atheroscler Rep, 9(6):48693, 12 2007. http://www. ncbi.nlm.nih.gov/pubmed/18377789. [223] Bhardwaj S, Passi SJ, and Misra A. Overview of trans fatty acids: biochemistry and health eects. Diabetes Metab Syndr, 5(3):1614, Jul-Sep 2011. http://www.ncbi. nlm.nih.gov/pubmed/22813572. [224] Dixit S and Das M. Fatty acid composition including trans-fatty acids in edible oils and fats: Probable intake in indian population. J Food Sci, 9 2012. http: //www.ncbi.nlm.nih.gov/pubmed/22950538. [225] Interim summary of conclusions and dietary recommendations on total fat & fatty acids from the joint fao/who expert consultation on fats and fatty acids in human nutrition, 10-14 november, 2008, who, geneva. http://www.who.int/nutrition/ topics/FFA_summary_rec_conclusion.pdf. [226] Smith,Trevor: Health Perspectives, Questions on fat vs. calories;Todays Chemist at Work/August 1998 pg 53. [227] http://www.ncbi.nlm.nih.gov/pubmed/20016010. Takachi R, Inoue M, Shimazu T, Sasazuki S, Ishihara J, Sawada N, Yamaji T, Iwasaki M, Iso H, Tsubono Y, Tsugane S.: Consumption of sodium and salted foods in relation to cancer and cardiovascular disease: the Japan Public Health Center-based Prospective Study. Am J Clin Nutr. 2009 Dec 16. [228] http://www.who.int/entity/tobacco/mpower/mpower_report_full_2008.pdf. WHO Report on the Global Tobacco Epidemic, 2008 - The MPOWER package. [229] Malaysia a healthy egg; World Food Law, november 1998 pg.17. [230] http://www.aap.org/advocacy/releases/july08lipidscreening.htm. New AAP policy on lipid screening and heart health in children. Release: July 7, 2008. [231] http://www.foodnavigator.com/news/ng.asp?n=86498&c=yvW%2FFaETORSd% 2ByeOz8%2BMIw%3D%3D. Foodnavigator: Diet better than statins in kids cholesterol control. 15.07.2008. [232] Savica V, Bellinghieri G, and Kopple JD. The eect of nutrition on blood pressure. Annu Rev Nutr, 30:365401, 8 2010. http://www.ncbi.nlm.nih.gov/pubmed/ 20645853. [233] http://en.wikipedia.org/wiki/Statin. Wikipedia: Statin, Controversy.
658
[234] http://www.ncbi.nlm.nih.gov/pubmed/20691321. Ferenczi EA, Asaria P, Hughes AD, Chaturvedi N, Francis DP: Can a Statin Neutralize the Cardiovascular Risk of Unhealthy Dietary Choices? Am J Cardiol. 2010 Aug 15;106(4):587-592. [235] http://www.sciencedaily.com/releases/2009/08/090820123923.htm. Little Known Type Of Cholesterol - Oxycholesterol- May Pose The Greatest Heart Disease Risk. ScienceDaily (Aug. 23, 2009). [236] http://www.ncbi.nlm.nih.gov/pubmed/19060413. Bang HJ, Arakawa C, Takada M, Sato M, Imaizumi K: A comparison of the potential unfavorable eects of oxycholesterol and oxyphytosterol in mice: dierent eects, on cerebral 24Shydroxychoelsterol and serum triacylglycerols levels. Biosci Biotechnol Biochem. 2008 Dec;72(12):3128-33. Epub 2008 Dec 7. [237] http://www.ncbi.nlm.nih.gov/pubmed/18022398. Hovenkamp E, Demonty I, Plat J, Ltjohann D, Mensink RP, Trautwein EA.: Biological eects of oxidized phytosterols: a review of the currentknowledge. Prog Lipid Res. 2008 Jan;47(1):37-49. Epub 2007 Nov 1. [238] http://www.ncbi.nlm.nih.gov/pubmed/9920502. Brown AJ, Jessup W.: Oxysterols and atherosclerosis. Atherosclerosis. 1999 Jan;142(1):1-28. [239] http://www.foodnavigator.com/news/ng.asp?n=80197&m=1fneo01&c= nfuzqfgkdkribxo. FoodNavigator: The red tape merry-go-round. By Stephen Daniells, the Science Editor for NutraIngredients.com and FoodNavigator.com. 01.10.2007. [240] http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=CELEX: 31997R0258:EN:HTML. Regulation (EC) No 258/97 of the European Parliament and of the Council of 27 January 1997 concerning novel foods and novel food ingredients. [241] http://www.cargill.com/news/news_releases/070312_regenasure.htm. Cargill: Cargill announces GRAS status for REGENASURE Glucosamine. 12.03.2007. [242] http://en.wikipedia.org/wiki/Thalidomide. Wikipedia: Thalidomide. [243] http://www.pnas.org/cgi/content/abstract/102/13/4896. F. de Nigris, S. Williams-Ignarro, L. O. Lerman, E. Crimi, C. Botti, G. Mansueto, F. P. DArmiento, G. De Rosa, V. Sica, L. J. Ignarro, and C. Napoli Benecial eects of pomegranate juice on oxidation-sensitive genes and endothelial nitric oxide synthase activity at sites of perturbed shear stress. PNAS, March 29, 2005; 102(13): 4896 - 4901. [244] http://www.heartuk.org.uk/new/pages/about/product.html. Cholesterol Charity: Product approval.
Heart UK, the
BIBLIOGRAPHY
659
[245] http://www.ajcn.org/cgi/content/abstract/84/3/513. T. A. Sanders, F. Lewis, S. Slaughter, B. A Grin, M. Grin, I. Davies, D J. Millward, J. A Cooper, and G. J Miller Eect of varying the ratio of n-6 to n-3 fatty acids by increasing the dietary intake of alfa-linolenic acid, eicosapentaenoic and docosahexaenoic acid, or both on brinogen and clotting factors VII and XII in persons aged 45-70 y: the OPTILIP Study. Am. J. Clinical Nutrition, September 1, 2006; 84(3): 513 - 522. [246] Kalea, A. Z., Lamari, F. N., Theocharis, A. D., Cordopatis, P., Schuschke, D. A., Karamanos, N. K., Klimis-Zacas, D. J.: Wild blueberry (Vaccinium angustifolium) consumption aects the composition and structure of glycosaminoglycans in SpragueDawley rat aorta; The Journal of Nutritional Biochemistry, Volume 17, Issue 2, February 2006, Pages 109 - 116 doi:10.1016/j.jnutbio.2005.05.015. [247] http://en.wikipedia.org/wiki/Mangostin. Wikipedia The Free Enzyclopedia: Mangostin. [248] http://www.ncbi.nlm.nih.gov/pubmed/16009519. Chomnawang MT, Surassmo S, Nukoolkarn VS, Gritsanapan W.: Antimicrobial eects of Thai medicinal plants against acne-inducing bacteria; J Ethnopharmacol. 2005 Oct 3;101(1-3):330-3. [249] Antibacterial activity of xanthones from guttiferaeous plants against methicillinresistant Staphylococcus aureus. J Pharm Pharmacol. 1996 Aug;48(8):861-5. Iinuma M, Tosa H, Tanaka T, Asai F, Kobayashi Y, Shimano R, Miyauchi K. Department of Pharmacognosy, Gifu Pharmaceutical University, Japan. [250] Furukawa K, Chairungsrilerd N, Ohta T, Nozoe S, Ohizumi Y: Novel types of receptor antagonists from the medicinal plant Garcinia mangostana; Nippon Yakurigaku Zasshi. 1997 Oct;110 Suppl 1:153P-158P. PMID: 9503424 (PubMed- MEDLINE). [251] Huang YL, Chen CC, ChenYJ, Huang RL,Shieh BJ: Three xanthones and a benzophenone from Garcinia mangostana. J Nat Prod. 2001 Jul;64(7):903-6. PMID: 11473420 (PubMed - MEDLINE). [252] Suksamram S, Suwannapoch N, Ratananukul P, Aroonlerk N, Suksamram A: Xanthones from the green fruit hulls of Garcinia mangostana. J Nat Prod. 2002 May;65(5):761-3. PMID: 12027762 (PubMed - MEDLINE). [253] Williams P, Ongskul M, Proudfoot J, Croft K, Beilin L: Mangostin inhibits the oxidative modication of human low density lipoprotein. Free Radic Res. 1995 Aug;23(2):175-84. PMID: 7581813 (PubMed - MEDLINE). [254] Moongkarndi P, Kosem N, Kaslugka S, Luanratana O, Pongpan N, Neungton N: Antiproliferation, antioxidation and induction of apoptosis by Garcinia mangostana (mangosteen) on SKBR3 human breast cancer cell line. J Ethnopharmacol. 2004 Jan;90(1):161-6. PMID: 14698525 (PubMed -MEDLINE).
660
[255] Shekelle RB, Shryock AM, Paul O, et al. Diet, serum cholesterol, and death from coronary heart disease. The Western Electric Study. N Engl J Med 1981;304:65-70 p://content.nejm.org/cgi/content/abstract/304/2/65. [256] http://aje.oxfordjournals.org/cgi/content/abstract/119/5/733. Kromhout D, Coulander CDL. Diet, prevalence and 10-year mortality from coronary heart disease in 871 middle-aged men. The Zutphen study. Am J Epidemiol 1984;119:733-41. [257] http://aje.oxfordjournals.org/cgi/content/abstract/119/5/667. McGee DL, Reed DM, Yano KY, Kagan A, Tillotson J. Ten-year incidence of coronary heart disease in the Honolulu Heart Program. Relationship to nutrient intake. Am J Epidemiol 1984;119:667-76. [258] http://www.ajcn.org/cgi/content/abstract/33/8/1818. Garcia-Palmieri MR, Sorlie P, Tillotson J, Costas R Jr, Cordero E, Rodriguez M. Relationship of dietary intake to subsequent coronary heart disease incidence: The Puerto Rico Heart Health Program. Am J Clin Nutr 1980;33:1818-27. [259] http://content.nejm.org/cgi/content/abstract/312/13/811. Kushi LH, Lew RA, Stare FJ, et al. Diet and 20-year mortality from coronary heart disease. The Ireland-Boston Diet-Heart Study. N Engl J Med 1985;312:811-8. [260] http://aje.oxfordjournals.org/cgi/content/abstract/124/6/903. Keys A, Menotti A, Karvonen MJ, et al. The diet and 15-year death rate in the Seven Countries Study. Am J Epidemiol 1986;124:903-15. [261] Stephen J. Nicholls, Pia Lundman, Jason A. Harmer, Belinda Cutri, Kaye A. Grifths, Kerry-Anne Rye, Philip J. Barter, David S. Celermajer: Consumption of Saturated Fat Impairs the Anti-Inammatory Properties of High-Density Lipoproteins and Endothelial Function; Journal of the American College of Cardiology; article in press doi:10.1016/jacc.2006.04.080. [262] Shin D, Choi SH, Go G, Park JH, Narciso-Gaytn C, Morgan CA, Smith SB, SnchezPlata MX, and Ruiz-Feria CA. Eects of dietary combination of n-3 and n-9 fatty acids on the deposition of linoleic and arachidonic acid in broiler chicken meats. Poult Sci, 91(4):100917, 4 2012. http://www.ncbi.nlm.nih.gov/pubmed/22399741. [263] Nakamura MT and Nara TY. Structure, function, and dietary regulation of delta6, delta5, and delta9 desaturases. Annu Rev Nutr, 24:34576, 2004. http://www.ncbi. nlm.nih.gov/pubmed/15189125. [264] Bourre JM. Eect of increasing the omega-3 fatty acid in the diets of animals on the animal products consumed by humans. Med Sci (Paris), 21(8-9):7739, Aug-Sep 2005. http://www.ncbi.nlm.nih.gov/pubmed/16115466.
BIBLIOGRAPHY
661
[265] Kouba M and Mourot J. A review of nutritional eects on fat composition of animal products with special emphasis on n-3 polyunsaturated fatty acids. Biochimie, 93(1):13, 1 2011. http://www.ncbi.nlm.nih.gov/pubmed/20188790. [266] Du Q, Martin JC, Agnani G, Pages N, Leruyet P, Carayon P, and Delplanque B. Dairy fat blends high in -linolenic acid are superior to n-3 fatty-acid-enriched palm oil blends for increasing dha levels in the brains of young rats. J Nutr Biochem, 23(12):157382, 12 2012. http://www.ncbi.nlm.nih.gov/pubmed/22445803. [267] Miles EA and Calder PC. Inuence of marine n-3 polyunsaturated fatty acids on immune function and a systematic review of their eects on clinical outcomes in rheumatoid arthritis. Br J Nutr, 107(Suppl 2):S17184, 6 2012. http://www.ncbi. nlm.nih.gov/pubmed/22591891. [268] Rontoyanni VG, Skakis PP, Kitas GD, and Protogerou AD. Marine n-3 fatty acids for cardiovascular risk reduction and disease control in rheumatoid arthritis: "kill two birds with one stone"? Curr Pharm Des, 18(11):153142, 2012. http://www. ncbi.nlm.nih.gov/pubmed/22364137. [269] Mittal A, Ranganath V, and Nichani A. Omega fatty acids and resolution of inammation: A new twist in an old tale. J Indian Soc Periodontol, 14(1):37, 1 2010. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2933521/. [270] Isobe Y, Arita M, Matsueda S, Iwamoto R, Fujihara T, Nakanishi H, Taguchi R, Masuda K, Sasaki K, Urabe D, Inoue M, and Arai H. Identication and structure determination of novel anti-inammatory mediator resolvin e3, 17,18dihydroxyeicosapentaenoic acid. J Biol Chem, 287(13):1052534, 3 2012. http: //www.jbc.org/content/287/13/10525.full.pdf#page=1&view=FitH. [271] Artemis P. and Simopoulos AP. Omega-3 fatty acids in inammation and autoimmune diseases. 21(6):495505, 12 2002. http://www.jacn.org/content/21/6/495. full. [272] Gillies PJ, Bhatia SK, Belcher LA, Hannon DB, Thompson JT, and Vanden Heuvel JP. Regulation of inammatory and lipid metabolism genes by eicosapentaenoic acid-rich oil. Journal of Lipid Research, 53(8):16791689, 2012. http://www.jlr. org/content/53/8/1679.abstract. [273] Erdinest N, Shmueli O, Grossman Y, Ovadia H, and Solomon A. Anti-inammatory eects of alpha linolenic acid on human corneal epithelial cells. Invest Ophthalmol Vis Sci, 53(8):4396406, 7 2012. http://www.ncbi.nlm.nih.gov/pubmed/22669722. [274] Kobayakawa M, Yamawaki S, Hamazaki K, Akechi T, Inagaki M and Uchitomi Y:Levels of omega-3 fatty acid in serum phospholipids and depression in patients with lung cancer. British Journal of Cancer (2005) 93, 1329-1333. doi:10.1038/sj.bjc.6602877 Published online 22 November 2005.
662
[275] Hirako S, Kim H, Shimizu S, Chiba H, and Matsumoto A. Low-dose sh oil consumption prevents hepatic lipid accumulation in high cholesterol diet fed mice. J Agric Food Chem, 11 2011. http://www.ncbi.nlm.nih.gov/pubmed/22066791. [276] http://www.nature.com/bjc/journal/v94/n6/abs/6603030a.html. Brown M D, Hart C A, Gazi E, Bagley S, and Clarke N W: Promotion of prostatic metastatic migration towards human bone marrow stoma by Omega 6 and its inhibition by Omega 3 PUFAs; British Journal of Cancer (2006) 94, 842-853. doi:10.1038/sj.bjc.6603030 Published online 7 march 2006. [277] Brasky TM, Till C, White E, Neuhouser ML, Song X, Goodman P, Thompson IM, King IB, Albanes D, and Kristal AR. Serum phospholipid fatty acids and prostate cancer risk: Results from the prostate cancer prevention trial. Am J Epidemiol, 4 2011. http://www.ncbi.nlm.nih.gov/pubmed/21518693. [278] Kristal AR, Arnold KB, Neuhouser ML, Goodman P, Platz EA, Albanes D, and Thompson IM. Diet, supplement use, and prostate cancer risk: results from the prostate cancer prevention trial. Am J Epidemiol, 172(5):56677, 9 2010. http: //www.ncbi.nlm.nih.gov/pubmed/20693267. [279] Bucher H C, Hengstler P, Schindler C and Meier G: N-3 polyunsaturated fatty acids in coronary heart disease: a meta-analysis of randomized controlled trial The American Journal of Medicine; Volume 112, Issue 4, March 2002, Pages 298-304 doi:10.1016/S0002-9343(01)01114-7. [280] Burr M L, Asheld-Watt P A L, Dunstan F D J, Fehily A M, Breay P, Tashton, Zotos P C, Haboubi N A A and Elwood P C: Lack of benet of dietary advice to men with angina: results of a controlled trial European Journal of Clinical Nutrition (2003) 57, 193-200. doi:10.1038/sj.ejcn.1601539. [281] Medizin: Mrchen vom Fisch; Der Spiegel Nr. 14/ 3.4.06 pp 163. [282] http://ajl.sagepub.com/cgi/content/abstract/2/1/51. Andon, Mark B.; Anderson, James W.: State of the Art Reviews: The Oatmeal-Cholesterol Connection: 10 Years Later. American Journal of Lifestyle Medicine 2008, Volume 2, Pages 51-57. DOI: 10.1177/1559827607309130. [283] http://www.cochrane.org/reviews/en/ab005051.htmlX. Kelly SAM, Summerbell CD, Brynes A, Whittaker V, Frost G. Wholegrain cereals for coronary heart disease. Cochrane Database of Systematic Reviews 2007, Issue 2. Art. No.: CD005051. DOI: 10.1002/14651858.CD005051.pub2. [284] http://bmj.bmjjournals.com/cgi/content/full/bmj;332/7544/752. Hooper L, Thompson R L, Harrison R A, Summerbell C D, Ness A R, Moore H J, Worthington H V, Durrington P N, Higgins J P T, Capps N E, Riemersma R A,
BIBLIOGRAPHY
663
Ebrahim S B J, Smith G D: Risks and benets of omega 3 fats for mortality, cardiovascular disease, and cancer: systematic review. BMJ 2006;332:752-760 (1 April), doi:10.1136/bmj.38755.366331.2F (published 24 March 2006). [285] http://bmj.bmjjournals.com/cgi/content/full/332/7544/739. Eric Brunner: Editorial: Oily sh and omega 3 fat supplements Health recommendations conict with concerns about dwindling supply. BMJ 2006;332:739-740 (1 April), doi:10.1136/bmj.38798.680185.47 (published 24 March 2006). [286] Larsson SC, Virtamo J, and Wolk A. Fish consumption and risk of stroke in swedish women. Am J Clin Nutr, 12 2010. http://www.ajcn.org/content/early/2010/ 12/29/ajcn.110.002287.abstract. [287] http://bmj.bmjjournals.com/cgi/content/full/332/7544/739. Michael J. James, Susanna M. Proudman and Leslie G. Cleland: Fish oil benets: awed intelligence on toxins of mass consumption 31 March 2006;332:739-740(1 April), doi:10.1136/bmj.38798.680185.47 (published 24 March 2006). [288] Sekikawa, Akira; Curb, J. David; Ueshima, Hirotsugu; El-Saed, Aiman; Kadowaki, Takashi; Abbott, Robert D.; Evans, Rhobert W.;Rodriguez, Beatriz L.; Okamura, Tomonori; Sutton-Tyrrell, Kim; Nakamura, Yasuyuki; Masaki, Kamal; Edmundowicz, Daniel; Kashiwagi, Atsunori; Willcox, Bradley J.; Takamiya, Tomoko; Mitsunami, Ken-ichi; Seto, Todd B.; Murata, Kiyoshi; White, Roger L.; Kuller, Lewis H.: Marine-Derived n-3 Fatty Acids and Atherosclerosis in Japanese, Japanese Americans, and White Men: A Cross-Sectional Study. Journal of the American College of Cardiology. Volume 52, Pages 417-424, doi:10.1016/j.jacc.2008.03.047. [289] http://www.advancedbionutrition.com/html/news_abn.html#improving. Advanced Bionutrition: The Daily Record September 2003 Improving the food chain with DHA By: Mary E. Medland. [290] http://dx.doi.org/10.1016/j.jfoodeng.2008.02.025. Corra, Ana Paula Antunes; Peixoto, Camila Arantes; Goncalves, Lireny Aparecida Guaraldo; Cabral, Fernando Antonio: Fractionation of sh oil with supercritical carbon dioxide. Journal of Food Engineering, Volume 88, Issue 3, October 2008 , Pages 381-387. [291] http://dx.doi.org/10.1016/j.supflu.2008.02.006. Espinosa, S.; Diaz, M.S.; Brignole, E.A.: Food additives obtained by supercritical extraction from natural sources. The Journal of Supercritical Fluids, Volume 45, Issue 2, June 2008, Pages 213-219. [292] http://cat.inist.fr/?aModele=afficheN&cpsidt=18591096. Perretti, G; Motori, A.; Bravi,E.; Favati, F.; Montanari, L.; Fantozzi, P.: Supercritical carbon dioxide fractionation of sh oil fatty acid ethyl esters. The Journal of supercritical uids 2007, vol. 40, nr.3, pp. 349-353.
664 [293] http://en.wikipedia.org/wiki/Feedlot. Feedlot.
CHAPTER 7. PHYSIOLOGY Wikipedia, The Free Enzyclopedia:
[294] http://www.animal-science.org/cgi/content/abstract/84/6/1544. T. D. Maddock, M. L. Bauer, K. B. Koch, V. L. Anderson, R. J. Maddock, G. BarceloCoblijn, E. J. Murphy, and G. P. Lardy: Eect of processing ax in beef feedlot diets on performance, carcass characteristics, and trained sensory panel ratings J Anim Sci, June 1, 2006; 84(6): 1544. [295] http://www.ajcn.org/cgi/content/abstract/71/1/171S. Connor, W.E. (2000): Importance of n-3 fatty acids in health and disease.Am. J. Clin. Nutr. 71:171S-175S. [296] http://jn.nutrition.org/cgi/content/abstract/134/7/1806. E. LopezGarcia, M. B. Schulze, J. E. Manson, J. B. Meigs, C. M. Albert, N. Rifai, W. C. Willett, and F. B. Hu: Consumption of (n-3) Fatty Acids Is Related to Plasma Biomarkers of Inammation and Endothelial Activation in Women J. Nutr., July 1, 2004; 134(7): 1806 - 1811. [297] http://content.onlinejacc.org/cgi/content/abstract/48/4/677. D. Giugliano, A. Ceriello, and K. Esposito: The Eects of Diet on Inammation: Emphasis on the Metabolic Syndrome J. Am. Coll. Cardiol., August 15, 2006; 48(4): 677-685 doi:10.1016/j.jacc.2006.03.052. [298] http://www.ajcn.org/cgi/content/abstract/84/1/223. K. Niu, A. Hozawa, S. Kuriyama, K. Ohmori-Matsuda, T. Shimazu, N. Nakaya, K. Fujita, I. Tsuji, and R. Nagatomi: Dietary long-chain n-3 fatty acids of marine origin and serum C-reactive protein concentrations are associated in a population with a diet rich in marine products. Am. J. Clinical Nutrition, July 1, 2006; 84(1): 223 - 229. [299] http://www.ajcn.org/cgi/content/abstract/83/6/S1477. J. L Breslow: n-3 Fatty acids and cardiovascular disease Am. J. Clinical Nutrition, June 1, 2006; 83(6): S1477 - 1482S. [300] http://www.ars.usda.gov/is/AR/archive/oct10/nutrition1010.htm. Eat Fish! Nutrition Studies Zero In on Health Benets. ARS October 5, 2010. [301] http://www.ajcn.org/cgi/content/abstract/84/1/5. Wang C, Harris WS, Chung M, Lichtenstein AH, Balk EM, Kupelnick B, Jordan HS, Lau J.: n-3 Fatty acids from sh or sh-oil supplements, but not alpha-linolenic acid, benet cardiovascular disease outcomes in primary-and secondary-prevention studies: a systematic review. Am J Clin Nutr. 2006 Jul;84(1):5-17. [302] http://archneur.ama-assn.org/cgi/content/abstract/62/12/1849. M. C. Morris, D. A. Evans, C. C. Tangney, J. L. Bienias, and R. S. Wilson: Fish Consumption and Cognitive Decline With Age in a Large Community Study. Arch Neurol, December 1, 2005; 62(12): 1849 - 1853.
BIBLIOGRAPHY
665
[303] http://fermat.nap.edu/openbook.php?record_id=11762&page=1. Seafood Choices: Balancing Benets and Risks (2006)Committee on Nutrient Relationships in Seafood. Malden C. Nesheim, and Ann L. Yaktine, Editors Food and Nutrition Board. [304] http://jama.ama-assn.org/cgi/content/abstract/296/15/1885. Fish Intake, Contaminants, and Human Health: Evaluating the Risks and the Benets. Mozaffarian and Rimm JAMA 2006;296:1885-1899. [305] http://www.heartfoundation.com.au/downloads/Nutrition in cardiac rehab.pdf. National Heart Foundation of Australia & Cardiac Society of Australia and New Zealand: Nutrition recommendations for cardiac rehabilitation 2002. [306] http://www.ajcn.org/cgi/content/abstract/85/3/803. Magnus Hgstrm, Peter Nordstrm, and Anna Nordstrm n-3 Fatty acids are positively associated with peak bone mineral density and bone accrual in healthy men: the NO2 Study Am J Clin Nutr March 2007 85: 803-807. [307] http://www.ajcn.org/cgi/content/full/85/3/647. Vanek, Chaim and Connor, Wiliam E.: Do n-3 fatty acids prevent osteoporosis? Editorial Am. J. Clinical Nutrition, March 1, 2007; 85(3): 647 - 648. [308] http://www.ajcn.org/cgi/content/full/85/3/647. Simopoulos AP. n-3 Fatty acids in inammation and autoimmune diseases. J Am Coll Nutr 2002;21:495-505. [309] http://www.ncbi.nlm.nih.gov/pubmed/12662148. Cather JC, Menter A. Modulating T cell responses for the treatment of psoriasis: a focus on efalizumab. Expert Opin Biol Ther 2003;3:361-370. [310] http://www.foodstandards.gov.au/newsroom/factsheets/factsheets2004/ mecuryinfishupdatedi2819.cfm. Food Standards Australia: Mercury in sh Updated information (22 December 2004). [311] http://www.epa.gov/waterscience/criteria/methylmercury/document.html. EPA: Fish tissue criterion for methylmercury to protect human health document. [312] http://www.ncbi.nlm.nih.gov/pubmed/17894202. Balshaw S, Edwards J, Daughtry B, Ross K. Rev Environ Health: Mercury in seafood: mechanisms of accumulation and consequences for consumer health. 2007 Apr-Jun;22(2):91-113. [313] http://www.ncbi.nlm.nih.gov/pubmed/18262700. Kehrig Hdo A, Howard BM, Malm O. Methylmercury in a predatory sh (Cichla spp.) inhabiting the Brazilian Amazon. Environ Pollut. 2008 Jul;154(1):68-76. [314] http://www.ncbi.nlm.nih.gov/pubmed/17625245. Drea JG, Barbosa AC: Anthropogenic impact of mercury accumulation in sh from the Rio Madeira and Rio Negro rivers (Amazonia). Biol Trace Elem Res. 2007 Mar;115(3):243-54.
666
[315] http://www.ncbi.nlm.nih.gov/pubmed/17825359. Jewett SC, Duy LK: Mercury in shes of Alaska, with emphasis on subsistence species. Sci Total Environ. 2007 Nov 15;387(1-3):3-27. [316] http://www.ncbi.nlm.nih.gov/pubmed/12775518. Campbell L, Dixon DG, Hecky RE: A review of mercury in Lake Victoria, East Africa: implications for human and ecosystem health. J Toxicol Environ Health B Crit Rev. 2003 Jul-Aug;6(4):325-56. [317] http://www.ehponline.org/docs/2006/9329/abstract.html. Fei Xue, Claudia Holzman, Mohammad Hossein Rahbar, Kay Trosko, Lawrence Fischer: Maternal Fish Consumption, Mercury Levels and Risk of Preterm Delivery. Environmental Health Perspectives doi:10.1289/ehp.9329. Online 25 September 2006. [318] http://jama.ama-assn.org/cgi/content/abstract/280/8/701. Philip W. Davidson; Gary J. Myers; Christopher Cox; Catherine Axtell; Conrad Shamlaye; Jean Sloane-Reeves; Elsa Cernichiari; Larry Needham; Anna Choi; Yining Wang; Maths Berlin; Thomas W. Clarkson: Eects of Prenatal and Postnatal Methylmercury Exposure From Fish Consumption on Neurodevelopment: Outcomes at 66 Months of Age in the Seychelles Child Development Study. JAMA. 1998;280:701707. [319] http://www.ncbi.nlm.nih.gov/pubmed/16527422. Kawakita E, Hashimoto M, Shido O.: Docosahexaenoic acid promotes production of new neurons in cells and animals. Neuroscience 2006;139(3):991-7. Epub 2006 Mar 9. [320] http://jn.nutrition.org/cgi/content/abstract/137/11/2377. Pepe, Salvatore; McLennan, Peter. L.: (n-3) Long Chain PUFA Dose-Dependently Increase Oxygen Utilization Eciency and Inhibit Arrhythmias after Saturated Fat Feeding in Rats J. Nutr., November 1, 2007; 137(11): 2377 - 2383. [321] Bang HO, Dyerberg J, Nielsen AB. Plasma lipid and lipoprote in pattern in Greenlandic west-coast Eskimos. Lancet 1971;i:1143-6. [322] http://www.ajcn.org/cgi/content/abstract/28/9/958. Dyerberg, J; Bang, H. O.; Hjorne, N.: Fatty acid composition of the plasma lipids in Greenland Eskimos. Am. J. Clinical Nutrition, Sep 1975; 28: 958 - 966. [323] http://www.bmj.com/cgi/content/full/310/6983/819. Prichard, B. N. C.; Smith, C. C .T.; Ling, K. L. E.; Betteridge, D. J.: Editorials Fish oils and cardiovascular disease. [324] http://www.jlr.org/cgi/content/abstract/47/8/1661. Lichtenstein, Alice, H.: Thematic review series: Patient-Oriented Research. Dietary fat, carbohydrate, and protein: eects on plasma lipoprotein patterns. Journal of Lipid Research, Vol. 47, 1661-1667, August 2006 doi:10.1194/jlr.R600019-JLR200.
BIBLIOGRAPHY [325] http://www.epa.gov/waterscience/fish/advisory.html. Fish Advisories Released for 2004.
667 National Listing of
[326] http://www.cfsan.fda.gov/~dms/mehg703b/sld045.htm. FDA and EPA Development of a Joint Advisory for Methylmercury-containing Fish Consumption for Women of Childbearing Age and Children July 2003. [327] http://www.epa.gov/waterscience/fish/MethylmercuryBrochure.pdf. What you need to know about mercury in sh and shellsh. Advice for women who might become pregnant, women who are pregnant, nursing mothers, young children. FDA and EPA consumption advice on mercury in Fish and Shellsh. [328] http://www.ewg.org/reports/BrainFood/pr.html. Government Seafood Consumption Advice Could Expose 1 In 4 Newborns to Elevated Mercury Levels Brain Food: What Women Should Know About Mercury Contamination in Fish Includes Expanded List of Fish to Avoid. [329] http://www.ehponline.org/press/mercury.html. Jane M. Hightower and Dan Moore: New Study Finds Upper-Income Fish Eaters Exposed to Dangerous Levels of Mercury. Environmental Health Perspectives, Volume 111, Number 4, April 2003 pp 609. [330] http://www.ewg.org/reports/mercuryfalling/MercuryFalling.pdf. John Coequyt and Richard Wiles: Mercury Falling: An Analysis of Mercury Pollution from Coal-Burning Power Plants. The Environmental Working Group (EWG). [331] http://www.epa.gov/oar/mercuryrule/. EPA: Clean air mercury rule 2005. [332] Grimm MO, Rothhaar TL, Grsgen S, Burg VK, Hundsdrfer B, Haupenthal VJ, Friess P, Kins S, Grimm HS, and Hartmann T. Trans fatty acids enhance amyloidogenic processing of the alzheimer amyloid precursor protein (app). J Nutr Biochem, 23(10):121423, 10 2012. http://www.ncbi.nlm.nih.gov/pubmed/22209004. [333] Danaei G, Ding EL, Mozaarian D, Taylor B, Rehm J, Murray CJ, and Ezzati M. The preventable causes of death in the united states: comparative risk assessment of dietary, lifestyle, and metabolic risk factors. PLoS Med, 6(4):e1000058, 4 2009. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2667673/. [334] Mozaarian D, Katan MB, Ascherio A, and et al. Trans fatty acids and cardiovascular disease. N Engl J Med, 354:1601, 2006. http://www.ncbi.nlm.nih.gov/pubmed/ 16611951. [335] http://www.euromilk.org/upload/docs/EDA/Dt%20237_en.pdf. European Dairy Association (EDA) : The Dairy Telegraph: EDA policy conference on trans fatty acids. 22.02.2008.
668
[336] http://www.euromilk.org/EDA/publications7.aspx?cid=2568&artid=2600#13. European Dairy Association (EDA) Position on dairy trans fatty acids. 13.02.2008. [337] Schneiter, Thomas: Transfettsuren (TFA) - Warum?; Lebensmittelidustrie 7/8 1997 pp 6. [338] http://www.ncbi.nlm.nih.gov/pubmed/20219966. Micha R, King IB, Lemaitre RN, Rimm EB, Sacks F, Song X, Siscovick DS, Mozaarian D: Food sources of individual plasma phospholipid trans fatty acid isomers: the Cardiovascular Health Study. Am J Clin Nutr. 2010 Apr;91(4):883-93. [339] http://cebp.aacrjournals.org/cgi/content/abstract/17/1/95. Chavarro, Jorge E.; Stampfer, Meir J.; Campos, Hannia; Kurth, Tobias; Willett, Walter C.; Ma, Jing: A Prospective Study of Trans-Fatty Acid Levels in Blood and Risk of Prostate Cancer. Cancer Epidemiology Biomarkers & Prevention. 1 January 2008, Volume 17, Pages 95-101, doi: 10.1158/1055-9965.EPI-07-0673. [340] http://www.ajcn.org/cgi/content/abstract/85/6/1503. St-Onge,Marie-Pierre; Aban, Inmaculada; Bosarge, Aubrey; Gower, Barbara; Hecker, Kari D.; Allison, David B.: Snack chips fried in corn oil alleviate cardiovascular disease risk factors when substituted for low-fat or high-fat snacks. American Journal of Clinical Nutrition, Vol. 85, No. 6, 1503-1510, June 2007. [341] http://www.ncbi.nlm.nih.gov/pubmed/20354806. Micha R, Mozaarian D: Saturated Fat and Cardiometabolic Risk Factors, Coronary Heart Disease, Stroke, and Diabetes: a Fresh Look at the Evidence. Lipids. 2010 Mar 31. [342] http://www.ncbi.nlm.nih.gov/pubmed/20351774. Mozaarian D, Micha R, Wallace S: Eects on coronary heart disease of increasing polyunsaturated fat in place of saturated fat: a systematic review and meta-analysis of randomized controlled trials. PLoS Med. 2010 Mar 23;7(3):e1000252. Review. [343] http://www.handelsblatt.com/news/default.aspx?_t=ft&_p=203116&_b= 1322532. Handelsblatt.com: Forscher warnen vor Gesundheitsgefahr aus der Keksdose. 13.09.07. [344] http://dx.doi.org/10.1016/j.lwt.2010.02.002. Matsakidou, Anthia; Blekas, Georgios; Paraskevopoulou, Adamantini: Aroma and physical characteristics of cakes prepared by replacing margarine with extra virgin olive oil. LWT - Food Science and Technology. Published online ahead of print, doi: 10.1016/j.lwt.2010.02.002. [345] http://en.wikipedia.org/wiki/Madeira_cake. Wikipedia: Madeira cake. [346] http://www.ajcn.org/cgi/content/abstract/84/5/981. Kuhnt, Katrin; Wagner, Andreas; Kraft, Jana; Basu, Samar; Jahreis, Gerhard: Dietary supplementation with 11trans- and 12trans-18:1 and oxidative stress in humans. American Journal of Clinical Nutrition, Vol. 84, No. 5, 981-988, November 2006.
BIBLIOGRAPHY
669
[347] http://www.cfsan.fda.gov/~lrd/fr03711a.html. (Federal Register: July 11, 2003 (Volume 68, Number 133))(Rules and Regulations) (Page 41433-41506) From the Federal Register Online via GPO Access (wais.access.gpo.gov) (DOCID:fr11jy0314)- Part III 21 CFR Part 101: Food Labeling; Trans Fatty Acids in Nutrition Labeling; Consumer Research to Consider Nutrient Content and Health Claims and Possible Footnote or Disclosure Statements; Final Rule and Proposed Rule. [348] http://dailynews.yahoo.com/h/ap/19991026/pl/soylabels. [349] http://content.karger.com/ProdukteDB/produkte.asp?Aktion= ShowAbstract&ArtikelNr=141484&Ausgabe=239033&ProduktNr=224226. Hogervorst,E.; Sadjimim, T.; Yesufu, A.; Kreager P.; Rahardjo,T.B.: High Tofu Intake Is Associated with Worse Memory in Elderly Indonesian Men and Women Dement Geriatr Cogn Disord 2008;26:50-57 (DOI:10.1159/000141484). [350] http://jama.ama-assn.org/cgi/content/abstract/276/12/955. L. White, H. Petrovitch, G. W. Ross, K. H. Masaki, R. D. Abbott, E. L. Teng, B. L. Rodriguez, P. L. Blanchette, R. J. Havlik, G. Wergowske, D. Chiu, D. J. Foley, C. Murdaugh and J. D. Curb: Prevalence of dementia in older Japanese-American men in Hawaii: The Honolulu-Asia Aging Study. JAMA. Vol. 276 No. 12, September 25, 1996. [351] http://www.jacn.org/cgi/content/abstract/19/2/242. White, Lon R.; Petrovitch, Helen; Ross, G. Webster; Masaki, Kamal; Hardman, John; Nelson, James; Davis, Daron; Markesbery, William: Brain Aging and Midlife Tofu Consumption. Journal of the American College of Nutrition, Vol. 19, No. 2, 242-255 (2000). [352] http://www.blackwell-synergy.com/doi/abs/10.1111/j.1467-789X.2007. 00390.x. Cope,M.B.; Erdman Jr, J.W. ; Allison, D.B.: The potential role of soyfoods in weight and adiposity reduction: an evidence-based review. Obesity Reviews doi: 10.1111/j.1467-789X.2007.00390.x. [353] http://www3.interscience.wiley.com/cgi-bin/abstract/114129504/ ABSTRACT. Rho, Shin Joung; Park, Soojin; Ahn, Chang-Won; Shin, Jae-Kil; Lee, Hyeon Gyu: Dietetic and hypocholesterolaemic action of black soy peptide in dietary obese rats. Journal of the Science of Food and Agriculture. Published Online: 26 Feb 2007. Doi:10.1002/jsfa.2808. [354] Foodnavigator: Dairy Crest misused omega-3 study, says ASA;By Chris Mercer 21.06.2006. [355] http://www.ahrq.gov/downloads/pub/evidence/pdf/o3mental/o3mental.pdf. Schachter H, Kourad K, Merali Z, Lumb A, Tran K, Miguelez M, et al. Eects of Omega-3 Fatty Acids on Mental Health. Evidence Report/Technology Assessment No. 116. (Prepared by the University of Ottawa Evidence-based Practice Center, Under Contract No. 290-02-0021.) AHRQ Publication No. 05-E022-2. Rockville, MD: Agency for Healthcare Research and Quality. July 2005.
670
[356] National Institute of Mental Health. The numbers count: mental disorders in America. A summary of statistics describing the prevalence of mental disorders in America. Bethesda, MD: National Institute of Mental Health, 2001. NIH Publication No. 014584. [357] The global burden of disease. Geneva: World Health Organization, 1996. [358] http://www.sustainweb.org/pdf/fmh_advance_statement.pdf. Advance statement to the Associate Parliamentary Food and Health Forum on its investigation into the links between food and mental health. Courtney Vande Weyer Sustain: the alliance for better food and farming April 2007. [359] http://www.wellcome.ac.uk/doc_WTX042970.html. Welcome Trust: Prison study to investigate link between diet and behaviour. 28 January 2008. [360] http://www.guardian.co.uk/life/feature/story/0,13026,1476219,00.html. The Guardian: Why its time we faced fats: New research establishes a link between nutrition and the management of many behaviour and learning disorders. Felicity Lawrence investigates. Thursday May 5, 2005. [361] http://www.durhamtrial.org/primary%20results%20new.htm. Study Using Fatty Acids for Learning Conditions. 2004. The Durham
[362] http://www.food.gov.uk/multimedia/pdfs/systemreview.pdf. Centre for Food, Physical Activity and Obesity Research University of Teesside: A systematic review of the eect of nutrition , diet and dietary change on learning, educationand performance of children of relevance to UK schools (Project Code: N05070). [363] http://ajp.psychiatryonline.org/cgi/content/abstract/ajp;163/6/1098. Hanah Nemets, Boris Nemets, Alan Apter, Ziva Bracha, and R.H. Belmaker Omega-3 Treatment of Childhood Depression: A Controlled, Double-Blind Pilot Study American Journal of Psychiatry 2006 163: 1098-1100. [364] http://ajp.psychiatryonline.org/cgi/content/abstract/ajp;163/6/1100. M. Elizabeth Sublette, Joseph R. Hibbeln, Hanga Galfalvy, Maria A. Oquendo, and J. John Mann: Omega-3 Polyunsaturated Essential Fatty Acid Status as a Predictor of Future Suicide Risk Am J Psychiatry 2006 163: 1100-1102. [365] http://ajp.psychiatryonline.org/cgi/content/abstract/ajp;163/6/969. Gordon Parker, Neville A. Gibson, Heather Brotchie, Gabriella Heruc, Anne-Marie Rees, and Dusan Hadzi-Pavlovic: Omega-3 Fatty Acids and Mood Disorders Am J Psychiatry 2006 163: 969-978. [366] http://www.jewishsf.com/content/2-0-/module/displaystory/story_id/ 2692/edition_id/46/format/html/displaystory.html. Jewish News Weekly of Nothern California: Israeli, U.S. scientists nd risk gene; Judy Siegel; Jerusalem Post Service January 5, 1996.
BIBLIOGRAPHY
671
[367] Serretti-A Macciardi-F Cusin-C Lattuada-E Lilli-R Smeraldi-E: Dopamine-Receptor D-4 Gene Is Associated with Delusional Symptomatology in Mood Disorders. [368] http://www.medikal.it/2001_03.cfm#6. EM Berry: Whos afraid of n-6 polyunsaturated fatty acids? Methodological considerations for assessing whether they are harmful. Nutrition Metabolism and Cardiovascular Diseases, 2001, Vol 11, Iss 3, pp 181-188. Hebrew Univ Jerusalem, Hadassah Med Sch, Fac Med, Dept Human Nutr & Metab, IL-91010 Jerusalem, ISRAEL. [369] Clinical Cancer Research (Vol. 12, Issue 15 British Journal of Cancer, doi: 10.1038/sj.bjc.6603030). [370] Margel D and Fleshner NE. Occupational and environmental medicine: Oral contraceptive use is associated with prostate cancer: an ecological study. BMJ, page e000311, 1 2011. http://bmjopen.bmj.com/content/1/2/e000311. [371] Barbara V. Howard, PhD and colleagues:Low-Fat Dietary Pattern and Risk of Cardiovascular Disease, The Womens Health Initiative Randomized Controlled Dietary Modication Trial; Journal of the American Medical Association (Vol. 295, pp. 655666). [372] http://www.nutraingredients.com/news/ng.asp?id=65682-low-fat-cvd. Nutraingrerdients.com: Low fat diet has no eect on heart risk. [373] http://www.ncbi.nlm.nih.gov/pubmed/16076983. Jrgens, Hella; Haass, Wiltrud; Castaneda, Tamara R.; Schrmann, Annette; Koebnick, Corinna; Dombrowski, Frank; Otto, Brbel; Nawrocki, Andrea R.; Scherer, Philipp E.; Spranger, Jochen; Ristow, Michael; Joost, Hans-Georg; Havel, Peter J. and Tschp Matthias H.: Consuming Fructose-sweetened Beverages Increases Body Adiposity in Mice Obes. Res. 2005 13: 1146-1156. [374] http://www.ajcn.org/cgi/content/abstract/84/6/1374. Le, Kim-Anne; Faeh, David; Stettler, Rodrigue; Ith, Michael; Kreis, Roland; Vermathen, Peter; Boesch, Chris; Ravussin, Eric and Tappy, Luc: A 4-week high-fructose diet alters lipid metabolism without aecting insulin sensitivity or ectopic lipids in healthy humans. Am. J. Clinical Nutrition, December 1, 2006; 84(6): 1374-1379. [375] Roglans, Nria; Vil, Laia; Farr, Mireia; Alegret, Marta; Snchez, Rosa Mara; Vzquez-Carrera, Manuel; Laguna, Juan Carlos: Impairment of hepatic Stat-3 activation and reduction of PPARalfa activity in fructose-fed rats . Hepatology (p 778-788) online 26 Feb 2007 Doi: 10.1002/hep.21499. [376] http://archinte.ama-assn.org/cgi/content/abstract/168/14/1487. Palmer, Julie R.; Boggs, Deborah A.; Krishnan, Supriya; Hu, Frank B.; Singer, Martha; Rosenberg, Lynn: Sugar-Sweetened Beverages and Incidence of Type 2 Diabetes Mellitus in African American Women. Arch Intern Med. 2008;168(14):1487-1492.
672
[377] Johnson, Richard J.; Perez-Pozo, Santos : Presentations, American Heart Association High Blood Pressure Research Conference, Chicago. Sept. 23-24, 2009. [378] Morris, Mariana: Presentations, American Heart Association High Blood Pressure Research Conference, Chicago. Sept. 23-24, 2009. [379] http://www.nlm.nih.gov/medlineplus/news/fullstory_89762.html. tied to higher blood pressure: study. Medline plus 23.09.2009. Fructose
[380] http://www.medscape.com/viewarticle/576945. Vos, Miriam B.;Kimmons, Joel E.; Gillespie, Cathleen; Welsh, Jean; Michels Blanck, Heidi: Dietary Fructose Consumption Among US Children and Adults: The Third National Health and Nutrition Examination Survey CME. Medscape. Posted 07/9/2008. [381] http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool= pubmed&pubmedid=18769693. Bray, George A.: Fructose-How Worried Should We Be?Medscape J Med. 2008; 10(7): 159. Published online 2008 July 9. [382] http://www.ajcn.org/cgi/content/abstract/88/6/1722S. Duey, Kiyah J.; Popkin, Barry M .: Supplement: High-Fructose Corn Syrup (HFCS): Everything You Wanted to Know, but Were Afraid to Ask. High-fructose corn syrup: is this whats for dinner? American Journal of Clinical Nutrition, Vol. 88, No. 6, 1722S1732S, December 2008 Doi:10.3945/ajcn.2008.25825C. [383] http://www.ncbi.nlm.nih.gov/pubmed/19759377. Brownell KD, Farley T, Willett WC, Popkin BM, Chaloupka FJ, Thompson JW, Ludwig DS.: The Public Health and Economic Benets of Taxing Sugar-Sweetened Beverages. N Engl J Med. 2009 Sep 16. [384] http://www.ajcn.org/cgi/content/abstract/88/6/1715S. Fulgoni III, V.: Highfructose corn syrup: everything you wanted to know, but were afraid to ask Am. J. Clinical Nutrition, December 1, 2008; 88(6): 1715S - 1715S. [385] http://www.ncbi.nlm.nih.gov/pubmed/19375714. Nguyen S, Choi HK, Lustig RH, Hsu CY.: Sugar-sweetened beverages, serum uric acid, and blood pressure in adolescents. J Pediatr. 2009 Jun;154(6):807-13. Epub 2009 Apr 17. [386] http://jn.nutrition.org/cgi/content/abstract/139/6/1219S. White, J.S.: Misconceptions about High-Fructose Corn Syrup: Is It Uniquely Responsible for Obesity, Reactive Dicarbonyl Compounds, and Advanced Glycation Endproducts? J. Nutr., June 1, 2009; 139(6): 1219S - 1227S. [387] http://www.ajcn.org/cgi/content/abstract/88/6/1733S. Stanhope, K.L.; Havel, P.J.: Endocrine and metabolic eects of consuming beverages sweetened with fructose, glucose, sucrose, or high-fructose corn syrup. Am. J. Clinical Nutrition, December 1, 2008; 88(6): 1733S - 1737S.
BIBLIOGRAPHY
673
[388] http://www.ajcn.org/cgi/content/abstract/88/6/1738S. Melanson, K.J. Angelopoulos, T.J.; Nguyen, V.; Zukley,L.; Lowndes, J.; Rippe, J.M.: High-fructose corn syrup, energy intake, and appetite regulation. Am. J. Clinical Nutrition, December 1, 2008; 88(6): 1738S - 1744S. [389] http://www.ncbi.nlm.nih.gov/pubmed/17901427. Mello MM, Pomeranz J, Moran P.: The interplay of public health law and industry self-regulation: the case of sugarsweetened beverage sales in schools. Am J Public Health. 2008 Apr;98(4):595-604. Epub 2007 Sep 27. [390] http://books.nap.edu/openbook.php?record_id=11899&page=103. Stallings, Virginia A.; Yaktine, Ann L.:Nutrition Standards for Foods in Schools. Leading the Way Toward Healthier Youth (2007). Food and Nutrition Board. [391] http://www.ameribev.org/nutrition--science/school-beverage-guidelines/. The School Beverage Guidelines. The American Beverage Association & The Alliance for a Healthier Generation. September 2008. [392] http://www.ncbi.nlm.nih.gov/pubmed/18519465. Wang YC, Bleich SN, Gortmaker SL: Increasing caloric contribution from sugar-sweetened beverages and 100% fruit juices among US children and adolescents, 1988-2004. Pediatrics. 2008 Jun;121(6):e1604-14. [393] http://www.ncbi.nlm.nih.gov/pubmed/19349562. Wang YC, Ludwig DS, Sonneville K, Gortmaker SL.: Impact of change in sweetened caloric beverage consumption on energy intake among children and adolescents. American Journal of Clinical Nutrition, doi:10.3945/ajcn.2008.25825B Vol. 88, No. 6, 1716S-1721S, December 2008. [394] http://www.ebmonline.org/cgi/content/abstract/234/6/651. Light, H.R.; Tsanzi, E.; Gigliotti, J.; Morgan, K.; Tou, J.C.: The Type of Caloric Sweetener Added to Water Inuences Weight Gain, Fat Mass, and Reproduction in Growing Sprague-Dawley Female Rats. Experimental Biology and Medicine, June 1, 2009; 234(6): 651 - 661. doi: 10.3181/0812-RM-368. [395] http://www.ncbi.nlm.nih.gov/pubmed/19381015. Stanhope KL, Schwarz JM, Keim NL, Grien SC, Bremer AA, Graham JL, Hatcher B, Cox CL, Dyachenko A, Zhang W, McGahan JP, Seibert A, Krauss RM, Chiu S, Schaefer EJ, Ai M, Otokozawa S, Nakajima K, Nakano T, Beysen C, Hellerstein MK, Berglund L, Havel PJ.: Consuming fructose-sweetened, not glucose-sweetened, beverages increases visceral adiposity and lipids and decreases insulin sensitivity in overweight/obese humans. J Clin Invest. 2009 Apr 20. pii: 37385. doi: 10.1172/JCI37385. [396] http://www.hfcsfacts.com/. Kathleen J Melanson (2006): Program Abstract # 391.2,.
674
[397] http://www.corn.org/CRAR2006.pdf. Martine Perrigue (2006): New Obesity Research Shows High Fructose Corn Syrup Similar to Sugar. Corn, Part of a sustainable environment . Corn Reners Association Annual Report 2006. [398] Ho, Chi-Tong: Report presented on at the 234th national meeting of the American Chemical Society, during the symposium, Food Bioactives and Nutraceuticals: Production, Chemistry, Analysis and Health Eects: Health Eects. August 23. 2007. [399] http://jn.nutrition.org/cgi/content/abstract/138/6/1039. Parks, Elizabeth J.; Skokan, Lauren E.; Timlin, Maureen T.; Dingfelder, Carlus S.: Dietary Sugars Stimulate Fatty Acid Synthesis in Adults. J. Nutr. 2008 138: 1039-1046. [400] http://jcem.endojournals.org/cgi/content/abstract/jc.2008-2192v1. Te, Karen L.;Grudziak, JoanneKaren L. Te; Townsend, Raymond R.; Dunn, Tamara N.; Grant, Ryan W.; Adams, Sean H.; Keim, Nancy L.;Cummings, Bethany P. ; Stanhope, Kimber L.; Havel, Peter J. : Endocrine and metabolic eects of consuming fructose- and glucose-sweetened beverages with meals in obese men and women: inuence of insulin resistance on plasma triglyceride responses. Journal of Clinical Endocrinology and Metabolism. Rapid Electronic Publication, available online 10 February 2009, doi:doi:10.1210/jc.2008-2192. [401] http://www.hfcsfacts.com/HighlyFatteningCrappyScience.html. About HFCS: HFCS (Highly Fattening or Crappy Science?) Empty calories, yes, but demon, no; the truth and friction behind high-fructose corn syrup. [402] Usda agricultural projections to 2021. interagency agricultural projections committee. february 2012. http://www.usda.gov/oce/commodity/archive_projections/ USDAAgriculturalProjections2021.pdf. [403] Usda economic researche service. http://www.ers.usda.gov/data-products/ sugar-and-sweeteners-yearbook-tables.aspx#25512. [404] Sugar and sweeteners outlook. u.s. sugar january 17, 2013. usda. http://www.ers. usda.gov/media/984570/sssm293.pdf. [405] Page KA, Chan O, Arora J, Belfort-Deaguiar R, Dzuira J, Roehmholdt B, Cline GW, Naik S, Sinha R, Constable RT, and Sherwin RS. Eects of fructose vs glucose on regional cerebral blood ow in brain regions involved with appetite and reward pathways. JAMA, 309(1):6370, 1 2013. http://www.ncbi.nlm.nih.gov/pubmed/ 23280226. [406] Goran MI, Ulijaszek SJ, and Ventura EE. High fructose corn syrup and diabetes prevalence: A global perspective. Glob Public Health, 11 2012. http://www.ncbi. nlm.nih.gov/pubmed/23181629.
BIBLIOGRAPHY
675
[407] Stanhope KL, Bremer AA, Medici V, Nakajima K, Ito Y, Nakano T, Chen G, Fong TH, Lee V, Menorca RI, Keim NL, and Havel PJ. Consumption of fructose and high fructose corn syrup increase postprandial triglycerides, ldl-cholesterol, and apolipoprotein-b in young men and women. J Clin Endocrinol Metab, 96(10):E1596 605, 10 2011. http://jcem.endojournals.org/content/96/10/E1596.long. [408] Stefaiska E, Falkowska A, and Ostrowska L. Selected nutritional habits children and teenagers aged 10-15 years. Rocz Panstw Zakl Hig, 63(1):917, 2012. http: //www.ncbi.nlm.nih.gov/pubmed/22642075. [409] Hammons AJ and Fiese BH. Is frequency of shared family meals related to the nutritional health of children and adolescents? Pediatrics, 127(6):e156574, 6 2011. . [410] Gatica G, Barros AJ, Madruga S, Matijasevich A, and Santos IS. Food intake proles of children aged 12, 24 and 48 months from the 2004 pelotas (brazil) birth cohort: an exploratory analysis using principal components. Int J Behav Nutr Phys Act, 9:43, 4 2012. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3424118/. [411] Romulus-Nieuwelink JJ, Doak C, Albernaz E, Victora CG, and Haisma H. Breast milk and complementary food intake in brazilian infants according to socio-economic position. Int J Pediatr Obes, 6(2-2):e50814, 6 2011. http://informahealthcare. com/doi/abs/10.3109/17477166.2010.512387. [412] Foreyt J Klurfeld DM, Angelopoulos TJ, and Rippe JM. Lack of evidence for high fructose corn syrup as the cause of the obesity epidemic. Int J Obes (Lond), 9 2012. http://www.nature.com/ijo/journal/vaop/ncurrent/full/ijo2012157a.html. [413] Eshak ES, Iso H, Kokubo Y, Saito I, Yamagishi K, Inoue M, and Tsugane S. Soft drink intake in relation to incident ischemic heart disease, stroke, and stroke subtypes in japanese men and women: the japan public health centre-based study cohort i. Am J Clin Nutr. http://www.ncbi.nlm.nih.gov/pubmed/23076619. [414] Nakayama K, Nakayama M, Terawaki H, Murata Y, Sato T, Kohno M, and Ito S. Carbonated soft drinks and carbonyl stress burden. J Toxicol Sci, 34(6):699702, 12 2009. https://www.jstage.jst.go.jp/article/jts/34/6/34_6_699/_pdf. [415] Li W, Maloney RE, Circu ML, Steven Alexander J, and Yee Aw T. Acute carbonyl stress induces occludin glycation and brain microvascular endothelial barrier dysfunction: Role for glutathione-dependent metabolism of methylglyoxal. Free Radic Biol Med, pii: S0891-5849(12):017947, 10 2012. http://www.ncbi.nlm.nih.gov/ pubmed/23108103. [416] Liu H, Yu S, Zhang H, and Xu J. Angiogenesis impairment in diabetes: role of methylglyoxal-induced receptor for advanced glycation endproducts, autophagy and
676
CHAPTER 7. PHYSIOLOGY vascular endothelial growth factor receptor 2. PLoS One, 7(10):e46720, 2012. http: //www.ncbi.nlm.nih.gov/pubmed/23056421.
[417] Majtan J. Commentarymethylglyoxal-a potential risk factor of manuka honey in healing of diabetic ulcers. article id 295494 , 5 pages. Evidence-Based Complementary and Alternative Medicine, 2011, 2011. http://www.hindawi.com/journals/ecam/ 2011/295494/. [418] http://en.wikipedia.org/wiki/Leptin. Wikipedia: Leptin. [419] Yoshida M, McKeown NM, Rogers G, Meigs JB, Saltzman E, DAgostino R, Jacques PF.: Surrogate markers of insulin resistance are associated with consumption of sugar-sweetened drinks and fruit juice in midlle and older-aged adults. The Journal of Nutrition, September 2007, 137: 2121-2127. [420] http://www.journals.cambridge.org/action/displayAbstract?fromPage= online%&aid=898900. Rennie, Kirsten and Livingstone, M Barbara E: Associations between dietary added sugar intake and micronutrient intake: a systematic review. British Journal of Nutrition 2007. doi:10.1017/S0007114507617206. [421] http://www.bfr.bund.de/cd/11165. Federal Institut for Risc Assessment: Diabetics do not need any special foods BfR, therefore, recommends uniform nutrition labelling 10/2008, 05.05.2008. [422] http://www.deutsche-diabetes-gesellschaft.de/redaktion/news/ Kennzeichnung_von_Diabetiker-Lebensmitteln_28102007.pdf. Deutsche Diabetiker Gesellschaft: Kennzeichnung von Diabetiker-Lebensmitteln muss sich ndern. [423] http://www.diaetverband.de/download/downloads/DiaetV_300108_070508. pdf. Verordnung ber ditetische Lebensmittel Vom 28.04.2005 (BGBl. I S. 1161), zuletzt gendert durch Art. 5 der VO vom 30.01.2008 (BGBl. I S. 132). [424] http://clinicaltrials.gov/show/NCT00000616. U.S. National Institutes of Health: PREMIER: Lifestyle Interventions for Blood Pressure Control. [425] http://www.ncbi.nlm.nih.gov/pubmed/19679672. Taylor, Eric N.; Fung, Teresa T.; Curhan, Gary C.: DASH-Style Diet Associates with Reduced Risk for Kidney Stones. Published ahead of print on August 13, 2009 Journal of the American Society of Nephrology. Doi: 10.1681/ASN.2009030276. [426] Matlaga BR. Toward a better understanding of kidney stone disease: Platinum priorities. Eur Urol, 62:e1e30, 4 2012. http://www.europeanurology.com/article/ S0302-2838%2812%2900493-9/fulltext.
BIBLIOGRAPHY
677
[427] Johri N, Cooper B, Robertson W, Choong S, Rickards D, and Unwin R. An update and practical guide to renal stone management. Nephron Clin Pract, 116(3):cl15971, 2010. http://content.karger.com/produktedb/produkte.asp? typ=fulltext&file=000317196#SC5. [428] Paterson R, Fernandez A, Razvi H, and Sutton R (2010). Evaluation and medical management of the kidney stone patient. Canadian Urological Association Journal, 4(6):3759. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2997825/ ?tool=pubmed. [429] Michael Liebman M and Al-Wahsh IA. Probiotics and other key determinants of dietary oxalate absorption. Adv. Nutr, 2:254260, 2011. http://advances. nutrition.org/content/2/3/254.full.pdf. [430] Moran ME. Uric acid stone disease. Front Biosci, 8:s133955, 9 2003. http://www. ncbi.nlm.nih.gov/pubmed/12957851. [431] Tin C Ngo and Dean G Assimos MD. Uric acid nephrolithiasis: Recent progress and future directions. Rev Urol, 9(1):1727, 2007. http://www.ncbi.nlm.nih.gov/pmc/ articles/PMC1831527/. [432] http://jama.ama-assn.org/cgi/content/abstract/289/16/2083. Appel LJ, Champagne CM, Harsha DW; Obarzanek E; Elmer PJ, Steves VJ, Vollmer WM, Lin PH, Svetkey LP, Stedman SW, Young DR; Writing Group of the PREMIERE Collaborative Research Group: Eects of comprehensive lifestyle modication on blood pressure control: main results of the PREMIER clinical trial.JAMA 2003 Apr 23-30;289(16):2083-93. [433] http://www.ajcn.org/cgi/content/abstract/87/6/1825. Nettleton, Jennifer A.; Steen, Lyn M .; Palmas, Walter; Burke, Gregory L.; Jacobs Jr.; David R.: Associations between microalbuminuria and animal foods, plant foods, and dietary patterns in the Multiethnic Study of Atherosclerosis (MESA) Am J Clin Nutr 2008 87: 18251836. [434] http://www.ajcn.org/cgi/content/abstract/85/5/1212. Ledikwe, Jenny H.; Rolls, Barbara J.; Smiciklas-Wright, Helen; Mitchell, Diane C.; Ard, Jamy D.; Champagne, Catherine;Karanja, Njeri; Lin, Pao-Hwa; Stevens, Victor and Appel, Lawrence J.: Reductions in dietary energy density are associated with weight loss in overweight and obese participants in the PREMIER trial.American Journal of Clinical Nutrition, Vol. 85, No. 5, 1212-1221, May 2007. [435] http://www.obesityresearch.org/cgi/content/abstract/15/5/1226. Cox, Tiany L.; Malpede, Christie Z.; Desmond, Renee A.; Faulk, Lori E.; Myer, Rory A.; Henson, ; Heimburger, Douglas C. and Ard, Jamy D.: Physical Activity Patterns During Weight Maintenance Following a Low-energy Density Dietary Intervention: Obesity 15:1226-1232 (2007).
678
CHAPTER 7. PHYSIOLOGY American
[436] http://www.eatright.org/cps/rde/xchg/ada/hs.xsl/index.html. Dietetic Association. [437] http://en.wikipedia.org/wiki/Magnesium. Wikipedia: Magnesium.
[438] Pudel, v.; Mller, M.J.:Leitfaden der Ernhrungsmedizin, Springer Verlag 1998, page 164. [439] Rayssiguier, Y.: Role of Magnesium and potassium in the pathogenesis of arteriosclerosis. Magnesium 3 1984 226. [440] http://jnci.oxfordjournals.org/cgi/content/abstract/99/10/754. Lawson, Karla, A.; Wright, Margaret E.; Subar, Amy; Mouw, Traci; Hollenbeck, Albert; Schatzkin, Arthur; Leitzmann, Michael F.: Multivitamin Use and Risk of Prostate Cancer in the National Institutes of Health-AARP Diet and Health Study. Journal of the National Cancer Institute Volume 99, Issue 10, Pages 754-764; doi:10.1093/jnci/djk177. [441] http://jnci.oxfordjournals.org/cgi/content/full/99/10/742. Bjelakovic, Goran and Gluud, Christian: Surviving Antioxidant Supplements Editorial. Journal of the National Cancer Institute, 2007 99(10):742-743; doi:10.1093/jnci/djk211. [442] http://news.bbc.co.uk/1/hi/health/6657795.stm. BBC News: Multivitamin prostate warning. [443] http://www.naturalproductsassoc.org/site/News2?abbr=pc_&page= NewsArticle&id=8731. Fabricant, Daniel: Natural Products Association Questions Conclusions of New Study on Multivitamins and Prostate Cancer. May 15, 2007. [444] http://www.jacn.org/cgi/content/abstract/26/2/170. Prior, R.L; Gu, L.; Wu, X.; Jacob, R.A.; Sotoudeh, G.; Kader, A.A.; Cook , R.A.: Plasma Antioxidant Capacity Changes Following a Meal as a Measure of the Ability of a Food to Alter In Vivo Antioxidant Status. Journal of the American College of Nutrition. Volume 26, Number 2, Pages 170-181. [445] http://www.sciencedaily.com/releases/2007/05/070521113628.htm. Science Daily: Some Vitamin Supplements Dont Protect Against Lung Cancer. May, 21, 2007. [446] http://www.cancer.gov/cancertopics/factsheet/Prevention/betacarotene. The National Cancer Institute: Questions and Answers About Beta Carotene Chemoprevention Trials. [447] http://www.naturalproductsassoc.org/site/News2?abbr=pc_&page= NewsArticle&id=8751. Fabricant, Daniel: Natural Products Association Challenges New Study on Lung Cancer and Vitamin Use May 21, 2007.
BIBLIOGRAPHY
679
[448] http://www.ncbi.nlm.nih.gov/pubmed/20068159. Stidley CA, Picchi MA, Leng S, Willink R, Crowell RE, Flores KG, Kang H, Byers T, Gilliland FD, Belinsky SA: Multivitamins, folate, and green vegetables protect against gene promoter methylation in the aerodigestive tract of smokers. Cancer Res. 2010 Jan 15;70(2):568-74. Epub 2010 Jan 12. [449] http://www.ncbi.nlm.nih.gov/pubmed/12192737. Romieu I, Trenga C: Diet and obstructive lung diseases. 2001;23(2):268-87.Epidemiol Rev. [450] http://www.cancer.gov/newscenter/pressreleases/ATBCfollowup. National Cancer Institute: Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Trial. [451] Albanes, Demetrius; Olli P. Heinonen, Philip R. Taylor, Jarmo Virtamo, Brenda K. Edwards, Matti Rautalahti, Anne M. Hartman, Juni Palmgren, Laurence S. Freedman, Jaason Haapakoski, Michael J. Barrett, Pirjo Pietinen, Nea Malila, Eero Tala, Kari Liippo, Eija-Riitta Salomaa, Joseph A. Tangrea, Lyly Teppo, Frederic B. Askin, Eero Taskinen, Yener Erozan, Peter Greenwald, and Jussi K. Huttunen: alfa-Tocopherol and beta- Carotene Supplements and Lung Cancer Incidence in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study: Eects of Base-line Characteristics and Study Compliance. J Natl Cancer Inst, Nov 1996; 88: 1560 1570. doi:10.1093/jnci/88.21.1560. [452] http://atvb.ahajournals.org/cgi/content/abstract/20/1/230. Jaana M. leppl, Jarmo Virtamo, Rainer Fogelholm, Jussi K. Huttunen, Demetrius Albanes, Philip R. Taylor, and Olli P. Heinonen : Controlled Trial of alfa-Tocopherol and beta-Carotene Supplements on Stroke Incidence and Mortality in Male Smokers. Arterioscler Thromb Vasc Biol 2000 20: 230 - 235. [453] http://jama.ama-assn.org/cgi/content/abstract/290/4/476. The ATBC Study Group: Incidence of Cancer and Mortality Following alfa-Tocopherol and betaCarotene Supplementation: A Postintervention Follow-up JAMA. 2003;290:476-485. [454] http://www3.interscience.wiley.com/cgi-bin/abstract/114110091/ ABSTRACT. Mitrou, Panagiota N.; Albanes, Demetrius; Weinstein, Stephanie J.; Pietinen, Pirjo; Taylor, Philip R.; Virtamo, Jarmo; Leitzmann, Michael F.: A prospective study of dietary calcium, dairy products and prostate cancer risk (Finland). International Journal of Cancer. DOI: 10.1002/ijc.22553 Published Online: 2 Feb 2007 1 June 2007, Volume120, Issue 11, Pages: 2466-2473. [455] http://www.ncbi.nlm.nih.gov/pubmed/19005195. Pischon T, Boeing H, Homann K, Bergmann M, Schulze MB, Overvad K, van der Schouw YT, Spencer E, Moons KG, Tjonneland A, Halkjaer J, Jensen MK, Stegger J, Clavel-Chapelon F, Boutron-Ruault MC, Chajes V, Linseisen J, Kaaks R, Trichopoulou A, Trichopoulos D, Bamia C, Sieri S, Palli D, Tumino R, Vineis P, Panico S, Peeters PH, May
680
CHAPTER 7. PHYSIOLOGY AM, Bueno-de-Mesquita HB, van Duijnhoven FJ, Hallmans G, Weinehall L, Manjer J, Hedblad B, Lund E, Agudo A, Arriola L, Barricarte A, Navarro C, Martinez C, Quirs JR, Key T, Bingham S, Khaw KT, Boetta P, Jenab M, Ferrari P, Riboli E.: General and abdominal adiposity and risk of death in Europe. N Engl J Med. 2008 Nov 13;359(20):2105-20.aqwxtdr.
[456] http://www.ncbi.nlm.nih.gov/pubmed/19223851. Besson H, Ekelund U, Luan J, May AM, Sharp S, Travier N, Agudo A, Slimani N, Rinaldi S, Jenab M, Norat T, Mouw T, Rohrmann S, Kaaks R, Bergmann M, Boeing H, Clavel-Chapelon F, Boutron-Ruault MC, Overvad K, Andreasen EL, Johnsen NF, Halkjaer J, Gonzalez C, Rodriguez L, Sanchez MJ, Arriola L, Barricarte A, Navarro C, Key TJ, Spencer EA, Orfanos P, Naska A, Trichopoulou A, Manjer J, Wirflt E, Lund E, Palli D, Agnoli C, Vineis P, Panico S, Tumino R, Bueno-de-Mesquita HB, van den Berg SW, Odysseos AD, Riboli E, Wareham NJ, Peeters PH.: A cross-sectional analysis of physical activity and obesity indicators in European participants of the EPICPANACEA study. Int J Obes (Lond). 2009 Apr;33(4):497-506. [457] http://www.ncbi.nlm.nih.gov/pubmed/19821492. Lahmann PH, Cust AE, Friedenreich CM, Schulz M, Lukanova A, Kaaks R, Lundin E, Tjonneland A, Halkjaer J, Severinsen MT, Overvad K, Fournier A, Chabbert-Buet N, Clavel-Chapelon F, Dossus L, Pischon T, Boeing H, Trichopoulou A, Lagiou P, Naska A, Palli D, Grioni S, Mattiello A, Tumino R, Sacerdote C, Redondo ML, Jakszyn P, Snchez MJ, Tormo MJ, Ardanaz E, Arriola L, Manjer J, Jirstrm K, Bueno-de-Mesquita HB, May AM, Peeters PH, Onland-Moret NC, Bingham S, Khaw KT, Allen NE, Spencer E, Rinaldi S, Slimani N, Chajes V, Michaud D, Norat T, Riboli E.: Anthropometric measures and epithelial ovarian cancer risk in the european prospective investigation into cancer and nutrition. Int J Cancer. 2009 Oct 9. [458] Mozaarian D, Hao T, Rimm EB, Willett WC, and Hu FB. Changes in diet and lifestyle and long-term weight gain in women and men. N Engl J Med, 364, 6 2011. http://www.nejm.org/doi/full/10.1056/NEJMoa1014296. [459] http://cebp.aacrjournals.org/cgi/content/abstract/15/10/1998. Susanna C. Larsson, Leif Bergkvist, and Alicja Wolk: Fruit and Vegetable Consumption and Incidence of Gastric Cancer: A Prospective Study; Cancer Epidemiol Biomarkers Prev 2006 15: 1998-2001. [460] http://www.pnas.org/cgi/content/abstract/93/8/3704. Mark Levine, Cathy Conry-Cantilena, Yaohui Wang, Richard W. Welch, Philip W. Washko, Kuldeep R. Dhariwal, Jae B. Park, Alexander Lazarev, James F. Graumlich, Jean King, and Louis R. Cantilena : Vitamin C pharmacokinetics in healthy volunteers: Evidence for a recommended dietary allowance Proc. Natl. Acad. Sci. 93, 3704-3709 (1996). [461] http://www.ajcn.org/cgi/content/abstract/83/3/567. S Goya Wannamethee, Gordon DO Lowe, Ann Rumley, K Richard Bruckdorfer, and Peter H Whincup :
BIBLIOGRAPHY
681
Associations of vitamin C status, fruit and vegetable intakes, and markers of inammation and hemostasis , Am J Clin Nutr 2006 83: 567-574. AJCN Doi: 2006 83: 525-526. [462] http://www.ajcn.org/cgi/content/full/83/3/525. Ishwarlal Jialal and Uma Singh: Is vitamin C an antiinammatory agent? Am J Clin Nutr 2006 83: 525526. [463] http://www3.interscience.wiley.com/cgi-bin/abstract/114171466/ ABSTRACT. Ra, Mohamed M.; Shafaie, Yassaman: Dietary lutein modulates inducible nitric oxide synthase (iNOS) gene and protein expression in mouse macrophage cells (RAW 264.7). Molecular Nutrition & Food Research. Volume 51, Issue 3, Pages 333-340. DOI:10.1002/mnfr.200600170. [464] Parisi, Vincenzo; Tedeschi, Massimiliano; Gallinaro, Geltrude; Varano, Monica; Saviano, Sandro; Piermarocchi, Stefano: Carotenoids and Antioxidants in Age-Related Maculopathy Italian Study: Multifocal Electroretinogram Modications after 1 Year. Ophthalmology (Elsevier) February 2008, Volume 115, Issue 2, Pages 324-333.e2 doi:10.1016/j.ophtha.2007.05.029. [465] http://www.amdalliance.org/. AMD Alliance International: AGE-RELATED MACULAR DEGENERATION. [466] http://www.ncbi.nlm.nih.gov/pubmed/19608872. Tuo J, Ross RJ, Herzlich AA, Shen D, Ding X, Zhou M, Coon SL, Hussein N, Salem N Jr, Chan CC: A High Omega-3 Fatty Acid Diet Reduces Retinal Lesions in a Murine Model of Macular Degeneration. American Journal Of Pathology, 2009; Am J Pathol. 2009 Jul 16. Doi: 10.2353/ajpath.2009.090089. [467] http://www.ajcn.org/cgi/content/abstract/87/4/964. Luc Djouss and J Michael Gaziano: Egg consumption in relation to cardiovascular disease and mortality: the Physicians Health Study. AJCN 2008 87: 964-969, April 2008. [468] http://www.ajcn.org/cgi/content/full/87/4/799. Eckel, Robert H.: Egg consumption in relation to cardiovascular disease and mortality: the story gets more complex. AJCN 2008 87: 799-800. [469] Jennifer S.L. Tan, Jie Jin Wang, Victoria Flood, Elena Rochtchina, Wayne Smith and Paul Mitchell: Dietary Antioxidants and the Long-term Incidence of Age-Related Macular Degeneration: The Blue Mountains Eye Study. Ophthalmology (Elsevier). February 2008, Volume 115, Issue 2, Pages 334-341. doi:10.1016/j.ophtha.2007.03.083. [470] http://www.efsa.europa.eu/EFSA/efsa_locale-1178620753812_ 1178717463740.htm. Scientic Opinion of the Panel on Dietetic Products Nutrition and Allergies on a request from the European Commission on the safety
682
CHAPTER 7. PHYSIOLOGY of synthetic Zeaxanthin as an ingredient in food supplements. The EFSA Journal (2008) 728, 1-28.
[471] http://en.wikipedia.org/wiki/Zeaxanthin. Wikipedia: Zeaxanthin. [472] http://archopht.ama-assn.org/cgi/content/abstract/125/9/1225. AgeRelated Eye Disease Study Research Group, SanGiovanni. John Paul; Chew, Emily Y. , et al.: The relationship of dietary carotenoid and vitamin A, E, and C intake with age-related macular degeneration in a case-control study: AREDS Report No. 22. (2007) Arch Ophthalmol 125 (9):1225-1232. [473] http://archopht.ama-assn.org/cgi/content/short/126/6/826. Chong, Elaine W-T.; Kreis, Andreas J.; Wong, Tien Y.; Simpson, Julie A.; Guymer, Robyn H.: Dietary omega-3 Fatty Acid and Fish Intake in the Primary Prevention of Age-Related Macular Degeneration. A Systematic Review and Meta-analysis. Arch Ophthalmol. 2008;126(6):826-833. [474] http://www.lshtm.ac.uk/ncdeu/currentresearch/eureye/. London School of Hygiene and Tropical Medicine: Age-related maculopathy and macular degeneration in elderly European populations: the EUREYE study. [475] http://www.ajcn.org/cgi/content/abstract/88/2/398. Augood, Cristina; Chakravarthy, Usha; Young, Ian; Vioque, Jesus; de Jong, Paulus TVM; Bentham, Graham; Rahu, Mati; Seland, Johan; Soubrane, Gisele; Tomazzoli, Laura; Topouzis, Fotis; Vingerling, Johannes R; Fletcher, Astrid E: Oily sh consumption, dietary docosahexaenoic acid and eicosapentaenoic acid intakes, and associations with neovascular age-related macular degeneration: American Journal of Clinical Nutrition, Vol. 88, No. 2, 398-406, August 2008. [476] http://archopht.ama-assn.org/cgi/content/abstract/126/6/834. Boekhoorn, Sharmila S.; Vingerling, Johannes R.; Hofman, Albert; de JonSg, Paulus T. V. M.: Alcohol Consumption and Risk of Aging Macula Disorder in a General Population. The Rotterdam Study. Arch Ophthalmol. 2008;126(6):834-839. [477] http://circ.ahajournals.org/cgi/content/abstract/103/24/2922. Dwyer, James H.; Navab, Mohamad; Dwyer, Kathleen M.; Hassan, Kholood; Sun, Ping; Shircore, Anne; Hama-Levy, Susan; Hough, Greg; Wang, Xuping; Drake, Thomas; Bairey Merz, C. Noel; Fogelman, Alan M.: Oxygenated Carotenoid Lutein and Progression of Early Atherosclerosis. The Los Angeles Atherosclerosis Study. Circulation. 2001;103:2922-2927. [478] http://www.nmcd-journal.com/article/PIIS0939475306000718/abstract. Lidebjer, C.; Leanderson, P.; Ernerudh, J.; Jonasson, L.: Low plasma levels of oxygenated carotenoids in patients with coronary artery disease. Nutrition, Metabolism and Cardiovascular Diseases, Volume 17, Issue 6, Pages 448-456 Juli 2007. Received
BIBLIOGRAPHY
683
24 June 2005; received in revised form 22 November 2005; accepted 17 February 2006. published online 28 June 2006. Doi: 10.1016/j.numecd.2006.02.006. [479] http://jn.nutrition.org/cgi/content/abstract/135/7/1763. Kato Kabagambe, Edmond; Furtado, Jeremy; Baylin, Ana; Campos, Hannia: Some Dietary and Adipose Tissue Carotenoids Are Associated with the Risk of Nonfatal Acute Myocardial Infarction in Costa Rica. J. Nutr. 2005 135: 1763-1769. [480] http://jn.nutrition.org/cgi/content/abstract/138/2/344. Buijsse, B.; Feskens, E. J. M.; Kwape, L.; Kok, F. J.; Kromhout, D.: Both (alpha)- and betaCarotene, but Not Tocopherols and Vitamin C, Are Inversely Related to 15-Year Cardiovascular Mortality in Dutch Elderly Men. J. Nutr., February 1, 2008; 138(2): 344 - 350. [481] http://www.ncbi.nlm.nih.gov/pubmed/18507882. Akbaraly TN, Favier A, Berr C: Total plasma carotenoids and mortality in the elderly: results of the Epidemiology of Vascular Ageing (EVA) study. Br J Nutr. 2009 Jan;101(1):86-92. Epub 2008 May 29. [482] Yoshiyuki Mizushina, Kiyotaka Nakagawa, Akira Shibata, Yasutoshi Awata, Isoko Kuriyama, Noriko Shimazaki, Osamu Koiwai, Yukinobu Uchiyama, Kengo Sakaguchi, Teruo Miyazawa and Hiromi Yoshida: Inhibitory eect of tocotrienol on eukaryotic DNA polymerase lambda and angiogenesis; Biochemical and Biophysical Research Communications; Pages 949-955. doi:10.1016/j.bbrc.2005.11.085. [483] Chandan K. Sen, Savita Khanna and Sashwati RoyTocotrienols: Vitamin E beyond tocopherols. Life Sciences; doi: 10.1016/j.lfs.2005.12.001. [484] http://aje.oxfordjournals.org/cgi/content/abstract/166/8/902. McCullough, Marjorie L.; Bandera, Elisa V.; Patel, Roshni; Patel, Alpa V.; Gansler, Ted; Kushi, Lawrence H.; Thun, Michael J.; Calle, Eugenia E.: A Prospective Study of Fruits, Vegetables, and Risk of Endometrial Cancer. American Journal of Epidemiology 2007 166(8):902-911; doi:10.1093/aje/kwm156. [485] http://aje.oxfordjournals.org/cgi/content/abstract/166/8/924. Ute Nthlings, Suzanne P. Murphy, Lynne R. Wilkens, Brian E. Henderson, and Laurence N. Kolonel: Flavonols and Pancreatic Cancer Risk: The Multiethnic Cohort Study. Advance Access published on August 9, 2007 . Am. J. Epidemiol. 2007 166: 924-931; doi:10.1093/aje/kwm172. [486] http://aje.oxfordjournals.org/cgi/content/abstract/kwm381v1. Kubo, Ai; Levin, T. R.; Block, Gladys; Rumore, Gregory J.; Quesenberry, Jr, Charles P. ; Buer, Patricia; Corley, Douglas A.: Dietary Patterns and the Risk of Barretts Esophagus. American Journal of Epidemiology. Published online ahead of print, doi:10.1093/aje/kwm381.
684
[487] http://www.blackwell-synergy.com/doi/abs/10.1111/j.1572-0241.2008. 01838.x. Kubo, Ai; Levin, Theodore R.;G. Block, Rumore, Gregory J.; Quesenberry, JrCharles P. Buer, Patricia; Corley, Douglas A.: Dietary Antioxidants, Fruits, and Vegetables and the Risk of Barretts Esophagus. American Journal of Gastroenterology. Volume 103, Pages 1-10, doi: 10.1111/j.1572-0241.2008.01838.x. [488] http://ajpregu.physiology.org/cgi/content/abstract/295/2/R505. Davis, J. M.; Murphy, E. A.; McClellan, J.L.; Carmichael, Gangemi, J. D.: Quercetin reduces susceptibility to inuenza infection following stressful exercise. Am J Physiol Regul Integr Comp Physiol 295: R505-R509, 2008. First published June 25, 2008; doi:10.1152/ajpregu.90319.2008. [489] http://www.cqvip.com/qk/84275X/200303/8153385.html. Wei, Hu; Ying, Sun; Ruiang, Ye; shushen, Wu; Honglai, Liu: Separation of Quercentin by Pre-dispersed Solvent Extraction. Chinese Journal of Chemical Engineering. 2003, Vol 11; Part 3, pages 367-370 . [490] Geleunse,J.M.;Launer,L.J., Hofman, A.; Pols, H.A.; Wittemann,J.C.: Tea avonoids may protect against atherosclerosis: The Rotterdam Study. Arch Intern. Med. 159 (18) (1999) 2170-4. [491] http://www.ncbi.nlm.nih.gov/pubmed/12845655. Wu AH, Yu MC, Tseng CC, Hankin J, Pike MC: Green tea and risk of breast cancer in Asian Americans.Int J Cancer, 2003 Sep 10;106(4):574-9. [492] http://jnci.oxfordjournals.org/cgi/content/abstract/89/7/488. Boyd NF, Greenberg C, Lockwood G, Little L, Martin L, Byng J, Yae M, Tritchler D.: Eects at two years of a low-fat, high-carbohydrate diet on radiologic features of the breast: results from a randomized trial. Canadian Diet and Breast Cancer Prevention Study Group. J Natl Cancer Inst. 1997 Apr 2;89(7):488-96. [493] http://cebp.aacrjournals.org/cgi/content/abstract/8/2/123. Knight JA, Martin LJ, Greenberg CV, Lockwood GA, Byng JW, Yae MJ, Tritchler DL, Boyd NF.: Macronutrient intake and change in mammographic density at menopause: results from a randomized trial.: Cancer Epidemiol Biomarkers Prev. 1999 Feb;8(2):123-8. [494] http://www.nature.com/bjc/journal/v83/n1/abs/6691151a.html. E Sala, R Warren, S Duy, A Welch, R Luben, N DayHigh risk mammographic parenchymal patterns and diet: a case-control study. Br J Cancer. 2000 Jul;83(1):121-6. doi:10.1054/bjoc.2000.1151. [495] http://www.springerlink.com/content/8143908638rr303j/. Martin LJ, Greenberg CV, Kriukov V, Minkin S, Jenkins DJ, Yae M, Hislop G, Boyd NF.: Eect of a low-fat, high-carbohydrate dietary intervention on change in mammographic density over menopause. Breast Cancer Res Treat. 2008 Jan 23.
BIBLIOGRAPHY
685
[496] http://www.thelancet.com/journals/lancet/article/ PIIS0140673697013391/abstract. Ingram D, Sanders K, Kolybaba M, Lopez D: Case-control study of phyto-oestrogens and breast cancer. Lancet. 1997 Oct 4;350(9083):990-4. [497] http://www3.interscience.wiley.com/cgi-bin/abstract/91015062/ABSTRACT. Dos Santos Silva I, Mangtani P, McCormack V, Bhakta D, Sevak L, McMichael AJ.: Lifelong vegetarianism and risk of breast cancer: a population-based case-control study among South Asian migrant women living in England. Int J Cancer. 2002 May 10;99(2):238-44. [498] http://www.springerlink.com/content/l55j08l3572683j0/. dos Santos Silva I, Mangtani P, McCormack V, Bhakta D, McMichael AJ, Sevak L.: Phyto-oestrogen intake and breast cancer risk in South Asian women in England: ndings from a population-based case-control study. Cancer Causes Control. 2004 Oct;15(8):805-18. 10.1023/B:CACO.0000043431.85706.d8. [499] http://www.dailymail.co.uk/health/article-1038118/ Are-danger-drinking-water.html#. Daily Mail : Are we in danger of drinking too much water? By Sarah Chalmers Last updated at 11:04 PM on 23rd July 2008. [500] Policy statement - climatic heat stress and exercising children and adolescents. Pediatrics Vol. http://pediatrics.aappublications.org/content/early/2011/08/ 04/peds.2011-1664.full.pdf. [501] Climatic heat stress and the exercising child and adolescent. american academy of pediatrics (aap). Pediatrics Vol, 106(1):158159, 2000. http://pediatrics. aappublications.org/content/106/1/158.full. [502] Nutrition-related policy statements. http://www.aap.org/visit/nutrpolicies. htm. [503] http://www.independent.co.uk/news/uk/home-news/ hydration-diet-woman-awarded-163810000-damages-874864.html. The Independent: Hydration Diet woman awarded 810,000 Pounds damages. 23.07.08. [504] http://www.thejoshiclinic.com/. The Joshi Clinic. [505] http://www.fsascience.net/2007/12/27/dump_the_detox?from=50&comments_ per_page=50. FSA: Dump the detox. Andrew Wadge, December 27. 2007. in Science, Safety and Health. [506] http://www.food.gov.uk/multimedia/pdfs/ec19242006complianceguide.pdf. FSA: Guidance to compliance with European Regulation (EC) No 1924/2006 on nutrition and health claims made on foods. Tuesday, 13 May 2008 Section 9 (9.1) 8Is detox a nutrition or a health claim?
686
[507] Menjong Sorig Pharmaceuticals. Http://www.menjongpharma.com.bt. [508] http://www.health.gov.bt/ITMS/01index/01htm/01index.htm. Institute of Traditional Medicine Services: Traditional Medicine, Wisdom of Nature. [509] http://www.senseaboutscience.org.uk/pdf/MakingSenseofChemicalStories. pdf. Sense about Science: Making sense of chemical stories. A brieng for the lifestyle sector on misconceptions about chemicals. [510] http://en.wikipedia.org/wiki/Detox_diet. Wikipedia: Detox diet. [511] http://nccam.nih.gov/health/whatiscam/. The National Center for Complementary and Alternative Medicine (NCCAM): What is CAM? [512] http://pediatrics.aappublications.org/cgi/content/full/122/6/1374. Kemper, Kathi J.; Vohra, Sunita; Walls, Richard, the Task Force on Complementary and Alternative Medicine the Provisional Section on Complementary, Holistic, and Integrative Medicine: The Use of Complementary and Alternative Medicine in Pediatrics. From the American Academy of Pediatrics. Pediatrics, Dec 2008; 122: 1374-1386. [513] http://www.legislation.gov.uk/uksi/2006/1952/contents/made. The Medicines for Human Use (National Rules for Homoeopathic Products) Regulations 2006 No.1952. [514] http://www.parliament.the-stationery-office.co.uk/pa/ld199900/ ldhansrd/pdvn/lds06/text/61026-0008.htm. Lord Taverne: Medicines for Human Use (National Rules for Homeopathic Products) Regulations 2006. 26 Oct 2006 : Column 1328. UK Parliament. [515] FDA. Supplemental petition for regulation of quicktest 5, inc.s nicowater. http: //www.fda.gov/ohrms/dockets/dailys/03/Mar03/032703/80059bae.pdf. [516] http://en.wikipedia.org/wiki/Current_Procedural_Terminology. Procedural Terminology. Current
[517] http://www.whccamp.hhs.gov/fr1.html. White House Commission on Complementary and Alternative Medicine Policy. Final report 2002. [518] http://www.fda.gov/Food/DietarySupplements/ucm109764.htm. FDA: New Dietary Ingredients in Dietary Supplements - Background for Industry. [519] http://www.fda.gov/opacom/laws/DSHEA.html. Dietary Supplement Health and Education Act of 1994. Public law No. 103-417 (1994). Accessed November 29, 2006.
BIBLIOGRAPHY
687
[520] http://jnci.oxfordjournals.org/cgi/content/abstract/88/6/340. Freudenheim JL, Marshall JR, Vena JE, Laughlin R, Brasure JR, Swanson MK, Nemoto T, Graham S.: Premenopausal breast cancer risk and intake of vegetables, fruits, and related nutrients. J Natl Cancer Inst. 1996 Mar 20;88(6):340-8. [521] http://www.informaworld.com/smpp/content~content=a785830981~db= all~order=page. Adzersen KH, Jess P, Freivogel KW, Gerhard I, Bastert G. Raw and cooked vegetables, fruits, selected micronutrients, and breast cancer risk: a case-control study in Germany. Nutr.Cancer. 2003;46(2):131-7. DOI: 10.1207/S15327914NC4602_05. [522] http://carcin.oxfordjournals.org/cgi/content/abstract/bgn072v1. Persson, Christina; Sasazuki, Shizuka;Inoue, Manami; Kurahashi, Norie; Iwasaki, Motoki; Miura, Tsutomu; Ye, Weimin; Tsugane Shoichiro: Plasma levels of carotenoids, retinol, and tocopherol and the risk of gastric cancer in Japan: A nested case-control study. Carcinogenesis, March 13, 2008. Doi:10.1093/carcin/bgn072. [523] http://www3.interscience.wiley.com/cgi-bin/abstract/112101282/ ABSTRACT. Shaun K. Rodriguez, Weimin Guo, Liping Liu, Michael A. Band, Eric K. Paulson, Mohsen MeydaniCancer Cell Biology: Green tea catechin, epigallocatechin-3-gallate, inhibits vascular endothelial growth factor angiogenic signalling by disrupting the formation of a receptor complex. International Journal of Cancer. Volume 118, Issue 7, Pages 1635-1544. Published Online: 10 Oct 2005. [524] http://jn.nutrition.org/cgi/content/full/138/2/323. Bruno, Richard S.; Dugan, Christine E.; Smyth, Joan A.; DiNatale, Dana A.; Koo, Sung I.: Green tea extract protects leptin-decient, spontaneously obese mice from hepatic steatosis and injury. Journal of Nutrition. February 2008, Volume 138, Pages 323-331. [525] http://aje.oxfordjournals.org/cgi/content/abstract/kwm338v1. Tan, Louis C.; Koh, Woon-Puay; Yuan, Jian-Min; Wang, Renwei; Au, Wing-Lok; Tan, June H.; Tan, Eng-King; Yu, Mimi C.: Dierential Eects of Black versus Green Tea on Risk of Parkinsons Disease in the Singapore Chinese Health Study. American Journal of Epidemiology Published online ahead of print 20 December 2007, doi:10.1093/aje/kwm338. [526] http://nutraingredients.com/news/ng.asp?n=83458-black-tea-catechins-parkinson-s. Nutraingredients: Black tea may slash Parkinsons disease risk. 22.02.2008. [527] Kumudavally, K.V; Phanindrakumar, H.S.; Tabassum, A.; Radhakrishna, K.; Bawa, A.S.: Green tea - A potential preservative for extending the shelf life of fresh mutton at ambient temperature (25 degrees Celsius). Food Chemistry (Elsevier) 1 March 2008, Volume 107, Issue 1, Pages 426-433, doi: 10.1016/j.foodchem.2007.08.045.
688
[528] http://www.joponline.org/doi/abs/10.1902/jop.2009.080510. Kushiyama, Mitoshi; Shimazaki, Yoshihiro; Murakami, Masatoshi; Yamashita, Yoshihisa: Relationship Between Intake of Green Tea and Periodontal Disease. Journal of Periodontology, 2009; 80 (3): 372 DOI: 10.1902/jop.2009.080510. [529] http://archinte.ama-assn.org/cgi/content/short/166/4/411. Brian Buijasse, Edith J.N. Feskens, Frans J. Kock, Daan Kromhout,: Cocoa Intake, Blood Pressure, and Cardiovascular Mortality. The Zutphen Elderly Study. Arch Intern Med. 2006; 166: 411-417. [530] http://news.bbc.co.uk/1/hi/health/4755108.stm. heart disease; Tuesday, 28 February 2006, 02:10 GMT. BBC News: Cocoa cuts
[531] http://www.kenes.com/easl2010/orals/124.htm. De Gottardi A, Berzigotti A, Seijo S, DAmico M, Abraldes J, Garcia-Pagn JC, Bosch J:Dark chocolate attenuates the post-prandial increase in HVPG in Patients with cirrhosis and portal hypertension. Oral Presentation at the International Liver Congress. April 15, 2010. [532] http://www.ncbi.nlm.nih.gov/pubmed/18806104. Di Giuseppe R, di Castelnuovo A, Centritto F, et al. Regular consumption of dark chocolate is associated with low serum concentrations of C-reactive protein in a healthy Italian population. J Nutr 2008; 138: 1939-1945. [533] http://www.ncbi.nlm.nih.gov/pubmed/19889244. Spadafranca A, Martinez Conesa C, Sirini S, Testolin G.: Eect of dark chocolate on plasma epicatechin levels, DNA resistance to oxidative stress and total antioxidant activity in healthy subjects. Br J Nutr. 2009 Nov 5:1-7. [534] http://www.ncbi.nlm.nih.gov/pubmed/19910929. Desch S, Schmidt J, Kobler D, Sonnabend M, Eitel I, Sareban M, Rahimi K, Schuler G, Thiele H.: Eect of Cocoa Products on Blood Pressure: Systematic Review and Meta-Analysis. Am J Hypertens. 2009 Nov 12. doi:10.1038/ajh.2009.213. [535] Nehlig A. The neuroprotective eects of cocoa avanol and its inuence on cognitive performance. Br J Clin Pharmacol, 7 2012. http://www.ncbi.nlm.nih.gov/ pubmed/22775434. [536] Williams RJ and Spencer JP. Flavonoids, cognition, and dementia: actions, mechanisms, and potential therapeutic utility for alzheimer disease. Free Radic Biol Med, 52(1):3545, 1 2012. http://www.ncbi.nlm.nih.gov/pubmed/21982844. [537] http://www.ncbi.nlm.nih.gov/pubmed/19883072. Arlorio M, Bottini C, Travaglia F, Locatelli M, Bordiga M, Coisson JD, Martelli A, Tessitore L.: Protective activity of Theobroma cacao L. phenolic extract on AML12 and MLP29 liver cells by preventing apoptosis and inducing autophagy. J Agric Food Chem. 2009 Nov 25;57(22):10612-8.
BIBLIOGRAPHY
689
[538] Neilson AP, Sapper TN, Janle EM, Rudolph R, Matusheski NV, and Ferruzzi MG. Chocolate matrix factors modulate the pharmacokinetic behavior of cocoa avan3-ol phase ii metabolites following oral consumption by sprague-dawley rats. J Agric Food Chem, 58(11):668591, 6 2010. http://www.ncbi.nlm.nih.gov/pmc/ articles/PMC2892903/?tool=pubmed. [539] http://www.ncbi.nlm.nih.gov/pubmed/19899259 http://pubs.acs.org/doi/ abs/10.1021/jf1005353. Rabinerson D, Melamed N.: On bitter and sweet-women and chocolate. Harefuah. 2009 Aug;148(8):539-42, 571, 570. Hebrew. [540] http://counsellingresource.com/quizzes/cesd/index.html. Welcome to the Center for Epidemiologic Studies Depression Scale (CES-D), A Screening Test for Depression. [541] http://pubs.acs.org/cgi-bin/abstract.cgi/jafcau/asap/abs/jf0728754. html. Andres-Lacueva, C.; Monagas, M.; Khan, N.; Izquierdo-Pulido, M.; UrpiSarda, M.; Permanyer, J.; Lamuela-Raverntos, R.M.: Flavanol and Flavanol Contents of Cocoa Powder Products: Inuence of the Manufacturing Process. Journal of Agricultural and Food Chemistry. Published online ahead of print April 2008, doi: 10.1021/jf0728754. [542] Othman, Azizah; Ismail, Amin; Ghani, Nawalyah Abdul; Adenan, Ilham: Antioxidant capacity and phenolic content of cocoa beans Food Chemistry, Volume 100, Issue 4, 2007, Pages 1523-1530 . Doi:10.1016/j.foodchem.2005.12.021. [543] Jona-Essien, W.A.; West, G.; Alderson, P.G.; Tucker, G.: Phenolic content and antioxidant capacity of hybrid variety cocoa beans. Food Chemistry 108 (2008) 11551159. Doi: 10.1016/j.foodchem.2007.12.001. [544] http://journals.cambridge.org/action/displayAbstract?fromPage= online&aid=1590848. Cooper, Karen A.; Donovan, J.L.; Waterhouse, A.L.; Williamson, G.: Cocoa and health: a decade of research. British Journal of NutritionPublished on-line ahead of print. Doi: 10.1017/S0007114507795296. [545] Sanderson J, Johnson L, Warnakula S, WoodA, Di Angelantonio E, and Franco OH. Chocolate consumption and cardiometabolic disorders: systematic review and metaanalysis. BMJ, 343:d4488, 8 2011. http://www.bmj.com/content/343/bmj.d4488. [546] Foodwatch geisselt werbung fuer milch-schnitte. 29.04.2011. Der Westen. http://www.derwesten.de/nachrichten/wirtschaft-und-finanzen/ Foodwatch-geisselt-Werbung-fuer-Milch-Schnitte-id4589486.html. [547] Golomb BA, Koperski S, and White HL. Association between more frequent chocolate consumption and lower body mass index. Arch Intern Med, 172(6):51921, 3 2012. http://archinte.ama-assn.org/cgi/content/extract/172/6/519.
690
[548] http://jxb.oxfordjournals.org/cgi/content/full/54/384/913. Yamagata,Tomomi; Kato, Hisanao; Kuroda, Satoshi; Abe, Shunnosuke and Davies, Eric: Uncleaved legumin in developing maize endosperm: identication, accumulation and putative subcellular localization. Journal of Experimental Botany, Vol. 54, No. 384, pp. 913-922, March 1, 2003. [549] http://www.springerlink.com/content/l36086uptv4hx874/. Boulter, Donald: Protein composition of grains of the leguminosae. Plant Foods for Human Nutrition DOI 10.1007/BF01091189. [550] http://pubs.acs.org/cgi-bin/abstract.cgi/jafcau/2002/50/i15/abs/ jf020007v.html. Shridhar K. Sathe, Walter J. Wolf, Kenneth H. Roux, Suzanne S. Teuber, Mahesh Venkatachalam, and Kar Wai Clara Sze-Tao Biochemical Characterization of Amandin, the Major Storage Protein in Almond (Prunus dulcis L.) J. Agric. Food Chem., 50 (15), 4333-4341. [551] http://www.genscript.com/product_001/western_application/grp_id/ 47065/op/protein/Legumin_protein_Western_Analysis.html. GenScript: One Step Western Kit. [552] http://en.wikipedia.org/wiki/Nopal. Wikipedia, the free enzyclopedia: Nopal. [553] http://care.diabetesjournals.org/cgi/content/extract/30/5/1264. Bacardi-Gascon, Montserrat; Duenas-Mena, Dulce; and Jimenez-Cruz, Arturo:Lowering Eect on Postprandial Glycemic Response of Nopales Added to Mexican Breakfasts. Diabetes Care 2007, Volume 30: 1264-1265. [554] http://www.invasivespeciesinfo.gov/animals/cactusmoth.shtml. USDA National Agricultural Library: Invasive Species: Cactus Moth. [555] Rozan, P.; Hidalgo, S.; Nejdi, A.; Bisson, J.-F.; Lalonde, R.; Messaoudi M. (2007): Preventive Antioxidant Eects of Cocoa Polyphenolic Extract on Free Radical Production and Cognitive Performances after Heat Exposure in Wistar Rats Journal of Food Science 72 (3), S203-S206. doi:10.1111/j.1750-3841.2007.00297.x https//dx.doi.org/10.1111/j.1750-3841.2007.00297.x. [556] http://www.dfhcc.harvard.edu/membership/member-profile/member/586/0/. Hollenberg Norman; Capone, Diana: Research Abstract: The Kuna indians of Panama, dietary avanoids, nitric oxide and vascular function. DF/HCC Program Aliation. Dana-Farber/Harvard Cancer Center. [557] http://www.timesonline.co.uk/tol/news/uk/science/article3471372.ece. The Times: Jungle frogs anti-infection agent may help millions of diabetics. March 3, 2008.
BIBLIOGRAPHY
691
[558] http://www.uspharmacist.com/index.asp?show=article&page=8_1377.htm. Schnabel, Catherine A.; White, Jr., John R.; Campbell, R. Keith: Incretin Mimetics and DPP-IV Inhibitors in the Treatment of Type 2 Diabetes Mellitus. US Pharm. 2004;11:35-49. [559] http://www.jem.org/cgi/content/abstract/jem;204/3/657. Jiang, Youchun; Reynolds, Corey; Xiao, Chang; Feng, Wenke; Zhou, Zhanxiang; Rodriguez, Walter; Tyagi, Suresh C.; Eaton, John W.; Saari, Jack T.; Kang, Y. James: Dietary copper supplementation reverses hypertrophic cardiomyopathy induced by chronic pressure overload in mice J. Exp. Med. 2007 204: 657-666. doi:10.1084/jem.20061943. [560] http://www.jem.org/cgi/content/full/jem;204/3/455a. Heavy metal for a troubled heart. J. Exp. Med. 2007 204: 455. Bashyam, Hema:
[561] http://www.nal.usda.gov/fnic/foodcomp/Data/SR17/wtrank/wt_rank.html. USDA National Nutrient Database for Standard Reference, Release 17 Nutrient Lists. [562] http://www.ajcn.org/cgi/content/abstract/86/2/373. Hartman, Joseph W; Tang, Jason E; Wilkinson, Sarah B; Tarnopolsky, Mark A; Lawrence, Randa L; Fullerton, Amy V; Phillips, Stuart M: Consumption of fat-free uid milk after resistance exercise promotes greater lean mass accretion than does consumption of soy or carbohydrate in young, novice, male weightlifters. American Journal of Clinical Nutrition, Vol. 86, No. 2, 373-381, August 2007. [563] http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5616a2.htm. CDC: Fixed Obstructive Lung Disease Among Workers in the Flavor-Manufacturing IndustryCalifornia, 2004-2007. 27.04.2007. [564] http://democrats.assembly.ca.gov/newsline/releases/20070221ad22pr01. htm. Democrats Assembly, California: Lieber Introduces Three-Bill Package To Reduce Toxic Chemicals. 21.02.2007. [565] http://www.osha.gov/pls/oshaweb/owadisp.show_document?p_table= TESTIMONIES&p_id=372. US Department of Labour. Ocupational Safety and Health Administration: Statement of Edwin G. Foulke, Jr. 24.04.2007. [566] http://toxsci.oxfordjournals.org/cgi/content/abstract/kfn016v1. Morgan, D.; Flake, G.; Kirby, P.;Palmer, S.: Respiratory Toxicity of Diacetyl in C57BI/6 mice. Toxicological Sciences ToxSci Advance Access publishedonline on January 27, 2008 DOI: 10.1093/toxsci/kfn016. [567] http://eur-lex.europa.eu/LexUriServ/site/en/oj/2005/l_128/l_ 12820050521en00730076.pdf. COMMISSION DECISION of 18 May 2005 amending Decision 1999/217/EC as regards the register of avouring substances used in or on foodstus.
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CHAPTER 7. PHYSIOLOGY Wikipedia:
[568] http://en.wikipedia.org/wiki/Image:Diacetyl_structure.png. Diketone.
[569] http://www.foodcomm.org.uk/latest_flavourings_Feb08.htm. The Food Magazine: Faking the avour. Issue 80, 25th February 2008. [570] http://www.foodcomm.org.uk/. 25.02.2008. The Food Commission: Faking the avour
[571] http://www.efsa.europa.eu/EFSA/efsa_locale-1178620753812_ 1211902029226.htm. EFSA: Camphor in avourings and other food ingredients with avouring properties - Opinion of the Scientic Panel on Food Additives, Flavourings, Processing Aids and Materials in Contact with Food on a request from the Commission Question number: EFSA-Q-2003-144 Publication date: 30/07/2008.
Chapter 8 Fruits and Vegetables

8.0.10 Fibre and sh reduces the risk of Colon cancer, while red and processed meats, alcohol and low physical activity increases that risk [1]
WHO presents a summary of the results of the EPIC Project: Colon Cancer The results of the study, together with the PLCO cohort of the NIH-NCI study, support that a diet high in bre reduces colorectal cancer risk. The EPIC also found that consumption of red and processed meat increases colorectal cancer risk while intake of sh decreases risk. The combination of these four dietary factors (i.e. bre, sh, red and processed meats) plays a major role in colorectal cancer aetiology in addition to alcohol intake, obesity and low physical activity. Breath cancer Obesity and the consumption of fruit and vegetables is not associated with breath cancer risk. We found that is not associated with breast cancer risk. Prostate cancer Prostate cancer risk is not related to fruit and vegetable consumption. Genetic factors The group has initiated large investigations of the role of polymorphisms in genes involved in the metabolism of steroid hormones and growth factors that have a role in the aetiology of breast and prostate cancers in combination with lifestyle and metabolic factors. Heart disease A higher intake of fruits and vegetables was found by the EIPC study to be linked to a lower risk of ischaemic heart disease (IHD), however, the study could not nd out whether this association is causal. Also remains unclear how fruits and vegetable act to reduce heart disease risks. [2]
8.0.11
Red meat may increase risk of aggressive prostate cancer
Witte et al.2011 write that increased consumption of ground beef or processed meat is positively associated with aggressive prostate cancer, whereas red meat that was grilled or well done barbeque is especially aggressive.[3] 693
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High levels of well or very well cooked ground beef were found in this study to double the risk of aggressive prostate cancer and low consumption raised the risk to 1.5 compared to men who ate none. However, consumption of rare or medium cooked ground beef was not linked to prostate cancer. The authors suggest that meat mutagens Dimethylimidazo-[4,5f]Quinoaxine(MelQx) and 2-amino-3,4,8-trimethylimidazo(4,5-f)qunioxaline(DiMelQx), formed during cooking meat at high temperatures. Carcinogenic heterocyclic amines (HCA). HCA and polycyclic aromatic hydrocarbon (PAHs) are formed in red meat at high temperatures, especially when fat and juice is burned at open re. Changing to Western diets high in red meat may increase risk of colon cancer of Asian population [4] Asian populations have changed from traditional to Westernized diets high in red meat. In a study of Sotos Prieto et al 2011 higher consumption of red meat was signicantly associated with a higher risk of proximal colon cancer among women and for distal colon cancer among men. The authors, however, found that processed meat did not cause colon or rectal cancer. High red meat consumption of Spanish men leads to cardiovascular risk and obesity [5] Sotos et al 2011 found that in the Spanish Mediterranean elderly population red meat consumption of 7.4 4.7 times/week is too high, being higher in men than in women. It was associated with obesity and cardiovascular risk (CVR). Fish consumption of 4.5 2.6 time/week is high and should be maintained at this level because it reduces the prevalence of diabetes. Processed meat and type 2 diabetes [6] A study by Lajous et al 2011 also found that high intake of processed meat, 5 servings/week (median, 48 g/day), was signicantly associated with type 2 diabetes, compared with low intake of less than 1 serving/week (median, 5 g/day) of processed meat. Unprocessed red meat was not associated with diabetes. Iron of red meat increase cancer risk [7] Ward et al 2011 report that high intakes of heme and iron from meat increase the risk of esophageal and stomach cancer, these ndings are associations with red meat. Iron intake from all other dietary sources were found not associated with risk of either cancer. The authors explains that heme iron can catalyse endogenous formation of carcinogenic N-nitroso compounds.
695 Genotoxicity of red meat may increase colorectal cancer risk [8] Hebels et al 2011 report that their study found that faecal water genotoxicity signicantly increased in response to red meat intake. Transcriptomic analyses revealed that activity of genes of biologic genotoxic pathway signicantly correlated with the increase in fecal water resulting from red meat intake. This included modications in DNA damage repair, cell cycle, and apoptosis pathways. Moreover, WNT signaling and nucleosome remodeling pathways were modulated, indicating human colorectal cancer development. The WNT signaling pathway is a network of proteins best known for their roles in embryogenesis and cancer, but also involved in normal physiological processes in adult animals. Red mead increases colorectal cancer, sh reduces the risk and poultry is not related to the disease [9] Riboldi et al 2005 found that colorectal cancer risk increases with the intake of read meat and processed meat. However, the risk decreased intake of sh. Poultry was found not to inuence risk of colorectal cancer. For subjects aged 50 years the risk is 1.71% for high of more than 160 g/d of processed meat intake, and 1.28% for less than 20 g/day of intake. For sh intake less than 10 g/d the risk is 1.86% and 1.28% for subjects with more than 80g/d of sh intake. Low consumption of red meat and high intake of poultry and sh reduces risk of ovarian cancer Kolahdoozmf2ausc A study of Kolahdooz and colleagues 2010 suggests that that low consumption of processed meat and higher consumption of poultry and sh are associated with reduce the risk of ovarian cancer. Red meat and processed meat increases pancreatic cancer risk [10] Larsson and Wolk 2012 conducted a meta-analysis of 11 prospective studies with 6643 pancreatic cancer cases. The authors found that consumption of red meat was associated with an increase in pancreatic cancer risk in men (RR=1.29), but not in women (RR=0.93) and 120g red meat per day was associated with an overall relative risk (RR=1.13), 50g per day increase in processed meat consumption was (RR=1.19). The 2007 World Cancer Research Fund/American Institute of Cancer Research [11] The 2007 report of the World Cancer Research Fund/American Institute of Cancer Research presented convincing evidence that red meats and processed meats are a cause of
696
colorectal cancer. There is limited evidence suggesting that red meat is a cause of cancers of the oesophagus, lung, pancreas and endometrium. Cantonese-style salted sh is a probable cause of nasopharyngeal cancer. There is also limited evidence that animal foods that are grilled (broiled), barbecued (charbroiled), or smoked, are a cause of stomach cancer. The report uses the term "red meat" to refer to beef, pork, lamb, and goat from domesticated animals, and the term "processed meat" to refer to meats preserved by smoking, curing, or salting, or addition of chemical preservatives. High intake of red and processed meat associated with colorectal, colon and rectal cancer [12] Ten recent prospective studies were assessed by Chan et al. 2011. They concluded that high intake of red and processed meat increases signicantly the risk of colorectal, colon and rectal cancers, and suggest to limit these foods in dietary recommendation. Of cancer prevention. Overall, the relative risk (RR) of colorectal cancer for the highest versus the lowest intake was 1.22 and the RR for every 100 g/day increase was 1.14, and the risk increases linearly with increasi intake of red and processed meats up to approximately 140 g/day, where the curve approaches its plateau. Red and processed meat intake not associated with prostate cancer [13] Alexander et al. 2012 analysed data of fteen studies of red meat and 11 studies of processed meat. No association with high red meat consumption and total prostate cancer was observed. However a weakly association between processed meat and total prostate cancer was found but data were not conclusive. The stress that independent positive association between red or processed meat intake and prostate cancer could not be supported. Red meat consumption increases mortality rates [14] A study of Pan et al. 2012 supports the long ongoing hypothesis that red meat consumption increases the risk of total, CVD, and cancer mortality. The data of more than 120.000 observations and dietary habits of 2 prospective cohort studies over the course of 20-30 years demonstrate that people eating daily red meats, such as hot dogs, sausages and other processed red meats, had a 20% increase in mortality rate. The substitutions of 1 serving of red meat per day by other foods, such as sh, poultry, nuts, legumes, low-fat dairy, and whole grains, reduces mortality risk by 7% to 19%, and 9.3% of deaths in men and 7.6% in women could be prevented when less than 0.5 servings per day (42 g/d) of red meat are consumed, estimate the authors. Pan and colleagues also stress that adjustment for saturated fat, dietary cholesterol, and
8.1. EFFECT OF FRUIT JUICES
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heme iron accounted for some but not all of the risk of eating red meat. Thus, other mechanisms such as nontraditional risk factors may be involved, such as healthy eects of plant based foods, rich in phytochemicals, bioavonoids replacing red meat. Considering isolated changes in weight, blood pressure, and lipid levels in High-Fat, HighProtein, Low-Carbohydrate (HPLC) diets may underestimate the negative inuence of HPLC diets on health outcomes, such as morbidity and mortality, comments Ornish 2012 He rearms the basis of healthy nutrition [15]: - Little or no red meat, - high vegetables, fruits, whole grains, legumes, and soy products, - low in simple and rened carbohydrates, such as sugar, high-fructose corn syrup, and white our, - high in omega-3 fatty acids found in sh oil, ax oil, - low in trans fats, saturated fats, and hydrogenated fats.
8.1
8.1.1
Eect of fruit juices

Concord grape juice may enhance memory in older people [16]
Robert Krikorian, Barbara Shukitt-Hale and colleagues 2009 claim that Concorde grape juice improved verbal learning and enhanced verbal and spatial recall in 12 older adults with memory decline but not dementia. A previous study by Shukitt-Hale and colleagues 2006 reported that Concord grape juice appeared to reverse the course of neuronal and behavioural ageing in rats. [17]
8.1.2
Eect of diets rich in fuits and vegetables on cognitive function
Healthy diet does not only reduce risk of heart disease, obesity and diabetes but has a deep impact on psychiatric and neurologic conditions, such as depression and dementia. Many studies assessed the improving of cognitive function are related to this issue. Polyphenol-rich Mediterranean diet and better cognitive function at old age [?] Studies suggest that consumption of antioxidant-rich foods may reduce brain oxidative processes, responsible for cognitive decline in aged persons. Valls-Pedret et al.2012 looked at the link between antioxidant-rich foods in the Mediterranean diet and cognitive function in elderly subjects enrolled in the PREDIMED study.
698
The authors determined apolipoprotein E genotype, measured urinary polyphenols as intake biomarker. Cognitive function was assessed by neuropsychological tests. Urinary polyphenols were associated with better scores in immediate verbal memory. The authors concluded that increased consumption of antioxidant-rich foods such as found in the Mediterranean diet, may reduce age-related cognitive decline.
Diet high in polyphenols, such as avonoids consumed in midlife improves brain functions 13 years later [18] Kesse-Guyot et al. 2012 report that high total polyphenol intake of catechins, theaavins, avonols, and hydroxybenzoic acids was positively associated with language and verbal memory, especially with episodic memory, but not with executive functioning. Intake of dihydrochalcones, catechins, proanthocyanidins, and avonols exert a negative eect on executive functioning . The authors stress that high intake of specic polyphenols, including avonoids and phenolic acids, found in plant-foods, may help to preserve verbal memory.
Dierential eect of fruit and vegetables groups on cognitive function in SU.VI.MAX 2 cohort study [19] A 13-years association between fruit and vegetables intake and cognitive performance of subjects which were part of the Supplementation with Antioxidant Vitamins and Minerals 2 (SU.VI.MAX 2) cohort was assessed by Pneau et al. 2011 with controversial nding. - Intake of fruit alone, vitamin C-rich FVs, vitamin C, and vitamin E were positively associated with verbal memory scores. - Intake of vegetables alone, and -carotene-rich fruit and vegetables were negatively associated with executive functioning scores. The authors point to a possible dierential eect of groups of plant-food on cognition and call for more studies to clarify these data on age-related cognitive impairment.
Blueberries improves memory in older adults [20] Krikorian and colleagues 2012 report that juice of wild blueberries have antioxidant and anti-inammatory eects because of their content of polyphenolic compounds, such as anthocyanins. Studies associated these anthocyanins with increased neuronal signaling in brain centers, mediating memory function as well as improved glucose disposal, all of what could reduce neurodegeneration. Krikorian found in the study that nine elderly persons improved memory and neurocognitive.
8.1. EFFECT OF FRUIT JUICES Blackberries improves motor and cognitive function in aged rats [21]
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The polyphenolics in fruits and vegetables have retarded and even reversed age-related decrements in motor and cognitive performance, which may be the result of the polyphenols increasing antioxidant and/or anti-inammatory levels, or by direct eects on signaling, in the brain, according to Shukitt-Hale and colleagues 2009. The authors report that a 2% blackberry-supplemented diet reversed age-related decits in behavioural and neuronal function, improving motor performance on three tasks which rely on balance and co-ordination.
Review on berry supplementation and age-related cognitive decline [22] Willis, Shukitt-Hale,and colleagues 2009, in a review found that antioxidant-rich berries consumed in the diet can positively impact learning and memory in the aged animal due to the direct interaction of berry polyphenols with ageing neurons, reducing the impact of stress-related cellular signals and increasing the capacity of neurons to maintain proper functioning during ageing.
Plum juice, but not dried plum powder, is eective in mitigating cognitive decits in aged rats [23] Shukitt-Hale and colleagues 2008 assessed the eect of supplementation of 2% of plum (Prunus domestica) as 100% juice und as plum powder. The authors found that plum juice improved working memory, whereas no improvement was noted with plum powder, compared with rats subjected to a diet without plum.
8.1.3
Ecology of the Amazon region endangered by worldwide acai marketing [24]
Protable market for palm hearts and acai products exert great pressure on the Amazon ecology. The natural rainforest lands are clear-cut for mass cultivation of acai, following a project of planting 5 billion acai trees in the next 10 years. Soy plantations, cattle farming and exotic plantations like acai endanger nature, deprive poor native population of acai as aordable food. In 2008 Marina Silva resigned as environment minister after the Amazon development project was taken away from her and given to the Harvard Professor Roberto Mangabeira Unger who wants to include the Amazon Region in one of the greatest agro-industry project ever seen. It will boost Brazilian ethanol production to replace 5% of crude oil by 20025. The sustainable use of the acai palm by the local population and indian tribes is changed to a mass-production to feed the international market. [25]
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Embrapa undermining the sustainability of the Amazon Region [26] Embrapa, a department of the Brazilian government, forces the development of acai production and export. Embrapa says that already 200,000 km2 of the region were deforested to give place for cattle farming, soy and sugar cane plantation. This is an area which is bigger than Swiss and Austria summed together. Covering such an area with a monoculture of palms repeat the errors of Indonesia and the palm oil production for biodiesel. Revenues will not benet the local indigenous population, but enrich commercial entities from abroad. Embrapa admits that the heavy export cause shortage of acai at the local market and exploding price make it unaordable for the poor population which used it as staple food. Plantations are located around the Maraj Island at Camet, Furos de Breves e Arari Ajuru, Abaetetuba, Igarap-Miri, Ponta de Pedras, Limoeiro e Mocajuba,which account for 90% of the commercial production. According to Embrapa the annual production of 15 thousand hectares naced by the state, and other plantations is 160,000 Tons, but will increase as soon new plantations start to produce fruits, which is estimated to become 8 tons/hectare. Embrapa product especications for acai [26] -Acai dense, or special (Type A): Pulp extracted with water. Total solids over 14%, appearance is very dense. - Acai medium or regular (Type B): Pulp extracted with water. Total solids between 11% and 14%. Appearance is dense. - Acai thin or popular (Tipe C) Pulp extracted with water. Total solids between 8% and 11%, appearance is less dense. Decontamination Decontamination with 10 to 60 minutes immersion in a solution of chlorine (20 ppm to 50 ppm active chlorine) Pasteurisation Pasteurisation is recommended by 800 C to 850 C during 10 seconds in a tubular heat exchanger. Final temperatur of the proiduct should be 50 C . Deep freezing -18 0 C a -20 0 C or below. Spay-drying To the production of acai powder temperatures of 135 0 C a 140 0 C are used. Outlet temperature of the system is 85 0 C a 90 0 C . Allied pressure is 4,9 a 6,2 kg/cm2 . The powder should be packed in aluminized plastic bags.
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8.1.4
Peach-palm [27]
Peach-palm also known as pupunheira, and pupunha in Brazil. Bactris gasipaes. The fruit is frequently stewed in salted water. It is used to make compotes and jellies, or also used to make our and edible oil. This palm is fast growing. Harvest of heart of palm can be accomplished 18 to 24 months after planting. The plant is a substitute for acai palm to produce hearts of palm. Its commercial cultivation increases environment degradation of the lower Amazon.
8.1.5
Date palm fruits
Production of fructose syrup from discarded Phoenix dactylifera dates: [28] According to Chaira and colleagues 2007, about 50,000 tons of dates are discarded by sorting each year in Tunisia. The authors developed a process to use these fruits for the production of fructose rich syrups at low costs. The invertase activity of date palm fruits from the Tunisian oasis of Gabes and Jerid were determined, whereas the Gabes variety had highest invertase activity with at least two isoforms. The invertase extracted from Korkobbi presented an optimal temperature of 450 C , optimum pH of 3,5 to 4,8. Using this invertase a high fructose syrup was obtained from aqueous extract of the Deglet Nour variety during 30 minutes of incubation. The authors used invertase extracted with distilled water and concentrated by ammonium sulfate precipitation at 80% saturation. Composition of Tunisia date [29] Chaira and colleagues determined the chemical composition and the radical scavenging activity of esh and pit of Deglet nour and Alig date. The total sugars may be more than 60% of the dry weight of date esh. Dates esh was found to be a good source of several minerals such as potassium varying between 0.61 and 0.72% (dry matter). Date pit oil content varied between 10.13% and 12.37%. Less than 6% sugars were determined, in addition, important free radical scavenging activity were found by the authors. Composition and quality of Tunisian date varieties [30] Mrabet and colleagues 2008 analysed the composition of Tunisian date palm fruit varieties, taking Deglet Nour as reference. They report that the littoral varieties were very rich in reducing sugars and were high in vitamin C, while Deglet Nour was rich in sucrose and were low in vitamin C. The littoral varieties were classied as soft dates due to their moisture content. The littoral dates were rich in potassium and low in sodium.
702 Review of date fruit composition [31]
Al-Farsi and Lee 2008 in a review write that the date esh is low in fat and protein but rich in sugars. Minerals are selenium, copper, potassium, and magnesium. Vitamins B-complex and C are the major vitamins in dates. The esh is high in dietary ber, carotenoids and phenolics. Date seeds contain higher protein as compared to the esh, have high dietary ber, phenolics (3942 mg/100 g) and antioxidants (80400 micromol/100 g). The authors suggest tat date seeds may be used as functional food ingredient.
Glycemic index of Omani dates [32] Ali, Al-Kindi and Al-Said 2009 determined the nutritional quality and glycemic index of three sun-dried date varieties (Khalas, Khsab and Fardh) grown in Oman. The glycemic index (GI) ranged between 47.6 and 57.7. The authors found an iinverse correlation between the fructose fraction and the GI value of dates.
8.1.6
Fruit Preserves
Fruit preserves are preparations of fruits, vegetables and sugar, often canned or sealed for long-term storage. The preparation of fruit preserves today often involves adding commercial or natural pectin as a gelling agent,
Goiabada Goiabada is a popular dessert throughout the Portuguese-speaking countries of the world, dating back to the colonial days in Brazil, where guavas (Psidium guajava) were used as a substitute for the quinces used to make marmelada (quince cheese). [33]
Marmalade Marmelade is a fruit preserve made from the juice and peel of citrus fruits, boiled with sugar and water. The benchmark citrus fruit for marmalade production in Britain is the Seville orange from Spain, Citrus aurantium var. aurantium - thus called because it was originally only grown in Seville in Spain- because it is higher in pectin than sweet oranges and therefore gives a good set. In languages other than English, "marmalade" can mean preserves made with fruit other than citrus. Greek term melimelon, "honey fruit" was transformed into "marmelo"-for a product quinces and honey. The name originates in Portuguese, where marmelada applies chiey to quince jam (from "marmelo", the Portuguese for quince). [34]
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8.1.7
Bioactive phenolics in jam
Reduction of bioactive phenolics in jam during processing and storage [35] Jam of strawberry, cherry, apricot, g and orange is considered as a source of bioactive phenolic compounds. Rababah and colleagues 2011 report that fresh strawberry had the highest contents of total phenolics of the analysed fruits. Bioactive phenolic compounds of all fruits decreased during jam processing. Storage of strawberry and cherry jam did not reduce phenolic compounds any further during 5 month. Apricot, g and orange jam, however reduced further the levels of phenolics during storage. Only strawberry jam did not experienced a further drop in antioxidant activity during storage, while all other jam types were found to have it reduced during storage. The highest levels of anthocyanins were found in strawberries. A decrease of anthocyanins and pH in apricot and g jams was found after 5 month storage, no further losses were found with other jams. The authors concluded that some of the of bioactive phenolics are lost during jam processing, however, it is still a good method to maintain these compounds during long storage. Strawberry jam performed best of all types of jams.
Bioactive phenolic content in domestically processed berrie [36] Savikin and colleagues 2009 studied the chemical composition of domestically processed organically cultivated or wild growing berries in Serbia. The total phenolics content in fresh berries varied between 380 and 1660 mg GAE/100 g. The phenolic content decreased during the processing to jams, and storage in almost all samples, except in black currant. Processing and storage caused decrease in anthocyanin content. Frozen as well as processed berries, despite presenting losses during processing and storage, had still high levels of radical scavenging activity, even after fter 9 months of storage and presented microbiological stability.
Process and storage eect on food ellagitannins [37] Bakkalbasi, Mentes and Artik 2009 reviewed studies related to ellagitannins and ellagic acid in fruits. Ellagic acid is a hydrolytic product of ellagitannins an give the characteristic taste to fruits.. There are controversies concerning health claims praising the antioxidant properties of ellagic acid. Despite unprecise evidence of health benets it was sold with the claim to benets against cancer, heart disease, and other medical problems. FDA recommended consumers should avoid ellagic classifying the claims as a fake. [38]
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8.2
8.2.1
Fruit and vegetables in local diets

Changing nutrition in Chile increases food related diseases [39]
The increased consumption of energy dense foods, such as meat, dairy processed foods (fat spreads, sweets and pastries) and foods rich in added sugars (sugary drinks and juices) are responsible for a rise of obesity, diabetes, heart diseases and cancer in Chile. The population has a low consumption of sh, whole grains, legumes, vegetables and fruits.
8.2.2
Protective eect of the Mediterranean diet [40]
The Mediterranean diet is rich in nuts, fruits, vegetables, legumes, whole-wheat bread, sh, and olive oil, with moderate amounts of red wine. The population adhering to this diet present a lower rate of cancer and cardiovascular disease. This diet is rich in antioxidants and anti-inammatory agents, such as omega-3 fatty acids, oleic acid, and phenolic compounds. Pauwels 2011 reviews studies related to the benets of the Mediterranean diet and its mechanisms of biological activity.
8.2.3
Controversy of brown rice versus white rice in risk reduction of diabetes 2 [41]
Sun et al 2010 postulate that dierences in processing and nutrients between brown rice and white rice may have dierent eects on risk of type 2 diabetes mellitus. Using data from the Health Professionals Follow-up Study and the Nurses Health Study I and II, the authors found that higher intake of white rice (>5 servings per week versus <1 per month) was associated with a higher risk of type 2 diabetes, compared to high brown rice intake (>2 servings per week versus <1 per month). According to the authors replacing 50 g/d (uncooked, equivalent to one-third serving per day) intake of white rice with brown rice may reduce the risk of type 2 diabetes by 16%, whereas whole grains as a group reduced diabetes risk by 36%. The authors concluded that substituting white rice by whole grains, including brown rice, reduces the risk of type 2 diabetes. The study supports the recommendation to consume whole grains instead of rened grains. Whole grain consumption may reduce body weight [42] Rening process removes many bioactive contents of whole grain. These contents are linked to health improving activities, modulate appetite, nutrient availability, and energy utilization. Saltzman 2012 stresses that whole grain was found to lower BMI and reduces risk of obesity, however, clinical trials were unable to conrm this armation. Salzman
8.2. FRUIT AND VEGETABLES IN LOCAL DIETS
705
writes that failing to conrm the positive eects of whole grain foods resulted in the fact that studies did not consider the type and amount of grain consumed as well as the nature of its consumption. These factors probably inuences body weight and may be increased by inappropriate processing methods of the food industry.
8.2.4
Brown rice does not reduce diabetes 2 risk, says new study [43]
A new study of Zhang et al 2011 analysed the eect of brown rice and risk reduction of diabetes 2 measuring during 16 weeks BMI, waist circumference, blood pressure, glycated hemoglobin, and serum lipid, glucose, and insulin concentrations. The authors report that there were no dierences found between the group with white rice in their diet and the group with brown rice. Only the serum LDL cholesterol concentration decreased more in the white rice group compared to the brown rice group, but this eect was observed only among participants with diabetes. Participants with diabetes within the brown rice group experienced a greater reduction in diastolic blood pressure compared to the white rice group. The authors concluded that brown rice does not improve metabolic risk factors of diabetes 2, however, further studies must conrm this armation.
8.2.5
High sugar and saturated fats diet increases incidence of diseases in Brazil [44]
Levi-Costa and colleagues report an increasing consumption of sugar leading to excess of calories and low intake of fruits and vegetables in Brazil. A high proportion of calories from saturated fats in urban regions displace traditional foods, like rice and beans. These local dishes are being replaced by processed foods, such as cookies and soft drinks, increasing the amount of sugar and saturated fats in the Brazilian diet. These changes in dietary habits leads to obesity chronic non-communicable diseases in morbidity and mortality and with the continuous increase in the prevalence of obesity. Relation of sugar purchases to other foods The authors stress that each calorie from sugar purchases increases the share of calories from fat by 0.3 calories and decreases the share of calories from protein by 0.7 calories. Relation of sugar from processed foods to other foods Each calorie of sugar from processed foods increases the share from fat by 1.6 calories and the share from saturated fatty acids by 0.4 calories and decreases the share from non-sugar carbohydrates by 0.8 calories. [45] The authors support the recommendations of the WHO and the Brazilian Ministry of Health which recommend to limit the consumption of sugar. [46]
706
8.2.6
Symbiogenics may adapt rice plants to the impact of climate change [47]
Rusty Rodriguez, a researcher at the United States Geological Survey (USGS) reports the development of rice variety with increased tolerance to cold, salt and drought. Heat stress resistance has still to be added, because rice production is known to decreases by 10 percent for every temperature increase of 1-degree centigrade during the rice-growing season. The researchers at USGS colonized two commercial varieties of rice with the spores of fungi that exist naturally within native coastal dunegrass. Fungi which colonize the rice plants may confer stress tolerance to drought, salt and temperature, as well as increased seed yields and root systems in rice These stressors are predicted to worsen due to climate change, and adapting rice plants to such changes is crucial because rice provides nearly half the daily calories for the worlds population. These small fungi act as endophytes. The term "endophytic" refers to a situation where one organism lives inside another. In this case, a fungus and grass form a relationship that is mutually benecial and enhances the reproductive success of each. Another example of endophytic relationship is provided by researchers of the University of Rhode Island. They roprt that the fungal endophytes Acremonium coenophialum and A. lolii live within perennial ryegrass hosts. These endophytes are transferred from plant to plant via seed. [48] Symbiogenics The USGS researchers named this emerging area of research "symbiogenics" for symbiosisaltered gene expression. The DNA of the rice plant itself is not changed. Removing the fungus from dunegrass, the plants are no longer salt tolerant, indicating that no DNA change took place. Pesticides in soils of litchi orchards [49] Pesticides were determined in Guandond/China soils of litchi orchards after harvesting the fruit. Yao and colleagues 2010, authors of the study, found concentrations of 39.05 microg/kg(-1) for mancozeb, 7.83 microg/kg(-1) for cypermethrin and 0.19 to 1.65 microg/kg(-1) for the other ve pesticides (carbendazim. metalaxyl, cyhalothrin. dimethoate and dichlorvos). Deltamethrin and dipterex were not found in all soil samples. The authors suggest that the range of pesticide residue in litchi orchards in Guangdong does not aect food safety. Modern horticulture wants to revive traditional African fruits [50] According to National Research Council in USA tropical fruit production in Africa is dominated by species introduced from Asia and the, such as bananas, pineapples, and papayas which displaced the traditional species that had fed Africans for thousands of years.
8.3. BROCCOLI
707
With renewed scientic and institutional support, however, native fruits could make a much greater contribution to nutrition and economic development, the new report says. Fruit trees and shrubs also oer long-term benets by improving the stability of the environment. The National Research Council report lists the benets of 24 fruits that are considered candidates for optimisation. The most important of this list are: Aizen - A large Saharan shrub that grows in particularly hostile places where few other plants can survive, aizen could protect eroding slopes, stabilise dunes and create windbreaks. The fruits are good source of vitamins A and C, calcium and some minerals, and the seeds a source of protein and zinc. Balanites - Also capable of thriving in the desert, balanites fruit are similar to dates and are already eaten in arid zones where food is scares. But their full potential is not being realised, particularly since their kernels are have a similar oil-protein balance to soybeans and sesame seeds (one half oil, one half protein). They could also help counter desertication. Boabab - A sticky pulp from the fruits can be dried and used as a nutritious powder that is high in protein, vitamins and minerals. This is drunk with milk or other beverages. The pulp is also made into thin pancakes that keep for a long time. The "almost indestructible" trees also yield a leafy vegetable. Butterfruit - Butterfruit is a small tree, but its fruit, high in calories and protein, are regarded as very promising to help reduce child malnutrition. It is also a cash crop, and the mahogany-like wood could show promise for plantations. Tamarind - The fruits are an excellent source of B vitamins and calcium, and last a long time with no refrigeration. The sweet-sour pulp can also be made into cakes. Tamarind trees also come with the promise of restoring damaged lands.
8.3
8.3.1
Broccoli
Sulforaphane from broccoli in the prevention of dierent cancers [51]
Phosphatase and tensin homolog (PTEN) is a protein that, in humans, is encoded by the PTEN gene.Mutations of this gene are a step in the development of many cancers. PTEN acts as a tumor suppressor gene through the action of its phosphatase protein product. This phosphatase is involved in the regulation of the cell cycle, preventing cells from growing and dividing too rapidly. PTEN is one of the most commonly lost tumor suppressors in human cancer. During tumor development, mutations and deletions of PTEN occur that
708
inactivate its enzymatic activity leading to increased cell proliferation and reduced cell death. Frequent genetic inactivation of PTEN occurs in glioblastoma, endometrial cancer, prostate cancer, and reduced expression is found in many other tumor types such as lung and breast cancer. [52] Traka and colleagues 2010 assessed the diet and its relation to counteract the loss of PTEN expression to contribute to the prevention of prostate cancer or reduce the rate of cancer progression. The authors focused on the interaction between sulforaphane, PTEN expression and gene expression in pre malignant prostate tissue. Sulforaphane is an organosulfur compound that exhibits anticancer, antidiabetic, and antimicrobial properties. It is obtained from cruciferous vegetables such as broccoli. The enzyme myrosinase transforms glucoraphanin, a glucosinolate, into sulforaphane upon damage to the plant (such as from chewing) [53] Traka and colleagues suggest that sulforaphane suppresses transcriptional changes induced by PTEN deletion and induces additional changes in gene expression associated with cell cycle arrest and programmed cell death Such changes can be induced in humans with a broccoli-rich diet. The authors point to the complex interaction between diet, genotype and gene expression, and the importance of small bioactive components of a varied diet.
8.3.2
Sulforaphane and iberin of broccoli are associated with a reduced risk of prostate cancer [54]
Chambers and colleagues 2009 report that isothiocyanates derived from glucosinolates that accumulate in broccoli are dietary compounds that have health eects. Sulforaphane derives from heading broccoli (calabrese) and iberin from sprouting broccoli, and both increase the expression of tumor suppressor gene PLAGL1 and suppressed expression of the tumor promoting genes IFITM1, CSPG2, and VIM in epithelial cells. The authors stress that sulforaphane and iberin interfere with cancer prevention genes, and recommend further studies on iberin.
8.3.3
Broccoli consumption interferes in its signalling pathway of inammation and cancer of prostate [55]
Traka and colleagues 2008 stress that eating more than one portion of cruciferous vegetables per week reduces the risk of prostate cancer. The authors report that a six month broccoli-rich diet induced a signicant increase of the gene expression of glutathione Stransferase mu 1 (GSTM1) associated with transforming growth factor beta 1 (TGFbeta1) and epidermal growth factor (EGF) signalling pathways. No such changes were found in a pea-rich diet.
8.4. THE EUROPEAN PROSPECTIVE INVESTIGATION INTO CANCER (EPIC) 2009 709 The authors explain further that sulforaphane from broccoli interacts with TGFbeta1, EGF and insulin peptides to form thioureas, and enhances TGFbeta1/Smad-mediated transcription reducing inammation and cancer risk of prostate. Sulforaphane derived from broccoli, may exhibit chemopreventive properties by inducing cell cycle arrest via induction of cyclin-dependent kinase inhibitor 1A (p21(waf1/cip1)). In 2009, Traka and colleagues explained the role of the transcription factor Kruppel-like factor 4 (KLF4) in mediating the induction of p21(waf1/cip1) and cellular dierentiation by sulforaphane and iberin from broccoli. These results suggest that induction of p21(waf1/cip1) by SF or IB may be partly mediated by KLF4 in some colon cancer cells and tissues. [56] Healt benets of a diet rich in broccoli sprouts are higher than consuming supplements [57] Cruciferous vegetables, such as broccoli, cauliower, cabbage and kale contain glucosinolates. These phytochemicals reduce the risk of prostate, breast, lung and colorectal cancer. Clarke et al. 2011 report that the enzyme myrosinase, present in these vegetables, is needed to break down glucosinolates in sulforaphane and erucin. Both metabolites are found in urine in concentrations eight times higher in people eating broccoli sprouts, compared to persons which receive in their diet glucosinolates as supplement instead of broccoli sprouts. The authors explain that supplements lack the myrosinase enzyme present in whole foods. It is being recommended not to cook vegetables too long, particularly broccoli sprouts. It should retain rmness to avoid destruction of natural enzymes and vitamins of the food.
8.4
8.4.1
The European Prospective Investigation into Cancer (EPIC) 2009

Alcohol reduces Coronary Heart Disease [58]
Spain, China, Switzerland, and France have the lowest CHD mortality rates in the world. Spain is the worlds third largest wine producer and ninth largest beer producer, and is in sixth position in the world ranking of alcohol consumption. Several studies postulate that moderate alcohol intake reduces Coronary Heart Disease (CHD) risk. Some studies highlight the benets of bioavonoids of red vine. A new study of Larraitz Arriola and colleagues, analysing data of the Spanish cohort of the European Prospective Investigation into Cancer (EPIC) found that moderate, high and very high consumption was associated with a more than 30% reduce risk of CHD in men aged 29-69 years, compared with nondrinkers, however, no signicant association could be demonstrated among women. Other scientists like William S. Harris disagree saying that the assertion that alcohol lowers heart disease misstates the ndings being an epidemiological study, not an interventional study. [59]
710
No cancer risk of pancreas and prostate linked to alcohol [60] Rohrmann and colleagues 2009 using EPIC data suggest no association of alcohol consumption with pancreatic cancer risk [60]. In a study of 2008 the same authors reported no increase risk of prostate cancer in this cohort of European men, related to alcohol consume. [61] Vegetables and fruits reduce the risk of lung cancer, this is valid also for smokers [62] An inverse associations between the consumption of vegetables and fruits and risk of lung cancer were reported by Bchner and colleagues 2009 which also stress that consumption of vegetables and fruits may reduce lung cancer risk, in particular the risk of squamous cell carcinomas in current smokers. The Mediterranean diet reduces risk of Coronary Heart Disease (CHD) according EPIC data [63] Buckland and colleagues 2009 examined the relation between Mediterranean diet adherence and risk of incident CHD events in the 5 Spanish centres of the European Prospective Investigation into Cancer and Nutrition. The authors report that the Mediterranean reduces CHD risk and exerts a role in primary prevention of CHD in healthy populations. Mediterranean diet reduces risk of gastric cancer [64] The Mediterranean diet is believed to protect against cancer. Buckland and colleagues 2010 explored the association between a relative Mediterranean diet and incident gastric adenocarcinoma within the European Prospective Investigation into Cancer and Nutrition study within a mean follow-up of 8.9 years. No association between moderate alcohol intake and risk of gastric cancer was found in this study. This legitimates the use of moderate consumption of red wine, a characteristic element of the Mediterranean diet. The authors conclude that a relative Mediterranean diet is associated with a signicant reduction of risk of gastric adenocarcinoma. High intake of fruit and vegetables does not signicantly reduce cancer risk, but reduce the risk of cardiovascular disease [65] Boetta and colleagues,assessing data of European EPIC study (European Prospective Investigation into Cancer and Nutrition) say found that eating ve portions of fruit and vegetables may not signicantly reduce the risk of developing cancer. The results from
8.4. THE EUROPEAN PROSPECTIVE INVESTIGATION INTO CANCER (EPIC) 2009 711 many studies are inconsistent and reduction of cancer risk was low, being 3% for fruit and vegetable combined, 1% reduction for fruit alone, and 2% reduction for vegetables alone. Other researchers point to the benets of high fruit and vegetable intake [66] Dr. Walter C. Willett, in an editorial 2010 says that even with the ndings of EPIC study report on low anti-cancer eect of fruit and vegetable consumption, their benet to reduce risks of cardiovascular disease, and a small benet for cancer make the eort worthwhile. Research should focus more sharply on specic fruits and vegetables and their constituents and on earlier periods of life. For prevention of cancer, the primary focus at present should be heightened eorts to reduce smoking and obesity because obesity in the United States has become similar in magnitude to smoking as an avoidable cause. Dr Rachel Thompson, Science Programme Manager for World Cancer Research Fund, said that the 2.5 per cent of prevented cancers found by the EPIC stand for impressing 7,000 cases a year alone in UK. The ve-a-day fruit and vegetables program also helps to reduce weight. Thompson also reminds that quit smoking, keeping a healthy weight, cutting down on alcohol, eating a healthy balanced diet, being physically active and staying safe in the sun are part of a good strategy to reduce cancer risk. [67]
8.4.2
The European Prospective Investigation into Cancer and Nutrition (EPIC) Study and gastric cancer [68]
Studying the protection of fruits and vegetables against oesophagus and gastric cancer Carlos A. Gonzlez and colleagues found in the EPIC study that total vegetable and onion and garlic intake has a protective role in the intestinal type of gastric cancer and the adenocarcinoma of oesophagus. Citrus fruit consumption may have a role in the protection against cardia gastric cancer and the adenocarcinoma of oesophagus, but no evidence of association between fresh fruit intake and gastric cancer risk was found. Dietary recommendations to increase vegetable consumption are being supported by this study because this may reduce the risk of intestinal type of gastric cancer.
8.4.3
Nutrition and prostata cancer prevention [69]
Schmidt and colleagues 2011 point out that heredity, ethnic origin, and increasing age are risk factors of prostate cancer. Environmental factors also play an important role in the development of the disease. Men with the same genetic background, but living in dierent environments diseased in association with the place where they lived. Nutritional factors Total energy intake (as reected by body mass index), dietary fat,
712
cooked meat, micronutrients and vitamins (carotenoids, retinoids, vitamins C, D and E), fruit and vegetable intake, minerals (calcium, selenium), and phytoestrogens (isoavonoids, avonoids, lignans) were found to reduce the risk of prostate cancer. However, selenium and vitamin E were found to be of no benet to cancer prevention by "The selenium and vitamin E cancer prevention trial" (SELECT). Therefore the trial was discontinued Overall the authors recommend lifestyle changes to reduce the risk of prostate cancer.
8.4.4
Kiwi
It is widely used as food because of its high content of vitamin C and its taste. Allergy is often cited in relation with kiwi. It is supposed that instable allergens are of importance. As possible allergen thio-proteinase actinidin 23,5 kD; pl 3,1 is cited. It is similar to bromelain in pineapple and papain in Papaya. Pastorello et al. (1996) has found as major allergen at 30kD the protein 22,24 (Actinidin) 28, 32, 38 and 41 kD. Any attempt to modify the genetic code of kiwi should try to suppress these fractions as possible allergens.
8.4.5
Papaya anti cancer and anti allergic eects in vitro [70]
Papaya (Carica papaya Linn.) is known by its papain from fruit and leaves. Teas from leaves of the papaya plant are also used in traditional medicine in case of various types of cancer. Recently Dang and colleagues 2010 report that aqueous-extracted Carica papaya leaf fraction inhibited the growth of various tumour cell lines and enhanced the expression of CCL2, CCL7, CCL8 and SERPINB2 genes. These genes are index markers of the immunomodulatory eect of the extract. The authors identied fraction with molecular weight less than 1000 as the active part to inhibits tumor cell growth and stimulates anti-tumor eects. Th1-type cytokine production is activated. The authors suggest that Carica papaya leaf extract can may be useful in treatment and prevention of cancer, various allergic disorders, and may also serve as immunoadjuvant for vaccine therapy. No toxic eects on normal cells were found.
8.4.6
Antioxidants of Mallotus nanus used in traditional medicine in Vietnam and China [71]
Van Kiem and colleagues 2010 report methanolic extract of the leaves of Mallotus nanus to contain two mallonanosides, which are 2-C-beta-D-glucopyranosyl benzoic acid derivatives. Other isolated avonoids were kaempferin, juglanin, quercitrin, myricitrin, and rhoifolin. Mallotus species are used in traditional medicine in Vietnam and China. Some also show interesting activities, such as antioxidant and cytotoxic ones. Tistaert and colleagues 2009
8.4. THE EUROPEAN PROSPECTIVE INVESTIGATION INTO CANCER (EPIC) 2009 713 used chromatographic ngerprints to reveal the peaks potentially responsible for the antioxidant activity of several Mallotus species. [72]
8.4.7
Antioxidant Capacities Tunisian Pomegranate (Punica granatum) Fruits [73]
Elfalleh et al 2011 assessed the Antioxidant Capacities Tunisian Pomegranate (Punica granatum) Fruits. The tocopherol (alfa-tocopherol, gama-tocopherol, and delta-tocopherol) contents were found by the author, respectively, 165.77, 107.38, and 27.29 mg/100 g from dry seed. The phenolic compounds were identied as 2 hydroxybenzoic acids (gallic and ellagic acids) and 2 hydroxycinnamic acids (caeic and rho-coumaric acids). The highest antioxidants values were found in peels, and less in juice and seed oil. The antioxidant activity of pomegranate extracts correlated with their phenolic compound content, being highest in peels. The antioxidant activity of the seed oil is mainly related to the content of tocopherols. The authors suggest that pomegranate may become a valuable antioxidant for dietary food. [74] Pomegranate seed oil: According to Elfalleh, Ying and colleagues 2011 Tunesia and China pomegranates had a total lipids content of 16% on a dry weight basis, of which 88% were unsaturated. The authors found linolenic acid (44.51-86.14%), linoleic acid (3.5713.92%), oleic acid (3.03-12.88%), palmitic acid (3.13-11.82%), stearic acid (1.68-15.64%), gadoleic acid (0.50-4.91%), lignoceric acid ( < 2.53%), arachidic acid ( < 1.70%) and myristic acid ( < 0.85%). The fatty acids content varied between Chinese and Tunisian pomegranate depending on the sampling location. [75] Lansky and Newman 2007 reviewed the medicinal and nutritional role of pomegranate (Punica granatum). The authors found that juice and peels possess potent antioxidant properties, while juice, peel and oil are all weakly estrogenic and are useful to treat menopausal symptoms and sequellae. Juice, peel and oil have anticancer activities, including interference with tumor cell proliferation, cell cycle, invasion and angiogenesis. The authors stress that all Punica granatum components may be use for treatment and prevention of diseases based on chronic inammation. [76]
8.4.8
Juniperus phoenicea berries are high in polyphenols and avonoids say researchers [77]
Nasri et al 2011 report a high content of gallic acid (1764 174.3 mg per 100 g DW) and rutin (890 47.6 mg per 100 g DW) in Juniperus phoenicea berries. High free radical scavenging activities were also found by the authors. The authors stress that Juniperus phoenicea may be used as supplements or as an ingredient in pharmacy.
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Spices in fatty meals may reduce risk of heart diseases [78] Spices were found to be potent antioxidant in vitro. Skulas-Ray et al. 2011 examined the postprandial activity of spices on human markers of plasma antioxidant status and metabolism. A meal of chicken curry with 5060-kJ (1200 kcal) was seasoned with two table spoons (14 g) of a blend of rosemary, oregano, cinnamon, turmeric, black pepper, cloves, garlic powder and paprika, Blood from the participants were taken every 30 minutes for 3.5 hours. Antioxidant activity in the blood was increased by 13 percent and insulin response decreased by about 21 percent, blood triglycerides decreased by 30 percent, and the ferric reducing antioxidant power increased 2-fold, compared with the unseasoned meal group. This was found to be equivalent to 5 ounces of red wine or 1.4 ounces of dark chocolate. Glucose, total thiols, lipophilic ORAC, or total ORAC remained unaltered. The authors concluded that spices may normalize postprandial insulin and TG and improve antioxidant defences.
8.4.9
White fruits (apple and pears) protect against stroke, but not coloured foods [79]
Bioactive compounds, such as carotenoids, anthocyanidins, and avonoids are known to be associated with health benets. These compounds bring colours to fruits and vegetables. The study of Oude Griep et al. 2011 looked at which fruit and vegetable colour groups may reduce the risk of stroke assessing the consumption of fruit and vegetable colour groups during a 10-year stroke incidence study. The authors found that coloured fruits and vegetables were not related to stroke. The coloured groups under the study were green (cabbages, lettuces), orange/yellow (citrus fruits), and red/purple (red vegetables) fruits and vegetables. Higher intake of whiteeshed fruits and vegetables (apple and pears) were inversely associated with incident stroke, and 25-g/day increase in white fruit and vegetable consumption was associated with a 9% lower risk of stroke. An average apple weighs 120 g. This suggests that high intake of apples and pears may reduce stroke incidence, The authors, however, call for more study to conrm the ndings. Dont turn your back to coloured fruits and vegetable, they protect against cancer and other diseases. Have in mind to eat more fruits and vegetables as a whole.
8.5. ANTIOXIDANT CAPACITY OF TOMATO AND TOMATO-BASED PRODUCTS 715 Diet high in vegetables and fruits reduces the risk of heart diseases interfering with the Chromosome 9p21 SNPsregion, which is associated with such diseases [80] Do et al. 2011 report that diet high in raw vegetables and fruits reduce the risk of myocardial infarction (MI) and cardiovascular disease (CVD). The chromosome 9p21 SNPs was found to be related to these heart diseases and diet may reduce the eect of this chromosome. The study used data of the INTERHEART study and the FINRISK. Participants were genotyped for four 9p21 SNPs. All four genes were associated with heart diseases. The combination of two copies of the risk allele and the least prudent diet correlated with a two-fold and 1.66-fold increase in the risk of MI and CVD respectively. This provides more evidences of the benets of diets high in raw vegetables and fruits.
8.5
Antioxidant capacity of tomato and tomato-based products
Tomato seed oil has high antioxidant capacity [81] Mueller et al. 2012 report that tomato seed oil has antioxidant capacities, such as inhibition of intracellular ROS production, which are higher than that of puried lycopene. The authors explain that the high antioxidant capacity of tomato seed oil is based on the aggregate of antioxidants which includes (5Z)-, (9Z)-, (13Z)-, (15Z)-lycopene isomers, beta-carotene, lutein and tocopheroles. The authors also highlight that tomato seed oil decreases the phosphorylation of the MAPK ERK1/2, JNK, p-38; reduces the activation of the redox-sensitive NF-kB, and the expression of the heat shock proteins 70 and 90.
Lycopene of tomato sauce-based pasta dishes shows promising results in prostata cancer study [82] In this study patients with prostate adenocarcinoma consumed tomato sauce for 3 weeks (30 mg of lycopene/day). Bowen et al. 2002 report a signicant uptake of lycopene into prostate tissue and a reduction in DNA damage in both leukocyte (8OHdG) and prostate tissue. Also reduced was serum prostate specic antigen (PSA). Further studies must clear if these ndings are benecial in controlling the disease. The authors refer to the reduction of serum prostate specic antigen (PSA) as promising.
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Carotenoid compositions of tomatoes and their protecting activity on cardiac cells [83] Li et al. 2013 studied the carotenoid compositions, antioxidant activities and the potential cardio-protective role of 13 tomato dierent cultivars. Red tomatoes had the highest total carotenoid contents and antioxidant activities, followed by purple, orange, pink and yellow ones. The lipophilic extracts prevent cell death of cardiac reducing the caspase-3 and matrix metalloproteinase-2 activities in a H9c2 cell model under H2O2 stress. Lycopene presented the highest activity. The authors write that these data may be used in developing new tomato cultivars. Ultrasound reduces bioavailability of lycopene in tomato pulp [84] Ultrasound applied to tomato pulp at a frequency and amplitude of 24kHz and 100m increased the gel-like rheologic properties of the pulp but reduced the tomato cell integrity and the degree of pectin esterication. Anese et al. 2013, authors of the study, explain that ultrasound causes the formation of a network of hydrogen bonding and hydrophobic interactions among the de-esteried pectin molecules, this stronger network reduces the bioaccessibility of lycopene in vitro, being less availiable to digestion. In vitro study of the eects of curcumin and lycopene upon oral squamous cell carcinoma cells [85] An in vitro study was carried out to evaluate the eect of curcumin, lycopene, and irradiation upon oral squamous cell carcinoma cells (PE/CA-PJ15 cell line). Curcumin and lycopene increase cytotoxic activity in the PE/CA-PJ15 cell line and reduce cell migration capacity. The combination of curcumin or lycopene with irradiation exerts a synergistic eect. Camacho-Alonso et al. 2012 found best results with 5.50 M curcumin and 6.75 M lycopene and 5 Gy of irradiation. For best antioxidant potential the correct genotype suited to the geographical region should be chosen [86] Chandra et al. 2012 found that cultivars developed for high altitude, such as Sindhu and Shalimar presented highest contents of lycopene, anthocyanin and free radical quenching ability. Plain region cultivars, however, have higher contents of total phenolics, ascorbic acid and titratable acidity. The authors concluded that the right genotype should be planted which is best for the geographical conditions. Lycopene of processed tomato products improves conditions of patients with heart failure independent of sodium intake [87] Processed tomato products are a major source of lycopene, although they are also high in sodium. Biddle et al. 2012 found in a study of 212 patients which suered heart failure,
8.5. ANTIOXIDANT CAPACITY OF TOMATO AND TOMATO-BASED PRODUCTS 717 that a diet containing 2471 g/day of lycopene and a mean sodium intake of 3 g/day was associated with longer cardiac event-free survival compared with lower lycopene intake, even with low sodium intake of less than 3 g/day. The authors concluded that increased lycopene intake improves cardiac event-free survival in patients with heart failure. Sodium intake independent of sodium intake.
8.5.1
Tomato and tomato products decrease oxidative stress biomarkers [88]
Martinez et al report that consuming 160 g/day tomato sauce with high lycopene content decreased levels of oxidised LDL cholesterol by 9%. A commercial tomato sauce did not show such improvement. Serum concentration of lycopene, blood pressure, general biochemical variables including total cholesterol, LDL-c, HDL-c, triglycerides insulin and glucose concentrations did not varied between the consumption of high lycopene sauce and the commercial sauce. The authors concluded that lycopene in combination with other bioactive compounds in products like tomato sauce rich in lycopene, has a role in the prevention of oxidative stress related diseases, such as atherosclerosis and coronary heart diseases.
8.5.2
Lycopene dietary eects
The carotenoid lycopene has been reported to protect against cancer associated with immunomodulation. Huand et al. 2013 investigated the immunomodulatory eect angiogenesis of lycopene. Lycopene up-regulated interleukin (IL)-12 by 163% and interferon (IFN)- by 531% in vitro at a concentration of 10 mol/L. The authors concluded that lycopene has a potent anti-angiogenic eect associated with its up-regulation of IL-12 and IFN- . [89] An anti-angiogenic eect inhibits the growth of new blood vessels (angiogenesis). Some angiogenesis inhibitors are used by the body as a normal blood vessels control to reduce cancer risk. Some of angiogenesis inhibitors, such as lycopene come from foods. Plant lycopene exhibits antioxidant activity in transient cerebral ischemia/reperfusion [90] Lycopene was found by Fujita et al. 2013 to delay neuronal death in hippocampal regions in gerbils attenuating ischemia-related neuronal damage by controlling apoptosis at the gene level. Food containing 5 mg/100 g was found to increase hippocampal superoxide dismutase (SOD) activity after ischemia. The authors concluded that orally administered lycopene, accumulates in the body and protects against ischemia brain injury by increasing the superoxide dismutase (SOD) activity and inhibiting apoptosis.
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Increased bioavailability of synthetic form of lycopene [91] Lycopene of tomatoes is a better antioxidant thant other antioxidants. Sarkar et al. 2012 found that supplementation of synthetic lycopene was even more ecient to reduce oxidative stress biomarkers SOD, GPX, GR, GSH, Catalase, vitamin C and E, except MDA, compared to natural lycopene. Bioavailiabilty of synthetic lycopene was found to be more bioavailable turning it more eective against oxidative stress. Tomato product supplementation, containing antioxidant carotenoids and lycopene, decreases oxidative stress. Devaraj et al 2008 report that puried lycopene presented a good bioavailability. It decreased DNA oxidative damage and urinary 8-OHdG at 30 mg lycopene/day. [92] Lycopene intake is too low in western Europe [93] Vandevijvere et al. 2013 criticises the low level of lycopene in diets of Belgiuans and European neighbours. The authors found an intake of 4,6 mg/day for men and 3,6 mg/day of lycopene for women. This was below the acceptable daily intake, according to the authors. Tomato and tomato products were considered to be the main dietary contributor of lycopene in this region. Degradation of anthocyanins in frozen raspberries and in freeze-dried raspberries [94] Syamaladevi et al. 2011 reports uctuation of anthocyanin degradation in frozen raspberries stored at temperatures between -800 C and -200 C . The total anthocyanin degradation in freeze-dried raspberries ranged from 27% to 32% and 78% to 89% at a(w) values of 0.05 to 0.07 and 0.11 to 0.43, respectively, at room temperature of 23 0 C for more than a year. Anthocyanins were completely degraded in freeze-dried raspberries stored at a(w) values of 0.53 and higher after 1 year. Glassy state reduced degradation compared to degradation in rubbery state in freeze-dried raspberries during storage. Roos 2010 write that the success of freeze drying, spray drying, and extrusion and the stability of dehydrated foods against ow, collapse, and crystallization is based on the control of the glassy state during the dehydration process and storage. Critical values for water activity and water content express the level of water plasticization leading to glass transition in food storage. [95] According to Syamaladevi et al. 2012 total anthocyanins, total phenolics and total antioxidant activity in canned blueberry solids decreased by up to 86, 69 and 52% respectively. In canned blueberry syrup, total anthocyanins and total antioxidant activity decreased by up to 68 and 15% respectively, while total phenolic content increased by up to 117%. Blanching before thermal processing helped to preserve the phytochemicals during storage
8.5. ANTIOXIDANT CAPACITY OF TOMATO AND TOMATO-BASED PRODUCTS 719 of blueberries. The production system of conventional versus organic did not inuence antioxidants stability in canned blueberry products. [96] Eect of thermal treatment on anthocyanin and phenolic contents of berries [97] According to Sablani et al. 2010 the total anthocyanins decreased by up to 44%, while phenolic contents and antioxidant activity of berries increased by up to 50 and 53% respectively in canned red raspberries and blueberries. The level of changes in phytochemicals during berry puree/juice processing was inuenced by blanching and type of berries. Blanching prior to processing improved the retention of phytochemicals in blueberries. Berries of normal agricultural origin did not varied from organic produced berries in relation to antocyanin and phenolic contents.
8.5.3
Food and hypertension
Unpeeled purple tomatoes reduce blood pressure [98] Antioxidant eects of a diet consisting of purple potatoes microwaved with skins were compared to a diet of rened starch as cooked biscuits by Vinson et al. 2012. The purple potato diet caused an increase in plasma and urine antioxidant capacity. People receiving rened potato starch diet had a decreased antioxidant status. Fasting plasma glucose, lipids and body weight remained unchanged by the potato diet. Diastolic blood pressure decreased by 4.3%, and systolic blood pressure decreased by 3.5%. The authors believe that purple potatoes are an eective hypotensive agent and lower the risk of heart disease and stroke in hypertensive subjects, due to their content of polyphenols, anthocyanins, and chlorogenic acids (CGA), which are found at higher concentration in purple than white potatoes, and keeping skins protect the antioxidants of potatoes during cooking.
8.5.4
Solanine and glycoalkaloids in potato [99]
In potato tubers, 30-80% of the solanine develops in and close to the skin. Greening of potatoes suggests solanine build-up, although each process can occur without the other. A bitter taste in a potato is another, potentially more reliable indicator of toxicity. The symptoms of solanine poisoning are mainly vomiting and diarrhea, and the condition may be misdiagnosed as gastroenteritis. Deep frying potatoes at 1700 C is known to eectively lower glycoalkaloid levels (because they move into the frying fat), whereas microwaving is only somewhat eective, freeze drying or dehydration has little eect, and boiling has no eect.
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8.5.5
Upper limit for glycoalkaloid content [100]
In potatoes, the commonly found glycoalkaloids are a-solanine and a-chaconine forming as high as 95% of total glycoalkaloids. The highest concentrations of total glycoalkaloids are found in the peel and in the tissue layer just below it. The levels of total glycoalkaloids in consumer varieties of potatoes range from 20-150 ppm. The potato alkaloids inhibiting cholinesterase leading to the accumulation of acetylcholine that is responsible for conducting nerve impulses, and 2 mg of glycoalkaloid/kg body weight produced classic symptoms of poisoning. For food safety purposes, an upper limit for glycoalkaloid content of 20 mg/100 g of potato is generally accepted. Commonly appreciated are varieties that contain 20 to 130 mg glycoalkaloids/kg fresh weight. Potatoes with solanine levels greater than 140 mg/kg have a bitter taste.
8.5.6
Toxic glycoalkaloids in Pakistani potatoes [101]
The toxic glycoalkaloids of potato tuber are poisonous to humans and may cause livestock deaths. Aziz et al. 2012 evaluated -chaconine, -solanine, and total glycoalkaloids (TGAs) contents in the peel and esh portions in selected Pakistani potato cultivars. These data may be important for the evaluation of cultivars and safety assessment in potato processing industry. The -solanine content varies 46 to 2743 in peel and from 4 to 2467 mg/100 g of dry weight in esh. The -chaconine content varied from 4 to 6818 in potato peel and from 4 to 475 mg/100 g of dry weight in esh portion. The TGA concentration varied from 177 to 5450 in peel and from 3 to 15 mg/100 g of dry weight in esh portion of all the potato cultivars tested. All the potato cultivars contained lower concentration of TGA than the limits recommended as safe, except 2 cultivars, that is FD8-3 (2539.18 89.77 mg/100 g of DW) and Cardinal (506.16 17.90 mg/kg). The dietary intake assessment of potato cultivars revealed that Cardinal, FD 35-36, FD 8-3, and FD 3-9 contained higher amount of TGA in whole potato, although FD 8-3 only possessed higher content of TGA (154.93 7.75) in its esh portion rendering it unt for human consumption.
8.5.7
Glycoalkaloid in peel and core of potato cultivars and potato food products [102]
Simoi et al 2007 assessed the content of potato glycoalkaloid (PGA) in 27 cultivars of raw potatoes and 31 potatoes in commercial foods. The cultivars "May queen" and "Sherry"
8.5. ANTIOXIDANT CAPACITY OF TOMATO AND TOMATO-BASED PRODUCTS 721 showed high contents of PGA of 180 mg/kg and 320 mg/kg, respectively, and "Inca red" showed the lowest content of 21 mg/kg. Small potatoes presented higher contents of PGA and commercial potato foods with peel ranged from 48 to 350 mg/kg. The complete data set is available at http://www.jstage.jst.go.jp/article/shokueishi/48/3/77/_pdf. Potatoes produce secondary metabolites, such as glycoalkaloids, calystegine alkaloids, protease inhibitors, lectins, phenolic compounds, and chlorophyl. Glycoalkaloids of potatoes are involved in host-plant resistance and to have a variety of adverse as well as benecial eects in animals and humans with possible dietary consequences if present in fresh and processed potatoes. [103] Inuence of production process of potato akes and byproducts [104] Mder, Rawel and Kroh 209 assessed the inuence of a commercial production process for dehydrated potato akes on the content of free phenolic compounds, total phenolics, and glycoalkaloids in potatoes byproducts, such as potato peel (steam peeling), mashed potato residues, and side streams (blanching and cooking waters), have also been investigated. Peeling and leaching reduces signicantly the content of undesired compounds. The processing temperature is less important. The authors found that 43% of the initial phenolic acids and 10% of the glycoalkaloids remain after processing. Steam peeling has a higher inuence on glycoalkaloid losses compared to that on phenolics. Peeling byprodukt had the highest amounts of phenolic compounds and glycoalkaloids. Processing reduces chlorogenic acid, however, isomeration increases the concentration of neochlorogenic acid. Weight loss to reduce blood pressure [105] Siebenhofer et al 2011 analysed the studies which focused on weight reduction and cardiovascular events associated with hypertension. Siebenhover and colleagues found that weight loss diets reduced body weight and blood pressure in primary hypertension patients, however there are uncertainties regarding the magnitude of this reduction, because only a reduced number of studies could qualify for their review. It remains unknown whether weight loss reduces mortality and morbidity. Mulrow et al. 2008 evaluated the eect of weight-reducing diets in overweight hypertensive persons. They found that a modest weight loss in the range of 3-9% of body weight may be associated with modest blood pressure decreases of roughly 3 mm Hg systolic and diastolic and may reduce dosage requirements of antihypertensive medications. [106] Blood metabolism altered by dietary carbohydrates modication patients with metabolic syndrome [107] To elucidate how whole-grain cereals and diets with a low glycemic index may protect against the development of type 2 diabetes and heart disease, Lankinen et al 2010 looked
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at subjects with metabolic syndrome submitted to either to a diet high in oat and wheat bread and potato (OWP) or rye bread and pasta (RP) diet. In the OWP group multiple proinammatory lysophosphatidylcholines increased, mRNA expression of stress reactions- and adipose tissue dierentiation-related genes were upregulated in adipose tissue. In the RP group docosahexaenoic acid (DHA 22:6n-3) increased and isoleucine decreased, and pathways related to stress reactions and insulin signaling and energy metabolism were down-regulated. The authors stress that dietary carbohydrate modication alters the serum metabolic prole contributing to proinammatory processes contributing to diabetes and heart diseases.
8.5.8
Relation of unhealthy diet with all-cause mortality and physical activity [108]
Hroux 2010 assessed the relation between dietary patterns with all-cause mortality, while controlling for the potentially confounding eects of tness. Using data of the prospective cohort study consisting of 13 621 men and women from the Aerobics Center Longitudinal Study (ACLS) one primary dietary pattern emerged and was labelled the Unhealthy Eating Index. The Unhealthy Eating Index In this study unhealthy eating food, associated with modest to strong risk factor for chronic disease and mortality risk, were grouped as follows: Red meat: Cooked meat from beef, pork, veal, lamb and game. Added fat: Added butter, margarine, oils and dressings. White potato products: White potatoes including such things as french fries and mashed potatoes. None-whole grains: All grain products that are enriched, unenriched, or fortied (e.g. white bread, white pasta, cereals). Processed meat: Frankfurters, sausages and luncheon meats. Non-citrus fruits: All fruit except for citrus (lemon, lime, orange, grapefruit). Cardiorespiratory tness inuencing factors Participants were divided into three categories: (i) inactive (no activity); (ii) moderately active (sporting or leisure-time physical activity other than walking or jogging; or walk or jog up to 16km/week); and (iii) highly active (walk or jog 16km/week). Study conclusion: A high Unhealthy Eating Index was associated with all-cause mortality risk, characterized by elevated consumption of processed and red meat, white potato
8.5. ANTIOXIDANT CAPACITY OF TOMATO AND TOMATO-BASED PRODUCTS 723 products, non-whole grains, added fat and reduced consumption of non-citrus fruits. The hazard ratio for all-cause mortality was reduced by 13.5 and 55.0% after controlling for self-reported physical activity and tness, respectively. Thus, the association between diet and overall mortality was, in large part, confounded by tness. Insucient evidence to recommend sweet potato for type 2 diabetes mellitu[109] Sweet potato (Ipomoea batatas) is also used in traditional medicine practices for type 2 diabetes mellitus. Ooi and Loke reviewed studies related with sweet potato and concluded that there is insucient evidence to recommend sweet potato for type 2 diabetes mellitus.
8.5.9
Iron and protein biofortication of cassava [110]
Cassava (Manihot esculenta) is a staple food for large African regions, but it has the lowest protein:energy ratio and cassava diet furnishes less than 30% of proteins and less than 10-20% of the required amounts of iron, zinc, vitamin A and vitamin E. According to Leyva-Guerrero et al 2012 the BioCassava Plus program tries to develop the cassava germplasm to increase the nutrient levels, mainly protein and iron. The authors discovered that cyanogens are related with the cassava nitrogen metabolism. Increasing protein levels in cassava reduces cyanogen levels, and rising iron uptake impacts the iron homeostasis in dierent tissues. The BioCassava plu program biofortication [111] The BioCassava Plus (BC+) program tries to improve the health of Africans through the development of GM cassava with increased nutrient (zinc, iron, protein, and vitamin A) levels, increased shelf life, reductions in toxic cyanogenic glycosides to safe levels, and resistance to viral disease. Bioforticated GM cassava was tested with good results in eld trials in Puerto Rico and Nigeria, report Sayre et al 2011. Hydroxynitrile lyase (HNL) increase protein and reduce toxicity of cassava roots [112] Narayanan points out that cassava roots contains toxic levels of cyanogenic glucosides such as linamarin which is stored in the vacuole. Linamarin is transformed by the enzyme linamarase in acetone cyanohydrin which decomposes to acetone and free cyanide by hydroxynitrile lyase (HNL) at pH >5.0 or temperatures >350 C , to acetone and free cyanide by hydroxynitrile lyase (HNL). The low HNL activity and accumulation of acetone in cassava roots may lead to toxicity of poorly processed roots. The authors suggest that a patatin promoter could induce overexpression of HNL increasing cyanogenic protein production and reducingthe toxicity of the Cassava roots. Initial linamarin levels were reduced by 80% in transgenic cassava roots, compared with wild cassava.
724
Biofortication of cassava acts as protein sink [113] GM cassava was found by Abhary et al. 2011 to produce 12,5% (dry weight) of storage protein zeolin under the control of the patatin promoter. Levels of cyanogenic compounds were reduced by up to 55% in transgenic plants, as compared to conventional plants.
8.5.10
Oyster leaf aroma secret unveiled [114]
Oyster leaf (Mertensia maritima), also referred to as vegetarian oyster. The leaves have an amazing oyster-like, marine aroma. Delort et al. 2012 identied 109 compounds which give the plant its remarkable taste. The oyster-like taste is caused by four compounds: (Z)3-nonenal, (Z)-1,5-octadien-3-ol, (Z,Z)-3,6-nonadienal, and (Z)-1,5-octadien-3-one. Oyster leaves can be added to sh dishes.
8.6
Triterpenoid compounds in fruits and plant in Bilberry and Lingonberry
Bilberry:Triterpenoid compounds found in fruits and leaves and in fruit and leaf cuticular waxes of bilberry (Vaccinium myrtillus L.) from Finland and Poland were found by Szakiel et al. 2012 to consist mainly of - and -amyrin, - and -amyrenone, campesterol, cholesterol, citrostadienol (in berries), cycloartanol, erythrodiol, lupeol, 24-methylenecycloartanol, sitosterol, sitostanol, stigmasterol, stigmasta-3,5-dien-7-one, uvaol, oleanolic and ursolic aldehydes, and oleanolic, ursolic, 2-hydroxyoleanolic, and 2-hydroxyursolic acids. Friedelin and D:A-friedooleanan-3 -ol were found only in Finnish plants, whereas D:Cfriedours-7-en-3 -ol and taraxasterol were found only in Polish plants. [115] Lingonberry:The triterpenoid prole of fruits and leaves of lingonberry ( Vaccinium vitis-idaea L.) from Finland and Poland, according to Szakiel et al. containes -amyrin, amyrin, betulin, campesterol, cycloartanol, erythrodiol, fern-7-en-3 -ol, friedelin, lupeol, sitosterol, stigmasterol, stigmasta-3,5-dien-7-one, swert-9(11)-en-3 -ol, taraxasterol, urs12-en-29-al, uvaol, oleanolic acid, and ursolic acid as a principal triterpene in lingonberry fruit. Fermenol was the major triterpenol in leaves of Finnish lingonberry and taraxasterol in Polnish plants. [116] Ltti et al. 2011 investigated the content of phenolic compounds in berries and owers of Vaccinium intermedium Ruthe, which is a rare natural hybrid between bilberry (Vaccinium myrtillus L.) and lingonberry (Vaccinium vitis-idaea L.). Bilberry produces anthocyanins and cyanidin, while lingonberry contains only cyanidin glycosides. Hybrid berries analysed by Ltti and colleagues, contained all bilberry anthocyanins with pronounced cyanidin content and present advantages compared to the natural breedings. [117] Mller, Schantz and Richling 2012 assessed the anthocyanin content of commercially availOurFood Database of Food and Related Sciences Copyright 1998-2010 Karl H. Wilm. All rights reserved.
8.6. TRITERPENOID COMPOUNDS IN FRUITS AND PLANT IN BILBERRY AND LINGONBERRY 725 able bilberry juices and fresh fruits available in Germany. They report that Delphinidin-3O-glucopyranoside, delphinidin-3-O-galactopyranoside, and cyanidin-3-O-arabinopyranoside were the major anthocyanins found in juices, nectar, and fresh bilberries. Fresh blueberries had higher concentrations of malvidin-3-O-arabinopyranoside and petunidin-3-Ogalactopyranoside. Other studies had been based on cyanidin-3-O-glucoside, which is not the main anthocyanin content of these fruits. Mller and colleagues used the anthocyanin references found which they found in 2012. The new quantication indicates values which are 53% and 64% higher in fresh bilberries and blueberries, respectively, compared to the older data. Bilberry Juices contain 3,8 times higher anthocyanin concentrations than those of blueberries. The content of anthocyanins of fresh fruits of bilberries was 2,3 times higher than that of blueberries. [118] Triterpenoids of heather owers [119] The content of triterpenoids of waxes of heather owers is 20% by mass and that of leaves is 65%. Heather leaves are a good source of triterpenoids, with predominance of ursolic acid in cutucular wax and friedelin predominated in owers and uvaol in leaves. Antitumor eect of triterpenoids [120] Triterpenoids such as ursolic and oleanolic acid, betulinic acid, celastrol, pristimerin, lupeol, and avicins possess antitumor and anti-inammatory properties. Synthetic triterpenoid derivatives were synthesized to boost antitumor eects. being under evaluation studies. Triterpenoids are known to block nuclear factor-kappaB activation, and induce apoptosis, stresses Petronelli et al. 2009. Betulinic acid is the most promissing antitumor compound of the triterpenoids. It is active against a variety of cancer cells in vitro and is relatively nontoxic for healthy cells. According to Mullauer et al. 2010 it induces Bax/Bak-independent cytochrome-c release in mitochondria. [121] Oleanolic acid, ursolic acid and betulinic acid are triterpenoids with antifungal, antibacterial, anti-human immunodeciency virus (HIV) and/or antitumor activities. Fukushima et al. 2011 found a strong correlation between CYP716A12 and -amyrin synthase (bAS),which produces -amyrin the basis for saponins. CYP716A12 also cooperates to modie -amyrin to oleanolic acid, and forms ursolic and betulinic acid. The authors found that CYP716A15 and CYP716A17, which are homologs of CYP716A12, produce triterpenoid in grapes. The data may become useful for the industrial synthesis of these triterpenoids. [122] Glycyrrhizin, the triterpenoid saponin of licorice [123] Glycyrrhizin, a triterpenoid saponin derived from the underground parts of Glycyrrhiza plants (licorice), is used in some countries as a natural sweetener. Seki et al 2011 explain the biosynthesis of glycyrrhizin involving the participation of a cytochrome P450
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monooxygenase (P450) gene encoding -amyrin 11-oxidase (CYP88D6) as the initial P450 gene in glycyrrhizin biosynthesis, followed by a second relevant P450 (CYP72A154) which promotes the C-30 oxidation in the glycyrrhizin pathway. Furthermore, CYP72A63 of Medicago truncatula, which has high sequence similarity to CYP72A154, was also able to catalyze C-30 oxidation of -amyrin. The authors stress the importance of the CYP72A subfamily proteins as triterpene-oxidizing enzymes in the production of the sweetener glycyrrhizin. Glycyrrhizin of liquorice [124] According to Insbrucker and Burdock 2006 liquorice has glycyrrhizin as main active component. It is used in foods, tobacco and has therapeutic applications. Glycyrrhizinates inhibit 11beta-hydroxysteroid dehydrogenase, an enzyme which inactivates cortisol and may produce hypermineralocorticoid-like eects if it is consumed over a log time at high concentrations. However, these eects are reversible when the consume is stopped. To avoid negative eects, the authors suggest an acceptable daily intake of 0.015-0.229 mg glycyrrhizin/kg body weight/day. Safety tests have shown that glycyrrhizin is not teratogenic or mutagenic but has antigenotoxic activities. Licorice is less bioavailable and thus less active than glycyrrhizin. Safety of glycyrrhetinic acid, glycyrrhizic aciud its salts and [125] The Cosmetic Ingredient Review Expert Panel in 2007 assessed the safety of glycyrrhetinic acid and its salts and esters and glycyrrhizic acid and its salts and esters used as cosmetic ingredients or as avoring agents. Glycyrrhetinic acid and glycyrrhizic acid and metabolites are mostly excreted in the bile, with very little excreted in urine. There are indications that babies whose mother consumed > 500 mg/wk of glycyrrhizic acid were more likely to be born before 38 weeks. Glycyrrhizic acid is cytotoxic at high doses and ingestion can have physiological eects, however, there is little acute, short-term, subchronic, or chronic toxicity. The Cosmetic Ingredient Review Expert Panel concluded that these ingredients are safe in the current practices of use and concentration.
Bibliography
[1] WHO. Who epic project: Key results and current scientic activity. http://epic. iarc.fr/keyfindings.php. [2] Crowe et al., European Prospective Investigation into Cancer, and Nutrition (EPIC)Heart Study Collaborators:. Fruit and vegetable intake and mortality from ischaemic heart disease: results from the european prospective investigation into cancer and nutrition (epic)-heart study. Eur Heart J, 2011. http://www.ncbi.nlm.nih.gov/ pubmed/21245490.
BIBLIOGRAPHY
727
[3] Punnen S, Hardin J, Cheng I, Klein EA, and Witte JS. Impact of meat consumption, preparation, and mutagens on aggressive prostate cancer. PLoS One, 6(11):e27711, 2011. http://www.ncbi.nlm.nih.gov/pubmed/22132129. [4] Takachi R, Tsubono Y, Baba K, Inoue M, Sasazuki S, Iwasaki M, Tsugane S, and For The Japan Public Health Center-Based Prospective Study Group. Red meat intake may increase the risk of colon cancer in japanese, a population with relatively low red meat consumption. Asia Pac J Clin Nutr, 20(4):60312, 2011. http://www. ncbi.nlm.nih.gov/pubmed/22072349. [5] Sotos Prieto M, Guillen M, Sorl JV, Asensio EM, Gillem Siz P, Gonzlez JI, and Corella D. Meat and sh consumption in a high cardiovascular risk spanish mediterranean population. Nutr Hosp, 26(5):103340, 10 2011. http://www.ncbi.nlm.nih. gov/pubmed/22072349. [6] Lajous, Tondeur L, Fagherazzi G, de Lauzon-Guillain B, Boutron-Ruaualt MC, and Clavel-Chapelon F. Processed and unprocessed red meat consumption and incident type 2 diabetes among french women. Diabetes Care, 11 2011. http://www.ncbi. nlm.nih.gov/pubmed/22100967. [7] Ward MH, Cross AJ, Abnet CC, Sinha R, Markin RS, and Weisenburger DD. Heme iron from meat and risk of adenocarcinoma of the esophagus and stomach. Eur J Cancer Prev, 10 2011. http://www.ncbi.nlm.nih.gov/pubmed/22044848. [8] Hebels DG, Sveje KM, de Kok MC, van Herwijnen MH, Kuhnle GG, Engels LG, Vleugels-Simon CB, Mares WG, Pierik M, Masclee AA, Kleinjans JC, and de Kok TM. Red meat intake-induced increases in fecal water genotoxicity correlate with pro-carcinogenic gene expression changes in the human colon. Food Chem Toxicol, 10 2011. http://www.ncbi.nlm.nih.gov/pubmed/22019696. [9] Riboli E et al 2005. Meat, sh, and colorectal cancer risk: the european prospective investigation into cancer and nutrition. J Natl Cancer Inst, 97(12):90616, 6 2005. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1913932/?tool=pubmed. [10] Larsson SC and Wolk A. Red and processed meat consumption and risk of pancreatic cancer: meta-analysis of prospective studies. Br J Cancer, 1 2012. http://www. ncbi.nlm.nih.gov/pubmed/22240790. [11] The 2007 world cancer research fund/american institute of cancer research report. http://eprints.ucl.ac.uk/4841/1/4841.pdf. [12] Chan DS, Lau R, Aune D, Vieira R, Greenwood DC, Kampman E, and Norat T. Red and processed meat and colorectal cancer incidence: meta-analysis of prospective studies. PLoS One, 6(6):e20456, 2011. http://www.plosone.org/article/info% 3Adoi%2F10.1371%2Fjournal.pone.0020456.
728
[13] Alexander DD, Mink PJ, Cushing CA, and Sceurman B. A review and meta-analysis of prospective studies of red and processed meat intake and prostate cancer. Nutr J, 9:50, 11 2010. http://www.nutritionj.com/content/9/1/50. [14] Pan A, Sun Q, Bernstein AM, Schulze MB, Manson JE, Stampfer MJ, Willett WC, and Hu FB. Red meat consumption and mortality: Results from 2 prospective cohort studies. Arch Intern Med, 3 2012. http://archinte.ama-assn.org/cgi/content/ full/archinternmed.2011.2287. [15] Ornish D. Holy cow! whats good for you is good for our planet: Comment on "red meat consumption and mortality". Arch Intern Med, 3 2012. http://archinte. ama-assn.org/cgi/content/full/archinternmed.2012.174v1. [16] http://journals.cambridge.org/action/displayAbstract?fromPage= online&aid=6906504. Krikorian, Robert; Nash, Tiany A.; Shidler, Marcelle D.;Shukitt-Hale, Barbara; Joseph, James A.: Concord grape juice supplementation improves memory function in older adults with mild cognitive impairment. British Journal of Nutrition. Published online ahead of print, First View Article, doi:10.1017/S0007114509992364. [17] http://www.nutritionjrnl.com/article/S0899-9007(05)00298-4/abstract. Shukitt-Hale, Barbara; Carey,Amanda; Simon,Laura; Mark, David A.; Joseph, James A.: Eects of Concord grape juice on cognitive and motor decits in aging. Volume 22, Issue 3, Pages 295-302 (March 2006). Doi:10.1016/j.nut.2005.07.016. [18] Kesse-Guyot E, Fezeu L, Andreeva VA, Touvier M, Scalbert A, Hercberg S, and Galan P. Total and specic polyphenol intakes in midlife are associated with cognitive function measured 13 years later. J Nutr, 142(1):7683, 1 2012. http://www.ncbi. nlm.nih.gov/pubmed/22090468. [19] Pneau S, Galan P, Jeandel C, Ferry M, Andreeva V, Hercberg S, Kesse-Guyot E, and SU.VI.MAX 2. Fruit and vegetable intake and cognitive function in the su.vi.max 2 prospective study. research group. Am J Clin Nutr, 94(5):1295303, 11 2011. http://www.ncbi.nlm.nih.gov/pubmed/21955649. [20] http://www.ncbi.nlm.nih.gov/pubmed/20047325. Krikorian R, Shidler MD, Nash TA, Kalt W, Vinqvist-Tymchuk MR, Shukitt-Hale B, Joseph JA.: Blueberry Supplementation Improves Memory in Older Adults (dagger). J Agric Food Chem. 2010 Jan 4. [21] http://www.ncbi.nlm.nih.gov/pubmed/19356316. Shukitt-Hale B, Cheng V, Joseph JA.: Eects of blackberries on motor and cognitive function in aged rats. Nutr Neurosci. 2009 Jun;12(3):135-40.
BIBLIOGRAPHY
729
[22] http://www.ncbi.nlm.nih.gov/pubmed/19057194. Willis LM, Shukitt-Hale B, Joseph JA.: Recent advances in berry supplementation and age-related cognitive decline. Curr Opin Clin Nutr Metab Care. 2009 Jan;12(1):91-4. [23] http://www.ncbi.nlm.nih.gov/pubmed/19097856. Shukitt-Hale B, Kalt W, Carey AN, Vinqvist-Tymchuk M, McDonald J, Joseph JA.: Plum juice, but not dried plum powder, is eective in mitigating cognitive decits in aged rats. Nutrition. 2009 May;25(5):567-73. Epub 2008 Dec 18. [24] http://www.rain-tree.com/acai.htm. Database.: Acai (Euterpe oleracea). Rain-Tree Nutrition: Tropical Plant
[25] http://www.ourfood-news.com/Biofuel_Impact.html. Our Food.com: Biofuel impact on biodiversity and food crops. [26] http://sistemaproducao.cnptia.embrapa.br/FontesHTML/Acai/ SistemaProducaoAcai_2ed/paginas/intro.htm. Embrapa: Sistema de producao do aca. [27] http://en.wikipedia.org/wiki/Bactris_gasipaes. Wikipedia: Bactris gasipaes. [28] Chaira N, Smaali I, Besbes S, Mrabet A, Lachiheb B, and Ferchichi A:. Production of fructose rich syrups using invertase from date palm fruits. Journal of Food Biochemistry, 10 2010. http://onlinelibrary.wiley.com/doi/10.1111/j. 1745-4514.2010.00487.x/abstract. [29] Chaira N, Ferchichi A, Mrabet A, and Sghairoun M:. Chemical composition of the esh and the pit of date palm fruit and radical scavenging activity of their extracts. Pak J Biol Sci, 10(13):22027, 6 2007. http://www.ncbi.nlm.nih.gov/pubmed/ 19070182. [30] Mrabet A, Ferchichi A, Chaira N, Mohamed BS, Baaziz Z, and Penny TM:. Physicochemical characteristics and total quality of date palm varieties grown in the southern of tunisia. Pak J Biol Sci, 11(7):10038, 4 2008. http://www.ncbi.nlm.nih.gov/ pubmed/18810969. [31] Al-Farsi MA and Lee CY:. Nutritional and functional properties of dates: a review. Crit Rev Food Sci Nutr, 48(10):87787, 11 2008. http://www.ncbi.nlm.nih.gov/ pubmed/18949591. [32] Ali A, Al-Kindi YS, and Al-Said F:. Chemical composition and glycemic index of three varieties of omani dates. Int J Food Sci Nutr, 60(Suppl 4):5162, 2009. http://www.ncbi.nlm.nih.gov/pubmed/18946799. [33] Goiabada. wikipedia. http://en.wikipedia.org/wiki/Goiabada. [34] Marmalade. wikipedia. http://en.wikipedia.org/wiki/Marmalade.
730
[35] Rababah TM, Al-Mahasneh MA, Kilani I, Yang W, Alhamad MN, Ereifej K, and Al-Udatt M:. Eect of jam processing and storage on total phenolics, antioxidant activity, and anthocyanins of dierent fruits. J Sci Food Agric, 1 2011. http: //www.ncbi.nlm.nih.gov/pubmed/21254073. [36] Savikin K, Zduni G, Jankovi T, Tasi S, Menkovi N, Stevi T, and Dordevi B. Phenolic content and radical scavenging capacity of berries and related jams from certicated area in serbia. Plant Foods Hum Nutr, 64(3):2127, 9 2009. http: //www.ncbi.nlm.nih.gov/pubmed/19468835. [37] Bakkalbai E, Mente O, and Artik N:. Food ellagitannins-occurrence, eects of processing and storage. Crit Rev Food Sci Nutr, pages 28398, 3 2009. http://www. ncbi.nlm.nih.gov/pubmed/19093271. [38] Wikipedia:. Ellagic acid. http://en.wikipedia.org/wiki/Ellagic_acid. [39] Crovetto M and Uauy R:. Changes in household food and nutrient consumption in metropolitan santiago 1988-97 by income. Rev Med Chil, 138(9):10911108, 9 210. http://www.ncbi.nlm.nih.gov/pubmed/21249277. [40] Pauwels EK:. The protective eect of the mediterranean diet: focus on cancer and cardiovascular risk. Med Princ Pract, 20(2):10311, 2011. http://www.ncbi.nlm. nih.gov/pubmed/21252562. [41] Sun Q, Spiegelman D, van Dam RM, Holmes MD, Malik VS, Willett WC, and Hu FB. White rice, brown rice, and risk of type 2 diabetes in us men and women. Arch Intern Med, 170(11):9619, 6 2010. http://archinte.ama-assn.org/cgi/content/full/ 170/11/961. [42] Karl JP and Saltzman E. The role of whole grains in body weight regulation. Advances in Nutrition, 3(697):697707, 98 2012. http://advances.nutrition.org/ content/3/5/697.abstract. [43] Zhang G, Pan A, Zong G, Yu Z, Wu H, Chen X, Tang L, Feng Y, Zhou H, Chen X, Li H, Hong B, Malik VS, Willett WC, Spiegelman D, Hu FB, and Lin X. Substituting white rice with brown rice for 16 weeks does not substantially aect metabolic risk factors in middle-aged chinese men and women with diabetes or a high risk for diabetes. J Nutr, 141(9):168590, 9. http://www.ncbi.nlm.nih.gov/pubmed/ 21795429. [44] Levy-Costa RB, Sichieri R, Pontes Ndos S, and Monteiro CA:. Household food availability in brazil: distribution and trends (1974-2003). Rev Saude Publica, 39(4):530 40, 8 2005. http://www.ncbi.nlm.nih.gov/pubmed/16113900. [45] Levy RB, Claro RM, and Monteiro CA:. Sugar and overall macronutrient prole in the brazilian family diet (2002-2003). Cad Saude Publica, 26(3):47280, 3 2010. http://www.ncbi.nlm.nih.gov/pubmed/20464066.
BIBLIOGRAPHY
731
[46] Levy RB, Claro RM, and Monteiro CA:. Sugar and total energy content of household food purchases in brazil. Public Health Nutr, 12(11):208491, 11 2009. http://www. ncbi.nlm.nih.gov/pubmed/19402945. [47] Rodriguez R and Puckett C. Climate adaptation of rice symbiogenics: a new strategy for reducing climate impacts on plants. released: 7/13/2011. The United States Geological Survey (USGS). http://www.usgs.gov/newsroom/article.asp? ID=2852&from=rss_home. [48] Endopyhte-enhanced grasses. endophyte.html. http://www.uri.edu/ce/factsheets/sheets/
[49] Yao LX, Huang LX, Li GL, He ZH, Zhou CM, Yang BM, and Guo B:. Pesticide residual status in litchi orchard soils in guangdong, china. Huan Jing Ke Xue, pages 27236, 11 2010. http://www.ncbi.nlm.nih.gov/pubmed/21250457. [50] http://www.nap.edu/catalog.php?record_id=11879. National Academic Press: Lost Crops of Africa: Vol 3, Fruits. [51] http://www.ncbi.nlm.nih.gov/pubmed/20626841. Traka MH, Spinks CA, Doleman JF, Melchini A, Ball RY, Mills RD, Mithen RF.The dietary isothiocyanate sulforaphane modulates gene expression and alternative gene splicing in a PTEN null preclinical murine model of prostate cancer. Mol Cancer. 2010 Jul 13;9(1):189. [52] http://en.wikipedia.org/wiki/PTEN_%28gene%29. Wikipedia: PTEN (gene). [53] http://en.wikipedia.org/wiki/Sulphoraphane. Wikipedia: Sulforaphane. [54] http://www.ncbi.nlm.nih.gov/pubmed/19489030. Chambers KF, Bacon JR, Kemsley EK, Mills RD, Ball RY, Mithen RF, Traka MH: Gene expression prole of primary prostate epithelial and stromal cells in response to sulforaphane or iberin exposure. Prostate. 2009 Sep 15;69(13):1411-21. [55] http://www.ncbi.nlm.nih.gov/pubmed/18596959. Traka M, Gasper AV, Melchini A, Bacon JR, Needs PW, Frost V, Chantry A, Jones AM, Ortori CA, Barrett DA, Ball RY, Mills RD, Mithen RF.Broccoli consumption interacts with GSTM1 to perturb oncogenic signalling pathways in the prostate. PLoS One. 2008 Jul 2;3(7):e2568. [56] http://www.ncbi.nlm.nih.gov/pubmed/19116884. Traka MH, Chambers KF, Lund EK, Goodlad RA, Johnson IT, Mithen RF: Involvement of KLF4 in sulforaphane- and iberin-mediated induction of p21(waf1/cip1). Nutr Cancer. 2009;61(1):137-45. [57] Clarke JD, Riedl K, Bella D, Schwartz SJ, Stevens JF, and Ho E. Comparison of isothiocyanate metabolite levels and histone deacetylase activity in human subjects consuming broccoli sprouts or broccoli supplement. 59(20):1095563, 10 2011. http: //www.ncbi.nlm.nih.gov/pubmed/21928849.
732
[58] http://www.ncbi.nlm.nih.gov/pubmed/19933099. Arriola L, Martinez-Camblor P, Larranaga N, Basterretxea M, Amiano P, Moreno-Iribas C, Carracedo R, Agudo A, Ardanaz E, Barricarte A, Buckland G, Cirera L, Chirlaque MD, Martinez C, Molina E, Navarro C, Quiros JR, Rodriguez L, Sanchez MJ, Tormo MJ, Gonzalez CA, Dorronsoro M.: Alcohol intake and the Risk of coronary heart disease in the Spanish EPIC cohort study. Heart. 2009 Nov 19. [59] http://www.medscape.com/viewarticle/712821. Alcohol Cuts Risk for Heart Disease by One Third. Fran Lowry. Medscape Today. November 20, 2009. [60] http://www.ncbi.nlm.nih.gov/pubmed/19145468. Rohrmann S, Linseisen J, Vrieling A, Boetta P, Stolzenberg-Solomon RZ, Lowenfels AB, Jensen MK, Overvad K, Olsen A, Tjonneland A, Boutron-Ruault MC, Clavel-Chapelon F, Fagherazzi G, Misirli G, Lagiou P, Trichopoulou A, Kaaks R, Bergmann MM, Boeing H, Bingham S, Khaw KT, Allen N, Roddam A, Palli D, Pala V, Panico S, Tumino R, Vineis P, Peeters PH, Hjartaker A, Lund E, Redondo Cornejo ML, Agudo A, Arriola L, Snchez MJ, Tormo MJ, Barricarte Gurrea A, Lindkvist B, Manjer J, Johansson I, Ye W, Slimani N, Duell EJ, Jenab M, Michaud DS, Mouw T, Riboli E, Buenode-Mesquita HB.: Ethanol intake and the risk of pancreatic cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC). Cancer Causes Control. 2009 Jul;20(5):785-94. [61] http://www.ncbi.nlm.nih.gov/pubmed/18483352. Rohrmann S, Linseisen J, Key TJ, Jensen MK, Overvad K, Johnsen NF, Tjonneland A, Kaaks R, Bergmann MM, Weikert C, Naska A, Trichopoulou A, Trichopoulos D, Pala V, Sacerdote C, Palli D, Tumino R, Bueno-de-Mesquita HB, Vrieling A, Gonzlez CA, Larranaga N, Navarro C, Barricarte A, Quiros JR, Martnez-Garca C, Hallmans G, Stattin P, Manjer J, Wirflt E, Bingham S, Khaw KT, Egevad L, Ferrari P, Jenab M, Riboli E.: Alcohol consumption and the risk for prostate cancer in the European Prospective Investigation into Cancer and Nutrition. Cancer Epidemiol Biomarkers Prev. 2008 May;17(5):1282-7. [62] http://www.ncbi.nlm.nih.gov/pubmed/19924549. Bchner FL, Bueno-deMesquita HB, Linseisen J, Boshuizen HC, Kiemeney LA, Ros MM, Overvad K, Hansen L, Tjonneland A, Raaschou-Nielsen O, Clavel-Chapelon F, Boutron-Ruault MC, Touillaud M, Kaaks R, Rohrmann S, Boeing H, Nthlings U, Trichopoulou A, Zylis D, Dilis V, Palli D, Sieri S, Vineis P, Tumino R, Panico S, Peeters PH, van Gils CH, Lund E, Gram IT, Braaten T, Martinez C, Agudo A, Arriola L, Ardanaz E, Navarro C, Rodrguez L, Manjer J, Wirflt E, Hallmans G, Rasmuson T, Key TJ, Roddam AW, Bingham S, Khaw KT, Slimani N, Bofetta P, Byrnes G, Norat T, Michaud D, Riboli E.: Fruits and vegetables consumption and the risk of histological subtypes of lung cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC). Cancer Causes Control. 2009 Nov 19.
BIBLIOGRAPHY
733
[63] http://www.ncbi.nlm.nih.gov/pubmed/19903723. Buckland G, Gonzlez CA, Agudo A, Vilardell M, Berenguer A, Amiano P, Ardanaz E, Arriola L, Barricarte A, Basterretxea M, Chirlaque MD, Cirera L, Dorronsoro M, Eges N, Huerta JM, Larranaga N, Marin P, Martnez C, Molina E, Navarro C, Quirs JR, Rodriguez L, Sanchez MJ, Tormo MJ, Moreno-Iribas C.: Adherence to the Mediterranean Diet and Risk of Coronary Heart Disease in the Spanish EPIC Cohort Study. Am J Epidemiol. 2009 Dec 15;170(12):1518-29. Epub 2009 Nov 10. [64] http://www.ncbi.nlm.nih.gov/pubmed/20007304. Buckland G, Agudo A, Lujn L, Jakszyn P, Bueno-de-Mesquita HB, Palli D, Boeing H, Carneiro F, Krogh V, Sacerdote C, Tumino R, Panico S, Nesi G, Manjer J, Regnr S, Johansson I, Stenling R, Sanchez MJ, Dorronsoro M, Barricarte A, Navarro C, Quirs JR, Allen NE, Key TJ, Bingham S, Kaaks R, Overvad K, Jensen M, Olsen A, Tjnneland A, Peeters PH, Numans ME, Ock MC, Clavel-Chapelon F, Morois S, Boutron-Ruault MC, Trichopoulou A, Lagiou P, Trichopoulos D, Lund E, Couto E, Boeta P, Jenab M, Riboli E, Romaguera D, Mouw T, Gonzlez CA: Adherence to a Mediterranean diet and risk of gastric adenocarcinoma within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort study. Am J Clin Nutr. 2010 Feb;91(2):38190. doi: 10.3945/ajcn.2009.28209. [65] http://jnci.oxfordjournals.org/cgi/content/abstract/djq072v1. Boetta et al: Fruit and Vegetable Intake and Overall Cancer Risk in the European Prospective Investigation Into Cancer and Nutrition (EPIC). JNCI Journal of the National Cancer Institute. Online 06.04.10. Doi:10.1093/jnci/djq072. [66] http://jnci.oxfordjournals.org/cgi/content/full/djq098. Willett WC.Fruits, Vegetables, and Cancer Prevention: Turmoil in the Produce Section. J Natl Cancer Inst. 2010 Apr 6. [Epub ahead of print]. Doi:10.1093/jnci/djq098. [67] http://www.telegraph.co.uk/health/healthnews/7559168/ Five-fruit-and-veg-a-day-does-not-significantly-reduce-cancer-risk-research. html. Five fruit and veg a day does not signicantly reduce cancer risk: research. Telegraph.co.uk 07.04.2010. [68] http://www3.interscience.wiley.com/cgi-bin/abstract/112222955/ ABSTRACT. Carlos A. Gonzlez, et al.: Fruit and vegetable intake and the risk of stomach and oesophagus adenocarcinoma in the European Prospective Investigation into Cancer and Nutrition (EPIC-EURGAST) (p 2559-2566) Published Online: 27 Dec 2005 DOI: 10.1002/ijc.21678. [69] Schmid HP, Fischer C, Engeler DS, Bendhack ML, and Schmitz-Draeger BJ:. Nutritional aspects of primary prostate cancer prevention. Recent Results Cancer Res, 188:1017, 2011. http://www.ncbi.nlm.nih.gov/pubmed/21253792.
734
[70] http://www.ncbi.nlm.nih.gov/pubmed/19961915. Otsuki N, Dang NH, Kumagai E, Kondo A, Iwata S, Morimoto C: Aqueous extract of Carica papaya leaves exhibits anti-tumor activity and immunomodulatory eects. J Ethnopharmacol. 2010 Feb 17;127(3):760-7. [71] http://www.ncbi.nlm.nih.gov/pubmed/20195819. Van Kiem P, Mai NT, Van Minh C, Khoi NH, Dang NH, Thao NP, Cuong NX, Nam NH, Nhiem NX, Heyden YV, Quetin-Leclercq J, Kim GN, Jang HD, Kim YH: Two new c-glucosyl benzoic acids and avonoids from Mallotus nanus and their antioxidant activity. Arch Pharm Res. 2010 Feb;33(2):203-8. Epub 2010 Feb 24. [72] http://www.ncbi.nlm.nih.gov/pubmed/19786180. Tistaert C, Dejaegher B, Nguyen HN, Chataign G, Rivire C, Nguyen TH, Chau VM, Quetin-Leclercq J, Vander Heyden Y: Potential antioxidant compounds in Mallotus species ngerprints. Part I: Indication, using linear multivariate calibration techniques. Anal Chim Acta. 2009 Oct 12;652(1-2):189-97. [73] Elfalleh W Tlili N, Nasri N, Yahia Y, Hannachi H, Chaira N, Ying M, and Ferchichi A. Antioxidant capacities of phenolic compounds and tocopherols from tunisian pomegranate (punica granatum) fruits. Journal of Food Science, 76(5):C707C713, June/July 2011. http://onlinelibrary.wiley.com/doi/10.1111/j.1750-3841. 2011.02179.x/abstract. [74] Elfalleh W, Nasri N, Marzougui N, Thabti I, Mrabet A, Yahya Y, Lachiheb B, Guasmi F, and Ferchichi A. Physico-chemical properties and dpph-abts scavenging activity of some local pomegranate (punica granatum) ecotypes. Int J Food Sci Nutr, 60(Suppl 2):197210, 2009. http://www.ncbi.nlm.nih.gov/pubmed/19629823. [75] Elfalleh W, Ying M, Nasri N, Sheng-Hua H, Guasmi F, and Ferchichi A. Fatty acids from tunisian and chinese pomegranate (punica granatum l.) seeds. Int J Food Sci Nutr, 62(3):2006, 5 2011. http://www.ncbi.nlm.nih.gov/pubmed/21118055. [76] Lansky EP and Newman R. Punica granatum (pomegranate) and its potential for prevention and treatment of inammation and cancer. J Ethnopharmacol, 109(2):177206, 1 2007. http://www.ncbi.nlm.nih.gov/pubmed/17157465. [77] Nasri N, Tlili N, Elfalleh W, Cherif E, Ferchichi A, Khaldi A, and Triki S. Chemical compounds from phoenician juniper berries (juniperus phoenicea). Nat Prod Res, 6 2011. http://www.ncbi.nlm.nih.gov/pubmed/21707254. [78] Skulas-Ray AC, Kris-Etherton PM, Teeter DL, Chen CY, Vanden Heuvel JP, and West SG. A high antioxidant spice blend attenuates postprandial insulin and triglyceride responses and increases some plasma measures of antioxidant activity in healthy, overweight men. Journal of Nutrition, 141(8):1451, 2011. http: //www.ncbi.nlm.nih.gov/pubmed/21697300.
BIBLIOGRAPHY
735
[79] Oude Griep LM, Verschuren WM, Kromhout D, Ock MC, and Geleijnse JM. Colors of fruit and vegetables and 10-year incidence of stroke. Stroke, 9 2011. http://www. ncbi.nlm.nih.gov/pubmed/21921279. [80] Do R, Xie C, Zhang X, Mnnist S, Harald K, and et al. The eect of chromosome 9p21 variants on cardiovascular disease may be modied by dietary intake: Evidence from a case/control and a prospective study. PLoS Med, 9(10):e1001106, 2011. http: //www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.1001106. [81] Mueller L, Catalano A, Simone R, Cittadini A, Froehlich K, Boehm V, and Palozza P. Antioxidant capacity of tomato seed oil in solution and its redox properties in cultured macrophages. J Agric Food Chem, 12 2012. http://www.ncbi.nlm.nih. gov/pubmed/23205576. [82] Bowen P, Chen L, Stacewicz-Sapuntzakis M, Duncan C, Shari R, Ghosh L, Kim HS, Christov-Tzelkov K, and van Breemen R. Tomato sauce supplementation and prostate cancer: lycopene accumulation and modulation of biomarkers of carcinogenesis. Exp Biol Med (Maywood), 227(10):88693, 11 2002. http://ebm.rsmjournals. com/content/227/10/886.long. [83] Li H, Deng Z, Liu R, Loewen S, and Tsao R. Carotenoid compositions of coloured tomato cultivars and contribution to antioxidant activities and protection against h(2)o(2)-induced cell death in h9c2. Food Chem, 136(2):87888, 2013. http://www. ncbi.nlm.nih.gov/pubmed/23122140. [84] Anese M, Mirolo G, Beraldo P, and Lippe G. Eect of ultrasound treatments of tomato pulp on microstructure and lycopene in vitro bioaccessibility. Food Chem, 136(2):45863, 2013. http://www.ncbi.nlm.nih.gov/pubmed/23122084. [85] Camacho-Alonso F, Lpez-Jornet P, and Tudela-Mulero M. Synergic eect of curcumin or lycopene with irradiation upon oral squamous cell carcinoma cells. Oral Dis, 9 2012. http://www.ncbi.nlm.nih.gov/pubmed/23107022. [86] Chandra HM, Shanmugaraj BM, Srinivasan B, and Ramalingam S. Inuence of genotypic variations on antioxidant properties in dierent fractions of tomato. J Food Sci, 77(11), 11 2012. http://www.ncbi.nlm.nih.gov/pubmed/23106237. [87] Biddle M, Moser D, Song EK, Heo S, Payne-Emerson H, Dunbar SB, Pressler S, and Lennie T. Higher dietary lycopene intake is associated with longer cardiac event-free survival in patients with heart failure. Eur J Cardiovasc Nurs, 10 2012. http://www.ncbi.nlm.nih.gov/pubmed/23076979. [88] Abete I, Perez-Cornago A, Navas-Carretero S, Bondia-Pons I, Zulet MA, and Martinez JA. A regular lycopene enriched tomato sauce consumption inuences antioxidant status of healthy young-subjects: A crossover study. Journal of Functional Foods, 11 2012. http://www.sciencedirect.com/science/article/pii/ S1756464612001120.
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[89] Huang CS, Chuang CH, Lo TF, and Hu ML. Anti-angiogenic eects of lycopene through immunomodualtion of cytokine secretion in human peripheral blood mononuclear cells. J Nutr Biochem, 24(2):42834, 2 2013. http://www.ncbi.nlm. nih.gov/pubmed/22704783. [90] Fujita K, Yoshimoto N, Kato T, Imada H, Matsumoto G, Inakuma T, Nagata Y, and Miyachi E. Lycopene inhibits ischemia/reperfusion-induced neuronal apoptosis in gerbil hippocampal tissue. Neurochem Res, 38(3):4619, 3 2013. http://www. ncbi.nlm.nih.gov/pubmed/23296626. [91] Sarkar PD, Gupt T, and Sahu A. Comparative analysis of lycopene in oxidative stress. J Assoc Physicians India, 60:179, 7 2012. http://www.ncbi.nlm.nih.gov/ pubmed/23405535. [92] Devaraj S, Mathur S, Basu A, Aung HH, Vasu VT, Meyers S, and Jialal I. A doseresponse study on the eects of puried lycopene supplementation on biomarkers of oxidative stress. J Am Coll Nutr, 27(2):26773, 4 2008. http://www.ncbi.nlm.nih. gov/pubmed/18689558. [93] Vandevijvere S, Cucu T, Vinkx C, Huvaere K, Huybrechts I, and Van Loco J. Dietary intake of lycopene by the belgian adult population. Public Health Nutr, pages 18, 1 2013. http://www.ncbi.nlm.nih.gov/pubmed/23286216. [94] Syamaladevi RM, Sablani SS, Tang J, Powers J, and Swanson BG. Stability of anthocyanins in frozen and freeze-dried raspberries during long-term storage: in relation to glass transition. J Food Sci, 76(6):E41421, 8 2011. http://www.ncbi. nlm.nih.gov/pubmed/22417493. [95] Roos YH. Glass transition temperature and its relevance in food processing. Annu Rev Food Sci Technol, 1:46996, 2010. http://www.ncbi.nlm.nih.gov/pubmed/ 22129345. [96] Syamaladevi RM, Andrews PK, Davies NM, Walters T, and Sablani SS. Storage eects on anthocyanins, phenolics and antioxidant activity of thermally processed conventional and organic blueberries. J Sci Food Agric, 92(4):91624, 3 2012. http: //www.ncbi.nlm.nih.gov/pubmed/21969304. [97] Sablani SS, Andrews PK, Davies NM, Walters T, Saez H, Syamaladevi RM, and Mohekar PR. Eect of thermal treatments on phytochemicals in conventionally and organically grown berries. J Sci Food Agric, 90(5):76978, 4 2010. http://www. ncbi.nlm.nih.gov/pubmed/20355111. [98] Vinson JA, Demkosky CA, Navarre DA, and Smyda MA. High-antioxidant potatoes: Acute in vivo antioxidant source and hypotensive agent in humans after supplementation to hypertensive subjects. J Agric Food Chem, 2 2012. http: //pubs.acs.org/doi/abs/10.1021/jf2045262.
BIBLIOGRAPHY
737
[99] Review of toxicological literature: a-chaconine and a-solanine. national toxicologic program. http://ntp.niehs.nih.gov/?objectid= 6F5E930D-F1F6-975E-7037ACA48ABB25F4. [100] Cantwell m: A review of important facts about potato glycoalkaloids. Perishables Handling Newsletter, 87:2627, 8 1996. http://ucce.ucdavis.edu/files/ datastore/234-182.pdf. [101] Aziz A, Randhawa MA, Butt MS, Asghar A, Yasin M, and Shibamoto T. Glycoalkaloids (-chaconine and -solanine) contents of selected pakistani potato cultivars and their dietary intake assessment. J Food Sci, 2012. http://www.ncbi.nlm.nih. gov/pubmed/22329893. [102] Shimoi T, Ushiyama H, Kan K, Saito K, Kamata K, and Hirokado M. Survey of glycoalkaloids content in the various potatoes. Shokuhin Eiseigaku Zasshi, 48(3):77 82, 6 2007. http://www.jstage.jst.go.jp/article/shokueishi/48/3/77/_pdf. [103] Friedman M. Potato glycoalkaloids and metabolites: roles in the plant and in the diet. J Agric Food Chem, 54(23):865581, 11 2006. http://www.ncbi.nlm.nih. gov/pubmed/17090106. [104] Mder J, Rawel H, and Kroh LW. Composition of phenolic compounds and glycoalkaloids alpha-solanine and alpha-chaconine during commercial potato processing. J Agric Food Chem, 57(14):62927, 7 2009. http://www.ncbi.nlm.nih.gov/pubmed/ 19534529. [105] Siebenhofer A, Jeitler K, Berghold A, Waltering A, Hemkens LG, Semlitsch T, Pachler C, Strametz R, and Horvath K. Long-term eects of weight-reducing diets in hypertensive patients. Cochrane Database Syst Rev, 7(9):CD008274, 9 2011. http://www.ncbi.nlm.nih.gov/pubmed/21901719. [106] Mulrow CD, Chiquette E, Angel L, Grimm R, Cornell J, Summerbell CD, Anagnostelis BB, and Brand M. Withdrawn: Dieting to reduce body weight for controlling hypertension in adults. Cochrane Database Syst Rev, 8(4):CD000484, 10 2008. http://www.ncbi.nlm.nih.gov/pubmed/18843609. [107] Lankinen M, Schwab U, Gopalacharyulu PV, Seppnen-Laakso T, Yetukuri L, SysiAho M, Kallio P, Suortti T, Laaksonen DE, Gylling H, Poutanen K, Kolehmainen M, and Oresic M. Dietary carbohydrate modication alters serum metabolic proles in individuals with the metabolic syndrome. Nutr Metab Cardiovasc Dis, 20(4):24957, 5 2010. http://www.ncbi.nlm.nih.gov/pubmed/19553094. [108] Hroux M, Janssen I, Lam M, Lee DC, Hebert JR, Sui X, and Blair SN. Dietary patterns and the risk of mortality: impact of cardiorespiratory tness. Int J Epidemiol, 39(1):197209, 2 2010. http://www.ncbi.nlm.nih.gov/pmc/articles/ PMC2912488/?tool=pubmed.
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[109] Ooi CP and Loke SC. Sweet potato for type 2 diabetes mellitus. Cochrane Database Syst Rev, 15(2):CD009128, 2 2012. http://www.ncbi.nlm.nih.gov/ pubmed/22336861. [110] Leyva-Guerrero E, Narayanan NN, Ihemere U, and Sayre RT. Iron and protein biofortication of cassava: lessons learned. Curr Opin Biotechnol, 1 2012. http: //www.ncbi.nlm.nih.gov/pubmed/22226461. [111] Sayre R, Beeching JR, Cahoon EB, Egesi C, Fauquet C, Fellman J, Fregene M, Gruissem W, Mallowa S, Manary M, Maziya-Dixon B, Mbanaso A, Schachtman DP, Siritunga D, Taylor N, Vanderschuren H, and Zhang P. The biocassava plus program: biofortication of cassava for sub-saharan africa. Annu Rev Plant Biol, 62:25172, 6 2011. http://www.ncbi.nlm.nih.gov/pubmed/21526968. [112] Narayanan NN, Ihemere U, Ellery C, and Sayre RT. Overexpression of hydroxynitrile lyase in cassava roots elevates protein and free amino acids while reducing residual cyanogen levels. PLoS One, 6(7):e21996, 2011. http://www.ncbi.nlm.nih.gov/ pubmed/21799761. [113] Abhary M, Siritunga D, Stevens G, Taylor NJ, and Fauquet CM. Transgenic biofortication of the starchy staple cassava (manihot esculenta) generates a novel sink for protein. PLoS One, 6(1):e16256, 1 2011. http://www.ncbi.nlm.nih.gov/pmc/ articles/PMC3026814/?tool=pubmed. [114] Delort E, Jaquier A, Chapuis C, Rubin M, and Starkenmann C. Volatile composition of oyster leaf ( mertensia maritima (l.) gray). J Agric Food Chem2012, 60(47):11681 90, 11. http://www.ncbi.nlm.nih.gov/pubmed/23140514. [115] Szakiel A, Pczkowski C, and Huttunen S. Triterpenoid content of berries and leaves of bilberry vaccinium myrtillus from nland and poland. J Agric Food Chem, 11 2012. http://www.ncbi.nlm.nih.gov/pubmed/23157739. [116] Szakiel A, Pczkowski C, Koivuniemi H, and Huttunen S. Comparison of the triterpenoid content of berries and leaves of lingonberry vaccinium vitis-idaea from nland and poland. J Agric Food Chem, 60(19):49945002, 5 2012. http://www.ncbi.nlm. nih.gov/pubmed/22490120. [117] Ltti AK, Riihinen KR, and Jaakola L. Phenolic compounds in berries and owers of a natural hybrid between bilberry and lingonberry (vaccinium intermedium ruthe). Phytochemistry, 72(8):8105, 6 2011. http://www.ncbi.nlm.nih.gov/ pubmed/21382629. [118] Mller D, Schantz M, and Richling E. High performance liquid chromatography analysis of anthocyanins in bilberries (vaccinium myrtillus l.), blueberries (vaccinium corymbosum l.), and corresponding juices. J Food Sci, 77(4):C3405, 4 2012. http: //www.ncbi.nlm.nih.gov/pubmed/22394068.
BIBLIOGRAPHY
739
[119] Szakiel A, Nizyski B, and Pczkowski C. Triterpenoid prole of ower and leaf cuticular waxes of heather calluna vulgaris. Nat Prod Res, 11 2012. http://www. ncbi.nlm.nih.gov/pubmed/23148482. [120] Petronelli A, Pannitteri G, and Testa U. Triterpenoids as new promising anticancer drugs. Anticancer Drugs, 20(10):88092, 11 2009. http://www.ncbi.nlm.nih.gov/ pubmed/19745720. [121] Mullauer FB, Kessler JH, and Medema JP. Betulinic acid, a natural compound with potent anticancer eects. Anticancer Drugs, 21(3):201527, 3 2010. http: //www.ncbi.nlm.nih.gov/pubmed/20075711. [122] Fukushima EO, Seki H, Ohyama K, Ono E, Umemoto N, Mizutani M, Saito K, and Muranaka T. Cyp716a subfamily members are multifunctional oxidases in triterpenoid biosynthesis. Plant Cell Physiol, 52(12):205061, 12 2011. http: //www.ncbi.nlm.nih.gov/pubmed/22039103. [123] Seki H, Sawai S, Ohyama K, Mizutani M, Ohnishi T, Sudo H, Fukushima EO, Akashi T, Aoki T, Saito K, and Muranaka T. Triterpene functional genomics in licorice for identication of cyp72a154 involved in the biosynthesis of glycyrrhizin. Plant Cell, 23(11):411223, 11 2011. http://www.ncbi.nlm.nih.gov/pmc/articles/ PMC3246328/. [124] Isbrucker RA and Burdock GA. Risk and safety assessment on the consumption of licorice root (glycyrrhiza sp.), its extract and powder as a food ingredient, with emphasis on the pharmacology and toxicology of glycyrrhizin. Regul Toxicol Pharmacol, 46(3):16792, 12 2006. http://www.ncbi.nlm.nih.gov/pubmed/16884839. [125] Cosmetic Ingredient Review Expert Panel. Final report on the safety assessment of glycyrrhetinic acid, potassium glycyrrhetinate, disodium succinoyl glycyrrhetinate, glyceryl glycyrrhetinate, glycyrrhetinyl stearate, stearyl glycyrrhetinate, glycyrrhizic acid, ammonium glycyrrhizate, dipotassium glycyrrhizate, disodium glycyrrhizate, trisodium glycyrrhizate, methyl glycyrrhizate, and potassium glycyrrhizinate. Int J Toxicol, 26, 2007. http://www.ncbi.nlm.nih.gov/pubmed/17613133.
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Chapter 9 Ingredients
9.1 No-eect-level
[1] One of the most eective argument to play down the danger of cancer is to classify the presence of a contaminant as not relevant because of the no-eect-level. According to that theory the reduction of the amount of contaminants leads to a point where a carcinogenic activity only develops after 100 to 150 years,that is after dying from other causes. Unfortunately cancer comes up sooner, for the time being 25% of all human beings die of cancer. More as 50% of all cases are caused by ecological factors. The theory of no-eect-level can only be applied on persons who wish not to reproduce himself. The genes who suered mutations because of ecological factors should not be passed on to following generations in order not to pass on the genetic predisposition to cancer. Carcinogenic activities are often analysed considering an isolated cause or a single agent. Today there are lots of chemicals with carcinogenic activity boosting the eects in a synergistic way. Examples of such synergistic activities are: Nitrosamines with PCB, benzpyrene BHT and traces of mercury. The international institute of cancer in Lyon, France has proved that damages on the structure of chromosomes caused by toxic substances are passed on from generation to generation. The institute gave small dose of nitrosamines to pregnant mice. Typical tumours were not only found on the mother but although on following generations who had no contact with nitrosamines. 741
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CHAPTER 9. INGREDIENTS
According to professor Schmhl, researcher on cancer in Heidelberg,Germany, there is no dose, even being very small, that is free of danger to cause cancer because of the eect of synergistic addition of the eects. The fact that a mouse can live with a small dose of carcinogen agents does not prove anything. The mouse does not smoke, it does not breathe sulphur dioxide, it does not take medicine, it does not eat ham, smoked salmon or hamburgers. Therefore we have to observe very critically all additives and all ingredients of our food. [2]
9.2
Additives in the European Food Law and the Codex Alimentarius
The European food law is more stringent as the Codex Alimentarius. If a food or any agricultural product meets European rules it is also t for Codex. The Codex used the principles of the EU food law. To instance, the E-Numbers of additives from the European numbering system are being used by the Codex deleting the E in front of the number.
9.2.1
Additives in brief
The Regulation of food additives in Europe changed. 1333/2008 will be in force. However, the lists of additives of older directives (94/35/EC, 94/36/EC and 95/2/EC) remain valid because new lists are not ready yet.
9.2.2
Additives in the European Union
The article of the European Commission on Food Additives and avourings gives a summery of European food law. http://ec.europa.eu/food/fs/sfp/av_index_en.html
9.2.3
Regulation 1333/208 on food additives
The Regulation brings together in a single legislative act all types of food additives including colours and sweeteners. http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=OJ:L:2008:354:0016:0033:EN:PDF Food enzymes are covered by Regulation (EC) No 1332/2008.
9.2.4
List of additives
Whilst these lists cited as "Annexes" in 133/2008 are being drawn up, the Annexes of Directives 94/35/EC, 94/36/EC and 95/2/EC remain in force.
9.3. CODEX ALIMENTARIUS
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9.2.5
Codex Food additives
The "Codex General Standard for Food Additives" (GSFA, Codex STAN 192-1995) sets forth the conditions under which permitted food additives may be used in all foods, whether or not they have previously been standardized by Codex. http://www.codexalimentarius.net/gsfaonline/CXS_192e.pdf http://www.codexalimentarius.net/gsfaonline/index.html?lang=en http://www.codexalimentarius.net/gsfaonline/additives/index.html
9.2.6
Contact between the European Commission and the Codex Alimentarius
The Codex Alimentarius Commission adopts standards, codes of practices and other related texts that are prepared by specialised Codex Committees and Ad hoc Task Forces. The 27 Member States of the European Union are all members of the Codex Alimentarius Commission. In 2003, the European Community (now the EU) also became a full member of the Codex Alimentarius Commission and shares the competence with its Member States on the basis of the level of harmonisation of the relevant legislation. Since the entry into force of the Treaty of Lisbon on 1 December 2009 the European Union replaced the European Community. The EU and its Member States elaborate EU position papers on issues discussed in the Codex Alimentarius Commission, the various Codex Committees and Task Forces. http://ec.europa.eu/food/international/organisations/codex_en.htm http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=OJ:L:2003:309:0014:0021:EN:PDF http://ec.europa.eu/food/fs/ifsi/eupositions/ccfa/index_en.html
9.2.7
European regulation
All directives are available at: http://eur-lex.europa.eu/RECH_naturel.do Year and Number of the Directive Old directives cite only the two last digits of the year. New directives give four digits such as: 91/414 = year 1991 Nr.414 and 2009/128 = year 2009 Nr.128 To search by one word Just type a word, such as "pesticides" http://eur-lex.europa.eu/RECH_mot.do
9.3
Codex Alimentarius
The Codex Alimentarius Commission was created in 1963 by FAO and WHO to develop food standards, guidelines and related texts such as codes of practice under the Joint
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FAO/WHO Food Standards Programme. The main purposes of this Programme are protecting health of the consumers and ensuring fair trade practices in the food trade, and promoting coordination of all food standards work undertaken by international governmental and non-governmental organizations. [3] - Current Standards: Here all Standards are available. http://www.codexalimentarius.net/web/standard_list.do?lang=en - Search system: Very ecient search engine of Codex http://www.codexalimentarius.net/search/advancedsearch.do - Codex database for limits of pesticides in foods http://www.codexalimentarius.net/mrls/pestdes/jsp/pest_q-e.jsp - Codex database for veterinary drugs residues in foods http://www.codexalimentarius.net/mrls/vetdrugs/jsp/vetd_q-e.jsp - Codex Food additives http://www.codexalimentarius.net/gsfaonline/CXS_192e.pdf http://www.codexalimentarius.net/gsfaonline/index.html?lang=en
9.3.1
Intensive farming in the European Union
Intensive farming bears the risk of overuse of antibiotics according the National Consumer Council March 11 1998 in London. The council blames in the words of his Director Ruth Evans the European Unions common agricultural policy encouraging intensive farming. Ruth Evans says:" The Common Agricultural policy is not just wasteful and costly to consumers,it also encourages farming practices which raise serious public health concerns. Overintensive farming methods led to the BSE/CJD crisis.So long as we reward high output rather than high quality of food further risks are likely" The Council enumerates in his report the following areas of concern:
9.3.2
1- Antibiotic
It is being used to treat , prevent and reduce disease and as a growth promoter in animals. The residues can be toxic and cause hypersensitivity to antibiotics in some humans. Uncontrolled use of antibiotics increase the resistance of certain bacteria to these therapeutics. Salmonella and Escherichia coli are developing the capacity to resist the medicine which treats diseases on humans and on animals.
9.3.3
2- Genetic modication
The introduction of selected properties of an organism into another bears unknown risks which cannot be estimated by risk analysis.
9.3. CODEX ALIMENTARIUS
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9.3.4
3- Hormones
Hormones are used to promote animal growth. This may lead to the development of sexual characteristics and certain cancers. In spite of being forbidden in the European Community many hormones are illegal sold and used.
9.3.5
4-Nitrates
Nitrates are used to enrich the soil and promote growth to vegetable crops. High use of nitrates are linked to the cyanosis called "blue baby Syndrome" and to stomach cancer. The maximum nitrate levels in vegetables and water which have been established are sometimes exceeded.
9.3.6
5-Pesticides
Pesticides are used to protect crops and increase productivity.Exposure to certain pesticides may weaken the immune system and reduce resistance to cancer. It has been noted that some pesticides are deposited in higher rates in the interior of fruits and vegetables as in the skin. Peeling and washing has therefore no eect in reducing the content of pesticides in food. According to Mrs. Evans the EU should promote the reduction of the use of antibiotics,pesticides and nitrates and strengthen the regulatory framework of the industry, which has proved to be inadequate. In 1988 began in United Kingdom a monitoring of pesticide residues in food. Since then there were no detectable levels of residues found in around 70% of examined samples.Only 1% exceeded the maximum residue levels. Eorts however should be undertaken to achieve further reduction , because there is noeect-level.
9.3.7
Red meat consumption and risk of cancer
The government of United Kingdom has made a statement that people who eat average 90 grams of cooked red meat per day, or around 8 to 10 portions a week need no reduction of red meat consumption.This includes beef, lamb and pork. A lower consumption of red meat would probably reduce the risk of colon rectal cancer. However eating to little meat could cause iron deciency. In order to correct wrong behaviour related to food it is recommended to: Maintain a healthy body weight. Increase the amount and variety of fruits, vegetables and bers.
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Be cautious about taking high dose of puried vitamin and mineral supplements.They are not fully free of risks.
9.3.8
Nitrates and nitrites are less detrimental to health as supposed
[4] Gastrointestinal cancer and methemoglobinemia risk in infants may be increased by nitrates and nitrites in food. Hord, Tang an Bryan 2009, however, claim that the risks and health benets associated with consumption of dietary nitrate and nitrite from fruits and leafy green vegetables should be re-evaluated. The authors stress that nitrates and nitrites from fruits and vegetables have a protective eect against coronary heart disease and ischemic stroke risk. 80 per cent of dietary nitrates are derived from vegetable consumption. The Dietary Approaches to Stop Hypertension (DASH) studies, using diets low in fat dairy products and 8-10 servings, lowered blood pressure to an extent similar to that achieved with medication. This was attributed to the high calcium, potassium and low sodium concentrations. Hord and colleagues, however, say that the nitrate contained in some fruit and vegetables may be associated with the blood pressure reduction. Mammalian enzymes were found to have nitrate reductase activity as well bacterial nitrate reductases in mouth and gastrointestinal tract reduce nitrate to nitrite. The authors found a variability on nitrate concentration in vegetables, fruit, juice and fresh and processed meats, varying between 174 to 1222 mg in patterns of the DASH diets.
9.3.9
Risks associated with excessive nitrate and nitrite consumption
Hord and colleagues say that infants under six months exposed to excess nitrite may suer from methhemoglobinemia and that infants fed home-prepared food are probably my be harmed by high nitrates in foods. Cured and processed meats with added nitrates have also a detrimental eect on health, but there are little evidences of cancer risk associated with cured meat. The authors stress that any health risk from nitrates in fruits and vegetables are outweighed by their benets, such as reduction of blood pressure. They call to reconsider the acceptable daily intake (ADI) levels for nitrites and nitrates and suggest to consider nitrates as nutrients.
9.4. EU FOOD ADDITIVES REGULATIONS
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9.4
EU food additives regulations
[5] The regulation 1331/2008 [6] lays down a common procedure for the assessment and authorisation of food additives, food enzymes, food avourings. It is therefore important for the procedure of approval of food additives, but not for the food industry and the consumer interested on positive lists of additives. These are given in 1332/2008 [7], 1333/2008 [8] and 1334/2008 [9] and the annexes Directives 94/35/EC [10], 94/36/EC [11]and 95/2/EC [12]. Feed additives 429/ 2008 should also be considered by animal breeders.
9.4.1
Transitional provisions for additives
In accordance with article 30 of Regulation (EC) No 1333/2008, additives that are permitted in food under Directives 94/35/EC, 94/36/EC and 95/2/EC and their conditions of use will be entered the Community list of food additives in Annex II to the regulation. To that end the compliance with their general and specic conditions of use must rst be reviewed. This review should be completed by January 2011. The use of food additives already permitted in Directives 94/35/EC, 94/36/EC and 95/2/EC will continue to be permitted until the review has been nalised and the additives have been transferred in the Community list of food additives in the Annex II of the new regulation. In the mean time, when necessary, until the establishment of the Community list of food additives, the annexes to the current directives can be amended based on a comitology procedure.
9.5
European food colours legislation
All colours which are allowed to be added to foods are included in positive lists. Substances therein have been tested for their safety and meet specic purity criteria. The Colour Directive 94/36/EC gives the actual permitted food colours. The safety of food colours and other food additives is evaluated by the Scientic Committee on Food (SCF), an advisory expert committee of the European Commission, located in Brussels. The EU Commission Directive 95/45/EC of 26 July 1995 lays down specic purity criteria concerning colours for use in foodstus with amendment Directives 1999/75/EC, 2001/50/EC and 2004/47/EC. The European Commission regulations are binding to all member countries of the EU, and have to be implemented into their national laws. Non-EU member states food additives are regulated by their national authorities.
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9.5.1
World Health Organisation
The WHO and the FAO members of the UN have an advisory committee, the Joint WHO/FAO Expert Committee on Food Additives (JECFA), The European SCF and JEFF As toxicological evaluation, an ADI (Acceptable Daily Intake) value, expressed in mg/kg body weight per day, is allocated to the additive, or its use is not recommended. The E numbers for colour additives range from E100 (curcumin) to E180 (lithorubine BK). Since a pigment derived from extraction may be dierently specied as the same pigment derived from chemical synthesis, it may be characterised by a dierentiated E number: beta- carotene extracts e.g. are listed under E160ai (mixed carotenes), and synthetic beta-carotene under E 160aii (beta-carotene). Food additive colours are dened in this regulation as: [11] "Substances which add or restore colour in a food, and include natural sources which are normally not consumed as a foodstu as such and not normally used as a characteristic ingredient in food . Thereby, the Colour Directive excludes colouring foodstus and food ingredients, which may be used in the preparation of a nal food, from the food additive regulation, such as tomato juice (lycopene) or red beet juice (betanine) which is added to some foods, colouring them. According to the Colour Directive, the legal situation of such pigments changes, when they are selectively extracted -relative to the nutritive or aromatic constituents -from the original source material, and (in line with Frame Directive 89/107 /EEC) intentionally added to foods for the purpose of their colouration. [13]
9.5.2
Global harmonisation of food colours
The global trade requires harmonisation of food regulations on a world-wide basis in order to abolish barriers of trade and to ensure that the economical and nutritional demands of all nations are considered. JECFA develops international standards for food additives considering toxicology and elaborating purity criteria. These standards are the basis of the standard for food colours of the General Standard for Food Additives from the Codex Alimentarius. It is not legally binding, but inuences food colour regulations all over the world. [14] Table 9.1: Natural food colours Colour EC No Re/blue E163 Natural occurrence Pigment Black grapes, blackcurrants, cherries Anthocyanins elderberries, red cabbage, strawberries
9.5. EUROPEAN FOOD COLOURS LEGISLATION Pink Red Green Carotinoids: E160a (i) E160a (ii) E160b E160c E160d E160e E160f E160b E161g E100 E101 E153 E150a-d Annatto Carrots Oranges Prawns Red pepper Tomatoes Palm fruit E162 E120 E140 E141 Beetroot Cochineal Alfafa grass, nettles, parley, spinach Betanin Carminik acid Chlorophylls Chlorophyllins
749
Yellow Orange Red
Yellow Yellow Black Brown
Turmeric Eggs, milk, yeast Carbonised vegetable material Melanoidins (caramel)
Mixed carotenes Beta-carotene Bixin, norbixin Capsanthin, Capsorubin Lycopene Apocarotenal Apocarotenal (ethyl ester) Lutein Canthaxanthin Curcumin Carbon black Melanoidins
9.5.3
B-coeritrina natural red colour
[15] Looking for alternatives to articial food colours such as sunset yellow, tartrazine and quinoline yellow Bermejo Ruperto, J. M. Alvarez-Pez and colleagues studied the marine algae Porphyridium cruentum and its protein B-coeritrina. Phycoerythrin is a pigment of red algae and cyanobacteria. B-phycoerythrin and Rphycocyanin in native state, were obtained by the authors using an inexpensive and simple process from the red alga Porphyridium cruentum.
9.5.4
Removable edible paint for candies and dietary supplements
[16] A new form of coloured coating is being suggested by D. Tyler McQuade and colleagues. The coating is based on coloured calcium alginate hydrogels being useful in food such as candies and dietary supplements, cosmetic, medicinal, and textile uses and to wherever nontoxic, easily removable coloured coating is desired. Tests were made on articial turf spraying aqueous solutions of gelling agents: One layer of calcium chloride solution was followed by spraying sodium alginate solution with one per cent red food colour. The sprayed solutions then combined into a coloured thin lm.
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Gels with dierent physical properties were obtained varying the concentrations of the gelling agent. Low concentration of 0.1 moles/l of calcium chloride resulted in a brittle, easily removable lm. High concentration of 2.0 moles/l of gelling agent resulted in a lm which adhered well and was dicult to remove.
9.5.5
Flavours,avour enhancer
These ingredients give taste,hide o avour and permit standardisation of the taste of food. They increase the value of the food bearing however the danger of excessive consume.
9.5.6
Aroma
According to labelling rules of the European Community aromes can be included in the label without mentioning their origin. Articial aromes and synthetic aromes are found under this class.Natural aromes are more valuable as articial ones.They are more complex having therefore a better taste.The composition of synthetic avours is more simple in their composition as natural ones. The taste is therefore not so specic. Natural aromes are extracts of of spices such as vanilla and orange peeling. Aroma, identical with natural aromas are synthetic origin.They have identical chemical structure of natural aromas. Articial aromas are of synthetical origin.They are not found in nature, for example: ethyl vanillin, methyl cumarine,resorcine dimethyl ether.
9.6
9.6.1
Smoke avourings
Smoke avourings: Only two out of 11 are safe, says EFSA
[17] Nine smoke avourings used in food production,were found not safe by the European Food Safety Authority (EFSA). Safety concerns, and possible risk of cancer could not be ruled out for one of those smoke avourings. Only two were found to be safe. All these avourings are currently, or have previously been, on the market in the EU. They are added to meat, sh, cheeses, soups, sauces, drinks and confectionery to give them a "smoked" avour, as an alternative to traditional smoking. Of concern were TRADISMOKE A MAX, Scansmoke R909, Scansmoke PB 1110, SmokEz C-10, SmokEz Enviro 23, SmokEz Enviro 23, Zesti Smoke Code 10, AM 01, and Fumokomp which presented insucient data. Of no concern were Scansmoke SEF7525 and Smoke Concentrate 809045. See the whole list [18] of assessed smoke avourings and safety concerns at: http://www.efsa.europa.eu/en/ceftopics/doc/ceftable.pdf All smoke avourings are being assessed according to EU Regulation 2065/2003 to see
9.6. SMOKE FLAVOURINGS
751
if they are suitable for human consumption. They will only be allowed for use in food if they are shown to be safe and are not a risk to health. The Regulation 2065/2003EC states: " Because smoke avourings are produced from smoke which is subjected to fractionation and purication processes, the use of smoke avourings is generally considered to be of less health concern than the traditional smoking process. Several international regulations cover smoke avourings because of the concern about PAHs (Polycyclic Aromatic Hydrocarbons). Summary of the Regulation EC 2065/2003 [19] The chemical composition of smoke depends among other things on the type of wood used, the method used for developing smoke, the water content of the wood and the temperature and oxygen concentration during smoke generation. Smoked foods in general give rise to health concerns, especially with respect to the presence of polycyclic aromatic hydrocarbons. The production of smoke avourings starts with the condensation of smoke. The condensed smoke is normally separated by physical processes into a water-based primary smoke condensate, a water-insoluble high-density tar phase and a water-insoluble oily phase. The water-insoluble oily phase is a by-product and unsuitable for the production of smoke avourings. The primary smoke condensates and fractions of the water-insoluble high density tar phase, the "primary tar fractions", are puried to remove components of smoke which are most harmful to human health. They may then be suitable for use as smoke avouring. Smoke is generated from wood which has not been treated with chemical substances during six month preceding felling. Herbs, spices, wigs of juniper and twigs, needles and cones of picea may be added if they are free of residues or chemical treatment. The source material is subjected to controlled burning, dry distillation or treatment with superheated steam in a controlled oxygen environment with a maximum temperature of 600o . The smoke is condensed. Water and/or solvents may be added to achieve phase separation. Physical processes may be used for isolation, fractionation and/or purication to obtain the following phases:
9.6.2
Water-based "primary smoke condensate"
It contains mainly carboxylic acids, carbonylic and phenolic compounds, having a maximum content of: benzo(a)pyrene 10g/kg benz(a)antracene 20g/kg
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9.6.3
"Water-insoluble high-density tar phase
This fraction precipitates during the separation phase and cannot be used as such for the production of smoke avourings but only after appropriate physical processing to obtain fractions from this water-insoluble tar phase which are low in polycyclic aromatic hydrocarbons, already dened as "primary tar fraction" having a maximum content of: benzo(a)pyrene 10g/kg benz(a)antracene 20g/kg
9.6.4
"Water-insoluble oily phase"
If no phase separation has occurred during or after the condensation, the smoke condensate obtained must be regarded as a water-insoluble high-density tar phase, and must be processed by appropriate physical processing to obtain primary tar fractions which stay within the specied limits. Contamination of foods with PAHs can happen by environmental PAHs that are present in air (by deposition), soil (by transfer) or water (by deposition or transfer), and during processing and cooking. The major contributors to PAH intake in the average diet are oils and fats, cereals, fruits and vegetables. The waxy surface of vegetables and fruits can concentrate low molecular mass PAH through surface adsorption and particle-bound high-molecular-mass PAH can contaminate the surface due to atmospheric fallout.
9.6.5
Flavour enhancer
Flavour enhancer intensify avour of food.Persons which are sensible to glutaminic acid may experience the "Chinese restaurant syndrome".There were related pressure on brainsides, headache,stiness of neck[20]. On rats avour enhancer cause alterations of reproduction and retarded learning. Flavour enhancer potentiate voracity. Flavour enhancer in human metabolism are transformed in uric acid which is undesired. Animals like rats do not form uric acid from avour enhancers because they metabolise them as alantoine. Toxicological tests on rats are therefore irrelevant. Glutaminic acid is part of the proteins of our body. However there is a capital dierence between glutaminic
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acid bound in a sequence of proteins and glutaminic acid or their salts being obtained synthetically. Glutaminic acid of the protein sequence is not free. It is liberated during digestion and reaches the bloodstream slowly. Flavour enhancer are already free and reach the bloodstream immediately in great amount and may cause the above mentioned syndrome.[21] People with the characteristic symptom should ask for food without glutamate. Industry should reduce glutamate in their formulas and try to avoid completely its use in dry soups,dry sauces and an innity of other product which are on market. Industry should return to natural ingredients avoiding synthetic other products. In doing so there is also a benet on marketing because the products from natural resource have great acceptance by consumers. Please read the list of ingredients on the label, carefully, especially those of dry soups and dried sauces because they have a great amount of salts of glutamic acid.
9.6.6
The INTERMAP study links glutamate to obesity
[22] Consumption of the avour enhancer monosodium glutamate (MSG) may increase the risk of gaining weight, regardless of energy intake according to a study on humans by Ka He and colleagues 2008. The authors cite that animal studies indicate that monosodium glutamate (MSG) can induce hypothalamic lesions and leptin resistance, possibly inuencing energy balance, leading to overweight. In his study He found that people with an average intake of 0.33 g/day of MSG in food preparation had an average BMI 23.5 kg per sq. m. and Non-MSG users had an average BMI of 22.3 kg per sq. m. The authors concluded that prevalence of overweight was signicantly higher in MSG users than in non-users.
9.6.7
Reaction of the Glutamate industry
[23] The Glutamate Association questions the study in a statement from 22.08.2008. The Association says that according to data of the WHO the countries with high intakes of glutamate do not have high population BMI. The average person in the United States consumes approximately 11 grams of glutamate daily from all food sources (primarily dietary protein), while the body produces about 50 grams of free glutamate daily. Dietary glutamate from MSG averages less than one half gram/person/day .
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Human studies where MSG was added to the diet have failed to show changes in body weight (Essed et al., Appetite 2007,48:29) [24] A study on rats suggests that MSG in the diet actually suppresses body weight. (Kondoh and Torii, PhysiolBehav2008,doi:10.1016/j.physbeh.2008.05.010) [25]
9.6.8
E620 Glutamic acid
Glutamic acid occurs naturally in many foods and contributes to their avour. Glutamic acid was rs obtained from gluten which gave the name to this aminoacid. The avour of its salt as monosodium glutamate was termed by professor Ikeda as umami.
9.6.9
E621 Sodium glutamate
Glutamate has a neurotransmitter function in the physiology of nervous cells.[26] The neural function was used to promote selling of Intelligence Drugs to improve marks at school. Unfortunately there was no such benet found. Monosodium glutamate is one of the most abundant naturally occurring non-essential amino acids. Monosodium glutamate is used to improve the avour and balances blends and rounds the total perception of other tastes in meals with meat, sh, poultry, many vegetables, sauces, soups, and marinades. It is, however not indicated in combination with sucrose. It improves the pleasantness only in the right concentration and becomes unpleasant in concentrations more than 1 gram per 100 ml in soups. Chinese Restaurant Syndrome:The "MSG symptom complex" was originally termed the "Chinese Restaurant Syndrome" MSG became the focus and the symptoms have been associated with MSG ever since. In normal conditions, humans have the ability to metabolize glutamate that has a very low acute toxicity. The oral lethal dose to 50% of subjects (LD50) is between 15 to 18 g/kg body weight in rats and mice respectively, ve times greater than the LD50 of salt (3 g/kg in rats). Therefore, the intake of MSG as a food additive and the natural level of glutamic acid in foods do not represent a toxicological concern in humans. [27]
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9.6.10 9.6.11 9.6.12 9.6.13 9.6.14 9.6.15 9.6.16 9.6.17 9.6.18 9.6.19 9.6.20 9.6.21 9.6.22 9.6.23 9.6.24 9.6.25
E622 Potassium glutamate E623 Calcium glutamate E624 Monoammonium glutamate E625 Magnesium glutamate E626 Guanylic acid E627 Sodium guanylate E628 Potassium guanylate E629 Calcium guanylate E630 Inosinic acid E631 Disodium inosinate E632 Dipotassium inosinate E633 Calcium inosinate E634 Calcium 5ribonucleotid E635 Disodium 5ribonucleotid E640 Glycine and salts Ethylmaltol
It is used as avour enhancer in sweet product mainly together with articial sweetener s.It is used in chocolate, cakes and desserts.There is doubt about ethylmaltol being responsible for talasemia (a rare anaemia).
9.6.26
E239 Hexamethylentetramin
It is a widely used substance. as medicine against gout and infections of the urinary tract.It is also a vulcanisation accelerator and is used in the chemistry of explosives.In food it is a donator of formaldehyd and is used to to improve the optical appearance of food.At the moment it is used only in some kind of cheese.
9.6.27
Natamycin
It is an antibiotic used in infections of mouth,foot and genitals.It is employed in food industry to treat the shell of cheese. Resistance against this antibiotic will soon be established
756
in bacteria coming in contact with it.His use should therefore forbidden in food industry
9.6.28
Antioxidants
Antioxidants are used to improve the shelf life of food interfering in the reaction of oxygen with dierent components of food avoiding their chemical decomposition. They are used in soups,sauces in powder,chewing gum,dried products of potatoes margarineoil, icecream.
9.7
Measuring the antioxidant activity of phytochemicals
The methods used to evaluate antioxidant activity of phytochemicals such as food extracts, dietary supplements, fruits and juices are:
9.7.1
Oxygen radical absorbance capacity (ORAC)
ORAC is a method of quantitating the oxygen-radical absorbing capacity (ORAC) of antioxidants in serum using a few microliter. The ORAC assay determines the total antioxidant capacity of a sample which is estimated by taking the oxidation reaction to completion when all of the nonprotein antioxidants (which include alpha-tocopherol, vitamin C, betacarotene, uric acid, and bilirubin) and most of the albumin in the sample are oxidized by the peroxyl radical. Results are quantied by measuring the protection produced by antioxidants. [28] When comparing ORAC data, care must be taken to ensure that the units and food being compared are similar. Some evaluations will compare ORAC units per grams dry weight, others will evaluate ORAC units wet weight and still others will look at ORAC units/serving. [29] Marketing uses ORAC as a selling argument for concentrated supplements claiming to be the number one ORAC product. However, there are no published the scientic literature so are dicult to evaluate on these values. [29]
9.7.2
Total radical-trapping antioxidant parameter (TRAP)
[30] According to Bortolotti and colleagues total radical-trapping antioxidant parameter (TRAP) is being proposed to measure antioxidant property of plasma of diabetes patients. It may be either directly measured by a uorescence-based method (TRAPm) or calculated (TRAPc) by a mathematicalformula, taking into account the serum levels of protein-bound SH (thiol) groups, uric acid, vitamin E, and vitamin C.
9.7. MEASURING THE ANTIOXIDANT ACTIVITY OF PHYTOCHEMICALS
757
The authors found decreased TRAP levels in patients suggesting that antioxidant defenses in diabetes are lower than normal. They conclude that TRAP is more reliable than the measurement of each known antioxidants. In their research the authors found a correlation between TRAPc and TRAPc values, and suggest TRAPc, for routine assessment of oxidative stress in diabetic patients.
9.7.3
Trolox equivalent antioxidant capacity (TEAC)
[31] The TEAC assay is based on the suppression of the absorbance of radical cations of 2,2azinobis(3-ethylbenzothiazoline 6-sulfonate) (ABTS) by antioxidants in the test sample when ABTS incubates with a peroxidase (metmyoglobin) and H2 O2 . If the inhibition time is xed at 3 min. There is lack of correlation between TEAC and other assays. This may result from underestimation of overall antioxidant capacity. Underestimation may be related to the eects of dilution and to premature measurement of inhibition percentage at a xed time of 3 minutes. Wang and colleagues conclude that the length of the inhibition time for the TEAC assay must be taken into account when determining the total antioxidant capacity of plasma, and that 30 min of inhibition is required for complete suppression of ABTS radical formation in the TEAC assay. The results from the TEAC assay at 30 min were similar and correlated with the results obtained by the ORAC assay over 70 min.
9.7.4
Total oxyradical scavenging capacity (TOSC)
[32] The total oxyradical scavenging capacity (TOSC) is based on the oxidation of alfa-keto-ymethiolbutyric acid (KMBA) by 2,2-azobis-amidinopropane (ABAP) with the evolution of ethylene as the quantiable end product. MacLean and colleagues modied the development of the assay of Winston et al. (Free Radical Biol. Med. 24 (1998) 480) and incorporated a standard curve resulting in a simple but reliable method to quantify the total water-soluble antioxidant capacity (TAC) of plant tissues such as apple fruit.
9.7.5
Peroxyl radical scavenging capacity (PSC)
[33] Rui Hai Liu and colleagues developed an assay for assessing peroxyl radical scavenging capacity (PSC) of both hydrophilic and lipophilic antioxidant compounds and food extracts. It is based on the inhibition of dichlorouorescin oxidation by antioxidants that scavenge
758
peroxyl radicals, generated from thermal degradation of 2,2-azobis(amidinopropane). According to the authors the PSC assay is used to analyse or screen both hydrophilic and lipophilic antioxidants or food extracts and will be a valuable alternative biomarker for future epidemiological studies of chronic diseases.
9.7.6
Ferric reducing/antioxidant power (FRAP)
[34] The ferric reducing antioxidant power (FRAP) assay determines directly the reducing capacity of a compound. Firuzi and colleagues used FRAP to study the antioxidant activities of 18 structurally dierent avonoids. In this study it was found that the o-dihydroxy structure in the B ring and the 3-hydroxy group and 2,3-double bond in the C ring give the highest contribution to the antioxidant activity. [34] Woodrow and colleagues used the FRAP assay, standardized against plant avonoids and ascorbic aci, to quantify total antioxidant power in fruit samples, such as currants (Ribes nigrum), gooseberries (Ribes grossularia), raspberries and blackberries (Rubus spp.). Black currant demonstrated the highest antioxidant activities followed by raspberries and gooseberries. Furthermore, the authors found that some wild Rubus species exhibited activities signicantly higher than the cultivars. [35]
9.7.7
DPPH free radical method
[36] Zheng DeYong and An XinNan presented a method for determining 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging activity of natural antioxidants. The DPPH free radical scavenging activity of 21 species of cluster-bamboos leaf were determined.
9.7.8
New cellular antioxidant activity (CAA) assay
[37] Kelly Wolf and colleague developed the cellular antioxidant activity (CAA) assay using the bioactivity inside human hepatocarcinoma HEPG2 cells, which relies on cellular biological activity rather than chemicalreactions which may not mirror reactions inside a living cell. Dichlorouorescin trapped within HEPG2 cells is subjected to oxidation by 2,2-azobis(2amidinopropane) dihydrochloride (ABAP)-generated peroxyl radicals. During the oxidation uorescent dichlorouorescein (DCF) and cellular uorescence is produced. The difference between the uorescence of control cells and those which with added solution of the foods on test indicates the antioxidant capacity of the compounds. Results of CAA assay are expressed in micromoles of quercetin equivalents per 100 micromol of phytochemical or micromoles of quercetin equivalents per 100 g of fresh fruit.
9.7. MEASURING THE ANTIOXIDANT ACTIVITY OF PHYTOCHEMICALS
759
The CAA values from phytochemicals decreased from quercentin, kaempferol, epigallocatechin gallate (EGCG myricetin, luteolin, gallic acid, ascorbic acid, caeic acid, to catechin. The CAA values decreased from Blueberries, craberry, apples, red grapes to green grapes. The authors conclude that the CAA assay is more biologically relevant than known chemical reaction because it considers uptake, metabolism, distribution and location of antioxidant compounds within cells.
9.7.9
Classes of Antioxidants
There are two main antioxidants classes: Enzymatic AntioxidantsThe most important enzymatic antioxidants are superoxide dismutase, glutathione peroxidase, and catalase. which are inherent to cell biochemistry and cannot be supplied by intake of food and supplements. Non-Enzymatic Antioxidants Vitamins E and C, and b -carotene are supplied by intake of food and supplements.
9.7.10
Vitamins as dietary supplements
There are many dietary supplements being sold at supermarkets.The prices dier enormously.The amount of vitamins are almost the same and cannot justify the dierence of price between the products. Some products have minerals and other trace elements varying from product to product.Their benet should be analysed considering the local nutritional habits. It is is very dicult to establish general rules concerning the amount of daily supplements to be taken because of dierent nutritional habits. To explain these problems the case of selenium, potassium, magnesium and vitamin A is here cited: Selenium is an essential part in the building of glutathione peroxidase. An undersupply of selenium causes diseases. An oversupply of selenium causes on his turn serious harm. Fish and meat bears much selenium and vegetables very little of it. Therefore a well balanced nutrition is important, and vegetarians should consider to take selenium as dietary supplement.[38]
9.7.11
Brazil nuts are a good source of selenium
[39] Christine D Thomson and colleagues 2008 assessed the bioavailability of selenium from Brazil nut, compared with seleniumethionine used to fortify foods and in dietary supplements. They found that the consumption of 2 Brazil nuts daily is as
760
CHAPTER 9. INGREDIENTS eective for increasing selenium status and enhancing GPx activity as 100 g Se as selenomethionine. The authors suggest to include Brazil nut in the diet to avoid to fortify foods or use supplementation of selenium in New Zealand. This would also benet residents in Europe where the recommended daily intake (RDI) is 65 micrograms. The selenium intake in UK is estimated to have fallen from 60 to 34 micrograms. on account of reduced import of selenium rich wheat from U.S.
9.7.12
Radioactivity of Brazil nuts
[40] However, an unhampered consume of Brazil nuts should consider the high radiactivity of the nut. According the UK DEFRA, among other foodstus, Brazil nuts contain some of the highest levels of natural radioactivity, in particular radium-226 and radium-228. The consumption of a 100g bag (about 30-40 nuts) per week (about 5 nuts a day) throughout the year would give rise to an annual dose of 0.2 mSv. Ingestion and inhalation of long-lived natural radionuclides are estimated to give rise to an average annual dose of 0.27 mSv. Potassium and magnesium stabilises heart rhythmic disturbaces. Both minerals should be supplemented up to 50% from the normal daily intake of 2-3 grams for potassium and 200-350 milligramme for magnesium. People with this kind of disorder need therefore supplementation of these minerals. Normal people can supply the minerals out of a balanced nutrition. [41] Vitamin A is important for the north and the south of the globe because of having less sun incidence. People living near the equator dont have to bother supplementing with vitamin A. Because of high incidence of sunlight boosting biological synthesis of vitamin A of the body in these countries one fears an hypervitaminosis of vitamin A. Therefore regulations in these countries forbid adding vitamin A to food.
9.8
Safety and bioavailability of Vanadium, EFSA and FSA assessment
[42] [43] EFSAs AFC Panel has issued an unfavourable opinion on vanadium containing compounds which may be added for nutritional purposes in foods for particularly uses and foods (including food supplements) intended for the general population. The assessed compounds were vanadium citrate, bismaltolato oxo vanadium and bisglycinato oxo vanadiumand vanadyl sulphate, vanadium pentoxide and ammonium vanadate. The non-vanadium constituents of these sources of vanadium are of no safety concern at the levels considered in
9.8. SAFETY AND BIOAVAILABILITY OF VANADIUM, EFSA AND FSA ASSESSMENT
761
this opinion. However, according to the FSA NDA Panel vanadium itself present various toxic eects, and a tolerable upper intake level could not be established in lack of appropriate data. The bioavailability of vanadium from ve of these six compounds is higher than that of vanadium absorbed from the normal diet. Consequently consumers could be exposed to higher levels of vanadium through products containing these ve compounds than from a normal diet. The Panel concluded that the safe use of the six sources for vanadium added to foods intended for the general population, including food supplements, and foods for particular nutritional uses, could not be established.
9.8.1
Uses of vanadium
[44] These sources for vanadium are not included in the list of vitamin and mineral substances which may be used in certain foods including food supplements. However they have been allowed to remain in use in Member States of the European Union. Vanadium forms are typically used as a dye and colour-xer in foods and supplements. Vanadyl sulfate, has been used to increase insulin sensitivity in supplements and has therefore been targeted at diabetes suerers and the body-building market.
9.8.2
Occurrence of vanadium in food, food supplements
According to the UK Food Standards AgencyBeverages, fats, oils, fresh fruits and vegetables contain the lowest levels of vanadium, whereas whole grains, seafood, meats and dairy products contain more (0.005 - 0.03 mg/kg). A few foods, including spinach, parsley, mushrooms and oysters, contain relatively high amounts of vanadium (>0.10 mg/kg). Vanadium is present in a number of multi-vitamin/mineral dietary supplements at levels of approximately 0.025 mg per day. There are no licensed medicines containing vanadium.
9.8.3
Other sources of exposure
Exposure to vanadium by inhalation may occur occupationally. In the production of vanadium pentoxide, dust concentrations of the pentoxide can range from 0.1 to 30 mg/m3 , and concentrations of 0.5-5 mg/m3 are not uncommon in the production of vanadium metal and vanadium catalysts.
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9.8.4
Recommended amounts
Vanadium has not yet been proven to be an essential trace element for mammals. There is no evidence to suggest that the vanadium we get from food is harmful. It is unlikely that we need vanadium for good health and too much could be harmful.
9.8.5
Function of vanadium
No specic function has been identied for vanadium in higher animals. In vitro and animal studies suggest that vanadium may function as an oxidation-reduction catalyst, and may regulate the sodium, potassiumadenosine triphosphatase enzyme, however, this has not been proven.
9.8.6
Deciency of vanadium
In humans, the reported signs of deciency are questionable, although it has been suggested that low intakes may be associated with cardiovascular disease.
9.8.7
Interactions
Although no specic data have been identied, it is possible that vanadium may interfere with the storage and metabolism of iron, because absorbed vanadium is bound to transferrin.
9.8.8
Absorption and bioavailability
Intestinal absorption of vanadium is low, less than 5%. The mechanism of absorption has not been dened.
9.8.9
Distribution
Absorbed vanadium is mainly transported in the plasma, associated with transferrin. Concentrations reported in human blood vary widely, with levels in whole blood and serum in the range of 0.01 - 0.4 mg/L. The concentrations in all tissues are low, but are higher in the liver, kidney and lung. Vanadium is also present in breast milk and saliva and passes through the blood brain barrier. Small amounts have been identied in the placenta. Based on animal studies, bones and teeth retain the highest concentrations of vanadium.
9.8.10
Excretion
Ingested vanadium is predominantly eliminated unabsorbed via the faeces. Absorbed vanadium is mainly excreted via the urine.
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9.8.11
Toxicity, Human data
The toxicity of vanadium compounds increases as valency increases, V5+ being the most toxic. In humans, exposure by inhalation causes diverse toxic eects on the respiratory, digestive, and central nervous systems, the kidney and skin. There are very few reported cases of vanadium toxicity in humans, when it is taken by mouth.
9.8.12
Supplementation trials
Supplementation of human volunteers with vanadyl compounds at oral doses of 50-125 mg/day caused cramps, loosened stools and "green tongue" in all patients, and fatigue and lethargy in a minority.
9.8.13
Animal data
Orally administered vanadium has low overt toxicity, but is reported to have adverse eects on reproduction and development in both males and females. There is some evidence of increased pre and post-implantation foetal loss and signicant accumulation of vanadium in the foetus. Skeletal anomalies and reduced ossication in the ospring, as well as an increased incidence of cleft palate have been reported.
9.8.14
Carcinogenicity and genotoxicity
Lifetime studies in animals indicate that vanadium is not carcinogenic. Positive results have been obtained in some in vitro mutagenicity tests.
9.8.15
Exposure assessment of vanadium, Total exposure/intake
Food Mean: 0.013 mg/day (1980 UK TDS) Supplements up to 0.025 mg/day (Annex 4) Drinking Water 0.01 mg/day (estimated from 0.005 mg/L, WHO 1988) Estimated maximum daily intake 0.013 + 0.025 + 0.01 = 0.05 mg/day The table below gives some information about the usual products on the German market:
Table 9.2: Dietary supplements,composition of one tablet Ingredients Vitamin A Provitamin A Vitamin E Vitamin C Centrum 800g 10 mg 60 mg Multibionta 12 mg 300 mg Multivitamin Krger 10 mg 60 mg Hermes Multivit 2 mg 12 mg 75 mg
764 Vitamin K1 Vitamin B1 Vitamin B2 Vitamin B6 Vitamin B12 Vitamin D Biotin Folic acid Nicotinamid Niacin Pantothenate Calcium Phosphate Iron Magnesium Iodine Potassium Chloride Copper Manganese Chromium Molybdenum Selenium Silicium Zinc 30g 1,4 mg 1,3 mg 1,4 mg 1,6 mg 1,7 mg 1,6 mg 2,0 mg 1,8 mg 2,0 mg 1 g 3 g 1 5 g 150 g 30 g 0,15 mg 200 g 150 g 200 g 18 mg 18 mg 18 mg 6 mg 8 mg 6,0 mg 162 mg 125 mg 4 mg 100 mg 100 g 40 mg 36,3 mg 1 mg 1 mg 25 g 25 g 25 g 2 g 1,6 mg 1,8 mg 2,1 mg 3 g 30 g 160 g 20 mg 6,5 mg 100 mg 10 g 2 mg
Food supplements should have a ratio of half as much magnesium as calcium. A daily intake of 1.200 mg calcium needs 600 mg of magnesium[45].
9.8.16
Ice structuring proteins
[46] Ice-structuring proteins (ISPs) in edible plants and sh that need to protect themselves against freeze damage. ISPs have potential applications in a number of areas including cryopreservation and frozen foods manufacture. ISP type III HPLC 12 being of particular interest. No evidence of a genotoxic potential or notable subchronic toxicity were found by T. Hall-Manning during a safety evaluation of ice-structuring protein (ISP) type III HPLC 12.[47] Anti-freeze protein, also called "ice structuring proteins" (ISPs) found in Ocean Pout (Marcrozoarces americanus) has been approved for use as ice structuring proteins in ice cream
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improving avour and texture of the product using less sugar and fat. It is obtained from the fermentation of a genetically modied food grade yeast (Saccharomyces cerevisiae). This aects a huge market of dairy ice cream, milk ice, water ice, fruit ice, sorbets, frozen deserts and any similar products. Professor Malcolm Hooper from Sunderland University, Professor Joe Cummins from the University of Western Ontario in Canada, and Dr Mae-Wan Ho, director of the Institute of Science in Society are against EU approval of ISP alleging that it could cause serious allergies. They say Unilever tests with people allergic to cod, not to ocean pout were insignicant. AFP claims that their antifreeze proteins type III are all puried from their natural sources cold ocean teleost sh.
9.8.17
EFSA considers ice structuring protein ISP as safe
[48] Ice structuring proteins (ISPs) are naturally produced by a variety of living organisms including certain sh, plants and vegetables - to help them cope with very cold environments by lowering the temperature at which ice crystals form. A joint opinion on the EFSA found these proteins to be safe for use in foods. They will be added to ice cream in order to control the formation of ice crystals during manufacture permitting a creamy consistency with lower fat content. The technique involves production of the isolated proteins using a genetically modied strain of bakers yeast. The protein produced does not contain any residual modied yeast cells or detectable recombinant DNA. EFSAs NDA and GMO Panels concluded that the proposed use of ISPs - in ice cream at no more than 0.01% of weight - is safe subject to the specication and production practices described by the applicant. The Panels found no evidence of genotoxic activity in a variety of trials. Based on a range of test results, the risk of an allergic reaction in sh-allergic people or the population at large is considered very unlikely, as is the possibility that allergic reactions to yeast allergens could occur due to eating the ISP-containing products. Ice structuring proteins are in common foods such as oats, rye, wheat, barley, carrot, potato and cold water sh. No safety issues have been reported either from consuming natural dietary sources or through the addition of ISPs to foods, which is authorized in countries including the United States, Australia and New Zealand.
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9.8.18
The organism used for the production of ISPs
The bakers yeast Saccharomyces cerevisiae. Strain CENPK338 has been used since 2003 for commercial production of the ISP for use in non European ice cream production. No gene encoding antibiotic resistance and no bacterial DNA were introduced. From 2003 to 2007 more than 470 million ISP-containing edible ice products have been sold in the USA and 47 thousand litres of ISP containing ice cream has been sold in Australia/New Zealand. There have been no reported safety issues. With regards to the potential of adverse allergic reactions against yeast allergens, the Panel considers it is unlikely that such reactions would occur after ingestion of the ISPcontaining products. The Panel concludes that the use of the ISP type III HPLC 12 preparation at a maximum level equivalent to 0.01% ISP type III HPLC 12 in edible ices is safe.
9.9
Enzymes
[49] Enzymes play an increasingly important role in food production, and can be used as alternatives to chemicals in improving the texture, appearance, nutritional value and avour of food, as well as helping in certain food production processes (e.g. helping bread to rise). Currently food enzymes used as processing aids are not covered by EU legislation. Member States legislation on food enzymes diers signicantly, which can lead to problems for the internal market and an unclear situation for the EU consumer. Historically, food enzymes were considered to be non-toxic. However, the food enzyme industry is continually striving to develop improved technology resulting in the development of food enzymes which became through the years more complex and sophisticated. There could be some potential hazards arising from their chemical nature and source such as allergenicity, activity-related toxicity, residual microbiological activity, and chemical toxicity. Therefore safety evaluation of all food enzymes, including those produced by genetically modied micro-organisms (GMOs), is essential in order to ensure consumer safety.
9.9.1
Existing provisions in the area of enzymes
Directive 95/2/EC on food additives other than colours and sweeteners allows for the use of two enzymes as food additives: E1103 Invertase and E1105 Lysozyme.In addition, Council Directive 2001/112/EC relating to fruit juices and certain similar products intended for human consumption, Council Directive 83/417/EEC relating to certain lactoproteins (caseins and caseinates) intended for human consumption and Council Regulation (EC) No 1493/1999 on the common organisation of the market in wine, regulate the use of certain food enzymes in these specic foods.
9.10. EZYME COMMISSION NUMBER (EC NUMBER)
767
Under the new proposed legislation, harmonised EU rules would be laid down for the evaluation, approval and control of enzymes used in food. The draft Regulation foresees the way to draw up an initial positive list of enzymes. The proposal also includes requirements for the labelling of food enzymes other than those used as processing aids. Food enzymes with a technological function in the nal food will have to be labelled as ingredients with their function (e.g. stabiliser) and name.
9.9.2
Labelling of enzymes
[49] In most cases food enzymes will be used as processing aids i.e. will be present in food in the form of a residue, if at all and will have no technological eect on the nished product. Taking into account that all food enzymes will be assessed for their safety, it is proposed that food enzymes which are used as processing aids are exempted from labelling. Food enzymes used to exert a technological function in the nal food, will be labelled with their function (e.g. stabiliser etc) and specic name.
9.10
Ezyme Commission number (EC number)
[50] The Enzyme Commission number (EC number) is a numerical classication scheme for enzymes, based on the chemical reactions they catalyze. As a system of enzyme nomenclature, every EC number is associated with a recommended name for the respective enzyme. Every enzyme code consists of the letters "EC" followed by four numbers separated by periods. Those numbers represent a progressively ner classication of the enzyme. For example, the enzyme tripeptide aminopeptidase has the code "EC 3.4.11.4", whose components indicate the following groups of enzymes: EC 3 enzymes are hydrolases (enzymes that use water to break up some other molecule), EC 3.4 are hydrolases that act on peptide bonds, EC 3.4.11 enzymes are only those hydrolases that cleave o the amino-terminal amino acid from a polypeptide, and EC 3.4.11.4 are those that cleave o the amino-terminal end from a tripeptide. Strictly speaking, EC numbers do not specify enzymes, but enzyme-catalyzed reactions. If dierent enzymes (for instance from dierent organisms) catalyze the same reaction, then they receive the same EC number.
Table 9.3: EC numbers
768 Group Reaction catalyzed
CHAPTER 9. INGREDIENTS Typical reactions AH + B A+ BH (reduced) A + O AO (oxidized) AB + C A + BC Trivial names Dehydrogenase, oxidase
EC 1 To catalyse oxidation/reduction Oxyreductases reactions; transfer of H and O atoms or electrons from one substance to another EC 2 Transfer of a functional group from one Transferases substance to another. The group may be methyl-, acyl-, amino- or phospate group. EC 3 Formation of two products from a Hydrolases substrate by hydrolyses EC 4 Non-hydrolytic addition or removal of Lyases groups from subnstrates. C-C, C-N, C-O or C-S bonds may be cleaved EC 5 Intramolecule rearrangement, i.e. Isomerases isomerization changes within a single molecule EC 6 Join together two molecules by Ligases sythesis of new C-O, C-S, C-N or C-C bonds withg simultaneous breakdown of ATP
Transaminase, Kinase
AB + H2 O AOH + BH RCOCOOH RCOH + CO2 AB BA
Lipase, amylase, peptidase
Isomerase, mutase Synthetase
X + Y + ATP > XY + ADP + Pi
9.11
UniProt
[51] UniProt is the universal protein database, a central repository of protein data created by combining Swiss-Prot, TrEMBL and PIR. This makes it the worlds most comprehensive resource on protein information. The UniProt Consortium is comprised of the European Bioinformatics Institute (EBI), the Swiss Institute of Bioinformatics (SIB), and the Protein Information Resource (PIR). UniProt identiers uniquely specify a protein by its amino acid sequence. EBI, located at the Wellcome Trust Genome Campus in Hinxton, UK, hosts a large resource of bioinformatics databases and services. SIB, located in Geneva, Switzerland, maintains the ExPASy (Exprt Protein Analysis System) servers that are a central resource for proteomics tools and databases. PIR, hosted by the National Biomedical Researche Foundation (NBRF) at the Georgetown University Medical Center in Washington, DC, USA, is the oldest protein sequence database, Margaret Dayhos Atlas of Protein Sequence and Structure.
9.11. UNIPROT
769
In 2002, EBI, SIB, and PIR joined forces as the UniProt Consortium.
9.11.1
Combination of food additives and interference with development of nervous cells
The eects of food colouring brilliant blue (E133) combined with monosodium glutamate (MSG; E621) and colouring quinoline yellow (E951) combined with the sweetener aspartame (E951) were tested at the University of Liverpool. This combination presented neurotoxic eects. The combination of brilliant blue and MSG could inhibit cell growth up to four times more than the additives on their own, while for quinoline yellow and aspartame the gure rises to seven. The research has been supported by Organix Brands. Inhibition of neurite outgrowth was found at concentrations of additives theoretically achievable in plasma by ingestion of processed foods like sweets and snacks they are typically present in combinations and are foods which are consumed by children whose nervous system is still developing. [52] In response to the study, UK regulatory body Food Standards Agency said that the safety of all additives is kept under review. The European Food Safety Authority (EFSA) had been asked to review food additives currently permitted within the EU in order to determine whether full re-evaluation is required. [53] The authors of the Liverpool study call upon the European Food Safety Authority (EFSA) to look upon the combined eects of the mentioned substances. Some researches concerning mixtures of substances are already being undertaken by FSA funding research on the eects of two groups of colour additives on the behaviour children is expected to report in 2007.
9.11.2
The European Commission protects European sodium glutamate producer
[54] Monosodium glutamate (MSG) is a avour enhancer for foods such as soups, sh and meat dishes, and ready meals in produces of Nestle, Unilever and others. Glutamate was linked to headache, known as the China restaurant syndrome and other problems. Ajinomoto Foods Europe, the only MSG producer in the EU, complainted of Chinese rms dumping sodium glutamate on the EU market undercutting Ajinomotos price by up to 24 per cent. Following the complaint, the European Commission imposed in 2008
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anti-dumping taris of 39,7 per cent on monosodium glutamate (MSG) imported to the EU from China.
9.11.3
Retinal cell destruction caused by sodium glutamate
[55] Ohguro Hirishi and colleagues 2002 found a signicant accumulation of glutamate in vitreous was observed in rats on high sodium glutamate. Thickness of retinal neuronal layers was remarkably thinner in rats fed on sodium glutamate diets than in those on a regular diet. The authors concluded that a diet high in sodium glutamate over a period of several years may increase glutamate concentrations in vitreous and may cause retinal cell destruction.
9.11.4
Monosodium Glutamate not related to the Chinese Restaurant Syndrome
[56] Jinab and Hajeb 2010 of the University Putra Malaysia reviewed application, benets of monosodium glutamate as avor enhancer. The authors say that glutamate adds a fth basic taste to the four basic ones, whicch are saltiness, sourness, sweetness and bitterness. It is also an energy source, acts as a substrate for glutathione synthesis and enhances food intake in older individuals. Glutamate may partially replace salt in food preparation. The Joint Expert Committee on Food Additives of the United Nations Food and Agriculture Organization and World Health Organization classied glutamate as safe. The authors stress that there are no consistent clinical data to support believes that glutamate causes asthma, migraine headache, Chinese Restaurant Syndrome, and there are no evidences indicating that individuals may be uniquely sensitive to glutamate.
9.11.5
The position of the Food Standards Australia New Zealand
[57] The Food Standards Australia New Zealand in a technical report of 2003 found that some studies reported a complex of symptoms which came to be known as the Chinese restaurant syndrome (CRS) because they typically followed ingestion of a Chinese meal. Two outstanding studies were Kwok, R. (1968) [58] and Schaumburg HH(1969) [59] suggesting monosodium glutamate as the causative agent in CRS embracing symptoms such as headache, numbness/tingling, ushing, muscle tightness, and generalised weakness. MSG symptom complex is now being used instead of CRS. A possible association between MSG and bronchospasm in asthmatic individuals were also suggested.
9.12. SODIUMBENZOATE AND CERTAIN COLOURS INCREASES HYPERACTIVITY IN CHILDREN
771
9.11.6
Conclusions
The FSA study found no convincing evidence that MSG is a signicant factor in causing systemic reactions resulting in severe illness or mortality, and studies have failed to demonstrate a causal association with MSG. Some reactions were noted by administrating large doses of 3g or more MSG without food were not serious and are likely to be attenuated when MSG is consumed with food. Bronchospasm in asthmatic individuals is, according to actual data, not signicantly triggered by MSG. Patricia Tagliaferro in an article of 1995 [60], stressed inconsistent data of studies on the possible eect ofMSG. The study of Jinab and Hajeb 2010 conrms that glutamate is not related to asthma, migraine headache and Chinese Restaurant Syndrome.
9.12
SodiumBenzoate and certain colours increases hyperactivity in children
[61] According to the UK Food Standards Agency, parents of children showing signs of hyperactivity are being advised that cutting certain articial colours from their diets might have some benecial eects. The colours found to give adverse reactions were: Sunset yellow (E110), Quinoline yellow (E104), Carmoisine (E122), Allura red (E129), Tartrazine (E102) Ponceau 4R (E124), and Sodium benzonate (E211)
9.12.1
Dening Hyperactivity
Hyperactivity is the occurrence of the following behaviours at the same time: over-activity, inattention and impulsivity. Attention Decit Hyperactivity Disorder (or Hyperkinetic Disorder) (ADHD) is an extreme form of hyperactivity that is clinically diagnosed when specic patterns of behaviour occur together to a strong degree. This comprises a behavioural disorder which adversely aects childrens function at home and in school.
9.12.2
The ndings
The Committee on Toxicity of Chemicals in Food (COT) reviewed a research, carried out by Southampton University, suggesting that eating or drinking certain mixes of these articial food colours together with the preservative sodium benzoate could be linked to a negative eect on childrens behaviour. The ndings of the research were presented to the European Food Safety Authority (EFSA), which is conducting a review of the safety of all food colours.
772
9.12.3
FSA Advice
Following the COT statement, the FSA holds on the following advice: FSA advice to consumers: if a child shows signs of hyperactivity or Attention Decit Hyperactivity Disorder (ADHD) then eliminating the colours used in the Southampton study from their diet might have some benecial eects. However, the FSA also reminds that there are many factors associated with hyperactive behaviour in children. These are thought to include genetic factors, being born prematurely, or environment and upbringing.
9.12.4
The Southampton Study
[62] [63] The study tested two combinations of colours and a preservative most likely to be found in foods popular with children such as soft drinks, confectionery, and ice cream. According to Professor Jim Stevenson from Southampton University, and author of the report, the consumption of certain mixtures of articial food colours and sodium benzoate preservative are associated with increases in hyperactive behaviour in children.
9.12.5
The POC Review on the Southampton Study
[64] According to Professor Ieuan Hughes, Chair of the COT, said that the study provides supporting evidence for a link between the colours used in the study and increased hyperactivity in children. He stresses that the available evidence does not identify whether this association would be restricted to certain food additives or combinations of them. The POC study concludes that the ndings are consistent with, and add weight to, previous published reports of behavioural changes occurring in children following consumption of particular food additives.
9.12.6
German BFR agrees with UK opinion on Hyperactivity and Additives
[65] A trial by Southampton University, commissioned by the British Food Standards Agency (FSA), examines a possible association between the intake of specic food additives (the food colourings E102, E104, E110, E122, E124, E129 and the preservative sodium benzoate E211) and the occurrence of Attention Decit Hyperactivity Disorder (ADHD) in children. The trial found that articial colours or a sodium benzoate preservative (or both) in the
773
diet result in increased hyperactivity in 3-year-old and 8/9-year-old children in the general population. [66]
9.12.7
The COT Opinion
[67] The UK Committee on Toxicity of Chemicals in Food, Consumer Products and the Environment (COT) considers the results of the trial by Southampton University as additional indications of a possible association between the intake of certain mixes of articial colouring agents containing the preservative sodium benzoate and increased hyperactivity in children. To the extent that there is a causal association, this could be of importance for individual children particularly for those who are in any case clearly hyperactive. However, COT stresses that the mean levels of observed hyperactivity are low compared to normal inter-individual variation and that behavioural changes did not occur in all children in one group, did not occur uniformly across all age groups and not in an even manner for the intake of all additive groups. Hence it is not possible to draw any more extensive conclusions. Nor is it possible to extrapolate the results to other additives.
9.12.8
The German BfR - Federal Institute for Risk Assessment opinion
After short-term examination of the publication by McCann et al. (2007) [66] BfR agrees with the conclusions in the COT opinion. As food additives must be included in the list of ingredients, consumers wishing to avoid any intake of the examined substances for precautionary reasons are able to refrain from consuming the corresponding foods and drinks.
9.12.9
Comment
The Southampton study, together with the review of COT, should encourage food producers to reformulate their products to reduce as much as possible the use of additives.
9.12.10
The Southampton Study on hyperactivity does not warrant an ADI change of colour and preservative, says EFSA.
[68] The European Food Safety Authoritys (EFSA) AFC Panel assessed the study of McCann and al 2007 on hyperactivity. The report was released on 14.03.08 concluding that the McCann study (2007) provided limited evidence that the mixtures of additives tested had
774
a small eect on the activity and attention of some children. However, the eects observed were not consistent for the two age groups and for the two mixtures used in the study. Considering the overall weight of evidence and in view of the considerable uncertainties the Panel concluded that the ndings of the McCann et al study could not be used as a basis for altering the ADI of the respective food colours or sodium benzoate. Although the ndings from the study could be relevant for specic individuals showing sensitivity to food additives in general or to food colours in particular, it is not possible at present to assess how widespread such sensitivity may be in the general population. The Panel noted that the majority of the previous studies used children described as hyperactive and these were therefore not representative of the general population.
9.12.11
Southampton team responds to EFSA evaluation
[69] The researcher of the Southampton study on hyperactivity caused by certain colourings and preservative, leaded by Jim Stevenson, Donna McCann, Edmund Sonuga-Barke and John Warner, responded to the EFSA evaluation of their study. They say that despite EFSA saying there is no justication from this research to change the limits on these additives, that does not mean there are no grounds for action at all. The team stresses that since the colours being tested in this study are of no nutritional value, even the small overall benet of removing them from childrens diets would come at no cost or risk to the child, and a benet, even a small one, would be worthwhile achieving. According to the authors added weight is given to this conclusion because other important inuences on hyperactivity in children, such as genetic factors, are dicult to address while the risk arising from exposure to food colours can be regulated.
9.12.12
Food colours and preservative should be eliminated despite all-clear of EFSA. Attention-Decit Hyperactivity Disorder (ADHD) and food additives
[70] The Southampton study found that a mix of food colours such as sunset yellow (E110), tartrazine (E102), carmoisine (E122), ponceau 4R (E124) quinoline yellow (E104), allura red (E129) and sodium benzoate (E210). exacerbate hyperactive behaviour in children at least up to middle childhood.
775
9.12.13
EFSA review
The European Food Safety Authority (EFSA) conducted a review of the Southampton study, as well as other studies and meta-analyses on additives and hyperactivity. EFSA also concluded that the Southampton study gave no basis for changing acceptable daily intakes (ADI) of food additives. EFSA stresses that hyperactivity results from a variety of social and biological causes, focusing on dietary strategy eliminating food additives alone may detract from the provision of adequate treatment.
9.12.14
Professor Kemp position
At present, there are three main approaches to tackling ADHD: drugs, behavioural therapy, and dietary management. Despite all controversies Professor Andrew Kemp writes that behavioural therapy is still considered necessary for adequate treatment even though there is less evidence for its ecacy than there is for eliminating food additives. He calls not to neglect the dietary factors. Cutting out colours and preservatives from the diets of hyperactive children should be standard part of the treatment of ADHD.
9.12.15
Aldi Australia banned six food colourings
[71] Aldi Australia said it will no longer wait for the food regulator to act. The supermarket chain has voluntary banned six food colourings from its products following the results of a research published by The Lancet in 2007. The articial colours sunset yellow (E110), tartrazine (E102), carmoisine (E122), ponceau 4R (E124), quinoline yellow (E104), and allura red (E129) have been linked to behavioural problems in children such as ADHD.
9.12.16
The Lancet Study
[63] The British Southampton study published in the "Lancet" in 2007 found a link between hyperactivity in children who consumed drinks that contained these additives. The study tested two combinations of colours and a preservative most likely to be found in foods popular with children such as soft drinks, confectionery, and ice cream. According to Professor Jim Stevenson from Southampton University, and author of the report, the consumption of certain mixtures of articial food colours and sodium benzoate preservative are associated with increases in hyperactive behaviour in children.
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9.12.17
List of additives you should avoid
[72] A list of food additives which should be avoided is given by Food Intolerance Network. Please see: http://www.fedupwithfoodadditives.info/information/nastyadditivecard.pdf
9.12.18
The European situation
[73] The European Parliament voted in July 2008 for products containing the colours to be labelled "may have an adverse eect on activity and attention in children". The European Food Safety Authority (EFSA) reviewing the methodology and results of the Southampton study stated it found no scientic evidence for altering intake recommendations of any of the additives, but will look again at the safety data on all food additives, including the Southampton colours. [74]
9.12.19
The power of marketing
Aldi Australia demonstrated a high level of quality and responsibility for the health of its customers. Aldi Europe and Lidl Europe still sell products with the Southampton colours. The marketing department should be aware of the possible image damage selling products which might harm children. Changing the six questioned articial colours to other innocuous ones clears the situation and demonstrates a precautious way to handle health issues.
9.12.20
Aldi Europe and LIDL still sell products with the Sothhampton colours
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9.12.21
Paprika food colour is safe
[75] Paprika as food colour is increasingly being used by the food industry. Safety tests on rats found paprika food colour as safe. The toxicity and carcinogenicity studies of paprika colour were performed by Inoue and colleagues 2008. Treatment with paprika colour caused a signicant increase in incidence of hepatocellular vacuolation, in 5% males, however, no toxicological eects or other abnormal eects such as tumors were noted. The authors concluded that, based on slight histopathological changes, noted as hepatocellular vacuolation, the no-observed-eect level (NOEL) was estimated to be 2.5% in the diet (1253 mg/kg bw/day) and the the no-observed-eect level (NOEL) was 2.5 per cent in the diet, or 1253 mg per kg of bodyweight per day, for the male rats. The NOEL for the female rats was determine to be ve per cent, or 2826 mg per kg of bodyweight per day. Paprika colour is therefore not carcinogenic nor toxic under present conditions.
9.12.22
Connection between diet and behaviour in attentiondecit hyperactivity disorder (ADHD) children
[76] As part of the Impact of Nutrition on Children with ADHD (INCA) study Pelsser and colleagues found that a 5 week restricted elimination diet consisting mainly of hypoallergenic foods such as rice, turkey, lamb, a range of vegetables (lettuce, carrots, cauliower, cabbage and beet), pears and water. The hipoallergic diet reduced the ADHS symptoms by at least 40% in 78% of the children, compared with a control group. Diets were composed of high-IgG or low-IgG foods, based on every childs individual IgG blood test results. Children which returned to high allergic diet had a relapse in symptoms with no dierence in the immunologic responses immunological response to the dierent diets. The authors concluded that food sensitivity plays a part in ADHD, but it is not caused by an allergic reaction, and diets on the basis of IgG blood tests should be discouraged. The same authors, in a foregoing study in 2010, report signicant reductions of complaints of these children related to three domains: headaches or bellyaches, unusual thirst or unusual perspiration, and sleep complaints were signicantly reduced by hypoallergenic diet, but these reductions were independent of the behavioural changes. An elimination diet may be an eective instrument to reduce aforementioned physical complaints in children with ADHD. [77]
778
9.12.23
Articial colour in drinks must be reduced: Sunset Yellow E110 [78]
The EU Standing Committee on the Food Chain and Animal Health followed the suggestion of the European Food Safety Authority (EFSA) to reduce the the usage levels of Sunset Yellow for avoured drinks from 50 mg/litre down to maximum 20 mg/Litre, to be valid by the end of the year. Articial colours are ruled by the Directive 94/36/EC [11]. The ADI for Sunset Yellow was reduced to 1 mg/kg/bw/day after noting that the exposure was too high in some population groups and was not safe at higher levels in food and drinks. Suggested limit of 10 mg/l was strongly rejected by the drink industry as too low Soft drink producer heavily lobbied the First Minister Alex Salmond who wrote to the European Commissioner for Health and Consumer Policy John Dalli warning that reducing the additive level to 10 mg could have a negative impact on the "iconic" drink. So AB Barr, producer of the ditching yellow drink, succeeded to have a minimum of 20 mg/litre of Sunset Yellow for Irn Bru. Safety of articial colours are being questioned following the Southampton study in 2007. [62] [64]
9.12.24
Articial colour E124 Ponceau 4R
To meet the regulations for food colouring of tThe U.S. Food and Drug Administration.prohibits the use of E124 Ponceau 4R (also called Cochenill Red A) used in the UK formulation. To meet US regulations Barr uses alternative food and drink colourants to market its soft drink in the US. [79]
9.13
9.13.1
Sugar, anti-social behaviour and ADHD

Sugar and adverse conduct problems
[80] Lien et al 2006 found a relationship between soft drink consumption and mental distress, conduct problems, and total mentalhealth diculties score. The higher the consumption of soft drinks, the more extreme symptoms of hyperactivity were observed. The highest adverse reaction observed for conduct problems were found among boys and girls who consumed 4 or more glasses of sugar-containing soft drinks per day. The authors concluded that high consumption levels of sugar-containing soft drinks were associated with mental health problems among adolescents.
9.14. SODIUM BENZOATE AS SOURCE OF BENZENE IN SOFT DRINKS
779
9.13.2
Sugar is not linked to anti-social behavior
[81] David Benton, in a response to the study of Lien et al 2006, reviewed studies on sucrose consumption found that food intolerance to sucrose is less frequent than many other foods. Low blood glucose levels, but higher than those that can be described clinically as hypoglycemic, is associated with irritability and violence. However, sucrose is not the predominant cause of swings in blood glucose levels. Micro-nutrient decreased anti-social behaviour. Micro-nutrient intake is more closely associated with the total energy rather than sucrose intake; typically the amount of sucrose in the diet does not lead to micro-nutrient deciency. Benton concluded that studies that have examined the impact of sucrose on the behaviour of children produced no evidence that it has an adverse inuence, such as attention decit hyperactivity disorder. However, sugar fat and salt-reduction should go on in face of the obesity and cardiovascular risks. Physical activity not also reduces risk of obesity, but also may improve mental health in adolescents.
9.13.3
Physical activity and mental health
[82] Five to seven weekly hours of physical activity at age 15-16 years was weakly associated with mental health. The authors called for further studies about physical activity as a possible protective factor in relation to mental health problems in adolescence.
9.14
Sodium benzoate as source of benzene in soft drinks
Benzene is listed as a poisonous chemical shown to increase the risk of leukaemia and other cancers. Drinking water limits range from 10 parts per billion (World Health Organisation), 5ppb in the US and one part per billion in the EU. Some soft drinks contain up to ve times this limit of benzene. The FDA assured benzene did not present an immediate health risk at the levels found to date in drinks.
9.14.1
Interaction among sodium benzoate and other ingredients
[83] Mike Redman the National Soft Drink Association (NSDA) in a meeting of the FDA in
780
1990 suggests that benzene formation occurs as an interaction among ingredients in the product for example, sodium Benzoate, ascorbic acid and FD&C yellow Nr. 5 under certain conditions might produce benzene.
9.14.2
Other interaction between sodium benzoate and other additives
Other chemicals such as erythorbic acid, EDTA, oxygen and sweeteners like high fructose corn syrup inuence benzene formation in the presence of benzoic acid. Sweeteners are thought to inhibit the reaction, as the problem seems most noticeable in diet drinks. EDTA appears to inhibit the reaction also, possibly by complexing metal ions that could act as catalysts. Companies added Calcium disodium ethylene diamine tetra-acetate (" EDTA") in the US to reduce benzene formation. The FDA, however noted that calcium disodium EDTA is not an approved food additive for non-carbonated soft drinks. [84] Erythorbic acid may lead to benzene formation in much the same fashion as ascorbic acid. Removal of oxygen by CO2 or N2 may inhibit benzene formation. Solutions containing sodium benzoate and citric acid also form benzene although perhaps not as readily as those with ascorbic acid. Benzene does not form in mineral acid pH adjusted sodium benzoate solutions subjected to heat and light. Benzene has also been observed to form after exposure to light for 24 hrs in ascorbic acid solutions of benzoic acid anhydride, acetophenone, and benzaldehyde. There is some data to suggest that benzene may form from a contaminate in sodium benzoate. Sodium benzoate and ascorbic acid (vitamin C) are still used together in a wide range of soft drinks and avoured waters across the world. They can react together to cause benzene formation. Ascorbic acid initially reacts with metals, such as iron or copper, found in the water to create free radical. These hydroxyl radicals break down Sodium benzoate into benzoic acid and benzene. Reactivity of Ascorbic acid in presence of ions of copper and iron has been studied by Hans Steinhart et col. in 1993. [85]
9.15. BENZENE IN FOODS WITHOUT ADDED BENZOATES
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9.14.3
Photolytic degradation of sodium benzoate (E211) in avoured mineral water
The State of Florida Laboratories found traces of benzene in Koala Springs avoured mineral water. There is speculation that the benzene traces originated from the sodium benzoate by way of photolytic degradation. [83]
9.15
Benzene in foods without added benzoates
The combination of sodium or potassium benzoate with ascorbic acid was shown to produce low levels (ng/g) of benzene in fruit-avoured soft drinks. The presence of benzene was also reported in butter, eggs, meat, and certain fruits; levels of these ndings ranged from 0.5 ng/g in butter to 500-1900 ng/g in eggs. Slightly higher levels were present in some foods and beverages containing both ascorbic acid and sodium benzoate. [86] Soft drinks, juices, beers, and waters from processed vegetables were analysed for trihalomethanes (THMs), benzene, and toluene. The THMs, which include chloroform, bromodichloromethane, dibromochloromethane, and bromoform, are reaction by-products of water disinfection by chlorination. In this study benzene residues were found typically <5 ng/g, except for 7 and 9 ng/g in 2 foods, compared to other contaminants: Toluene residues were typically <3 ng/g except for 23, 29, and 75 ng/g in 3 canned foods and chloroform was none detected to 94 ng/g in the 44 foods analysed. [87] Industry tests on soft drinks found that temperatures of 30o C and exposure to UV light for several hours were enough to more than triple benzene residues in some drinks. Americas soft drinks industry association said hot warehouses and cars parked in direct sunlight are examples of when soft drinks would be exposed to even higher temperatures as that. Benzene formation may also occur in dietary supplements, such as liquid aloe vera and vitamin formulations, and other acidic liquid food products, such as lemon juice where sodium benzoate and ascorbic acid are present.
9.15.1
How to avoid benzene in food
Producers should use predictive testing to simulate storage under UV and heat up to 50o C to survey their products for benzene.
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The consumer should carefully read the list of ingredients. When sodium benzoate is listed in soft drinks and other acidied foods do not buy it. Food regulations worldwide should demand sodium benzoate to be taken out of juices, soft drink and other acidied food formulas. Technology does not need sodium benzoate in drinks as modern heat sterilization and aseptic lling techniques make the use of this preservative unnecessary.
9.15.2
Belgian soft drinks with Benzene, benzoic acid and benzoates should be banned from acidic beverages
[88] Christof Van Poucke and colleagues 2008 analysed 134 Belgian soft drinks. The authors found that ten samples were above the European limit for benzene in drinking water of 1 g L, and one sample had a concentration of 10.98 g /L, thereby exceeding the action limit for benzene in soft drinks of 10 g/ L. The authors stress that benzene can be formed when benzoic acid, a food preservative, is combined with ascorbic acid acidity regulators and interaction with packaging materials in foods like soft drinks. Benzene oxidises in the body to produce an epoxide, benzene oxide, which is not excreted readily and can interact with DNA to produce harmful mutations. The use of preservatives like benzoic acid and benzoates can be avoided by sanitising lling lines and adopting sound hygienic strategies. Soft drinks and other beverages are very easy to handle in an sterile environment. Chemical preservatives are not needed in modern food technology.
9.15.3
Volatile organic compounds (VOCs)
[89] VOCs are a group of low molecular weight aliphatic and aromatic compounds with low boiling points. Sources of VOCs include solvents, dry cleaning compounds, degreasers, paints, chemical intermediates, and assorted industrial products. They are also products of combustion and the chlorination of drinking water. Additionally, VOCs can come from the process of microwaving foods. Some VOCs are even allowed as indirect food additives from components of commercial packaging. FDA study, published in 2003 a study of Fleming-Jones and Robert E. Smith. Volatile organic compounds (VOCs), such as benzene, were found in at least one sample of all foods tested, although no single compound was found in each of the foods. Benzene levels ranged from 1 to 190 ppb, Benzene is a human carcinogen and neurotoxin. Other VOCs reported to be human
9.15. BENZENE IN FOODS WITHOUT ADDED BENZOATES
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neurotoxins include 1,1,1- trichloroethane, styrene, toluene, trichloroethylene, and xylene. However, the doses needed to cause neurotoxicity are far greater than those detected in foods in the study of Fleming-Jones. [90] [91] [92] The amounts needed to cause these toxicities are much higher than those found in foods in this study. For all toxicities except carcinogenesis, a threshold approach is often used, which sets acceptable daily intake levels. However, it is sometimes stated that a nonthreshold approach is used for potential carcinogens and that a single molecular adduct can initiate the multistep process of carcinogenesis. [93] FDA concluded from data derived from the FDAs Total Diet Study that the American food supply is comparatively safe. Although there is some oral exposure to VOCs, they are usually inhaled at much higher doses through cigarette smoke, gasoline fumes, and industrial pollution.
9.15.4
Sodium benzoate enhances detrimental eects of free radicals
[94] Peter Piper proposes a Saccharomyces cerevisiae petri dish test, using yeast superoxide dismutase mutants to distinguish a compound that enhances the detrimental eects of endogenous reactive oxygen species production by the mitochondrial respiratory chain from another chemical that generates oxidative stress by redox cycling. Using this test system, Piper found that weak organic acid food preservatives exert strong pro-oxidant action on aerobic yeast cells, and are mutagenic toward the yeast mitochondrial genome. The author concluded that sodium benzoate may generate oxidative stress within the epithelia of the gastrointestinal tract.
9.15.5
ICBA Benzene Guidance
[95] The International Council of Beverages Associations (ICBA) is a non-governmental organization representing the interests of the worldwide beverage industry.
Today, as the beverage industry continues to grow and expand, the International Council of Beverages Associations (ICBA) is renewing its commitment to provide guidance on preventing/minimizing benzene formation. This guidance will be made available to all beverage companies worldwide. http://www.britishsoftdrinks.com/htm/sv/PDFs/IBCA%20nal%20220606.pdf#search=%22ICBA%20
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9.15.6
German assessment of benzene in foods
[96] The Federal Institute for Risk Assessment has issued an expert opinion on whether benzene may be formed in beverages from the food additive benzoic acid in the presence of ascorbic acid. It is advisable to minimise and/or avoid the intake of benzene as far as possible. This is the standard practice for substances which are to be considered as carcinogens and germ cell mutagens. However, further chemical-analytical data are needed in order to assess the possible risk from simultaneous use of benzoic acid and ascorbic acid in foods. If it turned out that the simultaneous use of benzoic acid and ascorbic acid in foods makes a signicant contribution to total benzene intake, it may be necessary to check whether the authorisation framework for a simultaneous use of benzoic acid and ascorbic acid in foods would have to be changed.
9.15.7
Brilliant Blue FCF E133
Other names: Other names(FD&C Blue No.1, Acid Blue 9, D&C Blue No. 4,Alzen Food Blue No. 1, Atracid Blue FG, Erioglaucine, Eriosky blue, Patent Blue AR, Xylene Blue VSG, C.I. 42090). [97] This colouring agent has previously been banned in Austria, Belgium, Denmark, France, Germany, Greece, Italy, Spain, Sweden, and Switzerland among others but has been certied as a safe food additive in the EU and is today legal in most of the countries. E133 was allowed to be used in some foods in the European Union by the Regulation 1129/2011. [98] It is allowed to be used in sweets, confectionery, dessert, ices, in some soft drinks, baked goods and tinned processed peas. It has the capacity for inducing an allergic reaction in individuals with pre-existing moderate asthma. In the United States production exceeds 1 million pounds annually, and daily consumption is around 16 mg per person. An ADI of 0,1 mg/Kg bodyweight was determinated. In animals high amounts of brilliant blue E133 produced depositions of the colour at kidneys and lymphatic system. Blue discoloration and death from FD&C Blue No. 1 used in enteral feeding solutions [99] The US Food and Drug Administration (FDA) has advised that several reports of toxicity, including death, have been associated with the use of FD&C Blue No. 1 (Blue 1) in enteral feeding solutions. Reported episodes were manifested by blue discolouration of the skin, urine, faeces, or serum and some were associated with serious complications such as
9.16. NATURAL CURE FOR MEATS
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refractory hypotension, metabolic acidosis and death. Case reports indicate that seriously ill patients, particularly those with a likely increase in gut permeability (e.g., patients with sepsis), may be at greater risk for these complications.
9.15.8
Quinoleine Yellow
Quinoline Yellow is absorbed from the gastro-intestinal tract to only a small extent in rats and dogs, and most of an orally administered dose is excreted unchanged. No adverse eects of treatment were seen in the two-generation long-term study in mice. In particular there was no observed eect on thyroid function or histopathology and no evidence of carcinogenicity. Quinoline yellow is banned in foods in Australia, the US and Norway. In UK it is used in sweets, smoked haddock, confectionery and pickles.
9.15.9
Evaluation
Level causing no toxicological eects: Mouse: 1% of the diet, equal to 1.500 mg/kg/ Estimate of an acceptable daily intake for man: 0-10 mg/kg bw. The committee noted that there are two quinoline yellows, one of which is about 30% methylated and the other non-methylated, and considered that data from both compounds could be used for toxicological evaluation of either of the quinoline yellows for food additive use.[100]
9.15.10
Monosodium glutamate
Monosodium glutamate is banned in baby food in the UK, but is used in a variety of crisps and snacks which are consumed by children. Parents should watch the ingredient list carefully in order to avoid to give products with these ingredients to children under 5 years.
9.16
[101]
Natural cure for meats
9.16.1
Nitrates and nitrites
They are used in cured meats such as ham and bacon, hot dogs and deli meats. Both nitrates and nitrites combine with other nitrogen-containing substances in the stomach to form N-nitroso compounds that are known to cause stomach cancer.
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9.16.2
Salted, smoked or pickled foods and red meat
Commonly preserved food by salting, smoking or pickling often contain large amounts of nitrites and nitrates. Countries where consumption of salted meat and sh and pickled vegetables is high, such as Japan and Korea tend to have correspondingly high rates of stomach cancer. Eating a diet high in red meat, especially when the meat is barbecued or well-done, also has been linked to stomach cancer. Traditional curing methods using nitrite or nitrate are being substituted by new products for the sake of a natural label. There are consumers which try to avoid nitrite cured meat because of health concerns.
9.16.3
Curing as food preservation
[102] In food preparation, curing refers to various preservation and avouring processes, especially of meat and sh by the addition of a combination of salt, sugar and either nitrate or nitrite. Many curing processes also involve smoking. Nitrite curing retards rancidity, stabilises avour, and establishes the characteristic pink colour of cured meat. Salt inhibits the growth of microorganism which cause spoilage by drawing water out of microbial cells through osmosis. As the unwanted bacterial population decreases, other benecial bacteria, primarily of the Lactobacillus genus, come to the fore and generate an acidic environment (around 4.5 pH). The sugar included in the cure is used as food by the lactobacilli; generally dextrose is preferred over sucrose, or table sugar, because it seems to be more thoroughly consumed by the bacteria. This process is in fact a form of fermentation and, in addition to reducing further the ability of the spoilage bacteria to grow, accounts for the tangy avour of some cured products. Concentrations of salt up to 20% are required to kill most species of bacteria. Smoking adds chemicals to the surface of an item which aect the ability of bacteria to grow, inhibit oxidation (and thus rancidity), and improve avour. Nitrates and nitrites not only help kill bacteria, but also produce a characteristic avour, and give meat an appealing pink or red color. Nitrate (NO3 ), in the form of either sodium nitrate or potassium nitrate is used as a source for nitrite (NO2 ). The nitrite further breaks down in the meat into nitric oxide (NO), which then binds to the iron atom in the center of mioglobins heme group, preventing oxidation.
9.16. NATURAL CURE FOR MEATS
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Commercially Curing salt containing small amounts of sodium nitrite or sodium nitrate is used in the preserving and curing of meats, and in sausage making. The nitrate component inhibits the growth of bacteria, specically botulism, and helps preserve the color of cured meat. The presence of nitrates and nitrites in food is controversial due to the development of nitrosamines when the food, primarily bacon, is cooked at high temperatures. The nitrate and nitrite compounds themselves are not harmful, however, and are among the antioxidants found in fresh vegetables. [103] The usage of either compound is carefully regulated in the production of cured products; in the United States, their concentration in nished products is limited to 200 ppm, and is usually found to be below. Finally, they are irreplaceable in the prevention of botulinum poisoning from consumption of dry-cured sausages.
9.16.4
Nitrite replacement for cured meats
[104] Chr. Hansen has developed a new natural cure for manufacturers as a nitrite replacement for cured meats. No synthetic nitrates or nitrites are added, labelling of nitrite or nitrate can be avoided. The product can be labelled as uncured in accordance with USDA 9CFR317.17 labelling regulations [101]. Naturally occurring nitrates are converted by the culture to nitrite which then accounts for the curing of the meat. According to papers of Chr. Hansen various strains are used. Lactobacillus sakei BJ33 was approved by the Danish authorities for bioprotective use. The bacteria multiplies at chill temperatures as low as 2o C /35o F and suppresses the spoilage ora of indigenous lactic acid bacteria and Brochothrix thermosphacta. The inhibitory eect possessed by the strain is due to competition since the ability to produce bacteriocins has not been detected. It is used in combination with a strain of Staphylococcus xylosus. Other strains used by Chr Hansen are Leuconostoc carnosum 4010 (formerly named Lc1043). Another strain used is B-LC-20 which is an adjunct culture that is added on top of the existing starter culture without changing the sausage recipe or the sausage processing procedure for the reduction of Listeria in fermented dried sausage.
9.16.5
Processed meat like bacon and sausages increase risk of heart disease and diabetes, says a meta-analysis
[105] Micha, Wallace and Mozaarian 2010 found that Consumption of processed meats, but not red meats, is associated with higher incidence of CHD and diabetes mellitus. It takes only 50 g (one hot Dog) of processed meat per day to increase heart disease by 42% and type 2 diabetes by 19%. No link between eating unprocessed red meat like beef or pork and risk of
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heart disease and diabetes was found by the authors. High levels of salt and nitrate preservatives in sausages, bacon and deli meats, rather than fats, might explain the higher risk of heart disease and diabetes seen with processed meats, but not with unprocessed red meats. The authors call for studies looking at processed and unprocessed meats separately and focus on salt and nitrate preservatives.
9.16.6
Researcher from Iran says that nitrite may be replaced by annatto up to 60 per cent
[106] A controversy concerns nitrites in cured meats. Some say it increases the risk of stomach cancer, or lung diseases [107], while other researchers found no proof of such armations. Cardiologists found that nitric oxide from bacterial breakdown of nitrite reduces blood pressure and avoids damages during an heart attack. [108] [109] Ribeiro and colleagues 2006 presents a summary of studies concerning anti-mutagenic and anti-carcinogenic potential of annatto, mushrooms and propolis in Brazilian natural diets. Their data shown a clear role for these compounds in preventing mutation and specic preneoplastic lesions. The authors stress that these agents may become a promising alternative for cancer prevention strategies. [110] Petersson, 2008 suggests that nitrites may protect the stomach from ulcers. The author says that mouth bacteria reduce nitrate to nitrite. Nitrous oxide NO produced in the gastric lumen after nitrate ingestion increased gastric mucosal blood ow and the thickness of the rmly adherent mucus layer in the stomach. The blood ow and mucus layer are essential defence mechanisms that protect the mucosa from luminal acid and noxious agents. [111] Zarringhalami, Sahari and Hamidi-Esfehani 2008, researchers from Iran, presented a study claiming that annatto (Bixa orellana L.) powder may replace up to 60 per cent of nitrite as ingredient of sausage. This might reduce excessive consumption of nitrite. According to the authors colour, avour, aroma, and microbial contamination did not dier signicantly compared with samples with 100 percent nitrite. [106] Annatto is not allowed in the European Union as ingredient of sausages and other meat products. Annex IV of the European directive 94/36/EC on colours for use in foodstus cites annatto in a positive list of colours permitted for certain uses only, meat products are allowed there. [11]
9.17. NITRITES AND NITRATES IN CURED MEAT FRUIT AND VEGETABLE MAY PROTECT AGAINST HEART ATTACK 789
9.16.7
Code of Federal Regulations 9CFR317.17
[101] With respect to sections 1(n) (7), (9), and (12) of the Act and Sec. 317.2, any substance mixed with another substance to cure a product must be identied in the ingredients statement on the label of such product. For example, curing mixtures composed of such ingredients as water, salt, sugar, sodium phosphate, sodium nitrate, and sodium nitrite or other permitted substances which are added to any product, must be identied on the label of the product by listing each such ingredient in accordance with the provisions of Sec. 317.2. (b) Any product, such as bacon and pepperoni, which is required to be labeled by a common or usual name or descriptive name in accordance with Sec. 317.2(c)(1) and to which nitrate or nitrite is permitted or required to be added may be prepared without nitrate or nitrite and labeled with such common or usual name or descriptive name when immediately preceded with the term "Uncured" as part of the product name in the same size and style of lettering as the product name, provided that the product is found by the Administrator to be similar in size, avour, consistency, and general appearance to such product as commonly prepared with nitrate or nitrite, or both. (c)(1) Products described in paragraph (b) of this section or Sec. 319.2 of this subchapter, which contain no nitrate or nitrite shall bear the statement "No Nitrate or Nitrite Added." This statement shall be adjacent to the product name in lettering of easily readable style and at least one-half the size of the product name. (2) Products described in paragraph (b) of this section and Sec. 319.2 of this subchapter shall bear, adjacent to the product name in lettering of easily readable style and at least one-half the size of the product name, the statement "Not Preserved-Keep Refrigerated Below 40 deg.F. At All Times" unless they have been thermally processed to Fo 3 or more; they have been fermented or pickled to pH of 4.6 or less; or they have been dried to a water activity of 0.92 or less. (3) Products described in paragraph (b) of this section and Sec. 319.2 of this subchapter shall not be subject to the labeling requirements of paragraphs (b) and (c) of this section if they contain an amount of salt sucient to achieve a brine concentration of 10 percent or more.
9.17
Nitrites and nitrates in cured meat fruit and vegetable may protect against heart attack
Sodium nitrite E250 produces the pink colour of cured meat. It also retards rancidity and stabilises the avour.
790
The third National Health and Nutritional Examination Survey (NHANES) on 7,352 subjects over the age of 45, have suggested that increased consumption of nitrites from cured meat could increase the risk of lung disease. [107] Other studies found nitrite and nitrate to be related to the incidence of cancer due to the formation of nitrosamines. But recent research has found no convincing evidence that nitrite and nitrate pose a cancer risk. In reality they seem to protect heart cells from death after an heart attack. The study published in the Proceedings of the National Academy of Sciences found that nitrites reduce heart cell death in mice by 48 per cent after an heart attack. Nathan S. Bryan and colleagues report that mice supplemented with 50 mg nitrite per litre of drinking water for seven days had a survival rate of 77 per cent compared to 58 per cent for the mice without supplementation. The researchers say that eating nitrite and nitrate rich foods such as fruits and vegetables and some meats in moderation can drastically improve outcome following a heart attack, They suggest to sty the eects of supplementation of nitrite/nitrate in the diet can decrease the incidence and severity of heart attack and stroke in patients with known cardiovascular risk factors. Bryan suggests the formation of nitric oxide (NO) from nitrites to be the mechanism of the heart protecting eect of nitrates. Nitric oxide causes the cells of the blood vessels to signal the surrounding muscles to relax. This results in a reduction in blood pressure, reduction of blood clotting and and protection against myocardial infarction and strokes. A betaine in chemistry is any neutral chemical compound with a positively charged cationic functional group such as ammonium ion or phosphonium ion and with a negatively charged functional group such as a carboxyl group. Historically the term was reserved for trimethylglycine only. [112] Betaine is found in high concentrations in sugar beet, improving consistency of pig and poultry performance improving the structure of the animals intestine, increasing gut tensile strength and the absorptive area for nutrients, which helps to maintain growth, feed conversion and protability in the absence of antibiotic growth promoters. Betaine (trimethylglycine) functions very closely with choline, folic acid, vitamin B12 and methionine. Betaine is necessary in the biochemistry of carnitine and serves to protect the kidneys from damage. [113] Barak proposed in 1983 that betaine may serve as an important methylating agent when normal methylating pathways are impaired by ethanol ingestion, drugs or nutritional imbalances. Furthermore, betaine may prove to have therapeutic application in cases of
9.17. NITRITES AND NITRATES IN CURED MEAT FRUIT AND VEGETABLE MAY PROTECT AGAINST HEART ATTACK 791 altered folate, vitamin B12 or methionine metabolism. [114] Glycine betaine (betaine hydrochloride) used as feeding attractant was found to have a positive eect on the growth and feed conversion of juveniles of Macrobrachium rosenbergii (deMan). Weight gain, feed intake and food conversion ratio (FCR) were higher in prawn fed glycine betaine-added diets compared with the control feed in a study made by Dr Nathan Felix. [115] Betaine is used in animal feeds as a source of essential methyl groups and as an osmoregulant. Its osmotic function is useful in maintaining gut wall integrity. Feeding betaine could compensate the removal of antibiotic growth promoters. Reduced control of Clostridium perfringens in birds could be countert with betaine which improves the hydration and integrity of the gut wall. [116] Betaine decays in the liver forming methionine. Dietary methionine is spared. saving feeding costs Feeding betaine saves methionine and choline costs Betaine also functions as osmoregulator. Betaine in feed or water can help reduce dehydration by facilitating water retention in the body in case of heat stress. [117] Advances in genetics and feed ingredients such as betaine from sugar beets and enzymes have reduce feed costs and generate a higher percentage of lean meat.
9.17.1
High content of nitrate in beetroot reduces blood pressure
[118] Amrita Ahluwalia and colleagues 2008 studied the benets of high nitrate content of vegetables like beetroot. The authors suggest that the nitrate content of the vegetables is responsible for a reduction of blood pressure , and not by the antioxidant vitamin content as assumed in foregoing studies. The authors say that drinking 500 ml beetroot juice a day reduces blood pressure signicantly three hours after the consumprtion. The authors explain that the high nitrate content of the juice increases nitrate content of the saliva, where it is converted to nitrite by bacteria living on the tong. When swallowed the nitrite is transformed in nitric oxide NO in the stomach and can the reenter the blood circulation as nitrite. The authors reported further that dietary nitrate load also prevented endothelial dysfunction induced by an acute ischemic insult in the human forearm and signicantly attenuated ex vivo platelet aggregation in response to collagen and ADP. Some studies suggest that nitrite (NO(2)(-)), is a physiological signaling molecule with potential roles in intravascular endocrine nitric oxide (NO) transport, hypoxic vasodilation, signaling, and cytoprotection after ischemia-reperfusion. There is evidence that nitrite meCopyright 1998-2010 Karl H. Wilm. All rights reserved. OurFood Database of Food and Related Sciences
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diates many of the systemic therapeutic eects of NO gas inhalation, including peripheral vasodilation and prevention of ischemia-reperfusion-mediated tissue infarction. [119] [120] Michael P. Frenneaux and colleagues 2008 found nitrite to be a potent venodilator in normoxia and hypoxia. The authors highlight the importance of nitrite as a selective arterial vasodilator in ischemic territories and as a potent venodilator in heart failure. [121] Other studies say that nitrate and nitrite are linked to stomach cancer and give advice to avoid food with high content of both substances. The Mayo Clinic names some factors which are believed to increase stomach cancer: [122]
9.17.2
Thickening agents from Algae
[123] Carrageenans extracted from red algae and alginates from brown algae are already being used as stabilisers and thickening agents. Albert Mihranyan and colleagues from Uppsala University in Sweden studied the properties of alpha - cellulose of the green algae Cladophora sp. They found that Cladophora cellulose powder could be a useful alternative to commercially available dispersible cellulose grades when very low quantities of stabilizing agents are required.
9.18
Cherry fruits or cherry extract may prevent recurrent gout attacks
[124] Researchers report that consuming up to three servings.cherries or cherry extract over two days, lowers the risk of gout attack. Cherry intake during a 2-day period was associated with a risk reduction of 35% gout attaks, and cherry extract intake was associated with a risk reduction of 45%. The risk was even further reduced to 75% when cherry was used together with allopurinol. Zhang et al. 2012, authors of the study explain that cherries may decrease serum uric acid levels by increasing glomerular ltration or reducing tubular reabsorption. This is Cherries have The high levels of anthocyanins of cherries have anti-inammatory activities. The authors stress that recommendations to reduce the risk of gout attack include moderation in alcohol consumption, weight reduction, decreased high-purine foods from the diet and eating cherries. However, cherries should not replace medication but should be consumed additionally to allopurinol.
9.18. CHERRY FRUITS OR CHERRY EXTRACT MAY PREVENT RECURRENT GOUT ATTACKS 793
9.18.1
Anthocyanin prole of sour cherry [125]
According to Damar and Eksi 2012 the antioxidant capacity, total polyphenolic content and monomeric anthocyanin contents of juices of dierent varieties of sour cherries were within the ranges 20.0-37.9mmol/L, 1510-2550 and 350.0-633.5mg/L, respectively. The main anthocyanin compound in sour cherry juice was cyanidin-3-glucosylrutinoside and cyanidin-3-rutinoside.Anthocyanin capacity correlates with total polyphenol content, however no correlation was found between the antioxidant capacity and monomeric anthocyanin content.
9.18.2
Soft drinks, fructose consumption, and the risk of gout in men
[126] A study by Choi and Curhan suggests that dietary fructose intake is a possible risk factors for gout increasing serum urate and is associated with hyperuraemia. Obesity, alcohol, and diet with the aree also associated with the onset of gout. Hyon K. Choi and Gary Curhan, authors of the 12 years follow-up study found a strong association between sugar sweetened soft drinks and gout. They wrote that two servings a day of a sugar sweetened soft drink, high in fructose, increased the risk of developing gout by 85% compared with consumption of less than one serving of sugar sweetened soft drinks a month. Fructose rich fruits and fruit juices may also increase the risk. Diet soft drinks were not associated with the risk of gout. [127] Other foods high in fructose are fruit-yoghurt, candies, backery where corn syrup is added.
9.18.3
Two or more soft drinks per week double pancreatic cancer risk
[128] Sugar-sweetened carbonated beverages and juices have a high glycemic load relative to other foods and beverages. Mark Pereira and colleagues 2010 write two or more soft drinks per week, but not juices, may increase the level of insulin in the body double the pancreatic cancer risk compared with persons which do not drink soft drinks. However limitations of this study are seen in the fact that soft drink consumption is often associated with overweight increase, smoking, red meat intake and reduced exercise and may not be suciently considered in this study. Interestingly South Chinese population dier from European and Western population regarding the eect of nutrition health related issues. Increased BMI is a robust risk factor for type 2 diabetes. This, however is not valid for South Asians which have relatively low BMIs despite a high prevalence of type 2 diabetes. Odegaard and colleagues 2009
794
found that Singaporean Chinese with lean or normal BMI have an increased risk of type 2 diabetes. [129]
9.18.4
Improving nutritional quality of chocolate products
A randomized controlled trial performed by Pase et al. 2013 provided evidences of positive eects of cocoa polyphenols on mood in healthy persons. However, cognitive performance remained inaltered during administration of cocoa polyphenols. The authors suggest further studies on cocoa polyphenols to ameliorate the symptoms associated with clinical anxiety or depression. Robson 2013 deplores the high content of sugar in chocolate. Current chocolate bars have a high energy density of more than 2 kcal/g. He makes a plea to improve the nutritional value of chocolate bars which should be based on the nutritional value of the low energy dense late Paleolithic human diet to help reduce mental ill health, obesity, and other postprandial diseases. [130] Robson stresses that the high energy density and low nutrient density that characterize the modern diet must be overcome simultaneously. People with a low-energy-dense diet (<1.6 kcal/g) have the lowest total intakes of energy, even though they consume the greatest amount of food. A processed food that is not both low energy dense and high nutrient dense is of poor dietary quality. Sugar in chocolate formulations should be replaced by natural non-caloric sweeteners, nanocellulose and calorie-free monk fruit extract (Siraitia grosvenorii) could be used to lower the energy density of chocolate. [131] The Paleolithic diet: Degenerative non-communicable diseases are rare or nonexistent in hunter-gatherers eating a late Paleolithic diet, that is, a low energy dense diet with a wild plant-to-animal energy intake ratio 1:1, with sh and shell sh providing a signicant proportion of the animal component. Nearly all the genes and epigenetic regulatory mechanisms humans carry today were originally selected for behaviourally modern humans who appeared in Africa between 100,000 and 50,000 years ago. Thus, it has been argued that the typical diet, physical activity patterns, and body composition of late Paleolithic humans remain normative for contemporary humans and models for disease prevention recommendations. [132] Bel-Serrat et al. 2012 report increased metabolic risk in 2 to 9 years old children with high intakes of solid hydrogenated fat and white bread, and low consumption of fruits, vegetables and dairy products. High consumption of chocolate, nut-based spreads, jam, honey, sweets, soft drinks and manufactured juices increased signicantly CVD risk. Children with high consumption of breakfast cereals presented a reduced CVD risk compared to those with little breakfast cereals intake. The authors stresses the role that diet may play on cardiovascular health, specically clustered cardiovascular disease risk. [133]
BIBLIOGRAPHY
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Added sugars to total energy value of 12,35 is too high, compared to the current recommended levels, says the study of Colucci et al 2012 of children in the city of So Paulo, Brazil. Highest sugar consume was due to soft drinks followed by sugars (sucrose and honey) and chocolate powder. [134] Adults consumed 9,1% of added sugar of energy intake and elderly 8.4%. Soft drink was the most important source of sugar among adults. Elderly consumed table sugar most frequently. Soft drink and table sugar were the source of more than 50% of added sugar wrtote Bueno et al. 2012.
Bibliography
[1] Kapfelsperger,Eva/Pollmer,Udo: Witsch,Kln,1982, S.122. Iss und stirb/Verlag Kiepenheuer und
[2] Habs M and Schmhl D. Synergistic eects of n-nitroso compounds in experimental long-term carcinogenesis studies. Oncology, 37(4):25965, 1980. http://www.ncbi. nlm.nih.gov/pubmed/7443158. [3] http://www.codexalimentarius.net/web/index_en.jsp. FAO/WHO Food Standards. Codex Alimentarius
[4] http://www.ncbi.nlm.nih.gov/pubmed/19439460. Hord, N.G.; Tang, Y.; Bryan, N.S.: Food sources of nitrates and nitrites: the physiologic context for potential health benets. Am J Clin Nutr. 2009 May 13. [5] http://ec.europa.eu/food/fs/sfp/flav_index_en.html. European Commission on Food Additives and avourings. [6] http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=OJ:L:2008:354: 0001:0006:EN:PDF. Regulation 1331/2008 establishing a common authorisation procedure for food additives, food enzymes and food avourings. [7] http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=OJ:L:2008:354: 0007:0015:EN:PDF. Regulation (EC) No 1332/2008 contains ruling of food enzymes. [8] http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=OJ:L:2008:354: 0016:003 3:EN:PDF. Regulation 1333/2008 on food additives: The Regulation brings together in a single legislative act all types of food additives including colours and sweeteners. [9] http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=OJ:L:2008:354: 0034:0050:EN:PDF. Regulation (EC) No 1334/2008 on avouring and certain food ingredients with avouring properties.
796
[10] http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=OJ:L:2009:344: 0037:0040:EN:PDF. Commission Directive 2009/163/EU of 22 December 2009 amending Directive 94/35/EC of the European Parliament and of the Council on sweeteners for use in foodstus with regard to neotam. [11] http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=CELEX: 31994L0036:EN:HTML. European Parliament and Council Directive 94/36/EC from 30 June 1994. [12] http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=CELEX: 31995L0002:EN:HTML. DirectiveNo 95/2/EC of 20 February 1995 on food additives other than colours and sweeteners. [13] F.K. Marcus and H.P. Hansen: Fiirbende Lebensmittelextrakte; Food Technology Magazin 3 (July 1996). [14] http://www.natcol.org/chart.htm. colours. NATCOL: The sources of natural food
[15] R. Bermejo Roman, J. M. Alvarez-Pez, F. G. Acien Fernandez and E. Molina Grima: Recovery of pure B-phycoerythrin from the microalga Porphyridium cruentum. Journal of Biotechnology, Volume 93, issue 1, Pages 73-85. doi.101016/S01681656(01)00385-6. [16] Muris Kobalija and D. Tyler McQuade: Removable Coloured Coatings Based on Calcium Alginate Hydrogels Biomacromolecules; 2006; 7(8) pp 2357 - 2361; DOI: 10.1021/bm060341q. [17] http://www.efsa.europa.eu/en/press/news/cef100108.htm?WT.mc_id= EFSAHL01&emt=1. EFSA completes rst safety assessments of smoke avourings. EFSA 8 January 2010. [18] http://www.efsa.europa.eu/en/ceftopics/doc/ceftable.pdf. Summary of the Opinions on Smoke Flavourings Adopted by the EFSA CEF Panel in 2009. [19] The European Commission: Regulation (EC)No 2065/2003 of the European Parliament and of the Council of 10 November 2003 on smoke avouring used or intended for use in or on foods. [20] Ghadimi H.et al; Biochem.Med.1971/5/S, 447. [21] Olney J.W.;Fd Cosmet.Toxicol. 1975/13/S. 595. [22] http://www.nature.com/oby/journal/v16/n8/abs/oby2008274a.html. He, K.; Zhao, L.; Daviglus, M.L; Dyer, A.R.; Van Horn, L.; Garside, D.; Zhu, L.; Guo, D.; Wu, Y.; Zhou, B.; Stamler J.: Association of Monosodium Glutamate Intake With Overweight in Chinese Adults: The INTERMAP Study. Obesity. Volume 16, Number 8, Pages 1875-1880. doi: 10.1038/oby.2008.274.
BIBLIOGRAPHY
797
[23] http://www.msgfacts.com/whatsnew/TGA_Statement_on_MSG_and_Body_ Weight.html. The Glutamate Association: Statement on MSG and Body Weight August 22, 2008. [24] http://www.ncbi.nlm.nih.gov/pubmed/16914226. Essed, Natasja H.; van Staveren, Wija A.; Kok, Frans J.; de Graaf, Cees: No eect of 16 weeks avor enhancement on dietary intake and nutritional status of nursing home elderly. Appetite 2007, 48 Pages 29-36. [25] http://www.ncbi.nlm.nih.gov/pubmed/18559279. Kondoh, Takashi; Torii, Kunio: MSG intake suppresses weight gain, fat deposition, and plasma leptin levels in male Sprague-Dawley rats. PhysiolBehav2008,doi:10.1016/j.physbeh.2008.05.010. [26] BaughamR.W.and Gilbert C.D.; Nature 1980/287/S. 848. [27] Walker R and Lupien JR. The safety evaluation of monosodium glutamate. J Nutr, 130(4S Suppl):1049S52S, 4 2000. http://jn.nutrition.org/content/130/ 4/1049.long. [28] http://www.ncbi.nlm.nih.gov/pubmed/8458588. Cao, G.; Alessio, H.M.; Cutler, R.G.: Oxygen-radical absorbance capacity assay for antioxidants. Free Radic Biol Med. 1993 Mar; 14(3):303-11. [29] http://en.wikipedia.org/wiki/Oxygen_radical_absorbance_capacity. Wikipedia: Oxygen radical absorbance capacity (ORAC). [30] http://care.diabetesjournals.org/cgi/content/abstract/20/2/194. Ceriello, A.; Bortolotti, N.; Falleti, E.; Taboga, C.; Tonutti, L.; Crescentini, A.; Motz, E.; Lizzio, S.; Russo A.; Bartoli, E. : Total radical-trapping antioxidant parameter in NIDDM patients. Diabetes Care, Vol 20, Issue 2 194-197. [31] http://www.clinchem.org/cgi/content/full/50/5/952. Wang, Chi Chiu; Chu, Ching Yan; Chu, Kai On; Choy, Kwong Wai; Khaw, Kim Sun; Rogers, Michael Scott; Pang, Chi Pui: Trolox-Equivalent Antioxidant Capacity Assay Versus Oxygen Radical Absorbance Capacity Assay in Plasma. Clinical Chemistry. 2004;50:952-954. [32] http://cat.inist.fr/?aModele=afficheN&cpsidt=15034568. MacLean, D. D.; Murr, D. P. ; Deell, J. R.: A modied total oxyradical scavengingcapacity assay for antioxidants in plant tissues. Postharvest biology and technology. 2003, vol. 29, nr 2, pp. 183-194 [12 page(s) (article)] (27 ref.). [33] http://vivo.cornell.edu/entity?home=1&id=15461. Adom, Kafui Kwami; Liu, Rui Hai |: Rapid peroxyl radical scavenging capacity (PSC) assay for assessing both hydrophilic and lipophilic antioxidants. J Agric Food Chem. 2005; 53(17): 6572-80.
798
[34] http://www.ncbi.nlm.nih.gov/pubmed/15652192. Firuzi O.; Lacanna, A.; Petrucci, R.; Marrosu, G.: Saso, L.: Evaluation of the antioxidant activity of avonoids by ferric reducing antioxidant power assay and cyclic voltammetry. Biochim Biophys Acta. 2005 Jan 18;1721(1-3):174-84. Epub 2004 Dec 22. [35] http://www.actahort.org/members/showpdf?booknrarnr=744_51. Woodrow, L.; Luman, M.; van der Leeuw, S.; Liptay, A.: Antioxidant Activity in Raspberry, Currant and Gooseberry Accessions of the Canadian Clonal Genebank ISHS Acta Horticulturae 744: I International Symposium on Human Health Eects of Fruits and Vegetables. International Society for Horticultural Science. [36] http://www.cababstractsplus.org/google/abstract.asp?AcNo=20053095214. DeYong, Zheng; XinNan, An: Determining method of DPPH free radical scavenging activity of bamboo leaf extractives. Journal of Fujian Agriculture and Forestry University (Natural Science Edition), 2005 (Vol. 34) (No. 1) 59-62. [37] http://pubs.acs.org/cgi-bin/abstract.cgi/jafcau/2007/55/i22/abs/ jf0715166.html. Wolfe, Kelly L.; Hai Liu, Rui Cellular Antioxidant Activity (CAA) Assay for Assessing Antioxidants, Foods, and Dietary Supplements. [38] R.Mller,I.Sander,M.Anke:Untersuchungen zur Selenversorgung Erwachsener in Deutschland.Lebensmittel-und Biotechnologie (1998) Nr.2,S.84-86. [39] http://www.ajcn.org/cgi/content/abstract/87/2/379. Thomson, Christine D; Chisholm, Alexandra; McLachlan, Sarah K. Campbell, Jennifer M: Brazil nuts: an eective way to improve selenium status. American Journal of Clinical Nutrition. February 2008, Volume 87, Pages 379-384. [40] http://www.defra.gov.uk/environment/statistics/radioact/radfood.htm. UK DEFRA: Natural Sources of Radiation. Food and drink. [41] Stabiles Herz durch Kalium und Magnesium;DAK Magazin, Deutsche AngestelltenKrankenkasse 3/98 S 8. [42] http://www.efsa.europa.eu/EFSA/efsa_locale-1178620753812_ 1178689482553.htm. EFSA issues opinion on nutrient sources containing vanadium. [43] http://www.efsa.europa.eu/EFSA/efsa_locale-1178620753812_ 1178620766253.htm. Opinion of the Scientic Panel on Dietetic products, nutrition and allergies [NDA] related to the Tolerable Upper Intake Level of Vanadium. [44] http://www.food.gov.uk/multimedia/pdfs/evm_vanadium.pdf. EVM Review of Vanadium. [45] Carper,Jean: Stop aging now, The ultimate plan for staying young and reversing the aging process;HarperCollins Publishers,Inc.East 53rd Street, New York,Ny: 1995.
BIBLIOGRAPHY
799
[46] T. Hall-Manning, M. Spurgeon, A. M. Wolfreys and A. P. Baldrick: Safety evaluation of ice-structuring protein (ISP) type III HPLC 12 preparation. Lack of genotoxicity and subchronic toxicity: Food and Chemical Toxicology; Volume 42, Issue 2, February 2004, Pages 321-333. [47] http://www.afprotein.com/table.htm. AFP Protein: Structural Characteristics of the Antifreeze Proteins (AFP) and Glycoproteins (AFGP). [48] http://www.efsa.europa.eu/EFSA/efsa_locale-1178620753812_ 1211902041128.htm. EFSA: Safety of Ice Structuring Protein (ISP) - Scientic Opinion of the Panel on Dietetic Products, Nutrition and Allergies and of the Panel on Genetically Modied Organisms Question number: EFSA-Q-2008-073 Published 08.08.2008. [49] http://eur-lex.europa.eu/LexUriServ/site/en/com/2006/com2006_ 0425en01.pdf. FOOD ENZYMES: Proposal for a Regulation on food enzymes and amending Council Directive 83/417/EEC, Council Regulation (EC) No 1493/1999, Directive 2000/13/EC, and Council Directive 2001/112/EC (COM(2006) 425) 28/07/06. [50] http://en.wikipedia.org/wiki/EC_number. Wikipedia, the free enzyclopedia: EC number. [51] http://en.wikipedia.org/wiki/UniProt. UniProt. Wikipedia, the free enzyclopedia:
[52] Karen Laa, W. Graham McLean, Dominic P. Williams, and C. Vyvyan Howard:Synergistic Interactions Between Commonly Used Food Additives in a Developmental Neurotoxicity Test; Toxicological Sciences, doi:10.1093/toxsci/kfj073 , December 13, 2005. [53] http://www.food.gov.uk/multimedia/pdfs/TOX-2005-18.pdf. UK Food Standards Agency: Committee on Toxicity of Chemicals in Food, Consumer Products and the Environment Food Additives and Developmental Neurotoxicity. TOX/2005/18. [54] http://vlex.com/vid/38605235. Commission Regulation (EC) No 492/2008 of 3 June 2008 imposing a provisional anti-dumping duty on imports of monosodium glutamate originating in the Peoples Republic of China. [55] http://cat.inist.fr/?aModele=afficheN&cpsidt=13901132. Hiroshi, Ohguro; Harumi, Katsushima; Ikuyo, Maruyama; Tadao, Maeda; Satsuki, Yanagihashi; Tomomi, Metoki; Mitsuru, Nakazawa: A high dietary intake of sodium glutamate as avoring (Ajinomoto) causes gross changes in retinal morphology and function. Experimental eye research. 2002, vol. 75, nr. 3, pp. 307-315.
800
[56] http://www.ncbi.nlm.nih.gov/pubmed/20470841. Jinap S and Hajeb B: Glutamate: Its applications in food and contribution to health. Appetite. Published online ahead of print, doi: 10.1016/j.appet.2010.05.002. [57] http://www.foodstandards.gov.au/_srcfiles/MSG%20Technical%20Report. pdf. Monosodium Glutamate, A safety Assessment. Food Standards Australia New Zealand 2003. [58] Kwok, R. (1968), Chinese Restaurant Syndrome (letter). N Engl J Med, 278:796. [59] http://www.ncbi.nlm.nih.gov/pubmed/5764480. Schaumburg HH, Byck R, Gerstl R, Mashman JH: Monosodium L-glutamate: its pharmacology and role in the Chinese restaurant syndrome. Science. 1969 Feb 21;163(869):826-8.
[60] http://www.thefreelibrary.com/Monosodium+glutamate+and+the+Chinese+Restaurant+Sy a017087836. Taliaferro, Patricia J.: Monosodium glutamate and the Chinese Restaurant Syndrome: a review of food additive safety. Journal of Environmental Health, Vol. 57, 1995. [61] http://www.food.gov.uk/news/newsarchive/2007/sep/foodcolours. revises advice on certain colours. Agency
[62] http://www.soton.ac.uk/mediacentre/news/2007/sep/07_99.shtml. University of Southampton: Major study indicates a link between hyperactivity in children and certain food additives. News Release Ref: 07/99. 06 September 2007. [63] http://www.thelancet.com/journals/lancet/article/ PIIS0140673607613063/abstract. McCann D, Barrett A, Cooper A, Crumpler D, Dalen L, Grimshaw K, et al: Food additives and hyperactive behaviour in 3-year-old and 8/9 year-old children in the community a randomised, double-blinded, placebocontrolled trial. The Lancet 2007; 370:1560-70 DOI:10.1016/S0140-6736(07)61306-3. [64] http://www.food.gov.uk/multimedia/pdfs/committee/colpreschil.pdf. COT statement 2007/04 September 2007. [65] http://www.bfr.bund.de/cm/245/hyperactivity_and_additives_is_there_ an_association.pdf. Hyperactivity and Additives - Is there an association? BfR Expert Opinion No. 040/2007, 13 September 2007. [66] http://www.thelancet.com/journals/lancet/article/ PIIS0140673607613063/abstract. McCann, D., Barrett, A., Cooper, A., Crumpler, D., Dalen, L., Grimshaw, K., Kitchin, E., Lock, K., Porteous, L., Prince, E., Sonuga-Barke, E., Warner, J.O., Stevenson, J. (2007) Food additives and hyperactive behaviour in 3 and 8/9 year old children in the community. The Lancet, 6 September 2007, DOI:10.1016/S0140-6736(07)61306-3.
BIBLIOGRAPHY
801
[67] http://www.food.gov.uk/multimedia/pdfs/committee/colpreschil.pdf. COT statement 2007/04 September 2007: Statement on Research Project (T07040) investigating the eect of mixtures of certain food colours and a preservative on behaviour in children. [68] http://www.efsa.europa.eu/EFSA/efsa_locale-1178620753812_ 1178694648892.htm. EFSA Scientic Opinion of the Panel on Food Additives, Flavourings, Processing Aids and Food Contact Materials (AFC) on a request from the Commission on the results of the study by McCann et al. (2007) on the eect of some colours and sodium benzoate on childrens behaviour. The EFSA Journal (2008) 660, 1-5. [69] http://www.soton.ac.uk/mediacentre/news/2008/mar/08_50.shtml. University of Southampton: Southampton response to EFSA evaluation of study on food additives and childrens behaviour. Ref: 08/50 14 March 2008. [70] http://www.bmj.com/cgi/content/extract/336/7654/1144. Kemp, Andrew: Editorial: Food additives and hyperactivity. British Medical Journal 2008; 336:1144 DOI: 10.1136/bmj.39582.375336.BE. [71] http://www.abc.net.au/worldtoday/content/2008/s2595445.htm. Aldi bans food colourings linked to ADHD. The World Today, 11 June, 2009 12:34:00. [72] http://www.fedupwithfoodadditives.info/information/nastyadditivecard. pdf. Food Intolerance Network: Nasty additives. [73] http://www.euractiv.com/en/cap/parliament-adopts-stricter-rules-food-additives/ article-174047. EurActiv: Parliament adopts stricter rules for food additives. 09.07.2008. [74] http://www.efsa.europa.eu/EFSA/efsa_locale-1178620753812_ 1178637756847.htm. EFSA: EFSA to consider new UK study on behavioural changes associated with certain food colours. 06.09.2007. [75] http://www.ncbi.nlm.nih.gov/pubmed/18539379. Inoue, T.; Umemura, T.; Maeda, M.; Ishii, Y.; Okamura, T.; Tasaki, M.; Nishikawa, A.: Safety assessment of dietary administered paprika colour in combined chronic toxicity and carcinogenicity studies using F344 rats. Food and Chemical Toxicology. August 2008, Volume 46, Issue 8, Pages 2689-2693. [76] Pelsser LM, Frankena K, Toorman J, Savelkoul HF, Dubois AE, Pereira RR, Haagen TA, Rommelse NN, and Buitelaar JK. Eects of a restricted elimination diet on the behaviour of children with attention-decit hyperactivity disorder (inca study): a randomised controlled trial. Lancet, 377(9764):494503, 2 2011. http://www.ncbi. nlm.nih.gov/pubmed/21296237.
802
[77] Pelsser LM, Frankena K, Buitelaar JK, and Rommelse NN. Eects of food on physical and sleep complaints in children with adhd: a randomised controlled pilot study. Eur J Pediatr, 169(9):112938, 9 2010. http://www.ncbi.nlm.nih.gov/pmc/articles/ PMC2908441/?tool=pubmed. [78] Irn bru will not change colour, says maker ag barr. bbc news scotland business 9. septempber 2011. http://www.bbc.co.uk/news/ uk-scotland-scotland-business-14857275. [79] Wikipedia. Irn-bru. http://en.wikipedia.org/wiki/Irn_Bru. [80] http://www.ncbi.nlm.nih.gov/pubmed/17008578. Lien, L.; Lien, N.; Heyerdahl, S.; Thoresen, M.; Bjertness E.: Consumption of soft drinks and hyperactivity, mental distress, and conduct problems among adolescents in Oslo, Norway. Am J Public Health. 2006 Oct;96(10):1815-20. [81] http://www.informaworld.com/smpp/content~db=all?content=10.1080/ 10408390701407316. Benton, David: Sucrose and behavioural problems. Critical Reviews in Food Science and Nutrition. Volume 48, issue 5, May 2008. Pages 385-401. Doi: 10.1080/10408390701407316. [82] http://www.ncbi.nlm.nih.gov/pubmed/17626617? Sagatun, A.; Sagaard, A.J.; Bjertness, E.; Selmer, R.; Heyerdahl, S.: The association between weekly hours of physical activity and mental health: a three-year follow-up study of 15-16-year-old students in the city of Oslo, Norway. BMC Public Health. 2007 Jul 12;7(147):155. [83] http://nyc.indymedia.org/en/2006/01/63228.html. FDA MEMORANDUM OF MEETING Date: December 7, 1990 Place: CFSAN, FB-8 Subject: Benzene residues in soft drinks Participants: Representing the National Soft Drink Association. [84] http://www.opinioneditorials.com/freedomwriters/rgetman_20060109.html. Ross E. Getman: Internal Soda Co Docs On Benzene Formation Uploaded Opinion Tutorials.Jan 15, 2006. [85] Hans Steinhart, Martin Vollmar, and Cornelia Sailer: Pro- and antioxidative eect of ascorbic acid on L-tryptophan in the system iron(3+)/ascorbic acid/oxygen; J. Agric. Food Chem.; 1993; 41(12) pp 2275 - 2277; DOI 10.1021/jf00036a010. [86] http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=8286958&dopt=Abstract. McNeal TP, Nyman PJ, Diachenko GW, Hollied HC: Survey of benzene in foods by using headspace concentration techniques and capillary gas chromatography. J AOAC Int. 1993 Nov-Dec;76(6):1213-9.
BIBLIOGRAPHY
803
[87] http://www.aoac.org/pubs/JOURNAL/1995/marapr95.htm. Timothy P. McNeal, Henry C. Hollield, and Gregory W. Diachenko: Survey of Trihalomethanes and Other Volatile Chemical Contaminants in Processed Foods by Purge-and-Trap Capillary Gas Chromatography with Mass Selective Detection. March/April 1995 Vol. 78, No. 2 JAINEE 78(2)289-584 (1995). [88] http://pubs.acs.org/cgi-bin/abstract.cgi/jafcau/2008/56/i12/abs/ jf072580q.html. Van Poucke, Christof; Detavernier, Christl; Van Bocxlaer, Jan; Vermeylen, Rudi; Van Peteghem, Carlos: Monitoring the benzene contents in soft drinks using headspace gas chromatography-mass spectrometry: A survey of the situation on the Belgian market. Journal of Agricultural and Food Chemistry. 4. June 2008. 56 (12), 4504 - 4510, 2008. DOI: 10.1021/jf072580q. [89] http://www.mindfully.org/Food/2003/VOCs-In-Foods1dec03.htm. Mary Ellen Fleming-Jones and Robert E. Smith: Volatile Organic Compounds in Foods: A Five Year Study; Journal of Agriculture and Food Chemistry 2003, 51, 8120-8127 1dec03. [90] IARC. Benzene. IARC Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans: Some Industrial Chemical Dyestus; IARC: Lyon, France, 1982; pp 93-148. [91] Snyder, R.; Kalf, G. F. Crit. ReV. Toxicol. 1994, 24, 177-209. [92] Andersen, H. R.; Nielsen, J. B.; Grandjean, P. Toxicology 2000, 144, 121-127. [93] Klaasen, C. D., Ed. Casarett and Doulls Toxicology. The Basic Science of Poisons: McGraw-Hill: New York, 1996; pp 740- 746. [94] http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&cmd=Retrieve&dopt= AbstractPlus&list_uids=10641714. Piper, Peter W.: Yeast superoxide dismutase mutants reveal a pro-oxidant action of weak organic acid food preservatives. Free Radic Biol Med.1999. Dec;27(11-12):1219-27. doi:10.1016/S0891-5849(99)00147-1. [95] http://www.britishsoftdrinks.com/htm/sv/PDFs/IBCA%20final%20220606. pdf#search=%22ICBA%20Benzene%20Guidance%22. International Council of Beverages Assotiation: ICBA Guidance Document to Mitigate the Potential for Benzene Formation in Beverages; Fist update 22 June 2006. [96] http://www.bfr.bund.de/cm/245/indications_of_the_possible_formation_ of_benzene_from_benzoic_acid_in_foods.pdf#search=%22benzene%20BfR% 20Expert%20Opinion%20No.%20013%2F2006%2C%201%20December%202005%22. German Federal Institute for Risk Assessment: Indications of the possible formation of benzene from benzoic acid in foods; BfR Expert Opinion No. 013/2006, 1 December 2005.
804
[97] Wikipedia: Brilliant blue fcf. http://en.wikipedia.org/wiki/FD%26C_Blue_No. _1#cite_note-3. [98] Commission regulation (eu) no 1129/2011 of 11 november 2011 amending annex ii to regulation (ec) no 1333/2008 of the european parliament and of the council by establishing a union list of food additives. http://eur-lex.europa.eu/LexUriServ/ LexUriServ.do?uri=OJ:L:2011:295:FULL:EN:PDF. [99] Blue discolouration and death from fd&c blue no. 1. who drug information vol. 17, no. 4, 2003. http://apps.who.int/medicinedocs/en/d/Js4956e/2.8.html. [100] http://www.inchem.org/documents/jecfa/jecmono/v19je10.htm. IPCS INCHEM, Chemical Safety Information from Intergovernmental Organizations: Quinoleine yellow. [101] http://a257.g.akamaitech.net/7/257/2422/14mar20010800/edocket.access. gpo.gov/cfr_2003/9CFR317.17.htm. Code of Federal Regulations; Title 9, Volume 2; Revised as of January 1, 2003; From the U.S. Government Printing Oce via GPO Access; CITE: 9CFR317.17 Page 173-174 TITLE 9ANIMALS AND ANIMAL PRODUCTS; CHAPTER IIIFOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE;PART 317LABELING, MARKING DEVICES, AND CONTAINERS. [102] http://en.wikipedia.org/wiki/Curing_%28food_preservation%29. Wikipedia, the free encyclopedia: Curing (food preservation). [103] http://en.wikipedia.org/wiki/Curing_salt. Wikipedia, the free encyclopedia: Curing salt. [104] http://www.chr-hansen.com/servlet/ContentServer?pagename= ThemeTestSite%2FContent%2FContent&c=Content&cid=1094110036796&p= 1113765066515. SafePro-trade mark- microbial protection of meat. [105] http://www.ncbi.nlm.nih.gov/pubmed/20479151. Micha R, Wallace SK, Mozaffarian D: Red and processed meat consumption and risk of incident coronary heart disease, stroke, and diabetes mellitus: a systematic review and meta-analysis. Circulation. 2010 Jun 1;121(21):2271-83. [106] Zarringhalami, S.; Sahari, M.A.; Hamidi-Esfehani, Z.: Partial replacement of nitrite by annatto as a colour additive in sausage. Meat Science. Published online ahead of print 8 August 2008. [107] http://findarticles.com/p/articles/mi_qa4085/is_20070415/ai_n19059628. Jiang, Rui; Paik, David C.; Hankinson, John L.; Barr, R. Graham: Cured Meat Consumption, Lung Function, and Chronic Obstructive Pulmonary Disease among United States Adults. American Journal of Respiratory and Critical Care Medicine. 15 April 2007, Volume 175, Pages 798-804.
BIBLIOGRAPHY
805
[108] http://www.pnas.org/content/101/37/13683.abstract. Webb, Andrew; Bond, Richard; Mc Lean, Peter; Uppal, Rakash, Benjamin Nigel; Ahluwalia, Amrita: Reduction of nitrite to nitric oxide during ischemia protects against myocardial ischemia-reperfusion damage. Proceedings of the Naional Academy of Sciences of the Uniteed States of America. PNAS | September 14, 2004 | vol. 101 | no. 37 | 13683-13688. [109] http://www.pnas.org/contents-by-date.0.shtml. Bryan, Nathan.S.; Calvert, J.W.;. Elrod, J.W.; Gundewar, S.; Ji, S.Y.; Lefer, David.J.: Eects of dietary nitrite and nitrate on myocardial ischemia/reperfusion injury. Proceedings of the National Academy of Sciences Published on-line ahead of print, 12 November 2007. [110] http://www.ncbi.nlm.nih.gov/pubmed/16758769. Ribeiro, L.R.; Mantovani, M.S.; Ribeiro, D.A.; Salvadori D.M.: Brazilian natural dietary components (annatto, propolis and mushrooms) protecting against mutation and cancer. Hum Exp Toxicol. 2006 May;25(5):267-72. [111] http://publications.uu.se/abstract.xsql?dbid=8624. Petersson, Joel: Nitrate, Nitrite and Nitric Oxide in Gastric Mucosal Defense. Doctoral thesis. Upsala University. 2008. [112] http://en.wikipedia.org/wiki/Betaine. [113] Selhub J. Homocysteine metabolism. Annu Rev Nutr 1999;19:217-46. [114] Barak AJ, Tuma DJ: Betaine, metabolic by-product or vital methylating agent?; Life Science 1983 Fe 14;32(7):711-4. [115] Felix, N. & Sudharsan, M. (2004): Eect of glycine betaine, a feed attractant aecting growth and feed conversion of juvenile freshwater prawn Macrobrachium rosenbergii. Aquaculture Nutrition 10 (3), 193-197. doi: 10.1111/ j.1365-2095.2004.00292.x. [116] http://www.ergromix.com/feed_enzymes_and_betaine_e_articles_68_AVG. htm. Drs. Lucy Tucker, Craig Wyatt and Michael Bedford, Finnfeeds, Marlborough, Wiltshire, UK: Feed enzymes and betaine in antibiotic free poultry diets. AFMA (Animal Feed Manufacturers Association). [117] Virtanen, E.: The biochemical relationship of methyl donors, betaine, methionine and choline. AFMA Matrix, March 1999 Vol. 8, No1. [118] http://hyper.ahajournals.org/cgi/content/abstract/HYPERTENSIONAHA. 107.103523v1. Webb, Andrew J.; Patel, Nakul; Loukogeorgakis, Stavros; Okorie, Mike; Aboud, Zainab; Misra, Shivani; Rashid, Rahim; Miall, Philip; Deaneld, John; Benjamin, Nigel; MacAllister, Raymond; Hobbs, Adrian J.; Ahluwalia, Amrita: Acute blood pressure lowering, vasoprotective and anti-platelet properties of dietary nitrate via bioconversion to nitrite. Hypertension - Journal of the
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CHAPTER 9. INGREDIENTS American Heart Association. Published online ahead of print 4 February 2008, doi: 10.1161/HYPERTENSIONAHA.107.103523.
[119] http://ajpheart.physiology.org/cgi/content/abstract/291/5/H2026. Gladwin, M.T.; Raat, N.J.; Shiva, S.; Dezfulian, C.; Hogg, N.; Kim-Shapiro D.B.; Pate, R.P.: , Nitrite as a vascular endocrine nitric oxide reservoir that contributes to hypoxic signaling, cytoprotection, and vasodilation. Am J Physiol Heart Circ Physiol. 2006. Nov;291(5):H2026-35. [120] http://circ.ahajournals.org/cgi/content/abstract/117/5/670. Gladwin, M.T.: Evidence mounts that nitrite contributes to hypoxic vasodilation in the human circulation. Circulation. 2008 Feb 5;117(5):594-7. Doi:10.1161/CIRCULATIONAHA.107.753897 Circulation. 2008;117:670-677. Doi: 10.1161/CIRCULATIONAHA.107.719591. [121] http://circ.ahajournals.org/cgi/content/abstract/117/5/670. Maher, Abdul R.; Milsom, Alexandra B.; Gunaruwan, Prasad; Abozguia, Khalid; Ahmed, Ibrar; Weaver, Rebekah A.; Thomas, Philip; Ashraan, Houman; Born, Gustav V.R.; James, Philip E.; Frenneaux, Michael P.: Hypoxic Modulation of Exogenous Nitrite-Induced Vasodilation in Humans. [122] http://www.mayoclinic.com/health/stomach-cancer/DS00301/DSECTION=3. Mayo Clinic.com: Stomach cancer. [123] Mihranyan, Albert; Edsman, Katarina and Stromme, Maria: Rheological properties of cellulose hydrogels prepared from Cladophora cellulose powder; Food Hydrocolloids Volume 21, Pages 267-272. [124] Zhang Y, Neogi T, Chen C, Chaisson C, Hunter D, and Choi HK. Cherry consumption and the risk of recurrent gout attacks. Arthritis Rheum, 9 2012. http: //www.ncbi.nlm.nih.gov/pubmed/23023818. [125] Damar I and Eksi A. Antioxidant capacity and anthocyanin prole of sour cherry (prunus cerasus l.) juice. Food Chem, 135(4):29104, 12 2012. http://www.ncbi. nlm.nih.gov/pubmed/22980889. [126] http://www.bmj.com/cgi/content/short/336/7639/285. Underwood, Martin: Sugary drinks, fruit, and increased risk of gout. Dietary fructose could be a contributing factor. BMJ 2008;336:285-286 (9 February), doi:10.1136/bmj.39479.667731.80. [127] http://www.bmj.com/cgi/content/abstract/336/7639/309. Choi, Hyon K; Curhan, Gary: Soft drinks, fructose consumption, and the risk of gout in men: prospective cohort study BMJ 2008 336: 309-312.
BIBLIOGRAPHY
807
[128] http://www.ncbi.nlm.nih.gov/pubmed/20142243. Mueller NT, Odegaard A, Anderson K, Yuan JM, Gross M, Koh WP, Pereira MA: Soft Drink and Juice Consumption and Risk of Pancreatic Cancer: The Singapore Chinese Health Study. Cancer Epidemiology, Biomarkers and Prevention. Doi: 10.1158/1055-9965.EPI-09-0862. [129] http://www.ncbi.nlm.nih.gov/pubmed/19324946. Odegaard AO, Koh WP, Vazquez G, Arakawa K, Lee HP, Yu MC, Pereira MA.: BMI and diabetes risk in Singaporean Chinese. Diabetes Care. 2009 Jun;32(6):1104-6. [130] Pase MP, Scholey AB, Pipingas A, Kras M, Nolidin K, Gibbs A, Wesnes K, and Stough C. Cocoa polyphenols enhance positive mood states but not cognitive performance: A randomized, placebo-controlled trial. J Psychopharmacol, 1 2013. http://www.ncbi.nlm.nih.gov/pubmed/23364814. [131] Robson AA. Chocolate bars based on human nutritional requirements. author manuscript, published in "chocolate in health and nutrition (2013) 143-148". http: //hal.univ-brest.fr/docs/00/75/95/12/PDF/2013_Chocolate_bars.pdf. [132] Paleolithic diet. wikipedia. http://en.wikipedia.org/wiki/Paleolithic_diet. [133] Bel-Serrat S, Mouratidou T, Brnhorst C, Peplies J, De Henauw S, Marild S, Molnr D, Siani A, Tornaritis M, Veidebaum T, Krogh V, and Moreno LA. Food consumption and cardiovascular risk factors in european children: the idecs study. Pediatr Obes, 12 2012. http://www.ncbi.nlm.nih.gov/pubmed/23225768. [134] Colucci AC, Cesar CL, Marchioni DM, and Fisberg RM. Factors associated with added sugars intake among adolescents living in sao paulo, brazil. J Am Coll Nutr, 31(4):25964, 8 2012. http://www.ncbi.nlm.nih.gov/pubmed/23378453.
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Chapter 10 Food Supplements

A food supplement is, typically, a nutrient added to a foodstu which would otherwise not contain that nutrient. In general, the term is restricted to those additives which are deemed to be positive for health, growth or well-being. [1] Food supplements are regulated in the EU by the Directive 2002/46/EC of the European Parliament of 10 June 2002 on the approximation of the laws of the Member States relating to food supplements.[2]
10.1
Medicinal products
Medicinal Products for human use are dened by Directive 2001/83/EC of the European Parliament and of the Council of 6 November 2001 on the Community code relating to medicinal products for human use and are a distinct category of products separated from food supplements. The food supplements directive states that there is an increasing number of products marketed in the Community as foods containing concentrated sources of nutrients and presented for supplementing the intake of those nutrients from the normal diet. An adequate and varied diet could, under normal circumstances, provide all necessary nutrients for normal development and maintenance of a healthy life in quantities which meet those established and recommended by generally acceptable scientic data. However, surveys show that this ideal situation is not being achieved for all nutrients and by all groups of the population across the Community. Consumers, because of their particular lifestyles or for other reasons, may choose to supplement their intake of some nutrients through food supplements. 809
810
CHAPTER 10. FOOD SUPPLEMENTS
10.1.1
Antioxidants in dietary supplements
Many dietary supplements are labelled as antioxidants. The price vary from product to product. Sometimes it possible to bye a cheap products which have the same activities as expensive products. Co-enzyme Q10 can be added using sheep products. Table 10.1: Dietary supplements Ingredient per capsule Oxano Health+ Fitness Vitamin A g -carotin mg Vitamin C mg Vitamin E mg Vitamin B1 mg Vitamin B2 mg Vitamin B6 mg Vitamin B12 g Vitamin D3 g Vitamin K1 g Pantothenic acid mg Folic acid g Niacinamide mg Biotin g Calcium mg Chloride mg Chromium g l-Cisteine mg Iron mg Potassium mg Copper mg Magnesium mg Manganese mg 275,2 225 36 Anti-Age Merz tetesept Multi A-Z in one vitamine Spencer Pharma Food Aldenhoven 800 900 60 10 1,40 1,60 1,60 1,00 5,00 80 6,00 200 18 150 200 36,4 60 9 6 60 1 120 1,2 850 75 12 1,40 1,70 1,80 3,00 5,00 6,00 150 18 100 200 5 1 150 1,0 Raucher Vitamine Abtei*** Recommended for
343,7 29,5 152 3 -
112,5 18 2,6 60 -
Cell growth,skin Vitamin A builder Bones, connective tissue Cell, metabolism Muscle,metabolism Skin, metabolism proteins physiol Cell, metabolism Bones Antihemorrhage Skin, metabolism Cell Cell energy Skin, hair, nail Bone, tooth Metabolism of carbohydrates Oxygen transport Cell physiology Muscle Cell physiology
10.1. MEDICINAL PRODUCTS Molybdenum g Phosphorus mg Selenium g Silicon mg Zinc mg Iodine g Fluoride g Co-enzyme Q10 mg Anthocyane*mg Bioavonoids** mg Borage oil mg Linseed oil mg Price per capsule EUR Ingredient per capsule 5 10 50 0.50 Oxano Health+ Fitness * from red grapes ** from citrus ***Vitamines for smoker 2,25 0,25 407 45 0.18 Anti-Age Merz 80 103 25 2 9,5 5 0.14 80 30 5 100 250 0.04 12 0.30 Raucher Vitamine Abtei***
811 Enzyme activity Cell activity Cell physiology Thyroid function Dental enamel Cell physiology Cell physiology Cell physiology Omega-6 acid Omega-3-acid
tetesept Multi A-Z in one vitamine Spencer Pharma Food Aldenhoven
Recommendet for
10.1.2
Food industry is challenged to produce food on basis of an "optimal nutrition" concept [3]
Food choice is increasingly being inuenced by health issues, creating opportunities for new product development, say El and Simsek in a 2012 review. Food scientists call for "optimal nutrition" as the optimization of a daily nutrition model with nutrients and bioactive compounds to prevent diseases an promote healthy life.
10.1.3
Legal bases of health claims
The Food-Based Dietary Guidelines of the World Health Organization (WHO) 2003 should be the bases of all activities, such as the European Union (EU) legislation on health claims and compulsory nutrition facts label in many countries increase the consumer awareness of calories, content of fat, trans-fatty acids, carbohydrates and salt. Australia and New Zealand, Canada, EU, India, Mexico, United States and others already implemented the nutritional label on foods. The WHO dietary guidelines recommend the limitation of total fat intake <30%, saturated fats <10%, and simple carbohydrates <10% of total caloric
812 intake. [4]
Similar data for healthy foods are supported by the 2010 Dietary Guidelines for Americans to promote health, reduce the risk of chronic diseases, and reduce the prevalence of overweight and obesity through improved nutrition and physical activity. [5]
10.1.4
Reducing energy density of foods
Reducing energy density of foods may be achieved by increasing water or air content, using intense sweeteners bulk agents, resistant starches, carbohydrate- and/or protein-based fat replacers. Other researches focus on energy reduction by the inhibition of enzymes in carbohydrate and/or fat digestion, but is limited to specic group of obese consumers.
10.1.5
Functional foods
Bioactive peptides are known to exert regulatory functions in humans. They are being isolated from milk, eggs, meat, marine organisms, soy, wheat, broccoli, and rice. Some bioactive compounds are used to enrich foods or as supplements. Most prominents are: Coenzyme Q10, L-carnitine, alpha-lipoic acid, lignan, isothiocyanates, curcumin, isoavone, resveratrol, lycopene, beta-glucan, inulin, omega-3 fatty acids, sterol and stanol. However, much still remains to be done. The authors call on the food industry to reduce the number of energy-dense products, to reduce salt, added sugar, trans-fatty acid, and saturated fat content in processed foods. Food science and technology need to introduce these new food-based dietary guidelines focusing on food physics, food storage and preservation, nutrient restoration and fortication of foods, and the development of designer foods and functional foods.
10.1.6
WHO diet guidelines 2003 [4]
Ranges of population nutrient intake goals Table 10.2: Diet Guidelines WHO Dietary factor Goal % of total energy Total fat 15-30% Saturated fatty acids <10% Polyunsaturated fatty acids (PUFAs) 6-10% n-6 Polyunsaturated fatty acids (PUFAs) 5-8% n-3 Polyunsaturated fatty acids (PUFAs) 1-2% Trans fatty acids <1%
10.1. MEDICINAL PRODUCTS Monounsaturated fatty acids (MUFAs) By dierence (a) Total carbohydrate 55-75% (b) Free sugars <10% (c) Protein 10-15% (d) Cholesterol <300 mg per day Sodium chloride (sodium) <5 g per day (<2 g per day) (e) Fruits and vegetables 5400 g per day Total dietary bre From foods (f) Non-starch polysaccharides (NSP) From foods (f)
813
(a)This is calculated as: total fat - (saturated fatty acids + polyunsaturated fatty acids + trans fatty acids). (b) The percentage of total energy available after taking into account that consumed as protein and fat, hence the wide range. (c) The term "free sugars" refers to all monosaccharides and disaccharides added to foods by the manufacturer, cook or consumer, plus sugars naturally present in honey, syrups and fruit juices. (d) The suggested range should be seen in the light of the Joint WHO/FAO/UNUExpert Consultation on Protein and Amino Acid Requirements in Human Nutrition, held in Geneva from 9 to 16 April 2002. (e) Salt should be iodized appropriately (6). The need to adjust salt iodization, depending on observed sodium intake and surveillance of iodine status of the population, should be recognized. (f) See "Non-starch polysaccharides" Non-starch polysaccharides (NSP) Wholegrain cereals, fruits and vegetables are the preferred sources of non-starch polysaccharides (NSP). The best denition of dietary bre remains to be established, given the potential health benets of resistant starch. The recommended intake of fruits and vegetables (see below) and consumption of wholegrain foods is likely to provide > 20 g per day of NSP (>25 g per day of total dietary bre).
10.1.7
Antioxidants reduce women fertility
[6] A study of Shkolnik and colleagues 2011 stresses that ovulation is stimulated the pituitary luteinizing hormone (LH). This process is related to inammation involving oxidant radicals (reactive oxygen species ROS). In their study the authors found that antioxidants reduced the rate of ovulation in rats preventing the modication of the local tissue, which prepares the ovulation. Progesterone production was also found to be reduced by antioxidants, together with up-regulation of genes by the LH hormone which were also signicantly reduced. Oxidants on their turn, were found to be implicated in phosphorylation and activation of the epidermal growth factor receptor (EGFR) and its downstream eector, p42/44 MAPK,
814
essential elements of ovulation. More studies related to antioxidants supplements and its possible implication in reduction of fertility are needed. The authors concluded that the production of ovary oxidant radicals is essential to fertility and antioxidants may become a non-hormonal contraceptive.
10.1.8
Oxano and Anti-Age
Oxano and Anti-Age are produced by Merz. Both are developed to avoid or even reverse damage caused by free radicals thus acting as anti-ageing agent. Dr. Mller-Wohlfahrt has created the "Formula" for both products. In his book "How to protect your health"[7] he explains his strategy to ght free radicals in an attempt to reduce the risk of cancer and early ageing. He suggests : 1.- Drink daily milk to supply calcium in prevention of late osteosporosis. 2.- Eat one banana for the meal between. It is rich in vitamins, minerals and new energy 3.- Eat dried fruits. They are good antioxidants and combat free radicals. 4.- For supper: Eat sliced fruits such as tomatoes and vegetables. If these conditions cannot be maintained dietary supplements should be taken such as Oxano. Oxano is supposed to act against jetset symptoms, fast food reactions, heavy smoking and parties. Dr. Mller-Wohlfahrt believes that people which think about dietary supplements takes care about healthy nutrition, does some sport, reduces smoking and moderates his profession. The president of the Deutsche Gesellschaft fr Sportmedizin und Prvention (German Society for Sportmedicine and Prevention) Prof Hans Hermann Dickhuth however does not agree with Dr. Mller-Wohlfahrt. According to Prof Dickhuth the antioxidants are not been proved yet by scientic researches to have any positive activity. [8] Five times a day there should be fruits and vegetables on the menu. Despite critics related to the activity of antioxidants the number of evidences speaking for good biochemical activities of antioxidants are growing from day to day. Linus Pauling with his book dated from 1970 was a pioneer of these ideas. [9]
10.1.9
Telesept and Multivitamine
Both products are example of inexpensive products which can replace the much costlier Oxano or even Anti-Age. As seen on the table the Composition of the sheep products has a wider range of ingredients. Co-enzyme Q10 and bioavonoids can be supplied by additional products.
10.1. MEDICINAL PRODUCTS
815
10.1.10
Nanosilimagna, nanoparticle claims controversy
[10] The report Panorama of the German TV station NDR declared in their program of 09.03.2006 that the product claim for Nanosilimagna having a higher absoption of calcium due to its nano structure was deceiving. The manufacturer of this product is Neosino Nanotechnologies which backs its claims on armations of a wellknown sport physician Dr. Hans-Wilhelm Mller-Wohlfahrt, doctor of the kickers of FC Bayern Munich and the German football team A strong controversy about the product arose and the German magazine Spiegel looked behind the story. Professor Markus Antonietti, Nano-researcher of the Max-Planck-Institute in Potsdam, Germany,said that consumer could get the same eect taking a low priced (less than 1 Euro) supplement instead of using the 50 Euro nano product.
10.1.11 10.1.12
NANOSILIMAGNA PROJECT Report of a Project performed for Spiegel Online [11] The Heaney-Study
Neosino Nanotechnologies Deutschland Vertriebs-GmbH, Griesheim, Germany, markets in Germany a nutritional supplement containing calcium, silicon, and magnesium (Nanosilimagna), in which the elements concerned are said to be in the form of nano particles, and for which the manufacturer claiming a absorbability superior to that of other physical forms of the same elemental nutrients. The news website Spiegel Online challenged the claims by the manufacturer of Nanosilimagna. Subsequently Spiegel Online asked the Osteoporosis Research Center (ORC) of Creighton University, Omaha, Nebraska, USA, to address the question of absorption of calcium and magnesium from Nanosilimagna with a specic study in 12 volunteers. As a comparator supplement, a widely used and inexpensive eervescent tablet from a German supermarket was used. The rises in urine calcium and magnesium and the excretion of creatinine and sodium were measured during the trial. The former was to permit adjustment for possibly large variations in salt intake or salt loss on the day(s) preceding any given test. The data generated in this study provide no evidence either for greater absorption or for faster absorption of the calcium in Nanosilimagna than from the eervescent calcium sources. By contrast, Nanosilimagna was clearly inferior to the eervescent tablet in magnesium absorption. At no time point did the magnesium excretion dier signicantly from zero, a nding compatible with a conclusion of essentially zero bioavailability for the magnesium component of Nanosilimagna. Because of the imprecision inherent in the urine excretion method, as well as the small
816
sample size, it is not possible to exclude some small dierence in absorbability of calcium from the two sources (in one direction or the other). Nevertheless there is no hint of signicant superiority of Nanosilimagna in the data generated by this study.
10.2
Energy drinks
The FDA is investigating reports of ve deaths after drinking high-caeine energy drinks made by the Monster Energy Company. The parents of a 14-year-old girl say her daughter collapsed after drinking her second 24-ounce Monster Energy drink in two days. She died six days later. Monster Energy Drink, comes in 24-ounce cans and contain 240 milligrams of caeine, or seven times the amount of the caeine in a 12-ounce cola. [12] In addition to caeine, energy drinks contain other stimulants, including taurine and guarana, a caeine-containing plant which are sold as nutritional supplements, they are not regulated as foods and may exceed the FDA-mandated limit of 71 milligrams of caeine for a 12-ounce soda. A series of incidences with energy drinks involve about 70% of teens aged 12 to 17. According to Seifert et al 2011 the eects of energy drinks varied from irregular heart rhythms and, in children who may have hidden heart risks, sudden death. Energy drinks are consumed by 30% to 50% of adolescents and young adults with serious adverse eects, especially in children, adolescents, and young adults with seizures, diabetes, cardiac abnormalities, or mood and behavioural disorders or those who take certain medications. There were 5448 US caeine overdoses reported in 2007 and 46% occurred in those younger than 19 years. The authors call on paediatricians to be aware of the possible eects of energy drinks in vulnerable populations, increase research on eects in at-risk populations and improve toxicity surveillance. Regulations of energy drink sales and consumption should be based on these researches claim the authors. [13] The American Beverage Association developed voluntary guidelines for labelling and marketing energy drinks. The guidelines are easy follow and are meant to avoid stier authority regulations. [14]
10.2.1
Toxicity of energy drink ingredients [15]
Wolk et al 2012 stress that the main active ingredient in energy drinks is caeine. Excessive consumption may result in tachycardia, vomiting, cardiac arrhythmias, seizures, and death. The eects of chronic high-dose caeine intake in children and adolescents is associated with high blood pressure, disruption of adolescent sleep patterns, physiologic dependence, and increased risk of subsequent addiction. The risk is further potentiated when caeine and alcohol are consumed together. Taurine, niacin, and pyridoxine are ingredients which present toxicity in energy drinks.
10.2. ENERGY DRINKS
817
Wolk and colleagues caution that chronic high-dose caeine intake in children and adolescents may raise blood pressure, disrupt adolescent sleep patterns, exacerbate psychiatric disease, cause physiologic dependence, and increase the risk of subsequent addiction. Ingesting caeine together with alcohol increases risk-taking behaviours, harms adolescent users, impairs driving, and increased use of other illicit substances. The authors call for a regulation of paediatric energy drink use. Caeine is readily available to minors being used as psychoactive substance. Energy drinks, herbal medications, and various other medications that promote alertness, contain caeine and can produce severe eects when taken together, writes Rath 2012. [16] Mixing energy drinks with alcohol, eects in adult persons According to Verster et al 2012 energy drinks do not antagonize the behavioural eects of alcohol, These drinks do not alter the perceived level of alcohol intoxication of healthy people and no clinically relevant cardiovascular or other adverse eects are known. The authors concluded that energy drinks do not increases alcohol consumption, or initiates drug and alcohol dependence or abuse. [17] Petit et al 2012 report that an occasional to a moderate consumption of energy drinks seems to present little risk for healthy adults, but high consumption mixed with alcohol or drugs. Consuming energy drinks together with alcohol is an eect of the type of lifestyle and personality, write the authors. [18] Greater energy drink consumption leads to an increase of alcohol intake and is also linked to consume both beverages together resulting in heavy episodes of drinking in students report Velazquez et al 2012. [19] Marczinski et al 2012 report that alcohol taken alone slowed dual-task information processing and impaired simple and complex motor coordination. These impairments were not reduced with the coadministration of energy drinks (0.65 g/kg alcohol + 3.57 ml/kg energy drink, or a placebo beverage), but reduced the perceptions of mental fatigue and enhanced feelings of stimulation compared to alcohol alone. The authors stress that the mix of behavioural impairment with reduced fatigue and enhanced stimulation of people consuming both beverages together may lead to false perception of their ability. [20]
10.2.2
Red bull energy drink does not improve athletes performance [21]
After ingestion of 255 mL of placebo or Red Bull 1h pre-exercise there was no dierence of performance of Red Bull on either variable versus placebo. Astorino et al 2012, authors of the study, found that ingesting 255 mL of Red Bull 1 h pre-exercise, containing 1.3 mg/kg
818
of caeine and 1 g of taurine did not improve sprint performance in women athletes versus placebo. Energy drinks and muscle performance [22] Del Coso et al 2012 tested the eect of caeine dose of 1 and 3 mg/kh to improve muscle performance in half-squat and bench-press actions, whereas at least 3 mg/kg of caeine in the form of an energy drink are necessary to increase muscle power. The dose of 3 mg caeine/kg in energy drinks was conrmed by Del Coso et al 2012 related to an increase of the ability of sprints and distance covered at high intensity and increased jump height during soccer games. [23] Gwachman and Wagner 2012 found no improvement of sprint performance or anaerobic power of college football players ingesting caeine-taurine energy drink. The level of caeine might have inuenced the eect of the drink, write the authors. [24]
10.2.3
Dental health and energy drinks [25]
The consumption of sports and energy drinks by children and adolescents is increasing and turns to become a problem for dental health of young people, says a study of Jain et al 2012. The titratable acidity of energy drinks was found to be signicantly higher than that of sports drinks, and enamel weight loss after exposure to energy drinks was more than two times higher than it was after exposure to sports drinks. Dental professionals are therefore suggested to include these ndings in the education of young patients.
10.3
Cherry juice and sports drinks
[26] Tart cherries are known to be rich in antioxidant and anti-inammatory agents. Such anti-inammatory agents may be benecial for the management and prevention of inammatory diseases. Darshan S. Kelley and colleagues propose that the avonoids and anthocyanins in the cherries exert an anti-inammatory eect and may lessen the damage response to exercise. [27] In another study Declan Connolly tested the ecacy of a tart cherry cherry juice blend in preventing the symptoms of exercise-induced muscle damage. This study was published in the British Journal of Sports Medicine, demonstrating that the strength loss and pain were signicantly lower in the cherry juice trial versus placebo. Relaxed elbow angle and muscle tenderness were not dierent between trials.
10.4. DIABETES AND CAROTENOIDS
819
Connolly came to the conclusion that cherry juice decreased some of the symptoms of exercise-induced muscle damage. These results have important practical applications for athletes aected by strength loss and pain after damaging exercises.
10.3.1
Adipose tissue is a major source of pro-inammatory molecules, such as interleukin-6, tumor necrosis factor-, and leptin which can contribute to chronic inammation in obese individuals. Strawberries contain high levels of antioxidants including ellagic acid, catechins, anthocyanins, and the avanols quercetin and kaempferol, all of which have displayed antiinammatory abilities. The specic hypothesis is that strawberries contain potent anti-inammatory antioxidants that can prevent the oxidization of LDL involved in the generation of atherosclerotic plaques, reduce the production of inammatory cytokines in obese individuals, and suppress the immune response.
10.3.2
Raucher Vitamine (Vitamines for smokers)
Is an example of special products which are developed for special needs. For smokers vitamin A and provitamin A are in this case not allowed.
10.4
Diabetes and carotenoids
Although obesity and physical inactivity are known to be major risk factors for type 2 diabetes, recent evidence suggests that oxidative stress may contribute to the pathogenesis of type 2 diabetes by increasing insulin resistance or impairing insulin secretion A Finnish study [29] by Jukka Montonen and colleagues investigated dietary vitamin E, four tocopherols, four tocotrienols, vitamin C, and six carotenoids for their ability to predict type 2 diabetes. Vitamin E intake was signicantly associated with a reduced risk of type 2 diabetes. Intakes of alfa-tocopherol, gama-tocopherol, delta-tocopherol, and beta-tocotrienol were inversely related to a risk of type 2 diabetes. Among single carotenoids, beta-cryptoxanthin intake was signicantly associated with a reduced risk of type 2 diabetes. According to
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the authors of the study development of type 2 diabetes may be reduced by the intake of antioxidants in the diet. No association was evident between intake of vitamin C and type 2-diabetes risk. The carotenoid beta-cryptoxanthin, found in citrus fruits had been studied. Lycopene of tomatoes and other red fruits vegetables, used as an ingredient in both functional foods and dietary supplements was not include in the study. A study from Lu Wang and colleagues from the Brigham and Womens Hospital in Boston found little evidence for an association between dietary intake of lycopene or lycopene-containing foods and the risk of type-2 diabetes and does not protect against the risk of type-2 diabetes. [30] Serum carotenoids alfa-carotene, beta-carotene, beta-cryptoxanthin, lutein/zeaxanthin are inversely associated with type 2 diabetes and impaired glucose metabolism, beta carotene being the most active carotenoid. No signicant activity was found in relation to lycopene in the study of Terry Coyne and colleagues. [31] The development of insulin resistance in mammals with elevated expression of an antioxidant enzyme were reported in an article of McClung JP and colleagues in Proceedings of the National Academy of Sciences. They suggest that increased glutathione peroxidase 1 (GPX1) activity may interfere with insulin function by overquenching intracellular reactive oxygen species required for insulin sensitizing. This leads to the assumption too many antioxidants in the diet could actually increase the risk of diabetes. [32]
10.4.1
Dietary supplements rise advantages expectation that are rather detrimental [33]
Chiou et al 2011 reports that the growing consumption of dietary supplements does not improve public health. The authors stress that taking dietary supplements, such as vitamins, the consumer expects health advantages, creating an illusory sense of invulnerability that disinhibits unhealthy behaviours. A subject group which received placebo pills, believing it contained dietary supplements, reduced exercise, preferred hedonic lifestile and were more inclined to a buet instead of an organic meal. They walked less compared to people which knew that they received placebo pills. The authors call this phenomena a perceived invulnerability which leads to such behaviour causing dietary supplements to alternately protect or endanger health. In another study Chiou et al 2011 found that smokers use of dietary supplements (e.g. vitamin C, multi-vitamins) induces illusory invulnerability that in turn disinhibits smoking. Participants who believed that they were taking a dietary supplement smoked more cigarettes than did controls. Again dietary supplement created illusory invulnerability, reducing the self-regulation of smoking. The authors stress the importance to remind the
821
public that multi-vitamins and other dietary supplements do not provide invulnerability and do not make healthy lifestyle out-dated. [34]
10.4.2
Extract of algae may reduce risk of cancer [35]
Kwang Hyun Cha, Song Yi Koo and Dong-Un Lee 2008 studied the antiproliferative activity of carotenoids from marine Chlorella ellipsoidea and freshwater Chlorella vulgaris. The authors found that the main carotenoid from C. ellipsoidea was composed of violaxanthin with two minor xanthophylls, antheraxanthin and zeaxanthin, and Chlorella vulgaris contained lutein. The extract of Chlorella ellipsoidea presented a 2.5 stronger apoptosis on HCT116 cells (colon cancer cells) compared with extracts of Chlostridium vulgaris. The authors concluded that extracts of Chlostridium ellipsoidea might be useful in the prevention of human cancers. The extracts had a more powerful anti-cancer eect when used in combination than used alone. The authors stress that their results support the theory that beta-carotene and lycopene, may interfere with the development of cancer. Cha, Koo and Lee commented former studies of Wu and colleagues [36]which reported in 2005 that Spirulina extracts inhibited human liver cancer cells, HepG2, but Chlorella extracts produced only a minor result. Cha and colleagues say that a poor result for Chlorella was probably to be related to the water extract used by Wu, whereas the actual study was performed with organic solvents giving better results. A foregoing study by Chew and colleagues 2003, had already reported that mice fed with dietary lutein, especially at 0.002% presented inhibition of mammary tumor growth by selectively modulating apoptosis and by inhibiting angiogenesis. [37]
10.4.3
Vitamin B10 (PABA) necessary for proper feather formation in chicks [38]
Briggs and colleagues reported in 1943 that chicks required two water-soluble vitamins designated as vitamin B10 , necessary for proper feather formation, and vitamin B11 , required for growth. These vitamins were shown to be distinct from "folic acid" as measured by Streptococcus lactis R and Lacto bacillus casei. Methods for the purication of vitamins B10 and B11 from solubilized liver were described by Briggs in 1945, dierentiating them from substances with high folic acid activity. Such substances were found to have growth, feathering, and haemoglobin activity when fed alone to chicks at relatively high levels. Briggs suggests, therefore, the existence of another unknown factor necessary to maintain normal haemoglobin formation.
822
10.4.4
FDA regulation for PABA as growth promotion and feed eciency for Feed [39]
PABA, together with microbicides is recognized by FDA as growth promotion and feed eciency for feed for chickens and swine, using not less than 0.1 percent para-aminobenzoic acid or the sodium or potassium salt or para-aminobenzoic acid by weight of feed. The usual dose of PABA for humans is between 30 to 100 mg. three times a day, 50 mg being mostly indicated. Natural source of PABA: Bran, eggs, kidney, liver, molasses, wheat germ, brewers yeast, whole grains, yogurt, mushrooms, and spinach. In humans,PABA is biosynthesized by intestinal bacteria.
10.4.5
PABA promoting thyroid carcinogenesis in rats initiated with N-bis(2-hydroxypropyl) nitrosamine [40]
Hasamura and colleagues (2005) found that PABA exerts promotion/progression eects on rat thyroid carcinogenesis as a result of hypothyroidism followed by negative-feedback via the thyroid-pituitary axis.
10.4.6
Carcinogenesis of PABA in sunscreen formulation [41]
In the past, PABA has been widely used as UV lter in sunscreen formulations. However, it has been determined that it increases the formation of a particular DNA defect in human cells, thus increasing the risk of skin cancer in people who lack the mechanisms to repair these cellular defects [42]. Currently, safer and more eective derivatives of PABA, such as octyl dimethyl PABA. Gasparro and colleagues (1998) in a review of sunscreen safety and ecacy concluded that sunscreen ingredients or products do not pose a human health concern. [43]
10.4.7
Cinnamon extract and diabetes mellitus 2 [44]
Cinnamon (Cinnamomum cassiae) bark used as spice is now being studied by B. Mang and colleagues for its eect of on glycated haemoglobin A1c HbA1c , fasting plasma glucose, total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL) and triacylglycerol concentrations in patients with diabetes mellitus type 2. Previous studies had found that cinnamon have a positive eect on the glycaemic control and the lipid prole in these patients. The scientists conclude that aqueous cinnamon extract has a moderate eect in reducing fasting plasma glucose concentrations in diabetic patients with poor glycaemic control.
823
The aqueous extract is with methylhydroxychalcone polymer as active substances, is nearly free of allergic oil present in powder of cinnamon is therefore safe for allergic patients.
10.4.8
Cinnamon extract reducing oxidative stress [45]
Dr. Anne-Marie Roussand colleagues presented the results of a researcher on a group of 24 patients with impaired fasting glucose levels at the 47th annual meeting of the American College of Nutrition in 2006. In this study Malondialdehyde (MDA) was chosen as an indicator of oxidative stress. Plasma antioxidant levels were measured by ferric-reducing ability of plasma (FRAP) and plasma SH (thiols). were both signicantly increased, After 12 weeks of 500 gram cinnamon extract supplementation there was a reduction of malondialdehyde. The authors found a reduction in blood glucose levels, triglycerides, LDL cholesterol and total cholesterol. All the participants had type-2 diabetes. Cinnamon extract in this study, caused an increase of plasma antioxidant levels. According to Dr. Richard Anderson the active compounds found in cinnamon extract may be helpful in reducing the risk of these diseases by providing cells protection from harmful oxidation and may reduce risk of metabolic syndrome which causes central obesity, hypertension, and unstable glucose and insulin metabolism.
10.4.9
Whole cinnamon and aqueous Extracts Ameliorate SucroseInduced Blood Pressure Elevations in Spontaneously Hypertensive Rats [46]
Dr Anderson and colleagues report that cinnamon and a cinnamon extract could reduce blood pressure in spontaneously hypertensive rats, according to a study of 2006.
10.4.10
Diabetes Care: Cinnamon Improves Glucose and Lipids of People With Type 2 Diabetes [47]
Alam Khan and colleagues found that 1g of cinnamon per day reduced blood glucose levels, as well as triglycerides, LLD cholesterol, and total cholesterol in a small group of people with type-2 diabetes. The authors suggest that the inclusion of cinnamon in the diet of people with type 2 diabetes will reduce risk factors associated with diabetes and cardiovascular diseases.
824
10.4.11
Cinnamon Supplementation Does Not Improve Glycemic Control in Postmenopausal Type 2 Diabetes Patients [48]
Vanschoonbeek and colleagues concluded that cinnamon supplementation (1.5 g/d) does not improve whole-body insulin sensitivity or oral glucose tolerance and does not modulate blood lipid prole in postmenopausal patients with type 2 diabetes. The authors call for more research on the proposed health benets of cinnamon supplementation, until then no health claims should be made.
10.4.12
Antioxidant potential of cinnamon tea [49]
Akram Ranjbar and colleagues 2006 studied the antioxidative stress capacity of cinnamon tea (Cinnamomum zeylanicum) in humans for 2 weeks. The authors found an increased in total antioxidant power and total thiols but a decrease in lipid peroxidation levels, compared with regular tea. The authors concluded that the antioxidant potential of cinamon tea may reduce the complications related to oxidative stress.
10.4.13
Antidiabetic eect of Cinnamomum cassia extract [50]
According to Verpohl, Bauer and Neddermann 2005 Cinnamomum cassia bark or extracts from Cinnamomum cassia and zeylanicum exerted an eect on blood glucose and plasma insulin levels in rats. The cassia extract was found to be superior to the zeylanicum extract. The extract of cassia was slightly more ecacious than its bark. The authors concluded that acassia extract reduced the blood glucose levels in a glucose tolerance test (GTT), and plasma insulin production was elevated responding to an in vitro stimulatory eect of insulin release from INS-1 cells. Cassia extract is, therefore, considered to have a direct antidiabetic eect.
10.4.14
Toxicity concerns of cinnamon [51]
Coumarin is a avouring which is found in higher concentrations in the types of cinnamon grouped together under the name "cassia cinnamon". Relatively small amounts of coumarin can already damage the liver of particularly sensitive individuals. However, this is not permanent damage. Isolated coumarin may not be added to foods. Synthetic coumarin is used in cosmetics. It smells of fresh hay. Coumarin is also used for medicinal purposes to treat oedemas. Isolated coumarin may not be added to foods. A rough distinction can be made between two types of cinnamon. Ceylon cinnamon only contains low levels of coumarin which are safe from the risk assessment perspective. By
825
contrast, cassia cinnamon contains high levels of coumarin and large amounts of this cinnamon should not, therefore, be eaten. It is almost impossible for consumers to distinguish between Ceylon cinnamon and Cassia cinnamon. If coumarin-containing plant parts like cinnamon are used for avouring, then the amount of coumarin is limited to 2 milligrams per kilogram food according to the Flavourings Ordinance. Food manufacturers and importers are responsible for ensuring compliance with maximum levels. BfR has assessed the potential health risk from coumarin in foods. It believes there is a risk of liver damage in particularly sensitive individuals. BfR has, therefore, established a tolerable daily intake (TDI). This amount can be consumed over a lifetime without posing a risk to health. The TDI is 0.1 milligram coumarin per kilogram body weight and day. This also applies to particularly sensitive individuals. The European Food Safety Authority (EFSA) decided on the same value in its coumarin assessment.
10.4.15
Saower extract reduces risk of renal brosis [52]
Akram Ranjbar and colleagues 2006 studied the blood-circulation-promoting Chinese herb, saower, on brosis status in NRK-49F cells, and the mechanism of transforming growth factor-beta (TGF-beta), a potent brogenic growth factor. They found that saower extract can suppress renal cellular brosis by inhibiting the TGF-beta autocrine loop, and less tissue collagen were noted in the nephron and serum TGF-beta1 compared with the untreated controls. The authors concluded that saower extract inhibits renal brosis by down-regulating TGF-beta signals.
10.4.16
Cassia gum as gelling agent and thickener in foods [53]
The European Food Safety Authority (EFSA) says that cassia gum as gelling agent and thickener in foods is not of safety concern. Cassia gum is the our from the puried endosperm of seeds from Cassia tora and Cassia obtusifolia. Cassia gum is intended to be used ice cream and frozen milk desserts certain baked goods soup mixes, sauces and selected oil-free salad dressings, yoghurt, sausages, corned beef, and canned poultry meats at levels up to 1.5 g/kg and in all other applications at levels
826 up to 2.5 g/kg.
Galactomannans are recognised as components of dietary bre and are resistant to digestive enzymes in the gastrointestinal tract. According to EFSA it is expected that cassia gum is excreted unchanged. Fermentation of cassia gum by gut microora may occur to a small extent. However, the Panel notes that any hydrolysed material would represent oligo- or monosaccharides that can be expected to be absorbed and metabolised in normal biochemical pathways. Long-term carcinogenicity studies on cassia gum were not available. Other related galactomannan gums, including locust (carob) bean, guar gum and tara gum were not carcinogenic when fed to mice and rats. Given that cassia gum is not genotoxic, and that many other related galactomannan gums are not carcinogenic, the Panel does not consider longterm carcinogenicity studies essential for the safety assessment of cassia gum. According to the EFSA panel the presence of seeds of Cassia occidentalis for the preparation of cassia gum should be less than 0.1 % selected by colour and shape.
10.4.17
Conclusion
Given these results from the toxicological studies, the very low absorption of cassia gum and the fact that, if hydrolysed at all, cassia gum would be degraded to compounds that will enter normal metabolic pathways, the EFSA Panel concludes that the use of cassia gum complying with the newly dened specications as an additive for the proposed food uses is not of safety concern.
10.4.18
Cassia occidentalis:
Cassia occidentalis (Syn.: Senna occidentalis) has been found by Tasaka to be toxic to heart and liver leading to death in rabbits and muscle necrosis in pigs by Tim. [54] [55] Cassia occidentalis is suggested to have antibiotic activity, immunostimulant actions, liver protective and detoxication actions, antimutagenic actions, laxative actions, anti-inamatory and anti-spasmotic actions, antimalarial and antiparasitic actions. [56]
10.4.19
Beta glucan
Beta Glucan is primarily cultured extract of Bakers Yeast cell wall. It is used as an immunostimulant. Beta glucans are sugar molecules (polysaccharides). Polysaccharides or polysaccharide-protein complexes are considered as multi-cytokine inducers that are able to induce gene expression of various immunomodulatory cytokines and
10.4. DIABETES AND CAROTENOIDS cytokine receptors.
827
Some interesting studies focus on investigation of the relationship between their structure and antitumor activity, elucidation of their antitumor mechanism at the molecular level, and improvement of their various biological activities by chemical modications. [57] In Japan, extracts containing various types of Beta glucan have been used to successfully assist in treating cancer patients for the last 20 years. See Aoki, T. Chapter 4, Lentinan. In: Modulation Agents and their Mechanism. Richard L. Fenichel (Ed), Marcel Dekker, Inc., New York and Basel, pp 63-77 (1984). [58] The two primary uses of beta-glucan are to enhance the immune system and to lower blood cholesterol levels. Numerous experimental studies in test tubes and animals have shown beta-glucan to activate white blood cells. [59], [60]
10.4.20
Beta-glucans [61]
Beta-glucans) are polysaccharides that only contain glucose as structural components. They occur in the bran of cereal grains, the cell wall of bakers yeast, certain types of fungi, and many kinds of mushrooms. The cereal based beta-glucans occur most abundantly in barley and oats and to a much lesser degree in rye and wheat. They are useful in human nutrition as texturing agents and as soluble ber supplements. One of the most common sources of Beta 1,3-D glucan is derived from the cell wall of bakers yeast (Saccharomyces cerevisiae), which are often insoluble. Those extracted from grains tend to be both soluble and insoluble.
10.4.21
Rice starch and beta-glucan [62]
Rawiwan Banchathanakij and Manop Suphantharika analysed the rice starch, its interactio9n with beta-glucan preparation, and conducted textural analysis. All tested betaglucans reduced the retrogradation of the rice starch gels under cold storage. The soluble oat and barley beta-glucans were more eective in reducing retrogadation than the insoluble curdlan and yeast beta-glucans. All beta-glucans did not aect gelatination behaviour of the rice starch.// // The authors stress that the eects are not related solely to betaglucan, but also to their molecular weight and structure, and impurities. The authors point out that, aside of its rheologic properties, the beta-glucans are being studied because of their immune stimulation, anti-inammatory, antimicrobial, antitumoural, heptoprotective and cholesterol-lowering properties. [61]
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10.4.22
Concentrated oat beta-glucan, a soluble bre as new supplement for cholesterol reduction. [63]
Joanne Slavin and colleagues studied soluble bre such as a concentrated oat beta-glucan on its eects on cardiovascular disease endpoints in human subjects.
10.4.23
Fermentability
In this study the fermentability of concentrated oat beta-glucan with inulin and guar gum in a model intestinal fermentation system was compared. It has been reported that fermentation products like propionate and acetate may suppress cholesterol synthesis and contribute to cholesterol lowering. All three were found to produced similar concentrations of short chain fatty acids and acetate, however, the oat beta-glucan was found to produce the highest concentrations of butyrate at 4, 8, and 12 hours, after which inulin produced the most. The authors found in their study that six grams concentrated oat beta-glucan per day for six weeks signicantly reduced total and LDL cholesterol in subjects with elevated cholesterol. No signicant changes were observed in HDL cholesterol, glucose, insulin, homocysteine or C-reactive protein (CRP) as a result of the beta-glucan intervention. This oat beta-glucan was fermentable, producing higher amounts of butyrate than other bers. The authors concluded that a practical dose of oat beta-glucan can signicantly lower serum lipids in a high-risk population and may improve colon health. The authors also stress the fact that concentrated oat beta-glucan is suitable as a "stand-alone" supplement for cholesterol reduction, it can also be used as a food ingredient to increase bre content of food.
10.4.24
Anti-atherosclerotic activity of avenanthramides from oat [64]
According to Chen and colleagues 2007 avenanthramides, alkaloids which occurre only in oats, may have anti-atherosclerotic activity. The authors found that after consumption of 1 g avenanthramide-enriched mixture extracted from oats, plasma reduced glutathione was elevated by 21% at 15 min and by 14% at 10 h . The authors concluded that oat avenanthramides are bioavailable and increase antioxidant capacity in healthy older adults.
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10.4.25
Greenish colour of oats and oat products is related to leavening agents and ferrous iron [65]
Doehlert, Simsek and Wise 2009 studied greenish colouring of steel cut oath when cooked. They found that ferrous iron (as little as 10 ppm Fe++) of tap water may cause a green gray colour on the seed coat of oats. This is more accentuated on steel cut groats where the seed coat layer is less disrupted than in oat akes. The authors recommend to let cooking water stand for a few hours so ferrous iron (Fe++) can react with atmospheric oxygen to form ferric iron (Fe+++) forming a cloudy precipitate which settles out. Using the supernatant water the colour of the oats will not be aected. Alkaline conditions (pH 9-12) may cause brown-green colour during cooking. Leavening agent such as bicarbonate (50 mM NaHCO3) may create such conditions during backing. This is associated with the phenolic acid or avenanthramide content of the oat. The authors also found that aleurone stained darker than the starchy endosperm. Calcium (Ca++) and magnesium (Mg++) had no colouring eect.
10.4.26
Garlic and garlic supplements without eect on hipercholesterolemia [66] [67]
Garlic (Allium sativum) and wild garlic (Allium ursinum)are used since long for treatment of cardiovascular and infectious diseases as antioxidant and also because of anticancer properties. Garlic supplements are therefore promoted as cholesterol-lowering agents. Crushing garlic promotes the formation of allicin which is told to be responsible for the activity of garlic. Gardner et al. evaluated the eect of raw garlic and two commonly used garlic supplements on cholesterol concentrations in adults with moderate hypercholesterolemia. The researchers found no statistically signicant eects of garlic on blood lipids. They conclude that none of the forms of garlic used in this study, including raw garlic, when given at an approximate dose of a 4-g clove per day, 6 d/wk for 6 months, had statistically or clinically signicant eects on LDL (low-density lipoprotein cholesterol), HDL (high-density lipoprotein cholesterol), triglyceride levels, or total cholesterol-high-density lipoprotein cholesterol ratio in adults with moderate hypercholesterolemia. According to this study physicians can advice patients with moderately elevated LDL cholesterol concentrations that garlic supplements or dietary garlic in reasonable doses are unlikely to produce lipid benets. The authors, however, stress the fact that this trial should not be generalized to other populations or health eects. Garlic might lower LDL in specic subpopulations, such as
830
those with higher LDL concentrations, or may have other benecial health eects.
10.4.27
Weight reduction ingrediets
Ephedra sinica (Ma huang) contains ephedrin. The FDA banned the use of Ephedra and dietary supplements containing ephedrin (an alcaloid) as an unreasonable risk of illness or injury in April 2004. Some species in the Ephedra genus have no alkaloid content and are therefore essentially inert; however, the most commonly used species, Ephedra sinica, has a total alkaloid content of 1-3% by dry weight. Ephedrine constitutes 40-90% of the alkaloid content, with the remainder consisting of pseudoephedrine and the demethylated forms of each compound. In February 2007 FDA rearmed the ban of Ephedra products saying that no dosage of dietary supplements containing ephedrine alkaloids is safe and the sale of these products in the United States is illegal and subject to FDA enforcement action. [68] Ingredients for weight loss with unproved eectiveness are guarana, yerba mate, ginseg, guar gum, psylium,lichorice, algae, apple cider vinegar and others. The only way to get rid of some extra pounds is to reduce intake of calories and to increase energy expediture such as sport.
10.4.28
Illegal ephedra plant based drug used as "fat burner"linked with death in Denmark [69]
The Danish Medicines Agency (DMA) reports a recent death caused by the Therma Red, which is being used to loose weight and to boost performance of sportspeople. The product contains ephedrine and caeine in extremely high concentrations. Serious reactions are expected, such as increased blood pressure and blood clotting. The DMA issued a warning of products containing ephedra and ephedrin. Ephedrine is a stimulant and thermogenic, also known as ma huang. It is not allowed as a food or supplement ingredient in the European Union, US and other states. It caused several death. The plant Ephedra sinica contains the alcaloids ephedrin and pseudoephedrin as active constituents. Haller and Benowitz 2000 report adverse events related to the use of supplements containing ephedra alkaloids such as hypertension, palpitations, tachycardia, stroke, and seizures. These eects resulted in death, and permanent disability. [70] Instead of using dangerous supplements exercise and low fat and low caloric diet are recommended. Instead of beer drink green tea with no sugar, or just choose sparkling mineral water as a drink at the bar.
10.5. PROS AND CONS RELATED TO SUPPLEMENTS
831
10.5
10.5.1
Pros and cons related to supplements

The vitamin E study [71]
A 10 per cent increased risk of mortality for people taking 400 International Units per day of vitamin E were reported by Miller and colleagues in 2005. A meta-analysis of 19 randomized, controlled trials involving more than 135 000 participants found that high-dosage vitamin E supplementation (400 IU/d for at least 1 year) increased all-cause mortality. The eects of lower-dosage supplementation were unclear. The authors concluded that high vitamin E supplementation should be avoided. This study has been highly criticised and discredited as awed.
10.5.2
The Bjelakovie meta-analysis 2007 [72]
Goran Bjelakovic and colleagues report results of a systematic literature review to assess the eects of beta carotene, vitamins A and E, ascorbic acid (vitamin C), and selenium on all-cause mortality among participants in primary and secondary disease prevention trials. Bjelakovic and colleages excluded studies which did not match the criteria of his metaanalysis. Only 68 randomised trials were included in the meta-analysis, comprising betacarotene doses ranging from 1.2 to 50 milligrams, vitamin A from 1333 to 200 000 International Units (RDI 5000 IU, Upper Safe Limit 10,000 IU), vitamin C from 60 to 2000 mg (RDI 60 mg, UL 2000 mg), vitamin E from 10 to 5000 IU (RDI 30 IU, UL 900 IU), and selenium from 20 to 200 micrograms (RDI 65 micrograms, UL 450 micrograms). The authors found that beta carotene, vitamin A, and vitamin E, taken singly or combined with other antioxidant supplements, were associated with increased all-cause mortality. The authors conclude that treatment with beta carotene, vitamin A, and vitamin E may increase mortality. The potential roles of vitamin C and selenium on mortality need further study. The authors say that although oxidative stress has a hypothesized role in the pathogenesis of many chronic diseases, it may be the consequence of pathological conditions. By eliminating free radicals from our organism, we interfere with some essential defensive mechanisms.
10.5.3
Critics on the Bjelakovie meta-analysis
Meir Stampfer, a professor of nutrition and epidemiology at the Harvard School of Public Health points out that the studies reviewed were too dierent to be able to pool them together.
832
Andrew Shao, vice president of the US-based Council for Responsible Nutrition said that the combined studies were far too diverse and dierent in terms of dosage, duration, study population and nutrients tested that the results of the analysis were compromised. According to Dr. Shao most of the trials included in the meta-analysis tested for secondary prevention in diseased populations, instead of primary prevention studies in healthy populations. Combining secondary prevention and primary prevention trials and then making conclusions for the entire population is an unsound scientic approach.
10.5.4
Vitamin E supplements may increase risk of lung cancer [73]
Christopher Slatore and colleagues 2007 assessed the association of the incidence of lung cancer and supplemental multivitamins such as vitamin C, vitamin E, and folate. The authors found that daily use of supplemental multivitamins, vitamin C, vitamin E, and folate did not reduce the risk of lung cancer. Supplemental vitamin E was even associated with a small increased risk of lung cancer in current smokers, the greatest incidence was found for non-small cell lung cancer.
10.5.5
Study nds no reduction of cancer risk with vitamin C, E and beta carotin supplementation [74]
Jennifer Lin and colleagues 2009 assessed the prevention of cancer due to a diet high in fruits and vegetables, rich in antioxidants. Supplementation of vitamin C (500 mg of ascorbic acid daily), natural-source vitamin E (600 IU of alfa-tocopherol every other day), and beta carotene (50 mg every other day) during an average 9.4 years of treatment no statistically signicant eects of use of any antioxidant on total cancer incidence was found. Duration and combined use of the three antioxidants also had no eect on cancer incidence and cancer death. The authors concluded that supplementation with vitamin C, vitamin E, or beta carotene oers no overall benets in cancer prevention.
10.5.6
Commentary on the study of Lin and colleagfues 2009 [75]
Demetrius Albanes, of the National Cancer Institute, stresses that negative trial data reported by Lin, the trend for a reduction in colon cancer with vitamin E supplementation, found in other studies, should not be forgotten. Beta carotene found by Linn to be associated with a modest excess of lung cancer, is consistent with previous reports. Overall Albanes says that even negative ndings such as those of the Linn study add to a better understanding of the causes of cancer.
10.6. SLIMMING INGREDIENTS, AN UNSERIOUS CATEGORY?
833
10.5.7
Breakdown of beta-carotin may form beta-apocarotenoids, suspected to cause lung cancer [76]
Eroglu et al 2012 report that the breakdown products of beta-carotene are mostly vitamin A when breakdown happens centrally. However, if the breakdown takes place decentrally beta-apocarotenoids may be formed. These compounds act in opposition to vitamin A. Vitamin A is important to human vision, bone and skin health, metabolism and immune function. The authors explain that beta-apocarotenoids act as antagonist to vitamin A suppressing the activation of retinoic receptors. Beta-apocarotenoids are found in blood of humans and animals and also in some foods like cantaloupe and other orange-eshed melons. The authors stress that high doses of beta-carotene may be unhealthy, explaining the negative eects of 30 mg/day beta-carotene supplementation found by the CARET trial such as lung cancer. Harrison et al.2010 wrote that biological eects of apocarotenoids, such as beta-apo-13carotenone (C13), do not activate retinoic acid receptors alpha and beta (RARs) pathway. [77] In fact, beta-apo-13-carotenone was found by Erogul et al. 2010 to antagonize the activation of RXR by 9-cis-retinoic acid, being eective at concentrations as low as 1 nM. The authors suggest that have a direct suppressing activity on the RXR signaling. [78]
10.6
Slimming ingredients, an unserious category?
Chitosan can be used in water processing engineering as a part of a ltration process. Chitosan causes the ne sediment particles to bind together and is subsequently removed with the sediment during sand ltration. Chitosan also removes phosphorus, heavy minerals, and oils from the water. [79] Chitosan is also useful in other ltration situations, is used to clarify wine, mead and beer, improves occulation, and removes yeast cells, fruit particles, and other detritus that cause hazy wine. Chitosan is supposed to have the capability of attracting fat from the digestive system and expelling it from the body so that users can, it is claimed, lose weight without eating less. However, some scientic research suggests that these claims are likely without substance. [79] With the unavailability of specic research studies to support the claims made on chiCopyright 1998-2010 Karl H. Wilm. All rights reserved. OurFood Database of Food and Related Sciences
834
tosan as a revolutionary weight loss supplements, one must be careful on what is fact and what is speculation. [79]
10.6.1
Chitosan reduces cholesterol and body weigt gain [80]
Dr. Shahdat Hossain and colleagues from Jahangirnagar University, studyed the eects of chitosan extracted from locally sourced shrimps Macrobracium rosenbergii using sequential decalcication, deproteination, deacetylation and the acid-extraction of chitin.on bodyweight, plasma lipid prole, fatty acid composition, liver lipid peroxide levels and plasma levels of glutamate pyruvate transaminase. The authors found that dietary supplementation of chitosan decreases the atherogenic lipid proles of both NC and HC rats and reduces the bodyweight gain of HC rats. Adequate anti-oxidants should be added to chitosan-enriched supplements in order to minimize the degree of oxidative stress to the liver. Further studies should clear whether the benets of chitosan noted in rats are also translated into humans.
10.6.2
International Conference on Innovations and Trends in Weight Loss and Weight Management [81]
At the First International Conference on Innovations and Trends in Weight Loss and Weight Management held in March 2007 in Berlin Dr. Jorg Gruenwald reviewed the European market of slimming ingredients and stated that the science supporting chitosans benets was limited. He Is a leading European expert in the eld of botanicals and natural products. According to an overview by Dr. Gruenwald, the slimming ingredients market can be divided into ve groups based on the mechanisms of action: Boosting fat burning/ thermogenesis Inhibiting protein breakdown Suppressing appetite/ boosting satiety (feeling of fullness) Blocking fat absorption Regulating mood According to Dr. Gruenwald supplements with weight reduction claims with various levels of supporting scientic evidence are green tea polyphenols, CLA, Hoodia gordonii, DHEA,
10.6. SLIMMING INGREDIENTS, AN UNSERIOUS CATEGORY?
835
hydroxy-methylbutyrate (a metabolit of leucine), and chromium picolinate, leading down to ingredients with only limited available data, like L-carnitinewith only limited available data, like L-carnitine, calcium and chitosan. The conference called for industry to make more eort with academia and clinical trials to obtain credibility.
10.6.3
Chitosan supplementation and fecal fat excretion [82]
Chitosan-based supplements are sold as fat trappers and fat magnets. Matthew Gades and Judith Stern quantied the in vivo eect of a chitosan product on fat absorption. In this study the authors concluded that the fat trapping claims associated with chitosan are unsubstantiated with no signicant eect on energy balance.
10.6.4
Chitosan supplementation and fat absorption [83]
Chitosan is a primary ingredient in dietary weight-loss supplements. Its claimed activity is the binding and trapping of dietary fat, leading to fat excretion and weight loss without caloric restriction. Gades and Stern (2005) tested the fat-trapping capacity of a chitosan product in men and women. The author conclude that the fat trapped was clinically insignicant. The product fails to meet claims.
10.6.5
Weight loss supplements [84]
According to Judith S. Stern there are not any supplements that cause substantial weight loss. Consumer rely on testimonials, and they erroneously assume that supplements are safe because they believe the federal government would not allow unsafe products on the market. Unfortunately, the federal government has limited power and money to stop the marketing of such supplements. According to the Dietary Supplement Act (DSHEA) of 1994, supplement manufacturers are not required to perform premarketing safety evaluations of their products. DSHEA leaves it to the federal government to prove that a specic supplement is not safe. The FDA and FTC simply do not have the budget to do that job. In April 2004, the Food and Drug Administration (FDA) made an eort in ensuring public safety by sending warning letters to 16 dietary supplement distributors for making false and misleading claims for weight-loss products promoted over the Internet. [85]
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10.6.6
Minimal eect of chitosan on body weight [86]
Ni Mhurchu and colleagues, in a review of studies related to chitosan, come to the conclusion that there is some evidence that chitosan is more eective than placebo in the short-term treatment of overweight and obesity. However, many trials to date have been of poor quality and results have been variable. Results obtained from high quality trials indicate that the eect of chitosan on body weight is minimal and unlikely to be of clinical signicance. Adequate anti-oxidants should be added to chitosan-enriched supplements in order to minimize the degree of oxidative stress to the liver. Further studies are certainly needed to clarify these aspects of chitosanand wether the benets of chitosan noted in rats are also translated into humans.
10.6.7
Touchi Extract [87]
Touchi is a fermented soy bean extract that has been used for centuries in Asia. It is a protein-rich product in powder form obtained by aqueous extraction of small soybeans that have been fermented using the fungus Aspergillus Oryzae , also known as "salted black beans". An application to the UK Food Standards Agency (FSA) requests to use touchi in food supplements and make health claims to combat metabolic syndrome, a collection of conditions associated with obesity and type-2 diabetes. It was lodged by a Japanese distributor, CBC Co Ltd planing to market the ingredient as a food supplement and a tea/soup style formulation at levels that would not exceed 4.5 g per daily serving/dose. One portion of black bean sauce contains 15g of fermented black beans, which corresponds to 4.5 g of Touchi extract.
10.6.8
Alpha-glucosidase Inhibitory Action [88]
According to CBC Co Ltd touchi extract can inhibit alpha-glucosidase action, when consumed as a food supplement alongside a meal. It can delay carbohydrate digestion in the small intestinal tract. Undigested carbohydrates or disaccharides are then excreted rather than being absorbed by the body thus providing possible assistance in weight control regimes. CBC points out that the inhibition of alpha-glucosidase is found only in beans fermented with Aspergillus sp.; it is absent in the raw or boiled bean, in bean whey or in beans fermented with Bacillus subtilis natto (a traditional Japanese appetiser). According to the UK FSA touchi will be marketed at anyone who wants to slow the breakdown of carbohydrates.
10.7. CONJUGATED LINOLEIC ACID (CLA) AS FOOD SUPPLEMENT
837
10.6.9
Antihyperglycemic eect of touchi extract [89]
Hiroyuki Fujita and colleagues 2001 found that water-extracted touchi presented antiglycemic eect at a minimum eective dose of 0.3 g. The researchers gave 0.3 g Touchi extract to diabetics before eating 200 g of cooked rice, the postprandial increases in blood glucose and mean insulin levels were signicantly depressed, compared with levels when no TE was administered. This eect was due to the alpha-glucosidase inhibitory activity of the extract. The authors suggest touchi extract in the management of patients with noninsulin-dependent diabetic mellitus.
10.6.10
Powdered Houji-tea long-term ingestion [90]
The eects of powdered Houji-tea was studied by Fujita and coleagues 2001 in humans with borderline and mild type-2 diabetes. All subjects ingested Houji-tea with or without 0.3 g of TE before each of three meals per day for 3 mo. The alpha-glucosidase inhibitory TE demonstrated an antihyperglycemic eect and may prove useful for improving glycemic control in subjects suering from borderline and type-2 diabetes mellitus.
10.7
Conjugated Linoleic Acid (CLA) as food supplement
Some substances can create a supplementation of food such as the Conjugated Linoleic Acid (CLA)[91]. It is a group of natural geometrical and position isomers of linoleic acid. A generical denition says that conjugated fatty acids are polyunsaturated fatty acids in which at least one pair of double bonds are separated by only one single bon such as:-C=CC=C-. The most important of these fatty acids is produced by bacterial fermentation in the digestive system of ruminants, being found in milk and meat of these animals. It is called rumenic acid(cis 9, trans 11, octadien acid) The bacterium which isomerates the linoleic acid to CLA is Butyrivibrio brisolvens. The conjugated linoleic acids are told to improve the resistance to carcinogenic diseases and to reduce the body fat. The natural amount of CLA in milk and meat is to small to induce anticarcinogenic and anti fat activities. CLA enriched oil is commercially available and can be used to supplement foods such as margarine, chococream, backery products and dairy products.
10.7.1 10.7.2
Claims of CLA acids are 1. Anticarcinogenic
This action was observed on mice.

838
10.7.3
2. Antiaterogenic
This action is not well known. Further studies are necessary.
10.7.4
3. Anabolic eect
Rumenic acid seems to reduce the body fat increasing at the same time the fat-free body mass (lean body mass). Muscle tissue and bone mass increases.It is why Conjugated Linoleic Acids are found in the formula of some anabolic preparations.
10.7.5
4. Activity on the immunological system
The immunoglobulinesIgA, IgG and IgM are increased and EgE reduced. This reduces the the risk of allergy
10.7.6
5. Antidiabetic
An antidiabetic activity of the CLA acids was found in rats.
10.7.7
6. Antithrombotic
The CLA acid group has a strong antithrombotic activity, contrary to linoleic acid which increases thrombotic. CLA is present in milk, milk derivates, meat and its derivates of ruminants. [92] Table 10.3: Amount of CLA in Foods according to Fritsche and Steinhart Food CLA (rumenic acid) in total fatty acids 0,86% 0,6% 0,32% 0,05% 0,14% <0,01%
Milk and derivates Meat and derivates Cakes and cookies Fish Chocolate Margarine, edible oil,fats and chips
The amount of CLA in milk and derivates can easily increased up to 500 times giving animal feed enriched with linolein acid such as sunower oil, about 50 g/kg dry feed[93]. Chemical synthesis is very dicult. Biological activity of lactobazillus, Candida antarctica have been tried to produce CLA, with minor success. Promising is the way of animal feed enriched with linoleic acid. Milk,
10.8. CONJUGATED LINOLEIC ACID (CLA), A REVIEW
839
its derivates and meat of ruminants being fed with such animal feed is a natural biological way to increase CLA as functional food.
10.7.8
Antidiabetic eects of CLA mediated via anti-inamatory eects in adipose tissue [94]
Helen M. Roche and colleagues investigated whether dietary fatty acids could attenuate the proinammatory insulin-resistant state in obese adipose tissue which may be the source of insulin desensitizing proinammatory molecules that predispose to insulin resistance. The authors found that c9,t11-Conjugated Linoleic Acid inhibited tumor necrosis factoralfa-induced downregulation of insulin receptor substrate 1 and GLUT4 mRNA expression and promoted insulin-stimulated glucose transport in 3T3-L1 adipocytes compared with linoleic acid. The authors suggest that altering fatty acid composition may attenuate the proinammatory state in adipose tissue that predisposes to obesity-induced insulin resistance.
10.8
Conjugated Linoleic Acid (CLA), a review
[95] Conjugated linoleic acid was proposed as supplement improving body composition, cancer prevention, diabetes, high cholesterol. It also has been promoted as a fat burning supplement. According to Emory Healthcare, however, there is little evidence that it works, and growing evidence that CLA might actually worsen blood sugar control in people who are overweight. The typical dosage of CLA ranges from 3 to 5 g daily even very small amounts of a toxic contaminant can quickly add up if low quality of CLA is used, warns Emory Healthcare.
10.8.1
Conjugated linoleic acid production in gut [96]
Devillard and colleagues (2007) found that the human gram-positive intestinal Roseburia spp.species were among the most active bacteria metabolizing linoleic acid (cis-9,cis-1218:2) and vaccenic acid (trans-11-18:1) or a 10-hydroxy-18:1, which are precursors of conjugated linoleic acid. Voevodin and colleaugues (2005) in a meta-analysis found only minimal benets, whether for weight or body composition, the evidence being more negative than positive in relation to weight loss supplement. [97] CLA does NOT appear to be a useful supplement for people with diabetes, and might in fact contribute to diabetes in overweight people. CLA might decrease insulin sensitivity, creating a pre-diabetic state. [98] [99] [100]. However, Syvertsen and colleagues did
840
not nd any harmful eect. [101] Emory Healthcare advices at present individuals with diabetes or at risk for it not to use CLA except under physician supervision. [95] One study found that CLA impairs endothelial function, suggesting that it might increase cardiovascular risk. [102] A small double-blind trial found weak evidence that CLA might be useful for high cholesterol. [103] Some animal and test tubes suggesting that CLA might help prevent cancer are based on animal and test tube researches, evidence is preliminary and inconsistent. [104] [105] One study failed to nd that CLA can enhance immune function. [106]
10.8.2
CLA and nursing mothers
Concerns have also been raised regarding use of CLA by nursing mothers. A study found that CLA reduces the fat content of human breast milk. [107] Since infants depend on the fat in breast milk to provide adequate calories and on certain fats to aid proper growth and development, it is probably prudent for nursing mothers to avoid CLA supplements. [95] Maximum safe dosages of CLA for young children, pregnant women, or those with severe liver or kidney disease have not been determined. [95]
10.9
Memory Supplements without solid scientic support
According to a review [108]of the Center for Science in the Public Interest (CSPI), there is no solid science indicating that any of the major ingredients of dietary supplements help protect or improve memory.
10.9.1
Antioxidants
Antioxidants are common ingredients in memory supplements, particularly lipoic acid and the Asian plant bacopa. The single study of lipoic acids eect on cognition found that it didnt help HIV patients with dementia. Of three Australian studies of bacopa, one found that 23 adolescents scored higher on memory tests but two bigger studies of middle-aged and older people found no eect.
10.9. MEMORY SUPPLEMENTS WITHOUT SOLID SCIENTIFIC SUPPORT
841
10.9.2
Vitamin E
Kang and colleages found in a study published in 2006, that long-term use of vitamin E supplements did not provide cognitive benets among generally healthy older women. [109]
10.9.3
No reduction of vascular diseases with antioxidants
The Heart Protection Study Collaborative Group 2002, made a study with 20 536 UK adults with coronary disease, other occlusive arterial disease, or diabetes. The Group wanted study the suggestion that increased intake of various antioxidant vitamins reduces the incidence rates of vascular disease, cancer, and other adverse outcomes. The patients received antioxidant vitamin supplementation (600 mg vitamin E, 250 mg vitamin C, and 20 mg beta-carotene daily) This suplementation did not produce any oxidative stress study, model for future studies [110] Jackson Roberts and colleaugues determined the dosage of vitamin E that decreases systemic oxidant stress in humans. The dose-dependent eects of vitamin E-alfa tocopherol was measured by the concentration of F2-isoprostanes, a biomarker of free radical-mediated lipid peroxidation. Foregoing clinical trials had found no signicant eects of vitamin E regarding protection against heart attack. The present study suspects that the studies had been poorly designed. The researchers say that these trials used a single dose of vitamin E and only looked for end points such as heart attack occurrence. In the present study the authors found a linear trend between the dosage of vitamin E and percentage reduction in plasma F2-isoprostane concentrations which reached signicance at doses of 1600 IU (reduction of 35 per cent) and 3200 IU (reduction of 49 per cent). In vitro studies that vitamin E may act as a pro-oxidant at certain concentrations were not backed by this study. The study informs the planning and evaluation of clinical studies that assess the ecacy of vitamin E to mitigate disease, and can serve as a model for further studies.
10.9.4
L-arginine supplementation improves arterial responses in disease with endothelial dysfunction [111]
According to Guttman and colleagues 2010 longterm supplementation of L-arginine improves large artery elasticity index (LAEI) in patients with multiple cardiovascular risk factors, and decreased systolic blood pressure, peripheral vascular resistance as well as a decrease in aldosterone levels. The authors stress that long term L-arginine supplementation may improve artery compromised by disease with endothelial dysfunction.
842
10.9.5
Long-term treatment with antioxidants (vitamin C, vitamin E, coenzyme Q10 and selenium) improves artery health, humoral factors and inamatory markers in case of multiple cardiovascular risk [112]
Shargorodsky and colleagues 2010 report that daily oral supplementation with vitamin C (1000 mg/day), vitamin E (400 i.u/day), coenzyme Q10 (120 mg/day) and selenium (200 mcg/day) during six month improved the large arterial elasticity index (LAEI) as well as small arterial elasticity index (SAEI). HbA1C was reduced and HDL-cholesterol was increased. The authors concluded that antioxidant supplementation signicantly improved vascular health, glucose and lipid metabolism as well as decrease in blood pressure.
10.9.6
Neurotransmitters [113]
Neurotransmitters relay signals from one nerve cell to another. A building block of one such neurotransmitter involved in memory is choline. However, studies show that in supplement form choline doesnt even reach the brain. No study has found DMAE, a building block of choline, to be helpful for memory, and several tests have found it not to be useful for Huntingtons or Alzheimers patients. B vitamins are included in some products because they can lower levels of homocysteine in blood, and high levels of homocysteine are linked to poor cognition. One Dutch study found that folic acid helped more than a placebo in folate-decient volunteers, but grain-based foods in the U.S. are already fortied with folic acid (the Dutch study looked at folate-decient volunteers.) Seventeen of the 18 other studies showed no eect of B vitamins on memory.
10.9.7
Ginkgo biloba
Ginkgo biloba helps increase blood ow, and is included in many memory formulas, yet studies are inconclusive at best. The most recent tests showed ginkgo takers scored better on just one of 14 tests of brain function-a result that may be due to chance. Gingo biloba extract causes liver cancer and thyroid gland cancer in mice and rats [114] Researchers of the National Toxicology Program (NTP) of the US Department of Health and Human Services report that Gingo biloba extract causes liver cancer and thyroid gland cancer in rats. The report of the NTP says that animals exposed to Ginkgo biloba extract experienced increased rates of a variety of lesions in the liver, thyroid gland, and nose, and male and female mice also experienced several dierent lesions in the forestomach in addition to
843
increased incidences of cancers of the thyroid gland and liver cancers in these animals. Pills or other products containing ginkgo are often marketed as having some benet for memory or concentration. Such claims are considered as dubious and are outweighed by the real harm caused by ginkgo and the cancer risk. Gingko also interferes with blood clotting. It should not be consumed before or after surgery, during labour and delivery, or by those with bleeding problems such as haemophilia. [115]
10.9.8
Bacopa
Stough and colleagues (2001) suggest that B. monniera may improve higher order cognitive processes that are critically dependent on the input of information from our environment such as learning and memory. [113] Extracts of Ginkgo biloba and Bacopa monniera have been shown to produce positive eects on cognitive function in healthy subjects, being antioxidant properties and cholinergic modulation the main cause. However, Nathan and colleagues (2004) found that extracts of Ginkgo biloba and Bacopa monniera had no cognitive enhancing eects in healthy subjects. [116] The results show a signicant eect of the Brahmi on a test for the retention of new information, but the rate of learning was unaected, suggesting that Brahmi decreases the rate of forgetting of newly acquired information. Tasks assessing attention, verbal and visual short-term memory and the retrieval of pre-experimental knowledge were unaected. Questionnaire measures of everyday memory function and anxiety levels were also unaffected. [117] Bacopa monnieri failed to improve mental function in studies. This type of inconsistency suggests that the limited benets seen in some studies were due to chance. [118]
10.9.9
Choline
Choline is widespread in the foods we eat. The average diet provides about 500 to 1,000 mg of choline per day. 2,4 Lecithin, a fatty constituent in foods, is a major source of choline; it is comprised mostly of a type of choline called phosphatidylcholine (PC). For some people, adequate choline supplies cannot be maintained by other nutrients, and must be obtained independently through diet or supplements. Choline and folate share methylation pathways. Robert and colleagues 1999 in a study found that choline is utilized as a methyl donor when folate intake is low, and the synthesis of phosphatidylcholine is insucient to maintain choline status when intakes of folate and choline are low. The authors call for a dietary choline of > 250 mg/d to maintain plasma choline and phosphatidylcholine when folate intake is low. [119]
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Huperzine A, a cholinesterase inhibitor, is derived from the Chinese herb Huperzia serrata. According to Dana Belongia of Georgetown University in Washington, products based on huperzine A have never been tested on memory or other brain functions in healthy adults, and there have been no controlled clinical trials outside China assessing its toxicity and ecacy. [108]
10.9.10
DMAE
There are no studies looking at DMAEs impact on memory or powers of concentration in healthy adults. DMAE has failed nearly every test concerning neurological diseases like Alzheimers and Huntingtons chorea. [108]
10.9.11
Phosphatidylserine (PS)
According to FDA very limited and preliminary scientic research suggests that phosphatidylserine may reduce the risk of dementia and the risk of cognitive dysfunction in the elderly. FDA concludes that there is little scientic evidence supporting these claims. [120]
10.9.12
Lipoic acid
According to study of Dana Consortium, treatment of HIV patients with thioctic acid, also known as alpha-lipoic acid did not improve cognitive function. According to this study thioctic acid has no benet. [121]
10.9.13
Folic acid
According to Durga and colleagues low folate and raised homocysteine concentrations in blood are associated with poor cognitive performance in the general population. The authors found, as part of the Dutch FACIT trial that folic acid supplementation for 3 years signicantly improved domains of cognitive function that tend to decline with age. [122] Martha Morris of the Rush Institute for Healthy Aging in Chicago says that this study is not relevant to people in USA because US grain supply is fortied with folate whereas European supply is not, and the Dutch volunteers lacked folate at the beginning of the trial. [108]
10.9.14
Folate reduces incidence of depression in man but not in women [123]
According to Simon Gilbody and colleagues low folate has been linked to depression, but research is contradictory. In a meta-analysis the researchers found signicant relationship
845
between folate status and depression. Folate levels were also lower in depression. The authors concluded that there is accumulating evidence that low folate status is associated with depression. Kentaro Murakami and colleagues in a study in Japan found that higher dietary intake of folate was associated with a lower prevalence of depressive symptoms in Japanese men but not women. In this study no signicant association with depression was observed for the intake of riboavin, pyridoxine, cobalamin, total omega 3 PUFAs, alfa linolenic acid, eicosapentaenoic acid, or docosahexaenoic acid in man and woman. The authors call for more research on this topic. They stress that there are hypotheses that omega-3 PUFA may have an important role in neurotransmitter synthesis, degradation, release, reuptake, and binding, resulting in a pattern of neurotransmitter activity that has been associated with depression [124]
10.9.15
Ginkgo biloba
Kennedy and colleagues 2007 assessed the eects of a low dose of GBE alone and complexed with the soy-derived phospholipids such as phosphatidylserine and phosphatidylcholine to enhances the bio-availability. No improved performance was found with 120 mg of GBE alone. Enhancement following GBE complexed with phosphatidylcholine resulted in modest cognitive enhancement, but GBE complexed with phosphatidylserine resulted in signicantly increased speed of memory task performance. The authors conclude that complexation with phosphatidylserine appears to potentiate the cognitive eects associated with a low dose of GBE and call for further research. [125]
10.9.16
Vinpocetine
Vinpocetine is a semi-synthetic derivative of vincamine. Vincamine is an alkaloid derived from the plant Vinca minor L. Vinpocetine, as well as vincamine, are used in Europe, Japan and Mexico as pharmaceutical agents for the treatment of cerebrovascular and cognitive disorders, and in the United States it is marketed as a dietary supplement as cognition enhancer. [126] Another study concerning the vinca alkaloid called vinconate was published in 1997 suggesting the alkaloid as possible cognition enhancer.[127] However, Schardt says that only preliminary studies exist dated 15 years ago, asessing vinpocetine for treatment of stroke or Alzheimers disease. [108] According to a study published in 1989 fteen Alzheimers patients were treated with vinpocetine in a trial during a one-year period. Vinpocetine failed to improve cognition on psychometric testing or overall functioning. The authors concluded that vinpocetine is inCopyright 1998-2010 Karl H. Wilm. All rights reserved. OurFood Database of Food and Related Sciences
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eective in improving cognitive decits and does not slow the rate of decline in individuals with Alzheimers disease. [128]
10.9.17
n-3 PUFAs and depressed mood
According to Appleton and colleagues 2006 trial evidence that examines the eects of n-3 PUFAs on depressed mood is limited and present considerable heterogeneity. The evidence available provides little support for the use of n-3 PUFAs to improve depressed mood. [129]
10.9.18
Supplementation with n-3 fatty acids reduce cancer risk of esophagus [130]
Samir P. Mehtan and colleagues in a study published in 2008 found that supplementation with EPA signicantly changed n-3 fatty acid concentrations and reduced COX-2 concentrations in human lower esophagus, reducing the risk of cancer. Population with a high consumption of sh and consequently, n-3 fatty acids had been found to have a reduced risk of esophageal adenocarcinoma. The researchers believe that the suppression of eicosanoid production through inhibition of cyclooxygenase 2 (COX-2) resulting from high intake of eicosapentaenoic acid (EPA) is responsible for a reduction of risc of the disease.
10.10
10.10.1
The controversity of bre and colorectal cancer

The legend of dietary bre
[131] The British surgeon Denis Burkit, working in an hospital in Uganda, developed the theory that Dietary bre could reduce the colorectal cancer risk and other diseases, because Africans consumed more fruit and vegetables as found in western diet. As a tribute to his outstanding contributions in the elds of medicine, nutrition and health the Kellogg Company of Great Britain Limited initiated the Denis Burkitt Study Awards in 1994. In an article in Zeit Wissen 5, 2006 Eva-Maria Schnurr looks at the evolution of the theory of dietary bre and colorectal cancer. In the 80s bran was added to cereals, yoghurt and even beverages in the hope to reduce risk of colorectal cancer. This theory is not being maintained any more by many scientists. According to the article from Eva-Maria Schnurr the English scientist Burkit, developing the initial theory of bre to reduce colorectal cancer did not consider the age of the people he considered for his work, most of them died so early that no cancer could show up. [132] Doubts about the theory came up due to the ndings of a series of researches on this matter:
10.10. THE CONTROVERSITY OF FIBRE AND COLORECTAL CANCER
847
10.10.2
Wheat Bran bre Trial [133]
Alberts and colleagues 2000 found in the Wheat Bran bre Trial that a dietary supplement of wheat-bran bre (of 13,5 g bre in two to three cups of cereal per day) does not protect against recurrent colorectal adenomas.
10.10.3
Polyp Prevention Trial [134]
According to their authors, the Polyp Prevention Trial provided no evidence that adopting a low-fat, high-bre fruit- and vegetable-enriched eating plan reduces the incidence of colorectal cancer.
10.10.4
The position of the National Institutes of Health related to dietary bre [135]
The National Institutes of Health in a release comments the ndings of the Wheat Bran Fibre Trial and the Polyp Prevention Trial: "The results provided no evidence that the particular dietary interventions employed (i.e., a low-fat, high-bre, high-fruit and -vegetable eating plan or a high-bre cereal supplement) in the particular population studied (individuals who had had one or more polyps removed at colonoscopy) were eective in preventing the recurrence of polyps. However, overall evidence suggests that a low-fat, high-fruit and - vegetable, high-bre diet has benet in reducing the risk of many chronic diseases - heart disease, hypertension, obesity, diabetes, and others. This trial specically looked at the eect of diet on the growth of new colorectal polyps in people who had already had a polyp removed. A healthy diet does not replace the need for people with a history of polyps to have regular checkups. "
10.10.5
Wheat-bran bre does not protect against colorectal adenomas [136]
Jacobs and colleagues 2006 assessed the epidemiologic evidence that cereal bre protects against colorectal cancer is equivocal, with a supplementation of 13.5 g per day of wheatbran bre to reduce the rate of recurrence of colorectal adenomas. The authors found that a dietary supplement of wheat-bran bre does not protect against recurrent colorectal adenomas.
10.10.6
The Womens Health Initiative (WHI) found no link between reduction of colorectal cancer and high fruit, vegetables and whole grain intake [137]
The clinical trials of the Womens Health Initiative (WHI) were designed to test the effects of postmenopausal hormone therapy, diet modication, and calcium and vitamin D
848
supplements on heart disease, fractures, and breast and colorectal cancer. The WHI trial also reported no link between a diet low in fat, and high in fruit, vegetables and whole-grain intake. This study was restricted to women and appears to agree with the results from Arizona.
10.10.7
The Womens Health Initiative (WHI) found no link between supplementation of calcium and vitamin D and reduction of colorectal cancer [138]
Higher intake of calcium and vitamin D has been associated with a reduced risk of colorectal cancer in epidemiologic studies and polyp recurrence in polyp-prevention trials. However, randomized-trial evidence that calcium with vitamin D supplementation is benecial in the primary prevention of colorectal cancer is lacking. However, the authors conclude that daily supplementation of calcium with vitamin D for seven years had no eect on the incidence of colorectal cancer among postmenopausal women. The long latency associated with the development of colorectal cancer, along with the seven-year duration of the trial, may have contributed to this null nding. Ongoing follow-up will assess the longer-term eect of this intervention.
10.10.8
Vitamin D3 and calcium supplementation reduces allcancer risk in women [139]
Joan M. Lappe and colleagues in a study of supplementation of 1,400-1,500 mg calcium and 1,100 IU vitamin D3 over 4 years the calcium/vitamin D3 group experienced a 60 per cent decrease in their cancer risk compared to the group taking placebos, but did not change signicantly for the group receiving only calcium. The authors concluded that mproving calcium and vitamin D nutritional status substantially reduces all-cancer risk in postmenopausal women.
10.10.9 10.10.10
Fibre and resistant starch [140] Soluble Fiber
(e.g., pectins, gums, mucillages, and some hemicellulose) - Soluble ber is found in fresh and dried fruit, vegetables, oats, legumes and seeds.
10.10.11
Insoluble bre
(e.g., cellulose, lignin and hemicellulose) - Insoluble ber is found in the plant cell walls of whole grain bread, whole grain cereals, fruits, vegetables, unprocessed bran and wheat
10.10. THE CONTROVERSITY OF FIBRE AND COLORECTAL CANCER germ. Many insoluble bres, including cellulose and psyllium, are not fermented.
849
10.10.12
Resistant Starch
- Starch that resists digestion is found in foods such as legumes, bananas (especially underripe, slightly green bananas), and unprocessed whole grains. Resistant starch incorporates some benets of insoluble bre as well as soluble bre, and acts like dietary bre. There are four types of resistant starches:
10.10.13
- RS1
Physically inaccessible or digestible resistant starch, such as that found in seeds or legumes and unprocessed whole grains.
10.10.14
- RS2
Resistant starch that occurs in its natural granular form, such as uncooked potato, green banana our and high amylose corn.
10.10.15
- RS3
Resistant starch that is formed when starch-containing foods are cooked and cooled such as in bread, cornakes and cooked-and-chilled potatoes or retrograded high amylose corn.
10.10.16
- RS4
Starches that have been chemically modied to resist digestion, and are not found in nature.
10.10.17
Improved gluten free breads [141]
Coeliac disease demands for gluten free foods. Starches from corn, rice, soy and buckwheat ours in stead of wheat our. However, according to Jaraslaw Korus and colleagues 2008, these products lack important nutrients and dietary bre. To improve the weaker structure of gluten-free bread compared with conventional bread and to increase its content of dietary bre Korus replaced partially corn starch in gluten free bread with resistant starch, aiding functioning of the digestive tract, microbial ora, blood cholesterol levels and can help in diabetes management. On the other hand, preparations using resistant starch are "less prone to pasting". Since the structure of bread depends on starch gelatinisation, it was thought that this could aect loaf quality. The gluten free breads containing corn starch, potato starch, guar gum, pectin, freeze dried yeast, sucrose, salt, plant oil and water was modied in that 10, 15, 20 and 50 per
850
cent of corn starch was replaced by corn resistant starch, and the same proportions of potato starch were replaced by tapioca resistant starch. The best results in lowering the hardness of the bread were obtained with tapioca resistant starch, however, other eects on rheological parameters, such as crumb texture were limited. The authors concluded that partial replacement if starch in recipes for gluten free bread with resistant starch preparation doesnt signicantly inuence organoleptic quality, but the breads with resistant starch were seen to have much high dietary bre content, as well as insoluble and soluble fractions. A total dietary bre of 6.30g per 100g had been achieved, which makes it advisable for practice.
10.10.18
Physical properties and biological impact of resistant starches RS3 [142]
According to Haralampu retrograded starch, and particularly retrograded amylose RS3, are the most thermally stable forms. Early studies on the digestibility stated that retrograded amylose was non-nutritive, a slow digestion by amylases, however, were recently discovered, releasing glucose and other oligosaccharides. The author stresses that the use of resistant starch in food products for certain target groups, such as diabetics and athletes should be considered. Haralampu reviews sources of resistant starches highly concentrated in retrograde amylose and describes a product for modulating the glucose response of diabetics, and eects on an extruded cereal product.
10.10.19
Wheat Bran bre Trial and the Polyp Prevention combined suggest benet of bre for men, but not women [143]
Elisabeth Jacobs and colleagues 2006 combined the Wheat Bran bre Trial and the Polyp Prevention Trial, Both studies separately presented no link between dietary bre and the risk of colon cancer, but pooled together a benet of bre was noted for men, but not women. According to Jacobs the conicting results from other studies can be explained by the dierence in benets between the sexes.
10.10.20
Warning about too much bre intake [144]
According to Goodlad the benets of bre have been attributed to its binding to bile acids but bre can also bind various other harmful materials. Vegetable bre has several times more galactose than cereal bre and this high galactose content will inhibit binding of mitogenic galactose binding lectins, such as peanut agglutinin, which has been shown to
851
stimulate cell proliferation in the human colon. Goodlad concludes that fermentable bre and resistant starch can give origin to colorectal adenomes. Increases in tumour in rats following supplementation with bre-like substrates such as resistant starch have also been reported. Williamson and colleagues 1999 conclude that it is possible that any increased risk posed by resistant starch is restricted to carriers of germline mutations in APC (adenomatous polyposis (Apc) gene). [145] [146] Another theory says that soluble bre and excessive cereal bre are being added to probiotic and functional foods as well as drinks by the producers trying to prot from a new wave toward high bre foods. This may lead to a negative health eect as excessive bre may lead to gas which can drive bacteria back to the small intestine where they may cause erosion of the gut. Goodlad reinforces the advice that bre is still an important aspect of a diet and in the diet bre should come from bre-rich food such as fruits and vegetables and less so from cereals, to have a balanced diet and everything in moderation,and that exercise and avoiding obesity is important.
10.10.21
The Channing Laboratory, Department of Medicine, Brigham and Womens Hospital and Harvard Medical School Report 1999 [147]
Fuchs and colleagues 1999 found no association between the intake of dietary bre itself and the risk of colorectal cancer. The researchers measured the contributions of dietary bre from cereals, fruits, and vegetables. Only fruit bre was associated with an appreciable but not signicant reduction in risk. In contrast, greater consumption of vegetable bre was associated with a small increase in the risk of colorectal cancer.
10.10.22
Nurses Health Studie found no link between Fibre and colon cancer [148]
Nurses Health Studie in USA observed 76 947 nurses starting in 1976 over 16 years. And the Nurses Healt Study II started in 1989 could not nd a link between dietary bre and colorectal cancer.
10.10.23
Limitations of Studies [149]
The validity of the results were questioned on account of the poor compliance with the dietary intervention in the WHI trial. Limitations of the wheat bran Fibre and the polyp
852
prevention trial had a follow- up period of only two to four years, ting into consideration that the latency period of the cancer is between 10 and 20 years. Another limitation with this new-pooled analysis is the use of polyps, as a marker for actual cancer.
10.10.24
Total dietary bre does not protect against colorectal cancer, but whole grain does [150]
In 2007 Schatzkin and colleagues found in a large prospective cohort study, that total dietary bre intake was not associated with colorectal cancer risk, whereas whole-grain consumption was associated with a modest reduced risk.The association with whole grain was stronger for rectal than for colon cancer.
10.10.25
Dietary bre and Risk of Colorectal Cancer in the Japan Collaborative Cohort Study [151]
Wakai and colleagues 2007 found no dierences in the strength of associations with the risk between water-soluble and insoluble dietary bre. For food sources of bre, bean bre intake was somewhat inversely correlated with colorectal cancer risk. This might point to the ndings that soluble bres from fruit and vegetable have shown to be protective towards colorectal cancer and insoluble cereal bre tends to increase the risk of cancer in humans. The authors concluded that dietary bre my be protective against colorectal cancer, mainly against colon cancer, however, the role of dietary bre in the prevention of colorectal cancer seems to remain inconsistent, and further investigations in various populations are being suggested by the authors.
10.10.26
The weak point of the Womens Health Initiative [152]
Martinez and Jacobs in an editorial in 2007 point out that most prospective studies of colorectal cancer and calcium intake suggests a threshold eect in that risk reduction is seen at intakes of approximately 600-1000 mg/day, with no further protection beyond these levels. These ndings might explain the null eects observed in the Womens Health Initiative, in which women received a total calcium intake of approximately 2150 mg/day, levels that, based on the prospective data, are consistent with no eect. Martinez and Jacobs rise again the question of whether calcium supplementation could protect individuals with low or moderately low baseline intakes of calcium.
853
Matinez and Jacobs also note that according to Grau and colleagues 2007 [153] the protective eect of calcium supplementation for colorectal adenoma recurrence extends as long as 5 years after cessation of supplementation and that this eect is slightly stronger than that observed during the intervention phase.
10.10.27
Calcium supplementation reduces the risc of colon cancer [154]
Dr. Baron and colleagues of The The Calcium Polyp Prevention Study Group conducted a randomized, double-blind trial of the eect of supplementation with 3 g calcium carbonate carbonate (1200 mg of elemental calcium daily) on the recurrence of colorectal adenomas. The authors found that Calcium supplementation is associated with a moderate reduction in the risk of recurrent colorectal adenomas.
10.10.28
No direct relation between calcium supplementation and colon cancer explained [155]
Weingarten, Zalmanovici and Yaphe 2008 reviewing the literature found two studies which suggest that there may be a moderate protective eect for dietary supplementation of at least 1200mg elemental calcium per day on the development of colorectal adenomatous polyps. The authors stress, however, that a direct relationship of an eect of calcium supplementation on colorectal cancer itself was not given.
10.10.29
Low calcium to magnesium ratio may reduce colorectal cancer risk [156]
Dr. Qi Dai presented the result of the Calcium Polyp Prevention Study in November 2008. According to the author the supplementation of 1,000 mg calcium daily for 4 years was found to have a moderate eect to prevent colorectal adenoma recurrence in subjects with a low calcium to magnesium intake ratio. The study says that the protective eect occurred only if the dietary ratio of calcium to magnesium intake was low before treatment and remained low during treatment. The authors suggests the use of a personalized ratio of calcium/magnesium ratio rather than supplementing with only one or the other alone.
10.10.30
Sphingadienes of soy may become a new therapy for colon cancer [157]
Dr. Julie Saba and colleagues 2009 found a class of substances called sphingadienes in the fruit y. Sphingadienes are also present in soy. According to the authors sphingadienes
854
are natural lipid molecules which promote the deaths of cancer cells. Sphingolipid metabolites regulate cell proliferation, migration, and stress responses and alterations of their metabolism may induce carcinogenesis, cancer progression, and drug resistance. Sphingadienes were found to block Akt translocation from the cytosol to the membrane causing the death of cancer cells. The authors conclude that these sphingadienes of soy may become a new therapeutic of cancer. Sphingolipids comprise a complex group of lipids concentrated in membrane rafts. Their metabolites function as signaling molecules. Sphingolipids were found by Saba and colleagues in 2008 in the fruit y Drosophila. They contained two double bonds in the long chain base of either 14 or 16 carbons with conjugated double bonds at C4,6. The Delta(4,6)-sphingadienes were found free , as phosphorylated , and as the sphingoid base in ceramides. The authors suggest that these lipids may contribute to the muscle degeneration in Drosophila Sply mutans. [158] Schmelz 2004 report that sphingolipids are lipid messengers in the signaling pathways of growth factors, cytokines, cellular stresses and others and cell death. Schmelz assessed the mechanisms sphingolipids utilize in the prevention of cancer in early carcinogenesis. [159]
10.10.31
Dietary factors and sphingomyelin [160]
Sphingomyelin metabolism envolve anticancer signals such as ceramide and sphingosine. Ateration of this metabolism is linked to various forms of cancer, especially colon cancer. Duan 2004, therefore, describes the sphingomyelin metabolism pathway and their link to colon cancer and stresses the dietary factors that aect the metabolism of sphingomyelin and may protect from colon cancer. Sphingomyelin occurs in modest amounts in the diet, in sloughed mucosal cells, and in bile. It is digested by the mucosal enzymes alkaline sphingomyelinase and ceramidase. In humans, alkaline sphingomyelinase is also secreted in bile. The digestion of sphingomyelin is slow and incomplete, which has been linked to the inhibition of cholesterol absorption and colonic carcinogenesis. However, Fyrst and colleagues 2009 assessing diet containing milk sphingomyelin found that the increase in ileostomy content of ceramide plus sphingomyelin amounted to 19 per cent of the fed dose of sphingomyelin. The authoirs concluded that more than 81 per cent of dietary sphingomyelin is digested and absorbed by humans, and the level of sphingolipid metabolites may be inuenced by diet. [161]
10.10.32
Inuence of the colorectal cancer behavioural risk factors of individuals [162]
Individuals who were not adherent to screening reported having a greater number of risk factors than adherent individuals. Risk factors were considered in this study to be low
855
physical activity, low fruit and vegetable intake, and low intake of multivitamins. The authors conclude that there is a need to develop interventions to modify the colorectal cancer behavioural risk factors that are common among screening-adherent and nonadherent individuals.
10.10.33
Prediction of the Spread of Colon Cancer [163]
Maode Lai and colleagues2010 identied two proteins (trefoil factor 3 and growth/dierentiation factor 15) that occurred at signicantly higher levels in the metastatic cells than in the primary colon cancer cells. This study may lead to a prediction of the spread of cancer cells after surgery. An earlier allowing treatment may be possible with this biomarkers blood test.
10.10.34
Heart drugs to ght colon cancer [164]
Cardiac glycosides, a family of naturally-derived drugs used to treat congestive heart failure and abnormal heart rhythms, were found useful in the treatment of colon cancer by Jenny Felth and colleagues 2009. The authors say that digitoxin in combionation with oxaliplatin exhibited synergism in treating the disease.
10.10.35
The European Prospective Investigation into Cancer and Nutrition (EPIC) study [162]
The European Prospective Investigation into Cancer and Nutrition (EPIC) study, found a very strong association between a high bre intake and a reduction in the instance of colorectal cancer. People who ate more than 35 g of bre a day had a 40 per cent reduced risk than those who consumed only 15 g. Colon cancer aetiology: - The hypothesis that a diet high in bre reduces colorectal cancer risk has been corroborated in the EPIC study. Our ndings were published in parallel with the results from the PLCO cohort of the NIH-NCI. In that study, a similar protective eect of bre on colorectal cancer polyps was observed. Together, these results indicate that bre is protective both for the development of adenomatous polyps and for their malignant transformation. - The hypotheses that consumption of red and processed meat increases colorectal cancer risk while intake of sh decreases risk is strongly supported by the EPIC results. - The combination of these four dietary factors (i.e. bre, sh, red and processed meats) plays a major role in colorectal cancer aetiology in addition to alcohol intake, obesity and low physical activity.
856
10.10.36
Summary of Scientic Activity on Colon Cancer in the EPIC Study [162]
Lancet 2003, Bingham and colleagues found an inverse relation of dietary bre with colorectal cancer incidence with the greatest protective eect in the left colon, and least in the rectum. No food source of bre is signicantly more protective than others. Bingham and colleagues 2004 conrmed the above ndings after adjustment for folate and with a longer follow-up. (Cancer Epidemiol Biomarkers Prev 2004, Jenab et al: Higher nut and seed intake is not signicantly associated to the risk of colorectal, colon, and rectal cancers in men but did show an inverse association with colon cancer in women.)
10.10.37
Greek EPIC study found moderate wine, little meat, many vegetables to be linked to longer life [165]
The largest eects on reduced mortality came from drinking moderate amounts of alcohol, eating little meat, eating lots of vegetables, eating fruits and nuts, and using olive oil. However, the individual components of the Mediterranean diet had an additive protective eect. The authors stress the importance of overall diet being more important than individual components, with emphasis on moderate wine consumption during meals, preference for olive oil, low consumption of meat, and high consumption of vegetables, fruits, and legumes The study of Trichpoulou and colleagues 2009 used data from the European Prospective Investigation into Cancer and Nutrition (EPIC) trial. The contribution of each of the diet components to lower mortality were: moderate consumption of alcohol (23.5% of the eect), low consumption of meat (16.6%), high consumption of vegetables (16.2%), high consumption of fruits and nuts (11.2%), high monounsaturated-to-saturated lipid ratio (10.6%), and high consumption of legumes (9.7%). The authors stress that eating lots of cereal products and few dairy products contributed to only 5% of the eect, and consumption of sh was associated with a nonsignicant increase in mortality. The study supports the armations of other authors which say that it is not one single component of the Mediterranean diet that is driving reduced risk of mortality. Focusing on one food such as blueberries or folic acid supplements is not enough, but a healthy lifestile and a balanced diet like the Mediterranean diet is of importance.
857
10.10.38
The marketing of bre
Dietary bre components such as pectins, gums, cellulose and others, used as functional ingredients by the food industry are being used in marketing strategy to claim high bre benets.
10.10.39
Dietary bre from cocoa suitable for low-calorie, highbre foodes preparations [166]
Elena Lecumberri and colleagues 2007 studied the composition and dietary bre obtained from cocoa bean hus, a waste product from cocoa. This product contained 60.54% of total dry matter as dietary bre, where 80% of these are insoluble bre and 10 % are soluble dietary bre and polyphenolic compounds (1.32% soluble polyphenols and 4.46% condensed tannins) The glucose retardation index of cocoa bre were similar to other natural commercial insoluble bres. Dietary guidelines recommend a minimum daily intake of dietary bre (DF) of 25 g (equivalent to 12.5 g dietary bre per 1000 calories consumed), dietary bre components like pectins, gums, cellulose and others have been used as functional ingredients. The authors conclude that the antioxidant capacity of this bre-rich cocoa powder and its physico-chemical properties render it a suitable product to be used in the preparation of low-calorie, high-bre foods like chocolate cookies, chocolate cakes, dietetic chocolate supplements, etc. where the colour and avour of this cocoa bre might be advantageous.
10.10.40
The ACS Nutrition and Physical Activity Guidelines represent the most current scientic evidence related to dietary and activity patterns and cancer risk [167]
The consumer is made insecure by conicting results of studies such as those commented above. Adherence to ACS Guidelines may clear the actual situation and provides a pattern to be followed. According to Kushi and colleagues 2006 the American Cancer Society (ACS) Nutrition and Physical Activity Guidelines are consistent with guidelines from the American Heart Association and the American Diabetes Association for the prevention of coronary heart disease and diabetes, as well as for general health promotion, as dened by the Department of Health and Human Services 2005 Dietary Guidelines for Americans. The ACS Guidelines include recommendations for individual choices regarding diet and physical activity patterns, but Kushi stresses that those choices occur within a community context that either facilitates or interferes with healthy behaviours. The authors recommendation are therefore to develop a supportive social environment for individuals to choose healthy behaviours.
858
10.10.41
Physical activity relation to coronary heart disease [168]
Sattelmair et al 2011 assessed the relation between quantity of the specic amounts of physical activity required and the reduction of coronary heart disease. Previous studies showed only qualitative estimates such as low, moderate, and high physical activity. Sattelmair and colleagues performed an aggregate data meta-analysis of related epidemiological studies. They found that 150 minutes of moderate-intensity exercise per week reduced the risk of coronary heart disease (CHD) by 14%, 300 minutes per week had a 20% lower risk of CHD, and 750 minutes per week of moderate intensity exercise had around a 25% reduction in risk of CHD compared with sedentary persons. Physical activity lower than the minimum recommended amount by the 2008 US federal guidelines (150 Minutes/week) [169], also caused a signicantly lower risk of coronary heart disease. Benets of physical activity, particularly walking was generally associated with lower risks of total, ischemic, and hemorrhagic stroke among women than men, but more data are needed to support this armation. [170] The study reinforce the US physical activity guidelines which say that some physical activity is better than none and additional benets occur with more physical activity.
10.10.42
Supplements with vitamin B may be harmful [171]
It is known that folate deciency induces DNA breaks and may alter cellular capacity for mutation and epigenetic methylation. However, Schernhammer and colleagues 2007 found that supplements did not reduce the risk of cancer. B vitamins from multivitamin pills increased risk of developing pancreatic cancer by 139 per cent. The mechanism of the dierent eect from vitamin from supplements and the eect of vitamins absorbed from food is unknown. The authors suggest that the growth of a dormant tumor may be stimulated by folate and other similar vitamins, especially in case if a person with chronic shortage of these nutrients in his diet suddenly starts taking multivitamins in an eort to become healthy. Similar results have been found studying oestrogen-rich soy. Women eating soy all life long reduced the risk of breast cancer, but those who suddenly started to eat soy did increase the risk. In this study nonusers of multivitamins were found to have a modest inverse trend between folate, PLP, and B12 and pancreatic cancer risk. This has not been observed among people using multivitamin supplement and among those who obtain these factors excluOurFood Database of Food and Related Sciences Copyright 1998-2010 Karl H. Wilm. All rights reserved.
859
sively through dietary sources, there may be an inverse relation between vitamin B and the risk. The authors advice is to maintain a normal weight and eat fruit and vegetables to avoid pancreatic cancer. Liver, wholegrain cereals, dairy products and green vegetables are good sources of B vitamins.
10.10.43
Folic acid increases the risk of some types of tumours [172]
Bernard Cole and colleagues 2007 found in a study that folate, when administered as folic acid for up to six years, does not decrease the risk of adenoma formation in the large intestine among individuals with previously removed adenomas. Another study by Schernhammer and colleagues 2007 (See www.ourfoo-news.com 03.06.2007: Supplements with vitamin B may be harmful) came to similar conclusion in relation to pancreatic cancer. [173] In the study of Cole participants were randomly assigned to receive 1 mg/day of folic acid or placebo and to receive aspirin or placebo and were then examined three and six or eight years later. The researchers concluded that folic acid at 1 mg/d does not reduce colorectal adenoma risk. Further research is needed to investigate the possibility that folic acid supplementation might increase the risk of colorectal neoplasia. Cornelia Ulrich and John Potter in an editorial said that folic acid promoted growth of carcinogenic lesions and calls of health professionals to rely carefully on multiagent chemoprevention and not to forget diet. [174] The study of Schernhammer and the study of Cole may be a warning for excessive consumption of supplementation of the vitamin B group. Both studies call for more studies. Mandatory fortication of certain foods with folic acid in the US and Canada were introduced in 1998 to reduce the incidence of pregnancies aected by neural tube defects. Andrew Shao US dietary supplements industry association, the Council for Responsible Nutrition (CRN) says that the benets of folic acid are well-documented, particularly in the area of reducing the risk of neural tube birth defect. There is also promising scientic evidence for folic acid in reducing the risk of congenital cardiovascular defects, stroke and Alzheimers disease. [175]
860
10.11
Zinc deciency
In 1974 the Food and Nutrition Board of the US National Academy of Sciences declared zinc an essential nutrient and establish recommended dietary allowances for humans and made zinc in total parenteral nutrition uids mandatory. Prasad 2003 stressed that dietary zinc deciency is very prevalent in the developing world, where mainly cereals are consumed. [176] Zinc supplementation improves growth and body weight gain, improves neuropsychological functions, reduces incidence and severity of acute and chronic diarrhoea and respiratory tract infections in children. Abnormal labour, retarded foetal growth, and foetal abnormalities are reported in case of zinc deciency during pregnancy. In the U.S., the Recommended Dietary Allowance (RDA) is 8 mg/day for women and 11 mg/day for men. Median intake in the U.S. around 2000 was 9 mg/day for women and 14 mg/day in men. Oysters, lobster and red meats, especially beef, lamb and liver have some of the highest concentrations of zinc in food. Harmful excessive supplementation is a problem among the relatively auent, and should probably not exceed 20 mg/day in healthy people. although the U.S. National Research Council set a Tolerable Upper Intake of 40 mg/day [177]. The best uptake was found to be zinc glycinate compared to gluconate, picolinat and zinc oxide [178]. Adequate intake of the nutrient can be achieved through diet or supplements, however, zinc levels intake above 40 milligrams should be avoided because of interference with iron and copper absorption. Zinc can be obtained in the diet from seafood and meats. Oysters have the highest zinc of all foods. The consumption of fruit juices stored in galvanized cans which leaches zinc has resulted in mass parrot dying. Human intoxication with zinc caused by storing potato salad in galvanized containers stored overnight are known. [179]
10.11.1
Zinc deciencylinked to Aging and multiple diseases [180]
Liuzzi et al. 2012 describe a biological mechanism by which zinc deciency may leade to a decline of the immune system and increased inammation associated with diseases such as cancer, heart disease, autoimmune disease and diabetes. The authors explain that the human suppressor of cytokine signaling 3 (SOCS3) gene contains four binding sites for the zinc regulatory transcription factor 1 (MTF-1), and the zinc transporter SLC39A14 is required for the expression of SOCS3 gene. The SOCS3 expression is regulated by zinc through an MTF-1-dependent mechanism. In this study dysregulation of zinc transporters were found in old animals with zinc deciency, increased inammatory response. The biomarkers of inammation returned to normal levels by increasing the dietary zinc intake by 10 times of normal requirements.
10.11. ZINC DEFICIENCY
861
The mechanisms to transport zinc are disrupted by these age-related epigenetic changes resulting in increased DNA methylation and histone modications that are related to cancer, immune system alterations and the ability to repair genetic damage decreases. Zinc depletion caused strands of their DNA to break, and increasing the intake of zinc reversed the damage back to normal levels. Studies focused on prostate cancer say that the prostate gland has high levels of zinc which drops rapidly when cancer starts. This suggests a possible zinc therapeutic strategy.
Anti-cancer metastasis activity of zinc [181] Lymburner et al. 2012 report that zinc, a divalent cation, can modulate breast cancer metastasis through interfering with the manganese and magnesium divalent cationdependent integrin-mediated cancer cell adhesion and migration. Metastasis depends on cell adhesion to extracellular matrix. Integrins are receptors that mediate the attachment between a cell and the tissues that surround it, such as other cells or the extracellular matrix, Binding of manganese and magnesium is vital to integrinmediated cancer cell adhesion and migration. inhibited MDA-MB-231 cell migration on bronectin by interfering with magnesium-dependent integrin-, likely integrin 5/ 1-, mediated adhesion.
Zinc signaling pathway, a target for anticancer drug development [182] Taylor et al. 2012 describe the activity of the protein kinase CK2 which triggers cytosolic zinc signalling pathways by phosphorylation of zinc channel ZIP7. The connection with proliferation and migration, as well as the activation of ZIP7 by CK2, a kinase that is antiapoptotic and promotes cell division, suggests that ZIP7 may provide a target for anticancer drug development. The discovery that CK2 opens ZIP7 suggests that drugs which block this release of zinc could also block cancer development. Zinc levels in cells are controlled by protein molecules called zinc transporters. Researchers found in this study that the protein CK2 opens the zinc transporter ZIP7. This zinc transportation is linked to some types of breast cancer.
Zinc deciency is related to alterations of the brain function [183] Zinc was found to be essential for brain growth and function. Subclinical zinc deciency described in Chinese, Mexican-American low-income children and middle income US citizens was associated with impaired brain function. A treatment with micronutrients and omnivorous diet improved brain status probably by enhancing zinc ecacy, writes Sandstead 2012.
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Adolescents in developing countries at high risk of zinc deciency [184] Unwholesome food habits and poor bioavailability of zinc from plant-based diets result in zinc deciency in developing countries such as India. Kawade 2012 reviewed studies on zink status of Indian adolescents. Indian girls showed a high prevalence of micronutrient deciencies. Half of the girls presented poor cognitive performance and 45% had poor salt taste perception. Results of the intervention trial indicated that supplementation of zinc-rich recipes improved cognitive performance and taste acuity in adolescent girls, stressing the importance of zinc and micronutrient-rich diets. Zinc deciency aects about two billion people in the developing world and is associated with many diseases. In children it causes growth retardation, delayed sexual maturation, infection susceptibility, and diarrhoea, contributing to the death of about 800,000 children worldwide per year. [185] There are 2-4 grams of zinc distributed throughout the human body. Most zinc is in the brain, muscle, bones, kidney, and liver, with the highest concentrations in the prostate and parts of the eye.
10.11.2
Food sources of Zinc [186]
A wide variety of foods contain zinc.Oysters contain more zinc per serving than any other food, but red meat and poultry provide the majority of zinc. Other good food sources include beans, nuts, certain types of seafood (such as crab and lobster), whole grains, fortied breakfast cereals, and dairy products.
Table 10.4: Recommended Dietary Allowances (RDAs) for Zinc [187] Age Male 0-6 month 2 mg* 7-12 month 3 mg 1-3 years 5 mg 4-8 years 8 mg 9-13 Years 11 mg 14-18 years 11 mg 19+ years Female Pregnancy 2 mg* 3 mg 5 mg 8 mg 9 mg 12 mg 8 mg 11 mg Lactation
13 mg 12 mg
U.S. Department of Agriculture, Agricultural Research Service. 2011. USDA National Nutrient Database for Standard Reference, Release 24. Nutrient Data Laboratory Home Page, http://www.ars.usda.gov/ba/bhnrc/ndl.
10.11. ZINC DEFICIENCY Table 10.5: Selected Food Sources of Zinc
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Food Mg/serving % DV* Oysters, cooked, breaded and fried, 3 ounces 74.0 493 Beef chuck roast, braised, 3 ounces 7.0 47 Crab, Alaska king, cooked, 3 ounces 6.5 43 Beef patty, broiled, 3 ounces 5.3 35 Breakfast cereal, fortied with 25% of the DV for zinc, 3/4cup 3.8 25 Lobster, cooked, 3 ounces 3.4 23 Pork chop, loin, cooked, 3 ounces 2.9 19 Baked beans, canned, plain or vegetarian,1/2 cup Chicken, dark meat, cooked, 3 ounces 2.4 16 Yogurt, fruit, low fat, 8 ounces 1.7 11 Cashews, dry roasted, 1 ounce 1.6 11 Chickpeas, cooked, 1/2 cup 1.3 9 Cheese, Swiss, 1 ounce 1.2 8 Oatmeal, instant, plain, prepared with water, 1 packet 1.1 7 Milk, low-fat or non fat, 1 cup 1.0 7 Almonds, dry roasted, 1 ounce 0.9 6 Kidney beans, cooked, 1/2 cup 0.0 6 Chicken breast, roasted, skin removed, 1/2 breast 0.9 6 Cheese, cheddar or mozzarella, 1 ounce 0.9 6 Peas, green, frozen, cooked, 1/2 cup 0.5 3 Flounder or sole, cooked, 3 ounces 0.3 2 DV = Daily Value. DVs were developed by the U.S. Food and Drug Administration to help consumers compare the nutrient contents of products within the context of a total diet. The DV for zinc is 15 mg for adults and children age 4 and older. Food labels, however, are not required to list zinc content unless a food has been fortied with this nutrient. Dietary supplements Supplements contain several forms of zinc, including zinc gluconate, zinc sulfate, and zinc acetate. The percentage of elemental zinc varies by form. For example, approximately 23% of zinc sulfate consists of elemental zinc; thus, 220 mg of zinc sulfate contains 50 mg of elemental zinc. Group at risk of zinc inadequacy People with gastrointestinal and other diseases People with gastrointestinal and other diseases Pregnant and lactating women Older infants who are exclusively breastfed People with sickle cell disease Alcoholics
864 Zinc Deciency [186]
Zinc deciency is characterized by growth retardation, loss of appetite, and impaired immune function. In more severe cases, zinc deciency causes hair loss, diarrhoea, delayed sexual maturation, impotence, hypogonadism in males, and eye and skin lesions. Weight loss, delayed healing of wounds, taste abnormalities, and mental lethargy can also occur. Many of these symptoms are non-specic and often associated with other health conditions; therefore, a medical examination is necessary to ascertain whether a zinc deciency is present. Dietary supplement Preparations mineral supplements include zinc oxide, zinc acetate, and zinc gluconate. Zink deciency aects the immune system. Zinc helps stimulate the action of more than 100 enzymes, and helps to stimulate the sense of smell. Zinc serves as a simple, inexpensive, and critical tool for treating diarrhoeal episodes among children in the developing world. Zinc becomes depleted in the body during diarrhoea, but recent studies suggest that replenishing zinc with a 10- to 14-day course of treatment can reduce the duration and severity of diarrhoeal episodes and may also prevent future episodes for up to three months. Zinc and common cold [188] The common cold is often caused by the rhinovirus. Zinc inhibits rhinoviral replication Singh et al. 2011 in a review of studies found that zinc administered within 24 hours of onset of symptoms reduces the duration and severity of the common cold in healthy people. When supplemented for at least ve months, it reduces cold incidence, school absenteeism and prescription of antibiotics in children. The authors warn of side eects of zinc side eects, therefore no recommendations are given about the dose, formulation and duration that should be used. Zinc supplement reduces severity of lower respiratory infections in young children [189] Shah et al 2012 report that the acute lower respiratory infections free days were higher in children less than 5 years supplemented with 10 mg zinc. The median recovery time of morbidity was signicantly shorter in zinc group. Micronutrients in milk products [190] Milk and dairy products are excellent sources of Calcium, Phosohor, Magnesium, Zinc, and Seandium. Vitamins A, D, E, and K are mainly located in the lipid phase and vitamins of group B and C in the aqueous phase. Milk and dairy products are excellent sources
10.11. ZINC DEFICIENCY
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of vitamins A, B(1), B(2), and B(12).B(3). In smaller concentrations the vitamins B(5), B(6), B(8), B(9) and C are present in the aqueous phase. According to Vissers et al.2011 dairy products contribute to the total intake intake in young children, of calcium (73%), selenium (21%), iron (8%), zinc (39%), copper (12%), folic acid (24%), vitamin C (18%), vitamin D (16%), and vitamin B(12) (58%). [191] Ergogenic supplements for performance enhancement for athletes [192] Mason and Lavalle 2012 found 6 common supplements which include glutamine, choline, methoxyisoavone, quercetin, zinc/magnesium aspartate, and nitric oxide. The authors call on health care professionals to advert athletes to safety and ecacy of supplements at tnes and bodybilding sites which are not supported by scientic evidence. Probiotics to increase bioavailiability of micronutrients [193] According to Mogna et al. 2012 micronutrient malnutrition aects >50% of the worldwide population. Zinc (Zn) deciency is considered a health problem in India and in other developing countries. The authors propose to use probiotic bacteria to assimilate Zn and Se to improve the bioavailiability of these elements. The authors report that Zn internalized by B. lactis Bb1 showed an absorption that was >16 times higher by Caco-2 cells compared with zinc gluconate and a 31.5 times higher absorption compared with zinc sulfate. Lactobacillus buchneri Lb26 (DSM 16341) turned Se 5.9, 9.4, and 65 times more absorbable than sodium selenite, seleno-L-methionine, and seleno-L-cysteine by Caco-2 cells. Probiotic bacteria may thus become a way to increase the bioavailiability of these microelements. Limited research on micronutrient supplementation and cognitive performance [194] More than 200 million young children worldwide fail to reach their potential in cognitive development owing to undernutrition. Micronutrient supplementation improve growth and cognitive development in infants, toddlers and preschoolers. Among key micronutrients assessed were iron, zinc, iodine and vitamin A. However, micronutrient interventions on the cognitive performance of older children aged 5-15 year are limited and remain equivocal. Zink supplementation during diarrhoea [195] Lazzerini and Ronfani report insucient evidence to evaluate whether zinc supplementation during acute diarrhoea reduces death or hospitalization. The authors write that in areas where the prevalence of zinc deciency or the prevalence of moderate malnutrition is high, zinc may be of benet in children aged six months or more. The use of zinc supplementation in children below six months of age is not indicated. Vomiting in both age groups are reported.
866
10.11.3
Bioavailability and food safety of L pidolic acid salts [196]
According to the Scientic Panel AFC of the European Food Safety Authority, the bioavailability of calcium, iron, magnesium, potassium and zinc are absorbed from their L-pidolic acid salts is comparable to that from other water-soluble and dissociable salts permitted to be used in food supplements and foods intended for particular nutritional uses. The use of calcium, iron, magnesium, potassium and zinc L-pidolic acid salts as source of these minerals for nutritional purposes to food supplements is of no safety concern at the maximum use levels of L-pidolic acid of 3 g/day.
10.11.4
Magnesium, calcium and zinc as L-lysinate in supplements were found safe by EFSA [197]
The European Food Safety Authoritys Panel on Food Additives found Magnesium Llysinate, calcium L-lysinate and zinc L-lysinate as sources for magnesium, calcium and zinc in supplements as safe. The Panel says that a dose twice of what is found in normal diets is considered of no safety concern. The used supplements are salts of the amino acid L-lysine. L-Lysine, following ingestion, is absorbed and transported to the liver. The Panel calculated that less than 9 g/day of lysine are ingested to provide a supplementation of 250 mg Mg/day, 800 mg Ca/day and 15 mg Zn/day. In a worst case assumption the Panel estimated the potential exposure to lysine to be up to 353 mg/kg bw/day for an adult with a standard body weight of 60 kg. These values are low compared to the level of lysine in protein rich foods. Based on present data the Panel concluded that the use of magnesium L-lysinate, calcium L-lysinate and zinc L-lysinate used in food supplements as a source of respectively magnesium, calcium and zinc is not of safety concern at the proposed use levels.
10.11.5
Fortication of dairy products with magnesium [198]
According to Maud Cansell and colleagues about 20 per cent of the French population present a magnesium deciency. Undersupply of this mineral has been linked to high blood pressure, cardiovascular diseases, muscular weakness, and diarrhoea. The authors studied the supplementation of magnesium in foods like dairy products. Magnesium can induce in these foods chemical degradations, protein aggregation and generate an unpleasant taste. To avoid this the researchers created a blend of rapeseed oil, olive oil, olein, and/or miglyol. Polyglycerol polyricinoleate and sodium caseinate which traps the magnesium in the interior of a Water/Oil/Water emulsion. The unwanted reactions are
10.12. BIOACTIVE COMPOUNDS OF TROPICAL FRUITS TO STABILISE NEURODEGENERATING DISEASES
867
avoided, and magnesium is released from the W/O/W emulsion by hydrolysis of the oil in the intestine. The emulsion is stable during pasteurisation.
10.11.6
Divalent ions decrease uptake of carotenoids [199]
Biehler et al 2011 stress that carotenoids, in order to become bioactive, require micellarization and intestinal uptake. Using an in vitro digestion model, the authors found that the divalent ions Ca and Mg and Zn and Fe reduced the necessary micellarization and cellular uptake of carotenoids of spinach. Fe and Zn presented the strongest inhibition. However, the authors found an improved fractional cellular uptake from the micelles for all ions by up to 5-10 times, including neochrome (from neoxanthin) and luteoxanthin+auroxanthin (from violaxanthin). Divalent ions inhibition of carotenoid micellarization and uptake must be considered, when supplementation with these four ions take place.
10.11.7
Eect of sport supplements are unknown [200]
Manson and Lavalle report that nutritional supplements advertised as ergogenic are commonly used by athletes at all levels. Common tness and bodybuilding supplement promotions include glutamine, choline, methoxyisoavone, quercetin, zinc/magnesium aspartate, and nitric oxide. The authors caution that the eects of these supplements on performance in athletes are not unknown and there are no studies which support the use of these supplements for performance enhancement.
10.12
10.12.1
Bioactive compounds of tropical fruits to stabilise neurodegenerating diseases

Anthocyanin-rich acai camu-camu, and blackberries stabilize the pro-/antioxidant balance
Ellinger et al 2012 report that exotic fruits like acai camu-camu, and blackberries are marketed as "functional" food supporting a pro-/antioxidant balance. Ellinger and colleagues, in a randomized controlled crossover trial, found that the anthocyanin-rich fruit juice may stabilize the pro-/antioxidant balance without aecting markers of oxidative stress. [201] Such oxidative stress may lead to nerve diseases such Alzheimers disease, Parkinson and even ALS, diseases linked to locomotor impairment resulting from damage of the neuronal system.
868
Bioactive Compounds in Tropical Fruits [202] Studies on Euterpe oleracea (aa) and Myrtillocactus schenckii (garambullo) revealed that the antioxidant capacity and amounts of phenolic compounds of aa and garambullo decreased in the course of ripening. However, Anacardium occidentale (cashew apple) was found to be rich in ascorbic acid, which even increased during maturity. Polyphenolic compounds in fruits from the Amazon region, Byrsonima crassifolia (muruci), Syzygium cumini (jambolo), Psidium guineense (ara), and Pouteria macrophylla (cutite) were gallotannins, ellagitannins, quinic acid gallates, avanonols, avonols, and proanthocyanidins. The determination of the antioxidant capacity resulted in following ranking: cutite > jambol o > arac > muruci. In regard to its radical scavenging properties, cutite fruits could be put in part on a level with the extremely eective acai. The study of Gordon 2012 also presents the chemical composition of ripe fruits of Clidemia rubra. The author found a high a high content of dietary ber and Ca, Mn, and Zn minerals. high concentrations of anthocyanins and various avonol glycosides. The author suggests to develop methods in order to isolate phenolic compounds as dietary supplements, functional foods or natural additives. Unsing high speed countercurrent chromatography the author isolated cyanidin 3-O-rutinoside from Clidemia rubra berries with 98% purity. Antioxidant capacity of berries of Clidemia rubra [203] According to Gordon et al 2011 Clidemia rubra (Aubl.) Mart.(mlastome rouge, mlastome velu.) presents anthocyanidins concentration of cyanidin 3-O-rutinoside 39.43, delphinidin 3-O-rutinoside 23.74, cyanidin 3-O-glucoside 11.68 and delphinidin 3-O-glucoside 6.08 mg/100 g fresh weight. Non-anthocyanin phenolic constituents were phenolic acids such as gallic, protocatechuic, p-hydroxy-benzoic, vanillic, and caeic acid), avan-3-ols (epigallocatechin, epigallocatechin gallate, and epicatechin gallate. Anthocyanins and ascorbic acid were mainly responsible for the antioxidant capacity of Clidemia rubra berries. Multivitamins May Lower Cancer Risk in Men [204] The daily use of multivitamins may reduce the risk for cancer in men, according to the results of a very large randomized trial. After about 11 years, multivitamin use resulted in a modest but statistically signicant 8% reduction in total cancer incidence. The authors stressed that the main reason to take a multivitamin is for nutritional deciencies but it certainly appears that there may be a modest benet in preventing cancer in men over the age of 50. High doses of individual vitamins and other studies of multivitamins have not shown any eect at preventing cancer, Dr. Gaziano explained. However, this study is a large-scale
10.13. PREVENTION OF PROSTATE CANCER
869
long follow up of 14 years. Their results showed that men taking a daily multivitamin had a statistically signicant reduction in the incidence of total cancer. However, when the cancers were considered separately, there was no signicant eect. There was no eect of the daily multivitamin on prostate cancer or any other site-specic cancers. Dr. Graziano will continue more analyses, looking at the nutritional status of the individuals. Controversial studies Some studies have reported conicting results. The use of multivitamins to reduce the risk of invasive breast cancer was examined in the Swedish Mammography Cohort. Larsson et al 2010 reported that multivitamin use is associated with an increased risk of breast cancer. [205] The study of the Womens Health Initiative performed a study with a median followup of 8.0 and 7.9 years looked at the results of the use of multivitamines documenting cancers of the breast (invasive), colon/rectum, endometrium, kidney, bladder, stomach, ovary, and lung; CVD (myocardial infarction, stroke, and venous thromboembolism); and total mortality. Neuhouser et al 2009 concluded that multivitamin use has little or no inuence on the risk of common cancers, CVD, or total mortality in postmenopausal women. [206] Following the latest data of the Physicians Health Study II Randomized Controlled Trial Dr. Graziano and colleagues concluded that daily multivitamin supplementation modestly but signicantly reduced the risk of total cancer.
10.13
Prevention of prostate cancer
Green tea and its major constituent epigallocatechin gallate (EGCG) have been studied in prevention and potential treatment for prostate cancer. The disease requires decades to develop and may therefore be inuenced by measures which demand long exposure to the active agent. [207] Wang, Heber and Henning 2012 found that green tea quercetin and (-)-epigallocatechin gallate (EGCG) synergistically inhibited cancer cells by increasing the intracellular concentration of EGCG and decreasing EGCG methylation. The synergistic eect of these 2 agents could be based on the fact that EGCG primarily inhibited catechol-O-methyl transferase (COMT) activity, whereas quercetin reduced the amount of COMT protein. [208]
10.13.1
Green tea as chemoprevention of prostate cancer
Prostate cancer is the second most common cause of cancer deaths in American. Multiple mechanisms are involved in the chemoprevention of prostate cancer with GTCs. Connors,
870
Chornokur and Kumar 2012 presented a review of major mechanisms of green tea catechins and the epigallocatechin gallate chemopreventative action on prostate cancer. [209] Green tea provides better protection of prostate cancer than black tea [210] The vast majority of the tea consumed in the world is black tea. Henning, Wang and Heber 2011 explain, however, that green tea contains higher concentrations of monomeric polyphenols which reduce the risk of prostate cancer development. Black tea polymers are poorly absorbed and are converted to phenolic acids by the colonic microora. Higher concentrations of polyphenols are found in the circulation consuming green tea compared to black tea consumption, which presents higher phenolic acid levels. The polyphenols and epigallocatechin gallate of green tea are protected from oxidising enzymes which are inactivated by heat during tea production. The incidence of prostate cancer is low in Asian countries, probably due to isoavones of high intake of soy and tea, sh, fruits and vegetables and the reduced intake of red meat and fatty foods by comparison to the Western diet. However, the incidence of the disease is increasing rapidly in Asian countries due to a more westernized lifestyle. [211] Brewed green tea inhibits prostate tumour growth in male rats [212] Henning et al. 2012 report that brewed green tea decreased the tumour volume of rats with prostate cancer. Green tea polyphenol content in tumour tissue correlated with tumour size decrease. The authors found a reduction in hypoxia-inducible factor 1-alpha and vascular endothelial growth factor protein expression, a reduction of oxidative DNA and protein damage in tumor tissue, and reduced methylation which inhibit antioxidative enzymes such as glutathione S-transferase pi. Such methylation is responsible for tumour growth. Green tea inhibited tumor 5-cytosine DNA methyltransferase 1 mRNA and its protein expression. Green tea polyphenoles and metabolites in tissue [213] Epidemiologic, preclinical, and clinical trials suggest that green tea consumption may prevent prostate cancer through the action of green tea polyphenols including (-)-epigallocatechin3-gallate (EGCG). Wang et al 2010 found that in the urine of men consuming green tea, 50% to 60% of both (-)-epigallocatechin and (-)-epicatechin were present in methylated form. Green tea polyphenols present in human prostate tissue following consumption of 6 cups of green tea, during two month, are EGCG and methylated EGCG, and to a lesser extent (-)-epicatechin-3-gallate (ECG). The methylation status of EGCG reduced the protective eect on prostate cancer. Green tea inhibits the growth of prostate cancer tumours by decreasing inammation and stimulating apoptosis aecting biomarkers in prostate tissue. The serum prostate-specic antigen (PSA) levels in serum and in prostate tissue was signicantly reduced by green tea
10.14. ACAI PROTECTION OF NEURONAL DAMAGE consumption. Other biomarkers also improved, concluded the authors.
871
In a study of 2006 Bettuzzi and colleagues write that green tea catechins are safe and very eective for treating premalignant lesions before prostate cancer develops. The green tea catechins also reduced lower urinary tract symptoms, and may be used in treating the symptoms of benign prostate hyperplasia. [214]
10.14
10.14.1
Acai protection of neuronal damage

Muscle-specic p38 MAPK/Mef2/MnSOD pathway regulates stress, motor function and lifespan [215]
Vrailas-Mortimer et al 2011 describes the p38 MAP kinase (p38K)/Mef2/MnSOD pathway which is a coregulator of stress and life span in Drosophila.the authors found that overexpression of p38K extends life span in a MnSOD-dependent manner. The inhibition of p38K causes early lethality and precipitates age-related motor dysfunction and stress sensitivity, that is rescued through muscle-restricted (but not neuronal) add-back of p38K. The p38K-Mef2-MnSOD signaling module is muscle-restricted and is distinct from the insulin/JNK/FOXO pathway. According to the authors the p38K pathway may be addressed to restore the mitochondrial detoxication and reduce stress-induced ageing. Disruption of the p38K and MAP signalin pathway may lead to muscle damage [216] The p38K and MAP are a member of the subfamily of the SAPKs (stress activated protein kinases). These protein kinases are involved in a variety of cellular signaling pathways. p38K is activated by a number of extracellular stressors, such as the reactive oxygen species (ROS) released by oxidative stress, leading to mitochondrial dysfunction and apoptotic death in many cell types such as happens in Parkinsons disease. Tania del Rivero and her team found that locomotor decits result from overexpressing the dominant-negative form of p38b in all cell types. These decits are observed when p38K is solely inhibited in muscle cells. del Rivero concluded that such locomotor impairment may be caused by an increase in oxidative stress-related damage in the muscles resulting from the disruption of the p38K signaling pathway. Oxidativer Stress and Acai extracts [217] Vrailas-Mortimer et al 2012 report that a large number of putative antioxidant compound formulations are often not tested for their ecacy or regulated for quality control. The authors developed a Drosophila model of oxidative-stress dependent ageing (p38 MAP K (p38K) mutants) to test the eect of some of these commonly available formulations against oxidative stress, in the p38K model. Chemically-induced models of oxidative stress
872
(paraquat and hydrogen peroxide exposure) was also used to test these supplements in their ability to protect against environmental exposure to oxidizing toxins which are linked to a series of human diseases. The authors found that some dietary supplement, containing acai extracts, confer significant protection for both the p38K-dependent genetic model as well as the toxin-induced model. They also reduced stress-induced expression of the detoxifying enzyme GSTD1 and helped to eliminating paraquat induced circadian rhythm decits. The authors concluded that some dietary supplements are especially eective when elevated oxidative stress is present.
10.15
Food marketing exagerate polyphenol rich fruits and juices health eects
The acai palm is native to Central and South America, from Belize southward to Brazil and Peru. These palms grow mainly in swamps and oodplains. Acai palms are fast-growing, and are cultivated for both their fruits and for their superior hearts of palm. Global demand for the fruit has expanded rapidly in recent years, and aca is now cultivated for that purpose primarily. [218] According to David Heber and colleagues 2008 claims to have superior antioxidants or the new marketing term "superfoods" and "superfruits" including acai, mangosteen, noni, sea buckthorn, and Chinese wolfberry (goji) is based on in vitro antioxidant assays, and most of them lack clinical evidence of the eects on physiological function [219]. Many foods are highlighted as disease ghting foods, awakening hope to cure cancer, Alzheimers disease, coronary artery diseases, improve sexual activity. The food and beverage industry and food supplement manufacturers explore the fears, the hope and eagerness to improve physical status or to look after anti-ageing products. The industry commercialised ready-to-drink polyphenol-rich beverages supported by heavy marketing activities covering health, sport and wellness. The study of David Heber compared the antioxidant content and the in vitro inhibition of LDL (average) of polyphenol-rich beverages on market. The researchers found that acai was in the middle of these products, far behind pomegranade juice (Punica granatum) (97%), Red wine (69%), Concorde grape juice (38.4%), blueberry juice (48.6%))and black cherry juice (34.2%), cranberry juice (38.8%), acai (19.6%). Other beverages presented low inhibition, such as orange juice(10.3%), apple juice (1,4%), iced green tea (12.5%), iced black tea (11.8%) and iced white tea (8.4%). The authors say that some beverages must be consumed in much larger amounts to have
10.15. FOOD MARKETING EXAGERATE POLYPHENOL RICH FRUITS AND JUICES HEALTH EFFECTS 873 the same eect of pomegranade juice or red wine. These two do have eects in humans including anti-inammatory eects.
10.15.1
No weight reduction and other miraculous eects with acai pills [220] [221]
The Center for Science in the Public Interest is warning consumers not to enroll online in supposedly free trials of diet products made with the trendy Brazilian berry acai. The Center says that there is no evidence whatsoever to suggest that acai pills will reduce body weight, atten tummies, cleanse colons, enhance sexual desire, or perform any of the other commonly advertised functions. Lyndy Johnson, a nutritionist of the University of Missouri Extension, recommends to eat more fresh or frozen blueberries and strawberries, which are readily available and less expensive than acai. Consumers are being warned about online vendors of acai products oering pricey monthly subscriptions that are dicult to cancel.[222] Bioactive compounds in plants [223] Kinghorn and colleagues 2010 assessed bioactive compounds from acai (Euterpe oleracea), baobab (Adansonia digitata), licorice (Glycyrrhiza glabra), mangosteen (Garcinia mangostana), and noni (Morinda citrifolia). Some of these compounds presented strong biological activity, however, their concentration in plants were very low. Acai increases lifespan of ies on high fat diet and reduces oxidative stress in aging [224] Sun and colleagues 2010 report that feed with 2% acai pulp increased the lifespan of female ies fed a high fat diet compared to the non-supplemented control through activation of stress response pathways and suppression of Pepck expression. The authors concluded that acai helps acts against the eect of fat in the diet and oxidative stress in ageing. Reduction of oxidative stress and improvement of blood fat prole of rats [225] The supplementation of 2% acai (Euterpe oleracea Mart.) pulp of a hypercholesterolemic diet improved the antioxidant status and has a hypocholesterolemic eect in an animal model on high fat diet reducing total and low-density lipoprotein cholesterol, compared with control groups. Acai pulp found to protect against cancer of liver and kidney cells [226] Acai pulp was found bei Ribeiro and colleagues to contain carotenoids, anthocyanins, phenolic, and avonoids in acai pulp. In this study the authors demonstrated the absence of genotoxic eects of acai and report protecte its protecting activity against DXR-induced
874
DNA damage in liver and kidney cells. The ndings are important for development of functional foods and provide informations for the study of acai as a health promoter. Acai may reduce development of neurodegenerative diseases [227] The authors suggest that acai may reduce impairments of age-related neurodegenerative diseases, such as Parkinsons and Alzheimers diseases, reducing the oxidative stress. The authors pretreated tissue of the cerebral cortex, hippocampus, and cerebellum of rats with acai pulp which performed better than not treated tissue when exposed to (H(2)O(2)) as oxidatve stress. Eect of berry juices are exagerated Commercial juices are labelled as nectar of fruit drinks. Their content of natural juice is 20 per cent or below. Their physiological eect is therefore comparable with a fruit and vegetable rich nutrition. Here are some publications which originated from a same group of researchers.
10.15.2
Anti-inammatory activity of green-lipped mussel extracts. [228] [229]
Treschow, together with Hodges and colleagues identied a family of omega-3 PUFAs which included C18:4, C19:4, C20:4, and C21:5 PUFAs in the green-lipped or green shell mussel Perna canaliculus. The C20:4 was the predominant PUFA in the extract, and was a structural isomer of arachidonic acid. These fatty acids presented signicant anti-inammatory activity in vitro. According to the authors, the special conguration of the double bonds, located at positions 7, 11, 14 and 17, and two methylene groups positioned between the rst and the second carbon atom inhibits the production of leukotriene and prostaglandin metabolites. The authors suggest that the novel compounds may be biologically signicant as anti inammatory agents, due to their in vitro inhibition of lipoxygenase products. Chronic inammation may be linked to heart disease, osteoporosis, cognitive decline and Alzheimers, and type-2 diabetes. Some producers extract the oil from the dried mussel meat for specic uses. The fat free powder is then marketed as food supplement rich in glycosaminglycane, which is told to be a base substance for connective tissue and cartilage. Some suppliers complain that extracts without the lipid fractions and with less anti-inammatory eect are cheaper than mussels with the oil fraction. They call for a correct labelling of the products which are degreased an those who are not.
10.15. FOOD MARKETING EXAGERATE POLYPHENOL RICH FRUITS AND JUICES HEALTH EFFECTS 875
10.15.3
Yeast extract under the inuence of expanding bioethanol [230]
Increased cost of sugar molasses due to the European sugar reform, together with the increased use of bioethanol which reduces supplies available to the food ingredients industry, and high fossil fuel cost for energy used by industry for process, increase the price of yeast extract. Yeast extract produced from sugar molasses by the yeast Saccharomyces cerevisiae, is increasingly being used in convenience foods as savoury ingredient and healthy ingredient as a substitute for salt and monosodium glutamate.
10.15.4
Fish oil supplementation improves large arterial elasticity [231]
Wang and colleagues 2007 found that a supplementation of 3 g sh oil during 8 weeks improved the large arterial elasticity (C1), but had no eect on blood pressure in overweight hypertensive patients. The elasticity of the small artery (C2),was not changed. The authors conclude that sh oil supplementation can improve large arterial elasticity but has no eect on blood pressure. They call for more studies on this matter.
10.15.5
Docosahexaenoic acid (DHA) improves cognition in agerelated cognitive decline (ARCD) and reduces the risk of Alzheimer disease [232]
The "Memory Improvement with Docosahexaenoic Acid Study" (MIDAS) by Yurko-Mauro and colleagues 2010 says that 6 month supplementation with 900 mg/d docosahexaenoic acid (DHA) may improve memory and learning in older adults with mild cognitive impairments. The authors say that low DHA levels are associated with cognitive decline in healthy elderly and Alzheimers patients, high DHA levels help reduce the risk of Alzheimers disease. The MIDAS study focused on a population of healthy adults with age-associated memory impairment.
10.15.6
No benet of DHA, however, in patients previously diagnosed with Alzheimers disease [233]
Quinn and colleagues found in a study published in 2010 that DHA did not caused signicant benet on cognitive function in patients previously diagnosed with Alzheimers disease. The authors stress that their results should not be applied to groups where DHA
876 is administered before the disease apparent.
DHA supplements, and other dietary supplements should be taken over time and before a disease becomes notorius. Heathy nutritional habits should include a well-balanced diet, regular physical activity and dietary supplements may slow down ageing impairments, such as age-associated memory impairment.
10.15.7
Polysaccharides from brown marine algae as health benets promising ingredient [234]
Seaweeds, such as Laminaria spp, are rich in polysaccharides which are classied as dietary bres, because they are resistant to hydrolysis in the upper gastrointestinal tract. Human digestive enzymes did not hydrolyse laminarin, so this polysaccharide can be considered as a dietary bre. Laminarin is a beta-1,3-Glucan and function as a storage substance which can be compared to starch in plantson land. It is commonly obtained from the brown kelp alga Laminaria digitata. [235] Alginates are currently used as low-cost thickening and viscosity stabilisers for such products as salad dressings, and for microencapsulated ingredients.
10.15.8
Isolation
Isolation of water insoluble laminarin-like polysaccharide has been achieved from Sargassum linifolium by extraction with hydrochloric acid and oxalic acid solutions, according to Abdel-Fattah and Hussein [236]. Devill and colleagues found a hot HCl-based method as best strategy to isolate laminarin. [234]
10.15.9
Laminarin as imuno-stimulant agent
K H Kim and colleagues suggest that laminarin oligosaccharides and polysaccharides from Laminaria japonica, can be utilized to develop new immunopotentiating substances and functional alternative medicines [237]. Franck Hennequart and colleagues from the National University of Ireland in Galway, Health Sea International Symposium in Granville, Normandy in October. 2007. announced to have produced and identied four dierent extracts from the seaweeds, intended to be used in a range of drinks, including mineral water, orange juice and cold tea. According to Hennequart crude fucodians seem to demonstrate a prebiotic eect. The seaweed extracts were found to have anti-bacterial activity on some bacteria. Some of the extracts seem to have an anti-inammatory eect. Tests on rats have shown no toxicological eects so far. [238]
10.15. FOOD MARKETING EXAGERATE POLYPHENOL RICH FRUITS AND JUICES HEALTH EFFECTS 877
10.15.10
Bioavailability of calcium from soymilk
Soymilk are often enriched with 120mg/100ml with calcium phosphate, calcium carbonate, or calcium chloride to obtain an equivalent content of calcium of cow milk. However poor solubility reduce bioavailability of calcium from soymilk. Tang and colleagues 2007 found that fermentation of calcium-fortied soymilk with probiotic bacteria such as Lactobacillus acidophilus ATCC 4962 and L. casei ASCC 290 increased the calcium solubility up to 89 per cent, enhancing bioavailability. The low pH resulted from the production of lactic and acetic acid was found to cause the increased solubility. The increase in calcium solubility observed was related to lowered pH associated with production of lactic and acetic acids. The conversion of the glucoside isoavones into the bioactive isoavone aglycone form was also observed. The fermentation signicantly increased also the conversion of isoavones from their natural glucoside form into the biologically active aglycone forms such as diadzein, genistein and glycetein.
10.15.11 10.15.12
Disagreement between epidemiological/observational studies and randomised clinical trials [239] Observational study
In statistics the goal of an observational study is to draw inferences about the possible eect of a treatment on subjects, where the assignment of subjects into a treated group versus a control group is outside the control of the investigator. This is in contrast with controlled experiments, such as randomized controlled trials, where each subject is randomly assigned to a treated group or a control group before the start of the treatment. A major challenge in conducting observational studies is to draw inferences that are acceptably free from inuences by overt biases, as well as to assess the inuence of potential hidden biases. A bias is a prejudice in a general or specic sense, usually in the sense for having a preference to one particular point of view or ideological perspective. However, one is generally only said to be biased if ones powers of judgement are inuenced by the biases one holds, to the extent that ones views could not be taken as being neutral or objective, but instead as subjective. Observational studies serve a wide range of purposes, on a continuum from the discovery of new ndings to the conrmation or refutation of previous nding. Some studies are essentially exploratory and raise interesting hypotheses. Others pursue clearly dened hypotheses in available data. In yet another type of studies, the collection of new data is planned carefully on the basis of an existing hypothesis. [240]
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STROBE
In 2007, several prominent medical researchers issued the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement, in which they called for observational studies to conform to 22 criteria that would make their conclusions easier to understand and generalise. [240]
10.15.14
Randomized controlled trial (RCT)
A randomized controlled trial (RCT) is a type of scientic experiment most commonly used in testing healthcare services. RCTs are considered the most reliable form of scientic evidence in healthcare because they eliminate spurious causality and bias. RCTs are mainly used in clinical studies, but are also employed in other sectors such as judicial, educational, and social research. involve the random allocation of dierent interventions (or treatments) to subjects. This ensures that known and unknown confounding factors are evenly distributed between treatment groups. Traditionally the control in randomized controlled trials refers to studying a group of treated patients not in isolation but in comparison to other groups of patients, the control groups, who by not receiving the treatment under study give investigators important clues to the eectiveness of the treatment, its side eects, and the parameters that modify these eects.
10.15.15
Open trial
In an open trial, the researcher knows the full details of the treatment, and so does the patient. These trials are open to challenge for bias, and they do nothing to reduce the placebo eect. However, sometimes they are unavoidable, particularly in relation to surgical techniques, where it may not be possible or ethical to hide from the patient which treatment he or she received. Usually this kind of study design is used in bioequivalence studies.
10.16
10.16.1
Blind trials
Single-blind trial
In a single-blind trial, the researcher knows the details of the treatment but the patient does not. Because thepatient does not know which treatment is being administered (the new treatment or another treatment) there might be no placebo eect.
10.16. BLIND TRIALS
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10.16.2
Double-blind trial
In a double bling trial, one researcher allocates a series of numbers to new treatment or old treatment. The second researcher is told the numbers, but not what they have been allocated to. Since the second researcher does not know, they cannot possibly tell the patient, directly or otherwise, and cannot give in to patient pressure to give them the new treatment. Therefore double-blind (or randomized) trials are preferred, as they tend to give the most accurate results.
10.16.3
Triple-blind trial
The most common meaning is that the subject, researcher and person administering the treatment are blinded to what is being given. Alternately, it may mean that the patient, researcher and statician are blinded.
10.16.4
Diculties
A major diculty in dealing with trial results comes from commercial, political and/or academic pressure. Most trials are expensive to run, and will be the result of signicant previous research, which is itself not cheap. There may be a political issue at stake (compare or vested interests . In such cases there is great pressure to interpret results in a way which suits the viewer, and great care must be taken by researchers to maintain emphasis on clinical facts.
10.16.5
The Tatsioni analysis on disagreements between epidemiological/ observational studies and randomised clinical trials [241]
Athina Tatsioni and colleagues evaluated the citations for two highly cited observational studies for cardiovascular benets associated with vitamin E supplementation and publications related to the protective eects of beta-carotene on cancer and estrogen on Alzheimers disease They looked for an explanation how these benets continue to be defended in literature, despite contradicting evidence from large RCTs. In this trial despite the eventual accumulation of strongly refuting evidence, even in 2005, half of the articles citing these epidemiological studies were still favourable to the vitamin E claim. The same situation was observed for beta-carotene, said the authors. "In 2006 more than half of the articles citing the highly cited epidemiologic articles on beta-carotene for cancer prevention remained favourable for these interventions. The authors concluded that Claims from highly cited observational studies persist and
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continue to be supported in the medical literature despite strong contradictory evidence from randomized trials. According to the authors dierential interpretation, inappropriate entrenchment of old information, lack of dissemination of newer data, or purposeful silencing of their existence is to be blamed for this situation. "
10.16.6
Controversity of results between observational and randomized clinical trials [242]
According to Andrew Shao, Ph.D., vice president, scientic and regulatory aairs, Council for Responsible Nutrition research may seem to contradict itself, however, that should not be interpreted to mean one type of study trumps another, particularly when dierent studies ask and answer dierent questions. Seemingly conicting data can exist side by side, when one understands that not all studies are asking the same questions in the same populations. Dr. Shao says "this suggests that researchers interpret research dierently, depending on their bias and expertise. For pure scientic purposes, heres a valid hypothesis to test: conduct a trial on secondary prevention in heart patients with a lifetime of bad habits that likely contributed to their heart disease to determine if a nutrient might provide some benet. But its not valid to conclude from the results of that study that the nutrient doesnt work. We cant expect a simple vitamin supplement to reverse heart disease. So if that doesnt happen, we must interpret the results appropriately by placing the study in the proper context and acknowledge that the results dont answer the question of whether supplemental amounts of vitamin E in a healthy population could have prevented heart disease had it been used consistently over time in combination with other antioxidants." Dr. Shao states, "The Randomized Clinical Trials RCTs with negative results attempted to answer the question, can a supplemental nutrient treat or reverse a disease or a lifetime of unhealthy habits in patients who are also taking prescription medications?" The observational studies with positive results attempted to answer the question, "if we start with a mostly healthy population generally free of disease, can we identify various diet/nutrient and lifestyle factors that make them more or less prone to disease?" "These are very dierent questions, making the studies incompatible for direct comparison and demonstrating that one type of study cant necessarily be used to refute the other. We rmly believe that RCTs should not be thought of as the only rigorous research approach. As the study authors point out, when randomized and observational studies disagree, it is incorrect to assume that nonrandomized studies are always wrong. Rather, we should put studies into the appropriate context and evaluate the total body of evidence, which includes RCTs and observational studies, and other types of research."
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10.16.7
The Chorane Study reinforces warning of antioxidants supplements [243]
The Cochrane study by Bjelakovic and colleagues was initially heavily criticised by the supplement industry, pointing out some errors. The authors published therefore a corrected version in JAMA (2008, Vol. 299, pp. 765-766). The new version reinforces the conclusions of the original version writing that current evidence does not support the use of antioxidant supplements in the general population or in patients with certain diseases. Vitamin A, beta-carotene, and vitamin E may increase mortality. The authors call for more studies on benecial and harmful eects on Vitamin C and selenium. The authors stress further that antioxidant supplements need to be considered medicinal products and should undergo sucient evaluation before marketing. Antioxidant supplements for treatment of specic diseases, supplementation for specic needs of antioxidants, or the eects of antioxidants contained in fruits or vegetable were not assessed by the study. and more studies on this matter are needed.
10.16.8
Researcher recommend to be cautious in taking antioxidants [244]
Chronic reactive oxygen species (ROS) production by mitochondria may contribute to the development of insulin resistance, a primary feature of type 2 diabetes. Rieusset and colleagues 2008 report that high-fat, high-sucrose diet resulted in mitochondrial defects, insulin resistance and type 2 diabetes in rats. The authors explained that alterations in mitochondrial function were the result, and not the cause, of insulin resistance in mice. Their data suggest that chronic reactive oxygen species (ROS) production was the cause of the mitochondrial dysfunction, and antioxidants could avoid it. The authors concluded that treatment of diabetics with medications to block ROS production or its eects might may help conventional diabetes therapies. [245] Dandona and colleaguies 2007 even state that caloric intake in the form of orange juice or fructose does not induce either oxidative or inammatory stress, possibly due to antioxidant activity of avonoids of the juice. [246] However, Tiganis and colleagues 2009 say that physiological low levels of Chronic reactive oxygen species (ROS) may promote the insulin response and attenuate insulin resistance early in the progression of type 2 diabetes, prior to overt obesity and hyperglycemia. The study lead by Tiganis found that mice lacking glutathione peroxidase 1 (Gpx1),an enzyme which eliminates ROS were protected against diabetes. The administration of anCopyright 1998-2010 Karl H. Wilm. All rights reserved. OurFood Database of Food and Related Sciences
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tioxidants started the type 2 diabetes in these rats. Tiganis says that antioxidants have negative eect in early type 2 diabetes and the development of insulin resistance. The increase of ROS may, under certain conditions, be helpful to avoid diabetes. However, it is necessary to determine when the eect of ROS are benecial or become harmful. The authors suggest not to take daily antioxidant vitamins when there are no special indications to do so, and recommend exercise as a sound source of ROS.
10.16.9
Extract from red yeast Chinese rice Xuezhikang (XZK) reduced cardiovascular events and death [247]
David M. Capuzzi and colleagues 2008, report that treatment with XZK decreased CV and total mortality by 30% and 33%, the need for coronary revascularization by 1/3. According to the authors total and low-density lipoprotein cholesterol and triglycerides were lowered, and the good high-density lipoprotein cholesterol levels were raised. They concluded that long-term therapy with XZK decreased the recurrence of coronary events. New cardiovascular events and deaths were reduced. Xuezhikang is prepared from rice cultivated with the mold Monascus purpureus. The extract contains components of lovastatin, a drug which lowers bad cholesterol. The FDA isued a safety warning on red rice extracts due to its content of this drug.
10.16.10
FDA warning to avoid red yeast rice products [248]
The products are promoted as dietary supplements for treating high cholesterol. FDA says that side eects associated with lovastatin of red yeast rice are adverse interaction with other medications, it can cause severe muscle problems leading to kidney impairment. See the FDA warning at: http://www.fda.gov/bbs/topics/news/2007/new01678.html
10.16.11
Functional cheese with increased polyphenols [249]
Han and colleagues 2010 developed a functional cheese with 0.5 mg/ml single phenolic compounds, including catechin, epigallocatechin gallate (EGCG), tannic acid, homovanillic acid, hesperetin and avones, and natural crude compounds, such as grape extract, green tea extract, and dehydrated cranberry powder in the cheese curd. The authors report good retention of the added polyphenols. The gel-formation depended on the molecular properties and the hydrophobicity of the added phenolic compounds. Homovanillic and tannic acids reduced the pH of the cheese curd more that the natural crude compounds. The free radical-scavenging activity of the cheese was better than the eect of control cheese without added polyphenols.
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Addition of polyphenols to dierent types of cheese, yoghurt, milk shakes or other dairy products may improve their quality and functionality, say the authors.
10.16.12
Development of functional ingredients and foods [250]
The market for functional ingredients and foods experiences a steadily growth resulting of healthier eating and lifestyle habits of the consumers. Day andd colleagues 2 009 stress the importance of functional ingredients not getting lost during the food processing, that they remain active and their bioavailability is guaranteed during storage. This should be tested before placing new bioactives and functional food ingredients on market. The authors present an approach of the development of functional ingredients and foods, using dermatan sulphate and black carrot concentrate as examples.
10.16.13
Nonmedical and medical literature often unreliable, says author [251]
Glisson and colleagues 2010 write that dietary supplements are not regulated by FDA and are often used as "alternative" or "complementary" therapy, leaded by subjective claims such as anticancer, anti-inammatory, cardiovascular protection. Safety and possible eect have often never been assessed. Pharmacodynamic and pharmacokinetic data of dietary supplements are limited and of meager quality. Nonmedical literature related to dietary supplements are often of poor quality. The authors advise physicians to take great care evaluating literature and advising patients, as even medical literature may present unreliable informations.
10.16.14
GMP for dietary supplements [252]
Melethil S 2006 stresses that the Dietary Supplement Health and Education Act (DSHEA) of October 1994 [253] ensures easier access to safe dietary supplements, which can be marketed without prior FDA approval; the burden is on this agency to show that a marketed dietary supplement is unsafe. However, FDA may issue regulations that require the manufacture to follow good manufacturing practice (GMP) standards to ensure their quality. The FDA in 2003 and 21007 proposed rules for GMP for the manufacture, packaging and storage of dietary supplements. [254]
10.16.15
Warning label on food supplements and tea containing ginger in Finnland [255]
EVIRA, the Finnish Food Safety Authority says there is reasons to limit the consumption of ginger products as well as the abundant or long-term consumption of ginger tea during pregnancy. A number of the chemical constituents of ginger could be harmful to foetal
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development; some of the chemical constituents have been found to cause e.g. cell mortality. In order to protect consumers against health hazards Evira says that as long as the eect of ginger on the foetus is not clear, the following foodstus shall bear a separate warning label for pregnant women: Food supplement containing ginger, ginger tea and corresponding drink powder must bear the following label: "Not recommended for pregnant women". Advertisements and other marketing eorts may not be targeted at pregnant mothers. The known chemical constituents of ginger include e.g. zingiberen (30%), b-bisabolene (10-15%), sesquiphellandrene (15-20%), ar-curcumene, geranial, citronellol acetate and gingerols (approx. 5%). Marcus and Snodgrass 2005 stress that the eect plant extracts are chemicals that have the same potential to cause serious adverse eects as found in conventional medicines. Rigorous scientic studies of the safety of dietary supplements during pregnancy are lacking. The authors urge obstetricians to advise women not to expose their fetuses to the risks of herbal medicines [256]
10.16.16
Researchers call for studies on the potential toxicity of ginger during pregnancy [257]
Chrubasik, Pittler and Roufogalis 2005 reviewed the pharmacological and clinical eects of ginger. Some antiemetic properties were found, however, clinical evidence beyond doubt is only available for pregnancy-related nausea and vomiting. The authors stress that conrmatory study to exclude interaction of ginger preparations with platelet aggregation are needed. Pharmacokinetic data are only available for [6]gingerol and zingiberene, and the potential toxicity should be monitored especially following ginger consumption over longer periods. However, concerns remain about the eect of ginger on the fetus because of its uncertain mechanism of action. One proposed mechanism is inhibition of thromboxane synthetase, described in rat models, which has the potential to aect sex steroid dierentiation of the fetal brain. [258]
10.16.17
Other studies found no safety risk of ginger use during pregnancy [258]
Portnoi and colleagues 2003 examined the safety of ginger use during pregnancy. The authors found no statistical dierences in the outcomes between the ginger group and the comparison group with the exception of more infants weighing less than 2500 g in the
10.16. BLIND TRIALS
885
comparison group. The authors concluded that ginger does not increase the risk of major malformations, and has a mild eect in the treatment of nausea and vomiting of pregnancy. Borelli and colleagues 2005 assessed safety of ginger (Zingiber ocinale) therapy for nausea and vomiting during pregnancy. The authors found no reports of adverse events during ginger treatment for nausea and vomiting in pregnancy, however, call for more studies to conrm the data on ginge safety. [259]
10.16.18
Phytate and phytic acid reduce the bioavailiability of micronutrients [260]
Rasmussen and colleagues 2008 describe phytate, phytic acid, phytase and its application in food and feed. The authors stress that phytic acid is the primary storage compound of phosphorus in seeds. Phytic acid strongly binds to metallic cations of Ca, Fe, K, Mg, Mn and Zn making them insoluble and thus unavailable as nutritional factors. This may be involved in worldwide nutrient deciency of iron, zinc, and vitamin A. Phytate is predominantly located in the aleurone layer (wheat, barley and rice) or in the embryo (maize). Phytic acid can be digested only by ruminants, because ot the microbes of their digestive system. In developing countries plant foods are the major staples of the diet and the bioavailability of several micronutrients can be quite low. The authors stress that improving the nutritional value of this type of foods would improve the nutritional status of the entire population. The rst commercially available phytase was from Aspergillus niger , but now several phytases are on the market, from e.g., Peniophora lycii, Escherichia coli and Schizosaccharomyces pombe. Microbial phytases are better suited for industrial processes, because they have higher pH and thermal stability compared to plant phytases. Production of phytase in transgenic plants using the Cauliower Mosaic Virus (CaMV) 35S promoter resulted in enzymes similar to fungal phytase. Aspergillus fumigatus enzyme is also promising because it withstand the pelleting temperatures.
10.16.19
Phytase as feed additive and food products
Adding phytase in feed increases mineral, phosphorous and energy uptake in pig and broiler chicken. The use of phytase in breadmaking, in tofu and other soy-bean products is in discussion. Phytase of Aspergillus niger is of interest because it could work under acidic conditions of the stomach. Rasmussen and colleagues say, however, that exogenous phytase is only required for breadmaking when whole grains are used.
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10.16.20
Bidobacterium strains may improve wholegrain bread [261]
The consumption of wholegrain bread or bre-enriched bread is increasing on regard of the benets of a high-bre diet, however, wholegrain foods are also seen to impair mineral absorption. Monika Haros and colleagues 2009 used strains of bidobacteria, such as B. infantis ATCC 15697 and B. pseudocatenulatum ATCC 27919 obtained from the American Type Culture Collection (ATCC), to reduce phytate and phytic acid levels in bread, because commercial phytases, used as feed additives, are not meant for human consumption. Fermentation of the wholegrain bread with the Bidobacterium strains reduced signicantly phytic acid levels of myo-inositol hexaphosphate (InsP6) but did not remove the myo-inositol triphosphates (InsP3) which is benecial to health. The authors conclude that the use of bidobacterium in wholegrain bread leavening may reduce the content of anti-nutrient compound phytate, resulting in a better absorption of minerals by the human gut.
10.16.21
Bidobacterium promising probiotic to improve mineral absorption [262]
Probiotics are live organisms which present health benets mainly in the gastrointestinal tract. Haros and colleagues 2009 suggest the use of the probiotic Bidobacterium pseudocatenulatum to degrade phytate of wholegrain and bre rich foods. The human strain, described by the authors, presented tolerance to bile as well as a selective adhesion capacity to human intestinal, similar to commercial probiotic B. lactis. The authors describe the degradation pathway of the myo-inositol hexaphosphate (InsP6) phytate by the B. pseudocatenulatum enzymes, and stress their probiotic contribution to the improvement of mineral absorption.
10.16.22
Various Bidobacterium reducing the antinutritional properties of phytate [263]
Haro and colleaguies 2005 describe various Bidobacterium spp. The authors wrote that B. globosum and B. pseudocatenulatum were optimally active at neutral-alkaline pH and B. adolescentis, B. angulatum and B. longum at acid pH. B. pseudocatenulatum showed the highest levels of phytase activity which dephosphorylate phytic acid (myo-inositol hexaphosphate, IP(6)) and generate several myo-inositol phosphate intermediates (IP(3)IP(5)).
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10.16.23
Fungal phytase as breadmaking improver [264]
Fungal phytase were used in the fermentation stage of the breadmaking of whole wheat bread by Haros and colleagues 2001. The possible use of phytase as a breadmaking improver has been tested in whole wheat breads by adding dierent amounts of fungal phytase. A considerable improvement of the bread characteristics were obtained. Phytase addition activated the alpha-amylase, due to the release of calcium ions from calcium-phytate complexes. The authors concluded that the use of phytase in breadmaking improves the nutritional value of the bread and presents the advantages of activating endogenous alpha-amylase.
10.16.24
Unsafe bleaching agent in our [265]
China daily reports that some our bleaching agents contain as much as 30 percent pulverized lime, a substance linked to gradual damage to the lungs and eventually the entire respiratory system. Pulverized lime was added to the bleaching agent to achieve low selling prices by the Yuzhong Food Additive Company in Rugao in East Chinas Jiangsu province. The bleaching agent used in our production is usually a blend of benzoyl peroxide (BPO) and corn our. Experts say the use of lime is forbidden in our production, because there are no regulations which allows its use, but no clear regulations exist. Benzoyl peroxide is one of the most important organic peroxides to improve our.
10.16.25
A social problem
Chen Junshi, of the national food safety and risk assessment committee, points out that the use of unregulated additives in food production is unavoidable in the current peasant population.
10.16.26
Allowed our bleaching agents [266]
Bread improvers and other bakery ingredients are used to make the bread white, soft and get the the dough optimized for industrial production lines. Flour bleaching agent is a food additive added to our in order to make it appear whiter (freshly milled our is yellowish) and to oxidize the surfaces of the our grains and help with developing of gluten.
10.16.27
Usual bleaching agents
Usual bleaching agents are organic peroxides, namely benzoyl peroxide, calcium peroxide, nitrogen dioxide, chlorine, chlorine dioxide (which is reported to produce diabetesCopyright 1998-2010 Karl H. Wilm. All rights reserved. OurFood Database of Food and Related Sciences
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causing contaminant alloxan when reacting with the proteins contained in our), Azodicarbonamide. Use of chlorine, bromates, and peroxides is not allowed in the European Union. Flours treated with bleaches and improving agents generally show higher loaf volume and ner grain. The oxygen from air bleaches our while it ages during storage. Chemical bleaching, however reduces the transit time and reduces costs.
10.16.28
Flour bleaching agents
Flour bleaching agents are added to our in order to make it appear whiter (freshly milled our is yellowish) and to oxidize the surfaces of the our grains and help with developing of gluten.
10.16.29
Maturing agents
Maturing agents are added to our in order to help with gluten development. They may or may not also act as bleaching agents. Common maturing agents are various our bleaching agents, azodicarbonamide (E927), carbamide (E927b), potassium bromate (E924), (acts as a bleaching agent in USA), ascorbic acid (helps form gluten), phosphates, malted barley.
10.16.30
Processing agents
Processing agents help with various aspects of handling the dough during baking. Lcysteine (E920, E921, quantities in the tens of ppm range help soften the dough and thus reduce processing time) The bromate, after reacting with the yellow compounds in the our, is converted into harmless bromide. Chlorine dioxide is a gas that dissipates, so there is none of that left in the our either. Any excess of benzoyl peroxide would (theoretically) decompose as soon as the our is heated.
10.16.31
Dough conditioners [267]
Dough conditioners contain emulsiers, such as DATEM (Diacetyl tartaric acids)Ester of Monoglyceride) and calcium stearoyl-2-lactylate, to increasing water absorption and gluten strength. Other dough conditioners are: Calcium carbonate or monocalcium phosphate adjust water hardness and pH. Calcium carbonate increases both water hardness and pH; monocalcium phosphate increases water hardness and decreases pH. Potassium bromate, ascorbic acid, potassium iodate, and azodicarbonamide (ADA), are maturing agents which improve gluten strength.
10.17. ARGAN OIL, A NUTRACEUTICAL?
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Ammonium salts improve yeast fermentation. Amylase and other enzymes are used to improve yeast fermentation and browning, and to delay staling. Dough conditioners are used to get dough better handled in automated equipment. Dough conditioners are added to frozen doughs to avoid damage of the gluten structure. Dough conditioners also reduce mixing and fermentation time.
10.16.32
Not allowed in the EU
Potassium bromate, azodicarbonamide, calcium peroxide, benzoyl peroxide.
10.16.33
Natural bleaching agents [268]
Roozen and colleagues 1993 looked for natural bleaching agents. Teey report that native soya our contains at least 3 lipoxygenase isoenzymes, which improve dough characteristics by peroxidizing unsaturated fatty acids followed by oxidation of proteins and carotenoids, improving rheology and bleaching of the dough. Their data suggest that bread improvers containing enzyme active soya our were more resistant to storage in form of powder compared with a paste type.
10.16.34
The Brazilian oil fruit pequi has antiinamatori eects and may reduce blood pressure [269]
The oil of the Brazilian pequi (Caryocar brasiliense Camb.) is mostly composed of oleic and palmitic fatty acids and may alter the ratio of triglyceride to cholesterol in postprandial lipidemia. Ana L. Miranda-Vilela and coleagues 2009 found further that pequi oil could reduce exercise-induced inammation and blood pressure, and modulate postprandial lipidemia in runners older than 45 years. The authors stress that pequi oil may become a valuable supplement for athletes. Pequi pulp is a very popular food in some parts of Brazil eaten by itself raw or prepared or used as an ingredient in cooking or to avor beverages. Pequi with rice and chicken is especially popular among locals.
10.17
Argan oil, a nutraceutical?
Argan oil is a plant oil produced from the kernels of the argan tree (Argania spinosa L.), endemic to Morocco, that is valued for its nutritive, cosmetic and numerous medicinal properties. The tree is extremely well adapted to drought and other environmentally harsh conditions of southwestern Morocco. The genus Argania once covered North Africa and is
890
now endangered and under protection of UNESCO. The argan trees protect the soil against erosion and the northern advance of the Sahara. Argan oil remains one of the rarest oils in the world due to the small and very specic growing areas. [270] The argan grove traditional dwellers, the amazighs, were the rst to be known to produce argan oil. Cooperatives employ now Berber women to produce the oil to be sold as far as China, Japan and Europe. The oil production in such cooperatives is completely based on ancient method such as manually crack open the nuts and extract the oil using stone grinding tools.anada and Japan. The Oil production is increasing steadily and bring nancial benets to the region. The local cooperatives also carry out conservation and reforestation projects to reverse the over-exploitation of the endemic tree, which are only present in southern Morocco and parts of Algeria. The UNESCO designated the argan region a "biosphere reserve" on behalf of its buer eect against desertication. [271] The RARBA (Rseau des Associations de la Rserve de Biosphre Arganeraie, Network of Associations of the Argan Biosphere Reserve) was founded in 2002 with the aim of ensuring sustainable development in the Arganeraie. Their work include the Moroccan national anti-desertication programme (Programme National de Lutte contre la desertication (PAN/LCD)) where argan oil production is placed. [272]
10.17.1
Health properties of argan oil
Argan oil contains a high level of oleic and linoleic acid and is also particularly rich in phenols. Which are said to have protective eects against cancer and coronary heart disease and suggesting other amazing medicine claims. Argan oil has the highest level of chemopreventive and anti-inammatory gamma-tocopherol compared to any other oil. [273] Minor compounds or argan oil are sterols, carotenoids, and squalene. The total antioxidant capacity of virgin argan oil is higher than that of other vegetable oils, suggesting hypolipidemic, hypocholesterolemic, hypoglycemic, and antihypertensive eects and a possible role in cancer prevention. Cabrera-Vinque 2012 stresses, however, poor clinical data which turns conclusions on therapeutic eects of virgin argan oil adventurous. [274]
Argan oil as nanoemulsion vehicle for chemotherapeutic agents [275] Jordan et al. 2012 report the research on nanoemulsion platform, using the PUFA-rich argan oil that contain several important anti-inammatory and antimitotic natural components. The authors write that such transport platforms for chemotherapeutic agents may potentially enhance overall the eect of such medication.
10.17. ARGAN OIL, A NUTRACEUTICAL? Antithrombotic activity of argan oil [276]
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According to Mekh et al. 2012 argan oil (1 mL/100 g/day), administered orally, showed an antithrombotic activity in an experimental thrombosis model in mice. The oil reduced the risk of acute pulmonary thromboembolism.The antithrombotic activity of argan oil seemed unrelated to the anticoagulant activity. The authors suggest argan oil as dietary source for the nutritional prevention of hemostasis and cardiovascular disorders. Clinical trials are, however, necessary to conrm these ndings. The therapeutic benets of argan oil consumption have been claimed by natives of Morocco. Polyphenols, tocopherols, sterols, squalene, and triterpene alcohols as minor components of argan oil are likely to cause health benets. Monfalouti et al 2010, however, criticise the lack of clinical data which hinders to explain reported pharmacological activities of argan oil. [277] Good oxidative stability of argan oil [278] Gharby et al. 2012 compared the physicochemical parameters of edible and beauty argan oil immediately after preparation and after a two-year storage. The authors found that virgin argan oil has excellent oxidative stability which is caused by phospholipids together with Maillard-reaction products, phenols, and tocopherols. Study recommends argan oil for the nutritional management of type 2 diabetes [279] The consumption of argan oil was found by Ould et al. 2011 to have an antiatherogenic eect by improving lipids, and the susceptibility of LDL to oxidation in type 2 diabetes patients with dyslipidemia. Serum lipids, apolipoproteins (AI and B), CRP, and LDL are susceptibility to oxidation in type 2 diabetic patients and cause high risk of cardiovascular incidents. Ould and colleagues report that serum triglycerides, total cholesterol, and LDLcholesterol decreased and HDL-cholesterol and Apo I increased by drinking 25 ml of argan oil/day, compared to subjects receiving 20 g butter/day. The authors recommend argan oil in the diet of type 2 diabetes patients. Chemistry of argan oil [280] Khallouki et a. 2003 compared the composition of argan oil with olive oil and sunower oil. Argan oil presented a mean content of tocopherol of 483+/-11 mg/kg, compared to olive oil with 190+/-1 mg/kg and sunower oil with 532+/-6 mg/kg. The squalene content of the argan oils presented a mean of 313+/-4 mg/100 g, compared to olive oil with 499 mg/100 g and sunower oil with only 6 mg/100 g. However, total phenolic compounds of argan oil was found with <5.0 mg/kg to be extremely low, compared to olive oil with 793 mg/kg. The authors conclude that the high content of tocopherol, squalen and oleic acid are likely to cause the reported cancer prevention eects of the Moroccan diet.
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A report in 2005 by Khallouki et al. deepened the knowledge on the composition of argan oil but did not alter the considerations of the article of 2003. [281] Argan oil boom resulted in degradation of the forest [282] The argan oil of Morocco is now the most expensive edible oil in the world. Lybbert et al 2011 report that nongovernmental organizations, international and domestic development agencies, and argan oil cooperatives compete aggressively among one another. Although the argan boom seems the education of the region, especially for girls, the argan forest has not improved, as a matter of fact, a degradation of the forest conservation and sustainability is being noted.
Bibliography
[1] http://en.wikipedia.org/wiki/Food_supplements. Wikipedia, the free enzyclopedia: Food supplements. [2] http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=OJ:L:2002:183: 0051:0057:EN:PDF. Directive 2002/46/EC of the European Parliament of 10 June 2002 on the approximation of the laws of the Member States relating to food supplements. [3] El SN and Simsek S. Food technological applications for optimal nutrition: An overview of opportunities for the food industry. Comprehensive Reviews in Food Science and Food Safety, 11(1):212, 1 2012. http://onlinelibrary.wiley.com/ doi/10.1111/j.1541-4337.2011.00167.x/full. [4] Diet, nutrition and prevention of chronic disease who technical report 916 geneva 2003: Population nutrient intake goals for preventing diet-related chronic diseases. http://www.who.int/hpr/NPH/docs/who_fao_expert_report.pdf. [5] U.S. Department of Agriculture. U.S. Department of Health and Human Services. Dietary guidelines for americans, 2010 (released 1/31/11). http://www.cnpp.usda. gov/Publications/DietaryGuidelines/2010/PolicyDoc/PolicyDoc.pdf. [6] Shkolnik K, Tadmor A, Ben-Dor S, Nevo N, Galiani D, and Dekel N:. Reactive oxygen species are indispensable in ovulation. Proc Natl Acad Sci U S A, 108(4):14627, 1 2011. http://www.pnas.org/content/108/4/1462.long. [7] Dr. Hans-Wilhelm Mller-Wohlfahrt: So schtzen Sie Ihre Gesundheit; Verlag Zabert Sandmann GmbH Mnchen. 6. Auage 2001. [8] Wilkens, Katrin: Der Arzt, seine Haut und die Pille; Die Zeit Nr.2 January, 2. 2003 pg 17.
BIBLIOGRAPHY
893
[9] Pauling, Linus: How to live longer and feel better; W.H.Freeman and Company, New York. [10] http://www.spiegel.de/wissenschaft/mensch/0,1518,428835,00.html. Spiegel Online, Markus Becker : Nano-Mineralien Billigbrause schlgt BayernPillen, SPIEGEL ONLINE - 03. August 2006, 13:55. [11] http://www.dasanwaltsbuero.de/aktuelle_rechtsfaelle/neosino_ag http:// www.dasanwaltsbuero.de/medienpraesenz/presseneosino. KTAG Rechtsanwlte Klberer Tittel Ahrens Gieschen Partnerschaftsgesellschaft: Neosino Ag. [12] Monster energy drink cited in deaths. the new york times. october 22, 2012. http://www.nytimes.com/2012/10/23/business/ fda-receives-death-reports-citing-monster-energy-a-high-caffeine-drink. html?_r=0. [13] Seifert SM, Schaechter JL, Hershorin ER, and Lipshultz SE. Health eects of energy drinks on children, adolescents, and young adults. published online feb. 14, 2011. Pediatrics. http://pediatrics.aappublications.org/content/127/3/511.full. pdf+html. [14] American beverage association: "aba guidance for the responsible labeling and marketing of energy drinks.". http://www.ameribev.org/files/339_Energy%20Drink% 20Guidelines%20(final).pdf. [15] Wolk BJ, Ganetsky M, and Babu KM. Toxicity of energy drinks. Curr Opin Pediatr, 24(2):24351, 4 2012. http://www.ncbi.nlm.nih.gov/pubmed/22426157. [16] Rath M. Energy drinks: what is all the hype? the dangers of energy drink consumption. J Am Acad Nurse Pract, 24(2):706, 2 2012. http://www.ncbi.nlm.nih.gov/ pubmed/22324861. [17] Verster JC, Aufricht C, and Alford C. Energy drinks mixed with alcohol: misconceptions, myths, and facts. Int J Gen Med, 5:18798, 2012. http://www.ncbi.nlm. nih.gov/pmc/articles/PMC3295617/. [18] Petit A, Levy F, Lejoyeux M, Reynaud M, and Karila L. Energy drinks: an unknown risk. Rev Prat, 62(5):6738, 5 2012. http://www.ncbi.nlm.nih.gov/ pubmed/22730801. [19] Velazquez CE, Poulos NS, Latimer LA, and Pasch KE. Associations between energy drink consumption and alcohol use behaviors among college students. Drug Alcohol Depend, 123(1-3):16772, 6 2012. http://www.ncbi.nlm.nih.gov/pubmed/ 22138539.
894
[20] Marczinski CA, Fillmore MT, Henges AL, Ramsey MA, and Young CR. Eects of energy drinks mixed with alcohol on information processing, motor coordination and subjective reports of intoxication. Exp Clin Psychopharmacol, 20(2):12938, 4 2012. http://www.ncbi.nlm.nih.gov/pubmed/22023670. [21] Astorino TA, Matera AJ, Basinger J, Evans M, Schurman T, and Marquez R. Eects of red bull energy drink on repeated sprint performance in women athletes. Amino Acids, 42(5):18038, 5 2012. http://www.ncbi.nlm.nih.gov/pubmed/21461905. [22] Del Coso J, Salinero JJ, Gonzlez-Milln C, Abin-Vicn J, and Prez-Gonzlez B. Dose response eects of a caeine-containing energy drink on muscle performance: a repeated measures design. J Int Soc Sports Nutr, 9(1):21, 5 2012. http://www. ncbi.nlm.nih.gov/pmc/articles/PMC3461468/. [23] Del Coso J, Mu noz Fernndez VE, Mu noz G, Fernndez-Elas VE, Ortega JF, Hamouti N, Barbero JC, and Mu noz Guerra J. Eects of a caeine-containing energy drink on simulated soccer performance. PLoS One, 7(2):e31380, 2012. http: //www.ncbi.nlm.nih.gov/pmc/articles/PMC3279366/. [24] Gwacham N and Wagner DR. Acute eects of a caeine-taurine energy drink on repeated sprint performance of american college football players. Int J Sport Nutr Exerc Metab, 22(2):10916, 4 2012. http://www.ncbi.nlm.nih.gov/pubmed/22349209. [25] Jain P, Hall-May E, Golabek K, and Agustin MZ. A comparison of sports and energy drinks-physiochemical properties and enamel dissolution. Gen Dent, 60(3):quiz1907, May-Jun 2012. http://www.ncbi.nlm.nih.gov/pubmed/22623458. [26] DAJ Connolly, Malachy Mc Hugh, and Olga Padilla-Zakour: The ecacy of a tart cherry juice blend in preventing the symptoms of muscle damage; Br. J. Sports Med., Jun 2006; doi:10.1136/bjsm.2005.025429. [27] Darshan S. Kelley, Reuven Rasooly, Robert A. Jacob, Adel A. Kader, and Bruce E. Mackey : Consumption of Bing Sweet Cherries Lowers Circulating Concentrations of Inammation Markers in Healthy Men and Women; J. Nutr. 2006 136: 981-986. [28] http://www.ars.usda.gov/research/projects/projects.htm?ACCN_NO=409033. Research Project: Anti-Inammatory Eects of Strawberries in Overweight/obese Individuals Project Number: 5306-51530-013-04 Start Date: Jul 01, 2005 End Date: Jun 30, 2007. [29] http://care.diabetesjournals.org/cgi/content/abstract/27/2/362. Jukka Montonen, MSC, Paul Knekt, PHD, Ritva Jrvinen, PHD and Antti Reunanen, PHD: Dietary Antioxidant Intake and Risk of Type 2 Diabetes. Diabetes Care 27:362366, 2004.
BIBLIOGRAPHY
895
[30] http://www.nutrition.org/cgi/content/abstract/136/3/620. Lu Wang, Simin Liu, JoAnn E. Manson, J. Michael Gaziano, Julie E. Buring and Howard D. Sesso: The Consumption of Lycopene and Tomato-Based Food Products Is Not Associated with the Risk of Type 2 Diabetes in Women; J. Nutr. 136:620-625, March 2006. [31] http://www.ajcn.org/cgi/content/abstract/82/3/685. Terry Coyne, Torukiri I Ibiebele, Peter D Baade, Annette Dobson, Christine McClintock, Sophie Dunn, Dympna Leonard and Jonathan Shaw Diabetes mellitus and serum carotenoids: ndings of a population-based study in Queensland, Australia.American Journal of Clinical Nutrition, Vol. 82, No. 3, 685-693, September 2005. [32] http://www.garfield.library.upenn.edu/histcomp/wallace-kywd_w-citing/ index-so-29.html. McClung JP; Roneker CA; Mu WP; Lisk DJ; Langlais P; Liu F; Lei XG: Development of insulin resistance and obesity in mice overexpressing cellular glutathione peroxidase. Proceedings of the National Academy of Sciences, 2004 Vol. 101, pp. 8852-8857). [33] Chiou WB, Yang CC, and Wan CS. Ironic eects of dietary supplementation: illusory invulnerability created by taking dietary supplements licenses health-risk behaviours. Psychol Sci, 22(8):10816, 8 2011. http://www.ncbi.nlm.nih.gov/ pubmed/21764996. [34] Chiou WB, Wan CS, Wu WH, and Lee KT. A randomized experiment to examine unintended consequences of dietary supplement use among daily smokers: taking supplements reduces self-regulation of smoking. Addiction, 2011. http: //researcher.nsc.gov.tw/public/wbchiou/Data/182317432071.pdf. [35] http://www.ncbi.nlm.nih.gov/pubmed/18942838. Cha, K.H.; Koo, S.Y.; Lee, D.U.: Antiproliferative Eects of Carotenoids Extracted from Chlorella ellipsoidea and Chlorella vulgaris on Human Colon Cancer Cells. J Agric Food Chem. 2008 Oct 23. [36] http://pubs.acs.org/cgi-bin/abstract.cgi/jafcau/2005/53/i10/abs/ jf0479517.html. Wu, Li-chen; Ho, Ja-an Annie; Shieh, Ming-Chen; In-Wei Lu, In-Wei: Antioxidant and Antiproliferative Activities of Spirulina and Chlorella Water Extracts. pp 4207 - 4212; (Article) DOI: 10.1021/jf0479517. [37] http://www.ncbi.nlm.nih.gov/pubmed/12926072. Chew, B.P.; Brown, C.M.; Park, J.S.; Mixter, P.F.: Dietary lutein inhibits mouse mammary tumor growth by regulating angiogenesis and apoptosis. Anticancer Res. 2003 Jul-Aug;23(4):3333-9. [38] http://www.jbc.org/cgi/reprint/158/1/303. Briggs, G. M.; Luckey, T. D.; Elvehjem, C. A and Harth C. B.: Studies on vitaminsB10 and B11 and related substances in chicken nutrition; J. Biol. Chem. Briggs et al. 158 (1): 303-312.
896
[39] http://a257.g.akamaitech.net/7/257/2422/12feb20041500/edocket.access. gpo.gov/cfr_2004/aprqtr/21cfr510.515.htm. (Code of Federal Regulations)(Title 21, Volume 6)(Revised as of April 1, 2004)From the U.S. Government Printing Oce via GPO Access (: 21CFR510.515)(Page 44-45)TITLE 21FOOD AND DRUGS: CHAPTER IFOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN; PART 510 NEW ANIMAL DRUGS-Subpart F Animal; Use Exemptions From Certication and Labeling Requirement. [40] http://toxsci.oxfordjournals.org/cgi/content/abstract/86/1/61. Hasumura, M.;Imai, T.; Takizawa, Ueda M.; Onose, J. and Hirose, M.: Promotion of Thyroid Carcinogenesis by para-aminobenzoic Acid in Rats Initiated with N-bis(2-hydroxypropyl)nitrosamine. Toxicological Sciences 2005 86(1):61-67; doi:10.1093/toxsci/k173. [41] http://en.wikipedia.org/wiki/Para-aminobenzoic_acid. Wikipedia, the free enzyclopedia: 4-Aminobenzoic acid. [42] http://www.nature.com/jid/journal/v79/n6/abs/5615301a.html. Osgood, P. J.; Moss, H.S., Davies, D.J. (1982): The sensitization of near-ultraviolet radiation killing of mammalian cells by the sunscreen agent para-aminobenzoic acid. Journal of Investigative Dermatology 79 (6): 354-357. [43] http://phot.allenpress.com/photonline/?request=get-abstract&doi=10. 1562%2F0031-8655(1998)068%3C0243:AROSSA%3E2.3.CO%3B2. Gasparro, Francis P.; Mitchnik, Mark and Nash, J. Frank: A Review of Sunscreen Safety and Ecacy. Photochemistry and Photobiology. Volume 68, Number 3 March 1998. [44] http://www.blackwell-synergy.com/. B. Mang, M. Wolters, B. Schmitt, K. Kelb, R. Lichtinghagen, D. O. Stichtenoth, A. Hahn: Eects of a cinnamon extract on plasma glucose, HbA1c, and serum lipids in diabetes mellitus type 2.European Journal of Clinical Investigation (Vol. 36, pp. 340-344) May 2006 doi/abs/10.1111/j.13652362.2006.01629.x. [45] http://www.amcollnutr.org/. 47th annual meeting of the American College of Nutrition: Nutrition in Preventive Medicine and Chronic Disease Management Oct 5-8, 2006. [46] http://www.jacn.org/cgi/content/abstract/25/2/144. Preuss, Harry G.; Echard, Bobby; Polansky, Marilyn M.; Anderson, Richard: Whole Cinnamon and Aqueous Extracts Ameliorate Sucrose-Induced Blood Pressure Elevations in Spontaneously Hypertensive Rats. J Am Coll Nutr 2006. 25: 144-150.Journal of the American College of Nutrition. [47] http://care.diabetesjournals.org/cgi/content/abstract/26/12/3215. Alam Khan, Mahpara Safdar, Mohammad Muzaar Ali Khan, Khan Nawaz Khattak, and
BIBLIOGRAPHY
897
Richard A. Anderson: Cinnamon Improves Glucose and Lipids of People With Type 2 Diabetes. Diabetes Care 2003 26: 3215-3218. [48] http://jn.nutrition.org/cgi/content/abstract/136/4/977. K. Vanschoonbeek, B. J. W. Thomassen, J. M. Senden, W. K. W. H. Wodzig, and L. J. C. van Loon: Cinnamon Supplementation Does Not Improve Glycemic Control in Postmenopausal Type 2 Diabetes Patients J. Nutr., April 1, 2006; 136(4): 977 980. [49] http://www.futuremedicine.com/doi/abs/10.2217/14750708.3.1.113. Ranjbar, Akram; Ghasmeinezhad, Sara; Zamani, Hosnieh; Malekirad, Ali Akbar; Baiaty, Akram; Mohammadirad, Azadeh; Abdollahi, Mohammad: Antioxidative stress potential of Cinnamomum zeylanicum in humans: a comparative crosssectional clinical study. Therapy, January 2006, Vol. 3, No. 1, Pages 113-117. Doi: 10.2217/14750708.3.1.113. [50] http://www3.interscience.wiley.com/journal/110511560/abstract?CRETRY= 1&SRETRY=0. Verspohl, Eugen J.; Bauer, Katrin; Neddermann, Eckhard: Antidiabetic eect of Cinnamomum cassia and Cinnamomum zeylanicum: In vivo and In vitro. Volume 19 Issue 3, March 2005. Pages 203-206. Doi:10.1002/ptr.1643. [51] http://www.bfr.bund.de/cd/8487. Coumarin. Federal Institute for Risk Assesment:
[52] http://www3.interscience.wiley.com/journal/117884760/abstract. Yu-Lin Yang, Shan-Yu Chang, Hsiang-Chun Teng, Yi-Shiuan Liu, Tao-Chen Lee, Lea-Yea Chuang, Jinn-Yuh Guh, Fang-Rong Chang, Tung-Nan Liao, Jau-Shyang Huang, Jeng-Hsien Yeh, Wen-Teng Chang, Min-Yuan Hung, Ching-Jen Wang, Tai-An Chiang, Chien-Ya Hung, Tsung-Jen Hung: Saower extract: A novel renal brosis antagonist that functions by suppressing autocrine TGF-beta. Journal of Cellular Biochemistry Volume 104 Issue 3, Pages 908-919 Doi:10.1002/jcb.21676. [53] http://www.efsa.europa.eu/en/science/afc/afc_opinions/ej389_ cassiagum.html. Opinion of the Scientic Panel on Food Additives, Flavourings, Processing Aids and Materials in Contact with Food on a request from the Commission related to an application on the use of cassia gum as a food additive; Question Nr EFSA-Q-2003-134 Adopted on 26 September 2006 Summary. [54] http://www.ncbi.nlm.nih.gov/pubmed/11305748. Tasaka AC; Weg R; Calore EE; Sinhorini IL; Dagli ML; Haraguchi M.; Gorniak SL: Toxicity testing of Senna occidentalis seed in rabbits. VetResCommun 2000 Dec;24(8):573-82. [55] Tim, CD; and Riet-Correa, F.; 1997 Plants toxic to pigs. Ciencia Rural 27 (3: 521528).
898
CHAPTER 10. FOOD SUPPLEMENTS Raintree Nutrition Inc.:
[56] http://www.rain-tree.com/fedegoso-powder.htm. Third-party published research.
[57] Ooi VE, Liu F: Immunomodulation and anti-cancer activity of polysaccharide-protein complexes: Curr Med Chem 2000 Jul;7(7):715-29. [58] http://www.cancure.org/beta_glucan.htm. The Cancer Cure Foundation: What is Beta Gluca? [59] Wakshull E, Brunke-Reese D, Lindermuth J, et al. PGG-glucan, a soluble beta-(1,3)glucan, enhances the oxidative burst response, microbicidal activity, and activates an NF-kappa B-like factor in human PMN: evidence for a glycosphingolipid beta-(1,3)glucan receptor. Immunopharmacology 1999;41:89-107. [60] http://www.ncbi.nlm.nih.gov/pubmed/3037509. Czop JK. The role of betaglucan receptors on blood and tissue leukocytes in phagocytosis and metabolic activation. Pathol Immunopathol Res 1986;5:286-96. [61] http://en.wikipedia.org/wiki/Beta-glucan. Wikipedia: Beta-glucan. [62] http://dx.doi.org/10.1016/j.foodchem.2008.09.016. Banchathanakij, Rawiwan; Suphantharika, Manop: Eect of dierent beta-glucans on the gelatinisation and retrogradation of rice starch. Food Chemistry (published online ahead of print) DOI: 10.1016/j.foodchem.2008.09/016. [63] http://www.nutritionj.com/content/pdf/1475-2891-6-6.pdf. Queenan, Katie M.; Stewart, Maria L.; Smith, Kristen N.; Thomas, William; Fulcher, Gary R.; Slavin, Joanne L.: Concentrated oat beta-glucan, a fermentable ber, lowers serum cholesterol in hypercholesterolemic adults in a randomized controlled trial Nutrition Journal 2007, 6:6 (26 March 2007) doi:10.1186/1475-2891-6-6. [64] http://jn.nutrition.org/cgi/content/abstract/137/6/1375. Chen, C.-Y. Oliver; Milbury, Paul E.; Collins, F. William ; BlumbergJ, erey B.: Avenanthramides Are Bioavailable and Have Antioxidant Activity in Humans after Acute Consumption of an Enriched Mixture from Oats J. Nutr., June 1, 2007; 137(6): 1375 - 1382. [65] http://www.ars.usda.gov/research/publications/publications.htm?SEQ_ NO_115=240802. Doehlert, D.C.; Simsek, S.; Wise, M.L.: The Green Oat Story: Possible Mechanisms of Green Color Formation in Oat Products during Cooking. Journal of Food Science. Volume 74, Number 6, Pages S226-S231. [66] http://archinte.ama-assn.org/cgi/content/abstract/167/4/346. Gardner, Christopher D; Lawson,Larry D; Block, Eric; Chatterjee, Lorraine M; Kiazand, Alexandre; Balise Raymond R; Kraemer, Helena C.Eect of Raw Garlic vs Commercial Garlic Supplements on Plasma Lipid Concentrations in Adults With Moderate
BIBLIOGRAPHY
899
Hypercholesterolemia: A Randomized Clinical Trial; Arch Intern Med. 2007;167:346353. [67] http://archinte.ama-assn.org/cgi/content/extract/167/4/325. Charlson, Mary; McFerren, Marcus: Editorial: Garlic: What We Know and What We Do not Know; Arch Intern Med. 2007;167:325-326. [68] http://www.fda.gov/bbs/topics/NEWS/2006/NEW01434.html. FDA Statement on Tenth Circuits Ruling to Uphold FDA Decision Banning Dietary Supplements Containing Ephedrine Alkaloids. [69] http://www.dkma.dk/1024/visUKLSArtikel.asp?artikelID=13640. Danish Medicines Agency warns against the weight-loss product Therma Power 27.05.2008. [70] http://www.ncbi.nlm.nih.gov/pubmed/11117974. Haller C, Benowitz N (2000). dverse cardiovascular and central nervous system events associated with dietary supplements containing ephedra alkaloids. N Engl J Med 343 (25): 1833-8. PMID 11117974. [71] http://www.annals.org/cgi/content/abstract/142/1/37. Miller,Edgar R.; Pastor-Barriuso, Roberto; Dalal, Darshan; Riemersma, Rudolph A.;Appel, Lawrence J. and Guallar Eliseo: Meta-Analysis: High-Dosage Vitamin E Supplementation May Increase All-Cause Mortality. Annals of Internal Medicine; 4 January 2005 Volume 142 Issue 1 Pages 37-46. [72] http://jama.ama-assn.org/cgi/content/abstract/297/8/842. Bjelakovic, Goran; Nikolova, Dimitrinka; Gluud, Lise Lotte; Simonetti, Rosa G.; Gluud, Christian: Mortality in Randomized Trials of Antioxidant Supplements for Primary and Secondary Prevention: Systematic Review and Meta-analysis Journal of the American Medical Association. February 28 2007;297:842-857. [73] http://ajrccm.atsjournals.org/cgi/content/abstract/177/5/524. Slatore, Christopher G.; Littman, Alyson J.; Au, David H.; Satia, Jessie A.; White, Emily: Long-Term Use of Supplemental Multivitamins, Vitamin C, Vitamin E, and Folate Does Not Reduce the Risk of Lung Cancer.American Journal of Respiratory and Critical Care Medicine Vol 177. pp. 524-530, (2008). Published ahead of print on November 7, 2007, doi:10.1164/rccm.200709-1398OC. [74] http://jnci.oxfordjournals.org/cgi/content/abstract/djn438. Lin, Jennifer; Cook, Nancy R.; Albert, Christine; Zaharris, Elaine ;Gaziano, J. Michael; Van Denburgh, Martin; Buring, Julie E.;Manson, JoAnn E. : Vitamins C and E and Beta Carotene Supplementation and Cancer Risk: A Randomized Controlled Trial. JNCI Journal of the National Cancer Institute 2009 101(1):14-23; doi:10.1093/jnci/djn438.
900
[75] http://jnci.oxfordjournals.org/cgi/content/full/101/1/2. Albanes, Demetrius: Vitamin Supplements and Cancer Prevention: Where Do Randomized Controlled Trials Stand? Journal of the National Cancer Institute Advance Access published on December 30, 2008. J. Natl. Cancer Inst. 2009 101: 2-4; doi:10.1093/jnci/djn453. [76] Eroglu A, Hruszkewycz DP, Dela Sena C, Narayanasamy S, Riedl KM, Kopec RE, Schwartz SJ, Curley RW Jr, and Harrison EH. Naturally occurring eccentric cleavage products of provitamin a beta-carotene function as antagonists of retinoic acid receptors. J Biol Chem, 287(19):1588695, 5 2012. http://www.ncbi.nlm.nih.gov/ pubmed/22418437. [77] Marsh RS, Yan Y, Reed VM, Hruszkewycz D, Curley RW, and Harrison EH. Betaapocarotenoids do not signicantly activate retinoic acid receptors alpha or beta. Exp Biol Med (Maywood), 235(3):3428, 3. http://ebm.rsmjournals.com/content/ 235/3/342.long. [78] Eroglu a and hruszkewycz dp and curley rw jr and harrison eh: The eccentric cleavage product of beta-carotene, beta-apo-13-carotenone, functions as an antagonist of rxr. Arch Biochem Biophys, 504(1):116, 12 2010. http://www.ncbi.nlm.nih. gov/pubmed/20678466. [79] http://en.wikipedia.org/wiki/Chitosan. Wikipedia, the free encyclopedia: Chitosan. [80] http://www.blackwell-synergy.com/doi/abs/10.1111/j.1440-1681.2007. 04568.x. Hossain, S.; Rahman, A.; Kabir, Y.; Shams, A.A.; Afros, F.; Hashimoto, M:Eects of shrimp (Macrobracium rosenbergii)-derived chitosan on plasma lipid prole and liver lipid peroxide levels in normo- and hypercholesterolaemic rats. Clinical and Experimental Pharmacology and Physiology (Wiley-Blackwell) March 2007, Volume 34, Issue 3, Pages 170-176. [81] http://www.foodnavigator-usa.com/news/ng.asp?n= 75497-chitosan-weight-management-cholesterol. www.Foodnavigator-USA: Science building for chitosan weight management benets. [82] http://www.obesityresearch.org/cgi/content/abstract/11/5/683?etoc. Gades Matthew D. and Stern, Judith S.: Chitosan Supplementation and Fecal Fat Excretion in Men. Obesity Research 11:683-688 (2003). [83] http://docnews.diabetesjournals.org/cgi/external_ref?access_num= 15635349%&link_type=MED. Gades MD, Stern JS: Chitosan supplementation and fat absorption in men and women. J Am Diet Assoc 105: 72-77, 2005.
BIBLIOGRAPHY
901
[84] http://docnews.diabetesjournals.org/cgi/content/full/4/3/3. Stern, J. S.: No Dietary Supplement Will Result in Substantial Weight Loss DOC News, March 1, 2007; 4(3): 3 - 3. [85] U.S. Food and Drug Administration: FDA warns distributors of dietary supplements promoted online for weight loss (Press Release P04-39). April 1, 2004. www.fda.gov/bbs/topics/news/2004/NEW01045.html. [86] http://www.cochrane.org/reviews/en/ab003892.html. Ni Mhurchu C, DunsheaMooij CAE, Bennett D, Rodgers A: Chitosan for overweight or obesity. The Cochrane Database of Systematic Reviews Date of last Subtantial Update: May 24. 2005. [87] http://www.acnfp.gov.uk/assess/fullapplics/touchiextract. ACNFP: July 2008: Application from CBC Co. Ltd., for the authorisation of Touchi extract under the Novel Food Regulation (EC) 258/97. [88] http://www.food.gov.uk/multimedia/pdfs/touchiapplication.pdf. tion for Touchi Extract. Applica-
[89] http://jn.nutrition.org/cgi/content/abstract/131/4/1211. Fujita, Hiroyuki; Yamagami, Tomohide; Ohshima, Kazunori: Fermented Soybean-Derived WaterSoluble Touchi Extract Inhibits alpha-Glucosidase and Is Antiglycemic in Rats and Humans after Single Oral Treatments Journal of Nutrition. 2001;131:1211-1213. [90] http://jn.nutrition.org/cgi/content/abstract/131/8/2105. Fujita, H.; Yamagami,T.; Ohshima, K.: Long-Term Ingestion of a Fermented Soybean-Derived Touchi-Extract with alpha-Glucosidase Inhibitory Activity Is Safe and Eective in Humans with Borderline and Mild Type-2 Diabetes J. Nutr., August 1, 2001; 131(8): 2105 - 2108. [91] Nahrungsmittelsupplementierung mit konjugierter Linolsure; 49(1998) Nr. 10. [92] Fritsche, J.Steinhart,H: Amounts of conjugated linoleic acid (CLA) in German foods and evaluation of daily intake, Z.Lebensm. Unters. Forsch. A, 206 (1998b) 77-82. [93] Kelly,: Dietary fatty acid sources aect conjugated linoleic acid concentrations in milk from lctating dairy cows, J. Nutr., 128 (1998) 881-885. [94] http://dx.doi.org/10.2337/db06-0384. Moloney, Fiona; Toomey, Sinead; Noone, Enda; Nugent, Anne; Allan, Bernard; Loscher, Christine E.; Roche, Hellen M.: Antidiabetic eects of cis-9, trans-11-conjugated linoleic acid may be mediated via antiinammatory eects in white adipose tissue. Diabetes 56(3):574-582 (2007). DOI: 10.2337/db06-0384. [95] http://healthlibrary.epnet.com/GetContent.aspx?token= 8482e079-8512-47c2-960c-a403c77a5e4c&chunkiid=21676. Emory Healthcare, Atlanta, Georgia: Conjugated Linoleic Acid, Supplement Forms CLA.:.
902
[96] http://jb.asm.org/cgi/content/abstract/189/6/2566. Devillard E, McIntosh FM, Duncan SH, Wallace RJ. Metabolism of linoleic acid by human gut bacteria: Dierent routes for biosynthesis of conjugated linoleic acid. J. Bact. 189(6):2566-2570 (2007). doi:10.1128/JB.01359-06. [97] Voevodin M, Sinclair A, Gibson R et al. The eect of CLA on body composition in humans: systematic review and meta-analysis. Asia Pac J Clin Nutr. 2005;14 Suppl:S55. [98] Riserus U, Arner P, Brismar K, et al. Treatment with dietary trans10cis12 conjugated linoleic acid causes isomer-specic insulin resistance in obese men with the metabolic syndrome. Diabetes Care. 2002;25:1516-1521. [99] Moloney F, Yeow TP, Mullen A, et al. Conjugated linoleic acid supplementation, insulin sensitivity, and lipoprotein metabolism in patients with type 2 diabetes mellitus. Am J Clin Nutr. 2004;80:887-95. [100] Larsen TM, Toubro S, Astrup A. Ecacy and safety of dietary supplements containing conjugated linoleic acid (CLA) for the treatment of obesity-evidence from animal and human studies. J Lipid Res. 2003. [101] Syvertsen C, Halse J, Hoivik HO et al. The eect of 6 months supplementation with conjugated linoleic acid on insulin resistance in overweight and obese. Int J Obes (Lond). 2006 Oct 10 (Epub ahead of print). [102] Taylor JS, Williams SR, Rhys R et al. Conjugated Linoleic Acid Impairs Endothelial Function. Arterioscler Thromb Vasc Biol. 2005 Dec 8 (Epub ahead of print). [103] http://www.ncbi.nlm.nih.gov/pubmed/12207834. Noone EJ, Noone EJ, Roche HM, et al. The eect of dietary supplementation using isomeric blends of conjugated linoleic acid on lipid metabolism in healthy human subjects. Br J Nutr. 2002;88:243251. [104] Chajes V, Lavillonniere F, Ferrari P, et al. Conjugated linoleic acid and the risk of breast cancer. Presented at: European Conference on Nutrition & Cancer; June 21-24, 2001; Lyon, France. [105] MacDonald HB. Conjugated linoleic acid and disease prevention: a review of current knowledge. J Am Coll Nutr. 2000;19(2 Suppl):111S-118S. [106] Nugent AP, Roche HM, Noone EJ et al. The eects of conjugated linoleic acid supplementation on immune function in healthy volunteers. Eur J Clin Nutr. 2005 Apr 13 (Epub ahead of print). [107] Masters N, McGuire MA, Beerman KA, et al. Maternal supplementation with CLA decreases milk fat in humans. Lipids. 2002;37:133-138.
BIBLIOGRAPHY
903
[108] http://www.cspinet.org/nah/05_07/supplements.pdf. Schardt, David: Brain teasers. Popping pills for better memory. Nutrition Action Healthletter , May 2007 , CSPI. [109] http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd= Retrieve&dopt=AbstractPlus. Kang, J.H.; Cook, N.; Manson, J.; Buring, J.E. And Grodstein, F.: A randomized trial of vitamin E supplementation and cognitive function in women. Arch. Intern. Med. 166: 2462, 2006. [110] http://www.ncbi.nlm.nih.gov/pubmed/17936185. Roberts LJ 2nd, Oates JA, Linton MF, Fazio S, Meador BP, Gross MD, Shyr Y, Morrow JD: The relationship between dose of vitamin E and suppression of oxidative stress in humans. Free Radical Biology and Medicine. 2007 Nov 15;43(10):1388-93. Doi:10.1016/j.freeradbiomed.2007.06.019. [111] http://www.ncbi.nlm.nih.gov/pubmed/20531213. Guttman H, Zimlichman R, Boaz M, Matas Z, Shargorodsky M: Eect of Long-Term L-Arginine Supplementation on Arterial Compliance and Metabolic Parameters in Patients with Multiple Cardiovascular risk Factors: Randomized, Placebo-Controlled Study. J Cardiovasc Pharmacol. 2010 Jun 7. [112] http://www.nutritionandmetabolism.com/content/7/1/55/abstract. Shargorodsky M, Debbi O, Matas Z, Zimlichman R: Eect of long-term treatment with antioxidants (vitamin C, vitamin E, coenzyme Q10 and selenium) on arterial compliance, humoral factors and inammatory markers in patients with multiple cardiovascular risk factors. Nutrition & Metabolism, 2010. [113] http://www.ncbi.nlm.nih.gov/pubmed/11498727. Stough, C.; Lloyd, J.; Clarke, J.; Downey, L.A.; Hutchison, C.W.; Rodgers, C.W. and Nathan, P.J.: The chronic eects of an extract of Bacopa monniera (Brahmi) on cognitive function in healthy human subjects. Psychopharmacology 156: 481, 2001. [114] Ntp technical report on the toxicology and cancinogenesis studies of ginkgo biloba extract in f344/n rats and b6c3f1/n mice.(cas no. 90045). march 2013. http://ntp. niehs.nih.gov/ntp/htdocs/LT_rpts/TR578_508.pdf. [115] Chemical cuisine learn about food additives : Ginkgo. pretend benets: Beverages. cspinet. https://www.cspinet.org/reports/chemcuisine.htm#GINKGO. [116] http://www.ncbi.nlm.nih.gov/pubmed/14994318. Nathan, P.J.; Tanner, S.; Lloyd J.; Harrison, B.; Curran, L.; Oliver, C.; Stough, C.: Eects of a combined extract of Ginkgo biloba and Bacopa monniera on cognitive function in healthy humans. Hum. Psychopharmacol. 19: 91, 2004.
904
[117] http://www.ncbi.nlm.nih.gov/pubmed/12093601. Roodenrys, S.; Booth, D.; Bulzomi, S.; Phillips, A.; Micallef, C. and Smoker, J.: Chronic eects of Brahmi (Bacopa monnieri) on human memory. Neuropsychopharmacology 27: 279, 2002. [118] http://healthlibrary.epnet.com/GetContent.aspx?token= e0498803-7f62-4563-8d47-5fe33da65dd4%20chunkiid=104655&chunkiid= 104655. The Natural Health Encyclopedia review of bacopa: Brahmi Bacopa monnieri. [119] http://jn.nutrition.org/cgi/content/abstract/129/3/712. Jacob,Robert A.; Jenden,Donald J.; Allman-Farinelli, Margaret A. and Swendseid, Marian E.: Folate Nutriture Alters Choline Status of Women and Men Fed Low Choline Diets J. Nutr. 1999 129: 712-717. [120] http://www.cfsan.fda.gov/~dms/ds-ltr36.html#note5. FDA: Phosphatidylserine and Cognitive Dysfunction and Dementia (Qualied Health Claim: Final Decision Letter). Oce of Nutritional Products, Labeling and Dietary Supplements. May 13, 2003. [121] Dana Consortium. A randomized, double-blind, placebo-controlled trial of deprenyl and thioctic acid in human immunodeciency virus-associated cognitive impairment. Dana Consortium on the Therapy of HIV Dementia and Related Cognitive Disorders. Neurology 1998; 50: 645-51. [122] http://www.ncbi.nlm.nih.gov/pubmed/17240287. Durga, Jane; van Boxtel, Martin P.J.; Schouten, Evert; Kok, Franz; Jolles, Jelle, Katan, Martin B. and Verhoef, Petra: Eect of 3-year folic acid supplementation on cognitive function in older adults in the FACIT trial: a randomised, double blind, controlled trial. The Lancet 2007; 369:208-216 DOI:10.1016/S0140-6736(07)60109-3. [123] http://jech.bmj.com/cgi/content/abstract/61/7/631. Gilbody, Simon; Lightfoot, Tracy; Sheldon, Trevor: Is low folate a risk factor for depression? A metaanalysis and exploration of heterogeneity. J Epidemiol Community Health 2007; 61: 631-637. doi:10.1136/jech.2006.050385. [124] http://www.nutritionjrnl.com/article/PIIS089990070700319X/abstract. Murakami,Kentaro; Mizoue, Tetsuya; Sasaki,Satoshi; Ohta, Masanori; Sato, Masao; Matsushita, Yumi; Mishima Norio: Dietary intake of folate, other B vitamins, and omega-3 polyunsaturated fatty acids in relation to depressive symptoms in Japanese adults. Published on-line ahead of print 3 December 2007,Nutrition (Elsevier) doi: 10.1016/j.nut.2007.10.013. [125] http://www3.interscience.wiley.com/cgi-bin/abstract/114219886/ ABSTRACT. Kennedy, D.O.; Haksell, C.F.; Mauri, P.L.; Schorley, A.B.: Acute cognitive eects of standardised Ginkgo biloba extract complexed with phosphatidylserine. Hum. Psychopharmacol 2007 Apr 25.
BIBLIOGRAPHY [126] http://www.greatvistachemicals.com/nutritional-supplements/ vinpocetine.html. China Great Vista Chemicals: Vinpocentine.
905
[127] http://www.ingentaconnect.com/content/els/01664328/1997/00000083/ 00000001/art86049. Katsura, M.; Tino, T.; Xu, J.; Ohkuma, S.; Kuriyama, K.: Vinconate, a cognitive enhancer, and PI turnover-phospholipase C systems in the brain. Behavioural Brain Research. Volume 83, Number 1, February 1997 , pp. 75-81(7). [128] http://www.lef.org/prod_hp/abstracts/vinpocetine.html#3. The safety and lack of ecacy of vinpocetine in Alzheimers disease. J Am Geriatr Soc (1989 Jun) 37(6):515-20. [129] http://www.ajcn.org/cgi/content/abstract/84/6/1308. Appleton, Katherine M.; Hayward, Robert C.; Gunnell, David ; Peters, Tim J.; Rogers, Peter J.; Kessler, David and Ness, Andrew R.: Eects of n-3 long-chain polyunsaturated fatty acids on depressed mood: systematic review of published trials. American Journal of Clinical Nutrition, Vol. 84, No. 6, 1308-1316, December 2006. [130] http://www.ajcn.org/cgi/content/abstract/87/4/949. Mehta, Samir P.;Boddy, Alex P.; Cook, Jane; Sams, Virginia; Lund, Elizabeth K.; Johnson, Ian T.; Rhodes, Michael: Eect of n-3 polyunsaturated fatty acids on Barretts epithelium in the human lower esophagus. Am J Clin Nutr April 2008 87: 949-956. [131] http://www.britishnutrition.org.uk/home.asp?siteId=43&sectionId=361. British Nutrition Foundation: The Denis Burkitt Study Award 2007. [132] http://www.zeit.de/zeit-wissen/2006/05/Titel_K-Ballaststoffe.xml. Schnurr, Eva-Maria: Unntzer Ballast fr den Darm. Die ZEIT Wissen 05/2006. 16.08.2006 pg 20-21. [133] http://content.nejm.org/cgi/content/abstract/342/16/1156. Alberts, D.S.; Martinez, M.E. ; Roe, D.J.; Guillen-Rodriguez, J.M.; Marshall, J.R.; van Leeuwen, J.B.; Reid, M.E.; Ritenbaugh, C.; Vargas, P.A.; Bhattacharyya, A.B.; Earnest,D.L.; Sampliner, R.E.; Parish, D.; Koonce, K.; Fales, L. and The Phoenix Colon Cancer Prevention Physicians Ne: Lack of Eect of a High-bre Cereal Supplement on the Recurrence of Colorectal Adenomas. N. Engl. J. Med., April 20, 2000; 342(16): 1156-1162. [134] http://content.nejm.org/cgi/content/abstract/342/16/1149. Schatzkin, Arthur and Others: Lack of Eect of a Low-Fat, High-bre Diet on the Recurrence of Colorectal Adenomas. The New England Journal of Medicine Volume 342:1149-1155 April 20, 2000 Number 16. [135] http://www.nih.gov/news/pr/apr2000/nci-19a.htm. National Institutes of Health: The Polyp Prevention Trial and the Wheat Bran bre Study.
906
[136] http://cebp.aacrjournals.org/cgi/content/abstract/11/9/906. Jacobs, Elizabeth T.; Giuliano, Anna R.; Roe, Denise J.; Guilln-Rodr guez, Jos M. ; Hess, Lisa M. ; Alberts, David S. and Martnez, Mara Elena: Intake of Supplemental and Total bre and Risk of Colorectal Adenoma Recurrence in the Wheat Bran bre Trial. [137] http://www.nhlbi.nih.gov/new/press/06-02-15.htm. Health: The Womens Health Initiative (WHI). National Institutes of
[138] http://content.nejm.org/cgi/content/abstract/354/7/684. Jean WactawskiWende, Jean and others for the Womens Health Initiative Investigators: Calcium plus Vitamin D Supplementation and the Risk of Colorectal Cancer. New English Journal of Medicine Volume 354:684-696Febraury 16, 2006 Number 7. [139] http://www.ajcn.org/cgi/content/abstract/85/6/1586. Lappe, Joan M.; Travers-Gustafson, Dianne; Davies, K. Michael; Recker, Robert R.; and Heaney, Robert P.: Vitamin D and calcium supplementation reduces cancer risk: results of a randomized trial. American Journal of Clinical Nutrition. June 8, Volume 85, Issue 6, Pages 1586-1591. [140] http://en.wikipedia.org/wiki/Resistant_starch. Wikipedia: Resistant starch. [141] Korus, Jaraslaw; Witczak, Mariusz; Ziobro, Rafal; Juszczak, Leslaw: The impact of resistant starch in characteristics of gluten-free dough and bread. Food Hydrocolloids (Elsevier) - online ahead of print DOI: 10.1016/j.foodhyd.2008.07.010. [142] Haralampu, S.G.: Resistant starch-a review of the physical properties and biological impact of RS3 Carbohydrate Polymers, Volume 41, Issue 3, March 2000, Pages 285292 doi:10.1016/S0144-8617(99)00147-2. [143] http://www.ajcn.org/cgi/content/abstract/83/2/343. Jacobs, Elizabeth T.; Lanza, Elaine; Alberts, David S.; Hsu, Chiu-Hsieh; Jiang, Ruiyun; Schatzkin, Arthur; Thompson Patricia A. and Martnez, Mara Elena.: bre, sex, and colorectal adenoma: results of a pooled analysis Am. J. Clinical Nutrition, February 1, 2006; 83(2): 343-349. [144] http://gut.bmj.com/cgi/content/extract/48/5/587. Goodlad, R.A.: Dietary bre and the risk of colorectal cancer. Gut, May 2001; 48: 587-589. [145] Bonithon-Kopp 2000 Bonithon-Kopp C, Kronborg O, Giacosa A. , et al. Calcium and bre supplementation in prevention of colorectal adenoma recurrence: a randomised intervention trial. Lancet, 2000;356:1300-1306. [146] http://carcin.oxfordjournals.org/cgi/content/abstract/20/5/805. Williamson S.L.; Kartheuser A.; Coaker J. ; Kooshkghazi M.D.; Fodde R. ; Burn, J.; Mathers C.C.: Intestinal tumorigenesis in the Apc1638N mouse treated with aspirin and resistant starch for up to 5 months. Carcinogenesis 1999 May;20(5):805-10.
BIBLIOGRAPHY
907
[147] http://content.nejm.org/cgi/content/abstract/340/3/169. Fuchs, Charles S.; Giovannucci, Edward L.; Golditz, Graham A.; Hunter, David J.; Stampfer, Meir J.; Rosner, Bernard.; Speizer, Frank E. and Willet, Walter C.: Dietary bre and the Risk of Colorectal Cancer and Adenoma in Women. New England Journal of Medicine. Volume 340:169-176 January 21, 1999 Number 3. [148] http://www.hsph.harvard.edu/nutritionsource/fruits.html. Harward School of Public Health: Fruits and vegetables. [149] http://de.wikipedia.org/wiki/Nurses_Health_Study. Wikipedia, the free enzyclopedia: Nurses Health Study. [150] http://www.ajcn.org/cgi/content/abstract/85/5/1353. Schatzkin, Arthur; Mouw, Traci; Park, Yikyung; Subar, Amy F; Kipnis, Victor; Hollenbeck, Albert; Leitzmann, Michael F. and Thompson, Frances E.: Dietary bre and whole-grain consumption in relation to colorectal cancer in the NIH-AARP Diet and Health Study. American Journal of Clinical Nutrition, Vol. 85, No. 5, 1353-1360, May 2007. [151] http://cebp.aacrjournals.org/cgi/content/abstract/16/4/668. Wakai, K., Date, C., Fukui, M., Tamakoshi, K., Watanabe, Y., Hayakawa, N., Kojima, M., Kawado, M., Suzuki, K., Hashimoto, S., Tokudome, S., Ozasa, K., Suzuki, S., Toyoshima, H., Ito, Y., Tamakoshi, A., for the JACC Study Group, (2007). Dietary bre and Risk of Colorectal Cancer in the Japan Collaborative Cohort Study. Cancer Epidemiol. Biomarkers Prev. 16: 668-675. [152] http://jnci.oxfordjournals.org/cgi/content/full/99/2/99. Martnez, Mara Elena and Jacobs , Elizabeth T.: Calcium Supplementation and Prevention of Colorectal Neoplasia: Lessons From Clinical Trials. JNCI Journal of the National Cancer Institute 2007 99(2):99-100; doi:10.1093/jnci/djk025. [153] Grau MV, Baron JA, Sandler RS, Wallace K, Haile RW, Church TR, et al. Prolonged eect of calcium supplementation on risk of colorectal adenomas in a randomized trial. J Natl Cancer Inst 2007;99:129-36. [154] http://content.nejm.org/cgi/content/full/340/2/101. Baron,J.A.; Beach,M.; Mandel,J.S.; van Stolk,R.U.; Haile,R.W.; Sandler,R.S.; Rothstein,R.; Summers,R.W.; Snover,D.C.; Beck,G.J.; Bond,J.H.; Greenberg,E.R.; Frankl,H.; Pearson,L. for The Calcium Polyp Prevention Study Group: Calcium Supplements for the Prevention of Colorectal Adenomas. The New England Journal of Medicine. Volume 340:101-107. January 14, 1999 Number 2. [155] http://mrw.interscience.wiley.com/cochrane/clsysrev/articles/ CD003548/frame.html. Weingarten, Michael Asher,M.A.; Zalmanovici, Anca.; Yaphe, John.: Dietary calcium supplementation for preventing colorectal cancer and adenomatous polyps. Cochrane Database of Systematic Reviews 2008, Issue 1. Art. No.: CD003548. DOI: 10.1002/14651858.CD003548.pub4.
908
[156] http://www.asco.org/ASCO/News/Cancer+News?&reuterview=detail_ view&reutersid=11838. American Society of Clinical Oncology: Calcium to Magnesium Ratio Important in Colorectal Cancer Prevention. Nov. 17, 2008. [157] http://www.ncbi.nlm.nih.gov/pubmed/19934323. Henrik Fyrst, Babak Oskouian, Padmavathi Bandhuvula, Yaqiong Gong, Hoe Sup Byun, Robert Bittman, Andrew R. Lee, and Julie D. Saba: Natural Sphingadienes Inhibit Akt-Dependent Signaling and Prevent Intestinal Tumorigenesis. Cancer Res 2009 69: 9457-9464. Published Online First November 24, 2009. doi: 10.1158/0008-5472.CAN-09-2341. [158] http://www.ncbi.nlm.nih.gov/pubmed/18156591. Fyrst H, Zhang X, Herr DR, Byun HS, Bittman R, Phan VH, Harris GL, Saba JD.: Identication and characterization by electrospray mass spectrometry of endogenous Drosophila sphingadienes. J Lipid Res. 2008 Mar;49(3):597-606. [159] http://www.ncbi.nlm.nih.gov/pubmed/15358586. Schmelz, E.M.: Sphingolipids in the chemoprevention of colon cancer. Front Biosci. 2004 Sep 1;9:2632-9. [160] http://www.ncbi.nlm.nih.gov/pubmed/15796189. Duan RD.: Anticancer compounds and sphingolipid metabolism in the colon.In Vivo. 2005 Jan-Feb;19(1):293300. [161] http://www.ncbi.nlm.nih.gov/pubmed/20071649. Ohlsson L, Hertervig E, Jonsson BA, Duan RD, Nyberg L, Svernlov R, Nilsson A.: Sphingolipids in human ileostomy content after meals containing milk sphingomyelin. Am J Clin Nutr. 2010 Jan 13. [162] http://www.iarc.fr/epic/Sup-default.html. European Prospective Investigation into Cancer and Nutrition: Key ndings. [163] http://pubs.acs.org/doi/abs/10.1021/pr9008817. Xue H, Lu B, Zhang J, Wu M, Huang Q, Wu Q, Sheng H, Wu D, Hu J, Lai M.: Identication of Serum Biomarkers for Colorectal Cancer Metastasis Using a Dierential Secretome Approach. Journal of Proteome Research, 2010; 9 (1): 545 DOI: 10.1021/pr9008817. [164] http://www.ncbi.nlm.nih.gov/pubmed/20071649. Felth J, Rickardson L, Rosn J, Wickstrm M, Frykns M, Lindskog M, Bohlin L, Gullbo J: Cytotoxic Eects of Cardiac Glycosides in Colon Cancer Cells, Alone and in Combination with Standard Chemotherapeutic Drugs. Journal of Natural Products, 2009; 72 (11): 1969 DOI: 10.1021/np900210m. [165] http://www.bmj.com/cgi/content/full/338/jun23_2/b2337?view=long&pmid= 19549997. Trichopoulou A, Bamia C, Trichopoulos D.: Anatomy of health eects of Mediterranean diet: Greek EPIC prospective cohort study. BMJ. 2009 Jun 23;338:b2337. doi: 10.1136/bmj.b2337. Doi:10.1136/bmj.b2337.
BIBLIOGRAPHY
909
[166] Lecumberri, E; Mateos, R.; Izquierdo-Pulido, M.; Ruperez, P.; Goya, L.; and Bravo, L.: Dietary bre composition, antioxidant capacity and physico-chemical properties of a bre-rich product from cocoa (Theobroma cacao L.). Food Chemistry (Elsevier). Volume 104, Issue 3, Pages 948-954, doi: 10.1016/j.foodchem.2006.12.054. [167] http://caonline.amcancersoc.org/cgi/content/abstract/56/5/254. Kushi, L. H., Byers, T., Doyle, C., Bandera, E. V., McCullough, M., Gansler, T., Andrews, K. S., Thun, M. J., The American Cancer Society 2006 Nutrition and Phy, (2006). American cancer society guidelines on nutrition and physical activity for cancer prevention: reducing the risk of cancer with healthy food choices and physical activity.CA Cancer J Clin 56: 254-281. [168] Sattelmair J, Pertman J, Ding EL, Kohl HW 3rd, Haskell W, and Lee IM. Dose response between physical activity and risk of coronary heart disease. a meta-analysis. Circulation, 2011. http://circ.ahajournals.org/content/early/2011/08/01/ CIRCULATIONAHA.110.010710. [169] Physical activity guidelines for americans. paguidelines/pdf/paguide.pdf. 2008. http://www.health.gov/
[170] Sattelmair jr and kurth t and buring je and lee im: Physical activity and risk of stroke in women. Stroke, 41(6):124350, 6 2010. http://www.ncbi.nlm.nih.gov/ pmc/articles/PMC2876221/?tool=pubmed. [171] http://cancerres.aacrjournals.org/cgi/content/abstract/67/11/5553. Schernhammer, Eva; Wolpin, Brian;Rifai, Nader; Cochrane, Barbara; Manson, Jo An; Ma, Jing; Giovannucci, Ed; Thomson, Cynthia; Stampfer, Meir and Fuchs, Charles: Plasma folate, vitamins B6, B12, and homocysteine and pancreatic cancer risk in four large cohorts Cancer Research 1 June 2007, Volume 67, Issue 11 5553-5560. [172] http://jama.ama-assn.org/cgi/content/full/297/21/2351. Cole, B.; Baron, J.; Sandler, R.; Haile, R.; Ahnen, D.; Bresalier,R.; McKeown-Eyssen, G.; Summers, R.; Rothstein, R.; Burke, C.; Snover,D.; Church, T.; Allen, J.; Robertson, D.; Beck, G.; Bond, J.; Byers, T.; Mandel, J.; Mott, L.; Pearson, L.; Barry, E.; Rees, J.; Marcon, N.; Saibil, F.; Magne Ueland, P.; Greenberg, E.: Folic Acid for the prevention of colorectal adenomas. Journal of the American Medical Association (JAMA) 6 June 2007, Volume 297, Issue 21, Pages 2351-2359. [173] http://cancerres.aacrjournals.org/cgi/content/abstract/67/11/5553. Schernhammer. Study on folate and pancreatic cancer. [174] http://jama.ama-assn.org/cgi/content/short/297/21/2408. Ulrich, Cornelia M.; Potter, John D.: Folate and Cancer-Timing is everything. Journal of the American Medical Association (JAMA) 6 June 2007, Volume 297, Issue 21, Pages 24082409.
910
CHAPTER 10. FOOD SUPPLEMENTS CRN Emphasizes
[175] http://www.crnusa.org/PR07_CRN_JAMA-FOLIC060707.html. Importance of Folic Acid Benets.
[176] Prasad AS. Zinc deciency. BMJ, 326(7386):409410, 2 2003. http://www.ncbi. nlm.nih.gov/pmc/articles/PMC1125304/. [177] Zinc. dietary reference intakes for vitamin a, vitamin k, arsenic, boron, chromium, copper, iodine, iron, manganese, molybdenum, nickel, silicon, vanadium, and zinc (2001). institute of medicine, food and nutrition board. retrieved 2010-03-30. http: //books.nap.edu/openbook.php?record_id=10026&page=442. [178] DiSilvestro RA and Swan M. Comparison of four commercially available zinc supplements for performance in a zinc tolerance test. march 2008 22 (meeting abstract supplement) 693.3 human nutrition, the ohio state university, columbus, oh. FASEB J, 3 2008. http://www.fasebj.org/cgi/content/meeting_abstract/22/ 1_MeetingAbstracts/693.3. [179] Zinc and its danger to parrots. The Parrot Society UK. http://www. theparrotsocietyuk.org/veterinary-advice/poisons-and-parrots/zinc. [180] Liuzzi JP, Wong CP, Ho E, and Tracey A. Regulation of hepatic suppressor of cytokine signaling 3 by zinc. The Journal of Nutritional Biochemistry, 2012. http: //www.jnutbio.com/article/S0955-2863%2812%2900204-5/abstract. [181] Lymburner S, McLeod S, Purtzki M, Roskelley C, and Xu Z. Zinc inhibits magnesium-dependent migration of human breast cancer mda-mb-231 cells on bronectin. The Journal of Nutritional Biochemistry, 10 2012. http://www.jnutbio. com/article/S0955-2863%2812%2900206-9/abstract. [182] Taylor KM, Hiscox S, Nicholson RI, Hogstrand C, and Kille P. Protein kinase ck2 triggers cytosolic zinc signaling pathways by phosphorylation of zinc channel zip7. Sci Signal, 5(210):ra11, 2 2012. http://www.ncbi.nlm.nih.gov/pmc/articles/ PMC3428905/. [183] Sandstead HH. Subclinical zinc deciency impairs human brain function. J Trace Elem Med Biol, 26(2-3):703, 6 2012. http://www.ncbi.nlm.nih.gov/pubmed/ 22673824. [184] Kawade R. Zinc status and its association with the health of adolescents: a review of studies in india. Glob Health Action, 5:7353, 2012. http://www.ncbi.nlm.nih. gov/pmc/articles/PMC3328203/. [185] Wikipedia. Zinc. http://en.wikipedia.org/wiki/Zinc. [186] Zinc and health : The common cold". oce of dietary supplements, national institutes of health. retrieved 2010-05-01. http://ods.od.nih.gov/factsheets/ Zinc-HealthProfessional/#h7.
BIBLIOGRAPHY
911
[187] Food Institute of Medicine and Nutrition Board. Dietary reference intakes for vitamin a, vitamin k, arsenic, boron, chromium, copper, iodine, iron, manganese, molybdenum, nickel, silicon, vanadium, and zinc. washington, dc: National academy press, 2001. http://search.nap.edu/nap-cgi/de.cgi?term=Dietary+ Reference+Intakes+for+Vitamin+A%2C+Vitamin+K%2C+Arsenic%2C+Boron%2C+ Chromium%2C+Copper%2C+Iodine%2C+Iron%2C+Manganese%2C+Molybdenum%2C+ Nickel%2C+Silicon%2C+Vanadium%2C+and+Zinc.&x=13&y=10. [188] Singh M and Das RR. Zinc for the common cold. Cochrane Database Syst Rev, 2:CD001364, 2001. http://www.ncbi.nlm.nih.gov/pubmed?term=21328251. [189] Shah UH, Abu-Shaheen AK, Malik MA, Alam S, Riaz M, and Al-Tannir MA. The ecacy of zinc supplementation in young children with acute lower respiratory infections: A randomized double-blind controlled trial. Clin Nutr, pages pii: S0261 5614(12)001859, 8 2012. http://www.ncbi.nlm.nih.gov/pubmed/22981241. [190] Gaucheron F. Milk and dairy products: a unique micronutrient combination. J Am Coll Nutr, 30(5 Suppl 1):400S9S, 10 2011. http://www.ncbi.nlm.nih.gov/ pubmed/22081685. [191] Vissers PA, Streppel MT, Feskens EJ, and de Groot LC. The contribution of dairy products to micronutrient intake in the netherlands. J Am Coll Nutr, 30(5 Suppl 1):415S21S, 10 2011. http://www.ncbi.nlm.nih.gov/pubmed/22081687. [192] Mason BC and Lavallee ME. Emerging supplements in sports. Sports Health, 4(2):1426, 3 2012. http://www.ncbi.nlm.nih.gov/pubmed/23016081. [193] Mogna L, Nicola S, Pane M, Lorenzini P, Strozzi G, and Mogna G. Selenium and zinc internalized by lactobacillus buchneri lb26 (dsm 16341) and bidobacterium lactis bb1 (dsm 17850): Improved bioavailability using a new biological approach. J Clin Gastroenterol, 46:Suppl:S415, 10 2012. http://www.ncbi.nlm.nih.gov/pubmed/ 22955356. [194] Khor GL and Misra S. Micronutrient interventions on cognitive performance of children aged 5-15 years in developing countries. Asia Pac J Clin Nutr, 21(4):476 86, 2012. http://www.ncbi.nlm.nih.gov/pubmed/23017305. [195] Lazzerini M and Ronfani L. Oral zinc for treating diarrhoea in children. Cochrane Database Syst Rev, 6:CD/22696352, 6 2012. http://www.ncbi.nlm.nih.gov/ pubmed/22696352. [196] http://www.efsa.europa.eu/en/science/afc/afc_opinions/ej495-503_ pidolates.html. Opinion of the Scientic Panel AFC related to Calcium, iron, magnesium, potassium and zinc L-pidolate as sources for calcium, iron, magnesium, potassium and zinc added for nutritional purposes to food supplements and to foods intended for particular nutritional uses.
912
[197] http://www.efsa.europa.eu/EFSA/Scientifi_Opinion/afc_ej761_lysinates_ op_en,0.pdf. EFSA: Magnesium L-lysinate, calcium L- lysinate, zinc L- lysinate as sources for magnesium, calcium and zinc added for nutritional purposes in food supplements - Scientic Opinion of the Panel on Food Additives, Flavourings, Processing Aids and Materials in Contact with Food. Question number: EFSA-Q-2005-142, EFSA-Q-2005-127, EFSA-Q-2005-218. Publication date: 21.07.2008. [198] Bonnet, M.; Cansell, M.; Berkaoui, A.; Ropers,; Anton, M. Leal-Calderon, F.: Release rate proles of magnesium from multiple W/O/W emulsions. Food Hydrocolloids (Elsevier) Published on-line ahead of print 5 December 2007, doi:10.1016/j.foodhyd.2007.11.016. [199] Biehler E, Homann L, Krause E, and Bohn T. Divalent minerals decrease micellarization and uptake of carotenoids and digestion products into caco-2 cells. J Nutr, 141(10):176976, 10 2011. http://www.ncbi.nlm.nih.gov/pubmed/21865558. [200] Mason BC and Lavallee ME. Emerging supplements in sports. Sports Health, 4(2):1426, 3 2012. http://www.ncbi.nlm.nih.gov/pubmed/23016081. Bllinger JMarx [201] Ellinger S, Gordon A, and Krten MJungfer EZimmermann BFZur F Stehle P. Bolus consumption of a specically designed fruit juice rich in anthocyanins and ascorbic acid did not inuence markers of antioxidative defense in healthy humans. J Agric Food Chem, 10 2012. http://www.ncbi.nlm.nih.gov/ pubmed/23072538. [202] Gordon A. Bioactive compounds in underutilized tropical fruits from latin america. institut fr ernhrungs- und lebensmittelwissenschaften (iel) fachgebiet lebensmittelchemie. 5 2012. http://hss.ulb.uni-bonn.de/2012/2986/2986.pdf. [203] Gordon A, Schadow B, Quijano CE, and Marx F. Chemical characterization and antioxidant capacity of berries from clidemia rubra (aubl.) mart. (melastomataceae). Food Research International, 44(7):21202127, 8 2011. http://www.sciencedirect. com/science/article/pii/S0963996911000275. [204] Gaziano JM, Sesso HD, Christen WG, Bubes V, Smith JP, MacFadyen J, Schvartz M, Manson JAE, Glynn RJ, and Buring JE. Multivitamins in the prevention of cancer in men the physicians health study ii randomized controlled trial. JAMA, pages 110, 2012. http://jama.jamanetwork.com/article.aspx?articleid=1380451. [205] Larsson SC, Akesson A, Bergkvist L, and Wolk A. Multivitamin use and breast cancer incidence in a prospective cohort of swedish women. Am J Clin Nutr, 91(5):126872, 5 2010. http://ajcn.nutrition.org/content/91/5/1268.long. [206] Neuhouser ML, Wassertheil-Smoller S, Thomson C, Aragaki A, Anderson GL, Manson JE, Patterson RE, Rohan TE, van Horn L, Shikany JM, Thomas A, LaCroix A, and Prentice RL. Multivitamin use and risk of cancer and cardiovascular disease
BIBLIOGRAPHY
913
in the womens health initiative cohorts. Arch Intern Med, 169(3):294304, 2 2009. http://www.ncbi.nlm.nih.gov/pubmed/19204221. [207] Khan N, Adhami VM, and Mukhtar H. Review: green tea polyphenols in chemoprevention of prostate cancer: preclinical and clinical studies. Nutr Cancer, 61(6):836 41, 2009. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2991093/. [208] Wang P, Heber D, and Henning SM. Quercetin increased the antiproliferative activity of green tea polyphenol (-)-epigallocatechin gallate in prostate cancer cells. Nutr Cancer, 64(4):5807, 2012. http://www.ncbi.nlm.nih.gov/pubmed/22452782. [209] Connors SK, Chornokur G, and Kumar NB. New insights into the mechanisms of green tea catechins in the chemoprevention of prostate cancer. Nutr Cancer, 64(1):4 22, 2012. http://www.ncbi.nlm.nih.gov/pubmed/22098273. [210] Henning SM, Wang P, and Heber D. Chemopreventive eects of tea in prostate cancer: green tea versus black tea. Mol Nutr Food Res, 55(6):90520, 6 2011. http: //www.ncbi.nlm.nih.gov/pmc/articles/PMC3163457/. [211] Namiki M, Akaza H, Lee SE, Song JM, Umbas R, Zhou L, Lee BC, Cheng C, Chung MK, Fukagai T, Hinotsu S, and Horie S. Prostate cancer working group report. Jpn J Clin Oncol, 40(sUPPL 1):i7075, 2010. http://jjco.oxfordjournals.org/ content/40/suppl_1/i70.long. [212] Henning SM, Wang P, Said J, Magyar C, Castor B, Doan N, Tosity C, Moro A, Gao K, Li L, and Heber D. Polyphenols in brewed green tea inhibit prostate tumor xenograft growth by localizing to the tumor and decreasing oxidative stress and angiogenesis. J Nutr Biochem, 23(11):153742, 11 2012. http://www.ncbi.nlm. nih.gov/pubmed/22405694. [213] Wang P, Aronson WJ, Huang M, Zhang Y, Lee RP, Heber D, and Henning SM. Green tea polyphenols and metabolites in prostatectomy tissue: implications for cancer prevention. Cancer Prev Res (Phila), 3(8):98593, 8 2010. http://www. ncbi.nlm.nih.gov/pmc/articles/PMC3163459/. [214] Bettuzzi S, Brausi M, Rizzi F, Castagnetti G, Peracchia G, and Corti A. Chemoprevention of human prostate cancer by oral administration of green tea catechins in volunteers with high-grade prostate intraepithelial neoplasia: a preliminary report from a one-year proof-of-principle study. Cancer Res, 66(2):123440, 1 2006. http://cancerres.aacrjournals.org/content/66/2/1234.long. [215] Vrailas-Mortimer A, delRivero T, Mukherjee S, Nag S, Gaitanidis A, Kadas D, Consoulas C, Duttaroy A, and Sanyal S. A muscle-specic p38 mapk/mef2/mnsod pathway regulates stress, motor function and lifespan in drosophila. author manuscript; available in pmc 2012 october 18. Dev Cell, 21(4):783795, 10 2011. 10.1016/j. devcel.2011.09.002.
914
[216] Tania del Rivero. Muscle-specic roles for p38k map kinase in the regulation of locomotor activity in drosophila. https://etd.library.emory.edu/file/view/ pid/emory:7tpj5/del%20rivero_dissertation.pdf. [217] Vrailas-Mortimer A, Gomez R, Dowse H, and Sanyal S. A survey of the protective eects of some commercially available antioxidant supplements in genetically and chemically induced models of oxidative stress in drosophila melanogaster. Exp Gerontol, 47(9):71222, Sep 2012. http://www.sciencedirect.com/science/article/ pii/S0531556512001891. [218] http://en.wikipedia.org/wiki/Acai. Wikipedia: Acai palm. [219] http://www.pomwonderful.com/pdf/Antioxidant_Beverage_Study.pdf. Seeram, Navindra P.; Airam, Michael; Zhang, Yanjun;Henning, Nusanne M.; Feng, Lydia; Dreher, Mark; Heber, David: Comparison of Antioxidant Potency of Commonly Consumed Polyphenol-Rich Beverages in the United States. J. Agric. Food Chem. 2008, 56, 1415-1422. [220] http://www.cspinet.org/new/200903231.html. CSPI: Consumers Warned of Web-Based Acai Scams. Companies Use Fake Blogs, Fake Endorsements, Fishy Science, and Hard-to-Cancel Credit Card Transactions to Bilk Consumers. March 23.2009.
[221] http://www.walletpop.com/blog/2009/01/08/bbb-warms-of-acai-berry-weight-loss-sca BBB warns of acai berry weight-loss scam Tom Barlow Jan 8th 2009. [222] Johnson L:. Evaluating acai berry health claims. 18 may 2009. University of Missouri Extension. http://extension.missouri.edu/news/DisplayStory.aspx?N=435. [223] Kinghorn AD, Chai HB, Sung CK, and Keller WJ:. The classical drug discovery approach to dening bioactive constituents of botanicals. Fitoterapia, 9 2010. http: //www.ncbi.nlm.nih.gov/pubmed/20804827. [224] Sun X, Seeberger J, Alberico T, Wang C, Wheeler CT, Schauss AG, and Zou S:. Acai palm fruit (euterpe oleracea mart.) pulp improves survival of ies on a high fat diet. 45(3):24351, 3 2010. http://www.ncbi.nlm.nih.gov/pubmed/20080168. [225] de Souza MO, Silva M, Silva ME, Oliveira Rde P, and Pedrosa ML:. Diet supplementation with acai pulp improves biomarkers of oxidative stress and the serum lipid prole in rats. Nutrition, 26(7-8):80410, Jul-Aug 2010. http://www.ncbi. nlm.nih.gov/pubmed/20022468. [226] Ribeiro JC, Antunes LM, Aissa AF, Darin JD, De Rosso VV, Mercadante AZ, and Bianchi Mde L:. Evaluation of the genotoxic and antigenotoxic eects after acute and subacute treatments with acai pulp (euterpe oleracea mart.) on mice using the erythrocytes micronucleus test and the comet assay. Mutat Res., 695(1-2):2228, 1 2010. http://www.ncbi.nlm.nih.gov/pubmed/19892033.
BIBLIOGRAPHY
915
[227] Spada PD, Dani C, Bortolini GV, Funchal C, Henriques JA, and Salvador M:. Frozen fruit pulp of euterpe oleraceae mart. (acai) prevents hydrogen peroxide-induced damage in the cerebral cortex, cerebellum, and hippocampus of rats. J Med Food, 12(5):10848, 10 2009. http://www.ncbi.nlm.nih.gov/pubmed/19857073. [228] McPhee, S., Hodges, L.D., Wright, P.F.A., Wynne, P.M. Kalafatis, N., Harney, D.W. and Macrides, T.A. (2007) Anti-cyclooxygenase eects of lipid extracts from the New Zealand green-lipped mussel Perna canaliculus. Comp Biochem Physiol Part B 146: 346-356. [229] Treschow, A.P., Hodges, L.D, Wright, P.F.A., Wynne, P.M., Kalafatis, N. and Macrides,T.A. (2007) Novel anti-inammatory omega-3 PUFAs from the New Zealand green-lipped mussel, Perna canaliculus. Comp Biochem Physiol 147: 645656.
[230] http://www.foodnavigator.com/news/ng.asp?n=80040-bio-springer-yeast-extract-suga FoodNavigator: Sugar reform and biofuel take toll on yeast extract prices25.09.2007. [231] http://www.nature.com/ejcn/journal/vaop/ncurrent/abs/1602886a.htm. Wang, S:Ma, A-Q; Song,S-W; Quan, Q-H; Zhao,X-F; Zheng X-H: Fish oil supplementation improves large arterial elasticity in overweight hypertensive patients.European Journal of Clinical Nutrition. Advance online publication 5 September 2007; doi: 10.1038/sj.ejcn.1602886. [232] http://www.ncbi.nlm.nih.gov/pubmed/20434961. Yurko-Mauro K, McCarthy D, Rom D, Nelson EB, Ryan AS, Blackwell A, Salem N Jr, Stedman M; on behalf of the MIDAS Investigators: Benecial eects of docosahexaenoic acid on cognition in age-related cognitive decline. Alzheimers Dement. 2010 Nov;6(6):456-464. [233] http://www.ncbi.nlm.nih.gov/pubmed/21045096. Quinn JF, Raman R, Thomas RG, Yurko-Mauro K, Nelson EB, Van Dyck C, Galvin JE, Emond J, Jack CR Jr, Weiner M, Shinto L, Aisen PS: Docosahexaenoic acid supplementation and cognitive decline in Alzheimer disease: a randomized trial. JAMA. 2010 Nov 3;304(17):1903-11. [234] http://www.ingentaconnect.com/content/jws/jsfa/2004/00000084/ 00000009/art00017. Devill C.; Damas J.; Forget P.; Dandrifosse G.; Peulen O. Laminarin in the dietary bre concept. Journal of the Science of Food and Agriculture. Volume 84, Number 9, July 2004 , pp. 1030-1038(9). [235] http://www.ingentaconnect.com/content/jws/jsfa/2004/00000084/ 00000009/art00017. University Hamburg: Chrysophyta. [236] http://www.springerlink.com/content/l544g0r384257p03/. Abdel-Fattah, A.F.; Hussein, M.M.: Isolation of water insoluble laminaran-like polysaccharide from Sargassum. Plant Foods for Human Nutrition. 181-187 Vol 22, Number 2, 1973.
916
[237] http://cat.inist.fr/?aModele=afficheN&cpsidt=17729255. Kim,K.H. et al: Anti-apoptotic activity of laminarin polysaccharides and their enzymatically hydrolyzed oligosaccharides from Laminaria japonica. Biotechnol Lett. 28/6/2006 S. 439-46. [238] http://www.foodnavigator.com/news/ng.asp?n=80978-algae-laminarans-fucoidans. Foodnavigator: Brown marine algae mined for functional ingredients. 30.10.2007. [239] http://en.wikipedia.org/wiki/Observational_studies. Wikipedia: Observational study. [240] http://www.ncbi.nlm.nih.gov/pubmed/18420014. von Elm, Erik; Altman, Douglas G.; Egger, Matthias; Pocock,; Gotzsche, Peter C.; Vandenbroucke, Jan P.: The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Statement: Guidelines for Reporting Observational Studies. PLoS Med. 4 (10): e296. Doi:10137/journal.pmed.0040296. PMID 17941714. [241] http://jama.ama-assn.org/cgi/content/abstract/298/21/2517. Tatsioni, Athina; Bonitsis, Nikolaos G.; Ioannidis, John P. A.: Persistence of Contradicted Claims in the Literature. JAMA. 5. December 2007;298(21):2517-2526. [242] http://www.crnusa.org/PR07_JAMAstudy071203.html. Council for Responsible Nutrition: New JAMA Study Raises Issue of How Nutrients Should be Researched. Press Room Washington D.C., December 4, 2007. [243] http://www.cochrane.org/reviews/en/ab007176.html. Bjelakovic, G.; Nikolova, D.; Gluud, L.L.; Simonetti, R.G.; Gluud, C.: Antioxidant supplements for prevention of mortality in healthy participants and patients with various diseases. Cochrane Database of Systematic Reviews 2008, Issue 2. Art. No.: CD007176. DOI: 10.1002/14651858.CD007176. Published online April 16. 2008. [244] http://www.ncbi.nlm.nih.gov/pubmed/19808019. Loh K, Deng H, Fukushima A, Cai X, Boivin B, Galic S, Bruce C, Shields BJ, Skiba B, Ooms LM, Stepto N, Wu B, Mitchell CA, Tonks NK, Watt MJ, Febbraio MA, Crack PJ, Andrikopoulos S, Tiganis: Reactive oxygen species enhance insulin sensitivity. Cell Metab. 2009 Oct;10(4):260-72. [245] http://www.jci.org/articles/view/32601. Bonnard, Charlotte; Durand, Annie; Peyrol, Simone; Chanseaume, Emilie; Chauvin, Marie-Agnes; Morio, Batrice; Vidal, Hubert; Rieusset, Jennifer: Mitochondrial dysfunction results from oxidative stress in the skeletal muscle of diet-induced insulin-resistant mice. Volume 118, Issue 2 (February 1,2008). J. Clin. Invest. 118(2): 789-800 (2008). doi:10.1172/JCI32601. [246] http://care.diabetesjournals.org/content/30/6/1406.long. Ghanim H, Mohanty P, Pathak R, Chaudhuri A, Sia CL, Dandona P: Orange juice or fructose
BIBLIOGRAPHY
917
intake does not induce oxidative and inammatory response. Diabetes Care. 2007 Jun;30(6):1406-11. Epub 2007 Mar 23. [247] http://www.ajconline.org/article/S0002-9149(08)00353-6/abstract. Lu, Zongliang; Kou, Wenrong; Du, Baomin; Wu, Yangfeng; Zhao, Shuiping; Brusco, Osvaldo A.; Morgan, John M.; Capuzzi, David M. and Chinese Coronary Secondary Prevention Study Group: Coronary artery disease: Eect of Xuezhikang, an Extract From Red Yeast Chinese Rice, on Coronary Events in a Chinese Population With Previous Myocardial Infarction. The American Journal of Cardiology. Volume 101, Issue 12, 15 June 2008, Pages 1689-1693 doi:10.1016/j.amjcard.2008.02.056. [248] http://www.fda.gov/bbs/topics/news/2007/new01678.html. FDA Warns Consumers to Avoid Red Yeast Rice Products Promoted on Internet as Treatments for High Cholesterol. August 9, 2007. [249] http://dx.doi.org/10.1016/j.foodchem.2010.08.021. Han J, Britten M, Daniel St-Gelais D, Champagne CP, Fustier P, Salmieri S, Lacroix M: Polyphenolic compounds as functional ingredients in cheese. Food Chemistry. Volume 124, Issue 4, 15 February 2011, Pages 1589-1594. Doi:10.1016/j.foodchem.2010.08.021. [250] http://dx.doi.org/doi:10.1016/j.tifs.2008.05.002. Day L, Seymour RB, Pitts KF, Izabela Konczak I, Lundin L: Incorporation of functional ingredients into foods. Trends in Food Science & Technology. Volume 20, Issue 9, September 2009, Pages 388-395. Natural and Safe Foods, IUFoST/Food Ingredients Asia-China Conference. Doi:10.1016/j.tifs.2008.05.002. [251] http://dx.doi.org/10.1016/j.amjmed.2009.10.017. Glisson JK, Walker LA: How Physicians Should Evaluate Dietary Supplement. The American Journal of Medicine. Volume 123, Issue 7, July 2010, Pages 577-582. Doi:10.1016/j.amjmed.2009.10.017. [252] http://dx.doi.org/10.1016/j.lfs.2005.12.020. Melethil S: Proposed rule: Current good manufacturing practice in manufacturing, packing, or holding dietary ingredients and dietary supplement. Life Sciences. Volume 78, Issue 18, 27 March 2006, Pages 2049-2053. Doi:10.1016/j.lfs.2005.12.020. [253] http://www.health.gov/dietsupp/ch1.htm. The Dietary Supplement Health and Education Act of 1994 (DSHEA).
[254] http://www.fda.gov/Food/DietarySupplements/GuidanceComplianceRegulatoryInformatio RegulationsLaws/ucm110858.htm. Dietary Supplement Current Good Manufacturing Practices (CGMPs) and Interim Final Rule (IFR) Facts. [255] http://www.evira.fi/portal/en/food/current_issues/?bid=1678. Evira requires a warning label on food supplements containing ginger as well as on ginger tea and corresponding drink powders.
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[256] http://www.ncbi.nlm.nih.gov/pubmed/15863553. Marcus DM, Snodgrass WR.: Do no harm: avoidance of herbal medicines during pregnancy. Obstet Gynecol. 2005 May;105(5 Pt 1):1119-22. Comment in: Obstet Gynecol. 2005 Aug;106(2):409-10; author reply 410-1. [257] http://www.ncbi.nlm.nih.gov/pubmed/16194058. Chrubasik S, Pittler MH, Roufogalis BD. Zingiberis rhizoma: a comprehensive review on the ginger eect and ecacy proles. Phytomedicine 2005; 12: 684-701. [258] Ginger Helpful for Nausea and Vomiting of Pregnancy. Annieappleseedproject.http:// www.annieappleseedproject.org/ginfornauspr.html. [259] http://www.ncbi.nlm.nih.gov/pubmed/15802416. Borelli F, Capasso R, Aviello G, Pittler MH, Izzo AA. Eectiveness and safety of ginger in the treatment of pregnancyinduced nausea and vomiting. Obstet Gynecol 2005; 105: 849-856. [260] http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool= pubmed&pubmedid=18357620. Bohn L, Meyer AS, Rasmussen SK: Phytate: impact on environment and human nutrition. A challenge for molecular breeding. J Zhejiang Univ Sci B. 2008 Mar;9(3):165-91. [261] http://pubs.acs.org/doi/abs/10.1021/jf9023678. Sanz-Penella, JM; TamayoRamos, JA; Sanz, Y; Haros, M: Phytate Reduction in Bran-Enriched Bread by Phytase-Producing Bidobacteria. Journal of Agricultural and Food Chemistry. Published online ahead of print, ASAP Article, doi: 10.1021/jf9023678. [262] http://www.ncbi.nlm.nih.gov/pubmed/19674804. Haros M, Carlsson NG, Almgren A, Larsson-Alminger M, Sandberg AS, Andlid T: Phytate degradation by human gut isolated Bidobacterium pseudocatenulatum ATCC27919 and its probiotic potential. Int J Food Microbiol. 2009 Sep 30;135(1):7-14. [263] http://www.ncbi.nlm.nih.gov/pubmed/15935567. Haros M, Bielecka M, Sanz Y: Phytase activity as a novel metabolic feature in Bidobacterium. FEMS Microbiol Lett. 2005 Jun 15;247(2):231-9. [264] http://www.ncbi.nlm.nih.gov/pubmed/11714342. Haros M, Rosell CM, Benedito C: Use of fungal phytase to improve breadmaking performance of whole wheat bread. J Agric Food Chem. 2001 Nov;49(11):5450-4. [265] http://www.chinadaily.com.cn/china/2010-04/08/content_9699679.htm. Unsafe ingredient in some ours. China Daily. 08.04.2010. [266] http://en.wikipedia.org/wiki/Benzoyl_peroxide. Wikipedia: Benzoyl peroxide. [267] http://media.wiley.com/product_data/excerpt/69/04712685/0471268569. pdf. Figoni: Wheat Flour.
BIBLIOGRAPHY
919
[268] http://pubs.acs.org/doi/abs/10.1021/bk-1993-0528.ch015. Roozen J P, Lining PA, van Ruth SM: Use of Enzyme-Active Soya Flour in Making White Bread. 1993, pp 192-199. ACS Symposium Series, Vol. 528. Doi:10.1021/bk-1993-0528.ch015. [269] http://www.nrjournal.com/article/S0271-5317(09)00207-3/abstract. Miranda-Vilela, Ana L.; Pereira, Luiz C.S.; Goncalves, Calos A.; Grisolia , Cesar K.: Pequi fruit (Caryocar brasiliense Camb.) pulp oil reduces exercise-induced inammatory markers and blood pressure of male and female runnersNutrition Research. Volume 29, Issue 12, Pages 850-858. Doi:10.1016/j.nutres.2009.10.022. [270] Argan oil. wikipedia. http://en.wikipedia.org/wiki/Argan_oil. [271] Moroccos liquid gold enriches berber women the national. 14 nov 2012. http://www.thenational.ae/news/world/africa/ moroccos-liquid-gold-enriches-berber-women. [272] Rseau des associations de la rserve de biosphre arganeraie rarba. http://www.remess.ma/index.php?option=com_content&view=article&id=64: rarba-chef-de-fil&catid=39:pole-sud&Itemid=68. [273] Guillaume D Charrouf Z. Should the amazing diet (regular and moderate argan-oil consumption) have a benecial impact on human health? Crit Rev Food Sci Nutr, pages 4737, 3 2010. http://www.ncbi.nlm.nih.gov/pubmed/20373191. [274] Cabrera-Vique C, Marl R, Gimnez R, and Martnez-Augustin O. Bioactive compounds and nutritional signicance of virgin argan oilan edible oil with potential as a functional food. Nutr Rev, 70(5):26679, 2012. http://www.ncbi.nlm.nih.gov/ pubmed/22537213. [275] Jordan M, Nayel A, Brownlow B, and Elbayoumi T. Development and evaluation of tocopherol-rich argan oil-based nanoemulsions as vehicles possessing anticancer activity. J Biomed Nanotechnol, 8(6):94456, 12 2012. http://www.ncbi.nlm.nih. gov/pubmed/23030003. [276] Mekh H, Belmekki F, Ziyyat A, Legssyer A, Bnouham M, and Aziz M. Antithrombotic activity of argan oil: an in vivo experimental study. Nutrition, 28(9):93741, 9 2012. http://www.ncbi.nlm.nih.gov/pubmed/22465906. [277] Monfalouti HE, Guillaume D, Denhez C, and Charrouf Z. Therapeutic potential of argan oil: a review. J Pharm Pharmacol, 62(12):166975, 12 2010. http://www. ncbi.nlm.nih.gov/pubmed/21054392. [278] Gharby S, Harhar H, Guillaume D, Haddad A, and Charrouf Z. The origin of virgin argan oils high oxidative stability unraveled. Nat Prod Commun, 7(5):6214, 5 2012. http://www.ncbi.nlm.nih.gov/pubmed/22799092.
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[279] Ould Mohamedou MM, Zouirech K, El Messal M, El Kebbaj MS, Chraibi A, and Adlouni A. Argan oil exerts an antiatherogenic eect by improving lipids and susceptibility of ldl to oxidation in type 2 diabetes patients. Int J Endocrinol, 2011:747835, 2011. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3206503/. [280] Khallouki F, Younos C, Soulimani R, Oster T, Charrouf Z, Spiegelhalder B, Bartsch H, and Owen RW. Consumption of argan oil (morocco) with its unique prole of fatty acids, tocopherols, squalene, sterols and phenolic compounds should confer valuable cancer chemopreventive eects. Eur J Cancer Prev, 12(1):6775, 2 2003. http://www.ncbi.nlm.nih.gov/pubmed/12548113. [281] Khallouki F, Spiegelhalder B, Bartsch H, and Owen RW. Secondary metabolites of the argan tree (morocco) may have disease prevention properties. review. African Journal of Biotechnology, 4(5):381388, 5 2005. http://www.academicjournals. org/AJB/PDF/Pdf2005/May/Khallouki%20et%20al.pdf. [282] Lybbert TJ, Aboudrare A, Chaloud D, Magnan N, and Nash M. Proc Natl Acad Sci U S A, 108(34):139638, 8 2011. http://www.ncbi.nlm.nih.gov/pmc/articles/ PMC3161605/.
Chapter 11 Vitamins
11.1 Vitamins
Vitamins are essential substances which act in very small quantities. Under- or oversupply of vitamins bears serious dangers.To avoid misuse in food production there were limits established by each country. Germany has a limit for vitamin A of 1000 and for vitamin D 2,5 microgramms/100g food. At the beginning of the research concerning vitamins no one knew their chemical structure and therefore proper scientic names could not be given. The vitamins were therefore designated by a letter of the alphabet. Some of the substances cited below are nowadays not considered as vitamins any more. However they are listed here as a reference to readers of old books searching historical development of the knowledge of vitamins. Important vitamins are: Vitamin A (retinol) Vitamin B-complex group B1 (thiamine) B2 (riboavin) B3 (niacin, niacinamide) B4 (adenine) B5 (pantothenic acid) B6 (pyridoxine) B10 also called Bx or PABA (para-aminobenzoic acid) B11 (growth factors, vitamin B11 B12 (cobalamin, Cyanocobalamin) B13 (orotic acid) B15 (pangamic acid) 921
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CHAPTER 11. VITAMINS
B17 (amygdalin) Bc (folic acid) Bt (carnitine) It is a non-essential aminoacid, and is not a vitamin. Choline Inositol C (ascorbic acid) D (calciferol, viosterol, ergosterol) E (tocopherol) F (fatty acids) Linoleic acid and linolenic acid were classied as vitamin F. Today this classication is not being used any more. G (riboavin) H (biotin) K (menadione) L (necessary for lactation) M (folic acid) P (bioavonoids) Rutin, hesperidin, Citrin and other bioavonoids were grouped under the name of vitamin P. They are not vitamins in its deep meaning because it is not possible to produce deciency sympotms with bioavonoid-free nutrition. Pp (niacinamide) P4 troxerutin T (growth-promotion substances, termitin, torutinin) Vitamin T was decribed by Goetsch in 1946. In 1955 it has been prooved that vitamin T was a mixture of vitmamin B1, B2, B6, nicotinic acid, pantothenic acid, folic acid, biotin, choline, para-aminobenzoic acid and small amounts of vitamin B12. Vitamin T was told to be responsible for building "giants" of ants and soldiers among the termites whith great heads. Without vitamin T the termites would retain a small head. The unspecic growth-promotion could not be observed in human.[1] U (extracted from cabbage juice)
11.1.1
Fruits and vegetables, protective factors
There are no evidences that isolated or in combination given antioxidants have a preventive activity against cancer or cardiac infarction The protective activity which is being found in natural food must therefore be active only in a natural system or in combinations with other active compounds presenting synergic eects. One should however not forget the preventive eect of folic acid during pregnancy preventing neural tube defects of the newborn (spina bida and hydrocephalus). (400microg folic acid/day) [2].
11.2. FOLIC ACID
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11.2
11.2.1
Folic acid
Folic acid fortication of cereal products
Folate deciency in early pregnancy is linked to increased risk of neural tube defects or spina bida and anencephaly in infants. Since 1998 all US all grain products are fortied with folic acid. There is an ongoing debate in UK to fortify our with folic acid. The Irelands National Committee on Folic Acid Fortication recommended that most white, brown and wholemeal breads sold in the country be fortied with 120 micrograms of folic acid per 100g of bread. Food Standards Australia New Zealand made a proposal top fortify all bread-making our with folic acid.
11.2.2
Results of folate study adverse to a fortication of food with folic acid
[3] Van Guelpen and colleagues found that plasma folate concentrations were strongly positively related to colorectal cancer CRC risk. They concluded that their ndings suggest a decreased CRC risk in subjects with low folate status. This possibility of a detrimental component to the role of folate in carcinogenesis could have implications in the ongoing debate in Europe concerning mandatory folate fortication of foods.
11.3
Folic acid supplementation of bread or ower
The UK Food Standards Agency recommended that bread or ower to be fortied with folic acid to reduce the number of cases of neural tube defects (spina bida) (March 2007). [4] The Institute of Food Research (IFR) warns of possible adverse eects of fortifying food with folic acid. According to Anthony Wright and colleagues, folates are metabolised in the gut, and folic acid is metabolised in the liver, which could easily become saturated. Supplementation may result in unmetabolised folic acid to enter the systemic circulation, since human livers low capacity for reduction may eventually give rise to saturation. [5]
11.3.1
Supplementation of Bread ower and cereals in USA and Canada
The FDA published in 1996 regulations requiring the addition of folic acid to enriched breads, cereals, ours, corn meals, pastas, rice, and other grain products.
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11.3.2
Suplementation in UK
The Foof Standards Agency considered mandatory fortication in 2002. However, the Scientic Advisory Committee on Nutrition (SACN) opposed to the fortication and issued an advice on the introduction of mandatory fortication of our with folic acid at current states saying that it beside reducing the risk of NTD-aected pregnancies in the UK, it would also increase the proportion of people in the population at risk of exceeding folic acid intakes above the UL/day and the number of people aged 65 years and over with low vitamin B12 status at risk of consuming more than 1mg/day of folic acid. The advice was linked to the condition that there be controls on voluntary fortication, and clear guidance be given on the appropriate use of supplements containing folic acid. [6] According to Kim and Solomons 2007, recent studies suggest that folic acid supplementation and fortication may promote the progression of already existing, undiagnosed, preneoplastic and neoplastic lesions. These observations are based on the increase in colon cancer diagnoses in the US and Canada. [7] Unmetabolised folic acid accelerates cognitive decline in the elderly with low vitamin B12 status. Dietary folates have a protect against cancer, but folic acid supplementation may increase the incidence of bowel cancer and breast cancer in postmenopausal women. [8]
11.3.3 11.3.4
Folic acid and Folate [4] Folate
is a generic term for a family of B-group vitamins. There are large numbers of naturally occurring folates but methyl- and formyltetrahydropteroylpolyglutamates are the main forms found in foods.
11.3.5
Folic acid
(pteroylmonoglutamic acid) is a synthetic form used in supplements and food fortication. Sometimes it is colled Vitamin B9.
11.3.6
Suplementation with folic acid
The reference nutrient intake (RNI) is the amount of a nutrient that is considered sucient to meet the requirements of 97.5% of the population. The lower reference nutrient intake (LRNI) is the amount of a nutrient that is considered sucient to meet the requirementsof 2.5% of the population. For adults, the RNI for folate is 200microg/day and the LRNI is 100microg/day. For infants and children, the RNIs are: 0-12 months, 50microg/day; 1-3 years, 70microg/day; 4-6
11.3. FOLIC ACID SUPPLEMENTATION OF BREAD OR FLOWER
925
years, 100microg/day; 7-10 years, 150microg/day; the RNI for children 11 years and above is the same as that for adults. The LRNIs for infants and children are: 0-12 months, 30microg/day; 1-3 years, 35microg/day; 4-6 years, 50microg/day; 7-10 years, 75microg/day; the LRNI for children 11 years and above is the same as that for adults. [6]
11.3.7
Maximum intake
For guidance purposes only, in the general population a supplemental dose of 1 mg/day (equivalent to 0.017 mg/kg bw/day in a 60 kg adult) would not be expected to cause adverse eects. Assuming a maximum intake from food of approximately 0.49 mg/day, a total dose of 1.5 mg/day (equivalent to 0.025 mg/kg bw/day in a 60 kg adult) would not be expected to have any adverse eects. [9]
11.3.8
The NIH study on folic acid study in preventing pregnancy complications
[10] Preconceptional folate supplementation for at least 1 year may halve number of premature birthsFolic acid reduces neural tube defects (spina bida) and anencephaly. Foli acid is already being added to cereal products in U.S. and Canada starting in 1998. Radek Bukowski and colleagues in a study concerning folate supplementation and pregnancy found that supplementation for at least 1 year before conception was associated with a 70% decrease in the incidence of spontaneous preterm delivery between 20 and 28 weeks and 50% decrease in the incidence of spontaneous preterm delivery between 28 and 32 weeks. Radek Bukowski and colleagues recommend that women of childbearing age take a daily dose of 400 micrograms starting at least 1 year before conception. The study was presented at the 28th Annual Society for Maternal-Fetal Medicine (SMFM) 2008 meeting.
11.3.9
Food fortication with Folic Acid [11]
According to a Health Food Manufacturers Association (HFMA) Report, the average intake of folic acid per day per person in the UK is 200 gram. But periconceptional requirement of folic acid per day is 400 gram. Supplementation in postconceptional period proved to be less eective in preventing NTD. Folic acid given in the periconceptional period prevents childhood leukaemia, decreases the incidence of Coronary Heart Disease and Stroke. The decrease in plasma homocysteine levels reduces the number of deaths due to stroke and Ischemic heart disease, and low levels of folate and Vitamin B12 were linked to depression.
926
In its paper Dhruvashree Somasundara also stresses that elderly are at risk primarily because they are commonly decient in Vitamin B12. He calls to fortify food with both folic acid and Vitamin B12.
11.3.10
Mandatory folic acid fortication [12]
According to Mark A. Lawrence concerns about the safety implications of mandatory folic acid fortication include possible increased risk of cancer particularly colorectal cancer, decreased cognitive function, increased risk of compromised immunity and lack of evidence of protection against coronary heart disease. Concern has also been raised regarding an increased proportion of methylenetetrahydrofolate reducatase homozygote births in women using folic acid supplements to prevent NTDs. This genotype is reliant on a high intake of folate to maintain health and is negatively associated with increased risk of several chronic diseases if diet quality is not maintained. Further it must be excluded that other phenotypic changes in ospring may take place when folic acid is supplemented in utero.
11.3.11
Lowering blood homocysteine with folic acid based supplements [13]
Robert Clarke (1998) advocated that daily supplementation with both 0.5-5 mg folic acid and about 0.5mg vitamin B-12 would be expected to reduce blood homocysteine concentrations by about a quarter to a third (for example, from about 12 mol/l to 8-9 mol/l). The author called for large scale randomised trials to determine whether lowering blood homocysteine concentrations reduces the risk of vascular disease. This publication initiated a high amount of research on the eect of homocysteine blood level.
11.3.12
Homocysteine Concentration in Early Pregnancy [14]
In 2008 Linda Dodds and colleagues found that increased total homocysteine (tHcy) was associated with placental-mediated adverse pregnancy outcomes. Increased tHcy concentrations increased risk of pregnancy loss or preeclampsia compared with subjects with lower tHcy concentrations, but it was not associated with increased risk of developing gestational hypertension or having an small for gestational age infant. The authors concluded that high tHcy in early pregnancy is a risk factor for pregnancy loss and preeclampsia and results in abnormalities of the placental vasculature.
11.3. FOLIC ACID SUPPLEMENTATION OF BREAD OR FLOWER
927
11.3.13
The Norway study [15]
Roi Miodini Nilsen and colleagues reported in 2007 a strong risk reduction of placental abruption when both folic acid and multivitamin were supplemented. The authors conclude that folic acid and other vitamin supplementation during pregnancy may be associated with reduced risk of placental abruption.
11.3.14
Voluntary food fortication policy on folate [16]
Leane Hoey and colleagues studied the eect of fortied foods on blood levels of biomarkers of folate, vitamin B and homocysteine. They wrote that mandatory folic acid fortication of food is eective in reducing neural tube defects and may even reduce stroke-related mortality, but it remains controversial because of concerns about potential adverse eects. Europe has therefore only a voluntary fortication. The authors found that voluntary food fortication increased dietary intake and biomarker status of folate and metabolically related B vitamins with potential benecial eects on health. In this research the authors stress that those who do not consume fortied foods regularly may have insucient B vitamin status and will not participate of these benets.
11.3.15
Homocysteine did not Lower Mortality and Vascular Disease in Advanced Chronic Kidney Disease [17]
High plasma homocysteine levels are a risk factor for mortality and vascular disease in observational studies of patients with chronic kidney disease. Folic acid and B vitamins decrease homocysteine levels in this population but whether they lower mortality is unknown. Treatment with high doses of folic acid and B vitamins did not improve survival or reduce the incidence of vascular disease in patients with advanced chronic kidney disease or end-stage renal disease.
11.3.16
Folates and facial clefts in newborn [18]
Allen J. Wilcox and colleagues found in a study published in 2007 that folic acid supplementation during early pregnancy (>400 g/day) was associated with a reduced risk of isolated cleft lip with or without cleft palate. The nds suggest that diets rich in fruits, vegetables, and other high folate containing foods reduced the risk somewhat, however, folic acid supplements and multivitamins added to a folate rich diets is the best protection. Folic acid provided no protection against cleft palate alone.
928
11.3.17
Multivitamins containing folic acid reduces risk of preeclampsia [19]
Shi Wu Wen and colleagues studied the eect of folic acid supplementation in early second trimester and reduction of risk of developing preeclampsia. The authors found that the supplementation of multivitamins containing folic acid was associated with increased serum folate (on average 10.51 mol/L), decreased plasma homocysteine (on average 0.39 mol/L), and reduced risk of preeclampsia. They concluded that supplementation of multivitamins containing folic acid in the second trimester is associated with reduced risk of preeclampsia. According to the authors these nding may become a new prevention strategy for pre-eclampsia.
11.3.18
Changes in plasma homocysteine during normal pregnancy [20]
Yoshihiro Sato and colleagues 2002 studied the changes in total plasma homocysteine concentration that occurred in the rst, second, and third trimesters of normal pregnancy in comparision with nonpregnant controls. The authors found that homocysteine decrease during pregnancy compared with nonpregnant controls. Homocysteine levels were decreased with folic acid supplementation. Homocysteine correlated with albumin levels, which decreased during pregnancy and with folic acid supplementation.
11.4
Vitamin K
[21] Vitamin K is an essential fat-soluble micronutrient, which is needed for a unique post-translational chemical modication in a small group of proteins with calcium-binding properties, collectively known as vitamin K-dependent proteins or Gla proteins. Thus far, the only unequivocal role of vitamin K in health is in the maintenance of normal coagulation. Nutritional vitamin K deciency is a bleeding tendency caused by the relative inactivity of the procoagulant proteins. Vitamin K dependent proteins synthesized by other tissues include the bone protein osteocalcin and matrix Gla protein, though their functions remain to be claried.
11.4.1
Chemical structure of vitamin K [22]
Vitamin K denotes a group of 2-methilo-naphthoquinone derivatives. They are human lipophilic vitamins linked to blood coagulation, bone health and liver cancer.
11.4. VITAMIN K
929
Vitamin K2 (menaquinone, menatetrenone) is normally produced by bacteria n the intestines and dietary deciency is extremely rare unless the intestines are heavily damaged. Vitamin K is a group name for a number of related compounds, which have in common a methylated naphthoquinone ring structure, and which vary in the aliphatic side chain attached at the 3-position. Phylloquinone(also known as vitamin K1 invariably contains in its side chain four isoprenoid residues, one of which is unsaturated. Menaquinones have side chains composed of a variable number of unsaturated isoprenoid residues; generally they are designated as MK-n where n species the number of isoprenoids. Naphthoquinone is the functional group. The mechanism of action is therefore similar for all K-vitamins but intestinal absorption, transport, tissue distribution, and bio-availability may dier due to dierent lipophilicity of the various side chains, and by the dierent food matrices in which they occur. The German Association for Nutrition (Deutsche Gesellschaft fr Ernhrung e.V.) recommend the consumption of vitamin K for Women 65 microg and for man 80 microg /day. There are two main forms of vitamin K:
11.4.2
Vitamin K1
The vitamin K1 It is the most important and is known as phylloquinone or phytonadione . It is present in green leafy vegetables such as lettuce, broccoli and spinach, and can be synthesised in the gut by microora.
11.4.3
Vitamin K-n
A group of compound called menaquinones (MK-n) is can also be found in foods, where " n "stands for a number of prenyl side chains. MK4 is found in meat. Fermented food like cheese and natto are rich in MK7 , MK8 , and MK9 . Sarah Cockayne and colleagues in a meta-analysis of human clinical trials using MK-4 supplements for bone health conclude that this systematic review suggests that supplementation with phytonadione and menaquinone-4 reduces bone loss. In the case of the latter, there is a strong eect on incident fractures among Japanese patients. [23] MK4 from natto and other forms of vitamin K were reported to reduce bone loss.
930
11.4.4
Vitamin K concentrations in elderly people [24]
Naoko Tsugawa and colleagues state in a researche communication that vitamin K deciency is associated with low bone mineral density and increased risk of bone fracture. Phylloquinone (K1 ) and menaquinone 4 (MK4 ) and 7 (MK7 ) are generally observed in human plasma; however, data are limited on their circulating concentrations and their associations with bone metabolism or with gama-carboxylation of the osteocalcin molecule. They conclude that submaximal gama-carboxylation being related to the prevention of fracture or bone mineral loss, circulating vitamin K concentrations in elderly people should be kept higher than those in young people.
11.4.5
Vitamin K deciency bleeding in infants [21]
According to WHO vitamin K deciency in infants up to around age 6 months, although rare, represents a signicant public health problem throughout the world. It is now being termed vitamin K deciency bleeding (VKDB). In adults, primary vitamin K-decient states that manifest as bleeding are almost unknown.
11.4.6
Danish Osteoporosis Prevention Study (DOPS) [25]
The Danish Osteoporosis Prevention Study (DOPS), however, found vitamin K1 to have no eect on the bone mineral density (BMD)reporting that reports that vitamin K1 intake had no impact on BMD and fracture risk of peri-menopausal women. This supports the statement of WHO/FAO that the only unequivocal role of vitamin K in health is in the maintenance of normal coagulation. citeWHObleeding
11.4.7
Vitamin K eect on diabetes [26]
Makiko Yoshida and colleagues 2008 in a study concerning the benecial eect of vitamin K on insulin resistance, found that supplementation with 500 g/day phylloquinone for 36 months improves the insulin resistance in older men and women. Insulin resistance was measured by homeostasis model assessment (HOMA-IR) at 36 months as primary outcome, and fasting plasma insulin and glucose were examined as the secondary outcomes. The authors concluded that Vitamin K supplementation for 36 months at doses attainable in the diet may reduce progression of insulin resistance in older men, but not in women.
11.4.8
The role of Vitamin K1 in BMD, reduced bone fractures and cancer [27]
The BMD, or Bone mineral density score is determined by methods using X-ray Absorptiometry, Computed Tomography or Quantitative Ultrasound to determine osteopenia (low
11.5. PROVITAMIN A CAROTENE
931
bone mass) or osteoporosis. The Dual Energy X-ray Absorptiometry or DXA is most frequently used in these cases. According to Cheung and colleagues 2008 vitamin K, aside of its role in blood coagulation, the deciency of vitamin K1 may play a role in low BMD and risk for fractures. The authors found in a study that daily 5 mg vitamin K1 supplementation for 2 to 4 years increased serum vitamin K1 levels by 10-fold, and decreased the percentage of undercarboxylated osteocalcin and total osteocalcin levels (bone formation marker), but did not change C-telopeptide levels (bone resorption marker). Women which received supplementation of vitamin K had a reduced number of clinical fractures and cancers. The authors concluded that daily 5 mg of vitamin K1 supplementation f does not protect against age-related decline in BMD, but may protect against fractures and cancers in postmenopausal women with osteopenia. The authors call for more studies oin this matter.
11.5
Provitamin A Carotene
Provitamin A can be modied by the body to vitamin A.This happens only to the extent of need. Therefore one says provitamin A to be a safe source of vitamin A bearing no danger of overfeeding.
11.5.1
Vitamin A derived light sensing system in cells [28]
Phototransduction is a process by which light is converted into electrical signals in the rod cells, cone cells and photosensitive ganglion cells of the retina of the eye. The retina is formed by rods and cone cells. These cells contain a chromophore, which are formed by membrane protein called opsin, connected with the aldehyde of Vitamin A1 (11-cis retinal). Retinol cannot be synthesised by humans and must be supplied by vitamin A in the diet. Deciency of all-trans retinol can lead to night blindness. Rod cells deal with low light level and do not mediate colour vision. Cone cells can code the color of an image. There are three dierent types of cones. Each cone type responds best to certain wavelengths, or colours, of light because each type has a slightly dierent opsin. Opsins transform a photon of light into an electrochemical signal, triggering the visual transduction cascade. Another opsin found in the mammalian retina, melanopsin, is involved in circadian rhythms and pupillary reex but not in image-forming. Opsins can change their conformation from a resting state to a signalling state upon light absorption, which activates the G protein, thereby resulting in a signalling cascade that produces physiological responses. [29]
932
11.5.2
Study urges policymakers to provide vitamin A supplementation for areas at risk [30]
Vitamin A deciency in children increases vulnerability to infections like diarrhoea and measles and may also lead to blindness. Globally, the World Health Organisation estimates that 190 million children under the age of 5 may be vitamin A decient. But, despite widespread eorts, vitamin A programmes do not reach all children who could benet. Mayo-Wilson et al 2011, say that vitamin A supplements reduce child mortality by 24% in low and middle income countries. It may also reduce mortality and disability by preventing measles, diarrhoea and vision problems, including night blindness. Vitamin A supplementation may save over 600,000 each year and 20 million disability-adjusted life years would be gained. The authors urge policymakers to provide vitamin A supplementation for children under 5 in decient areas.
11.5.3
Activities of the WHO and other organizations [31]
The WHO stresses that for pregnant women in high-risk areas, vitamin A deciency occurs especially during the last trimester when demand by both the unborn child and the mother is highest, seen as night blindness during this period. To combat vitamin A deciency, the WHO pursues short-term interventions and proper infant feeding backed up by long-term sustainable solutions, which includes a combination of breastfeeding and vitamin A supplementation, coupled with enduring solutions, such as promotion of vitamin A-rich diets and food fortication. Between 6 months and 6 years of age can reduce overall child mortality by a quarter in areas with signicant vitamin A deciency.. However, because breastfeeding is time-limited and the eect of vitamin A supplementation capsules lasts only 4-6 months, they are only initial steps towards ensuring better overall nutrition and not long-term solutions. In 1998 WHO and its partners UNICEF, the Canadian International Development Agency, the United States Agency for International Development and the Micronutrient Initiative - launched the Vitamin A Global Global Alliance for Vitamin A (GAVA), which is an informal partnership between the Canadian International Development Agency, Helen Keller International, Micronutrient Initiative, UNICEF, USAID, and the World Bank. About 75 per cent of the vitamin A required for supplementation activity by developing countries is supplied by the Micronutrient Initiative. Vitamin Angels was launched in 2007 and will cover 18 countries. The program gives children two high dose vitamin A and anti-parasitic supplements (twice a year for four years), which provides children with enough of the nutrient during their most vulnerable years in order to prevent them from going blind and suering from other life-threatening
11.6. VITAMIN B diseases caused by Vitamin A Deciency.
933
11.6
11.6.1
Vitamin B
Vitamin B2 phototransduction light sensing Cryptochrome photoreceptors [32]
The light sensing process so far had been exclusively linked to retinal. Holmes et al. 2011 discovered a second form of phototransduction light sensing in cells. This light sensing system uses cryptochromes coupled to a B2 vitamin derivate. Cryptochromes are blue-light photoreceptors found in circadian and arousal neurons. The research targeted the CRYPTOCHROME (CRY) gene of large lateral ventral arousal neurons (l-LNv) in Drosophila melanogaster. The authors report that cry-null lines are light unresponsive, but light response is restored when CRY expression is reactivated, requiring a avin redox-based mechanism which also depends on potassium channel conductance, but is independent of the classical circadian CRY-TIMELESS interaction. Neurons not light responsive could be activated when they were genetically induced to express cryptochrome.
11.6.2
Vitamin B1
Hipervitaminosis of vitamin B1 may lead to nervousness and headache.
11.6.3
Vitamin B2
There is no maximum limit for vitamin B2.Even in high dose there are no undesired reactions.
11.6.4
Vitamin B6
Accentuated hipervitaminosis of vitamin B6 causes alterations of the mobility,numbness and psychical alterations.Alterations similar to contergan in neonates were also observed. The UK Committee on Toxicity of Chemicals in Food recommend not to exceed 10 mg per day. A sucient supply of vitamin B6 is guaranteed with consumption of meat,sh,eggs, and some vegetables. Some food supplements contain up to 100 mg.The Committee tries to organise a voluntary producer limit of vitamin B6 in food supplements and include more informations on label.The commission is concerned about possible damage of the nervous system in case of high dose.
934
11.6.5
Vitamin B12
There are no major problems noted by excessive consumption of vitamin B12. A predisposition to thrombosis is possible.
11.6.6
Niacin
Niacin is also known as vitamin B3, nicotinic acid and vitamin PP. Niacin is a global denomination of nicotinic acid and her acid amid denominated as nicotinamide, also called niacinamide.Both vitamins have same properties. Nicotinamide is important to the transport of electrons in cells and is engaged in the following reactions: Anaerobic glicolysis In the cycle of cancer (oxidative phosphorilation) In the synthesis of fatty acids. Nicotinic acid and nicotinamide can be assimilated directly or are created by hydrolysis of coenzyme. Adenine is transformed in NAD(P) in the liver. NAD(P) stands for Nicotinamide-AdenineDinucleotide-Phosphate. To synthesises NAD in human cells 60 mg of tryptophane corresponding to 1 mg equivalents of nicotinamide are necessary.For this reason the unit "niacin equivalent" was created. 1 niacin equivalent = 1 mg niacin = 60 mg tryptophane Niacin is not deposited. Poisonings resulting from excessive addition of niacin to food are documented.Symptoms are ictericia, failures of liver, icteric skin with burning ushes. Toxic reactions were not noted after daily intake of 3 to 6 grams of nicotinic acid trying to inhibit the production of hepatic VLDL causing parallel dilatation of the peripheric vascular system producing the red ush which disappears after some days. Nicotinamide does not produce ush and does not reduce cholesterol. It is therefore that nicotinamide is being used in treatment of insuciency of niacin, using dose between 50 to 250 mg/day.
11.6.7
Sources of niacin
Niacin is present mainly in animal food (meat)as coenzymes. Absorption of Niacin from meat is near 100%.The amount of niacin in plants is very low. In cereals niacin is being found in the aleurone coat (external coat of the grain). Niacin is lost during polishing of grains to obtain white our. In cereal niacin is bound as a complex in macromolecules niacitine, therefore only 30% of vegetable niacin can be assimilated.
11.6. VITAMIN B
935
Triptophane is sometimes much higher as free niacin, therefore the equivalent of niacin is being used. In vivo conversion of triptophane in niacin depends on coexistence of vitamin B6.
Table 11.1: Niacin in food, according to DGE Food Meat Fish Sardine Tuna Mackerel Milk Butter Cheese Black bread White bread Lentil Soya meal Sunower seed Yeast, dry Yeast, fresh Fruits Vegetables 0,6 to 2,0 Coee, ground mg niacin in 100 g 5 to 11 3 to 4 9,7 8,5 7,5 0,09 0,03 1,2 3,3 0,9 2 2,2 4 45 17 0,65 13,7
Table 11.2: Daily intake of niacin in mg/day ,recommended by DGE Group babies Under 4 month 5 From 4 to 12 month 6 From 1 to 4 years Over 4 and under 7 years From 7 to under 10 years From 10 to 13 years From 13 to under 15 years From 15 to under 19 years From 19 years and up Pregnant children men women
9 12 13 15 20 20 18 14 16 16 15 17
936 During lactation 20
11.6.8
Natural vitamin nicotinamide riboside (NR) protects against obesity and age-related disorders [33]
According to Auwerx et al. 2012, the nicotinamide adenine dinucleotide (NAD) precursor nicotinamide riboside (NR) is linked to weight gain prevention, reduction of diabetes risk, improved muscular performance, better thermal resistance under temperature stress. NAD(+) acts as a cosubstrate for SIRT1 and SIRT3, both are sirtuin enzymes. These enzymes burn lipids and activate oxidative metabolism in mitocondria. The authors found that NR supplementation increases NAD(+) levels enhancing SIRT1 and SIRT3 activity protecting against the outcomes of high fat diet. Nicotinamide riboside (NR) is a novel form of vitamin B3, its supplementation is therefore being suggested to reduce the risk of fatty diets and age-related disorders. The natural content of NR in milk and other foods is small and the eect of high doses in humans must be evaluated, cautions the authors.
11.7
Bioavailability of vitamin C from kiwifruit
[34] Vitamin C is an essential nutrient. Humans do not synthesize ascorbic acid and require it in the diet. Carr et al. assessed the bioavailability of vitamin C consuming kiwifruit (Actinidia chinensis var. Hort. 16A), The authors report that one kiwifruit per day was required to reach what is considered healthy levels (>50 mol/l). Two kiwifruits per day increases vitamin C levels in plasma and urinary output of the vitamin, indicating the plasma vitamin C saturation level (>70 mol/l).
11.7.1
Transglutaminase [35]
Transglutaminase is an enzyme which polymerizes proteins with the result of a network like structures. This eect is used in the production of meat, sausages, cheese, yogurt and related products, ice creams and production of gelatin improving consistency and cream character of the products.
11.8
11.8.1
Vitamin D
Vitamin D
As sun incidence and the amount of natural vitamins in dierent geographical regions throughout the world vary, each country has its own regulations. France being nearer to the Equator and having thus a higher sun incidence as Germany has a limit of vitamin A which is very low. Vitamin D is there not allowed in order to avoid an oversupply.
11.8. VITAMIN D
937
11.8.2
Vitamin D2 is as eective as vitamin D3 [36]
Michael Holick and colleagues found that vitamin D2 daily was as eective as the same amount of vitamin D3 in maintaining serum 25-hydroxyvitamin D levels and did not negatively inuence serum 25-hydroxyvitamin D3 levels. Therefore, vitamin D2 is equally as eective as vitamin D3 in maintaining 25-hydroxyvitamin D status. This study was performed in response to two reports suggested that vitamin D2 is less eective than vitamin D3 in maintaining vitamin D status. The European Union advises not to exceed 1000 mg of complementary vitamin C in a daily personal feeding. Other specic legislations exists and should be observed for each vitamin and each kind of food.
11.8.3
Vitamin D status is unsucient [37]
According to US surveys the intake of vitamin D is insucient. Additional food fortication as well as dietary and supplement guidance are needed for the general population. Vitamin D status diers by latitude and race and variation of the sunlight during seasons, especially the winter month. Individuals with more skin pigmentation are at increased risk of deciency. It is synthesised in the body on exposure to sunlight. Food can not supply sucient amounts. To reduce cancer risk, exposure to sunlight or articial UVR sources should be accompanied by abundant fruit and vegetables intake and/or antioxidants, not smoking in order to help combat the free radicals generated from UVR exposure.
11.8.4
Skin pigmentation and Vitamin D deciency [38]
According to the study published by Garland, a scientist of the University of California Moores Cancer Centre, the vitamin D status diers by latitude and race, with residents of the northeastern United States and individuals with more skin pigmentation being at increased risk of deciency. The increased skin pigmentation of African-Americans reduces their ability to synthesize vitamin D, turning them more susceptible to breast cancer, colon, prostate and ovarian cancers as white women. Vitamin D fortied foods are consumed to reduce the risk of osteoporosis. The cancer risk reduction may become another important reason for the demand of this vitamin The authors suggest that eorts to improve vitamin D status, for example by vitamin D supplementation, could reduce cancer incidence and mortality at low cost, with few or no adverse eects.
938
11.8.5
Low levels of vitamin D are associated with all-cause and cardiovascular mortality [39]
Harald Dobnig and colleagues 2008 say that low 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D levels are independently associated with all-cause and cardiovascular mortality. Thes authors write that these ndings base on the correlation of low 25-hydroxyvitamin D levels of inammation indicators (C-reactive protein and interleukin 6 levels), oxidative burden (serum phospholipid and glutathione levels), and cell adhesion (vascular cell adhesion molecule 1 and intercellular adhesion molecule 1 levels). The authors point out that urbanization, demographic shifts, decreased outdoor activity, air pollution and global dimming, and decreases in the cutaneous production of vitamin D with age may account for 50% to 60% of people to have low vitamin-D status. The minimum desirable serum level of 25-hydroxyvitamin D has been suggested to be 20 to 30 ng/mL, and levels lower than this are clearly related to compromised bone-mineral density, falls, and fractures and more recently have also been linked to cancer and immune dysfunction, as well as cardiovascular disease, hypertension, and metabolic syndrome, the authors report. The study used data from the Ludwigshafen Risk and Cardiovascular Health (LURIC) study which investigated the eect of genetic polymorphisms and plasma biomarkers on cardiovascular health status. [40] However, they stress that aside of the eect of low vitamin D status, other factors may be associated with mortality including matrix metalloproteinases.
11.8.6
Low levels of 25(OH)D with higher risk of myocardial infarction [41]
Edward Giovannucci and colleagues in a study in 2008 found an association of low levels of 25(OH)D with higher risk of myocardial infarction.
11.8.7
Low Vitamin D Linked to Atherosclerosis [42]
Researchers found new evidence from the Northern Manhattan Study connecting low vitamin D levels to atherosclerosis. Silverberg et al. 2011, report that D levels 25hydroxyvitamin D levels were associated with increased intima-media and maximal carotid thickness in those with plaque. The authors studied 203 adults from the Northern Manhattan Study (NOMAS) which is a research study of stroke and stroke risk factors in the Northern Manhattan community. [43]
11.8. VITAMIN D
939
The authors assessed levels and eects of 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, calcium, phosphorus, and parathyroid hormone. They found that 25-hydroxyvitamin D was inversely associated with both intima-media thickness and maximal carotid plaque thickness. Plaque number was associated with phosphorus levels (beta, 0.39 per 1-mg/dL increase) and calcium-phosphorus product (beta, 0.36 per 10-U). 25-hydroxyvitamin D accounted for 13% of the var iance in both intima-media thickness and maximal carotid plaque thickness. Calcium, parathyroid hormone, and 1,25-dihydroxyvitamin D levels were not associated with carotid measures. There are still insucient data on the eect of vitamin D. The precise nature of this association and the optimum levels of vitamin D for vascular health remain unknown, say the authors.
11.8.8
Low vitamin D levels are associated with decline of cognitive function and high risk of Alzheimers disease [44]
Increasing number of studies link low vitamin D levels with dierent health issues, including poor cognition. Balion et al. 2012 report that with Alzheimers disease (AD) had lower concentrations of vitamin D than those without AD, and better cognitive test results were linked to higher vitamin D concentrations. The mean Mini-Mental State Examination (MMSE) scores were compared between participants with vitamin D <50 nmol/L to those with values 50 nmol/L. All studies included in this systematic review of the literature measured 25-hydroxyvitamin D (25(OH)D) concentrations except for 1 that measured 1,25-dihydroxyvitamin D (1.25(OH)D), 4 studies measured both. The authors stressed, however, that some factors aecting vitamin D concentrations, including skin pigmentation, age, genetics, poor nutrition, time of sun exposure and testing, were not considered by some studies. The results of vitamin D studies may depend on where participants live and the time of the year that testing was done. The authors concluded that lower vitamin D concentrations are associated with poorer cognitive function and a higher risk of Alzheimers disease. The neuroprotective action of vitamin D is not fully understood, however, it is being suggested that vitamin D acts as a neurosteroid. The active form D (1,25(OH)D) synthesized by the hypothalamus and large neurons in the substantia nigra at the brain. It is also known that vitamin D regulates many genes which contributes to neuroprotection by modulating the production of such things as nerve growth factor, and regulating neurotransmitters. The authors also remind that the ideal concentration of vitamin D is still under debate. However, two cut points are recommended worldwide: 50 and 75 nmol/L. Canada, for example, recommends the upper level for bone health. Physicians should recommend
940
supplements for patients not getting sucient vitamin D, said Dr. Balion. Canada, recommend 600 IU of vitamin D daily for older children and adults. Ongoing trials, such as the VITAL trial, will provide a better understanding of the physiology of vitamin D. The VITAL (VITamin D and OmegA-3 TriaL) [45] VITAL is a large 5-year clinical trial sponsored by the National Institutes of Health, is randomly assigning 20,000 people across the United States. The trial will investigate whether taking daily dietary supplements of vitamin D3 (2000 IU) or sh oil (1 gram of omega-3 fatty acids) reduces the risk of developing cancer, heart disease, and stroke in people who do not have a prior history of these illnesses. (in the form of vitamin D3, cholecalciferol) and marine omega-3 fatty acid eicosapentaenoic acid (EPA) + docosahexaenoic acid (DHA) supplements. Cerebrospinal uid biomarkers to dierentiate between neurological diseases [46] Hall et al. 2012 assessed the ability of 5 cerebrospinal uid (CSF) biomarkers to dierentiate between common dementia and parkinsonian disorders. with Parkinson disease (PD), PD with dementia (PDD), dementia with Lewy bodies (DLB), Alzheimer disease (AD), progressive supranuclear palsy (PSP), multiple system atrophy (MSA), or corticobasal degeneration (CBD). SETTING Neurology and memory disorder clinics. Four biomarkers, T-tau; P-tau; A 1-42 and -synuclein, can dierentiate patients with Alzheimers disease (AD) from those who have dementia with Lewy bodies (DLB) or Parkinsons disease with dementia (PDD). The neurolament light chain (NF-L) is a biomarker which can separate patients with PD from those with atypical parkinsonism, such as progressive supranuclear palsy, multiplesystem atrophy, and corticobasal degeneration, the researchers also report.
11.8.9
The Institute of Medicine (IOM) and the VITAL Study on vitamin D intake [47]
The Institute of Medicine (IOM) recommended 600 international units (IU) per day for people aged 1 to 70 and 800 IU per day for those aged 71 and older, and an acceptable upper limit of daily intake to 4000 IU for adults. Extremely high intakes of vitamin D can lead to too much calcium in the blood and damage the kidney and heart, but whether moderately high doses of vitamin D have side eects is not yet clear. The IOM says that vitamin D has bone benets but it is unknown whether vitamin D supplements prevent diseases cancer, heart disease, stroke, or other chronic diseases. Because of this uncertainty, the IOM called for more research to determine whether higher doses of vitamin D can lower the risk for cancer, heart disease, stroke, and other chronic
11.8. VITAMIN D
941
illnesses and whether such doses pose any health risks. The VITAL Study, also known as the Vitamin D and Omega-3 Trial, is designed to answer the scientic questions regarding vitamin D.
11.8.10
Nonvertebral Fracture Prevention With 482-770 IU/d Vitamin D [48]
Foregoing vitamin D studies said it could only reduce fracture risk in combination with calcium. However, according to Heike A. Bischo-Ferrari and colleagues 2009 the prevention of nonvertebral fractures with vitamin D is dose-dependent for individuals aged 65 years or older. The authors found that a high supplemental vitamin D dose (482-770 IU/d) should reduce nonvertebral fractures by at least 20% and hip fractures by at least 18%. The use of low-dose vitamin D with or without calcium in the prevention of fractures among older individuals is not being recommended by the authors, and greater benets may be achieved if vitamin D supplementation starts earlier.
11.8.11
Call for vitamin D supplementation of risk-group [49]
Bruce Ames and Joyce McCann in a critical review write that there is evidence to suggest an important role for vitamin D in brain development and function. The authors comment previous studies in both human and animal models which indicate that inadequate levels of vitamin D may also produce cognitive or behavioural consequences, although the evidence is not conclusive for the moment. The authors conclude that despite residual uncertainty, recommendations for vitamin D supplementation of at-risk groups, including nursing infants, the elderly, and AfricanAmericans appear warranted to ensure adequacy.
11.8.12
Low vitamin D may be linked to Alsheimers disease [50]
Marian Evatt and colleagues 2008 report that Fifty-ve per cent of patients with Parkinsons disease had insucient levels of plasma 25-hydroxyvitamin D (25[OH]D). The authors wrote that low vitamin D levels may contribute to the risk of developing Parkinsons disease. The group with Parkinsons disease in this study presented a vitamin D serum level of 31.9 ng/ml compared with 34.8 ng/ml of a group of Alzheimers disease and 37.0 ng/ml of healthy groups. The authors concluded that vitamin D insuciency may have a unique association with Parkinsons. The researchers continue their study to see if a dietary supplement, or increased exposure to sunlight may help alleviate symptoms or even retard progression of the disease.
942
11.8.13
Vitamin D and cognitive decline or dementia [51]
Llewellyn and colleagues 2010 studied the connection between cognitive decline and low levels of serum 25-hydroxyvitamin D (25[OH]D) using data of the InCHIANTI study [52] conducted in Italy between 1998 and 2006. The Mini-Mental State Examination (MMSE) [53] was used to evaluate cognitive decline. Severe serum 25(OH)D deciency were found with levels <25 nmol/L), levels >25 to <50 nmol/L were considered as insucient, whereas levels of 25(OH)D >/=75 nmol/L were considered as sucient. Evaluating their data, the authors state that low levels of vitamin D are associated with substantial cognitive decline in the elderly population, and status of vitamin D should be considered en treatment and prevention. Data from the Third National Health and Nutrition Survey (NHANES III) [54] also show that vitamin D deciency is associated with an increased risk for cognitive impairment in older persons. According to Dr. Llewellyn vitamin D seems to play a role in processes that may be important for dementia risk, including vascular health and amyloid clearance from the brain. Controversies McGrath and colleagues 2007 also using data from NHANES III did not nd an association between vitamin D levels and cognitive performance. Llewelly says that results of McGrath study may be related to methodology which used only delayed verbal memory from the Mini-Mental State Examination (MMSE) and the East Boston Memory Test. [55] Andrew Grey, MD, and Mark Bolland, in an editorial comment the study of Llewellyn and colleagues, pointing out that it is unlikely that a single vitamine could play such a substantial role in preventing diseases. The authors say that it is more likely that low vitamin D is not the cause, but only a marker of overall poor health, low sunlight exposure, low physical activity, high adiposity. [56]
11.8.14
Increased intake of Vitamin D3 to 1000 IU/day to lower colorectal cancer risk [57]
Overall, individuals with 1000 IU/day oral Vitamin D had 50% lower incidence of colorectal cancer compared to reference values. Cedric F. Garland urges for a prompt public health action to increase intake of Vitamin D3 to 1000 IU/day, and to raise 25-hydroxyvitamin D by encouraging a modest duration of sunlight exposure.
11.8.15
Sun exposure and prostate cancer risk reduction [58]
A study leaded by Esther M. John found that the risk of prostate cancer was reduced by 50 percent in men who had high levels of sun exposure during their lifetimes, compared
11.8. VITAMIN D
943
with men who had low lifetime levels. The ndings of this study support the hypothesis that sun exposure and vitamin D receptor (VDR) polymorphisms together play important roles in the aetiology of prostate cancer. The best source of vitamin D is from 20-30 minutes sun exposure. Long sun exposure is discouraged due to the risk of skin cancer. Other authors nd 5 to 10 minutes sun exposure on our face and arms during the summer time sucient to obtain the required daily amount of Vitamin D. [59]
11.8.16
Vitamin D supplementation in winter necessary [60] [61] [59]
Dr Julie Wallace and researchers from the Northern Ireland Centre for Food and Healthtogether with with colleagues from University College Cork to investigate what level of dietary vitamin D is needed in winter. According to Dr. Wallace higher levels of vitamin D fortication and supplementation are needed. Large population groups are at risk of having not sucient supply of vitamin D. Foods which are good sources of vitamin D like oily sh are not consumed regularly. The best source could be from fortied foods and supplements. Some authors point out that Asian children suer insucient levels of vitamin D with, risk of osteoporosis. Vitamin D2 is as eective as vitamin D3 Michael Holick and colleagues found that vitamin D2 daily was as eective as the same amount of vitamin D3 in maintaining serum 25-hydroxyvitamin D levels and did not negatively inuence serum 25-hydroxyvitamin D3 levels. Therefore, vitamin D2 is equally as eective as vitamin D3 in maintaining 25-hydroxyvitamin D status. This study was performed in response to two reports suggested that vitamin D2 is less eective than vitamin D3 in maintaining vitamin D status.
11.8.17
Vitamin D deciency in children and toddlers [62]
Gordon and colleagues 2008 found that a low degree of vitamin D insuciency is widespread in US. The authors also stress that breastfed infants in winter who did not receive vitamin D supplementation were the most severely vitamin D decient. The authors enforce the recommendations for health care providers and parents to ensure that breastfed infants receive daily vitamin D supplementation for the duration of breastfeeding In this study older age, winter season, higher body mass index, black race/ethnicity, and elevated parathyroid hormone concentrations were also associated with lower vitamin D status. One-third of vitamin D-decient participants exhibited demineralization.
944
11.8.18
Review of vitamin D deciency [63]
Rovner and OBrien 2008 found that there is still insuciency on vitamin D in children in the United States. The authors eorts call for eorts to improve the vitamin D status of children.
11.8.19
Low levels of vitamin D linked to increased deposition of fat in young women [64]
According to Kremer and colleagues 2010 vitamin D insuciency (25-hydroxyvitamin D) is linked to increased muscle fat and decreased muscle strength. Approximately 59% of subjects were 25OHD insucient (higher or equal to 29 ng/ml). Serum 25OHD wasa found to inversely related to percent muscle fat. The relation between 25OHD and muscle adiposity was independent of body mass or visceral fat. The authors concluded that vitamin D insuciency is associated with increased fat inltration in muscle young women but stress that more studies are necessary before a supplementation can be recommended. In a study of 2009 the group around Kremer found that vitamin D insuciency is associated with increased body fat and decreased height but not changes in peak bone mass. [65]
11.8.20
Increased intake of calcium and vitamin D from non-fat dairy reduces the risk of high blood pressure [66]
Lu Wang and colleagues 2008 investigated the associations of intake of dairy products, calcium, and vitamin D with the incidence of hypertension trend. The risk of hypertension decreased with high dietary calcium intake, but did not change with calcium or vitamin D supplements, or with high-fat dairy products for which the saturated fats in high-fat dairy products may my be responsible for. High calcium intake facilitates weight loss and enhances insulin sensitivity, which also contribute to blood pressure reduction. The study concluded that intakes of low-fat dairy products, calcium, and vitamin D reduced the risk of hypertension in middle-aged and older women, suggesting their potential roles in the primary prevention of hypertension and cardiovascular complications. The study supports the 2005 Dietary Guideline from the US Department of Agriculture recommending the intake of milk and milk products to three servings per day and stresses the importance of low-fat dairy products.
11.8.21
Diagnosis and treatment of Vitamin D deciency [67]
According to Cannell and colleagues 2008 the metabolic product of vitamin D is a potent, pleiotropic, repair and maintenance, secosteroid hormone. Vitamin D deciencies are comOurFood Database of Food and Related Sciences Copyright 1998-2010 Karl H. Wilm. All rights reserved.
11.8. VITAMIN D mon, standing for a host of diseases other than cancer.
945
Daily ingestion of 1100 IU of colecalciferol (vitamin D) over a 4-year period were suggested to reduced the incidence of non-skin cancers. The authors stress that ocial recommendations were never designed and are not eective in preventing or treating vitamin D deciency. Diagnosis of vitamin D deciency The authors say that assessing serum 25-hydroxy-vitamin D is the only way to make the diagnosis and to assure that treatment is adequate and safe. They recommend that the of serum levels of 25-hydroxy-vitamin D should be raised >40 ng/ml, year around, which is the level found in humans living naturally in a sun-rich environment. Sunlight, articial ultraviolet B radiation or supplementation are being suggested by the authors which say that benets of all treatment modalities outweigh potential risks. Cannell and colleauges suggest a supplementation of 5000 IU (125 microg) of vitamin D/day for obese, aged and/or dark-skinned patients to maintain adequate levels during the winter at many temperate latitudes
11.8.22
Vitamin D2 , ergocalciferol is not suitable for supplementation [68]
Both forms of vitamin D (D2 and D3 ) used in supplementation had been regarded as equivalent and interchangeable. However, according to Lisa A Houghton and Reinhold Vieth, ergocalciferol (Vitamin D2 should not be regarded as a nutrient suitable for supplementation or fortication because it is less ecient in raising serum 25-hydroxyvitamin D, its metabolites have a diminished binding to vitamin D binding protein in plasma, and a nonphysiologic metabolism and shorter shelf life compared with cholecalciferol (vitamin D3 ). Consumer should look at the ingredient list of fortied foods such as margarine, cereals and probiotics for good cholecalciferol (vitamin D) [68]
11.8.23
High vitamin D may increase pancreatic cancer risk in male smokers says a Finnish study [69]
The 25-(OH)D is the major circulating vitamin D metabolite found in human serum and is determined by diet and exposure to sun. Several recent studies advocate a high level of vitamin D to reduce risk of coronary and other diseases, such as pancreatic cancer. Pancreatic cells express 25-(OH) D(3)-1alpha-hydroxylase that generates the biologically active 1,25-dihydroxy(OH)(2) D form, and a high vitamin D status may aect the cells
946
of the pancreas. Stolzenberg-Solomon 2009, however, cites a nested case-control study conducted in a population of male Finnish smokers which showed a 3-fold increased risk for pancreatic cancer with high vitamin D status. This study was conducted in male smokers, limiting therefore its conclusions to this group. The author writes that there are more studies necessary to make a nal conclusion on the association of vitamin D and pancreatic cancer.
11.8.24
The Prostate, Lung, Colorectal, and Ovarian Screening Trial [70]
In a nested case-control study in the Prostate, Lung, Colorectal, and Ovarian Screening Trial cohort of men and women prediagnostic serum 25(OH)D concentrations study Stolzenberg-Solomon and colleagues found no association of Vitamin D with pancreatic cancer overall. This study could not support the strong positive association of 25(OH)D and pancreatic cancer of the foregoing Finnish study. However, increased risk of pancreatic cancer was found in persons with low solar exposure, but not in those with moderate to high annual exposure, which is similar to the Finish study. [71]
11.8.25
Vitamin D does not reduce Upper Respiratory Tract Infections [72]
A clear evidence of the benet of vitamin D exists only for bone health, measured by increased bone density and reduced fracture rates. According to the VIDARIS Randomized Controlled Trial, monthly dose of 100,000 IU of vitamin D3, 25-OHD (25-hydroxyvitamin D), in adults did not reduce the incidence or severity of Upper Respiratory Tract Infections (URTIs). The study of Murdoch et al. 2012 does not support observational studies which found an inverse association between 25-hydroxyvitamin D levels and URTIs. Participants received an initial oral vitamin D3 dose of 200,000 IU, followed by a second dose of 200,000 IU the following month, then 100,000 IU monthly for 16 months. At baseline, participants had an average 25-OHD level of 29 ng/mL. The mean level decreased to about 20 ng/mL during the winter in the placebo group. With vitamin D supplementation, the levels in the intervention group increased to 48 ng/mL. The authors stress that, despite the absence of benet recorded in this study, other populations with high vitamin D deciency might benet from vitamin D supplementation. Vitamin D supplementation others than musculoskeletal health is controversial [73] The 2010 report of the Institute of Medicine suggests that there are no adequate evidences supporting vitamin D supplementation for indications other than musculoskeletal health
11.8. VITAMIN D
947
and most North Americans receive sucient vitamin D from their diet and sun exposure. The report of the Institute of Medicine says the demarcations between deciency (< 20 ng/ml), insuciency (20-30 ng/ml), and optimal (30-80 ng/ml) serum concentrations are controversial. Vitamin D in doses of 800-5000 IU/day improve musculoskeletal health (e.g., reduces the rate of fractures and falls in older adults (aged 65 yrs). In patients with documented vitamin D deciency, a cumulative dose of at least 600,000 IU administered over several weeks appears to be necessary to replenish vitamin D stores. Single large doses of 300,000-500,000 IU should be avoided. The guideline recommends that clinicians screen for vitamin D deciency in people at risk for deciency, including obese individuals, blacks, pregnant and lactating women, and patients with malabsorption syndromes. Vitamin D supplementation should not be oered routinely to other patient populations, sensible sun exposure is an inexpensive and enjoyable way to maintain vitamin D stores. However, 200 IU/day or lower will cause no harm if taken on its own decision. Guidelines for vitamin D supplementation [74] To summarize recommendations from the 2011 US Institute of Medicine report (on vitamin D) [75] and the new guideline from the US Endocrine Society [76]. Dierence in the recommendations from the US Institute of Medicine and the US Endocrine Societys Practice Guideline reects dierent goals and views on current evidence. Table 11.3: Vitamin D Guidelines Vitamin D Institute of Endocrine RDA Medicine Societ less than 1 year 400 400-1000 IU older than 1 year 600 600-1000 IU 19 y until 70 years 600 1500-2000 IU older than 70 years 800 1500-2000 IU The US Institute of Medicine concluded that serum 25-hydroxyvitamin D (25(OH)D of 20 /ml or more will cover the requirements of 97.5% of the population. The US Endocrine Societys Clinical Practice Guideline recommend for adults aged 19 years or more to maintain 25(OH)D above the optimal level of 30 g/ml. The Endocrine Societys Clinical Guidelines stresses that vitamin D deciency is very common. The Guidelines of the Society, therefore, enforce the supplementation of vitamin D at suggested daily intake and tolerable upper limit levels. The measurement of serum 25-hydroxyvitamin D level is recommended as the initial diagnostic test in patients at risk for deciency. Screening individuals who are not at risk for deciency or to prescribe vitaCopyright 1998-2010 Karl H. Wilm. All rights reserved. OurFood Database of Food and Related Sciences
948
min D to attain the noncalcemic benet for cardiovascular protection is not recommended. [76]
11.8.26
Low protein diet, soy foods and osteoporosis [60] [61] [59]
Several recent epidemiological studies demonstrate reduced bone density and increased rates of bone loss in individuals habitually consuming low protein diets. In short term studies Womens Health Research at Yale found that a low animal and plant protein diet caused levels of certain hormones (calcitropic parathyroid hormone (PTH) ) to rise, which act to stimulate bone breakdown to compensate for the calcium it was not getting from the diet. The calcitropic hormones were NcAMP, Midmolecule PTH, Intact PTH and calcitriol. Replacing all meat and animal proteins with soy foods, the low soy protein diet seemed to interfere with intestinal calcium absorption to an even greater extent than did the low mixed source protein diet. Should this be conrmed in ongoing studies, inclusion of additional calcium when consuming soy foods will prove to be necessary.
11.8.27
Preeclampsia [77]
Preeclampsia is a pregnancy induced hypertension in association with signicant amounts of protein in the urine. There can be many dierent causes for the syndrome. While blood pressure elevation is the most visible sign of the disease, it involves generalized damage to the maternal endothelium and kidneys and liver, with the release of vasopressive factors only secondary to the original damage. Many strategies to reduce the risk of preeclampsia are being studied using vitamine or minerals as supplements:
11.8.28
Maternal Vitamin D Deciency Increases the Risk of Preeclampsia [78]
According to Lisa M. Bodnar and colleagues 2007 maternal vitamin D deciency may be an independent risk factor for preeclampsia. The authors suggest vitamin D supplementation in early pregnancy to prevent preeclampsia and promote neonatal well-being.
11.8.29
Sources of Vitamin D
Vitamin D is formed in the skin during exposure to sunlight. It is found in fatty sh, however, diet alone without supplementation may lead to an under supply. Urbanisation, demographic shifts, decreased outdoor activity, air pollution and global dimming, and increasing age are told to be responsible for wide population groups to be decient in vitamin D.
11.8. VITAMIN D
949
11.8.30
Call for increased supplementation with vitamin D [79]
Hypovitaminosis D is prevalent in youth worldwide, but the safety of vitamin D at doses exceeding 200 IU/day is unknown in this age group. We assessed the safety of high doses of vitamin D3 administered to apparently healthy school children. Ghada El-Ha Fuleihan and colleagues 2008 in a study with adolescents, gave vitamin D3 in 200 and 2.000 IU/day for one year. No vitamin D intoxication was detected with biochemical variables monitoring. The authors concluded that vitamin D3 at doses equivalent to 2,000 IU/day for one year is safe in adolescents and results in desirable vitamin D levels. According to Michael Holick, vitamin D deciency remains common in children and adults. In utero and during childhood, vitamin D deciency can cause growth retardation and skeletal deformities and may increase the risk of hip fracture later in life. Holick states that curret recommendations of 200 IU per day for children and adults up to 50 years of age for vitamin D need to be increased to 800 - 1000 IU vitamin D3. About 60 per cent of northern populations may be vitamin D decient. increasing the risk of osteopenia, osteoporosis, muscle weakness, fractures, common cancers, autoimmune diseases, infectious diseases and cardiovascular diseases. [80] According to Vieth and colleagues 2007, human diets do not provide sucient vitamin D, which is conrmed by low serum 25(OH)D concentrations. Vieth concludes that correction of low 25(OH)D concentrations can happen only if some or all of the following are implemented: the encouragement of safe, moderate exposure of skin to ultraviolet light; appropriate increases in food fortication with vitamin D; and the provision of higher doses of vitamin D in supplements for adults. [81] Holik and Chen 2008 recommends a circulating level of 25-hydroxyvitamin D of >75 nmol/L, or 30 ng/mL, to maximize vitamin Ds benecial eects for health. In the absence of adequate sun exposure, at least 800-1000 IU vitamin D3/d may be needed to achieve this in children and adults. Vitamin D2 may be equally eective for maintaining circulating concentrations of 25-hydroxyvitamin D when given in physiologic concentrations. [82]
11.8.31
Vitamin D supplementation may reduce systolic blood pressure [83]
According to Suzanne Judd and colleagues 2008, point out that recent clinical trials and animal studies have suggested that vitamin D insuciency may be associated with elevated blood pressure. In their study, the authors found that systolic blood pressure (SBP) is inversely associated with serum vitamin D concentrations in nonhypertensive white persons in the United States. The authors call for studies on the potential eects of vitamin D supplementation as a method to reduce SBP in persons at risk of hypertension.
950
11.8.32
Sunscreen-antioxidant reducing melanoma risk [84]
A novel sunscreen-antioxidant was developed by Damiani and colleagues contains the UVB absorber, 2-ethylhexyl-4-methoxycinnamate (OMC) combined with the piperidine nitroxide TEMPOL, which has antioxidant properties. This sunscreen could reduce the risk of melanoma caused by sun exposure.
11.8.33
Indoor tanning denitively linked to skin cancer [85]
According to DeAnn Lazovic and colleagues 2010 the use of indoor tanning devices increases the risk of melanoma by 74 percent if tanning beds are used for any amount of time. Frequent uses of tanning beds increases melanoma risk 2.5 to 3 times compared with persons who never use it. Frequent users of indoor tanning beds (50 plus hours, more than 100 sessions, or for 10-plus years.) are 2.5 to 3 times more likely to develop melanoma than those who never use tanning devices. The risk was directly related to the time spent tanning. These ndings were independent of the type of tanning device, gender or age, contradicting previous studies of Cokkinides and the position of the American Cancer Society which say that indoor tanning before the age of 35 years increases the risk of melanoma.
11.8.34
The Cokkinides study
The study of Cokkinides and colleagues 2010 refers to the meta analysis which says that indoor tanning use before the age of 35 years increases the risk of melanoma. These believes leaded to state legislation restricting minors access to indoor tanning. [86]
11.8.35
The American Cancer Society position
The American Cancer Society says that using a tanning bed before age 35 increases a persons risk of developing melanoma by 75 percent. Physicians hope that recent actions by the FTC, along with TMA-supported state legislation placing age restrictions on minors use of tanning beds, will spur the tanning industry to operate more responsibly and stop spreading false information to the public. [87]
11.8.36
Public health implication of tanning beds
Tanning bed proponents claim that vitamin D supplementation supports indoor tanning health eect. They support the theory that reduced vitamin D levels or certain vitamin D receptor polymorphisms may increase melanoma risk. Woo and Eide 2010 clarify that ultraviolet A is used by most tanning devices. This light is relatively ineective in stimulating vitamin D synthesis. Health benets from this association is therefore signicant. The authors stress, therefore, the importance of education of the general public and a stricter indoor tanning legislation to reduce public health risks.
11.8. VITAMIN D
951
11.8.37
The Tanning Bed Cancer Control Act [88]
The proposed Tanning Bed Cancer Control Act intends to regulate the use of tanning beds. It proposes a limit on the amount of UV rays emitted by a tanning bed and how long someone can be exposed to them, along with an age limit of over 18.
11.8.38
Occupational solar exposure and skin cancer [89]
Incidence rates of skin cancer are rising in Great Britain. Some occupations are exposed to sunlight, such as farmers, construction workers and some public service workers. Young 2009 found a clear association between solar radiation and skin cancer and calls for protective measures to reduce the burden of occupational skin cancer in Great Britain.
11.8.39
Vitamin D hormone to control malignant cell growth [90]
According to Dr. Anthony Norman of the University of California, Riverside and there are evidences that vitamin D, when converted into a hormone, promotes the normal growth of cells and has anticancer properties rising the interest to develop the vitamin D hormone or analogues for use in cancer treatment vitamin D hormone to decrease the proliferation of cells and control malignant cell growth.
11.8.40
Sunlight exposure of children in the United Arab Emirates [91]
According to the paediatrician Dr. Tamer Adham the children over eight years old in the United Arab Emirates (UAE) need 15-20 minutes of exposure to sunlight per day because they often have a high level of vitamin D deciency due to lack of exposure to sunlight in this region. This may be due to clothing habit of the region. Other authors recommend 2000 IU, equal to the so-called upper safe limit, however, scientists do not recommend taking high doses of the vitamin warning against increased calcium blood levels and kidney problems.
11.8.41
Vitamin D inhibits the function of tumour involved protease enzymes [92]
Bo-Ying Bao from the University of Rochester and Taipei Medical University found evidences that indicate that vitamin D, in the form of the highly active 1 alfa, 25-dihydroxyvitamin D3 (1,25-VD) suppresses prostate cancer progression by inhibition of tumour growth and metastasis. Vitamin D acts inhibiting the function of protease enzymes that are involved in tumour invasion. These ndings support the idea that vitamin D-based therapies might be benecial in
952 the management of advanced prostate cancer.
Bo-Ying Bao found that 1,25-Vitamin D decreased matric metalloproteinases (MMP-9) and cathepsins (CPs), while it also increased the activity of their counterparts, tissue inhibitors of metalloproteinase-1 (TIMP-1) and cathepsin inhibitors. 1,25-VD did not suppress MMP-9 expression at the transcriptional level, but reduced its mRNA stability.
11.8.42
Studies reveal hypovitaminosis of vitamin D and call to increase vitamin D intake [93]
Elina Hypponen and Chris Power in a British study found signicantly higher concentrations of vitamin D in persons which used vitamin D supplements or oily sh, but were not signicantly higher in participants who consumed vitamin D-fortied margarine than in those who did not. The authors conclude that the prevalence of hypovitaminosis D in the general population was alarmingly high duringthe winter and spring, which warrants action at a population level rather than at a risk group level. Julia Knight and colleagues found, in an epidemiological study, that reduced breast cancer risks were associated withincreasing sun exposure cod liver oil use and increasing milk consumption for more than 10 glasses per week from ages 10 to 19 but less in ages 20 to 29, no evidence was found for ages 45 to 54. The authors conclude that vitamin D could help to prevent breath cancer in early life, particularly during breast development, but found reduced and even no such eect in higher ages. [94] Evidences for a better survival of patients with non-small-cell lung cancer due to vitamin D were reported by Wei Zhou and colleagues (2007). The researchers investigated the results of circulating 25-hydroxyvitamin D (25(OH)D) levels on overall survival (OS) and recurrence-free survival (RFS) in early-stage non-small-cell lung cancer (NSCLC). For the joint eects of 25(OH)Dlevel and vitamin D intake, the combined high 25(OH)D levels and high vitamin D intake were associated with better survival than the combined low 25(OH)D levels and low vitamin D intake.. Similar eects of 25(OH)D levels and vitamin D intake were observed for RFS. The authors concluded that vitamin D may be associated with improved survival of patients with early-stage NSCLC. [95] Evaluation of most relations of health and disease that involve vitamin D leads to the conclusion that a desirable 25(OH)D concentration is >75 nmol/L (30 nanog/mL). [96] [97] Supplemental intake of 400 IU vitamin D/d has only a modest eect on blood concentrations of 25(OH)D, raising them by 7-12 nmol/L, depending on the starting point. To raise 25(OH)D from 50 to 80 nmol/L requires an additional intake of about 1700 IU vitaOurFood Database of Food and Related Sciences Copyright 1998-2010 Karl H. Wilm. All rights reserved.
11.9. VITAMIN E
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min D/d. The most advantageous serum concentrations of 25(OH)D begin at 75 nmol/L (30 ng/mL), and the best are between 90 and 100 nmol/L (36-40 ng/mL). In most persons, these concentrations could not be reached with the current recommendation of the Institute of Medicine of intakes are 200 IU/d from birth through age 50 years, 400 IU for those aged 51-70 years, and 600 IU for those aged >70 years. Bischo-Ferrari and colleagues suggest therefore in 2006 that an intake for all adults of >1000 IU (40 microg) vitamin D (cholecalciferol)/d is needed to bring vitamin D concentrations in no less than 50% of the population up to 75 nmol/L. The authors stress that the implications of higher doses for the entire adult population should be addressed in future studies. [96] Based on these facts Reihold Veight an colleagues call for international agencies such as the Food and Nutrition Board and the European Commissions Health and Consumer Protection Directorate-General to reassess as a matter of high priority their dietary recommendations for vitamin D, because the formal nationwide advice from health agencies needs to be changed. [98]
11.8.43
Calcium Plus Vitamin D Supplements May Reduce Fracture Risk [99]
A report of the DIPART (Vitamin D Individual Patient Analysis of Randomized Trials) Group says that Vitamin D plus calcium, but not vitamin D alone in doses of 10 to 20 g, reduces the risk for fractures and hip fractures. The link between vitamin D plus calcium and a reduced risk for fractures is not aected by age, sex, fracture history, or hormone replacement therapy. A better undestanding of the eect od vitamin D is essential because fragility fractures are a signicant source of morbidity and mortality in older persons.
11.9
11.9.1
Vitamin E
Genomics unveils how tocotrienols alpha and gamma support heart health [?] [100]
Clinical trials focused on vitamin E were not successful to lower cholesterol. Das et al 2012 assessed the LDL reducing role of isomers of vitamin E, the tocotrienols. Rabbits were submitted to cholesterol-rich diet supplemented with tocotrienols. The authors report that left ventricular function including aortic ow, the developed pressure, and the myocardial infarct size exhibited signicantly improved recovery with tocotrienol-gama and -alpha but not with tocotrienol-delta.
954
11.9.2
Genomics of improved heart conditions by tocotrienols
The authors explain that tocotrienol-gama and -alpha lower hypercholesterolemic proteins, such as the matrix metalloproteinase MMP2, MMP9(cholesterol regulates MMP2 and MMP9 expression), ET-1 which is increased by hypocholesterolemia, and SPOT 14 which is linked with hypercholesterolemia. The cholesterol suppressing TGF-beta was upregulated. Tocotrienol-delta had no eect.
11.9.3
Cardioprotection of red palmoil tocotrienols [101]
The tocotrienol-rich fraction (TRF) from red palm oil are being suggested by Das et al.2008 as cardioprotective. Tocotrienol were also found to act neuroprotective against stroke. TRF of palm oil consists of three isoforms of tocotrienols (alpha, gama, and delta) as well as alpha-tocopherol. The optimal concentration for TRF was determined by the authors being 3.5% TRF and 0.3 mg/kg body wt of tocotrienol given to rats for 4 weeks. TRF as well as all the isomers of tocotrienol used in our study provided cardioprotection, as evidenced by their ability to improve postischemic ventricular function and reduce myocardial infarct size. The gamma-isoform of tocotrienol was the most cardioprotective of all the isomers followed by the alpha- and delta-isoforms. The cardioprotection of tocotrienol isoforms were assessed by controlling their abilities to stabilize the proteasome, allowing it to maintain a balance between prodeath and prosurvival signals. Tocotrienol isoforms generated a survival signal by reducing c-Src and increasing the phosphorylation of Akt. Proteasomes are very large protein complexes located in the nucleus and the cytoplasm. They degrade unneeded or damaged proteins. of particular proteins and degrade misfolded proteins by proteolysis C-src tyrosine kinase, also known as CSK, is a human protein and gene. It includes an SH2 domain, an SH3 domain, and a tyrosine kinase domain. This protein specically phosphorylates Tyr-504 residue [102].
11.10
11.10.1
Biochemical indicators
Nutrition Report on Biochemical Indicators of Diet and Nutrition in the US Population [103]
A report published by the CDC on April 2012 is based on 58 biochemical indicators of diet and nutrition measured by the CDC, together with NHANES data collected from 1999 until 2006. The concentration of vitamins, fatty acids, trace elements, metabolites, isoavones, lignans, and acrylamide hemoglobin adducts were measured in blood or urine of demographic subgroups.
11.10. BIOCHEMICAL INDICATORS
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Interesting outcomes were that fortication of grain-based food products with folic acid (vitamin B9) reduced the chances for neural tube birth defects. Age, ethnicity, and sex inuence vitamin D deciency, polyunsaturated fatty acids and iron status. Vitaminn D deciency: Serum 25-hydroxyvitamin D deciency (<30 nmol/L) were present in 31% of the non-Hispanic blacks compared with 12% of Mexican Americans and 3% of non-Hispanic whites. The CDC summarises its ndings as follows: The rate of nutrient deciencies in the general U.S. population ranges from less than 1% for folate, vitamin A, and vitamin E to about 10% for vitamin B6, vitamin D, and iron. For most nutrition indicators, deciency rates vary by age, gender, or race/ethnicity, and can be as high as 31% for vitamin D deciency in non-Hispanic blacks. Folate deciency decreased to less than 1% after foods began being fortied with folic acid in 1998. Before fortication began, folate deciency, as determined by blood folate levels, was approximately 12% for women of childbearing age. The report also shows that blood folate levels in all race/ethnic groups were 50% higher since fortication. Young women (20 to 39 years of age) had iodine levels close to levels indicating iodine insuciency. This age group also had the lowest levels among any age group of women. Using a new marker of iron status, the report indicates higher rates of iron deciency in Mexican-American children aged 1 to 5 years (11%) and in non-Hispanic black (16%) and Mexican-American women (13%) of childbearing age (12 to 49 years) when compared to other race/ethnic groups. The new iron marker measurements will help doctors better interpret iron status in individuals, especially in persons with disease that includes inammation. The report oers rst-time data on blood levels of fatty acids in the U.S. population. These include heart-healthy polyunsaturated fatty acids as well as saturated fatty acids that increase risk for heart disease. These rst measurements in the U.S. population provide a baseline to track fatty acid levels over time. This will evaluate our nations progress toward heart-healthy diets. Data from the NHANES survey: B vitamins (water-soluble vitamins category): People aged 40 years or older exhibit a higher likelihood of deciency in vitamin B6 or vitamin B12 compared with younger individuals.
956
Fatty acids (fat-soluble vitamins and nutrients category): Low (<100 micromol/L) concentrations of saturated, monounsaturated, and polyunsaturated fatty acids were more likely to be found in younger adults. Heart-healthy polyunsaturated fatty acids such as eicosapentaenoic acid or docosahexaenoic acid were found at higher concentrations in non-Hispanic black adults than in other ethnic groups. The survey included rst-time measurements for 24 plasma fatty acids. Iron (trace elements category): According to the assessment of a new marker for iron status, the study reports iron deciencies in 10.9% of Mexican-American children aged 1 to 5 years, 16.0% of non-Hispanic blacks, and 13.2% of Mexican-American women aged 12 to 49 years. Adult males, however, showed a higher risk for iron excess. Iodine (trace elements category): Lower urinary iodine concentrations, which can elevate the risk for disorders such as mental retardation or hypothyroidism, were observed more often in women aged 20 to 39 years than in other groups. Children generally exhibited higher iodine concentrations. Overall iodine concentrations, however, were reported to be relatively stable since the late 1980s.
11.10.2
Germany declared war against vitamin supplements [104]
According to Professor Peter Jni, several thousand deaths per year in Germany may be caused by vitamin supplements consumption. Peter Jni is the Head of the Division of Clinical Epidemiology and Biostatistics and the Director of CTU Bern, the University hospitals clinical trials unit (Switzerland). He based his projections on studies which focus on vitamin dietary supplementation.
11.10.3
The German Federal Institute for Risk Assessment (BfR) cautions on vitamin supplementation [105]
The BfR at Berlin cautions that a one-sided, imbalanced diet cannot be corrected by taking food supplements. Food supplements are superuous for healthy individuals on a normal diet. In a balanced diet the body has all the nutrients it needs. Normally, the additional intake of individual nutrients is not, therefore, necessary. In some situations targeted supplementation with individual nutrients may make sense.
11.10.4
Uniform European maximum levels urgently needed
Unlike medicinal products food supplements do not have to be registered with the Federal Oce of Consumer Protection and Food Safety (BVL). There are currently no binding maximum levels for the ingredients (nutrients or other substances with nutritional or physiological action) of supplements on either the national or the European level. An EU-wide regulation on valid maximum levels for vitamins and minerals is in the process of being
11.10. BIOCHEMICAL INDICATORS elaborated.
957
Food supplements are foods and are intended to supplement the diet and must be safe. However, the mere fact that a food supplement is on the market does not mean that the purchaser can assume that this is a worthwhile or valuable food. Food supplements may also be on the market when their nutritional-physiological value is questionable.
11.10.5
In some situations targeted supplementation with individual nutrients may make sense, says the BfR:
During pregnancy and breastfeeding there is an elevated need for specic nutrients. The intake of essential nutrients by older people may also be insucient for instance as a consequence of chewing or swallowing disorders or a loss of appetite. In these cases, dietary supplementation may be necessary or advisable. This should be done under medical supervision. Data on nutrient intake indicate that the intake of a small number of vitamins and minerals like vitamin D, calcium, folic acid and iodine by some groups in the population is not in line with the intake recommendations of the German Nutrition Society (DGE e.V.). However this cannot generally be equated with insucient intake or even a deciency. In the same way, both an insucient and excessive supply of micro-nutrients, i.e. vitamins, minerals and trace elements, secondary plant substances can result in adverse health effects. Nevertheless, the best nutritional strategy is still a balanced, diverse diet with plenty of fruit and vegetables. Food supplements are not substitutes of equal value.
11.10.6
Vitamins may be life-threatening [106]
Pd Dr. Diana Rubin of the BfR reports that almost one third of Germans consume vitamins supplements aiming to stay healthy. Rubin says this is an ominous mistake, because vitamins may even be life-threatening, according to a broadcast program at NDR in July 2011. Rubin stated that vitamins are no youth or beauty fountain, do not protect against cancer or heart diseases. On the contrary, some studies say that special vitamins like vitamin E and Vitamin A increase cancer risk. Too much is dangerous when vitamins are taken in synthetic form as capsules or pils. Therefore most experts warn against doing so.
11.10.7
Politicians call for more informations on vitamins
Prof. Karl Lauterbach calls for a proactive education of health ocials, pharmacists and consumer concerning the health risks of vitamin supplements and have no mercy on the lobby of the supplement industry, according to Spiegel Online. Lauterbach is a German scientist and member of the Bundestag (SPD). He is professor of health economics and epidemiology at the University of Cologne.
958
11.10.8
Reliability of meta-analyses questioned due to multiplicity of data [107]
Tendal et al 2011 looked at the multiplicity of data in trial reports and assessed the impact of multiplicity on Cochrain meta-analysis results published from issue 3 in 2006 to issue 2 in 2007. The authors selected 19 Cochrain meta-analyses for their analysis. They found that 18 meta-analysis presented multiplicity of data. The authors stressed that such multiplicity of data can aect the ndings of systematic reviews and meta-analyses. They reinforce the need of reviews and meta-analyses to comply with prespecied protocols which identify time points, intervention groups, and scales of interest.
Bibliography
[1] Rmp, Hermann:Vitamine,Chemie Lexikon,fnfte Auage 1962. [2] Wolfram,G.: Bedarfsermittlung fr wirksame Stoe, Ableitung von Referenzwerten/Verzehrsempfehlungen; Funktionelle Lebensmittel- Lebensmittel der Zukunft, Erwartungen, Wirkungen, Risiken; Band 25 der Schriftenreihe Lebensmittechemie, Lebensmittelqualitt. (Hrsg) Lebensmittelchemische Gesellschaft-Fachgruppe in der GDCH.Behrs Verlag, page 64 and 66. [3] B Van Guelpen, J Hultdin, I Johansson, G Hallmans, R Stenling, E Riboli, A Winkvist and R Palmqvist: Colorectal Cancer; Low folate levels may protect against colorectal cancer Gut 2006;55:1461-1466; doi:10.1136/gut.2005.085480. [4] http://www.eatwell.gov.uk/healthydiet/nutritionessentials/ vitaminsandminerals/folicacid/. FSA eat well: Folic acid. [5] http://www.journals.cambridge.org/action/displayAbstract?fromPage= online%&aid=1343244&fulltextType=RV&fileId=S0007114507777140. Wright, Anthony J. A.; Dainty, Jack R.; Finglas, Paul M.: Folic acid metabolism in human subjects revisited: potential implications for proposed mandatory folic acid fortication in the UK. British Journal of Nutrition. (2007), 98: 667-675 Cambridge University Press . Doi: 10.107S0007777140. [6] http://www.sacn.gov.uk/reports/#. Scientic Advisory Committee on Nutrition: Folate and Disease prevention. [7] http://www.ingentaconnect.com/content/ilsi/nure/2007/00000065/ 00000011/art00004. Kim, Young-In; Solomons, Noel W. : Food Fortication with Folic Acid: Has the Other Shoe Dropped; Folic Acid Fortication and Supplementation-Good for Some but Not So Good for Others Nutrition Reviews: Volume 65, Number 11, November 2007 , pp. 504-511(8).
BIBLIOGRAPHY
959
[8] http://www.ifr.ac.uk/Media/NewsReleases/071030folic_acid_ fortification.html. Institute of Food Researche: Scientists question folic acid fortication. [9] http://www.food.gov.uk/multimedia/pdfs/evm_folicacid.pdf. EVM Review of Folic Acid. [10] http://www.hispanicprwire.com/print.php?l=in&id=10586&cha=9. Radek Bukowski, Fergal D. Malone, Flint Porter, David A. Nyberg, Christine Comstock, Gary Hankins, Keith Eddleman, Susan Gross, Lorraine Dugo, Sabrina Craigo, Ilan E. Timor-Tritsch, Stephen R. Carr, Honor M. Wolfe, Mary E. DAlton: Preconceptional Folate Prevents Preterm Delivery. 28th Annual Society for Maternal-Fetal Medicine (SMFM) meeting. Abstract. HispanicPRWire: Huge Drop in Preterm Birth-Risk Among Women Taking Folic Acid One Year Before Conception. Largest U.S. Study of Pre-conceptional Folic Acid Supplementation Receives March of Dimes Award. [11] http://www.bmj.com/cgi/eletters/334/7591/433#161482. Dhruvashree Somasundara: Food fortication with Folic Acid-Risks vs Benets. bmj.com, 6 Mar 2007. [12] http://www.bmj.com/cgi/eletters/334/7591/433#161592. Lawrence,Mark A. et al: Mandatory folic acid fortication - more than a theoretical risk less than a panacea. bmj.com, 7 Mar 2007. [13] http://www.bmj.com/cgi/content/abstract/316/7135/894. Clarke, Robert: Lowering blood homocysteine with folic acid based supplements: meta-analysis of randomised trials. Homocysteine Lowering Trialists Collaboration. BMJ 1998;316:894-898. 21March 1998. [14] http://www.clinchem.org/cgi/content/abstract/54/2/326. Dodds, Linda; Fell, Deshayne B.; Dooley, Kent C.; Armson, B. Anthony; Allen, Alexander C.; Nassar, Bassam A.; Perkins, Sherry; Joseph K.S. : Eect of Homocysteine Concentration in Early Pregnancy on Gestational Hypertensive Disorders and Other Pregnancy Outcomes Clinical Chemistry. 54: 326-334, 2008. First published December 10, 2007; 10.1373/clinchem.2007.097469 (Clinical Chemistry. 2008;54:326-334.). [15] http://aje.oxfordjournals.org/cgi/content/abstract/kwm373v1. Nilsen, Roy M.; Vollset, Stein E.; Rasmussen, Svein A.; Ueland, Per M.; Daltveit Anne K.: Folic Acid and Multivitamin Supplement Use and Risk of Placental Abruption: A Population-based Registry Study. American Journal of Epidemiology, doi:10.1093/aje/kwm373 Advance Access published online on January 10, 2008. [16] http://www.ajcn.org/cgi/content/abstract/86/5/1405. Hoey, Leane; McNulty, Helene; Askin, Nadina; Dunne, Adrian; Ward, Mary; Pentieva, Kristina; Strain, J.J.; Molloy, Anne M.; Flynn, Cliona A.; Scott, John M.: Eect of a voluntary food
960
CHAPTER 11. VITAMINS fortication policy on folate, related B vitamin status, and homocysteine in healthy adults. American Journal of Clinical Nutrition, Vol. 86, No. 5, 1405-1413, November 2007.
[17] http://jama.ama-assn.org/cgi/content/abstract/298/10/1163. Jamison, Rex L.; Hartigan, Pamela; Kaufman, James S.; Goldfarb, David S.; Warren, Stuart R.; Guarino, Peter D.; Gaziano, J. Michael: Eect of Homocysteine Lowering on Mortality and Vascular Disease in Advanced Chronic Kidney Disease and End-stage Renal Disease. JAMA 298: 1163-1170. [18] http://www.bmj.com/cgi/content/abstract/334/7591/464. Wilcox, Allen J.; Lie, Rolv Terje; Solvoll, Kari; Taylor, Jack; McConnaughey, D.Robert; Abyholm, Frank; Vindenes, Hallvard; Vollset, Stein Emil; Drevon Christian A.: Folic acid supplements and risk of facial clefts: national population based case-control study. BMJ 2007;334:464 (3 March), doi:10.1136/bmj.39079.618287.0B (published 26 January 2007). [19] Wen, Shi Wu; Chen, Xi-Kuan; Rodger, Marc; Rennicks White, Ruth; Yang, Qiuying; Smith, Graeme N.; Sigal, Ronald J.; Perkins, Sherry L.; Walker, Mark C.: Folic acid supplementation in early second trimester and the risk of preeclampsia. American Journal of Obstetrics and Gynecology, Volume 198, Issue 1, January 2008, Pages 45.e1-45.e7. doi:101016/j.ajog.2007.06.067. [20] Yoshihiro Sato; Kaji, Masahide; Kondo, Izumi; Yoshida, Hidemi; Satoh, Kei; Metoki, Norifumi: Hyperhomocysteinemia in Japanese patients with convalescent stage ischemic stroke: Eect of combined therapy with folic acid and mecobalamine. Journal of the Neurological Sciences, Volume 202, Issues 1-2, 15 October 2002, Pages 65-68. doi:10.1016/S0002-9378(99)70269-3. [21] http://whqlibdoc.who.int/publications/2004/9241546123_chap6.pdf. World Health Organization and Food and Agriculture Organization of the United Nations 2004: Vitamin and mineral requirements in huiman nutrition. [22] http://en.wikipedia.org/wiki/Vitamin_K. Wikipedia, the free encyclopaedia: Vitamin K. [23] http://archinte.ama-assn.org/cgi/content/abstract/166/12/1256. Sarah Cockayne, MSc; Joy Adamson, PhD; Susan Lanham-New, PhD; Martin J. Shearer, PhD, MRCPath; Simon Gilbody, DPhil; David J. Torgerson, PhD: Vitamin K and the Prevention of Fractures; Systematic Review and Meta-analysis of Randomized Controlled Trials; Arch Intern Med. 2006;166:1256-1261. [24] Naoko Tsugawa, Masataka Shiraki, Yoshitomo Suhara, Maya Kamao, Kiyoshi Tanaka and Toshio Okano : Vitamin K status of healthy Japanese women: agerelated vitamin K requirement for gama-carboxylation of osteocalcin; American Journal of Clinical Nutrition, Vol. 83, No. 2, 380-386, February 2006.
BIBLIOGRAPHY
961
[25] http://www.ncbi.nlm.nih.gov/pubmed/16683180. L. Rejnmark, P. Vestergaard, P. Charles, A. P. Hermann, C. Brot, P. Eiken, L. Mosekilde: No eect of vitamin K1 intake on bone mineral density and fracture risk in perimenopausal women; Osteoporosis International; Springer London Volume 17, Number 8 August 2006 Pages: 1122-1132. [26] http://care.diabetesjournals.org/cgi/content/abstract/31/11/2092. Yoshida, Makiko; Jacques, Paul F.; Meigs, James B.; Saltzman, Edward; Shea, M. Kyla; Gundberg, Caren; Dawson-Hughes, Bess; Dallal,; Booth, Sarah L.: Eect of Vitamin K Supplementation on Insulin Resistance in Older Men and Women Diabetes Care 31: 2092-2096; published online before print as 10.2337/dc08-1204. [27] http://www.ncbi.nlm.nih.gov/pubmed/18922041. Cheung AM, Tile L, Lee Y, Tomlinson G, Hawker G, Scher J, Hu H, Vieth R, Thompson L, Jamal S, Josse R.: Vitamin K supplementation in postmenopausal women with osteopenia (ECKO trial): a randomized controlled trial. PLoS Med. Published online October 14, 2008. 2008;5:e196. [28] Visual phototransduction. Phototransduction. Wikipedia. http://en.wikipedia.org/wiki/
[29] Shichida Y and Matsuyama T. Evolution of opsins and phototransduction. hilosophical Transactions. The Royal Society, 364:28812895, 10 2009. http://rstb. royalsocietypublishing.org/content/364/1531/2881.full.pdf+html. [30] Mayo-Wilson E, Imdad A, Herzer K, Yakoob MY, and Bhutta ZA. Vitamin a supplements for preventing mortality, illness, and blindness in children aged under 5: systematic review and meta-analysis. BMJ, 343(d5094), 8 2011. http: //www.bmj.com/content/343/bmj.d5094. [31] WHO. Micronutrient deciencies. vitamin a deciency. nutrition/topics/vad/en/index.html. http://www.who.int/
[32] Fogle KJ, Parson, and Dahm NA AND. Holmes TC. Cryptochrome is a blue-light sensor that regulates neuronal ring rate. Science, 3 2011. http://www.sciencemag. org/content/early/2011/03/02/science.1199702. [33] Cant C, Houtkooper RH, Pirinen E, Youn DY, Oosterveer MH, Cen Y, FernandezMarcos PJ, Yamamoto H, Andreux PA, Cettour-Rose P, Gademann K, Rinsch C, Schoonjans K, Sauve AA, and Auwerx J. The nad(+) precursor nicotinamide riboside enhances oxidative metabolism and protects against high-fat diet-induced obesity. Cell Metab, (6):83847, 6 2012. http://www.cell.com/cell-metabolism/ retrieve/pii/S1550413112001921. [34] Carr AC, Pullar JN, Moran S, and Vissers MCM. Bioavailability of vitamin c from kiwifruit in non-smoking males: determination of healthy and optimal
962
CHAPTER 11. VITAMINS intakes. journal of nutritional science. Journal of Nutritional Science, 1(e14):9, 10 2012. http://journals.cambridge.org/action/displayAbstract?fromPage= online&aid=8724815.
[35] Spektrum: Transglutaminase Feste Bindungen; Lebensmitteltechnik 3/1999 S. 32. [36] http://jcem.endojournals.org/cgi/content/abstract/jc.2007-2308v1. Holick, Michael F.; Biancuzzo, Rachael M.; Chen, Tai C.; Klein, Ellen K.; Young, Azzie; Bibuld, Douglass; Reitz, Richard; Salameh, Wael; Ameri, Allen; Tannenbaum, Andrew D. Vitamin D2 is as eective as vitamin D3 in maintaining circulating concentrations of 25-hydroxyvitamin D. Journal ofClinical Endocrinology & Metabolism Published online ahead of print, 18 December 2007. doi:10.1210/jc.2007-2308. [37] http://www.adajournal.org/article/PIIS0002822304004432. Moore C, Murphy MM, Keast DR, Holick MF. J Am Diet Assoc. 2004 Jun;104(6):980-3. Vitamin D intake in the United States. doi: 10.1016/j.jada.2004.03.028. [38] Cedric F. Garland, Frank C. Garland, Edward D. Gorham, Martin Lipkin, Harold Newmark, Sharif B. Mohr, Michael F. Holick:The Role of Vitamin D in Cancer Prevention; American Journal of Public Health, 10.2105/AJPH.2004.045260. [39] http://archinte.ama-assn.org/cgi/content/abstract/168/12/1340. Harald Dobnig; Stefan Pilz; Hubert Scharnagl; Wilfried Renner; Ursula Seelhorst; Britta Wellnitz; Jrgen Kinkeldei; Bernhard O. Boehm; Gisela Weihrauch; Winfried Maerz: Independent Association of Low Serum 25-Hydroxyvitamin D and 1,25Dihydroxyvitamin D Levels With All-Cause and Cardiovascular Mortality. Arch Intern Med. 2008;168(12):1340-1349. [40] http://www.ncbi.nlm.nih.gov/pubmed/11258203. Winkelmann BR, Mrz W, Boehm BO, Zotz R, Hager J, Hellstern P, Senges J; LURIC Study Group (LUdwigshafen RIsk and Cardiovascular Health): Rationale and design of the LURIC study a resource for functional genomics, pharmacogenomics and long-term prognosis of cardiovascular disease. Pharmacogenomics. 2001 Feb;2(1 Suppl 1):S1-73. Review. [41] http://archinte.ama-assn.org/cgi/content/abstract/168/11/1174? Giovannucci, Edward; Liu, Yan; Hollis, Bruce W.; Rimm, Eric B.: 25-Hydroxyvitamin D and Risk of Myocardial Infarction in Men. A Prospective Study. Arch Intern Med. 2008;168(11):1174-1180. [42] Carrelli AL, Walker MD, Lowe H, McMahon DJ, Rundek T, Sacco RL, and Silverberg SJ. Vitamin d deciency is associated with subclinical carotid atherosclerosis: the northern manhattan study. Stroke, 42(8):22405, 8 2011. http://stroke. ahajournals.org/content/42/8/2240.
BIBLIOGRAPHY
963
[43] Northern manhattan study (nomas) is a research study of stroke and stroke risk factors in the northern manhattan community conducted at the neurological. http: //www.columbianomas.org/study.html. [44] Balion C, Grith LE, Strier L, Henderson M, Patterson C, Heckman G, Llewellyn DJ, and Raina P. Vitamin d, cognition, and dementia: A systematic review and meta-analysis. 79:13971405, 9 2012. http://www.neurology.org/content/79/ 13/1397.abstract. [45] Vitamin d and omega-3 trial (vital). NCT01169259. http://clinicaltrials.gov/ct2/show/
[46] Hall S, Ohrfelt A, Constantinescu R, Andreasson U, Surova Y, Bostrom F, Nilsson C, Widner H, Decraemer H, Ngga K, Minthon L, Londos E, Vanmechelen E, Holmberg B, Zetterberg H, Blennow K, and Hansson O. Accuracy of a panel of 5 cerebrospinal uid biomarkers in the dierential diagnosis of patients with dementia and/or parkinsonian disorders. Arch Neurol, pages 18, 8 2012. http://www.ncbi.nlm.nih.gov/pubmed/22925882. [47] Vitamin d and omega-3 trial (vital study): New national guidelines for vitamin d intake highlight the need for the vital study. http://www.vitalstudy.org/ guidelines.html. [48] http://archinte.ama-assn.org/cgi/content/abstract/169/6/551. BischoFerrari, Heike A.; Willett, Walter C.; Wong, John B.; Stuck, Andreas E.; Staehelin, Hannes B.; Orav, E. John ;Thoma, Anna; Kiel, Douglas P.; Henschkowski, Jana.: Prevention of Nonvertebral Fractures With Oral Vitamin D and Dose Dependency. Arch Intern Med. 2009;169(6):551-561. [49] http://www.fasebj.org/cgi/content/abstract/22/4/982. McCann, Joyce C.; Ames, Bruce N.: Review Article: Is there convincing biological or behavioral evidence linking vitamin D deciency to brain dysfunction. Federation of American Societies for Experimental Biology (FASEB) Journal. Volume 22, Pages 982-1001 doi: 10.1096/fj.07-9326rev. [50] http://archneur.ama-assn.org/cgi/content/abstract/65/10/1348. Evatt, Marian L. ; DeLong, Mahlon R.; Khazai, Natasha; Rosen, Ami; Triche, Shirley; Tangpricha, Vin: Prevalence of Vitamin D Insuciency in Patients With Parkinson Disease and Alzheimer Disease. Arch Neurol. 2008;65(10):1348-1352. [51] http://www.ncbi.nlm.nih.gov/pubmed/20625021. Llewellyn DJ, Lang IA, Langa KM, Muniz-Terrera G, Phillips CL, Cherubini A, Ferrucci L, Melzer D: Vitamin d and risk of cognitive decline in elderly persons. Arch Intern Med. 2010 Jul 12;170(13):1135-41. [52] http://www.inchiantistudy.net/obtain_data.html. The InCHIANTI Study.
964
CHAPTER 11. VITAMINS Wikipedia:
[53] http://en.wikipedia.org/wiki/Mini-mental_state_examination. Mini-mental state examination.
[54] http://www.cdc.gov/nchs/products/elec_prods/subject/nhanes3.htm. Third National Health and Nutrition Examination Survey (NHANES III). [55] http://www.ncbi.nlm.nih.gov/pubmed/17898524. McGrath J, Scragg R, Chant D, Eyles D, Burne T, Obradovic D: No association between serum 25-hydroxyvitamin D3 level and performance on psychometric tests in NHANES III. Neuroepidemiology. 2007;29(1-2):49-54. [56] http://www.ncbi.nlm.nih.gov/pubmed/20625012. Grey A, Bolland M: Vitamin d: a place in the sun? Arch Intern Med. 2010 Jul 12;170(13):1099-100. [57] Edward D. Gorham, Cedric F. Garland, Frank C. Garland, William B. Grant, Sharif B. Mohr, Martin Lipkin, Harold L. Newmark, Edward Giovannucci, Melissa Wei and Michael F. Holick: Vitamin D and prevention of colorectal cancer; Volume 97, Issues 1-2, Pages 1-218 (October 2005). [58] http://cancerres.aacrjournals.org/cgi/content/abstract/65/12/5470. Esther M. John, Gary G. Schwartz, Jocelyn Koo, David Van Den Berg and Sue A. Ingles: Sun Exposure, Vitamin D Receptor Gene Polymorphisms, and Risk of Advanced Prostate Cancer; Cancer Research 65, 5470-5479, June 15, 2005. [59] http://www.innovations-report.de/html/berichte/medizin_gesundheit/ bericht-70130.html. Innovation Report: UU Scientists Probe Vitamin D/Sunshine Link. [60] http://jn.nutrition.org/cgi/content/full/133/3/855S. Jane E. Kerstetter, Kimberly O. OBrien and Karl L. Insogna: Low Protein Intake: The Impact on Calcium and Bone Homeostasis in Humans. J. Nutr. 133:855S-861S, March 2003. [61] http://www.yalewhr.org/pdf/bone_health.pdf. Womens Health Research at Yale: Understanding how nutrition aects bone health. 2006. [62] http://archpedi.ama-assn.org/cgi/content/short/162/6/505. Gordon, Catherine M.; Feldman, Henry A.; Sinclair, Linda; LeBo Williams, Avery; Kleinman; Paul K.; Perez-Rossello,Jeannette; Cox, Joanne E.: Prevalence of Vitamin D Deciency Among Healthy Infants and Toddlers. Archives of Paediatric Medicine. Arch Pediatr Adolesc Med. 2008;162(6):505-512. [63] http://archpedi.ama-assn.org/cgi/content/full/162/6/513. Rovner, Alisha J. ; OBrien, Kimberly O.: Hypovitaminosis D Among Healthy Children in the United States A Review of the Current Evidence Arch Pediatr Adolesc Med. 2008;162(6):513519.
BIBLIOGRAPHY
965
[64] http://jcem.endojournals.org/cgi/content/abstract/jc.2009-2309v1. Vicente Gilsanz, Arye Kremer, Ashley O. Mo, Tishya A. L. Wren, and Richard Kremer. Vitamin D Status and Its Relation to Muscle Mass and Muscle Fat in Young Women. Journal of Clinical Endocrinology & Metabolism, 2010; DOI: 10.1210/jc.2009-2309. [65] http://www.ncbi.nlm.nih.gov/pubmed/18984659. Kremer R, Campbell PP, Reinhardt T, Gilsanz V: Vitamin D status and its relationship to body fat, nal height, and peak bone mass in young women. J Clin Endocrinol Metab. 2009 Jan;94(1):67-73. [66] http://hyper.ahajournals.org/cgi/content/abstract/HYPERTENSIONAHA. 107.107821v1. Wang, Lu; Manson, JoAnn E.; Buring, Julie E.; Lee, I-M; Sesso, Howard D.: Dietary Intake of Dairy Products, Calcium, and Vitamin D and the Risk of Hypertension in Middle-Aged and Older Women. Hypertension. Volume 51, Pages 1-7, doi:10.1161/HYPERTENSIONAHA.107.107821. [67] http://www.expertopin.com/doi/abs/10.1517/14656566.9.1.107?cookieSet= 1&journalCode=eop. Cannell, JJ; Hollis, BW; Zaslo, M; Heaney , RP: Diagnosis and treatment of vitamin D deciency. Expert Opinion on Pharmacotherapy. January 2008, Vol. 9, No. 1, Pages 107-118 doi:10.1517/14656566.9.1.107. [68] http://www.ajcn.org/cgi/content/abstract/84/4/694. Lisa A Houghton and Reinhold Vieth The case against ergocalciferol (vitamin D2) as a vitamin supplement Am J Clin Nutr 2006 84: 694-697. [69] http://www.ncbi.nlm.nih.gov/pubmed/18504144. Stolzenberg-Solomon RZ: Vitamin D and pancreatic cancer. Ann Epidemiol. 2009 Feb;19(2):89-95. Epub 2008 May 27. [70] http://prevention.cancer.gov/programs-resources/groups/ed/programs/ plco. National Cancer Institute: Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. [71] http://www.ncbi.nlm.nih.gov/pubmed/19208842. Stolzenberg-Solomon RZ, Hayes RB, Horst RL, Anderson KE, Hollis BW, Silverman DT. Serum vitamin D and risk of pancreatic cancer in the prostate, lung, colorectal, and ovarian screening trial. Cancer Res. 2009 Feb 15;69(4):1439-47. Epub 2009 Feb 10. [72] Murdoch DR, Slow S, Chambers ST, Jennings LC, Stewart AW, Priest PC, Florkowski CM, Livesey JH, Camargo CA, and Scragg R. Eect of vitamin d3 supplementation on upper respiratory tract infections in healthy adults: The vidaris randomized controlled trial. JAMA, 308(13):13339, 10 2012. http://www.ncbi. nlm.nih.gov/pubmed/23032549. [73] Haines ST and Park SK. Vitamin d supplementation: whats known, what to do, and whats needed. Pharmacotherapy, 32(4):35482, 3 2012. http://www.ncbi.nlm. nih.gov/pubmed/22461123.
966
[74] Pramyothin P and Holick MF. Vitamin d supplementation: guidelines and evidence for subclinical deciency. Curr Opin Gastroenterol, 28(2):13950, 3 2012. http: //www.ncbi.nlm.nih.gov/pubmed/22274617. [75] Dietary reference intakes for calcium and vitamin d. us institute of medicine report. http://www.iom.edu/Reports/2010/ Dietary-Reference-Intakes-for-Calcium-and-Vitamin-D/Report-Brief. aspx. [76] Evaluation, treatment, and prevention of vitamin d deciency: An endocrine society clinical practice guideline 2011. http://www.endo-society.org/guidelines/ final/upload/FINAL-Standalone-Vitamin-D-Guideline.pdf. [77] http://en.wikipedia.org/wiki/Preeclampsia. Wikipedia: Pre-eclampsia. [78] http://jcem.endojournals.org/cgi/content/abstract/92/9/3517. Bodnar, Lisa M.; Catov, Janet M.V;. Simhan, Hyagriv N; Holick, Michael F.; Powers; Robert W.; Roberts, James M.: Maternal Vitamin D Deciency Increases the Risk of Preeclampsia. Journal of Clinical Endocrinology & Metabolism. Vol. 92, No. 9 35173522 doi:10.1210/jc.2007-0718. [79] http://jcem.endojournals.org/cgi/content/abstract/jc.2007-2530v1. Maalouf, Joyce; Nabulsi, Mona; Vieth, Reinhold; Kimball, Samantha; El-Rassi, Rola; Mahfoud, Ziyad; El-Hajj Fuleihan, Ghada : Short-term and long-term safety of weekly high-dose vitamin D3 supplementation in school children. Journal of Clinical Endocrinology & Metabolism Published online ahead of print 29 April 2008, doi:10.1210/jc.2007-2530. [80] http://content.nejm.org/cgi/content/extract/357/3/266. Holick, Michael F.: Vitamin D Deciency: New England Journal of Medicine July 19, 2007, Volume 357, Number 3, Pages 266-281. [81] http://www.ajcn.org/cgi/content/full/85/3/649. Vieth, Reinhold; BischoFerrari, Heike; Boucher, Barbara J.; Dawson-Hughes, Bess; Garland, Cedric F.; Heaney, Robert P.; Holick, Michael F.; Hollis, Bruce W.; Lamberg-Allardt, Christel; McGrath, John J.; Norman, Anthony W.; Scragg, Robert; Whiting, Susan J.: Willett, Walter C.; Zittermann, Armin: The urgent need to recommend an intake of vitamin D that is eective. The American Journal of Clinical Nutrition March 2007, Volume 85, Number 3, Pages 649-650. [82] http://www.ajcn.org/cgi/content/abstract/87/4/1080S. Holick, Michael F.; Chen, Tai C.: Vitamin D deciency: a worldwide problem with health consequences. Am. J. Clinical Nutrition, April 1, 2008; 87(4): 1080S - 1086S. [83] http://www.ajcn.org/cgi/content/abstract/87/1/136. Judd, Suzanne E.; Nanes, Mark S.; Ziegler, Thomas R.; Wilson, Peter W.F.; Tangpricha, Vin : Optimal
BIBLIOGRAPHY
967
vitamin D status attenuates the age-associated increase in systolic blood pressure in white Americans: results from the third National Health and Nutrition Examination Survey. American Journal of Clinical Nutrition, Vol. 87, No. 1, 136 -141, January 2008. [84] http://www.ingentaconnect.com/search/article?title=Vitamin+D&title_ type=tka&year_from=2005&year_to=2006&database=1&pageSize=20&index=14. Damiani, Elisabetta, Astol, Paola, Cionna, Laura, Ippoliti, Francesca, Greci, Lucedio: Synthesis and application of a novel sunscreen-antioxidant; IngentaConnect DOI: 10.1080/10715760600590065. [85] http://www.ahc.umn.edu/media/releases/indoortanning/index.htm. U of M study denitively links indoor tanning to melanoma. University of Minesota. May 27, 2010. [86] http://www.ncbi.nlm.nih.gov/pubmed/19085965. Cokkinides V, Weinstock M, Lazovich D, Ward E, Thun M: Indoor tanning use among adolescents in the US, 1998 to 2004. Cancer. 2009 Jan 1;115(1):190-8. [87] http://www.ncbi.nlm.nih.gov/pubmed/20437310. Conde C: Killer tans: state, feds crack down on indoor tanning. Tex Med. 2010 May 1;106(5):47-51. [88] http://maloney.house.gov/index.php?option=content&task=view&id= 2010&Itemid=61. New Bill to Help Prevent Tanning Bed Cancers -U.S. Reps. Maloney & Dent, Kate White, Doctors, Cancer Survivors Gather at Cosmo HQ to Discuss New Tanning Bed Cancer Control Act-. [89] http://www.ncbi.nlm.nih.gov/pubmed/19233827. Young C: Solar ultraviolet radiation and skin cancer. Occup Med (Lond). 2009 Mar;59(2):82-8. [90] http://www.cancer.gov/ncicancerbulletin/NCI_Cancer_Bulletin_062805/ page4. National Cancer Institute: Sunlight and Cancer: Testing the Vitamin D Hypothesis; June 28, 2005 Volume 2 / Number 26. [91] http://www.ameinfo.com/77619.html http://www.cancer.gov/ ncicancerbulletin/NCI_Cancer_Bulletin_062805/page4. Sunlight good for children United Arab Emirates: Sunday, February 12 - 2006 at 09:1. [92] Bo-Ying Bao, Shauh-Der Yeh and Yi-Fen Lee: 1 alfa, 25-dihydroxyvitamin D3 inhibits prostate cancer cell invasion via modulation of selective proteases; Carcinogenesis (Vol. 27, pp. 32-42) January 2006. [93] http://www.ajcn.org/cgi/content/abstract/85/3/860. Hypponen, Elina and; Power, Chris: Hypovitaminosis D in British adults at age 45 years: nationwide cohort study of dietary and lifestyle predictors Am J Clin Nutr 2007 85: 860-868.
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[94] Knight, Julia A.; Lesosky, Maia; Barnett, Heidi; Raboud, Janet M. and Vieth, Reinhold: Vitamin D and Reduced Risk of Breast Cancer: A Population-Based CaseControl Study Cancer Epidemiology Biomarkers & Prevention 2007 16: 422-429 doi: 10.1158/1055-9965.EPI-06-0865. [95] http://jnci.oxfordjournals.org/cgi/reprint/98/7/428. Zhou, Wei; Heist, Rebecca S.; Liu, Georey; Asomaning, Ko; Neuberg, Donna S.; Hollis, Bruce W.; Wain, John C.; Lynch, Thomas J.; Giovannucci, Edward; Su, Li ; Christiani, David C.: Circulating 25-Hydroxyvitamin D Levels Predict Survival in Early-Stage NonSmall-Cell Lung Cancer Patients J. Clin. Oncol., February 10, 2007; 25(5): 479 485. [96] http://www.ajcn.org/cgi/ijlink?linkType=ABST&journalCode=ajcn&resid= 84/1/18. Bischo-Ferrari HA, Giovannucci E, Willett WC, Dietrich T, DawsonHughes B. Estimation of optimal serum concentrations of 25-hydroxyvitamin D for multiple health outcomes. Am J Clin Nutr 2006;84:18-28. [97] http://www.ajcn.org/cgi/ijlink?linkType=ABST&journalCode=ajcn&resid= 84/1/18. Visser M, Deeg DJ, Puts MT, Seidell JC, Lips P. Low serum concentrations of 25-hydroxyvitamin D in older persons and the risk of nursing home admission. Am J Clin Nutr 2006;84:616-22. [98] http://www.ajcn.org/cgi/content/full/85/3/649. Vieth, Reinhold; BischoFerrari, Heike; Boucher, Barbara J.; Dawson-Hughes, Bess; Garland, Cedric F.; Heaney, Robert P.; Holick, Michael F.; Hollis, Bruce W.; Lamberg-Allardt, Christel; McGrath, John J.; Norman, Anthony W.; Scragg, Robert; Whiting, Susan J.; Willett, Walter C.; and Zittermann Armin: The urgent need to recommend an intake of vitamin D that is eective, AJCN 2007 85: 649-650. [99] http://www.ncbi.nlm.nih.gov/pubmed/20068257?dopt=Abstract. Patient level pooled analysis of 68 500 patients from seven major vitamin D fracture trials in US and Europe. DIPART (Vitamin D Individual Patient Analysis of Randomized Trials) Group. 2010 Jan 12;340:b5463. doi: 10.1136/bmj.b5463.BMJ. [100] Das S, Mukherjee S, Lekli I, Gurusamy N, Bardhan J, Raychoudhury U, Chakravarty R, Banerji S, Knowlton AA, and Das DK. Tocotrienols confer resistance to ischemia in hypercholesterolemic hearts: insight with genomics. Mol Cell Biochem, 360(12):3545, 1 2012. http://www.ncbi.nlm.nih.gov/pubmed/21918828. [101] Das S, Lekli I, Das M, Szabo G, Varadi J, Juhasz B, Bak I, Nesaretam K, Tosaki A, Powell SR, and Das DK. Cardioprotection with palm oil tocotrienols: comparision of dierent isomers. Am J Physiol Heart Circ Physiol, 294(2):H9708, 2 2008. http: //ajpheart.physiology.org/content/294/2/H970.long. [102] Proteasome. wikipedia. http://en.wikipedia.org/wiki/Proteasome.
BIBLIOGRAPHY
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[103] Second national report on biochemical indicators of diet and nutrition in the us population 2012. http://www.cdc.gov/nutritionreport/. [104] Gesundheitsrisiken. wissenschaftler raten von vitaminpillen ab. 15 jan 2012. http: //www.spiegel.de/wissenschaft/mensch/0,1518,809208,00.html. [105] Health assessment of food supplements. http://www.bfr.bund.de/en/health_ assessment_of_food_supplements-736.html. [106] Vitamine. die grten irrtmer. ndr 14 jul 2011. hauptsache-gesund/vitamine114-download.pdf. http://www.mdr.de/
[107] Nesch E Tendal B AND, Higgins JP, and Gotzsche PC Jni P AND. Multiplicity of data in trial reports and the reliability of meta-analyses: empirical study. BMJ, 343(d4829), 8 2011. http://www.bmj.com/content/343/bmj.d4829?view= long&pmid=21878462.
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Chapter 12 Additives and E-Numbers

Food additives are substances which are usually not consumed as a food in itself, whether or not of nutritive value, and which are intentionally added for their technological purpose.
12.1
International Numbering System for Ingredients INS- Number
[1] Labelling often uses numbers instead of the common names of the ingredients.These numbers dier from country to country. For international use the Codex Alimentarius proposes an international numbering system which largely uses the same numbers of the European Commission but without E.
12.2
EU food additives regulations
Food additives are regulate by the European Community under directives which specify the E-Numbers, their names and their use. Please see the latest regulations on food additives and their E-numbers at: Only food additives included in the Union list set out in Annex II to Regulation (EC) No 1333/2008 may be placed on the market and used in foods under the conditions of use specied therein. The additives should be listed on the basis of the categories of food to which they may be added. [2] The regulation of 2008 was amended in 2011 by the following regulations: Regulation 1129/2011: Established a Union list of food additives. [3] Regulation 1130/2011: Approved the use of food enzymes, food avourings and nutrients. [4] Regulation 1131/2011: Introduced amendment with regard to steviol glycosides. [5] 971
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CHAPTER 12. ADDITIVES AND E-NUMBERS
12.2.1
E-Numbers Descriptions [6]
As the European Market increases in importance throughout the world the E-numbers of the allowed ingredients are getting important and are used by the Codex Alimentarius for the International Numbering System INS. Therefore they are listed below with a short comment: E-number Ingredient E100 Turmeric 12.2.3 E101(i) Lactoavin 12.2.4 E101(ii) riboavin-5-phosphate E102 Tartrazin 12.3.4 E104 Chinolin yellow12.2.6 E110 Sunset Yellow FCF; Orange yellow S12.2.6
12.2.2
Colorants
Are used to improve the colour and the aspect of food being applied intern or extern on the outer layer to promote appetite, selling. In sweet products it may fake a high content of fruit,in mayonnaise it suggests a high content of egg yolk. Colours are used in candies, soft drinks, puddings, ice creams, liquors,margarine, cheese and seafood. Table 12.1: colorants E number range Subranges 100-109 110-119 120-129 130-139 140-149 150-159 160-199 Description yellows oranges reds blues and violets greens browns and blacks gold and others
100-199 Colorants
12.2.3
E100 Turmeric
It is the natural colour of the root of turmeric (Curcuma longa).It is the traditional ingredient of curry powder. It may be obtained by synthesis. Its colour is yellow.
12.3. STABILITY OF NATURAL FOOD COLOURS UNDER PRODUCTION CONDITIONS
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12.2.4 12.2.5 12.2.6
E101 (i) Lactoavin E101a Phosphate-5-riboavin Azo dyes
Azo dyes are members of a chemical group comprising the following colours: E102 tartrazin (May have an adverse eect on activity and attention in children.) (http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=OJ:L:2010:279:0022:0031:EN:PDF) E104 Chinolin yellow (May have an adverse eect on activity and attention in children.), E110 yellow-orange S (May have an adverse eect on activity and attention in children), E122 Azorubine(May have an adverse eect on activity and attention in children.), E123 amaranth, E124 cochineal red red A (Ponceau 4R) (May have an adverse eect on activity and attention in children.), E151 brilliant black BN, E180 Lithol rubine BK, E128 red 2G, E155 brown HT. Carcinogenic activity of azo colours were found in rats were due to impurities of the colours used for the test and could not be conrmed further on. Calcium deposits in the renal pelvis was found but it could not be put in relation to the dosage of the colours.
12.3
Stability of natural food colours under production conditions
Natural colours are becoming increasingly important. The consumer is becoming consious about the natural origin of all ingredients. Some challenges using natural colours are its bulkiness when fruits and vegetable extracts are used, reduced light and heat stability, changed storage conditions, eect of pH and increased costs. Fernndez-Lpez et al. 2013 assessed the color degradation of aqueous solutions of red pigment extracts 500 C and 900 C , measuring the absorbance at 535 nm to quantify the degradation process. The remaining absorbance at 535 nm after 6 h at 900 C were for red cochineal 95%, elderberry 63.8%, red cabbage 46.1%, hibiscus 26.7%, red beet 12.5%, Opuntia fruits 1.7% were the most thermosensitive maintaining only 12.5 and 1.7 % of the initial absorbance. The authors underline the high thermal stability of the red cochineal extract.[7] Unfortunately cochineal extract, known as E124 or ponceau 4R, as an azo dye, is an allergen. It may elicit intolerance in people allergic to salicylates (aspirin). Additionally, it is a histamine liberator, and may intensify symptoms of asthma. Ponceau 4R is considered carcinogenic in some countries, including the USA, Norway, and Finland, and it is currently listed as a banned substance by the U.S. Food and Drug Administration (FDA). EFSA has decided on 2009-09-23 to lower the Acceptable Daily Intake (ADI) for Ponceau 4R from 4 mg/kg to 0.7 mg/kg bodyweight per day. The substance is associated with increased
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migration of nuclear DNA in human tissues, increased intake of lead and aluminum. [8] Extraction conditions of natural colours inuences their stability Cisse et al. 2012 studied colour degradation of roselle extracts (Hibiscus sabdaria L.). The authors compared the Arrhenius, Eyring and Ball models to predict colour modications during 6 month storage at 4-45 0 C . The colour changed faster during storage especially when extraction with hot water and pasteurisation were used. [9] Fermented red rice is UHT heat stabel Fermented red rice and black carrot hat good colour stability under UHT-heating conditions, while all other red/pink natural colours were signicantly sensible to UHT. Lycopene presented the lowest stability compred to red radish which was the most stable after heat treatment.. Fermented red rice was observed to be heat-stable after exposure to UHT processing and also remained relatively stable during storage, as was black carrot. Fluctuations of about 50 C during processing may induce colour spoilage warn Crin et al.2012. [10] The colour of red wine may change during short exposure to elevated temperatures The chemical alterations of red wine were a considerable change in the quality of wines stored for a few hours at elevated temperatures at 20 0 C , 25 0 C , 30 0 C , 35 0 C , and 40 0 C , compared to normal storage temperature of 140 C . Higher polyphenolic content of wine helps to stabilize the product against detrimental temperature eects according to Czibulya et al. 2012. [11] He et al. 2012 stress that monomeric anthocyanins in young red wines are important for colour and benecial health eects of red wine. Their stability, the self-association and copigmentation increase the stability and improves the coloor of red wine during production and storage [12] The Panel of the EFSA in a a scientic opinion related to monacolin K of fermented red rice concluded that of red yeast rice preparations help the maintenance of normal blood LDL cholesterol concentrations provided a daily dose of about 10 mg monacolin K is maintained. [13] Citrinin is a mycotoxin originally isolated from Penicillium citrinum. It has since been found to be produced by a variety of other fungi which are found or used in the production of human foods, such as grain, cheese, sake and red pigments. Citrinin has also been found in commercial red yeast rice supplements. Gordon et al. 2010 found the presence of citrinin in one-third of the formulations of fermented red rice. The authors warns physicians to be cautious in recommending fermented red rice to their patients for the treatment of
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hyperlipidemia and primary and secondary prevention of cardiovascular disease until red yeast rice products are regulated and standardized. [14] [15] Red fermented rice (RFR) is now used as a natural colour and dietary supplement. Chen et al 2005 suggest the use of the mutant strain, Monascus spp. M12-69 instead of the vild types of Monascus yeasts used in China. The strain M12-69 can produce high monacolin and very low citrininn (2,5 mg/g monacolin K and 0,1 ng/g of citrinin dried at 50 degrees C). [16]
12.3.1
Amaranthus betacyanin pigments as natural food colour [17]
Harold Corke and his co-workers from the University of Hong Kong report that addition of betacyanin pigments from Amaranthus tricolour, led to pink-red noodles with good colour stability, without aecting the cooking and textural properties of cooked noodles. It also improved the protein content of the noodles. Amaranth is an approved natural colorant in China, at levels of 0.1 and 0.5 per cent. Natural red pigments in use are anthocyanins, betalains, and carotenoids sourced from berries and grapes, red beetroot, and red fruit, vegetables and owers, respectively. Natural red colours are betacyanins, and betalains which are stable in low acid foods. The natural amaranth should not be confused with a synthetic dye that has been named "amaranth" for its similarity in color to the natural amaranth pigments known as betalains. This synthetic dye is also known as Red No. 2 in North America and E123 in the European Union. The Regulation 94/36 EC allows amarath only in bitter soda, aperitiv vines, spirit drinks with less than 15% alcohol/volume and sh roe to be coloured with amaranth E123. [18]
12.3.2
Amarant as feed [19]
Alfaro and colleagues 2008 report that the amaranth plant could be a useful resource for animal feeding. Dehydrated amaranth leaves and stalks in levels up to 60%, were used to replace equal amounts of alfalfa leaf meal. The authors found that amaranth leaf meal contained 17.8% protein and 12.4% crude ber as compared with the alfalfa leaf meal which contained 22.0% protein and 23.3% crude ber. The authors reported that amaranth leaf meal can eciently replace alfalfa leaf meal up to 15% of the total weight of the diet, whereas growth retardation and interstitial nephrosis and edema, were observed at a 60%. The authors stress that steam treatment improves the nutritive quality of the amaranth meal.
12.3.3
Invasive weeds [20]
The following 9 species of Amaranthus are considered invasive and noxious weeds in the U.S and Canada: A. albus, A. blitoides, A. hybridus, A. palmeri, A. powellii, A. retroexus, A. spinosus, A. tuberculatus, and A. viridis. A new strain of the Palmer amaranth has
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appeared which is Glyphosate-resistant and so cannot be killed by the widely used Roundup herbicide. Also, this plant can survive in tough conditions. This could be of particular concern to cotton farmers using Roundup Ready cotton. The species Amaranthus palmeri (Palmer amaranth) causes the greatest reduction in soybean yields. Palmer amaranth is among the "top ve most troublesome weeds" in the Southeast and has already evolved resistances to dinitroanilines and acetolactate synthase inhibitors
12.3.4
E102 Tartrazin
It is a synthetic substance highly allergenic.His use is restricted and even forbidden in many European countries, such as Norway, Austria and UK. His colour is yellow. Synthetic colours such as tartrazin were found in some tests to cause behaviour disturbance in overactive children. Success of therapy with colours free diet were cited. High number of other tests could not conrm these results making it controversial. Natural food such as haddock, strawberries, tomatoes, celery and honey have higher allergy potentials as tartrazin. That is why tartrazin is still allowed. [21].
12.3.5
POP colour as alternative to tartrazine [22]
The Institute for Agronomy Research (INRA) studies a by-product of the cider industry as a natural alternative to tartrazine. The new colour is obtained from apples and is called POP (phloridzine oxidation product) Cider apples are rich in polyphenols forming colours as well as for the bitter and astringent avours of ciders. Phloridzine is a polyphenol which during the production of apple juice and cider is oxidised by polyphenoloxidase enzyme resulting in the yellow POP colour which has antioxidant properties. POP remains stable and resistant to the majority of food production processes. It is yellow at acidity less than pH 5 and orange at pH 6. It does not stain plastic packaging, unlike hydrophobic carotenoid pigments.
12.3.6
Synthetic organic colours not azo dyes
It is a group with dierent chemical composition. E131 patent blue V, E133 brilliant blue FCF, E 142 green S are members of the triarylmethan group. All other colours have dierent composition and cannot be grouped under a chemical terms: E104 Chinolin yellow, E132 indigotin I E127 erythrosine, Erythrosine bears iodine in its structure. This iodine is liberated in the body and acts upon the thyroid gland which
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causes thyroid tumours on rats but not in other animals. That is why some authors would like to see the allowance of this colours withdrawn.
12.3.7
E104 Chinolin yellow
Synthetic substance harmless to rats and mice and dogs.The physiology in humans is unknown.It is forbidden in food in USA.It has yellow colour.
12.3.8
E129 Allura red AC
(May have an adverse eect on activity and attention in children.)
12.3.9 12.3.10
E154 brown FK Colorants found in nature
E101 riboavin, E101a riboavin 5-phosphate, E100 curcumin, turmeric oleoresin, E120 carmine, E140 chlorophyll, E141 Chlorophyll-Cu, E163 Anthocyanin, E162 betanin, red beet juice, 160a beta-carotene, alfa, gama-carotene, E160f beta-apo-8-carotenal, E160b Bixin,norbixin, capsanthin, capsorubin, E160d lycopene, E161b lutein (xanthophyll).
12.3.11
Chlorophyll in ripe fruits breakdown in NCCs which are strong antioxidants [23]
According to Thomas Mller and colleagues the breakdown compounds of chlorophyll are strong antioxidants. The researchers found the reactions to be similar in leaves and in fruits. The rst decomposition products are colourless, polar NCCs (nonuorescing chlorophyll catabolytes), that contain four pyrrole rings which In ripe pears and apples, NCCs replace the chlorophyll, especially in the peel and the esh immediately below it. During the decomposition process chlorophyll is released from its protein complexes becoming phototoxic. At this stage it can transfer energy to oxygen which becomes highly destructive. The NCCs compounds, on the contrary, are powerful antioxidants in plant and humans.
12.3.12
Curcumin [24]
Stig Bengmark looking for therapeutic agents which can modulate the inammatory reaction , found that curcumin, a component of turmeric, to be non-toxic, to have antioxidant activity, and to inhibit such mediators of inammation as NFB, cyclooxygenase-2 (COX2), lipooxygenase (LOX), and inducible nitric oxide synthase (iNOS).
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According to Bengmark turmeric, an approved food additive, or its component curcumin, has shown surprisingly benecial eects in experimental studies of acute and chronic diseases characterized by an exaggerated inammatory reaction.
12.3.13 12.3.14
E160a beta-Carotene,alfa Carotene,gamma-Carotene E160b Bixin, Norbixin,annatto,orleana
It is the pigment of the annatto bush. The pigment is considered to be harmless. His colour is orange.
12.3.15 12.3.16
E160c Capsanthin,Capsorubin E160d Lycopene
It is the pigment of the red tomato, being used as tomato powder. It is also made synthetically.
12.3.17 12.3.18
E160e beta-Apo-8-carotenal E160f beta-Apo-8-ethyl ester of carotene acid
Is found in vegetables,in fruits, and in liver. there is also a synthetic production of the pigment. It has yellow colour.
12.3.19
Caramel colours [25]
Caramel colours are colouring substances authorised as food additives in the EU, and are classied according to the reactants used in their manufacture as follows: Class I Plain Caramel or Caustic Caramel (E 150a); Class II Caustic Sulphite Caramel (E 150b); Class III Ammonia Caramel (E 150c) and Class IV Sulphite Ammonia Caramel (E 150d).
12.3.20
E150a sugar colour
Class I: Plain caramel, caustic caramel. Prepared by heating carbohydrates with or without acids or alkalis; no ammonium or sulte compounds are used.
12.3.21
E150b sulte-sugar colour
Class II: Caustic sulte caramel. Prepared by heating carbohydrates with or without acids or alkalis in the presence of sulte compounds; no ammonium compounds are used.
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12.3.22
E150c ammonium sugar colour
Class III: Ammonia caramel. Prepared by heating carbohydrates with or without acids or alkalis in the presence of ammonium compounds; no sulte compounds are used.
12.3.23
E150d ammonium sulte-sugar colour
Class IV: Sulte ammonia caramel. Prepared by heating carbohydrates with or without acids or alkalis in the presence of both sulte and ammonium compounds.
12.3.24
EFSA safety report 2011 on caramel colours and their by-products [26]
Caramel colours are added to food to give a deeper shade of brown and are widely used in a large variety of foods such as non-alcoholic avoured drinks, confectionary, soups, seasonings, and beer. They are complex mixtures of compounds produced by carefully controlled heat treatment of sugars. They are classied into four classes depending on the reagent used in their manufacture (ammonia, sulphite or no reagent), and generally known by the E numbers E150a, E150b, E150c, and E150d. The European Food Safety Authority sets Acceptable Daily Intakes (ADIs) for all caramel colours. EFSA is concerned about the safety of by-products, such as furan and 5-hydroxymethyl2-furfural (5-HMF), which are formed during the manufacturing of caramel colours and vary considerably depending on the production process. The Panel recommended to keep the levels of the by-products in caramel colours as low as technologically possible as dened in Commission Directive 2008/128/CE laying down specic purity criteria concerning colours for use in foodstus [27]. However, the caramel specications which are dened there should be updated to include also maximum levels for these constituents. Purity criteria and tests on caramel colours had been developed by Joint FAO/WHO Expert Committee on Food Additives (JECFA) specication for Caramel Colours. [25] The Panel also states that caramel colours are neither genotoxic, nor carcinogenic and that there is no evidence to show that they have any adverse eects on human reproduction or for the developing child.
12.3.25
ADIs for caramel colours
An Acceptable Daily Intake (ADI) of 300 mg per kg body weight per day (mg/kg bw/day) applicable to E150a, E150b, and E150d colours, and ADI of 100 mg/kg bw/day for caramel E150c. the Panel has set a more restrictive ADI for E150c considering possible eects on the immune system of one of its constituents, 2-acetyl-4-tetrahydroxibutylimidazole (THI).
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The Panel also points out that adults and children who are high consumers of foods containing these colours could exceed the ADIs established for three of these colours (E150a, E150c, E150d) if they are used at the maximum levels reported by industry.
12.3.26
By-products of caramel colours
The scientists on the Panel also looked at other constituents resulting from the production process, namely 2-acetyl-4-tetrahydroxibutylimidazole (THI) present in E150c, and 4-methylimidazole (4-MEI) present in E150c and E150d, for which EU specications already foresee sucient protective maximum levels for their presence in the colours. However, the Panel considered it would be prudent to keep their levels in caramel colours as low as technologically feasible, recommending further research to reduce the formation of of these by-products during the production of caramel colours. Council Directive 89/107/EEC [28] states that all food additives must be kept under continuous observation and must be re-evaluated whenever necessary in the light of changing conditions of use and new scientic information. According to CSPI the articial caramel colours in colas and some other products is made by Reacting sugars with ammonia and sultes under high pressure and temperatures result in the formation of 2-methylimidazole and 4 methylimidazole (MEI), which cause lung, liver, or thyroid cancer or leukemia in laboratory mice or rats [29]. Some opinions say these diseases were caused by high doses. The beverage industry says that 2-MEI and 4-MEI are everywhere and see no reason to avoid the use of such caramel colours. If its everywhere it is time to start to get out of food chain. The consumer can set a sign avoiding to drink brown cola.
12.3.27
Ammoniated "Caramel Colouring" E150d contaminated with cancerous 4-MI in cola beverages, says the Center for Science in the Public Interest [30]
According to the Center for Science in the Public Interest (CSPI) Coca-Cola, Pepsi-Cola, Diet Coke, and Diet Pepsi contain high levels of 4-methylimidazole (4-MI), a known animal carcinogen. Ammonia-sulte caramel colouring E150d is the "caramel colouring"of colas. The carcinogen is formed when ammonia or ammonia and sultes are used to manufacture the "caramel colouring". The CSPI explains that in contrast to the caramel made at home by melting sugar in a saucepan, the articial brown colouring E150d in colas is made by reacting sugars with ammonia and sultes under high pressure and temperatures, resulting in the formation of 2-methylimidazole (2-MI) and 4 methylimidazole (4-MI), which cause lung, liver, or
12.3. STABILITY OF NATURAL FOOD COLOURS UNDER PRODUCTION CONDITIONS thyroid cancer or leukaemia in laboratory mice or rats.
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12.3.28
What food authorities should do [31]
The CSPI asks the Food and Drug Administration to revoke the authorization for caramel colourings that contain 4-MI. The phrase "caramel coloring" is misleading when used to describe colourings made with ammonia or sulte. Companies should not be allowed to label any products that contain such colourings as "natural," Carcinogen-free colour alternatives are available and some move in this direction in USA seems to take place, however, there is no will to quit the use of E150d colouring agent in Europe.
12.3.29
Levels of carcinogens found by CSPI [32]
Pepsis products had 145 to 153 micrograms (mcg) of 4-MI in two 12-ounce cans. Regular Coca-Cola had 142 mcg per 12 ounces in one sample and 146 mcg in another. Diet Coke had 103 mcg per 12 ounces in one sample and 113 mcg in another. CSPI estimates that the 4-MI in the Coke and Pepsi products tested is causing about 15,000 cancers in the U.S. population. In addition to the cancer risk, soda drinkers are much more likely than non-soda drinkers to develop weight gain, obesity, diabetes, and other health problems because of the high sugar content of non-diet products. The US National Toxicology Program, the division of the National Institute of Environmental Health Sciences wrote that there is "clear evidence" that both 2-MI and 4-MI are animal carcinogens. Chemicals that cause cancer in animals are considered to pose cancer threats to humans. Researchers at the University of California, Davis, found signicant levels of 4-MI in ve brands of cola. The CSPI urges the FDA to act quickly to revoke its approval of two caramel colourings made with ammonia.
12.3.30
Teenagers are at highest risk [33]
In a little-noticed regulatory proceeding in California, state health ocials have added 4 MI to the states list of "chemicals known to the state to cause cancer." Under that states Proposition 65, foods or other products containing more than certain levels of cancercausing chemicals must carry warning labels. For 4-MI, that level is 16 micrograms per person per day from an individual product. Popular brands of cola contain about 200 micrograms of 4-MI per 20-ounce bottle-and many people, especially teenagers, consume more than that each day.
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To put the risk from caramel colouring in context, CSPI says the sugar content in a nondiet can of soda presents a greater health risk than the ammonia sulte process caramel. But the levels of 4-MI in the tested colas still may be causing thousands of cancers in the U.S. population.
12.3.31
European soda producers stick to the carcinogen caramel colour E150d
Carcinogen-free colour alternatives are available and some move in this direction in USA seems to take place, however, there is no will to quit the use of E150d colouring agent in Europe. Sodas producers should keep not only their labels "clean" but also their products. According to professor Schmhl, researcher on cancer in Heidelberg, Germany, there is no dose, even being very small, that is free of danger to cause cancer because of the eect of synergistic addition of the eects of smoke,sulphur dioxide, nitrosamines of ham, smoked salmon, all add up. So take E150d out of colas or the consumer should avoid the beverage.
12.3.32
European caramel colours regulated under the Directive 2008/128/EC [27]
Caramel colours are colouring substances authorised as food additives in the EU, and are grouped in four classes according to the reactants used in their manufacture and their Acceptable Daily Intake (ADI) are as follows: Class Class Class Class I Plain Caramel, (E 150a), containing no added ammonia or sulphite, no limit set. II Caustic Sulphite Caramel, (E 150b), ADI of 0-160 mg/kg bw/day. III Ammonia Caramel, (E 150c) ADI of 200 mg/kg bw/day. IV Sulphite Ammonia Caramel, (E 150d), ADI of 200 mg/kg bw/day.
12.3.33
Maximum levels of 4-MEI and THI [34]
The maximum level of the constituent 4-methylimidazole (4-MEI), found in Class III Ammonia Caramel and Class IV Sulphite Ammonia Caramel only, is restricted to < 250 mg/kg caramel. 2-acetyl-4-tetrahydroxy-butylimidazole (THI), found in Class III Ammonia Caramel only, is restricted to < 10 mg/kg caramel on a colour intensity basis. (Both llevels are expressed on equivalent colour basis i.e. is expressed in terms of a product having a colour intensity of 0,1 absorbance units.) The Panel noted that the caramel colours are poorly characterised, and it is not clear whether the controls on manufacturing processes are sucient to minimise batch-to-batch variability, particularly with respect to levels of individual Low Molecular Weight (LMW)
983
constituents. The wide range of starting materials and reactants that may be used for the production of caramel colours may result in a variety of end products, with dierent physical, chemical and toxicological properties. The Panel noted that concerns about e.g. chemical composition, purity and similarity of various caramel colours have also been raised in the past by the SCF. The Panel also noted that a number of the identied or theoretical LMW constituents of caramel colours are genotoxic under certain experimental conditions and in some cases have carcinogenic potential, e.g. furan and 5-hydroxymethyl-2-furfural (5-HMF),g THI/kg bw/day (provided by a level of 0.4% Class III Ammonia Caramel in drinking water, in rats maintained on a low-pyridoxine diet, 2-3 mg/kg diet) to levels of 200 g THI/kg bw/day or higher.
12.3.34 12.3.35
E161b Lutein E162 Red beet colour, betanin, Beetroot red
Natural colour of red beet. When the concentrate of red beet juice is used as food colour specications need to be established. Because nitrate is a component of beet red, it is necessary to ensure that levels of nitrate do not exceed the specications, keeping in mind the need to limit the nitrate content of food produced for infants and young children.
12.3.36
E163 Anthocyanin
Natural colour of the skin of red grapes.
12.3.37 12.3.38
E170 calcium carbonate E171 Titanium dioxide
There is very little known about undesired reactions of this substance.It has white colour.
12.3.39
E172 Iron oxides and hydroxides
Their colour vary from yellow,to red,to brown and to black.
12.3.40
E579 Iron gluconate
Undesired reactions are unknown.The colours are yellow , red or black.
12.3.41
E17Aluminium
There are no arguments against intake by healthy people. In case of Alzheimer disease aluminium should be avoided.
984
12.3.42 12.3.43
E174 Silver E175 Gold
Gold and silver in high dosage are toxic.However there is no danger of poisoning because of the high price of gold and silver limiting in this way its use.The colour is silvery and golden.
12.3.44
E180 Rubin BK pigment
It is an azo pigment. There is very little known about its biochemical activity.
12.3.45
E141 Copper chlorophyll complex
This substance has green colour and is obtained by changing the magnesium radical of chlorophyll with copper.It is a risk to patients with syndrome of Wilson.An increase of the supply of copper is not advisable.
12.3.46
E142 Brilliant green acid
It is a synthetic substance being relatively harmless.
12.3.47
E239 Hexamethylene tetramine
It is a widely used substance, as medicine against gout and infections of the urinary tract.It is also a vulcanization accelerator and is used in the chemistry of explosives.In food it is a donator of formaldehyde.It was formerly used as preservative .At the moment it is used only in some kind of cheese.
12.3.48
Natamycin
Natamycin(it is also called pimaricin) is an antibiotic used in infections of mouth,foot and genitals. It is employed in food industry to treat the shell of cheese. Resistance against this antibiotic will soon be established in bacteria coming in contact with it.His use should therefore be forbidden in food industry
12.3.49
Antioxidants
Antioxidants are used to improve the shelf life of food interfering in the reaction of oxygen with dierent components of food avoiding their chemical decomposition. They are used in soups,sauces in powder, chewing gum,dried products of potatoes in margarine, salad oil and icecream.
985
12.3.50
Chemical preservatives
The chemical preservatives may prolong the shelf life of food retarding the growth of bacteria and moulds. The use of chemical preservatives enables the careless hygienic conditions by the processing of food. Chemical preservatives are used with sh products of all types, fruit juices, soft drinks, pastries, salads, margarine, sauces, vines , dried fruits, citric fruits, bananas, desiccated vegetables, sugar etc. Table 12.2: Preservatives E number range Subranges 200-209 210-219 220-229 230-239 240-259 260-269 270-279 280-289 290-299 Description sorbates benzoates sulphites phenols and formates (methanoates) nitrates acetates (ethanoates) lactates propionates (propanoates) others
200-299 Preservatives
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E200 Sorbic acid E202 Potassium sorbate E203 Calcium sorbate
Sorbic acid and his salts are considered as harmless because they are metabolised in human body like fatty acids. They may produce adverse taste in food, specially in bread.
12.3.54 12.3.55 12.3.56 12.3.57
E210 Benzoic acid E211 Sodium benzoate E212 Potassium benzoate E213 Calcium benzoate
The benzoic acid and their salts causes frequent allergy (asthma, urticaria) Cats are very sensible to benzoic acid. Even a very low concentration of 5 ppm may be mortal for cats (permitted in food are concentrations of sorbic acid up to 2500 ppm in herring salads and up to 4000 ppm in salmon products.Avoid to give these foods to your pets).
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In combination with sorbic acid and E227 calcium hydrogen sult the undesired reactions are potentiated.
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E214 Ethyl-p-hydroxi benzoate E215 PHB-ethyl ester sodium salt PHB-propyl ester E217 PHB-propyl ester E218 PHB- methyl ester E219 PHB-methyl ester,sodium salt
The esters of PHB cause frequently allergies.They act as vascular dilating and were indicated as anesthesics for frogs. His antispastic action exceeds the action of sodium benzoate by one hundred times. In high dosage they retard the growing of rats.
12.3.64 12.3.65 12.3.66 12.3.67 12.3.68 12.3.69 12.3.70 12.3.71
E220 Sulphur dioxide E221 Sodium sulphide E222 Sodium hydrogen sulphite E223 Sodium metabisulte E224 Potassium metabisulte E226 Calcium sulphide E227 Calcium bisulphide E228 potassium bisulphide
. Dioxides and sulphites liberating sulfur dioxide may cause headache and vomits.This is noted after drinking vine.They destroy vitamin B1 and may produce asthma attack.Sulphur dioxide is a typical pollution of nature being directly responsible for the dying of trees and pseudocroup disease.
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E230 Biphenyl E231 Ortophenylphenol E232 Sodium ortophenyphenol E233 Thiabendazol
Are substances used as antifungal on citric fruitsand promote cancer of the bladder in animals, being very strong in combination of E232 and E233. Thiabendazol is used in medicine and also in agriculture as pesticide.It is being frequently used to impregnate paper used to wrap up fruits. Avoid children playing with this paper or even putting in contact with the mouth.
12.3.76 12.3.77
E234 Nisin The food preservative nisin has anti-cancer properties [35]
Nisin, a bacteriocin is used as food preservative, mainly in dairy products. Joo et al. 2012 report that this antimicrobial peptide may be used to treat head and neck squamous cell carcinoma (HNSCC). Nisin induces cancer cell death, cell cycle arrest, and reduces cell proliferation in squamous cancer cells. Nisin triggers a cation transport regulator protein (CHACI) in cancer cells which causes the cancer cell to die. Additionally nisin promotes the ow of extracellular calcium to the inside of the diseased cell acting as a regulator of cell cycle.
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E235 Natamycin E236 Formic acid
(Not allowed as food ingredient.)
12.3.80
E237 Sodium formate
(Not allowed as food ingredient)
12.3.81
E238 Calcium formate
(Not allowed as food ingredient) Formic acid and their salts may be metabolised in the body.Undesired reactions only with high levels.
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E242 Dimethyl carbonate E249 Potassium nitrite E250 Sodium nitrite E251 Sodium nitrate E252 Potassium nitrate E 270 Lactic acid
. E270 stands for both (left or right) optical active forms.
12.3.88 12.3.89 12.3.90 12.3.91
E280 Propionic acid E281 Sodium propionate E282 Calcium propionate E283 Potassium propionate
Propionic acid is a natural compound of food being found in very small quantities.It produces cancer on the antestomach of rats. According to the health authorities it is not signicant to human because we do not have an antestomach.Propionic acid and their salts are used as preservative in bread. Sorbic acid could become an ideal replacement for calcium propionate as mould inhibitor, being thus a cost-saving method to keep bread fresh and mould-free for a couple of weeks. Sorbic acid can not generally be used as a suitable alternative as it destroys yeast. The process works by coating the sorbic acid within an invisible microlm of vegetable fat to create a free owing powder that can easily be blended with dry ingredients prior to baking. A controlled release mechanism ensures the sorbic acid is not released from its encapsulate until the bread is baked past 60o C , after the yeast has nished working. Preservatives in bread can be avoided as special care during production can achieve a reasonable shelf life. Cost cutting on cleaning and maintenance of the production line and reheating after packaging makes the use of preservatives and obscure microencapsulated ingredients attractive. Bread should be produced as natural as possible.
989
12.3.92 12.3.93 12.3.94
E284 Boric acid E285 Sodium tetraborate (borax) New preservative for meat products, non-alcoholic beverages energy and sport drinks [36]
The new preservative ethyl lauroyl arginate is awaiting approval in March by the European Commission. The application, Spains Laboratorios Miret SA (LAMIRSA), originally proposed to EFSA that the preservative be used in non alcoholic beverages made with fruit juice, energy and sports drinks, and meat products, at a dosage of 115 to 225 ppm. However EFSA saw that this dosage would mean the potential exposure to the chemical could be at or above the ADI of 0.5mg per kg of bodyweight per day.
12.3.95
Safety concerns
Studies in dierent rat strains and sexes showed that there was a consistent eect on white blood cell counts. Experts speaking for LAMIRSA, the company the preservative, say that "the data is toxicologically not signicant since the observed eects are inconsistent between the studies considered and did not demonstrate a dose-eect relationship", and the eects on white blood cells were not accompanied by changes to the tissue in any of the studies. Ethyl lauroyl arginate has been generally recognised as safe (GRAS) in the US since 2005, at levels up to up to 200 mg of the active ingredient ethyl-Nalfa-lauroyl-Larginate HCl /kg. Last year JECFA recognised it as a food additive and allocated an ADI of 0-4 mg/kg bw, and the additive was recently approved in Australia and New Zealand. EFSA, however, maintains that the toxicological relevance of the ndings could not be assessed, since the mechanism of action is not clear. The ANS panel of the EFSA concluded that the scientic evidence of a plausible mechanism for the alterations in white blood cell counts has not been provided and that the concerns and uncertainties related to white blood cell counts have not been addressed.
12.3.96
Acidulants, acidity regulators
Acidulants and acidity regulators are used to give a sour taste to food and to act as preservative.Some acidulants act as stabilisers, other help antioxidants or emulsiers. Acidity regulators adjust the pH like phosphates and citrates, acids and alkaline substances. Table 12.3: Antioxidants and acidity regulators
990 E number range
CHAPTER 12. ADDITIVES AND E-NUMBERS Description ascorbates (vitamin C) tocopherol (vitamin E) galates and erythorbates lactates citrates and tartrates phosphates malates and adipates succinates and fumarates others
Subranges 300-305 306-309 310-319 320-329 300-399 330-339 Antioxidants and acidity regulators 340-349 350-359 360-369 370-399
12.3.97 12.3.98 12.3.99 12.3.100
E260 Acetic acid E261Potassium acetate E262 Sodium acetate E263 Calcium acetate
Acetic acid(E260) is a harmless preservative. Acetic acid and his salts (acetates) are synthetically produced from light benzine. It is important for the production of leaven.The bread made with this leaven is however of inferior quality.
12.3.101 12.3.102 12.3.103 12.3.104
Other ingredients E325 Sodium lactate E326 Potassium lactate E327 Calcium lactate
Lactic acid is obtained from starch under the activity or bacteria.There are two types of lactic acids turning left and turning right.European legislation permits both form. Small children cannot metabolise the dextrorotatory Form. Its excessive ingestion may produce excessive blood acid.Food with D-lactic acid should be labelled with an warning.
12.3.105
E290 Carbon dioxide
Its harmless and is found normally in air.

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12.3.106 12.3.107
E296 Malic acid E331 Sodium citrate i) Monosodium citrate, ii) disodium citrate, iii) trisodium citrate
During heating procedure for infant formulae or follow-on formulae made from cows milk the surplus of ionised calcium results in denaturation and aggregation of proteins causing a phase separation of fat and proteins. Sodium or potassium citrate, as well as sodium and potassium phosphates are therefore used to complex free calcium ions reducing denaturation and aggregation of formulae containing milk. The use of sodium and potassium citrate is acceptable up to 2 g/l, either single or in combination, in infant formulae and follow-on formulae for infants and young children in good health and in FSMP. Sodium and potassium citrate are permitted in weaning foods at quantum satis levels for pH adjustment only (Directive 95/2/EC) and as source of nutrients in infant formula and follow-on formula for infants and young children in good health (Directive 91/321/EEC) [37].
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E335 Sodium tartrate i) monosodium tartrate ii) disodium tartrate E350 Sodium malate E351 Calcium malate
12.3.109 12.3.110
Malic acid is present in many fruits.It exists as two types ( levorotatory form and dextrorotatory form ) Malic acid and its salts (malates) are being produced starting from fumaric acid (E297 )
12.3.111
E297Fumaric acid
Fumaric acid can be obtained synthetically.It is also being used in the production of plastics.
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12.3.112 12.3.113 12.3.114 12.3.115 12.3.116 12.3.117 12.3.118 12.3.119 12.3.120 12.3.121 12.3.122 12.3.123 12.3.124 12.3.125 12.3.126 12.3.127
E300 Ascorbic acid E301 Sodium ascorbate E302 Calcium ascorbate E304 Fatty acid esters from ascorbic acid, i) ascorbyl palmitate, II)ascorbyl stearate E306 Heavy tocopherol bearing extracts E307 Alpha-tocopherol E308 Gama-tocopherol E309 Delta tocopherol E310 Propyl gallate E311 Octyl gallate E312 Dodecyl gallate E315 Isoascorbic acid E316 Sodium isoascorbate E320 Butylhydroxyanisole (BHA) E321 Butylhydroxytoluene (BHT) Modied starch
According to the European labeling legislation starch modied with enzymes or with physical methods are not declared as "modied". These ingredients are declared in the list of ingredients as "starch". Modied starch has its chemical structure changed with inorganic acids.Together with E339 disodium phosphate. E343 dimagnesium phosphate and E 450 orthophosphates modied starch can cause deposits of calcium in the pelvic region.
12.3.128
Emulsier
Emulsier are substances which make a mixture of water and oil possible. They reduce the surface tension between both liquids, so that small droplet of oil may swim in water. This emulsion is called "oil in water emulsion". When water swims droplets are swimming in oil it is called "water in oil emulsion".
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In food technology there are many new organoleptic properties caused by emulsions such as creamy,thickening,foaming. Emulsiers are used widely in food such as margarine, in bakery in candies,puddings bred, soups. Emulsiers have great biological activity.They should not be employed uncontrolled.There are very few toxicologic studies about emulsiers and were all made by their producers.In case of negative results they were not published.Recent tests have not found adverse activities.It is however believed that emulsiers have a role in the development of diseases of intestines and in allergies. Emulsiers modify the surface of the intestine making them permeable to allergens,contaminants and other additives. Table 12.4: Thickeners, stabilisers and emulsiers Subranges 400-409 410-419 420-429 430-439 400-499 440-449 Thickeners, stabilisers and emulsiers 450-459 460-469 470-489 490-499 E number range Description alginates natural gums other natural agents polyoxyethene compounds natural emulsiers phosphates cellulose compounds fatty acids and compounds others
12.3.129
E322 Lecithin
Lecithin is extracted from soya beans and colza.Enzymatic hydrolysis is permitted.
12.3.130
E442 Ammonium phosphatides
They are obtained from oil of colza treated with ammonium.
12.3.131
E470a Sodium,potassium and calcium salts of fatty acids
Fatty acids are natural elements of fats and oils. Their salts are obtained by treating them with alcaline substances in order to get soaps.
12.3.132 12.3.133
470b Magnesium salt of edible fatty acids E471 Mono and diglycerides of fatty acids esteried with organic acids
E471 reacts with tartaric acid,acetic acid or lactic acid.

994
12.4
Citric acid ester of mono- and di-glycerides replacing lecithin in chocolate applications.
Soy lecithin remains the most frequently used ingredient to lower the viscosity of liquid chocolate masses during processing. non-GM (genetically modied) soy lecithin with a full Identity Preserved (IP) status is, however, getting rare. Recent developments of new types of citric acid esters of mono- and diglycerides from castor oil are replacing soy lecithin to overcome the shortage of GM- free lecithin on the international market
12.4.1
Functional advantages of citric acid ester of mono- and di-glycerides
Dosages of lecithin higher than 0.4 per cent increase the yield value of the chocolate mass, making it necessary either to add extra cocoa butter or PGPR (Polyglycerol Polyricinoleate E476 obtained from ricinoleic acid and polyglycerol from canola) to the chocolate. Citric acid ester of mono- and di-glycerides act also as a wetting agent in instant chocolate drink powder an has an equivalent eect to soya lecithin when tested in a milk system. It is also used as an instantising agent for powdered food preparations and instant chocolate drink powders intended for re-hydration in water or milk.
12.4.2
E475 Polyglycerol ester of fatty acids
Possible name in the list of ingredients is polyglycerol ester. Polyglycerol Ester (PGE) is an emulsiers which may be used instead of emulsiers based on saturated fats. The bakery industry did little eorts to reduce the content of saturated fats and trans-fats of aerated and non-aerated cakes, sponge cakes, Swiss rolls, cup cakes, muns, biscuits and fatty llings. However, consumer pressure and an increasing number of studies made some manufacturers to reformulate their products leading to healthier bakeries with a leaner label and a positive nutritional prole. Emulsiers have a starch complexing eect, retard the retrogradation process of starch and increase the softness of cake. That is why industrial cakes have such long shelf life. Saturated fats of emulsiers in creams cause an unpleasant low melting sensation when they are consumed, because the melting point of the fats are 500 C and higher. The body temperature cannot melt them. New generations of food emulsiers allow to change hard fats with liquid oils in the formulation of industrial cakes. They also increase the tolerance to mechanical treatment, such as pumping of the cake batter, which acquires resistance to high shear und stress during mixing, pumping and baking, an important feature in industrial bakery.
12.4. CITRIC ACID ESTER OF MONO- AND DI-GLYCERIDES REPLACING LECITHIN IN CHOCOLATE APPLICATIONS.
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12.4.3 12.4.4
E477 Propylene glycol ester of fatty acids Propylene glycol monostearate [38]
Aleogon, Frochot and Go 2008 studied the eectiveness of propylene glycol monostearate (PGMS) to inhibit ice recrystallization in ice cream and frozen sucrose solutions. They found that 0.3 per cent of PGMS reduced ice crystal sizes in such solutions when frozen in a scraped-surface freezer. TheCho2009inc crystal morphology was highly irregular. No eect was found in quiescently frozen solutions, such as ice pop or ice lollies. The authors say that shear during freezing is necessary to distribute PGMS around the ice and cover the surface of the crystals. Danisco has a patent on this matter. Propylene glycol monostearate esters of fatty acids (E477) are classied as emulsiers,the authors, however, found the emulsifying eect of PGMS to be poor.
12.4.5 12.4.6 12.4.7 12.4.8 12.4.9 12.4.10 12.4.11 12.4.12 12.4.13 12.4.14 12.4.15 12.4.16 12.4.17
E479b Thermally oxidized soybean with mono- and diglycerides of fatty acids E481 Sodium stearyl-2-lactylate E482 Calcium stearyl-2-lactylate E483 Stearyl tartrate E491 Sorbitan monostearate E492 Sorbitan tristearate E493 Sorbitan monolaurate E494 Sorbitan monooleate E495 Sorbitan monopalmitate E330 Citric acid E331 Sodium citrate E332 Potassium citrate E333 Calcium citrate
Citric acid is present in many fruits, mainly in Kiwi and lemon. Citric acid is part of the biological cellular activity.By high levels of citric acid in food, the
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intestines are forced to assimilate higher rates of heavy metals and radionuclides. Citric acid is won from sugar by bacterial activity.
12.4.18 12.4.19 12.4.20 12.4.21 12.4.22 12.4.23
E334 Tartaric acid E335 Sodium tartrate E336 Calcium tartrate E337Sodium and potassium tartrate E353 Metatartaric acid E354 Calcium tartrate
Tartaric acid is a natural substance obtained from rests of wine reacting with calcium milk (E526) with potassium tartrate (E336) and nally with sulphuric acid.Only the harmless levorotatory form form (left turning form) is allowed.
12.4.24 12.4.25
E338 Phosphoric acid E339 Natrium phosphate i) monosodium phosphate, ii) disodium phosphate, iii) trisodium phosphate E340 Potassium phosphate, i) monopotassium phosphate, ii) dipotassium phosphate, iii) tripotassium phosphate E341 Calcium phosphate i) monocalcium phosphate, ii) dicalcium phosphate, iii) tricalcium phosphate E343 Magnesium orthophosphate
12.4.26
12.4.27
12.4.28
Not allowed any more as food ingredient.

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12.4.29 12.4.30 12.4.31 12.4.32 12.4.33 12.4.34 12.4.35 12.4.36 12.4.37 12.4.38 12.4.39 12.4.40 12.4.41 12.4.42 12.4.43
E352 Calcium malate i) calcium malate ii) calcium hydrogen malate E355 Adipic acid E356 Sodium adipate E357 Potassium adipate E363 E380 Triammonium citrate E385 Calcium disodium metylendiamine tetraacetate E400 Alginic acid E401 Sodium alginate E402 Potassium alginate E403 Ammonium alginate E404 Calcium alginate E405 Propylene glycol alginate E406 Agar-Agar E407Carrageenan
Carrageenan is obtained from red alga Irish Moss (Chondrus crispus) and is in use as stabiliser or thickening agent and as an encapsulation agent. New researches and experiments from the University Iowa (USA) with animals rise the suspicion that this ingredient has carcinogenic potential. Low molecular carrageenan was recognised long time ago as carcinogenic. That is the reason to use only the long chain molecular types or carrageenan. Researches in the University of Iowa have shown that carrageenan is broken in small molecules during processing and during digestion. These small parts can enter the bloodstream.[39]Carrageen is largely sourced from the Philippines and Indonesia. Thomas Karbowiak and colleagues found that adding high melting point fat to form an emulsied lm can reduce the transfer of water and enhance moisture barrier properties. This is important in the development of composite foods where Karbowiaks research can lead to edible lms and coatings applied between the dierent phases of this food.
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Blends of iota-carrageenan hydrocolloid matrix and fat developed by the researchers reduce the water transfer between compartments of dierent water activities in the same food. Increased shelf-life can thus be obtained. The authors conclude that carrageenan can be used for application such as encapsulation of active substances incorporated in biopolymer coatings or lms for food packaging.
12.4.44
Degraded carrageen [40]
Joanne Tobacman reviewing experimental data pertaining to carrageenans eects found that exposure to undegraded as well as to degraded carrageenan was associated with the occurrence of intestinal ulcerations and neoplasms. This association may be attributed to contamination of undegraded carrageenan by components of low molecular weight, spontaneous metabolism of undegraded carrageenan by acid hydrolysis under conditions of normal digestion, or the interactions with intestinal bacteria. Chemically degraded form of carrageen have lower molecular weight. factors such as bacterial action, stomach acid and food preparation may transform undegraded carrageenan into the more dangerous degraded type. The safety of carrageenan has recently been reviewed in 2001 by the Joint FAO/WHO Expert Committee on Food Additives (JECFA). The experts on this Committee did not nd evidence to suggest that the levels of carrageenan in foods posed any hazard to health. [?] [41] During the course of the re-evaluation, the JECFA specically reviewed the matter of the potential for gastrointestinal eects from ingestion of carrageenan. This included an evaluation of the eects of stomach ora on carrageenan, food processing conditions on carrageenan and the degradation of carrageenan in the stomach. Throughout the course of the re-evaluation, the JECFA considered genotoxicity studies, metabolism, reproduction and developmental toxicity, and short term and long-term mammalian feeding studies (including a 7.5 year feeding study in monkeys). The JECFA also considered information about the current understanding of the concept of cell proliferation and promotion of tumors. [?] [41] The fact that proliferative eects were seen at 2.6% in the diet is not being considered as relevant, because the estimated carrageenan consumption is below the threshold concentration for these eects. Further, the JECFA also noted that at 5% in the diet of rats, carrageenan did not act as at tumor promotor. Eects seen at exceptionally high levels of exposure to carrageenan were determined to be caused by altered toxicokinetics. [?] [41] Overall, the JECFA concluded that there was no concern to the continued consumption
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of carrageenan. It allows for the use of the additive at the level necessary to achieve the technical or functional eect in food, also referred to as the level of Good Manufacturing Practices (GMP). The complete report of this review was made publicly available in 2003 and therefore post dates the review by Dr. Tobacman. [42] [41]
12.4.45
Carrageenan is safe, says Cohen and Ito 2002 [43]
Cohen and Ito 2002 stress food-grade carrageenan has a weight average molecular weight greater than 100,000 Da, only small content of smaller particles are present. Carrageenan is not degraded in the gastrointestinal tract and is not absorbed. Systemically administered carrageenan has been reported to have an eect on the immune system, but this has no relation to an oral intake. Many toxicological studies on carrageenan have involved administration in high doses. The substance poligeenan (formerly referred to as degraded carrageenan) is not a food additive. It exhibits toxicological properties at high doses. The lack of carcinogenic, genotoxic, or tumor-promoting activity of carrageenan demonstrated in various studies, support the armation that carrageenans are safe under the actual food regulations.
12.4.46
EU Carrageenan opinion of 2002 [44]
The Committee consideres carrageenan as an additive for general food with an ADI of 0 - 75 mg/kg bw. The Committee notes that intakes are considerably below the ADI. However, a molecular weight limit of not >5% below 50 kDa should be introduced into the specication, in order to ensure that the presence of any degraded carrageenan is kept to a minimum. The Committee says that it is inadvisable to use carrageenan in infant formulae that are fed from birth, including those in the category of foods for special medical purposes, as low molecular weight carrageenan may be absorbed by the gut of the infant and interfere with the immune system. There are no objection to the use of carrageenan in foods for older infants, such as follow-on milks and weaning foods.
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E407a Processed Euchema algae E410 Carob seed
Also known as locust bean gum is allowed in follow-on formulae at a maximum level of 1g/l, and in weaning foods at a maximum level of 10g/kg under Directive 92/2/EC. Locust bean gum is rened from the endosperm of the carob tree Ceratonia siliqua. It contains tannins. The carbohydrate component is a galactomannan polymer consisting of linked D-mannose units with side chains of D-galactose. It is used as a stabiliser and thickening agent.
1000
12.4.49 12.4.50 12.4.51 12.4.52
E412 Guar gum E413 Tragacanth E414 Gum arabic Gum arabic, gum acacia
Gum arabic, acacia gum E414 is won from acacia trees in Sudan and Nigeria. Gum arabic is a complex mixture saccharides and glycoproteins, which gives it one of its most useful properties: it is perfectly edible. Other substances have replaced it in situations where toxicity is not an issue, as the proportions of the various chemicals in gum arabic varies widely and make its reliable performance troublesome. Still, it remains an important ingredient in soft drinks, syrups, hard gummy candies like gumdrops, and in marshmallows. [45]
12.4.53
Corn bre gums replacing acacia gum
Madhav P. Yadav and colleagues, in a study, extracted two dierent types of corn ber gum from the corn kernel pericarp and/or endosperm ber. The researchers found that the emulsifying properties of corn bre gums, an arabinoxylan (hemicellulose), were better than native and modied acacia gums and could domestically produced gum with a dependable supply and consistent quality replacing acacia gums.[46]
12.4.54 12.4.55 12.4.56 12.4.57 12.4.58
E415 Xanthan E416 Karaya gum E417 Tara seed E418 Gellan E425 Konjac
Konjac is approved by WHO, US Food and Drug Administration and the European Union with up to one per cent of the nal product. It is used for gel strength, viscosity in confectionery,as dietary ber,edible lms, improves mouthfeel. It is also called glucomannan being a hydrocolloidal polysaccharide obtained from the tuber of Amorphophallus Konjac, K.Koch, growing in East Asia. The chain of the molecules of the nonionic glucomannan is built mainly of mannose and glucose in a ratio of 1.6 : 1.0 the molecular weight is between 200,000 and 2,000,000 daltons. There are acetyl groups which are responsible for water solubility. There were rumours linking konjac with certain death cases after ingestion of jelly minicups and fruit gel sweets containing konjac.
12.5. BULK SWEETENERS AND INTERSITY SWEETENERS
1001
12.4.59
New hydrocolloid from process waters of Norway spruce [47]
Hydrocolloids are increasingly needed in the production of foods as stabilisers, thickeners, emulsiers and gelling agents, papermaking, textile and cosmetic industries. Stean Willfr and colleagues stress that mannans used as guar gum, Konjac glucomannan, locust bean gum, tara gum, and fenugreek gum are used, but mannans from wood are neglected. The researchers found that the process waters in mechanical pulp mills processing Norway spruce is high in dissolved O-acetylgalactoglucomannans (AcGGM). This hydrocolloid represents about 50 per cent of the dissolved matter in the process water.
12.5
12.5.1
Bulk sweeteners and intersity sweeteners

Bulk sweeteners are
Sugar, sorbitol, maltitol, isomalt, mannitol, erytritol, lactitol contribute to the bulk, the texture and the viscosity of foods.
12.5.2
FSA will look after food safety after tenfold increase of high-intensity sweetener use [48]
The world use of high intensity sweeteners rose tenfold in two years years up to over 700 thousand tonnes/y of saccharin, aspartame, acesulfame K, sucralose and cyclamate being consumed today.
12.5.3
Looking for a method to simultaneously extract and determine the currently permitted intense sweeteners
The UK Food Standards agency called for research proposals for a fully validated method to detect and measure the presence of sweeteners in food, including saccharin, aspartame, acesulfame K, NHDC, sucralose, cyclamic acid, neotame and stevia extracts. Validation should follow the guidelines for single laboratory validation of the International Union of Pure and Applied Chemistry (IUPAC). The Agency plans to test food products for their sweetener content, to ensure that the levels used are safe.
12.5.4
High-intensity sweeteners
High-intensity sweeteners are: Saccharin, aspartame, acesulfame K, sucralose and cyclamate do not contribute to the physical properties of a product and must be supplemented by bulking agents
1002
12.5.5
E420 Sorbitol, ii) sorbitol syrup
Sorbitol is widely used in diabetic foods. Can cause gastric disturbances.
12.5.6
Sorbitol in chewing gum and sweets may cause serious weight loss [49]
Sorbitol is a "sugar-free" sweetener found in chewing gum and sweets. The safety of sorbitol has been thoroughlylyols must be labelled with the statement, "Excessive consumption may produce laxative eects." According to Juergen Baudits and colleagues 2008 serious weight loss and diarrhoea were caused by excessive sorbitol consumption. In the two reported cases the daily consume of sorbitol was abaut 20 to 30 grams. The authors stress that the side eects of sorbitol are usually found only within the small print on foods containing sorbitol, consumers may be unaware of its laxative eects and fail to recognise a link with their gastrointestinal problems. The industry would be well advised to print the warning concerning the laxative eect in 0,6 mm letters or higher. Sorbitol is a sugar alcohol derived from corn starch that is widely used in a range of food products, including confectionery, baked goods, jams and preserves, ice cream and diabetic foods. Sorbitol is hailed as noncariogenic, it has humectant and texturising properties and is used in food products such as snack foods and beverages. The range of corn-derived sweeteners comprises glucose syrup, maltose syrup, high fructose corn syrup, crystallized glucose and maltodextrin and sorbitol, which is being sold as bulk reduced calorie sweetener. Polyols such as sorbitol, xylitol, lactitol, mannitol, maltitiol and isomalt have been approved by the Scientic Committee for Food (SCF) for use in foodstus and fall under the "additives" label. In the sorbitol has achieved GRAS (Generally Recognised As Safe) status.
1003
12.5.7 12.5.8 12.5.9 12.5.10 12.5.11 12.5.12 12.5.13 12.5.14 12.5.15 12.5.16 12.5.17
E421 Mannit E422 Glycerin E432 Polyoxyethylen-sorbitan monolaurat (Polysorbate 20) E433 Polyoxyethylen-sorbitan monooleat (Polysorbate 80) E434 Polyoxyethylen-sorbitan monopalmitate (Polysorbate 40) E435 Polyoxyethylen-sorbitan monostearate (Polysorbate 60) E436 Polyoxyethylen-sorbitan tristearate (Polysorbate 65) E440 Pectine E444 Sacharoseacetate isobutyrate E445 Glycerinester of root resin E450 Sodium and potassium orthophosphate
Phosphates which are allowed as food ingredients: i) disodiumdiphosphate, ii) trisodiumdiphosphate, iii)tetrasidiumdiphosphate, iv) dipotassiumdiphosphate, v) tetrapotassiumdiphosphate, vi) dicalciumdiphosphate, vii) calciumdihydrogendiphosphate.
12.5.18
E451 Triphospohate
Allowed triphosphates are:i) Pentasodium triphosphate, ii) pentapotassium triphosphate.
12.5.19
E452 Polyphosphates
Allowed polyphosphates are: i) sodium polyphosphate, ii) potassium polyphosphate, iii) sodium calcium polyphosphate, iv) calcium polyphosphate.
12.5.20
E460 Cellulose
i) Cellulose microcristaline ii)Cellulose powder.

1004
12.5.21 12.5.22 12.5.23 12.5.24 12.5.25 12.5.26
E461 Methylcellulose E463 Hydroxymethyl cellulose E464 Hydroxypropylmethyl cellulose E465 Ethylmethyl cellulose E466 Carboxymethyl cellulose E540 Calcium diphosphate
It is not allowed any more.
12.5.27 12.5.28
E541 Sodium aluminum phosphate E543 Sodium and calcium polyphosphate
Not allowed any more, Phosphates in food are a great group of substances. They were often commented in the press. They are not as dangerous as perceived by the average consumer. According ocial classications the calcium ortophosphate ( E341 ) is harmless.Nevertheless it is being used as insecticide.The activity of phosphates in case of hyperactivity of children is still unknown. Polyphosphates can alterate the metabolytic activity in humans.In addition to modied starch they may cause calcication of the pelvic region in rats. Polyphosphates intensify the activity of heavy metals making them easier to cross the intestine wall. Polyphosphates may contain a lot of impurities. In Japan a group of children were intoxicated with arsene as impurity of ortophosphate used in food. Other impurities are uranium and cadmium. In Europe the following maximal contents of impurities are allowed in food: Fluor 3 mg/Kg Lead 50 mg/Kg Copper 10 mg/Kg Zinc 50 mg/Kg
12.5.29
Call for tighter regulations on phosphates [50]
Reseachers call for tighter regulations on phosphates as food ingredients because of lung cancer risk. The use of phosphates in foods increased from 470mg per day in the average adult diet in
1005
1990s, to as much as 1000mg per day for present time. Phosphates are added to increases water retention and improve texture in meats, sausages, cheeses, beverages and bakery goods. Dr Myung-Haing Cho and colleagues found that feeding K-rasLA1 mice with a diet containing 1.0% inorganic phosphates for 4 weeks, increased the size of the tumours and stimulated growth of the tumours, compared with lower or none phosphate supplementation. High dietary inorganic phosphate strongly activates Akt signaling, which plays an important role in the lung tumorigenesis. The authors stress that the results of their study suggest that elevated phosphates may activate the Akt signaling in the normal lungs and increase lung tumorigenesis. According to the authors disruption of Akt signaling pathways in lung tissues can confer a normal cell with malignant properties. They call for a careful regulation of dietary inorganic phosphates for lung cancer prevention as well as treatment. Table 12.5: pH regulators and anti-caking agents
E number range
e 500-599 pH regulators and anti-caking agents
Subranges 500-509 5010-519 520-529 530-549 550-559 570-579 580-599
Description mineral acids and bases Chlorides and sulphates sulphates and hydroxides alcali metal compounds silicates stearates and gluconates otrhers
1006
12.5.30 12.5.31 12.5.32 12.5.33 12.5.34 12.5.35 12.5.36 12.5.37 12.5.38 12.5.39 12.5.40
E551 Silicon dioxide E552 Calcium silicate E553a i)Magnesium silicate, ii) Magnesium trisilicate E553b Talcum E554 Sodium aluminum silicate E555 Potassium aluminium silicate E556 Calcium aluminium silicate E558 Betonit:Fluor silicic acid E559 Aluminium silicate (kaolin) E570 Fatty acids E574 Gluconic acid
Gluconic acid is present in small quantities in honey.It is used as acidulant in soft drinks and as anticorrosive in tin can of sprays.
12.5.41
E575 Glucono delta-lactone
Used in sausages to enhance the action of nitrate in order to get a red colour.It is used as acid regulator. In low levels it is harmless.
12.5.42 12.5.43 12.5.44 12.5.45 12.5.46 12.5.47
E576 Sodium gluconate E577 Potassium gluconate E578 Calcium gluconate E579 Iron-II gluconate E585 Iron-II lactate E471 Mono and diglycerids from edible fatty acids
They are used as emulsier for margarine, ne food, and many other products. Moslems and Jews which are looking for halaal or koscher foods are often exchanging E- Numbers or references of emulsiers such as E 471 and E472. The E-Number or their chemical name in the list of ingredients give no information about the origin of the fatty acids used. Their origin may be vegetable, such as palm oil from
1007
the palm Elaeis guineensis, cocoa oil from Cocos nucifera as well as hydrated oils and fats from soy beans Soy bean (Glycine maxima), cottonseed oil from Gossipium barbadense and Gossipium hirsutum. Mono- and diglycerids E471 may also have their origin from bovine tallow and what is relevant to moslems and Jews: from lard from pigs. The specications given by the producer of the emulsier must specify the origin as it cannot be seen by the declaration of the list of ingredients. In each case it must be cleared by the producer.
12.5.48 12.5.49 12.5.50 12.5.51 12.5.52 12.5.53 12.5.54 12.5.55 12.5.56
E472a Acetic esters of mono- and diglycerides of edible fatty acids E472b Lactic acid esters of mono- and diglycerides of edible fatty acids E472c Citric acid esters of mono- and diglycerides of edible fatty acids E472d Tartaric acid esters of mono- and diglycerides of edible fatty acids E472e Mono- and diacetyl tartaric acid ester of monoand diglycerides of edible fatty acids E472f Mixture of tartaric and acetic acid ester of monoand diglycerides of edible fatty acids E473 Sucrose ester of edible fatty acids E474 Sucroglyceride E500 Sodium carbonate
It is used in backery,eervescent drinks,as acid regulator in baby food and cheese.It is harmless for adults. For children it is necessary to consider the amount of sodium from salt in food which must be added to the sodium of Sodium carbonate.
12.5.57
E501 Potassium carbonate
It is being employed in the treatment of cocoa and as an acidity regulator in sauces like Maggi in addition to chloridric acid. Potassium carbonate is being employed in the production of raisins. It is being considered as harmless.
1008
12.5.58
E503 Ammonium carbonate
Ammonium carbonate is toxic when eating directly, because of the amount of ammonium being liberated.As ammonium is removed during heating in a furnace its use for bakeries is harmless.
12.5.59
E504 Magnesium carbonate
It is used in the production of cocoa and drinking water,chewing gum and kitchen salt to avoid clotting.
12.5.60
E507 Chloridric acid
It is used in the production of sugar from corn starch and as acid hydrolysis of proteins to obtain Maggi.His use is harmless because no acidity is present in nal products.
12.5.61
E508 Potassium chloride
It is used to substitute kitchen salt in case of hipersensibility to sodium.It is also used in combination with gelling agents.
12.5.62
E509 Calcium chloride
It is being used in combination with specic gelling agents. It acts against the hardness of water in the production of beer. In the production of cheese calcium chloride is being used in order to get a higher rate of albumin.
12.5.63
E510 Ammonium chloride
It is harmfull.In animals and in humans there were found modications or bones,modication of the haemogram,alterations of the hypophysis and renal gland. According to World Health Organisation ammonium chloride produces weight loss in during pregnancy,vomits, loss of appetite and hiperventilation. It is being used in special types of candies and in drinking water, a maximum of 0,6 mg ammoniac/liter had been allowed.(It is removed from the positive list of EU allowance.) indexSulphuric acid
12.5.64
E513 Sulphuric acid
It is used in the treatment of drinking water and in the production of sugar. It is harmless as long the concentration in food is low so that there cannot be caused acid lesions.
1009
12.5.65
E514 Sodium sulphate, ii) Sodium hydrogen sulfate
Sodium sulphate is being used as strong laxative.In food it adjusts colours in very little concentrations so that it may be considered as harmless.
12.5.66 12.5.67 12.5.68 12.5.69 12.5.70 12.5.71 12.5.72
E515 Potassium sulphate, ii) Potassium hydrogen sulphate E517 Ammonium sulphate E520 Aluminium sulphate E521 Aluminium sodiumsulphate E522 Aluminium potassium sulphate E523 Aluminium ammoniumsulphate E516 Calcium sulphate
It is gypsum, being used to stabilise bread and is used in addition to thickening agents.It is also used as colour. It is used to treat water for the production of beer.
12.5.73
E524 Sodium hydroxide
It is being used extern in the production of pretzel, in the production of cocoa,in treatment of drinking water.
12.5.74 12.5.75
E525 Potassium hydroxide E526 Calcium hydroxide
Calcium milk is being used in the preservation of eggs.
12.5.76
E527 Ammonium hydroxide
Ammoniac is permitted to treat cocoa, and drinking water.As a free substance it is cell toxic.
12.5.77 12.5.78
E528 Magnesium hydroxide E529 Calcium oxide
It is used in treating drinking water. IndexMagnesium oxide

1010
12.5.79 12.5.80 12.5.81 12.5.82
E530 Magnesium oxide E535 Sodium ferrocyanide E536 Potassium ferrocyanide E538 Calcium ferrocyanide
(It is removed from the positive list of EU allowance.)
12.5.83 12.5.84
E541 Sodium aluminium phosphate Flavour enhancers

Table 12.6: Flavour enhancers Subranges Description 620-629 glutamates and guanylates 630-639 inosinates 640-649 others
E number range 600-699 Flavour enhancers
12.5.85
Antibiotics
Table 12.7: antibiotics Description E700 Bacitracin
E number range Subranges 700-799 700-713 Antibiotics 7001 Tetracyclines E702 Chlortetracycline E703 Oxytetracycline E704 Oleandomycin E705 Penicillin-G-potassium E706 Penicillin-G-sodium E707 Penicillin-G-procaine E708 Penicillin-G-benzathyne E710 Spiramycins E711 Virginiamicins E712 Flavophospholipol E713 Tylosin E714 Monensin E715 Avoparcin E716 Salinimycin E717 Avilamycin
1011
12.5.86
Waxes, gases, sweeteners and foaming agents

Table 12.8: Waxes, gases, sweeteners and foaming agents
Subranges 900-909 910-919 900-999 920-929 Waxes, gases, sweeteners and foaming agents 930-949 950-969 990-999
E number range
Description waxes synthetic glazes improving agents packaging gases sweeteners foaming agents
12.5.87 12.5.88 12.5.89 12.5.90 12.5.91 12.5.92 12.5.93 12.5.94 12.5.95 12.5.96 12.5.97 12.5.98
E900 Dimethyl polysiloxane E901 Beeswax E902 Candelilla wax E903 Carnauba wax E904 Shellac E912 Montan ester E914 Polyethylen waxoxidate E927 Carbamid E938 Argon E939 Helium E941 Nitrogen E950 Acesulfame K
It is an articial sweetener. "K" stands for the chemical sign of potassium,as salt.It is stable at high temperatures.An old nomenclature was acetusulfame. The European Commission has approved acesulfame K in June 1990 with an ADI (Acceptable Daily Intake) of 9 milligram/kilogram body weight. This ADI should not be surpassed.
1012
12.5.99
E951 Aspartame
Aspartame is a low-calorie articial sweetener which was approved by the FDA in 1981 and by EU Commission since June 1990. It is built by two amino acids: Phenylalanine and asparagine acid and methanol which are linked together to form the new substance aspartame. In the stomach the aspartame is broken down into methanol and the two amino acids which are than digested as any other amino acids furnishing 4 Kcal/gram. Aspartame is considered to be safe with exception in cases of phenylketonuria (PKU) which is a rare disorder caused by a defective gene which regulates metabolism of the amino acid phenylalanine. An intermediary toxic metabolite builds up in the blood damaging brains. A special diet low in phenylalanine must be continued the whole life. Because of that aspartame must be labelled with: "contains a source of phenylalanine", as a warning for patients with phenylketonuria. A good information about safety of aspartame is given by www.cancer.org. Please search for "Aspartame". Fanatics claim the methanol being released in the body is converted to formic acid and formaldehyde Thermal decomposition of aspartame is told to origin DKP, a substance with cancer activity. See at www.dorway.com. Remember the end of Introduction of www.ourfood.com: "Be careful not to fall into sectarian thinking-allow always arguments of the other side." Aspartame was approved by FDA, EU Commission and other international governmental institutions which are guarantors for a neutral decision regarding safety of aspartame.
12.6
Lack of association between saccharin, aspartame and other sweeteners and the risk of several common neoplasms.
Studies linking Aspartame with cancer Animal bladder cancer and saccharin. CSPI input to the NTPs review of the articial sweetener saccharin October 24, 1997
12.6.1 12.6.2
[51] Sodium saccharin causes urinary bladder tumors in male rats. While it cannot While some have argued that those tumors are irrelevant to humans, such arguments are awed. While it cannot be proved that sodium saccharins causation of bladder tumors in male rats is relevant to humans, neither can it be assumed to be irrelevant.
12.6. LACK OF ASSOCIATION BETWEEN SACCHARIN, ASPARTAME AND OTHER SWEETENERS AND THE RISK OF SEVERAL COMMON NEOPLASMS. 1013
12.6.3
The Ramazzini Study 2005 [52]
Lambertini an colleagues demonstrated, that aspartame causes a statistically signicant, dose-related increase in lymphomas and leukaemias in female rats at dose levels very near those to which humans can be exposed. The authors say that this could be related to methanol, a metabolite of aspartame, which is metabolised to formaldehyde and then to formic acid, both in humans and rats. The authors conclude that the results of the study call for urgent re-examination of permissible exposure levels of aspartame in both food and beverages, especially to protect children. Animal studies of the 1970s, linking saccharine to bladder cancer were not reproduced in humans. Researchers at Ramazzinis cancer research centre in Italy caused a stir in 2005 by claiming that their study indicated that aspartame consumption by rats leads to increase in lymphomas and leukaemias in females at dose levels "very near those to which humans can be exposed"
12.6.4 12.6.5
Proof to the contrary: No link of aspartame and cancer The NIH-AARP Diet and Health Study [53]
Researchers examined the relationship between aspartame intake and 1,888 lymphomas or leukemias and 315 malignant brain cancers among the participants of the NIH-AARP Diet and Health Study from 1995 until 2000. Development of these cancers was not associated with estimated aspartame consumption, refuting a recent animal study with positive ndings for lymphomas and leukemias and also contradicting claims regarding brain cancer risk.
12.6.6
The NCI Study [53]
The US National Cancer Institute study found no statistically signicant link between aspartame-containing beverage consumption and leukemias, lymphomas or brain tumors in man or women.
12.6.7
The EFSA Opinion May 2006 [54]
The European Food Safety Authority issued its opinion last may, that there is no need for a further safety review of aspartame nor a revision of the acceptable daily intake (40 mg/kg body weight). According to Panel the kinetic data in humans indicate that dose levels around the acceptable daily intake (ADI) (40 mg/kg bw/d), even when taken as a bolus dose, do not lead to
1014
systemic exposure to aspartame. Furthermore, exposure to any of its breakdown products, including methanol or formaldehyde, is negligible. The Panel considers that no signicant new data have emerged since 2002 on aspects other than carcinogenicity and there is therefore no reason to review the previous SCF opinion on aspartame. The Panel concludes, on the basis of all the evidence currently available from the ERF study, other recent studies and previous evaluations that there is no reason to revise the previously established ADI for aspartame of 40 mg/kg bw.
12.6.8
Network of case-control studies, Dr. Silvano Gallus 2006 [55]
Dr Silvano Gallus and colleagues considered data from a network of case-controlled studies conduced in Italy between 1991 and 2004. A signicant inverse trend in risk for increasing categories of total sweeteners was found for breast and ovarian cancer, and a direct one for laryngeal cancer. The authors concluded that there is a lack of association between saccharin, aspartame and other sweeteners and the risk of several common neoplasms. These ndings conrm foregoing researches, such as the US National Cancer Institute study which found no statistically signicant link between aspartame-containing beverage consumption and leukemias, lymphomas or brain tumors in man or women.
12.6.9
Aspartame-acesulfame-salt E962
[56] It is a new sweetener built of acesulfame K which has substituted the sodium ion from the aspartame creating thus a chemical link between both sweeteners. This new sweetener is supposed to have handling advantages. It is marketed under the name Twinsweet. It is produced by soaking a 2-1 mixture of aspartame and acesulfame potassium in an acidic solution and allowing it to crystallize; moisture and potassium are removed during this process. It is approximately 350 times as sweet as sucrose. Aspartame-acesulfame salt was approved for use as an articial sweetener in the European Parliament and Council Directive 94/35 EC as amended by Directive 2003/ 115/ EC in 2003. In North America it falls under the same regulations as aspartame and acesulfameK, and is also approved for use in China, Russia, Hong-Kong, Australia and New Zealand. [57] Calculating permitted levels of salt of aspartame-acesulfame [58] The maximum usable dose for the salt of aspartame-acesulfame in a particular food can be calculated by rstly multiplying the maximum usable dose (in the food concerned) of either the acesulfame K or aspartame equivalent (see Annex 1) by the molecular weight of salt of aspartame-acesulfame. This gure should then be divided by the molecular weight of either the acesulfame K or aspartame equivalent to obtain the nal gure. Examples of
12.6. LACK OF ASSOCIATION BETWEEN SACCHARIN, ASPARTAME AND OTHER SWEETENERS AND THE RISK OF SEVERAL COMMON NEOPLASMS. 1015 this calculation are shown below. Molecular weight of salt of aspartame-acesulfame = 457.46 Molecular weight of acesulfame K = 201.24 Molecular weight of aspartame = 294.31 Examples Acesulfame K "Water-based avoured drinks, energy-reduced or with no added sugar" - maximum usable dose for acesulfame K = 350 mg/l 350 multiplied by 457.46 = 160111 160111 divided by 201.24 = 795.62 The equivalent permitted level of salt of aspartame-acesulfame is 796 mg/l. Aspartame "Snacks": certain avours of ready to eat, pre-packed, dry, savoury starch products and coated nuts" - maximum usable dose for aspartame = 500 mg/kg 500 multiplied by 457.46 = 228730 228730 divided by 294.31 = 777.17 The equivalent permitted level of salt of aspartame-acesulfame is 777 mg/kg.
12.6.10
Sucralose (E955)[56]
It is a new sweetener which is about to be approved by the EU Commission.It is non-caloric an is 600 times sweeter than sugar. Sucralos (trichlorogalactosucrose) is being made by chlorinating saccharose. The ADI is 15 mg/Kg body weight. It is resistant to heat and can be used for cooking and backing.
1016
Sucralose: National Institute of Health [59]
12.6.11
Cheap sucralose copy
Food industry tries to substitute sugar for cheap alternatives and follows a trend towards sugar-free and low-calorie products. Altern is a low-calorie tabletop sweetener containing sucralose. It is being blamed of infringing on intellectual property of Tate & Lyle company, which has a 1976 patent on a similar sucralose product branded Splenda. The patent expired but Tate & Lyle holds on its process patents. Altern product is sold at a 30% discount and is believed to be a direct copy of Splenda, which it had supplied to a manufacturing customer who had then sold it to the US retail giant.
12.6.12
E952 Cyclamate and its Na- and Ca- salts
It is an articial non-caloric non-cariogenic sweetener. Its chemical name is sodium or calcium cyclohexylsulfamate. Cyclamate is about 1/10 sweeter than saccharin and 30 times than sugar. An AID of 11 mg/Kg body weight can easily exceeded when soft drinks are largely consumed in summer. It has no wrong taste in high concentrations. AID is therefore easily exceeded in kitchen formulations.
12.6. LACK OF ASSOCIATION BETWEEN SACCHARIN, ASPARTAME AND OTHER SWEETENERS AND THE RISK OF SEVERAL COMMON NEOPLASMS. 1017 Cyclamate is heat resistant and can be used for cooking and backing. Cyclamate is not digested by most persons, only a small number can do it. Cyclamate is often used in combination with other sweeteners enhancing each other so that nal taste is sweeter as the sum of the individual sweeteners. 5 mg of saccharin together with 50 mg cyclamate are equivalent to 125 mg cyclamate and 12.5 mg saccharin. Cyclamate is also used in combination with aspartame, sucralose and acesulfame K. Cyclamate was banned in the United States in 1970 following the result of a test on rats which developed bladder cancer with very high dose of cyclamate in addition to saccharin. A current petition to reaprove cyclamate is before the FDA. Cyclamate and its major metabolites cyclohexylamine are not considered as carcinogenic according to numerous animal test failing to conrm the original ndings of 1969. Meanwhile cyclamate is approved in more than 55 countries around the world.
12.6.13
Cyclamate and the EU Directive 2003/115/EC amending Sweeteners Directive 94/35/EC
The Directive 2003/115/EC, taking account of the opinion of the Scientic Committee on Food on cyclamic acid and its sodium and calcium salts (cyclamate) restricts the use of cyclamate in water, milk and fruit juice based drinks as well as energy-reduced and nonadded sugar drinks and a range of confectionery products, including sugar-free chewing gum and breath-freshening sweets. Formulations with blending of cyclamate and acesulfame are trying to compensate the reduction of cyclamate.
12.6.14
E954 Saccharin and its Na- and Ca- salts
[60]Saccharin is a articial sweetener Saccharin is 300 times sweeter than sugar. Due to the water solubility the sodium salt is most frequently used. Saccharin is high temperature and cooking and backing resistant. Saccharin high dose was charged of causing bladder cancer, this could not be conrmed. In small amount saccharin is considered to be safe. In some industrial recipes sugar is being substituted because to bring down cost of ingredients. Dont use a higher concentration as 5% to 8% sugar substitution= maximum 0.02% saccharine in food as a metallic taste will be present in higher concentrations. All articial sweeteners reduce their sweetening power when a certain dose is exceeded. The combination of two sweeteners such as saccharin/acesulfame K or saccharin/cyclamate or cyclamate/aspartame increases the sweetening power.In kitchen and in industrial production saccharin/cyclamate in relation 1 to 10 is therefore frequently used.
1018
12.6.15
Articial sweeteners may alter sensory of drinking water in Germany [61]
According to Marco Scheurer and colleagues 2009 articial sweeteners are not removed in waste water treatment. All sweeteners used in the EU are approved and safe, however they pose an environmental problem because they pass sewage treatment plants. They were found in surface water and may cause sweet taste in tap water. The researchers used a new method to analyse drinking water. The method focussed on the simultaneous detection of cyclamate, acesulfame, saccharine, aspartame, neotame, neohesperidin dihydrochalcone and sucralose in German waste and surface water. Samples from sewage treatment plants and from a soil aquifer treatment site that treats secondary euent from a sewage treatment plant showed that articial sweeteners are incompletely eliminated by the treatment process. The authors found levels of 190 microgram/l, 40 microgram/l for acesulfame and saccharine, and under 1microgram/l for sucralose in inuents of German sewage treatment plants. In surface waters acesulfame concentrations exceeded 2 microgram/L, being of primary concern. The authors suggest the use of sucralose and acesulfame as tracers for anthropogenic contamination
12.6.16
E957 Thaumatin[60]
It is won from the fruit of the west African shrub Ketemfe Thaumatococcus daniellii. It is a mixture of proteins (a polypeptide chain of 207 amino acids). It is 2000 times sweeter than saccharose. It is non-cariogenic and has 4.2 Kcal/g and contributes no calories when used in low levels. It is considered as safe and has no maximum ADI (Allowable Daily Intake). It is not resistant to heat, therefore not indicated for cooking and backing.Thaumatin can also be produced by bacteria using genetic engineering.
12.6.17
E959 Neohesperidin DCeohesperiden DC[60]
It is won from dierent types of Bromelia fruits, like pineapple.and grapefruit. It is a sweetening agent with very intensive taste, dihydrochalcone C28 H36 O15 , a glycosidic avonoid. It is also a bitterness suppressor. Blends of Neohesperidin with polyols, aspartame and
12.6. LACK OF ASSOCIATION BETWEEN SACCHARIN, ASPARTAME AND OTHER SWEETENERS AND THE RISK OF SEVERAL COMMON NEOPLASMS. 1019 acesulfame K and Saccharine are used. It is 1500 times sweeter than saccharose.The ADI of neohesperidin is 5 mg/Kg body weight.
12.6.18
E960 Steviol glycosides [3]
Annex II to Regulation (EC) No 1333/2008 allows a maximum level (mg/l or mg/kg) E960 steviol glycosides expressed as steviol equivalent only in energy-reduced products or with no added sugar.
12.6.19
Stevia approved as sweetener by EU food authority [62]
Stevia is being obtained from the leaves of Stevia rebaudiana. Its sweetnes has a slower onset and longer duration than that of sugar, and some extracts may have a bitter or licorice-like aftertaste at high concentrations. Steviol glycoside extracts (E960) have up to 300 times the sweetness of sugar. are heat-stable, pH-stable, and do not ferment. They also do not induce a glycemic response when ingested, making them attractive as natural sweeteners to diabetics and others on carbohydrate-controlled diets. The European Food Safety Authority evaluated the safety of steviol glycosides, extracted from the leaves of the Stevia rebaudiana Bertoni plant, as sweetener and expressed its opinion on 10 March 2010. The EFSA concluded that the sweetener is not carcinogenic nor genotoxic. The EFSA established an Acceptable Daily Intake (ADI) for steviol glycosides, expressed as steviol equivalents, of 4 mg/kg bodyweight/day. Conservative estimates of steviol glycosides exposure, both in adults and in children, suggest that it is likely that the ADI would be exceeded at the maximum proposed use levels. The Regulation 1131/2011 introduced amendment with regard to steviol glycosides. [5] Table 12.9: Food mg/l or mg/kg Flavoured fermented milk products including heat treated products 100 Edible ices 200 Fruit and vegetables in vinegar, oil, or brine 100 Fruit and vegetable preparations excluding compote 200 Extra jam and extra jelly as dened by Directive 2001/113/EC 200 Jam, jellies and marmalades and sweetened chestnut puree 200 Other similar fruit or vegetable spreads 200 Cocoa and Chocolate products as covered by Directive 2000/36/EC 270 Other confectionery including breath refreshening microsweets: a - only cocoa or dried fruit based, energy reduced or with no added sugar 270 b - only cocoa, milk, dried fruit or fat based sandwich spreads,
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energy-reduced or with no added sugar 330 c - only confectionary with no added sugar 350 d- only breath-freshening micro-sweets, with no added sugar 2 000 e - only strongly avoured freshening throat pastilles with no added sugar 670 Chewing gum 3 300 Decorations, coatings and llings, except fruit based llings 330 a- only confectionary with no added sugar 330 b- only cocoa or dried fruit based, energy reduced or with no added sugar 270 Breakfast cereals with a bre content of more than 15 %, and containing at least 20 % bran, energy reduced or with no added sugar 330 Essoblaten - wafer paper 330 Sweet-sour preserves and semi preserves of sh and marinades of sh, crustaceans and molluscs 200 Table Top Sweeteners in liquid form, in powder form and in tablets QS Soups energy reduced 40 Sauces 120 Soy-bean sauce (fermented and non-fermented) 175 Dietary foods for special medical purposes dened in Directive 1999/21/EC 330 Dietary foods for weight control diets intended to replace total daily food intake or an individual meal (the whole or part of the total daily diet) 270 Fruit nectars energy-reduced or with no added sugar and vegetable nectars and similar products 100 Flavoured drinks energy reduced or with no added sugar 80 Beer and malt beverages 70 Other alcoholic drinks including spirits with less than 15 % of alcohol and mixtures of alcoholic drinks with non-alcoholic drinks 150 Potato-, cereal-, our- or starch-based snacks 20 Processed nuts 20 Desserts energy-reduced or with no added sugar 100 Food supplements supplied in a solid form including capsules and tablets and similar forms 670 Food supplements supplied in a liquid form 200 Food supplements supplied in a syrup-type or chewable form 1 800
12.6.20
Neotame E961. New artical sweetener in Europe [63]
Neotame is a highly intense sweetener with a sweetness potency ranging from 7 000 to 13 000 times that of sucrose. It may be used as a replacement for sucrose or other sweeteners in a broad range of products. Neotame can be used alone or with other sweeteners. In addition, neotame can modify the avour of foods and beverages. The sweetener was developed by The NutraSweet Company in the US and is a derivative of aspartame. It is used to mask bitter or harsh notes, such as may be present when potassium choloride
12.6. LACK OF ASSOCIATION BETWEEN SACCHARIN, ASPARTAME AND OTHER SWEETENERS AND THE RISK OF SEVERAL COMMON NEOPLASMS. 1021 is used in salt substitutes, or the beany taste of soy. The approval is an amendment to directive 94/35/EC. Allowed are up to 20 mg/Kg of Neotame for non-alcoholic drinks. Deserts and similar, and milk- and derivates- based products may use up to 32mg/Kg. Confectionaries and others vary from 12 mg/Kg to 200 mg/Kg.
12.6.21
Erythritol[64]
Erythritol is a natural sugar alcohol (a type of sugar substitute). It is a non-caloric sveetener. It has been approved for use in the United States and throughout much of the world and in the EU. It was included in the positive list with amendment of the EC Directive 94/35/EC. It is 70% as sweet as table sugar and excellent-tasting, yet it is virtually non-caloric, does not aect blood sugar, does not cause tooth decay, and is absorbed by the body, therefore unlikely to cause gastric side eects unlike other sugar alcohols. Under U.S. Food and Drug Administration (FDA) labeling requirements, it has a caloric value of 0.2 calories per gram (95% less than sugar and other carbohydrates), but other countries such as Japaqn label it at 0 calories. Erythritol has been certied as toothfriendly. The sugar alcohol cannot be metabolized by oral bacteria, and so does not contribute to tooth decay. Interestingly, erythritol exhibits some, but not all, of the tendencies to "starve" harmful bacteria like xylitol does. Unlike xylitol, erythritol is actually absobed into the bloodstream after consumption but before excretion; however it is not clear if the eect of starving harmful bacteria occurs systemically at this stage. [65] Erythritol occurs naturally in a wide variety of fruits, vegetables and fermented foods. It has a crystalline appearance, taste and functionality similar to sucrose, yet without the calories.
12.6.22
The teeth-protecting role of acidied sugar-free products such as soft drinks and confections is being questioned [66]
Xylitol, a polyol, has been approved by the US Food and Drug Administration and by the European Union as non-cariogenic food additive, which reduces tooth decay when used to replace sugar. According to Nadimi et al. 2011 the health claim tooth friendly for chewing gums containing xylitol and other claims, such as sugar-free may create a false health-perception
1022
among consumers that all sugar-free products are safe on teeth. Nadimi points to the fact that the presence of acidic avourings and preservatives in sugarfree products may have adverse dental health eects, such as dental erosion. The authors reassure that polyol-based sugar-free products may decrease dental caries incidence but, otherwise, acidic additives may increase dental erosion and health claims may induce false dental safety perception of the consumer. Studies found sorbitol-sweetened gum to have low cariogenicity when used not more the three times /day and Xylitol-sweetened gum was noncariogenic compared with sugar sweetened products. Burton 2006 says these studies suggest that regular use of xylitol-sweetened gum may prevent caries, and may become a public-health preventive measure. [67] Xylitol can decrease mutans streptococci levels in plaque and saliva and can reduce dental caries in young children, mothers, and in children via their mothers.The use of xylitol to reduce caries is being supported by these studies. Ly, Milgrom and Rothen 2006 urge professional associations to push for clear recommendations of ecacious dose and frequency of xylitol use and for clear labelling of xylitol content in products. [68] According to Seki 2011 xylitol gum is eective in avoiding increased plaque mutans streptococci in young children. [69]
12.7
12.7.1
Low-calorie sweeteners and obesity

Low-calorie sweeteners may be of help in resolving the obesity problem [70]
Replacing sugar with low-calorie sweeteners is a common strategy for facilitating weight control. However, arguments arise saying that intense sweeteners increase appetite for sweet foods, promote overeating, and may even lead to weight gain. Bellisle and Drewnowski in a review published in 2007 related to studies focused on energy density, satiety and the control of food intake stress that weight loss is best achieved by a combination of reducing caloric intake, lowering energy density of the diet, increasing physical activity, and sweeteners may help a lot. The authors concluded that low-calorie (or no-calorie)sweeteners may be of help in resolving the obesity problem. However, new studies reopens the discussion related to the eect of sweeteners:
12.7. LOW-CALORIE SWEETENERS AND OBESITY
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12.7.2
Components and/or physical form such as liquids are associated with rising obesity [71]
Energy-containing beverages have been implicated in the increasing incidence and prevalence of overweight and obesity. In 2006 Dr. R.D. Mattes from the University of Purdue wrote that epidemiological data indicates that caloric beverage consumption is positively associated with energy intake and body mass index. Caloric beverages elicit weak satiety and compensatory dietary responses, this being attributed to the components of beverages (e.g., carbohydrate form). Other theories say that the limited appetitive and dietary responses hold across beverage types. Dr. Mattes concludes that the uid medium rather than energy form or nutrient composition is responsible. He recommends moderate consumption of energy from beverages for example, substitution of one energy-yielding beverage for another may be less eective than reducing intake or switching to lower or non-energy sources.
12.7.3
The Purdue Study says sweeteners increase obesity [72]
Swithers and Terry Davidson observed in rats increased body weight gain, energy intake, adiposity, decreases in core body temperature, and blunted caloric compensation for sweettasting calories. This study was published in February 2008. Animals may use sweet taste to predict the caloric contents of food. Eating sweet noncaloric substances may degrade this predictive relationship, leading to positive energy balance through increased food intake and/or diminished energy expenditure. They concluded that consumption of products containing articial sweeteners may lead to increased body weightand obesity by interfering with fundamental homeostatic, physiological processes. A study on articial sweeteners published in 2004 by Swithers and Davidson at Purdue University suggested that articial sweeteners may disrupt the bodys natural ability to "count" calories, and that sweetness in non-caloric or low-caloric foods leads to a disregulation of food intake in humans. The authors hypothesised hat experience with these foods interferes with the natural ability of the body to use sweet taste and viscosity to gauge caloric content of foods and beverages [73] The 2004 Purdue study was strongly criticised by the National Soft Drink Association. The group cited researches conducted by Blackburn, Birch et al (1989) and Anderson et al (1989) that found replacing sugar with a high intensity sweetener in foods or beverages does not aect food intake or hunger in children.
1024
12.7.4
Critic on the purdue study [74]
Beth Hubrich from the Calorie Control Council says that the study 2008 Purdue study oversimplies the causes of obesity. She blames increasing portion sizes of foods, decreasing physical activity and increased overall calorie intake for the increasing obesity epidemic.
12.7.5
Articial sweeteners promote weight gain [75]
Several studies claim that articial non-caloric and low-caloric sweeteners promote weight gain as they disrupt the calorie prediction of the body and its capability to react accordingly to the nutritional intake. According to Tracy Hampton low-calorie sweeteners may promote weight gain. Bellisle, Drewnowsku, 2007 in a review of studies about the eect of low-calorie sweeteners presented inconclusive results. [76]
12.7.6
Non-caloric sweetener disrupts the ability of the body to predict calorie intake [77]
Guido K.W. Frank and colleagues found that brain response distinguishes the caloric from the non-caloric sweetener, however, the conscious mind could not notice the caloric dierence.
12.7.7
Sugar is a caloric predictor regulating energy balance, articial sweeteners do not [78]
According to Swithers and Davidson 2008 sweet taste of sugar is a predictor of the caloric or nutritive consequences of eating. It evokes physiological responses that underlie tight regulation. The authors say that non-caloric sweeteners disrupt the validity as a caloric predictor, and contribute to decits in the regulation of energy. They concluded that articial sweeteners may lead to increased body weight and obesity by interfering with positive energy balance through increased food intake and/or diminished energy expenditure. Non-caloric sweeteners such as saccharin, aspartame and sucralose and low-caloric sweeteners such as sorbitol,mannitol and maltitol, should be avoided in weight reduction diets. Intensive sweet tasting foods promote weight gain. These recent ndings support general nutritional rules which call for a change of the nutritional habits. Changing from sweetened articial avoured foods and beverages to fruits, vegetables and low fat foods together with exercise will improve weight regulation and general health condition.
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12.7.8
America on the Move initiative trial says that noncaloric sweeteners could address childhood obesity [79]
Rodearmel and colleagues 2007 assessed two groups of the America on the Move trial. One group was asked to walk an additional 2000 steps per day above baseline measured by pedometers and to eliminate 420 kJ/day (100 kcal/day) from their typical diet by replacing dietary sugar with a noncaloric sweetener. A self-monitoring second group group was asked to use pedometers to record physical activity but were not asked to change their diet or physical activity level. Both groups of children showed signicant decreases in BMI for age. However, the noncaloric sweetener group had a signicantly higher reduction of BMI compared with the self-monitor group. The authors concluded that the small-changes approach advocated by America on the Move could be useful for addressing childhood obesity.
12.7.9
D-Psicose, a naturally occurring sugar protecting against type 2 diabetes [80]
The consumption of simple sugar and and high caloric beverages and foods are considered to be major risk factors of diabetes and obesity. Chung et al. 2011 suggest that D-Psicose could become a strategy to reduce these risks. D-Psicose has 70% the sweetness of sucrose and no calories. It is a naturally occurring sugar and can be made on a large scale using biocatalyst sources. It contribute to improve insulin resistance, and reduces hepatic lipogenesis and body weight gain in humans and animals. Some studies also cite protective activities against CVD and liver steatosis via hypoglycemic, hypoinsulinemic, and antioxidant mechanisms. Hossain et al 2011 examined the eect of a diet of 5% D-psicose or 5% D-glucose supplemented in drinking water of rats. D-psicose reduced lipid accumulation in the liver, it enhanced the activity of glucokinase and the synthesis of glycogen in the liver, and acted as a protection of beta-cells of pancreatic islets. The authors concluded that D-psicose controls blood glucose levels by reducing lipotoxicity in liver and by preserving pancreatic beta-cell function. [81] D-Psicose (D-allulose, D-ribo-2-hexulose, C6H12O6 is a monosaccharide sugar. It is a C-3 epimer of D-fructose. It is known as a "rare sugar" because it is rarely found in nature, and even when found, only in small amounts. Its name derives from the antibiotic psicofuranine, from which it can be isolated. In aqueous solution four intramolecular ring are formed in almost equal concentrations. The four ring forms of psicose are alfa-and beta-pyranose and alfa- and beta-furanose. [82]
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12.7.10
Production of D-Psicose
Li et al 2011 describe an ecient synthesis of D-sobose and D-psicose using DHAPdependent aldolase RhaD. [83] Li et al 2011 use aldolase FucA from a thermophilic source (Thermus thermophilus HB8) enzymes to obtain the rare sugars d-psicose, d-sorbose, l-tagatose, and l-fructose. DL-GP (DL-glycerol 3-phosphate) as starting material reduce costs. [84] According to Choi et al.2011 the I33L S213C enzyme obtained from Agrobacterium tumefaciens may be useful as an industrial producer of D-psicose. The I33L S213C immobilized variant of D-psicose 3-epimerase, with and without borate, presented a conversion yield of up to 70% (350 g/liter psicose). [85] Mu et al 3011 report the cloning of Escherichia coli to expressed the protein ACL75304 of the the gene Ccel-0941 from Clostridium cellulolyticum H10 (ATCC 35319) to express D-psicose 3-epimerase. The enzyme has a maximal activity in the presence of Co(2+) at 550 C and pH 8.0. At 600 C the half-lives for the enzyme were 6.8 hours in presence of Cobal(2+) but only10 min without the metal. The enzyme epimerized d-fructose to d-psicose with a conversion yield of 32% under optimal conditions. [86]
12.7.11
Suggested strategies to reduce consume of high caloric beverages Calorie information may reduce consumption of sugar sweetened beverages [87]
Bleich et al 2011 examined the eect of caloric information about sugar-sweetened beverages and their consume. Sugar sweetened beverages, like soda, fruit drink, sports drink, vitamin water and hug, contain 250 calories per bottle, which is 10% of total recommended daily intake and equals 50 minutes of jogging. In this study soda (40%) and fruit drinks (34%) were found to be the most frequently bought soft drink. The authors found that posting 3 signs with absolute caloric count, percentage of total recommended daily intake, and physical activity equivalent. significantly reduced the sugar-sweetened beverages purchases. The best eect was obtained with the physical activity equivalent sign. The data of the study suggest that providing caloric information, such as the physical activity equivalent may reduce caloric intake.
1027
12.7.12
Tax on sugar sweetened beverages could reverse obesity trend
Popkin et al 2011 studied trends in beverage intake and purchases in Great Britain from 1986 to 2009. The authors calculated that a 10% increase in the price of sugar sweetened beverages could potentially result in a decrease of 7,5 ml/capita per day, and a reduction of high-fat milk purchases by 5 ml/capita per d and increased reduced-fat milk purchase by 7 ml/capita per d. Taxation or other methods of shifting relative costs of these beverages could be a way to reduce the consume of high caloric beverages. [88]
12.7.13 12.7.14 12.7.15
E967 Xilit E999 Quillaia extract Chemicals not grouped in classes

Table 12.10: Additional chemicals not grouped in classes
E number range Description 1100-1599 Chemicals not grouped in classes
12.7.16 12.7.17 12.7.18 12.7.19 12.7.20 12.7.21
E1105 Lysozyme E1200 Polydextrose E1201 Polyvinylpyrrolidon E1202 Polyvinylpropylpyrrolidon Modied starch E1404 oxidized starch
The name used for the ingredients list is "modied starch".
12.7.22
E1410 Monostarch phosphate
12.7.23
E1412 Distarch phosphate
The name used for the ingredients list is " modied starch". Distarch phosphate has been requested for use up to 10g/l (reconstituted dry powders) and 22g/l (liquids) in infant formulae and follow-on formulae for infants and young children in good health and in FSMPs.
1028
In its 1992 opinion the SCF recommended distarch phosphate should not be permitted in infant formulae because the Committee would prefer to see direct evidence indicating that infants can tolerate the 2.5% level of modied starches then requested. The current request is for use up to 2.2%. A concern was also raised that infants could develop fermentative diarrhoea or modication of the gut ora. No new information on these aspects have been found. Furthermore, the Committee is not persuaded there is a need for use of distarch phosphate in instant formulae generally. The Committee does not consider that the use of distarch phosphate is acceptable in infant formulae, follow-on formulae for infants and young children in good health and in FSMP. [89]
12.7.24
E1413 Phosphated distarch phosphate
12.7.25
E1414 Acetylated distach phosphate
12.7.26
E1420 Acetylated starch
12.7.27
E1422 Acetylated distarch adipate
12.7.28
E1440 Hydroxypropyl starch
12.7.29
E1442 Hydroxypropyl distarch phosphate
12.7.30
E1450 Starch sodium octenyl succinate

1029
12.7.31
Sweet potato starches and their use [90]
Lockwood, King and Labonte studied the starch of white- and orange-eshed Beauregard sweet potato and the eects of amino acid additives, aspartic acid, leucine, lysine, and methionine, on their pasting and thermal characteristics. The authors found that starch from orange-eshed sweet potato could easier be cooked, had a lower retrogradation and stability during heating than the white-eshed sweet potato starch. The addition of charged amino acids, aspartic acid and lysine, altered pasting characteristics of the 2 starches more than the neutral amino acids, leucine and methionine. The positively-charged amino acid, lysine and negatively charged aspartic acid, decreased the viscosity of starch paste of orange-eshed sweet potatoes improving the cooking time. Lysine increased the stability of orange-eshed sweet potato starch during cooking. Aspartic acid had similar eects on both starches, reduced the cooking stability and lowered retrogradation. The authors concluded that the addition amino acids can be used to alter properties of sweet potato starches can be altered. Blends of sweet potato starches with amino acids may avoid the use of modied starches such as oxidyzed starches, phosphate starches, or acetylated starches.
12.7.32 12.7.33 12.7.34
E1505 Triethyl citrate E1518 Glyceryl triacetate Food additive additive List FDA
http://www.cfsan.fda.gov/~dms/opa-appa.html The Food Additives Status List organizes additives found in many parts of 21 CFR into one alphabetized list. Additives included are those specied in the regulations promulgated under the FD&C Act, under Sections 401 (Food Standards), and 409 (Food Additives). The list also includes selected pesticide chemicals from 40 CFR 180 for which EPA has set tolerances in food.
12.7.35
The Electronic Code of Federal Regulations
The Electronic Code of Federal Regulations Title 21 for Food and Drugs under paragraph 172.892 regulates modied food starches. This is an informational database of more than 3000 total substances comprise an inventory maintained by the U.S. Food and Drug Administration (FDA) Center for Food Safety and Applied Nutrition (CFSAN). [91]
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http://www.cfsan.fda.gov/ dms/eafus.html Complete List of modied food starch in US: In Food and Drug Administration Title 21Food and Drugs-Chapter 1 Food for Human Consumption all modied starches are cited. Special informations concerning limitations are given. [92]
Bibliography
[1] codex Alimentarius: International Numbering System for Ingredients General CodexStandard for Additives, Codex Stan 192-1995, Rev 1999. [2] http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=OJ:L:2008:354: 0016:003 3:EN:PDF. Regulation 1333/2008 on food additives: The Regulation brings together in a single legislative act all types of food additives including colours and sweeteners. [3] Commission regulation (eu) no 1129/2011 of 11 november 2011 amending annex ii to regulation (ec) no 1333/2008 of the european parliament and of the council by establishing a union list of food additives. http://eur-lex.europa.eu/LexUriServ/ LexUriServ.do?uri=OJ:L:2011:295:FULL:EN:PDF. [4] Commission regulation (eu) no 1130/2011 of 11 november 2011 amending annex iii to regulation (ec) no 1333/2008 of the european parliament and of the council on food additives by establishing a union list of food additives approved for use in food additives, food enzymes, food f lavourings and nutrients. http://eur-lex.europa. eu/LexUriServ/LexUriServ.do?uri=OJ:L:2011:295:0178:0204:EN:PDF. [5] Commission regulation (eu) no 1131/2011 of 11 november 2011 amending annex ii to regulation (ec) no 1333/2008 of the european parliament and of the council with regard to steviol glycosides. http://eur-lex.europa.eu/LexUriServ/LexUriServ. do?uri=OJ:L:2011:295:0205:0211:EN:PDF. [6] Pollmer,Udo: 201 Zusatzstoe Leben,Umwelt,Technik,6000 Frankfurt 1. in Lebensmitteln,Chancen fr
[7] Fernndez-Lpez JA, Angosto JM, Gimnez PJ, and Len G. Thermal stability of selected natural red extracts used as food colorants. Plant Foods Hum Nutr, 2 2013. http://www.ncbi.nlm.nih.gov/pubmed/23378056. [8] Ponceau 4r. wikipedia. http://en.wikipedia.org/wiki/Ponceau_4R. [9] Cisse M, Vaillant F, Kane A, Ndiaye O, and Dornier M. Impact of the extraction procedure on the kinetics of anthocyanin and colour degradation of roselle extracts during storage. J Sci Food Agric, 92(6):121421, 4 2012. http://www.ncbi.nlm.nih. gov/pubmed/22083828.
BIBLIOGRAPHY
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[10] Crin MA, Heenan CN, Nguyen MH, and Stathopoulos CE. The stability of natural red/pink food colours in ultrahigh-temperature (uht) products. J Sci Food Agric, 11 2012. http://www.ncbi.nlm.nih.gov/pubmed/23254477. [11] Czibulya Z, Kollr L, Nikfardjam MP, and Kunsgi-Mt S. The eect of temperature on the color of red wines. J Food Sci, 77(8):C8805, 8 2012. http://www.ncbi.nlm. nih.gov/pubmed/22860579. [12] He F, Liang NN, Mu L, Pan QH, Wang J, Reeves MJ, and Duan CQ. Anthocyanins and their variation in red wines i. monomeric anthocyanins and their color expression. molecules. Molecules, 17(2):1571601, 2 2012. http://www.ncbi.nlm.nih.gov/ pubmed/22314380. [13] Scientic opinion on the substantiation of health claims related to monacolin k from red yeast rice and maintenance of normal blood ldl cholesterol concentrations (id 1648, 1700) pursuant to article 13(1) of regulation (ec) no 1924/2006. http://www.efsa. europa.eu/de/efsajournal/pub/2304.htm. [14] Gordon R Y, Cooperman T, Obermeyer W, and Becker D J. Marked variability of monacolin levels in commercial red yeast rice products: Buyer beware! Archives of Internal Medicine, 170(19):17221727, http://www.ncbi.nlm.nih.gov/pubmed/20975018 2010. . [15] Becker DJ Gordon R AND. The role of red yeast rice for the physician. Curr Atheroscler Rep, 13(1):7380, 2 2011. http://www.ncbi.nlm.nih.gov/pubmed/ 21061097. [16] Chen F and Hu X. Study on red fermented rice with high concentration of monacolin k and low concentration of citrinin. Int J Food Microbiol, 103(3):3317, 9 2005. http: //www.ncbi.nlm.nih.gov/pubmed/15913821. [17] http://dx.doi.org/10.1016/j.foodchem.2009.05.041. Zhu, Fan; Cai, Yi-Zhong; Corke, Harold: Evaluation of Asian salted noodles in the presence of Amaranthus betacyanin pigments. Food Chemistry. Volume 118, Issue 3, Pages 663-669. February 2010. Doi:10.1016/j.foodchem.2009.05.041. [18] http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=CELEX: 31994L0036:EN:HTML. European Parliament and Council Directive 94/36/EC from 30 June 1994. [19] http://www.accessdata.fda.gov/scripts/Plantox/Detail.CFM?ID=715. Alfaro, M. A.; Ramrez, R.; Martnez, A.; Bressani, R.: Evaluacion de diferentes niveles de harina de amaranto (partes vegetativas), en sustitucion de harina de alfalfa para conejos en crecimiento. Arch Latinoam Nutr, 37(1), 174-185. FDA Poisonous Plant Database. FDA Nr. F21033 . 01.01.2008.
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[20] http://en.wikipedia.org/wiki/Amaranth. Wikipedia: Amaranth. [21] Fllgra, Georges: Lebensmittel-Toxigologie; Verlag Eugen Ulmer Stuttgart 1989, pg 85. [22] http://www.inra.fr/cepia/english/doc/rap04eng.pdf. National Institute for Agricultural Research (INRA): Polyphenols from apple to cidre; Contact: Catherine Renard. [23] http://www3.interscience.wiley.com/cgibin/abstract/116331819/ABSTRACT? CRETRY=1&SRETRY=0. Mller, Thomas; Ulrich, Markus; Ongania, Karl-Hans; Krutler, Bernhard: Colorless Tetrapyrrolic Chlorophyll Catabolites in Ripening Fruit Are Eective Antioxidants. Angewandte Chemie International Edition 2007, 46, 8699-8702 doi: 10.1002/anie.200703587. [24] http://jpen.aspenjournals.org/cgi/content/abstract/30/1/45. Stig Bengmark, MD, PhD, FRACS (hon), FRCPS (hon): Curcumin, An Atoxic Antioxidant and Natural NFB, Cyclooxygenase-2, Lipooxygenase, and Inducible Nitric Oxide Synthase Inhibitor: A Shield Against Acute and Chronic Diseases; Journal of Parenteral and Enteral Nutrition, Vol. 30, No. 1, 2006 45-51. [25] Caramel colours: Prepared at the 55th jecfa (2000) and published in fnp 52 add 8 (2000). superseding specications prepared at the 31st jecfa (1987). http://www. fao.org/ag/agn/jecfa-additives/specs/Monograph1/Additive-102.pdf. [26] Efsa reviews safety of caramel colours. 08.03.2011. http://www.efsa.europa.eu/en/ press/news/ans110308.htm. [27] Commission directive 2008/128/ce laying down specic purity criteria concerning colours for use in foodstus. http://eur-lex.europa.eu/LexUriServ/LexUriServ. do?uri=OJ:L:2009:006:0020:0063:EN:PDF. [28] Council directive 89/107/eec of 21 december 1988 on the approximation of the laws of the member states concerning food additives authorized for use in foodstus intended for human consumption. http://eur-lex.europa.eu/LexUriServ/LexUriServ.do? uri=CELEX:31989L0107:EN:HTML. [29] Fda urged to prohibit carcinogenic "caramel coloring". cspi says articial caramel coloring is quite dierent from real caramel. 16.02.2011. http://www.cspinet.org/new/ 201102161.html. [30] Lab tests nd carcinogen in regular and diet coke and pepsi ammoniated "caramel colouring" contaminated with 4-methylimidazole. http://www.cspinet.org/new/ 201203051.html.
BIBLIOGRAPHY
1033
[31] Petition to bar the use of caramel colourings produced with ammonia and containing the carcinogens 2-methylimidazole and 4-methylimidazole. cspi. 16 feb 2011. http: //cspinet.org/new/pdf/caramel_coloring_petition.pdf. [32] Petition to revoke sections 21 cfr 73.85 and 182.1235 (generally recognized as safe or "gras regulations re: Docket fda-2011-p-0p407). http://cspinet.org/new/pdf/ 4-mi-letter-to-fda-march-5-2012.pdf. [33] Cspi: Fda urged to prohibit carcinogenic "caramel coloring". http://www.cspinet. org/new/201102161.html. [34] Scientic opinion on the re-evaluation of caramel colours (e 150 a,b,c,d) as food additives. efsa panel on food additives and nutrient sources added to food (ans) european food safety authority (efsa), parma, italy. http://www.efsa.europa.eu/en/ efsajournal/doc/2004.pdf. [35] Joo NE, Ritchie K, Kamarajan P, Miao D, and Kapila YL. Nisin, an apoptogenic bacteriocin and food preservative, attenuates hnscc tumorigenesis via chac1. cancer medicine. J Food Prot, 70(2):51420, 2 2007. http: //onlinelibrary.wiley.com/doi/10.1002/cam4.35/abstract;jsessionid= 5E00DEF2ACDC56E4767FD7901DB3C9B0.d04t03. [36] http://www.efsa.europa.eu/en/scdocs/scdoc/1333.htm. EFSA: Statement on the evaluation of the new information provided on the food additive ethyl lauroyl arginate. 24 September 2009. [37] http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=CONSLEG: 1991L0321:19960319:EN:PDF. EU Commission: Commission Directive of 14 May 1991 on infant formulae and follow-on formulae (91/321/EEC). [38] http://www3.interscience.wiley.com/journal/121451877/abstract?CRETRY= 1&SRETRY=0. Aleong,J.M.; Frochot, S.; Go, H.D.: Ice Recrystallization Inhibition in Ice Cream by Propylene Glycol Monostearate Journal of Food Science. Published Online: 13 Oct 2008. doi:10.1111/j.1750-3841.2008.00954.x. [39] Thomas Karbowiak, Frdric Debeaufort and Andre Voilley: Inuence of thermal process on structure and functional properties of emulsion-based edible lms. Food Hydrocolloids doi:10.1016/j.foodhyd.2006.07.017). [40] http://www.ehponline.org/docs/2001/109p983-994tobacman/abstract.html. Joanne K. Tobacman: Review of Harmful Gastrointestinal Eects of Carrageenan in Animal Experiments. Environ Health Perspect 109:983-994 (2001). (Online 24 September 2001). [41] http://www.inchem.org/documents/jecfa/jecmono/v042je08.htm. JECFA:Carrageenan.
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[42] Tobacman jk: Review of harmful gastrointestinal eects of carrageenan in animal experiments. Environ Health Perspect, 109(10):98394, 10 2001. http://www.ncbi. nlm.nih.gov/pmc/articles/PMC1242073/?tool=pubmed. [43] Cohen SM and Ito N. A critical review of the toxicological eects of carrageenan and processed eucheuma seaweed on the gastrointestinal tract. Crit Rev Toxicol, 32(5):413 44, 9 2002. http://informahealthcare.com/doi/abs/10.1080/20024091064282. [44] Opinion of the scientic committee on food on carrageenan (expressed on 5 march 2003). european commission. http://www.cybercolloids.net/sites/default/ files/EU-carrageenan-opinion.pdf. [45] http://en.wikipedia.org/wiki/Acacia_gum. Wikipedia, The Free Enzyclopedia: Gum arabic,. [46] Madhav P. Yadav, David B. Johnston, Arland T. Hotchkiss, Jr and Kevin B. Hicks Corn ber gum: A potential gum arabic replacer for beverage avor emulsication. Food Hydrocolloids doi: 10.1016/j.foodhyd.2006.07.009. [47] Stefan Willfr, Stefan; Sundberg, Kenneth; Tenkanen, Maija; Holmbom, Bjarne: Spruce-derived mannans - A potential raw material for hydrocolloids and novel advanced natural materials. Carbohydrate Polymers. 52 (2), p.175-187, May 2003. [48] http://www.food.gov.uk/aboutus/how_we_work/procurement/resreq/proga01. Ad hoc: Programme A01-food additives-research. FSA 18.08.2010. [49] http://www.bmj.com/cgi/content/extract/336/7635/96. Bauditz, Juergen; Norman, Kristina; Biering, Henrik; Lochs, Herbert; Pirlich, Matthias: Lesson of the week: Severe weight loss caused by chewing gum. British Medical Journal 12 January 2008, Volume 336, Pages 96-97, doi:10.1136/bmj.39280.657350.BE. [50] http://ajrccm.atsjournals.org/cgi/content/abstract/179/1/59. Jin, Hua; Xu, Cheng-Xiong; Lim, Hwang-Tae; Park, Sung-Jin; Shin, Ji-Young; Chung, YounSun; Park, Se-Chang; Chang, Seung-Hee; Youn, Hee-Jeong; Lee, Kee-Ho; Lee, YeonSook; Ha, Yoon-Cheol; Chae, Chan-Hee; Beck Jr, George R.; Cho, Myung-Haing: High Dietary Inorganic Phosphate Increases Lung Tumorigenesis and Alters Akt Signaling. American Journal of Respiratory and Critical Care Medicine Vol 179. pp. 59-68, (2009) Doi: 10.1164/rccm.200802-306OC. [51] http://www.cspinet.org/reports/saccomnt.htm. CSPI input to the NTPs review of the articial sweetener saccharin October 24, 1997. [52] http://www.ncbi.nlm.nih.gov/pubmed/16507461. Soritti M, Belpoggi F, Degli Esposti D, Lambertini L, Tibaldi E, Rigano A. First experimental demonstration of the multipotential carcinogenic eects of aspartame administered in the feed to Sprague-Dawley rats. Environ Health Perspect. 2006 Mar;114(3):379-85.
BIBLIOGRAPHY
1035
[53] http://www.cancer.gov/cancertopics/factsheet/AspartameQandA. US National Cancer Institute: Aspartame and Cancer: Questions and Answers. [54] http://www.efsa.europa.eu/en/science/afc/afc_opinions/1471.html. Comprehensive Review of Ramazzini Study: Opinion of the Scientic Panel AFC related to a new long-term carcinogenicity study on aspartame. 4 May 2006. [55] http://annonc.oxfordjournals.org/cgi/content/abstract/18/1/40. Gallus, S.; Scotti, L.; Negri, E.;Talamini, R.; Franceschi, S.; Montella, M.; Giacosa, A.; Dal Maso, L. and La Vecchia, C.: Articial sweeteners and cancer risk in a network of case-control studies: The Annals of Oncology 18 (1) January 2007 Doi:10.1093/annonc/mdl346. [56] Commission of the European Union COM (2002) 375 nal 2002/0152 (COD) from July.11.2002. [57] Aspartame-acesulfame salt. wikipedia. Aspartame-acesulfame_salt. http://en.wikipedia.org/wiki/
[58] Method of calculating permitted levels of salt of aspartame-acesulfame. uk government. http://www.food.gov.uk/multimedia/pdfs/aspartamecalc.pdf. [59] http://en.wikipedia.org/wiki/Sucralose. Wikipedia, the free encyclopedia: Sucralose. [60] Elmadea,Prof.Dr.I.;Museat,Dr.E.;Fritsche,Dipl.Oec.Troph.D.:E-Nummern,Alles ber Lebensmittettelzusatzstoe.GU www.gu.online.de,Page 67. [61] http://www.springerlink.com/content/a15x761724884206/. Scheurer, Marco; Brauch, Heinz-J; Lange, Frank T.: Analysis and occurrence of seven articial sweeteners in German waste water and surface water and in soil aquifer treatment. Analytical & Bioanalytical Chemistry. Doi: 10.1007/s00216-009-2881-y. [62] European food safety authority; revised exposure assessment for steviol glycosides for the proposed uses as a food additive. efsa journal 2011;9(1):1972. [19 pp. doi:10.2903/j.efsa.2011.1972. 2011. http://www.efsa.europa.eu/en/efsajournal/ doc/1972.pdf. [63] http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=OJ:L:2009:344: 0037:0040:EN:PDF. Commission Directive 2009/163/EU of 22 December 2009 amending Directive 94/35/EC of the European Parliament and of the Council on sweeteners for use in foodstus with regard to neotam. [64] Wikipedia, The Free Encyclopedia: Erythritol. [65] http://en.wikipedia.org/wiki/Xylitol. Wikipedia, the free enzyclopedia: Xylitol.
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[66] Nadimi H, Wesamaa H, Janket SJ, Bollu P, and Meurman JH. Are sugar-free confections really benecial for dental health? Br Dent J, 211(7):E15, 10 2011. http://www.ncbi.nlm.nih.gov/pubmed/21979369. [67] Burt BA. The use of sorbitol- and xylitol-sweetened chewing gum in caries control. J Am Dent Assoc, 137(190-6):2, 2 2006. http://jada.ada.org/content/137/2/190. long. [68] Ly KA, Milgrom P, and Rothen M. Xylitol, sweeteners, and dental caries. Pediatr Dent, 28(2):15463, Mar-Apr 2006. http://www.ncbi.nlm.nih.gov/pubmed/ 16708791. [69] Seki M, Karakama F, Kawato T, Tanaka H, Saeki Y, and Yamashita Y. Eect of xylitol gum on the level of oral mutans streptococci of preschoolers: block-randomised trial. Int Dent J, 61(5):27480, 10 2011. http://www.ncbi.nlm.nih.gov/pubmed/ 21995376. [70] http://www.nature.com/ejcn/journal/v61/n6/abs/1602649a.html; jsessionid=A3FFFCF9617945B66E648D95A25B6E13. Bellisle, F.; Drewnowski, A.: Intense sweeteners, energy intake and the control of body weight. European Journal of Clinical Nutrition. Volume 61, Pages 691-700, doi:10.1038/sj.ejcn.1602649 Received 25 October 2006; Accepted 4 December 2006; Published online 7 February 2007. [71] http://www.nature.com/ijo/journal/v30/n3s/abs/0803494a.html. Mattes, R.D.: Beverages and positive energy balance: the menace is the medium. International Journal of Obesity (2006) 30, S60-S65. doi:10.1038/sj.ijo.0803494. [72] http://www.apa.org/journals/releases/bne-feb08-swithers.pdf. Swithers,Susan E.; Davidson, Terry L.: A Role for Sweet Taste: Calorie Predictive Relations in Energy Regulation by Rats. Behavioral Neuroscience. February 2008, Volume 122, Number 1, doi: 10.1037/0735-7044.00.0.000. [73] http://www.purdue.edu/UNS/html4ever/2004/040629.Swithers.research.html. Purdue University: June 29, 2004 Study: Articial sweetener may disrupt bodys ability to count calories. [74] http://www.caloriecontrol.org/pr_20080208.html. Calorie Control Council: Study Conrms that Low-Calorie Sweeteners Are Helpful in Weight Control LowCalorie Sweeteners May be One Piece in Solving the Obesity Puzzle. [75] Tracy Hampton: Sugar substitutes linked to weight gain. Journal of the American Medical Association. May 14 2008, Volume 299, 2137-2138. No 18, doi: 10:1001/jama.299.18.2137.
BIBLIOGRAPHY
1037
[76] http://www.nature.com/ejcn/journal/v61/n6/abs/1602649a.html; jsessionid=B2D090FF8BDD4B90E8CC27F8BBC794B. Bellisle, F.; Drewnowski, A.: European Journal of Clinical Nutrition. Volume 61, Pages 691-700, doi:10.1038/sj.ejcn.1602649 Intense sweeteners, energy intake and the control of body weight. [77] http://lib.bioinfo.pl/auid:8164696. Frank, Guido K.; Oberndorfer, Tyson A.; Simmons, Alan N.; Paulus, Martin P.; Fudge, Julie L.; Yang, Tony T.; Kaye, Walter H.: Sucrose activates human taste pathways dierently from articial sweetener. Neurimage 2008; 39(4): 1559-1569. [78] http://www.apa.org/journals/releases/bne-feb08-swithers.pdf. Swithers, Susan E.; Davidson, Terry L.: A Role for Sweet Taste: Calorie Predictive Relations in Energy Regulation by RatsBehavioral Neuroscience. February 2008, Volume 122, Number 1, 161-173 doi: 10.1037/0735-7044.00.0.000. [79] http://pediatrics.aappublications.org/cgi/content/abstract/120/4/e869. Rodearmel, Susan J.; Wyatt, Holly R.; Stroebele, Nanette; Smith, Sheila M.; Ogden, Lorraine G.; Hill, James O.: Small Changes in Dietary Sugar and Physical Activity as an Approach to Preventing Excessive Weight Gain: The America on the Move Family Study. Pediatrics 2007; 120: e869-e879. [80] Chung M-Y, Oh D-K, and Lee KW. Hypoglycemic health benets of d-psicose. J. Agric. Food Chem, 12 2011. http://pubs.acs.org/doi/abs/10.1021/jf204050w. [81] Hossain MA, Kitagaki S, Nakano D, Nishiyama A, Funamoto Y, Matsunaga T, Tsukamoto I, Yamaguchi F, Kamitori K, Dong Y, Hirata Y, Murao K, Toyoda Y, and Tokuda M. Rare sugar d-psicose improves insulin sensitivity and glucose tolerance in type 2 diabetes otsuka long-evans tokushima fatty (oletf) rats. Biochem Biophys Res Commun, 405(1):712, 2 2011. http://www.ncbi.nlm.nih.gov/pubmed/21187061. [82] Psicose. wikipedia. http://de.wikipedia.org/wiki/Psicose. [83] Li Z, Cai L, Qi Q, and Wang PG. Enzymatic synthesis of d-sorbose and d-psicose with aldolase rhad: eect of acceptor conguration on enzyme stereoselectivity. Bioorg Med Chem Lett, 21(23):70814, 12 2011. http://www.ncbi.nlm.nih.gov/pubmed/ 22018788. [84] Li Z, Cai L, Qi Q, Styslinger TJ, Zhao G, and Wang PG. Synthesis of rare sugars with l-fuculose-1-phosphate aldolase (fuca) from thermus thermophilus hb8. Bioorg Med Chem Lett, 21(17):50847, 9 2011. http://www.ncbi.nlm.nih.gov/pubmed/ 21482110. [85] Choi JG, Ju YH, Yeom SJ, and Oh DK. Improvement in the thermostability of d-psicose 3-epimerase from agrobacterium tumefaciens by random and site-directed
1038
CHAPTER 12. ADDITIVES AND E-NUMBERS mutagenesis. Appl Environ Microbiol, 77(20):731620, 10 2011. http://www.ncbi. nlm.nih.gov/pubmed/21873475.
[86] Mu W, Chu F, Xing Q, Yu S, Zhou L, and Jiang B. Cloning, expression, and characterization of a d-psicose 3-epimerase from clostridium cellulolyticum h10. J Agric Food Chem, 59(14):778592, 7 2011. http://www.ncbi.nlm.nih.gov/pubmed/21663329. [87] Bleich SN, Herring BJ, Flagg DD, and Gary-Webb TL. Reduction in purchases of sugar-sweetened beverages among low-income black adolescents after exposure to caloric information. Am J Public Health, pages e1e7, 12 2011. http://ajph. aphapublications.org/doi/abs/10.2105/AJPH.2011.300350. [88] Ng SW, Ni Mhurchu C, Jebb SA, and Popkin BM. Patterns and trends of beverage consumption among children and adults in great britain, 1986-2009. Br J Nutr, 20:1 16, 12 2011. http://www.ncbi.nlm.nih.gov/pubmed/22186747. [89] The European Commission, Food Safety: Opinion on Certain Additives for Use in Foods for Infants and Young Children in Good Health and in Foods for Special Medical Purposes for Infants and Young Children (expressed on 21 March 1997 and amended on 13 June 1997). [90] http://www.blackwell-synergy.com/doi/abs/10.1111/j.1750-3841.2008. 00755.x. Lockwood, S.; King, J.M.; Labonte, D.R.: Altering Pasting Characteristics of Sweet Potato Starches through Amino Acid Additives. Journal of Food Science. Published online ahead of print, 13 May 2008, doi: 10.1111/j.1750-3841.2008.00755.x. [91] http://www.cfsan.fda.gov/~dms/opa-appa.html. FDA: Food additive list. [92] http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm? CFRPart=172. Food and Drug Administration Title 21 - Food and Drugs - Chapter 1 Food for Human Consumption.
Part II Dietary Habits
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Chapter 13 Dieting and Dietary Habits

Failure of nutrition is responsible for most of our diseases and rotten health. Diets are a wide eld of incomprehensible eorts to correct mislead nutrition. The classic function of diets are to reduce body weight. A great number of women try diets to reduce their weight. They are looking for better health or want to improve aesthetics. Body culture is getting important in actual society. Weight reduction should only be considered if there are clinical reasons. Body weight is genetically controlled. If one feels good with a certain weight everything no diet should be considered. Much outdoor exercise keeps you healthy. There are some ways to determine normal weight[1]: Broca normal-weight Table of the American life insurance companies Bodymass Index BMI
13.0.36
The Broca normal-weight
The Broca normal weight is given in kg and is dened as body size in cm minus 100 for man. For women the body size minus 100 minus 5 to 10% is used. Over- and underweight in relation to broca normal weight is given in percent. The Broca-Indexis the quotient of the actual weight and the Broca normal-weight.
13.0.37
Table of the American life insurance companies
With this table the actual weight is put in relation to the normal weight for the corresponding age and body size. 1041
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CHAPTER 13. DIETING AND DIETARY HABITS
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The Bodymass Index BMI
The Bodymass index is the quotient of the body weight and the square of the body size (kg/m2 ). This index gives best informations about the mass of the body fat. It is less used as Broca because it is less informative for the patient.
Picture source: Wikipedia. [2]
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BMI
The dashed lines represent subdivisions within a major class. For instance the "Underweight" classication is further divided into "severe", "moderate", and "mild" subclasses.
Table 13.1: Ideal Bodymass index in relation to age Age 19 - 24 years 25 - 34 years 35 - 44 years 45 - 54 years 55 - 64 years over 65 years Bodymass index (kg/m2 ) 19 - 24 20 - 25 21 - 26 22 - 27 23 - 28 24 - 29
(National Research Council 1989) Table 13.2: Classication of overweight
1043 Grade of overweight Normal weight Moderate overweight Strong overweight Extreme overweight 0 I II III BMI(kg/m2 ) 20 up to 24,9 25 up to 29,9 30 - 40 > 40 Broca-overweight(%) 0 up to 20 (-40) 20 - 70 (-80) > 70 (>80)
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Classication of overweight in adults according to BMI
[3] Joint WHO/FAO Expert Consultation 2003 Classication BMI (kg/m2 ) Risk of comorbidities Underweight <18.5 Low (but risk of other clinical problems increased) Normal range 18.5-24.9 Average Overweight 25.0 Pre obese 25.0-29.9 Increased Obese class I 30.0-34.9 Moderate Obese class II 35.0-39.9 Severe Obese class III 40.0 Very severe These BMI values are age-independent and the same for both sexes. However, BMI may not correspond to the same degree of fatness in dierent populations due, in part, to dierences in body proportions.The interpretation of BMI gradings in relation to risk may dier for dierent populations. Both BMI and a measure of fat distribution (waist circumference or waist : hip ratio (WHR)) are important in calculating the risk of obesity comorbidities. The consultation considered that, to achieve optimum health, the median BMI for the adult population should be in the range 21-23 kg/m2 , while the goal for individuals should be to maintain BMI in the range 18.5-24.9 kg/m2 .
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Calculate your BMI
Please use the calculator of CDC at: http://www.cdc.gov/healthyweight/assessing/bmi/index.html
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Healthy weight- Its not a diet, its a lifestyle
[4] When it comes to weight loss, theres no lack of fad diets promising fast results. But such diets limit your nutritional intake, can be unhealthy, and tend to fail in the long run. The key to achieving and maintaining a healthy weight isnt about short-term dietary
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changes. Its about a lifestyle that includes healthy eating, regular physical activity, and balancing the number of calories you consume with the number of calories your body uses.
13.0.43
Waist circumference
Waist circumference is a convenient and simple measure which is unrelated to height, correlates closely with BMI and the ratio of waist-tohip circumference, and is an approximate index of intra-abdominal fat mass and total body fat. Furthermore, changes in waist circumference reect changes in risk factors for cardiovascular disease and other forms of chronic diseases, even though the risks seem to vary in dierent populations. There is an increased risk of metabolic complications for men with a waist circumference 102 cm, and women with a waist circumference 588 cm. [5] Dubious Pharmaceutical industry and at magazines recommend all kind of diets. There are made increasing turnovers in this eld, not always without damage of health of the consumer. Advertising uses terms like"slim", "calorie reduced", "light", "Du darfst"(You may), "fat reduced" and others to promote selling of their products. With great publicity campaigns in magazines, TV and radio appetite of the group of overeaters is stimulated rather then reduced. The result of these products are therefore negative. Examples of diets lacking any scientic background[6]: The apple diet The mayo diet The Max-Plank-diet The Book "Fit for live"H. and M. Diamond, USA The separation diet of DR. Howard Hay in USA and Dr. Walb in Germany the Atkins diet The point diet
13.0.44
Lowcarb diets
Lowcarb diets are low in carbohydrates and rich in protein and fat. The most prominent lowcarb diets are the Atkins diet, the Southbeach diet, the Ketogen diet the Anabole diet and the LOGI diet (Low Glycemic Index) from Dr. Nicolai Worm.
13.1. VEGETARIAN FOOD WITH ANIMAL INGREDIENTS
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13.1
Vegetarian food with animal ingredients
Many vegetarian labelled foods of industrial origin do contain animal ingredients such as bovine suet, lard, restaurants prepare their meals labelled as vegetarian with meat broth and marine oil. [7].
13.2
Psychology of diet plans
Diet plans and diet systems to be successful must observe some basic psychological rules: 1. At the beginning of a diet plan the dangers of overweight are enumerated. This is the most dangerous part of the plan as those who do not succeed with the diet will later on create a deeper psychological conict. Their real problems which took them to overeat will then be boosted. Such an introduction should always be banned from a diet plan as it frightens the reader, it increases the inferiority complexes. Instead of telling the reader how bad its life is, a diet plan should make its introduction enumerating the benets. 2. The promise that overweight can be reduced to normal values using a specic diet is not honest. As weight reduction is coupled to intake and output of calories over the whole life, the necessary modication of life style cannot be achieved in one or two weeks of sometimes strange procedures which lack any explanation of how it should work. The explanations should be short and come to the point precisely. If the principles are unknown this part should be omitted completely. 3. Reference of people who were successful with the diet. Usually well known people of the public life and TV stars are cited. This increases the desire to participate of the life of these persons. Awaking from the fairy tales the monotony of the daily round will be more sad then before. 4. Certainty that everyone can succeed with the diet is a claim which is untrue. Many people are unsuccessful and have great psychological distress failing in what is told to be easy for everyone. 5. Explanation of the foundations of the diet should only be given based on well known statements. If there is no explanation available no comment suggesting miracles should be given.
13.3
The cause of failure of diet plans and how to do it better
Mislead diets are not caused by alteration of the basic metabolism. The real cause is the lack of learn eect to adapt the life Style to a healthy way of life and to correct the bad
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habits. Wolfgang Stabel [8], during a course to get rid of smoking habit said: "Mankind can live 170 seconds without air, 12 days without water and 46 days without food. Without tobacco it can live a whole life." To this statement one can add: one can live without chocolate, without candies and hamburgers. The essential message of diet plans should be to change the life habits: How to to it better[9]: 1. Drink 2 litre of water per day, eat bre rich food. 2. Do not bother about calories, but spare fat and alcohol. 3. Eat on regular hours, do not eat in between. 4. Eat enough vitamins, minerals and proteins 5. Noting is forbidden, you can eat everything, but always without excesses 6. Enjoy a small dish. Eat always with attention. 7. Act against stress with physical activity and relaxation exercise and not with eating junk food 8. Stay realistic. Set small scores. Distrust crash-diets and miracle-diets. Do it the safe way changing food habits. 9. Activate the fat break down with physical activity. The more muscles you activate more calories are burned. 10. Money back guarantee in case of failure of the diet is a bad trick. Less than 10% complain in case of failure. The majority does not dare to do it. Who wants to admit to have failed when it is being told that all other do succeed ?
13.3.1
The National Weight Control Registry (NWCR)
[10] The National Weight Control Registry (NWCR), is a research study from the University of Colorado that seeks to gather information from people who have successfully lost weight and kept it o for long periods of time. The ndings of this study are: A little over one-half of the sample lost weight through formal programs (such as Weight Watchers, or professional assistance, such as Overeaters Anonymous, a psychologist or a registered dietitian; the remainder lost weight on their own.
13.4. THE SEPARATION DIET OF DR. HOWARD HAY
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Both groups reported having used both diet and exercise to lose weight and nearly 77% of the sample reported that a triggering event had preceded their successful weight loss. Mean (+/-SD) current consumption reported by registry members was 5778 +/- 2200 kJ/d, with 24 +/- 9% of energy from fat, Members also appear to be highly active: they reported expending approximately 11830 kJ/wk through physical activity. Surprisingly, 42% of the sample reported that maintaining their weight loss was less difcult than losing weight. Nearly all registry members indicated that weight loss led to improvements in their level of energy, physical mobility, general mood, self-condence, and physical health. [11]
13.4
The separation diet of Dr. Howard Hay
Dr. Howard Hay was during his life attacked by a renal insuciency. To help himself Dr. Hay studied the composition of the body noting that it was built of 80% of alkaline material and 20% of acid material. Starting from this hypothesis Dr. Hay divided food in alkaline generator and in acid generators. He introduced the following modication in his nutrition: Acid generators : Great part of the proteins and part of carbohydrates. Alkaline generators: Vegetables, fruits and salads. According to Dr. Hay the the alkaline generators may neutralize acid elements, helping their excretion. Dr. Hay augmented the amount of vegetables being half cooked and the other half raw. Dr. Hay says that the failure of balance between the acid generator food and the alkaline generator food is responsible for diseases like obesity, insomnia and depression. Dr. Hay separated the protein rich food from the carbohydrate rich food, putting them in dierent meals. This gave the name to his diet. Dr. Hay established the rules to his diet: Do not be hungry. The body should be supplied continuously with energy Distribute the food through 6 meals between 7:00 am and 10:00pm The portions should be small Between the meals there are only fruits permitted Chew long enough. The old saying "Chew every bit 36 time" is to be rejected. 20 times are enough. If food is not suciently ground the enzymes cannot do its job and repleteness cannot be achieved.
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Beverages: Mineral water is permitted. Herb tea and fruit tea, but not black tea is permitted Take the beverages before or after the meals in order not to disturb digestion. Most of the catabolists are excreted between 5:00 am and 12:00 am. It is that why Dr. Hay recommends to take great part of the liquid after wake up.
13.5
13.5.1
Good diets
Low Fat - 30 Diet
It is a weight reduction program for all who want to reduce their weight together with a group. Participation is for the time being limited to Germany. The most important facts about low fat nutrition is given in small groups. Meals should not contain more than 30% of calories coming from fat. You should eat only when feeling hungry. At the rst sign of satiation one should nish the meal. The diet is based on points. Minimum amounts of foods are given. Once a week brochures on special topics are given. A long-lasting modication of the nutritional habits are essential in order to avoid overweigh.
13.5.2
Natural Weight Program
This program was developed by Dr. Doris Wolf She herself had been overweighted and tried to amend it using here knowledge as a psychologist and psychotherapist developing the Natural Weight Program. Putting on weight because of emotional problems and stress are the main reasons for many people to skip all good intentions of an healthy nutrition. Frustration, anger and other negative emotions are compensated by eating. Alternatives to get emotionally balanced other than overeating are strategies of modern psychology. How to to handle ones emotions and how to accept ones own body not as an enemy, but as a fried, are important subjects of the Program. The negative attitude towards their body must be changed. According to Dr.Doris Wolf all kind of diets are unsuitable for the majority of persons. There are biological and psychological reasons which are responsible for the fact that only 2 to 5 per cent of those who follow a diet register lasting weight reduction. Dr. Wolf uses four principles as basis for her Program: The four principles 1 - Eat only when you are physically hungry and not when mental hungry. 2 - Eat what you like for the moment. 3 - Eat consciously, being aware of what you eat and how your body reacts.
13.6. THE RISKS OF BAD DIETS 4 - Stop eating when you feel satised
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13.6
13.6.1
The risks of bad diets

The potential risks of low-carbohydrate diets
The American Heart Association, the American Dietetic Association and the American Kidney Fund warn about the potential risks from the long-term use of low-carbohydrate, high-protein diets. Low-carbohydrate diets, like Atkins diet avoid carbohydrates (starches or sugar) reducing or even eliminating the intake of fruit, fruit juices, starchy vegetables, beans, bread, rice, cereals pasta and other grain products. This leads to a nutrition consisting mainly of fat and proteins. Permitted are meat, cheese, non-starchy vegetables. Everything else is limited to a minimum. Later on the carbohydrate restriction is reduced but high fat and proteins persists. Despite initial weight loss higher than rob obtained with other diets, low-carb diets however have a net weight loss after one year which is not signicantly different from other diets in comparison. Many nutritionists attack the Atkins weight loss regime for its high fat content, increasing the risk of clogged arteries heart attack, diabetes, stroke and several types of cancer in the long term. Deleterious eects on cardiovascular disease risk factors were demonstrated by Larosa [12] in a study of 24 obese individuals who followed the Atkins diet for 3 month. Caloric Intake declined, but LDL cholesterol levels rose despite the weight loss. Most of the weight loss occurred in the rst few weeks, which suggests the combined eects of uid loss and potential anorectic (reduction of desire to eat) eects of induced ketosis. The American Heart Association does not recommend high-protein diets because they restrict foods that provide essential nutrients. An undersupply of vitamins and minerals, as well as potential cardiac, renal, bone and liver abnormalities may result. A new study carried out at the University of Oxford demonstrates a direct aect on the heart caused by this diet. The results were presented at the American Heart Association conference in November 15, 2005, in Dalas. According to this study, the energy stores in the heart were reduced by an average of 16 per cent as a result of the Atkins diet recommendations. One of the authors , Dr. Damien Tyler says that similar patterns in a more severe form in patients with heart failure, and type 2 diabetics also suer from low energy stores.
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13.7
Evaluation of High-Protein Diets
[13] Evaluation of high-protein diets must be done ensuring that the American Heart Association Dietary Guidelines regarding eating patterns [14] and the primary prevention for coronary Omega 6 from the National Cholesterol Education Programme [15] are observed: 1 - Total Protein intake should not be excessive (average 50 to 100 g/d) and should reasonably proportional (around 15% of kilocalories per day) to carbohydrate (around 55% of kilocalories per day) and fat (around 30% of kilocalories per day) intake. 2 - Carbohydrates should not be omitted or severely restricted. A minimum of 100 g carbohydrate per day is recommended to ensure overall nutritional adequacy through the provision of a variety of healthful foods. 3 - Selected protein foods should not contribute excess total fat, saturated fat, or cholesterol. 4 - The diet should be safely implemented over the long term, i.e. it should provide adequate nutrients and support dietary compliance with a healthful eating plan to prevent increases in disease risk. The AHA summarises: "Successful weight loss occurs most frequently when a nutritionally adequate diet that allows for caloric decits (around 500 kcal/d for each 1 lb lost per week) is tailored according to individual food preferences. A minimum of 1200 kcal/d for women and 1500 kcal/d for men should be provided. Total energy decit has the greatest overall impact on weight reduction, especially when coupled with increased physical activity and behaviour modication to maintain negative energy balance. Over the long term, diet composition should be consistent with a balanced eating plan that supports weight maintenance and lowers chronic disease risk.
13.7.1
The Dietary Intervention Randomized Controlled Trial (DIRECT) says that weight-loss diets can be tailored to personal preferences
[16] Dr Iris Shai and colleagues 2008 studied the eects of three diets: low-fat/restricted-calorie diet; Mediterranean/restricted-calorie diet; or low-carbohydrate diet, with no restriction on calories. - The low-fat diet used the AHA guidelines with intake of 1500 kcal for women and 1800
13.8. WEIGHT REDUCTION
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kcal for men daily, with 30% of energy from fat, 10% from saturated fat, and 300 mg of cholesterol daily. - The Mediterranean diet had a high vegetable and low meat content with poultry and sh and similar amount of energy daily. - The low-carbohydrate diet provided 20 g of carbohydrate daily for 2 months with an increase to 120 g per day. Weight loss occurred in all three groups over the 24 months but was greater in the Mediterranean and low-carbohydrate groups. In men weight loss was greatest in the lowcarbohydrate group, whereas women appeared to lose more weight on the Mediterranean diet. Dr. Shai says that Mediterranean diet makes it easier to reduce calories because moderate fat consumption is permitted. Low-carbohydrate diet such as Atkins diet denes carbohydrate foods so the dieter can avoid them without counting calories. Craving in this diet is reduced, compared to other diets, it oers higher satiety, and it provides an encouraging immediate response of the body weight. The authors concluded that Mediterranean and low-carbohydrate diets are eective alternatives to low-fat diets. They call for individualized tailoring of dietary interventions.
13.8
13.8.1
Weight Reduction
Daily intake of energy
The only way to treat overweight is to bring the daily intake of energy down to the level of the daily output of energy. None of the above mentioned wonder diets have brought a durable weight reduction[1] "Eat half of what you eat now" can reduce intake of calories to an acceptable amount. Formula diets [17] Formula diets such as Cambridge-diet, Day-t , Slimfastor Herbalife according to DGE (Deutsche Gesellschaft fr Ernhrung ) are expensive, reduce life quality and destroy environment. Formula diets in Germany have to be in accordance to the Diet-directrix which prescribes the concentration of nutritional components. The amount of dietary bres of formula-diet is often to low, so bres and pellets of peelings and hull of cereals are added.
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13.8.2
Formula diets for weight reduction according to Codex Alimentarius, second edition,1994 part 3
Formula Foods for weight reduction diets are foods which are ready to serve or must be prepared according to instructions and are intended to replace one or more meals of the day.
13.8.3
Formula foods to replace all daily meals
They should have at least 800 kcal(3.350 kJ) and not more than 1.200 kcal (5020 kJ).for a day, divided in three or four meals with equal amount of calories.
13.8.4
Formula foods to replace one or more meals
To replace one or more meals they should have at least 200 kcal(835 kJ) and not more than 400 kcal (1.670 kJ) for each meal. If the formula foods are claimed to replace main meals they should not have more than 1.200 kcal (5.020 kJ). The formula diet system is not a safe system to reduce body weight. As soon as one comes back to former nutritional habits the overweight returns. This is called Jo-Jo-eect. Publicity campaigns using words like avour and delicious meals were prohibited in relation to formula diets because of their monotonous avour which becomes disgusting being used for a long period. To reduce body weight the DGE says to return to normal balanced nutritional habits. There should be no struggle with the body. A permanent bad conscience leads to stress. A good feeling is to achieve having no feeling of guilt. As an orientation about the amount of energy which is necessary in normal life a table of the daily required energy is given below. This table does not replace weighing. It is not possible to calculate the real daily intake of energy and there is not possible to determinate the ideal intake of energy because each individual has its own basal metabolism and has dierent jobs and do dierent sports requiring dierent amount of energy. The determination of nutritive value of carbohydrates and proteins in relation to their content in calories are calculated using calorie tables when recipes are known. If recipes are not available the content of fat by means of solvent extraction are determined. Proteins are measured by means of the Kjeldahl method using the factor of 6,25 for conversion of nitrogen to protein. The content of bres and water are determined at 105o C . Carbohydrates are calculated as being the rest of it. The energy of 100 g of food is calculated using the following values:
Table 13.3: Energy of food ingredient
13.8. WEIGHT REDUCTION Ingredient 1 g protein 1 g fat 1 g carbohydrate kJ kcal 17 kJ 4 kcal 37kJ 9 kcal 17 kJ 4 kcal
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Calorimetry Calorimetry burning the food in a closed system and measuring the rise of temperature is a method which is seldom used.
Table 13.4: Daily intake of energy as calories or Joules Age kCal/day(man/women) 0 to 2 month 550 2 to 5 month 750 6 to 11 month 850 1 to 3 years 1.100 4 to 6 years 1.500 7 to 9 years 1.900 10 to 12 years 2.300 / 2.200 13 to 14 years 2.700 / 2.500 15 to 18 years 3.000 / 2.400 19 to 35 years 2.600 / 2.000 36 to 50 years 2.400 / 2.000 51 to 65 years 2.200 / 1.800 > 65 years 1.900 / 1.700 Pregnancy + 300 Breath-feeding + 700 cJoules/day (man/women) 2.200 3.100 3.600 4.500 6.500 8.000 9.500 / 9.000 11.500 / 10.500 12.500 / 10.000 11.000 / 9.000 10.000 / 8.500 9.000 / 7.500 8.000 / 7.000 + 1.200 + 3.000
This table is made for people with normal activities. For hard workers please add: For moderate hard workers add 2.500 kJ (600 kcal) For very hard workers add 5.000 kJ (1.200 kcal For super hard workers add 6.700 kJ (1.600 kcal)
13.8.5
[18]
The Weight Loss Maintenance Behavioral Intervention
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Jack F. Hollis and colleagues from the Weight Loss Maintenance Trial Research Group in a randomized trial reported successfull short-term weight loss in a diverse population of high-risk patients. The Weight Loss Maintenance behavioral intervention was based on combined emphasis on dietary intake and physical activity to achieve short- and long-term weight-loss goals, The intensive weight-loss program was based on reduction of 500 calories per day, exercise for a total amount of 180 minutes each week, consumption of 2400 mg or less of sodium per day, and adherence to the DASH diet. Participants were encouraged to lose up to 2 pounds per week to achieve a total weight loss of at least 4 kg for 20 weeks. According to the authors behavioral strategies to modify health behaviors are important components of weight-loss interventions because the ability to monitor and regulate behavior, and help to overcome barriers of initial weight loss and long-term maintenance.
13.8.6
A minimum of exercise of 15 minutes/day is of health benet, says Taiwanese study
[19] Taiwan is known to have a population with very low leisure-time physical activity, according to studies of Ku 2006, 2009 and Wai 2008. Wen et al 2011 determined a minimum of exercise which is still benecient for this population. The authors calculated life expectancy for every group. The minimal amount of physical activity to reduce mortality risk iwas found to be 15 minutes a day of moderate-intensity exercise. Exercised for an average of 92 min per week or 15 min a day had a 14% reduced risk of all-cause mortality and had a 3 year longer life expectancy. Every additional 15 min of daily exercise beyond the minimum amount of 15 min a day further reduced all-cause mortality by 4% and all-cancer mortality by 1%. Individuals who were inactive had a 17% increased risk of mortality compared with individuals in the low-volume group. The authors concluded that 15 min a day or 90 minutes a week of moderate-intensity exercise might be of benet.
13.8.7
Low leisure-time physical activity in Taiwanese adults
[20] According to Ku et al. 2006 Asians tend to be less physically active compared to Western countries. The authors found that only 14% of Taiwanese adults met national recommendations for physical activity levels. In contrast to Western countries, adults 45 years and older were more likely to be active vs young people. Risk factors for physical inactivity were limited formal education and a paying job. The authors recommend to increase active leisure for improving health, of younger adults.
13.8. WEIGHT REDUCTION
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13.8.8
Expression of leisure-time physical activity LTPAin kcal
[21] Way et al.2008 write that using caloric equivalent to expressing the energy output could help nutritionists to improve informations related to energy equilibrium. The authors recommend a goal of >or=750 kcal/week for Asians, attainable by exercising 4 hours/week. The researchers found that actually 4/5 of adults in Taiwan failed to reach this goal, Only 1/7 (13.9%) reached a more desirable goal of >or=1,000 kcal/week, compared with 1/3 in the U.S. The 25-44 age group being the least active in Taiwan. Women, lower education or income, younger age, smokers and chewers of betel quid; exercised signicantly less than their counterparts.
13.8.9
Low leisure-time physical activity linked to depressive symptoms in Taiwanese older people
[22] Ku et al.2009, used data from the Taiwans Health and Living Status of the Elderly Survey in 1996, 1999 and 2003. Participants engaging in at least three activity sessions per week were classied as being physically active. Low leisure-time physical activity was found to increase the risk of developing depressive symptoms. The authors concluded that leisure-time physical activity reduces the risk of signicant depressive symptoms in older women.
13.8.10
Recommendations of the Physical Activity Guidelines for Americans
[23] Most health benets occur with at least 150 minutes (2 hours and 30 minutes) a week of moderate intensity physical activity, such as brisk walking. Additional benets occur with more physical activity. The Physical Activity Guidelines for Americans recommend: For adults - All adults should avoid inactivity. Some physical activity is better than none, and adults who participate in any amount of physical activity gain some health benets. - For substantial health benets, adults should do at least 150 minutes (2 hours and 30 minutes) a week of moderate-intensity, or 75 minutes (1 hour and 15 minutes) a week of vigorous-intensity aerobic physical activity, or an equivalent combination of moderate- and vigorous intensity aerobic activity. Aerobic activity should be performed in episodes of at least 10 minutes, and preferably, it should be spread throughout the week. - For additional and more extensive health benets, adults should increase their aerobic physical activity to 300 minutes (5 hours) a week of moderate intensity, or 150 minutes a week of vigorous intensity aerobic physical activity, or an equivalent combination of moderate- and vigorous-intensity activity. Additional health benets are gained by engaging in physical activity beyond this amount. Children and Adolescents (aged 617) - Children and adolescents should do 1 hour (60 minutes) or more of physical activity every
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day. - Most of the 1 hour or more a day should be either moderate- or vigorous-intensity aerobic physical activity. - As part of their daily physical activity, children and adolescents should do vigorousintensity activity on at least 3 days per week.
13.8.11
Publications biased by own understanding of their authors or editors
[24] James R Marshall and Zhao Chen argue that epidemiologic patterns of disease-exposure associations must be interpreted in light of the profound imprecision of exposure assessment that characterizes nutritional epidemiology. The authors highlight the imposition of publication bias: the failure of researchers to submit and of editors to publish ndings that do not t well with the their own understanding. The information extracted from assays of associations between exposure and disease is always estimated with serious imprecision or bias.
13.9
Physiology of hunger
Hunger has dierent phases:
13.9.1
Phase 1
The seat of the centre of hunger is located in the hipothalamus. Tiny sensors situated on the walls of the stomach and intestines communicate with the hipothalamus. They send informations about quantity of food lling the stomach and the intestines. Other biochemical sensors control the concentration of the dierent substances such as glucose, the amino acids and the concentration of fatty acids in blood. These informations are also send to the hipothalamus. When the level of glucose drops the hipothalamus sends signals to the brain where old habits related to the search for food are located.
13.9.2
Phase 2
If the body does not react on these signals the hipothalamus intensies the signals of hunger.
13.9.3
Phase 3
If these strong signals of hunger does not work the hipothalamus changes his tactic and starts to burn fatty acids, situated in the centres of reserve.
13.10. APPETITE TO SPECIFIC FOODS
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13.9.4
Phase 4
If this phase is also overcome the hipothalamus erases the signals of hunger. Hunger artists and Fakirs can overcome long periods of hunger. These people report that hunger vanishes after 2 to 3 days of starving being replaced by a feeling of wellnes which may escalate to euphoria.
13.10
Appetite to specic foods
The body can show unspecic hunger but also increase the desire to specic foods, for example: Noradrenalin, insulin and the neuropeptide Y are responsible for the desire to eat bread or noodles. Galanin is responsible for the desire to fatty food. As serotonin rises the desire for carbohydrates decreases increases the appetite to food rich in proteins such as fried meat. After a meal rich in proteins the blood level of serotonin decreases. The next meal will then be rich in carbohydrates.
13.11
Well-fed
The feeling of well-fed comes slowly. The rst signals come from the walls of the stomach and intestines indicating the stretch of these organs. These informations are centralized in the brain. The feeling of well-fed depends not only from the amount of food which had been eaten but also from the quality of food. One litre of water does not kill hunger. The seat of the feeling of well-fed is located in the hipothalamus controlling also the level of nutrient substances in blood. Noradrenalin and cholecystokinin are responsible for the informations of sucient quantity of energy being stored. Other substances such as serotonin modulate the informations with emotions. Serotonin is being produced in the brain and transported along the spinal cord to the neurons where it produces the feeling of well-fed.
13.12
Reductil, a suppressant of appetite
Reductil is being sold in the USA under the name of MERIDIA . It acts in the brain reducing appetite. The active substance of Reductil is sibutramin Reductil is being produced by BASF-Knoll (Badische Anilin und Soda Fabrik) . The drug has been liberated by the FDA (Food and Drug Administration) in USA only after a long time. A similar drug, the appetite suppressant REDUX with its active part the dexfenuramin presented dangerous secondary reactions. In Germany and in Austria Redux had been sold under the name of
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Isomeride. Redux has caused damage of cardiac valves as well as pulmonary hypertension. After many tests it has been proved that Reductil does not have these side reactions. Reductil or Plenty makes serotonin stay for a longer time between the neurons. By this mean the appetite is suppressed. The neurotransmitter serotonin transmits the feeling of well-fed in the sinapsis from one neuron to another. after some time serotonin is slowly catabolized and partially reabsorbed by the neurons. Reductil with sibutramine closes the way which exists in the cell membrane of the neurons in the region of the sinapsis avoiding serotonin being absorbed. Serotonin can therefore transmit for a longer time the feeling of well-fed. At the end of the decade of the 80 the WHO (World Health Organization) had obesity declared as being a worldwide epidemic. The FDA ( Food and Drug Administration) being conscious of the gravity of the problem had speeded the registration and the approval of weight reducing substances. This caused a ood of new drugs, bres to ll the stomach, laxatives, teas, special diets and appetite suppressants. All these products dont work or have serious side reactions.
13.12.1
Chinese slimming capsules contain sibutramine leading to serious side eects
[25][26] The Chinese slimming pills "Meizitanc" declared as a food supplement are on sale over the Internet. They are labelled to contains herbal substances, however, high levels of undeclared sibutramine (10 mg/capsule) were found in these pills. Sibutramine resembles amphetamine which inhibits the reuptake of serotonin and noradrenaline in the brain. Sibutramine is According to Dieter Mller et al. 2009, persons taking these pills are poisoned. They complain about nausea, tachycardia, headache, agitation, dyspnea, and insomnia, acute confusion and psychosis, mainly in combination with other drugs. On December 22, 2008, the Food and Drug Administration issued an alert to consumers naming 27 dierent products marketed as "dietary supplements" for weight loss, that illegally contain undisclosed amounts of sibutramine [27] [28]. The authors take for granted that the consumption of food supplements containing sibutramine is much greater than has been recorded. The authors urge that manufacturers should be obliged to declare ingredients.
13.12. REDUCTIL, A SUPPRESSANT OF APPETITE
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13.12.2
The Sibutramine Cardiovascular OUTcomes (SCOUT) trial
[29] The SCOUT trial has been designed to determine the impact of weight loss with sibutramine on cardiovascular endpoints in a large group of overweight and obese subjects at high risk for cardiovascular disease. Sibutramine is a neurotransmitter inhibitor and belongs to the family of amphetamines. It reduces appetite and cravings hence leading to weight loss. However, it must be supported by a healthy diet and regular exercise. Results from the SCOUT study indicating cardiovascular events occurred in 11.4% of patients using sibutramine compared to 10% of patients using a placebo. This dierence was higher than expected, suggesting that sibutramine was associated with an increased cardiovascular risk in the study population. The study reviewed by FDA indicate that the increased risk for cardiovascular events with sibutramine occurred only in patients with a history of cardiovascular disease. The use of Sibutramine is authorised in the EU since 1999. New concerns arise after the release of the Sibutramine Cardiovascular OUTcomes (SCOUT) trial. Weight reducing medicines containing Sibutramine are Reductil, Reduxade and Zelium and other tradenames in Europe, and Meridia in the United States. Sibutramine could increase blood pressure and heart rate.
13.12.3
FDA reviewing safety of sibutramine
[30] The FDA is reviewing preliminary data from a recent study suggesting that patients using sibutramine have a higher number of cardiovascular events (heart attack, stroke, resuscitated cardiac arrest, or death) than patients using a placebo. The additional data from the SCOUT study reviewed by FDA indicate that the increased risk for cardiovascular events with sibutramine occurred only in patients with a history of cardiovascular disease. [31] The European Medicines Agency (EMEA) urges ban on a weight loss pill containing sibutramine, which are sold under the names Reductil, Reduxade and Zelium in Europe and Meridia in the United States over fears that it could increase the risk of heart attacks and strokes. Acording to EMEA, data of the SCOUT study indicate an increased risk of serious cardiovascular events, such as stroke or heart attack, with medicines containing sibutramine [32]. Abbott will suspend the marketing of Abbott medicines under the brand names Reductil, Merindia, Sibutral, Ectiva and Raductil, containing sibutramine in all EU member CounCopyright 1998-2010 Karl H. Wilm. All rights reserved. OurFood Database of Food and Related Sciences
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tries, Iceland and Norway. Sibutramine remains available outside the EU. Abbott followed the recommendations of the Committee for Medicinal Products for Human Use (CHMP) of the European Medicine Agency (EMA), after evaluation of data of the SCOUT study [33].
13.13
Xenical, The ght against fat
Digestion of fat takes place with help of bilear acids and pancreatic lipases, which hydrolyzes the fat molecules enables thus the absorbtion by the gastric mucose. Xenical by means of its active substance orlistat blocs the lipases of pancreas avoiding 30% of fat to be hydrolysed in smaller parts. Fat which is not hydrolysed cannot be absobed by the gastric mucous. It remains in the faeces causing diarrhea when to much fat is consumed. This causes an educational eect which lead to a reduced intake of foods rich in fat. Xenical acts slowly. It is necessary to take the drug for a long period. It helps only in combination with a diet, together with a change of its nutritional habits towards a healthy composition: much fruits and vegetables, little meat, less fat accompanied by physical activities such as sport or garden work. One cannot escape the following overweight equation:
13.13.1
(Absorbed energy) - (Basal metabolism energy + physical activities energy) = Body fat
To reduce body weight it is necessary to eat less, to reduce fat intake, and practice more physical activities. All eorts to reduce overweight with drugs, even surgery of the adipose tissue are not lasting when they are not accompanied by a change of the nutritional habits.
13.13.2
Basal Metabolic Rate
The Basal Metabolic Rate (BMR) is the number of calories burned in a 24 hours period while lying down, but not sleeping in a comfortably warm environment.
13.13.3
Active Metabolic Rate
The Active Metabolic Rate (AMR) is estimated by adding the caloric cost of all activities throughout the day to the BMR. A person should not eat less than their BMR but not more then their ANR.
13.13. XENICAL, THE FIGHT AGAINST FAT
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13.13.4
Serotonin
Serotonin is a neurotransmitter which together with more than 100 other substances are active in the brain where nerve cells (neurons) link. Serotonin is 5-Hydroxytryptamine. Besides its biochemical activities in the neurophysiology it is also active as biogenic amine produced by bacteria. Serotonin is part of the blood clotting, being released by the trombocytes[34]. Serotonin causes a strong contraction of blood vessels resulting in an increase of blood pressure [35]
Tryptophane is basis for serotonin. It is broken down by monoamineoxidase The Institute of Technology of Massachusetts discovered that a high level of serotonin provides good mood and avoids uncontrolled hunger and continuous desire to sweet food. Serotonin is therefore also known as " Good mood hormone". Serotonin should be present in a steady concentration of about 10 mg. Some foods are rich in serotonin such as pineapple, banana, tomatoes. Other foods are rich in trytophan which can be used by the body to synthetize serotonin. These foods should therefore build the basis for a long lasting diet to reduce overweight.
13.13.5
Foods rich in serotonin and/or Tryptophan
[36] Fruits: Pineapple,avocado, banana, date, g, papaya. Vegetable: Lambs lettuce, carrot, round lettuce, leek, parsley, beetroot, spinach, tomato, onion. Meat: Chicken, veal, beef, pork, turkey breast. Seafood: Perch, catsh, trout, shrimp, herring, codsh, carp, salmon, spiny lobster, mackerel, mussel, sardine, haddock, plaice, pollack, sole, tuna. Cereals: Rolled oats, rice, rye bread, white bread, rusk. Milk and eggs: Buttermilk, eggs, fresh cheese, yoghurt, low fat curd cheese, milk. Nuts: Cashewkernel, peanuts, hazelnut, almond, Brazil nut, walnut.
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13.13.6
Overweight
The Body-Mass-Index (BMI) is used to indicate overweight.
13.13.7
BMI = Body weight divided by the square of body length in meters
International classication of BMI ( Please see also BMI at the beginning of the chapter "Physiology":
Table 13.5: Classication of overweight (National Research Council 1989) Normal weight Moderate overweight Strong overweight Extreme overweight Grade of overweight 0 I II III BMI(kg/m2 ) 20 up to 24,9 25 up to 29,9 30 - 40 > 40 Broca-overweight(%) 0 up to 20 (-40) 20 - 70 (-80) > 70 (>80)
13.13.8
Slimming ingredients
The slimming ingredients are based on the following mechanisms of action: Boosting fat burning (thermogenesis) Inhibiting protein breakdown Suppressing appetite/ boosting satiety (feeling of fullness) Blocking fat absorption Regulating mood (linked to food consumption).
13.14
Use of Xenical in case of low body weight (BMI below 30)
Xenical and Reductil were not developed to adjust cosmetic eects.They are drugs .0 to be used when there are clinical indications. Physicians and authorities of health departments refuse prescription of both drugs because new drugs may have serious side eects which are seen only after many years. It is necessary to compare the unknown risk of a new drug with the risk of obesity. The greatest eect of weight reduction with Xenical are due to reduction of fat in the food using the diet which should accompany the use of the drug. Chocolate, fat sausages, cheese
13.15. FOOD WITH REDUCED FAT
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with high fat content and similar food should be banned from the table when weight should be reduced. Reducing fat causes the weight return to normal in a healthy way without dependence on drugs.
13.15
Food with reduced fat
Curd cheese can be used in place of butter or margarine as bread spread. Avoid all white sauces like mayonnaise, use vinegar or sauces made with diluted yoghurt. Be careful not to use Sauces with yoghurt from the supermarket. they contain small amount of yoghurt together with a lot of oil in order to increase self life. Avoid peanuts, sunower nuts and other nuts. They contain much oil. Avoid fried potatoes and all fast food.
13.15.1
Food industry is not committed to healthy food
[37] Reduction of fat, sugar and salt was driven by marketing slogans using claims which were easy to full. The new products were primary developed in the fat reduced mayonnaise dressings, fat spreads and beverages. Ketchup light was "created" replacing fructose syrup with articial sweetener and a bit of guargum achieving cost reduction. Very little was achieved in meat products.
13.15.2
Low fat yoghurt
Consumer say that Aldi stores never oered yoghurt with 0,1% fat. This product had once been sold by LIDL where it was accepted by the consumer but suddenly it was taken from market and the 3% fat yoghurt is being aggressively oered. It is hard to nd some yoghurt with 0,1% fat at NETTO Stores. It is immediately outsold and high fat yoghurt has to be used as an alternative to 30% fat dressings. Only niche products are now introduced on market, most of them are bound to disappear soon after being linked to exotic herbs or ingredients with vague health claims linked to low fat, such as drinks based on milk. The concentration of retailer corporations reduces the diversity of food types which are sold. The customer gets used to a standardisation of articles which are similar in taste and packaging formate at all grocery stores, varying only by the layout of the label. Reformulating a product to reduce fat, sugar or salt should not try to copy all sensory characteristics. The taste should dier from the unhealthy product so that the consumer get aware of the healthy dierence. However, it is important to reduce the price accordingly to the reduction of the ingredients where water takes their place seen wit the example of kethup or fat spreads. As far as meat products concerns, lower fat means less lard and more lean meat which implies of higher price.
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Food industry should face the challenge to disrupt standardisation of food products and be truly committed to the reduction of the three killer: fat, sugar salt not only in the niche sector but in the primary foods.
13.16
Medical prescription of Xenical in case of BMI 30 to 40
In Germany Xenical is being sold only with medical prescription. The BMI must be at least 30 (obesity degree I and higher).
13.17
Use of Xenical in case of BMI over 40
In case of overweight with a BMI over 40 the use of Xenical should not be used. The loss of weight would be to slow. In these cases the use of the Optifast program is indicated or even a surgical reduction of the stomach.
13.18
Xenical, the drug of the rich society
The use of Xenical is very expensive. The medication of one month with Xenical costs 200 Dm in Germany [38] and 300 Reais in Brasil[39]. The use of Xenical for two years costs 2.400 Dm.
13.19
Dexfenuramin
Dexfenuramin acts on the brain reducing appetite. It was recalled from market because of serious side reactions such as coronary problems. Dexfenuramin had been sold under the name of Redux and is an example of serious side eects which are noted only after years of use. One of such horrible markers of the history of pharmacy Contergan which produced anatomical modications on unborn. Other drugs which are being studied as possible weight reduction are leptin , neuropeptide Y inhibitor, and CCK hormone . CCK hormone is produced by the small intestine and acts as message substance telling the brain that there is enough food which has been taken in. [39]. Instead of praising a new era of wellness-drugs (Viagra from Pzer, Prozac from Eli Lilly an antidepressant, Propecia from Merck Sharp and Dohme for better hairs, Xenical from BASF to ght overweight and Reductil from Roche an appetite suppressant) one should come back to the real values of life.
13.19. DEXFENFLURAMIN
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13.19.1
Industry asking to tighten the rules on weight-reduction drugs
[40] It is hard to believe but it is true, GlaxoSmithKline, owner of Alli weight-reduction OTC drug, instead of pledging for soft rules, issued a petition to the Food and Drug Administration (FDA) to ban dietary supplements from making weight loss claims. Dietary supplements and weight-loss aids arent subject to the same rigorous standards as are prescription drugs or medications sold over-the-counter. They can be marketed with limited proof of eectiveness or safety. Vendors can make health claims about products based on their own review and interpretation of studies without the authorization of the FDA. GSK says that the tria supporting botanical and other ingredients in benet of weight loss are not rigorous enough, or numerous enough. Classifying weight-loss products as prescription drugs or medication could eliminate nasty competitors which could not present clinical studies of their claims. The Mayo Clinic cites over the counter weight-loss drugs, all of them presenting serious inconveniences: Bitter Orange, Chitosan, Chromium, Conjugated linoleic acid (CLA), Country mallow (heartleaf), Ephedra, Green tea extract, Guar gum, Hoodia. [41] Consumer interest in weight management is stronger than ever as obesity-related problems have increased.
13.19.2
Drug for weight loss, limited ecacy and safety concerns.
[42] Alli acts as a fat blocker by preventing up to 25 percent of fat eaten from being digested. Alli has half the amount found in prescription Orlistat (Xenical). A low-fat (no more than 15 grams of fat per meal) and a reduced-calorie program must be followed. In April 2006, the consumer group Public Citizen petitioned the FDA to block Alli because of concerns of two studies suggesting that Xenical can cause these precancerous growths. [43] [44]
13.19.3
Mayo Clinic says Alli provides only modest results
[41] According to Donald Hensrud, M.D., a preventive medicine and nutrition specialist at Mayo Clinic, Rochester, Minn Alli could conceivably result in an average of 3 pounds lost
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in a year in addition to the approximately 8 pounds you could expect to lose from diet and exercise alone.
13.19.4
Spices and obesity
[45] Magriet Westerterp-Plantenga and colleagues found that consumption of spiced foods or herbal drinks leads to greater thermogenesis (heat generation) and in some cases to greater satiety. In this regard, capsaicin, black pepper, ginger, mixed spices, green tea, black tea and caeine are relevant examples. The authors conclude that thermogenic ingredients may be considered as functional agents that could help in preventing a positive energy balance and obesity. Active Capsaicin of red chilli pepper boosts heat generation by the body. More energy is therefore burned, reducing fat deposition. Gingerols and shogaols of ginger have thermogenic properties. Mixtures of of black pepper, red chilli, turmeric, cumin, ginger and other spices could therefore become interesting to help against obesity. Piperine of black pepper, is said to bind to so-called Transient Receptor Potential Vanilloid (TRPV1)receptors in the brain and other parts of the nervous system.
13.19.5
Hot ginger beverages helpful in weight-control Mansouroverw3811
A study of Mansour et al.2012 suggest the use of ginger in weight control. The authors demonstrated that 2g ginger powder (Zingiber ocinale) dissolved in a hot water beverage enhances thermogenesis and reduces feelings of hunger in overweight men. Ginger had a signicant eect of ginger on thermogenesis and reduced feelings of hunger, but did not alter total resting energy expenditure or respiratory quotient. Visual analog scales (VAS) ratings showed lower hunger, lower prospective food intake and greater fullness with ginger consumption, compared with the group which did not receive ginger. Ginger did not aect glucose, insulin, lipids, or inammatory markers. he authors suggest further studies of ginger in weight control.
13.19.6
Capsaicin from red pepper may avoid obesity
[46] Chin-Lin Hsu and Gow-Chin Yen of Taiwan have found that capsaicin,from red pepper cause apopteosis (death) of immature fat cells, the pre-adipocyte cells called 3T3-L1from mice. These cells dierentiate into mature adipocytes and increase fat mass, causing obesity. Capsaicin also decreased the amount of intracellular triglycerides and glycerol-3phosphate dehydrogenase activity in 3T3-L1 adipocytes. According to the authors, capOurFood Database of Food and Related Sciences Copyright 1998-2010 Karl H. Wilm. All rights reserved.
13.19. DEXFENFLURAMIN
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saicin inhibited the protein expression of PPAR which regulate several genes involved in the formation of fat cells, as well as making body fat. These results demonstrate that capsaicin eciently suppresses adipogenesis in 3T3-L1 pre-adipocytes and adipocytes. Red chilli pepper was also linked to inhibit the growth of pancreatic cancer cells. [47] However, high intake of hot chillies has been linked with increased risk of stomach cancers in the populations of India and Mexico. [48]
13.19.7
Body Clock linked by enzyme pathway to Metabolism
[49] [50] The circadian rhythms is the body clock which regulates energy levels in cells. It is linked with the bodys day-night patterns and metabolism, and ensure that cells function properly and remain healthy. These ndings open the pathway to new treatments for diseases caused by cell energy deciencies. Circadian rhythms of 24 hours govern physiological functions all over the organism. According to Sassone-Corsi, Professor at the University of California, disruption of these rhythms can profoundly inuence human health and has been linked to obesity, diabetes, insomnia, depression, coronary heart diseases and cancer. The researchers found that CLOCK[50], an essential molecular gear of the circadian machinery interacts with a protein, SIRT1, which senses cell energy levels and modulates aging and metabolism. The link between the circadian clock and metabolism is maintained by metabolic proteins which send signals called the NAD+ salvage pathway where NAMPT helps to control CLOCK levels, If balance of this pathway is disrupted cells cannot function properly. Sassone-Corsi and colleagues found that the core circadian regulator, CLOCK, is a histone acetyltransferase whose activity is counterbalanced by the NAD(+)-dependent histone deacetylase SIRT1. Proper sleep and diet may help maintain or rebuild the balance between CLOCK and SIRT1 and the NAD+ salvage pathway. Lack of rest or disruption of normal sleep patterns can also increase hunger, leading to obesity-related illnesses and accelerated ageing.
13.19.8
Fat tissue negative feedback to the brain may be important in obesity understanding
[51] Readily available energy storage in form of glycogen may be worn o by exercise or by hunger periods. Burning fat is then activated. The sympathetic nervous system, used to regulate functions of the body, independent of concious thoughts, communicates with the adipose cells to initiate, continue or stop the fat burning.
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It already had been known that peripheral pseudounipolar dorsal root ganglion sensory cells innervate fat tissue and play a role in the short-term burning of fat. The central nervous system projections of the white adipose tissue were now studied by the authors. Following their data, the authors suggest the existence of a sensory adipose tissue pathway to the brain important in the negative feedback control of lipid mobilization. This pathway stops lipolysis when no more energy is needed. This process seems to be involved with the long-term burning of fat and obesity.
13.19.9
Transient receptor potential or TRP
[52]The phrase Transient receptor potential or TRP is appended to at least three classes of ion channels which mediate the response of a cell to external stimuli (electrical charge, substances, and forces) by increasing or decreasing its selective permeability to particular ions. The eect of this change is to modify the potential dierence between inside and outside of the cell. Hence "receptor," for sensitivity to the environment, and "potential" for this dierence. TRPV1 to TRPV4 can basically be seen as thermometers on a molecular level, and are activated by various means. When TRPV1 gets activated, it turns up the heat by boosting heat production by the body. TRPV1 is activated by noxious heat, acidic pH and capsaicin. These new ndings should not lead to a higher consumption of chilli con carne. Obesity is the result of many biochemical psychological and environmental occurrences. Seasoning could be a small contribution to tackle the obesity problem.
13.19.10
Diet in the preconceptional phase inuences foetal sex
[53] Dr. Mathews, Johnson and Neil in 2008 presented a report which says that foetal sex is associated with maternal diet at conception. High caloric intake and cereals at breakfast in the preconceptional phase favour the birth of male child with odds of 56 %. High energy intake and breakfast cereal consumption around conception is associated with glucose. In vitro, glucose enhances the growth and development of male conceptuses while inhibiting that of females. Skipping breakfast extends the normal period of nocturnal fasting, depresses circulating glucose levels and may be interpreted by the body as indicative of poor environmental conditions. For many nutrients, circulating levels are highly dependent on recent intakes and not on stored fat reserves. Glucose levels are inuenced bythe glycaemic index of foods. This supports the assumption that sex ratio is linked more directly to diet than to maternal condition.
13.20. BREAKFAST
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The intake of sodium, and potassium was also a factor which aected gender. As possible explanation the researchers suggest that salty diet alter the acidity of the vagina to favour male sperm. Women in the study who had girls had low caloric food reduced cereals at breakfast in the time before conception. The authors also point out that these ndings may help to explain the falling proportion of boys born in developed countries, where low-calorie diets are preferred by young women.
13.20
Breakfast
Breakfast is the most important meal of the day. Researches on the eect on cognitive function, health and obesity are still unsucient, say researchers.
13.20.1
Reduction of breakfast calories reduces overall daily energy intake
[54] According to Schusdziarra and colleagues 2011 increasing breakfast calories is associated with greater overall energy intake. The increasing ratio of breakfast to total daily energy intake was associated with a signicant reduction of overall intake when postbreakfast energy was signicantly reduced. The authors stress that breakfast calories have the strongest inuence on daily energy intake. They recommend overweight and obese subjects should consider the reduction of breakfast calories to reduce their body-weight.
13.20.2
Daily breakfast consumers are less overweight, have improved cognitive functions and health
[55] A review by Rampersaud and colleagues 2005 stresses children which eat breakfast regularly have also a healthier dietary habits compared with breakfast-skipping children. Breakfast eaters consumed more daily calories but less overweight cases were reported. Breakfast consumption may improve memory, test grades, school attendance, health and well-being, according to some studies.. The authors strongly recommend the daily consumption of breakfast consisting of a variety of foods, especially high-bre and nutrient-rich whole grains, fruits, and dairy products.
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13.20.3
Breakfast improves school achievement of children with compromised nutritional status
[56] Breakfast is linked to healthier macro- and micronutrient intakes, BMI and lifestyle and improved cognitive function. Daily breakfast is therefore better than skipping it., but this is only in evidence in children with compromised nutritional status. Hoyland, Dye and Lawton 2009 say there are little studies on this matter and no studies were made with adolescents and make recommendations for future research design and policy priorities.
13.21
The Conference on Preventing Childhood Obesity, December 8, 2003
Rising childhood obesity were highlighted at the Conference trying to nd out how additional increases in obesity could be prevented. Matthew Gillman, MD, Harvard Medical School, Boston, Massachusetts, pointed out some of the highlights of the conference:
13.21.1
factors in foetal development and the rst six month of life
Preconception Maternal prepregnancy body mass index (BMI) may determine pregnancy glucose and insulin levels in the mother and fetus, with high levels increasing newborn weight. Postnatal The feeding of the newborn, infant, and child can determine the rate of growth and inuence the timing and magnitude of the adiposity rebound seen in childhood According to Dr. Gillman dierences in birth weight as well as subsequent BMI may be determined by some the prenatal and postnatal environments In addition, genes that cause birth-weight dierences may also determine BMI dierences.
13.21.2
Alterations in the foetal environment
Transfer of fatty acids, leptin, and other hormones, foetal hyperinsulinemia, and the functioning of the foetal/placental unit are here included. Other speakers pointed out: Breastfeeding is protective against obesity and should be encouraged to be practiced during the rst year of life. Foods and beverages that are energy dense and nutrient poor like soda and french fries
13.21. THE CONFERENCE ON PREVENTING CHILDHOOD OBESITY, DECEMBER 8, 2003
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should not be fed to infants as young as 7 months of age as they alter taste preferences. Authoritative versus permissive parenting styles and their role in childhood obesity should be subject of further research.
13.21.3
Relationship of birth weight and childhood
According to Dr S. Kramer from the McGill University, Montreal, Quebec, like the United States, Canada is experiencing an epidemic of obesity, not only among 6- to 17-year-old individuals but even in the toddler and preschool periods. During the course of life, exposures that determine obesity may be attributable to environmental, social, behavioural, or biological factors. He examined relationship of birth weight to weight in childhood data from the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) in Tennessee, and found that the 3.0- to 3.5-kg birth-weight grouping most closely approximated that value at 5 years of age. The lightest infants (1.0-1.5 kg) and the heaviest infants (4.5-5.0 kg) had the most extreme weight-for-age and height-for-age scores initially but moved to less extreme values within about 12 months. Overweight status at 7 years of age tended to increase as birth weight increased, with the greatest increase in prevalence in the highest birth-weight (3.61-5.56 kg).
13.21.4
Obesity during pregnancy linked to high birth weight
[57] Dr. Kramer examined a Swedish study linking womens weight in early pregnancy and their own birth weights. There was a statistically signicant increased risk of having a BMI of over 25 during pregnancy among women who were born large for gestional age. The eect of high birth weight may become more important as birth-weight distributions move toward higher weights.
13.21.5
Breathfeeding and obesity
[57] The relationship between breastfeeding and obesity data was also discussed by Dr Kramer. He found that high maternal BMI is associated with reduced breastfeeding initiation and duration. Therefore, the higher weight status of bottle-fed infants could be attributable to selection of children of higher-weight mothers, who were both less likely to have breastfed and more likely to have higher-weight children.
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In addition, highly controlling bottle feeding practices at 18 month may interfere with the childs ability to self-regulate energy intake, an eect that may be long-lasting. Dr Kramer concluded that there is probably a small protective eect of breastfeeding on child obesity but is not of major public health importance. Neither birth-weight changes nor breastfeeding explains the obesity epidemic.
13.21.6
Decreased physical activity as key role to the obesity epidemic
[57] Dr Kramer believes that a decrease in physical activity to be the main reason for the obesity epidemic and less the higher energy intake.
13.21.7
Inuences on the nutritional behaviour of children
[58] Barbara Devaney, PhD, Mathematica Policy Research, Princeton, New Jersey According to Dr Devaney reported energy intakes of infants and toddlers are exceeding estimated requirements. The transition in infant feeding from true infant foods to more adult foods occurs during a long period but begins mostly at 9 to 11 months. As infants start to make the transition, the adult diet has a signicant inuence on what children eat. With the importance of table foods in the diets of children through the second year, changing what toddlers are eating may require changing what adults and older siblings are eating.
13.21.8
Sti arteries found in obese children
[59] Dr. Catherine L. Davis, 2010, using a non-invasive measure of pulse wave velocity, report that children with a greater body mass index, more body fat and less endurance had stier central arteries compared to leaner and tter children. The researcher explained that sti arteries are the rst sign of atherosclerosis, and regular exercise decreases risks of cardiovascular disease and diabetes. The author continues her research on the eect of exercise on nonalcoholic fatty liver disease which is also associated with hardening of the arteries. This liver disease is found in 40 percent of obese children, and is often symptomless. It causes inammation and scarring and ends in liver damage and failure. Exercise of 20 to 40 minutes of daily exercise were found to reduces inammation, visceral fat, body mass index and insulin levels.
13.21. THE CONFERENCE ON PREVENTING CHILDHOOD OBESITY, DECEMBER 8, 2003
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13.21.9
Nutritional and avour programming early in life
[57] According to Dr. Julie Menella, of the Chemical Senses Center, Philadelphia, Pennsylvaniathe eating preferences of children are guided by their senses and not cognitive decisions. These senses are well developed in utero but continue to change during development. There is mounting evidence of nutritional and avour programming early in life. Infants can detect a diversity of avours in amniotic uid and mothers milk. They accept new foods, such as cereals, more readily if they are prepared with their mothers milk. The avour prole of human milk reects the mothers diet and the culture in which the infant is born and is similar to the avour prole experienced in utero. These ndings are the rst experimental demonstration that prenatal and early postnatal exposure to a avour enhances the acceptance and enjoyment of that avour during weaning. Dr. Menella concludes that the more varied the mothers diet is during pregnancy and lactation, the more likely it is that the infant will accept new avours, and that these very early avour experiences may provide the foundation for cultural and ethnic dierences in cuisine. Understanding both the causes of and likely solutions to poor food habits and choices requires attention to the complex interactions of our genes, experiences, and lifestyles.
13.21.10
Parental feeding styles and childrens eating and weight
[60] Dr Jane Wardle of the University College, London, presented an overview about the relationships between parental feeding styles and childrens eating and weight, and came to the conclusion that greater control is probably associated with slightly lower weight and lower weight gain.
13.21.11
Breathfeeding and the time of introduction of solids
[61] Dr Andrew Ness, from the University of Bristol, Bristol, England, presented results from the Avon Longitudinal Study of Parents and Children (ALSPAC). The associations of breastfeeding and introduction of solids with obesity risk were examined. Breastfeeding appeared to be protective against obesity in unadjusted models, but these associations did not remain after adjustment. Some models examined the eect of the timing of the introduction of solids. There was a suggestion in the unadjusted odds that the later introduction of solids reduced the risk of obesity, but this was not the case after adjustment.
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13.21.12
Family characteristics
[61] Dr. Ness found that for children whose mothers BMI was >30, there was a 4.5-fold increase in obesity risk, which was reduced to 4.2-fold after adjustment. For children whose fathers BMI was >30, there was a nearly 3-fold increase in obesity risk, which was reduced to 2.7-fold after adjustment. If both parents had BMIs of >30, then the childs risk was increased 11.7-fold. Children with no siblings had an increased risk of obesity, with an OR that increased to 2.2 and became statistically signicant with adjustment. None of the other family factors was a signicant predictor of obesity risk.
13.21.13
Eects of activity, several characteristics of childrens lifestyles
[57] Dr. Ness noted that the eect of activity measured at 38 month showed that watching television more than 8 hours//week increased obesity risk, compared with less than 4 hours/week. Obesity risk was increased if less time was spent asleep overnight. More active children sleep better in opposition to those who are sitting and eating in front of the television.
13.21.14
Dening obesity
[62] Obesity is dened according to sex- and age-specic BMI cut-o points proposed by the International Obesity Task Force and Dietary Recommendations for Children and Adolescents: A Guide for Practitioners; Pediatrics, February 1, 2006 from the American Heart Association.
13.21.15
Meal frequency and obesity
[63] Andr Michael Toschke from the Ludwig-Maximilians-University Munich, Germany and colleagues assessed the relationship between meal frequency and childhood obesity. An inverse association between meal frequency and the prevalence of obesity in adulthood had been related in previous studies. The scientists found that prevalence of obesity decreased by number of daily meals: three or fewer meals, 4.2%; four meals, 2.8%; and 5 or more meals, 1.7%. They concluded that the protective eect of an increased daily meal frequency on obesity in children appeared to be independent of other risk factors for childhood obesity, and might be due to a modulation of the response of hormones such as insulin.
13.22. FREQUENCY OF MEALS
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13.22
13.22.1
Frequency of meals
The hunger hormone Ghrelin defends against depression and anxiety of chronic stress but increases obesity.
[64] Zigman and Lutter found that the "hunger hormone" ghrelin might also defend against symptoms of stress-induced depression and anxiety, but also increases food intake and body weight. Ghrelin is produced in the gastrointestinal tract, ion and weight loss could have an antidepressant eect and be reinforcing for this illness. [65]
13.22.2
A single large daily meal is associated with elevated fasting glucose levels and delayed insulin response
[66] Marc P. Mattson and colleagues 2007 evaluated the inuence of reduced meal frequency without a reduction in energy intake on glucose metabolism in normal-weight, healthy male and female subjects. The authors found that consuming 1 meal per day elevates morning fasting plasma glucose levels, is associated with greater and more sustained elevations of plasma glucose concentrations, delayed insulin response in the oral glucose tolerance test, and elevated ghrelin levels compared with 3 meals per day. The impaired glucose tolerance was reversible.
13.22.3
Reduction of meal frequency may increase cardiovascular risks
[67] Researchers found that some rodent and monkey had an extend lifespan when meal frequency was reduced. Mark P. Mattson and colleagues 2007 in a follow article report the outcomes on humans of such a meal reduction frequency. They found that normal-weight subjects are able to comply with a 1 meal/d diet with no signicant eects on heart rate, body temperature, or most of the blood variables measured. However, hunger was signicantly increased, blood pressure and in total, LDL-, and HDL-cholesterol concentrations increased ; and cortisol signicant decreased. They concluded that Normal-weight subjects are able to comply with a 1 meal/d diet. However of concern were some cardiovascular disease risk factors, and hematologic variables.
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13.22.4
Overweight increases risk of cancer
[68] Andrew G. Renehan and colleagues 2008 assess the strength of associations between BMI and dierent sites of cancer and associations between sex and ethnic groups. The authors found a strong associations between a 5 kg/m2 increase in BMI and endometrial, gallbladder, oesophageal adenocarcinoma, and renal cancer, but a weaker association between BMI and postmenopausal breast, pancreatic, thyroid, and colon cancers in women. In man the positive associations between increased BMI and rectal cancer and malignant melanoma in men was weak. The association between BMI and leukaemia, multiple myeloma, and non-Hodgkin lymphoma in both sexes was weak. The authors concluded that increased BMI is associated with increased risk of malignancies, and diers between sexes. The risk of premenopausal and postmenopausal breast cancer is increased in the Asia-Pacic population.
13.22.5
Large body size at the age of seven reduces later breast cancer risk
[69] Li and colleagues 2010 report that a large body type at age seven years was associated with a decreased risk of postmenopausal breast cancer. A large body size at age seven was especially protective against estrogen receptor negative tumours, which generally fare worse in terms of prognosis.The authors, however, stress that other factors such as large birth weight and a high adult BMI increase breast cancer risk. Pictograms were used for the classication of childhood body size ranging from very skinny to very fat. Subjects may assess their own body type at present and how they remembered themselves at seven years old using the pictograms. The authors concluded that information on childhood shape from old photographs, childhood body size is potentially useful for building breast cancer risk or prognosis models. The authors could not explain the mechanisms of the protective eect.
13.23
A classication and regression trees analysis on risk factors for childhood overweight (CART analysis)
[70] Andr Michael Toschke and colleagues used high weight gain, parental overweight and obesity, lack of breastfeeding, parental education under 10 years, high birth weight, having older siblings, ethnic aliation, and maternal smoking in pregnancy as predictors for later
13.23. A CLASSIFICATION AND REGRESSION TREES ANALYSIS ON RISK FACTORS FOR CHILDHOOD OVERWEIGHT (CART ANALYSIS) 1077 overweight or obesity. The classication and regression trees (CART) was used as predictive analytical method. They found that identifying children at high risk for overweight at school entry by means of predictors detectable at 2 years of age the authors found that the Weight gain >10,000 grams and obese parents accounted for the best reliable positive predictive value of 40%. In this subgroup of 4% of the entire population, two of ve children will be overweight at school entry. These results reect an improved but still insucient identication of high-risk children even with an optimal set of of predictors. Toschke came to the conclusion that positive predictive values might be insucient to allow for decision-making regarding specic interventions targeted at high-risk children: Most children would undergo an unnecessary intervention with potential side eects if intervention were based on the sets of predictors assessed in this study.
13.23.1
Classication and regression trees (CART)
[71] Predictive analytics is an area of statistical analysis that deals with extracting information from data and using it to predict future trends and behaviour patterns. The core of predictive analytics relies on capturing relationships between explanatory variables and the predicted variables from past occurrences, and exploiting it to predict future outcomes. Such predictions rarely take the form of absolute statements, and are more likely to be expressed as numbers that correspond to the odds of a particular event or behaviour taking place in the future.
13.23.2
Classication and regression trees (CART)
CART is a non-parametric technique that produces either classication or regression trees, depending on whether the dependent variable is categorical or numeric, respectively. Predictive values are essential for objective evaluation of the predictive potential of tests under consideration for the general population or test results on the individual level. Furthermore, decision trees provide a useful and precise tool for decision-making in the physicians daily routine by simple visual assessment of disease probability without the need of any calculations.
1078
13.23.3
The Melbourne Collaborative Cohort Study: The combination of the ingredients of the Mediterranean diet and not vegetable and fruit considered separately reduce heart disease risk
[72] The Mediterranean diet has higher intake of plant foods and sh, moderate intake of wine and lower intake of animal products. It includes garlic, cucumber, olive oil, salad greens, capsicum, legumes, tomato, feta and ricotta cheeses, olives, onion, watermelon, steamed sh and boiled chicken. It is therefore a rich source of antioxidants reducing oxidative damage, moacids believed to stabilise the heart rhythm, and bre, and relatively few countries have lower mortality than do native-born Australians. The researchers found for the Mediterranean-style diet 41 per cent reduction, while for vegetables and fresh fruit considered separately, only 31-34 per cent mortality from cardiovascular disease (CVD)risk reduction was observed. The authors concluder that frequent consumption of traditional Mediterranean foods is associated with reduced cardiovascular mortality after controlling for important risk factors and country of birth.
13.23.4
Phytonutrients and necessity of balanced and varied diet [73]
A diet high in fruits and vegetables provides high levels of phytonutrients, vitamins, minerals, and ber. Murphy et al. 2011 estimating usual intakes of nine phytonutrients by Americans consuming recommended levels of fruits and vegetables found that such diet is rich in carotenoids and avonoids. The authors stress that for -carotene, -cryptoxanthin, lycopene, hesperetin, and ellagic acid, out of nine compounds included in the study, are supplied by a single food which account for 64% or more of the total intake of the phytonutrient. The report concluded that only a limited number of foods provide the majority of these phytonutrients which underlines the importance of a balanced and varied diet.
13.23.5
Recent studies underlining the important role of vegetable and marine food in healthy diet
According to the study of Rautiainen et al. 2012 consumption of antioxidant-rich foods may reduce the risk of stroke by inhibition of oxidative stress and inammation. The study used data from the Swedish Mammography Cohort. Dietary total antioxidant capacity (TAC), based on oxygen radical absorbance capacity values, was found found to be inversely associated with total stroke among CVD-free women and hemorrhagic stroke
13.23. A CLASSIFICATION AND REGRESSION TREES ANALYSIS ON RISK FACTORS FOR CHILDHOOD OVERWEIGHT (CART ANALYSIS) 1079 among women with CVD history, supporting the advice to increase the amount of fruits, vegetables in diet. [74] The study of Larsson, Virtamo and Wolk 2012 , also based on data of the Swedish Mammography Cohort, found that dietary cholesterol was positively associated with risk of total stroke and cerebral infarction. No association with stroke was found with the intake of total fat, saturated fat, monounsaturated fat, polyunsaturated fat, -linolenic acid, and omega-6 PUFA. However, intake of long-chain omega-3 PUFAs, fats commonly found in marine and plant oils, were inversely associated with risk of stroke, suggesting a positive health eect of marine and vegetable diet. [75]
13.23.6
Vegetarian nutrition
Vegetarian nutrition may lead to undersupply of iron, proteins, calcium, vitamin D and vitamin B12. Iron can be got from wholemeal bread and green vegetable such as broccoli or kale (Brassica oleracea sabellica). Proteins are get from vegetables wholemeal bread, cereals, legumes, nuts, milk, cheese and yoghurt. Calcium, vitamin D and vitamin B12 can be supplied by milk and milk products. Calcium supplementation is usually found in vitamin and mineral supplement formulas as calcium hydrogen phosphate. Gadot Biochemical company, however, oers a citrate based calcium compound, designed to supplement liquid food products conveniently with a readily absorbable form of calcium. The company claims the product to be suitable for soy milk and other soy based products, rice milk and other dairy alternative beverages fortication. According to Gadot specication it is free of raw materials from bovine origin and any food allergens according to annex 3a of EU directive 2003/89. Although soymilk is recognized as a nutritious beverage, it contains much less calcium than cowmilk (20-30 mg/100 ml vs. 100-120 mg/100 ml), so fortication is essential. Potassium, the major intracellular cation in the body, is required for normal cellular function. Severe potassium deciency is characterized by hypokalemia. Moderate potassium deciency, which typically occurs without hypokalemia, is characterized by increased blood pressure, increased salt sensitivity, an increased risk of kidney stones, and increased bone turnover (as indicated by greater urinary calcium excretion and biochemical evidence of reduced bone formation and increased bone resorption). An inadequate intake of dietary potassium may also increase the risk of cardiovascular disease, particularly stroke. On the basis of available data, an Adequate Intake (AI) for potassium is set at 4.7 g (120 mmol)/day for all adults. This level of dietary intake (i.e., from foods) should maintain lower blood pressure levels, reduce the adverse eects of sodium chloride intake on blood pressure, reduce the risk of recurrent kidney stones, and
1080
possibly decrease bone loss. It is generally agreed that the bioavailability of Organic Calcium is much higher than Inorganic Calcium. From the litreature it appears that the bioavailability of Organic Calcium is 2 to 5 times higher than Calcium Carbonate. On the other hand, the various organic forms of calcium show more or less the same bioavailability with slight advantage to Calcium Citrate. In addition, potassium/calcium combination may enhance calcium absorption. GADOCAL K contains therefore 15 % calcium and 6 % potassium. [76]
13.23.7
Magnesium supplementation reduces risk of ischemic stroke [77]
Larsson, Orsini and Wolk, in a meta- analysis of 2011, report a modest but statistically signicant inverse association between magnesium intake and risk of stroke. The authors found that intake increment of 100 mg Mg/day came along with 8% reduction in risk of total stroke, reduction of risk of ischemic stroke was also denoted. Intracerebral hemorrhage or subarachnoid hemorrhage did not respond to an increased magnesium intake.
13.24
Salt intake and hypertension
He and Mac Gregor 2004 assessed the eect of the modest reduction in salt intake recommended by WHO 2003, SACN 2003 and Whelton 2002, and looked at the magnitude of the reduction in blood pressure in relation to the magnitude of the reduction in salt intake. The authors concluded that a modest and long-term reduction in population salt intake could reduce strokes, heart attacks, and heart failure, and there is a correlation between the magnitude of salt reduction and the magnitude of blood pressure reduction. They suggest a daily intake range of 3 to 12 g/day. [78] Heikki Karppanen and Eero Mervaala in 2006 wrote that the level of sodium is very high, whereas that of potassium, calcium, and magnesium is low compared with the level in diets composed of unprocessed natural foods, resulting in hypertension. The authors stress that reduction of salt intake, alone or in combination with increase of potassium, calcium, and magnesium, can lower average blood pressure levels substantially. [79] He, Marrero and MacGregor in a study in 2007 note that an increase of 1 g/day in salt intake was related to an increase of 0.4 mm Hg in systolic and 0.6 mm Hg in pulse pressure. Their study provides further support for a reduction in salt intake in children and adolescents. [80] Alderman commenting the study of He and colleagues 2007 point to the fact that measures of discretionary sodium use did not correlate with blood pressure, supporting the Cochrane
13.24. SALT INTAKE AND HYPERTENSION
1081
Collaboration conclusion that there was not sucient evidence for a general dietary recommendation to reduce sodium intake. Alderman writes that the ndings in adults are probably true for youngsters as well. However, lowering sodium intake increases sympathetic nerve activity, reduces insulin sensitivity, increases the activity of the renin-angiotensin system, and increases aldosterone secretion. The author of the comment asks the question if these or other changes occur in children. He calls for solid knowledge based on evidence of benet and risk preceding any clinical or public health intervention. The outcomes of such interventions should be tested in clinical trials to avoid harm. [81] He, Marrero and MacGregor reviewed the evidence that relates salt intake to blood pressure and cardiovascular disease. They concluded that reducing salt from the current intake of 10-12 g/day to the recommended level of 5-6 g/day will have a major eect on blood pressure and cardiovascular mortality. [82]
13.24.1
Salt reduction in general population may increase mortality up to 50%, new study says
[83] A new European study leaded by Dr Katarzyna Stolarz-Skrzypek questions benets of salt reduction of the diet in populations around the world. The study also denies the calculations which estimate savings of lives and healthcare costs promoting diet salt reduction. The authors looked at the long term relationship of 24-hour urinary sodium excretion to blood pressure and health outcomes, using data of the Flemish Study on Genes, Environment, and Health Outcomes (1985-2004) and the European Project on Genes in Hypertension (1999-2001).
13.24.2
Mortality 50% Higher in the Lowest Tertile of Sodium Excretion
The study reports that among 3681 participants during 7.9 years, cardiovascular deaths decreased across increasing tertiles of 24-hour sodium excretion, from 50 deaths in the low(mean 107 mmol) to 24 in the medium- (mean 168 mmol) and 10 in the high-excretion group (mean 260 mmol, resulting in respective death rates of 4.1%, 1.9%, and 0.8%. The authors say that it might not be right to impose a general reduction on sodium intake. They also support the theory that sodium restriction is meaningful for patients who already have hypertension and perhaps for patients with heart failure, but there are very few arguments showing that reducing salt intake in the general population would reCopyright 1998-2010 Karl H. Wilm. All rights reserved. OurFood Database of Food and Related Sciences
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sult in substantial benet, despite a very small rise in systolic blood pressure of 1.71 mm Hg for each 100-mmol increment in sodium intake, during the follow-up of 6.2 years. The authors suggest that the inverse association between lower sodium intake and higher cardiovascular mortality, stating that a salt intake low enough to decrease blood pressure also increases sympathetic nerve activity, decreases insulin sensitivity, activates the renin-angiotensin system, and stimulates aldosterone secretion.
13.24.3
Advocates of salt reduction
Dr Graham MacGregor, an expert on salt reduction and campaigner to reduce salt content in foods, presents doubts on the conclusions of the paper of Stolarz-Skrzypek and colleagues arguing that it presents severe methodological problems. Mac Gregor rearms that everything. He calls on the overall evidence in favour of salt reduction and the recommendations of the World Health Organization which to reduce salt intake as the next thing after tobacco reduction. [84] MacGregor argues that the reduction of salt by the amounts of actual recommendations does not increase sympathetic tone, there is a trivial increase in renin, and no adverse eects result.
Table 13.6: Salt recommendations Salt grams/day Current daily intake in Europe [85] Recommendations WHO Recommendation [86] SACN Recommendation [87] 8 - 11 Sodium grams/day 3-5
<5 5-6
< 2,5 2 - 2,5
13.24.4
World Action on Salt and Health (WASH)
[88] He, Jenner and Macgregor 2010 refer to the overwhelming evidence that our current high-salt intake is the major factor increasing blood pressure, a major cause of cardiovascular disease and kidney disease worldwide. Reducing salt intake to less than 5-6 g/day could prevent yearly millions of deaths. Reduction of salt added to foods, clear labelling on food products, and increasing public awareness of the harmful eects of salt on health were already implemented in Finnland and UK and are being followed by many developed countries. However, much must be done in developing countries where up to 80% of global blood pressure diseases occur. World Action on Salt and Health (WASH) promotes worldwide reduction of salt intake. [89]
13.24. SALT INTAKE AND HYPERTENSION
1083
13.24.5
Low birth weight is associated with salt sensitivity
[90] Dr Giacomo Simonetti and colleagues 2008 found that children aged between 7 and 15 who had low birth weights are more likely to be salt sensitive, have increased blood pressure with higher intakes of salt, than children of the same age with normal birth weights, and are more likely to develop hypertension, cardiovascular disease, and renal disease later in life. Salt sensitivity was present in 37% and 47% of all of the low birth weight and small for gestational age children, respectively, kidney length. The authors believe that that smaller kidneys leading to salt sensitivity is probably one reason of that. They recommend that low-birth-weight infants avoid a lifelong excessive salt intake. They stress that fast food may also be harmful to these persons. Infants with low birth weights frequently come from complicated pregnancies. A healthy lifestyle during pregnancy is therefore benecial for mother and newborn. They call for more studies on this subject.
13.24.6
Conversion salt and sodium
Sodium is responsible for elevated blood pressure, heart diseases and stroke. UK Food Standards Agency recommends not to eat more than 6g salt a day and provides a salt calculator at http://www.salt.gov.uk/how_much_is_6.shtml In 1994, the Committee on Medical Aspects of Food and Nutrition Policy (COMA) recommended reducing the average salt intake of the population from 9g to 6g a day because of the link between high salt intake and high blood pressure. National guidance regarding salt varies in Europe. Belgium recommends less than 8.75 grams a day. Portgual recommends less than 5g and countries such as Greece and Hungary advice people to avoid salt and foods rich in salt.
13.24.7
The WHO intake goal
It is less than 5g per day and is contained in the joint WHO/FAO report on diet, nutrition, and the prevention of chronic diseases. The Expert Reports specic recommendations on diet include limiting fat to between 15 and 30 percent of total daily energy intake and saturated fats to less than 10 percent of this total. Carbohydrates, the report suggests, should provide the bulk of energy requirements - between 55 and 75 percent of daily intake and free sugars should remain beneath 10 percent. Protein should make up a further 10-15 percent of calorie intake and salt should be restricted to less than 5 grams a day. Intake of fruit and vegetables should be plumped up to reach at least 400 grams a day. [91]
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Australia, New Zealand, Canada and U.S. have a guidance of less than 6g salt intake/day. Singapore recommends less than 5g/day and Japan has a guidance of less than 10g salt/day. Brazil has a guidance of less than 5g salt intake/day all other countries of South America have no guidance on this matter, remaining a lot of work to be done by WHO to convince these countries to tackle the problem of salt-reduction.
13.24.8
Consensus Action on Salt and Health
This organization urges consumers to boycott foods that contain either more than 1.25g of salt (0.5g of sodium) per 100g or more than 2.4g of salt per serving, forcing manufacturers to reformulate excessively salty foods. World Action on Salt and Health (WASH) was established in 2005 and is a global group with the mission to improve the health of populations throughout the world by achieving a gradual reduction in salt intake. [92]
13.25
13.25.1
Salt reduction- Lower Sodium Intake Recommendations to Adults

USA
[93] According to the CDC actually about 70 percent of American adults fall into categories (African Americans, people over 40, and people with existing hypertension) of people who should consume no more than 1,500 mg of sodium per day. But to achieve recommended intakes, even most of the remaining 30 percent of adults should cut back, too. CDC says that the average sodium consumption for people aged 2 and over is about 3,400 mg per day. Recommended are a maximum of 2,300 mg daily for people who arent in the categories above. The Center for Science in the Public Interest notes that the 3,400-mg gure comes from a national survey that does not include salt added at the table or during home cooking and does not correct for the participants underreporting of foods eaten. Actual average consumption is probably closer to 4,000 mg. [94]
13.25.2
UK
[95] The Food Standards Agency has set a target of reducing the average salt consumption of adults to 6g a day by 2010. The Scientic Advisory Committee on Nutrition (SACN) also set lower recommended maximum levels of salt intake for babies and children for the rst time.
13.25. SALT REDUCTION- LOWER SODIUM INTAKE RECOMMENDATIONS TO ADULTS 1085
13.25.3
European Food Safety Authority
[96] Mean daily sodium intakes of populations in Europe range from about 3-5 g (about 8-11g salt) and are well in excess of dietary needs (about 1.5 g sodium/day in adults). The main source of sodium in the diet is from processed foods (about 70-75% of the total intake), with about 10-15% from naturally occurring sodium in unprocessed foods and about 10-15% from discretionary sodium added during cooking and at the table.
13.25.4
New uncertainty about benets of salt reduced diet
[97] Taylor et al.2011, reviewing dierent studies, grouped the patients into a group with normal blood pressure, a group with high blood pressure and a group diagnosed with heart failure and associated them with the nutritional habits of salt intake. The authors found no strong evidence of benet from salt reduction in the normal group and in the high blood pressure group, however, the group with congestive heart failure salt reduction increased the risk of death. The authors call for more studies on the eect of low salt diets and stress that there is need to conrm whether restriction of sodium is harmful for people with heart failure. However, the authors also say that consuming less salt could still be benecial to the health of people with both normal and high blood pressure. The salt intake limit of 6 g/day remains unchanged.
13.25.5
Salt fortied with iron and iodine to reduce micronutrients deciencies
[98] Researchers suggest iodine and iron fortication of salt to improve worldwide iron status in populations where fortication of other staple foods does not achieve the desired coverage [1]. Horton et al 2011 reports that iron deciency is one of the most widespread micronutrients deciencies worldwide, and is associated with health consequence and cognitive impairment. The authors suggests to fortify salt with iron and iodine at a level of 1 mg iron/g salt should provide 5 mg iron per day per person, depending on iodised salt consumption. Fortication of cereals may not be eective in developing countries because milling is often done in local mills. Double fortication of salt may be a little costlier as supplementing wheat. However it will reach the whole population, while wheat is not a major staple food.
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13.25.6
Malnutrition aects brain development, learning and behaviour
[99] According to Nevin and Scrimshaw 1998 the nutritional deciencies of protein-energy, iron, and iodine.may cause permanent adverse eects on learning and behaviour. The authors call for adequate protein-energy, iron, and iodine during the rst two years of life to improve the cognitive performance of children. Iron deciency aects irreversibly the brain enzymes involved in cognition and behaviour. Aside of deciency of protein-energy, iron, and iodine the authors also highlight insucient content of omega-3 fatty acids in cows milk and infant formulas. According to Melse-Boonstra A, Jaiswal 2010 iodine deciency during foetal development and early childhood is associated with cognitive impairment, this may be improved introducing maternal iodine supplementation. Iodine deciency in children can be detected measuring the thyroid-stimulating hormone in newborns and thyroglobulin in older children. Adequate salt iodisation will cover the requirements of infants and children as well as pregnant women. However, close monitoring remains essential. [100] The World Health Organization and the United Nations Childrens Fund aim the elimination of iodine deciency implementing universal salt supplementation. The organisations, however, recommend a complementary strategy of iodine supplements as a temporary measure when salt iodisation could not be implemented at high coverage, having in mind that universal salt iodisation should remain the primary strategy to eliminate iodine deciency. [101]
13.25.7
[102]
Claims
13.25.8
Low Sodium/Salt
A claim that a food is low in sodium/salt, and any claim likely to have the same meaning for the consumer, may only be made where the product contains no more than 0,12 g of sodium, or the equivalent value for salt, per 100 g or per 100 ml. For waters, other than natural mineral waters falling within the scope of Directive 80/777/EEC, this value should not exceed 2 mg of sodium per 100 ml.
13.25.9
Very Low Sodium/Salt
A claim that a food is very low in sodium/salt, and any claim likely to have the same meaning for the consumer, may only be made where the product contains no more than
13.25. SALT REDUCTION- LOWER SODIUM INTAKE RECOMMENDATIONS TO ADULTS 1087 0,04 g of sodium, or the equivalent value for salt, per 100 g or per 100 ml. This claim shall not be used for natural mineral waters and other waters.
13.25.10
Sodium-Free or Salt-Free
A claim that a food is sodium-free or salt-free, and any claim likely to have the same meaning for the consumer, may only be made where the product contains no more than 0,005 g of sodium, or the equivalent value for salt, per 100 g.
13.25.11
Labels
Sodium is usually listed in the nutritional information on food labels. If salt is listed, sodium chloride is meant.
13.25.12
Conversion Salt to sodium and sodium to salt
Salt = sodium X 2.5 Sodium = salt X 0,4 Conversion Potassium chloride and potassium Salt replacer Potassium chloride = potassium X 2 Potassium = potassium chloride X 0,5 Blends of KCl (potassium chloride), sugar, yeast extract, and avours are being developed to hide the bitterness of potassium chloride,with salty perception but does not work against the active yeast of a dough system.
Table 13.7: Daily Recommended Intakes of Fiber, Sodium, and Potassium by Age and Gender Gender/Age 1-3 y 4-8 y Female Male 9-13 y Female Male Fibre, g 19 25 25 26 31 Sodium, mg <1500 <1900 <1900 <2200 <2200 Potassium, mg 3000 3800 3800 4500 4500
1088 14-18 y Female Male
29 <2300 38 <2300
4700 4700
13.25.13
Complete low caloric servings
Low caloric serving "pro gur" are servings of 250 g of yoghurt enriched with vitamins, pineapple, cereals vitamins and minerals. The servings are to small to avoid hunger. Articial sweetener are used not being in consent to an organic food. The amount of cereals should be increased. the avouring of the product is very intensive turning it very soon to be felt awful. Intensive avouring should always be avoided in products which are supposed to be used over a long time. It is advisable to go back to the recommendations of the health departments and associations like the DGE in order to reduce or to avoid overweight: 1.- Increase the amount of vegetables and fruits. 2.- Reduce fat 3.- Eat sh 4.- Practice sport to burn excessive calories. These recommendations lead to normal weight without synthetic modied foods. The main goal which Nestl tries to achieve with "progur" is to boost sails taking out sails from drugstores where low caloric ready servings are well sold. However even there these servings have proven to bring no success on lasting weight reduction.
13.25.14
Low fat nutrition
[103] Low fat nutrition has proved to be suitable to reduce body weight. The Ernrungsphychologische Forschungsstelle in Gttingen[103] (Nutrition Psychology Research Center in Gttingen) has made a study related to body weight reducing diet changing from high fat to low fat nutrition. High fat sausages and cheese types were exchanged by low fat foods. Milk and yoghurt with 1,5 % fat were taken in the nutrition plan. Whipped-cream gateau was exchanged with fruit tart with a bottom of yeast pastry. Foods based on carbohydrates such as vegetables and fruits were unlimited allowed. The result of this study was successful. In 8 weeks weight reduction of 1,5 up to 2,9 Kg took place. This nutrition should be used to body weight reduction instead of pills or special foods which cannot be consumed a whole life. The low fat nutrition keeping the old nutrition habits can be followed for an unlimited period. It is therefore an alternative to the reduction diets which can be followed only during short time ending in the jo-jo eect.
13.25. SALT REDUCTION- LOWER SODIUM INTAKE RECOMMENDATIONS TO ADULTS 1089
13.25.15
Two-part drink to promote satiety
[104] Pelkman and colleagues designed a two-part beverage (a solution of alginate-pectine and a solution of calcium) producing a stable, high-bre gel in the stomach, thereby avoiding adverse palatability of the highly viscous bre. The drinks were administered twice a daily. A signicant reduction in food intake was observed. According to the authors the gel delays the absorption of nutrients stimulating the formation of incretins, which are gastrointestinal hormones, like glucagon-like peptide-1 (GLP-1) and gastric inhibitory peptide (GIP), that cause an increase in the amount of insulin released from the beta cells of the islets of Langerhans after eating. They also slow the rate of absorption of nutrients into the blood stream by reducing gastric emptying and may directly reduce food intake. [105] The authors concluded that foods designed to enhance satiety may be an eective adjunctive therapy for weight loss and call for more studies on this subject.
13.25.16
Salt intake, Recommendations of the American Heart Association
[106] According to the American Heart Association physicians recommend keeping salt intake below 2,300 milligrams sodium (mg)(one teaspoon of salt) per day. For people with heart failure, recommended sodium intake is no more than 2,000 mg per day. Sodium is present not alone in salt also in sodium alginate, sodium sulte, sodium caseinate, disodium phosphate, sodium benzoate, sodium hydroxide, monosodium glutamate, sodium citrate and other ingredients. High salt intake is the major reason of raising blood pressure, responsible for strokes and heart attacks. Current intake in Europe varies between 10 and 15 grams/day,WHO which recommends no more than 5 grams of salt intake per day for every adult in the world. The Consensus Action on Salt and Health, together with the UKs Specialist Advisory Committee on Nutrition, which advises the FSA, say that consumers should reduce their consumption to 6g a day. About 80 per cent of salt is consumed through the consumption of processed food. Salt makes the product cheap, tasteless food edible, and more water to products can be added because it acts as a binder.
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Robert Speiser, director of EuSalt, however, says that there is scientic evidence to suggest that reducing salt may not necessarily be in the interests of all consumers. He says that two recent studies that concluded that there was no need to reduce salt among healthy people were neglected by regulators. According to Speiser the UK Food Standards Agency (FSA) is the only ocial authority to propose a signposting initiative that says it is necessary to reduce salt. The scientic evidence for this doesnt exist. Salt intake should remain determined by the needs of the individual. The National Health and Nutrition Examination Surveys ( NHANES)1960 to 1994 shows that the intake of fat in percent has decreased but the average body weight has increased. This was caused by a steady increase of all other components of food. The NHANES paper shows that lowering fat intake lowers total cholesterol, lowers low density lipoprotein (LDL) cholesterol, reducing cardiovascular risks, but it also reduces the high density lipoprotein (HDL) cholesterol, increasing cardiovascular risk if it drops below 35 mg/decilitre. Trevor Smith says that a blanket condemnation of saturated fats is unwise. [107]. It has been shown by Scott Grundy that stearates (saturated fatty acids) does not raise blood cholesterol.[108] Lowering fat intake often lowers HDL cholesterol. According to Trevor Smith it is sucient to limit the fat intake to an average of one gram per kilogram of body weight, or target body weight per day. There is no need to count calories having a normal balanced diet. In addition one should limit animal fat intake avoid hydrogenated fats entirely, pefer olive and rapeseed oil, increase the consumption of fruits, vegetables, whole grains and prevention of excessive weight increasing physical activity like walking three miles a day at least ve days a week, or an hour a day [109].
13.25.17
Salt consumption
[110] The UK Food Standards Agency recommends for adults not to eat more than 6 gram salt a day. The daily recommended maximum for children depends on their age: 1 to 3 years - 2 g salt a day (0.8g sodium) 4 to 6 years - 3g salt a day (1.2g sodium) 7 to 10 years - 5g salt a day (2g sodium) 11 and over - 6g salt a day (2.5g sodium) These are the recommended maximums for children. It is better for them to have less. The Agency advises to look at the nutritional information on the label: High salted foods have 1.25g salt or more per 100g (0.5g sodium or more per 100g). Low salted foods have 0.25g salt or less per 100g (0.1g sodium or less per 100g The FSA classies foods between high and low, as moderate salted foods.
13.26. MEDITERRANEAN DIET
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13.25.18
Salt calculator
http://www.salt.gov.uk/salt_calculator.shtml
13.25.19
Nutritional habits
According to FSA, the taste buds get used to high levels of salt and may not notice the saltiness of some foods. Getting used to eating less salt the taste buds become more sensitive and can nd out how salty foods taste which had been considered as not salty before. Eating foods with less salt one gets used to this nutritional habit and they will become more tasty because lots of salt can hide more subtle avours. If children have too much salt, this could aect their health and give them a taste for salty food, being more likely to continue eating too much salt when they grow up. [111]
13.26
13.26.1
Mediterranean diet
Bone protective eect of Mediterranean diet and olive oil in the (PREDIMED) study
Consumption of a Mediterranean diet enriched with olive oil for two years is associated with increased serum osteocalcin and procollagen I N-terminal propeptide (P1NP) concentrations which are indicators of healthy bones, says a study of Fernndez-Real et al 2012. [112] The Prevencin con Dieta Mediterrnea (PREDIMED) study monitored men aged 55 to 80 years over 2 years divided in three groups: a low-fat control diet, a Mediterranean diet enriched with nuts, or a Mediterranean diet enriched with virgin olive oil. The traditional Mediterranean diet, rich in fruits and vegetables, with a high intake of olives and olive oil presented high blood levels of osteocalcin and P1NP. The authors stress that along bone protection, osteocalcin also increase insulin secretion, which may be helpful to reduce the risk of age-related diabetes.
13.26.2
Mediterranean diet and kidney function [113]
The eects of the Mediterranean diet on kidney was studied in a cohort of the PREDIMED (Prevencin con Dieta Mediterrnea) Study, estimating glomerular ltration rate and urinary albumin-creatinine ratio. Participants were assigned to a Mediterranean diet supplemented with virgin olive oil, a Mediterranean diet supplemented with mixed nuts, or a control low-fat diet. After a 1-year intervention all 3 dietary approaches were associated with similar improved kidney functions. Daz-Lpez et al.2012 concluded that the Mediterranean diet does not
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provide benecial eect on kidneys over and above that of low-fat diet in 55 to 80 years old persons at high cardiovascular risk.
13.26.3
Mediterranean population change from healthy traditional Mediterranean diet to unhealthy diets high in meat and fast foods
[114] According to a paper of the FAO, compiled by Josef Schmidhuber, the Mediterranean population is shifting from their traditional healthy diets, rich in cereals, fruits, vegetables, nuts, whole grains, sh and olive oil, to diets with more meat, saturated fats and timesaving processed foods. Studies say that the Mediterranean diet has benets for arthritis, Alzheimer s disease, hearth health and blood pressure, diabetes, asthma, lung disease, and allergies. Schmidhuber studied the compliance of the diets in relation to protein, total lipids, fatty acids, carbohydrates, total dietary bre, sugar, cholesterol, sodium chloride/sodium, and fruits and vegetables in the period of 1961 to 2003 compared with the recommendations of the WHO/FAO. The author blames the European agricultural policies as one of the main culprits, generating not only high costs for consumers and taxpayers when subsidies are paid to farmers, but even higher costs when consumers and taxpayers have to bear the health burden of over-consumption encouraged by these subsidies. The diet has become too fat, too salty and too sweet, calories rising by 20 per cent from 2960 kcal to 3340 kcal in the last 40 years for Europe and even by 40 per cent in the countries around the Mediterraean Sea. Spain had the highest shift to fatty foods from 25 percent of fat to 40 percent of the diet. Schmidhuber also stresses that in general the rise in supermarkets, changes in food distribution systems, and calorie needs declining as people lead more sedentary lifestyles are factors of the dietary shift in Europe. More women have jobs outside the home and convenience foods are preferred. Non-EU Mediterranean countries adhere to diets higher in carbohydrates. Egypt is cited with a diet of 400 g of glycaemic carbohydrates per person per day.
13.26.4
The Nicotera Diet as reference of the Italian Mediterranean diet
[115] Nicotera is a small town in the Calabria Region in Southern Italy which was selected as
13.26. MEDITERRANEAN DIET
1093
reference of Mediterranean diet studies. The population of Nicotera has a high consumption of virgin olive olive oil, legumes, vegetables, cereals and sh. Little meat, eggs, Cheese and milk are consumed and men drink red wine moderately. A very low myocardial infarction of 4 cases out of 598 examined in 1957 in men was reported, together with only few cases of hypertension, overweight and obesity. Similar ndings were observed in another study of 1960 at Corfu. The Nicotera Diet is rich in: Bread, Cereals, legumes, potatoes, vegetables, fresh fruit, nuts, sh, wine, vegetable oils-especially virgin olive oil). Milk, cheese, meat, eggs, animal fat and margarines, sweet beverages, cakes/pies/cookies, sugar are sparingly consumed in the Mediterranean diet.
13.26.5
Italian Mediterranean Diet reduces cardiovascular diseases risk factor and the progression of renal diseases
[116] De Lorenzo and colleagues 20101 compared the eects of the Italian Mediterranean Diet, consisting of organic versus conventional foods in a healthy individuals and in Chronic Kidney Disease (CKD) patients in order to decrease cardiovascular diseases risk factor and the progression of renal diseases. The body composition and biochemical parameters after 14 days of Italian Mediterranean Organic Diet, according to the "Nicotera diet" were measured. The authors report improvements in the levels tHcy, phosphorus, microalbuminuria levels and cardiovascular diseases risk in healthy individuals and in CDK patients.
13.26.6
Fatty foods reduce physical endurance and brain function
[117] Murray and colleagues 2009 found that high fat diet was detrimental for physical endurance capacity and cognitive functions in rats. The authors argue that fatty acid oxidation is less ecient than glucose oxidation. This can inuence the endurance capacity. Rats fed with a diet of 55 per cent calories from fat for nine days could run 50 per cent less far, and made more mistakes on a cognition test than animals fed a standard diet of 7.5 percent calories from fat. The authors found increased levels of a specic protein called the "uncoupling protein" in the muscle and heart cells of the high-fat diet-fed rats, uncoupling the process of burning food stus for energy in the cells reducing thus the eciency of the heart and muscles.
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Heart size in the high-fat diet-fed animals were increased. Skeletal muscle UCP3 expression was altered. This aects energy production and physical performance. The authors stress that an optimal nutrition could improve athletes performance. Food producers should reformulate their high-fat products.
13.26.7
The position of AHA
[118] The American Heart Association (AHA) commenting the study said that the outdated 2000 AHA guidelines had been used for the low-fat diet. The Association stresses that dietary fat restriction at 30% of calories is no longer part of the AHA guidelines 2005. The saturated-fat content has been reduced from 10% to 7% and the cholesterol content from 300 to 200 mg/day. The AHA does not support the Atkins diet. AHA remains rm in its proposition to reduce saturated fats stating that they raise LDL cholesterol. This is consistent with the National Cholesterol Education Program guidelines, the American Diabetes Association, and the US Department of Agriculture USDA. The American Diabetes Association stated in January 2008 that low-carbohydrate diets should be considered for a maximum of one year.
13.26.8
Fit for Live
The book "Fit for Life " describes a separation diet like that of Dr. Atkins. It gives an additional recommendation not to eat simultaneously products rich in proteins together with dietary bres.
13.26.9
Arguments against the diet of Dr. Atkins and the book "Fit for Live"
Traditional physiology does not agree with the diet of separation of Dr. Atkins. Meat does not have dietary bres. It is therefore necessary to eat meat together with vegetables and fruits. The bres absorb rests of digestion. Protein digestion starts in the stomach with chloridric acid, together with pepsin. In the intestines there are proteases such as produced by the pancreas and by the gall bladder. Important proteasesare: trypsin peptidase elastase ribonuclease and others. As the external layer of the intestines is also composed by proteins the danger of proteases to digest his own meat. Nature protects against an own digestion secreting a protective layer of mucus made of mucopolysaccharides . This is the origin of the denomination"mucous membrane" which is not attacked by proteases. Sometimes however particles of enzymes get through the mucus barrier. damaging mucous cells which can regenerate rapidly.With protein rich nutrition there are more proteolytic
13.27. OTHER LOW-CARBOHYDRATE DIETS
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enzymes secreted as in case which should of a normal nutrition. Fibres of vegetables, fruits and cereals absorb excesses of enzymes.Fibres also accelerates passage of not digestible material through the intestines. The diet of Dr. Hay advises the ingestion of proteins at night when the body rests permitting the enzymes to stay longer in the intestines. The danger of intestinal cancer and other gastric malfunctions are possible.
13.27
13.27.1
Other low-carbohydrate diets

Zone diet
The Zone Diet was developed by Barry Sears, a former researcher in biotechnology at the Massachusetts Institute of Technology. It is based on the control of insulin by balancing protein and carbohydrate at each meal (14). The American Heart Association notes that food must be eaten in required proportions of protein (40), fat (30), carbohydrates (30). Menues are not appealing. Vegetable portions are very large. Food is low in copper. Theories and long-term results are not validated. Couuld result in weight maintenance if carefully followed. [13]
13.27.2
Protein Power
The Protein Power diet was developed by Michael R. Eades, M.D., and Mary Dan Eades, M.D. The principle of Protein Power is the restriction of carbohydrates - in particular rened ones.[119] The American Heart Association notes that this diet is not practical for long term. Rigid rules must be observed. The diet is low in calcium, bre, pantothenic acid, copper, manganese. It has limited food choice and is not practical for long term. It is high in total fat and saturated fat. No long term, validated studies are published.[119]
13.27.3
Low-Carbohydrate diets, like the Atkins diet may reduce benecial gut bacteria
[120] Sylvia Duncan and colleagues 2007 found in a study that prolonged use of very lowcarbohydrate weight-loss diets may decreased concentrations of butyrate and butyrateproducing bacteria (mainly bidobacteria) in faeces. According to the authors butyrate production is determined by the content of fermentable carbohydrate in the diet. Other studies had found that butyrate stops cancer cells from growing, and so helps prevent colorectal cancer.
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The authors stress that plenty of sources of bre found in fruit and vegetables are important to provide the right sort of carbohydrates for the benecial bacteria if low carbohydrate diets are to be consumed for long periods of time. Other critics concerning this type of diet is the higher risk of clogged arteries and heart attack in the long-term.
13.27.4
Sugar Busters
[121] Sugar busters involves eating high bre vegetables and whole grains. Fruits are encouraged and discourages saturated fats and transfats. It is important to eat three regular meals daily. Moderation in portions size is most important. Exercise is also on the program. The American Heart Association notes that Sugar Buster eliminates many carbohydrate foods. Discourages eating fruit with meals. It is low in calcium, vitamin D, vitamin E, pantothenic acid, copper, potassium. [119]
13.27.5
Stillman Diet
[122] It is a severe form of ketogenic diet. Nothing is permitted if it is not mentioned in a list. The american Heart Association notes that Stillman diet is low in bre, vitamin A, thiamine, vitamin C, vitamin D, folate, pantothenic acid, calcium, copper, magnesium, manganese, potassium. There are no long-term, valid studies published. There are extreme limitations in food choice, and very little variety. [119]
13.27.6
Study comparing the Atkins, Zone, Ornish, and LEARN diets the A to Z Weight Loss Study recommends Atkins diet for weight loss
[123] [124] Gardner and colleagues 2007 compared Atkins, Zone, Ornish and LEARN weight-loss diets representing a spectrum of popular low to high carbohydrate intake for eects on weight loss and related risks. These diets have challenged recommendations advising a low-fat, high-carbohydrate diet for weight loss. The Atkins diet is the lowest in carbohydrate consumption of the other three groups: less than 20 grams of carbohydrates per day and increasing to 50 grams per day. The Zone dietis designed so that a persons daily calorie consumption is comprised of 40 percent carbohydrates, 30 percent protein, and 30 percent fat. The LEARN diet (Lifestyle, Exercise, Attitudes, Relationships, and Nutrition) instructs participants to get 55 to 60 percent of their calories from carbohydrates, and
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not more than 10 percent from saturated fat. This diet is based on the USDA food pyramid. The Ornish diets primary guideline states that participants should not get more than 10 percent of their calories from fat. The authors report weight loss was greater for women in the Atkins diet group compared with the other diet groups at 12 months: Atkins, -4.7 kg , Zone, -1.6 kg , LEARN, -2.6 kg , and Ornish, -2.2 kg. The metabolic eects of Atkins diet were comparable or more favourable than those found in the other diets. The researchers recommend a low-carbohydrate, high-protein, high-fat diet such as Atkins diet for weight loss. However, long-term eects and mechanisms are still unknown.
13.27.7
Ketosis and the ketogenic diet
[125] Elevated levels of ketones in the blood is called ketosis. It can occur during fasting, during a very high fat diet or during a long lasting deciency in carbohydrate supply. This is the principle of the ketogenic diet. Atkins diet, which is used basically as low-glycemic index diet, may also cause ketosis. There are three ketones formed under hunger (also called " ketone bodies"): acetoacetate, acetone and beta-hydroxybutyrate (BHBA). [126] The fatty acids with participation of glucagon are digested in the liver to ketone compounds in order to liberate the needed energy. This is to see in opposition to the formation of D-glucose from carbohydrates to liberate energy. Ketones are burned in muscle and other tissues. High levels of ketones in tissue reduce the pH level. This is called ketoacidosis. One ketone is acetone which may cross the blood/brain barrier and, if in high concentration, causes central nervous disorders. Deciency of insulin in diabetics may lead to ketosis. It seems that fasting or high fat diet known as ketogenic diet is appropriate to induce ketosis for medical treatment of a specic neurological disorder. It should not be used as a body weight reducing diet.
13.27.8
Triglycerides used in ketogenic diets
Medium-chain triglyceride ketogenic diet for adults is being suggested by Schi and colleagues. The researchers recommend a therapeutic trial of the ketogenic diet in intractable epilepsy for all ages. [127] Foods used in the diet include high - triglyceride dairy products (e.g., butter, cream), mayonnaise and peanut butter. Carbohydrates, found in bread and starches, are eliminated in the diet, and liquid and calorie intake are often restricted as well in order to aid ketone
1098 accumulation.
Dr. Richard Veech at NIH in a study, concludes that ketone bodies increase metabolic eciency, while decreasing production of free radicals, may treat neurological diseases such as Alzheimers and Parkinsons disease, and the heart and brain operate 25% more eciently using ketones as a source of energy. [128] [129]
13.27.9
Alternative sources of ketones to avoid high fat diet for Alzheimers and Parkinsons patients
[130] Richard Veech and colleagues (2000) found that the elevation of ketones may oer neuroprotection in the treatment or prevention of both Alzheimers disease, where therapy is lacking, and Parkinsons disease, where therapy with L-dopa is time limited. The researchers recommend alternative sources of ketones, produced biotechnologically to overcome the atherogenic potential of the high-fat ketogenic diet used in childhood epilepsy.
13.27.10
The Mayo diet
The Mayo diet has no connection with the famous Mayo-Clinic of USA. It is a protein rich and fat reduced diet (1.000 to 1.500 kcal) The diet includes 3 eggs every day, meat, fruits and vegetables. The diet is not well balanced. It is very high in cholesterol, and even for short time not suitable.
13.27.11 13.27.12
Ovo-lacto-vegetarian diets Bircher-Benner diet
It is the ovo-lacto-vegetarian diet from Dr. Max Bircher-Benner which according to Dr. Bircher-Benner Mobilizes the ability of self healing Stimulates the intestines Fresh vegetable food containing high energy of the sun contains only three meals
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13.27.13
The diet contains minimal amount of food
The diet contains lacto-vegetable food, at least 70% food of vegetable origin as muesli, fresh fruits, vegetable, salads, only moderate heat is used to prepare food. All ingredients should be of ecological origin. No potatoes and no sh is allowed The Birchner-Benner diet avoids meat and meat products being therefore low in animal fatty acids, cholesterol and purine. This is positive in case of gout, coronary diseases and disorder of the fatty acid metabolism. Like every lacto-vegetarian diet undersupply of iodine and iron can take place.
13.27.14
Evers diet from the physician Josev Evers
The Evers Diet was at rst developed to be applied in case of Multiple sclerosis. It is a moderate ovo-lacto-vegetarian diet with germinated cereals (containing high level of polyunsaturated fatty acids.) Ingredients should be of natural, unmodied origin. " Denaturated" food resulting from industrial processing was considered as being the reason for diseases of industrial era. The diet has dierent levels to be applied on dierent diseases: In case of disease only unheated vegetarian food, no potatoes are given. For convalescents low-fat meat, ground unheated meat, fresh sh and raw ham are given.
13.27.15
Comment
The ban of potatoes is unreasonable. Potatoes are low in calories, and dietary bres and vitamin rich. Ground, unheated meat is a danger to weak patients because of possible bacterial hazard.
13.27.16
Waerland diet, Waerland, Sweden
This diet was established to clean intestines, to balance acid and base metabolism. Regulate the intestinal ora. Useful bacteria from milk and plants are in confrontation with harmful bacteria from meat, eggs and sh. The diet has low amount of food. Raw vegetable meals are followed by cereals meals. Milk, fruits and vegetables are considered as alkaline food. Instructions about sleeping and working time are given. In the morning 1/2 litre of potato-vegetable soup is taken followed by warm bed rest lying on stomach. The Waerland diet cannot be explained. Meat, eggs and sh cannot be considered as harmful and many claims are not true.
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13.27.17
Danger of sudden changes of nutrition
Increasing Salads and other vegetables increase intake of certain vitamins like folate, vitamin A and K. Decreasing high caloric foods like dairy products, red meat, salad oil or eggs reduces intake of minerals such as calcium zinc and selenium, vitamin D, E, B12 and essential fatty acids.
13.27.18
Anthroposophical nutrition
[131] It was established by Rudolf Steiner. It should develop consciousness, to live in reconciliation with nature, nutrition as part of the holistic doctrine. Main recommendations are: Ovo-lacto-vegetable nutrition with low content of meat. Avoid potatoes as they destroy instinct and promote materialism. Ban of use of pressure cooking and frozen food as they are "enemies of life".
13.27.19
Comment
[132] [133] Many of the doctrines of anthroposophy cannot be followed. The ban of potatoes, pressure cooking and frozen food is not tenable.
13.27.20
Macrobiotic nutrition according M.Kushi
Macrobiotic nutrition was founded by G.Ohsawa, Japan. His nutrition was dangerous and some people died using this diet. In USA macrobiotic nutrition according Ohsawa was prohibited. M.Kushi modernized the content of macrobiotic nutrition. A short use of this nutrition is harmless. It is harmful and not indicated to be followed for a log period. Macrobiotic nutrition is a part of Zen-Buddhism a kind of philosophy of life. Life energy comes from vegetable nutrition, cereals in the highest form. Contrast from passive to active, from night to day, from feminine to masculine, is the principle of Yin and Yang which were transferred to food by Kushi. No milk, and milk products, no meat and tea are consumed.
13.28. NON-COMMUNICABLE DISEASES CAUSED BY IMPROPER DIET AND SEDENTARY LIFESTYLE 1101
13.28
Non-communicable diseases caused by improper diet and sedentary lifestyle
A non-communicable disease, or NCD, is a medical condition or disease which is noninfectious and non-transmissible between persons. They include autoimmune diseases, heart disease, stroke, many cancers, asthma, diabetes, chronic kidney disease, osteoporosis, Alzheimers disease, cataracts, and more. NCDs are distinguished only by their noninfectious cause, not necessarily by their duration. According to the World Health Organization (WHO) reports NCDs are the leading cause of mortality in the world, representing over 60% of all deaths. Out of the 35 million people who died from NCDs in 2005. The WHO, in its 2008-2013 Action plan for the global strategy for the prevention and control of non-communicable diseases, is focused on prevention and control of the four non-communicable diseases - cardiovascular diseases, diabetes, cancers and chronic respiratory diseases and the four shared risk factors - tobacco use, physical inactivity, unhealthy diets and the harmful use of alcohol. [134] In 2012 the WHO published new data on non-communicable diseases. According to these statistics largest proportion of NCD deaths is caused by cardiovascular disease (48%), followed by cancers (21%) and chronic respiratory diseases (12%). Diabetes is directly responsible for 3.5% of NCD deaths. Behavioural risk factors, including tobacco use, physical inactivity, unhealthy diet and the harmful use of alcohol, are estimated to be responsible for about 80% of coronary heart disease and cerebrovascular disease. The WHO stresses that behavioural risk factors are associated with four key metabolic and/or physiological changes - raised blood pressure, increased weight leading to obesity, hyperglycaemia and hyperlipidemia. The United Nations General Assembly passed a declaration in September 2011 delineating how to strengthen national capacities to address NCDs, reduce the risk factors, strengthen the health systems, and aiming to develop a global monitoring and recommendations for the prevention and control of NCDs through eective partnership. These actions are particularly focused on developing countries. [135]
13.28.1
The International Conference on Healthy Lifestyles and Non-communicable Diseases (NCDs) in the Arab World and the Middle East [136]
The conference was held on 9-12 September 2012 at the King Fahd Cultural Centre in Riyadh, Saudi Arabia. The conference aimed to create momentum for the implementation of the United Nations General Assembly Political Declaration on Prevention and Control of Non-communicable Diseases at the regional level. to strengthen political commitment for combating non-communicable diseases in the region.
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Cardiovascular disease (CVD) mortality is declining in developed countries, however, it is rather increasing in low and middle income countries. Tobacco, diet, alcohol and inactivity are the key factors. OFlaherty et al. 2012 stress the importance of population-wide policies, which could be eective and cost saving. [137] According to Poorolajal et al. 2012 the eight major causes of premature death in Hamadan Province, Iran, were non-communicable diseases, with ischemic heart diseases, cerebrovascular diseases, transport accidents, and intentional self-harm topping. The authors also stress the increasing role of non-communicable diseases in premature mortality. [138] Owen and Reisin 2012 points to the fact that the statistics of 2012 present a worldwide increases in obesity and metabolic syndrome, however, blood pressure rates have improved in wealthy nations and greatly increased in developing regions and particularly in Africa. The authors stress access to screening and treatment in the developed countries, and the rise of high sodium and low potassium processed foods in poorer nations. [139] Eeva Ollila writes that globalization transmitted the culture and behaviour with the noncommunicable diseases from North to South. Therefore, aside addressing infectious diseases the risk factors of non-communicable diseases and lifestyle risks in the countries of the South that cause disease, such as use or consumption of tobacco, alcohol, and unhealthy foods should not be neglected. [140]
13.29
The Jo-Jo eect reviewed
Two important studies recently reviewed the knowledge about the Jo-Jo eect, following a diet. These studies received much attention in 2007 following the eort to tackle the obesity problem in large parts of the population of developed countries. Rena Wing and James Hill of the University of Colorado started in 1994 "The National Weight-Control Register". [141] In Germany Joachim Westenhfer of the Hamburger Hochschule fr Angewandte Wissenschaften started years ago the "Lean Habits Study". [142]
13.29.1
The strategy
Both studies agreed with foregoing studies in the strategy to counter overweight: Reduction of intake of energy. Increase of energy
13.29. THE JO-JO EFFECT REVIEWED Overcome of the own psyche
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Only one of these three items may become a great help to reduce weight and keep it down, but using a bit of all three recommendations has the best chance to avoid Jo-Jo eect .
13.29.2
The physiology of overweight and Jo-Jo eect
The authors stress the fact that a variety of reasons account for overweight and a jo-jo eect following a diet. The body reacts to weight loss due to famine or diet with defence mechanisms such as increased hunger and reduced energy consume.This makes weightreduction and to keep it down so dicult, Thyroid gland The thyroid glad reduces the production of hormones as soon as the body weight diminishes. Some parts of the nervous system are also less active reducing thus the metabolism. Less calories are transformed. Adipous tissue The adipous tissue elaborates leptin, a compound which signalises the brain to increase the feeling of hunger, and the body temperature is slightly reduced, reducing thus the basal metabolism. Stomach The stomach produces ghrelin which is an hormone triggering hunger feeling in the brain. textbfPancreases The pancreases produces insulin which is reduced when the body weight falls. Less insulin brings the brain to increase appetite and reduces energy consumption. Muscle mass Body weight reduction is related with loss of muscle mass, this means that the overall consumption of calories is also reduced resulting again in weight gain. The studies clearly state that overweight is not bound to a genetic code, what is settled is the individual energy output. Seven strategies are recommended:
13.29.3
1 - Stay mobile
Sport and mobility during work reduces the risk of overweight. The main goal of sport and mobility is to keep, or build muscle mass. Walking, swimming or biking are recommended by the authors. Make sport of 30 minutes three times a week Dont use elevators. Use stairs instead of escalators. Use your bike or walk to your oce.
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13.29.4
2 - Never say "never"
Trying to avoid everything brings frustration the moment you make a small error. You may have a nice fatty dinner as long you compensate it the next day with vegetables or you insert an extra sport session.
13.29.5
3 - Dont loose the rhythm
Eat always at the same time. Take your time for your meals. Do not eat in a hurry. Do not miss your breakfast.
13.29.6
4 - Control is necessary
Weigh yourself once a day or at least once a week, so you can take countermeasures as soon as your weight rises.
13.29.7
5 - Be stingy with fat
You can do without butter, fatty cheese, heavy sauces and fatt pork. Instead of this you can eat vegetables and fruits instead.
13.29.8
6 - Fresh vegetables
You can eat as much vegetables and salad. as you wish. You get enough dietary bre and have a low calorie intake. Eat small portions of fruits spare with banana, raisins, grapes and dates.
13.29.9
7 - Join a weight club
You may feel strong in company of kindred spirit in a weight club. Avoid people who seduce you to eat the wrong foods.
13.29.10 13.29.11
Special nutrition Adventists of 7 Days
Nutrition of Adventists is reduced in proteins and may chose between 3 types: 1. Rigid vegetable nutrition (veganism) 2. Ovo-lacto-vegetable nutrition (approximately 50% of adventists follow this nutrition) 3. Conventional nutrition low in meat, avoiding completely the intake of pork and his derivatives, molluscs and blood. Every meal should have many grains of cereals, fruits and vegetables. Strong spices
13.29. THE JO-JO EFFECT REVIEWED
1105
are avoided, Old cheese and spicy cheese such as roquefort as well as alcoholic beverages or caeine are not allowed. There are only three meals each day without any coee break. It is interesting that there is a smaller number of cancer of adventists and Mormons as found in other groups. There is no doubt that the dierent nutrition of adventists and Mormons is one important factor of lower cancer rate.
13.29.12
Batiste
They have moderate meals and negation of alcohol.
13.29.13
Buddhists
Nutrition generally veganic, no bulb vegetables are eaten(onions, garlic etc). Ban of alcohol and caeine.
13.29.14
Hare Krishnas
Vegetarian nutrition, raw meals. Veganic nutrition is seldom followed. Ban of alcohol and caeine.
13.29.15
Hindus
1. Lower castes: Mixed nutrition with little meat, sheep, lamb, goats, pork, chicken and sh. Bovine and bualo meat are not eaten 2. High castes (Brahmans): Lacto-vegetal nutrition with exclusion of any kind of meat and sh, often exclusion of eggs. The nutrition avoids bulb vegetables (onions, garlic and leek). Alcohol is forbidden.
13.29.16
Mormons
Mormons are moderate in nutrition. They eat fruits and vegetables and have a moderate consumption of meat. Such moderate nutrition is reduced in fat, albumin, cholesterol and purines. Vitamins and dietary bres are higher as found in normal nutrition. Mormons and adventists have lower cancer rate as other groups. There way of life and their nutrition seems to be the reason for favorable statistics.
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13.29.17
Jews
Jews try to avoid any kind of excesses. There are detailed rules concerning consume of meat. The animals are chosen and killed ritualistic by a butcher which is determined by the community. Bovine meat is permitted, as well as goats, lamb, poultry (excluding carnivorous birds) sh with scales and ns. Forbidden is pork, meat of horses, camels, rodents, carrion eating animals, bird of prey, eel, octopus, Crustacea, milk and eggs of forbidden animals, blood and meat with rests of blood, fatty acids from organs such as kidneys, sciatic nerve. Supply of meat and derivatives is made by communities. Milk and meat are not consumed together. Milk has to be taken immediately before meals containing meat, or 5 to 6 hours after. Milk substitutes of vegetable origin have no restriction. Milk and milk products in soups, margarine, ice cream and chocolate must always be taken in consideration. Food containing milk are to be kept and handled separated from food containing meat and their derivatives. This refers also to utensils such as pots, knifes, forks and spoons, plates, napkin have to be used only for one type of food. Dish washing of both types of food must be separately. Fish, eggs and vegetable food can be consumed together with meat. There is no restriction. During Passah (the Jewish eastern) unleavened bread is eaten.
13.29.18
Kosher Foods
The food scares in Europe and in US shows a great need of further food quality control through ocial governmental ruled authorities. Industry and retail service are engaged in a catastrophic price war in the struggle for might and power. That is why the level of assessment between good and evil in the practice of business world is being lowered and gives chances to outlaw practices in food industry. In this struggle ethics are put aside, unfortunately also by governments such as the case of BSE meat being forced to be sold in the European Community by directives of the Commission of the European Community. It is that why US consumer starts to buy kosher foods in the hope to get food produced under strictly controlled environmental technologies. In US the market of kosher food is growing by over 10% each year and even over 40% of all grocery items are kosher certied in the Northeast America. Religion is not the only motivation for these customers. Over 60 % of kosher food buyers are not Jewish. Muslims, Seventh Day Adventists, vegetarians, people with specic allergies and consumer seeking extra quality look for food labelled as kosher[143].
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13.29.19
What is Kosher Food ?
Kosher means "t" and is regarded as prepared in accordance with Jewish food laws. The laws are biblical in origin coming from the ve books of the Bible. Interpretation and extentions were made by rabbits in order to include new foods and new processes such as new technologies.
13.29.20
Slavery of desires and emancipation of animal inclinations an the role of moral laws such as kosher dietary laws
[144] Rabbi Grunfeld wrote in 1972 an essay about why Jews follow kosher dietary laws: "Holiness or self sanctication is a moral term; it is identical with moral freedom or moral autonomy. Its aim is the complete self-mastery of man." "To the supercial observer it seems that men who do not obey the law are freer than law-abiding men because they can follow their own inclinations. In reality however, such men are subject to the most cruel bondage; they are slaves of their own instincts, impulses and desires. The rst step towards emancipation from the tyranny of animal inclination in man is , therefore, a voluntary submission to the moral law. The constraint of law is the beginning of human freedom...Thus the fundamental idea of Jewish ethics, holiness, is inseparably connected with the idea of law; and the dietary laws occupy a central position in that system of moral discipline which is the basis of all Jewish laws." "The three strongest natural instincts in man are the impulses of food, sex, and acquisition. Judaism does not aim at the destruction of these impulses but at their control and indeed their sanctication. It is the law which spiritualises their instincts and transgures them into legitimate joys of life."
13.29.21
Certication of kosher food
In USA an organization makes an audit on the production line of the food which is going to be certied as kosher. Ingredients and technology is examined in order to see if it is in accordance to the Jewish law. With a contract the producer signs an obligation to avoid any change. European certication is done by a rabbi which visits the plant. He alone decides if the product is kosher. There is no contract being made and the company can therefore change its produce after the rabbi has gone. This is a matter of ethics. A good company will maintain the rules imposed by the rabbi. Bad ethics will follow the way which is the best to it. In London the Beth Din companyis specialized in certication of kosher food plants all over Europe.
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13.29.22
Kosher laws
Jewish religion laws are the basis of kosher laws. It seems that the rules based on the Old Testament of the Holy Bible developed from experiences such as diseases coming from pork which was contaminated by Trichinella spiralis. Eating pork with trichinosis could cause disease thus proving that pigs were impure animals.
13.29.23
Kashrus
The Kashrus magazine lists foods and ingredients which are certied as kosher, as well all kosher certication agencies of the world down to single Rabbis
13.29.24
Kosher Status Of Mars Products
[145] According London Beth Din Kashrut Division Announcements articles in the UK press in 2007 say that whey derived from animal rennet is contained in Masterfoods (Mars) confectionery. Whey can be a by product of cheese-making and animal rennet can be used in cheese manufacture. Since whey derived from this source contains only trace amounts of rennet, it is permitted according to halacha. There is therefore no problem with any of the Masterfoods (Mars) products that are currently on the London Beth Din approved list.
13.29.25 13.29.26
Kosher laws First law: Allowed animals
Allowed are mammals which chew their cud and have a split hoof. So cows are permitted. Pigs and horses are forbidden. Birds: Chicken, ducks and goose are allowed. Ostrich and Emu are forbidden. Fish: All sh with ns and easily removable scales ( without tearing the skin ) are allowed. Molluscs and crustaceans: This includes shrimps lobsters and oysters are forbidden, such as lard, chitin and porcine lipase. Ingredients: All ingredients derived from not kosher foods are forbidden. Ingredients such as gelatin, tallow or lard, chemicals derived from animal fat such as glycerol or monoglycerides are prohibited. Emulsiers such as used in the production of margarine containing mono and diglycerides are of great concern as their plant or animal origin are often unknown.
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13.29.27
Second law: Animal blood
Blood is considered to be a special uid inherent to life. Consumption is forbidden. Slaughter must be performed by a trained person in a way to eliminate the blood from the remaining meat. Slaughter must therefore follow a specic procedure. Heat, hot water and various acids to prevent microbial contamination are forbidden at this stage of processing. Inspection of the meat must guarantee that there are no specic defects. After that the meat is soaked and salted to remove last remains of blood. The second law does not apply to sh.
13.29.28
Third law: Separation of dairy products from meat products and equipment used
The third law says that all kosher foods, ingredients and equipment are classied in three categories: 1.- Dairy products 2.- Meat products 3.- Pareve: Here are included all vegetable foods sh, eggs and honey. Pareve food and their ingredients must be dairy free. People with allergies to milk and their derivates, allergies to egg proteins and vegan vegetarians welcome the third law as they can nd the separation of these three categories which are not being observed by any other food laws. Pareve may contain a certain amount of milk and their derivates as it is sometimes not to be avoided. This may be tolerated for religious purposes but should be kept in mind of those who are very sensitive.
13.29.29
Ingredients allowed for pareve foods
Agar-agar, Carrageen, dextrose, gum arabic (Acacia), lecithin Chocolate may also contain milk and milk derivates. The technical equipment used for milk chocolate must be cleaned carefully before producing pareve chocolate. European chocolate may have up to 5% of other fats than cocoa fat. These fats can be of vegetable and of animal origin.
13.29.30
Fourth law: Ban of leavened products made from grains of wheat, oats, rye, barley and spelt during the Passover week
Permitted is matzo which is a specically prepared unleavened bread, matzo meal and matzo cake our. Many baked products are available completely grain free giving persons with grain allergies such as coeliac disease to get foods which are free of certain allergens.
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13.29.31
Grain-like materials
Rabbis in Europe have extended the prohibition of the grain rules to other grain-like materials such as legumes, corn, rice mustard and sesame seeds. Sugar and corn syrup are avoided as ingredients of many products during Passover The third rule supports the theory that the deep roots of the Jewish religious laws regarding kosher foods were unconciously based on veterinary and epidemiological experiences which had summed over centuries under the classication " this is good and that is bad".
13.29.32
Kosher technology
The production and marketing of kosher food require: 1.- A reputable rabbinical supervision agency (or a single Rabbi in Europe) must be contacted. 2.- All ingredients are checked are included in the Kashrus. The equipment and their material must be examined to be kosher. There are restrictions on account of parts made of rubber ceramics and some plastics. 3.- All ingredients must be completely labelled on kosher food thus providing a complete information for sensitive people, whereas normal food regulation use class names and exceptions allowed to hide some of the ingredients.
13.29.33
Ingredients which require kosher supervision
Casein, emulsiers fats, fatty acids, lipids and whey.
13.30
Moslems
Mosque in Kuwait city

13.30. MOSLEMS
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13.30.1
Halaal food
Halaal food means permitted, allowed lawful or legal for Muslims. The opposite of Halaal is Haraam meaning prohibited, not allowed, unlawful, illegal. Halaal is a set of Islamic dietary laws guided by the Quran the Holy Book and the teachings of Allahs profet Muhammad, may peace and blessing be upon him. Nutrition of Muslims diers from one region to another. There is a strong negation of pork and his derivates, gelatine, meat of dogs, birds of prey, frogs and snails. Killing of animals are ritually. Alcohol is forbidden. Consume of blood is not allowed. The use of animal fat in baking is forbidden. Gelatine is not allowed. Exceptions are allowed only in emergencies. The rules for Halaal are very similar to those of kosher foods The most important rules for Halaal are: 1.- Meat must be slaughtered in a particular way. 2.- Only certain animal products are allowed 3.- Technological processing , like Processing aids, cleaning materials and equipment used in production must be free from prohibited food traces. These restrictions are based on the Quran (The revealed book)and Sunna The Islamic dietary laws which rule the production of Halaal foods is a religious matter which can be handled only by a Muslim expert. The Quran is the holy book of Muslims, being the last testament and revealed from God (Allah) as the Holly bible. The Quran says: Sura ve ( The table) ( Al - Maida ) verse 4 to 5. "(4) It is forbidden to eat: From which has died by himself, blood and meat of swine and of that by whose slaughter another name as Allah has been invoked, and of that which has been suocated dead by beating or which has fallen to death or which has been killed by the horns of other animals or have been killed by other wild animals, (except the animal which has been wounded by wild animal came to your hands still alive and you have nally killed it by yourself), and this what has been slaughtered in honour to wrong idols." Other quotations are: The Hadith (sayings of the last Prophet, Muhammad The gh (jurisprudence) of the Muslim Jurists Hana, Shai, Maliki and Hanbali. The Muslim Food Board ( UK ) is one company which investigates and certies Halaal foods.Heat, hot water and various acids to prevent microbial contamination are permitted. Technology and science has deeply changed production, ingredients and packaging enhancing shelf life, food colour and texture. Global spread of exotic foods and rapid changing of nutritional habits make it important to verify the lawfulness of food in compliance with the commands of the Islam. Muslims are allowed to eat food prepared by people who are of other beliefs ( 5:5) and Muslim food is permitted to be eaten by them, on condition that these foods are pure and permitted foods. (5:88). This permits an interchange and living together of Muslims with other groups all over the world. This is very important for the functioning of our global
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However some precautions should be made: Do not eat unless Allahs name has been taken and this (not taking Allahs name) practice is transgression (Quran 6:121) The Ahlul-kitaab of today are recognized by name, less faith. There is no guarantee that they take the name of Allah/God when slaughtering an animal. Furthermore, they cannot be anymore trusted in matters pertaining to Halaal/haram. Unless there is certainty that the Ahlul-kitaab read the Tasmiyah i.e. take the name of God when slaughtering an animal, only then the meat will be permissible. It was suggested that the Muslims in the U.S.A. and U.K. slaughter the animals themselves. This will make them independent from Christian/Jewish sources. The meat sold on the market such as supermarkets should be packed, sealed and stamped by a Muslim organisation consisting of reliable scholars and lama who have proper Islamic knowledge of the principles pertaining to Halaal/haram. Intoxicants, such as alcohol are forbidden because they are harmful substances.(2:219) (5:91) Consume of blood is not allowed. The use of animal fat in baking is forbidden. Exceptions are allowed only in emergencies, such as being forced by hunger, without intention to practice sin (2:175, 5:5) The classication of new foods and their ingredients in Halaal and haram, based on the commandments of the Qumran the Holy Book can only be done by an Muslim expert. The Islamic religion does not have a central religious head which dictates latest ndings but some authorities are accepted in their leadership, such as the mufti of the Al Azhar University of Cairo. Due to dierent translations of the Koran the local interpretation of its content diers from country to country. Some experts which can classify food as Halaal or haaram are: halalexplorer.com; muslimconsumergroup.com;somalitalk.com; Joe M. Regenstein, Cornell University, USA; M. Chaudri, IFANCA International: Masood Khawaja, The Halaal Food Authority.
13.31
Haram Food List of Dubai
Dubai Municipalitys food control department published a list of Haram foods for travellers to non-Islamic countries.
13.31.1 13.31.2
The Haram food list of Dubai Municipalitys food control department 2011 Pork
Animal fat Animal fat from an unspecied source Bacon Salted pork, cut from the back or side
13.31. HARAM FOOD LIST OF DUBAI Bath chap Pork from the lower cheek, on the bone Belly Pork cut from the underside of the animal Brawn Marinated pork Bone broth Soup containing meat of unspecied origin Fish ham A Japanese sh sausage made with pork fat Gel Gelatinous material of unspecied source Gammon Smoked pork thigh Ham Pork thigh meat Haslet a herbed pork meatloaf Lard Pork fat Lardine Margarine made with pork fat
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Margarine Vegetable oil with 10 per cent added animal fat of unspecied source Pepsin An enzyme extracted from animals - especially pigs - stomach Pepperoni Sausage made from unspecied meat Rasher A slice of bacon Renin An enzyme extracted from calves and pigs stomach Saveloy Pork frankfurters
13.31.3
Alkohol
Burgundy, Whiskey, Gin, Scotch, Beer, Rum, Bordeaux, Malt, Liqueur, Vodka, Mescal, Marc, Maraschino, Alcohol, Vin rouge, Vin blanc.
13.31.4
Haram ingredients
Any product or by-product (including any product used temporarily as a substitute) which contains any one or more of haram products in however minute quantity, whether as an ingredient or sub-ingredient or as a processing aid or as a releasing agent or as a glazing agent or as an additive or as a colour or in any other form, is haram.
Table 13.8: Halaal Ingredients -A-
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HALAAL INGREDIENTS -AAcacia gum E414 Ammonium carrageenan Acetic acid Ammonium chloride Adipic acid (acidulant) E355 Ammonium sulfate Agar E406 Amylase Algin/calcium alginat E404 Amylose
Antioxidants (BHA and BHT) Arachidonic acids Articial colour Ascorbic acid E300 Aspartame
Table 13.9: Halaal Ingredients -BHALAAL INGREDIENTS -BBaking soda BHT Butylated hydroxytoluene Benzoate of soda E211 Bird, exclude bird of prey Benzoic acid E210 Chicken, duck, turkey, goose BHA Butylated Hydroxyyanisole E320 Pigeon, dove, partridge, quail Table 13.10: Halaal Ingredients -CHALAAL INGREDIENTS -CCalciferol (Vitamin D3 ) Calcium acid phosphate Calcium carrageenan Calcium disodium EDTA Calcium carbonate Calcium propionate Calcium saccharin Calcium silicate
E321
Sparrow, emu Ostrich Butyric acid
Calcium sorbate Carbohydrates (natural) CMC Carboxymethylcellulose Carotenoid Carrageenen E282 Carrot oil E954 Carrageenin E552 Carotene
casein Cellulose E460 E466 Cellulose gum Cholecalciferol E407 Choline from yeast, soy corn meal,corn starch E407 Corn syrup E160a Cultures,living microbes
E203
Table 13.11: Halaal Ingredients -DHALAAL INGREDIENTS -DDextrin Dextrose Dicalcium phosphate
E1499
Diglyceride (plant) Dipotassium phosphate Disodium inosinate
Disacharides E631
Table 13.12: Halaal Ingredients -EHALAAL INGREDIENTS -E-
13.31. HARAM FOOD LIST OF DUBAI Erythorbic acid Ergocalciferol E315 Ergosterol Enzyme (plant)
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Table 13.13: Halaal Ingredients -FHALAAL INGREDIENTS -FFarina Fatty acids (plant) Ferric orthophosphate Ferrous gluconate
Ferrous sulfate Fibre Ficin E579
Fructose Fumaric acid E297 Fungal protease enzyme
Table 13.14: Halaal Ingredients -GHALAAL INGREDIENTS -GGalactose Gallic acid Gliadin/ Gluten Glucose
Glutamic acid Gum acacia Glyceride (plant)
Glyceerol/Glycerin (plant) Glycine, sodium salt (plant) Guar gum Gum arabic
E422 E640 E412 E414
Table 13.15: Halaal Ingredients -HHALAAL INGREDIENTS -HHemicellulose Hormones (plant)
Honey Horse meat (sometimes)
Hydrogenated oil Hydrolysed vegetal protein
Table 13.16: Halaal Ingredients -IHALAAL INGREDIENTS -IInulin Invertase
Invertase Iodine
Isopropyl citrate
Table 13.17: Halaal Ingredients -LHALAAL INGREDIENTS -LLactic acid (synthetic) Lactose
Lactostearia Leavenings
Lecithin (soy or plant) Lysin
E322
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Table 13.18: Halaal Ingredients -MHALAAL INGREDIENTS -MMalt Mannitol Malic acid E296 Mannosan Malt diastase Methionine Maltic acid Methylcellulose Maltodextrin Methylsilicone Maltose/ maltitol E965 Molases from Halaal source Monocalcium phosphate Monoglycerides (plant) E471 Monosaccharides E461 MSG (monosodium glutamate) E621
Table 13.19: Halaal Ingredients -OHALAAL INGREDIENTS -OOxalic acid Table 13.20: Halaal Ingredients -PHALAAL INGREDIENTS -PPABA(para-aminobenzoic acid) from plants Papain Partially hydrogenated vegetable oil Pectic material
Pectin E440 Potassium bromate Phospholipi (plant) Potassium citrate E332 Propionate Potassium phosphate E340 Propionik Acid Potassium sorbate E202 Propyl gallate Propyl gallate E310 Potassium benzoate E212 Propylene glycol E1520
Table 13.21: Halaal Ingredients -RHALAAL INGREDIENTS -RRoughage Table 13.22: Halaal Ingredients -SHALAAL INGREDIENTS -SSilicon dioxide Smoke avourings
E551
Sodium erythorbate Sodium hexametaphosphate
E318
Stannous chloride Sucrose
13.31. HARAM FOOD LIST OF DUBAI Sodium acid pyrophosphate Sodium alginate Sodium aluminum sulfate Sodium ascorbate Sodium benzoate Sodium bicarbonate sodium caseinate Sodium citrate
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E450 Sodium phosphate E401 Sodium propionate Sodium propionate E301 Sodium silicon aluminate E211 Sodium sorbate E500 Sodium sulte E469 Sorbic acid E331 Soybean lecithin
E339 Suet E281 Sulphur dioxide E220 E281 Sweetener (natural) Sodium bisulte E222 E201 Sodium caseinate E469 E221 Sorbitol E420 E200
Table 13.23: Halaal Ingredients -THALAAL INGREDIENTS -TTannic acid Tapioca
Tartaric acid From grape only,not from wine
E334
Titanium dioxide E171 Tricalcium phosphate
Table 13.24: Halaal Ingredients -VHALAAL INGREDIENTS -VVanilla acid, Vanillin
Vitamines Tablets (A, D, E, C Table 13.25: Halaal Ingredients -Z-
HALAAL INGREDIENTS -ZZinc
13.31.5
Vinegar produced from alcohol
Vinegar Fermentation is only permitted when vinegar as nal product is wanted. A rest of 0,5% alcohol is permitted.
13.31.6
Natural alcohol content of foodstus
Apple juice 0,2 Vol%. According to guidelines of the German book of foodstus a maximum of 0,3% are allowed for apple juice. [146] Grape juice 0,4%.The guidelines of the German book of foodstus allows a maximum of 1,0% of alcohol in grape juice because grapes are associated with plenty of yeasts inducing a natural fermantation. Ker original maximum2%
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Ker mild contains only traces of alcohol. Kombucha 0,5% Malt beverage maximum 0,5% Malt bier up to 4% Sauerkraut (choucroute) 0,5% Vinegar from 0,2 % to 1,5% Ripe bananas 0,6% Rye bread (0,3 %), white bread (0,2%)
13.32
Shubhah (Mushbooh)
Shubhah or Mushbooh means "suspected" and is applied for foods or drinks from which it is not known to be Halaal or haram. Shubhah or Mushbooh foods, being doubtful foods or drinks should not be consumed.
Table 13.26: Mushbooh Ingredients MUSHBOOH INGREDIENTS Acetic acid ester of MonoAlanine diglycerides (animal) E272a Beta-carotene, apocarotenal Bile salts using animal based gelatine Brilliant blue E133 Carcium stearoyl lactylate E482 Chelate Cholesterol Citric acid ester of MonoCobalamine Diglycerides (animal) E272c Coloring extract Cures Cystine Diglyceride (animal) Dissodium inosinate Dripping (animal) Enzyme (animal) Etoxylated mono-/diglyceride Folic acid Glyceride (animal) Glycerol stearates Glycogen Histamine Hormones (animal) Inositol Insulin Lactic acid ester of Monodiglyceride (animal) E272 Lactose made from whey which is produced from animal rennet
Animal fat Broth (animal) Charcoal (animal) Chymotrypsin Cochineal E120 Cystein Disodium guanilate EDTA Fatty acids(animal) Glycerol/glycerin Gum traganth E413 Hydrolysed animal protein Keratin Lipids
13.32. SHUBHAH (MUSHBOOH)
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Monoglycerides (animal)
Monopotassium tartarate E336i (tartar Cream) from wine Oxysterin Phenyl alanine Polysacharides-glycogen Polyunsaturated (animal)
Niacin
Oleic acid Pepsin (animal) Phosphoric acid E338 Polysorbate 80 E433
Para amino benzoic acid Phospholipid (animal) Polysorbate 60 E435 Propylene glycol alginate E405 Renin/rennet (unless it is of plant/microbial/synthetic origin) Saccharine E954 Sodium stearate(animal) Sodium nitrate E251 Sweetener-Saccharine Sunset yellow E110 Tartaric acid ester of Monodiglycerides (animal) E272d Tonic
Propylene glycol monostearate
Quinoline yellow E104 if animal glycerol is use
Riboavin Rum avour Shortening(animal) Sodium lauryl sulfate Sodium stearoyl-2-lactylate E481 Sorbitan monostearate E491 Sweetener-Aspartame Sweentener-Cyclamate Stearate Stearic acid Sucroglycerides E474 Tartaric acid E 334 from wine Thiamin
Tartazine E102 Trypsin
Table 13.27: Haram Ingredients HARAM INGREDIENTS Alcohol Animal shortening Carmin E120 Carnivorous animal (Lion,tiger, cheetah, dog, cat) Codeine
Animal fat Alcoholic beverages Bacon (pork) Boar CochinealCollagen (pork) Cider (alcohol) Cocaine
Fermented malt
Gelatin
1120 Lipase(animal origin) Monkey Rennet Snakes Wine
CHAPTER 13. DIETING AND DIETARY HABITS Kosher gelatin Pepsin (Hog) Sodium nitrite E250 Tallow Whey (unless the rennet used is plant/microbial/ synthetic l-cysteine (if from human hair) Pork Uric acid Vanilla extract (alcohol)
13.32.1
The consumer does not understand the meaning of Halal and Kosher foods.
[147] [148] According to a reports from Packaged Facts and from Mintel the majority of American consumers buy kosher and/or halal foods foods expecting higher quality and safety, compared with normal foods. They are not motivated by religious or ethnic reasons. The reports stress that these products present best marketing conditions exploring the kosher or the halal certication label inducing safety image. This may be deceiving for the consumer.
13.32.2
The big run on organic foods and Halal foods by EU supermarkets
[149] The run on the organic foods (Biofoods) initiated a heavy lobbying on EU legislation ruling this group of foods. The standards were alleviated to enable mass production, use of non-organic ingredients and airfreight, all of what is not accepted by original organic farmers. The marketing power of the big retailers were keen to establish organic departments, which boosted sales gures to levels beyond the capability of sustainable farms. Heavy carbon footprints result from transportation which did not correlate with the initial ideal of organic food. It is laudable that food industry, such as Haribo and retailers launched Gummi Bears candy in Germany with bovine gelatine excluding pork. Here again question arises about alleviation of standards to make it feasible for food industry. Were all animals from which gelatine derived slaughtered following Muslim rules? Other foods with Halal label are extremely complicated when enclosed in industrial management. According to Mahmoud Tatari of the European halal control and certication authority in Ruesselsheim, there are about 400 companies in Germany oering halal products on a market of 4 to 5 billion Euros disputed by food giants like Nestl, Langnese, Elb-Milch, Pfanni, Gruenland and Ehrmann, together with pharmaceuticals rms Bayer, BASF and
13.32. SHUBHAH (MUSHBOOH)
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Merck. The largest halal markets are in Malaysia, Indonesia, the Middle East, Germany, France and Britain. Nestl makes more money on halal products than on organic products, making 5 per cent of its revenue last year with halal products, such as drinks, dairy products and chocolate and has more than 300 halal products. Mahamoud Tatari calls on a principal of Islam: "everything that is fair, correct and good for humans" may be certied such as nancial services oered by banks and even telephone cards which comply with Muslim precepts may bear the halal label. Such thinking is being questioned as it transforms the culture and the believes which survived over centuries by incorporating them into the machinery of global business opening doors for alleviating the halal rules, so as happened with organic foods which now diers from its origin.
13.32.3
Understanding Kosher and Halal Food
[150] Both ethnic foods do not mean that safety or quality is better than normal foods. They dier from western food because they are manufactured according to religious believes. Their principles are not based on science, but on rules found in the Holy Bible and in the Holy Quran. - Ritual slaughter by cutting the throat of the animal. - Negation of pork. - Kosher foods forbid mixing dairy products and meat. - Alcohol is strictly forbidden for Halal, and vanilla is not allowed because it may be produced using alcohol extraction. Some liquor and wine are kosher if made only by Jews. Gelatine is forbidden because it may come from pork. Certication of Kosher and Halal food: Certication can be made by private entities and varies according to the religious expert who emits the label. In some cases HACCP enquiries are added to the certication procedure, but this is not an essential part of the meaning of Halal or Kosher. Complying with HACCP standards and hygiene requirements are demanded by food regulation such as the Article 21. FDA and every food must comply with them and is not a speciality of ethnic food.
13.32.4
Pork in doner kebab in Leipzig, Germany. European meat scandal oends religious feeling of Muslims
Europes horsemeat scandal may have its origin in Romania, French companies, Dutch and Cypriot brokers are entangled. Horsemeat is cheaper than beef reducing the price of food. Horsemeaat was sold as ground beef for the production of frozen lasagne. Draap Trading, a
1122
trader based at Cyprus organised the deal between Romania and France. The French rm Spanghero processed the horsemeat from a Romanian slaughterhouse and labelled it as beef. This ground meat was sold to Comigel which produces lasagna and other products. Romanian horses were in headlines in 2010 when the EU restricted their export because equine infectious anemia, or "Horse Aids". Horses were then killed at home instead with no health checks and disregarding welfare conditions of the animals. Pork in doner kebab [151] DNA testing across European countries found mislabeled products containing not only horsemeat, but also pork in doner kebab. The RTL-Magazin "Extra" assigned the Instituts fr Produktqualitt ifp in Berlin to perform DNA tests of dierent meat products. The Institute found up to 7% pork in doner kebab of kebab shops in Leipzig, Germany. Ali Kizilkaya, the chairman of the Islamic Council for Germany deplores the European meat scandal and specically the oence of the Muslim feelings with the use of pork in doner kebab. According to Kizilkaya the use of pork in doner kebab in Leipzig is an oence of the Muslim religious commandments. Kizilkaya asks the German government to guarantee safety of the consumer. The Islamic Council for Germany itself will improve controls for the award of the "Halal" label. [152] In Turkey GIMDES, which is an Halal-label award organisation, advocates the opinion that the the Turkish parliament should amend the constitution with an article which guarantees the consumer to be able to purchase foods which are in accordance to their religious believes. Dr. Hseyin Kami Bykzer, chairman of GIMDES, refers to a dispute between private Halal award label certiers and the Turkish Standards Body TSE related to Halal label. The TSE had not been conform with the fact that some private organisations awarded the Halal label without the approval of TSE, alleging to be the only legal institution to issue such awards. The turkey lacked a specic certifying system before TSE was founded. [153] Pork DNA found in Halal food of UK prison [154] The Ministry of Justice is suspending one of the suppliers of meat to prisons. The halal pies and pasties from halal certicated supplier was found to be contaminated with traces of non-halal meat. Under Islamic law, Muslims are strictly forbidden to eat pork, as is the consumption of meat which has not been slaughtered in a way that is prescribed under their dietary requirements. Authorities admit that it is distressing for Muslims to have food served in prison labelled as Halal.
13.33. PORK DETECTION IN MEAT PRODUCTS
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13.33
Pork detection in meat products
Meat for species identication became Due to complicated global trade of foods and religious believes, reliable and specic methods of species determination in a variety of food items are needed. During Ramadan 2012 Brazilian hot dogs mixed with pork meat and fat were sold by several restaurants in Kuwait before laboratory tests were completed, violating the law. Today several technologies are described, based on the determination of protein, DNA and the faty acids of products like sausages. The technology comprises Isoelectric focusing (IEF), immunoassays (Elisa, immunostrip). [155]
13.33.1
The Tanaka Easy Pork Detection kit [156]
Minuscule amounts of pork must be found because, even traces of pork are not admissible for Muslims. The Tanaka pork detection kit uses nano-choloidal gold in an immunochromatography system placed on a test strip in form of a thin layer.
The "Tanaka Precious Metals" detects even extreme small accidental contaminations of pork which may occur during production procedures. The kit uses colloidal gold nanoparticles suspended in liquid that provide visual immunochromatographic assays in just 15 minutes. (See detailed instructions at http://www.tanaka.co.jp/english/topics/pdf/topics_20100405_01.pd This method can screen a large number of samples and submit positive samples to conrmation by standard methods such as Polymerase Chain Reaction (PCR) or Enzyme-linked immunosorbent assay (ELISA) PCR and ELISA require special techniques and equipment. They are unsuitable for many food processors and dealers because of their complexity.
13.33.2
Polymerase Chain Reaction (PCR) detects 0,1% pork, horse and donkey meat in cooked sausages [157]
Polymerase Chain Reaction (PCR) involves the amplication of a single or few copies of a piece of DNA to generate thousands to millions copies of a particular DNA sequence through an enzymatic assembling of the nucleotides. Kesmen, Sahin and Yetim 2007 developed a species-specic PCR assay for the detection of low levels of Oligonucleotid primers were designed for amplication of species-specic mitochondrial DNA sequences detecting pork, horse and donkey meat in cooked sausages at 0.1% level. A common primer for PCR assays was designed on a DNA sequence in the mitochondrial 12S ribosomal RNA gene (rRNA), together with reverse primers for were beef, sheep, goat, and pork in raw and heat-treated meat mixtures. Rodrguez et al 2004 used agarose gel electrophoresis to separate the species-specic amplicons identifying the identity of meat samples. [158]
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13.33.3
Heat processing decreases detectable pork contamination [159]
PCR species determination and quantication are aected by baking and boiling of the beef, pork, and chicken. Such treatment decreases the detectable copy numbers of specic genes, varying according to the heating time and degree, write Sakalar et al 2012.
13.33.4
The TaqMan-based real-time PCR assay for pork determination [160]
Species identication and their quantication in raw and cooked meat products using specic primers and TaqMan probes were designed on the mitochondrial ND2, ND5 and ATP 6-8 genes for donkey, pork and horse was developed by Kesmen et al. 2009. No cross-reaction with bovine, ovine, chicken and turkey. However, it cross reacted with horse DNA. The TaqMan probe assay is being suggested by the authors as a rapid and sensitive method for the routine meat species identications studies in raw or cooked meat products.
13.33.5
ELISA (Enzyme-linked immunosorbent assay) [?]
Analytical methods involve the binding of a soluble antigen or antibody to a solid support (immunosorbent) with an enzyme label being used to the detecting antigen or antibody to convert a colourless substrate to a coloured soluble product in the solution, thus generating a detectable signal for the assay. Azmi 2007 compared PCR-RFLP and the utilization of mt cyt b and 12S rRNA gene with ELISA method in detecting pork and lard adulteration. ELISA was found to be a fast and reliable method, however, PCR-RFLP and specic PCR techniques werefound to perform better in detecting pork and lard adulteration in food products.
13.33.6
Direct analysis in real time (DART) ionization-mass spectrometryto detect admixed lard [161]
A combination of direct analysis in real time (DART) ionization coupled to time-of-ight mass spectrometry (TOFMS) and chemometrics was used for animal fat (lard and beef tallow) authentication. Vaclavik et al. 2012 report a reliable detection of admixed lard and tallow of 5 and 10% (w/w), respectively, giving rapid proling of triacylglycerols and polar compounds present in fat samples and their mixtures. DART-TOFMS proles of triglycerols could better distinguish between lard and beef tallow than the proles of polar compounds. In minced meat 10% of added pork can be detected.
13.33. PORK DETECTION IN MEAT PRODUCTS
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13.33.7
Fourier transform infrared (FTIR) spectroscopy may detect pork in meat balls [162]
According to Rohman et al. 201 describe the detection and quantication of pork in beef meatball in Indonesia using Fourier transform infrared (FTIR) spectroscopy and partial least square (PLS) calibration. The authors stress that FTIR spectroscopy can be used for the detection and quantication of pork in beef products for Halal verication purposes. Near infrared spectroscopy to detect fatty acids of pork [163] Near infrared spectroscopy is being proposed by Hu et al. 2009 as a rapid and nondestructive measurement of fatty acid composition in intramuscular fat of packed pork loin. Near infrared spectroscopy in interactance mode provided best results.
13.33.8
Important genetic determinism aecting fatty acid prole conrmed
Genetic determinism is the belief that genes, along with environmental conditions, determine morphological and behavioural phenotypes [164]. Cecchinato et al. 2012 investigated the potential application of near-infrared spectroscopy (NIRS) to predict intramuscular fat and fatty acid composition of individual meat samples. The authors also estimated the heritability of intramuscular fat and fatty acid NIRS-based predictions. The Bayes factor procedure was used to determine the statistical relevance of the genetic background of the predictions. Intramuscular fat content and FA predictions were analysed under a Bayesian univariate animal linear models, The greatest Bayesian factor was reached by the fatty acid C20:2. The authors support the ndings that nearinfrared spectroscopy (NIRS) can predict some fatty acids of meat. The existence of an important genetic determinism aecting fatty acid prole has been conrmed, suggesting that fatty acid composition of meat can be genetically modied. [165]
13.33.9
Inter-species dierences in the expression of myosin light chain (MLC) isoforms to identify pork meat
The Myosin Light Chains have a molecular weight of about 20 Kda. These smaller subunits of myosins bind near the head groups of Myosin Heavy Chains which have a molecular weight of about 230 kDa. [166] The inter-species dierences in the expression of myosin light chain (MLC) isoforms of meat dier in the molecular weight and pI of individual MLC isoforms (MLC1f, MLC2f and MLC3f). The authors stress that even MLCs with only 2% dierence in amino acid sequences have dierent electrophoretic mobilities, according to Montowska and Pospiech 2011. [167] No signicant modication by heat processing of meat products was found in frankfurters
1126
and sausages made from cattle, pig, chicken, turkey, duck and goose, according to the authors. No signicant proteolytic changes during meat ageing were found. Two-dimensional gel electrophoresis (2-DE) analyses were used with a detection threshold of 10%. The method might become interesting to identify these 6 species, however, the threshold must be eectively reduced. [168]
13.33.10
Muslims say Walkers Crisps Muslims are not Halaal
[169] UK Muslims are upset on Walkers crisps containing traces of alcohol. The Muslim Council of Britain says that consuming food with alcohol in it is not permitted by the Muslim faith. Walkers should make ingredients such as alcohol clear on the packaging. Walkers have stated that only a minimal amount of alcohol is used in some products to extract avour added to the crisps. The food industry, however should select avourings which were extracted by other methods as using alcohol. Such methods are for instance, supercritical carbon dioxide extraction. This is a way to keep the list of ingredients small and satisfy all consumers.
13.33.11
Flavour containing alcohol as a solvent
[170] According to Halapreneur some Islamic Scholars considered a non Halal food product if it is made with avour containing alcohol as a solvent. But the others considered it Halal because they said the small or large quantity of the product does not intoxicate a person. According to Masood Khawaja, of the Halal Food Authority labelling issues and alcohol avouring had been raised with Walkers before. He says that the company should have solved it instead of hiding behind labelling regulations, because it does not matter what percentage of alcohol is involved. Snacks that are likely to be boycotted by Muslims are Sensations Thai Sweet Chilli, Doritos Chilli Heat Wave and Quavers Cheese.
13.34
Ritual slaughter
The Sunna describes the ritual slaughter. All animals should be slaughtered according to this Islamic ritual with exception to animals shot during hunting. Ritual slaughter should be done invoking the name of Allah and cutting the throat, artery and gullet with one stroke of a sharp knife. The animal must be alive at the moment of slaughter in order to allow total bleeding because consumption of blood is forbidden. Blood is therefore used as meal for animal feeding or dried together with the content of stomach and intestines as agriculture fertilizer.(Buckenhskes et al.,1996][171] In Germany the Islamic ritual slaughter is not allowed (BVerwG,Urt from 15.06.1995-BVerwG 3 C
13.34. RITUAL SLAUGHTER
1127
31.93 German resolution against ritual slaughter without stunning). According German veterinary rules animals have to be made unconscious before bleeding. The University Al Azhar of Cairo has accepted stunning with electro shocks.This however is not according to the opinion of the majority of Moslems which consider such slaughter as haraam. [171]
13.34.1
Animal slaughter research
At the University of Hanover, Germany Professor Schultz and Dr. Hazim used Electroencephalograph (EEG) and electrocardiogram (ECG) to compare the pain caused by Islamic slaughter and western method using captive bolt stunning. According to both scientists the Halaal method caused no change in the graph of the EEG the rst 3 minutes after cutting the throat of the animal according to Islamic ritual. The next tree minutes showed a condition of deep sleep, followed by a zero level.The heart was still pumping and convulsion of the animal due to a reex of the spinal cord driving maximum quantity of blood out of the body. Islamic slaughter was therefore classied as humane and hygienic method. Western method by captive bolting stunning showed in the graph of the EEG signs of severe pain. The heart stopped beating retaining much blood in the body. The western method was therefore classied by the authors as unhumane and unhygienic for the consumer because of increased amount of blood being retained in meat. [172]
13.34.2
The shock overlays pain says a German veterinarian
[173] According to the German veterinary Dr. Wolfgang Lutz in 2002 islamic slaughter, without stunning, can be tolerated if it is performed professionally Dr. Lutz is a referee for meat hygiene at the German Butchers association (Deutschen Fleischerverband (DFV)). His opinion followed a verdict of the constitutional court of Germany which was criticised by animal welfarist. The judges from Karlsruhe ruled that German authorities may not as a general rule deny permission to Muslim butchers to perform ritual slaughter. The spokesman of the association DFV Christoph Silber-Bonz said "according to our perception professional slaughter cannot get along without stunning. We, however, recognise that there are religious communities and cultural circles, which have other traditions." he added that it was not up to his association to evaluate this. Dr. Lutz stressed that the German animal welfare act provides the exceptions which include religious reasons. The constitutional court had to clear that a petitioner could be included in the exception. The judges ruled as yes, and nothing else did happen in 2002. Referring to the uncertainty about the question of the animal having pain Dr. Lutz stated: "If the butcher knows what he does, if he slaughters accordingly to the rule, I believe that the pain at slaughter will be overlayed by the shock. "
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13.34.3
Physiologic reactions during the slaughter of cattle and sheep with and without stunning
[174] Kallweit and colleagues 1989 report two trials concerning reaction during slaughter of cattle and sheep: The rst trial tested the cortical activity of cattle and sheep using electrocorticogram (EcoG). Stunned animals had a shorter phase until the ECoG disappearsafter sticking, but had a prolonged time until disappearance of the EcoG signals between stunning and the cervical state. However, this could not be statistically conrmed, and the authors concluded that the dierent slaughter methods could be regarded equivalent. The second trial with adult cattle included an extended ECoG and measuring visually and somatosensorically evoked potentials. Captive-bolt stunning resulted in shorter intervals until disappearance of cortical activities, and variance was much lower compared with ritual slaughter. The authors stress that after captivebolt stunning absolutely no evoked potentials could be registrated, whereas these potentials lasted for 77 seconds (somatosensorically evoked potentials) and 55 seconds respectively (visually evoked potentials) after the ritual slaughter cut. A nervous conduction was measured up to 126 seconds in the extreme cases after ritual slaughter. The authors wrote that their results do not permit the conclusion whether or not pain sensitivity occurred in the animals.
13.34.4
Animal welfare slaughter regulation
[175] The animal welfare regulation on the slaughter of animals, existing only as a draft for the time being, is designed not only to transpose EC-legislation into national law but also to update and strengthen preconstitutional national legislation on this matter. For a wide area related to the slaughter or killing of animals, animal welfare requirements are put in concrete terms. Among the topics belonging to this area are the theoretical and practical knowledge of the personnel, the handling of animals before slaughter or killing, stunning, the control of its ecacy and the permessibility of certain stunning or killing methods. Not only livestock but also, for example, fur animals and sh are concerned. In practice it will take some eorts in order to attain compliance with the provisions of the animal welfare slaughter regulation.
13.35. RITUAL SLAUGHTER
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13.34.5
Status of law-making on animal welfare
[176] The Commission has introduced a directly operative animal welfare legislation by adopting EC Regulation 1/2005 [177] on the protection of animals during transport. Since the rst animal welfare conference of the International Oce of epizootics (OlE) in February 2004 in Paris, two very comprehensive codes on slaughter of animals and on animal transport were adopted.
13.34.6
Ritual slaughter in Brazil is found to be painful
[178] Roberto de Oliveira Roca 2002 cites the problem with the Jewish ritual of cattle slaughter in Brazil is the restraint system, which is not ecient, and does not takes into consideration that most of the cattle is Zebu, which is more excitable than European cattle. According to Oliveira Roca the restraint and crude throat-cutting cause severe stress in the animals slaughtered by the Kasher method. This is evident observing the reactions of the animal, which show front leg exure and contraction of the muscles of the face soon after throat cutting and hoisting, animals. For humane and safety reasons, slaughter plants performing Jewish slaughter must have modern equipment for vertical restraint. The practice of hoisting live cattle or sheep must be eliminated. Roca points to schemes and restraint equipment which are recommended by the American Society for the Prevention of Cruelty to Animals (ASPCA) . Recommended restraint cabinet: The apparatus consists of a narrow cabinet with a front opening for the animals head. After the animal enter the cabinet, a gate pushed it forward and an abdominal lifter is placed under the chest. The head is restrained by a face lifter, so the rabbi can cut the throat. The movement of the abdominal lifter must be restricted to 70 cm so that the animal is not lifted from the oor. The gate pushing the rear must be equipped with a separate pressure regulator, allowing the operator to regulate the pressure on the animal.
13.35
Ritual slaughter
The most important rules for Halal foods are: 1.- Meat must be slaughtered in a particular way. Zibah 2.- Only certain animal products are allowed. 3.- Technological processing , like processing aids, cleaning materials and equipment used in production must be free from prohibited food traces. The Islamic dietary laws which rule the production of foods is a religious matter which can be handled only by a Muslim expert. Animals should be slaughtered according to Islam ritual. Exceptions: animals shot during hunting and regulations for wild life.
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Rules for ritual slaughter -Licensed Muslim slaughterer should slaughter invocating the name of Allah. -The animal must be alive and healthy at the moment of slaughter. - Animal skin or fur or feathers must be clean prior to slaughter, free of faeces, mud or other unhygienic substances -Cut the throat, jugular vein, carotid artery and gullet with one stroke without damage of the the spinal cord stunning is not permitted - Flowing blood drain out by natural convulsion The major concern during ritual slaughter are the stressful and cruel methods of restraint (holding) used in some plants such as hanging live animals upside down. Devices to hold the animal in a comfortable, upright position should be used.
13.36
13.36.1
Mechanical slaughter
Mechanical transportation but manual slaughter
Chickens are transported to the place of slaughter through a conveyer belt and are manually slaughtered. If there is certainty that the chicken is alive and the Muslim slaughterer recites the name of Allah upon slaughtering, then the chicken is Halal. In this case, only the transportation is mechanical but the slaughtering is manual. This procedure is unanimously permissible and recommended.
13.36.2
Mechanical transportation and slaughter
Chickens are transported by means of the conveyer belt to the mechanical slaughter blade. Once the mechanical plant comes into operation, the blade also comes into operation and cuts the chicken. This procedure is not permissible.
13.36.3 13.36.4
Stunning Austria
Muslims must stun prior to slaughter. Exemption in some areas for Jews.
13.36.5
Belgium
Muslims must stun prior to slaughter. Exemption in some areas for Jews.
13.36. MECHANICAL SLAUGHTER
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13.36.6
Denmark
Exemption for Jewish slaughter, but have to stun cattle after the throat is cut. Muslims stun cattle with captive bolt pistol. Lambs, goats and poultry do not have to be stunned.
13.36.7
Finland
Animals must be stunned immediately after they have been cut.
13.36.8
France
Exemption from stunning
13.36.9
Germany
The Islamic ritual slaughter is not allowed (BVerwG,Urt from 15.06.1995-BVerwG 3 C 31.93 German resolution against ritual slaughter without stunning). According German veterinary rules animals have to be made unconscious before bleeding. Religiously slaughtered meat is only for consumption by local communities and cannot be exported.
13.36.10
Greece, Italy, Ireland, Luxembourg, Netherlands, Portugal and USA
Exemption from stunning.
13.36.11
Spain
All animals except goats and sheep have to be stunned before their throats are cut.
13.36.12
Sweden
l992 decision by the Swedish Board of Agriculture to uphold its ban on slaughter without stunning.
13.36.13
Norway
All animals must be stunned prior to slaughter.
13.36.14
Egypt
The University Al Azhar of Cairo has accepted stunning with electro shocks. This, however, is not in accordance with the opinion of the majority of Moslems which consider such slaughter as haram.
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13.36.15
European Union
The Council Directive 93/119/EEC lays down the standards for killing animals. It states that "on animal welfare grounds, stunning methods should render animals unconscious until death supervenes through bleeding."
13.36.16
United Kingdom
In the UK specically, the law is laid down in (The Welfare of Animals (Slaughter or Killing) Regulations 1995). All mainstream slaughter is supposed to involve stunning the animals before their throat is cut. The methods used are as follows with the main concerns as stated by the Scientic Veterinary Committee of the EU :These rules apply to all mainstream slaughter. In fact animals have had to be stunned before slaughter in the UK since 1919. Religious or ritual slaughter is exempt. When the cut is done correctly, the animal appears not to feel it. There are a lot of publications which underpin this armation and refuse the arguments of FAWC.
13.36.17
Switzerland
Religious slaughter is forbidden on conscious animals (except poultry).
13.36.18
Denmark
Muslims accept the stunning of cattle with the captive bolt pistol.
13.36.19
Finland
Religious slaughter is only permitted if the animals are stunned immediately after they have been cut.
13.36.20
New Zealand
is the worlds largest exporter of halal-slaughtered sheep meat. All sheep are given a head-only electrical stun. In promotional literature, the New Zealand Meat Producers Board says that, "the slaughter methods adopted have been favourably commented on by delegations from the Islamic Republic of Iran, Malaysia, Kingdom of Saudi Arabia, Kuwait, Egypt, Syria and Jordan."
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13.36.21 13.36.22
Mechanical Methods of stunning in mainstream slaughter Captive bolt
This stunning method is widely used for all farm animals and rabbits. Gun powder (cartridge), compressed air and spring under tension drive bolts through the skull of animals. Main EU concerns: in approx. 10% of cattle the bolt is not applied correctly; animals remain conscious or regain consciousness because the bolt is not applied at the right part of the head; unsuitable cartridges used.
13.36.23
Concussion stunning
A mechanically operated instrument delivers a blow to the brain and concusses the brain. Used for cattle, sheep, calves, rabbits.
13.36.24
Main EU concerns
"The prevalence of miss-stuns under abattoir conditions is a major concern." Animals are not stunned properly and so are often fully conscious when their throat is cut.
13.36.25
Free bullets
Used for animals dicult to handle such as wild pigs, bison, deer, horses or in emergencies. Main EU concerns: Shooting in the chest or neck causes severe pain and distress (animals are supposed to be shot in the head); wrong strength of bullet used for a particular species.
13.36.26 13.36.27
Gas stunning Carbon dioxide
Carbon dioxide is used to stun pigs in the UK and other EU countries. Pigs exposed to 90% CO2 die within approx. 5 minutes, but times vary and can be signicantly longer.
13.36.28
Carbon dioxide and argon
This gas mixture is used for stun/kill chickens and turkeys.

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13.36.29 13.36.30
Electrical stunning Head-only stunning
An electric current is applied to the head which is supposed to cause temporary loss of consciousness.
13.36.31
Cardiac arrest stunning
An electric current is either sent through the head and body at the same time to span the brain and heart or is sent though the head rst and then across the chest.
13.36.32
Proper positioning of electrodes in Electrical stunning
[179] Blackmore and Petersen 1981 studied the eects of electrical stunning and slaughter in New Zealand sheep and calves. The authors stressed that electrical stunning must induce cardiac dysfunction to avoid that sheep and lambs regain sensibility during slaughter. Both "head-to-back"and "headto-leg" methods produces cardiac inhibition. It is important that electrodes are properly positioned and sucient electrical current is applied, bacuse increase petechial haemorrhages in the fat of lamb carcases were noted in "head-to-leg" stunned animals when the forelegs were not in contact with the leg electrode.
13.36.33
Waterbath stunning
Used for poultry. Birds are shackled upside down on a moving conveyor which carries them to an electried water bath into which their heads are supposed to be immersed.
13.36.34
The Law
Muslims interpret these commands dierently. Some say that regarding:
13.36.35
Gassing strangulation
Are considered as cruel and unlawful in Islam, therefore chemical gassing should not be used as a stunning method.
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13.36.36
Concussion
Animals that die from a violent blow - that although this rule was intended to stop animals being killed by a stick etc., some Muslims argue that today it means that electrical stunning and the bolt pistol should not be used.
13.36.37
Captive bolt pistol, water bath
Animals that die from a fall - some Muslims have interpreted this command to mean that if an animal has died from concussion or drowning (as a cow falling in a well would be killed by drowning) it is forbidden. Therefore, they say, the captive bolt pistol or concussion stunner should not be used as it may cause the animal to die from concussion and killing chickens in electried water baths may be unlawful as it causes death "partly by drowning"
13.36.38 13.36.39
Legal or not legal: Electrical stunning, Islam experts interpretation Dr Abdel Aziz El Khayat, Dean of the Faculty of Islamic Law, University of Jordan
Some say it is legal so long as the animal is still alive when slaughtered and so long as the motive is to ease suering and quicken the process; others say it is forbidden because the shock can cause pain; quickens decay of the esh; causes haemorrhaging so diseases cant be checked for and may kill the animal outright.
13.36.40
Van de Wals and Warrinton
All stunning methods trigger a massive secretion of epinephrine.
13.36.41
New Zealand and Australia
New Zealand has developed an electrical stunning apparatus that met a Muslim standard. Head-only electric stunning prior to Muslim slaughter is used in almost all sheep slaughter plants in New Zealand and Australia.
13.36.42
Dr Ahmad Sakr, expert on Halal certication in USA
He says it is not Halal because of the eect electric shock has on blood drainage. Using electric shock means that all of the animals blood does not leave its body, because electric shock aects the central nervous system.
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Captive bolt stunning, Islam experts interpretation
13.36.43
Sheikh Aboul Yusr Abdin former Syrian Mufti
Many Muslims do believe (and many do not!) that stunning is permitted so long as the animal is killed by cutting the throat. It is more acceptable to stun cows to speed up throughput but much less so to stun smaller animals which are easier to handle.
13.36.44
Dr Abdel Aziz El Khayat
He says that most Muslims allow the captive bolt.
13.36.45
Australia, New Zealand and Ireland
Non-penetrating concussion stunning prior to slaughter has received approval from some Muslim authorities.
13.36.46
The Talmud
The Talmud contains an entire section on slaughter and the subsequent inspection of animals to ensure that they are religiously "clean". The text includes detailed anatomical information what is to be done during slaughter and the subsequent post-mortem inspection. The Jewish religious codes require that allowed animals be slaughtered by a specially trained Jewish male called "shochet" using a special knife, called the "chalef". While the Muslims allow any believing Muslim man or women, to slaughter allowed animals.
13.36.47
Halal slaughter of animals and birds in abattoirs
The abattoir or factory must be under the close and constant supervision of a Halal Certier. The premises, machinery and equipment must be cleansed according to Islamic Sharia (law) before any production takes place. The slaughterer must be a mature and pious Muslim of sound mind who understands fully the fundamentals and conditions relating to Halal slaughter and be approved by the religious authorities. Only acceptable live animals and birds can be slaughtered. The slaughter must be done manually using a stainless steel knife. Facilities must be available for rinsing the knife after each kill. The slaughterer must sever the respiratory tract, oesophagus and jugular vein.
13.36. MECHANICAL SLAUGHTER The animal must be completely dead before skinning takes place. Only Halal animals and birds are Halal Slaughtered.
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13.36.48
GCC Standard for islamic slaughter regulation for meat and poultry 2004
[180] The Governments of Bahrain, Kuwait, Oman, Qatar and the United Arab Emirates adopted this standard. The authors of the article stress, however, that the standard should not be confused with the regulations of the "Halal" certicate. Please read the Standard at: http://www.thepoultrysite.com/articles/186/
13.36.49
Halal slaughter in UK
[181] Londons Halal Food Authority says animals have to be fed as normal and given water prior to slaughter and one animal must not see the other being killed. The authority also says the "knife should be four times the size of the neck and razor sharp, and as far as possible the slaughterer and the animal should face Qibla or Mecca." The organisation does not ban animals from being stunned before their throats are slit, but the UKs Halal Monitoring Committee insists that slaughter must take place without stunning the animals.
13.36.50
Halal labelling in UK
[182] Halal and kosher meat should be labelled when it is put on sale so the public can decide whether they want to buy food from animals that have bled to death, the Food and Farming minister Lord Rooker says. His oce will enforce the negotiations to introduce a European-wide labelling system by 2010.
13.36.51
Halal slaughter in Germany
[183] Germany grantes Muslim butchers an exceptional permission for ritual slaughter. (English version) http://www.bundesverfassungsgericht.de/entscheidungen/rs20020115_1bvr178399en.html
13.36.52
Animal welfare at ritual slaughter in Germany, Berlin Meeting 2005
[184] Please see also the Meeting in Berlin 2005. There are some very interesting comments
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which are worth reading. The English part starts at page 61. http://www.erna-gra-stiftung.de/cms/download/tierschutz_bei_der_rituellen_schlachtung.pdf
13.36.53
EU labelling proposal for shechita (religious slaughter) will impact on the kosher meat industry
[185] In some religious practices such as Jewish (Shechita) and Muslim (Halal) slaughter, animals must be killed without stunning. New regulations voted by the European Parliament could mean that animal slaughtered in compliance with either Islamic or Jewish regulations would receive distinct labelling from animals not killed through religious slaughter. The European Parliament recently voted on an amendment to an EU Regulation which will require meat products derived from animals that have been slaughtered by shechita, to be labelled as "meat from slaughter without stunning". This would signicantly impact on the kosher meat industry in the UK and across Europe, imperilling its economic viability. Requiring Kosher meat to be labelled but not meat from animals which have been gassed, shot at, electrocuted or worse is quite simply, discrimination. Shechita UK has in place a professionally managed A lobbying campaign of the European Governments by Shechita UK Website and promotes a mailing campaign to UK MEPs to avoid such labelling The amendment, proposed by German Christian Democratic Union MEP, Renate Sommer, passed 326-270 with 68 abstentions. Whilst Shechitah - animal killed according to Jewish law - is not pre-stunned, there is variation within the Islamic community, with several abattoirs pre-stunning animals, albeit using a signicantly lower voltage to that of non religious slaughter.
13.36.54
The muslim reaction to the labelling proposal to religious slaughter
[186] Muslim MEPs see the new regulation to be discriminatory since only animals which are killed for meat using the Halal or Shechita method would require a special label when sold to consumers or sold onto the processed meat industry, while animals which are shot, gassed or stunned would not be labelled as such. The Halal Monitoring Committee (HMC), also condemns the labelling of non-stunned slaughtered foods as "discriminatory".
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However, the Halal Food Authority, who pre-stun animals before slaughter, supported the amendment, favouring the labelling of meat, poultry and other food stus not only to verify a halal status but also for the use of human consumption: to ensure the quality of food, hygiene and origin of country, and welcomes a distinction to be made when labelling halal meat which may or may not be pre-stunned. The proposed measures can only be implemented if supported by all 27 EU Agricultural Ministers, later this year. All forms of religious slaughter are banned in Switzerland, Sweden, Norway and Iceland. [187] The Directive 93/119/EC lays down certain requirements for the protection of animals at the time of slaughter and killing. Ritual slaughter must comply with this Directive and other Community public health, animal health and welfare requirements. [188] A report of the EFSA states that there is a high risk that animals feel extreme pain during the cutting of the throat. The Report adds (p. 22) that during the period when the animal, whose throat has been cut, is still conscious, serious welfare problems are highly likely to occur since the animal can feel anxiety, pain, distress and other suering. Without stunning, the time between cutting through the major blood vessels and insensibility, as deduced from behavioural and brain response, is up to 20 seconds in sheep, up to 25 seconds in pigs, up to 2 minutes in cattle, up to 150 seconds or more in poultry, and sometimes 15 minutes or more in sh. [188]
13.36.55
Religious slaughter controversy
[189] The issue was raised by animal protection organisations such as Compassion in World Farming (CIWF) who requested that slaughter without prior stunning should be stopped. The Federation of Veterinarians of Europe (FVE) also considered it an unacceptable practice. The European Livestock and Meat Trading Union (UECBV) supported the actual status quo and considered that a good decision on religious practices should be taken only at a political level as, if it is carried out in an abattoir, performed by trained personal and mechanical restraining always applied (cattle and sheep), it does not pose any particular problem from an animal welfare point of view. UECBV underlined its wish to avoid any discrimination between Halal and/or Kosher meat because any interdiction might be translated in possibilities to fuel illegal slaughter already existing in some Countries. Animal Attitude (AA) also mentioned the problem of meat from animals slaughtered without stunning entering in the normal channel of distribution (i.e. non-labelled as religiously slaughtered meat) and considered that such practice did not allow consumers to be properly informed.
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The National Secular Society submitted a paper to Defra on the 20. April 2009 regarding the Consultation on the proposal for a Council regulation on the protection of animals at the time of killing. The paper stresses that "in kosher meat production, the meat from the hindquarters and any deemed unt is rejected. As a result, to get sucient meat to satisfy the demand, a larger numbers of animals are slaughtered without pre-stunning than would be necessary if all carcases, and the entire carcase were acceptable. The consumption of certain parts of the animals hindquarters such as veins, lymphatic and sciatic nerve and its branches, is forbidden under Jewish law. To remove them is a specialised task and one which has not been practised in the UK since the 1930s. Consequently, all hindquarters are rejected as not Kosher, as are any carcasses which cannot be consumed as Kosher meat for other reasons (for example, damage to the carcass). A high proportion of the meat which is declared non-Kosher is therefore sold on the open market but is not labelled as meat from animals that have been slaughtered without pre-stunning." [190]
13.36.56
Halal and Kosher slaughter according to FAO
[191] Guidelines for Humane Handling, Transport and Slaughter of Livestoc: Religious or ritual slaughter (Halal and Kosher). http://www.fao.org/docrep/003/X6909E/x6909e00.HTM
13.36.57
Halal slaughter in Thailand
[192] Notication of the National Committee on Agricultural Commodity and Food Standards Subject: The Agricultural Commodity and Food Standard: Halal Food B.E.2550 (2007) http://www.halal.or.th/uploadles/std_halal_food%20Eng.pdf
13.36.58
Evaluation of religious slaughter
Evaluation of religious slaughter is being done on three basic elds: - Stressfulness of restraint methods. - Pain perception during the incision. - Latency of onset of complete insensibility.
13.36.59 13.36.60
Restraint Europe
The casting pen inverts cattle onto their backs, being more stressful than upright restraint devices. Cattle resist inversion and twist their necks in an attempt to right their heads.
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13.36.61
Weinberg casting pen
It is very stressful
13.36.62
Facomia pen
It is less stressful than Weinberg pen but upright restraint would be better.
13.36.63
US
poorly designed upright restraint boxes apply excessive pressure to the thoracic and neck areas of cattle.
13.36.64 13.36.65
Time to lose consciousness Sheep and goats
2 to 15 seconds
13.36.66
Cattle
immediately to 30 seconds. Calm cattle will usually collapse within 10 to 15 seconds.
13.36.67
Upright restraint
Good upright restraint equipment is available for low stress, comfortable restraint of sheep, calves and cattle According to Grandin excessive bending of the neck,should be avoided. For that, the bovines forehead should be parallel to the oor. This positions the throat properly for ritual slaughter and stretches the neck skin minimizing discomfort. A relaxed, calm animal has improved bleedout and a rapid onset of unconsciousness. Excited animals are more likely to have a slower bleedout. The use of a comfortable upright restraint device would be advantageous from a religious standpoint because rapid bleedout and maximum loss of blood.
13.36.68
Welfare aspects of slaughter
Many welfare concerns are centred on restraint, driven by their concerns about forceful immobilisation and clamping of cattle. Proper design and operation of restraint devices can alleviate most of these concerns with cattle and sheep. Restraint devices are used for holding animals both for ritual slaughter and for conventional slaughter where animals are stunned. The use of a head restraint will improve the accuracy
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of captive bolt stunning. In large beef slaughter plants without head restraint captive bolt stunning has a failure rate of 3 to 5, a second shot is required.
13.36.69 13.36.70
Technological processing Slaughter by machines
Several supermarket chains have sold chicken slaughtered by machines with Halal labelling. Consumers do not agree with that.
13.36.71
Product change on line
Changing between dierent products of the same category with meat and vegetarian products on a same line is cost intensive with regard to loss of product and o-production time cleaning and disinfection. Changing product without cleaning is practised in actual food industry. However, changing from meat product to a vegetarian one, haram meat and animal fat can contaminate this product
13.36.72
Ramadan, the fast-month
Consumption of food and beverages during daytime. There is only one meal right after sunset and one meal before sunrise. This rule is very dicult to be followed by hard workers, persons exposed to high temperatures and travelers.
13.36.73
Halaal (lawful) food product denition
The Muslim Food Board (U.K.) [171] gives the following denition of food for Moslems [171]: Halaal food is dened as any food product that is free from all of the following: Any product or by-product derived from: a) Pig b) Blood c) Carnivorous animals (except sh] d) Reptiles and insects e) Any marine animals except sh f) The bodies of dead animals g) The bodies of Halaal animals (i.e. Bualo, Cow, Sheep, Lamb, Goat, Deer, Rabbit, Chicken etc.) which are not slaughtered according to the Islamic Law. h) Wine,Ethyl Alcohol or Spirits, where these remain in their original chemical form. Vinegar, produced from alcohol.
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Fermentation is only permitted when vinegar as nal product is wanted. A rest of 0,5% alcohol in the vinegar is permitted. A natural content of alcohol in fruit juices is tolerated even by deep religious people [171]. Any product or by-product (including any product used temporarily as a substitute] which contains any one or more of the above products in however minute quantity, whether as an ingredient or sub-ingredient or as a processing aid or as a releasing agent or as a glazing agent or as an additive or as a color or in any other form, is Haraam (unlawful) for Muslims. Some examples of Halaal food products are as follow: 1. Milk (Cow, Sheep and Goats) 2. Honey 3. Eggs 4. Fish 5. Edible plants (including sea plants), which are not intoxicant 6. Edible fresh or naturally frozen vegetables 7. Edible fresh or dried fruits 8. Edible nuts like peanuts,cashew nuts, hazel nuts, Walnuts etc. 9. Edible grains such as wheat, rice, rye, barley, oats etc. 10.Edible condiments such as cardamom, clove, sage leaves, turmeric, chilli, curcumin etc. Some common examples of Haraam (unlawful,forbidden) food products are as follows: 1. Bone stocks or animal fats (e.g.: Lard, suet, dripping, gelatine, aspic, glycerol, stearates, stearic acid, proteins, amino acids, bone, charcoal, pepsin, animal renet etc. ) At the beginning of 1998 the Al Azhar University of Cairo redened gelatine as Halaal. According to the University of Cairo is gelatine a food ingredient which is so strongly hydrolysed that there is no connection left with the original pig. This new point of view is ocial granted but not everywhere accepted by all Moslems. The industrial use of gelatine should therefore be avoided. The Islamic religion does not have a central religious head which dictates latest ndings but some authorities are accepted in their leadership, such as the mufti of the Al Azhar University of Cairo. Due to dierent translations of the Koran the local interpretation of its content diers from country to country[171]. 2. Any additive or color derived from animals: E 120 Cochineal E 104 Quinoline yellow (if glycerol is used) E 153 Carbon black (if animal charcoal is used) E 471 Mono and diglycerides of fatty acids (if animal products is used) E 472 (a to e) Acetic ,lactic, citric, tartaric acid esters of mono and diglycerides of fatty
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E 474 Sucroglycerides (if animal product is used) E 476 Polyglycerol esters of polycondensated fatty acids of castor oil (if animal product is used) 3. Production of whey powder or whey solids using animal based rennet. 4. Lactose made from whey which is produced using animal rennet. 5. Lining of containers with animals or alcohol products as used in baking of bread, cakes etc. 6. Production of beta-carotene and apocarotenal using animal based gelatine. 7. Use of animal based glycerine as a coating for raisins or as a ower improver. 8. Vitamins A, D and beta-carotene which is protected in a matrix that do not conform to the above Halaal Food Production denition. The above are some examples of Halaal and Haraam food products,the list is by no means complete. 9.- Plants which can cause drug addiction and cause doping.[171] Not permitted foods are called Haraam. The hypothesis that certain kinds of food were forbidden because of hygienic reasons was made by Lck in 1966 and Saleh in 1972. This hypothesis is nowadays denied unanimously.It is believed that all rules have strict religious origin[171]. A food does not lose his halaal character when it proves to be allergic to a small part of the population. Toxic foods such as containing aatoxins are haraam because they are harmful [171]
13.36.74
Denition of Halaal Food according to the Codex Alimentarius second edition:Food labeling 1998(General Guidelines for use of the term "halal")
[193] Muslim halal dietary laws are found in the Qumramand the books of Hadith (the Traditions). Interpretation of these laws are made by Muslim scholars over the years to make an update to modern nutritional knowledge including new processes which are being used in modern technology.The basic principles of the Islamic laws should however not be altered. Because of the growing global Moslem population the committee of the Codex Alimentarius has set up rules for a global denition of Halaal Foods. According to the Codex Alimentarius are Halaal Foods those which are conforming with the Islamic laws. They do not contain anything which is forbidden by the Islamic laws. They were handled stored and free of any forbidden materials.During their production they were kept away from other food which are not conforming with Islamic laws. The processing or storage of halaal foods is allowed in the same room where not halaal food is being processed or stored when it is absolutely sure that any contact between both foods are avoided. It is allowed to prepare Halaal foods which equipments which have been used to prepare not halaal foods when cleaning of the equipment according to Islamic laws have been performed.
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13.36.75
Basic foods which are Halaal according to the Codex Alimentarius
All foods are considered as Halaal with exception of specic animal origin or containing products or derivates from not law conform origin.
13.36.76
Haraam animal food
Pigs and boars Dogs, snakes and monkeys Carnivorous animals with claws and tusks such as lions, tigers, bears, and similar animals. Birds of prey with talons, such as eagle, vulture and similar animals Pests like rats,centipedes, scorpions and similar animals. Animals which according to Islamic laws should not be killed such as ants, bees and woodpecker Repulsive animals such as lice,ies worms and similar animals Animals which can live on land and in water such as frogs, crocodiles and similar animals Mules and similar animals All poisonous and dangerous animals of the sea All animals which have been slaughtered disregarding the Islamic laws. Blood
13.36.77
Haraam vegetable foods
All poisonous and dangerous plants are considered as Haraam, unless the poison or the danger is being discarded during processing.
13.36.78
Haraam beverages
All alcoholic beverages are haraam as well all forms of poisoning and dangerous beverages.
13.36.79
Haraam additives
All additives which originate from the foods cited before are considered as Haraam.
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13.36.80
Halaal slaughter
All animals living on land according to Islamic laws should be slaughtered in accordance to the Islamic hygienic rules. The person who slaughters the animal should be of Islamic religion and should know the Islamic slaughter procedure. The animals which are to be slaughtered should be in conformity with the Islamic laws "The sentence Bismillah" (in the name of Allah) should be uttered immediately before the slaughter of every animal. The slaughter instruments should be sharp and not withdrawn from the animal during slaughter Slaughter should happen cutting the windpipe,the gullet and the most important veins and arteries in the neck.
13.36.81
Labeling of Halaal food according to the Codex Alimentarius
If Halaal characteristics are mentioned in relation to food the term " Halaal" should be declared on the label. Claims suggesting that Halaal foods are more nourishing or healthier than other foods should be avoided.
13.37
United global halal standards
[194] Calls for global standards covering the sale of halal products have been backed by businesses. Halal standards dier according to individual countries regulations. A single international agency issuing regulations would boost the halal market by unifying the existing system, say experts at the launch of the 5th Halal Expo in Dubai. According to Datuk Hajah Rohani Binti Haji Abdul Karim, the Malaysian minister for domestic trade and consumerism, informal talks with the Dubai Chamber of Commerce have shown that this idea would be of benet to everyone. Some countries have more than one halal regulatory body and sometimes there is confusion about the rules. Getting something similar to the ISO (International Organisation for Standardisation), rules and standards could be the same for everyone. Mrs Abdul Karim believes a number of bodies, such as the Organisation of the Islamic Conference (OIC) and the World Halal Forum, could handle this.
13.37. UNITED GLOBAL HALAL STANDARDS
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The global halal industry, which includes food, health services and cosmetics, is estimated to be worth US$2.1 trillion in Muslim countries alone. Malaysia has one of the toughest regimes regulating its domestic halal market, which is under one governing body. The annual global halal food market is worth $667 billion, accounts for 20 per cent of the international food industry and is growing by 16 per cent each year.
13.37.1
Halal skincare products
The industry of halal and vegan skincare products, including hand creams and hair products designed specically for women who wear the hijab encourage such global standards for healthcare products. The managing director of Medina Health Care products in the UK, Ms Hameed Ahmed, goes even one step ahead and suggests Dubai as headquarters because of its importance of trading hub.
13.37.2
Elements of halal regulations
Important elements of halal regulation cover preparation, ingredients used and storage, ensuring there is no risk of contamination with pork products. According to Christopher Tay, executive director of Bangi Kopitiam, a Malaysian coee-shop chain, halal is not just for Muslims, it is also for non-Muslims because a vital aspect is hygiene and cleanliness. Halal products are interesting also for non-Muslim countries because they go through stringent tests and checks to maintain safety. Anup Lodaya, a sales representative with Emirates Gourmet, an importer of halal confectionary, beverages and cereals based in Dubai, said a universal standard would reduce paperwork and red tape. Halal certication in one country doesnt mean it will be accepted in another. Every import undergoes checks with Dubai Municipality before they are allowed on the market. A unied international system would help speed up that process.
How to get forward with an international halal Standard The best road to a global guideline which all nations can accept is to continue the work on the "General Guidelines for Use of the Term Halal" of the Codex Alimentarius of the WHO and FAO of the United Nations. (Guideline CAC/GL24-1997 AVI-6) [193]. The Organisation of the Islamic Conference (OIC) and the World Halal Forum should use the Codex Guideline and develop an international Standard of quality control which standardizes quality checks at production sites.
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13.38
13.38.1
What is behind a brand

Halaal chocolate confectioneries
[195] Confectionery is commonly forbidden as ingredients as gelatin, enzymes and emulsiers are considered Mashbooh because he origin of the ingredients is not known. Tesco, however wants to introduce the Ummah Foods chocolate range, being free of animal fat. "Ummah" means "the Muslim community" Ummah Foods already supplies the Halaal orange and caramel chocolate bars to Islamic bookshops, newsagents and universities in UK in 2006. Launching his products among the Muslim population of East-London, Mr.Kahlid Sharif, director of Ummah Foods, believes that winning over the Muslim customer base, rather than targeting a broader "ethical" market, is the key to success. Mr. Sharif says "You cannot put a Muslim name on a product and not expect the core customers to be Muslim". With Tesco targeting the ethnic foods, changes this marketing strategy.
13.38.2
Qibla Cola
[195] The brand has a presence as far as England, Canada, Pakistan and Africa. Since Qibla is an Islamic word used to describe the direction in which Muslims face to pray, one could think that the cola is aimed at Muslims. However, according to the producer the target is everyone who wants to make a conscious decision to buy an ethical brand.
13.38.3
Quakers
Quakers dont have a set of rules about anything including nutrition. Their principle is moderation in all things.
13.38.4
Rosacrucis
Lacto-vegetable, renunciation of alcohol. Not to be mistaken by A.M.O.R.C. Antiquus Misticus Ordae Rosae Cruzis who smoke, drink alcohol, all forms of nutrition are allowed.
13.38.5
Sikhs
Meat of bovines and alcohol are not allowed.

13.39. CASTRATION OF ANIMALS WITHOUT ANAESTHESIA
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13.39
13.39.1
Castration of animals without anaesthesia

Young animals feel pain during castration
[196] Yearly 20 million young boars are castrated without anaesthesia in Germany, despite painless alternatives. Farmers hold the animals at their hind legs and cut out both testicles without closing the wound which has to heal on its own. The bloody procedure aims to avoid the production of the hormone androstenone in boars giving the typical boars smell of the meat which resembles urine. Several researchers try to determine how strong the pain is which the animals feel during the castration. The animal squeak continuously as soon they are captured. Analysing this squeaking showed that the animals, during the surgical procedure, emit longer cries which are of higher frequency than those before and after the castration. The veterinarian Susanne Zls from the Ludwig-Maximilians-University of Munich demonstrated that the concentration of the stress hormone cortisol rises signicantly in the serum of the animals during castration and remains high for hours. Animal castrated under anaesthesia presented cortisol concentrations which were similar to those of animals which were only kept immobilized by their hind legs for some minutes. Human medicine believed that newborns have not developed pain sensory structures, so pain feeling is less intense as adult people. Dr. Zls transferred this perception to veterinary science. Meanwhile this perception is not valid any more. And the German animal welfare law limited the piglet age for the castration without anaesthesia to the rst seven days of life.
13.39.2
Use of anaesthetics during castration
[197] The current German animal welfare law, had allowed male piglets be surgical castrated without anaesthesia up to four weeks of life. Since April 2006 piglets in Germany can only be castrated without anaesthesia in the rst 7 days of life. This surgical procedure is painful during and also after the operation, for newborn animals as well as for adults. Zls and colleagues in a study of 2006 found that the use of Meloxicam, a non-steroidal anti-inammatory drug, produced a signicant relieve of pain during and after the castration, measured on the levels of the stress hormone Cortisol in the blood serum, compared with animals castrated without anaesthetics. However Zls and colleagues in 2007 found that the use of local anaesthetics (Procaine Hydrochloride and Lidocaine Hydrochloride) used in castration of four to six day old male piglets is not justied as increase of the stress hormone cortisol was noted in animals which received the anaesthetics, compared
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with control groups without the medication. [198] Zls and colleagues also assessed the use of isourane-anesthesia together with Meloxicam during castration of piglets. Cortisol did rise signicantly in castrated animals with or without isofrlurane-anaesthesia, compared with untreated animals. However, a signicant lower cortisol level after castration was attained with administrating Meloxicam prior to castration. The authors concluded that isourane-anaesthesia does not reduce pain after castration, only Meloxicam showed palliative eect after the castration. [199]
13.39.3
England
England avoids castration slaughtering boars before reaching puberty.
13.39.4
Norway
Castration without anaesthesia is not allowed in Norway since 2002 and a total prohibition of piglet castration was introduced in 2009.
13.39.5
Switzerland
Also in Switzerland no castration of piglets are allowed without anaesthesia, beginning in 2009.
13.39.6
Improvac, the immune sterility
[200] South Africa and New Zealand decided against surgical castration. They slaughter the animals before they become mature. Australia opted in 1998 for the immune castration using Improvac which must be injected two times. Improvac is a vaccine against the Gonadotropin Releasing Hormone (GnRH), which is secreted by the hypothalamus and regulates the production of Androstenon in the testicles of the boar. The immune system of the boar, activated by Improvac, destroys the Gonadotropin Releasing Hormon and Androstenon cannot be produced. Pzer notes in its site that the practice of physical castration is not 100% eective in controlling boar taint: studies show that up to 3% of gilts and physical castrates can have detectable taint levels. Heavily soiled living conditions can promote high levels of the taint compound skatole in any pig, including gilts, young boars and castrates. The company also stresses that castrated pigs are less ecient than intact boars at converting feed into lean body. The use of Improvac is approved by the EU since May 2008.
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The Danish agrarian organisation Landbrug & Fodevarer refuse the use of Improvac, alleging that customers from abroad did not accept the meat from imune sterilised boars. [201]
13.39.7
PIGCAS, a project to collect informations on pig castration in the EU
[202] The overall objective of the project PIGCAS is to provide information on pig castration that will support EU policy. In general NGOs, and in a weaker way Government/Administration are against castration and in favour of natural state of the animals and veterinarians, producers (main stream) and slaughter plants in favour of castration. The PIGCAS reports the opinion of the European countries in relation to castration: United Kingdom, Greece and The Netherlands are clearly against castration. Portugal, Ireland and Finland are moderately against castration. Spain, France, Austria, Denmark, Sweden, Switzerland, Norway, Estonia, Eslovenia, Poland, Germany and Lithuania had an undecided position about castration. Finally Cyprus, Italy, Slovakia, Hungary, Belgium and Latvia can be considered moderately in favour of castration. Use of anaesthesia prior to castration is more accepted unanimously than castration without anaesthesia. Stakeholders consider altogether that consumers, instead of producers should support extra cost entailed by anaesthesia. The biologist Hanno Wrbel, from the University of Giessen, Germany, says that unfortunately our animal welfare ethic is an utilitarian ethic, weighing between the suerings of animals and the benets for humans. He also points to the fact that the German animal welfare law also permits to trim the tail of animals, to grind down the teeth, to amputate one toe of chickens, castration of cattle,
13.39.8
Dehorning
[203] Staord and Mellor 2005 write that dehorning and disbudding are painful procedures which trigger cortisol response to a rapid rise, declining to normal values after about 8 h. They are carried out on cattle to facilitate management. The authors conclude that cautery disbudding is preferable to amputation dehorning, but for optimal pain relief xylazine sedation, local anaesthesia and a NSAID should be used with both procedures. The American Veterinary Medical Association (AVMA) supports the combination of a local anesthetic and ketoprofen administered prior to scoop dehorning of 3-to 4-month-old calves. It virtually abolished the rise in plasma cortisol concentration routinely observed
1152
after dehorning. The association deplores that regulatory access and cost remain obstacles to practical application. The use of pharmaceuticals can burden producers in terms of both direct and indirect costs, such as time delays and a potential need for more veterinary assistance. [204]
13.39.9
Halal food, the Muslim food is big business, but Germany fear the wrath of animal rights groups
[205] Almost 100 tons/week of halal salami and sausages are being produced by Meemken in Gehlenberg/Germany [206]. International food companies such as Nestl and Unilever entered this market years ago. German food producers and retailer are getting interested in this business which promises new ways to make money in face of the actual economic crysis. The industry is looking for the market of a purchasing power of EUR 20 billion per year of Turkish descent in Germany, and global sales of halal foods are expected to reach USD 641 billion and in the EU USD 67 billion in 2010. In France, the Casino chain of supermarkets supplies halal meat products, Britain Tesco and Sainsburys and the Netto chain sells halal products from Meemken. Some German supermarkets hesitate to oer halal food because they fear to get into trouble with animal protection groups which do not agree with slaughter of animals which are not previously stunned. German poultry producer Wiesenhof has had its products certied as halal for year but is afraid to deter non-Muslim customers and does not label their product as halal. Halal certication depends on the certier some are more stringent that others, such as Mahmoud Tatari of Halal Control in Ruesselsheim/Germany. Halal Control certies small businesses. The association says that industrially processed meat cannot be halal, because the livestock must not suer stress or agony, which is not attainable in mass production. Mahmoud Tatari says that his standard is based on the four existing Sunni law schools, which comprises twelve professors of Islamic science. Halal Control gave eighty meat product on market which were labelled as halal to be analysed. Within this test 30 percent were found to be contaminated with DNA of swine. [207] The giants Nestl and Unilever are making good business. Nestl already earns more from halal products than it does from organic food. The company also produces icecream cone chocolate vanilla, a dicult product because vanilla is considered haram as it is often extracted using alcohol. [208] Industrial products range from cheese without animal enzymes to biscuits, herbs and coee ant others. It is important that producers use detergents that contain no alcohol to clean theier production line.
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13.39.10
Nutraceuticals
are foods which can provide protection and/or treatment of diseases.
13.39.11
Fast food, Snacks and Finger Food
are foods served in canteens, Bakery shops and snack bars having a great segment with classic sandwiches as a small meal and the "mediterranean range" like baguettes, croissants, pita bread and ciabatta.
13.39.12
Convenience Foods
[209] Searching for new market segments Convenience Foods was increasingly considered to have great future. Convenient shops should sell small packages, ready to eat snacks. They should include a coee serve, have a post counter, a copy machine and very important for Germany: a counter for Toto-Lotto bets. All trials to install such a chain of such stores in Germany have failed mainly because of regulations concerning store opening time. Convenience Foods however is being sold as frozen food ready to serve, frozen vegetables already seasoned, dierent frozen sh dishes. A growing importance have convenience foods for restaurants and fast food restaurants as well as food industry which uses processed raw ware. The trend of Convenience Foods lies not in new stores but to place these products together with standard packagings where the consumer can choose between dierent price and quality of products.
13.39.13
Mood Food? The eect of chocolate on people suering depression
[210] Golomb and colleagues 2010 studied the eect of chocolate on people suering depression. In this study mood was assessed using the Center for Epidemiologic Studies Depression Scale (CES-D) [211]. People with positive depression screen result CES-D score higher than 16 presented chocolate consumption of 8.4 servings of chocolate per month and major depression with CES-D score higher than 22 consumed 11.8 servings, compared with 5.4 servings per month consumed by not screening positive people. Increased caeine, fat, carbohydrate, or energy intake, could not be related with the mood symptoms detected in this study, and chocolate seemed to be the causative of a mood lift,
1154
a reason why people with higher CES-D scores eat more chocolate. However, the authors presented no evidence that chocolate had a sustained benet on mood. They call for studies to elucidate the chocolate-mood association and its role in depression as a cause or cure.
Bibliography
[1] Ernhrungsmedizin: hrsg von Hans-Konrad Biesalzki; Stuttgart: Thieme 1995; pg 188,219. [2] http://en.wikipedia.org/wiki/Body_Mass_Index. Wikipedia: Body mass index. [3] WHO/FAO: Population nutrient intake goals for preventing diet-related chronic diseases. ftp://ftp.fao.org/docrep/fao/005/ac911e/ac911e02.pdf. [4] http://www.cdc.gov/healthyweight/index.html. CDC: Healthy weight- Its not a diet, its a lifestyle. [5] http://www.fao.org/docrep/005/AC911E/AC911E00.HTM. Joint WHO/FAO Expert Consultation Diet, Nutrition and the Prevention of Chronic Diseases, 2003. [6] Teufel, Prof.Dr.,Vortrag , Hygiene-Forum 9.-10.3.1999 Behrs Hamburg. [7] Auch Fleisch im Vegetarieressen, Verbraucherberatung gibt Tips zum Einkaufen; Jeversches Wochenblatt 21.5.99, page 9. [8] Emmrich, Michael: Wider den blauen Dunst; Frankfurter Rundschau am Wochenende, 29.5.99. [9] Hamm, Prof. Dr. Michael: Schlank und gesund ohne Dit, Mosaik Verlaag Mnchen, 1997. [10] http://www.nwcr.ws/. The National Weight Control Registry. [11] Klem ML, Wing RR, McGuire MT, Seagle HM, Hill JO: A descriptive study of individuals successful at long-term maintenance of substantial weight loss.; AmJ. Clin Nutr. 1998 May, 67(5):946. [12] JC, Fry AG, Muesing R. et al. Eects of high-protein, low carbohydratedieting on plasma lipoproteins and body weight. J Am Diet Assoc. 1980;77:264-270. [13] http://www.circulationaha.org. Sachiko T. St. Jeor,PhD; Barbara V. Howard, PhD; T. Elaine Prewitt, RD, Dr.PH; Vicki Bovee, RD, MS; Terry Bazzarre, PhD; Robert H. Eckel, MD: Dietary Protein and Weight Reduction, A Statement for Heathcare Professionals From the Nutrition Committee of the Council on Nutrition, Physical Activity, and Metabolism of the American Heart Association. AHA Science Advisory. 1870-1874 Circulation October 9, 2001.
BIBLIOGRAPHY
1155
[14] Kraus RM, Eckel RH, Howard B, et al. AHA Dietary Guidelines: revision 2000: a statement for healthcare professionals from the Nutrition Committee of the American Heart Association. 2000:102:2284-2299. [15] Executive summary of the Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Pressure (Adult Treatment Panel III). JAMA. 2001:285:2486-2497. [16] http://content.nejm.org/cgi/content/abstract/359/3/229. Shai I, Schwarzfuchs D, Henkin Y, et al. Weight loss with a low-carbohydrate, Mediterranean, or low-fat diet. N Engl J Med. 2008;359:229-241. July 17, 2008. [17] DGE: Formula-Diten wenig sinnvoll, Gericht untersagt; Der Lebensmittelbrief,6. Jahrgang, Juli/August 1995 ; pp 159. [18] http://www.sciencedirect.com/science/journal/07493797. Jack F. Hollis and colleaguesof the Weight Loss Maintenance Trial Research Group: Weight Loss During the Intensive Intervention Phase of the Weight-Loss Maintenance Trial. American Journal of Preventive Medicine. Volume 35, Issue 2, Pages 118-126 (August 2008). [19] Wen CP, Wai JP, Tsai MK, Yang YC, Cheng TY, Lee MC, Chan HT, Tsao CK, Tsai SP, and Wu X. Minimum amount of physical activity for reduced mortality and extended life expectancy: a prospective cohort study. Lancet, 8 2011. http://www.thelancet.com/journals/lancet/article/PIIS0140-6736% 2811%2960749-6/abstract. [20] Ku PW, Fox KR, McKenna J, and PengTL. Prevalence of leisure-time physical activity in taiwanese adults: Results of four national surveys (2006), 20002004. Preventive Medicine, 43(6):454457, 12 2006. http://www.ncbi.nlm.nih.gov/pubmed/ 16808968. [21] Wai JP, Wen CP, Chan HT, Chiang PH, Tsai MK, Tsai SP, and Chang HY. Assessing physical activity in an asian country: low energy expenditure and exercise frequency among adults in taiwan. Asia Pac J Clin Nutr, 17(2):297308, 2008. http://www. ncbi.nlm.nih.gov/pubmed/18586652. [22] Ku PW, Fox KR, and Chen LJ. Physical activity and depressive symptoms in taiwanese older adults: a seven-year follow-up study. Prev Med, 48(3):2505, 3 2009. http://www.ncbi.nlm.nih.gov/pubmed/19297687. [23] The us department of health and human services physical activity guidelines for americans. http://www.health.gov/paguidelines/guidelines/default.aspx. [24] http://www.ajcn.org/cgi/content/full/69/6/1351S#R1. James R Marshall and Zhao Chen: Diet and health risk: risk patterns and disease-specic associations; American Journal of Clinical Nutrition, Vol. 69, No. 6, 1351S-1356S, June 1999.
1156
[25] http://www.aerzteblatt.de/int/article.asp?id=63968. Mller, Dieter; Weinmann, W; Hermanns-Clausen, M: Chinese Slimming Capsules Containing Sibutramine Over The Internet-A Case Series. Dtsch Arztebl Int 2009; 106(13): 218-22 DOI: 10.3238/arztebl.2009.0218. [26] http://en.wikipedia.org/wiki/Sibutramine. Wikipedia: Sibutramine. [27] http://www.fda.gov/bbs/topics/NEWS/2008/NEW01933.html. U.S. Food and Drug Administration (22 December 2008). FDA warns consumers about tainted weight loss pills. Press release. [28] http://www.fda.gov/cder/consumerinfo/weight_loss_products.htm. U.S. Food and Drug Administration: Consumer directed questions and answers about FDAs initiative against contaminated weight loss products U.S. Food and Drug Administration Center for Drug Evaluation and Research. 22 December 2008. [29] http://www.medscape.com/viewarticle/561243_3. ESH 07: Blood Pressure Effects of Sibutramine in Hypertensive Patients: The SCOUT Trial. Medscape. [30] http://www.fda.gov/Drugs/DrugSafety/ucm191650.htm. Early Communication about an Ongoing Safety Review of Meridia (sibutramine hydrochloride), (U.S. Food and Drug Administration), November 20, 2009. [31] http://www.fda.gov/Drugs/DrugSafety/ucm198206.htm. Follow-Up to the November 2009 Early Communication about an Ongoing Safety Review of Sibutramine, Marketed as Meridia. U.S. Food and Drug Administration, January 21. 2010. [32] http://www.ema.europa.eu/pdfs/human/referral/sibutramine/3940810en. pdf. European Medicines Agency recommends suspension of marketing authorisations for sibutramine. Weight-loss medicine associated with increased risk of cardiovascular events to be removed from all markets in the European Union authorisations for 21 January 2010. [33] Abbott to Suspend Marketing of Obesity Medicine Sibutramine in European Union Countries. Abbot News. https://www.abbott.se/media/pdf/Sibutraminenews-release-01-21-10.pdf. [34] Der Grosse Brockhaus, Wiesbaden, 1980. [35] Rmpp,Hermann :Chemie Lexikon 1962 5.Auage Francvkhsche Verlagsbuchhandlung, Stuttgart. [36] Heepe,Fritz:Ditetische Indikationen; Springer Verlag, Heidelberg, 1994, pg. 229. [37] The low fat world is at... 23.02.2011. Food Navigator. http://www.foodnavigator. com/Financial-Industry/The-low-fat-world-is-flat.
BIBLIOGRAPHY
1157
[38] Langbein, Kurt; Skalnik, Christian: Endlich schlank mit Xenical? 1. Auage 1998 Verlag Kiepenheuer und Witsch,Kln. [39] Mezarobba, Glenda; Luna,Fernando: A pilula que faz a dieta; Veja ano 31 nr.42 Editora Abril. [40] http://www.foodnavigator.com/news/ng.asp?n=85498. GSK weight loss wake-up call. Food Navigator: The
[41] http://www.mayoclinic.com/health/alli/WT00030. MayoClinic.com: Alli weight-loss pill: Does it work? Is Alli the solution to your weight-loss woes? A Mayo Clinic specialist discusses the eectiveness of Alli, an over-the-counter weightloss pill. [42] http://www.washingtonpost.com/wp-dyn/content/article/2007/02/16/ AR2007021602319.html. Washington Post: Lowdown on OTC Weight-Loss Drug. 20.02.2007 Page HE05. [43] http://www.cancerletters.info/article/S0304-3835(05)00860-8/abstract. Garcia S, da Costa Barros L, Turatti A, Martinello F, Modiano P, Ribeiro-Silva A, de Oliveira Vespcio M, Uyemura S (2006). The anti-obesity agent Orlistat is associated to increase in colonic preneoplastic markers in rats treated with a chemical carcinogen. Cancer Lett 240 (2): 221-4. doi:10.1016/j.canlet.2005.09.011. PMID 16377080. [44] http://content.nejm.org/cgi/content/abstract/339/18/1277. Takayama T, Katsuki S, Takahashi Y, Ohi M, Nojiri S, Sakamaki S, Kato J, Kogawa K, Miyake H, Niitsu Y (1998). berrant crypt foci of the colon as precursors of adenoma and cancer. N Engl J Med 339(18): 1277-84. Doi:10.1056/NEJM199810293391803. PMID 9791143. [45] http://dx.doi.org/10.1016/j.physbeh.2006.05.023. Margriet WesterterpPlantenga, Kristel Diepvens, Annemiek M.C.P. Joosen, Sonia Brub-Parent and Angelo Tremblay: Metabolic eects of spices, teas, and caeine Journal Physiology & Behavior,. [46] http://pubs.acs.org/cgi-bin/sample.cgi/jafcau/2007/55/i05/html/ jf062912b.html. Hsu, C.-L, and Yen, G.-Ch: Eects of Capsaicin on Induction of Apoptosis and Inhibition of Adipogenesis in 3T3-L1 Cells, J. Agric. Food Chem. 55:1730-1736 (2007). Doi: 10.1021/jf062912b. [47] http://news.independent.co.uk/uk/health_medical/article2140277.ece. The Independent: Spicy food could provide compound to ght cancers 10.01.2007. [48] http://www3.interscience.wiley.com/cgi-bin/abstract/104529865/ ABSTRACT?CRETRY=1&SRETRY=0. Lpez-Carrillo, Lizbeth; Lpez-Cervantes,
1158
CHAPTER 13. DIETING AND DIETARY HABITS Malaquas; Robles-Daz, Guillermo; Ramrez-Espitia, Armando; Mohar-Betancout, Alejandro; Meneses-Garca, Abelardo; Lpez-Vidal, Yolanda; Blair, Aaron: Capsaicin consumption, Helicobacter pylori positivity and gastric cancer in Mexico. International Journal of Cancer Vol. 106, Issue 2, Pages 277 - 282 Published Online: 30 Apr 2003.
[49] http://www.universityofcalifornia.edu/news/article/18273. Tom Vasich: Circadian rhythm-metabolism link discovered. University of California. News 200807-24. [50] http://www.ncbi.nlm.nih.gov/pubmed/19286518. Nakahata Y, Sahar S, Astarita G, Kaluzova M, Sassone-Corsi P: Circadian Control of the NAD+ Salvage Pathway by CLOCK-SIRT1. Science. 2009 Mar 12. [51] http://ajpregu.physiology.org/cgi/content/abstract/90786.2008v1. Song, C.Kay; Schwartz, Gary J.; Bartness, Timothy J.: Anterograde Transneuronal Viral Tract Tracing Reveals Central Sensory Circuits From White Adipose Tissue. Am J Physiol Regul Integr Comp Physiol (December 24, 2008). Doi:10.1152/ajpregu.90786.2008. [52] Wikipedia, the free encyclopedia: Transient Receptor Potential. [53] http://journals.royalsociety.org/content/w260687441pp64w5/fulltext. pdf. Mathews, Fiona; Johnson, Paul J.; Neil, Andrew: You are what your mother eats: evidence for maternal preconception diet inuencing foetal sex in humans. Royal Society Publishing: Proceedings of the Royal Society B: Biology Sciences. 22.04.2008 Doi: 10.1098/rspb.2008.0105. [54] Schusdziarra V, Hausmann M, Wittke C, Mittermeier J, Kellner M, Naumann A, Wagenpfeil S, and Erdmann J:. Impact of breakfast on daily energy intake - an analysis of absolute versus relative breakfast calories. Nutr J, 10(1):5, 1 2011. http: //www.nutritionj.com/content/10/1/5. [55] Rampersaud GC, Pereira MA, Girard BL, Adams J, and Metzl JD:. Breakfast habits, nutritional status, body weight, and academic performance in children and adolescents. J Am Diet Assoc, 105(5):74360, 4 2005. http://www.ncbi.nlm.nih.gov/ pubmed/15883552. [56] Hoyland A, Dye L, and Lawton CL:. A systematic review of the eect of breakfast on the cognitive performance of children and adolescents. Nutr Res Rev, 22(2):22043, 12 2009. http://www.ncbi.nlm.nih.gov/pubmed/19930787. [57] http://pediatrics.aappublications.org/cgi/content/abstract/114/4/S1/ 1146 http://pediatrics.aappublications.org/cgi/content/abstract/113/ 4/840. Sally Ann Lederman, PhD, Sharon R. Akabas, PhD, Barbara J. Moore, PhD, Margaret E. Bentley, PhD, Barbara Devaney, PhD, Matthew W. Gillman,
BIBLIOGRAPHY
1159
MD, Michael S. Kramer, MD, Julie A. Mennella, PhD, Andrew Ness, PhD and Jane Wardle, PhD: Summary of the Presentations at the Conference on Preventing Childhood Obesity, December 8, 2003. Pediatrics, Oct 2004; 114: 1146 - 1173. (doi:10.1542/peds.2004-0347B). [58] http://www.adajournal.org/article/S0002-8223(03)01449-4/abstract. Michael Ponza, Barbara Devaney, Paula Ziegler, Kathleen Reidy, Cathie Squatrito:Nutrient intakes and food choices of infants and toddlers participating in WIC. Journal of the American Dietitian AssociationVolume 104, Supplement 1, Pages 71-79 (January 2004). [59] http://www.sciencedaily.com/releases/2010/04/100412095536.htm. Dr. Catherine L. Dawis: Childhood obesity linked to sti arteries. Medical College of Georgia. April 9, 20101. [60] http://www.ncbi.nlm.nih.gov/pubmed/15668680. Wardle J, Carnell S and Cooke L. Parental control over feeding and childrens fruit and vegetable intake: how are they related? Journal of the American Dietetic Association. 105, 2005, 227-232. [61] http://pediatrics.aappublications.org/cgi/content/abstract/120/5/ e1225?rss=1. Robyn J. Tapp, Cathy Williams, Nicholas Witt, Nish Chaturvedi, Richard Evans, Simon A. McG Thom, Alun D. Hughes, Andrew Ness: Impact of Size at Birth on the Microvasculature: The Avon Longitudinal Study of Parents and Children. PEDIATRICS Vol. 120 No. 5 November 2007, pp. e1225-e1228 (doi:10.1542/peds.2006-2951). [62] http://www.pediatrics.org/cgi/content/abstract/117/2/544. American Heart Association, S. S. Gidding, B. A. Dennison, L. L. Birch, S. R. Daniels, M. W. Gilman, A. H. Lichtenstein, K. T. Rattay, J. Steinberger, N. Stettler, and L. Van Horn: Dietary Recommendations for Children and Adolescents: A Guide for Practitioners; Pediatrics, February 1, 2006; 117(2): 544 - 559. doi:10.1542/peds.2005-2374. [63] http://www.obesityresearch.org/cgi/content/abstract/13/11/1932. Andr M. Toschke, Helmut Kchenho, Berthold Koletzko and Rdiger von Kries. Meal Frequency and Childhood Obesity; Obesity Research 13:1932-1938 (2005). [64] http://www.eurekalert.org/pub_releases/2008-06/usmc-hhi061208.php. Zigman, Jerey; Lutter, Michael: Hunger hormone increases during stress, may have antidepressant eect. Eurekalert. 15.06.2008. [65] http://www.nature.com/neuro/journal/vaop/ncurrent/abs/nn.2139.html. Lutter, Michael; Sakata, Ichiro; Osborne-Lawrence, Sherri; Rovinsky, Sherry A.; Anderson, Jason G.; Jung, Saendy; Birnbaum, Shari;Yanagisawa, Masashi; Elmquist, Joel K.; Nestler, Eric J.; Zigman, Jerey M.: The orexigenic hormone ghrelin defends against depressive symptoms of chronic stress. Nature Neuroscience. Published online: 15 June 2008 doi:10.1038/nn.2139.
1160
[66] http://www.metabolismjournal.com/article/S0026-0495(07)00280-6/ abstract. Carlson, Olga; Martin, Bronwen; Stote, Kim S.; Golden, Erin; Maudsley, Stuart; Najjar, Samer S.; Ferrucci, Luigi; Ingram,Donald K.; Longo,Dan L.; Rumpler William V.; Baerc, David J.; Egana, Josephine; Mattson, Marc B.: Impact of reduced meal frequency without caloric restriction on glucose regulation in healthy, normal-weight middle-aged men and women. Metabolism, Volume 56, Issue 12, Pages 1729-1734. [67] http://www.ajcn.org/cgi/content/abstract/85/4/981. Kim S Stote, David J Baer, Karen Spears, David R Paul, G Keith Harris, William V Rumpler, Pilar Strycula, Samer S Najjar, Luigi Ferrucci, Donald K Ingram, Dan L Longo and Mark P Mattson: A controlled trial of reduced meal frequency without caloric restriction in healthy, normal-weight, middle-aged adults. American Journal of Clinical Nutrition, Vol. 85, No. 4, 981-988, April 2007. [68] http://www.rssl.com/OurServices/FoodENews/NewsLetter.aspx? ENewsletterID=247#9. Renehan, Andrew G.; Tyson, Margaret; Egger, Matthias; Heller, Richard F.; Zwahlen,Marcel: Body-mass index and incidence of cancer: a systematic review and meta-analysis of prospective observational studies. The Lancet 2008; 371:569-578 DOI:10.1016/S0140-6736(08)60269-X. [69] http://breast-cancer-research.com/content/pdf/bcr2564.pdf. Li, Jingmei; Humphreys,Keith; Eriksson,Louise; Czene, Kamila; Liu, Jianjun; Hall, Per: Eects of childhood body size on breast cancer tumour characteristics. Breast Cancer Research 2010, 12:R23 (15 April 2010). [70] http://www.obesityresearch.org/cgi/content/full/13/7/1270. Andr Michael Toschke, Andreas Beyerlein and Rdiger von Kries: Children at High Risk for Overweight: A Classication and Regression Trees Analysis Approach. Obesity Research 13:1270-1274 (2005). [71] http://www.saem.org/download/lewis1.pdf. Lewis, Roger J.: An Introduction to Classication and Regression Tree (CART) Analysis. Presented at the 2000 Annual Meeting of the Society for Academic Emergency Medicine in San Francisco, California. [72] http://www.ajcn.org/cgi/content/abstract/86/1/221. Harriss, Linton R.; English, Dallas R.; Powles, John; Giles, Graham G.; Tonkin, Andrew M.; Hodge, Allison M.; Brazionis, Laima; ODea, Kerin: Dietary patterns and cardiovascular mortality in the Melbourne Collaborative Cohort Study. American Journal of Clinical Nutrition July 2007, Volume 86, Number 1, Pages 221-229. [73] Murphy MM, Barraj LM, Herman D, Bi X, Cheatham R, and Randolph RK. Phytonutrient intake by adults in the united states in relation to fruit and vegetable
BIBLIOGRAPHY
1161
consumption. J Am Diet Assoc, 11 2011. http://www.ncbi.nlm.nih.gov/pubmed/ 22078816. [74] Rautiainen S, Larsson S, Virtamo J, and Wolk A. Total antioxidant capacity of diet and risk of stroke: a population-based prospective cohort of women. Stroke, 43(2):33540, 2 2012. http://www.ncbi.nlm.nih.gov/pubmed/22135074. [75] Larsson SC, Virtamo J, and Wolk A. Dietary fats and dietary cholesterol and risk of stroke in women. Atherosclerosis, 221(1):2826, 3 2012. http://www.ncbi.nlm. nih.gov/pubmed/22265275. [76] http://www.tri-calcium-citrate.com/var/184/1416-Calcium%20-%20for% 20Soy%20.pdf. Gadot Biochemical Industries: Soy milk and soy product fortication with calcium. [77] Larsson SC, Orsini N, and Wolk A. Dietary magnesium intake and risk of stroke: a meta-analysis of prospective studies. Am J Clin Nutr, 12 2011. http://www.ncbi. nlm.nih.gov/pubmed/22205313. [78] http://mrw.interscience.wiley.com/cochrane/clsysrev/articles/ CD004937/frame.html. He FJ, MacGregor GA. Eect of longer-term modest salt reduction on blood pressure. Cochrane Database of Systematic Reviews 2004, Issue 1. Art. No.: CD004937.DOI: 10.1002/14651858.CD004937. [79] http://www.ncbi.nlm.nih.gov/pubmed/17046432. Karppanen, Heikki; Mervaala, Eero: Sodium Intake and Hypertension.Progress in Cardiovascular Diseases. Volume 49, Issue 2, September-October 2006. Pages 59-75. doi:10.1016/j.pcad.2006.07.001. [80] http://www.nature.com/jhh/journal/v22/n1/full/1002268a.html. He, F.J.; Marrero, N.M.; MacGregor, G.A.: Salt and blood pressure in children and adolescents .Journal of Human Hypertension (2008) 22, 4-11; doi:10.1038/sj.jhh.1002268; published online 6 September 2007. [81] http://www.nature.com/jhh/journal/v22/n1/full/1002269a.html. Alderman, H.M.: Salt and blood pressure in children. Commentary. Journal of Human Hypertension (2008) 22, 1-3; doi:10.1038/sj.jhh.1002269; published online 6 September 2007. [82] http://www.ncbi.nlm.nih.gov/pubmed/18287345. He, F.J.; Marrero, N.M.; MacGregor, G.A.: Salt intake is related to soft drink consumption in children and adolescents: a link to obesity? Hypertension. 2008 Mar; 51(3):629-34. [83] Stolarz-Skrzypek K, Kuznetsova T, Thijs L, Tikhono V, Seidlerov J, Richart T, Jin Y, Olszanecka A, Malyutina S, Casiglia E, Filipovsky J, Kawecka-Jaszcz K, Nikitin Y, Staessen JA, and for the European Project on Genes in Hypertension (EPOGH) Investigators. Fatal and nonfatal outcomes, incidence of hypertension, and
1162
CHAPTER 13. DIETING AND DIETARY HABITS blood pressure changes in relation to urinary sodium excretion. JAMA, 305(17):1777 1785, 5 2011. http://www.ncbi.nlm.nih.gov/pubmed/21540421.
[84] He FJ and MacGregor GA. A comprehensive review on salt and health and current experience of worldwide salt reduction programmes. J Hum Hypertens, 23(6):36384, 6 2009. http://www.ncbi.nlm.nih.gov/pubmed/19110538. [85] Opinion of the scientic panel on dietetic products, nutrition and allergies on a request from the commission related to the tolerable upper intake level of sodium. efsa 2005. 2005. http://www.efsa.europa.eu/en/scdocs/doc/s209.pdf. [86] Global strategy on diet, physical activity and health. population sodium reduction strategies. http://www.who.int/dietphysicalactivity/reducingsaltintake_ EN.pdf. [87] Scientic advisory committee on nutrition: Salt and health. http://www.sacn.gov. uk/pdfs/sacn_03_14.pdf. [88] World action on salt and health (wash). http://www.worldactiononsalt.com. [89] He FJ, Jenner KH, and Macgregor GA. Wash-world action on salt and health. Kidney Int, 78(8):74553, 10 2010. http://www.ncbi.nlm.nih.gov/pubmed/20720531. [90] http://hyper.ahajournals.org/cgi/content/abstract/HYPERTENSIONAHA. 108.114983v1. Simonetti, Giacomo D.; Raio, Luigi; Surbek, Daniel; Nelle, Mathias; Frey, Felix J.; Mohaupt, Markus G.: Salt Sensitivity of Children With Low Birth Weight. Hypertension, Aug 2008; doi:10.1161/HYPERTENSIONAHA.108.114983. [91] http://www.who.int/hpr/NPH/docs/who_fao_expert_report.pdf. WHO Media Centre: WHO/FAO release independent Expert Report on diet and chronic disease. Less saturated fats, sugar and salt, more fruit and vegetables and physical exercise, needed to counter cardiovascular diseases, cancer, diabetes and obesity. 3 March 2003. [92] http://www.actiononsalt.org.uk/home/wash.htm. Health. World Action on Salt and
[93] http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5811a2.htm. CDC: Application of Lower Sodium Intake Recommendations to Adults United States, 1999-2006. MMWR March 27, 2009 / 58(11);281-283. [94] http://www.cspinet.org/salt/index.html. Center for Science in the Public Interest: Salt. [95] http://www.salt.gov.uk/science_on_salt.html. Food Standards Agency: Science on salt.
BIBLIOGRAPHY
1163
[96] http://www.efsa.europa.eu/EFSA/efsa_locale-1178620753812_ 1178620767128.htm. European Food Safety Authority: Opinion of the Scientic Panel on Dietetic products, nutrition and allergies [NDA] related to the Tolerable Upper Intake Level of Sodium Question number: EFSA-Q-2003-018. 21 April 2005. [97] Taylor RS, Ashton KE, Moxham T, Hooper L, and Ebrahim S. Reduced dietary salt for the prevention of cardiovascular disease. Cochrane Database Syst Rev, 7(CD009217), 7 2011. http://www.ncbi.nlm.nih.gov/pubmed/21735439. [98] Horton S, Wesley, and Venkatesh Manna MG. Double-fortied salt reduces anemia, benet:cost ratio is modestly favourable. Food Policy. http://www.sciencedirect. com/science/article/pii/S030691921100073X. [99] Nevin S and Scrimshaw NS. Malnutrition, brain development, learning, and behavior. nutrition. Research, 18(2):351379, 2 1998. http://www.sciencedirect.com/ science/article/pii/S027153179800027X. [100] Melse-Boonstra A and Jaiswal N. Iodine deciency in pregnancy, infancy and childhood and its consequences for brain development. Best Practice & Research Clinical Endocrinology & Metabolism, 24(1):2938, 2 2010. http://www.sciencedirect. com/science/article/pii/S1521690X09001092. [101] Untoro J, Timmer A, and Schultink W. The challenges of iodine supplementation: a public health programme perspective. Best Practice & Research Clinical Endocrinology & Metabolism, 24(1):8999, 2 2010. http://www.ncbi.nlm.nih.gov/pubmed/ 20172473. [102] http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=OJ:L:2007:012: 0003:0018:EN:PDF. Corrigendum to Regulation (EC) No 1924/2006 of the European Parliament and of the Council of 20 December 2006 on nutrition and health claims made on foods ( OJ L 404, 30.12.2006 ). [103] Umstieg auf fettreduzierte Lebensmittel;Der Lebensmittelbrief 10. Jahrgang 5+6/1999. [104] http://www.ajcn.org/cgi/content/abstract/86/6/1595. Pelkman, Christine L; Navia, Juan L; Miller, Allison E; Pohle, Rachael J : Novel calcium-gelled, alginatepectin beverage reduced energy intake in nondieting overweight and obese women: interactions with dietary restraint status. Am J Clin Nutr 2007 86 Number 6, 15951602. [105] http://en.wikipedia.org/wiki/Incretins. Wikipedia: Incretins. [106] http://www.americanheart.org/presenter.jhtml?identifier=336. Heart Assitiation: Cutting Down on Salt.
American
1164
[107] Smith,Trevor: Health Perspectives, Questions on fat vs. calories;Todays Chemist at Work/August 1998 pg 53. [108] Katan,M.B.;Grundy,S.M.;Willet,W.C.N.Engl.J.Med. 1997,338 (8),562-63. [109] Smith,Trevor: Health Perspectives,Walk your weight down; Todays Chemist at Work/May 1998 pg 43. [110] http://www.salt.gov.uk/understanding_labels.shtml. Agency: Salt - Understanding labels. [111] http://www.salt.gov.uk/salt_myths.shtml. myths. Food Standards Salt
Food Standards Agency:
[112] Fernndez-Real JM, Bull M, Moreno-Navarrete JM, Ricart W, Ros E, Estruch R, and Salas-Salvad J. A mediterranean diet enriched with olive oil is associated with higher serum total osteocalcin levels in elderly men at high cardiovascular risk. J Clin Endocrinol Metab, 8 2012. http://www.ncbi.nlm.nih.gov/pubmed/22855341. [113] Daz-Lpez A, Bull M, Martnez-Gonzlez MA, Guasch-Ferr M, Ros E, Basora J, Covas MI, Lpez-Sabater MD, and Salas-Salvad J. Predimed (prevencin con dieta mediterrnea) reus study investigators: Eects of mediterranean diets on kidney function: A report from the predimed trial. Am J Kidney Dis, 4 2012. http: //www.ncbi.nlm.nih.gov/pubmed/22541738. [114] http://www.fao.org/es/esd/Montreal-JS.pdf. Schmidhuber, Josef: The EU Diet - Evolution, Evaluation and Impacts of the CAP. Senior Economist. Global Perspectives Studies Unit, FAO. [115] http://www.ncbi.nlm.nih.gov/pubmed/16151276. Flaminio Fidanza, Adalberta Alberti, Daniela Fruttini Simopoulos AP (ed): The Nicotera Diet: The Reference Italian Mediterranean Diet. Nutrition and Fitness: Mental Health, Aging, and the Implementation of a Healthy Diet and Physical Activity Lifestyle. World Rev Nutr Diet. Basel, Karger, 2005, vol 95, pp 115-121. [116] http://www.ncbi.nlm.nih.gov/pubmed/20388092. De Lorenzo A, Noce A, Bigioni M, Calabrese V, Della Rocca DG, Di Daniele N, Tozzo C, Di Renzo L: The eects of Italian Mediterranean organic diet (IMOD) on health status. Curr Pharm Des. 2010;16(7):814-24. [117] http://www.ncbi.nlm.nih.gov/pubmed/19667117. Murray AJ, Knight NS, Cochlin LE, McAleese S, Deacon RM, Rawlins JN, Clarke K. Deterioration of physical performance and cognitive function in rats with short-term high-fat feeding. FASEB J. 2009 Aug 10. Epub ahead of print. Doi: 10.1096/fj.09-139691. [118] http://www.americanheart.org/presenter.jhtml?identifier=532. Know your fats.
AHA:
BIBLIOGRAPHY [119] Eades M.R., Eades M.D. Protein Power. New York, NY Bantam Books 1996.
1165
[120] http://aem.asm.org/cgi/content/abstract/73/4/1073. Duncan, Sylvia H.; Belenguer, Alvaro; Holtrop, Grietje; Johnstone, Alexandra M.; Flint, Harry J.; Loble Gerald E.: Reduced Dietary Intake of Carbohydrates by Obese Subjects Results in Decreased Concentrations of Butyrate and Butyrate-Producing Bacteria in Faeces. Applied and Environmental Microbiology Volume 73, Number 4, Pages 1073-1078 doi:10.1128/AEM.02340-06. [121] Steward HL, Bethea MC, Andrews SS, et al. Sugar Busters New York, NY: Ballantine Books ; 1998. [122] Stillman IM, Baker SS. The Doctors Quick Weight Loss Diet. New York, NY: Dell Publishing Co; 1967. [123] http://jama.ama-assn.org/cgi/content/abstract/297/9/969. Gardner CD, Kiazand A, Alhassan S, Kim S, Staord RS, Balise RR, Kraemer HC, King AC.: Comparison of the Atkins, Zone, Ornish, and LEARN diets for change in weight and related risk factors among overweight premenopausal women: the A to Z Weight Loss Study: a randomized trial. JAMA. 2007 Mar 7;297(9):969-77. Erratum in: JAMA. 2007 Jul 11;298(2):178. [124] http://nccam.nih.gov/research/results/spotlight/030607.htm. NCAM National Center for Complementary Alternative Medicine: Study compares year-long eectiveness of four weight-loss plans. [125] http://www.mynchen.demon.co.uk/. The Ketogenic Resource. [126] http://www.en.wikipedia.org/wiki/Ketogenic_diet. Wikipedia, the free Enzyclopedia: Ketogenic diet. [127] http://www.ncbi.nlm.nih.gov/pubmed/10909595. Schi, Y; Lerman-Sagie, T: ketogenic diet for adults, Ketogenic diet-an alternative therapy for epilepsy in adults. Harefuah 1998 Apr 1;134(7):529-31, 591. [128] Kashiwaya, Yoshishiro; Sato, Kiyotaka; Tsuchiya, Naotaka; Thomas, Simon; Fell, David A.; Veech, Richard L. and Passonneau, Janet V.: Control of Glucose Utilization in Working Perfused Rat Heart 1994, The Journal of Biological Chemistry Vol.269, No. 41, Issue of October 14, pp. 25502-25514, 1994. [129] Gerngross, T. U. (1999) Nat. Biotechnol. 17, 541-542. [130] http://www.niaaa.nih.gov/NR/rdonlyres/084D048E-F200-425A9D46BE3979458F02/ 0/KashiwProcNatlAcadSci2000_5440.pdf. Kashiwaya, Yoshihiro; Takeshima, Takao; Mori, Nozomi; Nakashima, Kenji; Clarke, Kieran and Veech Richard L.: D-b-Hydroxybutyrate protects neurons in models of Alzheimers and Parkinsons disease. Proc Natl. Acad. Sci. 2000.
1166
[131] Husemann, Friedrich; Wol, Otto: Anthroposophical Approach to Medicine. Verlag Freies Geistesleben, Stuttgard. Anthroposophic Press 1982. [132] http://www.anthromedia.com/articles/agriculture/nutrition/practical_ nutrition/. Agriculture. Nutrition in Practice. Anthromedia.com. [133] http://www.waldorfcritics.org/active/articles/Smith-Hald.html. Growing Up Being Made Sick by Anthroposophy By Robert Smith-Hald, a survivor. January 30, 2007. [134] 2008-2013 action plan for the global strategy for the prevention and control of noncommunicable diseases. who. http://whqlibdoc.who.int/publications/2009/ 9789241597418_eng.pdf. [135] World health statistics 2012. who. http://www.who.int/healthinfo/EN_WHS2012_ Full.pdf.
[136] Saudi arabia hosts a conference on healthy lifestyles and noncommunicable diseases in the arab world and the middle east. who 912 september 2012. http://www.emro.who.int/press-releases/2012/ healthy-lifestyles-and-non-communicable-diseases-in-the-arab-world-and-the-middl html. [137] OFlaherty M, Buchan I, and Capewell S. Contributions of treatment and lifestyle to declining cvd mortality: Why have cvd mortality rates declined so much since the 1960s? Heart, 9 2012. http://www.ncbi.nlm.nih.gov/pubmed/22962283. [138] Poorolajal J, Esmailnasab N, Ahmadzadeh J, and Motlagh TA. The burden of premature mortality in hamadan province in 2006 and 2010 using standard expected years of potential life lost: A population-based study. Epidemiol Health, 34:e2012005, 2012. http://www.ncbi.nlm.nih.gov/pubmed/22977738. [139] Owen J and Reisin E. Non-communicable disease: A welcome and long needed addition to the whos 2012 world heath statistics. Curr Hypertens Rep, 9 2012. http://www.ncbi.nlm.nih.gov/pubmed/22972530. [140] Ollila E. Global health priorities-priorities of the wealthy? Globalization and Health, 1:6, 2005. http://www.globalizationandhealth.com/content/1/1/6. [141] http://www.nwcr.ws/NWCR_join.htm. Wing, R. and Hill, J.: Who succeeds in maintaining weight loss. Obesity Reviews. [142] J Westenhoefer,J.; von Falck, B.; Stellfeldt, A. and Fintelmann, S.: Behavioural correlates of successful weight reduction over 3 y. Results from the Lean Habits Study. International Journal of Obesity (2004) 28, 334-335. doi:10.1038/sj.ijo.0802530 Published online 25 November 2003.
BIBLIOGRAPHY
1167
[143] Why Kosher is cool for all,Food Ingredients and Analysis International, April 2000, page 13. [144] Regenstein,Joe M.:Kosher and halal laws impacting on biotechnology; Food technology international, issue 2001 pg. 77. [145] http://www.unitedsynagogue.org.uk/the_united_synagogue/media_centre/ press_releases/c-661/kosher-status-of-mars-products/. United Synagogue Website: Kosher Status of Mars Products. United Synagogue Press Release 15.05.2007. [146] Deutsches lebensmittelbuch. Lebensmittelbuch. http://de.wikipedia.org/wiki/Deutsches_
[147] http://www.packagedfacts.com/MarketTrend-Kosher-Halal-1282406/. Packaged Facts: Market Trend: Kosher- and Halal-Certied Foods in the U.S. Report May 1, 2009. [148] http://www.halaljournal.com/article/2753/halal,-kosher-and-the-usa. Kamaruzaman, Kamarul Aznam: Halal, Kosher and the USA. The Halal Journal May/June 2006. [149] http://www.kuwaittimes.net/read_news.php?newsid=ODUxODA1ODI0. Times: More halal foods on Europe store shelves. January 13, 2010. Kuwait
[150] http://www.chow.com/stories/10481. Chow: Mystery deli term. By Jason Horn. [151] Schweineeisch in dner gefunden. 18 febr 2013. thtp://www.fr-online. de/lebensmittel/fleischskandal-schweinefleisch-in-doener-gefunden, 21868140,21868096.html. [152] Islamrat: Schweineeisch im dner ist doppelter betrug am verbraucher deutsch trkische nachrichten 18.febr 2013. http: //www.deutsch-tuerkische-nachrichten.de/2013/02/468876/ islamrat-schweinefleisch-im-doener-ist-doppelter-betrug-am-verbraucher/. [153] Neue verfassung trkischer verein verlangt recht auf halalprodukte. deutsch trkische nachrichten. 11 dez 2011. http: //www.deutsch-tuerkische-nachrichten.de/2011/12/12115/ neue-verfassung-tuerkischer-verein-verlangt-recht-auf-halal-produkte/. [154] traces of pork found in prison food served as halal. supplier of meat pies and pasties to prisons suspended after fsa informed of contamination. the guardian. 1 february 2013. http://www.guardian.co.uk/business/2013/feb/01/ traces-pork-prison-food-halal.
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[155] New device to test meat. kuwait times. 2012 sept 09. http://news.kuwaittimes. net/2012/09/09/new-device-to-test-meat/. [156] Nano-colloidal gold enables simple, fast and economical detection of pork. http: //www.tanaka.co.jp/english/topics/pdf/topics_20100405_01.pdf. [157] Kesmen Z, Yetiman AE, Sahin F, and Yetim H. Detection of chicken and turkey meat in meat mixtures by using real-time pcr assays. J Food Sci, 77(2):C16773, 2 2012. http://www.ncbi.nlm.nih.gov/pubmed/22309374. [158] Rodrguez MA, Garca T, Gonzlez I, Asensio L, Hernndez PE, and Martn R. Pcr identication of beef, sheep, goat, and pork in raw and heat-treated meat mixtures. J Food Prot, 67(1):1727, 1 204. http://www.ncbi.nlm.nih.gov/pubmed/14717369. [159] Sakalar E, Abasiyanik MF, Bektik E, and Tayyrov A. Eect of heat processing on dna quantication of meat species. J Food Sci, 8 2012. http://www.ncbi.nlm.nih. gov/pubmed/22900921. [160] Kesmen Z, Gulluce A, Sahin F, and Yetim H. Identication of meat species by taqman-based real-time pcr assay. Meat Sci, 82(4):4449, 8 2009. http://www. ncbi.nlm.nih.gov/pubmed/20416686. [161] Vaclavik L, Hrbek V, Cajka T, Rohlik BA, Pipek P, and Hajslova J. Authentication of animal fats using direct analysis in real time (dart) ionization-mass spectrometry and chemometric tools. J Agric Food Chem, 59(11):591926, 6 2011. http://www. ncbi.nlm.nih.gov/pubmed/21526761. [162] Rohman A, Sismindari, Erwanto Y, and Che Man YB:. Analysis of pork adulteration in beef meatball using fourier transform infrared (ftir) spectroscopy. Meat Sci, 88(1):915, 5 2011. http://www.ncbi.nlm.nih.gov/pubmed/21227596. [163] Hu YH, Guo KQ, Noguchi G, and Satake T. Detection of fatty acid composition in intramuscular fat of packed pork loin by near infrared spectroscopy. Guang Pu Xue Yu Guang Pu Fen Xi, pages 207982, 8 2009. http://www.ncbi.nlm.nih.gov/ pubmed/19839312. [164] Determinism. wikipedia. http://en.wikipedia.org/wiki/Determinism. [165] Cecchinato A, De Marchi M, Penasa M, Casellas J, Schiavon S, and Bittante G. Genetic analysis of beef fatty acid composition predicted by near-infrared spectroscopy. J Anim Sci, 90(2):42938, 2 2012. http://www.ncbi.nlm.nih.gov/ pubmed/21948610. [166] Myosin light chains: The us national library of medicine. Medical Subject Headings (MeSH). http://www.nlm.nih.gov/cgi/mesh/2011/MB_cgi?mode=&term=Myosin+ Light+Chains.
BIBLIOGRAPHY
1169
[167] Montowska M and Pospiech E. Dierences in two-dimensional gel electrophoresis patterns of skeletal muscle myosin light chain isoforms between bos taurus, sus scrofa and selected poultry species. J Sci Food Agric, 91(13):244956, 10 2011. http: //www.ncbi.nlm.nih.gov/pubmed/21656778. [168] Montowska M and Pospiech E. Myosin light chain isoforms retain their speciesspecic electrophoretic mobility after processing, which enables dierentiation between six species: 2-de analysis of minced meat and meat products made from beef, pork and poultry. Proteomics, 7 2012. http://www.ncbi.nlm.nih.gov/pubmed/ 22851476. [169] http://www.timesonline.co.uk/tol/life_and_style/food_and_drink/ article3412749.ece. Times Online: Muslims shocked to learn that crisps contain alcohol. 22.02.2008. [170] http://www.ehalal.org/vanilla.html. Halalpreneur: Is Vanilla Halal or Haram? [171] Omran, Helmy T.; Buckenhskes,Herbert J.: Halal oder haram? Muslime leben nach strengen Speisegesetzen.:Lebensmitteltechnik 3/1999 S 47. [172] http://www.ncbi.nlm.nih.gov/pubmed/342225. Schulze W, Schultze-Petzold H, Hazem AS, Gross R.: Objectivization of pain and consciousness in the conventional (dart-gun anesthesia) as well as in ritual (kosher incision) slaughter of sheep and calf. Dtsch Tierarztl Wochenschr. 1978 Feb 5;85(2):62-6. PMID: 342225 [PubMed indexed for MEDLINE]. [173] http://www.handwerk.com/service/archiv/schaechten-fleisch.htm. Handwerk.com: Der Schock berlagert das Schmerzempnden. 17.01.2002. [174] http://www.ncbi.nlm.nih.gov/pubmed/2651084. Kallweit E, Ellendorf F, Daly C, Smidt D.: Physiologic reactions during the slaughter of cattle and sheep with and without stunning. Dtsch Tierarztl Wochenschr. 1989 Mar;96(3):89-92. [175] http://www.ncbi.nlm.nih.gov/pubmed/8720795. Knierim, U.: Animal welfare slaughter regulation. Dtsch Tierarztl Wochenschr. 1996 Feb;103(2):52-4. [176] http://www.ncbi.nlm.nih.gov/pubmed/17419542. Polten, B.: Status of lawmaking on animal welfare. Dtsch Tierarztl Wochenschr. 2007 Mar;114(3):98-103. [177] http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=OJ:L:2005:003: 0001:0044:EN:PDF. Council Regulation (EC) No 1/2005 of 22 December 2004 on the protection of animals during transport and related operations and amending Directives 64/432/EEC and 93/119/EC and Regulation (EC) No 1255/97. [178] http://www.cpap.embrapa.br/agencia/congressovirtual/pdf/ingles/ 02en03.pdf. de Oliveira Roca, Roberto: Humane slaughter of bovine. First
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CHAPTER 13. DIETING AND DIETARY HABITS Virtual Global Conference on Organic Beef Cattle Production . September, 02 to October,15 - 2002.
[179] http://www.ingentaconnect.com/content/nzva/nzvj/1981/00000029/ 00000006/art00004. Blackmore D.K.; Petersen G.V.: Stunning and slaughter of sheep and calves in New Zealand. New Zealand Veterinary Journal, Volume 29, Number 6, 1 June 1981 , pp. 99-102(4). [180] http://www.thepoultrysite.com/articles/186/. Service: GCC Standard. USDA Foreign Agricultural
[181] http://www.secularism.org.uk/muslim-smallholder-fined-for-ill.html. Secularism org: Muslim smallholder ned for illegal halal slaughter of sheep. 14.8.2009.
[182] http://www.independent.co.uk/news/uk/home-news/ halal-and-kosher-meat-should-not-be-slipped-in-to-food-chain-says-minister-80539 html. Halal and kosher meat should not be slipped in to food chain, says minister. 7 April 2008. [183] http://www.bundesverfassungsgericht.de/entscheidungen/rs20020115_ 1bvr178399en.html. Judgement of the First Senate of 15th January, 2002. Germany. [184] http://www.erna-graff-stiftung.de/cms/download/tierschutz_bei_der_ rituellen_schlachtung.pdf. Berlin Meeting 2005. [185] http://www.shechitauk.org/act-now-to-protect-shechita.html. Shechita the Jewish religious humane method of animal slaughter for food. Shechita UK. 04.10.2010. [186] http://www.muslimnews.co.uk/paper/index.php?article=4741. European Parliament vote to label meat slaughtered without pre-stunning. The Muslim News. Issue 255. 30.07.2010.
[187] http://halalfocus.net/2010/07/30/european-parliament-vote-to-label-meat-slaughte European Parliament vote to label meat slaughtered without pre-stunning. Halal Focus 30.07.2010. [188] http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=CELEX: 31993L0119:EN:HTML. Council Directive 93/119/EC of 22 December 1993 on the protection of animals at the time of slaughter or killing. [189] http://www.scotland.gov.uk/Resource/Doc/261684/0078279.pdf. Commission Sta Working Document accompanying the Proposal for a Council Regulation on the protection of animals at the time of killing. Impact Assessment Report. COM(2008) 553 SEC(2008) 2425 Brussels, 22 September 2008.
BIBLIOGRAPHY
1171
[190] http://www.secularism.org.uk/uploads/submission-to-defra-on-ritual-slaughter. pdf. Submission to Defra Animal Welfare Core Team animal welfare consultations. Consultation on the proposal for a Council regulation on the protection of animals at the time of killing. 20 April 2009. The National Secular Society. [191] http://www.fao.org/docrep/003/X6909E/x6909e00.HTM. Slaughter of livestock. FAO: Chapter 7:
[192] http://www.halal.or.th/uploadfiles/std_halal_food%20Eng.pdf. Halal Food in Thailand B.E.2550 (2007). [193] http://www.codexalimentarius.org/input/download/standards/352/CXG_ 024e.pdf. Codex Alimentarius CAC/GL 24-1997 AVI-6. [194] Calls to unify global halal standards gain ground at dubai expo. thenational, 13 nov 2012. http://www.thenational.ae/news/uae-news/health/ calls-to-unify-global-halal-standards-gain-ground-at-dubai-expo. [195] http://www.ummahfoods.com/aboutus.html. With a Bismillah and a yummy milk chocolate caramel bar, Ummah Foods began its journey in 2004. [196] http://www.zeit.de/2007/34/N-Ferkelkastration. Dr Schmerz der Schweine. Zeit Online. 19.08.2007. Hucklenbroich, Christina:
[197] http://www.ncbi.nlm.nih.gov/pubmed/16729464. Zls S, Ritzmann M, Heinritzi K: Eect of analgesics on the castration of male piglets. Berl Munch Tierarztl Wochenschr. 2006 May-Jun;119(5-6):193-6. German. [198] http://www.ncbi.nlm.nih.gov/pubmed/18077932. Zankl A, Ritzmann M, Zls S, Heinritzi K: The ecacy of local anaesthetics administered prior to castration of male suckling piglets. Dtsch Tierarztl Wochenschr. 2007 Nov;114(11):418-22. German. [199] http://www.ncbi.nlm.nih.gov/pubmed/17555035. Schulz C, Ritzmann M, Palzer A, Heinritzi K, Zls S: Eect of isourane inhalation anesthesia on postoperative pain due to castration of piglets. Berl Munch Tierarztl Wochenschr. 2007 May-Jun;120(56):177-82. German. [200] http://www.improvac.com/sites/improvac/en-NZ/pages/betterwayforward. aspx. Improvac: A better way forward. Pzer. [201] http://www.topagrar.com/index.php?option=com_content&task=view&id= 12822&Itemid=520]. Dnemark: Vorerst kein Improvac. TopAgrar.com. 12.08.2009. [202] http://w3.rennes.inra.fr/pigcas/Public%20reports/D1%205%20Report% 20Attitudes.pdf. PIGCAS: Attitudes, practices and state of the art regarding piglet castration in Europe.
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[203] http://www.ncbi.nlm.nih.gov/pubmed/15848777. Staord KJ, Mellor DJ: Dehorning and disbudding distress and its alleviation in calves. Vet J. 2005 May;169(3):337-49. [204] http://www.avma.org/reference/backgrounders/dehorning_cattle_bgnd.asp. American Veterinary Medical Association: Backgrounder: Welfare implications of the dehorning and disbudding of cattle. October 2, 2007. [205] http://www.spiegel.de/international/germany/0,1518,653585,00.html. Spiegel Online: Halal is Big Business. Germany Waking up to Growing Market for Muslim Food. 10.06.2009. [206] http://www.meemken.de/images/stories/Diesunddas/Meemken_ Imagefolder-100dpi.pdf. Meemken. Image Folder.
[207] http://www.fazfinance.net/Aktuell/Ist-da-auch-garantiert-kein-Schwein-drin-9119. faz. FAZ: Lebensmittelindustrie. Ist da auch garantiert kein Schwein drin? Iris Gutirrez. 10.05.2009. [208] http://www.nestle.com.my/nestle+in+your+life/whats+new/. Nestl Malaysia: Nestl in your life: New Products. [209] Juretko, Axel: Facts ber Functional Food Wissenschaftliche Informationstagung in Berlin; Lebensmitteltechnik 3/1999 S. 29. [210] http://www.ncbi.nlm.nih.gov/pubmed/20421555. Rose N, Koperski S, Golomb BA: Mood food: chocolate and depressive symptoms in a cross-sectional analysis. Arch Intern Med. 2010 Apr 26;170(8):699-703. [211] http://counsellingresource.com/quizzes/cesd/index.html. Welcome to the Center for Epidemiologic Studies Depression Scale (CES-D), A Screening Test for Depression.
Chapter 14 Vegetarianism
Nutrition authorities say that a properly planned vegan diet presents no signicant nutritional problems. Supplementation is, however, highly recommended. [1] There are several nutrients vegans should pay attention to. These include vitamin B12, iron and iodine: deciencies in these are more likely following a vegan diet, and deciencies of these have potentially serious consequences, including anemia, pernicious anemia, cretinism and hyperthyroidism.
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Vegetable iron fortication of foods to counter iron deciency
[2] Miret and colleagues 2009 report the development of sodium iron chlorophyllin from mulberries which could replace heme iron to fortify foods .The use of heme analogues from vegetable origin could provide an alternative iron source of potentially high bioavailability. Sodium iron chlorophyllin is vegetal semisynthetic chlorophyll derivative. The authors substituted the magnesium in the porphyrin ring by iron. Sodium iron chlorophyllin is stable under simulated gastrointestinal conditions and is able to deliver bioavailable iron. The authors stress that it may be inhibited with calcium. This combination should be avoided. The green colour may be covered by the colour of chocolate bars or drinks. Another way to fortify foods could be to combine it with the taste and colour of pistachio or kiwi, suggest the authors.
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Polyphenol antioxidants inhibit iron absorption
[3] Polyphenol are antioxidants substances found in many fruits and vegetables. They may prevent or delay certain types of cancer, enhancing bone metabolism and improving bone mineral density, and decreasing risk of heart disease. Okhee Hanand colleagues 2010 found 1173
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that these antioxidants, however, may decreased the amount of iron the body absorbs, and may cause iron deciency. Polyphenoles of grape seed extract and epigallocatechin-3-gallate (EGCG) found in green tea, bind to iron in the intestinal cells, forming a non-transportable complex and is excreted in the faeces when cells are sloughed o and replaced. Iron deciency is the most prevalent nutrient deciency in the world, especially in developing countries where little meats is being consumed. Bioactive dietary polyphenols inhibit heme iron absorption mainly by reducing iron exit rather than decreasing heme iron uptake in intestinal cells. The heme form of iron is found in meats, poultry, and sh. In a foregoing study the authors studied the uptake of non-heme iron found in plants. The bioavailiability of non-heme iron was also found to be impaired by grape seed extract and EGCG. [4] Both studies suggest that people at high risk of developing iron deciency, such as pregnant women and young children, should look at this issue, when taking polyphenols. Nutritional supplements often contain high concentration of active ingredients which surpass the natural content in foods by several times. This may lead to unwanted results such as iron deciency. Normal varied diet is therefore the best to keep a healthy nutritional balance.
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Guidance on food labelling for vegans and vegetarians
[5] The Food Standards Agency (FSA) issued the guidance on food labelling for vegans and vegetarians in 2006. These terms had not been dened by UK food labelling regulations. The FSA guidance was therefore welcomed by consumers and food industry. FSA denitions are:
14.0.17
Vegetarian
"The term vegetarian should not be applied to foods that are, or are made from, or with, the aid of products derived from animals that have died, have been slaughtered, or animals that die as a result of being eaten. Animals means farmed, wild or domestic animals, including for example, livestock poultry, game, sh, shellsh, crustacea, amphibians, tunicates, echinoderms, molluscs and insects."
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Vegan
"The term vegan should not be applied to foods that are, or are made from, or with, the aid of animals or animal products (including products from living animals)."
14.0.19
Reasons of veganism
[5] According to the UK FSA there are various reasons for people choosing vegetarian or vegan diets. Many prefer not to consume food that results from the slaughter of animals, or from animal products. Others are concerned particularly about ethical methods of farming, transport, and slaughter. An individuals choice to be vegetarian or vegan may be based entirely on religious grounds. Some people are allergic or intolerant to particular animal products. Personal choice may be based on a combination of these factors. The motives for individuals choosing a vegetarian or vegan diet are important, because they determine what particular foods or food ingredients are deemed to be acceptable.
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Small intakes of foods of animal origin associated with chronic degenerative diseases
[6] Campbell and colleagues found that rural China diets are substantially richer in foods of plant origin when compared with diets consumed in the more industrialized, Western societies. The scientists came to the conclusion that chronic degenerative diseases are prevented by an aggregate eect of nutrients and nutrient-intake amounts that are commonly supplied by foods of plant origin, and that even small intakes of foods of animal origin are associated with signicant increases in plasma cholesterol concentrations, which are associated, in turn, with signicant increases in chronic degenerative disease mortality rates.
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Vegetarianism, a good way to reduce greenhouse emission
[7] [8] citeIVU worldwide According to FAO , the livestock sector generates 18 percent of greenhouse gas emissions as measured in CO2 equivalent. This is more than transport. It is also a major source of land and water degradation. Global meat production is projected to more than double from 229 million tonnes in
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1999/2001 to 465 million tonnes in 2050, while milk output is set to climb from 580 to 1043 million tonnes. FAO says that the environmental costs per unit of livestock production must be cut by one half, just to avoid the level of damage worsening beyond its present level,
14.0.22
Suggested remedies by the FAO Report London 2007
FAO in its Report suggests:
14.0.23
Land degradation
controlling access and removing obstacles to mobility on common pastures. Use of soil conservation methods and silvopastoralism, together with controlled livestock exclusion from sensitive areas; payment schemes for environmental services in livestock-based land use to help reduce and reverse land degradation.
14.0.24
Atmosphere and climate
increasing the eciency of livestock production and feed crop agriculture. Improving animals diets to reduce enteric fermentation and consequent methane emissions, and setting up biogas plant initiatives to recycle manure. Water improving the eciency of irrigation systems. Introducing full-cost pricing for water together with taxes to discourage large-scale livestock concentration close to cities.
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Other suggestions to reduce emission from lifestock
Other suggestions are to eat more vegetables. Meat consumption should de reduced by half. The vegetarians suggest to stop eating meat at all.
14.0.26
Vegetarianism
Vegetarianism means nutrition without any products from dead animals such as meat, poultry or sh. Lacto-ovo vegetarians eat plant food plus dairy products and eggs. Lacto vegetarians dont eat eggs but they eat diary products. Vegans dont eat anything coming from an animal, therefore no diary products, eggs or honey for example.
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Conversion Plant to animal food
Meat based nutrition requires 20 times more land and 14 times more water than a plantbased diet. The production of 1kg of meat requires 10-16 kg of cereals and other plant food.
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Water consumption for fodder
70% of the worlds water consumption is needed for the production of fodder. It has been calculated that to produce 4kg of meat, the amount of water needed is equal to what a normal family consumes in one year.
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Manure pollution
Animal excrement which is responsible for half the pollution of our lakes, rivers and groundwater, amounts to 110t per second in Europe and America. 2/3 of it is liquid manure. The nitrate and ammonia in it contaminate our waters. The evaporation of the ammonia from this liquid manure causes part of the acid rains, after having changed to nitric acid.
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Compassion
The most important reason why we should not eat meat: sentient, suering creatures have to give their life for it. Every year 13 billion animals are slaughtered on earth.
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Nutrition transition toward animal foods implications in China
[9] B. M. Popkin and S. Du used China as a case study and found large shifts in the composition of diets and obesity across the developing world noting that these changes are accelerating. The authors point out that in developing countries the prevalence of obesity is greater than that of undernutrition and concerns related to intake of saturated fat and energy imbalance must be considered more seriously by the agriculture sector which is focused on livestock promotion. They come to the conclusion that although linkages between animal source foods intake and obesity cannot be established as clearly as they are for high animal source foods intakes, heart disease and cancer, the potential adverse health eects linked with an increased animal source foods intake should no longer be ignored.
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Animal origin may not be shown by the list of ingredients
[5] The animal origin of some ingredients may not be apparent from their names. For example, some additives may be carried on a gelatin base and therefore not be suitable for inclusion in a vegetarian or vegan diet. Food labelled as vegan or vegetarian may become contaminated during preparation, for example, outlets where deep fried food is cooked in oil that is used for both meat and non-meat products. This will not be apparent from the ingredients list. General EU rules already prohibit misleading labelling (Article 2 of Directive 2000/13/EC and Article 16 of EC Regulation 178/2002. However, there are no specic rules at EU level on vegetarian or vegan labelling, and this subject is not currently under discussion at EU level. Labelling food as suitable for vegetarian or vegans is entirely voluntary. However it does provide useful information to consumers and Government would not wish to discourage it. Legislation, including sanctions, is already in place to protect consumers against misleading labelling. Current enforcement activities involve industry inspections of labels to ensure they are not misleading. The advice set out in the proposed Guidance provide an interpretation of what should be considered as a minimum standard when labelling food as suitable for vegetarians or suitable for vegans (or other similar claims).
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Childhood intelligence and being a vegetarian
[10] [11] According to Marcus Richards evidence increasingly suggests that intelligence is associated with health and survival, and intelligence could mediate the impact of adverse circumstances (such as overcrowding), inuence the acquisition of factors that protect health, and reect underlying biological mechanisms that regulate health.
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IQ has nothing to do with vegetarianism
[12] Ramakant Sharma does not agree with the study. He says that vegetarianism has nothing to do with IQ. He claims that 60% of the population of India is vegetarian, even so this population is not more intelligent than the western counterparts who eat meat. The incidence of Indian CAD is 7 times higher than the western population. Sharma says that vegetarianism is a cultural phenomenon and it should be looked as that only. Sharma concludes that "vegetarian food is healthy" is a misconception. Probably, food has nothing to do with disease except malnutrition and deciencies.
14.1. FOOD AND ECOLOGY
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Food and ecology
About 6% of the population of Germany are vegetarians. They want to avoid to harm animals, to avoid food waist as animal feed and last, but not least to reduce greenhouse gases, such as carbon dioxide, methane, nitrous oxide emanating from animal breeding. FAO environmental scientist calculated the CO2 - equivalence of the dierent types of nutrition: The global animal population produce approximately one fth of greenhouse gases resulting from the activities of mankind. FAO stresses that this is more than the emission of global trac. CO2 emission results from burning forests to prepare land for pastures and feed crops. Dung and liquid manure produce nitrous oxide. Ruminants such as cattle and sheep emit methane. Mechanized agriculture of rape and soy produce more CO2 . Approximately 6 kilos of vegetable protein are necessary to produce one kilo animal protein.
14.1.1
Lacto-vegetarian nutrition
The Cornell University (Ithaca, USA) found in a study, that the production of one kilo milk protein needs 14 kilocalories of fossile energy, this is the same amount needed for the production of one kilo porc. The German Freiburger ko Institute writes that 8 litres milk are necessary to produce 1 kilo cheese.
14.1.2
The CO2 - equivalence of the production of 1 kilo, cheese, meat, egg and yoghurt
Product Emission of CO2 equivalece Cheese 8 kilo Meat 6 kilo Egg 2 kilo yoghurt 1 kilo
14.1.3
Soy and feed
According to Jrg Michael Greef from the German from the Bundesforschungsanstalt fr Landwirtscaft. The world production of soy is 220 million tons. Germany imports 40 million tons. Three million tons are used for the production of edible oil and other applications. The main core of 37 millions tons are transformed in animal feed. Soy farms built monocultures in USA, Argentina and Brazil, where they invade the tropical
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forest and savannahs. Centralised animal breeding, depending on soy are an environmental false step. Smaller units, depending on local feed are ecology friendly and create jobs.
14.1.4
Palmoil
According to the Environmental Program of the United Nations UNEP, 83% of palm oil comes from Indonesia and Malaisia. The consumption of Palm oil increases deforestation of these countries.
14.2
High consumption of red and processed meat linked breast cancer risk.
In a survival analysis to assess the eect of meat consumption and meat type on the risk of breast cancer in the UK it was found that women, both pre- and postmenopausal, who consumed the most meat and processed meats had a signicant increase in the risk of breast cancer. [13] According to Professor Janet Cade and colleagues from the University of Leeds, the high saturated fat content of the meat may be behind the apparent eects, with this kind of fat linked to cholesterol production which is a precursor for the female hormone oestrogen, linked to breast cancer risk. The disease is, however not limited to a sole cause, but many other factors may trigger breath cancer. The authors found a 64 per cent greater risk of breast cancer for post-menospausal women which consumed more than 20 grams per day processed meat, such as as bacon, sausages, ham or pies. An increased risk of 56found in women of the same age, which consumed more than 57 gram red meat per day. In pre-menospausal women consuming more than 20 grams processed meat per day an increase of breast cancer of 20 percent, compared with none meat eating women. The British Charity Breakthrough Breast Cancer denotes that there are other factors like age, weight, nutritional habits accounting for 30 per cent of the cases, and exercise which inuence health. It is being emphasized that all women eat a balanced diet, limit alcohol consumption, exercise regularly and keep a healthy weight in order to maintain general good health.
14.2. HIGH CONSUMPTION OF RED AND PROCESSED MEAT LINKED BREAST CANCER RISK. 1181 Eating less red and processed meat would bring health and environment benets says study [14] Using dietary intake data from the National Diet and Nutrition Survey of British Adults, Aston, Smith and Powels 2012 assessed the impact of reduction of consumption of red meat and processed meat on the reduction in risks of coronary heart disease, diabetes and colorectal cancer, and greenhouse gases (GHG) emissions. The authors stress that the UK will not meet the target of 80% of reduction by 2050 if domestic agricultural emissions is not dramatically reduced. The UK is approximately 50% to 90% self-sucient in livestock production with a high emission of GHG because of the emissions associated with cereal and soy imported to feed animals. Meat products are GHG intensive, with the Food and Agriculture Organisation attributing 18% of total global GHG emissions. [15] The authors calculated the emission of meat production based on a doubling of the number of vegetarians of today 2,3% of men and 6,2%of women to 4,7% and 12,3% respectively, and reducing the meat consume of non-vegetarians to a lowest basis would avoid the emission of 27,8 million tonnes/year in the UK which represents 3% of the current total. The proposed changes in dietary habits could reduce the meat consume from 91 to 53g/day for men and from 54 to 30 g for women. This would result in a reduction of 3,2% for diabetes in women and 12,2% for colorectal cancer in men.
14.2.1
Reduced bone mineral density of vegetarians and and vegans are of no concern
[16] A systematic electronic literature search was conducted by Ho-Pham to verify the association between vegetarian diets and bone mineral density. The authors found that bone mineral density was approximately 4% lower in vegetarians than in omnivores , and 6% lower in lumbar spine in vegans, whereas only 2% in lactoovovegetarians. The results suggest that vegetarian diets, particularly vegan diets, are associated with lower BMD, however it is not signicant.
14.2.2
Higher plasma homocysteine indicator of osteosporosis related to vegetarian diet
[17] Krivosikova and colleagues 2009 wrote that vegetarian diet is decient in vitamin B group, leading too hyperhomocysteinemia which,on its turn, is linked to increased bone turnover markers and increased fracture risk. The authors stresses that hyperhomocysteinemia, vitamin B(12) and folate deciency are risk factors for micronutrient deciency-related
1182 osteoporosis.
According to the authors homocysteine levels dependent on age as well as on nutritional habits, and can be regarded is one of the predictors of bone mineral density, homocysteine levels are. According to the data of the study elderly women on a vegetarian diet are at higher risk of osteoporosis development than nonvegetarian women.
14.2.3
Body fat was inversely correlated with the duration of vegetarianism found a Korean study.
[18] Lee and Krawinkel 2009 described the body composition and nutrient intake of Buddhist vegetarians nuns compared with omnivores Catholic nuns in South Korea. The found no height dierence between both dietary groups, however, the vegetarians had a signicantly higher body weight, fat free mass, body fat and body mass index than the omnivores. The authors stress that in vegetarians, body fat was inversely correlated with the duration of vegetarianism.
14.2.4
Vegetarians are more exposed to pesticides than omnivores
[19] Van Audenhaege and colleagues 2009 compare the pesticide residue dietary intake of the French general population and the vegetarian population. The authors found that the vegetarians are exposed to pesticides found in fruit, vegetables and cereals, such as tri-allate, chlorpyrifos-methyl and diazinon. Except for organochlorine compounds, the vegetarian population may be more exposed to pesticide residues than the general population due to specic dietary habits. Thus, this population should be considered for risk assessment of pesticide residues.
14.2.5
Vegetarian diet change gut microora, disease risks are unknown.
[20] Liszt and colleagues report that vegetarian diet changed the faecal microora in quantity and quality regarding Bacteroides, Bidobacterium and Clostridium cluster IV. Both bacteria Faecalibacterium sp. and a strain similar to gut bacterium DQ793301were more frequent in omnivores than vegetarians. Vegetarian diet reduced the amount and diversity of Clostridium cluster IV. The authors concluded that vegetarian diet changes the gut microbiota specically in relation to Clostridium cluster IV, and the eects of these shifts are unknown.
BIBLIOGRAPHY
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14.2.6
Variety of foods should be monitored in vegetarian diet for children
[21] In children vegetarian diets may bear risks with regard to growth, such as anaemia. Malnutrition risks even increase with vegan diets. Hackett and colleagues 1998 found that lacto-ovo-vegetarian diet is closer to recommendations and children on this diets grow similar to omnivores. The authors call on the industry to produce vegetarian convenience foods closer to recommendations. Recommendations are to avoid excessive reliance on convenience foods, lack of variety and lack of exercise.
14.2.7
Plant based diets develop high risk of mineral deciencies, specially zinc deciency
[22] Tupe and Chiplonkar 2009 report that Indian schollgirls had inadequate intakes of energy, protein, and micronutrients including zinc compared with the recommended dietary intakes of India. The authors developed new cereal-based recipes of which 200g could full 75% of the daily zinc requirement of adolescents and increase the intake of other micronutrient. They call on zinc-rich recipes with high bioavailability to counter zinc deciency in adolescents.
14.2.8
Vitamin B12 deciency may cause irreversible neurological damage
[23] Hartmann and colleagues 2009 point to the fact that even persons with normal vitamin B12 concentrations may present signs of deciency. The authors recommend to measure methyl malonic acid (MMA) in urine of risk group for deciency which include pregnant, breast feeding women and infants. The authors stress that prenatal and postnatal vitamin B12 deciency can cause severe irreversible neurological damage, and report of such cases caused by unidentied pernicious anemia and by vegan diet of the mothers. The researchers emphasize to measure MMA in the urine of all pregnant women to detect vitamin B12 deciency.
Bibliography
[1] Wikipedia, the free encyclopedia: Veganism.
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[2] http://www.ncbi.nlm.nih.gov/pubmed/20025224. Miret S, Tascioglu S, van der Burg M, Frenken L, Klake W.In Vitro Bioavailability of Iron from the Heme Analogue Sodium Iron Chlorophyllin. J Agric Food Chem. 2009 Dec 21. [3] http://jn.nutrition.org/cgi/content/abstract/140/6/1117. Ma Q, Kim EY, Han O: Bioactive Dietary Polyphenols Decrease Heme Iron Absorption by Decreasing Basolateral Iron Release in Human Intestinal Caco-2 Cells. J. Nutr., June 1, 2010; 140(6): 1117 - 1121. [4] http://jn.nutrition.org/cgi/content/full/138/9/1647. [2] Kim EY, Ham SK, Shigenaga MK, Han O: Bioactive dietary polyphenolic compounds reduce nonheme iron transport across human intestinal cell monolayers. J Nutr. 2008 Sep;138(9):164751. [5] http://www.food.gov.uk/multimedia/pdfs/vegitermsria.pdf. Food Standards Agency: Guidance on the use of the terms vegetarian and vegan in food labelling. [6] http://www.ajcn.org/cgi/content/abstract/59/5/1153S. TC Campbell and C Junshi: Diet and chronic degenerative diseases: perspectives from China; American Journal of Clinical Nutrition, Vol 59, 1153S-1161S. [7] http://www.virtualcentre.org/en/library/key_pub/longshad/A0701E00.pdf. Livestocks long shadow. Environmental issues and options. [8] http://www.european-vegetarian.org/evu/english/news/news. Vegetarianism is Love for Animals and Humans Speech given at the demonstration for animal rights in Zurich, October 1996 by Sigrid De Leo. [9] http://jn.nutrition.org/cgi/content/full/133/11/3898S. B. M. Popkin and S. Du: Dynamics of the Nutrition Transition toward the Animal Foods Sector in China and its Implications: A Worried Perspective; J. Nutr., November 1, 2003; 133(11): 3898S - 3906. [10] Richards, Marcus: Childhood intelligence and being a vegetarian ; BMJ, Feb 2007; 334; 2216-217; doi:10.1136/bmj.39107.671412.80. [11] Catharine R Gale, Ian J Deary, Ingrid Schoon, and G David Batty: IQ in childhood and vegetarianism in adulthood: 1970 British cohort study. BMJ, Feb 2007; 334:245 ; doi:10.1136/bmj.39030.675069.55. [12] http://www.bmj.com/cgi/eletters/334/7587/216#156886. Sharma, Ramakant: IQ has nothing to do with vegetarianism. Rapid Responses Published to Marcus Richards Childhood intelligence and being a vegetarian BMJ 2007; 334: 216-217(5 February 2007).
BIBLIOGRAPHY
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[13] http://www.nature.com/bjc/journal/v96/n7/abs/6603689a.html. Taylor, E F; Burley; V J; Greenwood, D C and Cade J E: Meat consumption and risk of breast cancer in the UK Womens Cohort Study British Journal of Cancer. Volume 96, Pages 1139-1146 doi:10.1038/sj.bjc.6603689. [14] Aston LM, Smith JN, and Powles JW. Impact of a reduced red and processed meat dietary pattern on disease risks and greenhouse gas emissions in the uk: a modelling study. BMJ Open, 2(5):pii:e001072, 9 2012. http://bmjopen.bmj.com/content/2/ 5/e001072.long. [15] Livestocks long shadow. food and agriculture organization (fao). ftp://ftp.fao. org/docrep/fao/010/a0701e/a0701e03.pdf. [16] http://www.ncbi.nlm.nih.gov/pubmed/19571226. Ho-Pham LT, Nguyen ND, Nguyen TV: Eect of vegetarian diets on bone mineral density: a Bayesian metaanalysis. Am J Clin Nutr. 2009 Oct;90(4):943-50. Epub 2009 Jul 1. [17] http://www.ncbi.nlm.nih.gov/pubmed/19809862. Krivosikova Z, KrajcovicovaKudlackova M, Spustova V, Stefkova K, Valachovicova M, Blazicek P, Nemcova T: The association between high plasma homocysteine levels and lower bone mineral density in Slovak women: the impact of vegetarian diet. Eur J Nutr.2009 Oct 7. [18] http://www.ncbi.nlm.nih.gov/pubmed/19713187. Lee Y, Krawinkel M.: Body composition and nutrient intake of Buddhist vegetarians. Asia Pac J Clin Nutr. 2009;18(2):265-71. [19] http://www.ncbi.nlm.nih.gov/pubmed/19707917. Van Audenhaege M, Heraud F, Menard C, Bouyrie J, Morois S, Calamassi-Tran G, Lesterle S, Volatier JL, Leblanc JC.: Impact of food consumption habits on the pesticide dietary intake: Comparison between a French vegetarian and the general population. Food Addit Contam Part A Chem Anal Control Expo Risk Assess. 2009 Oct;26(10):1372-88. [20] http://www.ncbi.nlm.nih.gov/pubmed/19641302. Liszt K, Zwielehner J, Handschur M, Hippe B, Thaler R, Haslberger AG.: Characterization of Bacteria, Clostridia and Bacteroides in Faeces of Vegetarians Using qPCR and PCR-DGGE Fingerprinting. Ann Nutr Metab. 2009 Jul 27;54(4):253-257. [21] http://www.ncbi.nlm.nih.gov/pubmed/9670174. Hackett A, Nathan I, Burgess L: Is a vegetarian diet adequate for children. Nutr Health. 1998;12(3):189-95. [22] http://www.ncbi.nlm.nih.gov/pubmed/19628369. Tupe R, Chiplonkar SA.: Diet patterns of lactovegetarian adolescent girls: Need for devising recipes with high zinc bioavailability. Nutrition. 2009 Jul 21. [23] http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2689578. Hartmann, Hans; Das, Anibh Martin; Lcke, Thomas: Correspondence (letter to the editor): Risk Group
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CHAPTER 14. VEGETARIANISM includes infants. Dtsch Arztebl Int. 2009 April; 106(17): 290-291. Published online 2009 April 24. doi: 10.3238/arztebl.2009.0291.
Chapter 15 Organic Food

15.1 New label: Organic food, holistic food, Biokost and Naturproduct
European organic food has mutated to mass production under the EU regulation 2092/91 and 1804/1999. [1] [2] The European Commission in their "European Action Plan for Organic Food and Farming" states: "Organic sales through supermarkets are the fastest-growing distribution channel in most markeFor consumers buying organic produce in supermarkets, environmental considerations are thought to be less important, compared to consumers buying produce in specialised organic shops." [3] The European organic food regulation clearly demonstrates its commitment to mass production and the supermarkets as distribution channel. This increases monoculture wide elds long transport ways and air freight. The new meaning of "organic food" The team of professor Carlo Leifert from the Univesity of Newcastle UK, is running the Quality Low Input Food (QLIF) project with a budget of 18 million Euro of the EU funding in 5 years. So far the team found that organic milk contains higher amounts of vitamin E, and fruits and vegetables have higher levels of vitamin C, minerals and antioxidants as found in non-organic ones [4] [5]. Some small studies were held on organic tomatos [6], Organic peaches had a 4.8 higher polyphenol content at harvest in 2004, whereas the same phenomenon was not observed in 2005 [7]. Total phenols, vitamin C, total avones and antioxdant capacity of organic apple pure was found to be higher than that of preserves prepared from conventional apples. 1187
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CHAPTER 15. ORGANIC FOOD
However, after pasteurization, the content of vitamin C, total phenols and avones and antioxidant properties decreased in the apple pure from both agricultural systems (organic and conventional) [8]. EU Organic Regulation 834/2007 [9] [10] Regulation (EEC) No 2092/91 is hereby repealed as from 1 January 2009. The new rules set out a complete set of objectives, principles and basic rules for organic production, and include a new permanent import regime and a more consistent control regime. The use of the EU organic logo will be mandatory, but it can be accompanied by national or private logos. The place where the products were farmed has to be indicated to inform consumers. Food will only be able to carry an organic logo if at least 95 percent of the ingredients are organic. But non-organic products will be entitled to indicate organic ingredients on the ingredients list only. The use of genetically modied organisms will remain prohibited. It will now be made explicit that the general limit of 0.9 percent for the accidental presence of authorised GMOs will also apply to organic products . The new rules also create the basis for adding rules on organic aquaculture, wine, seaweed and yeasts. The new organic regulation and labelling will come into force in January 2009 The EU followed the pressure of GM companies such as AstraZeneca, BASF Plant Science, Bayer CropScience, Dow AgroSciences, Du Pont, Monsanto and Syngenta. The new regulation increases the current threshold for GM contamination of organic food from 0.1 per cent to 0.9 per cent and allowing the use of GM-produced additives for which there is no GM-alternative the new regulation opens the way for genetically modied material to enter organic food. Implementation of organic products regulations The EU regulation 889/2008 lays down detailed rules for the implementation of the regulation 834/2007 on organic production and labelling. [11] Import of organic products Arrangements for imports of organic products from third countries are established in the regulation 1235/2008. [12] The implementation of the organic production logo of the European Union. [13]
15.2. ORGANIC FOODS COMPARED TO CONVENTIONAL PRODUCES Polyunsaturated fatty acids
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Ellis and colleagues Organic milk had a higher proportion of PUFA to monounsaturated fatty acids and of n-3 FA than conventional milk, and contained a consistently lower n6:n-3 FA ratio (which is considered benecial) compared with conventional milk [14]. Croissant and colleagues measured greater percentages of unsaturated fatty acids, including two common isomers of conjugated linoleic acid, in pasture based milks compared with milk of cattle fed a conventional total mixed ration. Distinct avour and compositional dierences between both types of milk were such that they did not aect consumer acceptance [15]. The UK Food Standards Agency says that the balance of current scientic evidence does not support the view that organic fruit, vegetable and meat are more nutritious than nonorganic foods [16]. FSA stresses also that milk contains the shorter chain form of omega-3 polyunsaturated fatty acids (alpha-linolenic acid), while the forms present in oily sh are the long chain fatty acids (eicosapentaenoic (EPA) and docosahexaenoic acids (DHA)). Research has shown that the short chain form found in plant and dairy sources does not appear to be as benecial as those found in oily sh, which have been shown to be protective for cardiovascular disease, and may alsohave benecial eects on foetal development. Although the shorter form can be metabolised to the longer forms, in humans the conversion appears limited. The FSA, however, will review the scientic literature on nutrients of organic food, which will be released in March 2008. [17] The Soil Association tries to set standards for and promote the consumption of organic meat and produces. The Association allows air freight despite the tremendous damage it causes to climate. [18]
15.2
Organic foods compared to conventional produces
Organic products are now sold in conventional supermarkets with high marketing eorts.
15.2.1
Health and environmental advantages of organic food [19]
Organic food has fewer pesticides associated with human disease. Organic farming causes a reduced environmental impact compared to conventional farming. There are, however, no convincing facts which support higher nutritional and health benets, or disease protection from organic diet compared to conventional diet. Having this in mind, Forman et al. 2012 call on pediatricians to encourage all patients and their families to attain optimal nutrition and dietary variety consistent with the US Department of Agricultures MyPlate
1190
recommendations [20]. Additional informations can can also be looked up at the USDA Super Tracker, My Plan [21]. The study also states that organic foods have the same vitamins, minerals, antioxidants, proteins, and other nutrients as conventional foods, however, these products have lower pesticide levels. Organic meat is less likely to be contaminated with drug-resistant bacteria, because antibiotics are not used in these animals. Organic milk is often bought to avoid growth hormones and estrogen that may be fed to conventionally raised cows. This is of no concern because bovine growth hormone has no eect on humans and estrogen is present in human breast milk at higher levels found in cow milk. Organic products cost up to 40% more. Forman and colleagues stress that families with low food budge should buy conventional foods as a good choice instead of reducing quantity and diversity on behalf of organic foods. Altogether, organic foods oer no meaningful nutritional benets, says the study of Forman and colleagues, supported by the American Academy of Pediatrics.
No data supporting nutritious gain overconventional foods [22] A study of Smith-Spangler et al. 2012 says that only a small number of studies analysed dierences between organic and conventional foods regarding the clinical data on allergic outcomes (eczema, wheeze, atopic sensitization) or symptomatic Campylobacter infection. These studies report no dierences between both food types. Signicantly lower urinary pesticide levels among children consuming organic versus conventional diets were found, but the risk for exceeding maximum allowed limits was small. Biomarker and nutrient levels in serum, urine, breast milk, and semen in adults did not identify clinically meaningful dierences. Escherichia coli contamination risk did not dier between both food types, and no difference could be found in the bacterial contamination of retail chicken and pork. The number of bacteria resistant to 3 or more antibiotics, however, was higher in conventional than in organic chicken and pork. The authors concluded that organic food is not more nutritious than conventional foods, but has less pesticide residues and antibiotic-resistant bacteria resistant to three or more drugs. Between 40% and 80% of antimicrobials used in the United States are used in farm animals, three quarters of which are for nontherapeutic uses increases the number of dangerous drug-resistant bacteria.
15.2. ORGANIC FOODS COMPARED TO CONVENTIONAL PRODUCES Lessons learned from agriculture in the Andes
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Work with multiple actors is needed to shift agriculture towards greater sustainability and human health, particularly for vulnerable smallholders such as poor countries like Ecuador. Mostly used are organophosphorus and carbamate compounds which are cheap but hazardous pesticides. Educational work among smallholder farmers in the Andes resulted in stronger involvement in organic agriculture increasing household food security and food sovereignty and reduce hazardous pesticide use. [23] While conventional agriculture in developed countries are heading to safe use of pesticides developing countries are disregarding safety issues on agrarian chemicals. Changing to organic agriculture is therefore imperious in these regions.
Studying environmental threats [24] The Center for Environmental Research and Childrens Health (CERCH) studies the risk of environmental threats to childrens health investigating exposures to future parents and children and develop sustainable strategies to reduce environment-related childhood disease. CERCH studies the association of dierent diseases with environmental factors. The center focusses on Asthma and respiratory health linked to moulds and pollen, Attention Decit Hyperactivity Disorder (ADHD) possibly linked to Mothers exposure to organophosphate pesticides during pregnancy, poor cognitive functioning in children and lower IQ is linked to mothers exposure to organophosphate pesticides during pregnancy. The ndings of the center demonstrates the need to reduce globally the use of toxic agrarian chemicals and educate smallholder farmers.
Comparing nutrient levels in organic and conventional foods [25] Charles Benbrook and colleagues published in March 2008. a study comparing nutrient levels in organic and conventional foods. The authors used data from scientic studies on published since 1980, including quercetin, kaempferol, total phenolics, antioxidant capacity, ascorbic acid, beta-carotene, vitamin E, potassium, phosphorous, nitrate, and total protein, between organically and conventionally grown food. In 236 samples of organic and conventional foods, which were equally measured on nutrient content, 61% of the organic samples were claimed to be nutritionally more dense. The organic samples were also said to have higher levels of polyphenols and antioxidants. Overall, across all 236 matched pairs and 11 nutrients, the nutritional premium of the organic foods was on average 25%.
1192 Quercetrin
Benbrook and colleagues say that organically grown vegetables contained 2.4 times more quercetrin (a precursor of quercetin) than conventionally grown ones. According to the author, quercetin is used by the plant to protect itself from pests and weeds. The organic samples contained higher concentrations of the very important polyphenols and antioxidants in about three-quarters of the 59 matched pairs representing those four phytonutrients. Increasing intakes of these nutrients is a vital goal to improve public health since daily intakes of antioxidants and polyphenols are less than one-half of recommended levels Critic of the Benbrook study [26] Dr Joseph Rosen, however, re-open the debate as to whether organic or conventionally produced foods are nutritionally superior. Rosen criticises the study of Benbrook because results which were not statistically signicant were included, while other important data were not. Rosen, recalculating data from Bonbrook, found that organic produces were actually 2% more nutritious that the organic produce. Rosen says that in the studied cases organic vegetables had been sprayed with an organic pesticide which would have increased the plants production of quercetin. In the study of Benbrook, the nutriet content of kiwi fruit, the skin which is not eaten by the consumer was included. The American Council on Science and Health say that Dr. Rosens analysis demonstrates how organic proponents have used misleading and inappropriately-evaluated data to support their agenda to promote organic foods. Charles Benbrook is a consultant for the Organic Trade Associations Organic Center. Higher bioactive polyphenols content in organic tomato juice than in conventional juice [27] Vallverd-Queralt et al 2011 write that phenolic compounds and hydrophilic antioxidant capacity were higher in organic tomato juice, compared with conventional tomato juices. The authors refer to numerous studies related to the ingestion of polyphenols in diet to a lower risk of cardiovascular diseases and development of cancers. An increasing demand for processed tomato products, rises the interest on tomato nutrients and the antioxidants of tomato. Polyphenol content in plants is inuenced by cultivation and harvesting conditions. Dierences between organic and conventional production systems, such as the use of inorganic
15.2. ORGANIC FOODS COMPARED TO CONVENTIONAL PRODUCES
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nitrogen may interfere in the production of secondary plant metabolites, proteins and soluble solids. The authors concluded that it seems that there is a dierence in the bioactive components of organic and conventional tomato juices that has been unknown. Dierent soil management between organic tomatoes and conventionally grown tomatoes [28] Barrett et al 2007 found that tomato juice prepared from organic tomatoes of some farms presented higher soluble solids ( degrees Brix), higher in consistency, and titratable acidity, but were lower in red colour, ascorbic acid, and total phenolics content, compared with conventional tomatoes. The authors also report signicant dierences among growers, due to dierent soil type, soil nutrients, tomato cultivar, environmental conditions, or other production-related factors. Important for the food industrial is that conventionally produced tomatoes, were more red in colour and the juice was higher in ascorbic acid and total phenolics. Activities of antioxidants in organic food are noted in vitro, but fail in humans [29] Crinnion 2010 writes that studies dier in the results of nutrient content in organic foods. This is related to soil management and maturity of the organic farming operation, from farmer to farmer and year to year. However, there is consistency in the armation that organic products have greater levels of vitamin C, iron, magnesium, and phosphorus; and lower contents of nitrates and pesticides than non-organic foods. The authors also highlight the greater levels of antioxidants found in organic foods. On this behalf, no dierences were noted with wheat, oats, and wine The authors, however, caution that the antioxidant and anti-cancer activities of these nutrients were demonstrated in vitro, in humans no additional benet could e demonstrated. Organic dairy products are told to reduce allergic dermatitis reactions.
15.2.2
No health benets but environmental gains consuming organic foods says study
A review of 223 studies of nutrient and contaminant levels of organic and conventional foods. Smith-Sprangler et al. 2012 found no dierence in nutritional value or bacterial contamination between both classes of foods. [30] There was no strong evidence that organic foods are signicantly more nutritious than conventional foods. However, a reduction of 30 per cent of exposure to pesticide residues and reduced exposure to antibiotic-resistant bacteria of chicken and pork may be a benet consuming organic foods. The authors point out that the dierence in pesticide residue in
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organics is not relevant because levels in conventional food are already low, much below allowed limits. No dierences in allergic reactions or Campylobacter infections were noted between organic and conventional foods. No clinical relevant dierences in biomarkers and nutrient levels in serum, urine, breast milk, and semen in adults which of organic food eaters compared with conventional food consumers were noted. Despite having no health benet over conventional foods, the consumer should still adhere to organic foods because of the contribution to a stable environment and to the welfare of the animal at the farm. The original ideas of "organic" food was the altruistic way of life to live in harmony with nature and not harm environment and animals. The position of the UK FSA: Isnt there evidence that organic food is safer and more nutritious? [31] The Agency says that some scientic papers reach conclusion that organic food is safer and more nutritious than conventional foods, but other studies nd no dierence. The agency calls to evaluate a range of publications to reach a robust conclusion and reliace should not depend on single papers.
15.2.3
New denition of organic food and holistic food
The organic food produced according to the EU regulation diers from the original way of production. It becomes necessary to separate the organic food from supermarkets from the original holistic food, produced under strict rules of certifying corporations which follow the principles of organic associations, like Demeter or follow a holistic way of farming. Denition To make the dierence between both types of food the following denition is being suggested: Holistic food (En), Ganzheitlich (D) Holistic food is produced according to rules of certifying corporations which follow the principles of other holistic ways of farming. These Foods are sold by the producer itself at its farm, at weekly markets or at nature shops. There competent informations are given concerning the origin of the food. The consumer understands that the higher price of nature products is due to diversication of crops at the farm, a species-appropriate animal raising, and environment conservation. The holistic food farmers and the specialised nature shops should distanciate itself from the words "Organic" or "Biokost" because they have become a domain of supermarkets and have undergone a mutation from the original food.
15.2. ORGANIC FOODS COMPARED TO CONVENTIONAL PRODUCES Organic Food (En), (Biokost D)
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Organicfood is produced according to the EU 2092/91 and 1804/1999 regulation. The consumer expects food produced without agrarian chemicals, like herbicides or pesticides. He expects better taste compared with conventional foods. He looks after low priced products. He is concerned with the welfare of his person and does not care about environment. He is not interested to know the food miles and airfreight of the items he buys. Organic food is primarily sold by supermarket chains. Some reaction of producer and customers have put the Basic chain of organic supermarkets under pressure not to sale its shares to the Swiss Schwarz group, owner of supermarket chain Lidl. New EU organic logo for supermarket organic quality [32] The European Commission has been under heavy pressure of lobbies by the some agrarian organisations, certiers and last, but not least, big supermarket chains. Taking organic food into the machinery of food industry promised new brands, new green image an a boost for sales volume. Strategists of their marketing and publicity department were. A new logo for the EU organic food will be on all packaged organic foods in your Supermarket in July 2010.
Remember If you buy organic food from your supermarket you by packaged food which has grown in large monoculture, with high carbon foot prints. Certiers also give certicates to food transported by aircraft.
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Do not believe on what is behind this logo, it is not the original food grown on small farms embedded in a sound environment. It is not healthier than conventionally grown food, which has to be healthy by stringent food regulations. The food under this logo wrecks the subsistence of small farms. Organic milk in USA under re [33] Aurora, selling milk under brands which include Costcos Kirkland and Targets Archer Farms in cartons marked "USDA organic," with pictures of pastures or other bucolic scenes, was lawsuited for not being organic at all. Aurora claims that there is absolutely no basis for claims that the company defrauded consumers by selling milk that isnt organic - none whatsoever. [34] [35] Consumers buy organic food believing it is free of hormones or pesticides and the production protects the environment. Organic products, however, are being sold in such quantities that it is not possible to follow organic rules established by the Organic Foods Production Act 1990 [36]. The "Harvey Rule", demande stricter rules governing organic milk production. It requires farmers to feed their livestock 100 percent organic grain, compared with the earlier standard of 80 percent organic grain and 20 percent conventional grain. The Harvey Rule went into eect in June 2007 [37] But rising corn prices are a problem for organic farmers, because corn farmers see few incentives to go organic because they can make so much money selling their crops to make ethanol. Meanwhile overproduction of organic milk drives to greater quantities of organic powdered milk, yogurt, ice cream, Omega-3-fortied organic milk and cheeses. New method detecting the use of synthetic fertiliser in organic produces [38] Organic farming is a form of agriculture that excludes the use of synthetic fertilizers, pesticides, and genetically modied organisms. Francisco M. del Amor and colleagues looked to a method to determine to what extent articial fertilisers have been used, unveiling possible frauds using organic label on conventional products. The authors found that synthetic fertilizers typically have a and almost all the content of nitrogen is 14 N.
15
N content close to zero
15.3. INTRODUCTION Table 15.1: Green Revolution Grains, million tons Population billions Cropland billion acres 1950 1992 Growth 692 1900 174% 2.2 5.6 154% 1.70 1.73 1.7%
1197
They concluded that the use of synthetic fertilizers signicantly reduced the proportion of nitrogen 15 N. This was pronounced in old leaves and fruits where the use of synthetic fertilizer cause a reductions in 15/14 N2 vsN2 atm of 24.1and 27.8%, respectively. The also found that no additional fertilization (synthetic or organic) is required before 106 days after transplanting at that dosage because plant fresh weight was not reduced.
15.3
Introduction
With the introduction of new seeds of wheat and rice, as well as the use of fertilizers, pesticides and irrigation Dr. Norman Borlaug started the "Green Revolution" in 1950. The Nobel Peace Price was awarded to him in 1970 for averting famine in India and Pakistan in the 1960s. Chemical fertilizers and pesticides rose the world grain production from 1950 to 1992 by 170 %,using only one percent more land. Another important step in agrarian technology is the development of new strains of wheat that can grow on pastures with a high aluminum content in Brazil, slowing down the cutting of the rain forest. Despite the protests of environmentalists, Borlaug brought high-yield agriculture to Africa, which still depends on slash-and-burn subsistence farming. Due to his eorts, Ethiopia recorded the greatest harvest of major crops in its history during the 1995-96 season with a 32 percent increase in production and a 15 percent increase in average yield over the previous season. Despite the benets of the green revolution other systems are being developed. No system alone can be the answer to the problems feeding the world: All of them allow positive results which can complement one another. Organic food Organic food production in large scale started in Europe in 1993 with the subventions of the governments trying to shift from chemical based to a natural agriculture. Austria and Swiss have about 10%f their area covered with organic elds. France plans to change 20% of the direct paid agrarian funds in ecological developing programs.
1198
CHAPTER 15. ORGANIC FOOD Table 15.2: Crop yields of organic and conventional products in Germany 1995
Product Milk/cow/year Wheat/dt/ha
Conventional Organic breeding breeding 4886 litres 4044 litres 61 dt/ha 38 dt/ha
Organic crop yields
The crop yields of organic farms are much lower as obtained by conventional farming. This means, the prices of these products are higher than conventional prices The dierence varies from 20 to 100%. A problem is the low acceptance of the organic products because of their price. As supermarkets started to sell these products, a higher output was possible, resulting in a small price reduction.
Due to the BSE scandal, organic farmers are getting better support from government. Global agriculture leads to a soybean-corn-beef agriculture, producing increasingly processed foods, fast foods and standard foods with higher yields, which are cheaper and less labor intensive. The demand from consumers for organically produced agricultural products and foodstus is increasing; whereas a new market for agricultural products is thus being created with a higher market price as for conventional products because the way in which they are produced involves less intensive use of land. Unfortunately a great group of consumer buy organic foods only because of their own health. Comparing prices, the positive impact on environment, ecology and conservation of the countryside are not taken into consideration. Organics in USA, regulations According to Ronnie Cummins, writing for The Progressive Populisat The USDA is caught in a familiar predicament given the agencys dual role. On the one hand it is set up ostensibly to protect consumers by ensuring a safe food supply and guarantee the economic livelihood of Americas farmers, the majority of whom continue to operate small and medium-sized farms. On the other hand, USDA also sees as its role to promote the industrialization and globalization of American agriculture which means working closely with large agribusiness, chemical, and biotechnology corporations. The natural food industry, with its small stores, small family farms, and discriminating consumers, has begun to pose a direct threat to the market share of large-scale agribusiness. [39]
15.3. INTRODUCTION US regulation
1199
[40] National Organics Standards Board (NOSB)composed of industry representatives, farmers, environmentalists and food processors. The NOSB, established by the Organic Foods Production Act in 1990, made recommendations to the USDA that explicitly banned genetically engineered foods, irradiation, farming with sewage sludge, and intensive connement factory farm type animal husbandry practices. Organic Foods Production Standards regulates the certication of organic producers. USDAs National Organic Program (NOP), authorized under the Organic Foods Production Act of 1990 regulates organic foods in USA. European regulation [1] [2] To create a framework of Community rules on production, labelling and inspection of organic farming, the Council Regulation No 2092/91 EWG on organic production of agricultural products, the No 1804/1999 which includes livestock production, and the No 207/93EEC [41] were adopted. Organic farming involving varied cultivation practices and limited use of non-synthetic fertilizers are specied in these regulations. Conditions for the use of certain non-synthetic products are there laid down. Specic provisions are made, aiming to avoid the presence of certain residues of synthetic chemicals from sources other than agriculture (environmental contamination). Organic production methods entail signicant restrictions on the use of fertilizers and pesticides which may have detrimental eects on the environment or result in the presence of residues in agricultural produce. Ingredients for processed organic foods are specied in the regulation. Organic food is produced by farmers who emphasize the use of renewable resources and the conservation of soil and water to enhance environmental quality for future generations. Organic meat, poultry, eggs, and dairy products come from animals that are given no antibiotics or growth hormones. Organic food is produced without using most conventional pesticides; fertilizers made with synthetic ingredients or sewage sludge; bioengineering; or ionizing radiation. The demand from consumers for organically produced agricultural products and foodstus is increasing; whereas a new market for agricultural products is thus being created with a higher market price as for conventional products because the way in which they are proCopyright 1998-2010 Karl H. Wilm. All rights reserved. OurFood Database of Food and Related Sciences
1200 duced involves less intensive use of land.
Unfortunately a great group of consumer buy organic foods only because of their own health. Comparing prices, the positive impact on environment, ecology and conservation of the countryside are not taken into consideration.
15.4
Organic Food in Europe
In 1991 the Council created with Council Regulation (EEC) No 2092/91 the rst ever Community framework for organic farming and food production. Organic food production in large scale started 1993 in Europe with the subventions of the governments trying to shift from chemical based to a natural agriculture. Austria and Swiss have about 10% of their area covered with organic elds. France plans to change 20% of the direct paid agrarian funds in ecological developing programs. In 2001, the Council under Swedish Presidency,invited the Commission to propose a European Action Plan for Organic Food and Farming (EAP). The Commission adopted the Communication on the EAP in June 2004.
Organic production Organic production is an overall system of farm management and food production that combines best environmental practices, a high level of biodiversity, preservation of natural resources, application of high animal welfare standards and production in line with the preference of certain consumers for products produced using natural substances and processes. The organic production method thus plays a dual societal role, where it on the one hand provides for a specic market responding to a consumer demand for organic products, and on the other hand delivers public goods contributing to the protection of the environment and animal welfare, as well as to rural development. The essential requirements dening organic production and labelling of organic products are laid down by the principles and production rules formulated in this proposal.
15.5
The Proposal on Organic Food
The proposal covers all organic products.

15.6. ORGANIC FARMING Exceptions
1201
The preparation and sale to the nal consumer of meals in large scale kitchens; for example in restaurants, hotels, hospitals and canteens, or in bars and coee shops are not covered by the Proposal. The EU logo should continue to be available on all products that comply with the Regulation, including for all imported products.
GMOs Genetically modied organisms (GMOs) and products produced from or by GMOs are incompatible with the concept of organic production and consumers perception of organic products. They should therefore not be deliberately used in organic farming or in the processing of organic products. The Proposal prohibits the use of the term organic for GMO labelled products. At least 95 percent of the nal product must be organic for it to be labelled as such. Although products containing GMOs may not be labelled as organic, there is an exception for those with up to 0.9 percent GMO content from accidental contamination.
15.6
Organic farming
Organic farming should primarily rely on renewable resources within locally organised agricultural systems. In order to minimise the use of non-renewable resources, wastes of plant and animal origin should be recycled to return nutrients to the land and for energy production. Organic plant production should contribute to maintaining and enhancing soil fertility as well as to preventing soil erosion. Plants should preferably be fed through the soil ecosystem and not through soluble fertilisers added to the soil. The essential elements of the organic plant production management system are soil fertility management, choice of species and varieties, multi-annual crop rotation, recycling organic materials and cultivation techniques. Additional fertilisers, soil conditioners and plant protection products should only be used if they are compatible with the objectives and principles of organic production.
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15.7
Controls
With regard to controls, Regulation (EC) No 882/2004 of the European Parliament and of the Council on ocial food and feed controls (OFFC) entered into application on 1 January 2006 covering organic farming. Organic Logos Organic foods may bear the organic logo for their individual member state. Under the new regulation it will be compulsory for them to also carry either the EU logo, which has existed for a number of years, or to wording EU organic. The regulations COM(2005) 671 nal 2005/0278 (CNS) 2005/0279 (CNS) will come into force for EU member states in January 2009. For imports, for which there are presently no rules, they will be eective from January 2007. Such imports must comply with EU standards or come with equivalent guarantees from their country of origin.
15.8
Principles applicable to all organic production
The use of living organisms and mechanical production methods shall be preferred to the use of synthetic materials. Natural substances shall be used in preference to chemically synthesised substances, which may be used only where natural substances are not commercially available. GMOs and products produced from or by GMOs may not be used, with the exception of veterinary medicinal products. Rules of organic production shall be adapted to local conditions, stages of development and specic husbandry practices, while maintaining the common concept of organic production.
15.9
Principles applicable to organic farming
Farming shall maintain and enhance soil fertility, prevent and combat soil erosion, and minimise pollution. Farming shall aim at producing products of high quality instead of maximising production. The use of non-renewable resources and o-farm inputs shall be minimized;
15.10. PRODUCTION OF PROCESSED ORGANIC FEED AND FOOD
1203
Wastes and by-products of plant and animal origin shall be recycled as input in plant and livestock production and for energy production. Production decisions shall take account of the local or regional ecological balance. Plants shall be primarily fed through the soil ecosystem. Maintenance of animal and plant health shall be based on preventative techniques including selection of appropriate breeds and varieties. Feed for livestock shall come primarily from the holding where the animals are kept or shall be produced in cooperation with other organic farms in the same region. The highest level of animal welfare shall be observed. Products of organic livestock production shall come from animals that since birth or hatching and throughout their life have been raised on organic holdings. Breeds shall be chosen favouring slow growing strains and having regard to the capacity of animals to adapt to local conditions, their vitality and their resistance to disease or health problems. Organic livestock feed shall be composed essentially of agricultural ingredients from organic farming and of natural non-agricultural substances. Husbandry practices which enhance the immune system and strengthen the natural defence against diseases shall be used. Aquaculture production shall minimise the negative eect on the aquatic environment. Feed used in aquaculture shall be from sustainable sheries or composed essentially of agricultural ingredients from organic farming and of natural non-agricultural substances. Polyploid animals may not be used.
15.10
Production of processed organic feed and food
Organic food and feed shall be produced essentially from agricultural ingredients which shall be organic, except where an organic ingredient is not commercially available. Additives and processing aids shall be used to a minimum extent and only in case of essential technological need. Ionising radiation may not be used.
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15.11
General farm production rules
Where not all of a farm is used for organic production, the holding may be split up into clearly separated units which are not all managed under organic production. In this case, adequate records to show the separation must be kept. Farmers are required not to use GMOs or products produced from GMOs. Where farmers use products purchased from third parties to produce organic food or feedstus, they shall require the vendor to conrm that the products supplied have not been produced by +Os.
15.12
Plant production rules
Organic plant production should comply with the following rules: Organic plant production shall be based on tillage and cultivation practices that maintain or increase soil organic matter, enhance soil stability and soil biodiversity, and prevent soil compaction and soil erosion. Fertility and biological activity of the soil shall be maintained and increased by multiannual crop rotation including green manure, application of manure and organic material from organic farms. Fertilisers and soil conditioners compatible with the objectives and principles of organic production may be used if they have been approved Mineral nitrogen fertilisers shall not be used. All plant production techniques used shall prevent or minimise any contribution to contamination of the environment. Prevention of damage caused by pests, diseases and weeds shall rely primarily on the choice of species and varieties, crop rotation and cultivation techniques. In the case of threat to a crop, plant protection products compatible with the objectives and principles of organic production may be used if they have been approved. The use of any approved synthetic substances shall be subject to conditions and limits as regards the crops that they can be applied to, the application method, the dosage, the time limits for use and the contact with crop. Only organically produced seed and propagating material may be used. To this end, the mother plant in the case of seeds and the parent plant in the case of vegetative propagating material shall have been produced in accordance with the rules laid down
15.13. LIVESTOCK PRODUCTION RULES
1205
in this Regulation for at least one generation, or, in the case of perennial crops, two growing seasons. The collection of edible plants and parts thereof, growing naturally in natural areas, forests and agricultural areas, is considered an organic production method provided that Those areas have not, for a period of three years before the collection, received treatments with not approved products. The collection does not aect the stability of the natural habitat or the maintenance of the species in the collection area.
15.13
Livestock production rules
Livestock production should complie with the following rules: With regard to husbandry practices and housing conditions: Personnel keeping animals shall possess the necessary knowledge and competence as regards the health and the welfare needs of the animals. Husbandry practices, including stocking densities, and housing conditions shall ensure that developmental, physiological and ethological needs of animals are met. The livestock shall have permanent access to a free-range area, preferably pasture, whenever weather conditions and the state of the ground allow this. The number of livestock shall be limited with a view to minimising overgrazing, poaching of soil, erosion, or pollution caused by animals or by the spreading of their manure. Organic livestock shall be kept separate or readily separable from other livestock. Tethering or isolation of livestock shall be prohibited, unless for individual animals for a limited period of time and justied for safety, welfare or veterinary reasons. Duration of transport of livestock to slaughterhouses shall be minimised. Any suering, including mutilation, shall be kept to a minimum. Apiaries must be placed in areas which ensure nectar and pollen sources consisting essentially of organically produced crops and/or spontaneous vegetation and must keep enough distance from sources leading to contamination of products from beekeeping. Hives and materials used in bee-keeping must be made of natural materials.
1206
The destruction of bees in the combs as a method associated with the harvesting of bee-keeping products is prohibited. With regard to breeding: Reproduction shall not be induced by hormone treatment, unless in order to treat reproduction disorders. Cloning and embryo transfer shall not be used. An appropriate choice of breed shall contribute to the prevention of any suering and to avoiding the need for mutilation of animals. With regard to feed: Livestock shall be fed with organic feed, which may include proportions of feed from farm units which are in conversion to organic farming, that meet the animals nutritional requirements at the various stages of its development. Animals shall have permanent access to pasture or roughage. Feed additives may be used only if they have been approved. Growth promoters and synthetic amino-acids may not be used. Suckling mammals shall be fed with natural, preferably maternal, milk. With regard to disease prevention and veterinary treatment: Disease prevention shall be based on breed and strain selection, husbandry management practices, high quality feed and exercise, appropriate stocking density and adequate and appropriate housing maintained in hygienic conditions. Disease outbreaks shall be treated immediately to avoid suering to the animal. Allopathic products including antibiotics may be used where necessary, when the use of phytotherapeutic, homeopathic and other products is inappropriate.
15.14
Production rules for feed
Production of organic feed shall be kept separate from production of non organic feed. Organic feed materials, and/or feed materials from production in conversion, shall not enter simultaneously with the same feed materials produced by non organic means into the composition of the organic feed product. Hexane and other organic solvents may not be used.
15.15. GENERAL RULES ON THE PRODUCTION OF PROCESSED FOOD
1207
Feed manufacturers are required not to use GMOs or products produced from GMOs where they should have knowledge of their presence due to information on any label accompanying the product or from other accompanying documents. Where feed manufacturers use ingredients and additives purchased from third parties to produce feedstus for organic livestock, they shall require the vendor to conrm that the products supplied have not been produced by GMOs.
15.15
General rules on the production of processed food
The following criteria shall apply to the composition of organic processed food:
At least 95%, by weight, of the ingredients of agricultural origin of the product shall be organic. Ingredients of non-agricultural origin and processing aids may be used only if they have been approved. Non-organic agricultural ingredients may be used only if they have been approved.
15.16
Label and advertising claims
The terms listed in in Annex I of the Proposal, such as organic, ecologico, kologisch, biologisch, their derivatives or diminutives, alone or combined, may be used throughout the Community and in any Community language for the labelling and advertising of a product which is produced and controlled, or imported, in accordance with this Regulation. These terms may not be used for a product which bears a label indicating that it contains GMOs, consists of GMOs or is produced from GMOs. General claims that a particular set of private or national organic standards is stricter, more organic or otherwise superior to the rules laid down in this Regulation, or to any other set of organic standards, may not be used on labels or in advertising. However, indications referring to specic elements of the production method used for a certain product may only be used on labels or in advertising on condition that they are true statements of fact and otherwise in conformity with the general labelling requirements set out in Directive 2000/13/EC.
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15.17
Certication
The competent authority and the approved control bodies may grant certicates, including the right to use their marks of conformity with organic standards, to operators which are subject to the control system.
15.18
Imports from third countries
A product imported from a third country may be placed on the Community market labelled as organic where it complies with standards equivalent to those applied to organic production in the Community, or is in accordance with the internationally recognised standards set out in the Codex Alimentarius guidelines.
15.19
Aquaculture
As regards to aquaculture the proposal achieves one of the actions of the Commission Communication to the Council and the European Parliament of 2002 on the sustainable development of European aquaculture, namely "harmonisation of the rules on organic aquaculture under Regulation (EEC) No 2092/91".
15.20
International harmonization of organic food Codex Alimentarius
[42] The Guidelines for the Production, Processing, Labelling and Marketing of Organically Produced Foods provide the requirements of production, the labelling and claims for organic foods. These guidelines are at this stage a rst step into ocial international harmonization of the requirements for organic products in terms of production and marketing standards, inspection arrangements and labelling requirements. Main subjects of the organic foods Codex guidelines The main subjects of these guidelines are: Organic agriculture is a holistic production management system which promotes and enhances agroecosystem health, including biodiversity, biological cycles, and soil biological activity. Apart from a small portion of agricultural commodities marketed directly from the farm to consumers, most products nd their way to consumers via established trade channels. To
15.20. INTERNATIONAL HARMONIZATION OF ORGANIC FOOD - CODEX ALIMENTARIUS
1209
minimize deceptive practices in the market place, specic measures are necessary to ensure that trade and processing enterprises can be audited eectively. Therefore, the regulation of a process, rather than a nal product, demands responsible action by all involved parties. Import requirements of organic products should be based on the principles of equivalency and transparency as set out in the Principles for Food Import and Export Inspection and Certication.
Labelling of organic products Organic products should be labelled in accordance with the Codex General Standard for the Labelling of Prepackaged Foods (CODEX STAN 1-1985, Rev 1-1991) [43] in addition to Guidelines for the Production, Processing, Marketing and Labelling of Organically Produced Foods 2005 (GL 32 - 1999, Rev. 1 - 2001) [42] Rules of production and preparation Permitted substance lists
Inspection According to the Codex Alimentarius Guidelines for Organic Foods inspection measures are necessary across the whole of the food chain to verify product labelled according to the guidelines conforms to internationally agreed practices. Access by the inspection body to all written and/or documentary records and to the establishment under the inspection scheme is essential. The operator under an inspection should also give access to the competent or designated authority and provide any necessary information for third party audit purposes.
Rules of production and preparation of organic products according to the Codex Organic products should be stored and transported according to the requirements dened in the guidelines.
Plant and plant products Special principles dened in the guidelines should have been applied on the parcels, farm or farm units during a conversion period of at least two years before sowing, or in the case of perennial crops other than grassland, at least three years before the rst harvest of products labelled as organic.
1210 Livestock and livestock products
Where livestock for organic production are maintained, they should be an integral part of the organic farm unit and should be raised and held according to these guidelines. Compliance periods for livestock Once the land has reached organic status and livestock from a non-organic source is introduced, and if the products are to be sold as organic, such livestock must be reared according to these Guidelines for at least the following compliance periods: Bovine and equine Meat products 12 months and at least 75% of their life span in the organic management system. Calves for meat production 6 months when brought in as soon as they are weaned and less than 6 months old. Milk products 90 days during the implementation period established by the competent authority, after that, six months. Ovine and caprine Meat products six months. Milk products 90 days during the implementation period established by the competent authority, after that, six months. Porcine Meat products Six months. Poultry/laying hens Meat products whole of life span as determined by the competent authority. Eggs: six weeks. Nutrition All livestock systems should provide the optimum level of 100% of the diet from feedstus produced to the requirements of these guidelines. For an implementation period to be set by the competent authority, livestock products will maintain their organic status providing feed, consisting of at least 85% for ruminants
15.20. INTERNATIONAL HARMONIZATION OF ORGANIC FOOD - CODEX ALIMENTARIUS
1211
and 80% for non-ruminants and calculated on a dry matter basis, is from organic sources produced in compliance with these Guidelines. Specic criteria for feedstus, nutritional elements, additives and Processing Aids are dened in the guidelines. Livestock husbandry, transport and slughter Maintenance of livestock should be guided by an attitude of care, responsibility and respect for living creatures. Beekeeping and bee products Bee keeping is an important activity that contributes to the enhancement of the environment, agriculture and forestry production through the pollination action of bees. The treatment and management of hives should respect the principles of organic farming. Collection areas must be large enough to provide adequate and sucient nutrition and access to water.The sources of natural nectar, honeydew and pollen shall consist essentially of organically produced plants and/or spontaneous (wild) vegetation. Handling, storage, transportation, processing and packaging The integrity of the organic product must be maintained throughout the processing phase. This is achieved by the use of techniques appropriate to the specics of the ingredients with careful processing methods limiting rening and the use of additives and processing aids. Ionizing radiation should not be used on organic products for the purpose of pest control, food preservation, elimination of pathogens or sanitation. Pest management For pest management and control the following measures, in order of preference, should be used: Preventative methods, such as disruption and elimination of habitat and access to facilities by pest organisms, should be the primary methodology of pest management. If preventative methods are inadequate, the rst choice for pest control should be mechanical/physical and biological methods. If mechanical/physical and biological methods are inadequate for pest control, pesticidal substances listet in these guidelines (or other substances allowed for use by a competent authority) may be used.
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Harmonisation of dierent standards to improve trade in organic produces between dierent regions [44] The new tools being introduced, called Equitool and IROCB (International Requirements for Organic Certication Bodies), were released in October 2008 by the FAO, the UN Conference on Trade and Development (UNCTAD), and the International Federation of Organic Agriculture Movements (IFOAM) According to the Food and Agriculture Organization (FAO), there are some 400 dierent public and private certication bodies. The Equitool and IROCB are intended to establish equivalence between standards in order to harmonise trade in organic produce between markets with dierent standards and environmental conditions, such severe winter in northern countries where animals are kept indoor, and mild climate conditions in subtropical regions where cattle lives outdoor the whole year. Equitool assesses the equivalence between standards, and IROCB enable the recognition of organic certication bodies around the world.
15.21
Global situation of organic farming
Organic food in Africa SEKEM, an Egyptian organic agriculture company, won the Right Livelihood Award in 2003. Uganda, is the rst country that has reached 1 percent of agricultural land to be certied organic. Dr. Thomas van Elsen speaking about Biologic-dynamical farming and landscape states: "Ecological - also known as biologic - dynamical managing alone is no guaranty for a manifold landscape" New strategies concerning farming are necessary. USA USDAs National Organic Program (NOP), authorized under the Organic Foods Production Act of 1990 regulates organic foods in USA. [45] The US National Organic Program presents a domestic and a foreign list of the USDA Accredited Certifying Agents (ACAs), application for certication, applications for cost sharing programmes for organic crops and livestock producers. The U.S. Department of Agriculture (USDA) will accredit State, private, and foreign orOurFood Database of Food and Related Sciences Copyright 1998-2010 Karl H. Wilm. All rights reserved.
15.22. NOP STANDARDS (7 CFR PART 205)
1213
ganizations or persons to become "certifying agents". Certifying agents will certify that production and handling practices meet the national standards The US Certication Operations or portions of operations that produce or handle agricultural products that are intended to be sold, labelled, or represented as "100 percent organic," "organic," or "made with organic ingredients" or food group(s). Excepted from certication are: Farms and handling operations that sell less than $5,000 a year in organic agricultural products. Although exempt from certication, these producers and handlers must abide by the national standards for organic products and may label their products as organic. Handlers, including nal retailers, that do not process or repackage products. Handlers that only handle products with less than 70 percent organic ingredients. A handling operation or portion of an operation that is a retail food establishment that processes or prepares, on the premises of the establishment, raw and ready-to-eat food labelled organic. A handling operation that chooses to use the word organic only on the information panel. A handling operation that handles products that are packaged or otherwise enclosed in a container prior to being received by the operation and remain in the same package.
15.22
[46] Summary
NOP Standards (7 CFR Part 205)
NOP Standards became eective in 2002. It will facilitate domestic and international marketing of fresh and processed food that is organically produced and assure consumers that such products meet consistent, uniform standards. This program establishes national standards for the production and handling of organically produced products, including a National List of substances approved for and prohibited from use in organic production and handling. It establishes an accreditation program for State ocials and private persons who want to be accredited as certifying agents. It includes requirements for labeling products as
1214
organic and containing organic ingredients. It provides rules for importation of organic agricultural products with equivalent organic program requirements. Allowed and Prohibited Substances A certied operation must only use allowed substances, methods, and ingredients for the production and handling of agricultural products that are sold, labeled, or represented as "100 percent organic," "organic," or made with..." for these products to be in compliance with the Act and the NOP regulations. Use of ionizing radiation, sewage sludge, and excluded methods are prohibited in the production and handling of organic agricultural products. The National List (7 CFR 205.600-606) as published in the regulations is the ocial source for decisions concerning approved and prohibited materials for organic operations. No other citation is allowed. The OMRI Generic Materials List (GML) is therefore not to be applied for any decisions concerning organic foods certication. [47]
[45] Table 15.3: Labelling Consumer Product Packages Labelling category "100 percent Organic" Entirely whole, organic: whole, raw or processed product) "organic" (95% or more organic ingredients) principle display panel "100 percent organic (optional) USDA seal and certifying agent seal(s) (optional) Information panel "100 percent organic (optional) Certifying agent name (required) business/internet address tele nr. (optional) "X% organic" (optional) Ingredient statement If multiingredient product, identify each ingredient as "organic" (optional) Other package panels "100 percent organic" (optional) USDA seal and certifying agent seal(s) (optional) Identify organic ingredients as "organic" (required if other organic labelling is shown "X% organic" (optional) USDA seal and certifying agent seal(s) (optional)
"Made with organic
"Organic" plus product name) (optional) "X% organic" (optional) USDA seal and certifying agents seal(s) (optional) "made with organic (ingredients or
Certifying agent name(required) business/internet address tele nr. 8optional9 "X% organic Identify organic ingredients" ingredients as
"made with organic
15.23. OTHER SPECIAL FOOD SYSTEMS WITH ORGANIC CLAIMS ingredients" (70 to 95% organic ingredients) food group(s) (optional) "organic (required" if other organic Certifying agent labelling is shown) address tele nr. Certifying agent (optional) seal of nal Prohibited product handler USDA seal (optional) Prohibited seal USDA Prohibited "X% organic" Identify organic Any reference (optional) ingredients as to organic "organic" (optional) content of product Prohibited Prohibited (required if % USDA seal USDA seal organic is and certifying and certifying displayed) agent seal agent seal (optional)
1215 (ingredients or food group(s) (optional) Certifying agent seal of nal product handler (optional) Prohibited USDA seal Prohibited USDA seal and certifying agent
Less-than 70% organic ingredients
seal
15.23
Other special food systems with organic claims
AGL and IFOAM These systems are regulated by rules which have been established by their own organization. The principles of organic agriculture was rst described in 8 lectures held by Rudolf Steiner in 1924 and was also based on Goethe and his recognition of nature. Demeter farmers deal with their farms as a unique living organism. They call this kind of farming "biodinamic". The organizations which follow these principles are united under the cover of AGL , an agricultural cooperative bringing together all the Organic inspection bodies. It was founded in Germany in 1988, through the initiative of Demeter.
15.24
The International Federation of Organic Agriculture Movements (IFOAM)
[48] The International Federation of Organic Agriculture Movements (IFOAM) embraces worldwide all organic federations, whose goal is the worldwide adoption of ecologically, socially and economically sound systems based on the principles of Organic Agriculture.
1216
The Movement was founded in 1972 and is an independent global non-prot organization.
15.25
The IFOAM Principles of Organic Agriculture
[49] In its Principles the IFOAM denes agriculture as one of humankinds most basic activities because all people need to nourish themselves daily. History, culture and community values are embedded in agriculture. The Principles apply to agriculture in the broadest sense and is concerned with the way people interact with living landscapes, relate to one another and shape the legacy of future generations. The Principles of Organic Agriculture serve to inspire the organic movement in its full diversity and are presented with a vision of their world-wide adoption. Organic agriculture is based on: The principle of health The principle of ecology The principle of fairness The principle of care Each principle is articulated through a statement followed by an explanation. The principles are to be used as a whole. They are composed as ethical principles to inspire action. Principle of health Organic Agriculture should sustain and enhance the health of soil, plant, animal, human and planet as one and indivisible. This principle points out that the health of individuals and communities cannot be separated from the health of ecosystems - healthy soils produce healthy crops that foster the health of animals and people. Health is the wholeness and integrity of living systems. It is not simply the absence of illness, but the maintenance of physical, mental, social and ecological well-being. Immunity, resilience and regeneration are key characteristics of health. The role of organic agriculture, whether in farming, processing, distribution, or consumption, is to sustain and enhance the health of ecosystems and organisms from the smallest in the soil to human beings. In particular, organic agriculture is intended to produce high quality, nutritious food that contributes to preventive health care and well-being. In view
15.25. THE IFOAM PRINCIPLES OF ORGANIC AGRICULTURE
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of this it should avoid the use of fertilizers, pesticides, animal drugs and food additives that may have adverse health eects. Principle of ecology Organic Agriculture should be based on living ecological systems and cycles, work with them, emulate them and help sustain them. This principle roots organic agriculture within living ecological systems. It states that production is to be based on ecological processes, and recycling. Nourishment and well-being are achieved through the ecology of the specic production environment. For example, in the case of crops this is the living soil; for animals it is the farm ecosystem; for sh and marine organisms, the aquatic environment. Organic farming, pastoral and wild harvest systems should t the cycles and ecological balances in nature. These cycles are universal but their operation is site-specic. Organic management must be adapted to local conditions, ecology, culture and scale. Inputs should be reduced by reuse, recycling and ecient management of materials and energy in order to maintain and improve environmental quality and conserve resources. Organic agriculture should attain ecological balance through the design of farming systems, establishment of habitats and maintenance of genetic and agricultural diversity. Those who produce, process, trade, or consume organic products should protect and benet the common environment including landscapes, climate, habitats, biodiversity, air and water. Principle of fairness Organic Agriculture should build on relationships that ensure fairness with regard to the common environment and life opportunities Fairness is characterized by equity, respect, justice and stewardship of the shared world, both among people and in their relations to other living beings. This principle emphasizes that those involved in organic agriculture should conduct human relationships in a manner that ensures fairness at all levels and to all parties - farmers, workers, processors, distributors, traders and consumers. Organic agriculture should provide everyone involved with a good quality of life, and contribute to food sovereignty and reduction of poverty. It aims to produce a sucient supply of good quality food and other products. This principle insists that animals should be provided with the conditions and opportunities of life that accord with their physiology, natural behaviour and well-being.
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Natural and environmental resources that are used for production and consumption should be managed in a way that is socially and ecologically just and should be held in trust for future generations. Fairness requires systems of production, distribution and trade that are open and equitable and account for real environmental and social costs. Principle of care Organic Agriculture should be managed in a precautionary and responsible manner to protect the health and well-being of current and future generations and the environment. Organic agriculture is a living and dynamic system that responds to internal and external demands and conditions. Practitioners of organic agriculture can enhance eciency and increase productivity, but this should not be at the risk of jeopardizing health and wellbeing. Consequently, new technologies need to be assessed and existing methods reviewed. Given the incomplete understanding of ecosystems and agriculture, care must be taken. This principle states that precaution and responsibility are the key concerns in management, development and technology choices in organic agriculture. Science is necessary to ensure that organic agriculture is healthy, safe and ecologically sound. However, scientic knowledge alone is not sucient. Practical experience, accumulated wisdom and traditional and indigenous knowledge oer valid solutions, tested by time. Organic agriculture should prevent signicant risks by adopting appropriate technologies and rejecting unpredictable ones, such as genetic engineering. Decisions should reect the values and needs of all who might be aected, through transparent and participatory processes.
15.26
Other special food systems with organic claims
AGL and IFOAM These systems are regulated by rules which have been established by their own organization. The principles of organic agriculture was rst described in 8 lectures held by Rudolf Steiner in 1924 and was also based on Goetheand his recognition of nature. Demeter farmers [50] Demeter farmers deal with their farms as a unique living organism. They call their farming biodinamic.
15.26. OTHER SPECIAL FOOD SYSTEMS WITH ORGANIC CLAIMS
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The organizations which follow these principles are united under the cover of AGL (Arbeitsgemeinschaft kologischer Landbau) (Working group for organic farming) , an agricultural cooperative bringing together all the Organic inspection bodies. It was founded in Germany in 1988, through the initiative of Demeter. The International Federation of Organic Agriculture Movements (IFOAM) embraces worldwide all organic federations, whose goal is the worldwide adoption of ecologically, socially and economically sound systems based on the principles of Organic Agriculture. Diversication and periodic crop changes are the basis of organic farming. It tries to control weeds, to provide soil nutrients and guarantee soil fertility. Synthetic pesticides are not used. Useful antagonists of pest are supported keeping pests under control. Genetic modied plants and seeds are not allowed. Landscape conservation such as planting bushes to avoid wind erosion and provide breeding places for birds are part of these regulations. Changing from conventional to organic farming takes two to three years. Demeter is a member of the AGL. It is the only ecological association that has built up a network of individual certication organisations world-wide. In 1997 Demeter-International was founded for closer co-operation in the legal, economic and spiritual spheres. Presently Demeter International has 18 members from Demeter organisations from Europe, America, Africa and New Zealand. Thus Demeter-International represents around 3.000 Demeter producers in nearly 40 countries. Greek mythology: The name of the organization comes from the goddess of grain and fertility in ancient Greek, Demeter. The Greeks, like most ancient cultures, relied upon agriculture for their sustenance. As the patron deity of agriculture her association with grain also translated into a close relationship with human fertility. There are, consequently, many myths dealing with Demeter in her capacity as a fertility goddess. Homeric Hymn to Demeter, in which the story of the goddess and the abduction of her daughter Persephone and the consequent anger of Demeter is told. The Hymn also alludes to aspects of the mystery cult referred to as the Eleusinian Mysteries. The goddess Demeter was known as Ceres in Roman mythology.
History of the organization 1927 First co-operative was formed to market Bio-Dynamic produce. 1928 At the Sierra Madre, Mexico start the rst Bio-Dynamic Coee Plantation. 1939 In New Zealand the Bio-Dynamic Association was founded. 1941 All Demeter-Organisations and the monthly magazine "Demeter" are forbidden in Germany through the NSDAP.
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1946 The Experimental Circle for Bio-Dynamic farming methods restarts the movement. 1963 Maria Thun comprehensive work on the cosmic inuences upon plants and the sowing calendar"The Star Calendar". 1994 Demeter Standards for Food Processing. The rst Doctorate on a Bio-Dynamic theme (The rhythms of the moon) is written by Dr. Hartmut Spiess, a fellow worker at the Institute for Bio-Dynamic Research. Demeter is restructured in accordance with the threefold social order, and this, together with the importance of regional impulses, becomes the main focus of the work. Further AGL organisations Bioland, organic biologic agriculture Biokreis Ostbayern Naturland ANOG (Arbeitsgemeinschaft fr Naturnahen Obst-, Gemse und Feldfruchtanbau e.V. ECO VIN (Bundesverband kologisher Weinbau (BW) Ga e.V. ( Had its roots in the former DDR) kosiegel
15.27
AGL regulation for organic animal farming
The farmer does not see the animal as a mean of production, but he considers it as a component of the cycle soil-plant-animal-human. Dairy cattle: Dairy cattle and calves must have access to pasture in summer or access to the open air all the year round. To tie up young and fattening stock all the year round is not allowed. Access to the open air has to be available ever where possible. Sleeping stalls are to be spread with straw (or other organic litter). Farming is limited to two cows per hectare. Poultry Caged systems are prohibited for poultry. In ground managed systems at least one third of the oor area is to be available as scratching area. Open-air runs are required for young birds and laying hens. Other poultry are to have access to an outside run, waterfowl also having access to open water. Feeds Feeds must be appropriate to the class of animal, its age and its physiological needs, with care also being given to provide sucient mineral nutrition. The necessary minerals and
15.28. LABELLING OF ORGANICS
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trace elements should be of natural origin as far as possible (herbs, leaf forage etc.). Fodder produced on the farm forms the basis of animal nutrition. At least 50% of the feed for each animal type respectively, must originate on the farm or in co-operation with another Demeter farm. Hormones are not allowed. Antibiotics, sulphonamide drugs, coccidiostats, synthetic compounds from organic chemistry and pharmaceuticals are not permitted as additives to feed. Isolated amino acids, growth promoters, production enhancers (feed antibiotics and enhancers) and synthetic chemical feed additives (except vitamins) are not allowed.
15.28
Labelling of organics
The Regulation 2092/91 EWG regulates standards for the production and the control of organics. These standards are intended to protect farmers and consumers from misleading use of "Bio" and "Organics". They should only be used if at least 95% of ingredients are organic. The regulation denes also a clear dierence between organic foods and conventional ones. All regulations refer to vegetable origin. Organic animal breeding is not mentioned in the regulation 2092/91 EWG. Very detailed description of organic breeding of meat producing animals are found in "Demeter Production standards" and "International Demeter Processing Standards" which were implemented by all international members and the AGL members Germany by the 1st January 2003. The general rules of the AGL are tighter than the regulations of the European Organic regulation which permits a registration as organic of a part of the farm. The rule of AGL , does not. Specic terms: Terms such as integrated, controlled, environment sustainable, ecologically friendly do not mean they are conform to the organic regulations from the EU or AGL. These are pseudo organic products.
15.29
Global situation of organic farming
[51] Organic food in Africa: SEKEM, an Egyptian organic agriculture company, won the Right Livelihood Award in 2003. Uganda, is the rst country that has reached 1 percent of agricultural land to be certied organic.
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Dr. Thomas van Elsen (University of Kassel, Faculty of Ecological Agriculture Sciences, Department of Organic Farming and Cropping Systems Witzenhausen, Germany) speaking about Biologic-dynamical farming and landscape states: "Ecological - also known as biologic-dynamical managing alone is no guaranty for a manifold landscape. New strategies concerning farming are necessary."
Table 15.4: Global situation Land Percent of total land area under organic 2001 management Switzerland 9.0 Austria 8.6 Italy 6.8 Sweden 5.8 Czech Republic 3.9 UK 3.3 Uganda 1.0 USA 0.3 Source:Economic Research Service USDA AIB-780 [51] On behalf of the organic ideas, centres have been created to develop organic agriculture, farming an manifold landscapes, beekeeping and nature conservation.
15.30
Social economic environment
Sustainable agriculture can only succeed if environment, social interests and global aairs are treated in a holistic way. Social economic environmental research is done by Dr. C. Krotscheck or Prof. Dr. M. Narodoslawsky at the Institute of Chemical Engineering, Graz, University of Technology dealing with the sustainable development of two partners: ecosphere and sociosphere. The Node of Social Economic Environmental Research in Austria has collected encompassing information about the current state and direction of Austrian research eorts in this highly dynamic area.
15.31. ALTERNATIVE DIETS
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15.31
Alternative Diets
Acceptance of organic food is strongly bounded to dietary believes of the consumers. Some knowledge in this eld is necessary to understand the dierent ways they are going. A variety of alternative diets are oered for treating cancer, cardiovascular disease, and food allergies. Virtually all of these interventions focus on freshly prepared vegetables, fruits, whole grains, and legumes. Food allergy and intolerance are being studied as contributing factors in rheumatoid arthritis. Other benets attributed to alternate dietary lifestyles include a greater resistance to illness and improved control for hyperactive children. Most diets include variations of the vegetarian, macrobiotic, and cultural diets of Asian and Mediterranean nations. Studies report a signicant lowering of risk factors for heart disease and certain forms of cancer in these groups. Although few controlled studies of traditional diets exist, such as those originally consumed by Native American Indians, diseases such as diabetes and cancer were not a problem for these populations until their diets became more Westernized. Vegetarian and vegan diets Many people choose these diets to improve their health or to decrease the risk of chronic diseases, Others are concerned about the presence of antibiotics, hormones, pesticide residues or disease-causing agents (as with mad cow disease) that may be present in meat. Some vegetarians object to inhumane practices of modern-day animal farming, so their reasons for being vegetarian are largely ethical Some vegetarians believe that humans are not physiologically suited to meat eating; humans have more in common with herbivorous animals than with carnivorous animals in terms of the structure and function of the digestive tract. Some people choose vegetarianism in an attempt to live more simply and economically, and in closer harmony with nature. Others go vegetarian due to concerns about world hunger and the environment, because large-scale production of animal foods uses land that could otherwise be used to grow plant-based foods, and is a major cause of deforestation and soil erosion worldwide.
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- It takes 7 kilograms of grain to produce a kilogram of beef, - 4 for a kilogram of pork. - over a third of the worlds annual 640 million tons grain harvest is to fatten animals. Vegetarians are healthier than people who eat meat. In some cases, vegans have better health than lacto-ovo vegetarians. The vegetarians were less likely to be obese, or to have high blood pressure, diabetes, arthritis or colon cancer. They were also less likely to die from heart disease. Many factors in vegetarian diets contribute to the better health of vegetarians. Dierence between vegetarian diet and meat-eaters: Vegetarians consume more ber as do meat-eaters, consume more antioxidants and phytochemicals such as isoavones, much less saturated fat and cholesterol. Vegetarians do not consume heme iron, a type of iron found in meat that may increase the risk of heart disease and cancer.
Possible deciencies: Balanced protein and calcium - Soy foods and dairy products prevent any deciency.
Vitamin B12 - Vitamin B12-fortied foods or taking vitamin supplements on a daily basis prevents a deciency.
Iron and iodine for strict veganes - iodized salt, fruits(0,1-0,7mg iron/100 g), vegetables (1-1,5), dried bean (7), nuts (4-8), grain products such as bread (1-5), and fortied breakfast cereals, in addition to vitamin C to improve absorption of iron. People who live in cloudy, smoggy, or northern areas, and people who do not leave their residences, need foods fortied with vitamin D. Vegetarians who do not consume milk should be sure to get 20 to 30 minutes of sun exposure every day since this promotes the synthesis of vitamin D in the body.
15.32. MACROBIOTICS
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15.32
Macrobiotics
[52] Macrobiotics is based mainly on consumption of soup, unpolished brown rice or other whole grain dish and cooked vegetables. Macrobiotic cooking prefers to add salt to a level which is comfortable for everyone, but not more. In this way, there is always some salt in meals, but not excessive amounts. For those who desire more salt, they can obtain this by adding Macrobiotic condiments like goma-sio, tekka, tamari-kombu, tsukemono (pickled vegetables). Testing macrobiotics Macrobiotics oers a cup of cooked, unpolished brown rice seasoned only with sun-evaporated salt and goma-sio, miso soup with vegetables and seaweed, simply-cooked and lightly salted garden vegetables, and a small cup of unsweetened, un-dyed, 3-year-old, roasted twig tea. All that is asked to chew each mouthful of food at least 50 times before swallowing, and to try this for at least 10 (ten) days, and forsake other forms of nourishment during that time. The dierence to other diets Liquid intake: Drinking only when thirsty. When one switches to a Macrobiotic diet composed of largely vegetable-based foods that are inherently balanced, the need to dilute and re-distribute excesses and deciencies in blood chemistry is naturally reduced dramatically. Adding Salt to Food during Meals: Macrobiotics addresses the individualized need for added salt by including goma-sio (sesame salt) or other condiment on the table, but not plain salt. Macrobiotic cooking prefers to add salt to a level which is comfortable for everyone, but not more. For those who desire more salt, they can obtain this by adding Macrobiotic condiments like goma-sio, tekka, tamari-kombu, tsukemono (pickled vegetables) etc. Modern dietary thinking for the most part downplays the value of salt in the human diet, and even considers it harmful and a cause of high blood pressure, heart disease, kidney disorders and other complications. This is due to the fact that rened salt can harm cells and organs because it lacks buering trace minerals. Unrened rock or sea salt contains trace minerals so important to buer and assist body functions. Macrobiotics teaches to drink tea plain:This is because tea is usually served at the end of a meal, and is not to be considered a dessert beverage, but a balanced way to end a meal. Also, the Macrobiotic way is a journey away from a way of eating that bombards the senses with exaggerated levels of sweetness, saltiness, spiciness and sourness in foods and beverages back to an appreciation of lifes simplicity and subtlety.
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The following are basic concepts of the Macrobiotic Way of Eating: Consume organically and locally-grown foods in season as they become available, or foods that will store without articial preservation or refrigeration. Alternatively, eat foods grown in the same latitude. Consume cooked whole grains primarily, and recipes made from whole grains; secondarily in quantity, cooked vegetables, adjusting proportions and preparation methods according to activity, climate and seasonal uctuations of temperature and humidity. Use solar-evaporated sea water salts in preparation of foods, as well as traditionally-aged miso and shoyu, umeboshi and seaweeds. Drink undyed, 3-year old roasted twig tea (kukicha) as preferred beverage. Use unrened, cold-pressed seed oils sparingly, made from organically-grown seeds, like sesame, corn, saower, sunower, axseed, etc. Use roasted seeds and nuts, fruit, salads and sh occasionally as desired, in smaller quantities, as provided in season. Use beans and bean products frequently, as primary sources of protein, along with whole grain and vegetable dishes. Avoid all foods and beverages containing rened sweeteners, chemical dyes, synthetic avorings or seasonings, rened oils, chemical preservatives, or made from foods grown with chemical insecticides, herbicides, fungicides, chemical fertilizers, or produced by bioengineering or grown under green house conditions. Avoid foods grown in, and shipped from, warmer latitudes. Avoid "soft" (carbonated, sweetened) beverages, canned goods, alcoholic beverages, articial sweeteners or products containing these ingredients. Chew each mouthful thoroughly before swallowing.
15.33
Water for agriculture
All form of diets depend on farming and farming depends on water management. It is important to nd a solution to diminish the impact of droughts erosion and environmental changes. The University of Chile (UCH) is charged with developing and disseminating knowledge about the nature and resolution of these problems. It is undertaking the mulOurFood Database of Food and Related Sciences Copyright 1998-2010 Karl H. Wilm. All rights reserved.
15.34. ENVIRONMENTAL DEVELOPMENT tidisciplinary Program of Arid Lands
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Chile and the State of Arizona face similar problems and issues in dealing with arid lands and the environment. Examples include: Rapidly increasing population pressure, which threatens agricultural sustainability. Problems with water availability, allocation, distribution, and quality. Increasing soil erosion owing to inadequate agricultural practices. Pollution of air, soil, and water as a result of industrial (mining and emerging agroindustry), agricultural, and urban exploitation of basic resources Growing concern among the human population about the feasibility of maintaining and enhancing environment quality, a precondition for sustainable agricultural development. Biosaline Agriculture Center (BAC) in Dubai is focusing its initial eorts on countries of the Arabian Peninsula. This choice is dictated by the urgent need to address water use and quality issues in this region, whose renewable water resources per person are less than 3% of the global average. The Middle East region (dened here as the North African countries from Mauritania, through the countries of the Fertile Crescent, the Arabian Peninsula, Turkey, Iran, Pakistan, Afghanistan, and the former Soviet republics in Central Asia) covers 14% of the total area of the world and is home to 10% of its population, yet has only 2% of the worlds renewable water resources. Renewable water resources per inhabitant are among the lowest in the world at an average of 1577 m3/ person per year, compared with the global average of 7000 m3. Sixteen of the 29 countries in the region have internal renewable water resources of less than 500 m3/person per year. Saline and brackish water resources are far more abundant than fresh water and little used at present. Bringing these resources into sustainable productive use will oer opportunities to increase food. Water management is therefore of main interest in a global world. Some systmes are under trial to improve agriculture in arid zones.
15.34
Environmental development
Several movements are engaged in environmental development: Earth Council, best known from its program National Councils for Sustainable Development (NCSDs) supported by
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the United Nations Development Program with activities in: Burkina Faso National Council for Environmental Management Costa Rica National Council for Sustainable Development Dominican Republic National Follow-up Commission Mexico National Consultative Council for Sustainable Development Philippines Philippine Council for Sustainable Development Uganda National Environment Management Authority Working under the premise that changes are not brought about by governments alone, the Earth Council set out after Rio to support and empower people in building a more secure, equitable and sustainable future (Agenda 21). To bring more coherence and cooperation among the 140 major conventions relevant to the environment, and the 30 regional shery bodies, consideration should be given to the establishment of the Inter-agency Coordination. This would cause: Avoiding duplication of eort. Identifying gaps in research. Identifying opportunities for collaboration. Promoting synergy through combined resources. Earth Council sees the issue of enhancing "synergies" between environmental conventions at the national level as central to their core objective of sustainability. "Sustainability" includes not only addressing economic and nancial issues, but also environmental and social development issues. Sustainability means also the integration of all ecological, economical, social, political, cultural and spiritual aspects.
Burkina Faso The conservation of the biological diversity (priority domain of the Agreement on Biological Diversity), in a Sahelian country as Burkina Faso, cannot be conceived separately from a coherent program to ght desertication (Agreement on Combating Desertication). Also, ghting against desertication in an arid or semi-arid zone cannot be conceived without a sound water management policy (Ramsar Convention). The water resources are themselves dependent upon the climactic risks (Agreement on the Climactic Changes). Recent droughts and desertication severely aecting agricultural activities, population distribution, and the economy, overgrazing, soil degradation, deforestation.
15.34. ENVIRONMENTAL DEVELOPMENT Mexico
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Recommendations on ecological management and planning of land resources and climatic change with 35 items were established. The main obstacle that the CCDSs faces in Mexico is that the local authorities identify the CCDS as groups of environmentalists, exclusively. Therefore their analytical work about the relationships between the government,legislative, non-governmental, business, social and academic actors, is not considered by the local authorities. Scarcity of hazardous waste disposal facilities; rural to urban migration; natural fresh water resources scarce and polluted in north, inaccessible and of poor quality in center and extreme southeast; raw sewage and industrial euents polluting rivers in urban areas; deforestation; widespread erosion; desertication; deteriorating agricultural lands; serious air and water pollution in the national capital and urban centers along US-Mexico border; land subsidence in Valley of Mexico caused by groundwater depletion.
Philippines Uncontrolled deforestation in watershed areas; soil erosion; air and water pollution in Manila; increasing pollution of coastal mangrove swamps that are important sh breeding grounds.
Agreements Biodiversity, Climate Change, Desertication, Endangered Species, Hazardous Wastes, Law of the Sea, Marine Dumping, Nuclear Test Ban, Ozone Layer Protection, Ship Pollution, Tropical Timber 83, Tropical Timber 94, Wetlands signed, but not ratied: Climate Change-Kyoto Protocol These two variables also cause a negative chain of reactions in the social and natural fabric of Philippine life - tenurial problems, denudation of eco-system and watershed areas, soil erosion, siltation, and the breakdown in food chain checks and balances. Concrete manifestations of these problems are reected in the following indicators: 1. Forest cover on the Philippines has been reduced from more than 50% to less than 24% over a 40-years period (1948-1987) 2. Only about 5% of the countrys coral reefs remain in excellent condition. 3. 30%-50% of the sea grass beds in the last 50 years have been lost. 4. 80% of the mangrove areas in the last 75 years have been lost. 5. It is estimated that about 50% of national parks are no longer biologically important.
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Air pollution from vehicle emissions; water pollution from organic and factory wastes; deforestation; soil erosion; wildlife populations threatened by illegal hunting. Uganda Uganda is well endowed with good climate due to a variety of factors such as its equatorial location, high elevation and the presence of numerous lakes, rivers, wetlands and mountains. This partly explains the high diversity of plants and animals and the scenic beauty of the country that is rivaled by few countries in the world. However, this beautiful landscape is rapidly deteriorating due to a growing population, which is putting more pressure on land for food production and other socio-economic development activities.Draining of wetlands for agricultural use, deforestation, overgrazing, soil erosion, water hyacinth infestation in Lake Victoria is the result of nature exploit. The Importance of biodiversity for Uganda is linked with tourism.
15.35
Other Agricultural Systems
Modern conventional and organic agricultural methods should be assessed in terms of sustainability. Precision Farming. A project of the Oce of Technology Assessment at the German Parliament (TAB) has started on 1.1.2004. Precision farming is based on the combination of satellite-supported navigation systems (e.g. GPS - Global Positioning System), geographical information systems (GIS), computerised control of agricultural machinery, and corresponding software for farm management. In other words, this represents modern applications of information and control technology, combined with optimisation of arable farming. Only large farms will benet with reduction in inputs of production factors (fertiliser, pesticides/plant protection agents). Achieving positive ecological eects depends on a range of factors, e.g. the level of production inputs, potential location-specic hazards, and the general trend in production intensity. Biotechnology-especially genetic modication-represents an important technology option for meeting the long-term food needs of developing countries. However, this technology must be used within a policy framework that recognizes the importance of managing the health, environmental, and socioeconomic risks associated with it. Conservation agriculture: Introduction: Growing world population and a rapid destruction of nature resources make it necessary to look upon alternative systems with sustainable character. One of these
15.35. OTHER AGRICULTURAL SYSTEMS system is the conservation agriculture.
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It is a method which tries to improve soil humidity and soil conditions. It is based on no soil inversion and reduction or total elimination of mechanical soil disturbance, except to inject seeds or plants into the soil by direct drilling techniques (Zero-Tillage,No-Tillage or No-Till). Zero-tillage is an agricultural concept that conserves soil fertility, improves the availability of soil moisture, and increases the soils biological resources. Zero-tillage is often used to express all measures which are part of the conservation agriculture, such as maintenance at all times of a complete soil cover consisting of cover crops and/or crop residues and crop rotations to enhance environment and to avoid pests and diseases. Position of FAO: FAO promotes vigorously conservation agriculture. Plowing experiment at the ARS Research Unit in Coshocton, Ohio:Over the past four decades, no-till has done more to reduce soil erosion on more acres than any other DDR conservation practice. It improves soil structure and increases inltration. Several years without tillage are needed to maximize these benets. Plowing a eld once ( such as to reduce slug infestations ) causes hardly any carbon loss from the plow layer. It may take 3 to 5 consecutive years of plowing before signicant losses show up. But even a year of tillage greatly damages soil structure, which increases erosion and impairs water inltration and soil health. According to Loyd Owens, in order to conserve carbon, farmers should choose a practice with a focus on how erosive it is, rather than on how much carbon it leaves in the soil. Conservation Agriculture in Europe: The European Conservation Agriculture Federation (ECAF) brings together eleven national associations which promote among Europes farmers the soil management "best practice" aspects of conservation agriculture. With member associations in Belgium, Denmark, France, Germany, Greece, Italy, Portugal, Slovakia, Spain, Switzerland and the United Kingdom, ECAF represents the interests of the majority of the European Unions cropped farmland. ECAF was constituted in Brussels on 14th January 1999, as a non-prot making association, subjected to the Belgium laws. It was conceived to encourage any issue focused on maintaining the agrarian soil and its biodiversity in the context of sustainable agriculture.
1232 Elements of conservation agriculture
No-Tillage: Instead of burning crop residues after the harvest, or ploughing biomass into the ground, everything is left in place, as soil cover. At the start of the next cropping season, the eld is not ploughed at all - instead, special equipment is used to drill the seeds directly into the soil. Besides reducing mineralization, erosion and water loss, the surface cover inhibits the germination of weeds, protects soil microorganisms and helps build up organic matter. Less time and labour spent on land preparation, lower fuel consumption and less air pollution, reduced need for chemical inputs, and increasing yields and farm income. Soil cover: At all time the soil should be covered with cover-crops or crop residues. Herbicides used: Weeds are controlled by desiccant herbicides applied pre-planting. Further weed control is made with post-emergent herbicide of normal used in conventional agriculture. Crop rotation: Conservation Agriculture also requires careful planning of crop rotations, new approaches to weed control and pest management, and a range of other "precision farming" skills. Conservation Agriculture is being adopted by increasing numbers of farmers on about 58 million ha of farm land, mainly in North and South America, but also in Southern Africa and South Asia. Farmers like it because it gives them a means of conserving, improving and making more ecient use of their natural resources, Conservation Agriculture may require the application of herbicides where there is heavy weed infestation. During the transition phase from conventional to conservation agriculture, certain soil-borne pests or pathogens might create new problems due to the change in the biological equilibrium. But once the CA environment has stabilized, it tends to be more manageable and productive than conventional agriculture. So far there has been no pest problem that could not be overcome in Conservation agriculture.
Table 15.5: Conservation Agriculture and organic farming Dierences Herbicides Fertilizers Tillage IPM Conservation Agriculture Desiccant herbicides used Chemical fertilizers are used No cultivation of soil works on the principles of Organic Agriculture No chemical herbicides used Only organic fertilizers used Intensive soil ploughing Based on a biological balance
15.35. OTHER AGRICULTURAL SYSTEMS Integrated Pest Management
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Herbicides and fertlilizers Conservation Agriculture doesnt prohibit the use of chemical inputs, herbicides are an important component in this system, particularly in the transition phase. until a new balance in the weed population is achieved. Farm chemicals, including fertilizer, are applied very carefully. In general, conservation agriculture farmers use fewer chemical inputs than comparable conventional farmers and, over the years, quantities of chemical inputs tend to decline. Tillage The adoption of CA is in contrast with the notion in force for thousands of years that soil must be cultivated before sowing or planting. Conservation agriculture works on the principles of Integrated Pest Management in view of the importance of soil life in the system. Without the use of IPM practices, the build up of soil biota would not be possible. Monocropping under zero-tillage is possible, but not recommended, because - just as in conventional farming - it creates pest problems. The system has also been adapted for vegetables, root crops, grain crops as sugar cane. Potatoes, beets, cassava, fruit and vines can also be grown using CA techniques. So far the only areas where the concept has not been successfully adapted are arid areas with extreme water shortages and low production of organic matter. The Gulf region, however, would benet of this system using plastic foils instead of organic matters to cover the elds. Changing later to traditional CA. Conservation agriculture adapted to Gulf region would reduce signicantly water evaporation. Excessive irrigation would be avoided and progressive salinity of the soil could be retarded. This system is broadly used in heavy cropping of cucumber in Germany with best results in last drought periods. Livestock can be fully integrated into conservation agriculture, by exploiting the recycling of nutrients. This reduces the environmental problems caused by concentrated, intensive livestock production. The farmer can introduce forage crops into the crop rotation, thus broadening it and reducing pest problems.
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Forage crops can often be used as dual-purpose crops for fodder and soil cover. However, conicts between the use of organic matter to feed the animals or to cover the soil has to be resolved, particularly in arid areas with low production of biomass. Conservation Agriculture is being accepted in tropical climates such as Latin America, rather than in temperate climates like Europe. Generally, pressure from environmental indicators are not yet taken seriously enough. ECAF (European Conservation Agriculture Federation) Conservation Agriculture has great potential in sub-Saharan Africa because it can control erosion, gives more stable yields and reduces labour. In the South Asian rice-wheat area, there have been 50% increases in net benets through the direct seeding of wheat in the rice crop or stubble, compared with conventional tillage before seeding. Consevation Agriculture requires management skills and equipment that might not be available, especially to small-scale farmers, technical and nancial support is needed. To get started with cnservation agriculture, the minimum a farmer needs, is a zero tillage planter. Buying one without knowing the system or even having seen it, is a risk that few farmers are prepared to take and poor populations will never succeed in getting one. Dissemination of the concept of Conservatory Agriculture in Latin America, has turned out a major success. Africa, Central Asia and the Indo-Ganges Plains are now on target.
Biosaline Agriculture and aquaculture in the West Asia and North Africa (WANA) region [53] West Asia and North Africa (WANA) region has extensive desert areas and high salinity of the soil due to the invasion of sea water and the irrigation with saline water. Recovering unproductive salty areas with halophyte plants may help food security in these regions. The Inter-Islamic Network for Biosaline Agriculture INBA, together with International Center for Biosaline Agriculture ICBApromote biosaline agriculture coordinates the researche on biosaline agriculture and the development of a database on this subject. Halophyte plants [54] A halophyte plants grows where it is aected by salinity in the root area or by salt spray, such as in saline semi-deserts, mangrove swamps, marshes and sloughs, and seashores. An example of a halophyte is the salt marsh grass Spartina alterniora (smooth cordgrass).
15.35. OTHER AGRICULTURAL SYSTEMS
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Relatively few plant species are halophytes - perhaps only 2% of all plant species. The large majority of plant species are "glycophytes," and are damaged fairly easily by salinity. One quantitative measure of salt tolerance is the "total dissolved solids" in irrigation water that a plant can tolerate. Sea water typically contains 40 grams per liter (g/l) of dissolved salts. Beans and rice can tolerate about 1-3 g/l, and are considered glycophytes (as are most crop plants). At the other extreme, Salicornia bigalovii (dwarf glasswort) grows well at 70 g/l of dissolved solids, and is a promising halophyte for use as a crop. Plants such as barley (Hordeum vulgare) and the date palm (Phoenix dactylifera) can tolerate about 5 g/l, and can be considered as marginal halophytes. Seed collection of halophytes for the WANA region [53] ICBA maintains a collection of seeds of salt-tolerant grasses, vegetables. It also develops sustainable water management systems to irrigate food and forage crops and ornamental plants with marginal and saline water. The collection comprises seeds from other regions such as fodder beet, brassica/rape from Denmark indexFodder beeteand indigenous plant species from the Arabian Peninsula. Moreover, seeds will be produced in sucient quantity for distribution among partner countries in the WANA region for evaluation and trials. Other plants of interest for the region are sorghum (Sorghum bicolor), pearl millet (Pennisetum glaucum) ICBA says that the saltbush Atriplex and buelgrass (Cenchrus ciliaris) have signicant potential for saline environment, including. Seeds from promising varieties were multiplied. Wheat (triticum aestivum) salt-resistant seeds from Oman were planted for seed multiplication. The center newly acquired germplasm of sunower, canola, guar, pigeonpea, cowpea and chickpea, quinoa, barnyard millet, fodder beet, hyacinth bean, sorghum, pearl millet barley and lupine. Salinity-tolerant sorghum and pearl millet and barley varieties for saline lands Large areas are potentially vulnerable and could easily be damaged by salinization through irrigation. The development of salt-tolerant crop varieties is a cost-eective option for the management of salt-aected lands. Both pearl millet and sorghum are two main fodder crops of the WANA region that can play a signicant role in lling gaps in farm productivity and crop-livestock systems. Pearl millet and sorghum were evaluated under eld conditions at three salinity levels (EC 5, 10 and 15 dS m-1) at ICBA , in Oman, India, Iran, and Egypt. Pearl millet and sorghum are the fth and sixth most important cereal crops worldwide.
1236 Drip irrigation on raised beds in Bangladesh
This technology is being proposed by researchers of ICBA for Bangladesh to bring saltaected lands estimated at 0.88 million hectares under cultivation. During the driest months of March and April, salinity problems resulting from seawater intrusion are acute and no cultivation is possible. Cash crops like tomato, watermelon, cucumber and chili may, however, be cultivated using the drip irrigation on raised mulch beds technology. This permits the leaching of salts from the root zone and provides a fourfold crop compared with traditional practices. ICBA says that rainwater harvesting provides a reliable source of irrigation water during the dry season. The ponds where water is stored can also be used for aquaculture.
Return Water from Prawn farm in Saudi Arabia The National Prawn Company NPC located on the Red Sea coast in Al-Laith, about 450 km from Jeddah. has an annual production of 10,000 tons. Seawater is pumped to the shrimp ponds. The return water contains a signicant load of nutrients and organic residue from the prawn farming activities, is being used in agricultural production as well as coastal rehabilitation. A nearby lagoon has potential for rehabilitation with local mangrove species (Avicennia marina) along the inner shores. The return seawater for the production of halophytes for forage, environmental beautication, biomass energy and organic fertilizers. Further mangrove plantation will be expanded at the barrier island and the return water canal. ICBA scientists planted seedlings in the eld, for use mainly as windbreaks. Conocarpus and Salvadora spp. were suciently sturdy to protect other species inside the area. Mangrove seeds collected from the coastal plantations were acclimatized under dierent salinity conditions and currently kept in the shallow water of the lagoon at high salinity levels.
Mangroves species According to ICBA around 42 per cent of mangroves grow in South and South East Asia, 27 per cent in Americas, 16 per cent in West Africa, 10 per cent in Australia, 6 per cent in East Africa and the Middle East. Avicennia marina is the only native mangrove species growing in the UAE.
1237
Forage production systems using nonconventional salt-tolerant grasses and highly saline water A long-term eld studies on sustainable and economically feasible forage production systems using nonconventional salt-tolerant grasses and highly saline water were performed. The researchers from ICBA found two highly salt-tolerant grass species, Sporobolus virginicus and Distichlis spicata suitable as forage production systems. The authors concluded that maximum dry matter yield is achieved at higher levels of fertilizer and irrigation in Distichlis and by high levels of fertilizer and medium levels of irrigation in Sporobolus. Both plants were found to be extremely productive under saline irrigation presenting good quality of the forage nearly comparable to green barley. Distichlis can be irrigated with the salinity equivalent of seawater, and Sporobolus presents a high growth at high salinity level.
Atriplex species under high salinity conditions Atriplex lentiformis, A. nummularia and A. halimus are salt tolerance and value are highprotein animal feed. However, animals do not thrive if fed solely on Atriplex because it contains high concentrations of mineral salts. A 50:50 mixture of salt-tolerant Atriplex shrubs and grasses such as Sporobolus can provide a balanced diet, and lead to growth comparable to that of Rhodes grass.
Recovering salinity damaged land A farm which had been abandoned due to high salinity damage was recovered with highly salt-tolerant plants and halophytes in 2006 using grasses and shrubs such as Sporobolus, Distichlis and Atriplex . Cenchrus ciliaris (buelgrass) and fodder beet were among the few non-halophytic species which gre w there. An African Cenchrus ciliaris variety showed excellent growth under Irrigation water salinity reaching up to EC 20-22 dS m-1
Development of sustainable salt-tolerant forages for sheep and goat production This project aims at improving the sustainability of sheep and goat production systems by increasing the availability of forage resources through the introduction of salt-tolerant forages.
Halophytic grasses Sporobolus virginicus, Distichlis spicata, Paspalum and Kallar grass, all provided by ICBA, showed excellent growth under dierent salinity treatments.
1238 Shrubs and trees
Three shrubs (Atriplex lentiformis, A. nummularia and A. halimus) and one tree species (Acacia ampliceps) showed excellent growth under salinity treatment. Fodder beet Varieties Turbo, Adagio and Abando showed the highest yield, despite high salinity level. NyPa Forage grass [55] Halophytes that can ourish under seawater irrigation have huge potential in many coastal regions. NyPa grass (Distichlis spicata var.Yensen 4a) developed by NyPa International is one such halophyte. It can be grown with seawater and has a good forage/forage/fodder value. The variety is currently marketed internationally as NyPa Forage. ICBA and NyPa signed an MoU to test the germplasm for its growth and forage potential in the coastal conditions - both arid and humid - of the Middle East. Using seawater for irrigation, NyPa Forage has proved to be successful and feasible, providing an excellent opportunity for converting barren coastal areas into forage production areas. Water logging is also not an issue with NyPa Forage due to specialised tissue running the length of the root system, which allows oxygen from the leaves to be transported down to the roots, allowing them to grow in waterlogged conditions, the same mechanism which allows rice to grow in waterlogged conditions. It has a deep roots system, that has been traced down to 1.5m, which allows it to access the watertable. Currently NyPa Forage is being assessed across Victoria, South Australia and Western Australia. Agroforestry trial using Acacia ampliceps, Sporobolus arabicus and Paspalum vaginatum at dierent salinity levels An agroforestry system includes production of tree species along with other plants so that the species benet each other through nutrient and water management Sporobolus (foreground) and Acacia (background) have proved complementary crops in agroforestry trials. Date palms Among imported cultivars, Um-Al-Hamam showed the weakest performance and could not survive at any salinity levels. Among other varieties, Ajwat-ul-Madinah, Nabatat Saif, Nabatat Sultan and Sukkari showed best growth indicators. Average fruit production of the imported varieties was lower than the local varieties. Ajwat-ul- Madinah, Rhothan and Sukkari showed best performance among the varieties tested
15.35. OTHER AGRICULTURAL SYSTEMS Zero-tillage
1239
Special seeding equipment should be used. During tillage elimination herbicides will be necessary. Specialized drills to get the seeding in the earth are necessary. Straw and cha must be well spread across the width of the swath at harvest.
Table 15.6: Zero Tillage
Land USA Brazil Australia Canada Mexico Bolivia Chile Colombia Uruguay Venezuela
1999-2000 Hectares 19,760,000 13,470,000 8,640,000 4,080,000 800.000 200.000 96.000 70.000 50.000 50.000
Government farm programs and market conditions are sometimes against good crop rotation practices. Disease, weed and insect control must be kept in mind. Diseases are a major concern and must be handled with by rotation and other management practices. The ideal crop rotation alternates between cereal crops and oilseeds or legumes from one year to the next. For example, a wheat canola barley ax rotation allows to avoid disease carryover from one crop to the next. It allows the control of volunteer plants from the previous crop and the control of weeds which might not have been controlled by herbicides used the year before. The yearly switch from cereals to broadleaf crops makes it possible to break the cycle of insects and diseases attacking a crop grown continuously on the same eld. Residue of wheat contains survival structures for many pathogens such as tan spot fungus, septoria leaf and glume blotch fungi, scab or head blight. Zero-tillage increases risks of diseases because the fungal structures are not incorporated into the soil where microbes degrade straw and destroy the disease organism. Alternating cereal/broadleaf rotation will help to get this under control.
1240 Decades of Zero Tillage In In In In the 40s - The chemical 2.4 D released to farmers. the 50s - Grammoxone synthesis (UK: 1955). the 60s - Grammoxone released to farmers in 1961. Brazil: late 60s and early 70s.
The 70s ZT started in Paran. Machinery development. Release of modern herbicides beginning with glyphosate purpose-built herbicides). ZT in the decade was more expensive than CT. In the 80s - Cover crops and crop rotations, weed control mechanization introduced. Better understanding of ZT system. Direct costs turned equal to conventional tillage (late 80s) First university chair in Zero Tillage (Paran). In the 90s - Cover crops for Cerrado were introduced. EMBRAPA and "Friends of the Land" clubs started project of Water Resources Research and extension courses on ZT increasing interest by Universities. The wet/dry tropical savannah region, known as the Cerrado, covers approx. 204 million hectares in tropical Brazil. Its development is regarded by Dr. Norman Borlaug the winner of the Nobel Peace Prize for his plant breeding work that founded the Green Revolution - as the worlds most important agricultural expansion zone of the 20th century. But that development depends mainly on soil improvements. The areas of pastures, annual crops, permanent crops and forestry is not less than 47 million hectares. The recent and rapid adoption of Zero Tillage in this region has been phenomenal. Zero-Tillage in Brazil It began with the implementation of Zero Tillage by one farmer in 1972 on less than 500 hectares. By 1980 about 200,000 hectares were recorded, mainly in the subtropical conditions of the State of Paran. Since then - mostly within the last 9 years - the growth in area has been exponential, with now over 9,000,000 hectares in the country as a whole, about two-thirds of which to date have been in the southerly States of Paran, Sta. Catarina, Rio Grande do Sul, and Mato Grosso do Sul. Most of the other one third of the area under ZT has developed in the subhumid tropical region of the Cerrado, from almost nothing in 1990 to about about 3,000,000 hectares to date. The methodology has recently begun to spread also into the humid tropical Amazon region, where positive initial results are reported from the States of Mato Grosso, Rondonia, Roraima, Acre, Amap and Par. Indications are that spread continues very rapidly in
1241
all areas. The technology thus works in Brazil, both agronomically and economically, in a range of diverse soil/climate conditions. It is notable that the expansion of ZT has most eectively been by farmer-to-farmer spread Brazil-wide, particularly through the aliated network of Friends of the Land Clubs and State Extension services of Brazils southern States and Mato Grosso do Sul. It includes the land of small farmers with manual planters or animal-drawn implements up to large mechanised units of 5,000 hectares or more. The following benets are recorded to have owed from zero-tillage farming, both individuals and wider society: - Conservation of bio-diversity in soil, terrestrial and aquatic fauna and ora; - Sustainable high yield levels, resulting in lessened pressure to open new land; - Heightened environmental awareness among farmers; - Winter feed, and shelter for fauna; - Economies of 10-20% in use of water in irrigation; - Undecomposed crop residues acting as a carbon sink, estimated as xing about 1 tonne of carbon per hectare; - Fossil fuel use reduced by 40-70- Enhanced food security through greater resistance to drought eects; - Reduction of erosion losses by around 90%, with many consequential benets: -Signicantly less silting of surface waters including reservoirs for hydroelectricity and irrigation; -Virtual elimination of pollution of these waters by soil-applied agricultural chemicals; -More groundwater recharge, and less ooding: "Zero Tillage is the only macro-economic solution which can respond to the conicting demands of more food at lower prices while ensuring sustainability - in fact land quality is continually increasing under ZT." (Landers, 1999). Zero-tillage and environment Here again the modication of environment due to extreme application of manure and other animal wastes of heavy breeding can be compared with the problems created by sugar cane in the sugar-cane belt with the spread of Cholera epidemics. Zero-tillage could be an instrument to diminish the impact an the environment from heavy breeding populations. Zero-tillage, a hope for the Amazon region There are many millions of hectares of degraded pastures in the Amazon and Cerrado regions. ZT technology now exists to turn these pastures into productive cropland, which
1242
would reduce the pressure to open new lands for crop production. Especially relevant is the potential to rotate these crop areas with highly productive pastures, allowing absorption of herd growth without the need to form new pastures on newly cleared land. This potential is so great that even a total ban on clearing would not have a signicant impact on agricultural production for many years. It should be possible to promote a policy of incentives to this end, supported by international funding. The incentives would have to be adequate to cover extraction of old stumps and leveling of irregularities caused by erosion so that the reclamation of these old cleared areas would become signicantly more protable than clearing new land. Diseases and pests End-of-season leaf diseases in late-planted maize (especially Phaeospheria and some new ones for which there is no resistance); - In the Dourados municipality of Mato Grosso do Sul, the ZT Club reported a reversion of 50% of area to CT because of the chestnut soil beetle. This pest is extremely erratic in its appearance and can be controlled by insecticide at planting. - Control of persistent weeds where herbicide control is very expensive. A more diverse rotation is the solution to these ills. Some strategies and concepts that could be examined are : - Legume-enriched fallows or grass/legume mixtures for weed control, biomass generation, and nitrogen accumulation, taking advantage of sporadic rains; these could be selectively grazed as protein banks in an emergency; - Legal provisions in rental agreements to give sharecroppers or tenants the use of their land all year round without the obligation of having to allow the landowners cattle to graze in the dry season, and with the provision for a fallow period, all within a fenced area; - Large paddock grazing of livestock with management of native species for maximum regeneration and fodder production; for example Stylosanhtes humilis is native in the region and responds with heavy seed set under zero grazing in this period; - A rotation where a long fallow generates high-lignin and durable residues for a short crop sequence; A total ban on burning; (Villagers in Madagascar passed a local law forbidding the burning of the savannah because they had learnt to cut and carry this material for mulching annual crops under Zero Tillage; in the Northeast of Brazil, this no-burning strategy is already customary since re destroys the fodder for the landlords cattle!) The mulch cover of Zero Tillage and Conservation Agriculture in semi-arid areas would improve the soil water balance and promote higher yields, while the greater inltration capacity would ensure more rainfall stored in the soil prole when the heavy rains, which do occasionally occur in semi-arid areas, would run o under Conventional Tillage.
15.35. OTHER AGRICULTURAL SYSTEMS Sri Lanka, the price of conventional farming
1243
The Polonnaruwa district, in the North Central Province, is one of the best areas in Sri Lanka for crops. It has a favourable climate and good soil, backed by a network of irrigation canals providing a regular supply of water. But 30 of its small farmers committed suicide in 1995. They struggled in vain to get the minimum needed to keep their heads above water. They had borrowed heavily to buy chemicals and fertilizers and hire tractors and were now unable to pay back the debts. Modern agricultural methods have eroded fertile land in Sri Lanka, marginalized poor farmers, indigenous farming knowledge was lost in the name of scientic progress. Local food varieties and farming systems, adapted to environmental conditions had been abandoned Alternative systems must be reintroduced in the areas where conventional agriculture has not been successful. Harmony with the environment G. K. Upawansa, is rediscovering and promoting indigenous farming systems in Nawalapitiya, some 40 kilometres from Kandy. Rice is the staple food of Sri Lankans. Nearly 80 per cent of the population live in rural areas and paddy (rough rice) is the main peasant crop. [56] Reduced yelds of less than one and half tons per acre, compared with normal three tons of conventional paddy rice cultivation in Shi Lankla are seen by G. K. Upawansa to be caused by indiscriminate agro chemical application and the eects of soil erosion caused by inappropriate land preparation techniques responsible for low yelds. He shows alternatives to further disruption of agriculture and new techniques for small peasants. [57] Working together with a group of non-governmental organizations in Sri Lanka, Upawansa developed an alternative process of agriculture. the basis of rural subsistence.This consists of:
Table 15.7: Green Revolution Items Conventional agriculture Chemical-Free FarmingOrganic farming in Sri Lanka Minimal tillage is benecial
Intensive tillage Slowly degrades farmland
1244
CHAPTER 15. ORGANIC FOOD to farmland
Chemical ferlizers
Kill microbes in soil aecting ability to x nitrogen. Destroy insects and animals which maintain a check on pests. Wipe out insect predators. Resistance to pesticides develops. Keeps the land free of weeds as they compete with crops for nutrients and harbour pests.
Natural resources and atmosphere nitrogen.
Pesticides
Natural predators of crop pests build up.
Weed control
Weeds harbour predators of crop pests and enrich and conserve the soil.
Trees
Remove trees to allow more Removal of trees harms soil sunlight. fertility. During the planting and harvesting of crops, some people perform religious practices to invoke the blessings and protection of the Gods. Important psychological eects in case of a bad crop. The farmer can nd solace in religious practice, which would sustain his commitment
Religious beliefs and With monetary values. In values times of need, farmers now have nothing to hold on to.
Cropping
Mono cropping
Mixed cropping
The simple rules of the system: - Cropping according to the needs of communities and local methods of cultivation. - Composting farm waste and organic matters. - Plant extracts used as biological pesticides and natural predators as pest control.
15.36. SUSTAINABLE AGRICULTURE
1245
- Local weather patterns and climatic rhythms should determine cropping pattern. - Minimal tillage using village implements like country ploughs which only loosens but never turns the soil. - Mixed cropping. Reintroduce cultural and religious practices when harvesting and planting crops. Several considerations must be kept in mind: 1- Some degraded resources can be restored or rehabilitated and every eort must be made to do this wherever feasible. 2- Degraded or depleted natural resources may be partly substituted by man-made or alternative ones. 3- Techniques to avoid degradation exist which could be developed if eorts are accelerated. 4- Such institutions as land rights and the security or management of common resources can be organized or improved to greatly enhance incentives and opportunities for conservation. 5- Price incentives and regulations can be used to reduce pressure on natural resources. 6- Decentralization of resource management combined with local-level decision-making and implementation should be encouraged as environmental problems are often location-specic and need local and traditional knowledge, together with new and modern technology, if they are to be solved successfully. There are indications that about one-fth of the worlds land area is degraded to some extent, though this should be considered only as a preliminary estimate, since the data are rather weak both on the extent of land degradation and on its eect on productivity and sustainability. But it is widely agreed that losses in crop productivity due to degradation are signicant and widespread in rangelands and hilly and dryland areas. And between 0.3 and 1.5 million hectares of irrigated land are lost each year through waterlogging and salinization.
15.36
Sustainable agriculture
The concept of sustainable agriculture is a relatively recent response to the decline in the quality of the natural resource base associated with modern agriculture. It has its roots in the value that reecst a state of empowerment, of ecological and social responsibilities and of ones ability to take eective action. It involves management procedures that work with the natural process to conserve resources, promote agroecosystem self regulation and minimize waste and environmental
1246
impact while maintaining or enhancing protability of the production system.
15.37
Agroecosystem
The prevalent philosophy is that pests, nutrient deciencies or other factors are the cause of low productivity, as opposed to the view that pests or nutrients only become limiting if conditions in the agroecosystem are not in equilibrium. For this reason, there still prevails a narrow view that specic causes aect productivity, and overcoming the limiting factor via new technologies, continues to be the main goal. This view has diverted agriculturists from realizing that limiting factors only represent symptoms of a more systemic disease inherent to unbalances within the agroecosystem and from an appreciation of the context and complexity of agroecological processes thus underestimating the root causes of agricultural limitations (Altieri et al. 1993).
Principles of Agroecosystem Agroecology goes beyond a one-dimensional view of agroecosystems - their genetics, agronomy, edaphology, and so on,- to embrace an understanding of ecological and social levels of co-evolution, structure and function. Instead of focusing on one particular component of the agroecosystem, agroecology emphasizes the interrelatedness of all agroecosystem components and the complex dynamics of ecological processes. Agroecosystems are communities of plants and animals interacting with their physical and chemical environments that have been modied by people to produce food, bre, fuel and other products for human consumption and processing. The design of such systems is based on the application of the following ecological principles: 1. Enhance recycling of biomass and optimizing nutrient availability and balancing nutrient ow. 2. Securing favorable soil conditions for plant growth, particularly by managing organic matter and enhancing soil biotic activity. 3. Minimizing losses due to ows of solar radiation, air and water by way of microclimate management, water harvesting and soil management through increased soil cover. 4. Species and genetic diversication of the agroecosystem in time and space. 5. Enhance benecial biological interactions and synergisms among agrobiodiversity components thus resulting in the promotion of key ecological processes and services.
15.38. CAMPYLOBACTER IN ORGANIC POULTRY Strategies of Agroecosystem
1247
Various strategies to restore agricultural diversity in time and space include crop rotations, cover crops, intercropping, crop/livestock mixtures, and so on, which exhibit the following ecological features: 1. Crop Rotations. Temporal diversity incorporated into cropping systems, providing crop nutrients and breaking the life cycles of several insect pests, diseases, and weed life cycles (Sumner 1982). 2. Polycultures. Complex cropping systems in which tow or more crop species are planted within sucient spatial proximity to result in competition or complementation, thus enhancing yields (Francis 1986, Vandermeer 1989). 3. Agroforestry Systems. An agricultural system where trees are grown together with annual crops and/or animals, resulting in enhanced complementary relations between components increasing multiple use of the agroecosystem (Nair 1982). 4. Cover Crops. The use of pure or mixed stands of legumes or other annual plant species under fruit trees for the purpose of improving soil fertility, enhancing biological control of pests, and modifying the orchard microclimate (Finch and Sharp 1976). 5. Animal integration in agroecosystems aids in achieving high biomass output and optimal recycling (Pearson and Ison 1987).
15.38
Campylobacter in organic poultry
Tom Humphrey, Professor of Food Safety at Bristol University was engaged in a governmentfonded survey ob bacteria in poultry in November 2003. Free-range and organic chickens were found twice as likely as battery hens to be contaminated with the food-poisoning bacteria Campylobacter. The strains of Campylobacter collected have not yet been identied so it is impossible to know whether the organic chickens tested contained strains of Campylobacter capable of causing food poisoning, According to Richard Young from the Soil Association the lower use of antibiotics in organic poultry farms will make it less likely that such strains are resistant to antibiotics. These ndings were also conrmed in November 2003 by Swiss researches. Chickens raised in an animal-friendly way are more healthy, so they need less treatment with antibiotics and so their Campylobacter are less resistant to antibiotics. But the other side of the story is that these chickens go outside more often, so they are in more contact with wild birds, which is the reservoir of Campylobacter. In the US, 90 per cent of Campylobacter strains isolated from poultry meat had resistance to at least one, and 45 per cent to at least two
1248 antibiotics, commented the researchers.
Worries over antibiotic resistant bacteria led the EU, in 1999, to ban the use of four antibiotics as growth promoters in chickens. The US Food and Drugs administration (FDA) followed their lead in late 2000 by banning the use of a particular class of antibiotics called uorquinolones in poultry farming. Resistance to ciprooxacin, tetracycline and erythromycin - the most important antibiotics for treating Campylobacter infection in humans are developing. Conclusion Increase of fertilizer fail to increase yields accordingly:It seems that the old formula of combining more and more fertilizer with ever higher-yielding varieties to expand the grain harvest is no longer working very well. The future of global food will relay on a conventional farming implementing new ndings of pest control in the developed world. The food supply in the third world will depend on local systems which uses knowledge of ancestry specically suited for the local need. The green revolution will hardly succeed in taking foot in arid and poverish regions because there are no funds to pay for pesticides and fertilizers. Systems like the no-chemicals agriculture from Upawanza should be strongly supported as a sustainable agriculture with local importance.
Organic agriculture and nitrogen fertilizer [58] Research made by Sasha B. Kramer and colleagues at the Stanford University found that fertilising apple trees with synthetic chemicals produced more adverse environmental effects than feeding them with organic manure or alfalfa. They claim that the increase use of nitrogen-based fertilizer to cause a substantial nitrogen pollution and ecological damage. Harold A. Mooney, Professor of Environmental Biology at Stanford, co-author of the study, says that the use of organic versus chemical fertilizers can play a role in reducing these adverse eects. The PNAS (Proceedings of the National Academy of Sciences)study was conducted in an apple orchard in central Washington. Three dierent groups of trees had been raised, one with conventional synthetic fertilizers, one grown organically, and a third group by integrated farming combining organic and conventional agricultural techniques.
15.38. CAMPYLOBACTER IN ORGANIC POULTRY
1249
The authors come to the conclusion that conventional agriculture has made tremendous improvements in crop yield but at large costs to the environment, an organic farming cannot provide for all of our food needs, but it is certainly one important tool for use in our striving for sustainable agricultural systems. Falling nutritional quality of vegetables from conventional agriculture [59] Dr David Thomas from the SEER (Sustainable Ecological Earth Regeneration) Centre, backed organic agriculture as he made a comparison of government tables published in 1940, and again in 2002 suggesting that modern farming practices have led to nutrientpoor food. According to Dr. Thomas the data of these tables show that the nutritional quality of vegetables has signicantly fallen over the last few decades. As an outcome of this study Dr. Thomas says that food manufacturers need to promote not just good looking, wonderful tasting and great smelling food, but also nutrient-rich food. He says that iron content in meat and milk, as well as minerals like magnesium and copper which are essential for enzyme functioning had dropped signicantly. David Pimentel comparing statistics on soil erosion calls on the fact that soil from land areas is being lost faster than it is renewed. Erosion is fast in China and India. Pimentel suggests that demineralisation of the soil could be stopped using cover crops when the land is not in use. [60] Pesticides and changes to the diets of animals has altered their body fat composition, omega-3 has declined but omega-6 has increased. Together with a general lack of vitamins and minerals these changes can lead to depression, concentration and memory problems. Mental Health and nutrition. [61] The Mental Health Foundation Sustain: The alliance for better food and farming say that there is growing evidence that diet plays an important contributory role in specic mental health problems including Attention Decit Hyperactivity Disorder (ADHD), depression, schizophrenia and Alzheimers disease. According to the Foundation a generally healthy diet, as recommended for the physical health of the body - containing the necessary range of micro- and macronutrients and minimising the consumption of unhealthy nutrients, and no single nutrient can assure good brain development. [62] Omega-3 fatty acids may interfere with the development of Alzheimer Disease [63] Yvonne Freund-Levi and colleagues found in a study published in the Archives of NeuCopyright 1998-2010 Karl H. Wilm. All rights reserved. OurFood Database of Food and Related Sciences
1250
rology , that the administration of omega-3 fatty acid in patients with mild to moderate Alzheimer disease did not delay the rate of cognitive decline. However, positive eects were observed in a small group of patients with very mild Alzheimer disease. The authors cannot explain how omega-3 fatty acids may interfere with the development of Alzheimers disease, but suggest that the benets in the very mild forms of the disease may be linked to the sh oils anti-inammatory eects. However, when the disease is clinically apparent, the neurological tissue damage is too advanced to be attenuated by anti-inammatory eects of the omega-3 fatty acids. The authors cite a critical period of two years or more before the onset of dementia to be critical for the anti-inammatory eects of the omega-3 fatty acids. This calls for an increase of omega-3 fatty acid intake from dietary or supplemental sources. Mediterranean diet may reduce the risk of development of Alzheimer Disease [64] Dr Nikolaos Scarmeas and colleagues studied the diet of Alzheimer disease patients. They found that those in the top third of scores for consumption of the Mediterranean diet, had 68% lower odds of having AD than those in the bottom one third. Subjects in the middle third, had 53% lower odds of getting AD. The authors suggest that the diets AD protective eects may be related to its antioxidant or anti-inammatory eects and to a positive eect on blood vessel health. Curry spice tumeric may reduce the risk of development of Alzheimer Disease [65] Milan Fiala and colleagues studyed the activity of curcuminoids from curry spice turmeric. The authors found that curcuminoids could help the bodys immune system clear away plaques composed of beta-amyloid deposits. Macrophages from Alzheimer disease patients were exposed in vitro to curcuminoids, improving the ingestion of amiloid deposits. Macrophages o younger patients in an early stage of the disease were beneting the most. The authors suggest that immunomodulation of the innate immune system by curcuminoids might be a safe approach to immune clearance of amyloidosis in Alsheimer disease brain. Pomegranate juice and reduction of risk of Azheimer disease [66] In a study conducted by R. E. Hartman the high content of polyphenols of pomegranate juice reduced the deposition of amyloid beta deposition in brains of rats. The author calls
15.39. RECOVER OF NATURAL ANTIOXIDANTS OF INDUSTRIAL FRUIT AND VEGETABLE WASTE 1251 for further studies whether pomegranate Juice can protect against Alzheimer disease in humans. Ellagic acid in pomegranates The highest levels of ellagic acid are found in raspberries, strawberries, and pomegranates. Extracts from red raspberry leaves or seeds, pomegranates, or other sources are said to contain high levels of ellagic acid, and are available as dietary supplements in capsule, powder, or liquid forms. The best dose of these preparations is not known. Because they are sold as dietary supplements (as opposed to drugs), companies that sell them do not have to prove they are eective, or even safe, as long as they dont claim they can prevent, treat, or cure a specic disease. [67] Ellagic acid is not the most signicant of the polyphenol content of pomegranade, but was proposed to be used as indicator of the concentration of pomegranate in juices, other probiotic foods and dietary supplements. A test procedure for ellagic acid has been developed. [68]
15.39
Recover of natural antioxidants of industrial fruit and vegetable waste
[69] Looking for an alternative to synthetic preservatives such as like BHA and BHT Wieland Peschel and colleagues analysed waste products from processing of fruit and vegetables of the juice and canning industry as well of the remains from harvesting from fruits and vegetables. Extraction yield, total phenolic content, and antioxidants with the highest activity, economic justication and phenolic content were found in this study in apple, pear, tomato, golden rod and artichoke. The best yields were obtained with polar solvents like water and methanol. Supercritical uid extraction was also used in this screening. This study demonstrates the possibility of recovering high amounts of phenolics with antioxidant properties from fruit and vegetable residuals not only for food as preservative but also cosmetic applications. Golden rod and artichoke had high radical scavenging. The apple extract yield was higher and had high eciency in two of the antioxidant tests. Eciency of golden rod, artichoke and apple extract was lower compared with commercial
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BHT. Golden rod extract and the apple extracts were more ecient in the DPPH free radical scavenging test than BHT. Omega-3 fatty acids in Alpine cheese [70] Hauwith and colleagues compared the fatty acid composition of Alpine cheese and cheese of other origin. Fresh alpine grass contains high amounts of alfa linoleic acid (ALA) and may inuence the levels of omega-3 fatty acids in the cheese of milk from cows with alpine grass feeding compared with cheese from silage and concentrate feeding. The authors found that the Emmental reached 40% of the ALA content compared with alpine cheese, and surprisingly, cheese from linseed-supplemented cows contained only 49% of that of the alpine cheese. They concluded that cheese made of milk from cows grazed on alpine pastures had a more favourable fatty acid prole than all other cheese types. Alpine cheese may be a relevant source of ALA and other cardioprotective fatty acids. Milk from the Himalayas healthier than milk from dairy cattle fed grain-based diets [71] Mamun Or-Rashid and colleagues 2008 compared the fatty acid composition of cheese from yak (Bos grunniens) from Nepalese Himalayas with that of Canadian dairy cow Cheddar cheese. The authors found that the yak cheese had a higher level of total long-chain saturated fatty acids and a 3.2 times higher content of total n-3 PUFA than cow cheese. The total conjugated linoleic acid (CLA) content in YC was 2.3% of total fatty acids compared to 0.57% in DC. The cis-9, trans-11 CLA isomer in YC constituted 88.5% of the total CLA. CLA from dairy products such as milk, cheese and meat are formed by bacteria in ruminants that convert plant linoleic acid into conjugated linoleic acid. The researchers concluded that cheese from yak, grazed on Himalayan alpine pastures, may have a more healthful fatty acid composition compared to cheese manufactured from dairy cattle fed grain-based diets. This may support studies claiming the milk from organically reared cows at mountain pastures to be healthier compared with conventional rearing at lower altitude. Comparison of the fatty acid composition of organic and conventional milk [72] Ellis and colleagues compared the fatty acid composition of organic and conventional milk. They identied a number of factors other than farming system which aected milk fatty acid content including month of year, herd average milk yield, breed type, use of a total
15.40. REPCO: REPLACEMENT OF COPPER FUNGICIDES IN ORGANIC PRODUCTION OF GRAPEVINE AND APPLE IN EUROPE mixed ration, and access to fresh grazing.
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The authors concluded that organic dairy farms in the United Kingdom produce milk with a higher polyunsaturated fatty acids content, particularly n-3 fatty acids, throughout the year, stressing that knowledge of the eects of season, access to fresh grazing, or use of specic silage types could be used by producers to enhance the content of benecial FA in milk. Reduction of copper as fungicide in organic agriculture The downy mildew (Plasmopara viticola) is a fungus which was brought from America to Europe in 1878 spreading quickly through wine yards. Apple orchards are now menaced by Venturia inaequalis causing scab in cool, rainy conditions in the spring. Early leaf loss reduces the vitality of the trees and spots on apples render them dicult to sell. Organic growers in Europe use copper, sulphur and lime sulphur. Copper will be banned turning it necessary to search for a replacement.
15.40
REPCO: Replacement of copper fungicides in organic production of grapevine and apple in Europe
[73] [74] Replacement of Copper Fungicides in Organic Production of Grapevine and Apple in Europe The objective of REPCO is to replace copper fungicides in organic agriculture by new measures. Up to 38 kg had been permitted for organic agriculture. The Council Regulation (EEC) 2092/91, Annex II demands a gradual reduction of copper with start in 2007 to protect environment Knowledge and material of the REPCO project will be exchanged with ongoing projects on potato late blight control in organically grown potato. Yucca extract preventive eect on scab in apples [75] Yucca extract was found to have preventive and curative eect on scab in apples by researchers of Wageningen University and Research Centre (Netherlands). The researchers, participating with the REPCO program, point out that the extract prevents the fungus from budding, avoiding an infection of the plant. The curative eect lasts one day the plant is infected. A patented product will be placed on market.
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No genetic pressure by organic copper replacement [76] Cesare Gessler analysing the genetic code of Plasmopara viticola found that no variant of the fungus could develop resistance and to pass it on. The authors of the study say that there is no genetic pressure by organic replacement because the fungus is attacked from various sides and cannot nd a way to counter. In one case treated plants developed resistance to the infection., The authors say that synthetic fungicides attack the fungus from one side, therefore resistance can develop. Citrus-extract comparable to copperoxychlorid treatment against scab [77] Collar and Pfeifer in 2003 found that mixtures of Quillaja-saponine and sulphur reduced eectively apple scab incidence, but rain stability of citrus-extract and Quillaja-saponine showed a lower ecacy against scab after 5 mm rain. They suggest mixtures of Citrusextract with the adhesives GREEMAX and BIOPLUSS to be comparable to copperoxychloride corresponding to 400 g elementary copper per ha. Vinasse as an alternative to copper fungicides citeWageningen vinasse [78] [79] According to researchers at Wagendingen University and Research Centre the application of vinasse can reduce the formation of apple scab ascospores by more than 95 per cent and stimulates leaf degradation during winter. Vinasse is a fermented waste product of the sugar processing industry and is seen as an alternative to copper.
15.41
Food and ecology
About 6% of the population of Germany are vegetarians. They want to avoid to harm animals, to avoid food waist as animal feed and last, but not least to reduce greenhouse gases, such as carbon dioxide, methane, nitrous oxide emanating from animal breeding. FAO environmental scientist calculated the CO2 - equivalence of the dierent types of nutrition: The global animal population produce approximately one fth of greenhouse gases resulting from the activities of mankind. FAO stresses that this is more than the emission of global trac. CO2 emission results from burning forests to prepare land for pastures and feed crops. Dung and liquid manure produce nitrous oxide. Ruminants such as cattle and sheep emit methane. Mechanized agriculture of rape and soy produce more CO2 . Approximately 6 kilos of vegetable protein are necessary to produce one kilo animal protein.
15.41. FOOD AND ECOLOGY Methane to Markets Partnership
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[80] The Methane to Markets Partnership is an international initiative that advances costeective, near-term methane recovery and use as a clean energy source. The goal of the Partnership is to reduce global methane emissions in order to enhance economic growth, strengthen energy security, improve air quality, improve industrial safety, and reduce emissions of greenhouse gases. Main targets are: Agriculture and food waste Livestock enteric fermentation, livestock waste management, rice cultivation, and agricultural waste burning. Institutional systems are being developed to capture the methane of livestock waste such as farms of farrow-to-nish swine operation in Brazil, dairy farms in India , or sheep herds in Australia. Anaerobic technology with solids separation will be used Researchers have estimated cattle produce an average of 250 litres of methane a day. It represents a 15 per cent loss in potential energy. The current manure management method is lagoon storage of the waste in a leaky anaerobic digester lagoon. A covered lagoon digester is a large anaerobic lagoon with a long retention time and a high dilution factor. Typically covered lagoons are used with ush manure management systems that discharge manure at 0.5 to 2 percent solids. The in-ground, earth or lined lagoon is covered with a exible or oating gas tight cover. Retention time is usually 30-45 days or longer depending on lagoon size. Landlls Landll gas, composed of about 50 percent methane, is a natural by-product of decomposing organic matter. It can be used to produce electricity with engines, turbines, or other technologies, and can be rened and injected into a natural gas pipeline. Coal mines Removing fugitive methane gas from underground coal mines and using it in protable and practical ways can improve worker safety, enhance mine productivity, increase revenues, and reduce greenhouse gas emissions. Oil and gas systems Methane emissions from oil and natural gas systems are primarily the result of normal operations and system disruptions. These emissions can be cost-eectively reduced by upgrading technologies or equipment, and by improving operations.
1256 Methane from livestock
[81] According to professor Andre-Denis Wright an average U.S. beef cow burps up more than a hundred pounds of methane each year. Multiplying this by 99 million cows it is about 2% of the greenhouse gases emission. Wright wants to reduce it and turn it protable for farmers. Wright develops a vaccine which decreases methanogenic bacteria in the digestive track of the animals. This may reduce emissions and increases meat and milk production by 5% returning the lost energy back to the animal. Athol Klieve wants to build fermenter which digests the feed similar what is happening in kangurus, which do not emit methane. Klieve is looking for bacteria that are able to out compete the methanogens that are present in the rumen and produce acetate instead of methane. Acetate is an energy material available for the animal. Wright and his former colleagues in Australia demonstrated that in 30 sheep a vaccine could reduce methane output by almost 8%. Wright collected gut bacteria from South American birds to Norwegian reindeer and beyond, to cover all the methanogens. A new species was named after Dr. Wright, Apokeronopsis wrighti n. sp.
Vaccine against methane producing bacteria [82] Wright and colleagues 2009 tried to develop a vaccine targeted against methanogenic bacteria present in sheep to decrease the methane output of the sheep. Five phylotypes which account for >52% of the methanogens were used for the production of a vaccine. The authors reported that the vaccine may have altered the composition of the methanogen population and a more broad-spectrum approach. Our data also suggest that methanogens take longer than 4 weeks to adapt to dietary changes. 2 to 4-week acclimatization period normally observed for bacteria are too short, say the authors.
Methanogenic bacteria and ciliate protozoa in reindeer [83] In a study of 2009 wright and colleagues report the diversity of ruminal methanogens, bacteria and ciliate protozoa of Svalbard reindeer. In this study they used a 16S rRNA gene library prepared from pooled PCR products from reindeer. Eleven of the 22 distinct operational taxonomic units were similar to methanogens aliated with Methanobacteriales, Methanomicrobiales and Methanosarcinales, and the remaining 11 operational taxonomic units (53% ) were associated with a cluster of uncultivated ruminal archaea. The authors state further that host type aects the population size of ruminal methanogens.
15.41. FOOD AND ECOLOGY
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Rumen-like methanogens identied from the crop of the South American bird, the hoatzin [84] The hoatzin is the only known avian species with foregut fermentation. Wright and colleagues examined the methanogens of the crop of hoatzin using 16S rRNA gene clone libraries. The authors found similarities with Methanobrevibacter ruminantium and Methanosphaera stadtmanae. Possible new genera and new species were identied. The authors concluded that although none of bacteria had 100% sequence identity to any of the the GenBank database, the hoatzin crop methanogen sequences formed sister groups with known rumen methanogens and demonstrate the convergent evolution of foregut fermentation in the hoatzin, similar to that of ruminants.
Methanogens in sheep from Venezuela [85] Rumen methanogens in sheep from Venezuela, using 16S rRNA gene libraries, were found to belong to the genus Methanobrevibacter and Methanobrevibacter gottschalkii. Two possible new species, one belonging to the genus Methanobrevibacter and the other belonging to the genus Methanobacterium were reported by Wright, Ma and Obispo 2008.
Articial stimulation of the rumen wall and low grain diet decreases methane emission of sheep [86] Studying the interaction of retention time in the rumen and concentrate diet on methane production in vitro, Wright and colleagues 2008 found that pot scrubbers combined with grain alter the rumen fermentation. They suggest that the introduction of pot scrubbers into the rumens of livestock consuming low levels of grain may be a way to lower methane emissions.
Molecular diversity of methanogens in feedlot cattle [87] Wright and colleagues 2007 compared the composition of the methanogenic bacteria of the rumen of of corn based diet animals in Ontario and Prince Edward Island fed with potato by-products. One-third of the bacteria were identied as Methanobrevibacter ruminantium, also Methanobacteriales, Methanomicrobiales, and Methanosarcinales were found. The two herds diered in composition and in new species found in the methanogenic population. The authors could not conclude whether the geographical isolation or the dierent diets of both herds were responsible for these dierences.
1258 Two new methanogenic bacteria classied
[88] Wright and colleagues, based on 16S rRNA gene sequence analysis, classied four bacteria belonging to the order Methanobacteriales in the genus Methanobrevibacter. living in the rumen of sheep and cattle. Two were found to be Methanobrevibacter thaueri and Methanobrevibacter ruminantium, and the other two strains were novel species for which the researchers proposed the names of Methanobrevibacter millerae sp. nov. and Methanobrevibacter olleyae sp. nov. Detection and cultivation of bacteria to inhibit growth of methanogens [89] Gilbert and colleagues 2010 describe a method for screening bacterial isolates for their potential to inhibit the growth of ruminal methanogenic Archaea using modication of the soft agar overlay technique. Streptococcus bovis from gastrointestinal tract of animals and humans [90] Herrera and colleagues 2009 highlight the importance of Streptococcus bovis present in the gastrointestinal tracts of humans and animals. S.bovis is one of the major causes of bacterial endocarditis and is implicated in colon cancer. Certain diets may lead to overgrowth of S.bovis in the rumen. Resulting over-production of lactate and capsular polysaccharide cause acute ruminal acidosis and bloat. This demands a diet of grain and coarsely chopped roughage. Ionophores, enhancing feed conversion and growth rate in cattle, have also inhibiting eect on lactic acid bacteria in the rumen. Also supplementation of longchain fatty acids, vaccines, and the use of lytic bacteriophages) have also been proposed. The authors hope that the outcomes of these studies may lead to more eective control strategies of these bacteria. Joachimsthal and colleagues 2009 found that Streptococcus bovis Sb 15 isolates from Australian ruminants may be used for commercial production of bacteriocin to prevent food spoilage or as a feed additive to promote growth in ruminant species. [91] Ruminococcus bromii YE282 may become a supplement to improve barley feed [92] Klieve and colleagues 2007 studied the bacteria population in grain (barley)-fed cattle aiming to increase the eciency of starch utilization.One of the most common and dominant bacteria present was identied as Ruminococcus bromii YE282, counting for about 10% of the total bacterial population. The authors suggest that this strain may be used as probiotic supplement to increase the starch utilization in barley-fed cattle.
15.41. FOOD AND ECOLOGY Forrage diet related eects on Escherichia coli
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[93] Callaway and colleagues 2003 stress that the enterohemorragic Escherichia coli (EHEC) strain O157:H7 is found in about 30 to 80% of feedlot and dairy cattle. The authors explain that some of the starch of this grain is not fully digested and gets to the hindgut where the pathogenic Escherischia coli may prot, because this bacteria can ferment sugars. Changing from high grain (corn) diet to a forage diet, generic E. coli populations declined 1000-fold within 5 days. The authors write that changing the diet of cattle from grain to forage may reduce EHEC populations prior to slaughter. Dietary inuences, such as grain type, processing method, forage quality, and distillers grains have all been associated with E. coli O157 prevalence. Also several plant compounds, including phenolic acids and essential oils, have been proposed to reduce Escherichia coli prior to slaughter. The specic mechanisms of this eect are unknown and a better understanding of them may improve preharvest strategies, says a group around Callaway in 2009. [94] Recent research has shown that diet does aect E. coli O157:H7 populations, but the eects have varied in magnitude and impact and their eect may be due to concentrations of tannins and phenolic acids in forages. Other diets containing grains which are rapidly fermented, such as barley, reduce the number of E. coli and distillers grains can increase faecal shedding of E. coli O157:H7 due to volatile fatty acids concentrations.The authors concluded that diet may inuence STEC/EHEC populations prior to slaughter; but must be put in line with the economic and practical impacts. [95]
Lacto-vegetarian nutrition The Cornell University (Ithaca, USA) found in a study, that the production of one kilo milk protein needs 14 kilocalories of fossile energy, this is the same amount needed for the production of one kilo porc. The German Freiburger ko Institute writes that 8 litres milk are necessary to produce 1 kilo cheese. [96]
The CO2 - equivalence of the production of 1 kilo, cheese, meat, egg and yoghurt Product Cheese Meat Egg yoghurt Emission of CO2 equivalece 8 kilo 6 kilo 2 kilo 1 kilo
1260 Soy and feed
According to Jrg Michael Greef from the German from the Bundesforschungsanstalt fr Landwirtscaft. The world production of soy is 220 million tons. Germany imports 40 million tons. Three million tons are used for the production of edible oil and other applications. The main core of 37 millions tons are transformed in animal feed. [97] Soy farms built monocultures in USA, Argentina and Brazil, where they invade the tropical forest and savannahs. Centralised animal breeding, depending on soy are an environmental false step. Smaller units, depending on local feed are ecology friendly and create jobs.
Palmoil According to the Environmental Program of the United Nations UNEP, 83% of palm oil comes from Indonesia and Malaysia. The consumption of Palm oil increase , because it is used as food as well as biofuel. Great plantations destroy the tropic forests of Indonesia and Malaysia. [98] Kurt-Jrgen Hlsbergen, expert in ecology, says that we need animals, because their manure is an important fertilizer which replaces mineral fertilizers which demand enormous amount of energy in their production. Hlsbergen says that regenerative farming should consider not to have more than one cow or seven pigs on one hectare. This lets nature assimilate manure. [99] To protect environment and the global climate the consumer should look for products from their region to avoid transportation over long distances. There is no need to avoid meat, eggs or dairy products, as long as they come from regenerative biologic farms.
Higher levels of ascorbic acid, minerals and antioxidant activity in organic kiwi fruit than in conventional fruits may be due to less pesticides in organic elds [100] Maria Amodio and colleagues write that all the main mineral constituents were more concentrated in organic kiwifruits, which also had higher levels of ascorbic acid and total phenol content, resulting in a higher antioxidant activity. Sugars and organic acids composition was not aected by the production system. The authors believe that the dierence between the content of total phenols in plants may be due to the fact that conventional growing practices utilize levels of pesticides that can result in a disruption of phenolic metabolites in the plant, that have a protective role in plant defense mechanisms.
15.42. BETTER CHEESE WITH CORN SILAGE FEED MILK THAN FROM FRESH PASTURE MILK 1261 Strategy revealing dierences between conventionally and organically grown grapefruit [101] Lester and colleagues 2010 describe dierences between conventional or organic farming of Rio Red grapefruit, using a method which shows their spectral ngerprints. The methode is based on ow injection electrospray ionization with ion trap and time-of-ight mass spectrometry (FI-ESI-IT-MS and FI-ESI-TOF-MS). Beside dierences between conventional and organic farming, growing year and time of harvest also caused variations, which could be seen using analysis of variance principal component analysis (ANOVA-PCA). The authors suggest that spectral ngerprints provided a better picture of the chemical dierences between conventionally and organically grown Rio Red grapefruit. Comparing conventionally and organically grown Rio Red grapefruit [102] Lester and colleagues 2007 state that claiming organic produce to taste better and are more nutritious than conventional produce are unsubstantiated because they often do not consider common production variables, such as microclimate, soil type, fertilizer elemental concentration, previous crop, irrigation source and application, plant age, and cultivar. Adjusting these variable, the authors found that conventional fruit was better coloured and higher in lycopene, and the juice was less tart, lower in the bitter principle naringin, and better accepted by the consumer panel than the organic fruit. Whereas organic fruit had a thinner peel, higher ascorbic acid and sugars levels and were lower in nitrate and furanocoumarins. Furanocoumarins such as bergamottin and dihydroxybergamottin are responsible for the "grapefruit juice eect", in which these furanocoumarins aect the metabolism of certain drugs.
15.42
Better cheese with corn silage feed milk than from fresh pasture milk
[103] Hurtaud and colleauges compared the milk from dairy cows secreting small milk fat globules ( 3.44 millimicra) with that of cows with large milk fat globules (4.53 millimicra) and looked at the eect of pasture feed and soybean meal feed. Small (SMFG)and large milk fat globules (LMFG) secreting cows The SMFG dairy cows produced higher yields of milk, protein, and calcium, their milk had lower fat and protein contents a higher concentration of monounsaturated fatty acids and a lower concentration of short-chain fatty acids, and a higher C18:1/C18:0 ratio which suggests a higher fatty acid elongation and desaturation. than LMFG cows.
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The authors suggest that higher calcium of this milk improves cheese despite lower yield because of reduced protein content. Fresh pasture Feed and corn silage feed The authors compared fresh pasture supplemented with cereal concentrate against corn silage treatment supplemented with soybean meal. The fresh pasture feed led to an increase in milk and protein yields lower milk fat yield, to a decrease in milk fat globule size and an increase in monounsaturated and polyunsaturated fatty acid contents, decreased protein content, lower calcium mineralization of casein micelles, turning the milk less suitable for cheese production. The authors found no correlation between the cows, based on milk fat globule size and diet. The authors suggest milk fat quality improvement based on milk fat globule size, and composition. Open Skies deal between EU and US, a rabbit punch to environment The EU hails the new deal saying that the agreement opens the possibility of an additional 26 million extra passengers on transatlantic ights over a period of 5 years. This compares with current annual trac of just under 50 million. At the end of the fth year, this will mean that the market will be 34% higher with the agreement than without the agreement. The cargo market would see growth of between 1 and 2 percent, which is highly signicant given the size of the market globally (with the European and American industry accounting for 70% of the global eet). [104] The sad truth A single ight across the Atlantic can guzzle about 60,000 litres - more fuel than an average motorist uses in 50 years of driving - generating around 140 tonnes of carbon dioxide, along with 750 kilograms of Nitrogen Oxides Emissions. The net result is that pollution from high-ying jets is up to four times as damaging as the same amount released from chimneys and exhaust pipes at ground level. [105] All politicians should work together to permit air trac only to those presenting a satisfactory evidence of extreme necessity of this voyage. Instead of reducing harmful air trac politicians like Chancellor Angela Merkel, George W. Bush and Tony Blair, support an increase of climate pollution. Not enough nutritional evidence to recommend organic foods over other foods [106] According to ClaireWilliamson 2007 writing in an article in the Journal of the Science of
15.42. BETTER CHEESE WITH CORN SILAGE FEED MILK THAN FROM FRESH PASTURE MILK 1263 Food and Agriculture there are limited data claiming that organic foods are more nutritious than conventionally produced foods. In this review no overall dierences in nutritional proles for food grown conventionally or organically were reported. Only few exceptions were found, such as organic potatoes and leafy organic vegetables which were richer sources of vitamin C than their conventionally grown vegetables. No dierences were found in nutrients of main concern in dairy products such as calcium, zinc, vitamin B2 or vitamin B12. Only in milk less sought after nutrients like linoleic acids , vitamin E, beta- carotene and poyunsaturated fatty acids were found higher in organic milk. However these items are sourced from other foods. The world market of certied organic foods is growing rapidly. Behind the marketing efforts of retailers international exporters a huge interest of the international business groups is ourishing. Transportation over long distances and even air freight is being considered by the certication boards. [107] Avoiding pollution of the environment with pesticides and chemical fertilisers, using crop rotation and good animal husbandry to control pests and diseases are the basics of a sustainable method of agriculture. The primary goal is the protection of the environment. A side-product is the food which is harvested in such environment. Buying organics grown far away you are doing the best for your supermarket corporation but its not better for your health or the environment than choosing cheaper conventional produces. If you want to go organics look for small organic farmers, small organic stores which have their ware supplied by surrounding farms, and look for weekly markets of your town. Ingredients: Organic products of the shelves of your supermarket often do not dier from conventional ones such as organic fruit yoghurt. It has the same addition of 10 per cent of sugar-glucose syrup increasing the risc of obesity and diabetes. Organics is a philosophy of cohabitation of mankind and nature. On the other hand supermarket shelf ware organics is a genial marketing eort to boost business, the contact with the roots of organics are blurred. No dierence between organic foods and conventional foods concerning trace elements and bioavailability [108] Dr Susanne Bgel and colleagues from the University of Copenhagen investigated major
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and trace element contents of dried carrots, kale, peas, potatoes and apples and the mineral retention determined in rats fed diets based on these foodstus in comparison to conventional foods. The minerals Ca, P, Mg, Na, K, Fe, Zn, Cu, Mo, Co, Cd, and V. were studied in this research. The authors found no dierences in content and in retention of minerals between both cultivation systems. In conclusion of the study the belief that organically grown foodstus generally contain more major and trace elements than conventionally grown foodstus is not supported, neither is the bioavailability of major and trace minerals increased in rats. No support for conclusion that rats prefer organic feed to conventional ones [109] A study of Young and colleagues 2005 did not support foregoing studies which claimed that rats prefered organic foodstus. The authors wrote that many rats showed individual preference for the experimental diets, but totally no clear dierence among the dietary treatments could be obtained, as our data showed preferences conditional on mothers diet treatments. The present study could therefore not support some of the previous reports (Plochberger and Velmirov, 1992, Mder et al., 1993, Malheiros et al., 2003, concluding that rats prefer organic feeds to conventional ones. No denite conclusion could be drawn with regard to the selection of food from one cultivation system in preference to food of another. Opinions supporting organic food claims The Danish governments International Centre for Research in Organic Food Systems The Centre says that it is generally accepted that food grown organically is better for human health than food grown in the conventional way using pesticides, but no scientic studies to back these claims are presented. The Soil Association in UK The Association says that consumers consider aspects like lower pesticide residue levels and less impact on the environment when buying organic produces. The Association criticizes the study of Bgel alleging that results were based on dry weight basis and not on a fresh weight basis, the results were therefore not comparable.The majority of the non-organic fruit and vegetables in soil that had previously been under organic, rather than non-organic, management. The Association cited also the study of Lauridsen 2008 which found that dierent cultivation methods caused dierences in some health-related biomarkers.
15.42. BETTER CHEESE WITH CORN SILAGE FEED MILK THAN FROM FRESH PASTURE MILK 1265 Organic foodstus cause dierences in health-related biomarkers [110] Lauridsen and colleagues 2008 studied the health-related biomarkers eects of dierent growth conditions of plant foods. They found that rats fed with low pesticides input fodder had a higher serum IgG concentration compared to rats fed with high pesticide input fodder and 14% less adipose tissue, and showed less movement during the day than the other treatments. The liver metabolic function and free malonedialdehyde and fatty acid and alfa tocopherol and the liver concentration of lipid hydroperoxides diered between these two treatments. The authors concluded that dierent cultivation methods caused dierences in some health-related biomarkers and called for more studies on the subject. Organic milk is better during summer compared with conventional milk, but there is no dierence when cows are kept indoor [111] Gillian Butler and colleagues 2008 studied the dierences in fatty acid (FA) and antioxidant proles seasonal dierences between organic, high-input, conventional, low-input, organic, and low-input non-organic milk. Lower input farming, relates to the reduced use, and possible complete elimination, of chemical-based fertilizers, insecticides, and herbicides in the food supply. The authors found that during the outdoor grazing period, milk from the organic and nonorganic low-input systems had lower saturated FAs, but higher mono- and polyunsaturated FA concentrations compared with milk from the high-input system. Higher concentrations of nutritionally desirable FAs and antioxidants, conjugated linoleic and -linolenic acids, tocopherol and carotenoids, and lower levels of more fatty acids like omega-6 and CLA10, which are linked to detrimental health impacts. compared with milk from conventional milk were also found. However, high-input and low-input organic systems did not dier in composition when cows were housed. The authors concluded that milk composition is aected by production systems by mechanisms likely to be linked to the stage and length of the grazing period, and diet composition. Soil Association Standards dept: Airfreight consultation [107] From: Karl Heinz Wilm Muelenweg 5 26419 Schortens Germany [email protected]
1266 To: Soil Association Standards dept. South Plaza, Bristol BS1 3NX
Subject: Airfreight consultation Shortens, 05.06.2007 Dear Sirs! I appeal to you to stay rm in banning airfreight from organics. Allowing airfreight destroys the foundation of the organic movement, adapting it to the supermarket logistics. This will undermine the condence of the consumer on the producers and make certication watery. Organic eyewash Here are some of your arguments and my comment: -Isolated initiatives like Tesco and Mark & Spencer: These initiatives are bound to specic produces and are not part of an all round organic label. Only clear commitment to guidelines bringing all products and all producers in one boat. - Air freight has the highest global warming potential of any form of transport: It is opposed to the deepest principles of organic philosophy. Opening the door for niche products, the whole organic segment will be questionable. - Air freight enables producers in some of the poorest regions of the world to supply high value fresh fruit and vegetables to Europe.: This is not true, as the poorest have no access to the high technical logistic of air trac. Only the Australian lobby, specialised on air trac to USA is interested to sell their surplus to Europe, after a sudden wave of US own produces. - Empty shelves: Worse than empty shelves is the loss of condence of the consumer. Airfreighting organics is a scandal. Your Questions 1- If no ban of air freight is possible the declaration "Transported by Air" in close proximity to the word ORGANIC should be compulsory. 2- But, a ban is indispensable. 3- The next certication renewal should withdraw the approval of the product. You are doing a good job, and stay rm to the principles of the organic movement Best regards Karl Heinz Wilm www.ourfod-news.com
15.42. BETTER CHEESE WITH CORN SILAGE FEED MILK THAN FROM FRESH PASTURE MILK 1267 Soil Association air freighted organic food ensures benets poor farmers [107] Fraud with organic label comes hand in hand with the discussion about air freight being accepted during organic certication by Soil Association, the UK certifying group. The Soil Associations Standards Board proposed changes to the Soil Associations standards to ensure that organic food is only air freighted to the UK if it delivers genuine benets for farmers in developing countries. Air freighted organic foods harm climate and environment and is against the primary meaning or "organic" to a supermarket well selling standard product mass article. The International Trade Centre (ITC) campaigns the certiers to allow air freight in organic certication procedures. ITC says that the Swiss organic certier Bio Suisse will certify airfreighted products under their standard. The Centre fear that if the proposal is approved other European organic certiers will also ban air freight in order to maintain green "parity" with the Swiss certier. [112] To cope with the mutating meaning of organic produces under mass production it is being suggested to use "Organic" for mass produces from the supermarkets, and another denomination for real organic food fromn small traditional farms. The absurd Flybe ecolabel [113] According to Ecolabelling Flybe is Europes largest regional airline, and which has invested over $2 billion in new, environmentally sensitive aircraft over the last two years, has become the rst airline in the world to introduce an aircraft eco-labelling scheme. The scheme is in response to the Stern Reports call for "labelling" to help consumers and businesses make sound decisions. Flybe passengers will be provided at the time of booking via the internet with a detailed but user-friendly breakdown of the fuel consumption, carbon emissions and noise patterns of the aircraft type to be used on their journey. Air trac destroys the world of tomorrow. Flybe, Europes largest regional airline is therefore the largest emission producer high up, where it hurts the most. Regional business ights are responsible for the crowded European Sky. Its is amazing to see that airlines advertise in environment sites and hide their malpractices under an ecolabel. This discredits labels. Another discrediting action is admitting air transportation for organic foods.
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OurFood calls on the European Commission and the NGOs to impose a 100 percent tax on ight tickets. Unnecessary meetings and conferences must be stopped. The work can be done by video conferences and other commodities.
Figure: Contrails at the sky of Wilhelmshaven, Germany. These contrails resulted from heavy domestic air trac which expand to clouds. CO2, NO2, NOX are a deadly mixture of emission in 10.000 metres.
The loophole of organic food air freighting [114]
Soil Association mutates organic food to supermarket standards According to a press release 06.03.2008, the Soil Associations Standards Board recommended that the organisations standards should be changed so that organic produce can only be air-freighted if it also meets the Soil Associations own Ethical Trade or the Fairtrade Foundations standard [115]. The Association launched a second round of open consultation launched to comment on the implementation of this recommendation. Airfreighted foods are not organic. They may be sold as healthy, good delicious foods, but NOT under an organic label. Admitting airfreight, under whatsoever ethical standards, mutates organic food in the supermarket niche. Airfreight is not conform with the principles of the initial organic movement. If the organic certication organisation Soil Association accepts airfreight in their statute a new denomination should be created:
15.42. BETTER CHEESE WITH CORN SILAGE FEED MILK THAN FROM FRESH PASTURE MILK 1269 Organic as described by the European Organic Directive, airfreighted and marketed by supermarket chains. Holistic Food, or Nature Food Produced at small farms following the original principles of organic farming and sold at the farm or small speciality shops. [116] International Conference on Organic Agriculture and Food Security [117] The UNs FAO held a conference in Rome last week on Organic Agriculture and Food Security, in partnership with the International Federation of Organic Agriculture Movements (IFOAM) Rome, 03 - 05 May 2007.The transcription of the documents presented at the Conference are available at : http://www.fao.org/organicag/ofs/docs_en.htm Summary of outcomes of the Conference [118] FAO underlines in a paper, Organic Agriculture and Food Security, presented at an International Conference on Organic Agriculture and Food Security. The paper identies the strengths and weaknesses of organic agriculture with regards to its contribution to food security, analyses attributes of organic supply chains against the Right to Food framework and proposes policy and research actions for improving the performance of organic agriculture at the national, international and institutional levels. "The strongest feature of organic agriculture is its reliance on fossil-fuel independent and locally-available production assets; working with natural processes increases costeectiveness and resilience of agro-ecosystems to climatic stress," the paper says. "By managing biodiversity in time (rotations) and space (mixed cropping), organic farmers use their labour and environmental services to intensify production in a sustainable way. Organic agriculture also breaks the vicious circle of indebtedness for agricultural inputs which causes an alarming rate of farmers suicides." The paper recognizes that "most certied organic food production in developing countries goes to export" and adds that "when certied cash crops are linked with agro-ecological improvements and accrued income for poor farmers, this leads to improved food self-reliance and revitalization of small holder agriculture."
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[118] The paper underlines that some requirements should be met when converting to organic agriculture, mainly agro-ecological knowledge and labour availability. "Organic management is a knowledge-based approach requiring understanding of agro-ecological processes and it remains a constraint where labour is scarce, such as in populations decimated by HIV/AIDS." However, labour requirements on organic farms, and the better return on labour, provide employment opportunities where this resource is most abundant, thus safeguarding rural livelihoods, according to FAO expert Nadia Scialabba. The paper also quotes recent models of a global food supply grown organically which indicate that organic agriculture could produce enough food on a global per capita basis for the current world population. "These models suggest that organic agriculture has the potential to secure a global food supply, just as conventional agriculture is today, but with reduced environmental impact," according to FAO. The paper calls on governments to "allocate resources for organic agriculture and to integrate its objectives and actions within their national agricultural development and poverty reduction strategies, with particular emphasis on the needs of vulnerable groups." It also insists on investment in human resource development and skill training in organic agriculture as part of sustainable development strategies. The report from the conference will be presented to the 33rd committee on World Food Security. IFOAM expects this will result in FAO policy chances that favour organic agriculture.
Denition of organic agriculture [119] According to the Codex Alimentarius Commission and all existing national regulations, "organic agriculture is a holistic production management system that avoids use of synthetic fertilizers, pesticides and genetically modied organisms, minimizes pollution of air, soil and water, and optimizes the health and productivity of interdependent communities of plants, animals and people."
15.43. NEW DEFINITION OF ORGANIC FOOD AND NATURE FOOD Links
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Important links to Organic Agriculture at FAO FAO websites of interest to organic agriculture and database. http://www.fao.org/organicag/frame9-e.htm Pre-storage treatment reduces scald losses on organic apple [120] Low-oxygen atmosphere for seven days at 20o C prior to cold storage extends shelf life of organic fruit and vegetable according to Edna Pesis. Only 10% of apples were lost due to scald after 8 month of cold storage. Pesis says that ware which had not been pre-storage treated was completely lost under the same condition. According to the article of Pesis published in the Journal of the Science of Food and Agriculture and reported on in Chemistry & Industry, storage of avocados, tomatoes and other organic produce may prot from this technique. Conventional produce can be treated with chemicals, but no articial chemicals are used for organics during processing. Treatment of organic apples with a solution of the antioxidant diphenylamine (DPA) is being used for years to reduce scald. This treatment may now be substituted by the none-chemical pre-storage treatment of Pesis. New label: Organic food nature food, Biokost and Naturproduct European organic food has mutated to mass production under the EU regulation 2092/91 and 1804/1999. [121] [122] The European Commission in their "European Action Plan for Organic Food and Farming" states: "Organic sales through supermarkets are the fastest-growing distribution channel in most markets.For consumers buying organic produce in supermarkets, environmental considerations are thought to be less important, compared to consumers buying produce in specialised organic shops." [123] The European organic food regulation clearly demonstrates its commitment to mass production and the supermarkets as distribution channel. This increases monoculture wide elds long transport ways and air freight.
15.43
New denition of organic food and nature food
The organic food produced according to the EU regulation diers from the original way of production. It becomes necessary to separate the organic food from supermarkets from the original nature food, produced under strict rules of certifying corporations which follow
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the original principles of a holistic way of farming. To make the dierence between both types of food the following denition is being suggested:
Nature food (En), Naturkost (D) Nature food is produced according to rules of certifying corporations which follow the principles of a holistic way of farming. These Foods are sold by the producer itself at their farm, at weekly markets or at specialised nature shops. In these shops competent informations are given concerning the origin of the food. The consumer understands that the higher price of nature products is due to diversication of crops at the farm, a species-appropriate animal raising, and environment conservation. The nature food farmers and the specialised nature shops should keep distance from the words "Organic" or "Biokost because they have become a domain of supermarkets and have undergone a mutation from the original food.
Organic Food (En), (Biokost D) Organic food is produced according to the EU 2092/91 and 1804/1999 regulation. The consumer expects food produced without agrarian chemicals, like herbicides or pesticides. He expects better taste compared with conventional foods.He looks after low priced products. He is concerned with the welfare of his person and does not care about environment. He is not interested to know the food miles and airfreight of the items he buys. Organic food is primarily sold by supermarket chains. Some reaction of producer and customers have put the Basic chain of organic supermarkets under pressure not to sale its shares to the Swiss Schwarz group, owner of supermarket chain Lidl. Farmers market, a sustainable solution for small farmers [124] Products at farmers markets are renowned for being locally grown and very fresh. Farmers markets advocates believe the markets help farmers stay in business as well as preserve natural resources. Wholesale prices farmers get for their produce are very low, often near the cost of production. It can be shown that the preservation of farmland is important for the health of the
15.43. NEW DEFINITION OF ORGANIC FOOD AND NATURE FOOD
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environment and water supply. Sustainably-managed farms conserve soil and clean water in our communities and provide a habitat for wildlife. UK farmers markets [125] According to the Councillor Handbook farmers markets give smaller local producers an outlet direct to the public enabling them to become less reliant on wholesalers and supermarkets. The Handbook stresses that Trading Standards and Environmental Health Services are closely involved in ensuring the markets achieve the standards required. The Handbook cites Hampshire farmers markets as a case study. The market has been certied by the National Association of Farmers Markets [126]. Produce being sold at all Hampshires farmers markets must have been grown, reared, caught, brewed, pickled, baked, or processed within Hampshire or ten miles of the border. US Farmland preservation [127] American Farmland Trust is helping the countys farmland preservation program into opportunities for direct marketing, value-added products and a vibrant local food and farming system by: Identifying municipal barriers that hinder local farmers ability to connect directly with local consumers; Creating a model ordinance that supports a local food system and protects farmers from rural-urban conicts; and, Finding out what other places have done to increase the access of low income populations to local food through token payment programs at farmers markets. Farmers markets in Germany [128] These markets are regulated by Germany the Gewerbeordnung [Trade Code). There is no Farmers markets certication body in Germany. There are no restrictions like those found in Hampshire which allow only products have been grown, reared, caught, brewed, pickled, baked, or processed within the region where markets are taking place or ten miles of the border. Other great markets like the Hamburger Gromarkt market which supplies foodstus from international origin to the great supermarket chains are quite dierent. Their aim as commercial entity is to make prot. They do not protect local farmers and they have no restrictions on carbon footprint.
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Conventional foods labelled as organic by Italian food companies and organic label certication body [129] Seven executives of the Italian food companies Sunny Land, Sona and Bioecoitalia and the director of a certifying body from the Marche farming region of central Italy faked the origin of food, labelled as "organic" over years. It is assumed that 700 tons (valued 220 million Euros) of faked foods were sold all over Europe. Only 2.500 tons could be arrested.
Italian organic certication system [130] Italy has currently 16 organic certifying bodies, majority of which were founded in the last ten years. Older Italian certifying bodies are AIAB, Suolo e Salute, the Biodynamic Association, and CCPB which is a consortium of large agricultural cooperatives, processors, and the Coop Italia supermarket chain. The criminal Italian companies had bought conventional agrarian foods in Romania and Italy, labelled them as "organic" and added faked papers. The largest certication association, the Italian Association of Organic Producers (AIAB) admits weaknesses of the sector in controls over the import of raw materials, particularly those used for livestock like soya and barley. There are also insucient checks in the production of organic bread and pasta. Other farm groups stress insucient traceability of organic food. The organic food business tripled in last ten years, with a turnover of three billion Euros, mainly sold at supermarkets.
Organic Foods in Canada [131] Organic industry is now a billion-dollar industry that has moved from small specialty shops to the countrys largest supermarket chains. The federal government of Canada announced in December 2006 the unied regulation plan, after the European Union had threatened to ban Canadian produce. Canada exports half of its production of organic wheat. Fearing to lose the half a billion dollars deal over the next decade, Canada introduced the regulation plan.
"Natural" in Canada There are currently no standards on the use of the word "natural" when labelling agricultural products.
15.43. NEW DEFINITION OF ORGANIC FOOD AND NATURE FOOD Organics in Brazil
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[132] It is estimated that the country is sixth in the world in terms of area turned to organic production, with around 890,000 hectares. Brazil is only behind Australia, China, Argentina, Italy and the United States. The main production of organics takes place in the state of Paran. Organics Brazil maintains a database of organic export products, their producers and the certifying organisations. [133] The Law 10831, [134] promulgated by the Brazilian President, Luiz Incio Lula da Silva, in 2003 and that launches sector guidelines denes that organic products are all those produced in "organic systems", i.e., free of "synthetic material", "genetically modied organisms" and "ionizing radiations" - which cause cancer. The concept involves social, cultural and environmental aspects. Hen battery cages in UK banned in 2012 [135] Battery cages for hens are scheduled to come under an EU-wide ban in 2012. The European Commission conrmed that the ban will go ahead. The National Farmers Union says the ban must also be applied to imports. The British Egg Industry Council also says that more than 85 per cent of UK egg producers subscribe to its British Lion Code of Practice which sets animal welfare requirements. [136] There is a growing pressure of more ethical food sourcing and livestock treatment to both regulators and consumers. "Organic food" with GM ingredients [137] The European organic farming legislation at EU was changed in June 2007 and will come into force in January 2009. The legislation allow the use of GM-produced additives for which there is no alternative non-GM method in organic farming, such as animal-derived material raised with feed enriched with GM vitamins and GM enzymes. The nished product may then be labelled as "organic". German "Non-GM food" with GM components Based on the new legislation for organics, the German the Federal Ministry of Food, Agriculture and Consumer Protection (BMELV) reached a political agreement products using GM vitamins, additives and processing aids where there is no non-GM alternative available
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may be labelled as "non-GM". This is to encourage the food industry to start using the non-GM labels. German food industry federation, BLL The German food industry federation, BLL says this misleads the consumer, thinking there is no intentional touch of GM in the product and the the credibility of the product will be reduced. The BLL will present its arguments at the hearing of the parliament. EU Organic Regulation 834/2007 [138] [10] The Regulation (EEC) No 2092/91 is repealed as from 1 January 2009. The new rules set out a complete set of objectives, principles and basic rules for organic production, and include a new permanent import regime and a more consistent control regime. The use of the EU organic logo will be mandatory, but it can be accompanied by national or private logos. The place where the products were farmed has to be indicated to inform consumers. Food will only be able to carry an organic logo if at least 95 percent of the ingredients are organic. But non-organic products will be entitled to indicate organic ingredients on the ingredients list only. The use of genetically modied organisms will remain prohibited. It will now be made explicit that the general limit of 0.9 percent for the accidental presence of authorised GMOs will also apply to organic products. The new rules also create the basis for adding rules on organic aquaculture, wine, seaweed and yeasts. The new organic regulation and labelling will come into force in January 2009. The EU followed the pressure of GM companies including AstraZeneca, BASF Plant Science, Bayer CropScience, Dow AgroSciences, Du Pont, Monsanto and Syngenta. The new regulation increases the current threshold for GM contamination of organic food from 0.1 per cent to 0.9 per cent and allowing the use of GM-produced additives for which there is no GM-alternative the new regulation opens the way for genetically modied material to enter organic food. High quality of meat from animals raised on biodiverse pastures [139] Prof Henry Buller and colleagues 2008 compared meat quality of animals grazing on natural grasslands and animals raised on intensive systems. The researchers found lamb meat from biodiverse pastures to have increased vitamin E content with improved shelf life, compared with conventional lamb meat. Higher levels of polyunsaturated fatty acids and conjugated linoleic acid were also associated with the
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biodiverse origin, and the negative taste of grilled meat, caused by the rumen fermentation product skatole was decreased. The authors recommend the Longhorn variety of cattle for biodiverse pastures and conclude that biodiverse grasslands farming is good for the environment, the consumer and the producer. They call for more support from the policy makers and underlay the necessity to nd ways to label and promote meat reared on biodiverse principals. Authentication of organic milk [140] Joachim Molketin 2009 developed a method for the authentication of German organic retail milk. It is based on the distribution of carbon delta 13 and the alfa-linolenic acid (C18:3omega3) in milk fat. Maize accumulates more the heavier carbon 13 isotope than the normal carbon 12 isotope found in grass sillage and hay. Increase of alfa-linoleic acid is a result from reduced maize sillage and high portion of roughage during the whole year, with fresh grass in the summer and grass/clover silage or hay in the winter. According to Molketin, organic milk was always above a minimum C18:3omega3 content of 0.50% and below a maximum delta 13 carbon of -26.5 per mil. The author found that, contrary to the general opinion, organic milk did not generally contain more c9,t11-C18:2 (CLA) than conventional milk. The authors writes that the method is valid for German milk. The proposed limit may vary in milk and their products with foreign origin. German farmer defeated a marketing giant [141] Georg Heitlinger, fought against a mighty lobby of the CMA, the Farmerss Association and the Government. The German Federal Constitutional Court decided the Marketing Fund Law from 1969 as unconstitutional. This law forced farmers to fund the Central Marketing. The verdict of the highest court is the end of Central Marketing Association of the German Farmers (CMA). [142] Heitlingers farm produces eggs. He has to pay a fee for every egg his farm produces, following the Marketing Fund Law (Absatzfondsgesetz). This money goes to the CMA which is in charge advertise German agrarian products and protect them from cheap import products.
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The Farmers pay hundreds and hundreds of million Euro each year to the CMA without any prot. Heitlinger saw at a Dutch packing station eggs for ALDI NORD stores being labelled with the CMA logo. Heitlingers money was being used to pep up the products of his competitor from abroad. On his long ght against the CMA and its logo, one lonely farmer, the German version of the French Bov, defeated the mighty organisation. Heitlinger says that farmer pay 30 Cents to the marketing fund for each 1000 eggs they produce. This is 0.6% of the price of the egg. In other products the fee amounts 0,4% of the price of the product. [143] The Marketing Fund Law (Absatzfondsgesetz) [144] The German law says that every agrarian product has to pay a fee for a central association which is in charge of marketing activities to promote sales of German products and increase its strength toward import products. The CMA [145] The CMA has its seat in Bonn with up to 150 employees. The organisation will have to undergo stringent structural modications and concentrate its marketing eorts to boost export rather than promote homeland based consume. Critics on CMA [146] The CMA in the name of German farmers published advertising who lack tight connections with agricultural products. The farmers do not feel any benet from the activities of CMA. In his homepage Heitlinger presents the arguments of his ght against the lobby of marketing associations and its logos. CMA accused of sexist slogans [147] Heitlinger says that sexist advertising is felt as funny somewhere. Many German farmers, however, feel themselves not well represented with such a forced marketing image for which they have to pay heavily. The sexist slogans are: I like beautiful legs. Milk turns me on. You never forget the rst time. Guys with coal (bucks) turn me on. See the CMA advertising: http://www.absatzfondsabschaen.de/sexistisch.html
15.43. NEW DEFINITION OF ORGANIC FOOD AND NATURE FOOD Parallels to French movements
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The unexpected victory of a small farmer against the system shows parallels to the the French environmentalist Jos Bov and rises hopes that a new reaction may reverse a negativ trend to monster marketing organisations and certication companies dominating the market. These logos and certication adverts are protable primarily by multinational supermarket stores. One of these excess is the building of national and internartional logos for organic foodstus. Lobbying of the food store chains were successful in establishing organic logos, certication companies and watered-down laws and directives. Small organic farm working under the original ideals of ecologic friendly farming could not compete with big monocultures of organic mass production for the big store chains. [148] [149] All marketing associations, the certication companies working on a global platform, their logos, label mount tags, advertisings and other marketing promotions should be put under close scrutiny. The real message, their eectiveness and the organisation which is in charge should be analysed. The ght of Heitling should inspire all experts and all consumers alike, to look who is behingd food logos. UK Soil Association calls to allows the use of sewage sludge (Biosolids) on organic land [150] A 2010 report on phosphorus input in organic farming, released by the UK organic certication body, the Soil Association, calls on the EU Commission to allow the use of sewage sludge (Biosolids) on organic elds. The use of biosolids in organic farming is not allowed by European regulations due to increased concentration of heavy metals originated from industrial euent which is treated together with communal sewage. The Soil Association argues that the heavy metal levels in biosolids recently declined to a level which permits the use in organic farming. This could help to tackle the decline of phosphate mining peaking in 2033. Phosphate will then become scarce and recycling the phosphate from human excreta using biosolids may increase productivity of elds. The report also calls to reduce meat amount in human diet, as meat production demands for higher input of phosphorus then agrarian products, this could reduce the need of phosphate rock-based fertiliser. The Soil association stresses that organic farming relies on closed systems of fertility on the farm. Manure and compost is put back onto the land, while plants that x nitrogen in their roots are used to build soil fertility. Agro-ecological approach to farming is opposite of
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more intensive approaches where large amounts of fertiliser and pesticide are added. This leaves the eco-system out of balance and deplete these resources. The report points to the fact that globally only 10% of human waste is returned to agricultural soils. Urine alone contains more than 50% of the phosphorus excreted by humans. The recycle of human excreta in organic elds,may reduce the reliance on mined phosphate. IAASTD Report (2009) focuses on high Pesticides and chemical fertilizers agricultural runo [151] The report says that agricultural runo pollutes ground and surface waters with large amounts of nitrogen and phosphorus from fertilizers, pesticides and agricultural waste. Agriculture is the main cause of pollution in US rivers and contributes to 70% of all water quality problems identied in rivers and streams. The livestock sector has enormous impacts on the environment. It is responsible for 18% of greenhouse gases emissions measured in CO2 equivalents, and 9% of anthropogenic CO2 emissions, livestock production accounts for 70% of agricultural land and 30% of land globally Sewage treatment and phosphorus recycling to improve water of UK rivers [152] The Centre Europen dEstudes de Polyphosphates cites in its newsletter municipal wastewater as an important source of phosphorus to UK rivers and the eorts to remove phosphorus from sewage, and to bringing soluble phosphorus levels down low enough to prevent eutrophication risks and meet EU Water Framework objectives (Directive 2000/60/EC [153]). Other studies found that excessive algal growth (eutrophication eects) can be eectively controlled by reducing sewage phosphorus inputs. [154] To improve Thames water a full-scale phosphorus recovery and recycling will be installed at the Slough sewage works. The unit will recover phosphorus and ammonia from the wastewater and produce environment-friendly struvite fertiliser ((NH 4)MgPO 46H 2 O) which provides phosphorus, magnesium and ammonium to the plants. Struvite dissolves slowly over 6 - 9 months, thus avoiding nutrient leaching to the environment. [152]
15.43.1
Bhutan makes a commitment to organic agriculture [155]
The kingdom of Bhutan had adopted years ago Gross National Happiness instead of gross domestic product (GDP) to measure the progress of the nation. At the United Nations Conference on Sustainable Development (Rio+20) in June 2012, His Excellency Jigmi Y. Thinley, Prime Minnister of the Kingdom of Bhutan announced Bhutans commitment to organic agriculture to include the environmental, spiritual and mental well-being in their
15.43. NEW DEFINITION OF ORGANIC FOOD AND NATURE FOOD calculations.
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According to the Minister, the country is determined to become the rst wholly organic food producing country, avoiding agrarian chemicals to ensure food security and sustainable agriculture. The minister also mentioned the greenhouse gas emission from countries as far as the Americas which are causing, among other devastations, the rapid melting of glaciers in Bhutans mountains to threaten oods in the valleys. Thinley explains further that the three conditions of sustainability, wellbeing and happiness are interdependent. Without happiness, there can be no appreciation of the beauty and preciousness of life and our natural world. Karma Tshiteem (Secretary of Happiness, Bhutan) explains that Bhutan is focused on creating the right conditions that can lead people to fullling and hopefully, happy lives. The Gross National Happiness is being measured by applying nine key indicators: Psychological well-being, community vitality, cultural diversity, time use, good governance, health, education, ecology, and living standards. A better GNH may lead to a better sense of well-being - such as low crime, healthy environment and other benets to the community. The gross domestic product (GDP) measures the economy. Some economists to consider other factors,such as happiness. GPD, however is focused on money and economic growth, negleting factors in social well-being along with economic growth. Chris Wood, a member of the hippie movement launched a new movement in western countries to introduce the Bhutan idea of Gross National Happiness. [156] According to the World Food Program, Bhutanese farmers mainly grow rice and corn, as well as some fruits and vegetables, including potatoes and oranges. But as demand for food has grown in recent years, the country has been forced to import rice and other foods from India, and today Bhutan is a net food importer. Synthetic chemicals and fertilizers are only available and aordable to a few of Bhutans farmers. Agriculture production is hampered by the dicult terrain that reduces the possible available land for mechanized farming, poor soil quality and low levels of nitrogen and phosphorous content, inadequate irrigation infrastructure, lack of access to and quality of seeds, fertilizers and other essential inputs, and issues of access to credit, markets information, post-harvest services and facilities. [157] National Framework for Organic Farming in Bhutan [158] The National Framework for Organic Farming in Bhutan outlines key approaches and strategies to promote organic farming in the country. It hopes to develop and promote organic farming as a way of life among Bhutanese farmers and trade in organic produce to enhance their incomes. Starting with niche crops and products with established markets is seen to ensure success. It advocates establishing organic "communities" and pilot activities in areas of high potential. Development of organic markets, both internal and external, is
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seen as crucial to promotion of organic farming.@article,
15.43.2
Terminalia chebula
Terminalia chebula Retz. (Fam. Combretaceae)is listed in "Ayurvedic Materia Medica" because of its healing properties. In Tibetan medicine uses the fruits of the plant which is known as Arura. According to Bag et al.2013, Terminalia chebula was found to be active as antioxidant, antimicrobial, antidiabetic, hepatoprotective, anti-inammatory, antimutagenic, antiproliferative, radioprotective, cardioprotective, antiarthritic, anticaries, gastrointestinal motility and wound healing activity. Four major compounds (ellagic acid, gallic acid, punicalagin, terchebulin) could be identied in the T extract. Three other compounds (3,3di-O-methylellagic acid, 3,4,3,4-tetra-O-methylellagic acid, teravin A) were also isolated and identied. [159] Terminalia chebula fruit extract eective against uropathogens [160] The hydroalcoholic extract of Terminalia chebula fruit extract was found by Bag et al. to contain 1, 2, 6-tri-O-galloyl- -D-glucopyranose, which is active against multidrug-resistant uropathogens. The compound presents synergy with trimethoprim and gentamicin, with iron-complexing property. [161] Terminalia chebula eective against against dental caries causing bacteria [162] Pratap et al. 2012 determined the anti-microbial activity of aqueous extract of the fruits of Terminalia chebula, owers of Clitoria ternatea, and leaves of Wedelia chinensis. The extract of Terminalia chebula was the most active of the tree plants, followed by Clitoria ternatea and Wedelia chinesis as less active against dental caries causing bacteria. Improving shelf-life of West African soft cheese wara with extracts of Carica papaya and Terminalia cattapa [163] According to Adetunji 2012, the microbial "Wara" soft cheese produced in Nigeria has a poor microbial quality. Vacuum packaging and addition of crude extracts (Carica papaya, Terminalia cattapa but not nisin) in soft cheese storage can suppress enterobacteriacea, molds and yeasts. The author suggests to add extract of Carica papaya and Terminalia cattapa to industrialised wara cheese, and storage it at 150 C to extend shelf-life of this soft cheese. Vacuum packaging did not suppress Listeria monocytogenes. Antimicrobial Compounds in Plant Extracts against Multidrug-Resistant Acinetobacter baumannii [164] Miyasaki determined the antimicrobial activity of fraction of plant extractions against Acinetobacter baumannii. This bacterium is known by its multidrug-resistant. The authors report active compounds in in Rosa rugosa as ellagic acid, norwogonin in Scutellaria
BIBLIOGRAPHY
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baicalensis, and chebulagic acid, chebulinic acid, corilagin, and terchebulin in Terminalia chebula. The most potent compound was identied as Norwogonin was found by the authors to have the highest activity against the bacterium. Its minimum inhibitory concentration wa determined as 128 g/mL, and the minimum bactericidal concentration of 256 g/mL. Terminalia chebula extract possesses strong antioxidative and antiinamation activity [165] Gaire et al. 2013, report that the fruit extract of Terminalia chebula, known as a natural herbal medicine, may help to protect the cells from ischemic damage. The authors suggest the inhibition of oxidative and inammatory processes as possible mechanism of such activity.
Bibliography
[1] http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=CELEX: 31991R2092:EN:HTML. Council Regulation (EEC) No 2092/91 of 24 June 1991 on organic production of agricultural products and indications referring thereto on agricultural products and foodstus (OJ L 198, 22.7.1991, p. 1). [2] http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=OJ:L:1999:222: 0001:0028:EN:PDF. Council Regulation (EC) No 1804/1999 of 19 July 1999 supplementing Council Regulation (EEC) No 2092/91 on organic production of agricultural products and indications referring thereto on agricultural products and foodstus to include livestock production (OJ L 222, 24.8.1999, p. 1). [3] http://ec.europa.eu/agriculture/qual/organic/plan/workdoc_en.pdf. Commission of the European Communities: European Action Plan for Organic Food and Farming. Brussels, 10 June 2004 SEC(2004) 739. [4] http://environment.independent.co.uk/green_living/article3106906.ece. Organic food is healthier and safer, four-year EU investigation shows. The Independent (29/10/07). [5] Niggli, Urs; Leifert, Carlo; Alfldi, Thomas; Lck, Lorna; Willer, Helga: Improving sustainability in organic and low input production systems. Proceedings of the 3rd International Congress of European Integrated Project Quality Low Input Food; 20-23 March 2007; University of Hohenheim, Germany. https://www.bl.org/shop/pdf/hb1455-organic-food-production.pdf. [6] http://orgprints.org/9944/. Hollmann, E; Rembialkowska, E; Comparison of the Nutritive Quality of Tomato Fruits from Organic and Conventional Production in
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CHAPTER 15. ORGANIC FOOD Poland; Improving Sustainability in Organic and Low Input Food Production Systems; Proceedings of the 3rd International Congress of European Integrated Project Quality Low Input Food; March 2007; University of Hohenheim, Germany.
[7] http://orgprints.org/9855/. Fauriel, J, Bellon, S, Plenet, D, Amiot, M-J; OnFarm Inuence of Production Patterns on Total Polyphenol Content in Peach; Improving Sustainability in Organic and Low Input Food Production Systems; Proceedings of the 3rd International Congress of European Integrated Project Quality Low Input Food; March 2007; University of Hohenheim, Germany. [8] http://orgprints.org/9943/. Rembialkowska, E, Hollmann, E, Rusakzonek, A; Inuencing a process on bio-actvie substances content and anti-oxidant properties of apple puree from organic and conventional production in poland; Improving Sustainability in Organic and Low Input Food Production Systems; Proceedings of the 3rd International Congress of European Integrated Project Quality Low Input Food; March 2007; University of Hohenheim, Germany. [9] http://eur-lex.europa.eu/LexUriServ/site/en/oj/2007/l_189/l_ 18920070720en00010023.pdf. Council Regulation (EC) No 834/2007 of 28 June 2007 on organic production and labelling of organic products and repealing Regulation (EEC) No 2092/91. [10] http://europa.eu/rapid/pressReleasesAction.do?reference=IP/07/ 807&format=HTML&aged= 0&language=EN&guiLanguage=en. Europa Rapid: Organic Food: New Regulation to foster the further development of Europes organic food sector. [11] http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=OJ:L:2008:250: 0001:0084:EN:PDF. Commission Regulation (EU) No 889/2008 of 5 September 2008 laying down detailed rules for the implementation of Council Regulation (EC) No 834/2007 on organic production and labelling of organic products with regard to organic production, labelling and control. [12] http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=OJ:L:2008:334: 0025:0052:EN:PDF. Commission Regulation (EC) No 1235/2008 of 8 December 2008 laying down detailed rules for implementation of Council Regulation (EC) No 834/2007 as regards the arrangements for imports of organic products from third countries. [13] http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=OJ:L:2010:084: 0019:0022:EN:PDF. Commission Regulation (EU) No 271/2010 of 24 March 2010 amending Regulation (EC) No 889/2008 laying down detailed rules for the implementation of Council Regulation (EC) No 834/2007, as regards the organic production logo of the European Union.
BIBLIOGRAPHY
1285
[14] http://www.ncbi.nlm.nih.gov/pubmed/16702257. Ellis K, G Innocent, D GroveWhite, P Cripps, W G McLean, C V Howard and M Mihm (2006) Comparing the Fatty Acid Composition of Organic and Conventional Milk. J. Dairy Sci., 89: 1938:1950. J Dairy Sci. [15] http://jds.fass.org/cgi/content/abstract/90/11/4942. A. E. Croissant, S. P. Washburn, L. L. Dean, and M. A. Drake Chemical Properties and Consumer Perception of Fluid Milk from Conventional and Pasture-Based Production Systems. J Dairy Sci, November 1, 2007; 90(11): 4942 - 4953. [16] http://www.food.gov.uk/foodindustry/farmingfood/organicfood/. Standards Agency: Organic Food. Food
[17] http://www.food.gov.uk/foodindustry/farmingfood/organicfood/#h_9. Food Standards Agency: Is organic food and milk more nutritious? [18] http://www.soilassociation.org/airfreight. Soil Association Food and Farming: Airfreight. [19] Forman J and Silverstein J; COMMITTEE ON NUTRITION; COUNCIL ON ENVIRONMENTAL HEALTH. Organic foods: Health and environmental advantages and disadvantages. Pediatrics, 10 2012. http://pediatrics.aappublications. org/content/early/2012/10/15/peds.2012-2579.long. [20] Usda: Choosemyplate food-groups/. food groups. http://www.choosemyplate.gov/
[21] Usda: Super tracker my plan. aspx.
https://www.supertracker.usda.gov/myplan.
[22] Smith-Spangler C, Brandeau ML, Hunter GE, Bavinger JC, Pearson M, Eschbach PJ, Sundaram V, Liu H, Schirmer P, Stave C, Olkin I, and Bravata DM. Are organic foods safer or healthier than conventional alternatives?: a systematic review. Ann Intern Med, 157(5):34866, 9 2012. http://www.annals.org/article.aspx? volume=157&page=348. [23] Cole DC, Orozco T F, Pradel W, Suquillo J, Mera X, Chacon A, Prain G, Wanigaratne S, and Leah J. An agriculture and health inter-sectorial research process to reduce hazardous pesticide health impacts among smallholder farmers in the andes. BMC Int Health Hum Rights, 11(Suppl 2):S6, 11 2011. http://www.ncbi.nlm.nih. gov/pmc/articles/PMC3247837/. [24] Center for environmental research and childrens health (cerch). http://cerch.org/ about/our-mission/.
1286
[25] http://www.organic-center.org/reportfiles/5367_Nutrient_Content_SSR_ FINAL_V2.pdf. Benbrook, Charles; Zhao, Xin; Yanez, Jaime; Davies, Neal; Andrews, Preston: State of Science Review: Nutritional Superiority ofOrganic Foods. March 2008. GMO Pundit a.k.a. April 04, 2008. [26] http://gmopundit.blogspot.com/2008/04/much-ado-about-phytochemical-diffrences. html. Rosen, Joseph D.: Quercetin Content in Organic and Conventional Crops: A Revie of the Evidence Today in AgBioView from AgBioWorld, Apr. 3, 2008. [27] Vallverd-Queralt A, Medina-Remn A Casals-Ribes I, and Lamuela-Raventos RM. Is there any dierence between the phenolic content of organic and conventional tomato juices? Food Chemistry, 130(1):222227. http://www.sciencedirect.com/ science/article/pii/S0308814611009642. [28] Barrett DM, Weakley C, Diaz JV, and Watnik M. Qualitative and nutritional differences in processing tomatoes grown under commercial organic and conventional production systems. J Food Sci, 72(9):C44151, 11 2007. http://ucce.ucdavis. edu/files/datastore/234-857.pdf. [29] Crinnion WJ. Organic foods contain higher levels of certain nutrients, lower levels of pesticides, and may provide health benets for the consumer. Altern Med Rev, 15(1):412, 4 2010. http://www.ncbi.nlm.nih.gov/pubmed/20359265. [30] Smith-Spangler C, Brandeau ML, Hunter GE, Bavinger JC, Pearson M, Eschbach PJ, Sundaram V, Liu H, Schirmer P, Stave C, Olkin I, and Bravata DM. Are organic foods safer or healthier than conventional alternatives?: a systematic review. Ann Intern Med, 157(5):34866, 9 2012. http://www.ncbi.nlm.nih.gov/pubmed/22944875. [31] Food standard agency: Organic food. http://www.food.gov.uk/foodindustry/ farmingfood/organicfood/. [32] http://ec.europa.eu/agriculture/organic/logo/index_en.htm. European Commission: We are very happy to present the winner that the European citizens chose! [33] http://www.democracyinaction.org/dia/organizationsORG/oca/campaign. jsp?campaign_KEY=4756. Organic Consumer Association: Boycott the shameless seven-organic outlaws labelling factory farm milk as SDA ORGANIC. [34] http://www.auroraorganic.com/aodweb/site/news/press_14.pdf. Aurora Press Release: Aurora Organic Dairy Will Fight Purported Class-Action Lawsuits. October 17, 2007. [35] http://www.auroraorganic.com/aodweb/site/news/press_12.pdf. Aurora Press Release: USDA Dismisses Complaints Against Aurora Organbic Dairy. August 29, 2007.
BIBLIOGRAPHY [36] http://www.ams.usda.gov/nop/archive/OFPA.html. ganic Program: Organic Foods Production Act 1990.
1287 USDA: The National Or-
[37] http://www.nationalaglawcenter.org/assets/cases/harvey3.html. The National AgriculturalLaw Center Magistrate Issues Decision on Inconsistency of Organic Program Final Rule and Organic Foods Production Act. [38] http://jeq.scijournals.org/cgi/content/abstract/37/1/182. del Amor, Francisco M.; Navarro, Joaqun, Aparicio, Pedro M.: Isotopic Discrimination as a Tool for Organic Farming Certication in Sweet Pepper. The Journal of Environmental Quality. 2008 37: 182-185. Published online 4 January 2008; doi:10.2134/jeq2007.0329. [39] http://www.populist.com/8.97.cover.standards.html. Whose Organic Standards? USDA Prepares an Unfriendly Takeover of the Natural Foods Industry By Ben Lilliston and Ronnie Cummins. Special to The Progressive Populist. [40] http://www.ams.usda.gov/nosb/. National Organic Standards Board. [41] http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=CELEX: 31993R0207:EN:HTML. Commission Regulation (EEC) No 207/93 of 29 January 1993 dening the content of Annex VI to Regulation (EEC) No 2092/91 on organic production of agricultural products and indications referring thereto on agricultural products and foodstus and laying down detailed rules for implementing the provisions of Article 5 (4) thereto. [42] http://www.codexalimentarius.net/download/standards/360/CXG_032e.pdf. CODEX: CAC/GL 32 Page 1 of 52 Guidelines for the Production , Processing, Labelling and Marketing of Organically Produced foods. [43] Codex Alimentarius: General Standard for the Labelling of Prepacked Foods; STAN 1-1985 (Rev. 1-1991). [44] http://www.unctad.org/trade_env/itf-organic/meetings/itf8/ITF_ EquiTool_finaldraft_080909db.pdf. IFOAM: Guide for Assessing Equivalence of Organic Standards and Technical Regulations. October 2008. [45] http://www.ams.usda.gov/nop/indexNet.htm. The National Organic Program. [46] http://www.ams.usda.gov/nop/NOP/standards.html. United States Department of Agriculture, Agricultural Marketing Service: (7 CFR Part 205) The National Organic Program Standards. [47] http://www.ams.usda.gov/nop/CertifyingAgents/NOPCorrespondence/ OMRIRevisionLetter.pdf. OMRI Revisional Letter: Informational Memorandum to USDA-Accredited Certifying Agents; USDA, from Richard Mathews.
1288
[48] http://www.ifoam.org/. IFOAM: Uniting the organic world. [49] http://www.ifoam.org/organic_facts/principles/pdfs/Principles_ Organic_Agriculture.pdf. IFOAM: Priciples of Organic Agriculture. [50] http://www.demeter.de/demeter/dem_biodyn.php?pagegroup= Das+ist+Demeter&pageaction=biodyn. [51] http://www.ers.usda.gov/publications/aib780/aib780b.pdf. Catherine Greene Amy Kremen: U.S. Organic Farming in 2000-2001 Adoption of Certied Systems; USDA Gov. publlications; AIB-780; USDA/Economic Research Service. [52] http://en.wikipedia.org/wiki/Macrobiotics. Wikipedia, the free encyclopedia: Macrobiotic diet. [53] http://www.biosaline.org/admin/pressreleases/Annual_Report_2006.pdf. ICBA. 2007. Annual Report 2006 (1426-27H). International Center for Biosaline Agriculture, Dubai, UAE. [54] http://www.uaeinteract.com/docs/Experts_call_to_protect_mangroves/ 2327.htm. UAE interact: Experts call to protect mangroves posted on 24/12/2001. [55] http://www.nypa.com.au/Forage.html. What is NyPa Forage? [56] http://www.newint.org/issue331/door.htm. Kurukulasuriya, Lasanda: The Shi Lanka le: Lasanda Kurukulasuriyareports on an agrarian crisis that is driving Sri Lankan farmers to suicide. [57] G.K. Upawansa: New Kekulam rice cultivation: a practical and scientic ecological approach; ILEIA Newsletter Vol. 13 No. 3 p. 20. [58] http://www.tdc.ca/food.htm. Stanford University; tdcs FarmGate Food Issues: New study conrms the ecological virtues of organic farming. [59] http://www.nutraingredients.com/news/ng.asp?id= 65716-minerals-nutrition-magnesium. Anthony Fletcher: Mineral deciency in food must be tackled, says expert; Nutra Ingredients.com Europe 09.02.2006. [60] Pimentel, David: Soil Erosion: A Food and Environmental Threat; Environment, Development and Sustainability, Volume 8 Number 1 Pages: 119 - 137. [61] http://www.mentalhealth.org.uk/html/content/feedingminds_exec_ summary.pdf. Food and mental health campaign: Feeding minds, the impact of food on mental health. January 2006. [62] http://www.mentalhealth.org.uk/html/content/changing_minds.pdf. Food and mental health campaign:Changing Diets, Changing Minds: how food aects mental well being and behaviour. January 2006.
BIBLIOGRAPHY
1289
[63] http://archneur.ama-assn.org/cgi/content/abstract/63/10/1402. Yvonne Freund-Levi; Maria Eriksdotter-Jnhagen; Tommy Cederholm; Hans Basun; Gerd Faxn-Irving; Anita Garlind; Inger Vedin; Bengt Vessby; Lars-Olof Wahlund; Jan Palmblad: Omega-3 Fatty Acid Treatment in 174 Patients With Mild to Moderate Alzheimer Disease: OmegAD Study: A Randomized Double-blind Trial Arch Neurol. 2006;63:1402-1408. [64] http://archneur.ama-assn.org/cgi/content/full/63.12.noc60109 http://www.eurekalert.org/pub_releases/2006-10/jaaj-mda100506.php. Nikolaos Scarmeas, Yaakow Stern, Richard Mayeux, Jos A. Luchsinger: Mediterranean diet, Alzheimer Disease and Vascular Mediation. Arch Neurol. 2006;63:(doi:10.1001/archneur.63.12.noc60109). [65] http://www.j-alz.com/issues/10/vol10-1.html. Laura Zhang, Milan Fiala, John Cashman, James Sayre, Araceli Espinosa, Michelle Mahanian, Justin Zaghi, Vladimir Badmaev, Michael C. Graves, George Bernard, Mark Rosenthal: Curcuminoids enhance amyloid-Beta uptake by macrophages of Alzheimers disease patients. Journal of Alzheimers Disease, Volume 10, Number 1, September 2006, pages 1-7. [66] http://www.ncbi.nlm.nih.gov/pubmed/17010630. Hartman, R.E., et al. 2005. Pomegranate juice decreases amyloid load and improves behavior in an APP transgenic mouse model with Alzheimers disease-like pathology. Society for Neuroscience 35th Annual Meeting. Nov. 12-16. Washington, D.C. [67] http://en.wikipedia.org/wiki/Ellagic_acid. Wikipedia, the Free Encyclopedia: Ellagic acid. [68] http://www.rssl.com/AboutUs/PressReleases/New+test+for+pomegranate.htm. RSSL Reading Scientic Services Limited: New Test For Pomegranate. [69] Wieland Peschel, Ferran Snchez-Rabaneda, Wilfried Diekmann, Andreas Plescher, Irene Gartza, Diego Jimnez, Rosa Lamuela-Ravents, Susana Buxaderas and Carles Codina: An industrial approach in the search of natural antioxidants from vegetable and fruit wastes; Food Chemistry Volume 97, Issue 1, Pages 137-150 (July 2006). doi:10.1016/j.foodchem.2005.03.033. [70] http://circ.ahajournals.org/cgi/content/abstract/109/1/103. C. B. Hauswirth, M. R.L. Scheeder, and J. H. Beer: High omega-3 Fatty Acid Content in Alpine Cheese: The Basis for an Alpine Paradox Circulation, January 6, 2004; 109(1): 103 - 107. [71] http://pubs.acs.org/cgi-bin/abstract.cgi/jafcau/2008/56/i05/abs/ jf0725225.html. Or-Rashid, Mamun M.; Odongo, Nicholas E.; Subedi, Bhishma; Karki, Pralhad; McBride, Brian W: Fatty Acid Composition of Yak (Bos grunniens) Cheese Including Conjugated Linoleic Acid and trans-18:1 Fatty Acids Journal
1290
CHAPTER 15. ORGANIC FOOD of Agricultural and Food Chemistry. Volume 56, pp 1654 - 1660; (Article). Doi: 10.1021/jf0725225.
[72] http://www.dairy-science.org/cgi/content/abstract/89/6/1938. K. A. Ellis, G. Innocent, D. Grove-White, P. Cripps, W. G. McLean, C. V. Howard, and M. Mihm Comparing the Fatty Acid Composition of Organic and Conventional Milk. J Dairy Sci, June 1, 2006; 89(6): 1938 - 1950. [73] http://orgprints.org/6304/. Tamm, Lucius:Replacement of Copper Fungicides in Organic Production of Grapevine and Apple in Europe. Organic Eprints-6304 2005. [74] http://www.path.ethz.ch/research/projects/active/12381/index. Swiss Federal Institute of technology Zurich: REPCO: Replacement of copper fungicides in organic production of grapevine and apple in Europe. [75] http://www.innovations-report.de/html/berichte/agrar_ forstwissenschaften/bericht-67590.html. Innovations report: tract eective against scab in apple cultivation. 12.07.2006. Yucca ex-
[76] http://www.ethlife.ethz.ch/articles/news/falschermehltau.html. News: ETH Life: Organische Fungizide gegen Falschen Mehltau. Noch stimmt die Mischung. [77] http://orgprints.org/4743/. Kollar, Andreas und Pfeier, Barbara (2003): Investigations on alternative substances for control of apple scab. Organic eprints 4743. [78] http://www.usl.uni-bonn.de/pdf/Forschungsbericht%20101.pdf. Portz, Christina; Noga, Georg und Steiner, Ulrike: Massnahmen zur Verbesserung der Bltenknospenqualitt und des Fruchtansatzes im integrierten und organischen Apfelanbau; Forschungsbericht Nr. 101 ; Institut fur Obstbau und Gemusebau. [79] http://fag.mnd.fh-wiesbaden.de/fagall/Jahresberichte/jb00/jb00.pdf. Liquid organic fertilizer for apple trees. Jahresbericht 2000 Forschungsanstalt Geisenheim und Fachbereiche Weinbau und Getrnketechnologie, Gartenbau und Landespege der Fachhochschule Wiesbaden. [80] http://www.epa.gov/methanetomarkets/. EPA: Methane to Markets Partnership. [81] http://www.abc.net.au/ra/innovations/stories/s1159618.htm. Agriculture : Radio Australia. 15. August 2004. Methane In
[82] http://www.ncbi.nlm.nih.gov/pubmed/19201957. Williams YJ, Popovski S, Rea SM, Skillman LC, Toovey AF, Northwood KS, Wright AD: A vaccine against rumen methanogens can alter the composition of archaeal populations: Appl Environ Microbiol. 2009 Apr;75(7):1860-6. Epub 2009 Feb 6.
BIBLIOGRAPHY
1291
[83] http://www.ncbi.nlm.nih.gov/pubmed/19702875. Sundset MA, Edwards JE, Cheng YF, Senosiain RS, Fraile MN, Northwood KS, Praesteng KE, Glad T, Mathiesen SD, Wright AD: Rumen microbial diversity in Svalbard reindeer, with particular emphasis on methanogenic archaea. FEMS Microbiol Ecol. 2009 Jul 29. [84] http://www.ncbi.nlm.nih.gov/pubmed/19387486. Wright AD, Northwood KS, Obispo NE: Rumen-like methanogens identied from the crop of the folivorous South American bird, the hoatzin (Opisthocomus hoazin). ISME J. 2009 Oct;3(10):1120-6. Epub 2009 Apr 23. [85] http://www.ncbi.nlm.nih.gov/pubmed/18165875. Wright AD, Ma X, Obispo NE: Methanobrevibacter phylotypes are the dominant methanogens in sheep from Venezuela. Microb Ecol. 2008 Aug;56(2):390-4. Epub 2007 Dec 29. [86] http://www.ncbi.nlm.nih.gov/pubmed/18042816. Christophersen CT, Wright AD, Vercoe PE: In vitro methane emission and acetate:propionate ratio are decreased when articial stimulation of the rumen wall is combined with increasing grain diets in sheep. J Anim Sci. 2008 Feb;86(2):384-9. Epub 2007 Nov 27. [87] http://www.ncbi.nlm.nih.gov/pubmed/17483285. Wright AD, Auckland CH, Lynn DH: Molecular diversity of methanogens in feedlot cattle from Ontario and Prince Edward Island, Canada. Appl Environ Microbiol. 2007 Jul;73(13):4206-10. Epub 2007 May 4. [88] http://www.ncbi.nlm.nih.gov/pubmed/17329767. Rea S, Bowman JP, Popovski S, Pimm C, Wright AD: Methanobrevibacter millerae sp. nov. and Methanobrevibacter olleyae sp. nov., methanogens from the ovine and bovine rumen that can utilize formate for growth. Int J Syst Evol Microbiol. 2007 Mar;57(Pt 3):450-6. [89] http://www.ncbi.nlm.nih.gov/pubmed/20005266. Gilbert RA, Ouwerkerk D, Zhang LH, Klieve AV: Cooperative Research Centre for Beef Genetic Technologies. In vitro detection and primary cultivation of bacteria producing materials inhibitory to ruminal methanogens. J Microbiol Methods. 2010 Feb;80(2):217-8. Epub 2009 Dec 11. [90] http://www.ncbi.nlm.nih.gov/pubmed/19100852. Herrera P, Kwon YM, Ricke SC. Ecology and pathogenicity of gastrointestinal Streptococcus bovis. Anaerobe. 2009 Feb-Apr;15(1-2):44-54. Epub 2008 Dec 7. [91] http://www.ncbi.nlm.nih.gov/pubmed/19614851. Joachimsthal EL, Reeves RK, Hung J, Nielsen LK, Ouwerkerk D, Klieve AV, Vickers CE: Production of bacteriocins by Streptococcus bovis strains from Australian ruminants. J Appl Microbiol. 2009 Jul 15. [92] http://www.ncbi.nlm.nih.gov/pubmed/18045390. Klieve AV, OLeary MN, McMillen L, Ouwerkerk D: Ruminococcus bromii, identication and isolation as a
1292
CHAPTER 15. ORGANIC FOOD dominant community member in the rumen of cattle fed a barley diet. J Appl Microbiol. 2007 Dec;103(6):2065-73.
[93] http://www.ncbi.nlm.nih.gov/pubmed/12703622. Callaway TR, Elder RO, Keen JE, Anderson RC, Nisbet DJ: Forage feeding to reduce preharvest Escherichia coli populations in cattle, a review. J Dairy Sci. 2003 Mar;86(3):852-60. [94] http://www.ncbi.nlm.nih.gov/pubmed/19737058. Jacob ME, Callaway TR, Nagaraja TG: Dietary interactions and interventions aecting Escherichia coli O157 colonization and shedding in cattle. Foodborne Pathog Dis. 2009 Sep;6(7):785-92. [95] http://www.ncbi.nlm.nih.gov/pubmed/19351974. Callaway TR, Carr MA, Edrington TS, Anderson RC, Nisbet DJ: Diet, Escherichia coli O157:H7, and cattle: a review after 10 years. Curr Issues Mol Biol. 2009;11(2):67-79. [96] Wood, Stanley; Sebastian, Kate; Scherr, Sara J.: Pilot analysis of global ecosystems, Agroecosystems.International Food Policy Research Institute and World Resources Institute.2000. www.ifpri.org/pubs/books/page/agroeco.pdf. [97] Lanbauforschung Vlkenrode FAL Agricultural Researche Special Issue 274, 2004. [98] http://www.regenwald.org/news.php?id=591. Rettet den Regenwald: Kenya: UNEP Meeting Warns of Dangers of Biofuel Production. February 6, 2007. [99] http://www.oekolandbau.nrw.de/fachinfo/pflanzenbau/klimaschutz_ tagung.html. Landwirtschaftskammer Nordrhein-Westfalen: Internationale Fachtagung Klimawandel und Biolandbau: Biolandbau ist aktiver Klimaschutz. [100] http://www3.interscience.wiley.com/cgi-bin/abstract/114202162/ ABSTRACT?CRETRY=1&SRETRY=0. Amodio,M. L.; Colelli, G.; Hasey, J. K.; Kader, A.A.: A comparative study of composition and postharvest performance of organically and conventionally grown kiwifruitsJournal of the Science of Food and Agriculture Jounal of the Science of Food and Agriculture 27 March 2007 doi:10.1002/jsfa.2820. [101] http://www.ncbi.nlm.nih.gov/pubmed/20337420. Chen P, Harnly JM, Lester GE: Flow Injection Mass Spectral Fingerprints Demonstrate Chemical Dierences in Rio Red Grapefruit with Respect to Year, Harvest Time, and Conventional versus Organic Farming. J Agric Food Chem. 2010 Mar 25. [102] http://www.ncbi.nlm.nih.gov/pubmed/17474757. Lester GE, Manthey JA, Buslig BS: Organic vs conventionally grown Rio Red whole grapefruit and juice: comparison of production inputs, market quality, consumer acceptance, and human healthbioactive compounds. J Agric Food Chem. 2007 May 30;55(11):4474-80.
BIBLIOGRAPHY
1293
[103] http://www.ncbi.nlm.nih.gov/pubmed/17183107. Couvreur S, Hurtaud C, Marnet PG, Faverdin P, Peyraud JL. Composition of milk fat from cows selected for milk fat globule size and oered either fresh pasture or a corn silage-based diet. J. Dairy Sci.90(1):392-403 (2007). [104] http://europa.eu/rapid/pressReleasesAction.do?reference=IP/07/277. Europa-Rapid Release: Open sky: Jacques Barrot welcomes the draft aviation agreement reached by the EU-US negotiators. IP/07/277 Date: 05/03/2007. [105] http://www.democraticdeficit.org.uk/open_skies_pollute.html. New Scientist: Green Sky thinking, eight ways to a cleaner ying future. 24. February 2007 p.33-34. [106] Williamson, Claire S.: Is organic food better for our health?; Nutrition Bulletin, June 2007, Volume 32, Issue 2, Pages 104-108. [107] http://www.soilassociation.org/airfreight. Soil Assotiation. [108] http://www3.interscience.wiley.com/journal/121370817/abstract?CRETRY= 1&SRETRY=0. Kristensen, Mette; Ostengaard, Halekoh, Lars Ulrich; Jorgensen, Henry; Lauridsen, Charlotte; Brandt, Kirsten; Bgel, Suzanne. Eect of plant cultivation methods on content of major and trace elements in foodstus and retention in rats. Journal of the Science of Food and Agriculture Doi: 10.1002/jsfa.3328. [109] http://orgprints.org/9344/01/9344.pdf. Yong, C.; Halekoh, Ulrich; Jorgensen, Henry und Lauridsen, Charlotte (2005) Dependent on dietary treatments of mothers, rats showed individual preference of diets containing ingredients produced with dierent cultivation strategies. Journal of Animal and Feed Sciences 2005, 14:pp. 715-726. [110] http://www3.interscience.wiley.com/journal/117858067/abstract. Lauridsen, C. Yong, C. Halekoh, U. Bugel, S. H. Brandt, K. Christensen, L. P. Jorgensen, H.: Rats show dierences in some biomarkers of health when eating diets based on ingredients produced with three dierent cultivation strategies: Journal of the Science of Food and Agriculture. 2008, Vol. 88; Number 4, pages 720-732. [111] Butler, Gillian; Nielsen, Jacob H; Slots, Tina; Seal, Chris; Eyre, Mick D; Sanderson, Roy; Leifert, Carlo: Fatty acid and fat-soluble antioxidant concentrations in milk from high- and low-input conventional and organic systems: seasonal variation. Journal of Science of Food and Agriculture. Volume 88, Number 8, June 2008 , pp. 1431-1441(11). Published online ahead of print. [112] http://www.intracen.org/organics/documents/Economic%20Impact%20of% 20Restricting%20Airfreght.pdf. International Trade Centre (ITC): The Economic Impact of Restricting Airfreight Imports to the EU.
1294
CHAPTER 15. ORGANIC FOOD ecola-
[113] http://ecolabelling.org/ecolabel/flybe-aircraft-ecolabel/. belling.org: Flybe Aircraft Ecolabel.
[114] http://www.soilassociation.org/web/sa/saweb.nsf/ 848d689047cb466780256a6b00298980/4cd8fffaf33bced18025740400535855!OpenDocument. Ensuring limited organic air freight is fair and ethical Press release 06.03.2008 (version 2). [115] http://www.soilassociation.org/web/sa/saweb.nsf/ 848d689047cb466780256a6b00298980/4cd8fffaf33bced18025740400535855/ FILE/Chapter%2070%20(Ethical%20Trade).pdf. Soil Association Ethical Trade standards. [116] http://www.ourfood-news.com/SURVEY_Organic_Food.html. Food. Survey Organic
[117] http://www.fao.org/organicag/ofs/press_en.htm. International Conference on Organic Agriculture and Food Security (3-5 May 2007). Press Releases. [118] http://www.fao.org/newsroom/en/news/2007/1000550/index.html. FAO Newsroom 03.05.2007: Meeting the food security challenge through organic agriculture States should integrate organic agriculture objectives within national priorities, FAO says. [119] http://www.codexalimentarius.net/download/standards/360/CXG_032e.pdf. Codex Alimentarius: Guidelines for the Production, Processing, Labelling and Marketing of Organically Produced Foods. CAC/GL32 2004. [120] http://www.foodnavigator.com/news/ng.asp?id=77240. Foodnavigator: Oxygen treatment found to extend shelf life. 11.06.2007. [121] http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=CELEX: 31991R2092:EN:HTML. Council Regulation (EEC) No 2092/91 of 24 June 1991 on organic production of agricultural products and indications referring thereto on agricultural products and foodstus (OJ L 198, 22.7.1991, p. 1). [122] http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=OJ:L:1999:222: 0001:0028:EN:PDF. Council Regulation (EC) No 1804/1999 of 19 July 1999 supplementing Council Regulation (EEC) No 2092/91 on organic production of agricultural products and indications referring thereto on agricultural products and foodstus to include livestock production (OJ L 222, 24.8.1999, p. 1). [123] http://ec.europa.eu/agriculture/qual/organic/plan/workdoc_en.pdf. Commission of the European Communities: European Action Plan for Organic Food and Farming. Brussels, 10 June 2004 SEC(2004) 739.
BIBLIOGRAPHY
1295
[124] http://en.wikipedia.org/wiki/Farmers%27_Market. Wikipedia: Farmers markets. [125] http://www.lacors.gov.uk/lacors/upload/17351.pdf. Councillors Handbook: Food matters at your Council. LACORS and FSA:
[126] http://www.farmersmarkets.net/. FARMA, the National Farmers Retail & Markets Association: What is a farmers market and what makes them special? [127] http://www.farmland.org/programs/states/NJ/default.asp. American Farmland Trust: Growing a Community Food System that Sustains Local Agriculture. [128] http://www.gesetze-im-internet.de/bundesrecht/gewo/gesamt.pdf. beordnung; Art.:67 Wochenmnarkt. Gewer-
[129] Fake italian organic food sold around europe: police. http://www.france24.com/ en/20111206-fake-italian-organic-food-sold-around-europe-police. [130] Growing organic. italian organisation structure. http://www.ifoam.org/growing_ organic/2_policy/case_studies/italy_organisation_structure.php. [131] http://www.cbc.ca/news/background/food-supply/certifying-organic.html. CBC News: Food Supply Certifying Organic. [132] http://www.apexbrasil.com.br/eng/noticia_detalhe.aspx?idnot=54. APEX: Organic products: Brazil enters the game. [133] http://www.organicsbrasil.org/eng/importador_buscaporproduto.ph. ganicsBrasil: Which product are you looking for? Or-
[134] http://www.planalto.gov.br/ccivil/LEIS/2003/L10.831.htm. Lei Nr. 10831 de 23 de dezembro de 2003. [135] http://www.nfuonline.com/x25126.xml. National Farmers Union: Poultry welfare facts. [136] http://www.stonegate.co.uk/pdfs/lioncodeofpractice.pdf. dustry Council: British Lion Code of Practice. British Egg In-
[137] http://www.bll.de/presse/pressemitteilungen/pm_20080116_ohne_ gentechnik/. BLL: Pressemitteilung Regierungsentwurf zur nderung der hne Gentechnik-Kennzeichnung fhrt zu Verbrauchertuschung. [138] http://eur-lex.europa.eu/LexUriServ/site/en/oj/2007/l_189/l_ 18920070720en00010023.pdf. Council Regulation (EC) No 834/2007 of 28 June 2007 on organic production and labelling of organic products and repealing Regulation (EEC) No 2092/91.
1296
[139] http://www.relu.ac.uk/news/policy%20and%20practice%20notes/May% 202008%20Henry%20Buller.pdf. Buller, Henry; Morris, Carol; Kirwan, James; Wood, Je; Hopkins, Alan; Dunn, Robert: Eating biodiversity: An investigation ofthe links between quality food production and biodiversity protection. Rural Economy and Land Use Programme (RELU). ESRC End of Award Report, RES-224-25-0041 (2008). [140] Molkentin, Joachim: Authentication of Organic Milk Using delta 13C and the alfaLinolenic Acid Content of Milk Fat. J. Agric. Food Chem., Article. [141] http://www.spiegel.de/wirtschaft/0,1518,604980,00.html. SpiegelOnline: Klage gegen Agrarverband Bauer Heitlinger bekaempft das System. 03.02.09. [142] http://www.-marketing.de/static/media/09-02-03_wa_Urteil_BVerfG.pdf. CMA: Absatzfoerderung ist auch zuknftig unverzichtbar Verfassungswidrigkeit des Absatzfondsgesetzes erfordert Alternativen. 03.02.2009. [143] http://www.absatzfonds-abschaffen.de/download/Bauernstimme_0408-CMA. pdf. Bauernstimme von April 2008, CMA-Abgaben unterschiedlich hoch. [144] http://bundesrecht.juris.de/absfondsg/BJNR006350969.html. Gesetz ueber die Errichtung eines zentralen Fonds zur Absatzfoerderung der deutschen Land- und Ernaehrungswirtschaft (Absatzfondsgesetz). [145] http://www.-marketing.de/content/ueber_die_/ueber-die-cma.php. ber die CMA. [146] http://www.absatzfonds-abschaffen.de/. Absatzfondsabschaen.de: CMA abschaen. [147] http://www.absatzfonds-abschaffen.de/sexistisch.html. schaen.de: Sexistische Werbung der CMA. Absatzfondsab-
[148] http://www.ourfood.com/Organic_food.html. OurFood.com: (1560) Soil Association air freighted organic food ensures benets poor farmers? [149] http://www.ourfood-news.com/SURVEY_Organic_Food.html. OurFood-news.com: Mutated organic food from supermarkets. [150] http://www.soilassociation.org/Whyorganic/Climatefriendlyfoodandfarming/ Resourcedepletion/tabid/1259/Default.aspx. A Rock and a Hard Place. Peak Phosphorus and the threat to our food security. UK Soil Association. 2010. [151] http://www.agassessment.org/reports/IAASTD/EN/Agriculture%20at%20a% 20Crossroads_Global%20Report%20%28English%29.pdf. IAASTD (2009), Agriculture at the Crossroads, International Assessment of Agricultural Knowledge, Science and Technology for Development.
BIBLIOGRAPHY
1297
[152] http://ceep-phosphates.eu/Files/Newsletter/Scope%20Newsletter%2076. pdf. Scope Newsletter 76. Centre Europen dEstudes de Polyphosphates. November 2010. [153] http://ec.europa.eu/environment/water/water-framework/index_en.html. Directive 2000/60/EC of the European Parliament and of the Council establishing a framework for the Community action in the eld of water policy. [154] http://www.ncbi.nlm.nih.gov/pubmed/16226299. Jarvie HP, Neal C, Withers PJA. Sewage-euent phosphorus: a greater risk to river eutrophication than agricultural phosphorus? Sci Total Environ 2006, 360(1-3): pages 246-53. [155] Statement by his excellency jigmi y. thinley, prime minnister of the kingdom of bhutan: Living gnh: Making a full policy commitment to organic agriculture 19th june 2012 uncsd rio+20. http://www.uncsd2012.org/content/documents/ 904bhutan.pdf. [156] Gross national happiness measures quality of life. npr. august 5, 2012. http://www. npr.org/templates/story/story.php?storyId=127586501. [157] Bhutan: Agricultural production. world food programme. http://www.foodsecurityatlas.org/btn/country/availability/ agricultural-production. [158] Duba S. Promoting organic farming in bhutan: A review of policy, implementation and constraints. http://www.fao.org/sard/common/ecg/3120/en/ BhutanEngNov08case.pdf. [159] Silva O, Gomes ET, Wolfender JL, Marston A, and Hostettmann K. Application of high performance liquid chromatography coupled with ultraviolet spectroscopy and electrospray mass spectrometry to the characterisation of ellagitannins from terminalia macroptera roots. Pharm Res, 17(11):1396401, 11 2000. http://www. ncbi.nlm.nih.gov/pubmed/11205733. [160] Bhattacharyya SK Bag A, Chattopadhyay RR, and Rashid RA. The development of terminalia chebula retz. (combretaceae) in clinical research. Asian Pac J Trop Biomed, (3):24452, 3 2013. http://www.ncbi.nlm.nih.gov/pmc/articles/ PMC3631759/. [161] Bag A, Bhattacharyya SK, and Chattopadhyay RR. Isolation and identication of a gallotannin 1,2,6-tri-o-galloyl- -d-glucopyranose from hydroalcoholic extract of terminalia chebula fruits eective against multidrug-resistant uropathogens. J Appl Microbiol, 5 2013. http://www.ncbi.nlm.nih.gov/pubmed/23683054. [162] Pratap GM, Manoj KM, Sai SA, Sujatha B, and Sreedevi E. Evaluation of three medicinal plants for anti-microbial activity. Ayu, 33(3):4238, 7 2012. http://www. ncbi.nlm.nih.gov/pubmed/23723653.
1298
[163] Adetunji VO. Survival of listeria monocytogenes, and other food spoilage microbes in vacuum packaged west african soft cheese wara. Afr J Med Med Sci, 41:Suppl:1116, 12 2012. http://www.ncbi.nlm.nih.gov/pubmed/23678645. [164] Miyasaki Y, Rabenstein JD, Rhea J, Crouch ML, Mocek UM, Kittell PE, Morgan MA, Nichols WS, Van Benschoten MM, Hardy WD, and Liu GY. Isolation and characterization of antimicrobial compounds in plant extracts against multidrugresistant acinetobacter baumannii. PLoS One, 8(4):e61594, 4 2013. http://www. ncbi.nlm.nih.gov/pmc/articles/PMC3632535/. [165] Gaire BP, Jamarkattel-Pandit N, Lee D, Song J, Kim JY, Park J, Jung S, Choi HY, and Kim H. Terminalia chebula extract protects ogd-r induced pc12 cell death and inhibits lps induced microglia activation. Molecules, 18(3):352942, 3 2013. http://www.ncbi.nlm.nih.gov/pubmed/23519197.
Part III Food Related Diseases
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Chapter 16 Food-Borne Diseases

16.1 Introduction
Search for food has always been a struggle to survive. The discovery of re by the cave man was an important step in food handling. Spices triggered the great voyages looking for a new way to the spices from India. Nowadays the rarest of dishes are available everywhere and there are no restrictions as to the seasons. Global trade of food has made it possible. These modern achievements, however, bear the danger to destruct the economic, ecological and cultural isolated units destabilising the economy of a region because manpower and products of other regions, with lower production costs, compete with high cost regions. Ecology is endangered, due to increase of trac, and last but not least, the culture and beliefs of isolated regions are washed out. Growing international business leads to ever growing food batches, spreading them over great areas. The control of hazards in food production, transportation and handling and even the menace of terrorist actions are getting high priority in the concern of industry, commerce and food health departments of every nation and is subject of many international standards. Food producers (agriculture, breeders, shery, processing factories) are concerned about these hazards which may cause tremendous costs, loss of crops, and even lead to bankruptcy. Catering service establishments and restaurants are liable to recourse in case of harmful food. The loss of condence of their customers due to headlines involving a recall of a spoiled brand is a nightmare for every manager of discount stores or global food trade business. 1301
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CHAPTER 16. FOOD-BORNE DISEASES
Food health departments and government ministry of consumer safety, such as Minister Kynast in Germany in the case of BSE scandal are top headlines.
16.2
16.2.1
Bacterial infections
Zoonotic disease in humans within the EU
[1] Zoonoses are diseases or infections, which are transmissible from animals to humans. The infection can be acquired directly from animals, or through ingestion of contaminated foodstus. The European Food Safety Authority analysed the data from 2005 and published a report on zoonotic diseases in humans in December 2006. EFSA found campylobacteriosis as the most frequently reported zoonotic disease in humans within the EU. Reported Campylobacter cases increased by 7.8% compared to the previous year. Fresh poultry meat was found to have the highest contamination rate with Campylobacter with 66% of samples positive and was also commonly detected from live poultry, pigs and cattle. The largest Campylobacter outbreaks were caused by contaminated drinking water. Salmonellosis remained the second most frequent zoonosis despite the fall of 9.5% compared to 2004.Salmonella was most often reported from fresh poultry and pig meat where proportions of positive samples up to 18% were detected. In table eggs, ndings of positive samples ranged from 0% to 6%, but over the past 5 years an overall decreasing trend in occurrence of Salmonella in eggs was observed. In animal populations, Salmonella was most frequently detected in poultry ocks. Egg and bakery products were the most common sources of Salmonella outbreaks, whereas broiler meat was an important source for both Salmonella and Campylobacter outbreaks. Foodborne virus outbreaks were most often caused by drinking water, fruit and vegetables. For Verotoxigenic Escherichia coli (VTEC) infections and yersiniosis more informations are needed concerning the serotypes and other virulence factors related to human pathogenic serotypes. The authors of the Report call for a harmonisation of the analytical methodology. [1]
16.2. BACTERIAL INFECTIONS Table 16.1: Reported incidences of the zoonoses in humans, EFSA 2005 Incidence Number of Disease 100,000 people reported cases Campylobacteriosis 51.6 197.363 Salmonellosis 38.2 176.395 Yersiniosis 2.6 9.630 Verotoxigenic Escherichia coli VTEC 1.2 3.314 Listeriosis 0.3 1.439 Brucellosis 0.2 1.218 Echinococcosis <0.01 320 Trichinellosis <0.01 175 Tuberculosis due to M. bovis <0.01 119 Rabies <0.01 4 Incidence Number of Disease 100,000 people reported cases
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16.2.2
Survey on the prevalence of Salmonella in EU poultry in 2006
[2] European Community legislation foresees setting of Salmonella reduction targets for animal population including broiler ocks. The survey was the second of several baseline surveys to be conducted in the Community. The sampling of the broiler ocks took place between October 2005 and September 2006. A total of 11.0% of the broiler ocks was estimated to be positive for Salmonella Enteritidis and/or Salmonella Typhimurium, the two most common serovars found in Salmonella infection cases in humans. The Member State-specic observed ock prevalence of S. Enteritidis and/or S. Typhimurium varied also greatly, from 0% to 39.3%. The number of positive samples in a Salmonella positive ock ranged between one and ve but at European Union level 42% of the positive ocks was found positive for all the ve samples taken. The ve most frequently isolated Salmonella serovars from broiler ocks in the European Union were respectively in decreasing order S. Enteritidis, S. Infantis, S. Mbandaka, S. Typhimurium and S. Hadar. All these serovars, with the exception of S. Mbandaka, are frequent causes of Salmonella infections in humans within the European Union. S. Enteritidis was the most common serovar and it was detected in 37% of the Salmonella positive ocks. S. Infantis accounted also for an important proportion of positive ocks (20%). The serovar distribution varied amongst the Member States, many of them having a specic
1304 distribution pattern of their own.
While the Community reduction target will most likely be set for a transitional period only for S. Enteritidis and S. Typhimurium, it is recommended that Member States would address in their national Salmonella control programmes also other serovars when these serovars are of public health importance in their country.
16.2.3
Verotoxigenic Escherichia coli (VTEC) in foods
The majority of the data derives from food of bovine origin (bovine meat, raw milk, cheese and dairy products, other or mixed meat). The report also contains information about Bovine Spongiform Encephalopathy, Avian Inuenza, Cysticerci and Sarcocystis parasites and Q fever in animal populations. [1] Germany reported the highest number of tuberculosis due to Mycobacterium bovis in 2005, followed by The United Kingdom Bovine tuberculosis and bovine or caprine/ovine brucellosis is still present in 3-4% in bovine/sheep/goat populations.The highest incidences of human brucellosis have been recorded in Greece, Italy, Portugal and Spain, mostly Brucella melitensis were responsible for the disease. Yersinia enterocolitica 0:3 serotype was the dominant type found in the EU. Germany had the highest number of human infections. Y. enterocolitica is found in meat and milk, especially pig meat.
16.2.4
Q Fever increasing in Germany and The Netherlands
[3] Q fever is an infectious disease caused by the bacterium Coxiella burnetii that aects both animals and humans. It has been reported to be present in a wide range of species, including cattle, sheep and goats, as well as birds and arthropods in many areas in the world. It was rst recognised as a disease transmissible from animals to humans in abattoir workers in 1935 in Australia. In recent years, the number of conrmed cases in humans increased, in particular in Germany and The Netherlands. Coxiella burnetii does not usually cause clinical diseases in animals, although abortion in goats and sheep has been linked to infection with this bacterium. In humans, Q fever may cause u-like symptoms, including fever and headache, diarrhea and vomiting. In some cases it can cause pneumonia and hepatitis. Chronic Q fever (characterized by an infection lasting more than 6 months) is uncommon but a much more serious disease with complications such as inammation of the inner lining of the heart (endocarditis).
16.2. BACTERIAL INFECTIONS
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Most human infections result from the inhalation of dust contaminated with bacteria from the placenta and birth uids or faeces from infected animals. In some cases the disease can be transmitted by the consumption of contaminated milk or contact with infected animals, especially animals that are giving birth. Other modes of transmission, including tick bites and human to human transmission are extremely rare.
16.2.5
French Cheese under safety concern
Various types of French cheese are prepared from raw milk. The denition of Camembert dated December 1986, says that temperatures not higher than 37o C may be used during production process and only milk from cattle which tuberculosis and brucellosis free may be used. [4] Safety concern which were nourished by a series of cheese poisoning by Listeria monocitogenes and salmonella made some producers like Lactalis to apply a mild heat of 60o C (thermised milk), which may inactivate these pathogens. The AOC do not approve this safety measure claiming that quality and avour of the camembert will be compromised. The AOC members voted to keep the denition of 1986 unaltered. It is expected that ocial ruling will forbid the use of raw milk for cheese production in France. [5]
16.2.6
Raw milk
[6] The U.S. Food and Drug Administration (FDA)and the Centers for Disease Control and Prevention (CDC) are reminding consumers of the dangers of drinking milk that has not been pasteurized, known as raw milk. Raw milk potentially contains a wide variety of harmful bacteria - including Salmonella, E. coli O157:H7, Listeria, Campylobacter and Brucella - that may cause illness and possibly death. Since 1987 FDA has required all milk packaged for human consumption be pasteurized before being delivered for introduction into interstate commerce. This also applies to other milk products, with the exception of a few aged cheeses. According to FDA, proponents of drinking raw milk often claim that raw milk is more nutritious than pasteurized milk and that raw milk is inherently antimicrobial, thus making pasteurization unnecessary. Research has shown that these claims are myths. There is no meaningful nutritional dierence between pasteurized and raw milk, and raw milk does not contain compounds that will kill harmful bacteria. In fact, raw milk, no matter how carefully produced, may be unsafe.
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16.2.7
Listeria monocitogenes in US milk
[7] The Massachusetts Department of Public Health located the source of the outbreak at the beginning of January 2007. after four people had become ill, two of whom fatally, The bacteria is believed to have entered the dairys milk supply after it was pasteurized.
16.2.8
Milk pasteurisation and Listeria
[8] Current state and local regulations throughout the United States specify time and temperature conditions for pasteurization. These regulations call for milk to be heated to at least 71.7o C for 15 seconds (i.e., high-temperature short-time (HTST) process) or to 62.8 C for 30 minutes. Viable L. monocytogenes could berecovered after minimum HTST treatment (71.7o C for 15 seconds), although not after treatment at 76.4 C-77.8o C for 15 seconds. This survival was attributed in part to protection of L. monocytogenes within leukocytes in milk (intracellular L. monocytogenes organisms are found in milk from infected cows but not in articially inoculated milk), but these ndings may not be applicable to usual production conditions. In another study in which investigators identied cows that had been naturally infected with L. monocytogenes, proper pasteurization was found to inactivate L. monocytogenes in milk contaminated through natural infection as well as in articially inoculated milk. World Health Organization Working Group on foodborne listeriosis recently concluded that "pasteurization is a safe process which reduces the number of L. monocytogenes occurring in raw milk to levels that do not pose an appreciable risk to human health" CDC concludes that improperly performedpasteurization and the occurrence of contamination after pasteurization are the most likely explanations for the presence of L. monocytogenes in pasteurized milk. Eorts to ensure that milk is safe from L. monocytogenes contamination should focus on promoting proper methods of pasteurization and on identifying and eliminating sources of postpasteurization contamination. This risk is ingreased in food processing environments, where Listeria bacteria tend to thrive, particularly in oor drains and other cool, damp areas. According to health ocials, they suspect the Whittier Farms pasteurized milk was contaminated after the pasteurization process. The Massachusetts Department of Public Health (MDPH) is recommending that consumers do not consume Whittier Farms milk products. Because the incubation period
1307
for Listeria can be as long as 70 days, anyone who has consumed the milk should watch for Listeria symptoms, including fever, muscle aches and sometimes gastrointestinal symptoms such as nausea or diarrhea. In pregnant women, the symptoms may be mild, but an infection can cause miscarriage, stillbirth or early delivery.
16.2.9
USDA measures to close recent food safety loopholes
[9] In November 2007 the USDA launched a new Food Protection Plan, combining science and information technology to identify potential hazards before they have an impact. The Food Protection Plan comprises:
16.2.10
Prevention of foodborne contamination
This aims to increase corporate responsibility to prevent illness. It seeks to identify and assess vulnerabilities and expand understanding and use of mitigation measures.
16.2.11
Intervention at critical stages in the food supply chain
This includes inspections and risk-based sampling, risk-based surveillance, and better detection of signals that indicate contamination has occurred.
16.2.12
FDA more rapide respond to problems
This reduces the impact, and improve its communication on risks to the public, industry, and other stakeholders.
16.2.13
Growing resistance to antimicrobials
Relatively high proportions of Campylobacter and Salmonella isolates from animals and food were resistant to antimicrobials commonly used in treatment of human diseases. This is especially the case of resistance to uoroquinolones in Campylobacter isolates from poultry, where up to 94% of isolates were reported resistant to ciprooxacin. Foodborne infections caused by these resistant bacteria pose a particular risk to humans due to possible treatment failure. [1]
16.2.14
German Federal Institute for Risk Assessment (BfR) warn about pink duck breast
[10] High temperatures during preparation prevent Campylobacter infections Examinations by the German ocial food control authorities of the federal states detected Campylobacter in around one-third of the poultry meat samples. Duck meat is also frequently involved.
1308
Campylobacter infections in humans are frequently caused by poultry meat, including duck breast. Campylobacter bacteria are heat-sensitive and die when meat is cooked through. As duck breast in traditional recipes is often not cooked through ("pink duck breast"), its consumption can lead to unpleasant gastrointestinal disorders caused by Campylobacter bacteria. This risk, including Salmonella, Listeria, noroviruses and hepatitis viruses, can be completely ruled out when the internal temperature of the meat during preparation on the stove or in the oven is 74 degrees Celsius or higher for more than 10 minutes.
16.2.15
Basic hygiene rules for handling poultry: Kitchen hygiene and sucient cooking
Thaw water and packaging should be disposed of appropriately. All kitchen utensils and surfaces, which have been in contact with the meat, should be thoroughly cleaned. Hands should be washed thoroughly after each stage of preparation. During preparation internal temperature of 74 degrees Celsius or higher must be attained. The use of a meat thermometer is highly recommendated.
16.2.16
Antimocrobial-resistant bacteria draft opinion of the European Food Safety Authority
[11] According to a draft opinion of the European Food Safety Authoritys BIOHAZ Panel the use of antimicrobial agents produced resistant bacteria such as Meticillin-resistant Staphylococcus aureus which can be found in foods such as poultry meat, eggs, pork or beef and foods of plant origin like salads. The panel cites some transmission ways to human: Direct transfer of antimicrobial-resistant bacteria from food originated from animals carrying resistant bacteria. Transfer of antimicrobial-resistant bacteria on fresh produce from land recently irrigated with water contaminated by farm slurry or municipal sewage. Transfer of antimicrobial-resistant bacteria caused by contamination of food during the handling and preparation process. The Panel also said that bacteria deliberately introduced into the food and feed chain for manufacturing and preservation processes, such as fermentation cultures, and also probiotics, have on occasion exhibited antimicrobial resistance and should also be considered as a possible route for the transfer of antimicrobial resistance through food.
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16.2.17
Escherichia coli
Escherichia coli is indicator of fecal pollution of drinking water supplies, swimming beaches, foods, etc. A few strains of Escherichia coli are pathogenic such as the strain 0157:H7 in raw hamburgers (Shiga toxin-producing Escherichia coli (STEC) O157 ).
16.2.18 16.2.19
Reduction of E. coli O157:H7 in cattle with feed strategy Changing grain to forage
[12] Callaway and colleagues found that feeding cattle with large grain rations, some starch escapes ruminal microbial degradation and passes to the hindgut where it is fermented to sugars. EHEC can use these sugars for their grow. The authors say that this may be the reason of E. coli O157:H7 shedding in barley fed cattle. Changing high grain (corn) diet to a forage diet, generic E. coli populations declined 1000-fold within 5 d, and the ability of the faecal generic E. coli population to survive an acid shock similar to the human gastric stomach decreased, but this has not been observed in other studies. The authors conclude that switching cattle from grain to forage could potentially reduce EHEC populations in cattle prior to slaughter, but the economic impact should be taken into consideration.
16.2.20
Outbreak of deadly EHEC Escherichia coli in Germany spreads quickly
[13] A rising number of acute infections and fatalities caused by the Enterohemorrhagic Escherichia coli (EHEC) have occurred especially in Lower Saxony, Bremen and SchleswigHolstein, but spreads quickly southward in May 2011. The German Robert Koch Institute could not determine the infection source yet, however, it is supposed that contaminated vegetable and salads are to be blamed. In the actual epidemic the source is not raw milk, cream cheese or meat. Women are more often preparing food and are therefore at higher risk to be contaminated while washing and preparing vegetables. It is supposed that deposition of the life-threatening bacterium on vegetables and fruits resulting of spraying liquid manure in plantations are the cause of the epidemic. Escherichia coli O157:H7 can be found in the intestinal tract of cattle. Multiple factors contribute to the fact that the bacterium does not cause disease in ruminants and is considered commensal. [14] Health ocials advice to wash carefully vegetables, especially green leafy salads. Sanitise carefully cutting boards and knives and wash hands. Escherichia coli O157:H7 is an enterohemorrhagic strain of the bacterium Escherichia coli. Transmission is via the fecalCopyright 1998-2010 Karl H. Wilm. All rights reserved. OurFood Database of Food and Related Sciences
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oral route, and most illness has been associated with eating undercooked, contaminated ground beef, swimming in or drinking contaminated water, and eating contaminated vegetables. Laboratory tests need 36 hours to be accomplished. Some strains of the German outbreak present antibiotics resistance.
16.2.21
Lactobacillus acidophilus in feed to counter E.coli O157:H7
[15] According to Reillyl the prevention of outbreaks of E. coli O157:H7 should begin with a proper cattle management system together with a supplementation of cattle feed with probiotics such as Lactobacillus acidophilus as a possible antagonist to several pathogens in the intestine.
16.2.22
Escherichia coli and enterococci in water
Recent epidemiological studies indicate that E.coli and enterococci show a direct correlation with swimming-associated gastrointestinal illness rates, while fecal coliforms do not. As the concentration of E. coli and/or enterococci increase(s), the illness rates also increase. These indicators are used as part of the bacterial water quality criteria and standards to enhance the protection of human health and the environment.
16.2.23
Enterococci
Enterococci, which include Enterococcus faecalis and Enterococcus faecium, are enteric bacteria used to indicate faecal contamination and the possible presence of pathogens, in water. Total and faecal coliform bacteria currently have been included in many water quality standards as indicators of bacterial contamination.
16.2.24
Salmonella
The enteric group also includes some other intestinal pathogens of human beings such as Shigella dysenteriae, cause of bacillary dysentery, and Salmonella typhimurium, cause of gastroenteritis. Typhoid fever is an acute, life-threatening febrile illness caused by the bacterium Salmonella enterica serovar Typhi.
16.2.25
Old nomenclature
Bergys Manual: "The names given to salmonellae do not follow the usual rules of nomenclature
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Because of their importance in pathology, the rst salmonellae were given names which indicated the disease and/or the animal from which the organism was isolated, and names of this kind (such as S. typhy, S. paratyphy-A, S. choleraesuis, S. typhymurium, S. abortusovis) continue to be used in clinical bacteriology. Scientically, none of the present methods of nomenclature of salmonellae is satisfactory. Nomenclature changes will be needed in order to account to new DNA ndings."
16.2.26
New nomenclature according to DNA ndings
The new nomenclature comprises only two species:
16.2.27
Salmonella enterica
meaning all human pathogens subdivided into serovars using the old genus names. Example: Salmonella typhy = Salmonella enterica serovar Typhi, Abbreviation S. Typhi. Salmonella enteritidis = Salmonella enterica serovar Enteritidis, Abbreviation S.Enteritidis
16.2.28
Salmonella bongori
Associated with cold-blood animals. Most of human infections are due to contact with reptiles.
16.2.29
Basics of Salmonella prophylaxis
Never eat undercooked ground beef and poultry, raw eggs, not pasteurised dairy products. and raw shellsh. Medical inspection of all people handling food is to be periodic repeated and documented. This includes clinical inspection, bacteriological examination of faeces with regard to Salmonella bacteria, daily control of the personal to avoid purulent wounds, persons with diarrhoea and other problems to come in contact with food. These persons should be transferred to areas were they cannot come in contact with unpacked food.
16.2.30
Salmonellosis
Salmonellosis ranges clinically from the common Salmonellae diarrhoea abdominal cramps, and fever to enteric fevers such as typhoid fever caused by Salmonella Typhi. The most common form of salmonellosis is a self-limited, uncomplicated gastroenteritis.
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16.2.31
Non-typhoid salmonellosis
It is caused by any serotype of Salmonella other than Salmonella Typhi. It is a worldwide disease of humans and animals. Animals are the main reservoir, and the disease is usually food borne, although it can also be spread from person to person.
16.2.32
Typhoid fever
( Synonym: Enteric fever) is caused by Salmonella Typhi. Incubation can last up to two months. It is therefore dicult to remember the food which might have been the source of infection. Hosts are humans, which became carriers after an infection. Several negative microbiological tests should be made, to let a food worker go back to his working place after a salmonellosis. Should this not be a demand of the local medical regulations, auditing should try to get it listed as additional HACCP item. Typhoid fever spread mainly from person to person via the fecal-oral route and have no signicant animal reservoirs. Asymptomatic human carriers may spread the disease. Paratyphoid fever is caused by Salmonella paratyphi and is milder than typhoid fever. Host are humans, which became carriers after an infection.
16.2.33
Typhoid Mary
Here name was Marry Mallone. She was an Irish immigrant. She was a healthy carrier of typhoid fever. From 1900 to 1907 she worked as a cook, infecting many people. Being caught after a long search, she was put in reclusion on North Brother Island and released in 1910 telling her not to work as cook again. In 1915 she was found working as cook in an Hospital infecting people there too. She was sent back to connement where she died in 1938. Other carrier such as Tony Labellaand Alphonse Cotils both handling foods remained free, being an inconsequent attitude of the health authorities managing the epidemic in NY. Please remember this, otherwise you will have typhoid Mary on your suppliers-list. The major reservoir of Salmonella is poultry and livestock, ground meat and eggs.
16.2.34
Measures to reduce salmonellosis in poultry
All animal feed should be salmonellae free. Feed was the main cause of large distribution of Salmonella in poultry.
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Slaughtering practices with reduced cross-contamination of carcasses. Avoid cross-contamination of processed and raw food. Training in hygienic practices for all food-handling personnel. Cooking and refrigerating food adequately. Radiation of poultry to reduce contamination by pathogenic bacteria, such as Salmonella and Campylobacter. Irradiation of food is, however, not much in use.
16.2.35
Shigella
Infection with Shigella is often cause of bloody diarrhoea, and stomach cramps starting a day or two after exposure to the bacterium, usually resolving in 5 to 7 days. Some persons who are infected may have no symptoms at all and pass the Shigella bacteria to others. They are a menace in food production when basic hygiene, hand washing and disinfection habits are not observed. Contaminated food is the result. Dierent kinds of Shigella bacteria: Shigella sonnei, also known as "Group D" Shigella Shigella exneri,Shigella exneri or "group B" Shigella, accounts for almost all of the rest. Shigella dysenteriae type 1 causes deadly epidemics in the developing world. Shigella boydii.
16.2.36
Common causes of food contamination with Shigella
Infected food workers who forget to wash their hands with soap and do not use disinfectant after using bathroom and before preparing food or beverages. Vegetables which were contaminated with sewage. Flies living on infected feces can contaminate food. Drinking or swimming in contaminated water with sewage or sick person swimming in it. Improvements in hygiene for vegetables and fruit picking, water used to rinse vegetable, appropriate packing may prevent shigellosis caused by contaminated products.
16.2.37
Other bacteria related to food born diseases
Listeria monocytogenes:Outbreaks in cheese and meat. Yersinia enterocolitica: Causes enterocolitis in children.
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Cryptosporidium parvum: Infects many herd animals (cows, goats, sheep among domesticated animals, and deer and elk among wild animals) and humans. Cyclospora cayetanensis: Watery diarrhoea. Campylobacter jejuni: It produces diarrhoea bloody stool, fever, lasting seven to ten days. It produces a heat-labile toxin that may cause diarrhoea. Many chicken ocks are silently infected with Campylobacter jejuni, which can be easily spread through a common water source or contact with infected feces. On occasion of slaughter it can be transferred from the intestines to the meat and giblets, especially the liver. Not pasteurised milk can become contaminated if the cow has an infection in her udder or the milk is contaminated with manure. Surface water and mountain streams can become contaminated from infected feces from cows or wild birds. It is often isolated from healthy cattle, chickens, birds and even ies. There are pathogenic and nonpathogenic strains. Cooking chicken, pasteurising milk, and chlorinating drinking water will avoid the bacteria to spread. Not pasteurised milk is therefore a possible source of bacteria such as Campylobacter and tuberculosis. Pasteurisation time/temperature standards should be 145F for 30 minutes (63C for 30 minutes).
16.2.38
Bacteria Rapid Detection Using Optical Scattering Technology
[16] Arun K. Bhunia and colleagues developed an identication process using an imaging approach, analysing bacterial colonies grown on solid surfaces. Using a laser scatterometer, the system classies scatter patterns formed by Listeria monocytogenes colonies. Dierent strains and pathogenic of Listeria can be recognised with a low error rate. It is based on Zernike moment invariants. The detection of other pathogenic bacteria may also be included in the system. The authors point out the feasibility of image-based biodetection systems.
16.3
Cholera
Vibrios (which have a curved rod morphology or comma shape) are very common bacteria in aquatic environments. Pseudomonads favour fresh water and vibrios prefer salt water.
16.3. CHOLERA The genus Vibrio contains an important human pathogen.
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Vibrio cholerae, the cause of Asiatic cholera. Cholera is an intestinal disease with a pathology related diarrhoeal diseases caused by the enteric bacteria. The source of the contamination is usually the feces of an infected person. Incubation is one to two days. The cholera bacteria produces a toxin that inhibits the absorption of liquids by the body. It kills because it dehydrates the body. The disease can spread rapidly in areas with inadequate treatment of sewage and drinking water, brackish rivers and coastal waters, raw or undercooked shellsh from the Gulf of Mexico. In 1991 Cholera was present in coastal areas of Peru. The disease spread rapidly throughout Peru and into other countries in South, Central and North America. The Minister of Fishery of Peru wanting to restore public condence on marine food ate in a TV-show an undercooked sh. The day after he was hospitalised with cholera. Cholera is a disease associated with poverty, inadequate sanitation and low medical care. The key to eective control is environmental sanitation. Whenever these conditions are present in a region from where food and raw materials are imported, auditing should keep this in mind.
16.3.1
Contaminated water and food are the main cause of cholera in Zimbabwe
[17] Cholera is a disease associated with poverty, inadequate sanitation and low medical care. The key to eective control is environmental sanitation. The cholera bacteria (Vibrio cholerae) produces a toxin that inhibits the absorption of liquids by the body. It kills because it dehydrates the body. Zimbabwes cholera outbreak, one of the worlds largest ever recorded, is far from being brought under control. An enhanced response is needed to urgently reverse an epidemic that has so far infected more than 60,000 people and killed more than 3,100 since August 2008. Former Cholera outbreaks took place in Gorna in 1994 aecting Rwandan refugees and killed 50,000 people within 3 weeks. The outbreak in 2006 killed 2.700 persons in Angola.
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16.3.2
Transmission of Cholera through contaminated food and water
[18] Cholera is mainly transmitted through contaminated water and food and is closely linked to inadequate environmental management. Recent interruptions to the water supplies, together with overcrowding, are aggravating factors in this epidemic. Communities are being encouraged to protect themselves against cholera by adhering to proper food safety practices as well as to good personal hygiene. Early rehydration at home by using oral rehydration salts is paramount to diminishing mortality. Mass chemoprophylaxis with antibiotics is strongly discouraged, as it has no eect on the spread of cholera, can have adverse eects by increasing antimicrobial resistance and provides a false sense of security.
16.3.3
How to reduce cholera risk in epidemic regions
[19] [20] - Drink water that you have boiled for at least one minute or treated with chlorine or iodine. Other safe beverages include tea and coee made with boiled or treated water, as well as drinks that have been bottled and sealed (such as bottled water, carbonated drinks, and sports drinks). -Do not put ice in drinks, unless the ice is made from boiled or treated water. - Eat only foods that have been thoroughly cooked and are still hot, or fruit that you have peeled yourself. - Do not eat undercooked or raw sh or shellsh, including ceviche. - Make sure all vegetables are cooked. Do not eat salads or other raw vegetables. - Do not eat foods and drink beverages from street vendors.
16.3.4
Cholera epidemic 2010 in Haiti
[21] Cholera is transmitted through fecal contamination of water or food and causes an acute, severe, watery diarrhoea that can result in hypovolemic shock and death if not treated with uid replacement promptly. The cholera epidemic in Haiti killed 1400 people. 50000 went sick and are being medicated. According to Dr. Scott Dowell of CDC it is not possible to nd out how the cholera came to Haiti. Cholera can be treated with antibiotics but the usual best course is giving intravenous uids, salts and sugars to restore what is lost through diarrhoea and vomiting. It seems
16.3. CHOLERA
1317
hard to get the bacterium out of Haiti and the country will have to deal with the disease for a long time. Genetic tests show the Vibrio cholerae bacteria isolated in Haiti is almost identical to one another, which supports the theory of a single source. It is the same strain previously found in countries in South Asia and elsewhere, and can be trace. Back to a pandemic in Indonesia 49 years in Sulawesi, Indonesia. The outbreak of cholera in Haiti was rst seen aecting workers in rice paddies in the Artibonite Department. They were drinking untreated water and practiced open defecation. Haiti lacks piped, treated water and adequate sanitation. The Haitian population has no pre-existing immunity to cholera. The toxigenic strain Vibrio cholerae O1, serotype Ogawa, biotype El Tor was identied. The strain is susceptible to tetracycline, ciprooxacin, and kanamycin; and resistant to trimethoprimsulfamethoxazole, furazolidone, nalidixic acid, sulsoxazole, and streptomycin. The CDC stresses the importance of preventing infection by promoting water treatment, adequate sanitation and hygiene, and safe food preparation. [22]
16.3.5
Prevention and control measures
[23] The CDC reports that prevention and control measures are focused on 1) providing better access to treated drinking water; 2) providing education on improvement of sanitation, hygiene, and food preparation practices; 3) advising ill persons to begin using oral rehydration solution immediately and seek health care at the onset of watery diarrhoea; 4) enhancing cholera treatment capacity at existing health-care institutions; and 5) establishing cholera treatment centres.
16.3.6
Individual protection from Cholera
[24] The CDC recommends individual measures to protect from the disease: - Drink and use safe water. Boil it for at least 1 minute, or treat it with chlorine. - Wash your hands often with soap and safe water. - Use latrines or bury your faeces; do not defecate in any body of water. If there are no latrines installed, defecate at least 30 meters away from any body of water and then bury your faeces. - Cook food well, especially seafood, keep it covered, eat it hot, and peel fruits and vegetables. Boil it, Cook it, Peel it, or Leave it. - Clean up safely - in the kitchen and in places where the family bathes and washes clothes. Read more at http://www.cdc.gov/haiticholera/pdf/cholera_preventionmessages.pdf
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16.3.7
Ongoing cholera epidemic in Congo and Haiti in 2011
[25] Cholera is an acute intestinal infection transmited by faecal contaminated food or drinking water. The agent of the disease is the Vibrio cholerae bacterium. The disease has an incubation period of 1 to 2 days causing watery diarrhoea, vomiting, severe dehydration and death if treatment is not administered promptly. Vomiting also occurs in most patients. According to WHO cholera no longer poses a threat to countries with high standards of hygiene, however, it remains a challenge in countries with unsafe drinking water and inappropriate sanitation. Congo: The disease has spread to the provinces of Equateur, Bandundu and the capital, Kinshasa, from where it spreads downstream along the River Congo. At least 3,896 cases, with 265 fatalities have been reported in the Democratic Republic of Congo (DRC) since March. In the Republic of Congo 181 cases are suspected, and six people died, following a report issued by WHO. The WHO and partners, together with the government promote hygiene campaigns, send experts to the aected regions, set up water chlorination points and provide treatment for infected persons.
16.3.8
Cholera cases increasing in Haiti
[26] Cases of cholera are on the rise in Haiti and neighbouring Dominican Republic. Since the beginning of the outbreak last October til 12 June 2011, there had been 344,623 cases of cholera and 5,397 deaths. Access to clean water and proper sanitation in Haiti remains the main challenge in ghting the epidemic, according to WHO. In the Dominican Republic there have been 1,727 conrmed cases, including 46 deaths. The country is improving water quality and sanitation services, and public awareness campaigns on prevention.
16.3.9
Consumers feel no health benets of bottled water over tap water, says study
[27] Bottled water became an important business. It is a bulky department of food stores. Ward and colleagues 2009 assessed the health beliefs of consumers concerning bottled mineral water. The authors found that drinking bottled water was motivated by the believe it may confer general health benets linked to the minerals in bottled water. This, however, plays a minor role in the decision to buy bottled water, where convenience, cost and taste are the important criterion. Links between plastic bottle and cancer, also detrimental eect on the environment were of concern.
16.4. STAPHYLOCOCCUS AUREUS
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This study supports an earlier study of Napier and Kodner 2008 which say that health benets of bottled water for routine use is unclear. The authors stress, however the importance of bottled water in handling emergencies or natural disasters, compromising safety of tap water. [28]
16.3.10
US Regulations for bottled water
[29] The Institute of Food Technologists: published in 2008 an overview of drinking water standards and regulations, freshwater resources, water pollution and predominant sources of contamination, and the eects of agriculture and food processing on water quality and wastewater treatment. The overview also describes bottled water as dened by the U.S. Food and Drug Administration (FDA) as water intended for human consumption that is enclosed in a sanitary container, contains no added ingredients (except or optional antimicrobial agents or FDA-specied amounts of uoride), and meets all applicable federal and state standards. It must comply with FDAs standards of quality, standards of identity (including labelling requirements), and current good manufacturing practices, and FDAs standards of quality (21 CFR 165.110[b]) [30] establishing maximum allowable levels of contaminants such asd chemical, physical, microbiological, and radiological in bottled water.
16.4
Staphylococcus aureus
Staphylococcus aureus causes suppurative infections in animals and man. It can form toxins which cause food poisoning. The contamination of food with Staphylococcus aureus occurs due to contact with infected wounds of animals or hands of food workers. That is why gloves are indispensable. Contaminated sh caused intoxication with staphylotoxin which is resistant to heat. The sh had been left for hours without cooling, the bacteria produced the toxin which can be present in deep frozen sh and its products.
16.4.1
Half of US meat and poultry found contaminated with antibiotic resistant Staphylococcus aureus
[31] Waters et al. 2011 found that 47 % of meat and poultry were contaminated with Staphylococcus . aureus, of which 52 % were resistant to at least three classes of antibiotics. The genotypes and resistant proles suggest that the source of these bacteria come from food animals.
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Low doses of antibiotics used as feed supplements industrial farms are ideal places for the development of drug-resistant bacteria.
16.4.2
Staphylococcal enterotoxin is resistant to cooking temperatures
Staphylococcus aureus causes cause a range of illnesses from skin infections to life-threatening diseases, such as pneumonia, endocarditis and sepsis in animals and man. Important for the food industry is the fact that Staphylococcus aureus may form toxins which cause food poisoning. Contamination of meat, poultry or even eggs may be traced back to contact with infected wounds of animals or hands of food workers. Waters and colleagues 2011 stress the need to wear gloves when handling foodstus and refer to proper cooling of meat and poultry to avoid the development of staphylococcal enterotoxin. There are about 14 dierent staphylococcal enterotoxins which are highly resistant to digestion by proteolytic enzymes such as pepsin and trypsin. Staphylococcus enterotoxins are highly resistant to heat.
16.4.3
Staphylococcal enterotoxin A in pasteurised milk
[32] Staphylococcal enterotoxin A is an exotoxin is resposible for frequent staphylococca food poisoning worldwide. The toxin is heat-resistant, and are not completely inactivated by usual cooking procedures. Sospedra et al. 2011 describe a method to detect Staphylococcal enterotoxin A from pasteurised milk.
16.4.4
Ham staphylococcal food poisoning
[33] Staphylococcal enterotoxin D production in boiled ham, smoked ham and dry-curred Serrano after 7 days at room temperature were analysed by Mrta et al 2011. Smoked ham developed nine times less Staphylococcal enterotoxin D per colony-forming unit of Staphylococcus aureus than in boiled ham. In boiled ham, the SED levels unpredictably decreased after three days of incubation. The authors stress that production levels of SED vary in the dierent ham products, but after ve days all ham products developed staphylococcal enterotoxin D sucient to cause staphylococcal food poisoning.
16.4.5
Other bacteria producing toxins
Powerful toxins are also known from Bacillus anthracis causing Anthrax, a disease of cattle, sheep and humans. Clostridium botulinum causes food poisoning, mainly in low acidic foods. Clostridium perfringens also produces an enterotoxin and is an important cause of food poisoning and infections such as gas gangrene. (Ernest Hemingway describes a case of gas
16.5. MOULDS gangrene in his book " The snows of Kilimanjaro ").
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Botulism: Many human deaths have also been attributed to the consumption of food or water containing the toxin. Clostridium botulinum is widely dispersed in soils. Ingestion of the organism is not harmful. It becomes dangerous only when conditions are favourable for its growth and subsequent toxin formation. The organism in an environment containing decaying plant or animal organic material. Stagnant pools or damp areas with buried decaying matter are danger areas for toxin development Decaying carcasses are a frequent source of the toxin, as are many insects feeding in the same tissue. The insects may contain enough toxin to cause the disease in any bird and chicken that ingests it. Since the toxin is water soluble, water sources may become contaminated and provide a reservoir for the disease.Keeping the environment clean is important to avoid botulic poisoning of birds and water contamination. There are dierent types of the toxin; types A and C cause the disease in birds while type B frequently produces the disease in man.
16.5
Moulds
Some strains of moulds produce mycotoxins. Mycotoxins in eggs and meat is mainly inuenced by the concentration of mycotoxins in fodder. Auditing should always look after fodder quality of breeding stations. Bad hygienic condition during harvest, drying, transport of gs and weather conditions such as high humidity and high temperatures are the cause of rising mould spoilage. Consumer should look inside the gs and discard those which are dark. Several brands of dried gs with origin from Turkey and Greece have high amount of aatoxin B1,B2, G1 and G from Aspergillus avus. The aatoxins which are found on these samples are located in the interior of the fruits. As spoiled gs are detected under UV light when they are packed, only the fruits with mould contamination from inside are not removed and are often eaten despite a high level up to 900 microgram/kg of aatoxin B1. (Only 2 micrograms are allowed). It is estimated that 25 per cent of all agricultural crops worldwide are contaminated by molds that produce mycotoxins. The toxins are mostly found in cereals, nuts, cocoa and coee beans and other foods like dried fruits and meat, particularly when the water conCopyright 1998-2010 Karl H. Wilm. All rights reserved. OurFood Database of Food and Related Sciences
1322
tent/activity and the temperature are poorly controlled. The EC Scientic Committee for Food endorsed in 2004 a provisional maximum TDI (Tolerable Daily Intake) for: Patulin 0.4 g/kg bw/day Ochratoxin A 5 ng/kg bw/day
16.6
Prevention and reduction of mycotoxin contamination in cereals
The complete elimination of mycotoxin such as Ochratoxin, Zearalenone, Fumonisis and tricothecenes is not achievable at this time, according to Codex CAC/RCP- 2003. Good agricultural practices (GAP) represent the measures against contamination of cereals with mycotoxins during handling, storage, processing, and distribution of cereals for human food and animal feed. Wheat and maize are hosts to Fusarium. A crop rotation using potato, other vegetables, clover and alfalfa can reduce the spores of the mold in the eld. Old seed heads should be removed, destroyed or plowing under. Make soil tests to ensure adequate soil pH and optimal fertilisation. Seed varieties particularly resistant to molds and pests should be used. Moisture boosts mould infections. Irrigation during owering and during the ripening of the normal crops, specically wheat, barley, and rye, should, therefore, be avoided. If the crop is harvested with a water activity higher than 0.70, the grain must be dried immediately to less than 14% moisture content in small grain. Moisture levels of the crop during storage should be less than 15%. Kernels containing symptomless infections cannot be removed by standard cleaning methods. Seed cleaning procedures, such as gravity tables, may remove some infected kernels. A temperature rise of 2-3C may indicate microbial growth and/or insect infestation in stored grains.
16.6.1
Intermediate storage
Buer storage resulting from low drying capacity should only be made when the moisture is less than 16%, the storage time is less than 10 days, and the temperature is less than 20 C.
16.6. PREVENTION AND REDUCTION OF MYCOTOXIN CONTAMINATION IN CEREALS 1323 Organic acids, like propionic acid may be used as preservatives. These acids are eective in killing various fungi and thus prevent the production of mycotoxins in grains intended only for animal feed. The salts of the acids are usually more eective for long-term storage. Care must be taken because these compounds can negatively aect the taste and odour of the grain. Small, shriveled grain may contain more zearalenone than healthy normal grain. Winnowing grains at harvest or later will remove shriveled grain. Mature grains should not remain in the eld for extended periods of time, particularly in cold, wet weather. T-2 and HT-2 toxins are not usually found in grains at harvest, but can result from grains that are water-damaged in the eld or grains that become wet at harvest or during storage.
16.6.2
Candida albicans as example of microorganism which can act as opportunists
Candida albicans can cause infections of mouth and digestive tract by persons with weak immunological system. Yeasts being found in food should be controlled on regard of the presence of Candida albicans.
16.6.3
Infectious coryza
Infectious coryza is a specic respiratory disease in chickens The disease is caused by a bacterium known as Hemophilus gallinarum.
16.6.4
Pullorum Disease
It is caused by Salmonella pullorum and is primarily egg transmitted. It is also known as "bacillary white diarrhoea" Fowl typhoid It is caused by Salmonella gallinarum. The transmission includes eggs. The poultry infections with Salmonella gallinarum and Salmonella pullorum killed large numbers of birds and were therefore eradicated in the 1970s. They had not cause harm in humans and were acting as a natural vaccine against Salmonella enteritidis. The chickens immunity was lost and this opened the door for Salmonella enteritidis.
16.6.5
Fowl Cholera
It is an infectious disease of turkeys caused by Pasteurella multocida with watery yellowish orgreen diarrhoea.The current bird u scenario should not cause panic and fear; instead it calls for rational and immediate action to ght the disease at its origin - that means in animals.
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Avian inuenza is rst of all an animal disease that requires a veterinarian response. The virus can be defeated and contained if countries and the international community work closely together and set up ecient surveillance and disease control programs. Virus outbreaks in animals need to be detected at a very early stage, infected poultry must be slaughtered and animals at risk have to be vaccinated. Reducing avian inuenza in animals contributes directly to protecting peoples health. Aected countries in Southeast Asia are proving that the virus can be successfully contained. Thailand has obtained an impressive reduction of outbreaks through massive investment in controlling the disease in poultry, using slaughtering and improved surveillance and active disease search. In Viet Nam, improved on-farm hygiene, farming practices, poultry movement controls and vaccination campaigns will reduce the frequency of bird u outbreaks. Several countries such as Malaysia, South Korea and Japan have eliminated the disease rapidly after the occurrence of new outbreaks. Regrettably, most of the public discussion focuses on the human-health aspects of bird u, while the weak state of veterinary services in many poor countries is being ignored. Aected countries and the international community urgently need to invest more in support of veterinarians and animal health workers, because they represent the rst line of defence against the virus. [34] A Swedish study leaded by Anna Thorson says that epidemiological data from a rural Area in Vietnam suggest that transmission of highly pathogenic avian inuenza to humans could be more common than anticipated, though close contact seems required. Thorsons group found that simply having sick or dead poultry in the house did not signicantly increase the risk of u-like illness; those people only showed a 14 percent higher risk of u-like illness compared to someone without poultry. However, having direct contact with sick or dead poultry raised that increased risk to 73 percent, Thorson said. [35]
16.7
Disaster plans
Every business, especially those which are engaged in food production should develop a disaster plan. This plan should be integrated in the biological safety plan to avoid major business disruptions: Key points of a disaster plan should be: Designate a group (preferably an already existing one) within the department or ministry of health responsible for coordinating the collection and dissemination of information related to the pandemic in all its phases and levels.
16.7. DISASTER PLANS
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Make the WHO/OHMS Checklist: Epidemic Alert and Response: WHO checklist for inuenza pandemic preparedness planning WHO/CDS/CSR/GIP/2005.4 part of your disaster plan. [36] Observe carefuly part 4. Preventing spread of the disease in the community of the WHO/OHMS Checklist. [37] Nominate pandemic spokespersons at the national and regional levels. These persons would be responsible for all media presentations to the broader community. Isolate people which are in direct contact with poultry from sensible production points. Poultry contact embraces professional or private avian contact such as having pets at home. Depending on the type of the production the people with near contact to poultry can be kept working in sections were there is no contact with unprotected foods. If necessary these persons should be sent home. Mild signs of respiratory illness must report to the leading and must be isolated from production. Stock piling of packed products should be available in case of an outbreak of the disease in humans which could severely impact employees and their ability to operate. A shortcoming of manpower in the production area may be avoided with such stock pilings. Interruption of supplies due to epidemics in ocks or import bans and political instability of the producing country may result in a shortage of certain raw ware. Stock piling of raw ware and alternative addresses of possible. News from aected areas (countries regions or continents) should be carefully analysed and contact by telephone, fax and email with suppliers should be established and situation should be checked daily. Make a risk assessment of of the vulnerability of the business taking into account a high level of urbanisation, population density and a large number of foreign visitors increase the possibility of a pandemic. Reduced import supply pressures can cause prices rising. Feed grain and soy costs is also a factor of meat price instability. Long leading contracts of raw ware must be included in the disaster plan to avoid the eects of epidemics, political instability of the supplying country. Changing consumption habits should be studied to avoid excessive stock piling, such as happened in 1996 when poultry consumption overtook beef and veal because of BSE headlines. Pork holds the number one position in the EU gaining from avian inuenza damaging the poutry industry.
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Brazil and the United States are supplying approximately 70 percent of global poultry trade. The largest poultry producers and exporters are the United States, Brazil and the EU. Any market uctuation in these three economic zones produces worldwide economic changes. Backyard producers in many developing countries are losing income and are facing increased livelihood and food security risks. In Nigeria, for example, some producers are losing their means of livelihood as birds are culled and prices drop and employees on farms are losing their jobs. FAO stressed that poultry products, properly cooked at or above 70o C throughout the product, are safe to eat [36]. It also noted the importance of preventing products from infected ocks to enter the food chain. All products should be heated above this temperature. This can be cited on the label to strengthen the condence of the consumer on your product. Get your sta to know the food safety implications of H5N1 avian inuenza virus, released by FAO: [37] 1. Conventional cooking (temperatures at or above 70o C in all parts of a food item) will inactivate the H5N1 virus. Properly cooked poultry meat is therefore safe to consume. 2. The H5N1 virus, if present in poultry meat, is not killed by refrigeration or freezing. 3. Home slaughtering and preparation of sick or dead poultry for food is hazardous: this practice must be stopped. 4. Eggs can contain H5N1 virus both on the outside (shell) and the inside (whites and yolk). Eggs from areas with H5N1 outbreaks in poultry should not be consumed raw or partially cooked (runny yolk); uncooked eggs should not be used in foods that will not be cooked, baked or heat-treated in other ways. 5. There is no epidemiological evidence to indicate that people have been infected with the H5N1 virus following consumption of properly cooked poultry or eggs. 6. The greatest risk of exposure to the virus is through the handling and slaughter of live infected poultry. Good hygiene practices are essential during slaughter and postslaughter handling to prevent exposure via raw poultry meat or cross contamination from poultry to other foods, food preparation surfaces or equipment. Educate workers about the importance of strict adherence to and proper use of hand hygiene after contact with infected or exposed poultry, contact with contaminated surfaces, or after removing gloves.
16.7. DISASTER PLANS
1327
Hand hygiene should consist of washing with soap and water for 15-20 seconds or the use of other standard hand-disinfection procedures as specied by state government, industry, or USDA outbreak-response guidelines. [38] The following personal protective equipment should be worn [38] Disposable gloves made of lightweight nitrile or vinyl or heavy duty rubber work gloves that can be disinfected should be worn. To protect against dermatitis, which can occur from prolonged exposure of the skin to moisture in gloves caused by perspiration, a thin cotton glove can be worn inside the external glove. Gloves should be changed if torn or otherwise damaged. Remove gloves promptly after use, before touching non-contaminated items and environmental surfaces. Protective clothing, preferably disposable outer garments or coveralls, an impermeable apron or surgical gowns with long cued sleeves, plus an impermeable apron should be worn. Disposable protective shoe covers or rubber or polyurethane boots that can be cleaned and disinfected should be worn. Safety goggles should be worn to protect the mucous membranes of eyes. Disposable particulate respirators (e.g., N-95, N-99, or N-100) are the minimum level of respiratory protection that should be worn. This level or higher respiratory protection may already be in use in poultry operations due to other hazards that exist in the environment (e.g., other vapors and dusts). Workers must be t-tested to the respirator model that they will wear and also know how to check the face-piece to face seal. Workers who cannot wear a disposable particulate respirator because of facial hair or other t limitations should wear a loose-tting (i.e., helmeted or hooded) powered air purifying respirator equipped with high-eciency lters. Disposable PPE should be properly discarded, and non-disposable PPE should be cleaned and disinfected as specied in state government, industry, or USDA outbreakresponse guidelines. Hand hygiene measures should be performed after removal of PPE. Ax posters with basic u personal hygiene from the CDC at strategic places Cover your nose and mouth with a tissue when you cough or sneeze-throw the tissue away after you use it.
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Wash your hands often with soap and water, especially after you cough or sneeze. If you are not near water, use an alcohol-based hand cleaner. Stay away as much as you can from people who are sick. If you get the u, stay home from work. If you are sick, do not go near other people so that you dont make them sick too. Try not to touch your eyes, nose, or mouth. Germs often spread this way. Keep in mind: Birds that are infected with avian inuenza viruses can shed virus in saliva, nasal secretions, and feces. Contact with feces or respiratory secretions is important in the transmission of infection among poultry. Between ocks, infection usually spreads due to movement of infected birds and the actions of humans in moving feedstu, personnel, equipment, and vehicles into and from premises that are contaminated with infected feces or respiratory secretions. The duration that these viruses can survive in the environment depends on temperature and humidity conditions, but they may survive up to weeks in cool and humid atmosphere. Surveillance and monitoring of workers Instruct workers to be vigilant for the development of fever, respiratory symptoms, and/or conjunctivitis (i.e., eye infections) for 1 week after last exposure to avian inuenza-infected or exposed birds or to potentially avian inuenza-contaminated environmental surfaces. Individuals who become ill should seek medical care and, prior to arrival, notify their health care provider that they may have been exposed to avian inuenza. In addition, employees should notify their health and safety representative. With the exception of visiting a health care provider, individuals who become ill should be advised to stay home until 24 hours after resolution of fever, unless an alternative diagnosis is established or diagnostic test results indicate the patient is not infected with inuenza A virus. While at home, ill persons should practice good respiratory and hand hygiene to lower the risk of transmission of virus to others. The enterprise should plan how to get a population through one to three years of a pandemic. Transport enterprises will be forced to reduce their services. Global airline industry will be seriously reducing their service so important raw ware, products and even personal movement will be dicult. Widespread infection and economic collapse can destabilize a government.
16.8. REVIEW OF PATHOGENS HEAT-RESISTANCE
1329
The sta of the enterprise should be vaccinated against seasonal inuenza and a protection against pneumococcal pneumonia with a Pneumovax vaccination making it compulsory to all employees. This reduces the severity of an H5N1 infection and let the employee be back to his work earlier. All items of the disaster plan should be discussed with a risk assessment rm and should be revised by the local veterinary authority. It would be unrealistic for any country, unless it has a very small population with a centralized infrastructure and bureaucracy, to consider that it could prepare and implement a detailed and comprehensive pandemic plan in weeks, or even months. The two main reasons are that there is a need for a multisectoral approach and that the community should be involved. A multisectoral approach means the involvement of many levels of government, and of people with various specialties including policy development, legislative review and drafting, animal health, public health, patient care, laboratory diagnosis, laboratory test development, communication expertise and disaster management. Community involvement means making optimal use of local knowledge, expertise, resources and networks. It is a powerful way to engage people and to build the commitment needed for policy decisions.
16.8
Review of pathogens heat-resistance
[39] OBryan and colleagues summarize the heat-resistance of several strains of pathogenic bacteria The authors conclude that heat-resistance of these organism are inuenced by : Dierent response to heat between strains of the same organism. Age of the culture Growth conditions pH Other factors Processors may nd useful data in this review for the validation of times and temperatures for thermal processing of meat and poultry. They stress that under the HACCP regulations, 9 CFR 417, employees of food processing operations must validate the elements of their HACCP plans through: references to scientic publications that demonstrate pathogen reduction under laboratory conditions somewhat similar to those used in the production plant, the use of HACCP consultants who are processing authorities or they can validate their plan using experiments using
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surrogates, non-pathogenic organisms that can mimic pathogens killed in a process. Using data reported from laboratory inactivation of pathogens and predictive models is much more rapid and less expensive than testing surrogate organisms under actual processing operations. However, almost all of the reported thermal inactivation has been done in a media solution under ideal single culture laboratory conditions and not in an actual food matrix under conditions approximating commercial thermal processing. Because of USDA-FSIS Notice 25-05, it was suggested that computer modelling should not be used solely as validation of RTE products and that independent microbiology laboratories be used for complete and thorough analysis. Therefore, this thermal inactivation validation is also useful in combination with computer modelling for aid in HACCP compliance (USDA-FSIS 9 CFR 417). The authors point out the need to know key descriptive factors should be considered such as the particular pathogen of interest, the log or stationary phase, freshness state , frozen, or cooked and fat content of the meat, or other ingredients instead of one single element, validating the lethality of thermal processes. The authors encourage the development of surrogates able to be used in an actual environment.
16.8.1
Cattle ranch as source of spinach contamination with Escherichia coli 0157:H7
[40] In September 2006 199 people in 26 US states diseased with Escherichia coli 0157:H7 strain and three died after eating contaminated spinach. Heath ocials said that the bacteria could have been transmitted by irrigation water, fertilizer, farm equipment or workers, livestock and wild animals, or it could have contaminated the spinach inside processing plants, during transport or on store shelves. Later, in October 2006 three samples of cattle fecal matter from one ranch in Californias Salinas Valley have tested positive for the same strain of E. coli bacteria which had caused the disease. The ranch included both a beef cattle operation as well as elds where spinach and other ready-to-eat produce were grown. The fecal-matter specimens were found half a mile to a mile from the produce elds themselves. Ocials said that wandering livestock, substandard worker hygiene, irrigation practices or even wild boar could have transported the
16.8. REVIEW OF PATHOGENS HEAT-RESISTANCE bacteria to the spinach elds.
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The proximity of fresh produce elds to farm animals has long been a concern to agricultural and health authorities, and a minimum distance between them must be found out.
16.8.2
[41] [42]
HACCP plans for fresh produce
16.8.3
The Fresh Produce Safety Act of 2007
A legislation was introduced by by Senate Agriculture Committee Chairman Tom Harkin requiring the FDA to assess farms and processing facilities on the basis of risk. Producers will be required to maintain written hazard control plans. High-risk facilities that washes and bags salad greens would be inspected at least once a growing season instead of once every 5 or 10 years. The FDA would also develop standards and practices for manure application, irrigation water, and for excluding domestic animals from elds where produce is grown. The bill would also require rulemaking to ensure that imported produce has been grown and processed with the same standards that we will have in the U.S. The bill follows the great recalls of spinach and lettuce.
16.8.4
Strategies to reduce person-to-person transmission during epidemics
[43] Seto and colleagues 2007 studied the spinach Escherichia coli O157:H7 (E. coli O157) outbreak in the United States in 2006 with 173 cases and one death. During the spread of the disease the Centers for Disease Control and Prevention CDC and the US Food and Drug Administration advised consumers not to eat spinach as the primary strategy for protecting against foodborne transmission of E. coli O157. No warnings, however, were issued regarding the prevention of person-to-person (secondary) transmission. The authors assume that a combination of possible intervention strategies to interrupt secondary transmission would have a range of possible levels of eectiveness in epidemics like this. These strategies would include strongly recommending handwashing, avoiding contact with persons with diarrhoea, meticulously preparing food, and avoiding work or school when ill with any gastrointestinal sign or symptom. The researchers found in this study that an intervention such as a campaign to encourage handwashing and isolation of persons with diarrhoea can substantially reduce secondary transmission. Even if a campaign were initiated relatively late in the outbreak,
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the number of cases would be reduced. Such advice was not a focus of the public health messages disseminated for the 2006 E. coli O157 outbreak. The interruption of secondary transmission might have had a useful role as an additional tool in managing this outbreak.
16.8.5
Public Health Implications
Public health strategies for preventing secondary transmission could include public media campaigns reminding the population of the importance of handwashing, avoiding contact with faeces, minimizing nonessential contact with persons with diarrhoea, meticulous care when preparing and consuming food, and staying at home from work or school when having any diarrhoea during the outbreak period. Messages for all of these strategies can be delivered inexpensively to large or targeted populations through a variety of media (television, radio, print, Internet) The authors conclude that health ocials should consider rapidly delivering widespread public health messages with specic advice on how to interrupt secondary transmission of E. coli O157. Such an intervention, even if only modestly successful, could meaningfully reduce the number of cases. Erwinia chrysanthemi
16.8.6
[44]
Pathogens on raw produces
16.8.7
Pathogen contamination of produce
typically consumed raw has caused large scale foodborne illness. According to Robert Mandrell and colleagues 2008 pathogenic microbes often need the help of other microbial species to make the jump from their usual residents (in the intestines of warm blooded animals) to inhabit plants
16.8.8
Pathogens on lettuce, tomatoes and herbs
The researchers at US ARS found that pathogens such as Eschericia coli and Salmonella develop better on younger leaves with about three times as much nitrogen as in the middle leaves. Therefore strategies to minimise use of nitrogen fertilisers may help reduce E. coli contamination of produce. On romaine lettuce and on the herb cilantro E. coli and Salmonella are aided by Erwinia chrysanthemi which causes soft rot of the vegetable and biolms of E. coli and Salmonella. Xanthomonas campestris (bacterial leaf spot of tomato) helps Salmonella to bind and grow on or in tomato plants. The researchers say that Xanthomonas campestris may disable the plants immune response, allowing both it and Salmonella to multiply. Soil ooded with Salmonella contaminated water remained infectious to tomato seeds for six weeks and may infect the new plant. Crop debris can also serve as a reservoir of viable Salmonella for at least a week. The authors recommend a fallow period of about two weeks, before replanting
1333
elds with lettuce and tomatoes. The team suggest that potentially contaminated elds could benet from a fallow period of perhaps a few weeks. The bacterium Wausteria paucula enhances E. coli survival on lettuce leaves by six fold. However, Enterobacter asburiae, living on plants such as beans, cotton and cucumbers without harming them, reduces levels of E. coli and Salmonella on seeds of thale cress. The survival rate of E.coli fell by 20 - 30 fold when Enterobacter asburiae, Wausteria paucula and E.coli come together. The authors suggest to control and to introduce certain microbes to crops in order to reduce the risk of pathogen spread on fresh produce like tomatoes lettuce and cilantro.
16.8.9
Safety of fresh-cut produces
[45] According to the USDA, between 1996 and 2006, there were 24 reported incidents of foodborne illness caused by contaminated fresh-cut produce in the United States, such as the E. coli O157:H7 contamination of spinach. To increase the safety of fresh-cut produces the department published some important recommendations:
16.8.10
Farming
Anything that comes into contact with fresh produce has the potential to contaminate it, such as indirect or direct contact with feces. Sources of fecal contamination include animals, untreated manure used as a soil amendment, water, infected workers, or conditions in the eld or packing facility, such as unclean containers and tools used in harvesting and packing. Multiple farming activities come close together making it harder to keep livestock and produce separate. Livestock and wildlife are likely to be drinking from the same creek that irrigates a crop eld.
16.8.11
Transport
Transport also presents opportunities for contamination, such as unclean oors and walls of the vehicles or unclean containers.
16.8.12
Processing facilities
Processing fresh produce into fresh-cut products further increases the risk of contamination by breaking the natural exterior barrier of the produce. The release of plant cellular components when produce is shredded or chopped provides a nutritive medium in which pathogen can grow and contamination can spread. Improper sanitation during processing is another major potential point of contamination by
1334
pathogens, followed by the absence of a lethal process, such as a heat step during production to eliminate pathogens; and the potential for temperature change during processing, storage, transport, and retail display.
16.8.13
Ultrasound cleaning of equipment
[46] Ultrasound technology is being used to sterilize equipment without chemicals. Utrasound treatments, around 20 kHz, collapse bubbles in the cleaning liquid and releases energy that kills bacteria.
16.8.14
Rapid microbe removal
Bacteria such as Listeria monocytogenes on the belt surfaces are eliminated in only 10-20 seconds. Cleaning with ultrasound saves about 50 percent of energy and water, and avoids blind spots of the conveyor. The sanitation system includes precleaning with degreasers and caustics, followed with ultrasonic sterilization of the belt surface. The USDA said that researchers at its Produce Quality and Safety Laboratory (PQSL) in Maryland have been focusing on ways to keep salads safe at processing plants before and after bagging. Cutting fresh produce during harvesting removes natural protective barriers, exposing cut surfaces to potential contaminants. Combining sanitizers with ultrasound, optimizing oxygen conditions and not reusing washing water can reduce bacterial contamination of lettuce and leafy greens. Young leaves of lettuce have higher risk of pathogen contamination.
16.8.15
Nitrogen fertilizers may increase risk of pathogens on lettuce
[47] Brandl and Amundson 2008 found that the increases in population size of E. coli O157:H7 on lettuce plants was 10-fold higher on the young (inner) leaves than on the middle leaves, suggesting that leaf age aects preharvest as well as postharvest colonization. The authors say that young-leaf exudates were 2.9 and 1.5 times richer in total nitrogen and carbon, respectively, than middle-leaf exudates. The low nitrogen limits the growth of pathogens on these leaves. The authors concluded that leaf age and nitrogen content in young lettuce leaves may be associated with a greater risk of contamination with E. coli O157:H7. Maria Brandl calls for a strategy of reduction of nitrogen fertilizers to increase safety of lettuce.
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16.8.16
Washing and ultrasound
[48] Yaguang Luo, studied the safety and quality of precut lettuce. He found that sliced romaine lettuce leaves rinsed in fresh wash water, dried, packed in bags and stored for 14 days by 5o C had lower bacterial counts than leaves which were unwashed or were washed with reused water. Luo also found that the combination of a sanitizer with ultrasound treatment for industrial-scale reduced substantially the number of bacteria on the surface of vegetables.
16.8.17
Irradiation of spinach and lettuce
[49] The FDA announced that it will allow food processors to irradiate some leafy greens (spinach and iceberg lettuce). The Center for Science in the Public Interest (CSPI) says that this action may be safe and eective in treating some pathogens, however, it will not solve all problems of pathogenic bacteria on leafy vegetables. The CSPI recommends FDA to adopt a series of preventive measures starting at the farm that could control foodborne pathogens. Our suggestions, outlined in 2006 petition to FDA, include common-sense food safety control measures: 1. Farmers and processors should be required to keep a written food safety plan specic to the environmental conditions on that particular farm. 2. FDA should develop uniform standards to evaluate those plans, for water quality, worker sanitation, and manure use and management. 3. Written plans should be audited once per season, either by FDA or a 3rd party auditor (whose audits should be reviewed by FDA). With the approval of irradiation on spinach and lettuce, FDA should also specify that these products should be clearly labelled with the radura symbol and the words "treated with irradiation." This labelling-required for other irradiated products-provides consumers with the information to make choices about the food they purchase. It is clear that produce safety must become a priority for FDA, starting at the farm. Congress should also act to ensure that the agency has the authority and the resources to fulll its critical public health mandate. The CSPI Petition also includes further details: [50]
16.8.18
Manure
Appropriate manure management is required. Composting of manure intended for use on food crops should be monitored and records should be maintained to ensure eective
1336
controls are used to destroy pathogens. Domestic animals should be excluded from elds and orchards during the growing and harvesting season, and growing areas should have wildlife deterrents.
16.8.19
Water
Growers and producers should ensure that the water supply used for irrigation and in food processing plants is suitable for its intended use. Facilities should have an environmental monitoring program that includes sampling for pathogens to detect areas of harborage and to verify the eectiveness of cleaning and sanitizing programs in preventing cross-contamination. Water used for washing produce should be monitored for the presence of pathogens at a rate adequate to ensure highly contaminated batches are identied and either destroyed or sent for further processing.
16.8.20
Hygiene
Growers and processors should ensure that employees have close access to bathrooms and that handwashing facilities are visible to supervisors. Employees with direct and indirect access to the production areas should be trained in preventive controls that will help to eliminate or minimize contamination of produce.
16.8.21
Traceback
Processors should mark packaging to ensure easy traceback to the farm of origin when fruits and vegetables are implicated in an outbreak.
16.8.22
Modied atmosphere and temperature may alter bacterial resistance to gastric juice
[51] Arvind Bhagwatand colleagues 2008 studied the eect of low-oxygen based modied atmosphere packaging (MAP) and temperature after 8 days storage of fresh lettuce. The authors found that bacteria acquired resistance to synthetic gastric juice when stored under extremely low-oxygen conditions ( between 0,5 and one per cent of oxygen) and at temperatures of 15o C or above. No resistance was induced among bacteria stored under extremely low-oxygen conditions and at temperatures of 10o C or below. Proper storage temperatures are, therefore, essential to minimize bacterial growth and adaptability inside sealed, bagged salad greens under MAP. The authors concluded that MAP must be supported by proper storage temperature to minimizing bacterial adaptability.
16.9. IMPROVED SANITATION OF LARGE FOOD SYSTEMS
1337
16.9
Improved sanitation of large food systems
HACCP programs place greater emphasis on record keeping and personal accountability, which, in turn, puts greater demand on systems and employees. Manually operated, sanitation depend on the people which do not exclude human failures. An automated system is more reliable, because it follows a prescribed cleaning pattern. However, failure of automatic valves and dead ends in the system must always be considered by those who are in charge of the safety of the production.
16.9.1
Sanitation Performance Standards Compliance Guide
[52] The Sanitation Performance Standards issued by the Food Safety and Inspection Service (FSIS) establishes a exible regulatory method based on HACCP philosophy. It denes rule on sanitation requirements for meat and poultry plants. The standards dene the desired sanitation results, but not the specic means to achieve those results abolishing specic methods for cleaning equipment and utensils. The new standards remove obstacles to innovation, allowing innovative sanitation processing procedures. Past FSIS regulations and guidance, as well as recommendations from the 1999 Food Code and other technical sources, are included or cited.
16.9.2
Construction problems with stainless tubes, tanks and vessels
[53] Fit and nish troubles with equipment that make it dicult to clean. Smoothness of welds and open bearings may present problems in food plants. The American Welding Society published a guideline regarding tubes, pipes stainless tanks. describing the welding requirements for tubing systems pipes and stainless steel tankls built to 3-A standards, but also apply to meat production: Specication for Welding of Austenitic Stainless Steel Tube and Pipe Systems in Sanitary (Hygienic) Applications (D18.1:1999) [54] AWS D18.3/D18.3M Specication for Welding of Tanks, Vessels, and Other Equipment in Sanitary (Hygienic) Applications. Document AWS D18.3/D18.3M [55]
16.9.3
Sanitizing chemicals ozone and chlorine
Ozone is making strides as a safe alternative and a powerful oxidant that destroys microbes, being nearly 3,000 times faster than chlorine. It is used as the primary agent of sanitation
1338
for more than 80 percent of the bottled water supplied to the U.S. Aqueous ozone is used both to clean apples and its juice storage tanks. Salad makers uses aqueous ozone to disinfect vegetables and its associated equipment, replacing chlorine. Ozonated water is used to sanitize work areas and processing equipment used at the meat industry. Ozone rapidly decomposes into oxygen. Chlorine rinses uses 100 ppm chlorine. The same eect is attained with water containing 1 ppm ozone.
16.9.4
Bonamia ostreae oyster parasite in UK
[56] The UK Department for Environment, Food and Rural Aairs has issued a notice in 2007 conrming the presence of the parasite Bonamia ostreae in a bed of native oysters from Whitstable Bay. The area subject to movement controls has been selected to ensure maximum protection against further spread of the disease. Bonamia ostreae causes the serious disease Bonamiosis in native oyster stocks, but does not have any clinical eect on any other species of shellsh. Cefas will be monitoring the extent and eect of the disease in the controlled area. It is not expected that the controls will interfere with current commercial activity. Bonamiosis has no implications for human health, and native oysters from this area can still be eaten. The Notice, issued under Regulation 14 of the Fish Health Regulations 1997 (as amended), restricts the movement of any live molluscan shellsh out of the specied area, for the purposes of relaying or re-immersion in the aquatic environment, without the prior written consent of Defra. Bonamia ostreae is a protistan parasite (2-3m) infecting the blood cells of the at oyster (Ostrea edulis). The bonamiasis disesas is considered as a haemocytic parasitosis developing in older oysters. The transmission of the parasite can occur between cohabiting oysters. The parasite is present at the coasts of the USA, continental Europe and the Irish and English coastlines. Once Bonamia gets into an area it is not possible to eradicate the disease. However, stocks Irish oysters seem to have developed a degree of resistance to the disease. [57]
16.10
16.10.1
Antimicrobial Products
Non-public health products
are used to control growth of algae, odour causing bacteria, bacteria which cause spoilage, deterioration or fouling of materials and microorganisms infectious only to animals. They
16.10. ANTIMICROBIAL PRODUCTS
1339
are used in cooling towers, jet fuel, paints, and treatments for textile and paper products. Public health products They are intended to control microorganisms infectious to humans in any inanimate environment. The more commonly used public health antimicrobial products are:
16.10.2
Sterilisers (Sporicides)
Used to destroy or eliminate all forms of microbial life including fungi, viruses, bacteria and their spores. The term Sporicide is to be considered synonymous with "Steriliser". Sterilisations used to control infection and is widely used in hospitals on medical and surgical instruments and equipment. Types of sterilisers include steam under pressure (autoclaving), dry heat ovens,UV rays, low temperature gas (ethylene oxide), and liquid chemical sterilants. Gaseous and dry heat sterilisers are used primarily for sterilisation of medical instruments. Liquid sterilants are primarily used for delicate instruments which cannot withstand high temperature and gases.
16.10.3
Disinfectants
Disinfectants are used to destroy or inactivate infectious fungi and bacteria but not necessarily their spores. There are the type for hospital and the type for general use. Hospital type disinfectants They are the most critical to infection control and are used on medical and dental instruments, oors, walls, bed linens, toilet seats, and other surfaces.
16.10.4
General disinfectants
They are the major source of products used in households, swimming pools, and water puriers.
16.10.5
Sanitizers
Sanitizers reduce, but not necessarily eliminate, microorganisms from the inanimate environment to levels considered safe. Sanitizers include food contact and non-food contact products. The food contact sanitizers are used to rinse surfaces and cooking utensils, as well as equipment of food-processing plants, and eating and drinking establishments.
16.10.6
Non-food contact surface sanitizers
include carpet sanitizers, air sanitizers, laundry additives, and in-tank toilet bowl sanitizers.
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Bibliography
[1] http://www.efsa.europa.eu/etc/medialib/efsa/science/monitoring_ zoonoses/reports/zoonoses_report_2005.Par.0001.File.dat/Zoonoses_ report_2005.pdf. The Community Summary Report on Trends and Sources of Zoonoses, Zoonotic Agents, Antimicrobial Resistance and Foodborne Outbreaks in the European Union in 2005, The EFSA Journal (2006), 94. [2] http://www.efsa.europa.eu/en/science/monitoring_zoonoses/reports/zoon_ report_finbroilers.html. Report of the Task Force on Zoonoses Data Collection on the Analysis of the baseline survey on the prevalence of Salmonella in broiler ocks of Gallus gallus, Part A, The EFSA Journal (2007) 98, 1-85. [3] http://www.efsa.europa.eu/en/ahawtopics/topic/qfever.htm? Q fever. EFSA. [4] http://www.camembert-aoc.org/unil-uk/htm/aoc-uk.htm. AOC: Dnition du Camembert. [5] http://www.foodsafety.iastate.edu/news/. Food Safety Consortium, Iowa State University: FRANCE: Raw milk camembert poses safety concern says manufacturer. 14.03.2008. [6] http://www.fda.gov/bbs/topics/NEWS/2007/NEW01576.html. FDA News, March 1, 2007: FDA and CDC Remind Consumers of the Dangers of Drinking Raw Milk. [7] http://www.mass.gov/?pageID=pressreleases&agId=Eeohhs2&prModName= dphpressrelease&prFile=080108_listeria_investigation.xml. The Massachusetts Department of Public Health (MDPH): MDPH continues Listeria investigation. [8] http://www.cdc.gov/mmwr/preview/mmwrhtml/00001316.htm. CDC: Epidemiologic Notes and Reports Update Listeriosis and Pasteurized Milk. December 16, 1988 / 37(49);764-766. [9] http://www.fda.gov/oc/initiatives/advance/food/plan.html. FDA: Food Protection Plan: An integrated strategy for protecting the nations food supply. November 2007. [10] http://www.bfr.bund.de/cd/10703. BfR: Risky delicacy: Pink duck breast. High temperatures during preparation prevent Campylobacter infections. 28.01.2008. [11] http://www.efsa.europa.eu/EFSA/efsa_locale-1178620753812_ 1178700897302.htm. EFSA: The role of food in human exposure to antimicrobial resistant bacteria.
BIBLIOGRAPHY
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[12] http://jds.fass.org/cgi/content/full/86/3/852. Callaway, T.R.; Elder, R.O.; Keen, J.E.; Anderson, R.C. and Nisbet D.J.: Forage Feeding to Reduce Preharvest Escherichia coli Populations in Cattle, a Review; J. Dairy Sci. 86:852-860. [13] Gefhrlicher darmkeim. erste todesopfer nach ehec-infektion. 24.05.2011. Spiegel Online. http://www.spiegel.de/wissenschaft/medizin/0,1518,764576,00.html. [14] Quantrell RJO, Naylor SW, Roe AJ, Spears K, and Gally DL. Ehec o157:h7 - getting to the bottom of the burger bug. Microbiology Today, 31(8), 2004. http://www.sgm. ac.uk/pubs/micro_today/pdf/080407.pdf. [15] http://www.ansi.okstate.edu/research/1996rr/8.pdf. Reilly1, S. S.; and Gilliland, S. E: Inhibition of Escherichia coli O157:H7 by Lactobacillus acidophilus isolated from calves. [16] Bulent Bayraktar, Padmapriya P. Banada, E. Daniel Hirleman, Arun K. Bhunia, J. Paul Robinson and Bartek Rajwa: Feature extraction from light-scatter patterns of Listeria colonies for identication and classication; J. Biomed. Opt. Vol. 11, 034006 (May. 19, 2006). [17] http://www.who.int/mediacentre/news/releases/2009/cholera_zim_ 20090130/en/index.html. WHO: Global, national eorts must be urgently intensied to control Zimbabwe cholera outbreak. [18] http://www.who.int/csr/don/2008_12_02/en/index.html. WHO: Cholera in Zimbabwe 2.12.2008. [19] http://wwwn.cdc.gov/travel/contentCholeraZimbabwe.aspx. CDC: Cholera in Zimbabwe and Neighboring Countries. January 16, 2009. [20] http://wwwn.cdc.gov/travel/contentSafeFoodWater.aspx. CDC: Safe Food and water. [21] http://www.who.int/csr/don/2010_11_24/en/index.html. Cholera in Haiti - update 4 WHO Cholera Tahiti 24.11.2010. [22] http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5943a4.htm. Centers for Disease Control and Prevention (CDC): Cholera outbreak - Haiti, October 2010. MMWR Morb Mortal Wkly Rep. 2010 Nov 5;59(43):1411. [23] http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5945a1.htm. Centers for Disease Control and Prevention (CDC): Update. [24] http://www.cdc.gov/haiticholera/pdf/cholera_preventionmessages.pdf. Protect Yourself from Cholera. CDC Prevention Message.
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[25] UN. Congolese cholera outbreak continues to spread, un health agency says. un 15 jul 2011. 7 2011. http://www.un.org/apps/news/story.asp?NewsID=39145&Cr= cholera&Cr1=. [26] UN. Cholera cases increasing in haiti and dominican republic, un reports. 24 jun 2011. 6 2011. http://www.un.org/apps/news/story.asp?NewsID=38834&Cr= haiti&Cr1=. [27] http://www.ncbi.nlm.nih.gov/pubmed/19545357. Ward, L.A.; Cain, O.L.; Mullaly, R.A.; Holliday, K.S.; Wernham, A.G.; Baillie, P.D.; Greeneld, S.M.: Health beliefs about bottled water: a qualitative study. BMC Public Health. 2009 June 19;9(1):196. [28] http://www.ncbi.nlm.nih.gov/pubmed/18928830. Napier, G.L.; Kodner, C.M..: Health risks and benets of bottled water. Prim Care. 2008 Dec;35(4):789-802. [29] http://members.ift.org/NR/rdonlyres/54EF1203-B11E-4A0B-A78B-525CB8D98ED3/ 0/JustAddWater.pdf. Tarver, T.: Just add water: regulating and protecting the most common ingredient. The Institute of Food Technologists:Vol. 73, Nr. 1, 2008-Journal of Food Science. [30] http://cfr.vlex.com/vid/165-110-bottled-water-19705533. 21 CFR 165.110 Bottled water. [31] A. E. Waters, T. Contente-Cuomo, J. Buchhagen, C. M. Liu, L. Watson, K. Pearce, J. T. Foster, J. Bowers, E. M. Driebe, D. M. Engelthaler, P. S. Keim, and L. B. Price. Multidrug-resistant staphylococcus aureus in us meat and poultry. Clinical Infectious Diseases, 2011. http://cid.oxfordjournals.org/content/52/10/1227. [32] Sospedra I, Soler C, Manes J, and Soriano JM. Analysis of staphylococcal enterotoxin a in milk by matrix-assisted laser desorption/ionization-time of ight mass spectrometry. Anal Bioanal Chem, 400(5):152531, 5 2011. http://www.ncbi.nlm.nih.gov/ pubmed/21442364. [33] Mrta D, Wallin-Carlquist N, Schelin J, Borch E, and Radstrm P. Extended staphylococcal enterotoxin d expression in ham products. Food Microbiol, 28(3):61720, 5 2011. http://www.ncbi.nlm.nih.gov/pubmed/21356473. [34] http://www.fao.org/newsroom/en/news/2005/1000105/index.html. Jacques Diouf, FAO Director-General: How to Stop Bird Flu; 28 October 2005, Rome. [35] Anna Thorson, MD, PhD; Max Petzold, PhD; Nguyen Thi Kim Chuc, PhD; Karl Ekdahl, MD, PhD: Is Exposure to Sick or Dead Poultry Associated With Flulike Illness?A Population-Based Study From a Rural Area in Vietnam With Outbreaks of Highly Pathogenic Avian Inuenza; Arch Intern Med. 2006;166:119-123.
BIBLIOGRAPHY
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[36] http://www.fao.org/newsroom/en/news/2006/1000240.html. FAO Newsroom:Escalating bird u crisis jeopardizes global poultry trade prospects. Reduced consumption is lowering poultry prices and import demand. 28 February 2006. Rome. [37] http://www.who.int/mediacentre/news/releases/2005/pr66/en/index.html. FAO: No bird u risk for consumers from properly cooked poultry and eggs. [38] http://www.who.int/foodsafety/fs_management/No_07_AI_Nov05_en.pdf. WHO: Highly pathogenic H5N1 avian inuenza outbreaks in poultry and in humans: Food safety implications. [39] http://www3.interscience.wiley.com/journal/118601213/abstract. OBryan CA, Crandall PG, Martin EM, Gris CL, and Johnson MG: Heat Resistance of Salmonella spp., Listeria monocytogenes, Escherichia coli 0157:H7, and Listeria innocua M1, a Potential Surrogate for Listeria monocytogenes, in Meat and Poultry: A Review; JFS Online, April 2006, Vol 71, Nr. 3. [40] http://www.nlm.nih.gov/medlineplus/news/fullstory_39955.html. Plus: Cattle ranch may be source of spinach contamination. Medline-
[41] http://www.cspinet.org/new/200709201.html. CSPI: Food Safety Act Calls For Inspections on Produce Farms. Bill Comes One Year After Massive Spinach Recall. [42] http://agriculture.senate.gov/news2/record.cfm?id=283764. Press Release of Agriculture, Nutrition & Forestry DEM Committee. Harkin measure creates rst of its kind national food safety framework for all fresh produce. [43] http://www.cdc.gov/eid/content/13/6/860.htm. Seto EYW, Soller JA, Colford JM Jr. Strategies to reduce person-to-person transmission during widespread Escherichia coli O157:H7 outbreak. Emerg Infect Dis. 2007 Jun. [44] http://www.ars.usda.gov/is/AR/archive/jul08/pathogen0708.htm. FDA: Outmaneuvering Foodborne Pathogens. July 2008. [45] http://www.ars.usda.gov/is/AR/archive/jul08/form0708.htm. USDA: ForumMaking Sure Leafy Greens and Other Produce Stay Safe. [46] http://www.ars.usda.gov/is/AR/archive/jul08/greens0708.htm. USDA Agricultural Research Service: Which treatment to use. July 2008 - Vol. 56, No. 6. [47] http://aem.asm.org/cgi/content/abstract/74/8/2298. Brandl,M.T.; Amundson, R.: Leaf Age as a Risk Factor in Contamination of Lettuce with Escherichia coli O157:H7 and Salmonella enterica. Appl. Environ. Microbiol. 2008 74: 2298-2306. [48] http://www.ars.usda.gov/is/pr/2008/080724.htm. USDA Agricultural Research Service: Cold Temperature is Key to Quality of Bagged Salads. Agricultural Research Magazine. July 2008 - Vol. 56, No. 6.
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[49] http://www.cspinet.org/new/200808212.html. FDA Approves Irradiation for Spinach, Lettuce. Statement of CSPI Food Safety Director Caroline Smith DeWaal. 21.08.2008. [50] http://www.cspinet.org/new/pdf/fda_produce_petition.pdf. CSPI: Citizen Petition. November 15, 2006. [51] http://www.ars.usda.gov/is/AR/archive/jul08/greens0708.htm. USDA Agricultural Research Service: Safe Leafy Greens-Before and After Bagging. Agricultural Research Magazine. July 2008 - Vol. 56, No. 6. [52] http://www.fsis.usda.gov/OPPDE/rdad/frpubs/sanitationguide.htm. Sanitation Performance Standards Compliance Guide. FSIS:
[53] http://www.tubenet.org.uk/technical/arctech3_m.html. Henon, Barbara K.; Brond Angel: Latest Developments in Welding Specications for Sanitary Process Piping. Tubenet.org, The Site for Tube and Pipe Industries. [54] http://webstore.ansi.org/RecordDetail.aspx?sku=AWS+d18.1-1999-all-color. AWS D18.1Specication for Welding of Austenitic Stainless Steel Tube and Pipe Systems in Sanitary (Hygienic) Applications AWS d18.1-1999-all-color. [55] http://engineers.ihs.com/document/abstract/XNYMIBAAAAAAAAAA. AWS D18.3/D18.3M Specication for Welding of Tanks, Vessels, and Other Equipment in Sanitary (Hygienic) Applications. Document AWS D18.3/D18.3M. [56] http://www.defra.gov.uk/news/2008/080215b.htm. Department for Environment, Food and Rural Aairs: Conrmation of oyster parasite in north Kent. 15 February 2008. [57] http://www.bonamia.com/. BOLCI - Bonamia ostreae life cycle investigations:The Latest Research on the Flat Oyster Disease Bonamia ostreae.
Chapter 17 Moulds and Yeasts

Moulds cause spoilage of food and fodder. Some strains produce mycotoxines such as ochratoxin in coee and in cocoa which spreads out over the entire chocolate market. They cause o avour in food and destroy paper, wood, drugs, cosmetics etc. Moulds can cause allergies and infections. Picture: Moulds spoiling orange crop
17.0.7
Mouldy coee in Trieste
In August 2006 great amount of Robusta coee were found to be mouldy in Triest warehouse. The beans in Trieste are thought to have been damaged by excess moisture on transport. Bags of coee are dumped if they contain more than ve mouldy beans or 10 partially mouldy beans per 500g. 1345
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CHAPTER 17. MOULDS AND YEASTS
17.0.8
Allergies
Allergies caused by moulds however are not so frequent as they seem to be. The most important sources of allergies are: Dogs,cats and other pets as 70% of all allergy cases. Get rid of dogs and cats and you have solved 70% of your problems. House dust, furniture, mites Pollen, grass Trees and shrubs Food with chemical preservatives, lactose, albumen, milk, eggs Odorous substances Moulds as last item of the list of allergenic sources. To avoid mould allergy dont get in contact with cheese like Roquefort , Camembert or Brie cheese. Keep perishable food always refrigerated to reduce mould growth. Dont keep restover of fruits and vegetables in the kitchen. Keep it outside of the house. Keep away from garbage [1].
17.0.9
Fungal meningitis outbreak among patients who received contaminated steroid injections
Fungus contaminated methylprednisolone acetate injections from the New England Compounding Center (NECC) caused more than 300 cases of infections in 2012, including 24 deaths. Fungus causing the infection were Exserohilum rostratum. Aspergillus fumigatus and Cladosporium species. These fungi are common in the environment but were not a recognized cause of meningitis before this outbreak, says CDC and FDA researchers. The onset of symptoms is typically 1-4 weeks following injection, however, it may take more time till onset of symptoms. CDC is recommending voriconazole, which is an eective agent for treating infections due to brown-black molds, such as Exserohilum, as well as infections due to Aspergillus species, and has good penetration into the central nervous system. [2]
17.1
Culture media for moulds and yeasts
Moulds and yeasts spoil foods. It is therefore important to control raw materials and nished. A useful medium is the Yeast Chloranphenicol dextrose Agar. Moulds grow as large
17.1. CULTURE MEDIA FOR MOULDS AND YEASTS
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colonies and are easily identied. Yeasts grow as small colonies, Both types of microorganism can grow with beautiful colors. Moulds can be phytopathogen and can cause serious damage to agriculture. Moulds have also a good side. They produce antibiotica like Penicillin, Cephalosporin and Griseofulvin and many substances in industrial scale such as citric acid, succinic acid, glucuronic acid, and malic acid. Moulds can also be used in the production of polymer such as Pullulan. They are used to produce beta-carotene, enzymes such as amylase glucoamylase, Protease, Lipase, pectinase, cellulase, lactase, catalase some types of cheese, sausages, fermentation of certain food such as soya, rice and corn. Examples of pathogen moulds: Aspergillus candidus: It has slow growth. It produces infections. Citrinin is formed. A. candidus grows down to a pH of 2.1 and aw 0,75. Aspergillus scherianus: A.scherianus can survive 100o C for over 60 minutes ! Aspergillus avus: Aspergillus avus causes broncopulmonary allergy. It grows up to 42 to 45o C . It produces aatoxins B1, B2, G1, G2, sterigmatocystin and other mycotoxins. The toxins are present in peanuts and their products, pistachio nuts and Brazil nuts.In cereals from warm regions (corn,wheat rice) Several brands of dried gs with origin from Turkey and Greece have high amount of aatoxin B1,B2, G1 and G2. The aatoxins which are found on these samples are located in the interior of the fruits. As spoiled gs are detected under UV light as they are packed, only the fruits with mould contamination from inside are not removed and are often eaten despite a high level up to 900 microgram/Kg of aatoxin B1. (Only 2 microgram are allowed). Bad hygienic condition during harvest, drying, transport of gs and weather conditions such as high humidity and high temperatures are the cause of rising mould spoilage. Consumer should look inside the gs and discard those which are dark. [3] Detection of Aspergillus avus and Aspergillus parasiticus Detection of Aspergillus avus and Aspergillus parasiticus For the detection of A. avus and A parasiticus the use of AFPA (Aspergillus avus and parasiticus Agar). Incubation at 30o C during 42-48 hours (not longer). Reading of the plate: A. avus, A. parasiticus, and A. nomius grow leaving orangeyellow color under the colony. Aspergillus niger can produce yellow but not orange color under the colony.
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Aspergillus fumigatus: Grows rapidly. It is present in ower pots, compost, garbage and cereals It grows at a minimum of 10-12o grows best at 37-43o C and as maximum 52-55o C . Conids may survive 60 minutes at 80o C and 10 minutes at 85o C . Aspergillus fumigatus is the most pathogen Aspergillus. It may act as secondary pathogen but also as primary agent. It does not attack the skin, but it causes severe infections of ear, of synus and the respiratory tract (lungs) The temperature optimum of growth is 50o C , but it also grows at 50o C . Its spores are very small. It causes allergies an produces fumigatin Interaction of Aspergillus fumigatus and host during lung infection: Aspergillus fumigatus can be found in hay, soils and compost piles. It may cause invasive aspergillosis in lungs of immunosuppressed hosts. Grahl et al 2011 studied invasive pulmonary aspergillosis in rats adding new understanding of the interactivity of Aspergillus fumigatus and the host.. The authors report that Aspergillus fumigatus is exposed to oxygen depleted microenvironments during infection of the lung tissue by the mould. This reduces the oxygen available to the invading pathogenic mould which respond changing its energy path to fermentation producing ethanol. According to the authors the fermentation cycle of the mould also inuences the host immune response to the pathogen.[4] Aspergillus glaucus : Its growth is quick,it is worldwide spread in nature. It is xerotolerant spoiling food with low water content such as oat akes and dried fruits, food with high amount of sugar such as jam, syrups and sweets, meat products with low water content, such as ham, in cereals ,in breads and pastries.In East Asia Aspergillus glaucus is used for the fermentation of soy and sh products. Aspergillus nidulans: It grows rapidly from 6o C to 48o C and aw-0,80. It is pathogenic and builds Sterigmatocystin It is present in cereals, breads and pastries an wet leather. Aspergillus niger : Black, rapid growing colonies is infectious, allergenic and produces the mycotoxin koji acid . It is present in soil, dust, on cereals and fruits. It is strong lipolytic. It spoils food such as cereals, breads and pastries, meat products, fats, nuts, raisins and onions. It can spoil material such as paper, leather,plastics and paint. In biotechnology Aspergillu niger is used for the production of organic acids and enzymes. Aspergillus ochraceus:
17.1. CULTURE MEDIA FOR MOULDS AND YEASTS Slow growing, produces ochratoxin A. It is present in cereal storehouse, bread, pistachio, salami and ham.
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Ochratoxin Ochratoxin is a mycotoxin which was rst described in 1965 starting from cultures of Aspergillus ochraceus. It stays for long time in blood stream. It is toxic for kidneys being responsible for kidney diseases in pigs from Norway. Aspergillus oryzae: Rapid growing from 7o C to 47o C . It is used for fermentation of many East Asia foods. Aspergillus penicilloides: Very slow growth, pathogenic. It can grow at aw- 0.75. It is present in cereal storehouse. It grows on cereals and meat products with low content of water. Aspergillus tamarii: Rapid growing even at aw 0.78. Aspergillus terreus: It is infectious and produces citrinin and patulin. It is present in cereals and corn,leather and paper. Aspergillus versicolor: It is pathogenic and produces Sterigmatocystin It grows by aw 0.75 and is present on cereals, corn,nuts, rice and meat products. Aspergillus wentii: It is present on salami, ham, barley, leather and nuts. Fusarium culmorum Fusarium oxysporum Microsporum gypseum Penicillium aurantiogriseum: Grows from -4o C to 35o C producing patulin,Penicillin and nephotoxic mycotoxins. It is present on damp or wet cereals.It can create heat up to 64o C . Fusarium bacteria grow at CZID (Czapek Iprodione Dichloran Agar) Penicillium brevicompactum: Allergenic,growing from 12o C to 30o C Penicillium camemberti: Produces mycotoxins cyclopiazon acid, toxic concentrations are not built during the production of camembert cheese.
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Penicillium chrysogenum: Allergenic, produces ochratoxin A, patulin and penicillin. It grows from -4o C up to 33o C it is found in soil and in cereal storehouses, on bread, meat products, very often on leather, fruit juices, nuts and damp stored books. Penicillium expansum: Spoils stored fruits such as apples and decaying plants. It produces citrinin and patulin.In juices there is a rapid decay of taste due to production of acetoinand diacetyl. Active enzymes such as proteases,cellulases, lipases, amylases are build, spoiling leather and other materials. Grows from -6o C up to 35o C Penicillium glabrum: It is frequent and produces various toxins Penicillium hirsutum: Grows on onions and horseradish. Penicillium italicum: It grows with a pH 1.6 up to 9.8 and from -3o C up to 34o C . It is very frequent on citric fruits and all kind of food. Penicillium roquefortii: Produces roquefortine A and B, patulin, festuclavine,emerofortine, cyclopiazon acid and others. Cultures of P.roquefortii sold for the production of cheese do not form cancerogenic substances. It is present in refrigerators, on fat, cereals, sliced bread and juices. Penicillium verrucosum: Produces ochratoxin A, citrinin and penicillin. It is present on cereals, peanuts and vegetables. Penicillium verrucosum grows on DRYS (Dichloran rosebengal yeast extract sucrose agar at 20o C for 7 to 8 days and produces under the colonies a violet color. On DRYS there also can grow Penicillium aurantiogriseum and Penicillium viridicatum producing xanthomegnin and Viomellein Stachybotrys chartarum Thrichophyton mentagrophytes Trichothecium roseum Extreme xerophylic moulds: Extreme xerophylic moulds like Xeromyces bisporum, moulds of the Eremascus genus
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and Erotium halophilicum grow on Malt extract agar+50% Glucose (MY50G) incubating at 25o C for 1 to 3 weeks. A small pice of the sample is placed on the medium. Malt extract agar+70% glucose fructose (MY70GF) The medium contains 35% Glucose and 35% fructose. Incubation at 25o C for 4 weeks. Eroticum spp. shows black conids under a stereo microscope. Heat-resistant moulds Heat-resistant moulds which can produce spoilage are Byssochlamys spp, Talaromyces spp, Neosartorya spp and Eupenicillium in fruit juices , concentrated products and jams. Neosartorya scheri has D88o C = 1,4 min, z= 5,6o C Culture of heat-resistant moulds[5] Adjust the samples at 35o Brix and pH 3,54,0. Heat two 50 ml portions of the sample in water bath 30 minutes at 80o C , cool down quickly. Add double concentrated malt extract agar to the portions and distribute it in Petri dishes. Incubate at 30o C for 30 days. Readings should be made weekly. If bacteria may be present add 100 mg/l chloramphenicol. Colonies of Penicillium and Aspergillus growing on the dishes come from a contamination during handling of the samples as they can not resist heating up to 80o C . Table 17.1: Special moulds and their importance Gliocladium species Isaria species Paecilomyces species Destroys paper, may be present in fuel. Pathogen to insects. grows very quickly, infectious. Produces mycotoxines such as patulin and Byssochlamin acid in fruit and juices.The ascospores resist Temperatures up to 85o C during 30 minutes 96o , the plant must be dismantled to get rid of Paecilomyces. grows quickly,sometimes pathogenic. pH optimum 9 - 10,grows in tilsit cheese and camembert cheese and meat and derivates Produces trichothecenes and T-2-toxin grows at pH 2.5 up to 9.5 and can
Scopulariopsis brevicaulis
Trichoderma species
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CHAPTER 17. MOULDS AND YEASTS grow on sour food, is found an corn, rice and wheat.
Verticillium species
pathogenic for plants.
Botrytis cinerea: Spoils fruits on trees. Chrysonilia sitophila: Produces contamination in laboratories. Often associated with bakers asthma Mucorales: Mucorales have a rapid growth within 2 days. The best growing temperature is 37 to 41oC. It produces gas even under vacuum.Mucorales have a broad variety of enzymes such as: -alfa-amylase,glucoamylase and cellulase. -Pectinase -Protease -Lipase -Esterase Important genus of Mucorales are: -Mucor -Rhizopus -Absidia -Phycomyces
There are many types of Candida,some important genra are cited below Candida albicans: Can produce gastrointestinal infections. Candida glabrata Candida krusei: It is less pathogenic as C.albicans. Candida catenulata Candida colliculosa Candida dattila Candida famata
17.1. CULTURE MEDIA FOR MOULDS AND YEASTS Candida guillermondii Candida inconspicua Candida Kephyr,also named Candida pseudotropicalis. Candida lipolytica Candida norvegiensis Candida pelliculosa Candida rugosa Candida sake Candida tropilalis Candida utilis
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17.1.1
Selective culture of Candida albicans
The selective culture of Candida albicans uses Merck Fluoroplate Candida -Agar (1.11011) . It is a modied SABOURAUD with the addition of uorogene substrate (MUGal) which can be hydrolysed by the enzyme Galactosaminidase resulting a uorescent compound. 99% of Candida albicans bear this enzyme. Incubate at 37o C for 2-3 days. Read the plates under UV light. All uorescent colonies are Candida albicans.
17.1.2
Candida albicans ID
Another selective and chromogenic medium for identication of Candida albicans is the albicans ID medium bio Mrieux Nr.43 121 citealbicans
Table 17.2: albicans ID medium Ingredient bio-Thione Yeast extract Monopotassium phosphate Dipotassium phosphate Chromogen substrate (hexosamine) ADA butter Amount for 1.000 ml 2,00 6,00 0,5 0,5 0,05 0,6 g g g g g g
1354 Gentamicin sulfate Chloranphenicol Agar pH 6.6 0,10 g 0,05 14,00 g
Albicans ID is a medium to isolate yeasts and immediately identify Candida. Colonies of Candida albicans grow as blue colonies on Albicans ID medium due to hydrolysis of hexosaminidase chromogen substrate. The two antibiotic which are present in albicans ID inhibit the bacterial ora. The buer system of the medium facilitates the growth of yeasts and optimizes the enzyme reaction. Albicans ID medium is used to detect yeasts by direct inoculation of pathological specimens (buccal, vaginal, rectal swabs,feces, scales, pus, urine. It should also be suitable to control food), Reading of the culture is made after incubation at 30 to 37o C for 24 to 48 hours. The colonies have a round, smooth,slightly domed shape, with a clearly dened border, and blue coloration. This coloration does not diuse into the medium and turns from pale to dark blue depending on the incubation time.The size of the colonies is 0.5 to 1.5 mm. Other yeast species have a creamy-white color and the size is 0.25 to 2 mm. A complete biochemical identication should be carried out if required. Albicans ID medium must always be stored and incubated in the dark. Some strains of yeasts such as Saccharomyces cerevisiae and Cryptococcus neoformansgive small colonies and require an incubation of more than 48 hours. A small percentage of Candida tropicalis strains give blue colonies within 48 hours. Certain strains of Trichosporon cutaneum can give cotton-like bluey-green colonies, which can be easily dierentiated from Candida albicans colonies. More attention should be payed to Candida albicans on bacteriological control of food as this yeast can cause diseases of the intestinal tract. The Fluoroplate Candida-Agar contains chloranphenicol and gentamycine to inhibit accompanying bacteria. The isolation can be made directly from faecis or vaginal samples. Moulds attack human when there is a lesion such as burns, frost, injuries, immuno insuciency, serious diseases such as tumor, diabetes, leucosis, transplantations, use of immunosupresives, therapy with antibiotic.
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17.1.3
Growing conditions
Molds can grow at a wide rage of temperature:
Table 17.3: Mesophylic moulds Growth of mycelium Temperature optimum growth of mycelium 25-30o C maximum growth of mycelium 30-40o C As example Penicillium optimum 20-25o C As example Aspergillus optimum 25-35o C Table 17.4: Thermotolerant moulds Minimum growth of mycelium optimum growth of mycelium maximum growth of mycelium As example Mucorales optimum 0o C 30-40o C 50o C 30-41o C
Some moulds may grow under 0o C , such as Chladosporium growing at -6o C .
Table 17.5: Thermophile moulds Minimum growth of mycelium optimum growth of mycelium maximum growth of mycelium As example Rhizomucor pusillus 25o C 35-45o C 55-60o C
Temperatures for best production of toxins dier often from growth optimum Spores and sclerotias can survive high temperatures. Only molds which can grow at 37o C can cause a systemic mycose.
Table 17.6: pH and growth of moulds pH-optimum pH-maximum in the majority 4.5 - 6.5 8.0 Exceptions are 9.8 - 10.5 for: Aspergillus niger, Penicillium italicum,
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Aspergillus avus. pH-minimum for growth of moulds 2.0 and below Table 17.7: Oxygen and growth of moulds Moulds are aerobic They grow however also as microaerobic Many Mucorales can produce fermentation. Increasing CO2 reduces growth of many moulds. At the same time reducing oxygen stops completely growth of molds on fruits.
17.1.4
Culture and microscopy of moulds
The morphology of colonies vary with the culture media employed, age of the culture, the species and the temperature of incubation. Preparations for microscopy should be made with 50% alcohol because moulds are not water soluble. Dont use very old colonies because only spores are present.
17.1.5
Black moulds
Black moulds have their color due to melanin in their mycelium. They are UV-resistant and very frequent in the environment. They destroy materials and spoil food. They are potential allergens.
17.2
17.2.1
Determination of yeasts and moulds

Optimal media for the determination of yeasts and moulds
Wort agar and Malt extract agar
17.2.2 17.2.3
Selective media DRBC (Dichloran-Rosebengal-Chloramphenicol-agar)
. This culture medium is suitable for fresh food with high water activity. It contains 25 ml/l Rosebengal and 2 mg/l Dichloran. Culture on surface and incubation at 25o for 5 days.
17.2. DETERMINATION OF YEASTS AND MOULDS
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17.2.4
DG 18 (Dichloran 18% glycerol agar)
This medium is suitable for xerophile moulds from cereals, nuts, our and spices.
17.2.5
OGY (Oxytetracyclin glucose yeast extract agar
This medium is suitable for determination of yeasts and moulds simultaneously.
Table 17.8: Culture media for yeasts and moulds, according Baumgart Fresh food moulds yeasts yeasts and moulds Nuts,cereals yeasts and moulds yeasts xerophile yeasts yeasts and moulds yeasts molds xerophile aatoxins DRBC TGY MEA, OGY DRBC on surface pourplate
DRBC
on surface
Fruit juice Concentrated fruits Dried food
TGY, MEA, OGY MY50G
pourplate pourplate
DG18
on surface
dried fruits and chocolate
MY50G
on surface
All samples on surface or All samples
AFPA pourplate
Ochratoxin
DRYS
on surface or pourplate
DRBC= Dichloran-Rosebengal-Chloranphenicol-Agar TGY= Tryptone glucose yeast extract agar MEA= Maltextract-agar OGY= Oxytetracyclin glucose yeast extract agar MY50G = Malt extract agar, 50% glucose DG18= Dichloran, 18% Glycerol
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AFPA= Aspergillus avus parasiticus agar DRYS= Dichloran rosebengal yeast extract saccharose agar
17.2.6
Contamination of cereals with Fusarium graminearum and Fusarium culmorum
According to a denition of the food regulation of the EU cereal grains are to be classies as unusable when : Mycotoxines are present. The value of the grains is reduced because of bacterial activity. There are changes of smell and color Bacterial count is high Tolerated by EU regulation are 0,5% of grains with black Fusarium contamination.
17.2.7 17.2.8
Trichotecene Zearalenon
Zearalenon is a mycotoxin which can be present in animal feed and can cause be found in muscles and organs of animals with destination as human food.
17.2.9 17.2.10
Citrinin Patulin
Patulin is frequently produced by Penicillium expansum on fruit juices when sterilization is using spoiled fruits. Very important for the production of juices is to select rotten and mouldy fruits on the transportation belt, use fresh and not contaminated water, a brush station for some kind of fruits. extreme care should done to keep all machines and the surroundings always clean to avoid the growths of bacteria and moulds. Be always aware that the bacteria and moulds can be killed by sterilization, the poisons such as patulin however are not inactivated by heat.Quality and safety of food depend on careful handling through the whole production process. Pasteurization of fruit juicesshould be done at 60 to 90o C , orange juice at 85 to 90o C for several minutes. Enzymes such pectin esterase are also inactivated during this procedure. Yeasts which can spoil wrong treated juices are Candida, Cryptococcus, Hanseniaspora, Rhodotorula and Saccharomyces cerevisiae Common moulds on fruit juices are Geotrichum, Mucor, Penicillium and Phialophora.
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Fruits as raw ware for juice industry should have not more than 2 X 106 yeasts and not more than 2X 105 moulds/g otherwise alcohol and toxic products are formed.[6]. Talaromyces trachyspermus, Talaromyces avus and Neosartorya scheri are moulds which may develop heat resistant organisms an may spoil juices during storage. In storage tanks dripping water from condensation may dissolve the juice at that point making it possible for moulds and yeasts to grow. Green colonies may be the result of growth of Penicillium expansum, black colonies of Aspergillus niger. One percent of N2 of the atmosphere of storage tanks may be useful to avoid growing of moulds. Bottles and other packaging materials should have less than 1 mikroorganism/cm2 . Layer yeasts such as Candida boidinii,Candida intermedia, Candida parapsilosis and Debaryomyces hansenii produce a slimy yeast skin.
17.2.11
Measures to reduce the risk of contamination of juices with yeasts and moulds
Use good raw material, not spoiled, with low bacterial count. Look out for proper cleaning and disinfection of the equipment. Avoid underheat of the juice. Use 2% of N2 or CO2 in the atmosphere of storage tanks. Cool storage tanks down to 2o C . Avoid dripping of condensation water in storage tanks. Use bacterial lter on air inlet of tanks.
17.2.12
Ryegrass staggers
[7][8] Feed grass such as lolium (Lollium perenne which grows in North America and Australia also called "English ryegrass" and festuca (such as Festuca ovina) may have a symbiotic community with a mould which rises the vitality of the gras, reducing drought damage and resistance to various pests. The mould may produce under certain weather conditions alkaloids such as lolitrem B which may have an adverse eect on the cattle.This toxicosis is called "ryegrass staggers" and is common in North America and in New Zealand and in some cases also in Europe.
17.2.13
Moulds and bacteria found in spices
Spices grow in tropics and subtropics and are therefore submitted to ideal temperatures and humidity conditions for the growth of bacteria and moulds.
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17.2.14
Lactic acid bacteria against Fusarium mycotoxins
[9] According to Biotechnology Ireland the study of specic lactic acid bacteria (LAB) may help to reduce Fusarium mycotoxins and ochratoxinin in grain production. New legislative requirements for the reduction of mycotoxin content in cereal-based products demand for alternative methods to prevent mould growth. Scientists at the University College Cork are screening food grade la
17.2.15
Yeasts
[10] For practical purposes, yeasts may be dened as unicellular fungi in which assexual reproduction occurs mainly by budding. Budding was dened by von Arx 1979, as a type of conidiation and the buds are blastoconidia. Yeasts are characterized, classied and identied traditionally by morphological, physiological, and biochemical criteria Yeasts area phylogenetically diverse group of fungi. Their sexual states (teleomorphs) can be classied among two major fungal classes, the Ascomycetes and the Basidiomycetes. A classication should also consider genetic similarities and dierences. The application of molecular biology has already made a large impact on the systematics of yeasts. Yeasts are generally unicellular, some may, however, develop hyphae or pseudohyphae. True hyphaelack constriction at the cross walls, pseudohyphae cells are formed by budding and elongation. [11]
17.2.16
Yeast-like organis
Buds arising from true hiphae. Hyphae may separate into arthoconidia. Both lamentous forms are collectively called yeast-like organism. Growth temperature Most yeasts do not grow under 0 o C , psychrophilic can grow at temperature which go down to -7o C . Freezing and subsequent thawing can cause loss of viability. Lethality is reduced when cells are rapidly frozen and rapidly thawed. The degradation of membrane phospholipids and cell water permeability may cause the death to yeast cells subjected to freezing and thawing. [12] [13]
17.2.17
Novel yeast species
A novel yeast species (Saturnispora quitensis) was isolated from the fruit of an unidentied species of bramble (Rubus sp.), collected from a forest reserve, near Quito, in Ecuador. Genetic sequency presented close relationship to Saturnispora hagleri, a Drosophila-associated
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yeast found in Brazil. The research was made by James et al. 2011 of the National Collection of Yeast Cultures at the Institute of Food Research in Norwich, and Professor Javier Carvajal of the Ecuadorian team from the Coleccin de Levaduras Quito. The yeasts collection at the institute is used for bread, brewing and other biotechnological applications. [14] Two new yeast species, Wickerhamiella pagnoccae sp. nov. and Candida tocantinsensis sp nov., were isolated by Barbos et al 2011 from the nectar of ower bracts of Heliconia psittacorum collected in a Cerrado ecosystem of the state of Tocantins, Northern Brazil. The authors found Wickerhamiella pagnoccae sp. nov. closely related to Candida jalapaonensis. [15]
17.2.18
New yeast strains Candida uthaithanina sp. nov. identied in Thailand [16]
Limtong et al. 2011 describe three yeast stains isolated from fruits in Thailand: Strains DD2-22-1(T) and SK44 and moss (strain ST-449) in Thailand. According to data of gene sequences the three strains belonge to the same species. The three strains were assigned to a single novel species of Candida, for which the name Candida uthaithanina sp. nov is proposed. The type strain is DD2-22-1(T) (= BCC 29899(T) = NBRC 104876(T) = CBS 10932(T)).
17.2.19
Issatchenkia orientalis (Candida krusei) [17]
Issatchenkia orientalis (Candida krusei), a contaminant of bakers yeast. Candida krusei is also known as fungal pathogen. In chocolate production Candida krusei, Geotrichum candidum and Acaulospora scrobiculata are used to ferment cacao beans. This process removes the bitter taste and break down the pulp. During the fermentation acetic acid is also produced, killing the cacao embryo of the seed, and the typical chocolate aroma evolves.
17.2.20
Fermentation technology
[18] Yeast fermentation technology comprises the production of bread, wine, beer, cheese and other dairy products. Specic microorganisms present desirable properties such as bacteriocin production, and probiotic properties produced mainly by yeasts and lactic acid bacteria. Fermentation improves the avour, aroma and texture and increase the nutritional quality. Starter culture technology can be used for the control of the manufacturing operation, and management of product quality. Plessas et al. 2011 reviewed these new trends in fermented food products focusing in ker grains and bread production.
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Bautista-Gallego et al. 2011 assessed the yeast populations associated with table olive production analysing the of the 5.8S-ITS region and sequencing of the D1/D2 domains of the 26S rDNA gene. The authors found two isolates of Wickerhamomyces anomalus with a strong beta-glucosidase and esterase activity, and a moderate catalase and lipolytic activity. These yeasts might be important for starters, alone or in combination with lactic acid bacteria, to improve olive processing. [19] Aroma compound production of important yeast strains such as Saccharomyces ( Saccharomyces cerevisiae, Saccharomyces uvarum Saccharomyces kudriavzevii) and hybrids were analysed by Gamero and colleagues 2011. The authors stress that de novo synthesis by yeasts aects some lipid derivatives, shikimic derivatives and terpenes including varietal aroma compounds, such as gama-lactones, benzenoids, volatile phenols, vanillin derivatives and terpenols, inuencing the modulation of wine aroma depending on the used yeast species. [20] Mendoza and colleagues 2011 proposes the inclusion of Kloeckera apiculata mc1 as an adjunct culture to Saccharomyces cerevisiae mc2 to improve organoleptic properties of red wines. Oenococcus oeni X(2)L should be added after completion of the alcoholic fermentation to enhance sensory characteristics. [21]
17.2.21
Oil producing yeasts
[22] Some yeasts, such as Lipomyces starkeyi, Rhodosporidium toruloides, Rhodotorula glutinis, and Yarrowia lipolytica present advantages over microalgae in the production of oil. According to Ageitos et al. 2011 the duplication times of yeasts are lower than 1 h, they are less dependent on season or climate conditions, and their cultures can be easily scaled up, and some yeasts may accumulate oil up to 80% of their dry weight. Yu and colleagues 2011 demonstrated the production of oil by the yeast Cryptococcus curvatus using dilute sulfuric acid pretreatment of wheat straw. The hydrolysate was composed of sugars, along with acetic acid, furfural, and hydroxymethylfurfural. Cryptococcus curvatus showed the highest lipid concentrations with insignicant impacts caused by hydroxymethylfurfural while furfural inhibited cell growth and lipid content up to 72
17.2.22
Sourdough fermentation
[23] Vrancken et al. 2011 found that increased expression of genes involved in peptide and amino acid metabolism and genes involved in plantaricin production and lipoteichoic acid biosynthesis cellular mechanism allow Lactobacillus plantarum to function at low pH values of sourdough environment.
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17.2.23
Fructose increases yeast ageing
[24] Semchyshyn et al. 2011 found that fructose media resulted in more pronounced agerelated decline in yeast reproductive ability and higher cell mortality compared with yeast cells grown on glucose The authors draw their conclusions on viability and markers of carbonyl/oxidative stress data. Yeast growing on fructose has higher levels of carbonyl groups in proteins, alfadicarbonyl compounds and reactive oxygen species resulting in increased age-related decline in yeast reproductive ability and higher cell mortality.
17.2.24
Candida albicans
Yeasts are mainly known to have impact on food spoilage, formation of haze, sediment and o-avour in carbonated drinks and juices, as well as bulging cans and exploding bottles. There are, however, some yeasts which are pathogen to humans such as Candida albicans. Candida albicans can be diagnosed by the formation of germ tubes and clamydospores. Candida albicans can be found in foods such as soft drinks, must, wine and others. Candida tropicalis is also present on food and should be diferentiated from Candida albicans.
17.2.25
Dierentiation of Candida albicans and Candida tropicalis

sucrose + maltose + +
Yeast Candida albicans Candida tropicalis
17.2.26
Molecular biology and Classication
Studies on DNA base composition, nuclear DNA homology, and sequences of ribosomal RNA are used to elucidate the degree of relatedness and evolutionary relationship of yeasts. These methods, however cannot be easily applied in routine identication procedures, therefore, the classication of yeasts is still primarily based on characteristics of sexual reproduction. The species Saccharomyces cerevisiae, for instance, described by Hansen in 1888, suered important changes and in 1985 , 1987 and 1989 Vaughan-Martini and Kurtzman separated the genus Saccharomyces in four genra: S. cerevisiae, S bayanus and S. pastorianus which are used in industrial fermenting. A fourth genus S. paradoxus has no relation to alcoholic fermentation. [25] [26] [27] [28]
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17.2.27
Saccharomyces cerevisiae
Is the leavening of bread and the fermenter of alkoholic beverages. Saccharomyces cerevisiae has one or more genes coding for alfa-glucosidase and maltose permease.
17.2.28
Chalky bread
Yeasts and yeast-like organisms may develop white spots in the crumb, which is called chalky bread. According to Spicher (1986), envolved in chalky bread are Endomycopsis buliger, Pichia burtonii, Zygosaccharomyces bailii, Saccharomyces cerevisiae, Torulaspora delbrueckii, Pichia membranaefaciens and Candida parapsilosis. [29] [30]
17.2.29
Spoilage of soft drinks
Spoilage of carbonated soft drinks are most frequently being caused by Saccharomyces cerevisiae and Saccharomyces pastorianus. Contamination most often results from incorrect sanitation of processing line which includes, holding tanks, proportioning pumps and bottle washers. Gas production may be very heavy leading to the explosion of the bottle. [31] [32]
17.2.30
Wine, Beer and distilled spirits
Crushed grapes which stand on the start of the production line of wine contain species like Hanseniaspora uvarum, Candida stellata, Issathenkia orientalis, Metschnikowia pulcherrima and Pichia anomala. [33] [34] According to Fleet a denite succession of yeasts takes place during the fermentation under the inuence of growing alcohol. The non-Saccharomyces species die o with an increase of ethanol content. These yeasts are more tolerant to alcohol at lower fermentation temperatures [35] The population of yeasts in the fermentation phase depends on the variations in the ecosystem of dierent vineyards. Hanseniaspora uvarum in Middle-Europe, Japan and California whereas Hanseniaspora osmophila in warmer regions like Italy, Israel or Southern US. Dominate the early fermentation. [36] According to Martini Kloeckera apiculata initiates fermentation and is followed by Saccharomyces cerevisiae. [37] As ethanol concentration rises between 2 to 6% wild yeasts die and Saccharomyces cerevisiae dominates till the fermentation is complete. Inoculating strains of Saccharomyces cerevisiae at the beginning of the fermentation does not change this sequence. [38] After the fermentation any further yeast activity harms the quality of the product. Yeasts are therefore removed by racking, ltration and other cellar. Dekkera species, Saccharomycodes ludwiglii may impair avour of bulk wine. Candida vini, Candida zeylanoides,
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Candida rugosa, Issatchenkia orientalis, and Pichia membranaefaciens are responsible for spoilage of wine in tanks and in wooden barrels. They are lm-forming species. [39] [40]
17.2.31
Spoilage of bottled wines
Bottled wines, according to Minarik, are often spoiled by Zygosaccharomyces bailii (considered as the main cause of spoilage), Saccharomyces cerevisiae, Candida rugosa, Pichia membranaefaciens and Candida vini. Activity of these yeasts cause cloudy appearance, sediment and poor avour. [41]
17.2.32
Beer
Lager beer is fermented by Saccharomyces pastorianus. This strain is a bottom fermenter and produces alfa-galactosidase, hydrolysing melibiose and ranose. The fructose part of the ranose molecule is fermented. The yeasts occulate and settle on the bottom of the fermenter. Fermentation takes place only up to 34o C . Ale beer is being produced with Saccharomyces cerevisiae which is unable to ferment melibiose and only the fructose part of the ranose molecule is fermented. It tends less to occulate than S. pastorianus. Fermentation of sugars takes place up to 38o C . [42]
17.2.33
Silage
Silage is an important part of animal feed in northern regions. It is a product of a lactic acid fermentation. Yeasts may cause alcoholic fermentation. According to Engel, the most frequent yeasts which may spoil silage are Pichia fermentans, Issatchenkia orientalis, Saccharomyces cerevisiae and Geotrichium candidum [43] [44]. These yeasts assimilate lactic and acetic acid, resulting in silage spoilage if exposed to oxygen of air.
17.2.34
Fermentation of cocoa beans
Yeasts, together with lactic acid bacteria present the traditional cocoa fermentation process for removing the mucilaginous pulp around the seed. Sanches found the following species of yeasts to be involved in this process: Hanseniaspora uvarum, Saccharomyces cerevisiae, Pichia membranaefaciens, Pichia fermentans and Issatchenkia orientalis.[45]
17.2.35
Yeasts identication methods
[46] Various systems of identication of food-borne yeasts have been developed. Deak compared three yeast identication methods: The Simplied Identication Method (SIM) (identifying 91% of the samples correctly), the commercial kits, the Analytab API 20X (86% correct identication) and the BioMerieux Vitek Yeast ID 32C strips(76% correct identications).
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Discrepant test reactions and errors in the database had caused the false identications. Whereas, the accuracy of individual test were high with discrepant results of 1,6%, 2,5% and 1,7% respectively. Deak notes, therefore, that with a supplement of a few tests, the described commercial kits can be easily applied to the SIM database. Other commercial systems for the identication of food-borne yeasts are Minitek, AutoMicrobic, ATB 32 ID YeastIdent. Based on foregoing experiences Deak suggests a revised SIM version which includes 99 of the most common food-borne yeasts, and 30 tests are applied. In the SIM key, great reliance is given to sugar and nitrogen assimilation tests. As the keys uses tests in which yeasts give 85% to 100% unequivocal responses, a certain probability exists that the results do not t the identication scheme. The author stresses therefore that species identication should never be based only on those features included in the keys.
17.2.36
DNA identication
A technique revealing restriction fragment length polymorphism (RFLP) have been used in taxonomic evaluation of yeasts. It is based on the activity of restriction enzymes which generate numerous fragments of variable length, resulting in characteristic banding patterns. Degr found that DNA ngerprinting, using RFLP found it to be the most reliable method to identify brewers yeast strains. [47] Casey, however, using RFLP, could not dierentiate ale from bakers yeasts and concluded that RLFP pattern not to be suitable as an universal method to identify dierent strains within the same yeast species. [48].
17.2.37
Electrophoretic Kariotyping
Electrophoretic Kariotyping determines the chromosomal number and size which can be achieved by electrophoretic separation of whole chromosomes in agarose gel. Trk used whole chromosomes from yeasts as templates for probe preparation to distinguish between closely related yeast species. [49] [50]
17.2.38
DNA Probes and PCR Amplications
The PCR technique and specic probes are promising as reliable and rapid molecular methods for the identication of yeasts.
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17.2.39
Protein Elektrophoresis
Soluble protein electrophoresis using polyacrylamide gel, sometimes with sodium dodecyl sulfate was used by Bruneau and Giunet to identify medical important yeasts. [51] Degr, however, found contradictory results using this technique depending on growth conditions. Degr concluded that the reproducibility of protein and fatty acids patterns requires rigidly standardized methods. [47]
17.2.40
Fatty acid Analysis
It uses gaschromatography of cellular volatile fatty acids. A commercial identication system of fatty acids from yeasts has been developed by MIDI. [52] Augustyn, however, using the fatty acid analysis technique, could not dierentiate between Saccharomyces cerevisia, Saccharomyces bayanus and Saccharomyces pastorianus, important for the beer and wine brewery. [53] Rozes found that the method has potentials for distinguishing fermenting wine yeasts from spoilage yeasts. [54]
17.2.41
Humanised yeast cells
[55] [56] In 2000 Tillman U. Gerngross co-founded GlycoFi, Inc., base in Lebanon, It is a company pioneering the "humanization" of yeast and fungal protein expression systems. Professor Gerngross research examines both the macroscopic and the microscopic scale of biotechnology. Protein-based therapies have to be manufactured by living cells, which are genetically engineered to produce a given protein of interest often requiring the attachment of sugar structures (glycosylation). This could only be performed in mammalian cells. Human glycosylation can now take place within a yeast cells of Pichia pastoris, eliminating the need for mammalian cells. The new technique reduces the risk of contamination by pathogens and infectious agents. According to Stephen Hamilton from GlycoFi, humanizing the glycosylation in yeast required the silencing of four yeast genes and the introduction of over 14 heterologous genes. With this engineered yeast some glycoproteins were produced such as erythropoietin, used to treat anemia, and other glycoproteins such as antibodies with improved anti-cancer properties.
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The study details the genetic engineering of the yeast to secrete human glycoproteins with fully complex, terminally sialyated N-glycans. The authors conclude that the ability to generate human glycoproteins with homogeneous N-glycan structures in a fungal host is a step toward producing therapeutic glycoproteins and could become a tool for elucidating the structure-function relation of glycoproteins. According to Y. Ma and colleagues, Pichia pastoris is already being used to elaborate the human adenovirus type 5 (Ad5) early-region 1A (E1A) proteins which have strong tumor-suppressive activities in human tumor cells. The authors stress that the E1A protein overcame the limitations of gene therapy and may be a useful therapeutic agent for some malignant tumors. [57]
17.2.42
Identication of yeasts
[58] Identication can be performed either phenotypically usind fermentation reactions of sugars or growth on carbon and nitrogen sources or other compounds. These characteristics can vary, depending the physiological state of the cell. Molecular biology techniques are independent of the state of the cell as they analyse the genome of the cell. The nucleotide sequences of the domains D1 and D2 located at the 5 end of gene 26S (Kurtzman and Robnett, 1998) and PCR amplication of ribosomal DNA regions and restriction of the gene 5.8S rRNA gene and the adjacent intergenic regions ITS1 and ITS2 are the molecular methods commonly used for the identication of yeasts (Fernandez-Espinar et al.,2006). These techniques are more reproducible and faster that the conventional methods based on physiological and morphological characteristics. [59]
17.2.43
Yeast pathogenic for humans
[60] The principal yeasts pathogenic for humans are Candida albicans and Cryptococcus neoformans which cause a range of mucocutaneous, cutaneous, respiratory, central nervous, systemic and organ infections. Usually, healthy, immunocompetent individuals are not at risk of such infections. Generally, individuals with weakened health and immune function are at greatest risk, and include cancer and AIDS patients, hospitalised patients and patients who are administered immunosuppressive drugs, broad-spectrum bacterial antibiotics and radio- and chemotherapies. This includes species that are frequently found in food such as Candida krusei/orientalis, P. anomala, Kluy. marxianus, S. cerevisiae and various Rhodotorula.
17.3. EFSA QUALIFIED PRESUMPTION OF SAFETY (QPS) OF YEASTS
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17.2.44
Cryptococcus gattii, a pathogenic yeast
[61] Cryptococcus gattii, formerly known as Cryptococcus neoformans var gattii, is an encapsulated yeast found primarily in tropical and subtropical climates. It causes the human diseases of pulmonary cryptococcosis, basal meningitis, and cerebral cryptococcomas. Occasionally, the fungus is associated with skin, soft tissue, lymph node, bone, and joint infections. The infection is caused by inhaling spores. The fungus is not transmitted from person to person or from animal to person. A person with cryptococcal disease is not contagious. Human infections by Cryptococcus gattii are found in Papua New Guinea, Northern Australia. British Columbia, Canada, Brazil, India and the Pacic. The fungus also infects animals, such as dogs, koalas and dolphins. Cryptococcus gattii spreads to Oregon and Washington. The highly virulent strain VGIIc is related to a high mortility. Macdougall 2010 reports that had the largest number of infections with Cryptococcus gattii worldwide. The most frequent ailments were respiratory illness or lung cryptococcoma. The older persons, and those who had central nervous system disease. [62] Cryptcoccus gattii may infect healthy persons, however several immunosuppressive and pulmonary conditions seem to be risk factors, such as oral steroids, pneumonia, and other lung conditions, age of 50 years and higher, current smokers, infected with HIV, or have a history of invasive cancer were associated which increased number of infections.
17.2.45
Cryptococcus gattii ability to survive in human body
To cause infection in humans, Cryptococcus gatti must have a gene that encodes the Cryptococcus gatti calcineurin A catalytic subunit. Calcineurin is a serine-threonine specic phosphatase that is activated by Ca(2+)-calmodulin and is involved in stress responses in yeasts. Odom and colleagues 1997 found that calcineurin A is a basic requirement for Cryptococcus gattii to survive in the host at 370 C and factor for the pathogenicity of the organism. [63] The ability to survive and proliferate at the human body temperature is controlled in part by the Ca(2)-calcineurin pathway, which senses and utilizes cytosolic calcium for signaling. Kmetzsch and colleagues 2010 identied the Cryptococcus neoformans gene VCX1, which encodes a vacuolar calcium exchanger and acts in parallel with calcineurin. [64]
17.3
[60]
EFSA Qualied Presumption of Safety (QPS) of Yeasts
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17.3.1
Candida
The genus Candida comprises 163 species, of which around 60 species are present in food. Only a small number of Candida are used in food processing, as biocontrol agents such as C. glabrata is used to control lamentous fungi in plants. The list of species that are commonly used in the food industry include: C. zelanoydes, which contributes to the avour and texture during the maturation of cheese and in the production of fermented milks (ker and koumiss), C. milleri for avour and rheology in sourdough breads, C. tropicalis, C. parapsilopsis produces skin lesions and C. pelliculosa, which occur in the wet fermentation of coee, C. etchellsii and C. versatilis, which contribute to the avour of soy sauce, C. rugosa, which is involved in cocoa fermentations, C. utilis (=P. haidinii) and C. maltosa, which are used for biomass production from carbohydrate and hydrocarbon substrates respectively, C. oleophila and C. sake, which are commercialised for use as fungal biocontrol agents.
17.3.2
Pathogenic Candida spp.
The principal human pathogenic yeasts are species of Candida, such as C. albicans, C. glabrata , both as most frequent pathogenic yeasts. C. guilliermondii, C. krusei, C. lusitaniae, C. parasilopsis, C. tropicalis produces deep seated micoses, C. viswanathiin and new emerging pathogen is C. dubliniensis. The Candida genus is not suitable for QPS status, as more species are today considered as emergent pathogens.
17.3.3
Debaryomyces
The genus Debaryomyces comprises 15 species. Many representatives can be isolated from natural habitats such as air, soil, pollen, tree exudates, plants, fruits, insects, and faeces and gut of vertebrates. Nine of these Debaryomyces species: D. carsonii, D. etchellsii, D. hansenii, D. maramus, D. melissophilus, D. polymorphus, D. pseudopolymorphus, D. robertsiae and D. vanrijiae, have been found in a variety of processed foods; such as fruit juices and soft drinks, wine, beer, sugary products, bakery products, dairy products and meat or processed meats. The presence of Debaryomyces species in foods usually has no detrimental eects and in some cases is benecial to the food. Some Debaryomyces species are important in the ripening of fermented food products such as cheese and meat products. Where D. hansenii is used in the ripening of cheeses they metabolise lactic acid, raising the pH to allow the growth of proteolytic bacteria, and the yeast exhibits lipolytic activity that contributes to the development of cheese aromas.
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Proteolytic and lipolytic activities of D. hansenii have been described in the curing of ham and ripening of sausages and their presence in salami inuences the red coloration and improves the quality of the product. Nevertheless, excessive growth of Debaryomyces species may cause undesirable sensory changes due to the formation of o-odours and o-avours. These species have also been found as frequent contaminants of spoiled yoghurts, ice creams, sh, shellsh, etc. Very often, fungi have got two forms : the sexual form (teleomorph) is considered as perfect while the asexual form (anamorph) is considered as imperfect form. The Fungi imperfecti are only known by their asexual form (Conidia). [65] The main species of Debaryomyces used in food processing is D. hansenii, the anamorph form of which is Candida famata. C. famata has been repeatedly associated with catheterrelated bloodstream infections, and occasionally with infections of the central nervous system. The reservoir of C. famata is not known but there is a possibility that nosocomial infections can occur via air contamination (Wagner et al., 2005). No studies on antifungal susceptibility of Debaryomyces are available. It is proposed to grant D. hansenii QPS status.
17.3.4
Hanseniaspora
The species are most frequently isolated from soil, fruits and plant exudates, grapes and processed fruit. Hanseniaspora uvarum is important in the rst phase of grape fermentation and play a role in the production of certain avours benecial for the quality of wine and cider. Little is known regarding the other species.H. uvarum is proposed for QPS status.
17.3.5
Kluyveromyces
There are six species present in this genus.The most important are K. lactis and K. marxianus (anamorph C. kefyr) for their capacity to ferment lactose. This microorganism can be isolated from milk products and is used as a starter to set up the medium for cheese and ker production. Kluyveromyces marxianus and K. lactis are associated with smear-ripened cheeses and contribute to the aromas that cheeses develop. These species are considered to be generally regarded as safe organisms and have been approved as a food additive. Kluyveromyces is used in animal feeds in Europe as a probiotic and is apparently safe (reviewed in Anadon et al., 2006). Candida kefyr, the anamorph of K. marxianus, has occasionally been involved in opportunistic infections in immunocompromised persons. However, considering the history of
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apparent safe use and the rarity of infections in humans, there are no safety concerns. It is proposed to grant K. lactis and K. marxianus QPS status.
17.3.6
Pichia
Yeasts of the genus Pichia are widely distributed; they can be found in natural habitats, such as soil, freshwater, tree exudates, insects, plants and fruits, and also as contaminants in a variety of foods and beverages. Some Pichia species contribute desired eects in the early stages of wine fermentation, several types of brines, and dierent types of cheeses; while others have been described as human pathogens (Bakir et al., 2004; Otag et al., 2005). Pichia currently contains 91 species with 30 being related to food production and processing, the majority of them are spoilage organisms. The genus contains the species previously encompassed in the genus Hansenula, which is reported to be one of the safest microorganisms; it is used by the WHO for the development of vaccines and as a producer organism such as phytases. The main species are P. anomala (previously Hansenula anomala) and P. angusta (previously Hansenula polymorpha). P. anomala is also used for the fermentation of bakery products, while P. roqueforti is used as a post-harvest biocontrol agent for wheat and barley, or for food application in olive fermentations. Some species of Pichia are used for feed (source of proteins) and production of glucan for feed. It is proposed that P. angusta and P. anomala have QPS status.
17.3.7
Saccharomyces
These species are strongly fermentative, and are commonly isolated from soil, fruits, foods and beverages. S. cerevisiae, S. pastorianus and S. bayanus are widely used for making bread and in the production of beer, wine, distilled beverages and fuel alcohol. S. cerevisiae occurs on fruit, in processed fruits, dairy products and plays a role in the fermentation of ker, coee, cocoa, and the production of traditional fermented products. S. cerevisiae and S. bayanus cause spoilage of soft drinks. In one review, cases of Saccharomyces invasive infection were presented (Enache-Angoulvant and Hennequin, 2005). Predisposing factors were similar to those of invasive candidosis, with intravascular and antibiotic therapy being the most frequent. Blood was the most frequent site of isolation. S. cerevisiae (subtype S. boulardii) accounted for 51.3% of fungaemias and was exclusively isolated from blood. Special caution should be taken regarding the use of S. cerevisiae (subtype S. boulardii) preparations (Fleet and Roostita, 2006). There are number of recent reports and reviews regarding the safety of S. cerevisiae (subtype S. boulardii). The authors concluded that probiotics should be used cautiously in certain high-risk populations.
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A review of the current literature reinforces the view that fungaemia and sepsis are rare complications of the administration of S. cerevisiae (subtype S. boulardii) in immunocompromised patients but conrms that the most important risk factor for S. cerevisiae fungaemia is the use of probiotics (Herbrecht and Nivoix, 2005; Munoz et al., 2005). This raises the question of the risk-benet ratio of these agents in critically ill or immunocompromised patients who are likely to develop an infection after exposure to high amounts of a microorganism with a low virulence. The authors concluded that S. cerevisiae (subtype S. boulardii) should certainly be contraindicated for patients of fragile health, as well as for patients with a central venous catheter in place. It is recommended that a specic protocol concerning the use of probiotics needs to be formulated. It is possible to propose some species of the genus for QPS status with the following qualication: "provided the proposed species does not grow at 42o C and is not lamentous" S. bayanus, S. cerevisiae and S. pastorianus (syn of S. carlsbergensis) are proposed for QPS status with the above qualication.
17.3.8
Schizosaccharomyces
Three species are included in this genus, Sch. japonicus, Sch. octosporus and Sch. Pombe, living on fruits and fruit juices, wines, tequila fermentation and high sugar concentration. They are strong fermenters of sugars and have been used for the production of ethanol. The species Sch. pombe is used as a phytase producer for animal feed; minimum safety precautions should be taken for the handling and storage. No infection issues have been reported. Sch. pombe is proposed for QPS status.
17.3.9
Xanthophyllomyces
Phaa rhodozyma ferments D-glucose and occurs in slime uxes of deciduous trees. The anamorph Phaa rhodozyma and the teleomorph Xanthophyllomyces dendrorhous forms are known. The yeast is used to synthesize the carotenoid astaxanthin (3,3-dihydroxy- , -carotene4,4-dione), a dietary source for aquaculture and poultry industries, including salmonids, lobsters and the egg yolks of chickens and quail. Xanthophyllomyces dendrorhous is proposed for QPS status.
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17.3.10
Fungal DNA and galactomannan and glucan antigens as screening of high-risc patients
[66] Accordingt to Jones and McLintock (2003) reduction of the mortality of invasive fungal infection could depend on the development of rapid, sensitive diagnostic methods such as serological and molecular techniques, assessing the utility of these methods and consider their role in management strategies. The authors propose the detection of fungal DNA and antigens such as galactomannan and glucan which have been prospectively evaluated in the clinical setting in early diagnosis of invasive fungal infection of high-risk patients. The sensitivity and specicity of the assays depends on patient selection, clinical application of the test, and release and circulation of galactomannan and fungal DNA. The authors conclude that it is essential these tests to be incorporated into management strategies and call for further clinical trials.
17.3.11
Invasive aspergillosis and galactomannan test
[67] According to Gonzalo Bearman the invasive aspergillosis is acquired by inhalation of airborne conidia by susceptible host. Its incidence is 5 out of 100,000 people and can develop: Pulmonary aspergillosis(most common), CNS aspergillosis, sinonasalaspergillosis, osteomyelitis endophthalmitis, endocarditis, renal abscesses, cutaneous. Denitive diagnosis requires the demonstration of tissue invasion, and positive culture from biopsy specimen. Invasive tissue biopsy is often impossible due the debilitated state of the patient. Less or non-invasive tests that may suggest the diagnosis.are isolation of Aspergillus from sputum and testing for galactomannans. Serologic Aspergillusprecipitin assays are rarely elevated in IA.
17.3.12
Testing for Galactomannans
[67] Galactomannan is a component of the fungal cell wall and an exoantigen of Aspergillus. PlateliaTM AspergillusEIA[68] was approved by the FDA in 2003 and detects galactomannan in serum. In the dataset evaluated by FDA, the overall sensitivity and specicity of the method were 80.7% and 89.2%, respectively. However, Bearmann found that signicant test variability has been reported post marketing which show a sensitivity 29-100% and specicity >85% . The test performance is likely aected by: in vivo characteristics of galactomannan secretion of Aspergillus the patient population, and other factors.
17.4. MOULD IN BUILDINGS
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Antigenic cross reactivity with other fungi such as Penicillium chrysogenum, Penicillium digitatum, and Paecilomyces variotii may result in false positive testing.
17.3.13
Conclusion
Bearman concludes that the use and interpretation of PlateliaTM AspergillusEIA may be of some, yet limited, value in the diagnosis of IA in high risk patients.
17.4
Mould in Buildings
[69] Mouldy smell or mould growth are associated with airborne diseases, because some molds are human pathogens. The most frequently indoor isolated moulds are Penicillium, Cladosporium, Ulocladium, Geomyces pannorum, Sistronema brinkmannii and Stachybotrys. However, according to Kuhn and Ghannoum 2003, many studies related to the importance of Stachybotrys chartarum in buildings are inconclusive. Kuhn and Ghannoum stress the urgent need to use objective markers of illness, relevant animal models, proper epidemiologic techniques, and careful examination of confounding factors including bacteria, endotoxin, man-made chemicals, and nutritional factors to study the relation between building and health of their inhabitants.
17.4.1
Mould in Dubai buildings
[70] Rushed construction and poorly designed air-conditioning systems in almost nine out of 10 buildings of Dubai present serious problems with air conditioning system. The equipment is unable to dry the air properly. Mould develops and spores of Aspergillus and Alternaria intensify allergies and asthma. Another health threat is Legionella pneumophila, a bacterium which breeds in air-conditioning systems and in water tanks and ttings. Air conditioners must, therefore, be capable to dehumidify incoming air, and regular maintenance is necessary. Faulty placed airconditioning vents and insucient airing of rooms are common reason of mould in housings. Maintaining the room temperature at 240 C instead of 200 C will rise the dew point, but soon or later humidity will settle at less aerated places. Air humidity of the air should be kept below 52% and rooms should be aerated properly. Hygrometers which measure the air humidity are cheap and give information on the quality of indoor air quality.
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17.4.2
Prediction of increase of spores in air using an articial neural network (ANN)
[71] Grinn-Gofro and colleagues 2010 examined the incidence of the airborne fungi Alternaria and Cladosporium related to meteorological parameters and air pollutant concentrations. The authors also created an articial neural network (ANN) forecasting model to predict the rise of spore concentration and environmental parameters as well as pollutants. Results could be conrmed by the Spearmans correlation rank analysis. Alternaria and Cladosporium spores may thus be predicted from meteorological conditions and air pollution recorded three days in advance.
17.4.3
Meteorological factors inuencing transportation of air particulates
[72] According to Jones 2004 pollen, fungal spores, bacteria, viruses, or fragments of plant and animal matter make up a quarter of the total airborne particulate. Meteorological variables, such as temperature, humidity and wind speed will aect the release and the transportation of pollen, fungal spores, bacteria and viruses. The authors stress, however, that the concentration of bacteria declines less rapidly than that of fungal spores and can therefore be transported at longer distances as noted with spores.
17.4.4
Fungi harmful to humans, animals and plants
[73] De Lucca 2007 points out that most fungi are saprophytic and not pathogenic to plants, animals and humans. However, few fungal species such as members of the Aspergillus, Fusarium Alternaria, Mucor genera may produce diseases in humans, animals and plants. Death due to aatoxins has been reported in humans, animals and birds. Saprophytic fungi can be opportunistic pathogens that enter via wounds or due to a weakened state of the host and true pathogens may depend on living plant or human tissues for nutrients but can also survive outside of the hosts.
17.4.5
Suggested guidelines for acceptable levels of fungi in indoor ambient air
[74] Gots, Layton and Pirages 2003 report noncomplaint for commercial buildings with 233 colony forming units (CFU) per cubic meter, with outdoor ambient air levels averaged 983 CFU/m(3). However, some commercial building presented total indoor spore counts ranging from 610 to 1040 spores/m(3), associated with outdoor spore counts of 400 to 80,000 spores/m(3). In residential building noncomplaint count was 1252 CFU/m(3) with an average outdoor level of 1524 CFU/m(3). Total spore counts detected indoors ranged between 68 and 2307
17.4. MOULD IN BUILDINGS
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spores/m(3), with associated outdoor spore levels between 400 to 80,000 spores/m(3). The authors stress that many buildings have a noncomplaint indoor ambient air fungal concentrations above 500 CFU/m(3), which however, requires remediation when nonspecic adverse health symptoms occur.
17.4.6
Data to set quality standards for animal dwellings air
[75] Matkovi, Vucemilo and Vinkovi 2009 found that fungi sore count in the stable housing dairy cows ranged from 3.98 x 103 CFU m-3 to 5.11 x 104 CFU m-3 and in the coop for laying hens from 6.89 x 104 CFU m-3 to 1.13 x 105 CFU m-3. The most common were the fungi Aspergillus sp., Penicillium sp., and yeasts, followed by Cladosporium sp., Fusarium sp., Mucor sp., Scopulariopsis sp., Alternaria sp., and Rhizopus sp. The authors call for more studies to sett air quality standards for animal dwellings.
17.4.7
Sick building syndrome
[76] Symptoms of sick building syndrome (SBS) was found to be associated with mould, mites, and volatile organic compounds, renovation, air freshener, carpet, use of benzine, use of thinner, use of coating materials, smell of house, and feeling of having insucient sleeping hours. Important moulds were Auerbasidum genus, Alternaria alternata, Aspergillus sp., Aureobasidium pullulans, Cladosporium cladosporioides, Fusarium sp., Penicillium sp., Rhodotorula minuta, and Wallemia sebi, and volatile organic compounds of concern were limonene, o,m-tolualdehyde, 2-pentanone, tetrachloroethylene, n-decane, and n-heptane. Nakayama and Morimoto 2009 recommend modication of lifestyle and ways of living factors. One technique to reduce energy consumption while maintaining adequate air quality, is "demand controlled ventilation". Instead of setting throughput at a xed air replacement rate, carbon dioxide sensors are used to control the rate dynamically, based on the emissions of actual building occupants. [77] The publication CDC "Building Air Quality: A Guide for Building Owners and Facility Managers" practical indoor air quality advice to prevent, identify, and correct indoor air quality problems.[78] In the UK classrooms are required to have 2.5 outdoor air changes per hour. In halls, gym, dining, and physiotherapy spaces, the ventilation should be sucient to limit carbon dioxide to 1,500 ppm. In the USA, and according to ASHRAE Standards, ventilation in classrooms is based on the amount of outdoor air per occupant plus the amount of outdoor air per unit of oor area, not air changes per hour. In classrooms, the requirements in the ASHRAE standard 62.1, Ventilation for Acceptable Indoor Air Quality, would typically result in about 3 air changes per hour, depending on the occupant density. [79]
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17.4.8
Mould grows at cold spots of the room
[80] The ability of air to hold water vapour decreases as the air temperature is lowered. If a unit of air contains half of the water vapour it can hold, it is said to be at 50% relative humidity (RH). As the air cools, the relative humidity increases. Relative humidity and temperature often vary within a room, while the absolute humidity in the room air can usually be assumed to be uniform. Therefore, if one side of the room is warm and the other side cool, the cool side of the room has a higher RH than the warm side. The highest relative humidity in a room is always next to the coldest surface, mould will grow there.
17.4.9
Keep humidity under 45-50%
Mould and mites need a relative humidity in excess of 4550%. The relative humidity during the heating season should be below this value. Even under such conditions, however, relative humidity can be higher on colder internal surfaces. Heat and moisture transfer analyses should search for defective thermal isolation and avoid thermal bridges.
17.4.10
Visual Inspection
[81] Currently there are no United States Federal, New York State, or New York City regulations for the assessment or remediation of mould growth. A visual inspection is the most important initial step in identifying a possible mold problem and in determining remedial strategies. The extent of any water damage and mold growth should be visually assessed and the aected building materials identied. A visual inspection should also include observations of hidden areas where damages may be present, such as crawl spaces, attics, and behind wallboard. Carpet backing and padding, wallpaper, moldings (e.g. baseboards), insulation and other materials that are suspected of hiding mold growth should also be assessed. Ventilation systems should be visually checked for damp conditions and/or mould growth on system components such as lters, insulation, and coils/ns, as well as for overall cleanliness. Equipment such as a moisture meter or infrared camera (to detect moisture in building materials) or a borescope (to view spaces in ductwork or behind walls) may be helpful in identifying hidden sources of mould growth, the extent of water damage, and in determining if the water source is active.
17.4.11
Measuring concentrations of microorganisms (particularly fungi) in indoor air
[82] Culture-based methods: To date, no standard methods are available for detecting and enumerating fungi in indoor environments. Traditional culture methods have proven to
17.5. DISEASE OF THE NAILS
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be of limited use for quantitative assessment of exposure. Culture-based techniques thus usually provide qualitative rather than quantitative data.
17.5
Disease of the nails
The causative pathogens of disease of the nails include dermatophytes, Candida, and nondermatophytic moulds. Dermatophytes are the fungi most commonly responsible for onychomycosis in the temperate western countries; while Candida and nondermatophytic moulds are more frequently involved in the tropics and subtropics with a hot and humid climate. [83]
17.5.1
Dermatophytes
Trichophyton rubrum is the most common dermatophyte involved in deformation of nger nail and toe nail. Other dermatophytes that may be involved are T. interdigitale, Epidermophyton occosum, T. violaceum, Microsporum gypseum, T. tonsurans, T. soudanense (considered by some to be an African variant of T. rubrum rather than a full-edged separate species) and the cattle ringworm fungus T. verrucosum. Other causative pathogens include Candida and nondermatophytic moulds, in particular members of the mold generation Neoscytalidium), Scopulariopsis, and Aspergillus. Mgge, Haustein and Neno 2006 looked at the frequency of causative agents of nail diseases. Dermatophytes, in particular T.rubrum, but also T. mentagrophytes, are the most frequently isolated causative agents in nail diseases (onychomycosis). Yeasts may be isolated relatively frequently, Candida parapsilosis was most common, followed by C.andida guilliermondii, Candida albicans, and Trichosporon spp.. Moulds are uncommon. Scopulariopsis brevicaularis was the most frequent mould. [84]
17.5.2
Treatment of ngernail infections
Amorolne is a morpholine antifungal drug which is eective in treatment of nail diseases.in the form of a nail lacquer. [85]
Bibliography
[1] Leibold, Gerhard: So besiegen Sie Ihre Allergie; Wiesbaden, Englisch Verlag 1987. [2] Chiller TM. Fungal infection outbreak: What should physicians be doing? cdc expert commentary. medscape today. 31 oct 2012. http://www.medscape.com/ viewarticle/773493?src=mp.
1380
[3] Trockenfeigentest: Nicht gleich reinbeissen;Test februar 2001,Stiftung Warentest Pg 81. [4] Grahl N, Puttikamonkul S, Macdonald JM, Gamcsik MP, Ngo LY, Hohl TM, and Cramer RA. In vivo hypoxia and a fungal alcohol dehydrogenase inuence the pathogenesis of invasive pulmonary aspergillosis. PLoS Pathogens, 7(7):e1002145, 2011. http://www.plospathogens.org/article/info%3Adoi%2F10. 1371%2Fjournal.ppat.1002145. [5] Baumgart, Prof dr. Jrgen Baumgart: Moderne Standard- und Schnellmethoden in der Lebensmittelmikrobiologie; Weiterbildungsseminar; Lemgo 17/19.3.99. [6] Weidenbrner,Martin: Lebensmittel-Mykologie, 1. Au. Behr, 1998, page 190. [7] Grser plus pilz knnen auf den Magen schlagen; vwd /7.2.00/12/mi. [8] Der Grosse Brockhaus 1979, Wiesbaden volume 7, page 203 and volume 10 pg 332. [9] http://pharmalicensing.com/licensing/displicopp/3903. Enterprise Ireland Biotechnology Dictorate: The use of food grade bacteria with anti-fungal activity to improve safety, quality and processability of cereal products such as malt, beer and bread. [10] Deak, Tibor; Beuchat, Larry L.: Handbook of food spoilage yeasts; CRC Press LLC 1996 ISBN 0-8493-2703-2.pp.7-16. [11] Von Arx (1979) Propagation in the yeast and yeast-like fungi. In: The Whole Fungus ed. Kendrik, B. Vol.2, pp. 555-556 National Museum of Canada, Kananaskis Foundation, Ottawa, Canada. [12] Stokes, J. L.: Inuence of temperature on the growth and metabolism of yeasts. The yeasts, Vol. 2 (eds. Rose, A. H. and Harrison, J. S. ). Academic Press, New York. 1971. [13] Gelinas, P., Toupin, C. J. and Goulet, J.: Cell water permeability and crytolerance of Saccharomyces cerevisiae. Lett. Appl. Microbiol. 1991, 12:236-240. [14] James SA, Cadet GM, Carvajal EJ, Portero PB, Cross K, Bond CJ, and Roberts IN. Saturnispora quitensis sp. nov., a yeast species isolated from the maquipucuna cloud forest reserve in ecuador. Int J Syst Evol Microbiol, 2 2011. http://www.ncbi.nlm. nih.gov/pubmed/21335499. [15] Barbosa A, Morais C, Morais P, Rosa L, Pimenta R, Lachance MA, and Rosa C. Wickerhamiella pagnoccae sp. nov. and candida tocantinsensis sp nov., two ascomycetous yeasts from ower bracts of heliconia psittacorum (heliconiaceae). Int J Syst Evol Microbiol, 5 2011. http://www.ncbi.nlm.nih.gov/pubmed/21478396.
BIBLIOGRAPHY
1381
[16] Limtong S, Jindamorakot S, Am-In S, Kaewwichian R, Nitiyon S, Yongmanitchai W, and Nakase T. Candida uthaithanina sp. nov., an anamorphic yeast species in nakaseomyces clade isolated in thailand. Antonie Van Leeuwenhoek, 99(4):86571, 5 2011. http://www.ncbi.nlm.nih.gov/pubmed/21311971. [17] The chocolate tree. bioweb. university of wisconsinla crosse. http: //bioweb.uwlax.edu/bio203/s2008/boland_kirs/Friends,%20Enemies%20and% 20Acquaintances.htm. [18] Plessas S, Alexopoulos A, Voidarou C, Stavropoulou E, and Bezirtzoglou E. Microbial ecology and quality assurance in food fermentation systems. the case of ker grains application. Anaerobe, 5 2011. http://www.ncbi.nlm.nih.gov/pubmed/21497663. [19] Bautista-Gallego J, Rodrguez-Gmez F, Barrio E, Querol A, Garrido-Fernndez A, and Arroyo-Lpez FN. Exploring the yeast biodiversity of green table olive industrial fermentations for technological applications. Int J Food Microbiol, 3 2011. http: //www.ncbi.nlm.nih.gov/pubmed/21497408. [20] Gamero A, Hernndez-Orte P, Querol A, and Ferreira V. Eect of aromatic precursor addition to wine fermentations carried out with dierent saccharomyces species and their hybrids. Int J Food Microbiol, 147(1):3344, 5 2011. http://www.ncbi.nlm. nih.gov/pubmed/21474195. [21] Mendoza LM, Mern MG, Morata VI, and Faras ME. Characterization of wines produced by mixed culture of autochthonous yeasts and oenococcus oeni from the northwest region of argentina. J Ind Microbiol Biotechnol, 5 2011. http://www. ncbi.nlm.nih.gov/pubmed/21461745. [22] Ageitos JM, Vallejo JA, Veiga-Crespo P, and Villa TG. Oily yeasts as oleaginous cell factories. Appl Microbiol Biotechnol, 5 2011. http://www.ncbi.nlm.nih.gov/ pubmed/21465305. [23] Vrancken G, De Vuyst L, Rimaux T, Allemeersch J, and Weckx S. Lactobacillus plantarum imdo 130201, a wheat sourdough isolate, adapts to growth in wheat sourdough simulation medium at dierent ph values through dierential gene expression. Appl Environ Microbiol, 5 2011. http://www.ncbi.nlm.nih.gov/pubmed/21460118. [24] Semchyshyn HM, Lozinska LM, Miedzobrodzki J, and Lushchak VI. Fructose and glucose dierentially aect ageing and carbonyl/oxidative stress parameters in saccharomyces cerevisiae cells. Carbohydr Res, 346(7):9338, 5 2011. http://www.ncbi. nlm.nih.gov/pubmed/21459368. [25] Vaughan-Martini A., Kurtman P.: Desoxyribonucleic acid relatedness among species of the genus Saccharomyces sensu stricto. Int. J. Syst. Bacterol. 1985, 35:508-511.
1382
[26] Vaughan-Martini A., Kurtman C. P.: Three newly delimited species of Saccharomyces sensu stricto. Antonie van Leeuwenhoek 1987, 53:77-84. [27] Vaughan-Martini A., Kurtman P.: Desoxyribonucleic acid relatedness among species of the genus Saccharomyces sensu stricto. Mycologia 1988, 80:241-243. [28] Vaughan-Martini A., Kurtman P.: A proposal for correct nomenclature of the domesticated species of the genus of Saccharomyces. In: Biotechnology and Applications in Beverage Production, pp. 1-16. Edited by C. Cantarelli & G. Lanzarini. London: Elsevier. [29] Spicher, G.: Die Erreger der Schimmelbildung bei Backwaren III. Einige Beobachtungen ueber die Biologie der Erreger der Kreidenkrankheit des Brotes. Getreide, Mehl, Brot 1984, 38:178-182. [30] Spicher, G.: Neue Erkenntnisse ueber die Erreger der Kreidekrankheit und Moeglichkeiten der Wachstumsverhinderung. Brot Backwaren 1986, 34:208-213. [31] Sand F. E. M. J.: An ecological survey of yeasts within a soft drinks plant. Proc. 4. Int.Symp. on yeasts (Eds. Klaushover, H. and Sleytr, U. B.) Part I Hochschule fr Bodenkultur, Vienna. pp.263-264. [32] Sand F. E. M. J.; Kolfschoten, G.A. and Van Grinsven, A.M.: Yeasts isolated from proportioning pumps employed in soft drinks plant. Brauwissenschaft 1976 29:313-355. [33] Parish, M.E.; Carroll, D.E. Indigenous yeasts associated with muscadine (Vitis rotundifolia) grapes and musts. Am. J. Enol. Vitic. 1985, 36:165-169. [34] Holloway P., Subden R. E. and Lachance, M. A.: The yeasts in a Riesling must from the Niagara grape growing region of Ontario Cn. Inst. Food. Sci. Technol. J. 1990 23:212-216. [35] Fleet, G. H., Heard, G. M.. and Gao, G.: The eect of temperature on the growth and ethanol tolerance of yeasts during wine fermentation Yeast 5 Special Edition, 1989 , 543-546. [36] Goto, S. and Yokotsuka, I: Wild yeast population in fresh grape must of dierent harvest time. J.Ferment. Technol. 1977, 55: 417-422. [37] Martini, A.:Origin and domestication of the wine yeast Saccharomyces cerevisiae. J. Wine Res. 1993, 4:165-176. [38] Fleet, G. H.; Lafon-Lafourcade, S. and Ribereau-Gayon, P.: Evolutions of yeasts and lactic acid bacteria during fermentation and storage of Bordeaux wines. Appl. Environ. Microbiol. 1984, 48: 1034-1038.
BIBLIOGRAPHY
1383
[39] Minarik, E.: Zur kologie von Hefen und hefeartigen Mikroorganismen abgefllter Weine. Wein-Wiss. 1981, 36:280-285. [40] W.R. Wine spoilage by microorganism. In: Wine Microbiology and Biotechnology (ed. Fleet, G.H.) Harwood AcademicPublishers, Camberwell, Victoria, Australia. 1993, pp. 396-420. [41] Minarik, E.: Levure de contamination des vines embuteills. Bull OIV 1983, 56:414419. [42] Steward, G. G. and Russel I.: One hundred years of yeasts research and development in the brewing industry. J. Inst. Brew. 1986, 92:537-558. [43] Engel, G.: Hefen und Schimmelpilze in Futtermittlen, Rohmilch und Milchprodukten. Dtsch. Molk. Ztg. 1986, 107:2286-2292. [44] Engel, G.: Hefen in Silage und Rohmilch. Milchwissenschaft,1986, 41:633-637. [45] Sanchez, J; Daguenet, G; Guiraud, J. P; Vincent, J. C. and Galzy, P.: A study of the yeast ora and the eect of pure culture seeding during the fermentation process of cocoa beans. Lebensm. Wiss. Technol., 1985, 18:69. [46] Deak, Tibor; Beuchat Larry R.: Handbook of food spoilage yeasts; CRC Press LLC 1996 ISBN 0-8493-2703-2.pp. 111-154. [47] Degre, R.; Thomas, D. Y.; Ash, J.; Mailhot, K.; Morin A. and Dubord, C.: Wine yeast strain identication Am. J. Enol.Vitic. 1989, 40:309-315. [48] Casey G. P.; Pringle, A. T. and Erdmann, P. A.: Evaluation of recent techniques used to identify individual strains of Saccharomyces yeasts. Am. Soc. Brew. Chem 1990, 48:100-106. [49] Trk, T.; Royer, C. ; Rockhold, D. and King A.D.: Electrophoretic kariotyping of yeasts, and Southern blotting using whole chromosoms as templates for the probe preparation. J. Gen. Appl. Microbiol. 1992, 38:313-325. [50] Trk, T.; Rockhold, D. and King A.D.: Use of electrophoretic kariotyping and DNADNA hybridization in yeast identication. Int. J. Food Microbiol 1993, 19:63-80. [51] Bruneau S. and Guinet, R.: Rapid identication of medically important yeasts by electrophoretic protein patterns. FEMS Microbiol. Lett. 1989, 58:329-339. [52] MIDI: Microbial Identication System 1992, Newark, DE. [53] Augustyn, O. P. H.; Koch, J. L. F. and Ferreira D.: Dierentiation between yeast species, and strains within a species, by cellular fatty acid analysis. A feasible technique? Sys. Appl. Microbiol. 1992, 15:105-115.
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[54] Rozes, N.; Garcia-Jares, C.; Larue, F. and Lonvaud-Funel, A.: Dierentiation between fermenting and spoilage yeasts in wine by total fatty acid analysis. J. Sci. Food. Agric., 1992, 59:351-357. [55] http://www.sciencemag.org/cgi/content/abstract/sci;301/5637/1244. Hamilton, Stephen R.; Bobrowicz, Piotr; Bobrowicz, Beata; Davidson, Robert C.; Li, Huijuan; Mitchell, Teresa; Nett, Juergen H.; Rausch, Sebastian; Stadheim, Terrance A.; Wischnewski, Harry; Wildt, Stefan and Gerngross, Tillman U.: Production of Complex Human Glycoproteins in Yeast Science 301 (5637), 1244. (DOI: 10.1126/science.1088166) (29 August 2003). [56] http://www.sciencedaily.com/releases/2006/09/060911104500.htm. Science Daily: Full Humanization Of Therapeutic Proteins From Yeast. Septempber 11, 2006. [57] http://www.ncbi.nlm.nih.gov/pubmed/12576670. Ma, Y; Zhou, X; Zhao, Q; Li Y; Liu, Y; Wang, Z; Zhang Y: Expression of adenovirus type 5 E1A in the methylotrophic yeast Pachia pastoris and the inhibitory eect on S-180 tumor growth. [58] http://www.efsa.europa.eu/en/science/sc_commitee/sc_consultations/sc_ consultation_qps.html. EFSA public consultation on the Qualied Presumption of Safety (QPS) approach for the safety assessment of microorganisms deliberately added to food and feed. [59] http://www.ncbi.nlm.nih.gov/pubmed/12898400. Querol A, Belloch C, FernandezEspinar MT, Barrio E. Molecular evolution in yeast of biotechnological interest. Int Microbiol 2003; 6: 201-205. [60] http://www.efsa.europa.eu/etc/medialib/efsa/science/sc_commitee/sc_ consultations/qps.Par.0006.File.dat/Annex5.pdf. EFSA: Annex 5: Assessment of Yeasts with respect to a Qualied Presumption of Safety. [61] MacDougall L, Fyfe M, Romney M, Starr M, and Galanis E. Risk factors for cryptcoccus gattii infection, british columbia, canada. Emerg Infect Dis, 2 2011. http://www.cdc.gov/EID/content/17/2/193.htm. [62] Galanis E and Macdougall L. Epidemiology of cryptococcus gattii, british columbia, canada,. Emerg Infect Dis, 16(2):19992007, 2 2010. http://www.ncbi.nlm.nih. gov/pmc/articles/PMC2958008. [63] Odom A, Muir S, Lim E, Toaletti DL, Perfect J, and Heitman J. Calcineurin is required for virulence of cryptococcus neoformans. EMBO J, 6:257689, 1 1997. http: //www.nature.com/emboj/journal/v16/n10/full/7590243a.html. [64] Kmetzsch L, Staats CC, Simon E, Fonseca F, de Oliveira DL, Sobrino L, Rodrigues J, Leal AL, Nimrichter L, Rodrigues M, Schrank A, and Vainstein MH. The vacuolar ca(2+) exchanger vcx1 is involved in calcineurin-dependent ca(2+) tolerance
BIBLIOGRAPHY
1385
and virulence in cryptococcus neoformans. Eukaryot Cell, 9(11):1798805, 11 2010. http://www.ncbi.nlm.nih.gov/pubmed/20889719. [65] http://www.inra.fr/internet/Produits/HYP3/pgloss/6---318.htm //www.codexalimentarius.net/web/standard_list.do?lang=en. National de la Recherche Agronomique. http: LInstitut
[66] http://www.co-infectiousdiseases.com/pt/re/coinfdis/abstract. 00001432-200312000-00002.htm. Jones, Brian L. a; McLintock, Lorna A. B: Impact of diagnostic markers on early antifungal therapy. Antimicrobial agents. Current Opinion in Infectious Diseases. 16(6):521-526, December 2003. [67] Bearman, Gonzalo: Rapid Diagnosis of invasive Aspergillosis. Virginia Commonwealth Univiersity Medical Center. [68] http://www.medcompare.com/details/39455/Bio-Rad-Platelia-Aspergillus-EIA. html. Platelia Aspergillus EIA. [69] Kuhn DM and Ghannoum MA. Indoor mold, toxigenic fungi, and stachybotrys chartarum: infectious disease perspective. Clin Microbiol Rev, 16(1):14472, 1 2003. http://cmr.asm.org/cgi/content/full/16/1/144?view=long&pmid=12525430. [70] Complaints of mould in homes on increase 31.10.2010. The National. http://www.thenational.ae/news/uae-news/environment/ complaints-of-mould-in-homes-on-increase. [71] Grinn-Gofro A, Strzelczak A, and Wolski T. The relationships between air pollutants, meteorological parameters and concentration of airborne fungal spores. Environ Pollut, 10 2010. http://www.ncbi.nlm.nih.gov/pubmed/21030122. [72] Jones AM and Harrison RM. The eects of meteorological factors on atmospheric bioaerosol concentrations - a review. Sci Total Environ, 326(1-3):15180, 6 2004. http://www.ncbi.nlm.nih.gov/pubmed/15142773. [73] De Lucca AJ. Harmful fungi in both agriculture and medicine. Rev Iberoam Micol, 24(1):313, 3 2007. http://www.reviberoammicol.com/2007-24/003013.pdf. [74] Gots RE, Layton NJ, and Pirages SW. Indoor health: background levels of fungi. AIHA J (Fairfax, Va), 64(4):42738, Jul-Aug 2003. http://www.ncbi.nlm.nih.gov/ pubmed/12908856. [75] Matkovi K, Vucemilo M, and Vinkovi B. Airborne fungi in dwellings for dairy cows and laying hens. Arh Hig Rada Toksikol, 60(4):3959, 12 2009. http://www.ncbi. nlm.nih.gov/pubmed/20061239.
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[76] Nakayama K and Morimoto K. Risk factor for lifestyle and way of living for symptoms of sick building syndrome: epidemiological survey in japan. Nippon Eiseigaku Zasshi, 64(3):68998, 5 2009. http://www.ncbi.nlm.nih.gov/pubmed/19502765. [77] Wikipedia. quality. Indoor air quality. http://en.wikipedia.org/wiki/Indoor_air_ http://www.cdc.gov/niosh/topics/
[78] CDC. Indoor environmental quality. indoorenv/.
[79] American society of heating and air-conditioning engineers. inc: Ashrae standard 62.12010. vetilation for acceptable indoor air quality. http://openpub.realread.com/ rrserver/browser?title=/ASHRAE_1/ashrae_62_1_2010_1024. [80] CDC. Moisture, mold and mildew. http://www.cdc.gov/niosh/pdfs/appenc.pdf. [81] New york city department of health and mental hygiene (dohmh): Guidelines on assessment and remediation of fungi in indoor environments. 2008. http://home2. nyc.gov/html/doh/html/epi/moldrpt1.shtml. [82] Who guidelines for indoor air quality: dampness and mould. http://www.euro.who. int/__data/assets/pdf_file/0017/43325/E92645.pdf. [83] Chi CC, Wang SH, and Chou MC. The causative pathogens of onychomycosis in southern taiwan. Mycoses, 48(6):41320, 11 2005. http://www.ncbi.nlm.nih.gov/ pubmed/16262878. [84] Mgge C, Haustein UF, and Neno P. Causative agents of onychomycosis-a retrospective study. J Dtsch Dermatol Ges, 4(3):21828, 3 2006. http://www.ncbi.nlm. nih.gov/pubmed/16626318. [85] Amorolne. wikipedia. http://en.wikipedia.org/wiki/Amorolfine.
Chapter 18 BSE
Bovine Spongiform Encephalopathy (B S E) was rst described in 1986 related to cattle feed containing meet and bones from carcasses of sheep being feed to bovines. On the 70th the preparation of animal feed was simplied, and the temperature reduced. The agent of BSE could now survive and Great Britain became the hotbed of the mad cow disease. The zoologist Sir Richard Southwood [1] blames us all because we all want to eat cheap food. Science, agriculture and politics have failed to get the disease under control. In the meanwhile 27 persons died on CJD "new variant Creutzfeldt-Jacob-Disease". It seems to be the start of a horrible epidemic.
18.1
The prion diseases still endemic in 2011
The 2011 report of the National CJD Research and Surveillance Unit Western General Hospital, Edinburgh (NCJDRSU), published on Oct 8, 2012, says that the number of sporadic cases remains relatively stable for the past 15 years, varying around 70 deaths/year. There has been a small rise to 85 deaths or higher in 2008, 2009, and 2011. [2]
18.1.1
Prion diseases (CJD)
The "sporadic CJD" occurs worldwide causing around 1-2 deaths per million population per year. It is the most frequent prion disease. The "variant CJD" was a form found to be linked to bovine spongiform encephalopathy (BSE). It was described during the European CJD ewpidemic beginning in1990. The "inherited" forms of human prion disease are linked to mutations of the prion protein. "Iatrogenic CJD" is caused by infection or by medical treatment. All 2011 deaths were related to the prion-protein genotype methionine homozygotes at codon 129. A longer incubation time is being expected for persons with genotype homozygous for valine or heterozygous at this codon. A second wave of vCJD is, therefore, 1387
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expected coming from people which consumed diseased meat at the peak of the epidemic around the year 2000. One in 2000 persons is an asymptomatic carrier of the defective prions Moreover, there is evidence that as many as one in 2000 people of all genotypes are asymptomatic carriers of the defective prions. They may develop the disease later on, or may infect other individuals donating tissue or transplants. Therefore surveillance and further research is imperious to avoid an increase of cases of this deadly disease. The NCJDRSU Unit provides surveillance investigating clinical and diagnostic features, epidemiology, neuropathology, prion protein biochemistry, molecular genetics, and develops diagnosis methods. The Unit is focused to determine the risk of secondary transmission of vCJD and atypical animal TSEs infecting humans. [3] Blood transfusion is a transmission route for vCJD Four cases of infections transmitted by blood transfusion are reported. Both, the donor and the recipient developed symptoms of vCJD. The symptoms were noted 7 to 8 years after transfusion. These cases demonstrate that blood transfusion is a transmission route for vCJD. The report also stresses that in the UK, during 2011, the number of cases of vCJD declined and the sporadic form sC JD increased, compared to number of cases in the previous year. Fewer cases of vCJD were reported outside the UK. Table 18.1: CJD genotypes GENOTYPES Sporadic sCJD Variant vCJD Iatrogenic CJD Genetic CJD PRNP genotype CJD cases in 2011 M/M M/V V/V M/M M/V E211Q-MM 7X1NS-MM
Prion Protein detection and typing [2] The 2011 report of the Unit uses the following prion protein classication: Prion Type 1:The nonglycosylated form has a molecular weight of 21kDa. Prion Type 2: The nonglycosylated form has a molecular weight of 19kDa. Prion Type 2B: The diglycosylated band predominates. (Is characteristic of variant CJD) Prion Type 2A: The diglycosylated band does not predominate. Low molecular weight (< 10kDa) PrPres fragments are considered as characteristic of certain cases of Gerstmann-Straussler-Scheinker (GSS) disease, and the Variably Protease
18.1. THE PRION DISEASES STILL ENDEMIC IN 2011 Sensitive
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18.1.2
Kuru
Human diseases caused by priones have dierent forms
The tribe of fore in Papua-Newguinea were cannibals, eating brains of diseased.After ceasing the cannibalic practice new infections were no more recorded. The disease was called Kuru and was characterized by loss of coordination of movements developing until madness.
Creutzfeldt-Jakob disease Is spread through out the world, being described in 1920 by Creutzfeldt and Jacob. The disease begins at the age of 60 with disturbed sleep, hallucination, dementia, unable to speak and to read, and alterations of movements. It leads to death within several month up to two years 10 to 15% of all cases of CJD are of hereditary origin.A small number is transmitted by surgical interventions, such as transplants.
Gerstmann-Strussler-Scheinker Syndrome and Lethal Familiar Insomnia [4] The signs of the disease are similar to those of the CJ disease.All these diseases are caused by proteins priones (PrP) (Proteinaceus infectious Particles)[5]. These proteins remain infectious even after being treated by methods of lesion of nucleic acid, however lose their virulence when treated with hydrolysing or denaturing substances. Genetic cause Priones or PrP - Proteins exist in two forms: One form causes the CJD (Creutzfeldt-Jakob Disease) disease being infectious. The other form of PrP- Proteins is not pathogenic and is synthesized by the organism himself. It is not contagious. The theory that priones also can cause CJD through a genetic mechanism was explained by Prusiner. In 1988 it was discovered that patients with Gerstmann-Strussler-Scheinker syndrome had a change in their genetic code, compared with healthy persons. The contagious PrP-protein may be inherited. The dierence between the genetic code from these patients compared with healthy persons lies in a change at the Gen-PrP from the DNA, one of the 750 radicals from the part of the DNA responsible for the synthesis of PrP protein. These radicals are the alphabet from which the genetic code is composed. Her sequence in the molecule of DNA decides the composition of the proteins. The code for
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the synthesis of each aminoacid is represented by three basic radicals. This part is called CONDOM. In the case of the syndrome of GSS the condom 102 suers a mutation. The PrP protein has a proline aminoacid in the place where normally the basic radical leucine is located. This small change in the structure of the PrP is responsible for the start of the disease of GSS. Today 18 types of genetic modications which are responsible for the synthesis of PrP-scrapie are known. The normal form of PrP protein found in healthy people is called PrP-cellular. PrP-scrapie has turned out to be the global denomination for all diseases close related to the human and animal scrapie. The specic activity of PrP scrapie consists in its stereoisomeric conguration. The PrP scrapie does not necessarily present a genetic mutation related to a change of leucine by proline. What matters is that molecules of PrP having the same distribution of aminoacids dier in their stereoisomeric conguration. The priones are able to transfer her stereoisomeric conguration to other normal molecules of PrP-cellular which now turn out to be infectious. The structure with this property is called twisted beta structure. The aminoacids have a beta-helicoidal twisted screw form and represent the scrapie PrP. The cellular PrP form has a twisted alfa-helicoidal chain. In some places of the alfa-helicoidal chain there may be a change of aminoacids which cause an unstable condition in the molecule being therefore vulnerable to an inversion of her twist, acquiring the same conguration of the scrapie PrP molecule thus becoming infectious. The pathological activity of scrapie PrP is still partially unknown. It seems that PrP destroys the nervous cells producing amylaceous substances which accumulate as amylaceous plaques which can be seen under microscope. These plaques are also found in the Alsheimer Disease, Parkinson and amiotroc lateral sclerosis, demonstrating certain link between these groups of anomalies.
18.1.3
Diseases caused by priones
Priones are particles of infectious proteins causing degenerative diseases of the central nervous system in human and in animals. Unlike other substances which are situated between priones and other superior elements the prions do not have the form of nucleic acid which could be made responsible for reproduction as below: Phytopathogenic viroids are composed of nucleic acid having some times no supercial protective layer. Virus with RNA and DNA, genetic material necessary to imprint the informations
18.1. THE PRION DISEASES STILL ENDEMIC IN 2011 in the invaded cell forcing the cell to produce new proteins Priones distinguishes itself from virus or viroids by the following qualities: They cause infectious diseases. They cause diseases of hereditary origin. Prions may inuence other proteins to become dangerous.
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Prions always cause mortal diseases.They are localized in brain and stay without symptoms for decades. They have their inuence spread over the muscular system.
18.1.4
Usual spongiform encephalopathies
Scrapie in lamb and goats The animals can no more coordinate the movements and cannot maintain itself on foot, being frightened and scrape itself until there is no skin left. This gave origin to the name of the disease = to SCRAPE. Other encephalopathies Encephalopathies of Canadian marten, chronic degenerative disease of elk, feline spongiform encephalopathy of cat and the bovine spongiform encephalopathy (B S E).
18.1.5
Short story of the measure to control and eradicate BSE in cattle
1963- The agent of the disease proved to get from one species to another as BSE contaminated material was fed to minks in a farm of Idaho. All animals died of spongiform encephalopathy. The possibility of scrapie agent to overcome the species-barrier was again proved in 1986 by veterinarians in Weybridge nding an antelope with scrapie encephalopathy. 70th decade: The preparation of fodder containing carcasses of diseased animals was simplied.The temperature reduced to lower costs. The agent of BSE could survive.As this fodder was also exported, BSE reached Switzerland, France and other countries. It was used to feed not only bovines but also pigs, chicken and sh. pork, chicken and sh do not live long enough to show the signs of the disease even being infectious, representing therefore a deadly menace. December 1984: The veterinarian Dr. David Bee treating cases of BSE sent samples to a national central veterinary laboratory in Weybridge. The results of these analysis never reached Dr. Bee. [1]
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Up to 1985 before the disease was known, 54.000 BSE infected cattle entered the human food chain. It is supposed that later on the number of infected cows which were already consumed as human food mount up to 750.000. April 1986: Dr Collin told that probably there was a new disease coming up. Nobody took care of that. 1986- The rst case of BSE was described related to meal from carcasses of diseased animals. June 1987 Dr.Howard Rees, then chief veterinarian of the Ministry of Agriculture, Fisheries and Food (MAFF) forwarding informations regarding to BSE to the MAFF Secretary Sir Michael Franklin added his concern about possible public misrepresentation which could cause serious nancial damage.[1] Meanwhile in Sweden the ban of animal feed with animal meal was imposed.Only two years later Germany reacted stopping the import of animal meal from Great Britain. July 1987: Dr Whitaker, preparing a report on cases of BSE he had worked on, was advised by the Ministry of Agriculture of Great Britain not to use the word "scrapie-like". April 1988 The Government of UK organized a body of experts under the zoologist Richard Southwood. This committee wrote to be absurd human being in danger because of BSE.[1] 1989 - British government installed a follower group "Spongiform Encephalopathy Advisory Committee" (SEAC)under medical advice of David Tyrrell The Group conrmed the statement of Minister Gummer UK beef being safe.Later on Tyrell gave an explanation about the meaning of the word "safe".He said: "It does not mean there is no risk, it only means that the risk is very small." The SEAC Group failed to set strong measures against the spreading disease, still allowing the sell of fodder made of BSE corpses. 1990 The Agricultural minister John Gummer and his chief veterinary Meldrum stated "British beef is safe ". May 1990 - The rst British cat died of BSE. Meldrum said: "There is no reason to be worried. It was just a cat out of seven millions. [1] September 1990 - The "Veterinary Record" reported a pig being infected by BSE. 1998 - Prohibition to use ruminant-derived protein in form of meat and bone meal (mbm) in ruminant feed, which was the main cause of BSE cases in Switzerland and France. The incubation of 5 years caused this prohibition not to show immediate eect. The number of cases of BSE doubled from one year to another until having his peak in 1992.
18.1. THE PRION DISEASES STILL ENDEMIC IN 2011
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1999.- Germany has closed his frontiers for living cattle but allowed the import of meat of cattle from Great Britain.
1994.-German veterinary ocials stated human safety regarding BSE, existing no possibility of human contamination by consuming BSE-positive beef. This cannot be sustained today and shows how careless BSE meat was ocially handled !
1994.- One case of BSE on a cow in Diepholz (Germany, near Osnabrck). This cow had been imported from Great Britain.
German Health Minister Horst Seehofer will determine all 5 000 cattle imported from England to be slaughtered. The agriculture lobby did succeed to stop the killing.
1995- Further measures against BSE and prevention to transmission to humans: 1- Slaughter of suspect cases 2- Destruction of carcasses 3- Ban of specied oal 4- Ban on using bovine vertebral column to produce mechanically recovered meat 5- Ban on using beef from cattle over 8 month old. 6- Ban of use of intestines and thymus from calves under 6 month old. 7- Ban of using the entire head. Despite the growing menace of spreading BSE in cattle mainly in France, Portugal and Switzerland the EU Commission is not willing to forbid animal meal made of bones,carcasses, brains, spinal cord, blood, gelatine, lard and marrow as animal feed for pigs, poultry and sh. Ruminants are not allowed any more to be fed with animal meal. Animal feed free of animal meal is now being produced in Germany with main ingredients: Soy bean from USA, Argentina and Brazil. Rapeseed cake from Pakistan, India and Germany. Peas, broad been (Vicia faba), sunower seed cake, maize germ cake and maize gluten feed. 400.000 tons of animal meal can thus be replaced by vegetable ingredients supplying the aminoacids which are necessary for a healthy growth. Genetic modied Soybean, rapeseed and maize gluten feed must be replaced by NON-GMO to avoid another loss of condence of the consumer
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18.1.6
Live-animal test to detect scrapie in goats [6]
Scrapie is a form of transmissible spongiform encephalopathy in goat and sheep. The degenerative disease causes tremors, lip-smacking, weight loss, a hopping gait, and other peculiar symptoms. Scrapie-aicted animals cannot be cured, and they eventually die. Rectal mucosal-associated lymphoid tissue (RMALT) Katherine ORourke and Tom Truscott developed the rectal mucosa biopsy test(RMBT) or rectal biopsy, which consists of snipping a tiny piece of lymphoid tissue from the animals rectum using local anesthesia. Lymphoid tissue is used because it collects malformed proteins called prions, which are thought to cause scrapie. The RMALT test is based on the currently used third-eyelid test. The rectal biopsy has also been used in deer, elk, sheep, and now goats. The third-eyelid test The third-eyelid test has been used by APHIS and state veterinarians since 2002 as an ocial test to detect scrapie in sheep. It involves snipping a tiny piece of lymphoid tissue from the animals nictitating membrane, or third eyelid, staining it with antibodies, and examining it under a microscope. The ARS characterizes the prion protein gene of goats to identify dierences between individual animals and those who are diseased. Their work, together with APHIS aims to eliminate scrapie from US herds to reduce costs of physical loss of animals, disposal of carcasses and oal, trade restrictions and diminished domestic and international markets for breeding stock, semen and embryos.
18.1.7
Early Detection method for Prion Diseases
Infectious prions can be present decades before symptons appear, an early detection method is needed for early treatment to stop the spread of the Creutzfeldt-Jakob disease in humans. Prion diseases are dicult to diagnose, untreatable and ultimately fatal. Brain tissue dies out and sponge-like holes are formed in the brain. Real time quaking induced conversion assay, or RT-QuIC prion detection method [7] Infectious prions are also found outside the brain, in saliva, blood, breast milk, urine and the nasal and cerebral spinal uids, however, their concentrations in these bodily uids are to low to be measured with available methods. A new prion detection method, called real time quaking induced conversion assay, or RT-QuIC was has been developed by by Byron Caughey. Using this technique the small
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amounts of infectious prions are leaded to convert large amounts of normal prion protein into an abnormal form which enables their detection. The test detected high levels of prions in nasal uids of hamsters, pointing to such uids as possible sources of contagion in various prion diseases. RT-QuIC related applications might also be used to diagnose similar neurodegenerative protein diseases, such as Alzheimers, Huntingtons and Parkinsons diseases. William and colleagues 2010 estimate the relative amount of prions using the RT-QuIC prion detection method. [8] Quantitative N-terminal amino acid proling (N-TAAP) for TSE diagnosis [9] Gielbert and colleagues 2009 report a method to identify dierences between bovine spongiform encephalopathy (BSE), the classical scrapie and experimental transmissible spongiform encephalopathy strains. Diagnosis of TSE is based on the detection of the abnormal protease-resistant prion protein (PrP(Sc)). Proteolysis by proteinase K (PK) generates protease-resistant products (PrP(res)) with partially variable N-termini.The N-terminal aminoacid proles (N-TAAPs) is, and can be determined with the method developed by Gilbert and colleagues Fluorescence Spectroscopy of the Retina for Diagnosis to detect mad cow disease [10] Fluorescence spectra of the eye for diagnosis of transmissible spongiform encephalopathies (TSEs) may become a new diagnostic tool analysing dierences in the uorescence intensity and spectroscopic signatures. It is based on the accumulation of lipofuscin in the retina. The detection of infectious prion diseases in animals could help prevent the disease from spreading in the food supply.
18.1.8
Scrapie prevention in sheep ocks [11]
ARS uses selective breeding of sheep with the version of the prion protein gene (dubbed "R171") that confers resistance. The R171 prion gene version has never been found in goats, but there are several gene variants in goats which might confer resistance to scrapie. These ndings are used in ocks where scrapie is found. Only the genetically susceptible sheep are removed. The researchers found four gene variants (R143, S146, H154, and K222) which were relatively rare or absent in animals that developed scrapie in previous outbreaks, suggesting that they might increase resistance to scrapie. The current eradication eort includes early detection through slaughter surveillance and reporting of clinical suspects, ock management and selective breeding in sheep, scrapiefree ock certication, and producer outreach and education.
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ARS will continue to do research on genetic resistance, diagnostic testing, and transmission modes. To improve prevention rather than removing infected animals.
18.1.9
Milk substitute in organic farming
Milk substitute being fed to young animals should contain only milk fat. other animal fat is to be banned. Milk substitute should therefor be made out of half unskimmed milk and half vegetable fat. The cheap variant using animal fat from condemned animals was certainly a vector of BSE disease which had been fed until December 2000. It had been discovered that the BSE pathogens are very resistant in fat and can be destroyed only with temperatures of mor than 150o C . Fat used in powdered milk substitutes had only been heated up to 100o C . All German farmers with BSE in their herd had fed powdered milk substitutes of low temperature origin. All eorts should be undertaken to reduce spreading of BSE regardless to costs and industrial interests. To inactivate the BSE agents Germany uses 133o C heat and 3 bar pressure during 20 minutes to decontaminate the meal. This method is not being used in other countries. France is willing to forbid therefore completely the use of animal meal. The problem arises how to get rid of 300.000 tons of meal/year which have to be burned, causing dioxins. The proteins demand of 55 to 66% in animal meal must be covered with soybean meal ( 44 to 46 % protein). Stock market reacted immediately with rising prices for soybean meal. BSE was present in cattle in the Northern Ireland, in Great Britain, Switzerland and in France in the Departments 22 (Cte du Nord), 29 (Finistere), 35 (Ile de Vilalne), 50 (Manche). In February 1997 was discovered a case of BSE in Germany. This cow had been imported from England. Her identication mark had been falsied as being original German. In Switzerland there has been reported recently a case of BSE The contamination in this case was told to be interplacental or over the milk. Since January 1977 until march there were 15 cases of BSE in Switzerland. (Welt am Sonntag 3.3.97).
February 1996- The SEAC-Committee admits the situation to be "dramatical". There were already 10 patients having Creutzfeldt-Jakob-disease. 1998.- At the beginning of 1998 there were two more cases of BSE on Belgian cattle (in Ruddervoorde) reported. 1998, 11. February. The daily newspaper Jeversches Wochenblatt reports. human disease caused by infectious BSE meat in Great Britain in France and in two cases in Portugal.
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1998, march.Within two month the beef ban for Northern Ireland will be lowered to permit the export of beef from certied herds being free of BSE for a period of eight years. The province of Northern Ireland had "only" 1.766 cases of BSE and 28 cases last year,compared with 170.000 cases in the rest of the United Kingdom. The UK Ministry of Agriculture announces further pressure to liberate export of cattle born after August 1,1996 when all stocks of potentially contaminated feed at farms and mills were destroyed. From January to October 1998 there were 66 new cases of BSE in Portuguese cattle, summing up to 380 cases. The European Commission decided to forbid the exportation of meat of Portuguese cattle.[12] BSE seems to continue to spread on the continent of Europe. 1999, April[13] A new case of BSE was diagnosed on French cattle. Since 1990 there were 103 cases in France reported. 1998 brought 18 cases. The Minister of Agriculture of France Jean Glavany says that these cases have resulted from contaminated feed made from carcasses of cattle dened of BSE. Starting at the end of 1996 stronger regulations concerning animal meal were introduced. Glavany says that infected meal which in France is allowed for chicken, pig and sh were fed to ruminants by mistake. Glavany expects BSE cases to reduce in 20002. What about the menace of contaminated fodder which is still fed to pigs, chicken and sh ? Safety of meat is of no concern 11 cases of BSE reported in Belgium. Netherlands 6 reported cases. Germany: 6 reported cases Italy: 2 cases of BSE Ireland: 471 cases of BSE. In the European Union there were 183.639 cases of BSE. 95% of these cases were reported in the United Kingdom [14] 1999.- The European Commission lifts the export prohibition of meat from great Britain. The agricultural Minister of Germany Karl-Heinz Funke states: Nowhere can the consumer be so safe as by us September 2000.- The EU Commission discovers on control of animal feed in Bavaria 75% of samples to contain animal meal. There is no reaction of the authorities of Bavaria November 22.- The German Heath Minister Funke take position against the prohibition of animal meal as fodder.
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CHAPTER 18. BSE
Two German cows were tested positive for BSE on 24 of November 2000. One had been slaughtered and the meat had been distributed for sell. All parts could be recalled. The other cow had been sold two years to Portugal were the test was made. Germany turned out to be considered as not BSE free country. December, 6. 2000The Institute for Meat research of Germany sends a warning to the Government of Germany telling that there is a great danger emanating from meat from separator meat used in sausages. December, 19.- EU Commissioner David Byrne urges the German Government to stop the sell of sausages with bovine meat as ingredient and to start a recall of these products. 30.November 2001: There are 124 BSE cases in Germany of which 39 had no sings of the disease. The selling of this meat was avoided by the test of BSE. Half of these animals were born in Bavaria[15] The birthday of 90% of these positive animals dates on 1995 and 1996. BSE is reported from Austria and Japan. In Japan contaminated British animal meal had been fed. BSE is therefore not under control. The European Commission has therefore established a decision in order to strengthen the rules related to BSE: Starting with 1.10.00 the parts like head, brains, eyes, tonsils, spinal cord and a part of the intestine of cattle with more than 12 month of age must be separated and incinerated. In case of sheep and goats additionally the melt must be removed and incinerated. This rule is valid in all countries of the EU, This rule is also valid for the production of animal our for feedstu. Germany in level two of BSE-risk The European Commission in its report from June 2000 has classied Germany as level two of the risk of BSE. Germany is surpassed only by Great Britain and Portugal in BSE risk. During the time of uncontrolled spread of infected corpses Germany had imported infected meat and animal feed from great Britain. The EU Commission expects therefore many cases of BSE and CJD in Germany. In February 2001 the total number of 41 BSE positive cases had been reported in Germany.
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Concerns over gelatin (used in Food and medicaments capsules dragees etc) following the BSE crisis in Europe and thus being spread over the whole world have led researchers to look after alternatives.
Alternatives to gelatin E 406 Agar-Agar E 412 Guar gum E 410 Carob seed Inulin:Inulin is made from chicory.It has good technological properties and a stimulating eect on Bidus bacteria which are part of the normal intestinal ora building therefore a protective wall against the Helicobacter pylori which is known as agent of intestinal ulcers which escalate to cancer. Amylopectic potato starch, produced from genetically modied Potatoes with 25% more amylopectin with no amylose is told to be another substitute to gelatin. Amylopectic potato starch after processing has no genetically modied material left. According to the European Novel Food Directive there is no need to declare the GM origin on food label. Amylopectic potato starch is gluten-free and has a function as food ber. Sugar beet ber is used to improve the consistency and taste of meet products such as meet balls, hamburgers and meat loaf improving its juiciness. Another ingredient to improve exact portioning and specic shapes, sizes and weights is a frozen coagulated protein in combination with thrombin, an enzyme that will catalyze cross-linking between brinogen and meat collagen. All these new ingredients may become important alternatives to gelatin in case of BSE spreading. Agar Agar E 406 is a gelling agent extracted from the cell walls of red algae. Guar meal E 412 is a gelling agent from the seeds of the guar plant which grows in India. Locust bean gum E 410indexLocust bean gum, alternative to gelatine is a gelling agent of the seeds of the locust tree. Lecithin from brains and nervous system material Lecithin extracted from brains and nervous systems from BSE cattle was used in the production of chocolate.
1400 What is safe and what is a deadly menace?
CHAPTER 18. BSE
As BSE still keeps going and meal from diseased animals is still being fed there is no safety for European beef. All BSE-tests like Prionics are only safe when the animal already has clinical signs of the disease. In Germany 60% of cattle is slaughtered being under two years of age when tests fail. To be sure not to get the deadly CJ disease try to get beef from Argentina,Australia, Chile, New Zealand and Paraguay. There is canned meat imported from these countries. Corned beef is safe, but it is very salty. Very dangerous is meat from Great Britain, Portugal, France,Switzerland,Spain, Germany and everything which comes from eastern countries like Poland, because contaminated, unsafe meat is sold there to be imported in the European Community. In USA there are cases of BSE in wild animals. All care should be made to avoid the spread of BSE in USA cattle. Wild animals should therefore not be used in the production of meal for animal feed because transmission of priones is still unknown. Unsafe are stock cubes and dry soups and sauces as they contain meat extracts .
18.1.10
Prion tests for animals and human use
As The menace of BSE disease and CJD increases the search for a safe test on blood which can demonstrate the presence of the disease in animal and in human beings turned out to be a run against the time. There are other diseases which are probably caused by priones like parkinson and Alzheimer, rheumatic forms and some sort of tumors which may interfere in the immunological reactions used for the diagnosis. Boehringer Ingelheim ( Germany ) tries to nd such a test. Prionics is now in use to test animals on BSE but it is not safe as there are many false negative results. Rapid post mortem tests to detect TSE (Transmissible Spongiform Encephalopathy) in small ruminants not safe [16] The situation of Transmissible Spongiform Encephalopathy (TSE) of small ruminants like goats and sheep in Europe is analysed by the EU Food Safety in its release "new information about TSE in goats". [17] Evaluation of the validated TSE tests found that they do not perform equally toward atypical cases and that dierence in performance result in under- or non recognition of various types of scrapie. Moreover, a new type of TSE (atypical scrapie cases/NOR98)
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not previously recognized in the EU, was detected in small ruminants. Currently atypical/Nor98 has been detected in a large number of European countries and approximately constitutes 80% of test positive cases identied in EU. New tests have to successfully pass all stages of a new evaluation process. New tests should detect classical scrapie, atypical scrapie and BSE in sheep and detection of preclinical cases and comply with criteria on limitations posed by analytical sensitivity in comparison with bioassay. The criteria set higher standards than have previously been approved for validation of small ruminant post mortem TSE tests for classical scrapie and BSE as well as for atypical scrapie. Considering data available about abnormal PrP distribution in the three recognized small ruminants TSE forms (BSE, classical scrapie and atypical scrapie) the use of brainstem appears to be the best compromise for detection of all TSE agents in small ruminants. In consequence, ocially conrmed (by CRL and NRL) positive/negative brainstem will be used for the evaluation of tests. The BIOHAZ panel recommends that tests already approved for the detection of TSE in small ruminants should be required to participate in the new evaluation in order to conrm their robustness and their ability to full the additional performance requirements (e.g. atypical cases and analytical sensitivity).
18.1.11
New method to detect BSE infectious mad cow prions [18]
Christina J Sigurdson and colleagues 2007 developed a method based on a uorescent molecule, a conjugated polymer for detecting and characterizing prions. The new method can distinguish between dierent strains of prions, whereas the classic methods like antibodies detection and the Congo red staining do not make the distinction. As the disease was narrowed down public concern about BSE ebbed away. New methods of diagnosis are, however, being developed, because scientists are aware of a possible species barrier braking of the disease, what could make them rapidly contagious within the species. The method was tested on BSE, scrapie and mad elk disease (CWD) infected mice. New strains of prions emerged throughout several generations which could be identied with the new method. According to the authors the luminescent conjugated polymers (LCPs) method, emit conformation-dependent uorescence spectra, for characterizing prion strains, helping to detect structural dierences among discrete protein aggregates and to link protein conformational features with disease phenotypes.
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CHAPTER 18. BSE
The method is now being adapted to blood controls as several cases are known of human BSE infected donors have transmitted the vCJD disease to other patients during the blood transfusion. [19]
18.1.12
Milk and related products an the risk of transmission of BSE
According to Martin Krnke, professor of microbiology at the University of Cologne milk and related products from diseased cows may contain pathogenic agents of BSE. The transmission of the disease to mankind through milk products is theoretically possible. Krnke is Leibniz-Prize winner 2001 regarding his researches on immunology and cell biology.
18.1.13
Clinical signs of BSE in cows[20]
Cows with BSE disease loss weight, reduce milk. The disease is marked by: Disorder of behaviorRestlessness, nervousness, fearfulness or start to bite. Disorder of sensitivity Lash out when the hind foots are touched with a broom. Striking with the head and horn and grinding of teeth when touched with a pencil on head and neck. Wince with sudden noise such as clapping. Disorder of motility Ataxia, plunge down and impossibility to stand up. Buckle up or wavering during free walking and loose of balance with break down. Animals start suddenly to lash out during milking. Excessive licking of the nose. Goggle-eye. Refusal to cross a small ditch followed by sudden jump over. Refusal to cross the door of the stable followed by sudden jump through. All clinical signs may be intensied by stress such as transport or diminished under calm conditions. There are no signs that certain breeds or a sex are more susceptible to BSE disease.Incubation period is two to eight years. Infected animals disease between 2 to 12 years, most frequently 4 to 6 years of age.
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On living cattle with signs of BSE normal liquor stands for BSE disease meanwhile central nervous system diseases change liquor with signs of infection. A nal diagnosis is the histological alterations of the brain. In advanced stage of the disease these sings may be absent. The clinical signs can be used to monitor a herd without complicated tests. These signs should be carefully observed all over the world to avoid an outbreak in other continents. The WHO warns for possible outbreaks of BSE worldwide. According to WHO it may be that the disease is already present in Argentina and Brazil only not being noted because no tests are being made. Brazil is already told to be careless in relation to BSE making no eort to test their cattle. The clinical signs may become useful as they are not expensive and very useful to detect outbreaks of BSE in developing countries. Cows with the clinical signs of BSE should be burned and not be used as human food or animal feed.
18.1.14
Elk Disease in Canada
In western Canada 14.000 domestic elks were slaughtered to control the Elk Disease which is a BSE-like neuropathological disease. 14 elks were found to have clinical signs such as: Swallow complaints Loss of orientation Rapid loss of weight Death by starving Canada has about 54.000 domestic elks for meat production which is an important industry in the province of Saskatchewan. Globalization and the destruction of geographical, economic and ecological isolated units are the main cause of the spread of diseases such as BSE, Elk Disease, Foot and Mouth Disease and other epidemiological relevant epidemics.
18.1.15
BSE-Risk material
BSE-Risk material according to resolutions of the European Commission 2000/418/EG (29.6.2000) and 2001/2/EG (27.9.2001): Skull, including brain, eyes, tonsils, spinal cord and intestines from cattle, sheep and goats over twelve month of age. Spleen of sheep and goats of all age There is a strong possibility that prions reach the blood stream, lung and heart during slaughter by bolt with the slaughter gun as material of the brain squirts all around.
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CHAPTER 18. BSE
18.1.16
EU rises age of cattle for BSE risk material removal to reduce costs [21]
The European Commission Regulation EC 357/2008 from 22.04.2008 raising the age limit at which the bovine vertebral column must be removed from beef from 24 to 30 months. [22] The Regulation, based on scientic advice from the European Food Safety Authority (EFSA), increases the age at which the vertebral column of slaughtered cattle must be removed from 24 to 30 months. This measure was possible due to the improvement in the BSE situation and was considered to be safe up to 33 month of age by EFSA in 2007. [23] The vertebral column is included in the EU list of Specied Risk Material (SRM), considered to pose the greatest risk of BSE transmission, and is required to be removed and destroyed in bovine animals over a certain age, to prevent it entering the food and feed chain. The European Commission says that the higher age limit for vertebral column removal rises the competitiveness of farmers and meat industries, and reduces the cost of destruction of SMR waste.
18.1.17
BSE infection danger from contaminated pastures
The Ministry of Environment of Germany was concerned with the possibility of cattle infection with BSE prions due to pastures contaminated with manure from diseased animals (early 2000). According to professor Georg Pauli from the Robert-Koch Institute in Berlin, there is not such a danger. Sheep which lamb outdoor can deposit infectios placenta on the ground. This material is being ingested by other sheep spreading in this way scrapie. Manure contaminated pastures do not present such danger because the prions are unable to multiplicate or stay infectious over more than several weeks on ground but are not assimilated by plants. Not free of any doubt is the possibility of a direct intake of prions of fresh manure contamination of pastures without the way over a plant host.
18.1.18
BSE infection danger for humans
BSE infection danger for humans are often underestimated. Infectious prions may come from primary infective material from diseased animals. Secondary infective material is all material coming from slaughterhouse which processes cattle. utensils are contaminated by risk material such as spinal cord cutting the animal corps on halves or the spreading of brain material by the slaughter gun. Cleaning and
18.1. THE PRION DISEASES STILL ENDEMIC IN 2011 disinfection in normal industrial processing are not sucient to avoid BSE risk.
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Temperature inactivation of prions takes place only at 330o C and a pressure of 3 bar during 30 minutes. Normal cooking, heating and freezing do not inactivate the prions. It is believed small wounds make a direct infection due to contact with BSE material possible. Butchers are therefore advised to take safety precautions.
18.1.19
Risk of disease from animal proteins in feed [24]
According to the EFSA the ruminant epidemic of bovine spongiform encephalopathy was spread in cattle due to feed containing BSE contaminated animal proteins. The practice of feeding animal proteins to cattle and other farmed animals destined for the human food chain had been banned since 2001. The EFSA assessed now the risks certain uses of animal proteins in animal feed. In their report the EFSA says that no Transmissible Spongiform Encephalopathies (TSEs) have been identied as occurring in pigs or poultry under natural conditions. The EFSA concluded that the risk of transmitting BSE to pigs utilizing poultry Processed Animal Proteins PAPs and vice versa, that means, feeding pigs with poultry proteins and visa versa is negligible. In this case human risk of BSE would be negligible, as long no future TSE infection is found in pigs and poultry. The risk of transmitting BSE through small quantities of animal proteins in feed to ruminants can not be excluded and would increase the human exposure the risk of BSE. The risk of transmitting BSE to non-ruminants is considered to be lower than to ruminants, as long as intra-species recycling is avoided, and the increase in the exposure risk of BSE to humans is negligible. The Commission may now lift the ban of PAPs in feed between pigs and birds and vice versa.
18.1.20
Health and nutrition authorities from European countries and EU- Commission
Health and nutrition authorities have failed to protect the population from the hazards of BSE and have made it possible the disease to keep on spreading all over the word. In France the families of four people which died of the new variant of Creutzfeldt-Jakob disease blame the government of having failed to react properly in the years of 1988 to 1996 causing their death. According to documents concerning this matter which have been presented by the plaintier the French government had knowledge since 1990 of the risk of human BSE-contamination. The government banned the import of beef from Great Britain with delay of 6 years.
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CHAPTER 18. BSE
There is also a charge against the European Union which did not stopped the trade of animal feed from UK with the Continent in order not to delay the opening of the European Market in 1992. France supported this decision in order to protect her meat industry[25]. On December 6, 2001 the scientic committee which advises the EU-Commission has conrmed that prions of unknown origin are responsible for the transmission of the BSE disease by means of feed and other contaminations and in a small number from the animal mother to its child.[26] tests Such meager statement is a sign of disorientation on regard to BSE. Since 1995 there were 101 n CJD cases reported. [27] Table 18.2: New variant of Creutzfeld-Jakob-Disease (n CJD ) in UK Reported cases of nCJD 1995 3 1996 10 Reported total cases of vCJD in humans until 2007 in UK are 1997 10 1998 18 1999 15 2000 28 158.[28] Reported total cases of vCJD in France until 2007 are 21 [29] Year
18.1.21
Chronic Wasting Disease CWD
Chronic Wasting Disease in whitetail deer and elk is found in Colorado,Wyoming, Nebraska, Wisconsin and Illinois, Kansas, South Dakota,Montana, Oklahoma,New Mexico, Alberta and Saskatchewan. It causes spongy holes in the brains of the animals. They slobber, stagger, lose weight and die. There is no cure. The disease belongs to the family of disorders that includes scrapie in sheep, mad cow disease in cattle and Creutzfeldt-Jakob disease in humans. Research is being done in order to see whether Chronic Wasting Disease can jump from deer to other species such as cattle and even humans through exposure to infectious agents such as venison and velvet antler used in food supplements.[30] The prions that cause CWD may persist in the environment for years. It is therefore suggested to avoid plowing under the carcasses of animals that have died of scrapie, mad cow disease or other prion disease or use these carcasses in fertilizer because animals may consume contaminated soil while grazing. There is although the possibility that prions in the soil could be absorbed by plants and worms which are consumed by the animals.
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18.1.22
Greater potential of CWD-infected deer than elk to transmit the disease to other species [31]
Brent L. Race and colleagues 2007 studied the potential for cross-species transmission of chronic wasting disease (CWD) of deer and elk. According to he researchers CWD prevalence in wild elk is much lower than its prevalence in wild deer. The researchers found that the quantication of prion protein from tonsil and retropharyngeal lymph nodes showed much higher levels of PrPres in deer than in elk, suggesting that CWD-infected deer may be more likely than elk to transmit the disease to other cervids and have a greater potential to transmit CWD to noncervids. The high presence of PrPres in deer lymphoid tissues suggest that infectivity might also be present in other peripheral tissues such as intestine, kidney, or salivary glands, which could possibly lead to excretion or secretion of infectivity in faeces, urine, or saliva. in conned settings, where animal-to-animal contact increases. CWD transmission to humans Earlier studies have not shown any evidence for transmission of CWD to humans. CWD has been transmitted to cattle by intracerebral but not by oral inoculation, and no reports have found that co-pasturing of CWD-infected deer or elk with cattle has resulted in transmission. Raymond and colleagues 2000 [30] found in vitro assays designed to test the susceptibility of humans or cattle to CWD suggested a very low probability of transmission to humans. Raymond suggests that there might be a barrier at the molecular level that should limit the susceptibility of non-cervid species to CWD. Sheep might cross CWD species barrier Race and colleagues suggest that among livestock, sheep might be a possible target for CWD infection in appropriate situations such as co-pasturing. Also, a CWD agent from putatively infected sheep could have a host range not usually associated with CWD and might cross species barriers more readily than CWD from cervids. Thus, if CWD continues to expand in deer and elk populations, the possibility of transmission to noncervid species will require continued surveillance.
18.1.23
Natural cross-species transmission of 263 K scrapie in hamster [32]
Transmissible spongiform encephalopathy (TSE) diseases are known to cross species barriers. New TSE diseases have been identied in deer and elk, in domestic cattle, and in humans. The amino acid sequence of the prion protein (PrP) is known to be an inuential factor for cross-species transmission of TSE disease to a new host.
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CHAPTER 18. BSE
Meade-White and colleagues 2009 reported that hamsters, infected with original Syrian hamster 263 K prions, presented prole changes of the PrP amino acid sequences within dierent hamster species. The authors suggest that the PrP sequences of a new host can change the phenotype presentation of the infecting agent. Identication of cross-species transmission events are thereby very dicult.
18.1.24
Human prion protein polymorphism 171S resistance to murine scrapie [33]
Transmissible spongiform encephalopathies (TSE) or prion diseases are neurodegenerative disorders associated with conversion of normal host prion protein (PrP) to a misfolded, protease-resistant form (PrPres). PrP expression is required for prion disease, and PrP knockout mice are resistant to both infection and disease. PrP gene polymorphisms occur naturally in many species. Polymorphisms in sheep and in mice may inuence susceptibility to scrapie infection. .. Striebel et al 2011 describe the inuence of prion disease on a rare human polymorphism PrP N171S using a mouse PrP homolog, PrP-170S. The scrapie strains 22L and ME7 were highly pathogen for PrP 170S mice. Strains RML and 79A produced clinical disease and PrPres formation in only a small subset of mice at very late times. Resistance to infections in mice, but no resistance to infectious prions in vitro suggest that in vivo conversion of PrP-170S by RML and 79A scrapie strains is prevented by PrP molecules expressing certain polymorphisms, factors or conditions not present in vitro.
18.1.25
Prion protein membrane anchoring is necessary for prion infection [34]
According to Klingeborn et al. 2011 a glycosylphosphatidylinositol (GPI)-anchored membrane glycoprotein is necessary for prion protein PrP to become neuroinvasive. The authors tested various innoculation routes in mice. Prion diseases are transmitted by extracerebral prion infection, anchored PrP are therefore important for the infection to take place.
18.1.26
CWD infection depends on the amino acid sequence of host prions [35]
Chronic wasting disease (CWD) is a prion disease aecting deer, elk, and moose. Race et al. 2011 point out that susceptibility to infections depends on the amino acid sequence of the host prion protein (PrP). The authors found that mice expressing 96GG deer PrP protein were highly succeptible to CWD, but mice which expressed 96SS PrP prion protein were immune to the disease. These data support the assumption that susceptibility to CWD infection depends on the amino acid sequence of host prions.
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18.1.27
Humans may be resistant to chronic wasting disease (CWD) of deer, elk and moose [36]
To verify human susceptibility to CWD Race et al. 2009 used cynomolgus macaques and squirrel monkeys as human models. Feeding infectious CWD materials caused the disease in squirrel monkeys but cynomolgus macaques did not diseased. The authors stress that humans are evolutionarily closer to macaques than to squirrel monkeys, suggesting that humans are also resistant to chronic wasting disease.
18.1.28
Chronic wasting disease (CWD) infectious prion materials in deer fat [37]
CWD infectious prion materials are found in central nervous system and lymphoid tissues, with smaller amounts in intestine and muscle of ruminants, and also in fat of mice. Fat of ruminants, such as deer should be considered as CWD infection of other species. Soil as reservoir of prions [38] Farm soil is a potential long-term reservoir for BSE infective agents according to ndings that point out that prions bind tightly to clay. Ban of import of all cervids in Oregon To avoid further spreading of the CWD Oregon has imposed a permanent ban on the import of all live grazing deerlike animals called cervids. allowed are only boned wrapped and cut meat. Not allowed are brainparts, whole heads or spines. Allowed are hides and portions of clean skull plates with antler attached.[39]
18.1.29
History of CWD
mid-1990s: For years the disease remained conned to Colorado and Wyoming. 1996: The disease was found on an elk farm in Saskatchewan 1997 Signs of the disease in an elk farm of South Dakota. 1998: Elk farms of Nebraska were found to be infected, followed by Oklahoma an in subsequent years Montana, Kansas and Alberta followed. 2002: New Mexico, Minnesota Wisconsin and Illinois reported cases of CWD. The National Institutes of Health researchers warn that prion diseases may be more common than originally thought, raising public health concerns about the practice of giving other farm animals feed made from the byproducts of other animals.
18.1.30
French BSE goat 2002 [40] [41] [42]
Goats can suer from scrapie, which is a type of TSE (Transmissible Spongiform Encephalopathy), a group of diseases that also includes BSE in cattle. Scrapie has been
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CHAPTER 18. BSE
known for centuries. A goat slaughtered in France in 2002 has a type of TSE which might be BSE. the mouse bioassay (which takes two years to complete) was conrmed on the 28.01.2005. This TSE was detected in a healthy goat as part of the normal surveillance measures which have been in place in the EU for many years.BSE has never been found under natural circumstances in ruminants other than cattle. Its presence in goats or other ruminants has been viewed as theoretically possible but has never been detected. Arising from this EU testing programme, a healthy goat slaughtered in 2002 in France was tested at random for TSEs. Now preliminary results indicate that a goat slaughtered in France in 2002 has a type of TSE which might be BSE. It is believed that the goat was infected by feed with BSE prion contaminated meat. As this feed was banned for use in all ruminants, there is no risk of a widespread problem. Based on these facts, the European Food Safety Authority (EFSA) has advised that goat milk and derived products are unlikely to present any risk of TSE contamination if the milk comes from healthy animals. Currently, as a precautionary measure and following scientic advice, milk and meat from goats which are aected by TSE cannot be used. These rules were in place before the case of BSE in a goat was discovered. As for cattle and sheep, specied risk materials (the tissues most likely to carry infectivity if the disease is present) are also removed from all goats even if there is no infection detected. While it is not possible to say that there is absolutely no risk, any potential risk will be mitigated by the safety measures put in place. In light of the above, the European Commission advises no change in current consumption of goat milk, cheese and meat.
18.1.31
BSE/TSE Statement 2004 of the EFSA on health risks of the consumption of milk from goats
Since the early 1990s, the BSE/TSE risk for milk and milk products has been discussed by scientic organisations, risk assessment bodies and public health organisations. Research has focused predominantly on the bovine species, while data on small ruminants, particularly goats, are limited. Indeed, epidemiological and experimental data on ruminants so far available have not provided evidence that milk or milk products harbour prion infectivity. Some research data support the nding that milk, colostrum and tissues of the mammary gland from bovine can be classied in the category of no detectable infectivity. However, based on a number of observations from research data, mainly research concerning sheep, there are indications that infectivity in the milk from small ruminants cannot be totally excluded. In case of mastitis, one could expect an inltration of potentially infected blood
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into the milk as the blood-milk barrier may not or only partly exist. But even in the case of absence of mastitis the barrier may not be 100% eective. From the limited data available today it is concluded that in the light of current scientic knowledge and irrespective of their geographical origin, milk and milk derivatives (e.g. lactoferrin, lactose) from small ruminants are unlikely to present any risk of TSE contamination provided that milk is sourced from clinically healthy animals. Exclusion of animals with mastitis is considered to reduce the potential risk. Further assurance of healthy milk could include milk tests for total somatic cell counts indicative of inammation.
18.1.32
Diculties with somatic cell count
The EFSA in its statement of 2005 enumerates some of the diculties concerning somatic cell count accuracy of goat milk: [43] The somatic cell count accuracy is aected by the apocrine nature of milk secretion in goats. Cytoplasmic particles, which derive from the apical part of secretory cells, are normal constituents in goat milk. Certain methods used to count somatic cells cannot distinguish these cytoplasmic particles, similar in size to somatic cells, from real somatic cells, which may lead to false readings. Moreover, the reference microscopy method, which is based on staining procedures, does not give satisfactory results in the majority of laboratories, when used on goat milk. Somatic cells that are identied in milk from healthy cows or ewes are mainly macrophages. Less than 30 % are other leukocytes. Higher levels of the latter are considered to be indicative of inammation. On the other hand, leukocytes can reach up to 60 % of total cells in normal goat milk. The somatic cell count is therefore dicult to interpret in terms of udder inammation. Non infectious factors greatly inuence the somatic cell count in goats. Physiological normality is dependent on the stage of lactation, age, time of sampling, the oestrus period, feed, stress, breed and the region. Most experts in this eld therefore consider that a specic somatic cell count-value derived from one population of goats may describe a normal animal health status in a second population and indicate mastitis in a third population. The panel concluded in 2005 [43] that due to the high variability of SCC in goat milk, even in healthy animals, SCC cannot be relied on neither as a specic indicator for TSE risk nor as an indicator of udder health. It is recommended to continue the increased surveillance in goats and to initiate additional research that would allow for a Quantitative Risk Assessment in goats. The above recommendations should be extended to include sheep. BSE in SwedenOne cow was tested positive for BSE in Sweden in 2006.The Swedish Board of Agriculture (BOA) believes that the cow had been fed meat and bone meal by
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CHAPTER 18. BSE
mistake. Not all safety routines were in place during the rst years of the infected cows life. The animal was probably infected about ten years ago. An investigation has started in order to nd what feedingstus the animal may have eaten during its lifetime. This investigation will also nd so-called risk animals on the farm, for instance animals in the same age bracket that have eaten the same feedingstus. [44] In the EU, BSE incidents have been falling dramatically since 1992. Extensive testing and controls programmes are responsible for the decline of incidences of the disease from 37,280 cases in 1992 to recent gures reported by the OIE. The favorable development led the EC to adopt a roadmap in July of 2005, with the aim of softening restrictions and reducing testing costs. The World Organisation for Animal Health published the details of BSE in countries that reported cases in 2004. According to this report Ireland found 126 cases of BSE in its cattle in 2004, compared with 137 found in Spain. The UK had the highest incidence of BSE cases in the world in 2004 with 343 cases conrmed, followed by Spain, Ireland. Portugal was fourth in the BSE league, reporting 92 cases in 2004, followed by Germany with 59 cases. France reported 54 cases of BSE in the same year. [45]
18.1.33
Production process for gelatine [46]
According to the Corrigendum to Regulation (EC) No 853/2004 of the European Parliament and of the Council of 29April 2004 laying down specic hygiene rules for food of animal origin, the production process for gelatine must ensure that: 1. For the production of gelatine intended for use in food, the following raw materials may be used: (a) bones; (b) hides and skins of farmed ruminant animals; (c) pig skins; (d) poultry skin; (e) tendons and sinews; (f) wild game hides and skins; and (g) sh skin and bones. 2. The use of hides and skins is prohibited if they have undergone any tanning process, regardless of whether this process was completed. 3. Raw materials listed in point1(a) to(e) must derive from animals which have been slaughtered in a slaughterhouse and whose carcases have been found t for human consumption following ante-mortem and post-mortem inspection or, in the case of hides and
18.1. THE PRION DISEASES STILL ENDEMIC IN 2011 skins from wild game, found t for human consumption.
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4. Raw materials must come from establishments registered or approved pursuant to Regulation (EC) No 852/2004 or in accordance with this Regulation. 5. Collection centres and tanneries may also supply raw material for the production of gelatine intended for human consumption if the competent authority specically authorises them for this purpose and they full the following requirements. (a) They must have storage rooms with hard oors and smooth walls that are easy to clean and disinfect and, where appropriate, provided with refrigeration facilities. (b) The storage rooms must be kept in a satisfactory state of cleanliness and repair, so that they do not constitute a source of contamination for the raw materials. (c) If raw material not in conformity with this chapter is stored and/or processed in these premises, it must be segregated from raw material in conformity with this chapter throughout the period of receipt, storage, processing and dispatch.
18.1.34
Chapter II: Transport and Storage of Raw Materials
In place of the identication mark provided for in Annex II, Section I, a document indicating the establishment of origin and containing the information set out in the Appendix to this Annex must accompany raw materials during transport, when delivered to a collection centre or tannery and when delivered to the gelatine-processing establishment. Raw materials must be transported and stored chilled or frozen unless they are processed within 24 hours after their departure. However, degreased and dried bones or ossein, salted, dried and limed hides, and hides and skins treated with alkali or acid may be transported and stored at ambient temperature. Chapter III: Requirements for the Manufacture of Gelatine 1. The production process for gelatine must ensure that: (a) all ruminant bone material derived from animals born, reared or slaughtered in countries or regions classied as having a low incidence of BSE in accordance with Community legislation is subjected to a process which ensures that all bone material is nely crushed and degreased with hot water and treated with dilute hydrochloric acid (at minimum concentration of 4% and pH 12.5) for a period of at least 20 days with a sterilisation step of 138 to 140C o during four seconds or by any approved equivalent process; and (b) other raw material is subjected to a treatment with acid or alkali, followed by one
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CHAPTER 18. BSE
or more rinses. The pH must be adjusted subsequently. Gelatine must be extracted by heating one or several times in succession, followed by purication by means of ltration and sterilisation. 2. If a food business operator manufacturing gelatine complies with the requirements applying to gelatine intended for human consumption in respect of all the gelatine that it produces, it may produce and store gelatine not intended for human consumption in the same establishment. Chapter IV: Requirements for Finished Products Food business operators must ensure that gelatine complies with the residue limits set out in the following table: Residue Limit As 1 ppm Pb 5 ppm Cd 0,5 ppm Hg 0,15 ppm Cr 10 ppm Cu 30 ppm Zn 50 ppm
18.1.35
Reduction of BSE tests on US cows [47]
Over the last few years, a type of Acquired CJD called variant (vCJD) has been identied in young people. vCJD has been linked to ingestion of beef tainted with BSE (bovine spongiform encephalopathy), most cases have occurred in the United Kingdom. Testing cows being slaughtered helped to reduce the risk of vCJD. However, according to Florences Newsletter, the USDA tests so few cows it would be impossible for anyone to know how prevalent U.S. BSE really is. Cattle testing was increased from 40,000 per year to 375,000 for an 18 month period following the discovery there are 35 million cattle slaughtered for the U.S. food supply each year. The Secretary of Agriculture Mike Johanns was asked last July by a commission leaded by CDJ Disease Foundation that the increased number of BSE testing should not be cut back but instead that it be increased. One week after this petition USDA cut back to the previous 40,000. In a letter to Florence at the Creutzfeld-Jacobs Disease Foundation dated October 3, 2006 Mr. Johanns stated.... "With regard to USDAs activities, it is important to understand ...USDAs BSE surveillance is being conducted not as a food safety measure but rather as a monitoring eort designed to evaluate the eectiveness of the United States BSE safeguarding measures with respect to animal health".
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According to Florence it is dicult to understand how human risk from infected meat takes a back seat to what appears to be a policy beneting specic special interest groups. A statement released end May2007 reported that Japan and South Korea will soon be opening their borders to US cattle again based on the U.S. upgraded rating from the OIE (World Organization for Animal Health) from "possible risk" to "controlled risk". The USDAs Chief Veterinary Oce Dr. Ron DeHaven serves as the U.S. ocial delegate to the OIE. Through the OIE decision the USDA is now able to avoid accountability at all costs, even those directly related to human lives. The role of meat and bone meal (MBM) in the epidemiology of BSE [48] Mathilde Paul and colleagues 2007 studied the role of meat and bone meal (MBM), animal fat and dicalcium phosphate (DCP) after the feed ban on the risk for BSE epidemics. In France, meat-and-bone meal (MBM) has been banned from cattle feed since July 30, 1990. However, through January 1, 2007, 957 cases of bovine spongiform encephalopathy (BSE) have been detected in cattle born after the ban. Meat bone meal (MBM) According to the authors the source of infection in cattle born after the MBM ban still involves MBM. The BSE agent may have entered cattle feed by cross-contamination with feed for monogastric species (pigs and poultry) in which MBM was still authorized until November 2000. Cross-contamination could have occurred within factories, during feed delivery to the farm, or on mixed farms that have cattle and pigs or poultry. The authors raise the question of eectiveness of the ban that was initially restricted to bovines and belatedly extended to other species to reduce cross-contamination. The role of MBM as a source of BSE after the ban of MBM for cattle is well documented through cross-contamination in feed factories. The authors found that the total ban of MBM for farm animals in November 2000 was essential for controlling the spread of BSE.
18.1.36
Other animal by products
Animal dicalcium phosphate (DCP) According to Paul and colleagues, together with other studies say that the implication of animal DCP as a source of BSE, if it existed, should have been marginal. In contrast, a risk analysis by the European Food Safety Agency [2] considers the poCopyright 1998-2010 Karl H. Wilm. All rights reserved. OurFood Database of Food and Related Sciences
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CHAPTER 18. BSE
tential role of animal DCP in cattle infection as to be of the same order of magnitude as the residual risk from cross-contamination with MBM. Animal fat in milk replacers This study cannot exclude a minor eect of animal fat in milk replacers because of the solubility of prions and the possible contamination with protein impurities by contact with other infectious materials at the slaughterhouse. Animal fat is incorporated in cattle feed in milk replacer and in proprietary concentrates. The authors point to the fact that in current context of the decreasing epidemic, economic pressure is increasing to release the ban of MBM in feed for monogastric species.
18.1.37
Detection of prion infection in vCJD disease associated with the ingestion of BSE food [49]
Variant Creutzfeldt-Jakob disease (vCJD) is a fatal neurodegenerative disorder originating from exposure to bovine-spongiform-encephalopathy-like prions. This disease has a long and clinically silent incubationsposing and is a risk to others via blood transfusion, blood products, organ or tissue grafts, and contaminated medical instruments. The authors report the development of an assay for detection dormant infections. It is based on a solid-state binding matrix to capture and concentrate disease-associated prion proteins coupled with direct immunodetection of this surface-bound material. The authors stress that it is a prototype blood test for diagnosis and can be further developed to allow largescale screening tests for asymptomatic vCJD prion infection. People become infected by BSE prions by eating food containing material from BSEinfected cattle, although other sources of exposure are possible. Much of the UK population born before 1996 (when rigorous measures to limit exposure were enforced) have potentially been exposed to BSE-contaminated food and the number of people who may carry the infection but remain healthy is unknown. [50]
Bibliography
[1] Supp,Barbara: Rinderwahn,Auch Minister haben Angst;Der Spiegel Nr.41 5.10.98. [2] Twentieth annual report 2011. the national cjd research and surveillance unit (ncjdrsu). oct 8, 2012. http://www.cjd.ed.ac.uk/documents/report20.pdf. [3] Research, the national cjd research and surveillance unit (ncjdrsu). http://www.cjd. ed.ac.uk/research.html. [4] Kster-Lsche,Kari: Rinderwahnsinn,BSE:die neue Gefahr aus dem Kochtopf/Kari Kster-Lsche-Mnchen:Ehrenwirth,1995 (Ratgeber Ehrenwirth).
BIBLIOGRAPHY
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[5] Krmer,Johannes: Lebensmittel-Mikrobiologie - 2.Auage-Stuttgart: Ulmer 1992. [6] http://www.ars.usda.gov/is/AR/archive/apr09/goats0409.htm. USDA ARS: News and Events: ARS and Partners Set Their Sights on Scrapie in Goats. [7] National Institute of Allergy and Infectious Diseases (NIAID):. Nih study suggests that early detection is possible for prion diseases. 02.10.2010. http://www.niaid. nih.gov/news/newsreleases/2010/Pages/prionCaughey.aspx. [8] Wilham JM, Orr CD, Bessen RA, Atarashi R, Sano K, Race B, Meade-White KD, Taubner LM, Timmes A, and Caughey B:. Rapid end-point quantitation of prion seeding activity with sensitivity comparable to bioassays. PLoS Pathog, 6(12):e1001217, 12 2010. http://www.plospathogens.org/article/info%3Adoi% 2F10.1371%2Fjournal.ppat.1001217. [9] Gielbert A, Davis LA, Sayers AR, Hope J, Gill AC, and Sauer MJ:. High-resolution dierentiation of transmissible spongiform encephalopathy strains by quantitative nterminal amino acid proling (n-taap) of pk-digested abnormal prion protein. J Mass Spectrom, 44(3):38496, 3 2009. http://www.ncbi.nlm.nih.gov/pubmed/19053160. [10] Adhikary R, Mukherjee P, Krishnamoorthy G, Kunkle RA, Casey TA, Rasmussen MA, and Petrich JW:. Fluorescence spectroscopy of the retina for diagnosis of transmissible spongiform encephalopathies. Analytical Chemistry, 82(10):4097, 2010. http://www. ncbi.nlm.nih.gov/pubmed/20411920. [11] http://www.gse-journal.org/articles/gse/pdf/2008/05/g07098.pdf. White, Stephen; Herrmann-Hoesing, Lynn; Orourke, Katherine; Waldron, Daniel; Rowe, Joan; Alverson, Janet: Prion gene (PRNP) haplotype variation in United States goat breeds (Open Access publication) p. 553. [12] Rindeisch-Importverbot besttigt; Lebensmittelzeitung LZ 9 from 5. march 1999. [13] Neuer BSE-Fall in Frankreich Lebensmittel Zeitung 14 from 9.april 1999. [14] Birne, David; European Commissioner for Health and Consumer Protection: BSE in Europe- The EU Response to a Major Public Health and Food Safety Challenge; New Food 14, page 9. [15] 124 BSE-Flle bei zwei Millionen Tests;Lebensmittel Zeitung LZ 48 30.November 2001. [16] http://www.efsa.europa.eu/etc/medialib/efsa/science/biohaz/biohaz_ opinions/ej509_postmortem_smru.Par.0002.File.dat/biohaz_op_ej509_post_ mortem_smru_summary_en.pdf. EFSA: Opinion of the Scientic Panel BIOHAZ: Protocol for the evaluation of rapid post mortem tests to detect TSE in small ruminants.
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CHAPTER 18. BSE EFSA:
[17] http://ec.europa.eu/food/food/biosafety/bse/goats_index_en.htm. What is the new information about TSE in goats?
[18] http://www.nature.com/nmeth/journal/vaop/ncurrent/abs/nmeth1131.html; jsessionid=0ED2A795CB25F93232293D90C074A862. Sigurdson, Christina J.; Nilsson, K. Peter R.; Hornemann, Simone; Manco, Guiseppe; Polymenidou, Magdalini; Schwartz, Petra; Leclerc, Mario; Hammarstrm, Per; Wthrich, Kurt; Aguzzi, Adriano: Prion strain discrimination using luminescent conjugated polymers. Nature Methods. Published online: 18 November 2007; | doi:10.1038/nmeth1131. [19] http://www.hpa.org.uk/hpa/news/articles/press_releases/2007/070118_ vCJD.htm. Health Protection Agency: 4th case of variant CJD infection associated with blood transfusion. 18 January 2007. [20] Braun,Ueli: BSE und andere spongiforme Enzephalopathien; Parey Buchverlag Berlin 1998,Page 33. [21] http://europa.eu/rapid/pressReleasesAction.do?reference=IP/08/ 624&format=HTML&aged=0&language=EN&guiLanguage=en. European Commission: Beef on the bone: Commission increases the age limit at which the vertebral column must be removed from beef. 22.04.2008. [22] http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=OJ:L:2008:111: 0003:0004:EN:PDF. Commission Regulation (EC) No 357/2008 of 22 April 2008 amending Annex V to Regulation (EC) No 999/2001 of the European Parliament and of the Council laying down rules for the prevention, control and eradication of certain transmissible spongiform encephalopathies. [23] http://www.efsa.europa.eu/EFSA/efsa_locale-1178620753812_ 1178620774854.htm. European Food Safety Authority: Opinion of the Scientic Panel on biological hazards (BIOHAZ) on on the assessment of the likelihood of the infectivity in SRM derived from cattle at dierent age groups estimated by back calculation modelling. 19/04/2007. [24] http://www.efsa.europa.eu/EFSA/efsa_locale-1178620753812_ 1178659674335.htm. EFSA: Opinion of the Scientic Panel on Biological Hazards on a request from the European Parliament on Certain Aspects related to the Feeding of Animal Proteins to Farm Animals, The EFSA Journal (2007) Journal number 576, 1-41. [25] BSE-Opferanklage in Paris.Lebensmittel Zeitung LZ 49 7.Dezember 2001. [26] Kein Zweifel an Prionen-Theorie, Lebensmittel Zeitschrift LZ 49 7. Dezember 2001 Page 24. [27] http://www.doh.gov.uk/cjd. National CJD Surveillance Unit.
BIBLIOGRAPHY [28] United Kingdom consulted March 12, 2007 www.cjd.ed.ac.uk/gures.htm. [29] France consulted March 12, 2007 www.invs.sante.fr/recherche. [30] Associated Press, December 23, 2001.
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[31] http://jvi.asm.org/cgi/content/abstract/78/23/13345. Browning and colleagues: Transmission of Prions from Mule Deer and Elk with Chronic Wasting Disease to Transgenic Mice Expressing Cervid PrP Journal of Virology, December 2004, p. 13345-13350, Vol. 78, No. 23. DOI: 10.1128/JVI.78.23.13345-13350.2004. [32] Meade-White KD, Barbian KD, Race B, Favara C, Gardner D, Taubner L, and et al. Characteristics of 263k scrapie agent in multiple hamster species. Emerg Infect Dis, 15(2):207215, 2 2009. http://www.ncbi.nlm.nih.gov/pmc/articles/ PMC2657641/?tool=pubmed. [33] Striebel JF, Race B, Meade-White KD, Lacasse R, and Chesebro B. Strain specic resistance to murine scrapie associated with a naturally occurring human prion protein polymorphism at residue 171. PLoS Pathog, 7(9):E1002275, 9 2011. http://www. ncbi.nlm.nih.gov/pmc/articles/PMC3182929/?tool=pubmed. [34] Klingeborn M, Race B, Meade-White KD, Rosenke R, Striebel JF, and Chesebro B. Crucial role for prion protein membrane anchoring in the neuroinvasion and neural spread of prion infection. J Virol, 85(4):148494, 2 2011. http://www.ncbi.nlm. nih.gov/pmc/articles/PMC3028874/?tool=pubmed. [35] Race B, Meade-White K, Miller MW, Fox KA, and Chesebro B. In vivo comparison of chronic wasting disease infectivity from deer with variation at prion protein residue 96. J Virol, 85(17):92358, 9 2011. http://www.ncbi.nlm.nih.gov/pubmed/21697479. [36] Race B, Meade-White KD, Miller MW, Barbian KD, Rubenstein R, LaFauci G, Cervenakova L, Favara C, Gardner D, Long D, Parnell M, Striebel J, Priola SA, Ward A, Williams ES, Race R, and Chesebro B. Susceptibilities of nonhuman primates to chronic wasting disease. Emerg Infect Dis, 15(9):136676, 9 2009. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2819871/?tool=pubmed. [37] Race B, Meade-White KV, Race R, and Chesebro B. Prion infectivity in fat of deer with chronic wasting disease. J Virol, 83(18):960810, 9 2009. http://www.ncbi. nlm.nih.gov/pmc/articles/PMC2738259/?tool=pubmed. [38] http://www.sciencenews.org/articles/20060211/toc.asp. Janet Ralo: Prions dirty little secret; Science News Online; Week of Feb. 11, 2006; Vol. 169, No. 6. [39] The Oregonian, November 9, 2002. [40] http://ec.europa.eu/food/food/biosafety/bse/goats_index_en.htm. Are goat milk, cheese and meat safe?
EFSA:
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[41] http://europa.eu/rapid/pressReleasesAction.do?reference=IP/04/ 1324&format=HTML&aged=0 &language=EN&guiLanguage=en. EFSA: Commission submits French Research Findings on TSE in a goat to Expert Panel. [42] http://www.efsa.europa.eu/science/biohaz/biohaz_documents/709/bdoc_ statement_goatsmilk_ en1.pdf. Statement of the EFSA Scientic Expert Working Group on BSE/TSE of the Scientic Panel on Biological Hazards on the health risks of the consumption of milk and milk derived products from goats. Brussels, 26 November 2004. [43] http://www.efsa.eu.int/science/biohaz/biohaz_opinions/1273/biohaz_op_ ej305_tse_safety_goatmilk_en1.pdf. EFSA Journal (2005) 305, 1-19 Opinion on the usefulness of somatic cell counts for safety of milk and milk derived products from goats. [44] http://www.sjv.se/presskontakten/pressmeddelanden/pressmeddelanden/5. 1d9d55b109ba1250a780001727.html. Jordbruks Verket: BSE conrmed in cow from the province of Vstmanland. 08.03.2006. [45] http://www.oie.int/downld/SG/2005/A_73_SG_2.PDF. OIE: World Organisation for Animal Health; 73rd General Session: Animal Health Status Worldwide in 2004 and Early. 2005. [46] http://europa.eu.int/eur-lex/lex/LexUriServ/site/en/oj/2004/l_226/l_ 22620040625en00220082.pdf. Corrigendum to Regulation (EC) No 853/2004 of the European Parliament and of the Council of 29 April 2004 laying down specic hygiene rules for food of animal origin (OJ L 139, 30.4.2004) 32004R0853R(01) Ocial Journal L 226, 25/06/2004 P. 0022 - 0082. [47] http://www.cjdfoundation.org/headlines.php?ptime=1167759120. Newsletter by wanda May 30, 2007 02:03 PM News; May 23, 2007. May
[48] http://www.cdc.gov/eid/content/13/6/867.htm. Paul, Mathilde; Abrial, David; Jarrige, Nathalie; Rican, Stphane;Garrido, Myriam; Calavas, Didier; Ducrot Christian:Bovine Spongiform Encephalopathy and Spatial Analysis of the Feed Industry. Emerging Infectious Diseases, Volume 13, Number 6-June 2007. [49] Edgeworth JA, Farmer M, Sicilia A, Tavares P, Beck J, Campbell T, Lowe J, Mead S, Rudge P, Collinge J, and Jackson GS. Detection of prion infection in variant creutzfeldt-jakob disease: a blood-based assay. Lancet, 377(9764):48793, 2 2011. http://www.thelancet.com/journals/lancet/article/PIIS0140-6736% 2810%2962308-2/abstract. [50] National Prion Clinic at the National Hospital for Neurology and Neurosurgery. Blood test for variant cjd. 2 2011. http://www.prion.ucl.ac.uk/clinic-services/ investigations-tests/#BloodTest.
Chapter 19 Parasites and Protozoa

A great deal of chronical diseases is caused by parasites and pathogenic protozoa due to consumption of infected water and foods, mainly in underdeveloped countries.
19.0.38
Endamoeba histolytica
The vegetative form of Endamoeba histolytica is motile and uninucleate. It multiplies by ssion and is able to invade the mucosa of the large intestine where it causes ulcerations. The invasion of the mucosa of the colon takes place by using histolytic enzymes what gave the name to the species. It comes to abscesses and destruction of the intestinal capillarities raspberry red bloody stool is the result. It may be carried to the liver, lung or brain and causes abscesses in those organs. In the intestine, the ameboid form may develop into cyst, a spherical body containing four nuclei and one or more rod shaped chromatoid bodies.Cysts are resistant to chemical and physical agents. Ninety per cent of infected people are not obviously ill. Only about 10 per cent have active dysentery, discharging trophozoites (motile cells).AS trophozoites die outside of the body and are killed by gastric juice and bile if they are ingested, the disenteric cases are not important as source of infection. The cysts however are able to survive for sometime outside the body and can pass uninjured through the alimentary canal to the ileum. Here each cyst gives rise to eight small infective trophozoites. Important source of infection are cyst passers which do not have signs of any disease but produce great amount of cysts which are spread by contaminated food and polluted water. If polluted water is used to irrigate plantations of vegetable and salads and human faecis are used as fertilizer the spread of Endamoeba histolytica can take place in large group of persons. Imported vegetables and salads should therefore carefully rinsed or bet1421
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CHAPTER 19. PARASITES AND PROTOZOA
ter cooked when the origin of it is unknown. With modern logistic service throughout the world, contaminated food can easily be imported from the most exotic parts of the world. Amebiasis is considered to be a tropical disease however occasional epidemics in the temperate zone are possible. The cyst-passers state is common in all parts of the world. About 10% of Americans are carriers.Also in Germany cyst carriers of Endamoeba histolytica are present. The incidence is highest in areas where sanitation is poor. In concentration camps, prisons and in homes with poor sanitation like favelas direct transfer and ies spread the disease. [1].
19.0.39
Prophylaxis of amebiasis
Improve the sanitary facilities, boil the infected water before drinking, avoid ingestion of infected vegetables, cook all meals and make combat to ies. It is obvious that there must be a decline of resistance of the human body to open the way to an infection. It is also admitted that warm climate rises the disposition to the disease. Other factors which help the eclosion of the disease are bacterial infections, disorders of nutrition and cold. Endamoeba histolytica was rst seen and described in feces of diseased persons in 1875 by Lsch. The disease in Germany is also known as Ambenruhr called after the region around the river Ruhr in Germany where great epidemics took place around 1875.
19.0.40 19.0.41
Other amebae Endamoeba gingivalis
It is harmless and lives around gums and teeth.
19.0.42
Endamoeba hartmanii
Is a small ameba which may live in the intestines producing subclinical or mild infections.
19.0.43
Dientamoeba fragilis
Is an intestinal form causing infections.It is not common.
19.0.44
Endamoeba coli
It is not pathogen.
19.1. FREE-LIVING AMOEBAE AS HUMAN PATHOGENS
1423
19.0.45
Endolimax nana
It is not pathogen.
19.0.46
Iodameba btschlii
It is not pathogen.
19.1
Free-living amoebae as human pathogens
Free-living amoebae belonging to the genus Acanthamoeba are the causative agents of granulomatous amoebic encephalitis (GAE), a fatal disease of the central nervous system (CNS), amebic keratitis (AK), a painful sight-threatening disease of the eyes, cutaneous lesions and sinusitis in AIDS patients and other immunocompromised individuals. Spiny surface structures called acanthopodia distinguish Acanthamoeba from other freeliving amoebae that infect humans, such as Balamuthia mandrillaris, Naegleria fowleri, and Sappinia diploidea Cysts are resistant to biocides, chlorination, and antibiotics and survive low temperatures (0 to 2o C ) Meisler et al., however, have shown that treatment with Freon or methylene oxide or autoclaving destroys cysts. Excystment occurs when trophozoites emerge from the cyst under suitable environmental conditions. Mazur et al. demonstrated that cysts retained viable amoebae for over 24 years after storage in water at 4o C and were tested for pathogenicity by intranasal inoculation of mice. Fewer deaths were recorded for mice inoculated with amoebae which had been encysted for 24 years than for mice inoculated with the same environmental isolates when tested initially. Marciano-Cabral and Cabral 2003 conclude that it is becoming increasingly apparent that free-living amoebae cause human disease. Furthermore, with increasing awareness of the potential of free-living amoebae to cause disease, amoebae from other genera may be found to be causative agents of human infections. [2]
19.2
Primary amoebic meningoencephalitis kills 10 in Pakistan
Primary amoebic meningoencephalitis caused the death of 10 Pakistan in the city of Karachi from March to September. According to the WHO people dont usually get the
1424
brain-aecting form of the disease by drinking water, but by swimming in dirty water or cleaning their nostrils with contaminated water. From the nostrils, the parasite (Naegleria fowleri) travels to the brain where it destroys tissue. [3] Symptoms include fever, nausea, vomiting, sti neck and headaches. The amoeba, Naegleria fowleri, lives in warm, unclean water. It can infect the human nervous system, though this occurs rarely. In those cases it is dicult to treat and can lead to death in about a week, says Musa Khan, in charge of WHOs Disease Early Warning System in Pakistan. The disease has killed people in other countries as well. About 300 cases of Primary Amoebic Meningoencephalitis (PAM) have been reported in the world, mostly in USA, Australia, and Europe. These infections are nearly uniformly fatal with only few survivors of PAM reported. [4] Free-living amoebae are widely distributed in soil and water. Small number of them was implicated in human disease: Acanthamoeba spp., Naegleria fowleri, Balamuthia mandrillaris and Sappinia diploidea. Some of the infections were opportunistic, occurring mainly in immunocompromised hosts (Acanthamoeba and Balamuthia encephalitis) while others are non opportunistic (Acanthamoeba keratitis, Naegleria meningoencephalitis and some cases of Balamuthia encephalitis). Although, the number of infections caused by these amoebae is low, their diagnosis was still dicult to conrm and so there was a higher mortality, particularly, associated with encephalitis. [5] In 2010 a case of Primary amebic meningoencephalitis (PAM) in Minnesota after freshwater exposure occurred 550 miles north of the previously reported northernmost case in the Americas. Kemble et al advert clinicians to be aware that Naegleria fowleri-associated PAM can occur in areas at much higher latitude than previously described. [6]
19.2.1
Vaccine to treat Naegleria fowleri infection [7]
Kim et al. 2012 evaluated the immune responses as DNA vaccination in Naegleria fowleri infection unsing nfal vaccination. The nfa1 gene of N. fowleri is located on pseudopodia and plays an important role in the pathogenesis of Naegleria fowleri. The authors suggest that this method may become a treatment of Naegleria fowleri infection.
19.2. PRIMARY AMOEBIC MENINGOENCEPHALITIS KILLS 10 IN PAKISTAN 1425
Picture: Life cycle Naegleria fowleri http://www.dpd.cdc.gov/dpdx/HTML/FreeLivingAmebic.htm Life cycle Naegleria fowleri Naegleria fowleri has three stages in its life cycle: cysts 1, trophozoites 2, and agellated forms 3. The trophozoites replicate by promitosis (nuclear membrane remains intact). Naegleria fowleri is found in fresh water, soil, thermal discharges of power plants, geothermal wells, and poorly-chlorinated swimming pools. Trophozoites can turn into temporary nonfeeding agellated forms which usually revert back to the trophozoite stage. Trophozoites infect humans or animals by penetrating the nasal mucosa 5 and migrating to the brain 6 via the olfactory nerves causing primary amebic meningoencephalitis (PAM). Naegleria fowleri trophozoites are found in cerebrospinal uid (CSF) and tissue, while agellated forms are occasionally found in CSF. Cysts are not seen in brain tissue.
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19.3
Acanthamoeba
Acanthamoeba lenticulata causes cutaneous lesions and sinusitis in AIDS patients and other immunocompromised individuals. Disseminated acanthamebiasis (DA), which is dened as widespread extracerebral disease, is extremely rare, but its incidence has increased in recent years such as occurred on account of organ transplants such as lung and kidneys. Marciano-Cabral 2007 reports a fatal case of disseminated acanthamebiasis in a heart transplant recipient and identify Acanthamoeba lenticulata (genotype T5, commonly found in the environment) as the cause of disease. Disseminated acanthamebiasis is dicult to diagnose, being made postmortem in most of the cases. [8] Acanthamoeba spp. are free-living amoebae found in soil, water, air, humans, and various animals. All known species of Achantamoeba spp are listed in the Taxonomy Browser of NCBI: http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?id=5754
19.3.1
Giardia lamblia
Giardia lamblia is a pathogenic protozoa living in the duodenum often without symptoms. Giardia lamblia adheres to the surface of the epithelian cells of the mucosa of the duodenum. When millions are present the mucosa is completely covered. Fat absorption and digestion is disturbed. Dietary deciency, diarrhea and bad smelling atulence takes place. The disease is spread over cysts in Water and foods.
19.3.2
Coinfections of Giardia intestinalis and Helicobacter pilori
The protozoan parasite Giardia intestinalis and the pathogenic bacterium Helicobacter pylori, both in association are found infesting concomitant in high number of mostly children in densely populated regions. [9] Ankarklev et al. 2012 examined children living in urban Kampala, Uganda, Giardia intestinalis was found in 20.1% of the children. Helicobacter pylori was found in 44.3% children with a 3-fold higher risk of concomitant Giardia intestinalis and H. pylori infections compared to non-concomitant infections. Giardia intestinalis multi-locus genotyping (MLG) analysis found assemblage B to be the most frequent Giardia infestation in Kampala children. The assemblage B was highly variable without association with Hellicobacter pilori but presents a risk factor for concomitant infections.
19.3. ACANTHAMOEBA
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19.3.3
Giardiasis in U.S.A. [10]
Giardia lamblia is a protozoan which is also known as Giardia lamblia or Giardia duodenalis. Giardiasis does not spread via the bloodstream, nor does it spread to other parts of the gastro-intestinal tract. It remains conned to the lumen of the small intestine. Giardiasis is a nationally notiable gastrointestinal illness. Yoder analysed the reported cases of giardiasis through CDCs National Notiable Diseases Surveillance System. In the period of 2009 until 2010 there was a slight increse of number of cases which peaked during early summer through early fall, with higher frequency in northern states. The highest frequency of Giardiasis was found in young children. This may have its origin in higher contact with contaminated water or ill persons.
19.3.4
Cryptosporidium
Oocysts of Cryptosporidium are widespread in the environment and can be found in lakes and streams. It is found in North America and Caribian islands, infesting animals which just had been born and adult animals which produce oocysts and serves as a source of infection for neonates. Breakdowns of public sewage systems have occasionally resulted in community outbreaks of cryptosporidiosis. Diarrhea, some weight loss and abdominal cramping are the sign of the disease. Many cases of cryptosporidiosis are caused by contamination by pet animals or by contact with other humans.
19.3.5
Balantidium coli
It is a very large protozoan which may cause severe ulcerations of the large intestine. Cysts and motile forms are found in feces. Hogs harbor commonly Balantidium coli.Infection of men is caused by contaminated food and water.
19.3.6
Importance of Giardia and Cryptosporidium in water manegement [11]
From approximately 40 names of Giardia spp only ve to six morphologically distinct species are recognised. Giardia lamblia (=G. intestinalis, =G. duodenalis) infect humans and other mammals, Giardia muris is found from other mammals, Giardia ardeae and Giardia psittaci from birds, Giardia agilis from amphibians and Giardia microti from voles. Recent studies demonstrated genetic heterogeneity among Giardia isolates and brought a better understanding of the role of wild and domestic animals as sources of human infection.
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19.3.7
Genotypes of Giardia duodenalis [12]
According to Caccio and Rian there are seven genetic groups within the species Giardia duodenalis identied by molecular assays. The groups A and B are found in both humans and animals, and the remaining groups C to G are host-specic. Sequence-based surveys have identied a number of genotypes within assemblages A and B in animal species which may be infectious to humans.
19.3.8
Eimeria
Eimeria is a genus of parasites that includes various species responsible for the poultry disease coccidiosis. Human infections Five genera are known to cause infections in humans: Cryptosporidium, Cyclospora, Isospora, Sarcocystis and Toxoplasma. Of these the rst three normally are conned to the gastrointestinal tract and cause diarrhoea and abdominal pain. The other two invade the body tissues and many be found in multiple organs. [13] Coccidiosis [14] Coccidiosis is a parasitic disease of the intestinal tract of animals, caused by coccidian protozoa. The disease spreads from one animal to another by contact with infected feces or ingestion of infected tissue. Diarrhea, which may become bloody in severe cases, is the primary symptom. Most animals infected with coccidia are asymptomatic; however, young or immuno-compromised animals may suer severe symptoms, including death. While coccidian organisms can infect a wide variety of animals, including humans, birds, and livestock, they are usually species-specic. One well-known exception is toxoplasmosis caused by Toxoplasma gondii. Genera and species that cause coccidiosis: Genus Isospora is the most common cause of intestinal coccidiosis in dogs and cats and is usually what is meant by coccidiosis. Species of Isospora are species specic, meaning they only infect one type of species, such as Isospora canis, Isospora ohioensis, Isospora burrowsi, and Isospora Neorivolta which infects dogs. Isospora felis and Isospora rivolta infect cats. The most common symptom is diarrhea. Genus Cryptosporidium contains Cryptosporidium parvum and Cryptosporidium Muris infecting cattle and other mammals including humans. Cryptosporidium hominis is specic for immunocompromised individuals, such as humans, dogs and cats.
19.3. ACANTHAMOEBA
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Genus Hammondia does not cause disease. It is transmitted by ingestion of cysts found in the tissue of grazing animals and rodents. Hammondia heydorni infecting dogs. Hammondia hammondi and Hammondia pardalis infecting cats. Genus Sarcocystis infect carnivores such as dogs and cats that ingest cysts from various intermediate hosts. Genus Toxoplasma has one important species, Toxoplasma gondii. Cats are the denitive host but all mammals and some sh, reptiles, and amphibians can be intermediate hosts. Only cat feces will hold infective oocysts but infection through ingestion of cysts can occur with the tissue of any intermediate host.
Eimeria Transcript Database The assembled transcripts of the three Eimeria species Eimeria acervulina, Eimeria maxima and Eimeria tenellaare are published in the the Eimeria Transcript Database (EimeriaTDB). The Eimeria Transcript Database (EimeriaTDB) is an integrated resource of cDNA sequencing and annotation data of Eimeria spp. of domestic fowl. EimeriaTDB is maintained by the Coccidia Molecular Biology Research Group at the Institute of Biomedical Sciences, University of So Paulo, Brazil. [15] Parasites of the genus Eimeria infect a wide range of vertebrate hosts, including chickens. The Eimeria Transcript Database contains the transcriptomes of Eimeria acervulina, Eimeria maxima and Eimeria tenella, All cDNA reads have been assembled, and the reconstructed transcripts. The main goal is to oer a public repository of sequence and functional annotation data of reconstructed transcripts of parasites of the genus Eimeria. [16] New Zealand native passerines are hosts to a large variety of gastrointestinal parasites, including coccidia. Schoener et al. 2013 found a prevalence of coccidian infection in the New Zealand bird species up to 38 %, primary of the family Eimeriidae. [17] The prevalence of coccidia infection in goats were found by Balicka-Ramisz et al. 2012 to be up to 100% in Poland and Ukraine. Nine Eimeria spp. were identied in feces samples in Western Pomerania and Lviv regions: E. arloingi, E. chrisienseni, E. jolchijevi, E. ninakohlyakimovae, E. alijevi, E. capina, E. caprovina, E. hirci, E. apsheronica. The prevalence of infection in Western Pomerania of adult goats was 74% and 100% in kids. The results of the present investigation have implications for the control of coccidial infections in goats in Europe. [18]
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Toxoplasmosis and Neosporosis in beef cattle in Thailand Wiengcharoen et al. 2012 report that beef cattle in Thailand had a greater exposure to Toxoplasma gondii than Neospora caninum, and they should be regarded as a potential source of Toxoplasma gondii infection to humans. According to the authors neosporosis, despite low prevalence, is still a risk for morbidity among cattle, including abortions in Thailand. [19] Moisture and temperature inuences Coccidiosis in poultry [20] Coccidiosis is one of the most prevalent diseases in poultry. Abd El-Wahab et al. report that oor heating with exposure to wet litter increased the Eimeria adenoeides oocyst count in the excreta of secondary infected birds compared with poults which were not exposed to wet litter. Floor heating decreased foot pad dermatitis scores compared with groups in housings without oor heating. The authors stress that the process of sporulation is aected by moisture and temperature of the litter. Diagnostic marker for cattle neosporosis [21] Neospora caninum infects domestic and wild canids as well as many warm-blooded animals. He et al. 2013 present a specic diagnostic assay using the N. caninum 40-kD surface antigen (p40), similar to NcSAG1 and NcSRS2. The authors writ that the assay is an excellent marker for the diagnosis of neosporosis in cattle.
19.3.9
Giardia and Cryptosporidium
Giardia and Cryptosporidium are common enteric parasites of domestic animals, particularly dogs, cats and livestock. The epidemiology of infections was recently cleared using molecular epidemiological. [22] These data support the hypothesis that Cryptosporidium hominis is spread only between humans. However domestic livestock, predominantly cattle is reservoir for Cryptosporidium parvum. Transmission takes place by direct contact with infected cattle but also indirectly through drinking water. Giardia duodenalis zoonotic transmission is not considered as a major risk for human infections. [23] Cryptosporidium has become the most important contaminant found in drinking water, and 12 waterborne outbreaks in North America since 1985 with a mortality rate in the immunocompromised the ranged from 52% to 68%. The immunouorescence antibody assay (IFA) using epiuorescence microscopy has been used to examine the occurrence of Cryptosporidium in sewage. [24] OHandley and Olson 2009 describe the eects of giardiasis and cryptosporidiosis in ruminats. The authors report that Giardia duodenalis infections are acquired during the
19.3. ACANTHAMOEBA
1431
rst few months of life, tend to be chronic, and may be a production-limiting disease of ruminants. Cryptosporidia parvum infections causes diarrhoea in neonatal ruminants and Cryptosporidia andersoni, is seen as an emerging disease of cattle. [25]
19.3.10
Giardia and Cryptosporidium spp agents of waterborne diseases [26]
Brandonisio 2006 stresses that Giardia and Cryptosporidium spp. are parasitic protozoa which are frequent etiologic agents of waterborne diseases, particularly in Italy The author reviews current methods for evaluating the presence of Giardia cysts and Cryptosporidium oocysts in water and new methods for cyst/oocyst removal from drinking water and wastewater. The resistant stages produced by Cryptosporidium and Giardia (oocysts and cysts, respectively) are remarkably stable, and can survive for weeks to months in the environment. The infective dose is low, even a single oocyst or cyst may cause an infection. Most faeces that contain (oo)cysts end up in the environment and can be spread to foods by irrigation or by direct contact, and can persist in the water, as routine treatments eliminate only a fraction of these stages. [27] Smith and Nichols 2006 refer to the reasons why outbreaks of water- and foodborne diseases caused by Cryptosporidium, Giardia and Toxoplasma are successful. They are pathogen for many hosts including man and have a low infectious dose their infectious stages are small and resistant to the linking media, and they resistant to usual water disinfectants. The authors also refers to infection of humans by the microsporidia, Balantidium and Blastocystis being transported by food and water. [28] Fayer, Dubey and Lindsay 2004 drawed attention upon Giardia, Cryptosporidium, Toxoplasma and the worldwide pollution of coastal marine environment when great amounts of feces from humans, their pets, and their domesticated animals enter estuaries and coastal waters. The authors stress that sewage carries encysted zoonotic protozoan parasites contaminating bathing beaches, are ltered and concentrated by shellsh eaten by humans and marine mammals, and infect a wide range of marine animal hosts. [29] Appelbee and colleagues looked at the diversity of free-living and captive terrestrial and marine mammalian wildlife species infected with Giardia and Cryptosporidium. The authors highlight the importance of environmental pollution with human and domestic-animal fecal material as a pathway for wildlife infections with protozoan parasites such as Giardia and Cryptosporidium. Molecular-genotyping techniques oer deeper insights to host specicity and possible transmission routes of these parasites. [30]
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19.3.11
Methods for the diagnosis of Cryptosporidium and Giardia [27]
Caccion 2004 highlights the necessity of the accurate identication of a parasite at the species and/or genotype level in human and veterinary parasitology, including the diagnosis, the taxonomy, the treatment and the control. Giardia and cryptosporidium, despite diering in biology, share a complex series of transmission routes turning molecular assays very useful to clarie their epidemiology. The author stresses that PCR does not provide information on the viability and infectivity of the pathogen. These informations may be obtained using indirect methods, such as inclusion/exclusion assays using vital dyes or the Reverse-Transcriptase PCR (RT-PCR) RT which usually targets the heat shock protein (hsp) 70 gene. Heat shock proteins hsps are eciently formed by stressed organisms, such as (oo)cysts exposed to a thermal shock. The hsps wehich are formed under such conditions increase the detection sensitivity and are an index of viability of the cysts. The real-time PCR allows the continuous monitoring of amplicon which are pieces of DNA formed during the amplication reaction, quantitative aspect of the infection could be studied with exquisite sensitivity.
19.3.12
Molecular characterization of Giardia duodenalis and Cryptosporidium spp [31]
A high prevalence of G. duodenalis of 42.0%, Cryptosporidium parvum 21.7% and Cryptosporidium bovis 1,4% was found by Coklin and colleagues 2007 in Canadian cattle in Ontario. Mainly calves were aected. Molecular characterization of the genotypes conrmed a frequent infestation of humans by these parasites.
19.3.13
Methodology used by the authors
Following DNA extractions from faecal samples, nested-PCR protocols were used to amplify fragments of the 16S rRNA gene andthe heat-shock protein 70 (HSP-70) gene for determining the prevalence of G. duodenalis and Cryptosporidium spp. infections, respectively. Genotypes of G. duodenalis, and species of Cryptosporidium, were determined by means of DNA sequencing of amplicons, and subsequent sequence alignment. The authors concluded that there risk of transmission of Giardia duodenalis and Cryptosporidium parvum between cattle and humans by contaminated water or food, or direct faecal-oral transmission. In 2009 Coklin and colleagues found 6.2% infections of Cryptosporidium parvum in dairy calves in Prince Edward Island, Canada. The authors stress the potential risk of zoonotic
19.3. ACANTHAMOEBA
1433
transmission between dairy calves and humans in this region.The presence of oocysts in the fecal samples was determined , using immunouorescence microscopy. Molecular characterization was done using a nested-PCR protocol to amplify fragments of the Cryptosporidium heat-shock protein 70 gene, followed by DNA sequencing. [32]
19.3.14
New sub-genotype of Cryptosporidium parvum [33]
In cattle from the Qazvin province , Iran 72.6% of the positive samples as Cryptosporidium parvum, 17.7% as Cryptosporidium andersoni, 7.8% as Cryptosporidium bovis were found by Keshavarz and colleagues. The authors report the nding of a novel genotype of C. parvum possessing a single mutation on MboII restriction. This new sub-genotype represented 1.9% of the analysed samples. The authors used microscopic characterization and ocysts were analyzed using PCR assay of 18S SSU rRNA, restriction fragment length polymorphism (RFLP) and sequencing. In Teheran Pirestani and colleagues 2007 found a zoonotic or 2 genotype (C. parvum) in isolates from bovine samples. In human samples anthroponotic or 1 (C. hominis) and zoonotic genotype or 2 (C. parvum) were found. Ooicysts were isolated and genotyped by means of a Nested-polymerase chain reaction/restriction fragment length polymorphism analysis of the 18s rRNA gene. [34] Eastwood and colleagues 2008 identied two subgenotypes of Cryptosporidium hominis and four subgenotypes of Cryptosporidium parvum species from humans from farms in New South Wales. All four of the C. parvum subtypes found in humans were also found in the cattle. This suggests that zoonotic transmission is an important factor of Cryptosporidium transmission in rural regions. PCR sequence analysis of the 18S rRNA was used to determine species/genotype and subgenotype by sequence analysis of the GP60 gene. [35] Geurden and colleagues 2009 report that Cryptosporidium and Giardia are frequently found in the stool of domestic ruminants, especially young animals. The authors assessed the occurrence of these protozoan in captive wild ruminats at the Antwerp Zoo (Belgium) where 8.9% for Giardia duodenalis assemblage A and American bison (Bison bison) calves on a commercial breeding farm and 23.2% for Giardia duodenalis assemblage A and E. Cryptosporidium-positive cases were 7.5% in the Antwerp Zoo animals and 3.7% in the Bisons from the breeding farm. The authors concluded that captive wild ruminants can serve as reservoir Cryptosporidium and Giardia. Detailed methodology is described by the authors. [36]
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19.3.15
Solar UV inactivates Cryptosporidium oocysts [37]
King and colleagues 2008 found that natural sunlight inactivated up to 90% of Cryptosporidium parvum oocysts in drinking water and environmental waters within the rst hour. The solar ultraviolet UV-B wawelength had the highest germicidal eect, whereas dissolved organic material decreased the eect of solar light.
19.3.16
Water treatments to control Cryptosporidium and Giardia [38]
Betancourt and Rose 2004 report that Cryptosporidium parvum oocysts are particularly more resistant than Giardia lamblia cysts to removal and inactivation by conventional water treatment (coagulation, sedimentation, ltration and chlorine disinfection). Success of conventional treatment depends on the eectiveness of coagulation pretreatment and properly functioning conventional lters. Additional disinfection procedures, such as chlorination, chlorine dioxide, ozonation and ultra violet [UV] irradiation) disinfection procedures by chemical or physical methods are required.
19.3.17
The eectiveness of inactivation of protozoan parasites in food, water and environment [39]
According to Erickson and Ortega 2006 treatments used to inactivate protozoan parasites (Giardia, Cryptosporidium, and Cyclospora) in food, water, and environmental systems include freezing, heating, ltration, sedimentation, UV light, irradiation, high pressure, and ultrasound. The authors stress that ozone is a more eective than chlorine or chlorine dioxide. However, one should have in mind that synergistic eects of sequential inactivation treatments of conventional systems may increase their eciency.
19.3.18
Eect of temperature on the die-o rate for Cryptosporidium parvum oocysts in water, soils, and faeces [40]
Oocysts survival in water: Cryptosporidium parvum oocysts are inactivated when exposed to a temperature of 72.40 C for 1 min or 64.20 C for more than 2 min. The lowest die-o rate was found at 40 C . Freezingt is predicted to inactivate 99.99% of oocysts in 853 days at -40 C or 64 days at -220 C . The die-o rate for oocysts in river water at 50 C is similar to that in autoclaved river water, but at 150 C , oocyst die-o occurs more rapidly in natural than in autoclaved river water. The dierence is perhaps due to increased biological or biochemical activity at 150 C .
19.3. ACANTHAMOEBA
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19.3.19
Oocysts survival in soil
Desiccation is probably lethal to oocysts. Reports say that decreasing the soil water potential by adjusting NaCl solution linearly increases the rate of population degradation.
19.3.20
Oocysts survival in faecis
Temperature is a key factor inuencing oocyst survival in feces. A strong exponential relationship between the die-o rate and the temperature was found, being stronger in faeces than in water. The viability of oocysts excreted by calves in solar housing did no dier from those in conventional housing.
19.3.21
Cryptosporidium, a major cause of diarrhoeal disease
Cryptosporidium and Giardia are the most common cause of protozoal diarrhea worldwide. One to ten Cryptosporidiumm oocysts or Giardia cysts are sucient to get sick. Cryptosporidium oocysts and Giardia cysts can resist to dierent physical and chemical treatments. In water, they can persist in dierent forms a few months. Contamination of foods occur by unhygienic food handling or by the environment. Cryptosporidium oocysts and Giardia cysts can survive to dierent food process. Cryptosporidium and Giardia present anthroponotic, zoonotic transmission, waterborne and foodborne transmission. The oocysts and cysts can survive for weeks to months in the environment. Faeces that contain oocysts or cysts may be spread to foods by irrigation or by direct contact. Routine treatments of drinking water eliminate only a fraction of these stages. The detection by immunouorescence methods like ELISA or by microscopy method are not recommended due to genetic diversity, lack of sensitivity and subjectivity of the analyse. Molecular techniques (real time RT-PCR) are the methods of choice for Cryptosporidium and Giardia detection after DNA extraction and purication from the sample, and special commercial kits were developed. [41]
19.3.22
Molecular tools improving detection and understanding of Cryptosporidium infections [42]
A review conducted by Xiao 2009 highlights molecular tools detecting and dierentiating Cryptosporidium at the species/genotype and subtype levels in humans and animals. These molecular epidemic studies show the importance of Cryptosporidium infections and improves the understanding of their sources. The author stresses the importance of genotyping and subtyping tools to improve the understanding of the epidemiology of cryptosporidiosis.
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19.3.23
Understanding of the dierent metabolic pathways of Plasmodium and Cryptosporidium [43]
According to Mogi and Kita 20101 the Apicomplexans, obligate intracellular parasites, have undergone a reductive evolution like the Plasmodium, which in the blood stages of mammalian hosts, has its mitochondrial enzymes down-regulated and its energy metabolism relies mainly on glycolysis. Mitosomes of Cryptosporidium parvum and Cryptosporidium hominis (in humans) lack mtDNA and other metabolic pathways, which are still present in mitosomes of Cryptosporidium muris (in rodents). The authors write further that Cryptosporidium and Perkinsus use pyruvate-NADP(+) oxidoreductase (PNO), malate-quinone oxidoreductase(MQO), and alternative oxidase (AOX). All apicomplexan parasites and dinoagellates share MQO. The authors hope that understanding mitochondrial metabolic pathways of Plasmodium, Cryptosporidium and Perkinsus will help the development of new chemotherapeutics
19.3.24
Detection of mutations in the 60 kDa glycoprotein gene (gp60) of Cryptosporidium [44]
Pangansa and colleagues 2010 assessed the eectiveness of a PCR-based restriction endonuclease ngerprinting (REF) method for the detection of mutations in the 60 kDa glycoprotein gene (gp60) of Cryptosporidium. This gene displays substantial intraspecic variability in sequence, particularly in a TCA microsatellite region, and is used as a marker in molecular epidemiological studies of Cryptosporidium hominis and Cryptosporidium parvum. REF is useful to detect the nucleotide variability in the gp60 gene within each of the two species. The authors highlight the high-throughput potential and relatively lowcost of REF for genetic analyses of C. hominis and C. parvum, and to identifying sources of infection. REF may also be useful to study other protozoan and metazoan parasites.
19.3.25
Cryptosporidium, the the major cause of dysentery [45]
According to Jex and Gasser 2010 the prevention of cryptosporidiosis in humans should focus on prevention and control strategies and epidemiology using the 60-kDa glycoprotein gene (gp60) as genetic marker for Cryptosporidium infections. The authors provide a global analysis which reveals a low diversity of Cryptosporidium, however, there is a limited knowledge about the genetics of cryptosporidiosis in developing nations in Africa and Asia, and about many animals infection sources. The authors call for comparative genome sequence surveys based on gp60 data to improve intervention strategies against cryptosporidiosis.
19.3. ACANTHAMOEBA
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19.3.26
Importance of specic methods to detect diarrhoea agents among tourists [46]
Agnamey and colleagues 2010 report diarrhoea among tourists returning from West Africa due to Cryptosporidium hominis and Isospora belli. The authors stress the importance of the detection of coccidiosis in diarrhoeic travellers with the use of specic methods.
19.3.27
New Cryptosporidium parvum subgenotype IIn in Indian children [47]
Analysing diarrhoeal stools from hospitalized Indian children aged under 5 years Agnamey and colleagues 2010 found that 2.7% were positive for Cryptosporidium. Microscopy, PCRRFLP and/or sequencing at the SSU rRNA and Cpgp40/15 loci for species determination and subgenotyping were used. Cryptosporidium hominis was the most frequent genus and subgenotypes Ie, Ia, Ib and Id was spread over all places. The authors report a novel Cryptosporidium parvum subgenotype, IIn. The rate of cryptosporidiosis was reported to increase during hotter and drier weather.
19.3.28
Norway sheep are reservoir of zoonotic Cryptosporidium [48]
Robertson and colleagues 2010 assessed cryptosoridiosis and giardiasis of Norwegian lamb farms using immunouorescent antibody test detecting Cryptosporidium oocysts and Giardia cysts. Findings of Giardia were 31% and 24% for Cryptosporidium. PCR analysis targeted glutamate dehydrogenase and beta-giardin genes for Giardia, and SSU rRNA and actin genes for Cryptosporidium. Only one isolate of Giardia was Assemblage B (zoonotic), but 35 isolates of Cryptosporidium were cervine genotype (potentially zoonotic). The authors concluded that sheep in Norway are a reservoir of zoonotic Cryptosporidium, but Giardia are of no concern.
19.3.29
Genotypes of Cryptosporidium parvum from calves and sheep in Spain [49]
In Galicia, Spain 49.2% of diarrhoeic calves and 30.7% lambs were tested positive for Cryptosporidium by microscopy and molecular tests. Cryptosporydium parvum from calves belonged to the subtype IiaA15G2R1, and one was of the novel subtype IIaA13G1R1. In sheep the subtipes IiaA16G3R1 and IIaA15G2R1suggest a limited genetic diversity in calves. The authors stress that calves and lambs should be considered as zoonotic reservoirs.
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19.3.30
Seasonal variation of the genetic morfology of Cryptosporidium with implication on parasite control in preweaned cattle [50]
Szonyi and colleagues 2010 report that 5% Cryptosporidium parvum-like species and 1% Cryptosporidium andersoni were found using the otation method. C. parvum-like species was found in 26% of the samples among preweaned calves in summer, compared with 11% in winter, and no oocysts of C. parvum-like in cattle older than 5 months were detected. The 18s rRNA gene revealed that in the summer, 42% of the C. parvum-like oocysts were zoonotic, compared with less than 74% during the rest of the year. Better understanding of management practices or ecological factors will improve the control of this parasite in preweaned calves say the authors.
19.3.31
Cattle may be a source of Cryptosporidium in Hungary [51]
Plutzer and Karanis 2007 determined the genotype and subtypes of Cryptosporidium from faecal samples from calves with diarrhoea in Hungary Genomic DNA was extracted and nested PCR amplied the partial SSU rRNA and GP60 genes digested by SspI, VspI and MboII restriction enzymes. Cryptosporidium parvum IiaA16G1R1 was found to be the most common subtype and two isolates were found to contain the C. parvum allele IId and a new Cryptosporidium parvum IIa A18G1R1 subgenotype. The authors concluded that cattle can be a source of cryptosporidial infections for humans and animals in Hungary.
19.3.32
Cryptosporidium detection method in water [52]
Nichols, Campbell and Smith 2007 presented a nested PCR-restriction fragment length polymorphism (RFLP) method for the detection Cryptosporidium spp. oocysts in natural mineral waters and drinking waters, detecteding less than 5 oocysts per sample.
19.3.33
Transmission of Cryptosporidium from cattle to man an dairy farms [53]
Khan and colleagues 2010 assessed the importance of animals as source of human Cryptosporidiosis in West Bengal, India. A total of 11.7% of the cattle were found positive for Cryptosporidium parvum, Cryptosporidium bovis, Cryptosporidium ryanae, Cryptosporidium andersoni and Cryptosporidium suis-like genotype. Infection of farm workers comprised Cryptosporidium hominis, C. parvum and a novel C. bovis genotype. The authors highlight the risk of Cryptosporidium transmission from cattle to humans on dairy farms.
19.3. ACANTHAMOEBA
1439
19.3.34
Cryptosporidium parvum dominant infections in young calves in France [54]
A study by Follet et al. 2011 revealed the presence of Cryptosporidium parvum (43.8%), Cryptosporidium ryanae (28.5%), and Cryptosporidium bovis (27%) in stool samples of young calves. One animal was infected with Cryptosporidium ubiquitum. The prevalence of species varied with the age of the animal. Cryptosporidium parvum caused 86.7% of Cryptosporidium infections in 5-week-old calves, but declined to 1.7% in 15-week-old animals. The authors extracted the DNAfrom the stool samples and the partial 18S-rDNA and 60 kDa glycoprotein genes of Cryptosporidium were amplied by nested PCR. Overall 70,4% of the calves were found positive for Cryptosporidium. The authors concluded that zoonotic Cryptosporidium parvum is the dominant species in young calves.
19.3.35
Cryptosporidium oocysts in paddock and forage [55]
According to Boyer and Kuczynska 2010 adult beef cattle shed oocysts into the environment. The oocysts of Cryptosporidium oocysts are often found in streams and groundwater in livestock agriculture areas. Mean annual oocyst prevalences on forage were 52.4% in pasture and hay paddocks 40.5%. Wild animals act as vector among paddocks. The authors suggest canopy management, short-cycle rotational grazing, and control of wildlife as strategies to reduce number of Cryptosporidium oocysts in pasture and protect water supplies.
19.3.36
Modied method for purifying Cryptosporidium oocysts [56]
Huang and colleagues 2010 describe a modication of the purication method of Cryptosporidium oocysts. They used Sheathers sucrose solution diluted with distilled water as an alternative to PBS. A high viability of the oocysts of more that 96% after 1 hour incubation in 37 degrees C were attained.
19.3.37
Parasitic contamination in wastewater and sludge samples in Tunisia [57]
According to Khouja and colleagues 2010 water scarcity compel to the reuse of wastewater or sludge in Tunisia. Wastewater guidelines specic limits for ova of helminths less than 1 egg/l. Protozoan parasite contamination is not specied. The authors assessed, therefore the Tunisian water treatment and found a high diversity of helminth and protozoa contamination of raw wastewater. Six of eight treated wastewater presented parasite contamination with helminths, Cryptosporidium, Giuardia and Entamoeba. Sludge samples presented parasites, Cryptosporidium and Giardia in high frequence from human and
1440
animal origin. The authors stress the importance to monitor wastewater and sludge concerning these pathogens.
19.3.38
Monitoring wastewater plants in China [58]
The removal of Cryptosporidium, Giardia, and microbial indicators, including somatic coliphages and faecal coliforms by treatment plants in Beijing, China presented reduction ratios of 0.12 log for Cryptosporidium and 0.18 log for Giardia by the primary treatment process. The authors note further that oxidation ditch process had higher reduction eciency to Cryptosporidium and Giardia than anaerobic-anoxic-oxic process and conventional activated sludge process, due to longer retention time and higher concentration. As tertiary treatment greater reduction of pathogens were attained using membrane ultraltration, compared with conventional occulation sedimentation and sand ltration process, as the tertiary treatment.
19.3.39
Outbreaks of waterborne transmission of parasitic protozoa in humans [59]
Cryptosporidium is a protozoan that can cause gastro-intestinal illness with diarrhea in humans. Cryptosporidiosis is a zoonosis found in goats and sheep and pigs. Baldursson and Karanis 2011 report at least one hundred and ninety-nine outbreaks of waterborne transmission of parasitic protozoa between 2004 and 2010. Almost half of the outbreaks occurred in Australia, a third in North America and less than a fth in Europe. The most frequent parasitic infection was Cryptosporidium spp. With a frequency of 60.3% of all outbreaks, Giardia lamblia with 35.2% and other protozoa with 4.5%. Less frequent were outbreaks of Toxoplasma gondii, Cyclospora cayetanensis. Acanthamoeba spp. Giardia lamblia Cryptosporidiumparvum, Entamoeba histolytica and Blastocystishominis Countries at highest risk of such outbreaks lack surveillance systems.
19.3.40
Source of human infections of Cryptosporidium sp.
Fiuza et al. 2011 found 4,54% of samples of faeces of dairy cattle positive for Cryptospporidium andersoni at farms in the state of Rio de Janeiro, Brazil. Molecular analysis by polymerase chain reaction (nested PCR) of the 18S rRNA were used in this study. The authors stress that such infections may aect cattle productivity and represent a source for human infection. [60] Fiuza et al. used nested polymerase chain reaction (PCR) to amplify an 830-bp fragment of the small subunit rDNA (SSU rRNA) gene and sequencing of all positive PCR samples. Cryptosporidium sp, pig genotype type II (PGII) was positive in 2.2% of the samples were positive and were identied as pig genotype type II (PGII). This genotype was
19.3. ACANTHAMOEBA
1441
found also found in cattle which had no contact with pigs and in humans. The authors call for more studies on possible human infections with Cryptosporidium from animal source. [61] In Brazilian lambs 1,6% of samples of faeces were positive for Cryptosporidium ubiquitum using polymerase chain reaction (nested PCR) in two steps of the SSU rRNA. Cryptosporidium ubiquitum is considered a zoonotic pathogen, however, its local low frequency may not present a high risk to humans. [62]
19.3.41
Cryptosporidium in water samples in Brazil [63]
Arajo et al 2011 reports the detection of Cryptosporidium oocysts in 30% of water samples. Collected in the state of So Paulo, Brazil. Using nested-polymerase chain reaction 18S ribosomal RNA gene sequences Cryptosporidium hominis and Cryptosporidium sp. were identied in recreational water and Cryptosporidium. meleagridis in surface water samples. The authors stress that the identication of Cryptosporidium is dicult because of the small size and morphology of the oocysts when the identication is being done by microscopy. Molecular methods are therefore suggested by the authors to study the epidemiology of Cryptosporidium. Cryptosporidium is which is one of the most important water contaminants, causing waterborne outbreaks of diarrhoeal diseases worldwide.
19.3.42
Giardia canis virus as genetic tool to alter Giardia canis [64]
Chen and colleagues 2006 described the cultivation of Giardia canis trophozoites infected with Giardia canis virus. Chen and colleagues 2009 explain the structure of this virus and its eects on Giardia canis trophozoites being released to the media as mature infectious viral particles. The authors suggest that Giardia canis virus may be used for gene manipulation of Giardia canis. [65]
19.3.43
Sewage treatment [66]
Sewage sludge intended for arable land use needs to be rigorously assessed for quality due to the high content of metals (cadmium, arsenic, copper, lead, mercury, and zinc), persistent organic pollutants (the organochlorines aldrin, dieldrin, heptachlor, dichlorodiphenyltrichloroethane, and lindane), and pathogenic microorganisms (bacteria, viruses, protozoa, and helminths) to ensure no transmission of harmful elements to humans through entry into the food chain via crops or grazing animals. According to European Union regulations
1442
(EEC 1774/2002) [67], stabilized organic residues must be adequately treated and proven hygienically safe, prior to the application of sewage sludge to arable land.
19.3.44
Storage of Sewage
Storage of sewage sludge was applied as the sole treatment, with the aim of sanitization in terms of destroying pathogenic microorganisms, a method proven not eective and therefore discontinued. The most frequently used stabilization methods for sewage sludge are biological anaerobic and aerobic digestion. However, neither of these two procedures generates sludge that is better quality than class B grade, promoting a future shift to the use of alternative methods, such as alkaline stabilization and heat drying, to further reduce pathogen level resulting in class A sludge with fewer user restrictions. An additional promising option of producing hygienically safe material for arable recycling is to combine stabilization procedures, such as digestion, with pasteurization or liquid composting.
19.3.45
Chemical treatment
Lime stabilization (calcium hydroxide) to raise the pH to 12.0 for at least 2 hours. It is an interesting alternative to anaerobic and aerobic digestion.
19.3.46
Composting;
In composting, liquid sludge is treated with a bulking agent, such as wood chips, dry compost, or municipal refuse.
19.3.47
Pasteurization
Pasteurization of biowaste at 700 C for at least 1 h is an eective approach to eliminate most pathogens.
19.3.48
Toxoplasma gondii [68]
Toxoplasma gondii is capable of infecting all warm-blooded animals including humans, such as congenitally infected children which presente hydrocephalus, retinochoroiditis and encephalitis. The parasites are associated with severe intraocular inammation and was the major cause of abortion in sheep in New Zealand. The cat is a denitive host. The oocyst stage of Toxoplasma gondii is shed in the faeces of infected cats and acts as a source of infection for many intermediate hosts. It causes infection in herbivorous animals and people with vegetarian diet. The life cycle of Toxoplasma gondii comprises the sexual stage (coccidia like) wich takes place only in domestic and wild cats, which makes these animals the parasites primary
19.3. ACANTHAMOEBA
1443
host. The asexual part of the life cycle can take place in any warm-blooded animal, including birds. Infection of humans occur ingesting oocysts on unwashed vegetables of improper cooked infected meat.Acute stage Toxoplasma infections can be asymptomatic, but often give ulike symptoms in the early acute stages, and like u can become, in very rare cases, fatal. The acute stage fades in a few days to months, leading to the latent stage. Latent infection is normally asymptomatic. If infection with T. gondii occurs for the rst time during pregnancy, the parasite can cross the placenta, possibly leading to hydrocephalus or microcephaly, intracranial calcication, and chorioretinitis, with the possibility of spontaneous abortion (miscarriage) or intrauterine death. [69]
19.3.49
Reducing Toxoplasma infection risk [70]
Cook all meats thoroughly before eating. Whole chicken and parts should be cooked to 820 C -850 C (1800 F -1850 F ) and turkey pieces to 770 C (1700 F ). Beef steaks and roasts should be cooked asfollows: medium rare at 630 C (145 0 F ), medium at 710 C (1600 F ), and well at 750 C (1700 F ). Pork chops and ribs should be cooked to 710 C (1600 F ). Freeze meats to -180 C (00 F ). After handling and preparing raw meat and poultry, wash your hands and sanitize all utensils and work surfaces with a mild bleach solution (5 /1. bleach per 750 /3 cups water). Pregnant women and people with weak immune systems should avoid handling raw meat, eating lightly cooked meat, handling cats and cat litter, and gardening. Wash all fruits and vegetables thoroughly. Change cat litter daily. Cats should be prevented from catching and consuming rodents and birds and should not be fed any raw meat.
19.3.50
Toxoplasma gondii infection from cat litter [71]
According to Dubey et al 2011, oocysts of Toxoplasma gondii remain infectious to people for 14 days in all types of commercial cat litters. The denitive host of Toxoplasma gondii is the cat, but the parasite can be carried by birds, rats, other warm- blooded animals and humans. The parasite may cause serious or even fatal eects on a fetus during pregnancy. or on an immunocompromised humans are also seriously aected by the disease caused by Toxoplasma gondii. The infection infection may present u-like symptoms in the early acute
1444
stages. The acute stage fades in a few days to months, leading to the latent stage. The authors recommend to change cat litter daily to avoid human infections with Toxoplasma gondii. Vyas and Sapolsky 2010 report that Toxoplasma infections change the behaviour of rats and mice, making them drawn to, rather than fearful of, the scent of cats, but does not change any other fears, like the aversion to open spaces or of unfamiliar-smelling food. It is being suggested that the parasite causes the behavioural change to prot from the cycle in the cat. [72] Studies have also shown behavioural changes in humans, such as slower reaction times, increased risk of trac accidents, links to schizophrenia and reckless behaviour.
19.3.51
Toxoplasma gondii in Brazilian dairy cows and their foetuses [73]
Macedo et al. 2012 describe the serology and isolation of Toxoplasma gondii strains from blood and tissue of pregnant dairy cows and foetuses in Southern Brazil. Antibodies against Toxoplasma gondii were observed in 48.3% of cows and 3.7% of fetuses. Bioassay found 23% of fetuses and 10.0% of cows as positive. Toxoplasma gondii type II strain was isolated from a blood sample of a cow and of a foetus. The authors stress that transplacental transmission of Toxoplasma gondii occurs in dairy cows.
19.3.52
Genetics may reduce impact of African trypanosomiasis in cattle [74]
Human African trypanosomiasis, or sleeping sickness is a parasitic disease of people and animals, caused by protozoa of the species Trypanosoma brucei and transmitted by the tsetse y. The disease is endemic in some regions of sub-Saharan Africa. According to the World Health Organization around 30,000 Africans a year get sleeping sickness mainly in sub-Saharan African nations and disease of cattle leads to annual losses of up to $5 billion. Goodhead et al 2011 report the nding of two genes which may help cattle breeders to select animals more able to survive an infection of Trypanosoma congolense, such as the humpless West African breed which is less susceptible to the disease compared with the high susceptible humped breed. However, the resistant humpless cattle is smaller, produce less milk, and is less docile than the humped the humped breed. Trypanosoma congolense is responsible for the disease nagana in cattle and other aniOurFood Database of Food and Related Sciences Copyright 1998-2010 Karl H. Wilm. All rights reserved.
19.3. ACANTHAMOEBA
1445
mals including sheep, pigs, goats, horses and camels, as well as laboratory mice. It is spread by tsetse ies. Laboratory mice, infected by trypanosomes presented dierent survival time after infection is controlled by three genomic regions Tir1, Tir2 and Tir3 which contain over one thousand genes. In these regions two genes, Pram1 at Tir1 and Cd244 at Tir3, were found to reduce survival time, and Tir2 increased survival time after an infection. The Tir2 loci was absent in trypanosomiasis susceptible animals. These ndings may be useful for breeding programs to screen African cattle and nd animals which are more resistant to the disease and combine them with traits of increased productivity and drought tolerance.
19.3.53
The genome sequence of the agent of trypanosomiasis [75]
Trypanosomiasis, also called "sleeping sickness", is common in Western and Central Africa. The symptoms include changes in personality, alteration of the biological clock, confusion, slurred speech, seizures, and diculty walking and talking. The disease is caused by Trypanosoma parasites and is transmitted by the female tsetse y. It aects the human central nervous system. Berriman and colleagues 2010 describe the genome sequence for the strain of Trypanosoma brucei gambiense which is the most common causer of the sleeping sickness. The authors compared this genome with that of Trypanosoma brucei brucei (T. b. brucei 927), a non-human infecting parasite from bovine infections. The sequence of genes were identical in 98.2 per cent in both genomes, varying only on one locus. However, ability to infect humans cannot be explained simply by the addition or removal of a few genes. The authors postulate that single letter changes in the genome, dierences in the number of copies of genes; changes in how the activity of genes is regulated may be the cause of the virulence of Trypanosoma brucei gambienses. The genome sequences may help to nd new drugs to ght the disease. The authors also described a group of VSG proteins which gather at the surface of the Trypanosoma, protecting the parasite from the immune system of the host. A catalogue of VSGs might also provide valuable informations for further immunologic studies.
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19.4
19.4.1
Human genetic resistance against falciparum malariae

IL3 variant at the chromosomal region 5q31-33 is protectiv against falciparum malriae in Ghana [76]
Meyer et al. 2011 write that the IL3 genotypes are implicated in the pathophysiology of falciparum malaria. The authors stress that in the control of malaria parasites is linked to the interleukin 3 gene (IL3) SNP rs40401, the IL3 genotypes rs40401(CT) and the rs40401(TT) were found to exert a protective eect of 25% and 33%, respectively, against malaria attacks. These genes are located in the chromosomal region 5q31-33.
19.4.2
Two loci associated with severe falciparum malaria were identied by German and African cooperation [77]
Timmann et al 2012 used the Genome-wide association (GWA) technique to compare the blood of 1300 severely diseased Ghana children with blood of healthy children. The authors identied two loci associated with severe falciparum malaria in patients. The chromosome 1q32 within the ATP2B4 gene encoding the main calcium pump of erythrocytes, necessary for the growth of the parasite inside of the red blood cell was an important loci. A polymorphism on chromosome 16q22.2, linked to a gene encoding the tight-junction protein MARVELD3 was the second loci which were found in diseased persons. The protein is expressed at this loci playing a role in microvascular damage caused by parasitized erythrocytes. Other genetic variant implicated in protection against the malaria disease are known from studies related to the sickle-cell trait and blood group O. Our ndings underline the potential of the GWA approach to provide candidates for the development of control measures against infectious diseases in humans. The results of this study, and further use of GWA technique, may help to develop new drugs against malaria which tropical disease aecting primary underdeveloped countries, causing the death of 655 000 persons in 2010, mainly children in Africa, says the WHO.
19.5
Parasitic worms
Parasitic worms are described under helmiths , comprising three groups:
19.5. PARASITIC WORMS
1447
19.5.1
Nematodes
also called roundworms.
19.5.2
Trematodes
like the ukes.
19.5.3
Cestodes
which are the tapeworms. Bacteria can multiply in the human body almost indenitely. Worm parasites do not multiply in the human host, they usually need to pass through stages in the human host and then they have to undergo other stages in one or more animals, im soil or water. Some persons may harbor only few worm parasites, the infestation remains subclinical and symptomless. However with repeated exposures a massive infestation takes place and illness comes up.
19.5.4
Roundworms: Ancylostoma duodenale and Necator americanus
The infestation with both worms are alike and no laboratory attempt is made to dierentiate among them, reporting as larvae of ancylostomideans.
19.5.5
Capillaria philippinensis
C. philippinensis is a roundworm causing intestinal capillariasis which appeared rst in the Philippines and subsequently in Thailand, Japan, Iran, Egypt, and Taiwan. Humans acquire the infection by eating small freshwater sh raw. It is considered a zoonotic disease of migratory sh-eating birds.The parasite multiplies, and symptoms of diarrhea, borborygmus, abdominal pain, and edema. Pictures and full article by J H Cross are available at http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=358231 [78]
19.5.6
Angiostrongylus costaricensis
A.costaricensis Morera and Cespedes, 1971 is a parasitic nematode of wild rodents that may produce abdominal disease in humans, already reported from most countries in the Americas, from Mexico to Argentina. Molluscs are intermediate hosts and shed infective third stage larvae (L3) in their mucus secretions. One possible mode of infection is the ingestion of raw vegetables and unpeeled fruits containing small molluscs or their contaminated mucous secretions. MORERA suggested refrigeration of food as part of prophylaxis
1448
based on experiments demonstrating a deleterious eect of low temperatures on the viability of L3. [79]
19.5.7
Life cycle of ancylostomideans
The hookworms are a quarter to halve an inch long. They attache themselves to the wall of the small intestines. The females produce eggs which are carried by feces. In warm moist soil the eggs develop within a day or two into a larval form which is capable to penetrate human skin between toes if no shoes are worn. It causes local itch. The blood stream carries the larva to the lungs where it gets though the lung wall and reaches the bronchi, the trachea and being swallowed getting to stomach and intestines, where it settles growing to an adult male and a female form. After fertilization of the eggs a new cycle starts.
19.5.8
Infestation from contaminated food and water
The larvae can be ingested from food and water lead to an infestation without the skinblood-lung-cycle.This way of infestation is less common but should not be neglected handling with food, specially imported vegetables and fruits being eaten without proper washing and cooking. Each worm can suck 0,5 ml or more blood from its host per day. Few worms do not get noticed but when more then two hundred are present severe anemia and intoxication takes place causing the hookworm disease. The use of shoes reduces the possibility of an infection by the larva through the skin of the foot.
19.5.9
Strongyloides stercoralis
The disease caused by Strogyloides stercoralis is similar to the hookworm disease. The eggs can develop to small larvae and are carried by feces. In soil the larvae can reinfect man in the same way hookworm do. The use of shoes reduces the possibility of an infection by the larva through the skin of the foot.
19.5.10
Trichuris trichiura
Is also called whipworm because of its shape. The ova are discharged in great number in the feces. In the soil they need several days to develop to infective larvae. They enter through the mouth in contaminated food and water.
1449
19.5.11
Ascaris lumbricoides
Is is the largest roundworm being up to 12 inches long. The eggs deposited in feces develop in soil during several weeks to infective stage. When swallowed the larvae penetrate the intestinal wall and a similar cycle as known as Ancylostomideans. If a considerable number of larvae are ingested at one time high fever and pneumonitis are caused. The vermifuge principle of santonica seeds is santonin which is used to expulse Ascaris lumbricoides
Ascaris lumbricoides from infected humans.
19.5.12
Pig farms source of human infection with round worm [80]
Ascaris lumbricoides/suum mainly infect humans and pigs. Ascaris lumbricoides worms usually infect humans, mainly in regions with poor sanitation, where the environment is contaminated with human feces. However, pig farms are a risk of nearby population. In industrialized countries, human ascariasis is uncommon and cases are generally believed to have been imported. However, Ascaris suum infection of pigs occurs worldwide; in the United Kingdom, 3.4%6.5% of pigs at slaughter have evidence of infection Bendall et colleagues 2011 describe a total of 63 acariasis cases in Cornwall, in England, between 1995 to 2010. Higher infection rates were found at children aged <5 years and living near pig farms. All worms from humans in Cornwall had pig-like DNA sequences, suggesting pigs as a source. The authors calls for more studies to conrm that pigs are the source. Modication of animal husbandry and faecal waste disposal will be necessary.
1450
19.5.13
The genetic region ITS1 is not suitable for epidemiology of Ascaris from pigs says study [81]
The internal transcribed spacer 1 (ITS1) was suggested to investigate the epidemiology of Ascaris infecting pigs. Leles et al 2010 found that the value of Ascaris ITS1 as a molecular marker should be reconsidered, due to a high intra-individual variability of ITS1 genotypes/halotypes. Analysing dierent samples of Ascaris eggs, the authors found two genotypes, G1 and G6, and 13 new haplotypes, G1 and G6, were found in all Brazilian samples. Only genotype G1 could be found as relationship between Brazilian ITS1 genotypes/haplotypes and studies of Ascaris in China, Bangladesh, Japan, United Kingdom, Australia, and Denmark,
19.5.14
Prevalence of intestinal parasites
Data concerning soil-transmitted helminth infections reported infections of the population of the southern United States and Appalachia for hookworm 19,6%, Trichuris trichiura 55,2%, Ascaris lumbricoides 49,4%, and Strongyloides stercoralis 3,8%) in the United States is poorly understood. Starr and Montgomery 2011, however, stress that these data lay 25 years back and call for new studies to determine ther actual status. [82] A prevalence of intestinal parasites up to 97,8% among pupils in rural schools in Nigeria were reported by Damen et al. 2011. Most frequent parasite found was Ascaris lumbricoides 19,1% and less frequently found was Trichuris trichiura 3,5%. The authors stressed the high prevalence rate of intestinal parasites amon the Almajiris population of northeast ern Nigeria with increases the risk of intestinal obstruction. [83] Alyouse et al. 2011 report infection rates of Giardia duodenalis and Entamoeba histolytica/dispar ver 17% each, and Cryptosporidium 1%. Also detected were Ascaris lumbricoides 2.4%, Schistosoma mansoni 0.3%, Hymenolepis nana 1.4% and Enterobius vermicularis 0.4%. in Jemen. The high prevalence of Giardia and Entamoeba is linked to low personal hygiene because 95% of the studied cases take bath less than twice a week and/or have contact with animals. The authors suggest preventive measures which include good hygienic practices, good animal husbandry practices, heightened provision of educational health programs, health services in all governorates including rural areas, and improve access to water. [84] In Mugla city, south-west of Turkey, about 11% of elementary school students were found to be infested by intestinal parasites, with Ascaris lumbricoides being most common. Ekinci et al 2011 criticizes the lack of a sewage system in the Mugla province and recommends health education and periodically parasite examinations to be administered to the students and their families. [85]
1451
19.5.15
Manual of methods of the investigation of intestinal parasites [86]
A very useful manual of standard methods of the investigation of intestinal parasites was compiled by the Health Protection Agency and can be downloaded.
19.5.16
Enterobius vermicularis
It is also called pinworm or seat worm The female migrate through the anus and deposit thousands of ova on the skin of the perianal region. When these eggs are ingested they develop into larvae and adult worms in the intestine. Laboratory diagnosis is done by microscopic examination of anal swabs.
19.5.17
Trichinella spiralis
Is a common parasite of esh eating animals. It causes thichinosis.Adult trichina worms are just barely visible to the naked eye. They live in the duodenum.The female worm penetrates the intestinal wall and deposits its larvae in the mucosa. The larvae are carried by blood to all parts of the body. In the striated muscle tissue these larvae can grow and be surrounded by capsules, calcied cysts. When these cysts are ingested by other animals or by men the material is digested and the larvae gets free. In the duodenum the larvae develop to mature worms. The cycle begins again. Trichinella spiralis parasites many esh eating animals like hogs. Eating raw meat or not suciently heated pork containing larvae. As many infections of hooks are not noted there
1452
is pork on market with larvae. Due to growing of the global market veterinary control is not always perfect. If undercooked food with larvae is eaten infestation of man can take place. To avoid trichinosis cook meat appropriately. Avoid contaminated meat be eaten by hogs. As imported meat from unknown and sometimes dubious origin are coming on market the number of human trichinosis is increasing again. As treatment is very dicult all care should be made to avoid ingestion of meat with living larvae of Trichinella spiralis by refusing any food with raw or not suciently heated meat, this includes also all kinds of unheated sausages.
19.5.18
Flukes (Trematodes)
Flukes are uncommon in developed countries. However due to increased travels and adventure trips their importance is growing. One divides the ukes according to the place where they live:
19.5. PARASITIC WORMS Blood ukes Liver ukes and Lung ukes
1453
19.5.19
Blood ukes
There are three important blood ukes:Schistosoma haematobium, Schistosoma mansoni and Schistosoma japonicum.
19.5.20
Schistosoma mekongi [87]
Schistosomiasis is caused by a variety of atworm species. The blood uke Schistosoma mekongi is known as a cause oif schistosomiasis in the Mekong River basin in South-East Asia where a mass treatment program in the mid-1990s reduced the prevalence of the disease. Attwood, Fatih and Upatham 2008 compared DNA sequences of Schistosoma mekongi from the Mekong river and its tributaries in Cambodia, Laos and Malaysia. The authors fopund that Schistosoma mekongi is not conned the lower Mekong River, but migrates northwards from Vietnam, towards Cambodia and Laos. Human population at risk of infection could be up to 10 times greater than previously estimated. The authors expect the disease to spread into Laos. Schistosoma mekongi is found aecting communities along the Mekong River in northern Cambodia and Laos causing severe intestinal and hepatosplenic disease with high mortality rates Control programmes with praziquantel and information and education campaigns, reduced the numbers of infection, but small foci still exist. According Muth and colleagues 2010 the snail intermediate host, Neotricula aperta, present in the Mekong River and tributaries, may migrate further on. The authors call therefore for guidelines for the control of Sachistosoma mekongi and bilateral eorts between Cambodia and Laos. [88]
19.5.21
Polymerase chain reaction (PCR) to avoid spread of the schistosomiasis to non-endemic areas [89]
Kato-Hayashi et al. 2010 developed polymerase chain reaction (PCR) primers specic for human schistosome species (479 bp, Schistosoma mansoni; 365 bp, S. haematobium; 614 bp, S. japonicum; 303 bp, S. mekongi). The authors could detect schistosome DNA in animals one day post infection. This increases the eectiveness of the diagnosis in face of increased importation of schistosomiasis to non-endemic regions by travellers, immigrants and foreign workers coming from endemic areas. Schistosoma haematobium, a human parasite, and Schistosoma bovis from ruminants are known in Kenya to inhabit the same Bulinus snails, live in the same freshwater habitat, and have similar cercariae. Barber, Mkoji and Loker 2000 described the second internal
1454
transcribed spacer (ITS2) region of the ribosomal gene complex (rDNA) of Kenyan, allowing successful identication of a single S. haematobium cercaria. The method used by the authors may help epidemiological studies to determine whether snails are transmitting a human or an animal schistosome, or both. [90] Leshem et al 2009 report infection of twelve Israeli travellers infected by Schistosoma mekongi in southern Laos. This report includes also some cases which were infected in northern Laos. [91]
19.5.22
Decreasing ecacy of artesunate in treatment and prevention of schistosomiasis [92]
Artesunate has been extensively used to treat and prevent Schistosoma japonicum infections in China with a high ecacy. Hua et al. 2010 report that the sensitivity of the uke to artesunate has decreased from 100% to 13,5% during the last 10 years. Identical resistance to the medication have been found in Schistosoma mekongi and Schistosoma mansoni.
19.5.23
Mathematical models of Schistosoma transmission [93]
Ishikawa H, Ohmae reviewed epidemiology and environmental factors related to Schistosoma japonicum and Schistosoma mekongi infections. The authors focused on recent advances in mathematical models of Schistosoma transmission, stressing the usefulness of such models to predict the eects of control measures on suppression of the disease.
19.5.24
Schistosoma haematobium
Is found as chronic disease in Africa and in Asia. The female gets her way to the capillaries of the lower intestinal or bladder wall where she discharges the ova which passes the wall of intestine or bladder to reach excreta causing inammatory reactions which can turn out to malignant tumors. Inammatory reactions on the portal vessels to the liver are also known. The ova in the excreta can only develop when they get into water. There small free swimming larvae are formed. These larvae penetrate certain snails where three stages of development are passed. The last stage emerges from the snail and swims in the water until it comes in contact with human skin penetrating it and entering the blood stream. Avoid to take bath in swallow water with low stream velocity. Hygienic condition of drinking and water used in the preparation of food in these areas in endemic areas should be looked upon.
19.5.25
Schistosoma mansoni
Causes endemic infections of man in the Caribbeans and the northern part of South America. The adult worms are much narrower and more elongated than other ukes.
19.6. FISHBORN FLUKES
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19.5.26 19.5.27
Schistosoma japonicum Fasciola hepatica [94]
Human infections with Fasciola hepatica are seldom. Generally they are single cases,and rarely epidemic, However, the number of infections are rising being endemic in Bolivia.Adult parasites settle in hepatic biliary ducts. The main source of infection are salads of wild growing water plants like water cress and dandelion. Infection is frequent in cattle and goats.
19.5.28
Fasciola hepatica screening of milk cattle [95]
Sandra Koch says that the used f2 antigen detecting ELISA presents a suitable screening method for the diagnosis on herd level and large scale surveillance programs of Fasciola hepatica and is to perform automatically from easily obtained bulk tank milk samples. On a screening of milk herd Koch found an overall prevalence of 32.2% infestation with Fasciola hepatica in Bavaria. A remarkable high prevalence of 95% was found in the rural district Wunsiedel im Fichtelgebirge (Oberfranken). Because of the river systems in the Fichtelgebirge there exist a lot of wetlands and ood plains.
19.6
Fishborn ukes
The widspread shborn ukes are Clonorchis sinensis, Opisthorchis viverrini and Opisthorchis felineus. Human infection takes place when raw, slightly salted and frozen sh is eaten.
19.6.1
Clonorchis sinensis
The Clonorchis sinensis is a human liver uke in the class Trematoda, Phylum Platyhelminthes. This parasite lives in the liver of humans, and is found mainly in the common bile duct and gall bladder, feeding on bile. These animals, which are believed to be the third most prevalent worm parasite in the world, are endemic to Japan, China, Taiwan, and Sotheast Asia, currently infecting an estimated 30,000,000 humans. The metacercariae can then be ingested by humans who eat undercooked or raw sh, who in turn become infected at the same time. These metacercariae enterthe small intestine and migrate into, and mature in the human liver, inside of the common bile duct and gall bladder.
1456
C.H.Kim observed the prevalence of intestinal parasites and Clonorchis sinensis infection in the upper stream of Kumgang (River)in 1991 using cellophane thick smear and formalin-ether concentration technique. The parasite positive rate including helminth eggs and protozoan cysts was 40.8%, the paarasite positive rates for Clonorchis sinensis was 30.8%, Metagonimus spp. 14.5%, Taenia spp. 1.5%,while the rest of all other parasites summed only 4.6%. The authors concluded that the soil transmitted intestinal parasites including helminths eggs and protozoan cysts have been decreased remarkably among the inhabitants along the upper stream of Taechong Dam, Kum-gang (River), but Clonorchis sinensis, Metagonimus spp. and Taenia spp. are still morderate prevalent. [96] Despite a gradual decrease in prevalence, clonorchiasis is still prevalent in East Asia. A large and compelling body of evidence links clonorchiasis and cholangiocarcinoma, although the mechanisms involved are not completely understood. Clonorchiasis induces biliary epithelial hyperplasia and metaplasia, and this could facilitate at least one stage of the carcinogenesis. [97]
19.6.2
Fishborne intestinal parasites are a risk for raw sh eating community [98]
According to Do Trung Dung and colleagues metacercarial stage of shborne zoonotic trematodes were found in wild and farmed shes. Fecal survey of a community that eats raw sh showed 64,9% of infected persons. with liver trematode Clonorchis sinensis recovered from 51.5%. The most numerous intestinal species of the family Heterophyidae were Haplorchis spp. (Haplorchis pumilio. H. taichui. H. yokogawai) (90.4% of all worms recovered). The authors conclude that shborne intestinal parasites are an unrecognized food safety risk in a country whose people have a strong tradition of eating raw sh.
19.6.3
Opisthorchis viverrini
Opisthorchis viverrini is a food borne trematode, important because of the sheer numbers of people infected and its serious morbidities such as hepatobiliary diseases and cholangiocarcinoma. It is found in Asia. Thailand have the highest number of infections. [99]
19.6.4
Opisthorchis felineus
It is widely spread in russia and is sometimes called Siberian liver uke. Infection by undercooked sh eating. The cat liver uke is especially common in Siberia and the Ukraine, where up to 80% of the population is infected. Although these regions being the main endemic areas, it can also be found in Europe, Asia and North America. Domestic animals, especially cats, become infected by eating insuciently cooked sh. Clinical signs are variable, and infestation with
1457
a moderate number of parasites is usually asymptomatic, however with a high quantity of parasites it may lead to hepatic insuciency. This parasitosis is relevant to ichthyophagous animals (dogs, cats, pigs, foxes, wolverine, martens, beavers, otters, European pole cats, Siberian weasels, sables, Norway rats, water vole, rabbits, seals and lions) (Mehlhorn et al., 1992; Kelly, 1993; Mas-Coma et al., 2000; Cullen and Maclachlan, 2001). [100]
19.6.5 19.6.6
Intestinal ukes Fasciolopsis buski
The uke Fasciolopsis lives in the upper part of the small intestine. It contains both mail and female reproductive systems causing diarrhea and anemia. The ova in faecis develop to larvae and penetrate certain types of snails as intermediate host. Leaving the snail the larvae becomes encysted on plants like nuts of the red ling or water chestnut which are eaten by man. Here again the hygienic condition of water is important in the areas where trematodes may be found. Cooking of all foods, sanitary disposal of sewage and the elimination of snail hosts. This is not always possible due to high costs.
19.6.7
Echinostoma spp.[101]
They are intestinal ukes which are common in South-East AsiaThere are about 15 species of Echinostoma from which the most common is Echinostoma ilocanum The infections are acquired by eating raw or undercooked freshwater snails,clams, and sh containing the metacercariae. Pila luzonica is eaten uncooked by some people in the Philippines, and metacercariae from these snails developed into adults in a number of laboratory animals. Rats, mice and hamsters were the most susceptible. There seems to be little disease in humans and animals infected with Echinostoma ilocanum.
19.6.8
Tapeworms
Tapeworms are Cestodes with ve important species: Taenia solium Taenia saginata Diphyllobotrium latum Hymenolepsis nana Echinococcus granulosus
19.6.9
Taenia solium
Is the tapeworm of pork. The ova leave the body with the faecis free or in the interior of proglotides.
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When these ova or proglotides are ingested by animals the larvae develop in the intestine, penetrate the wall and are carried by the blood to the muscles where they become bladder worms or cysticerci. When the muscles are eaten the cyst wall is digested. The tapeworm the head of the worm adheres to the wall of the intestines and proglotides start to grow.
Neurocysticercosis caused by tapeworm Taenia solium [102] Cysticercosis, a human infestation by Taenia solium is endemic in many resource-limited countries. In developed countries it is mostly encountered among immigrant populations. Leshem et al 2011 diagnosed between 1994 and 2009 nine cases of neurocysticercosis in Israeli travellers to South and/or Southeast Asia. Onset of symptoms, such as seizure, were reported to be 3.2 varying by 1.8 years after infection. [103] Cysticerci can develop in any voluntary muscle in humans. In most cases, it is asymptomatic since the cysticerci die and become calcied. The cysticerci may also be found in the eye, causing visual diculties or a visual loss. Subcutaneous cysts are nodules occurring mainly on the trunk and extremities. Neurocysticercosis generally refers to cysts in the brain. It presents seizures and, less commonly, headaches. Neurocysticercosis is a parasitic infection of the central nervous system caused by Taenia solium larval cysts. It is the most common helminthic infection of the central nervous system and a leading cause of acquired epilepsy in Latin America, Southeast Asia, and central Africa. ONeal et al 2011 determined the incidence of NCC and screened household contacts for tapeworms in Oregon during 2006 - 2009. They screened available data and collected faecal and blood samples from household contacts of recent case-patients. The authors report an annual incidence of 0.5 cases per 100,000 general population and 5.8 cases per 100,000 Hispanics. In 22 households, 2 additional NCC case-patients but no current adult intestinal tapeworm infections were identied. The authors concluded that neurocysticercosis is of clinical and public health concern in Oregon, particularly among Hispanics, and suggest that public health intervention should focus on family members to identify additional case-patients. Cysticercosis is acquired through faecal-oral transmission of tapeworm eggs shed in the faeces of a human carrying intestinal tapeworms. Ingested eggs release oncospheres, which invade the intestinal mucosa and disseminate throughout the body to form larval cysts. NCC occurs when cysts develop in the central nervous system and is the primary source of illness and death. The tapeworms complete life cycle occurs in regions with poor sanitary infrastructure, where foraging pigs have access to human faeces. Improved screening methods have been developed in the interim, including an ELISA for Taenia sp. coproantigens in faeces and an enzyme-linked immunoelectrotransfer blot
1459
(EITB) for serum antibodies against Taenia solium tapeworm. Serologic methods are desirable because they are specic to Taenia solium intestinal infection and highly sensitive (99%) and avoid the collection and processing of potentially infectious faeces. Laboratory Methods used for this study Fecal samples can be examined by light microscopy for Taenia spp. eggs or proglottids and by ELISA for Taenia spp. coproantigens. Serum samples were analyzed by EITB for antibodies against Taenia solium cysts (EITB lentil lectionbound glycoprotein) and against Taenia solium adult tapeworms (recombinant EITB). The rEITB for taeniasis is based on baculovirus expression-puried recombinant antigen rES33. Detection assays using recombinant and synthetic antigens originating from the lentil lectin-puried glycoproteins (LLGPs) of Taenia solium cysticerci were developed by Lee and colleagues 2011 in a QuickELISAT M format. for detecting cases with multiple, viable cysts. T24H QuickELISAT M presented sensitivity and specicity values comparable to those of the LLGP enzyme-linked immunosorbent blot to detect cases of viable cysts. [104] The recombinant EITB method for diagnosis of Taenia solium taeniasis [105] Levine et al 2007 describe two serological taeniasis diagnostic tests using recombinant antigens rES33 and rES38 expressed by baculovirus in insect cells in an EITB format. Independent eld testing in Peru showed 97% of the taeniasis sera were positive with rES33, and 98% of taeniasis sera were positive with rES38. rES33 and rES38 tests oer sensitive and specic diagnosis of taeniasis and simple to perform. PCR test to detect Taenia solium muscle infection [106] Polymerase chain reaction (PCR) test was employed to detect Taenia solium DNA in muscle lesions by Sreedevi et al 2011. TBR primers was targeted against the large subunit rRNA gene. Cox1 primers was targeted against cytochrome c oxidase subunit 1 gene of T. solium. The authors concluded that both PCR tests are ecient tools for validation of meat inspection results and rule out doubts in porcine cysticercosis.
19.6.10
Taenia saginata
Is the tapeworm of beef. The adults are 6 to 20 feet long. The proglottids contain male and female reproductive organs. The ova leave the body with the feces and are ingested from contaminated soil by the intermediate host like cattle. The larvae develop in the intestine, penetrate the wall and are carried by the blood stream to the skeletal muscles becoming bladder worms or cysticerci being spherical an inverted scolex. When beef containing these cysts are undercooked eaten the cyst wall is digested and the scolex may attache to the intestinal wall and the proglotids develop to form the adult parasites.
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If ova of Taenia saginata are ingested by men the same cycle observed in cattle take place. The larvae migrate through the body and cyst formation in various organs may take place. To control spreading of Taenia saginata it is important to avoid cattle to get in contact with human feces contaminated soil. Dont eat raw or undercooked meat as they may contain cysts of Taenia. Dont drink water from suspected areas without boiling as they may contain ova of Taenia.
19.6.11
Diphyllobotrium latum
Diphyllobotrium latum is the sh tapeworm causing the broad tapeworm infection. The proglotids are much broader then long. Denitive hosts are man, cats, and bears. In water the ova develop to ciliated embryos which must be ingested by a copepod where they develop during 2 to 3 weeks. If the copepod is swallowed by a sh the parasite develops in the muscle tissue of the sh. If the contaminated sh is eaten by men, cat or bear the ova develop to larvae and form the adult tapeworm. Diphyllobotrium latum may cause severe anemia since it utilizes the vitamin B12 of the host diet. It is common in North Europe and also USA. Fish should therefore not be eaten raw or undercooked specially fresh-water pike.
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19.6.12
Hymenolepis nana
It causes the dwarf tapeworm infection. It is a very small tapeworm which does not need an intermediate host. The ova may remain in the intestine and develop to the larval form and nally to the adult tapeworm. In this way heavy infestation can take place. Contamination takes place through fecal contaminated food and hands. Mice and rats may also bear Hymenolepis nana.
19.6.13
Hymenolepis diminuta
Hymenolepis diminuta (rat tapeworm, adults measuring 20 to 60 cm in length). Hymenolepis diminuta is a cestode of rodents infrequently seen in humans and frequently found in rodents.
19.6.14
Echinococcus granulosus
It causes the hydatid cyst. The adult stage lives in dog. The ova of the dog feces when ingested by sheep, hogs or cattle develops as larvae in the liver. If dogs feed from these animals during slaughter the ingested ova develop to adult tapeworms. Human beings may contaminate itself ingesting ova from food or hands contaminated by feces of dogs.This kind of contamination is common in sheep-raising countries. The ova so ingested develops to the larval form which penetrates liver or other organs forming the hydatid cyst which is a bladder-like growth containing uid and many small capsules with scolices inside. The cyst may grow for years and cause severe reactions. Cutaneous larval migration:Larvae of the dog and cat hookworms can infect humans as unnatural hosts. They will not turn into adult worms. The larvae remain in the skin where they continue to migrate for months, causing a creeping eruption under the skin and die at the end. Treatment is surgical removal of the migrating larvae. A common source of infection are sandboxes contaminated by cats. Sandboxes are ideal environment for the hookworm eggs to develop and hatch and for the larvae to survive. Keep sandboxes covered. Other places where cats like to go are ower beds and vegetable gardens. Cats and dogs should be kept away from food production and vegetable farming. Recent records indicate that the prevalence of cystic echinococcosis is increasing in Russia, suggesting that dogs are used there in herding. [107]
19.6.15
Other pet parasites
There are several examples of parasites that are normally found in pets which can be transmitted to humans:
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19.6.16
Dipylidium caninum
It is the common tapeworm of dogs. It can be transmitted to humans. The life cycle of Dipylidium caninum involves dogs or cats as the denitive host and eas or lice as the intermediate host. The ea or louse ingests the eggs. The dog or cat (or human) is infected when they ingest a ea or louse infected with the cysticercoids. Fleas or louse on dogs and cats should be eliminated as they transmit not only bacteria, viruses but also parasites.
19.6.17
Mesocestoides lineatus
Mesoscestoides tapeworm is a common cestode in carnivorous mammals, but human infection with the tapeworm of this genus have been infrequent.
19.6.18
Taenia pisiformis
Immature forms of the common roundworm of dogs, Toxocara canis can also cause migration in human visceral tissue. The feces of an infected dog or cat (or human) may contain proglotids of Taenia pisiformis.
19.6.19
Echinococcus multilocularis
The "small fox tapeworm" Echinococcus multilocularis causes alveolar echinococcosis (AE) in intermediate hosts. It is a small tapeworm (less than 4,5 mm in lenght) that parasites red and arctic foxes (dogs and cats are the denitive hosts). It is found in wild foxes in parts of Europe, Siberia, China, Japan, and arctic Alaska and in foxes and coyotes in Canada and north-central North America. Denitive hosts are always carnivores.In the denitive hosts the adult tapeworm, consisting of 2 to 6 proglottids, living attached to the luminal surface of the small intestine. The terminal proglottid contains mature eggs (ovoid, 30-40 m in diameter). The embryonated eggs, the infectious stage, are long-lived and highly resistant to high and low temperature (more than 50o C and down to -40o C). The mature eggs are shed with faeces and are spread in the environment. It is assumed that the intermediate host acquires the infections through the ingestion of contaminated fruits and vegetables.
19.6.20
Human Alveolar Echinococcosis [108]
According to Schweiger and colleagues 2007 human alveolar echinococcosis, a hepatic disorder that resembles liver cancer, is a highly aggressive and lethal zoonotic infection caused by the larval stage of the fox tapeworm, Echinococcus multilocularis Humans and intermediate host animals acquire the infection by ingesting E. multilocularis eggs in contaminated food or water or by having close physical contact with infected foxes, dogs, or host faeces.
19.7. ANISAKIS AND HERRING
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Annual incidence of human alveolar echinococcis increased recently in zwitzerland.with fox population highly increasing. The authors warn from an emerging epidemic of AE. Future trends will depend on the intensity of present and future contamination of the environment with E. multilocularis eggs as well as on the number of susceptible persons exposed to the parasite. Increasing fox population has increased the infection pressure for a large part of the human population such as coyotes in the United States and Canada, as suitable denitive host of E. multilocularis have become established in suburban areas with moderate to dense human populations, and other canids such as domestic dogs as denitive hosts. The authors conclude that public health authorities in echinococcosis-endemic areas should establish coordinated systems of continuous surveillance and risk assessment, combined with measures to reduce illness and death from AE in human populations They suggest control strategies,such as deworming of foxes and other wild canids by using anthelminthic baiting. target suburban areas that have high human and wild canid population densities.
19.7
Anisakis and Herring
Anisakis simplex (herring worm), Pseudoterranova (Phocanema, Terranova) decipiens (cod or seal worm), Contracaecum spp., and Hysterothylacium (Thynnascaris) spp. are anisakid nematodes (roundworms) that have been implicated in human infections caused by the consumption of raw or undercooked seafood. To date, only A. simplex and Pseudoterranova decipiens are reported from human cases in North America. Anisakiasis is most frequently diagnosed when the aected individual feels a tingling or tickling sensation in the throat and coughs up or manually extracts a nematode. In more severe cases there is acute abdominal pain, much like acute appendicitis accompanied by a nauseous feeling. Symptoms occur from as little as an hour to about 2 weeks after consumption of raw or undercooked seafoods. (SUSHIS). With their anterior ends, these larval nematodes from sh or shellsh usually burrow into the wall of the digestive tract (occasionally they penetrate the intestinal wall completely and are found in the body cavity). Anisakis rarely reach full maturity in humans and usually are eliminated spontaneously from the digestive tract lumen within 3 weeks of infection. In cases where the patient vomits or coughs up the worm, the disease may be diagnosed by morphological examination of the nematode. (Ascaris lumbricoides, the large roundworm of humans, is a terrestrial relative of anisakines and sometimes these larvae also crawl up into the throat and nasal
1464 passages.)
Seafoods are the principal sources of human infections with these larval worms. The adults of A. simplex are found in the stomachs of whales and dolphins. Fertilized eggs from the female parasite pass out of the host with the hosts feces. In seawater, the eggs embryonate, developing into larvae that hatch in sea water. These larvae are infective to copepods (minute crustaceans related to shrimp) and other small invertebrates. The larvae grow in the invertebrate and become infective for the next host, a sh or larger invertebrate host such as a squid. The larvae may penetrate through the digestive tract into the muscle of the second host. Some evidence exists that the nematode larvae move from the viscera to the esh if the sh hosts are not gutted promptly after catching. These parasites are known to occur frequently in the esh of cod, haddock, uke, pacic salmon, herring, ounder, and monksh. Severe cases of anisakiasis are extremely painful and require surgical intervention.
19.7.1
Food Analysis
Candling or examining sh on a light table is used by commercial processors to reduce the number of nematodes in certain white-esh sh that are known to be infected frequently. This method is not totally eective, nor is it very adequate to remove even the majority of nematodes from sh with pigmented esh.
19.7.2
Identication guide for sh parasites in stained tissue sections [109]
Identication of protozoan and metazoan parasites is performed carried using a series of classical keys based upon the morphology of the whole organism. Bruno, Nowak and Elliot 2006 provide an additional guide to the identication of sh protozoan and metazoan parasites in stained tissue sections. Identication of protozoan and small metazoan parasites (such as Myxosporidia) are stressed, because small organisms are often not recognized during gross examination.
19.7.3
Parasitic worm Thelazia callipaeda infecting eye associated tissues [110]
Thelazia callipaeda is a parasitic nematode which causes "thelaziasis" (or "eyeworm" infestation) in humans, dogs and cats and other carnivores. It infects orbital cavities and associated tissues. Drosophila is the vector host, Amiota (Phortica) variegata (Diptera: Drosophilidae) in Europe, and Phortica okadai in China. These ies feed on tears and
19.7. ANISAKIS AND HERRING infects individuals residing in poor communities in Asia, particularly in China.
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A second species, Thelazia californiensis Price, 1930, has been reported to infect humans in the United States. Diagnosis may be dicult when infestation is caused by small larval stages that are dicult to detect and identify, or only small numbers of nematodes are present and clinical signs resemble allergic conjunctivitis. [111]
19.7.4
Parasites of cetaceans
Oliveira et al. 2011 assessed the parasitic fauna of stranded dolphins and whales at the Pacic coast of Costa Rica were examined between 2001 and 2009. In striped dolphin (Stenella coeruleoalba) the prevalence of parasites was 89.5%. In dwarf sperm whale (Kogia sima) no parasites could be found. In this study the authors report that they found six species of cestodes (Strobilocephalus triangularis, Tetrabothrius forsteri, Trigonocotyle sp., Phyllobothrium delphini, Monorygma grimaldi, Tetraphyllidea gen. sp. plerocercoid), four digeneans (Nasitrema globicephalae, Brachycladium palliatum, B. pacicum and Oschmarinella albamarina) and four nematodes (Anisakis spp., Halocercus lagenorhynchi, Halocercus sp. and Crassicauda anthonyi). A commensal crustacean, Xenobalanus globicipitis, was also identied. [112] Parasitic fauna of 14 species of cetaceans o the northeastern coast of Brazil, including the archipelago of Fernando de Noronha were examined bei Carvalho et al 2010. Parasites were xed and preserved in 70% ethanol or alcohol-formalin-acetic acid solution (AFA), claried in phenol and mounted on slides for morphological identication. Halocercus brasiliensis, Halocercus kleinenbergi, Stenurus globicephalae, Halocercus sp., Anisakis sp., Crassicauda sp. (Nematoda), Phyllobothrium delphini, Monorygma grimaldii, Scolex pleuronectis, Strobicephalus triangularis, Tetrabothrius forsteri, Tetrabothrius sp., Trigonocotyle sp., Diphyllobothrium sp. (Cestoda), Campula sp. (Trematoda), Bolbosoma sp. (Acanthocephala), Cyamus boopis, Syncyamus pseudorcae and Xenobalanus globicipitis (Crustacea) were found. [113]
19.7.5
Genetic analysis identies three new denite hosts of Anisakis typica [114]
Anisakis typica collected from the cetaceans Peponocephala electra, Kogia breviceps, and Stenella clymene, found at the coastal waters of Brazil, were submitted to genetic analysis by Inigues et al. 2011. Identication was performed using the18S rDNA gene, ITS1, and specic Anisakis typica ITS regions amplied by PCR. The authors stress that the cetaceans P. electra, K. breviceps, and S. clymene, are therefore to be considered as new denitive hosts of Anisakis typica.
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19.7.6
Tapeworm alters host behaviour to reach nal host to complete life cycle [115]
Schistocephalus solidus is a tapeworm with a three-host life cycle. Free-swimming coracidia are eaten by copepods, the rst host. After 2 weeks of development in copepods,the tapeworm can infest the second intermediate host, three-spined sticklebacks which soon presents altered behaviours, such as splash along at the surface of the water enhancing the vulnerability to sh-eating birds, the nal host of S. solidus where it attains maturity, produces eggs and dies after about a week.
19.7.7 19.7.8
FDA Fish and Fishery Products Hazards and Controls Guidance [116] Parasites of human concern
Parasites (in the larval stage) consumed in uncooked or undercooked seafood can present a human health hazard. Among parasites, the nematodes or roundworms (Anisakis spp., Pseudoterranova spp., Eustrongylides spp., and Gnathostoma spp.), cestodes or tapeworms (Diphyllobothrium spp.), and trematodes or ukes (Chlonorchis sinensis (C. sinensis), Opisthorchis spp., Heterophyes spp., Metagonimus spp., Nanophyetes salmincola, and Paragonimus spp.) are of most concern in seafood. Most of these parasites cause mild-tomoderate illness, but severe symptoms can occur. Roundworms may embed in the intestinal wall and cause nausea, vomiting, diarrhoea, and severe abdominal pain and sometimes may penetrate the intestine. Tapeworms can cause abdominal swelling and abdominal cramps and may lead to weight loss and anemia. Intestinal ukes (Heterophyes spp., Metagonimus spp., and Nanophyetes salmincola) may cause abdominal discomfort and diarrhea. Some intestinal ukes may also migrate to and damage the heart and central nervous system. Liver ukes (C. sinensis and Opisthorchis spp.) and lung ukes (Paragonimus spp.) may migrate to the liver and lung and sometimes cause serious problems in other vital organs. The FDA recommends preventive controls during the processing of parasite-containing species of sh that are intended for raw consumption, such as sushi, cold smoked sh, maties (salted herring) or undercooked sh.
19.7.9
Pathogenic bacteria in sh products
The survival of pathogenic bacteria through cooking or pasteurization can cause consumer illness. The primary pathogens of concern are Clostridium botulinum (C. botulinum), Listeria monocytogenes (L. monocytogenes), Campylobacter jejuni (C. jejuni), pathogenic strains of Escherichia coli (E. coli), Salmonella spp., Shigella spp., Yersinia enterocolitica (Y. enterocolitica), Staphylococcus aureus (S. aureus), Vibrio cholera (V. cholera), Vibrio vulnicus (V. vulnicus), and Vibrio parahaemolyticus (V. parahaemolyticus).
19.8. CLIMATE CHANGE INFLUENCING PARASITES AND PATHOGEN DEVELOPMENT
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It is not practical to target viral pathogens in cooking or pasteurization processes because of their extreme heat resistance. Viral pathogens should be controlled through a rigorous sanitation regime as part of a prerequisite program or as part of Hazard Analysis Critical Control Point (HACCP) itself.
19.7.10
FDA recommendations to controlling sh parasites and pathogen bacteria
The process of heating raw sh suciently to kill bacterial pathogens is also sucient to kill parasites. Guidance concerning cooking and pasteurizing to kill bacterial pathogens is provided in Chapters 13 (hot smoking) and 16 (cooking and pasteurization). The eectiveness of freezing to kill parasites depends on the temperature of the freezing process, the length of time the sh is held frozen, and the type of parasite appear to be the most important factors. For example, tapeworms are more susceptible to freezing than are roundworms. Flukes appear to be more resistant to freezing than roundworms. Freezing and storing at an ambient temperature of -200 C or below for 7 days (total time), or freezing at an ambient temperature of -350 C or below until solid and storing at an ambient temperature of -350 C or below for 15 hours, or freezing at an ambient temperature of -350 C or below until solid and storing at an ambient temperature of -200 C ) or below for 24 hours are sucient to kill parasites. Note that these conditions may not be suitable for freezing particularly large sh (e.g., thicker than 6 inches). Brining and pickling may reduce the parasite hazard in a sh, but they do not eliminate it, nor do they minimize it to an acceptable level. Nematode larvae have been shown to survive 28 days in an 800 salinometer brine (21% salt by weight). Trimming away the belly aps of sh or candling and physically removing parasites are eective methods for reducing the numbers of parasites. However, they do not completely eliminate the hazard, nor do they minimize it to an acceptable level.
19.8
19.8.1
Climate change inuencing parasites and pathogen development

Biological systems are responding to climate change [117]
According to Kovats and colleagues shifts in the distribution and behaviour of insect and bird species indicate that biological systems are already responding to the worldsclimate change. The authors point to the task of detection of health impact of vector-borne diseases (i.e. malaria, dengue, leishmaniasis, tick-borne diseases) caused by global change.
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19.8.2
Parasites my skip evolutionary changes [118]
Brooks and colleagues say that the intersection of climate change with evolutionary conservative aspects of host specicity and transmission dynamics, called ecological tting, permits emergence of parasites and diseases without evolutionary changes in their capacity for host utilization.
19.8.3
Climate warming may increase pathogen development [119]
Climate warming can increase pathogen development and survival rates, disease transmission, and host susceptibility. Recently, changes in El Ninho-Southern Oscillation events have had a detectable inuence on marine and terrestrial pathogens, including coral diseases, oyster pathogens, crop pathogens, Rift Valley fever, and human cholera.
19.8.4
Integrative approaches to assess changes caused by global climate [120]
According to Hoberg and colleagues investigations of emerging infectious diseases associated with parasites in northern wildlife involved a network of multidisciplinary collaboratorsand incorporated geographic surveys, archival collections, historical foundations for diversity, and laboratory and eld studies exploring the interface for hosts, parasites, and the environment. In this system, emergence of parasitic disease was linked to geographic expansion, host switching, resurgence due to climate change, and newly recognized parasite species. Such integrative approaches serve as cornerstones for detection, prediction, and potential mitigation of emerging infectious diseases in wildlife and persons in the North and elsewhere under a changing global climate. The authors investigating parasitic diseases in northern wildlif stress that small changes in absolute temperatures can have substantial eects on the transmission dynamics of protostrongylid lungworms and muscleworms (species of Parelaphostrongylus, Protostrongylus, and Umingmakstrongylus), which cycle among the environment, gastropod (slug and snail) intermediate hosts, and ungulate (caribou, muskoxen, thinhorn sheep, moose) denitive hosts.
19.8.5
Freshwater parasites
A number of internal and external parasites are of importance in aquaculture.

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19.8.6 19.8.7
Ciliates Ichthyophthirius multiliis [121]
The disease called "Ich" or "white spot disease" has been a problem to aquarists for generations. Fish infected with this organism typically develop small blister-like raised lesions along the body wall and/or ns. Tavares-Dias, Lemos and Martins 2010 report that 64% of ornamental sh collected from the middle Negro River, State of Amazonas were parasitized by at least one parasite species. The authors found infection as follows: Monogenea 36.7%, Ichthyophthirius multiliis (Ciliophora) 20.6%, Trichodina spp. (Ciliophora) 4.0%, Piscinoodinium pillulare (Dinoagellida) 1.3%, Tetrahymena sp. (Ciliophora) 0.89%, and Procamallanus sp. (Nematoda) 0.4%. [122]
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Chilodonella and Tetrahymena [123]
Dopheide et al. 2011 assessed the feeding preferences of the free-swimming lter feeder Tetrahymena sp. and the surface-associated predator Chilodonella sp. Both protozoans feed on bacteria such as Pseudomonas costantinii and Serratia plymuthica, found on bacterial biolms, and exert an important impact on the morphology of such biolms.
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Climate change increases incidence of some parasitic diseases [124]
Global warming may increase the incidence of parasitic diseases. Karvonen et al. 2010 presented a long-term multi-pathogen data sets on the occurrence of pathogenic bacterial and parasitic infections in relation to increasing temperatures in aquatic systems. The authors found that the prevalence of infections increased with temperature. Diseases caused by Ichthyophthirius multiliis and Flavobacterium columnare increase with elevation of temperature of the water. However, Karvonen and colleagues caution that the biology of each disease and local conditions must be considered, because the incidence of some diseases respond inversely to a temperature increase, such as noted with diseases caused by Ichthyobodo necator, and some do not respond to temperature variations, such is the case of Chilodonella spp.
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Piscinoodinium pillulare and Tricodina [125]
Nile tilapia from Brazilian sh farms were found by Jeronimo et al. 2011 to be infested by Piscinoodinium pillulare (Dinoagellida), which was the most dominant parasite followed by Trichodina magna e T. compacta (Ciliophora), Cichlydogyrus sclerosus, C halli, C. thurstonae, Scutogyrus longicornis (Monogenoidea), copepodids Lernaeidae gen. sp. The
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authors reported higher infestations by protozoan during autumn and winter and higher infestations by metazoan in spring and summer.
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Ambiphyra Apiosoma and Epistylis [126]
Ambiphyra and Apiosoma are a sessile ciliates that can be found on the skin, gills, and ns of sh. Both are not particularly pathogenic if present in low numbers, but in high numbers, these parasites can cause signicant damage. Overpopulation and poor sanitation, high organic loads and deterioration of water quality are frequently associated with heavy infestations. Apiosoma piscicola (Blanchard 1885) was reported from fry of Carassius auratus (Var. pengze) and Ctenopharyngodon idella during parasite surveys in May 2005 and June 2006 at Hongze Lake, China. Its synonyms, Glossatella cylindriformis (Chen 1955) and Apiosoma magna (Banina 1968), were claried by Li et al 2011 in their study. [127]
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Epistylis [128]
Wu et al 2011 describe the morphology of the oligohalobic peritrichous ciliate, Epistylis chlorelligerum Shen, 1980. Zooids of Epistylis. chlorelligerum are characterized by greencolored endoplasm containing symbiotic algae.
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Capriniana [129]
Ferguson et al.2011 studies the impacts of parasites on Oregon coastal coho salmon (Oncorhynchus kistuch), identifying 21 dierent species of parasites, such as Nanophyetus salmincola, Myxobolus insidiosus, Apophallus sp., Sanguinicola sp., Trichodina truttae, Epistylis sp., Capriniana piscium, an unidentied metacercariae in gills, Myxobolus sp. in brain, Myxidium salvelini and Chloromyxum majori in kidney, Pseudocapillaria salvelini and adult digenean spp. in the intestine.
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Flagellates Hexamita [130]
Hexamita is a small intestinal Flagellate parasite commonly found in the intestinal tract of freshwater sh. Hexamita sp.with morphological characteristics similar to Hexamita meleagridis was identied in stunted diarrhoeic 1- 12 week old native turkey poults by Dezfoulian et al.2010.
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19.8.16
Ichthyobodo [131]
Two Ichthyobodo species are known to infect Atlantic salmon (Salmo salar L.). Ichthyobodo necator sensu stricto (s.s.) is a freshwater parasite, and Ichthyobodo sp. II sensu Todal et al. (2004), found in both fresh- and seawater. Isaksenet al. 2011 found that Ichthyobodo sp. II present a unique SSU rDNA sequences and dierent morphology, compared with Ichthyobodo necator ss. The authors concluded that Ichthyobodo sp. II. represents a novel species and propose the name Ichthyobodo salmonis sp. n.
19.8.17
Cryptobia [132]
Guo and Woo 2009 describe important sh parasites causing disease outbreaks in sh farms and transmission of diseases between farmed and wild sh. The authors highlight the importance of four economically important sh parasites: Cryptobia salmositica (haemoagellate), Loma salmonae (microsporidian), Gyrodactylus salaries (monogenean), Lepeophtheirus salmonis (copepod), and Caligus rogercresseyi (copepod).
19.8.18
Myxozoa [133]
The Myxozoa are a group of parasitic animals of aquatic environments. Many have a twohost lifecycle, involving a sh and an annelid worm or bryozoan. The most signicant diseases worldwide caused by myxosporeas in cultured shes are PKD-Proliferative Kidney Disease, caused by a Malacosporea member,Tetracapsuloides bryosalmonae, and whirling disease, caused by a Myxosporea member Myxobolus cerebralis; both diseases aect salmonids. Furthermore, Enteromyxosis is caused by Enteromyxum leei in cultured marine sparids, while "Hamburger disease or Proliferative Gill Disease is caused by Henneguya ictaluri in catsh and Sphaerosphora renicola infections occur in common carp.
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Microsporidia [134]
All microspoidia are intracellular parasites that require host tissue for reproduction. They invade vertebrates and invertebrates. such as insects, crustaceans, sh and humans. The microsporidia have recently been recognized as a group of pathogens that have potential for waterborne transmission. Of primary concern are the microsporidian species that infect the human gastrointestinal tract, Enterocytozoon bieneusi and Encephalitozoon syn. Septata intestinalis. they present a special challenge to the water treatment industry with regard to detection and ltration. Wolk et al. 1999 presented a spore counting and cell culture model for microsporidia. [135]
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Eimeria
Eimeria is a genus of parasites that includes various species responsible for the poultry disease coccidiosis. Eimeria are a member of the suborder Eimeriorina of the phylum Apicomplexa. Human infections Five genera are known to cause infections in humans: Cryptosporidium, Cyclospora, Isospora, Sarcocystis and Toxoplasma. Of these the rst three normally are conned to the gastrointestinal tract and cause diarrhoea and abdominal pain. The other two invade the body tissues and many be found in multiple organs. [136] Coccidiosis [137] Coccidiosis is a parasitic disease of the intestinal tract of animals, caused by coccidian protozoa. The disease spreads from one animal to another by contact with infected feces or ingestion of infected tissue. Diarrhea, which may become bloody in severe cases, is the primary symptom. Most animals infected with coccidia are asymptomatic; however, young or immuno-compromised animals may suer severe symptoms, including death. While coccidian organisms can infect a wide variety of animals, including humans, birds, and livestock, they are usually species-specic. One well-known exception is toxoplasmosis caused by Toxoplasma gondii.
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Genera and species that cause coccidiosis
Genus Isospora is the most common cause of intestinal coccidiosis in dogs and cats and is usually what is meant by coccidiosis. Species of Isospora are species specic, meaning they only infect one type of species, such as Isospora canis, Isospora ohioensis, Isospora burrowsi, and Isospora Neorivolta which infects dogs. Isospora felis and Isospora rivolta infect cats. The most common symptom is diarrhea. Genus Cryptosporidium contains Cryptosporidium parvum and Cryptosporidium Muris infecting cattle and other mammals including humans. Cryptosporidium hominis is specic for immunocompromised individuals, such as humans, dogs and cats. Genus Hammondia does not cause disease. It is transmitted by ingestion of cysts found in the tissue of grazing animals and rodents. Hammondia heydorni infecting dogs. Hammondia hammondi and Hammondia pardalis infecting cats. Genus Sarcocystis infect carnivores such as dogs and cats that ingest cysts from various intermediate hosts.
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Genus Toxoplasma has one important species, Toxoplasma gondii. Cats are the denitive host but all mammals and some sh, reptiles, and amphibians can be intermediate hosts. Only cat feces will hold infective oocysts but infection through ingestion of cysts can occur with the tissue of any intermediate host.
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Eimeria Transcript Database
The assembled transcripts of the three Eimeria species Eimeria acervulina, Eimeria maxima and Eimeria tenellaare are published in the the Eimeria Transcript Database (EimeriaTDB) The Eimeria Transcript Database (EimeriaTDB) is an integrated resource of cDNA sequencing and annotation data of Eimeria spp. of domestic fowl. EimeriaTDB is maintained by the Coccidia Molecular Biology Research Group at the Institute of Biomedical Sciences, University of So Paulo, Brazil. [138] Parasites of the genus Eimeria infect a wide range of vertebrate hosts, including chickens. The Eimeria Transcript Database contains the transcriptomes of Eimeria acervulina, Eimeria maxima and Eimeria tenella, All cDNA reads have been assembled, and the reconstructed transcripts. The main goal is to oer a public repository of sequence and functional annotation data of reconstructed transcripts of parasites of the genus Eimeria. [139] New Zealand native passerines are hosts to a large variety of gastrointestinal parasites, including coccidia. Schoener et al. 2013 found a prevalence of coccidian infection in the New Zealand bird species up to 38 %, primary of the family Eimeriidae. [140] The prevalence of coccidia infection in goats were found by Balicka-Ramisz et al. 2012 to be up to 100% in Poland and Ukraine. Nine Eimeria spp. were identied in feces samples in Western Pomerania and Lviv regions: E. arloingi, E. chrisienseni, E. jolchijevi, E. ninakohlyakimovae, E. alijevi, E. capina, E. caprovina, E. hirci, E. apsheronica. The prevalence of infection in Western Pomerania of adult goats was 74% and 100% in kids. The results of the present investigation have implications for the control of coccidial infections in goats in Europe. [141]
19.8.23
Toxoplasmosis and Neosporosis in beef cattle in Thailand
Wiengcharoen et al. 2012 report that beef cattle in Thailand had a greater exposure to Toxoplasma gondii than Neospora caninum, and they should be regarded as a potential source of Toxoplasma gondii infection to humans. According to the authors neosporosis, despite low prevalence, is still a risk for morbidity among cattle, including abortions in Thailand. [142] He et al. 2013 present a specic diagnostic assay using the Neospora caninum 40-kD
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surface antigen (p40) which is a marker for the diagnosis of neosporosis. The rNcp40 ELISA developed by the authors is a sensitive assay for detecting neosporosis in cattle. [143]
19.8.24
Two new species of coccidia identied
Jeanes et al. 2013 describe two new species of coccidia found in faeces of corncrake (Crex crex) in Scotland (U.K.). The new genes, Eimeria crecis n. sp. and Eimeria nenei n. sp. are widespread and cause enteric disease in corncrakes. [144]
19.8.25
Coccidia
Coccidia are intracellular parasites found in wild-caught and cultured sh. They are potential pathogens. According to Bangoura 2011 the pathogenic coccidia species Eimeria bovis and Eimeria zuernii are widespread in German dairy and fattening facilities. Eimeria oocysts were found positive in 95.4% of samples. Eimeria bovis was found in 76.9% of samples and Eimeria. Zuerniib in 83.1%. The number of oocysts excreted depended on the oor type, the age of the calves and the time after rehousing. Eimeria zuernii had a greater inuence on the occurrence of diarrhoea than Eimeria bovis. The authors concluded that control measures to reduce coccidia incidence should be improved in Germany. [145]
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Detection of coccidian parasites [146]
Honma, Suyama and Nakai 2011 investigated the coccidian parasites in cranes using faecal DNA using polymerase chain reaction-based capillary electrophoresis (PCR-CE), employing genetic markers in the second internal transcribed spacer (ITS2) of nuclear ribosomal DNA to detect crane coccidia. The authors stress that the sensitivity of detection of PCRCE using faecal DNA was inferior to that with traditional microscopy, but was superior in solving the coccidia diversity and describe the community composition of the parasites in a host population.
19.8.27
Monogenean Trematodes
Monogenean trematodes, also called atworms or ukes, commonly invade the gills, skin, and ns of sh. Monogeneans have a direct life cycle (no intermediate host). Gyrodactylus and Dactylogyrus are the two most common genera of monogeneans that infect freshwater sh
19.8.28
Digenean Trematodes
Digenean trematodes have a complex life cycle involving a series of hosts. The genus Posthodiplostonum has caused mortalities in baitsh.
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19.8.29
Nematodes
Nematodes, also called roundworms, occur worldwide in all animals. They can infect all organs of the host, causing loss of function of the damaged area. Camillanus and Capillaria: Camillanus protrudes from the anus of the sh which makes identication easier. Camillanus and Capillaria are the most frequent infestations of sh.
19.8.30
Cestodes
Cestodes, also called tapeworms, are found in a wide variety of animals, including sh. The life cycle of cestodes is extremely varied with sh used as the primary or intermediate host. Cestodes infect the alimentary tract, muscle or other internal organs. One of the most serious adult cestodes that aect sh is the Asian tapeworm, Bothriocephalus acheilognathi. According to Bean and Bonner 2010 the Asian sh tapeworm Bothriocephalus acheilognathi in the Rio Grande raised concern about imperiled shes. The prevalence of Bothriocephalus acheilognathi infestation was found to be 15% in samples of red shiners in January-March and December and below 10% during April-June and October. The authors stress that over 50% of the Rio Grande sh fauna in Texas are considered imperiled. A new stress caused by the Asian sh tapeworm in combination with reduced water quantity and quality and increased habitat fragmentation is of concern. [147]
19.8.31
Parasitic Crustacea
Parasitic crustacea are increasingly serious problems in cultured sh and can impact wild populations. Ergasilus: Ergasilus infestations aect the gills of freshwater sh, commonly seen in warm weather. Dezfuli et a. 2011 assessed the immunobiology of sea bream, Sparus aurata L. infected with the important parasitic copepod Ergasilus sp. Their study revealed that the sea bream respond to massive infections of Ergasilus sp.sending mast cells and their antimicrobial peptides (AMPs). [148]
19.8.32
Lernaea
Lernaea , or anchor worm , is a common parasite of goldsh and koi. Hemaprasanth et al. 2011 studied the susceptibility of ngerlings of dierent species of carps to Lernaea cyprinacea infection. Cyprinus carpio, Labeo rohita and Labeo calbasu were found to be resistant to Lernae infections in monocultures, but only Labeo calbasu resisted to the infection when the carps were reared under polyculture conditions.The authors concluded
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that Labeo calbasu is the most resistant to Lernaea cyprinacea infections. Monoculture of the discussed carp species are suggested to control this parasite in culture ponds.[149]
19.8.33
Argulus
Freswater lice Argulus siamensis: According to Saurabh, Mohanty and Sahoo 2011 there are no suitable measure known to control the crustacean ectoparasite, Argulus which threatens carp cultures. The authors looked at the dierent expression of TLR 22-like, lysozyme G, beta 2-microglobulin genes, CXCa, lysozyme C, TNFalpha and complement component 3 (C3) between uninfected control and dierent degrees of lice infected sh. The majority of the genes showed down-regulation in kidney tissue whereas up-regulation in liver and skin tissues except C3 in Argulus-infected sh. The authors concluded that infection with Argulus siamensis result in immune gene expression changes in tissues situated away from the site of parasite attachment and feeding. This knowledge may be important to develop a control strategy for Argulus infections.
Bibliography
[1] Young,Genevieve Gray: Inc.1961. Wittons Mikrobiology;McGraw-Hill Book Company,
[2] http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12692099&dopt=Abstract. Marciano-Cabral F, Cabral G.: Acanthamoeba spp. as agents of disease in humans. Clin Microbiol Rev. 2003;16:273-307. [3] Who: Brain-eating amoeba kills 10 in pakistan. arab news 10 oct 2012. http: //www.arabnews.com/who-brain-eating-amoeba-kills-10-pakistan. [4] Movahedi Z, Shokrollahi MR, Aghaali M, and Heydari H. Primary amoebic meningoencephalitis in an iranian infant. Case Report Med, page 782854, http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3412107/ 2012. [5] Trabelsi H, Dendana F, Sellami A, Sellami H, Cheikhrouhou F, Neji S, Makni F, and Ayadi A. Pathogenic free-living amoebae: Epidemiology and clinical review. Pathol Biol (Paris), 4 2012. http://www.ncbi.nlm.nih.gov/pubmed/22520593. [6] Kemble SK, Lyneld R, DeVries AS, Drehner DM, Pomputius WF 3rd, Beach MJ, Visvesvara GS, da Silva AJ, Hill VR, Yoder JS, Xiao L, Smith KE, and Danila R. Fatal naegleria fowleri infection acquired in minnesota: possible expanded range of a deadly thermophilic organism. Clin Infect Dis, 54(6):8059, 3 2012. http: //www.ncbi.nlm.nih.gov/pubmed/22238170.
BIBLIOGRAPHY
1477
[7] Kim JH, Lee SH, Sohn HJ, Lee J, Chwae YJ, Park S, Kim K, and Shin HJ. The immune response induced by dna vaccine expressing nfa1 gene against naegleria fowleri. Parasitol Res, 9 2012. http://www.ncbi.nlm.nih.gov/pubmed/22955499#. [8] http://www.cdc.gov/eid/content/13/5/736.htm?s_cid=eid736_e. MarcianoCabral F.; Cabral G.: Acanthamoeba lenticulata Infection in a Heart Transplant Patient. Emerging Infectious Diseases Volume 13, Number 5-May 2007. [9] Ankarklev J, Hestvik E, Lebbad M, Lindh J, Kaddu-Mulindwa DH, Andersson JO, Tylleskr T, Tumwine JK, and Svrd SG. Common coinfections of giardia intestinalis and helicobacter pylori in non-symptomatic ugandan children. PLoS Negl Trop Dis, 6(8):e1780, 8 2012. http://www.ncbi.nlm.nih.gov/pubmed/22953010. [10] Yoder JS, Gargano JW, Wallace RM, and Beach MJ. Division of foodborne, waterborne, and environmental diseases, national center for emerging and zoonotic infectious diseases. cdc. giardiasis surveillance - united states, 2009-2010. MMWR Surveill Summ, 61(5):1323, 9 2012. http://www.ncbi.nlm.nih.gov/pubmed/22951494. [11] http://www.ncbi.nlm.nih.gov/pubmed/19135417. Monis PT, Caccio SM, Thompson RC.: Variation in Giardia: towards a taxonomic revision of the genus. Trends Parasitol. 2009 Feb;25(2):93-100. Epub 2009 Jan 8. [12] http://www.ncbi.nlm.nih.gov/pubmed/18501440. Caccio SM, Ryan U.: Molecular epidemiology of giardiasis. Mol Biochem Parasitol. 2008 Aug;160(2):75-80. Epub 2008 May 5. [13] Eimeria. http://en.wikipedia.org/wiki/Eimeria. [14] Coccidiosis. http://en.wikipedia.org/wiki/Coccidiosis. [15] The eimeria transcript database. http://www.coccidia.icb.usp.br/eimeriatdb/. [16] Rangel LT, Novaes J, Durham AM, Madeira AM, and Gruber A. The eimeria transcript db: an integrated resource for annotated transcripts of protozoan parasites of the genus eimeria. database (oxford). 2013 feb 14;2013:bat006. 2013. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3572530/. [17] Schoener ER, Alley MR, Howe L, and Castro I. Coccidia species in endemic and native new zealand passerines. Parasitol Res, 3 2013. http://www.ncbi.nlm.nih. gov/pubmed/23468142. [18] Balicka-Ramisz A, Ramisz A, Vovk S, and Snitynskyj V. Prevalence of coccidia infection in goats in western pomerania (poland) and west ukraine region. Ann Parasitol, 58(3):16771, 2012. http://www.ncbi.nlm.nih.gov/pubmed/23444800.
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[19] Wiengcharoen J, Nakthong C, Mitchaothai J, Udonsom R, and Sukthana Y. Toxoplasmosis and neosporosis among beef cattle slaughtered for food in western thailand. Southeast Asian J Trop Med Public Health, 43(5):108793, 9 2012. http: //www.ncbi.nlm.nih.gov/pubmed/23431814. [20] Abd El-Wahab A, Visscher CF, Wolken S, Reperant LM, Beineke A, Beyerbach M, and Kamphues J. Outcome of an articial coccidial infection in poults under the inuence of oor heating. Poult Sci, 92(3):62937, 3 2013. http://www.ncbi.nlm. nih.gov/pubmed/23436513. [21] He P, Li J, Gong P, Liu C, Zhang G, Yang J, Tuo W, Yang B, and Zhang X. Neospora caninum surface antigen (p40) is a potential diagnostic marker for cattle neosporosis. Parasitol Res, 2 2013. http://www.ncbi.nlm.nih.gov/pubmed/23435920. [22] http://www.ncbi.nlm.nih.gov/pubmed/18032076. Thompson RC, Palmer CS, OHandley R.The public health and clinical signicance of Giardia and Cryptosporidium in domestic animals. Vet J. 2008 Jul;177(1):18-25. Epub 2007 Nov 26. [23] http://www.ncbi.nlm.nih.gov/pubmed/16159658. Hunter PR, Thompson RC.: The zoonotic transmission of Giardia and Cryptosporidium. Int J Parasitol. 2005 Oct;35(11-12):1181-90. [24] http://www.ncbi.nlm.nih.gov/pubmed/9143715. Rose JB.: Environmental ecology of Cryptosporidium and public health implications. Annu Rev Public Health. 1997;18:135-61. [25] http://www.ncbi.nlm.nih.gov/pubmed/17071357. OHandley RM, Olson ME.: Giardiasis and cryptosporidiosis in ruminants. Vet Clin North Am Food Anim Pract. 2006 Nov;22(3):623-43. [26] http://www.ncbi.nlm.nih.gov/pubmed/16881405. Brandonisio O.: Waterborne transmission of Giardia and Cryptosporidium. Parassitologia. 2006 Jun;48(1-2):91-4. [27] http://www.ncbi.nlm.nih.gov/pubmed/15305706. Caccio SM.: New methods for the diagnosis of Cryptosporidium and Giardia. Parassitologia. 2004 Jun;46(1-2):1515. [28] http://www.ncbi.nlm.nih.gov/pubmed/16881407. Smith H, Nichols RA.: Zoonotic protozoa-food for thought. Parassitologia. 2006 Jun;48(1-2):101-4. [29] http://www.ncbi.nlm.nih.gov/pubmed/15471705. Fayer R, Dubey JP, Lindsay DS.: Zoonotic protozoa: from land to sea. Trends Parasitol. 2004 Nov;20(11):531-6. [30] http://www.ncbi.nlm.nih.gov/pubmed/15982929. Appelbee AJ, Thompson RC, Olson ME.: Giardia and Cryptosporidium in mammalian wildlifecurrent status and future needs. Trends Parasitol. 2005 Aug;21(8):370-6.
BIBLIOGRAPHY
1479
[31] http://www.ncbi.nlm.nih.gov/pubmed/17964724. Coklin T, Farber J, Parrington L, Dixon B.: Prevalence and molecular characterization of Giardia duodenalis and Cryptosporidium spp. in dairy cattle in Ontario, Canada. Vet Parasitol. 2007 Dec 25;150(4):297-305. Epub 2007 Oct 26. [32] http://www.ncbi.nlm.nih.gov/pubmed/19070965. Coklin T, Uehlinger FD, Farber JM, Barkema HW, OHandley RM, Dixon BR.: Prevalence and molecular characterization of Cryptosporidium spp. in dairy calves from 11 farms in Prince Edward Island, Canada. Vet Parasitol. 2009 Mar 23;160(3-4):323-6. Epub 2008 Nov 5. [33] http://www.ncbi.nlm.nih.gov/pubmed/19091477. Keshavarz A, Haghighi A, Athari A, Kazemi B, Abadi A, Mojarad EN.: Prevalence and molecular characterization of bovine Cryptosporidium in Qazvin province, Iran. Vet Parasitol. 2009 Mar 23;160(3-4):316-8. Epub 2008 Nov 13. [34] http://www.ncbi.nlm.nih.gov/pubmed/18478266. Pirestani M, Sadraei J, Dalimi Asl A, Zavvar M, Vaeznia H.Molecular characterization of Cryptosporidium isolates from human and bovine using 18s rRNA gene in Shahriar county of Tehran, Iran. Vet Parasitol. 2007 Dec 25;150(4):297-305. Epub 2007 Oct 26. [35] http://www.ncbi.nlm.nih.gov/pubmed/18343369. Ng J, Eastwood K, Durrheim D, Massey P, Walker B, Armson A, Ryan U.: Evidence supporting zoonotic transmission of Cryptosporidium in rural New South Wales.Exp Parasitol. 2008 May;119(1):192-5. Epub 2008 Feb 2. [36] http://www.ncbi.nlm.nih.gov/pubmed/19368251. Geurden T, Goossens E, Levecke B, Vercammen F, Vercruysse J, Claerebout E.: Occurrence and molecular characterization of Cryptosporidium and Giardia in captive wild ruminants in Belgium. J Zoo Wildl Med. 2009 Mar;40(1):126-30. [37] http://www.ncbi.nlm.nih.gov/pubmed/18248370. King BJ, Hoefel D, Daminato DP, Fanok S, Monis PT.: Solar UV reduces Cryptosporidium parvum oocyst infectivity in environmental waters. J Appl Microbiol. 2008 May;104(5):1311-23. Epub 2008 Jan 31. [38] http://www.ncbi.nlm.nih.gov/pubmed/15567586. Betancourt WQ, Rose JB.: Drinking water treatment processes for removal of Cryptosporidium and Giardia. Vet Parasitol. 2004 Dec 9;126(1-2):219-34. [39] http://www.ncbi.nlm.nih.gov/pubmed/17133829. Erickson MC, Ortega YR.: Inactivation of protozoan parasites in food, water, and environmental systems. J Food Prot. 2006 Nov;69(11):2786-808. [40] http://aem.asm.org/cgi/content/full/74/23/7101?view=long&pmid= 18849452. Peng X, Murphy T, Holden NM.: Evaluation of the eect of temperature on the die-o rate for Cryptosporidium parvum oocysts in water, soils, and feces. Appl Environ Microbiol. 2008 Dec;74(23):7101-7. Epub 2008 Oct 10.
1480
[41] http://www.ceeramtools.com/pdf/ceeram-tools.pdf. Ceeram Cryptosporidium Giargia tools. Ceeram publication. [42] http://www.ncbi.nlm.nih.gov/pubmed/19358845. Xiao L: Molecular epidemiology of cryptosporidiosis: an update. Exp Parasitol. 2010 Jan;124(1):80-9. Epub 2009 Apr 7. [43] http://www.ncbi.nlm.nih.gov/pubmed/20433942. Mogi T, Kita K: Diversity in mitochondrial metabolic pathways in parasitic protists Plasmodium and Cryptosporidium. Parasitol Int. 2010 Apr 27. [44] http://www3.interscience.wiley.com/journal/123373630/abstract. Pangasa A, Jex AR, Nolan MJ, Campbell BE, Haydon SR, Stevens MA, Gasser RB: Highly sensitive non-isotopic restriction endonuclease ngerprinting of nucleotide variability in the gp60 gene within Cryptosporidium species, genotypes and subgenotypes infective to humans, and its implications. Electrophoresis. 2010 Apr 23. [45] http://www.ncbi.nlm.nih.gov/pubmed/19699288. Jex AR, Gasser RB: Genetic richness and diversity in Cryptosporidium hominis and C. parvum reveals major knowledge gaps and a need for the application of next generation technologiesresearch review. Biotechnol Adv. 2010 Jan-Feb; 28(1):17-26. [46] http://www.ncbi.nlm.nih.gov/pubmed/20412184. Agnamey P, Djeddi D, Oukachbi Z, Totet A, Raccurt CP: Cryptosporidium hominis and Isospora belli diarrhea in travelers returning from West Africa. J Travel Med. 2010 Mar 1;17(2):141-2. [47] http://www.ncbi.nlm.nih.gov/pubmed/20392919. Ajjampur SS, Liakath FB, Kannan A, Rajendran P, Sarkar R, Moses PD, Simon A, Agarwal I, Mathew A, OConnor R, Ward H, Kang G: Multi-site Study of Cryptosporidiosis in Indian Children with Diarrhea. J Clin Microbiol. 2010 Apr 14. [48] http://www.ncbi.nlm.nih.gov/pubmed/20381251. Robertson LJ, Gjerde BK, Furuseth Hansen E: The zoonotic potential of Giardia and Cryptosporidium in Norwegian sheep: A longitudinal investigation of 6 ocks of lambs. Vet Parasitol. 2010 Mar 17. [49] http://www.ncbi.nlm.nih.gov/pubmed/20380767. Diaz P, Quilez J, Chalmers RM, Panadero R, Lopez C, Sanchez-Acedo C, Morrondo P, Diez-Banos P: Genotype and subtype analysis of Cryptosporidium isolates from calves and lambs in Galicia (NW Spain). Parasitology. 2010 Apr 12:1-7. [50] http://www.ncbi.nlm.nih.gov/pubmed/20397026. Szonyi B, Bordonaro R, Wade SE, Mohammed HO: Seasonal variation in the prevalence and molecular epidemiology of Cryptosporidium infection in dairy cattle in the New York City Watershed. Parasitol Res. 2010 Apr 16.
BIBLIOGRAPHY
1481
[51] http://www.ncbi.nlm.nih.gov/pubmed/17391853. Plutzer J, Karanis P: Genotype and subtype analyses of Cryptosporidium isolates from cattle in Hungary. Vet Parasitol. 2007 May 31;146(3-4):357-62. Epub 2007 Mar 27. [52] http://www.ncbi.nlm.nih.gov/pubmed/12839797. Nichols RA, Campbell BM, Smith HV: Identication of Cryptosporidium spp. oocysts in United Kingdom noncarbonated natural mineral waters and drinking waters by using a modied nested PCR-restriction fragment length polymorphism assay. Appl Environ Microbiol. 2003 Jul;69(7):4183-9. [53] http://www.ncbi.nlm.nih.gov/pubmed/20356678. Khan SM, Debnath C, Pramanik AK, Xiao L, Nozaki T, Ganguly S: Molecular characterization and assessment of zoonotic transmission of Cryptosporidium from dairy cattle in West Bengal, India. Vet Parasitol. 2010 Mar 11. [54] Follet J, Guyot K, Leruste H, Follet-Dumoulin A, Hammouma-Ghelboun O, Certad G, Dei-Cas E, and Halama P. Cryptosporidium infection in a veal calf cohort in france: molecular characterization of species in a longitudinal study. Veterinary Resesarch, 42(116), 12 2011. http://www.veterinaryresearch.org/content/42/ 1/116/abstract. [55] http://www.ncbi.nlm.nih.gov/pubmed/20353289. Boyer DG, Kuczynska E: Prevalence and Concentration of Cryptosporidium Oocysts in Beef Cattle Paddock Soils and Forage. Foodborne Pathog Dis. 2010 Mar 30. [56] http://www.ncbi.nlm.nih.gov/pubmed/20411762. Huang L, An CX, Zhang SM, Ning CS, Zhang LX: Modied method for purifying Cryptosporidium oocysts. Zhongguo Ji Sheng Chong Xue Yu Ji Sheng Chong Bing Za Zhi. 2010 Feb;28(1):79-80. Chinese. [57] http://www.ncbi.nlm.nih.gov/pubmed/20352447. Khouja LB, Cama V, Xiao L: Parasitic contamination in wastewater and sludge samples in Tunisia using three dierent detection techniques. Parasitol Res. 2010 Mar 30. [58] http://www.ncbi.nlm.nih.gov/pubmed/20351439. Fu CY, Xie X, Huang JJ, Zhang T, Wu QY, Chen JN, Hu HY: Monitoring and evaluation of removal of pathogens at municipal wastewater treatment plants. Water Sci Technol. 2010;61(6):1589-99. [59] Baldursson S and Karanis P. Waterborne transmission of protozoan parasites: Review of worldwide outbreaks-an update 2004-2010. Water Res, 10 2011. http: //www.ncbi.nlm.nih.gov/pubmed/22048017. [60] Fiuza VR, Almeida AJ, Fraz ao Teixeira E, Santn M, Fayer R, and Oliveira FC. Occurrence of cryptosporidium andersoni in brazilian cattle. J Parasitol, 97(5):952 3, 10 2011. http://www.ncbi.nlm.nih.gov/pubmed/21526922.
1482
[61] Fiuza VR, Gallo SS, Fraz ao Teixeira E, Santn M, Fayer R, and Oliveira FC. Cryptosporidium pig genotype ii diagnosed in pigs from the state of rio de janeiro, brazil. J Parasitol, 97(1):1467, 2 2011. http://www.ncbi.nlm.nih.gov/pubmed/21348623. [62] Fiuza VR, Cosendey RI, Fraz ao Teixeira E, Santn M, Fayer R, and de Oliveira FC. Molecular characterization of cryptosporidium in brazilian sheep. Vet Parasitol, 175(3-4):3602, 2 2011. http://www.ncbi.nlm.nih.gov/pubmed/21075526. [63] Arajo RS, Dropa M, Fernandes LN, Carvalho TT, Sato MI, Soares RM, Matt GR, and Matt MH. Genotypic characterization of cryptosporidium hominis from water samples in sao paulo, brazil. Am J Trop Med Hyg, 85(5):8348, 11 2011. http://www.ncbi.nlm.nih.gov/pubmed/22049036. [64] http://www.ncbi.nlm.nih.gov/pubmed/17094593. Chen LF, Li JH, Zhang XC, Liu Q, Zhao YP, Cao LL.: Establishment of in vitro cultivation of Giardia canis trophozoites infected with Giardia canis virus Zhongguo Ji Sheng Chong Xue Yu Ji Sheng Chong Bing Za Zhi. 2006 Aug;24(4):261-5. [65] http://www.ncbi.nlm.nih.gov/pubmed/19619539. Cao L, Gong P, Li J, Zhang X, Zou X, Tuo W, Liu Q, Wang Q, Zhang G, Chen L, Li L, Su L. Giardia canis: ultrastructural analysis of G. canis trophozoites transfected with full length G. canis virus cDNA transcripts. Exp Parasitol. 2009 Jul 17. [66] http://www.ncbi.nlm.nih.gov/pubmed/18606792. Arthurson, Veronica: Proper sanitization of sewage sludge: a critical issue for a sustainable society.Appl Environ Microbiol. 2008 Sep;74(17):5267-75. Epub 2008 Jul 7. [67] http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=OJ:L:2002:273: 0001:0095:EN:PDF. Regulation (EC) No 1774/2002 of the European Parliament and of the Council of 3 October 2002 laying down health rules concerning animal by-products not intended for human consumption. [68] http://www.ncbi.nlm.nih.gov/pubmed/19744303. Innes EA: A Brief History and Overview of Toxoplasma gondii. Zoonoses Public Health. 2009 Sep 10. [69] http://en.wikipedia.org/wiki/Toxoplasma_gondii. gondii. Wikipedia: Toxoplasma
[70] http://www.inspection.gc.ca/english/fssa/concen/cause/toxoplasmae. shtml. Canadian Food Inspection Agency: Food safety facts on Toxoplasma. [71] Dubey JP, Ferreira LR, Martins J, and Jones JL. Sporulation and survival of toxoplasma gondii oocysts in dierent types of commercial cat litter. Journal of Parasitology, 97(5):751754, 2011. http://www.journalofparasitology.org/doi/abs/ 10.1645/GE-2774.1.
BIBLIOGRAPHY
1483
[72] Vyas A and Sapolsky R. Manipulation of host behaviour by toxoplasma gondii: what is the minimum a proposed proximate mechanism should explain? Folia Parasitol (Praha), 57(2):8894, 6 2010. http://www.ncbi.nlm.nih.gov/pubmed/20608470. [73] Macedo MF, Macedo CA, Ewald MP, Martins GF, Zulpo DL, Cunha IA, Taroda A, Cardim ST, Su C, and Garcia JL. Isolation and genotyping of toxoplasma gondii from pregnant dairy cows (bos taurus) slaughtered. Rev Bras Parasitol Vet, 21(1):747, 3 2012. http://www.scielo.br/scielo.php?script=sci_ arttext&pid=S1984-29612012000100016&lng=en&nrm=iso&tlng=en. [74] Goodhead I, Archibald A, Amwayi P, Brass A, Gibson J, Hall N, Hughes MA, Limo M, Iraqi F, Kemp SJ, and Noyes HA. A comprehensive genetic analysis of candidate genes regulating response to trypanosoma congolense infection in mice. PLoS Negl Trop Dis, 4(11):e880, 11 2010. http://www.plosntds.org/article/info%3Adoi% 2F10.1371%2Fjournal.pntd.0000880. [75] http://www.plosntds.org/article/info%3Adoi%2F10.1371%2Fjournal.pntd. 0000658. Jackson AP, Sanders M, Berry A, McQuillan J, Aslett MA, et al. (2010) The Genome Sequence of Trypanosoma brucei gambiense, Causative Agent of Chronic Human African Trypanosomiasis. PLoS Negl Trop Dis 4(4): e658. doi:10.1371/journal.pntd.0000658. [76] Meyer CG, Calixto Fernandes MH, Intemann CD, Kreuels B, Kobbe R, Kreuzberg C, Ayim M, Ruether A, Loag W, Ehmen C, Adjei S, Adjei O, Horstmann RD, and May J. Il3 variant on chromosomal region 5q31-33 and protection from recurrent malaria attacks. Hum Mol Genet, 20(6), 3 2011. http://hmg.oxfordjournals. org/content/20/6/1173.long. [77] Christian Timmann et al. Genome-wide association study indicates two novel resistance loci for severe malaria. Nature, 6 2012. http://www.nature.com/nature/ journal/vaop/ncurrent/full/nature11334.html. [78] http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=358231. Cross J. H.: Intestinal capillariasis; Clin Microbiol Rev. 1992 April; 5(2): 120-129. [79] Richinitti, Lucia M.Z.; Fonseca, Nivaldo, A.; Grae-Teixeira, Carlos: The eect of temperature on mobility of Angiostrongylus costaricensis third stage larvae; Revista do Instituto de Medicina Tropical de So Paulo, Julio/Agosto 1999. [80] Bendall RP, Barlow M, Betson M, Stothard JR, and Nejsum P. Zoonotic ascariasis, united kingdom [letter]. Emerg Infect Dis, 10 2011. http://dx.doi.org/10.3201/ eid1710.101826. [81] Leles D, Arajo A, Vicente AC, and Iiguez AM. Its1 intra-individual variability of ascaris isolates from brazil. Parasitol Int, 59(1):936, 3 2010. http://www.ncbi. nlm.nih.gov/pubmed/19819347.
1484
[82] Starr MC and Montgomery SP. Soil-transmitted helminthiasis in the united states: a systematic review-1940-2010. Am J Trop Med Hyg, 85(4):6804, 10 2011. http: //www.ncbi.nlm.nih.gov/pubmed/21976572. [83] Damen JG, Luka J, Biwan EI, and Lugos M. Prevalence of intestinal parasites among pupils in rural north eastern, nigeria. Niger Med J, 52(1):46, 1 2011. http: //www.ncbi.nlm.nih.gov/pubmed/21969128. [84] Alyouse NA, Mahdy MA, Mahmud R, and Lim YA. Factors associated with high prevalence of intestinal protozoan infections among patients in sanaa city, yemen. PLoS One, 6(7):e22044, 2011. http://www.plosone.org/article/info%3Adoi% 2F10.1371%2Fjournal.pone.0022044. [85] Ekinci B, Karacaoglan E, Bulucu E, and Sl N. Investigation of intestinal parasites among elementary school students in the mugla province. Turkiye Parazitol Derg, 35(2):925, 2011. http://www.ncbi.nlm.nih.gov/pubmed/21776594. [86] Health protection agency (2008): National standard method: Investigation of specimens other than blood for parasites bsop 31. http://www.hpa-standardmethods. org.uk/documents/bsop/pdf/bsop31.pdf. [87] Attwood SW, Fatih FA, and Upatham ES. Dna-sequence variation among schistosoma mekongi populations and related taxa; phylogeography and the current distribution of asian schistosomiasis. PLoS Negl Trop Dis, 2(3):e200, 2008. http://www. plosntds.org/article/info%3Adoi%2F10.1371%2Fjournal.pntd.0000200. [88] Muth S, Sayasone S, Odermatt-Biays S, Phompida S, Duong S, and Odermatt P. Schistosoma mekongi in cambodia and lao peoples democratic republic. Adv Parasitol, 72:179203, 2010. http://www.ncbi.nlm.nih.gov/pubmed/20624532. [89] Kato-Hayashi N, Kirinoki M, Iwamura Y, Kanazawa T, Kitikoon V, Matsuda H, and Chigusa Y. Identication and dierentiation of human schistosomes by polymerase chain reaction. Exp Parasitol, 124(3):3259, 3 2010. http://www.ncbi.nlm.nih. gov/pubmed/19948171. [90] Barber KE, Mkoji GM, and Loker ES. Pcr-rp analysis of the its2 region to identify schistosoma haematobium and s. bovis from kenya. Am J Trop Med Hyg, 62(4):434 40, 4 2000. http://www.ajtmh.org/cgi/reprint/62/4/434. [91] Leshem E, Meltzer E, Marva E, and Schwartz E. Travel-related schistosomiasis acquired in laos. Emerg Infect Dis, 15(11):18236, 11 2009. http://www.cdc.gov/ eid/content/15/11/1823.htm. [92] Hua HY, Liang YS, Zhang Y, Wei JF, and Guo HX. The sensitivity of artesunate against schistosoma japonicum decreased after 10 years of use in china. Parasitol Res, 107(4):8738, 9 2010. http://www.ncbi.nlm.nih.gov/pubmed/20549236.
BIBLIOGRAPHY
1485
[93] Ishikawa H and Ohmae H. Modeling the dynamics and control of transmission of schistosoma japonicum and s. mekongi in southeast asia. Korean J Parasitol, 47(1):1 5, 3 2009. http://www.ncbi.nlm.nih.gov/pubmed/19290084. [94] http://www.thieme.de/fz/roefo/06_00/fall_02.html. Brenner-Maucher K., Szeimies U., Mannstadt M., Gross M.: Fasciola hepatica: Sonographische und computertomographische Vernderungen bei Befall mit einem Leberegel; Rfo Der Interesstante Fall; Thieme Fachzeitschriften. [95] http://edoc.ub.uni-muenchen.de/archive/00004024/. Koch, Sandra: Untersuchungen zur Verbreitung von Fasciola hepatica im bayerischen Milchviehbestand Dissertation, LMU Munich: Faculty of Veterinary Medicine. 2005. [96] http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=7834237&dopt=Abstract. Kim CH, Na YE, Kim NM, Shin DW, Chang Dy: Intestinal parasite and Clonorchis sinensis infection among the inhabitants in the upper stream of Taechong Dam, Kumgang (River); Korean J Parasitology, 1994 Dec; 32(4):207-214. [97] http://cmr.asm.org/cgi/content/abstract/17/3/540. Byung Ihn Choi, Joon Koo Han, Sung Tae Hona, and Kyoung Ho Lee: Clonorchiasis and Cholangiocarcinoma: Etiologic Relationship and Imaging Diagnosis. Clinical Microbiology Reviews, July 2004, p. 540-552, Vol. 17, No. 3 DOI: 10.1128/CMR.17.3.540-552.2004. [98] http://www.cdc.gov/eid/content/13/12/1828.htm?s_cid=eid1828_e. Do Trung Dung, Nguyen Van De, Jitra Waikagul, Anders Dalsgaard, Jong-Yil Chai, Woon-Mok Sohn, K. Darwin Murrell: Fishborne Zoonotic Intestinal Trematodes, Vietnam. [99] http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db= PubMed&listuids=14611873&dopt=Abstract. Sithithaworn P, Haswell-Elkins M: Epidemiology of Opisthorchis viverrini; Acta Trop. 2003 Nov;88(3):187-94. [100] http://www.scielo.br/pdf/abmvz/v57n4/26080.pdf. P. Oliveira; M.A. Pires; P. Rodrigues; M. Ginja; M.J. Pires; I. Pires; L. Cardoso; L. Antunes; M. Rodrigues: Opisthorchis felineus in cat: case report Arq. Bras. Med. Vet. Zootec. vol.57 no.4 Belo Horizonte Aug. 2005. doi: 10.1590/S0102-09352005000400020. [101] http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=3090713&dopt=Abstract. Cross J.H., Basaca-Sevilla V.: Studies on Echinostoma ilocanum in the Philippines. Southeast Asian J Trop Med Public Health 1986 Mar;17(1):23-7. [102] ONeal S, Noh J, Wilkins P, Keene W, Lambert W, Anderson J, Luman JC, and Towne J. Taenia solium tapeworm infection, oregon, 20062009. EID, 17(6), 6 2011. http://www.cdc.gov/eid/content/17/6/1030.htm.
1486
[103] Leshem E, Kliers I, Bakon M, Gomori M, Karplus R, and Schwartz E. Neurocysticercosis in travelers: a nation-wide study in israel. J Travel Med, 18(3):1917, 5 2011. http://www.ncbi.nlm.nih.gov/pubmed/21539659. [104] Lee YM, Handali S, Hancock K, Pattabhi S, Kovalenko VA, Levin A, Rodriguez S, Lin S, Scheel CM, Gonzalez AE, Gilman RH, Garcia HH, and Tsang VC. Serologic diagnosis of human taenia solium cysticercosis by using recombinant and synthetic antigens in quickelisaT M . Am J Trop Med Hyg, 84(4):58793, 4 2011. http://www. ncbi.nlm.nih.gov/pubmed/21460015. [105] Levine MZ, Lewis MM, Rodriquez S, Jimenez JA, Khan A, Lin S, Garcia HH, Gonzales AE, Gilman RH, and Tsang VC. Development of an enzyme-linked immunoelectrotransfer blot (eitb) assay using two baculovirus expressed recombinant antigens for diagnosis of taenia solium taeniasis. J Parasitol, 93:40917, 2007. http://www. journalofparasitology.org/doi/abs/10.1645/GE-938R.1?journalCode=para. [106] Sreedevi C, Hafeez M, Kumar PA, Rayulu VC, Subramanyam KV, and Sudhakar K. Pcr test for detecting taenia solium cysticercosis in pig carcasses. Trop Anim Health Prod, 6 2011. http://www.ncbi.nlm.nih.gov/pubmed/21633923. [107] http://www.ncbi.nlm.nih.gov/pubmed/15027606?dopt=Abstract. Rausch RL.: Cystic echinococcosis in the Arctic and Sub-Arctic. Parasitology. 2003;127:S73-85. [108] http://www.cdc.gov/EID/content/13/6/878.htm. Schweiger A, Ammann RW, Candinas D, Clavien P-A, Eckert J, Gottstein B, et al. Human alveolar echinococcosis after fox population increase, Switzerland. Emerg Infect Dis. 2007 Jun Available from. [109] Bruno DW, Nowak B, and Elliott DG. Guide to the identication of sh protozoan and metazoan parasites in stained tissue sections. Dis Aquat Organ, 70(1-2):136, 6 2006. http://www.ncbi.nlm.nih.gov/pubmed/16875388. [110] Eye can see a nest of worms! The Lancet, 379(9820):e42, 3 2012. http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2811% 2961455-4/fulltext. [111] Otranto D and Dutto D. Human thelaziasis. Europe. Emerg Infect Dis, 2008. http: //wwwnc.cdc.gov/eid/article/14/4/07-1205.htm. [112] Oliveira JB, Morales JA, Gonzlez-Barrientos RC, Hernndez-Gamboa J, and Hernndez-Mora G. Parasites of cetaceans stranded on the pacic coast of costa rica. 2011. http://www.ncbi.nlm.nih.gov/pubmed/21665367. [113] Carvalho VL, Bevilaqua CM, Iniguez AM, Mathews-Cascon H, Ribeiro FB, Pessoa LM, de Meirelles AC, Borges JC, Marigo J, Soares L, and de Lima Silva FJ. Metazoan parasites of cetaceans o the northeastern coast of brazil. Vet Parasitol, 173(1-2):116 22, 2010. http://www.ncbi.nlm.nih.gov/pubmed/20638793.
BIBLIOGRAPHY
1487
[114] Iniguez AM, Carvalho VL, Motta MR, Pinheiro DC, and Vicente AC. Genetic analysis of anisakis typica (nematoda: Anisakidae) from cetaceans of the northeast coast of brazil: New data on its denitive hosts. Vet Parasitol, 178(3-4):2939, 6 2011. http://www.ncbi.nlm.nih.gov/pubmed/21324600. [115] Quinn TP, Kendall NW, Rich HB Jr, and Chasco BE. Diel vertical movements, and eects of infection by the cestode schistocephalus solidus on daytime proximity of three-spined sticklebacks gasterosteus aculeatus to the surface of a large alaskan lake. Oecologia, 6 2011. http://www.ncbi.nlm.nih.gov/pubmed/21748321. [116] Guidance for the industry: Fish and shery products hazards and controls guidance. http://www.fda.gov/Food/ GuidanceComplianceRegulatoryInformation/GuidanceDocuments/Seafood/ FishandFisheriesProductsHazardsandControlsGuide/default.htm#TOC. [117] http://www.ncbi.nlm.nih.gov/pubmed/11516383?dopt=Abstract. Kovats, RS; Campbell-Lendrum, DH; McMichael, AJ; Woodward, A; Cox, JS: Early eects of climate change: do they include changes in vector-borne disease? Philos Trans R Soc Lond B Biol Sci 2001 Jul 29;356(1411):1057-68. PMID: 11516383 [PubMed indexed for MEDLINE]. [118] http://www.ncbi.nlm.nih.gov/pubmed/17962073?dopt=Abstract. Brooks DR, Hoberg EP. How will global climate change aect parasite-host assemblages? Trends Parasitol. 2007 Oct 23; [Epub ahead of print]. [119] http://www.ncbi.nlm.nih.gov/pubmed/12077394?dopt=Abstract. Harvell CD, Mitchell CE, Ward JR, Altizer S, Dobson AP, Ostfeld RS, et al. : Climate warming and disease risks for terrestrial and marine biota. Science. 2002;296:2158-62. [120] http://www.cdc.gov/eid/content/14/1/10.htm?s_cid=eid10_e. Hoberg, Eric P.; Polley, Lydden; Jenkins, Emily J.; Kutz, Susan J.; Veitch, Alasdair M.; Elkin, Brett T.: Integrated Approaches and Empirical Models for Investigation of Parasitic Diseases in Northern Wildlife. CDC Emerging Infectious Diseases. Volume 14, Number 1-January 2008. [121] Introduction to freshwater sh parasites. http://edis.ifas.ufl.edu/fa041. [122] Tavares-Dias M, Lemos JR, and Martins ML. Parasitic fauna of eight species of ornamental freshwater sh species from the middle negro river in the brazilian amazon region. Rev Bras Parasitol Vet, 19(2):1037, Apr-Jun. http://www.ncbi.nlm.nih. gov/pubmed/20624347. [123] Dopheide A, Lear G, Stott R, and Lewis G. Preferential feeding by the ciliates chilodonella and tetrahymena spp. and eects of these protozoa on bacterial biolm structure and composition. Appl Environ Microbiol, 77(3):456472, 7 2011. http: //www.ncbi.nlm.nih.gov/pubmed/21602372.
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[124] Karvonen A, Rintamki P, Jokela J, and Valtonen ET. Increasing water temperature and disease risks in aquatic systems: climate change increases the risk of some, but not all, diseases. Int J Parasitol, 40(13):14838, 11 2010. http://www.ncbi.nlm. nih.gov/pubmed/20580904. [125] Jeronimo G, Speck G, Cechinel M, Gonalves E, and Martins M. Seasonal variation on the ectoparasitic communities of nile tilapia cultured in three regions in southern brazil. Braz J Biol, 71(2):36573, 5 2011. http://www.scielo.br/scielo.php? pid=S1519-69842011000300005&script=sci_arttext. [126] Protozoa infecting gills and skin. The Merck Veterinary Manual. http://www. merckvetmanual.com/mvm/index.jsp?cfile=htm/bc/170410.htm. [127] Li M, Wang J, Zhu D, Gu Z, Zhang J, and Gong X. Study of apiosoma piscicola (blanchard 1885) occurring on fry of freshwater shes in hongze, china with consideration of the genus apiosoma. Parasitol Res, 102(5):9317, 4 2008. http://www.ncbi.nlm.nih.gov/pubmed/18247054. [128] Wu S, Shi X, Utz LR, Liu G, Ji D, Zhao Y, and Wang H. Morphology and morphogenesis of a freshwater ciliate, epistylis chlorelligerum shen, 1980 (ciliophora, peritrichia). J Eukaryot Microbiol, 58(2), Mar-Apr 2011. http://www.ncbi.nlm. nih.gov/pubmed/21332874. [129] Ferguson JA, St-Hilaire S, Peterson TS, Rodnick KJ, and Kent ML. Survey of parasites in threatened stocks of coho salmon (oncorhynchus kisutch) in oregon by examination of wet tissues and histology. J Parasitol, 6 2011. http://www.ncbi. nlm.nih.gov/pubmed/21668345. [130] Dezfoulian O, Gharagozlou MJ, and Rahbari S. Hexamita infection associated with diarrhoea and stunting in native turkey poults. Trop Biomed, 27(3):5048, 12 2010. http://www.msptm.org/files/504_-_508_Dezfoulian_O.pdf. [131] Isaksen TE, Karlsbakk E, Watanabe K, and Nylund A. Ichthyobodo salmonis sp. n. (ichthyobodonidae, kinetoplastida), an euryhaline ectoparasite infecting atlantic salmon (salmo salar l.). Parasitology, 138(9):116475, 8 2011. http://www.ncbi. nlm.nih.gov/pubmed/21756424. [132] Guo FC and Woo PT. Selected parasitosis in cultured and wild sh. Vet Parasitol, 163(3):20716, 8 2009. http://www.ncbi.nlm.nih.gov/pubmed/19573992. [133] Wikipedia. Myxozoa. http://en.wikipedia.org/wiki/Myxozoa. [134] Wikipedia. Microsporidia. http://www.stanford.edu/class/humbio103/ ParaSites2006/Microsporidiosis/microsporidia1.html.
BIBLIOGRAPHY
1489
[135] Wolk DM, Johnson CH, Rice EW, Marshall MM, Grahn KF, Plummer CB, and Sterling CR:. A spore counting method and cell culture model for chlorine disinfection studies of encephalitozoon syn. septata intestinalis. Appl Environ Microbiol, 66(4):126673, 4 2000. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC91979/ ?tool=pubmed. [136] Eimeria. Wikipedia. http://en.wikipedia.org/wiki/Eimeria. [137] Coccidiosis. Wikipedia. http://en.wikipedia.org/wiki/Coccidiosis. [138] The eimeria transcript database. http://www.coccidia.icb.usp.br/eimeriatdb/. [139] Rangel LT, Novaes J, Durham AM, Madeira AM, and Gruber A. The eimeria transcript db: an integrated resource for annotated transcripts of protozoan parasites of the genus eimeria. Database (Oxford), 2 2013. http://www.ncbi.nlm.nih.gov/ pmc/articles/PMC3572530/. [140] Schoener ER, Alley MR, Howe L, and Castro I. Coccidia species in endemic and native new zealand passerines. Parasitol Res, 3 2013. http://www.ncbi.nlm.nih. gov/pubmed/23468142. [141] Balicka-Ramisz A, Ramisz A, Vovk S, and Snitynskyj V. Prevalence of coccidia infection in goats in western pomerania (poland) and west ukraine region. Ann Parasitol, 58(3):16771, 2012. http://www.ncbi.nlm.nih.gov/pubmed/23444800. [142] Wiengcharoen J, Nakthong C, Mitchaothai J, Udonsom R, and Sukthana Y. Toxoplasmosis and neosporosis among beef cattle slaughtered for food in western thailand. Southeast Asian J Trop Med Public Health, 43(5):108793, 9 2012. http: //www.ncbi.nlm.nih.gov/pubmed/23431814. [143] He P, Li J, Gong P, Liu C, Zhang G, Yang J, Tuo W, Yang B, and Zhang X. Neospora caninum surface antigen (p40) is a potential diagnostic marker for cattle neosporosis. Parasitol Res, 2 2013. http://www.ncbi.nlm.nih.gov/pubmed/23435920. [144] Jeanes C, Vaughan-Higgins R, Green RE, Sainsbury AW, Marshall RN, and Blake DP. Two new eimeria species parasitic in corncrakes (crex crex ) (gruiformes: Rallidae) in the united kingdom. J Parasitol, 1 3013. http://www.ncbi.nlm.nih.gov/ pubmed/23347228. [145] Bangoura B, Mundt HC, Schmschke R, Westphal B, and Daugschies A. Prevalence of eimeria bovis and eimeria zuernii in german cattle herds and factors inuencing oocyst excretion. Parasitol Res, 8 2011. http://www.ncbi.nlm.nih.gov/pubmed/ 21808979. [146] Honma H, Suyama Y, and Nakai Y. Detection of parasitizing coccidia and determination of host crane species, sex and genotype by faecal dna analysis. Mol Ecol Resour, 7 2011. http://www.ncbi.nlm.nih.gov/pubmed/21791031.
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[147] Bean MG and Bonner TH. Spatial and temporal distribution of the asian sh tapeworm bothriocephalus acheilognathi (cestoda: Bothriocephalidea) in the rio grande (ro bravo del norte). J Aquat Anim Health, 22(3):1829, 9 2010. http: //www.ncbi.nlm.nih.gov/pubmed/21192548. [148] Dezfuli BS, Giari L, Lui A, Lorenzoni M, and Noga EJ. Mast cell responses to ergasilus (copepoda), a gill ectoparasite of sea bream. Fish Shellsh Immunol, 30(45):108794, Apr-May 2011. http://www.ncbi.nlm.nih.gov/pubmed/21316458. [149] Hemaprasanth, Singh R, Raghavendra A, Sridhar N, Raghunath MR, and Eknath AE. Comparative susceptibility of carp ngerlings to lernaea cyprinacea infection. Vet Parasitol, 178(1-2):15662, 5 2011. http://www.ncbi.nlm.nih.gov/pubmed/ 21255932.
Chapter 20 Anthrax
20.1 Introduction
Anthrax is a zoonosis, a pick it up from contaminated soil by either eating or inhaling the spores. Animals which suer a sudden death caused by Anthrax show blood and bloody uids coming out of body orices. Anthrax bacteria which are present in this blood and uids draining into the soil form spores which were proved to be alive after 70 years. Burying infected materials such as carcasses, blood into pits is a menace to further generations as memory of the site goes lost and spores are liberated because of earth work such as construction of roads, new plantations or even installing a new grave. The anthrax bacteria in the carcass of died animals are likely to be killed by the bacteria of putrefaction. The main danger lies therefore on blood and uids draining into soil as due to specic conditions of environment and temperatures sporulation can take place [1].
20.2
History of Anthrax
The Bible as deep source of ancient knowledge of food, veterinary, and human medicine cites at Exodus the Sixth Plague killing livestock and aecting people with black spots. Homer in his Iliad refers to what probably was a plague of Anthrax as a punishment imposed by Apollo. Virgil in his Georgics writes about a disease spreading from animal to human[1] 1491
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20.3
Bacillus anthracis Cohn 1872,177.Al
Anthrax bacteria belong to the Bacillus genus which has only one aerobic form. This form is Bacillus anthracis which causes skin anthrax or if inhaled the serious form of pulmonary anthraxThe spores are ellipsoidal, located in the middle of the vegetative form, without enlarging the original form. After a certain time the vegetative form decays due to autolysis. The spores remain in union with the previous spores through a thin layer. In this manner log chains of spores are formed. This organism was seen hundred years ago in the blood of animals ill with anthrax. Robert Koch 1877 proved it to be the cause of the disease by inoculating pure cultures into susceptible cattle: Characteristics Gram-positive rods with square end shape, tending to form long chains (Bamboo cane like), which is very specic. The germ is not motile. This is important to distinguish it from other sporulating aerobic bacteria. The rods measure 1-1,2 micra in width and 3,5 micra in length. The vegetative form are destroyed by chemical and physical agents but the spores can survive for decades in dust or soil and on other objects. The spores survive 5 minutes boiling and ordinary disinfectants.
20.3.1
Signs of the disease
The rst symptoms of gastrointestinal anthrax are nausea, loss of appetite, bloody diarrhea, and fever, followed by severe stomach pain. One-fourth to more than half of GI anthrax cases lead to death.
20.3.2
Sterilisation and disinfection
The spores are sterile in dry heat of 150o C only after 60 minutes. In humid atmosphere anthrax spores die in 5 to 10 minutes at 100o C . In threads of silk the anthrax spores are sterilised at 121o C in 15 minutes. This has been used to test the function of autoclaves using dried threads of silk or hair which had been inoculated with anthrax spores. Because of the danger of handling such pathogen germ anthrax spores are now substituted by not pathogenic earth bacteria. Disinfection of hands Wash carefully with water and soap. Do not use nail brushes as small damage to the skin may happen permitting anthrax spores to get into deeper layers of the skin. Hands may be disinfected using 0,2% peracetic acid (or 0,5% Wolfasteril 2 X 1 minute. Disinfection is made with 10% formalin for 2 hours. The spores are resistant to 5% solution
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of phenol. Surfaces can be disinfected with 1% peracetic acid (or 2,5% Wolfasteril for 20 minutes) The spores are not formed in living animals or even mankind, but are present in large number in agar culture and in dead organism.
20.4
20.4.1
Culture of Bacillus anthracis

Media
Anthrax bacteria grow well in standard media. For diagnostic blood-agar is often used with little or no hemolysis. The bacilli have capsules in the animal body but are not capsulated in articial culture. Morphology of the colonies On agar plates the colonies are large, white and rough and have "curled hair" edges. Identication of Bacillus anthracis Direct sputum, smears of wounds, stool, from hairs, hides, feedstus,fertilisers, soil or enrichment broth are plated on blood-trimethoprim-agar plates ( Art nr. 1611e Heipha Diagnostika), incubation for 18 to 24 hours at 36+-1o C Morphology of colonies on BTP-Agar Most of Bacillus spp can grow rapidly on this Agar.The selective supplement Trimethoprim/sulfamethoxazol inhibits completely Bacillus subtilis and to a high degree the Bacillus licheniformis is suppressed. The growth of Gram-positive cocci such as Staphylococcus and Enterococcus as well as Enterobactericeae is very reduced. Sheep blood supports the growth. A strong hemolysis is typical for other Bacillus spp. such as Bacillus cereus, Bacillus thuringiensis, Bacillus mycoides. All colonies of Bacillus anthracis present denitely no hemolysis at Blood-TrimethoprimAgar. Bacillus anthracis grows as white, great colonies (2-6 mm in diameter) with characteristic dull surface. Gram-positive rods,spores, smooth ends, no beta-hemolysis, capsules.
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CHAPTER 20. ANTHRAX Table 20.1: Blood-Trimethoprim-Agar
Substance Peptone from casein Peptone from beef Yeast extract NaCl Agar Sheep blood Trimethoprim Sulfamethoxasol pH 7,3 +- 0,2 light-red colour
gram/litre 14,0 g 4,5 g 4,5 g 5,0 g 16,0 g 50 ml 1,6 mg 6,4 mg
Identication on Cereus-Ident-Agar should be made of the suspected colonies:
Table 20.2: Cereus-Ident-Agar
Substance Special peptone Growth supplement Chromogenic selective supplement Agar pH 7,3 +- 0,1 teh medium is clear and light-yellow
gram/litre 21,0 g 17,0 g 2,7 g
The chromogenic substrate X-myoinositol-1-phosphate can be broken by enzymes from Bacillus cereus to the chromophor X-(5-bromo-4-chloro-3-indoxyl) which precipitate in the inside of the colony with the characteristic turquoise colour.
20.4.2
Dierentiation between Bacillus anthracis and Bacillus cereus
The suspected colonies from the Blood-Trimethoprim-agar plate should be transfered to a Cereus-Ident-Agar (Art Nr. 174e Heipha Diagnostika). Bacillus cereus and Bacillus thuringiensis as colonies with up to 4 mm as diameter and turquoise colour. Bacillus anthracis colonies have the same size ( up to 4 mm ) but they are white. Biochemical reactions and PCR should be performed with these colonies.[2]
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20.4.3
Disease
Anthrax disease is found in sheep,cattle and pigs. Before terrorists disseminated spores of anthrax in America infection in human was rare and occurred by handling products or eating meat from infected animals. Today the disease is still common in South and Central America, Southern and Eastern Europe, Asia, Africa and the Caribbean.
20.4.4
Intestinal anthrax
The spores in animal feed, in dust of infected soil with excreta or carcasses of diseased animals are ingested and can cause an intestinal infection. Contaminated food can also bear anthrax bacteria. The disease can turn out to be fatal if not treated.
20.4.5
Skin anthrax
Man can get skin anthrax handling infected animals, their hides, wool, hair and bristles. Diagnosis is done by gram-colouring and culture of exudates or smear.
20.4.6
Pulmonary anthrax
Is acquired by inhaling anthrax spores from wool or hair of diseased animals.The disease can turn out to be fatal if not treated Diagnosis is made from culture of blood. The culture of the sputum is often negative. The source of animal epidemics is animal feed. The source of infections of man is wool, hair or hides. Contaminated bristles of shaving brushes causing facial pustules have been reported. [3] [4] [5] [6]
20.4.7
Revocation of the Lather Brushes Regulation in 1998
[7] All these reported cases of human anthrax infection with hairs and brushes date before 1930. FDA states that no case of cutaneous anthrax in the United States has been associated with lather brushes since 1930, and the continuation of existing requirements is unnecessary to protect the public health. And CDC revoked the Lather Brushes Regulation pertaining to the treatment, sterilization, handling, storage, marking, and inspection of lather brushes. 42 CFR 71.151 on January 11, 1985 (50 FR 1516), in 1998.
20.4.8
Therapy
Beta-lactame, Penicillin and other antibiotics such as Ciprooxacin and Penicillin V Fluorochinolone, Doxycyline and macrolide (erytromicin, spiramycin, josamycin and azalide)
1496 [8].
CHAPTER 20. ANTHRAX
20.5
Pathogenesis of Bacillus anthracis
Death is most likely due to O2 depletion, secondary shock, increased vascular permeability followed by respiratory and cardiac failure. The pathogenesis depends on two virulence factors[9]:
1. Poly-D-glutamic acid capsule 2. tripartite toxin
20.5.1
Poly-D-glutamic acid capsule
is encoded by the plasmid pX02, which can be transferred to a nonencapsulated Bacillus anthracis by transduction resulting in a capsulated phenotype. The capsule is non toxic but protects the bacterium from bactericidal components and from phagocytosis.
20.5.2
Tripartite toxin
is mediated by the temperature sensitive plasmid pX01. The toxin consists of three parts: 82.7 kDa protective antigen (PA) 90.2 kDa lethal factor (LF) 88.9 kDa oedema faktor (OF) -Remark: "Da" stands for Dalton- other ndings of Bradley et al and Andrew Panifer et al published in Nature 2001,414 225-233 give hope to the development of new therapeutics against anthrax and the tumours caused, being interesting for farmers of the regions where anthrax is prevailing.
20.5.3
Host cell invasion strategy of Bacillus antracis discovered
[10] Lethal toxin is a virulence factor of Bacillus anthracis in the pulmonary anthrax form. This disease is fatal when not treated. The host responds with inammatory process of the lung. Raymond and colleagues 2009 found that Bacillus anthracis strain expressing active lethal toxin represses the inammation in part by altering chromatin accessibility of IL-8 promoter to NF-kappaB in epithelial cells. The authors concluded that the epigenetic reprogramming of the lethal toxin is an ecient strategy for host invasion used by Bacillus anthracis.
20.5. PATHOGENESIS OF BACILLUS ANTHRACIS
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20.5.4
Control of animal anthrax
The spread of the disease is being controlled by use of a vaccine of avirulent spores and safe disposal of carcasses. The disease may be imported from other countries by means of hides, leather and wool with origin from anthrax epidemic regions.
20.5.5
Diagnosis
The diagnosis is positive when large gram-positive rods are found in smears of pus from a typical malignant pustule with black edges giving the skin anthrax disease the name of "carbuncle" which means "charcoal". Further cultivation may be necessary, showing characteristic colonies on nutrient agar. Genetic identication follows. In the mid 70th a 48 years old German died of intestinal anthrax after eating meat and sausages from an animal from emergency slaughtering. A sever intestinal disease caused by Anthrax took place in April 1979 in the city Sverdloosk causing 64 human death resulting from tainted meat. In 1994 one case of skin Anthrax was known in Germany. Bacillus anthracis is similar to Bacillus cereus Virulent and avirulent strains can be dierentiated from Bacillus cereus using the API system. [11] Table 20.3: Dierent characteristics of B. anthracis and B. cereus Characteristics Motility Lysis by gama phage String of perl test(10 U ml 1 penicillin G) Growth on Chloralhydrate agar 2-Phenylethanol agar Polymyxin-lysozymeEDTA-thallous acetate agar Phosphatase Degradation of tyrosine B. anthracis + + B. cereus + -
d + -
+ + d d
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CHAPTER 20. ANTHRAX
20.5.6
Security of BioSafety Level 4 laboratories
[12] LeDuc and colleagues report that BioSafety Level 4 (BSL-4) laboratories directors in the United States reviewed in 2008 the current status of biocontainment laboratory operations. Various approaches to strengthen the safety and security of maximum-containment laboratory workers and their environment have been proposed: 1. Having 2 persons physically present within the BSL-4 facility any time that work is being performed (the 2-person rule). This was discarded as being to expensive, challenged its value and considered the risks that would result from a requirement that 2 persons be physically present in the laboratory at all times. 2. Use of surveillance cameras to monitor workers in the BSL-4 facility; and 3) use of radios or other means of communication between workers inside the laboratory and qualied contact persons outside the actual BSL-4 environment. This was found to present the best results, because the video material can be achieved for years and video cameras are already present in these departments, presenting no additional expenses. 3. All BSL-4 laboratories today are equipped with remote-controlled surveillance cameras that can track a person within the maximum-containment laboratory. 4. Use of radios or other means of communication between workers inside the laboratory and qualied contact persons outside the actual BSL-4 environment. All BSL-4 laboratories have telephones, and most BSL-4 facilities in the United States have some form of radio communication available to persons working in the suite.
20.5.7
Personnel screening
According to CDC persons who have gained the right of independent access to maximumcontainment facilities are highly trained professionals who have earned the condence of the laboratory director and are generally well respected and trusted by their colleagues. In addition, all such persons have had satisfactory background investigations and have obtained Department of Justice numbers in compliance with the Centers for Disease Control and Prevention Select Agent Program requirements. Furthermore, several BSL-4 laboratories are enacting some form of enhanced psychological screening and formal periodic monitoring of these persons. US Biosafety Level 4 (BSL-4) maximum-containment laboratories work with biologic war organisms like Anthrax, plague, smallpox, botulism, Viral Hemorrhagic Fevers, tularemie. Although no clinical infections, or major incidents in operation of the physical facilities were publicly known, a serious lack of security of these laboratories is its own personal which can steal powerful bacteria and viruses from their working place to use it as blackmail, avenge or even selling it to terrorists. The anthax terror attacks 2001/2002 were
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caused by a security leak of a government laboratory. [13] [14] Such a lack of security has been crucially demonstrated by Dr. Bruve Ivins working for years at Fort Detrick, Maryland, known for military research and development of infectious pathogens and biological weapons. The anthrax bacteria of this laboratory killed ve people and sickened 17 others. This incidence demonstrates the eminent public threat of keeping, multiplying and potentiating virulence of disease agents for biologic weapons. The anthrax spores used in the 2001/2002 attacks came from a single ask of spores known as Bacillus anthracis RMR-1029 that was created and solely maintained by Dr. Ivins. While working inordinate hours alone at night and on the weekend in the lab where the ask of spores and production equipment were stored. Ivins had a history of mental health problems, including paranoid delusions. The government closed the case after Dr. Ivins committed suicide in 2008. The threat is still existent and it comes from the evil created by the US public paranoia of self defence building up an arsenal of re arms scattered at households all over the country, together with government activities building up biologic chemical and nuclear weapons. The USA must now be protect against itself, so as happened in 2001 with Anthrax bacteria from Fort Detrick.
20.5.8
War reminescence
During the cold war several tons of Anthrax bacteria were stock piled in the city of Sverdlovsk as a weapon. Later on, Mikhail Gorbachev decided the Anthrax should be destroyed. The whole stockpile was bleached and poured into the ground of Vosrozhdeniya (Renaissance) island in the Aral Sea. Tests of soil samples from six of 11 vast burial pits show that some of the spores were still alive in 1999. The spores are highly resistant to inactivation and may be present in soil for decades. They may infect animals that ingest the spores while grazing. Uzbek and Kazakh experts fear the buried anthrax spores could escape their sandy tomb, stirred up by carriers like gophers and other rodents, lizards and birds, and be brought to Uzbek and Kazak territory. Central Asian and U.S. ocials fear that, as access to the island eases, the buried anthrax could be used by terrorists to make more of the deadly agent. [15] The Pentagon sent a team of 113 people to the island to neutralize between 100 and 200 tons of anthrax in 2002. [16]
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CHAPTER 20. ANTHRAX
20.5.9
Cities Readiness Initiative CRI-compliant mass prophylaxis campaigns not ecient in case of a large scale anthrax attack
[17] Hupert and colleagues 2009 in a study on the a large-scale anthrax attack on a large city found that such an attack would overwhelm hospital resources even with an extremely eective public health response. The authors found that such a breakdown of the health service would result primarily of expected delays in detecting the attack and initiating a response to it varying from 2.4% to 6.5% of the population which would need hospitalisation, depending on how many days the campaign would be delayed to start. The authors concluded that Cities Readiness Initiative CRI-compliant mass prophylaxis campaigns may not cope with aerosol anthrax releases in major cities. They urge for more attention on such subject. Baccam and Boechler in a study of came to the conclusion that all protective measures and medical assistance activities are inuenced by a rapid and eective post-attack activity. Uncertainty in medical ecacy and the time to initiate a post-exposure prophylaxis campaign were found to have the greatest impact on the number of predicted deaths. [18]
20.5.10
Lysozyme to increase food safety
[19] Lysozymes are enzymes which can hydrolyse peptidoglycan, the major bacterial cell wall polymer. These enzymes damage the bacterial cell walls. Lysozyme is abundant in a number of secretions, such as tears, saliva, human milk, and mucus. It is also present in cytoplasmic granules of the polymorphonuclear neutrophils (PMN). Large amounts of lysozyme can be found in egg white, protecting developing chick from infections. Dr. Saeed A. Khan and his colleagues 2010 found that the lysozyme in egg white was very eective in killing anthrax spores. Lysozyme also showed some activity in killing spores added to ground beef and milk. According to the authors lysozumes could be used to increase food safety using this potential to eliminate anthrax producing bacteria in processed foods, such as ground beef, milk, fruit juices, and vegetables. Three major distinct lysozyme types have been identied: the c-type (chicken or conventional type), the g-type (goose-type) and the i-type (invertebrate type) lysozyme. Lysozyme function as an antibacterial defence. Some lysozymes act as digestive enzymes. [20]
BIBLIOGRAPHY
1501
20.5.11
Anthrax on ground beef
[21] Bacillus anthracis is an atypical food-borne pathogen with a high level of interest as a threat agent. This bacterium has been used in acts of terrorism by an American employee of a US military laboratory in 2001. Following this incidence, anthrax is being considered to be a potential agent of bioterrorism and biowarfare against civilian populations. Tamplin and colleagues 2008 analysed the fate of Bacillus anthracis spores on ground beef. They found that spores on ground beef would not be expected to reproduce but to slowly die o under the typical lower storage temperatures (5 to 100 C ) in commercial and home settings. Numerous spoilage bacteria found in ground beef increase the weak eect of storage temperature and cooking causes decisive reduction in anthrax spore and vegetative-cell.
20.5.12
Anthrax cases in Bangladesh in 2010
[22] The government of Bangladesh reported that 585 people contracted anthrax infection since late August 2010. Infection occurs while touching infected animals or animal products, such as blood, meat or skin of an infected animal. Cattle can be infected ingesting or inhaling the bacterium during grazing. The victims fell sick after eating beef from anthrax-aected cattle, however, it does not spread from human to human. Cutaneous infections cause fever, severe pain and swollen tissues, often with lesions. The disease may be fatal, however, none of the actual cases in Bangladesh were seriously ill, but its rapid spreading is of concern. The government of Bangladesh coordinates all measures of anthrax prevention, treatment and control. Livestocks are controlled for sick cows which are culled immediately, Cattle is being vaccinated to avoid further spread of the disease. Anthrax is a bacterium which lives in the soil. It may be brought up to the surface by the water of heavy rain like the monsoon.
Bibliography
[1] Guillemin,Jeane: The Investigation of a Deadly Outbreak. [2] Nhrmedien fr die Mikrobiologische Untersuchung von Bacillus anthracis; Bolletin of Heipha Diagnostika 2001. [3] http://www.cdc.gov/ncidod/EID/vol9no12/02-0718_03-0019_03-0758.htm# 0758. Jernigan JA, Stephens DS. Industry-related outbreak of human anthrax, Massachusetts, 1868 (reply to Macher). Emerg Infect Dis 2003 Dec. [4] Severn AGM. Anthrax septicemia-a fatal case. Lancet 1942;1:9-10.
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CHAPTER 20. ANTHRAX
[5] Gilmour CH, Campbell AR. Anthrax in man with a report of two cases. Can Med Assoc J 1918;8:97-107. [6] http://www.cdc.gov/ncidod/EID/vol8no10/01-0509.htm. Macher A. An industryrelated outbreak of human anthrax: Massachusetts, 1868. Emerg Infect Dis 2002;8:1182. [7] http://www.epa.gov/fedrgstr/EPA-GENERAL/1997/October/Day-20/g27694.htm. Food and Drug Administration: 21 CFR Part 1240 (Docket No. 97N-0418) Revocation of Lather Brushes Regulation 1997 Volume 62, Number 202. [8] Waizmann, Michael; Grnwald, Thomas: Milzbrand (Anthrax)- neue Aspekte einer lten Krankheit; GIT Labor-Fachzeitschrift 12/2001 Pg.1272. [9] Anthrax Researche Update - new ndings oer hope; Bio Tech International November/December 2001 Pg 12. [10] http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal. ppat.1000359. Raymond, B.; Batsche, E.; Boutillon, F.; Wu, Y.Z.; Leduc, D.; Balloy, V.; Raoust, E.; Muchardt, C.; Goossens, P.L.; Touqui, L.: Anthrax lethal toxin impairs IL-8 expression in epithelial cells through inhibition of histone H3 modication. PLoS Pathog. 2009 Apr;5(4):e1000359. Epub 2009 Apr 3. [11] Bergeys Manual of Systematic Bacteriology Volume 2 , pg 1131. [12] http://www.cdc.gov/eid/content/15/7/e1.htm. LeDuc JW, Anderson K, Bloom ME, Carrion R Jr, Feldmann H, Fitch JP, et al. Potential impact of a 2-person security rule on BioSafety Level 4 laboratory workers. Emerg Infect Dis. Volume 15, Number 7-July 2009. Doi: 10.3201/eid1507.081523. [13] http://www.pbs.org/newshour/bb/terrorism/july-dec08/bioterrorprep_ 08-07.html. Years After Anthrax Attacks, Bioterrorism Threat Still Looms. Trnascript August 7. 2008. [14] http://www.pbs.org/newshour/updates/law/july-dec08/anthrax_08-06.html. Justice Department, Unsealed Papers Outline Anthrax Case Against Dead Scientist. Auguist 6. 2008. [15] http://phaster.com/unpretentious/uzbekistan_anthrax.html. Miller, Judith: Cold war leaves a deadly anthrax legacy; New York Times News Service, June 2, 1999. [16] http://en.wikipedia.org/wiki/Vozrozhdeniya_Island. Wikipedia, the free encyclopedia: Vozrozhdeniya Island.
BIBLIOGRAPHY
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[17] http://www.ncbi.nlm.nih.gov/pubmed/19617582. Hupert N, Wattson D, Cuomo J, Hollingsworth E, Neukermans K, Xiong W.: Predicting Hospital Surge after a LargeScale Anthrax Attack: A Model-Based Analysis of CDCs Cities Readiness Initiative Prophylaxis Recommendations. Med Decis Making. 2009 Jul-Aug;29(4):424-37. Epub 2009 Jul 17. [18] http://www.ncbi.nlm.nih.gov/pubmed/17437349. Baccam, P,; Boechler, M.: Public health response to an anthrax attack: an evaluation of vaccination policy options. Biosecur Bioterror. 2007 Mar;5(1):26-34. [19] http://portal.acs.org/portal/PublicWebSite/pressroom/newsreleases/ CNBP_025398. Toward safer foods for human consumption with anthrax protection. American Chemical Society. 26.08.2010. [20] http://www.ias.ac.in/jbiosci/mar2010/127.pdf. Callewaert L, Michiels CW: Lysozymes in the animal kingdom. J Biosci. 2010 Mar;35(1):127-60. Review. [21] http://aem.asm.org/cgi/content/full/74/4/1111. Tamplin ML, Phillips R, Stewart TA, Luchansky JB, Kelley LC. Behavior of Bacillus anthracis strains Sterne and Ames K0610 in sterile raw ground beef. Appl Environ Microbiol. 2008 Feb;74(4):1111-6. [22] http://www.bbc.co.uk/news/world-south-asia-11183617. Anthrax outbreak hits Bangladesh. BBC News. 03.09.2010.
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CHAPTER 20. ANTHRAX
Chapter 21 Foot and Mouth Disease

The foot and mouth disease is widespread. It is an infection of cloven hooved animals and is highly infectious. The pathogenic agent is a picornavirus known as FMD-virus. It is a RNA-virus with 7 serotypes ( A, O, C, SAT 1, 2, 3, Asia 1 and about 50 subtypes, 20 - 25 nm and is very resistant. The food and mouth disease virus is sensitive to environmental inuences such as pH less than 5, sunlight and desiccation. It can survive at freezing temperatures.
21.0.13
Infection with foot and mouth disease
The infection with foot and mouth disease occurs by direct contact with animals having the disease, or by contact with infected utensils, infected animal feed. The routes of spread of the virus are the contact with infected animals, by people exposed to the virus who develop no symptoms or just skin lesions, but who harbour and spread the FMD virus. Other routes are shoes, clothing, vehicles, meat, milk and garbage and air contaminated with virus
21.0.14
Symptoms of the disease
Fever,refusal of fodder, ow of saliva and characteristic bubbles (aphthous ulcers) in the region of the mouth, teats and claws. Pigs have bubbles at the claws with paralysis symptoms. The disease in humans is rare and of mild symptoms.
21.0.15
Specic medication
There is no specic medication available. Due to vaccination the number of new cases can be reduced considerably. 1505
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CHAPTER 21. FOOT AND MOUTH DISEASE
21.0.16
Spread of foot and mouth disease in South America
The International Epizootias Oce accepted that most of the Center West of Brazil was foot and mouth disease free, with vaccination. The State of Rio Grande do Sul and Santa Catarina had been free of the disease for almost ten years. Vaccination had been therefore stopped. In August 2000 the disease was found to explode again in Rio Grande do Sul. About 10.000 head of cattle, cheep and pigs had to be killed. It is seems that illegally imported breed stock from Argentina or Paraguay was the cause. Brazilian failing to control the spread of the disease is due to insucient supervision by veterinary ocials and vaccination was not made properly. Argentina and Uruguay are concerned with the possibility the disease spreading from Rio Grande do Sul to their countries.
21.0.17
New Outbreak of FMD in Brazilian cattle
Outbreak of FMD in Brazilians state of Mato Grosso do Sul in November 2005 is due to Brazilian cattle rangers who smuggle unvaccinated animals in from neighgboring Paraguay to increase their herds at lower prices. Cattle is about 30 per cent cheaper in Paraguay than in Brazil.(Animal Health Department of Mato Grosso do Sul)
21.0.18
Geography of foot and mouth disease
The Brazilian State of Rio Grande do Sul, Paraguay and Bolivia are strongly aected by the disease. Considered as free from foot and mouth disease are North America, Central America (North of Panama, Australia, New Zeeland and Scandinavia. The new outbreak of FMD menaces Great Britain Netherlands and all eorts are made to avoid it from spreading all over the European Country The last case of the disease was detected in 1929 in California. In Canada the last case was found in 1952. United States and Japan refuses to import fresh beef from Brazil as long as the disease is not under control. In 2004 foot and mouth disease entered Japan with straw imported from China. FMD had not been seen in Japan since 1980. An outbreak of MD in South Africa was caused by garbage which had been picked up by a farmer from a tramp steamer anchored oshore. He fed the garbage to his pigs a deleting epidemic started. The outbreak in Great Britain is thought to have started is a similar way. Hamburger use lower quality beef imported from developing countries. Australia is notable to send more meat in this quality to USA. The price of beef in Brazil is among the lowest of the world. Everything is done to reduce costs of irrigation, improving pastures,
1507 fertiliser and irrigation. Advisors say that herds should be moved from the south to the center and north of Brazil. This includes the states of Mato Grosso, a Rondonia and Par.
21.0.19
Foot and Mouth Disease 2001 in England
The disaster which has hit European meat market beginning with BSE which started in England has been boosted by the FMD. Spreading all over the island it was menacing to get to the European countries because of commerce between England and the continent. Dust carried by wind can spread the picornavirus as far as 100 kilometers infecting pastures and animals. One of the reasons of the spread of the disease is concentration of business. In England 1000 local abattoirs were concentrated in past years down to 340 mighty factories making transportation of cattle and living animals necessary over hundred of miles. Measures to control the epidemic such as disinfectants for the shoes and tires of Queen Mom are nice for news but they do not hit the primary cause of the disease. Tourism in England has been reduced as the possibility of carrying the virus particles in cloth and shoes entering thus the continent is eminent. The trac of car and transportation of all kind of goods between the island and the continent cannot be stopped. Air travel is another way to spread the disease. Organic food such as being done in the English Highgrove on the Farm of Prince Charles seems to be the way to ght back modern epidemic animal diseases. It includes however that a local economy should be sponsored. Global business spreads diseases, destroys environment and global climate.
21.0.20
Foot-and-mouth disease outbreak in 2007, Surrey, England
[1] Cattle on a farm outside Wanborough, 30 miles southwest of London, tested positive for Foot-and mouth disease. The virus aects cloven-hoofed animals including cows, sheep, pigs and goats. It does not aect humans. All livestock at the farm and nearby were slaughtered on the 4.08.2007. Biosafety experts scoured a rural laboratory of Merial Animal Health searching for the possible source of the outbreak of the disease. Few days before several sheep had been exported from Britain to a German Farm which is now being isolated by German veterinaries. [2] Merial Animal Health is a world-leading animal health company producing pharmaceutical products and vaccines for livestock, pets and wildlife. [3]
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The virus of the outbreak is unusual in wildlife but is identical with the virus used by Merial Animal Health. The vaccine manufacturing site of Merial may be the source of the epidemic. It is situated only four miles from the aected farm. The last foot-and-mouth disease epidemic in England occurred in 2001.
21.0.21
UKs Foot and Mouth Status
[4] Foot and Mouth (FMD) has been conrmed in domestic cattle. This means that the United Kingdom (UK) has lost its ocial "country freedom" status for this disease. This criteria is set by OIE, the International Health Organisation, which is recognised by the world community.
21.0.22
Intra-Community Trade
You cannot export susceptible live animals to EU member states because there is a prohibition on the movement of susceptible live animals within GB. Meat and other animal products (including genetic material, dairy products, petfoods, hides/skins etc) from susceptible species should not be exported to EU member states. The exact details will be included in new a EU Decision expected on Monday.
21.0.23
Third Country Exports
You cannot export any susceptible animals or their products (including genetic material, dairy products, petfoods, hides/skins etc) to third countries because we have suspended all relevant export health certicates. Animal Health are recalling export health certicates issued for consignments which have not yet been exported.
21.0.24
Infection way
Pigs are infected by ingesting infected food and waste. Cattle is infected by inhalation of respiratory aerosols emitted from pigs which excrete large amounts of virus by this way. Wind is able to carry this aerosol over long distances. People can be infected through skin, wounds or oral mucosa working in a stable or getting infected through milk.
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21.0.25
Incubation
Incubation: 2 to 21 days as average 3 to 8 Days. Infection morbidity period: 100% Mortality:5% of adults and 75% sucking pigs and sheep. Cattle which recovers from the disease may be carrier for 18 to 24 month. Sheep can be carrier for 1 to 2 month. Pigs are not carrier.
21.0.26
Clinical signs of foot and mouth disease
Animals: Salivation,depression, anorexia and lameness caused by the presence of painful vesicles ( blisters ) in the skin of the lips, tongue gums, nostrils, coronary bands, interdigital spaces and teats, Fever and decreased milk production. In pigs the signs are the same but milder, Lameness is predominant. People:Exanthemas on ngertips and interdigital spaces, fever and miocarditis.
21.0.27
Foot and mouth disease in England
Foot and mouth disease is spreading in England in February 2001. As infection is very easy and many living animals were exported to the continent it is likely that the disease has crossed the channel and entered the continent. Every eort should be undertaken to reduce transportation of animals, reduce tourism (the virus can be carried as dust on clothes and foods used during journeys and air trac). Farmers should look for correct disinfection facilities. Visitors should not allowed to get to the Farm. This includes the mailman as a vector from farm to farm. Mail should be deposited centralised somewere away from the farm. When casual visitors must get into the stables it should be done after careful disinfection of shoes and the use of plastic overalls.
21.0.28
Food-and-mouth Disease serotypes A and O spread to Japan and South Korea citeKnowles JapSkor12
Knowles et al. 2012 report that foot-and-mouth disease (FMD) outbreaks recently aected Japan and South Kore in eastern Asia that were free of FM. The serotype A and O viruses caused these outbreaks.The origin of the viruses was the mainland Southeast Asia. The FMD virus (FMDV), is a small, nonenveloped, picornavirus (genus Aphthovirus) that has 7 serotypes. FMDV serotypes O, A, and Asia 1 are endemic to countries in mainland Southeast Asia, namely Cambodia, Laos, peninsula Malaysia, Myanmar, Thailand, and Vietnam. The FMDV O/SEA topotype (Mya-98) was also detected in China in 2003 and in Mongolia in 2004. This virus is easily transmitted by movement of infected livestock or animal products,
1510
contaminated persons, objects, and aerosols. It aects domesticated animals and wildlife in Africa, Asia and parts of South America. Outbreaks of FMD in these disease-endemic regions continuously threaten livestock industries in countries that are free of FMD. The authors point to the porous nature of borders between mainland Southeast Asia and neighboring. This provides a continuous threat as a transboundary disease in the region. Currently available vaccine strains A/May/97and O/Manisa should protect against representative isolates of serotypes A and O. Additionaly close monitoring of antigenicity and spread from Southeast Asia is essential to reduce the risk of other distant outbreaks can be reduced.
21.1
New strain of Asia 1 FMD of Central Asia and China
[5] All eorts are being done to avoid the new emerging strain of Asia 1 FMD foot and mouth disease from Central Asia and China to enter the EU.
21.1.1
Risk of international spread.
[6] The reservoir of FMDV type Asia-1 is generally considered to be in south Asia, particularly India and Pakistan, countries with very high bovine and bualo population densities. This virus type has often been associated with epidemic spread out of these reservoir animal populations into west Asia as far as Turkey, and even in 2000 to Greece, but eastwards spread to involve dispersed, possibly widespread outbreaks on Chinese mainland appears to be a new and worrying development. The development in China appears to be the consequence of a failure of the disease reporting system in a number of countries, mostly in central Asia, resulting in country to country spread, and it would appear, spread from western China to eastern China in 2005. The currently available information is limited. Each country needs to conduct their own risk analysis. However the distribution of the reports suggest an increased incidence of infection and this may contribute to increased risk through the pathway of animal products, live animals or other routes (such as contamination of fodder).
21.1.2
Risk to Europe
The last major FMD outbreak in Europe started in the UK in 2001 and spread to several other member states before it was eradicated. Assessing the risk to Europe of the reintroduction of FMD in the European Union, the
21.1. NEW STRAIN OF ASIA 1 FMD OF CENTRAL ASIA AND CHINA
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EFSA came to the conclusion that most of the factors and circumstances which aected the introduction and spread of the disease in Europe from 1991 to 2001 have not changed. There are no indications that the risks could be expected to decrease. Therefore, many of the historical observations on in remain relevant for the future. Imports of live animals originating from the Middle East represent a threat to the EU primarily, but not exclusively, to south-eastern Europe. Illegal importation of infected meat and meat products and possibly legal importation of other animal products such as casings (derived from intestines) from South-East Asia & China and South Asia are a threat that is more evenly spread throughout the EU. It is by reducing the global weight of infection that the EU and other FMD-free areas of the world can achieve a sustainable reduction in their own risk. Past FMD virus introductions into Europe were via imports from South America (meat) and south eastern Europe (live animals), a strategy for risk reduction has been implemented for imports from these areas. These have included a strategy for reduction in the prevalence of FMD in these areas. However, these areas remain at risk to (re-)infection. A sustainable FMD risk reduction strategy for the protection of Europe will need to address not only the targeted and progressive control of FMD in the high risk primary endemic epidemiological clusters of South-East Asia & China (Indo-China) and South Asia, which currently represent the biggest threat to Europe, but also in eastern Africa and the Sahel. Global progressive control of FMD is a protracted process which is anticipated to require 20-30 years. Therefore, FMD control in endemic areas supplements rather than replaces the current EU strategy. In the context of increasing globalisation with increasing imports of animals and animal products into the EU, not to mention the expansion of the borders of the EU itself, the risk from both legal and illegal activities is likely to increase. The only feasible way of reducing the prevalence of, or eradicating, FMD in endemic areas is through a three-pronged approach comprising the following:
Regional control programmes with a package of interventions and whereby the regions are dened on the basis of their epidemiological characteristics. A global surveillance partnership for FMD to reduce risk in all regions. parallel strategy for promoting the safe trading of livestock commodities through formal channels and in promotion of policies and international standards which provide alternatives to reduce illegal shipments.
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Increasing international travel from endemic areas is increasing the number of illegal imports of meat and meat products in passengers luggage.
21.1.3
Specic recommendations for reduction of the risk of virus import
Enforcement in the exporting third countries of pre-export treatments for animal products other than meat merits verication. It may be worthwhile to examine whether the EU could share some of the burden of verifying compliance with other importing countries. Veterinary checks at the borders should be enforced with: More use of targeted resources i.e. snier dogs and scanners. Tighter control of suppliers of food to ships and better recording and co-ordination of catering waste disposal. Controls on travelers at the points of entry are still weak in most of countries in Europe. Signicant quantities of meat and meat products are introduced illegally into Europe in the luggage of travelers. Commercial heat treatment: The presentation of an international veterinary certicate attesting that the manufacturing method for these products included heating to a minimum internal temperature of 70o C for at least 30 minutes for importing foods from countries where MFD is present. [7] Other routes of introduction of FMD virus are: Aerial introduction Bioterrorism Import of inadequately inactivated vaccines. The EU should encourage and support countries that are still vaccinating against FMD to use vaccines that meet international (EP, OIE, VICH) quality and safety standards. These countries should only allow FMD vaccine production in plants fully complying with all international bio-safety rules. The ecacy and safety of the nal product should be controlled independently. [5] Virus escape from laboratories. The 2004 Edition of the OIE Manual of Diagnostic Tests and Vaccines for Terrestrial Animals indicates that FMDV for diagnostic (and vaccine production) purposes should be handled under P3 biocontainment facilities. According to EFSA the biosecurity standards for laboratories in countries where FMD is still endemic often meet the lower P2 standard. From the perspective of risk analysis, the objective for FMD vaccine production laboratories should be for them to be at P3 containment level. However, it should be acceptable for diagnostic laboratories to target P2 in endemic
21.1. NEW STRAIN OF ASIA 1 FMD OF CENTRAL ASIA AND CHINA
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countries, as has been the practice in South America. It is more important to facilitate diagnosis across a wide area of FMD endemic regions than to impede it through unrealistic and unnecessary high containment demands. [5] [8]
21.1.4
Human infections
Human infections include the handling of animals and inhalation of airborne viral particles, but probably the most frequent routes of infection has been ingestion of unpasteurized milk, cheese and other dairy products. The disease in humans are usually of a mild nature. After an incubation period of 2-4 days, suerers start experiencing symptoms such as fever, headaches, shivering and thirst. Later, itchiness, pharyngitis, tonsillitis and, rarely, gastro-enteritis precede the appearance of crops of painful blisters on the suerers hands and between their toes. Blisters can also form on the lips and inside the mouth, causing extensive ulceration and marked discomfort. Skin peeling of the palms and soles of feet is also known to occur. Recovery is usually complete within 2 weeks.
21.1.5
An EFSA subset of relevant legislative references
Commission Decision 2004/438/EC of 29 April 2004 laying down animal and public health and veterinary certications conditions for introduction in the Community of heat-treated milk, milkbased products and raw milk intended for human consumption (OJ No. L 154, 30.04.2004, p. 72) Commission Decision 94/360/EC of 20 May 1994 on the reduced frequency of physical checks of consignments of certain products to be implemented from third countries, under Council Directive 90/675/EEC (OJ L 158, 25.6.1994, p. 41). Commission Decision 2003/779/EC of 31 October 2003 laying down animal health requirements and the veterinary certication for the import of animal casings from third countries (OJ L 285, 1.11.2003, Commission Decision 2005/432/EC of 3 June 2005 laying down the animal and public health conditions and model certicates for imports of meat products for human consumption from third countries and repealing Decisions 97/41/EC, 97/221/EC and 97/222/EC (OJ L 151, 14.6.2005, p. 3). Commission Regulation 745/2004 of 16 April 2004 laying down measures with regard to imports of products of animal origin for personal consumption (OJ L 122, 26.4.2004, p. 1) Council Decision 79/542/EEC of 21 December 1976 drawing up a list of third countries or parts of third countries, and laying down animal and public health and veterinary certication conditions, for importation into the Community of certain live animals and their fresh meat (OJ L 146, 14.6.1979 p. 15)
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Council Directive 92/118/EEC of 17 December 1992 laying down animal health and public health requirements governing trade in and imports into the Community of products not subject to the said requirements laid down in specic Community rules referred to in Annex A (I) to Directive 89/662/EEC and, as regards pathogens, to Directive 90/425/EEC (OJ L 62, 15.3.93. p.49). Council Directive 2002/99/EC of 16 December 2002 laying down the animal health rules governing the production, processing, distribution and introduction of products of animal origin for human consumption (OJ L 18, 23.1.2003, p. 11) ANNEX I of (EC) No 853/2004 Regulation of the European Parliament and of the Council of 29 April 2004 laying down specic hygiene rules for on the hygiene of foodstus (OJ L 139, 30.4.2004, p. 55).
Bibliography
[1] http://www.cnbc.com/id/20134004. CNBC: Health Experts Search UK Lab for FootAnd-Mouth Disease. [2] http://www.spiegel.de/wissenschaft/mensch/0,1518,498243,00.html. Online 05.08.2007: Britische Viehzchter emprt ber verdchtiges Labor. Spiegel
[3] http://www.merial.com/our_company/index.asp. Merial, a world-leading animal health company. [4] http://www.defra.gov.uk/animalh/int-trde/cins/2007/07200.htm. Defra, UK: Animal Health and welfare. [5] http://www.efsa.eu.int/science/ahaw/ahaw_opinions/1357/ahaw_op_ej313_ fmd_summary_en2.pdf. EFSA: Opinion of the Scientic Panel on Animal Health and Welfare on request from the European Commission related to: Assessing the risk of Foot and Mouth Disease introduction into the EU from developing countries, Assessing the reduction of this risk through interventions in developing countries / regions aiming at controlling / eradicating the disease, and Tools for the control of a Foot and Mouth Disease outbreak: update on diagnostics and vaccines (Question Nr EFSA-Q-2004-113) Adopted 5 February 2006. [6] http://www.fao.org/docs/eims/upload//191450/FMD_China_EMPRES.pdf. EMPRES WATCH: Special disease analysis report Issue: Foot-and-mouth disease type Asia-1 in China Information compiled by EMPRES working with the EUFMD Commission Secretariat, FAO. [7] http://www.oie.int/eng/normes/Mcode/en_sommaire.htm. OIE: Terrestrial Animal Health Code - 2005; Foot and Mouth Disease Article 2.2.10.26.
BIBLIOGRAPHY
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[8] http://www.oie.int/Eng/Normes/Mmanual/A_00016.htm. OIE: Diagnostic Tests and Vaccines for Terrestrial Animals; Human Safety in the Veterinary Microbiology Laboratory. Chapter I.1.6 2004.
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Chapter 22 Livestock Diseases

22.0.6 Infectious diseases of livestock
Disease management of livestock include biosecurity measures, such as controlling animal mixing, controlling entry to farm lots and the use of protective clothing, and quarantining sick animals. Diseases also may be controlled by the use of vaccines and antibiotics. Antibiotics in sub-therapeutic doses may also be used as a growth-promoter such as antibioticlaced feed increased growth by 10-15%, however, it soon leaded to antibiotics resistance of pathogen bacteria. Disease-free areas often impose quarantine and other measures or even import ban of animals from areas with epidemics. Leptospirosis [1] Leptospirosis is caused by a spirochaete bacterium called Leptospira spp. that has at least 5 serovars of importance in the United States and Canada causing disease in dogs (Icterohaemorrhagiae, Canicola, Pomona, Grippotyphosa, and Bratislava). There are over 200 known serovars of Leptospira, however only few are known to cause the "leptospirosis" disease. The pathogenic bacteria are almost entirely within the Leptospira interrogans genomospecies, serogroup Icterohaemorrhagiae. Risk groups are workers in rice elds, sugar cane plantations, mines, sewer systems, and slaughterhouses; animal caretakers and veterinarians; and travelers to tropical parts of the world involved in recreational activities in fresh water. Recreational exposures can include rafting, kayaking, and swimming, in tropical and temperate climates. [2] Leptospirosis is transmitted by the urine of an infected animal and is contagious as long as it is still moist. Although rats, mice and moles are important primary hosts, a wide range of other mammals including dogs, deer, rabbits, hedgehogs, cows, sheep, raccoons, possums, skunks, and certain marine mammals are able to carry and transmit the disease as secondary hosts. The type of habitats most likely to carry infective bacteria are muddy riverbanks, ditches, gullies, and muddy livestock rearing areas where there is regular pas1517
1518 sage of either wild or farm mammals.
CHAPTER 22. LIVESTOCK DISEASES
Humans become infected through contact with water, food, or soil containing urine from these infected animals. Occupations at risk include veterinarians, slaughterhouse workers, farmers, sewer workers, and people working on derelict buildings. Rowers are also sometimes known to contract the disease.
22.0.7
Co-infection of malaria and leptospirosis [3]
Baliga et al. 2011 report the simultaneous infections of malaria and leptospirosis One was a case of infection with Plasmodium falciparum together with Leptospira serovar icterohaemorrhagiae another case was the simultaneous infection with Plasmodium vivax together with Leptospira serovar batavia. The authors propose that febrile cases presenting hepato-renal dysfunction may be caused by a co-infection of malaria and leptospirosis.
22.0.8
Tuberculosis
Milk was a frequent vector of tuberculosis. Only after research of Louis Pasteur introducing the technology of pasteurisation milk turned out to be safe. Bovine TB: Pre-movement testing for all cattle over 42 days old in UK. [4] [5] Defra wants to reduce the risk of the spread of bovine tuberculosis by TB pre-movement tests as well as routine surveillance tests. The tests were extended beginning with the age of 42 days as it was noted that infection is also being picked up earlier in high-risk herds. With this policy the Defra hopes to prevent 610 new incidents a year. Pre-movement testing was introduced in March 2006 in England and May 2006 in Wales. To avoid human tuberculosis adquired from infectuous milk consume only pasteurized milk(heat treated milk). [5] According to FDA [6] more than 300 people in the United States got sick from drinking raw milk or eating cheese made from raw milk in 2001, and nearly 200 became ill from these products in 2002, according to the Centers for Disease Control and Prevention. Some of the diseases that pasteurization can prevent are tuberculosis, diphtheria, polio, salmonellosis, strep throat, scarlet fever, and typhoid fever.
22.0.9
Enzootic bovine leucosis [7]
EBL is a transmissible disease caused by a virus. It can be transmitted both vertically, mother to calf, and horizontally, cow to cow; causing leukaemia and multiple tumours. Only cattle is aected. No transmission to humans are known. Clinical signs are usually apparent in cattle between 4 and 8 years of age and are only rarely seen in animals under
1519 2 years old. In the live animal the disease is characterised by chronic ill health, progressive loss of condition, weakness, anaemia and anorexia, attributable to tumorous inltration of various organs throughout the body, with serological antibody response. Lymphocytosis occurs, however, not always. Serological evidence of EBL is more specic; it may be demonstrated within a few months after infection. Conrmation of the existence of the disease depends upon laboratory detection of the EBL virus. Under natural conditions the disease is transmitted mainly by milk to the calf. Infected lymphocytes transmit the disease too. Bovine immunodeciency virus [8] The bovine immunodeciency virus (BIV) was found to cause wasting syndrome suggesting bovine leucosis. The virus is a lentivirus similar to the human immunodeciency virus (HIV). Bovine leukemia virus (BLV) BLV is a bovine virus closely related to HTLV-1, a human tumour virus. BLV is a retrovirus which integrates a DNA intermediate as a provirus into the DNA of B-lymphocytes of blood and milk. It contains an oncogene coding for a protein called Tax. Council Directive 64/432/EEC as amended on health problems aecting intra-Community trade in bovine animals and swine, and Council Directive 77/391/EEC as amended introducing Community measures for the eradication of brucellosis, tuberculosis and leukosis. All infected cattle and contacts which have been exposed to infection must be slaughtered. No treatment is allowed. New case of enzootic bovine leucosis in Germany [9] According to the OIE immediate notication report 23/12/2010 a case of enzootic bovine leucosis was detected in Germany All cattle for slaughter in Germany are subjected to an ante and post mortem inspection which, in the case of suspicion, includes enzootic bovine leucosis test. Germany still fullls the requirements of freedom from leucosis according to the chapter 11.9.2. of the OIE Terrestrial Animal Health Feline leukaemia The feline leukemia virus (FeLV) is a retrovirus which causes blood cell cancer (leukemia) domestic cats. FeLV can be transmitted between infected cats when the transfer of saliva or nasal secretions is involved. An infected mother cat can transmit the virus to her kittens, either before they are born or while they are nursing. If not defeated by the animals immune system, the virus can be lethal. Overwhelming epidemiologic evidence suggests FeLV is not transmissible to either humans or dogs.
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Feline immunodeciency virus (FIV) [10] Feline immunodeciency virus (FIV) is a lentivirus that aects domestic cats and causes feline AIDS. FIV diers taxonomically from two other feline retroviruses, feline leukemia virus (FeLV) and feline foamy virus (FFV), and is more closely related to human immunodeciency virus HIV. FIV is the only non-primate lentivirus to cause an AIDS-like syndrome.FIV and HIV are both lentiviruses; however, neither can infect the others usual host: humans cannot be infected by FIV nor can cats be infected by HIV. FIV is transmitted primarily through saliva (bites), such as those incurred during territorial battles between males. Canine distemper [11] Is caused by paramyxovirus. It is a single-stranded RNA virus of the family paramyxovirus, and thus a close relative of measles and rinderpest. Human infection Smith 2010 reviewed studies related to human multiple sclerosis (MS) concluded that canine distemper virus (CDV) may be responsible for the causation of multiple sclerosis. However, it is not the only factor in the causal pathway. This implies that CDV may be a necessary factor in the development of MS as could be other infectious agents (bacterial or viral). The authors stresses that an individuals environment, genetics and immune system are other sucient factors crucial in disease causation.
22.0.10
Rinderpest vaccine provide a lesson for the eradication of measles
Rinderpest (cattle plage) is an ancient viral infection of cattle and other large ruminants, It is caused by a member of the genus morbillivirus, of the Paramyxovirus family closely related to human measles virus and canine distemper virus. The disease is characterized by fever, oral erosions, diarrhea, lymphoid necrosis, and high mortality. [12] After the Global Rinderpest Eradication Programme (GREP) of the Food and Agriculture Organization of the United Nations (FAO), the last conrmed case of rinderpest was diagnosed in 2001. On 8 August 2011, the United Nations held a ceremony declaring the disease eradicated, making rinderpest the second disease in history to be fully wiped out, following smallpox. [13] The disease was eectively eradicated by developing a vaccine which could be kept unchilled, solving logistical and nancial problems and delivery to the remote areas of Africa and Asia allowing veterinary personnel to interact directly with aected cattle herders. Vaccinations were accompanied by expansive disease surveillance. Blood samples were collected from herds to determine the extent of immunity. But most important, there was a concerted, well-funded, and unparalleled international response to eradicate rinderpest.
22.1. THE NEW "SCHMALLENBERG VIRUS" AFFECTS EUROPEAN LIVESTOCK (EUROPEAN SHAMONDA-LIKE ORTHOBUNYAVIRUS) 1521 [14] Measles is caused by measles virus (MeV). Also member of the genus Morbillivirus. It is a common infection in children. Measles virus is closely related to rinderpest virus (RPV), which is a pathogen of cattle. MeV evolved in an environment where cattle and humans lived in close proximity and is thought to be mutation of the rinderpest virus. According to Furuse et al. 2010, divergence between MeV and RPV occurred around the 11th to 12th centuries, contrary to previous believes it dated of the prehistoric age. [15]
22.0.11
Parvoviruses
Parvoviruses which causes human and animal diseases are not in the genus Parvovirus, though they are casually called parvoviruses. Parvoviruses are typically linear, nonsegmented single-stranded DNA viruses, with an average genome size of 5000 nucleotides. Parvoviruses are some of the smallest viruses and are 1826 nm in diameter.
22.1
The new "Schmallenberg virus" aects European livestock (European Shamonda-like orthobunyavirus)
A new virus, the "Schmallenberg virus" (SBV) was reported in Autumn 2011 aecting livestoch in Europe. The virus has been found in sheep, cattle and goats and has to date infected animals in Belgium, France, Germany, the Netherlands and the United Kingdom. [16] The "Schmallenberg virus" is a part of the Simbu serogroup of viruses belonging to the Bunyaviridae family, genus Orthobunyavirus. These serogroup viruses have mostly been found in ruminants in Asia, Australia, Africa and the Middle East. The Friedrich-Loeer-Institut (FLI) reported on 21 Nov 2011 data of genetic material of an unknown pathogen by means of metagenomic analysis. First comparative investigations indicate that the pathogen is a virus of the genus Orthobunyavirus, which is related with the group of Akabane-like viruses. [17] Similarly to the bluetongue disease virus, these pathogens are mainly transmitted by biting midges. The virus belongs to the Simbu serogroup (Shamonda, Aina, Akabane viruses). The S segment of Schmallenbergs genome is most closely related to sequences of a dierent orthobunyavirus called Shamonda virus. The virus could be isolated, cultivated and replicated and named "Schmallenberg virus". It is still unclear whether this exotic virus has been newly introduced or whether orthobunyaviruses already have been present in ruminants in Europe for some time. Therefore, further investigations are necessary to assess this virus detection.
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In absence of specic data on the new "Schmallenberg virus", analogy was made with knowledge on Akabane virus, another representative of the of the Simbu serogroup. The Akabane virus has previously been reported in cattle in Turkey. It is supposed that the Schmallenberg virus is being transmitted by midges and mosquitoes. However, the possibility of direct animal-to-animal transmission cannot be excluded. The virus causes fever, diarrhoea and reduced milk production for up to a week. If infection occurs in pregnant animals during a short, vulnerable stage of the pregnancy it can result in severe birth defects of the ospring. There is currently no evidence that the virus could cause illness in humans. As the genetically most related viruses do not cause disease in humans, it is unlikely that this new virus will cause disease in humans but it cannot be excluded at this stage. It is known that the pathogenic eects of infection with Akabane virus are only seen when the virus exceeds the geographical boundaries of the endemic area and infects susceptible animals in early stage of pregnancy. Such a situation is likely to occur at the edges of an endemic area and may be due to the movement of either infected hosts or infected vectors. The EFSA developed dierent scenarios based on the hypothesis that the transmission mode and the vectors transmitting the virus are similar to that of Bluetongue virus (BTV8) model to assess under which conditions SBV could spread into susceptible populations. The number of vectors and the temperature have an impact on the possible spread of the virus. However, it is unknown how likely animals are to become immune. EFSA proposes a coordinated data collection in all Member States related to Schmallenberg virus. Bluetongue is a non-contagious infection transmitted by midge insects aecting domestic and wild ruminants including sheep, goats and deer. [18] In Germany animals from 506 holdings have been tested positiv for "Schmallenberg virus" so far. The cases occurred in 15 cattle holdings, 470 sheep holdings and 21 goat holdings. [19] FLI developed a detection method and provides reagents, materials and sequence informations to institutions on request. [20] Dutch experts expect that the Dutch calves were infected in August / September 2011, and that therefore that the peak of calves infected with the virus will be born during March / April this year. The major negative eect on the production of the virus is the cause of abnormalities of the born animals.
22.1.1
Russia banned import [21]
The Russian Government banned the import of sheep and goats, including related products from Germany and the Netherlands. Mexico banned imports of sperm and embryos of
22.1. THE NEW "SCHMALLENBERG VIRUS" AFFECTS EUROPEAN LIVESTOCK (EUROPEAN SHAMONDA-LIKE ORTHOBUNYAVIRUS) 1523 sheep, goats and cattle from the Netherlands. A Russian ban on the import of live cattle, mostly heifers, would have signicant trade implications. Another important trade ow is the export of beef from Germany to Russia.
22.1.2
Recommendations of the Friedrich-Loeer-Institute related to Schmallenberg virus [22]
Control: The Friedrich-Loeer-Institute recommends for the forthcoming season, the protection of susceptible animals from biting midges/mosquitoes will be the only possibility to reduce the number of cases. A vaccine is not available. Recommendations for animal holders and veterinarians: If symptoms occurr (drop in milk yield, fever and diarrhoea) in cattle during insect activity, suitable samples should be sent to responsible diagnostic agencies for detection of a possible infection with "Schmallenber virus." The same applies for clinically suspicious newborns.
22.1.3
Risk assessment.of the European Center for Disease Prevention and Control regarding the Schmallenberg virus [23]
Previously, genetically similar orthobunyaviruses have not caused disease in humans. It is therefore unlikely that this virus will cause disease in humans, but it cannot be excluded at this stage. Close collaboration between animal and human health services is necessary to ensure rapid detection of any change in the epidemiology of animals and humans. In particular, the health of farmers and veterinarians in close contact with potentially infected animals should be carefully monitored.
22.1.4
The Schmallenberg virus epidemic in Europe [24]
The German Friedrich-Loeer-Institut discovered the Schmallenberg virus which caused an undetermined disease in animals in late 2011. Sheep, cattle and goats presented fever, decreased milk production, and diarrhoea, malformed newborn animals and stillborn calves, goats an lambs. A study leaded by Martin Beer used metagenomic analysis to identify the novel orthobunyavirus. The epidemic spread from Germany to the Netherlands, Belgium, Great Britain, France, Italy, Luxembourg and Spain . The Schmallenberg virus is part of the Simbu serogroup of the Bunyaviridae family, genus Orthobunyavirus. Viruses of this group are mostly found in ruminants in Asia, Oceania, Australia, Africa and the Middle East ( Israel). Especially the Simbu serogroup, which includes Akabane, Aino, and Shamonda viruses, can play a role as pathogens of ruminants. They are mainly transmitted by mosquitoes (Culicidae) or midges (Culicoides). Direct
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transmission from animal to animal has not been demonstrated except trans-placental from a viremic dam to the foetus. Metagenomic approach to identify the Schmallenberg virus A newly developed real-time quantitative reverse transcription PCR (RT-qPCR) demonstrated the power of a metagenomic approach to discovering emerging pathogens. Specic and sensitive RT-qPCRs could be developed quickly and used in analysing infected herds. Abdominal uid was PCR positive for the novel virus, with a Ct value of 27. Beer et al. note that some members of the Simbu serogroup, such as the Oropouche virus, are zoonotic. The Schmallenberg virus, however, presents a very low to negligible risk to humans, because of the close relationship to Shamonda virus and the absence of reports of clinical signs in humans,. Nevertheless, clinical and serologic surveillance in humans should be conducted in regions with infected animals to update the risk assessments. The Schmalleng virus in The Netherlands [25] Muskens et al 2012 reported that Dutch dairy herds presented sudden decreased milk production, watery diarrhea and sometimes fever. Bacteriological, virological and parasitological testing of the faeces of sick cows did not reveal an infectious cause of the clinical problems, but 36% tested positiv for Schmallenberg virus. This suggests that the Schmallenberg virus was the primary cause of the disease. Congenital malformation in lamb caused by Schmallenberg virus [26] Epizootic outbreaks of congenital malformations in sheep was reported in The Netherlands by van den Brom et al. 2012. The main deformations included arthrogryposis, torticollis, scoliosis and kyphosis, brachygnathia inferior, and mild-to-marked hypoplasia of the cerebrum, cerebellum and spinal cord. Nutritional deciencies, intoxication, and genetic factors border disease virus, bovine viral diarrhoea virus, and bluetongue virus were excluded as cause of the malformations, The Schmallenberg virus was detected in brain samples of aected animals and is considered to be the cause of the disease. OIE recommendations on safety precautions related to Schmallenberg virus [27] Meat: Only clinically healthy animals should be slaughtered. Transmission of the virus is most likely by vectors. Risk of transmission to animals and humans is negligible. Milk: Milk should only be collected from clinically healthy animals. Risk of transmission to animals and humans is negligible. Safety recommendations related to semen,embryos, live adult non-pregnant and pregnant
22.1. THE NEW "SCHMALLENBERG VIRUS" AFFECTS EUROPEAN LIVESTOCK (EUROPEAN SHAMONDA-LIKE ORTHOBUNYAVIRUS) 1525
animals, and live newborns are available at: http://www.oie.int/leadmin/Home/eng/Our_scientic_expertise/docs/pdf/A_Recommendations_S Position of the European Commission [28] The European Commission notes that there is no evidence that the virus could cause illness in people. The European Centre for Disease Prevention and Control (ECDC) assessed the zoonotic risks and concluded "it is unlikely that this virus can cause disease in humans, but it cannot be completely excluded at this stage". Recommendations of the Institute in Bilthoven, The Netherlands. 21 Dec 2011 [29] Zoonotic transmission of Schmallenberg virus can not be excluded but is considered unlikely when considering the vectorial transmission route (most likely midges). However, exposure risk during abortion or delivery of aected ruminants due to Schmallenberg virus is unknown. There have been no reports of unusual illness in humans in the months when the cattle syndrome peaked. However, new outbreaks should be monitored closely from a public health perspective. The institute advices to initiate a monitoring system for diseases among professionals (farmers, veterinarians) that have been in close contact with abortion products or who conducted deliveries of aected calves/lambs.
22.1.5
Schmallenberg virus in Great Britain [30]
Species aected: The Defra notes that the Schmallenberg virus has been detected in the United Kingdom. The virus is known to infect and cause disease in sheep, cattle and goats. Keepers of exotic or wild ruminants, such as the camelid and cervid family (alpacas, llamas and deer) should also be vigilant. The virus circulates in the blood system of infected animals for two to ve days, when biting insects may acquire the virus which they can then transmit to another susceptible animal during blood-feeding. It is likely that initial introduction of the virus to the UK resulted from wind-blown insect vectors. Risk to humans: An Europe-wide risk assessment has concluded that Schmallenberg virus is unlikely to cause illness in people, no human cases have been detected in any country, and the most closely related viruses only cause animal disease, a gene sequence which carries the ability to infect humans is not present in Schmallenber virus. However, Defra advices farmers and veterinary surgeons to take sensible hygiene precautions when working with livestock and abortion material. Pregnant women should not have contact with sheep and goats at lambing/kidding time due to risks of exposure to other disease causing organisms.
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22.1.6
Schmallenberg virus does not infect humans [31]
Schmallenberg virus (SBV), a novel orthobunyavirus, is spreading, since November 2011, among ruminants, especially sheep, cattle, and goats throughout Europe. Infection causes acute fever, diarrhea, severe congenital malformation, and a high proportion of stillbirths. The virus is transmitted by midges (Culicoides spp.). The Schmallenberg virus is closely related to the Simbu serogroup of which no zoonotic transmission are known. However, several other close related viruses are also transmitted by culicoids and cause serious outbreaks in humans. High numbers of Schmallenberg virus are found in infected animals and their birth products. Shepherds, assisting lamb births, are therefore strongly exposed. Ducomble et al 2012 conducted a study to determine whether zoonotic or vector-borne infections occur in humans. The authors used an indirect uorescent antibody test with antihuman uorescein isothiocyanate-conjugated secondary antibodies against SBV-specic IgM or IgG.. No evidence of SBV infection among the shepherds was found by molecular and serologic tests, even in highly exposed shepherds. Participants reported frequent insect bites. Some symptoms experienced by shepherds were compatible with illnesses commonly experienced during the winter caused by respiratory human viruses. The authors concluded that the Schmallenberg virus is unlikely to pose a threat to humans by transmission from infected livestock or from midges.
22.1.7
Impact and prediction of the Schmallenberg virus epidemic [32]
Since its rst detection in Germany in 2011, til mid May 2012, the "Schmallenberg" virus (SBV) has been reported in 3745 holdings. The impact of this animal disease on holdings does not exceed 4% for sheep or 2% for cattle in member states Goats and a bison. SBV were also infected. SBV antibodies have been detected in deer but no other species. It is unlikely that SBV poses a risk to humans. The EFSA assumes that animals in previous aected regions aquire imunity. Should the virus survive the winter, EFSAs geographical spread model predicts that SBV is most likely to re-emerge between mid-April and the end of May and is likely to aect regions previously unaected, that is, south and east of the aected areas.
22.2. FUNGAL DISEASES
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22.1.8
Novel duck reovirus, DRV-TH11, caused Pekin ducks disease in 2011 [33]
In 2011, an unidentied disease in Pekin ducks (Anas platyrhynchos) was reported in China. The infection caused unstable gait, weakness in legs, diarrhea.and death in 40% of ocks. At necropsy, large necrotic foci were observed in the spleens and alterations in liver. All classical endemic viruses such as duck enteritis virus, duck hepatitis virus, duck avivirus, duck parvovirus, and avian inuenza virus, could be excluded as the causative agent by PCR and serologic methods. The authors isolated a novel duck-pathogenic avian orthoreovirus (ARVs) of the family Reoviridae, genus Orthoreovirus. ARVs also have been isolated from the Muscovy duck (Cairina moschata). Muscovy duck reovirus infection caused illness in 30% and death in 20% of ducks on poultry farms in Israel. In China, reovirus infection has been reported in Muscovy ducklings, however, the Muscovy duck reovirus isolate was nonpathogenic for Pekin ducks. Since 2007, three isolates of orthoreovirus were conrmed in Pekin ducks from several duck farms in China. However, experiment infection with the isolates did not cause death. The disease of Pekin ducks in 2011 was found to be caused by a virus with 10 dsRNA segments in 3 size classes (L1-3, M1-3, and S1-4). The isolate was designated as novel duck reovirus, DRV-TH11. The sequence of S2 gene is distinct but clusters closely with sequences from all 3 Pekin duck isolates within the ARVs serogroup, which suggests that the novel virus is an ARV-like virus within the genus Orthoreovirus. The authors concluded that the duck reovirus, DRV-TH11 is a highly transmissible infectious agent of high mortality. They call for further studies to determine the role of the virus in the 2011 epidemic and their prevention and control.
22.2
Fungal diseases
Fungi are eukaryotic microorganisms which can occur as yeasts, molds, or as a combination of both forms. Yeasts are microscopic fungi consisting of solitary cells that reproduce by budding. Molds occur in long laments known as hyphae, which grow by apical extension. Hyphae may present septa and several nuclei. Fungi are all heterotrophic and digest their food externally by releasing hydrolytic enzymes into their surroundings.Fungi are associated with allergies and diseases.
22.2.1
Histoplasma capsulatum
Histoplasma capsulatum was found by Dias and colleagues 2010 in bats living in Brazilian urban areas. The authors stress the epidemiological importance of data regarding HistoCopyright 1998-2010 Karl H. Wilm. All rights reserved. OurFood Database of Food and Related Sciences
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plasma casulatum which is included in the mandatory disease notication system. Bats living in caves, attics, ceilings, and roofs increase the risk of human infection with the Histoplasma. [34] Fungus present the ability to convert from hyphal cells to yeast forms. This capacity is called dimorphism. Dimorphism in Histoplasma capsulatum involves three stages and is induced by an increase in temperature. The conversion of terminal or intercalary hyphal cells to a yeast form requires 3 to 14 days. [35] Human infections by Histoplasma capsulatum is very common in United States. In Africa infections by Histoplasma. capsulatum and Histoplasma duboisii were reported. Dietrich and colleagues 1987 describe a fatal case of disseminated histoplasmois due to Histoplasma capsulatum. [36] Inhalation of conidial forms present in dust of caves where bats live and soils inhabited by chickens is often the source of infection. Histoplasmosis represents one of the most important systemic mycosis in the Americas, with broad distribution in all regions of Brazil. Vaccine against three main human fungal infections [37] Wuethrich and colleagues 2011 report a rise of systemic fungal infections by Coccidioides posadasii, Histoplasma capsulatum, and Blastomyces dermatitidis. The authors reports that vaccine-induced Th17 cells were necessary and sucient to protect against the three major systemic mycoses in North America. The vaccine immunity required the adapter molecule Myd88 but not the fungal pathogen recognition receptor Dectin-1. The authors recommend to design vaccines to be eective against these three fungal infections. Candida albicans Candida albicans may form a budding yeast, pseudohyphae, germ tubes, true hyphae, and chlamydospores. The transition between a yeast and a mold is triggered by either low temperature or pH. Substances such as biotin, cysteine, serum transferrin, and zinc stimulate dimorphism in Candida albicans. [35] Coccidiosis Coccidiosis is caused by protozoan parasites. Coccidiosis in goats can cause ill thrift, severe diarrhoea and sometimes death. It is most often seen in kids and stressed animals. Good husbandry practices are required to minimise its occurrence.
22.3
Brucellosis in pigs
Brucellosis in pigs is caused by the Brucella suis (B. suis) bacterium. Infection of feral pigs has been reported in Northern Australia, and a number of human infections have been
22.4. SAFE DISPOSAL OF CARCASSES AND MANURE
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reported in people who hunt and handle tissues from feral pigs. Brucellosis is endemic in Asia, Sub-Saharan Africa, some countries of Latin America, the Middle East and the Mediterranean and South Eastern Europe Region. Cvetni and colleagues 2009 found that several pig herds in Croatia tested positive for antibodies against brucellosis. Almost every positive herd was reared outdoors. Brucella suis biovar 2 and biovar 3 could be isolated from pigs with positive sera, and the same biovars were identied in wild boars. The authors concluded that wild boars represent a brucellosis reservoir for free-range pig farms in Croatia and other countries of Central and Western Europe. [38]
22.3.1
Control and Prevention of Brucellosis
According to Dr Trish Holyoake Brucella suis is usually introduced into a herd via an infected animal or through the introduction of infected semen. Herds should be avoided to contact feral pigs. The author recommends the construction of pig-proof fences with electric wire, and control the feral pig populations. Transmission of Brucella suis to pigs may also occur eating contaminated feedstus, usually birth and/or abortion products and uterine discharges. Human infection occurs by contacting infected animals or parts of those animals. Hunters were reported to become sick after contacting infected wild boars. [39] Nicoletti stresses that there are no easy solutions to control brucellosis, widespread vaccination is the most rapid, ecient and eective procedure in addition to hygiene, and test and slaughter of infected animals. He recommends to increase thhe research on alternative strategies in vaccines and their usage, diagnostic tests, and treatments. [40]
22.4
22.4.1
Safe disposal of carcasses and manure

Safe disposal of carcasses for control of infectious disease outbreak in livestock [41]
Usually infectious material is incinerated, however, alternatives must be developed in case pandemics exceed capacities. Reuter and colleagues 2010 developed a bio-contained mortality composting procedure and tested its ecacy for bovine tissue degradation and microbial deactivation. The implementation of the composting system used materials available onfarm or purchasable from local farm supply stores. Carcass composting can take place at the site of a disease outbreak, when large number of diseased animals and manure must be safely discarded. A bunker is constructed using barley straw bales lined with heavy black silage plastic
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sheeting. The bunker was loaded with 40-cm loose straw, carcasses overlaid with 1,6 m moist aerated feedlot manure and sealed with the plastic foil. Temperatures exceeded 55 degrees C for more than one month. Infectious agents in beef cattle carcasses and manure were inactivated within 14 days of composting. After 147 days, carcasses were almost completely degraded. The authors suggest composting as a rapid-response disposal method for infected carcasses, manure and soil.
22.4.2
Composting of FMD virus of infected pig carcasses [42]
Guan and colleagues 2010 report the inactivation and degradation of foot-and-mouth disease (FMD) virus during composting of infected pig carcasses, covered with a mixture of chicken manure and wood shavings in a biocontainment level 3 facility. The FMD virus was inactivated in 10 days when temperature reached 50 degrees C. The viral RNA was degraded in skin and organs after 21 days of composting and temperatures reached 70 degrees C. The virus and the RNA survived composting at temperatures near 20 degree C. The authors concluded that composting of FMD carcasses is safe under the mentioned conditions.
22.4.3
Poultry and livestock waste treatment [43]
Sakar and colleagues reviewed studies related to poultry and livestock waste treatment under anaerobic conditions between 25 and 35 degrees C. Poultry manure wastewater Up-ow anaerobic sludge blanket (UASB) is indicated to treat poultry manure wastewater and the liquid fraction of hen manure. Cattle manure Dierent systems were considered to be eective, such as such as xedlm reactor, attached-lm bioreactor, anaerobic rotating biological reactor, batch reactors, downow anaerobic lter, xed dome plant, UASB, continuously stirred tank reactor (CSTR), up-ow anaerobic lter (UAF), temperature-phased anaerobic digestion (TPAD), anaerobic hybrid reactor (AHR), and two-stage anaerobic systems are well suited to anaerobic processing of cattle manure. Swine manure Up-ow anaerobic sludge blanket, anaerobic baed reactors, continuously stirred tank reactor, and anaerobic sequencing batch reactor are used in mesophilic or thermophilic systems to precess swine manure.
22.5
Zoonoses
A zoonosis or zoonose is any infectious disease that can be transmitted from animals to humans or from humans to animals (reverse zoonosis or anthroponosis). The interdisciplinary eld of conservation medicine, integrating human and veterinary medicine, and environmental sciences, is largely concerned with zoonoses.
22.5. ZOONOSES
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22.5.1
Bats as disease vectors
Viruses of bats which can infect animals and humans [44] Bats species hosts viruses which can infect animals and humans, such as rabies viruses. (Lyssaviruses) of dierent genotypes which have emerged from bats in America (Genotype 1 rabies virus; RABV), Europe (European bat lyssavirus; EBLV), and Australia (Australian bat lyssavirus; ABLV), Hendra virus and Marburg virus. Nipah virus is the most important recent disease of bat origin in Asia. SARS coronavirus is being found in insectivorous bat, and Ebola virus has been detected in some fruit bats. The implementation of an European surveillance systems for EBLVs in bats. a rapid response system is being suggested by van der Poel, Lina and Kramps 2006 to enhance publik health awareness related to viruses of bats. The migratory tree-roosting hoary bat and silver-haired bat are hots of rabies in North America. Klung and colleagues found that the prevalence of rabies was about 1 percent, which is signicantly lower than reported in previous studies. [45] Surveillance still necessary despite low incidence of rabies in Swiss bats [46] Rabies remains a residual risk to public health in Western Europe due to bat-specic viruses, such as European bat lyssaviruses (EBLVs). European bat lyssavirus types 1 and 2. A survey in 2009 by Megali and colleagues detected RNA corresponding to EBLV-2 in one western Switzerland bat, resembling ndings of Geneva 2002. However, no infectious virus was found. Three bats were found to be seropositive. The authors stress the importance of continuous management and surveillance are required to avoid any risk to public health, even with a low incidence of rabies in bat population. Rabis in German bats identied as European Bat Lyssavirus (EBLV-2) [47] In Europe, rabies in bats is caused by European Bat Lyssavirus (EBLV) type 1 (EBLV1) or type 2 (EBLV-2) which form two distinct genotypes (gt 5 and 6) within the genus Lyssavirus of the family of Rhadoviridae.Fatal human rabis were reported. German bats were found to be infected with the EBLV-1 variant. In The Netherlands and the United Kingdom the EBLV-2 was found. Freuling and colleagues 2008 detected one bat infected with EBLV-2 in Germany in a Daubentons bat (Myotis daubentonii) in August 2007. Bat guano virome acquired through diet of insects and plants [48] Contact between bats, humans, and other animal species increases the possibility exists for cross-species transmissions. Li and colleagues 20101 describe full and partial viral genomes identied using metagenomics in the guano of bats from California and Texas.
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The characterization of the bat guano virome is a metagenomic analysis which found the presence of previously unidentied viral species, genera, and possibly families. The viral metagenomic data describes the viromes in bat guano, and may help to detect zoonotic viruses in bat and A better knowledge concerning the distribution of pathogens in bat may preserve their population. SARS-like Coronavirus in bats [49] Viruses closely related to members of the genus Coronavirus associated with severe acute respiratory syndrome (SARS) were detected in faeces of horseshoe bat species in Slovenia. The related virus sequence in GenBank was SARS bat isolate Rp3/2004 (DQ071615) within the SARS-like CoV cluster. Rihtaric and colleagues 2010 underline the risk of a new group of bat coronaviruses as a reservoir for human respiratory infections and call for epidemiological studies. White-nose syndrome [50] White-nose syndrome is a fatal disease of hibernating bats with a mortality higher than 95%. It is caused by the fungus Geomyces destructans under low temperatures and humid conditions of caves. Foley and colleagues 2011 gathered new informations on the pathogenesis of Geomyces destructans and white-nose syndrome, using descriptive and analytical epidemiology, which includes epidemiology and disease ecology. The infection has also been conrmed in European bats, however, no epidemic similar to USA has been registered. Instead of culling aected populations of bats the group around Foley try to conserve the genetic diversity of bat populations, combined with a program of public educating of cave tourists. Bats as source of human infections [51] Bats are known to host 60 viral species, of which 59 may generate RNA viruses capable of infecting humans. The most important are lyssaviruses and Henipavirus. Human infections with Nipah, Hendra, SARS coronavirus and Ebola virus may involve intermediate hosts such as pigs, horses, civets and primates. Wong and colleagues 2007, authors of the study, warn that cross-infection between bat species may generate new viruses which can infect humans more easily. According to the authors Pteropodidae, Molossidae, Phyllostomidae, and Vespertilionidae bats are the most frequent hosts of human pathogens.
22.5.2
Pigs may transmit ebolavirus to other animals and humans [52]
Reston ebolavirus, an ebolavirus which is not pathogen to humans, was detected in pigs in the Philippines, and specic antibodies were found in pig farmers which did not develop
22.5. ZOONOSES the disease.
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Kobinger et al 2011, found that the human highly pathogen Zaire ebolavirus may infect pigs, replicate, cause disease of the respiratory tract and is transmitted to other animals. Shedding of the virus from nasal mucosa was detected for up to 14 days post-infection, and severe lung disease was observed. Human outbreaks of Ebola hemorrhagic fever, caused by the Zaire ebolavirus (ZEBOV) has a fatality rate as high as 90 percent in humans. The ndings of the authors suggest that pigs may be able to transmit virulent ebolavirus to humans as well. The authors stress that in primates Zaire ebolavirus aects multiple organs, leading to shock and death, but in pigs the virus causes respiratory syndromes which may be mistaken for other porcine respiratory diseases.
22.5.3
Dogs and cats as disease vectors
Dogs and cats as vectors of human diseases in Italy [53] Otranto D, Dantas-Torres highlight the risk of dogs and cats infection in Italy. Various vectors of disease agents were identied, such as ticks, eas, phlebotomine sand ies, and mosquitoes. Of human concern are Anaplasma phagocytophilum, Borrelia burgdorferi, Dipylidium caninum, Leishmania infantum, Dirolaria immitis, and Dirolaria repens. Fleas are recognised as vectors of pathogens transmissible to humans, such as Rickettsia felis. The authors stress that control strategies based on acaricides and insecticides should consider the vector behaviour during seasons of the year and use it accordingly. In Italy ticks and eas are present throughout the year in certain regions, and phlebotomine sand ies are most active during the summer.
22.5.4
Rickettsia massiliae in brown dog ticks in California [54]
Rickettsia massiliae DNA was detected.in brown dog tick (Rhipicephalus sanguineus) in southern California by Beeler and colleagues 2011. Serum samples from adogs of the property contained antibodies reactive with R. massiliae, R. rhipicephali, R. rickettsii, and 364D Rickettsia but no rickettsial DNA was detected, with Rickettsia massiliae being the probable causative agent of the seroposivity. The brown dog tick Rhipicephalus sanguineus also hosts the Rocky Mountain spotted fever, a tickborne disease caused by the bacterium Rickettsia rickettsii, described by Beati and Raoult 1993. [55] Babesiosis Babesiosis is tick borne zoonotic disease caused by invasion of the red cells of the blood by parasites of the genus Babesia in free-living animals, such as rodents, carnivores, and
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cattle. This fact increases the concern about the emerging zoonosis. Babesia microti and Babesia divergens cause human infections which vary from silent infection to a fulminant, malaria-like disease. Babesia is a protozoan parasite of the blood causing hemolytic disease known as Babesiosis. There exist many Babesia, however, only few are pathogenic. [56] Canine babesiosis is an important disease of dogs all over the world, resulting in anemia, thrombocytopenia varying from nonspecic illness to peracute collapse and death. Human infectios should be considered, in connection to travel or blood transfusion history. [57] A case of malaria-like babesiosis after a travel to Nicaragua,conrmed by molecular characterization by polymerase chain reaction and sequence analysis was reported in Austria. [58] Zinc deciency induces a wide range of disorders including immunodeciency which rises the risk of bacterial infections. Hamaguch and colleagues found that zinc deciency increased the severity of Babesia microti and Babesia rodhaini infections of mice, resulting growth retardation, reduction of immunity and the decrease in Packed cell volume (PCV). PCV is a measure of the proportion of blood volume that is occupied by red blood cells. [59] [60] The Ixodes ricinus tick removed from dogs in Warsawm (Poland) were found infected by Babesia microti, demonstrating their presence in ticks in Poland. [61]
22.5.5
Human pathogens in ticks living on birds [62]
Franke and colleagues 20101 found European Ixodes ricinus (Acari: Ixodidae) ticks infected by Borrelia spp., Anaplasma phagocytophilum, Rickettsia spp. and Babesia spp. The majority of birds with ticks testing positive were European robins and thrushes. Data of this study suggest that birds may also serve as host for Borrelia afzelii. Rickettsia monacensis and Rickettsia helvetica were also found. The authors found Babesia divergens and Babesie microti in ticks living on infected birds. This demonstrates that birds may infect ticks with Ricketsia spp.
22.5.6
Anaplasmosis in hoses in Brazil [63]
Equine Granulocytic Anaplasmosis - EGA (formerly Equine Granulocytic Ehrlichiosis, EGE) is a disease aecting horses. EGA infection is suspected when horses present symptoms of ehrlichiosis but do not respond to piroplasmosis treatment. (Equine piroplasmosis may be caused by Babesia caballi and Babesia equi) Salvagni et al. 2010 found horse serum samples from the central West region of Brazil 65% positive for Anaplasma phagocytophilum and 85% positive for Theileria equi by ELISAe of EGA and equine piroplasmosis in central West Brazil.
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22.5.7
Coexistence of Borrelia spp. and Babesia spp. in ticks [64]
Hildebrandt and et al. 2010 determined the infection of Ixodes ricinus ticks with borrelia spp. (ospA gene) and Babesia spp18S rRNA gene) in Middle Germany. Borrelia garinii was detected most frequently, but mixed infections occurred. Frequency of species and OspA types are described. Some ticks were infected with a combination of Borrelia spp. and Babesia microti, Babesia divergens. The authors stress the importance of the knowledge of the population of Borrelia species and OspA types, development of diagnostic tests and vaccines.
22.5.8
Ticks as hosts of piroplasm parasites in Italy
[65] Piroplasms are protozoan parasite which divide by binary ssion and as sporozoan parasites they possess sexual and asexual phases. They include the tick parasites Babesia and Theileria. Ticks, collected in central and northern Italy from pets, livestock, wild animals and the environment act as a reservoir for piroplasms such as Theileria equi and Babesia species. Ixodes ricinus hosted the highest number of piroplasm species, although the highest infection rate was recorded in Hyalomma marginatum Dermacentor marginatus, Rhipicephalus turanicus and Rhipicephalus sanguineus were also found infected with the pathogens.
22.5.9
Anaplasmosis
The Anaplasma marginale (Rickettsiales: Anaplasmataceae) is an obligate intraerythrocytic rickettsial gram-negative bacterium which infects cattle causing a mild to severe hemolytic disease. Anaplasmosis is responsible for dairy and beef industries losses. Cattle becomes infected through bites of ticks, biting ies or blood-cotaminated fomites. Intradermal needles, ear tagging, dehorning and castration equipment may also spread the disease.Determining msp1alpha. Distribution and the evolution of Anaplasma marginale is being studied by determining msp4 and msp1alpha genotypes. Vaccines may prevented clinical anaplasmosis in cattle but are unable to avoid infection. Kocan et al. 2010 call for vaccines which prevent clinical disease and also prevent infection in cattle and ticks. Fever, anemia, jaundice, weakness, and/or respiratory distress in infected animals and milk production decline in dairy cattle are reported. Clinically aected dairy cattle may also have a rapid decline in milk production. Anaplasmosis is a global disease of ruminants which presents clinical signs only in cattle. Anaplasmosis poses no direct human health or food safety. Howden et al. 2010 report that Dermacentor andersoni and Dermacentor variabilis are vector ticks in Canada.[66]
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Severity of anaplasmosis in cattle increases with age. Anaplasma marginale can be detected on stained blood smears from animals during the acute phase, but is not always found in pre-symptomatic or carrier animals, when serology of antibodies and molecular detection methods are necessary. According to Aubry and Geale 2011 the role of wild ruminants in the epidemiology of bovine anaplasmosis is needed to be further evaluated. The authors cite the maintenance of Anaplasma-free herds, vector control, administration of antibiotics and vaccination as actual control measures for bovine anaplasmosis. [67]
22.5.10
Anaplasma phagocytophilum [68]
The bacterium Anaplasma phagocytophilum is known to infect sheep, goat, cattle, horse, dog, cat, roe deer, reindeer and humans in Europe, with Ixodes ricinus as vector. It may cause high fever, cytoplasmatic inclusions in phagocytes and severe neutropenia, but is seldom fatal unless complicated by other infections. The predisposing factor of anaplasmosis for other infections is very relevant, especially in sheeps. Stuen 2007 reports that several variants based on 16S rRNA gene sequences may exist in the same herd or even in the same animal.
22.5.11
Inadequate vector control of Bovine anaplasmosis in Costa Rica [69]
Bovine anaplasmosis in dairy farms of Costa Rica was determined by Oliveira et al., using recombinant truncated MSP-5 (rMSP-5) enzyme-linked immunosorbent assay (ELISA). Herd seroprevalence ranged from 20.0 to 72.0%. The authors stress that the endemic situation is due to inadequate vector control associated, among others, with rainy season, presence of tabanids and stable ies.
22.5.12
Human granulocytic anaplasmosis (HGA) [70]
Anaplasma phagocytophilum cause human granulocytic anaplasmosis (HGA) in USA, Europe and the Far East of Russia, with ticks as the main vector and mammalian species as reservoirs. The disease was previously knowm as human granulocytotropic ehrlichiosis [71]. Ixodes ricinus ticks from Estonia, Belarus and the European part of Russia were found to be infected by Anaplasma phagocytophilum. Katargina et al. 2011 assigned these strains to dierent groESL lineages and 16S rRNA gene variants with variable numbers of repetitive elements within ankA gene. The tick-borne fever (TBF) and pasture fever in sheep, ruminants, horses and humans are caused by variants of Anaplasma phagocytophilum. The diseases present high fever, recurrent bacteremia, neutropenia, lymphocytopenia, thrombocytopenia, general immunosuppression, and secondary infections such as tick pyemia, pneumonic pasteurellosis, listeriosis, and enterotoxemia. Vector is the hard tick Ixodes ricinus, and possibly other ticks.
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Some cases of human granulocytic anaplasmosis (HGA) have been reported in Europe, but Woldehiwet 2006 stresses that it is not yet cleared if there is a dierence between the variants causing HGA and those causing TBF in ruminants. [72]
22.5.13
Ehrlichia chaeensis as human pathogen [73]
The Ehrlichia chaeensis is an obligately intracellular bacterium lives in mononuclear phagocytes. It causes the human monocytotropic ehrlichiosis. Thomas, Popov and Walker 2010 studied the infection mechanism of ehrlichiosis using Ehrlichia muris and Ixodes ovatus Ehrlichia (IOE) as mouse models of the disease. The authors found that Ehrlichia was transported through the lopodia of macrophages during early stages of infection. Cytochalasin could inhibit the formation of lopodia, preventing the transport of the bacteria to the interior of the macrophages. The erlichia cells are released when the cell membrane of the macrophage ruptures in a late phase of the disease.
22.5.14
Advice to prevent outdoor vector-borne diseases in USA [74]
Hayes 2010 advises travellers visit the United States to practice personal protection against arthropod bites, including appropriate use of insect repellents, especially when visiting rural and suburban areas during the warm months, to prevent Lyme disease, anaplasmosis and babesiosis in the northeast and north central States, West Nile virus disease in western plains States, and Rocky Mountain spotted fever and tularemia in the southeast of the USA.
22.5.15
Ehrlichiosis and anaplsmosis disease in dogs and cats in USA [75]
Ehrlichia canis is known since 1935, however, and was found in the United States for the rst time in 1962. It may infect dogs and sometimes cats. Little 2010 describes the transmission, diagnosis, and management of ehrlichiosis and anaplasmosis in these animals.
22.5.16
Determination of Anaplasma phagocytophilum clusters using ankA gene [76]
Scharf et al.sequenced the 16S rRNA and ankA genes of Anaplasma. phagocytophilum strains from humans and several animal species to explain host preference and epidemiological diversity. The authors stress that analysis using 16S rRNA gene sequences is not sucient to determine clusters of Anaplasma phagocytophilum, therefore ankA gene should be included in such determinations.
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22.5.17
Diagnosis of anaplasmosis in dogs [77]
Ravnik et al. report that antibody titre and haematological parameters are not sucient to conrm the clinical relevance of exposure to Anaplasmosis phagocytophilum. The authors suggest to include additional diagnostic tools, such as PCR in the diagnosis of such infections.
22.5.18
Fatal bovine anaplasmosis outbreak in Hungary [78]
Hornok et al. 2010 studied the occurrence of a fatal outbreak of bovine anaplasmosis in Hungary. An Anaplasma-carrier state of 92% of the cattle and cases of concurrent infections with Mycoplasma wenyonii, CandidatusMycoplasma haemobos and rickettsaemia were reported by the authors. This outbreak was associated with divergent Anaplasma marginale genotypes and concurrent Candidatus Mycoplasma haemobos infection, as well as of an Anaplasma ovis strain in ticks.
22.5.19
Lyme disease
Lyme disease, or Lyme borreliosis is an infectious disease caused by Borrelia bacteria.Borrelia burgdorferi sensu stricto causes Lyme disease in the United States. In Europa Borrelia afzelii and Borrelia garinii are the cause of Lyme disease. Borrelia is transmitted to humans by the bite of infected ticks belonging to a few species of the genus Ixodes ("hard ticks"). For the transmission of the disease, the presence of ticks is a prerequisite. Early symptoms may include fever, headache, fatigue, depression, and a characteristic circular skin rash called erythema migrans. Left untreated, later symptoms may involve the joints, heart, and central nervous system.
22.5.20
Lyme neuroborreliosis in horses [79]
Imai et al. 2011 describe Lyme disease in horses with progressive neurologic symptoms. Borrelia burgdorferi sensu stricto was identied by polymerase chain reaction amplication of B burgdorferi sensu stricto-specic gene targets (ospA, ospC, aB, dbpA, arp). Spirochaetes were found in tissues with inammation, including spinal cord, muscle, and joint capsule. Sequence analysis was identical to a human isolate of Borrelia burgdorferi strain 297, demonstrating inter-species infectivity of neuroborreliosis.
22.5.21
Borrelia burgdorferi in tick and dogs in Serbia [80]
Savi et al. 2010 studied Ixodes ricinus ticks and dogs in Serbia. The authors found 22.12% of ticks infected with Borrelia burgdorferi s.l and specic antibodies were determined in 25.81% of dogs. The authors stress the actual risk of Borrelia to infect other animals and humans, because ticks and dogs of Serbia represent a reservoir of the disease agent.
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22.5.22
Low risk of tick-borne disease in the Netherlands [81]
Tiisse-Klasen et al.2011 determined the risk of developing tick-borne diseases. They collected Ixodes ricinus ticks and found PCR positive for Borrelia burgdorferi s.l (60%), Rickettsia spp.(19%), Ehrlichia/Anaplasma spp.(12%), and Babesia spp.(10%). After six month following a tick bite, the participants of the study reported reddening at the bite site (8.3%) and systemic symptoms (4.1%). However, no association between symptoms and tick-borne microorganisms was found. The authors concluded that the risk in the Netherlands of contracting acute Lyme borreliosis, rickettsiosis, babesiosis or ehrlichiosis from a single tick bite was less than 1%.
22.5.23
Failing to develop a Lyme vaccine [82]
According to Poland 2011 the withdrawal of the 1998 FDA approved Lyme vaccine resulted from safety concerns suggesting that the vaccine antigen was arthritogenic, produced high costs, the vaccination had a dicult schedule, might need boosters, risk of the disease was uncertain, and there was low public demand. Poland deplores that no protection from Lyme disease will be available as no US vaccine will be developed in near future. A new vaccine should overcome such hurdles. According to Shen, Mead and Beard 2011 the Lyme disease preventions include area acaricides, landscape management, host-targeted interventions, management of deer populations, use of insect repellent and tick checks. However, rates of compliance are poor. [83] Nardelli et al. 2009 call for the development of a new vaccine, because Lyme disease cases increase and diagnoses is dicult. [84]
22.5.24
STARI (Southern Tick-Associated Rash Illness)
STARI is transmitted via bites from the lone star tick (Ambylomma americanum), found in the southeastern and eastern U.S. It is also called Master Disease. [85] This illness is a tick-borne disease carried by the Lone Star Tick Amblyomma americanum, which is caused, according to some authors, by the spirochaete bacterium Borrelia lonestari, but it fails to be detected this in most cases of STARI. The CDC says, therefore, that the pathogen of the disease is still unknown. Erythema migrans (EM) is an annular, erythematous, expanding rash that is characteristic of early Lyme disease. Many cases of EM seem to have an aetiology dierent from that of Lyme disease and are called Southern tick-associated rash illness. Microbiologists from the Centers for Disease Control and Prevention contacted the North Carolina Network Consortium, a statewide consortium of practice-based research networks joined to identify the aetiological agents of the STARI. Vaughn et al. 2010 describe the
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practice-based research network used to identify patients and collect specimens for clinical research. [86]
22.5.25
CDC recommendations on prevention of tick-borne diseases [87]
CDC recommends to avoid tick habitat (dense woods and brushy areas), to use insect repellents containing DEET or permethrin, wear long pants and socks, and perform tick checks and promptly removing ticks after outdoor activity. After tick bites it is important to monitor the onset of a rash, fever, headache, joint or muscle pains, or swollen lymph nodes within 30. In this case a doctor should be consulted immediately. According to the CDC in most circumstances, treating persons who only have a tick bite is not recommended. Tickborne relapsing fever (TBRF) is transmitted to humans through the bite of infected soft ticks, feeding on rodents. TBRF is found primarily in Africa, Spain, Saudi Arabia, Asia, and certain areas in the Western U.S. and Canada. It is associated with sleeping in rustic cabins and vacation homes. Relapsing infections are acquired from other Borrelia species, such as Borrelia hermsii, Borrelia recurrentis, Borrelia parkeri and Borrelia duttoni, transmitted by the soft-bodied African tick Ornithodoros moubata.
22.5.26
The Eurasia strains of Tick-borne relapsing fever [88]
Tick-borne relapsing fever in Eurasia is attributed mainly to Borrelia persica with Ornithodoros tholozani as important tick vector, in India and Kashmir, the southern countries of the former USSR, Iran, Iraq, Syria, Jordan, Turkey, Israel, Egypt, and Cyprus. It inhabits caves, ruins, houses, cowsheds and burrows of rodents and small mammals, with an incubation period is 5-9 days. Borrelia caucasica, Borrelia latyschewii, Borrelia microtii, and Borrelia baltazardi were also described. To clear taxonomic confusion 16S rRNA and aB genes were used. Sequencing of Israeli TBRF aB genes identies the Eurasia strains, the New World cluster and the Old World cluster.
22.5.27
Louse-borne relapsing fever
Borrelia recurrentis is one of three pathogens (along with Rickettsia prowazekii and Bartonella quintana) of which the body louse, or Pediculus humanus humanus is a vector.Louseborne relapsing fever is more severe than the tick-borne variety and occurs in epidemics in poor regions in the developing world, such as Ethiopia and Sudan. Mortality rate is 1% with treatment; 30-70% without treatment. Borrelia organisms multiply in the gut of the louse. The bacterium can infect humans when the louse is crushed by the victim or by scratches. The transmission occurs from person to person using the louse, no animal reservoir exists.
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The number of cases or relapsing fever, once a worldwide epidemic disease, is now diminishing, because of improvements in housings and insecticides reducing body louse incidence. Cutler, Abdissa and Trape2009 report that the infection is caused by a louse-adapted variant of Borrelia duttonii, transmitted by Ornithodoros moubata soft ticks in East Africa, and recently by Borrelia crocidurae, transmitted by Ornithodoros sonrai ticks.
22.5.28
Food-borne tularemia in Bulgaria [89]
Tularemia is caused by the bacterium Francisella tularensis. A Gram-negative, nonmotile coccobacillus, the bacterium has several subspecies with varying degrees of virulence. The most important of those is F. tularensis tularensis (Type A), which is found in lagomorphs in North America and is highly virulent in humans and domestic rabbits. F. tularensis palaearctica (Type B) occurs mainly in aquatic rodents (beavers, muskrats) in North America and in hares and small rodents in northern Eurasia. It is less virulent for humans and rabbits. The primary vectors are ticks and deer ies Chrysops discalis, but the disease can also be spread through other arthropods. Rodents, rabbits, and hares often serve as reservoir hosts, Tularemia may also be spread by direct contact with contaminated animals or material, by ingestion of poorly cooked esh of infected animals or contaminated water, or by inhalation. Komitova et al. 2010 describe the outbreak of tularemia in Bulgaria and its reemerging in 2003. Francisella tularensis (F. tularensis) was detected by PCR. The authors concluded that the tularemia outbreak was probably food-borne and was associated with a surge in the rodent population. [90]
22.5.29
Chlorine disinfection of Francisella tularensis in drinking water [91]
OConnell et al. 2011 determined the resistance to chlorine of live vaccine strain (LVS) and wild-type strains of Francisella tularensis. The authors found that free available chlorine residual concentrations routinely maintained in drinking water distribution systems would require up to two hours to reduce all F. tularensis strains by 4 log10. LVS should not be used for disinfection studies, because this strain dies earlier compared with the wild type strain.
22.5.30
Rickettsiosis
Members of the order Rickettsiales (alpha-proteobacteria), transmitted by ticks, include the genera Rickettsia and Ehrlichia. The Mediterranean Spotted Fever (MSF), caused by Rickettsia conorii, the pathogens Rickettsia helvetica and Rickettsia slovaca Rickettsia monacensis and Rickettsia sp. IRS4 are frequent disease agents in Europe.
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Lo et al. 2004 describe a novel alphaproteobacterium IricES1 found in the tick Ixodes ricinus. This bacterium can existing within the mitochondria, as well as the cytoplasm, of ovarian cells. The authors found that the bacterium enters mitochondria between the inner and outer membranes, and then proceeds to consume the inner mitochondrial matrix. [92]
22.5.31
Evaluation of disease caused by Rickettsia 364D [93]
364D Rickettsiosis (Rickettsia phillipi, proposed) is transmitted to humans by the Pacic Coast tick (Dermacentor occidentalis ticks). This is a new disease that has been found in California. Shapiro et al. 2010 report that "spotless" Rocky Mountain spotted fever may be associated with the spotted fever group rickettsiae SFGR 364D, transmitted by the tick Dermacentor occidentalis. The authors stress that possible infection with 364D or other SFGR should be conrmed through molecular techniques in patients who present with "spotless" Rocky Mountain spotted fever or have serum antibodies to R. rickettsii with group-specic assays. Wikswo et al.2008 provided molecular data on the prevalence and species identication of spotted fever group SFG rickettsiae circulating in populations of southern California ticks. They stress that neither Dermacentor variabilis nor R. rickettsii were often found, 364D should therefore be evaluated further as a potential cause of human SFG rickettsioses. [94]
22.5.32
Diseases transmitted by ticks in Swizerland [95]
Gern et al. 2010 report that Ixodes ricinus is the most frequent tick in Switzerland which transmit Lyme borreliosis (Borrelia burgdorferi group) and tick-borne encephalitis (TBE), the major tick-borne diseases transmitted to human. According to the authors there are several factors which inuence infection, such as stage of the vector, the multiple hosts, the pathogenic agent, as well as human behaviour in nature, and the presence of co-infection agents in ticks such as Anaplasma, Babesia and Rickettsia. The authors call to evaluate the importance of such infections.
22.5.33
Spotted Fever Rickettsioses in Poland [96]
Podsiady et al. 2010 found antibodies to specic Spotted Fever Rickettsioses rickettsiae antibodies in 14.7% of tested Poland forest workers, whereas most of these cases were due to Rickettsia massiliae. No antibodies to Rickettsia helvetica and Rickettsia slovaca in human sera were found, despite the presence of such bacteria in local ticks. Antibodies to Borrelia burgdorferi was most often found, isolated or in coinfection with Bartonella spp. The authors stress that no infections with spotted fever group rickettsiae have been reported, however, monitoring of any changes is necessary, because of the local presence of the bacteria in ticks and specic antibodies in humans.
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22.5.34
Tick-borne encephalitis
Tick-borne encephalitis (TBE) is a central nervous system infection caused by a avivirus [tick-borne encephalitis virus (TBEV). It is transmitted by the bite of several species of infected ticks, including Ixodes scapularis, Ixodes ricinus and Ixodes persulcatus, or (rarely) through the non-pasteurized milk of infected cows. The virus can infect the brain (encephalitis), the meninges (meningitis) or both. The disease is caused by the tick-borne encephalitis virus, a member of the genus Flavivirus in the family Flaviviridae. Mortality is 1% to 2%, with deaths occurring 5 to 7 days after the onset of neurologic signs. Three virus sub-types are described: European or Western tick-borne encephalitis virus, Siberian tick-borne encephalitis virus, and Far-Eastern tickborne encephalitis virus (formerly known as Russian Spring Summer encephalitis virus). Russia and Europe report about 5,000-7,000 human cases annually.
22.5.35
Tick-borne encephalitis moves northward triggered by climate change [97]
The northernmost tick-borne encephalitis (TBE) focus is in Simo, Finnish Lapland. Four TBE cases were conrmed during 2008-2009 by Jskelinen et al. 2011. The virus has 3 subtypes: European (TBEV-Eur), Siberian (TBEV-Sib), and Far Eastern (TBEV-FE). TBEV-Eur is mainly transmitted by Ixodes ricinus ticks (sheep ticks) and the 2 other subtypes by Ixodes persulcatus ticks (taiga ticks). Tick-borne encephalitis seems to be moving northward in Europe and shifting upward to higher elevations in the mountains, apparently inuenced by climate change and an unusual combination of the TBEV-Eur strain and Ixodes persulcatus ticks. Jskelinen et al. 2010 describe two European-subtype strains from human serum samples containing tick-borne encephalitis virus (TBEV) RNA. The authors also analysed the variations within European-subtype strains, Siberian-subtype strains and Far Eastern-subtype strains using TBEV E and NS3 gene sequences. [98]
22.5.36
Complete genome sequences of two Korean strains of the tick-borne encephalitis virus [99]
Yun at al. 2011report the complete genome sequences of two Korean strains of the tickborne encephalitis virus (TBEV), designated KrM 93 and KrM 213. The data of the study demonstrates that the Korean TBEV strains clustered with the Western subtype rather than with Far-Eastern or Siberian subtypes.
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22.5.37
Rift Valley Fever [100]
Rift valley fever is a disease of domestic livestock and humans. It is spread by the bite of infected mosquitoes, such as Aedes or Culex genera. The disease is caused by the RVF virus, a member of the genus Phlebovirus (family Bunyaviridae). RVF outbreaks occur across sub-Saharan Africa. An outbreak in Egypt in 1977-78, several million people were infected and thousands died. Over 400 persons died in Kenya in 1998. Small outbreaks in 2006 and 2007 forced the closure of livestock markets hitting the economy of the region. In September 2000 an outbreak was conrmed in Saudi Arabia and Yemen). In April 2010 fatal human cases of the disease were reported, together with ongoing outbreaks of Rift Valley Fever Virus infection aecting sheep, goats, cattle and wildlife on farms in South Africa with massive livestock deaths. Rift valley fever is able to infect many species of animals including cattle, sheep, camels and goats. Sheep appear to be more susceptible than cattle or camels. Age is a factor in the animals susceptibility to the severe form of the disease: over 90% of lambs infected with RVF die, whereas mortality among adult sheep can be as low as 10%. Infection of livestock during pregnancy leads to abortion of all foetuses.
22.5.38
Stable ies may play a role in the spread of rift valley fever [101]
Turell et al. 2010 analysed the possibility of the transmission of the rift valley fever virus byt he house ies (Musca domestica), and stable ies (Stomoxys calcitrans). The disease is known to be transmitted by mosquitoes. It is of importance to know whether other insects are also capable to replicate the virus. The authors found that house ies and stable ies could not support the replication, but Stomoxis calcitrans, the stable y, could mechanically transmit the virus to hamsters. The authors stress therefore that the stable y and other Stomoxys may play a role in a rapid spread of the disease, due to their close association with a possible contaminated livestock.
22.5.39
African swine fever [102]
African swine fever (ASF) is a hemorrhagic fever in domestic pigs that causes serious economic losses and high mortality rates in countries in sub-Saharan Africa, the island of Sardinia, Europe , Brazil, the Caribbean region and island of Mauritius. There is no vaccine against ASF, and disease control relies on rapid diagnosis and implementation of quarantine and slaughter policies. African swine fever virus (ASFV) is a large, icosahedral, cytoplasmic, double-stranded DNA virus; it is the only member of the family Asfaviridae, although it shares similarities with other virus families in the superfamily of nucleo-cytoplasmic large DNA viruses. In 2007 a new outbreak of ASF was conrmed in the Republic of Georgia. The GeorOurFood Database of Food and Related Sciences Copyright 1998-2010 Karl H. Wilm. All rights reserved.
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gia 2007/1isolate was closely related to isolates of genotype II, which has been identied in Mozambique, Madagascar, and Zambia. Chapman et al. 2011 report the complete genomic coding sequence of the Georgia 2007/1 isolate and compared it with other strains. Phylogeny based on concatenated sequences of 125 conserved ORFs showed that this isolate clustered most closely with the Mkuzi 1979 isolate. Some ORFs clustered dierently, suggesting that recombination may have occurred. Results provide a baseline for monitoring genomic changes in this virus. In the Russian Federation, the deaths of near 48,000 animals and a loss of US$ 1 billion were reported in 2009. The authors stress the risk of African swine fever for pig farming worldwide which may result from a rapid spread of the virus.
22.5.40
Risk of African swine fever in the European Union
[103] The risk that African Swine Fever virus (ASFV) remains endemic in the Trans Caucasian Countries and the Russian Federation is moderate, while the risk of its spread in these regions is high. The resulting risk of introduction from these regions into the EU is moderate most likely through food waste. Within the EU, mainly domestic pigs in the free range (FR) and the limited biosecurity sector (LB) are likely to be exposed to African Swine Fever virus via swill feeding, with low risk. Once infected, the risk of spread from the LB and FR sectors prior detection is high, mainly due to movement of pigs, people and vehicles and moderate from the High Biosecurity (HB) sector. Because of their long life, ticks of the Ornithodoros erraticus complex can be important in maintaining local foci of African Swine Fever virus, where pigs are kept under traditional systems. Ticks do not, play an active role in the geographical spread of the virus. Wild boar have never been found infested because they do not rest inside burrows potentially infested by ticks.
22.5.41
West Nile virus [104]
West Nile virus is a member of the family Flaviviridae. It mainly infects wild birds, but is known to infect humans, horses, dogs, cats, bats, chipmunks, skunks, squirrels, and domestic rabbits. The main route of human infection is through the bite of an infected mosquito. Approximately 90% of West Nile Virus infections in humans are without any symptoms.It is found in Africa, Middle East, United States, Italy and spreads Asia. The genetic material of WNV is a positive-sense, single strand of RNA, which is between 11,000 and 12,000 nucleotides long; these genes encode seven non-structural proteins and three structural proteins. The RNA strand is held within a nucleocapsid formed from 12
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kDa protein blocks; the capsid is contained within a host-derived membrane altered by two viral glycoproteins. The most eective method to detect risk of West Nile fever to humans and horses is sampling of sick or dead birds and test for the virus. Yeh et al. 2011 say that West Nile fever has not been detected in South Korea so far, however the disease may spread to the country because many Russian migratory birds share yways over South Korea and Japan. The authors refer to recent ndings of the virus in cinereous vulture and cattle egrets in the Russian region , which is adjacent to the Korean peninsula. Flavivirus antibodies were already detected in migrating birds in Japan. The spread of the West Nile virus from Russia to South Korea and Japan is therefore possible due to the migration of infected birds to their breeding places.
22.5.42
Chikungunya virus [105]
Chikungunya virus (CHIKV) is an insect-borne virus, of the genus Alphavirus, that is transmitted to humans by virus-carrying female Aedes aegypti or Aedes albopictus mosquitos. There have been recent breakouts of CHIKV associated with severe illness. CHIKV causes an illness with symptoms similar to dengue fever. CHIKV manifests itself with an acute febrile phase of the illness lasting only two to ve days, followed by a prolonged arthralgic disease that aects the joints of the extremities. The pain associated with CHIKV infection of the joints persists for weeks or months, or in some cases years. Chikungunya virus is indigenous to tropical Africa and Asia, where it is transmitted to humans by the bite of infected mosquitoes, usually of the genus Aedes. Chikungunya virus belongs to alphavirus genus of the Togaviridae family. It is an "Arbovirus" (Ar-arthropod, bo-borne). CHIK fever epidemics are sustained by human-mosquito-human transmission. The word "chikungunya" is thought to derive from description in local dialect of the contorted posture of patients aicted with the severe joint pain associated with this disease. The main virus reservoirs are monkeys, but other species can also be aected, including humans. Although CHIK is endemic in Africa/Southeast Asia, recent outbreaks during 20042007 have reached new geographical areas where cases are now reported in Europe, Hong-Kong, Canada, Taiwan and the USA. In some cases, these are directly associated with the return of infected tourists from India and islands of the Indian Ocean. Moreover, in 2007, the rst CHIK outbreak was recorded in a temperate region of North Eastern of Italy with Aedes albopictus mosquitos as vector.
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Chikungunya Fever in in Singapore [106]
Ho et al. 2011 reviewed the epidemiological control of the Chikungunya Fever in Singapore. Some cases were related to Aedes aegypti as vector. Another rapid spread was due to a
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mutant viral strain (A226V) introduced from India and Malaysia with Aedes albopictus as primary vector. The authors report that the number of new cases declined due to aggressive control of the vector Aedes albopictus, however mosquito control program must be maintained to prevent recurrence of the disease.
22.5.44
Clenbuterol in pork
Clenbuterol is a beta-2 agonist and sympathomimetic amine that is used to treat breathing disorders. When fed to livestock it accelerates growth and increases the proportion of lean meat. In 2002 China banned the use of clenbuterol in feed after complaints of consumers suering from nausea, dizziness, hypertension and hyperglycemia after eating pork raised with such feed.
In March 2011 Shuanghui, largest meat producer of China was cited to produce meat tainted with illegal clenbuterol. People producing, selling or using clenbuterol were arrested. All meat product sales of Shuanghui have been suspended. Pleadin et al. 2010 determined the concentration of clenbuterol in meat of pigs which were fed a growth-promoting dose of clenbuterol of 20 microg/kg body mass per day during 28 days. Residues of Clenbuterol in meat is found up to 7 days after treatment discontinuation.The chemical could not be detected only after 14 days of cessation of clenbuterol administration. [107] Clenbuterol has also been used as a performance-enhancing drug and a number of athletes were banned after using the drug in 2008 to 2010. Traces of the amine from meat in the diet is regularly turning up in athletes blood. A lab in Cologne, Germany, found that 22 of 28 travellers returning from China tested positive for low levels of clenbuterol, probably from food contamination. This may also aect athletes travelling to China. [108] Veterinary professionals say the number of tests for clenbuterolin pig is to low because
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these tests are too costly. They call for the development of easier, cheaper, more convenient and wider-spectrum testing methods for regular food products. Liu and colleagues 2011 report the development of a method to determine 20 illegal residual beta-agonists in pork tissues, including muscle and liver simultaneously. [109]
22.5.45
Monocultures of non-edible oil plants for Biodiesel endanger native bees [110]
Castor bean (Ricinus communis) is largely cultivated in the region of northeastern Brazil for the production of biodiesel. Assessing the toxicity of pollen samples of Ricinus communis to honey bees de Assis Junior and colleagues 2011 found that the survival of honey bees were signicantly reduced if they had access to castor bean pollen. The authors concluded that expansion of castor bean plantations in Brazilian may endanger native and domestic honey bees. The authors call for more studies on the eect of non-edible oil plants to honey bees.
22.5.46
Honey containing pollen of GM plants will be ruled under the GM legislation [111]
The attorney general of the Court of Justice of the European Union, Yves Bot ruled that honey containing pollen derived from GM maize requires approval to be marketed within the Community. Pollen is a genetic modied organism which bears genetic informations of the plant of origin and must be ruled according to genetic engineering legislation [112]. Under this legislation it is irrelevant how the pollen found its way to the honey and if it is fertile or not. If this rule comes into eect honey containing pollen of not allowed GM plants, such as the Canadian rapeseed honey needs to be approved by regulators before it can be sold in the European Union. [113] Traces of genetically-modied pollen from a Monsanto maize crop (MON 810) in honey samples ignited the debate on how to reform the GM approval system. More than one third of crop plants depend on the pollination by honeybees. Interests of beekeepers are therefore of vital importance for agriculture.
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Honey with traces of GMO pollen must be labelled as GM produce and be submitted to safety authorisation [114]
Honey with traces of GMO pollen must be labelled as GM produce and be submitted to safety authorisation, following new ruling by the European Court of Justice. The ruling stated that GM pollen produced by MON810 maize and present in honey falls under the scope of Regulation 1829/2003 on GM food and feed and is therefore subject to authorisation prior to placement on the market.
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MON810 pollen in honey was not included in the original scope of the authorisation application for maize MON810, meaning that honey containing the GM pollen became illegal following the court ruling. The decision will have an impact on the 140,000 tonnes/y honey which the EU imports from Argentina and China, both GM-friendly countries.
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Production of GM-free honey will be endangered by the activities of biotech corporations and law makers
The decision will also collide with he EU regulation of July 2011 which permits traces of GMOs in animal feed without safety review. [115] The regulation of 24/06/2011 which came for low level presence of non-EU approved genetically modied organisms (GMOs) in feed sets a 0.1% threshold replacing the former zero tolerance level for unapproved GMOs. It applies for GM material authorised for commercialisation in a third country, and for which the EU approval procedure has been pending for more than three months, and certain GMOs for which the authorisation has expired. [116]
22.5.49
Heavy pressure of biotech on Vatican and on EU countries says a WikiLeak report [117]
Craig Stapleton US ambassador in Paris urged Washington to penalise the EU after France moved to ban a Monsanto GM corn variety. Catholic bishops in developing countries have been opposed to the GM crops, because peasant could not pay the seeds and additional chemicals. The US embassy in the Vatican believed that the pope might support biotech and order these bishops to accept GM crops. The embassy lobbied the Cardinal Renato Martino which is the adviser of the pope. The Cardinal, trying to keep good relations to the US government, cooperated with biotech to compensate the Vatican refusal of the Iraq war. "Recently, however, the Cardinal no longer feels the need to take this approach," says the US embassy cable. US authorities have asked Turkey to change their legislation on GMO which demands 5 years prison for GMO foods importers in Turkey. The request was launched in exchange to a Turkish request to . to ease customs regulations for importing fruits and vegetables to the U.S. market. Negotiations ended without results on both sides. [118]
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Biotech disapproved by most consumers
Most people disapprove GM food and avoid it whenever the products are clearly labelled and there are alternatives. The strategy of corporations introducing GM foods is to blur the boundaries between GM-NonGM crops starting with GMO contaminated animal feeds or staple foods, leaving the consumer without choice. [119]
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Peru approves GMO ban [120]
In 5 November 2011 the Congress of Peru approved a 10-year moratorium on imports of genetically modied organisms, including seeds, livestock, and sh in order to safeguard the countrys biodiversity. Peru is one of the worlds leading exporters of organic food, including coee and cocoa. The country has 40,000 certied producers.
22.5.52
The Gates Foundation embraces biotech instead of agroecological techniques disregarding sustainability [121]
The Gates Foundation collaborates with agri-biotechnology companies including Monsanto, BASF, Du Pont, Dow and the Syngenta Foundation in projects to develop GM seeds and promote fertilisers, pesticides and hybrid seeds to small African farmers, says a GM Freeze report of October 2011. According to the report the strategy of the Gates Foundation relies on input of petrochemicals and GMO plants. This may lead to degradation of soils, water supplies and biodiversity. The report urges the Gates Foundation to re-assess their approach and focus on developing agroecological techniques that have already been demonstrated as eective at providing environmental, social and economic solutions.
22.5.53
New Porcine Calicivirus in US Swine [?]
Wang and colleagues report that new St-Valerien-like porcine caliciviruses are prevalent in up to 80% in nisher pigs in North Carolina. One strain, NC-WGP93C, shares over 89 genomic nucleotide identity with Canadian strains. The authors could not say whether these strains are pathogenic for animals or humans or may aect food safety. The caliciviruses have been found in humans, cattle, pigs, cats, chickens, reptiles, dolphins and amphibians.Viruses in the family Caliciviridae are nonenveloped, polyadenylated, single-stranded, positive-sense RNA viruses with 5 genera (Norovirus, Sapovirus, Vesivirus, Lagovirus, and Nebovirus). The nonhuman primate Tulane virus and the porcine St-Valerien-like viruses, may become a new genera in the Caliciviridae family. St-Valerien-like viruses have been detected in Canada, the United States, and Italy. In order to support the classication of St-Valerien-like viruses as a member of Casliciviridae it is important to demonstrate the presence of the virus in other regions and determine the genetic dierences between strains. St-Valerien-like viruses are close to Tulane virus and human noroviruses, and more data may may help to clear if an interspecies transmission may take place, and nd the bst way to control the spread of the new viruses.
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22.5.54
Chronic and visceral botulism may impact birds, cattle and humans [122]
Bhnel, Schwagerick and Gessler 2001 describe a bovine disease in lower Saxony, Germany and named it "visceral botulism". The symptoms are constipation alternating with diarrhoea, non-infectious chronic laminitis, engorged veins, oedemas, retracted abdomen, emaciation and apathy. Unexpected death, delayed growth and wasting in heifers, and decreasing milk yield are reported. The authors found Clostridium botulinum bacteria, their spores and toxins in animals of aected farms. Free botulinum toxin was found in lower sections of the intestine. In farms with healthy animals all tests were negative. According to Professor Dr. Helge Bhnel of the University of Gttingen and his colleagues, longlasting absorption of low quantities of botulinum toxin may interfere with the neurological control of intestinal physiology.
22.5.55
Botulinum neurotoxin and Sudden Infant Death Syndrome [123]
Bhnel et al 2001 studied case of unexpected infant death up to 12 months of age. Free botulinum neurotoxin (BoNT) and bacterial forms were detected. Toxin neutralisation revealed the denite presence of BoNT/BoNT producing bacteria (mainly type E). The authors found a remarkable incidence of infant botulism hidden as sudden infant death. They suggest to systematically search for botulism in cases of sudden infant death. Clostridium botulinum produce botulinum neurotoxin (BoNT) which acts by blocking the neural transmission in the cholinergic synapses. Ingesting food contaminated by BoNT toxin botulismus symptom may arise, ranging from asymptomatic, mild with subtle paralysis ("failure to thrive") oder severe with generalized paralysis or sudden death may occur (Sudden Infant Death Syndrome). Fischer et al. 2004 report two cases which shows that botulism is a potential cause of unexpected infant deaths. The study of Fischer supports the Botulinum/Sudden Infant Death Syndrome hypothesis of Bhnel. [124]
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Infant botulism sudden infant death syndrome linked to ingestion of spores of Clostridium botulinum [125]
Infant botulism results of the ingestion of spores of Clostridium botulinum leading to germination of the organism and neurotoxin production in the intestine. Symptoms typically develop gradually in contrast to classical food botulism in which an acute onset of symptoms shortly after the ingestion of preformed toxin in a food is characteristic. The toxin irreversibly blocks the release of acetylcholin in the nerve synapses resulting in muscle weakness and paralysis. depending on the amount of toxin produced and may cause sudden infant death, says Bartram and Singer 2004.
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Plastic-wrapped and nonacidied silage as cattle feed increase risk of botulism [126]
Lindstrm et al 2010 report botulism outbreaks in cattle due to the use of plastic-wrapped and nonacidied silage as cattle feed. Clostridium botulinum in silage and in the gastrointestinal tract of cattle with botulism has been reported. The authors warns of human contamination with spores of Clostridium botulinum in dairy products. The standard milk pasteurization treatment does not eliminate these spores. Outbreaks in dairy products may be initiated by failures during production and lack of adequate quality control of ingredients.
22.5.58
Chronic visceral botulism from biogas plants [127]
Since the studies related to chronic botulismus were made public, the citizens living in the proximitiy of biogas plant became worried about the residue from biogas plants containing botulism bacteria which threatens domestic, wild animals and humans- chronic botulism. In the German region of Vogtland in Lower Saxony, Germany, cows diseased of what Professor Dr. Helge Bhnel of the University of Gttingen called, chronic and visceral botulism. Bhnel studied diseased cows at the farm of Hermann Bormann. These animals present chronic botulism. The researcher says that slaughterhouse waste and other meat, such as old hens, along with manure slurry, are used as raw material of biogas plants. At temperature of 400 C anaerobic bacteria, such as Chlostridium are bred. Their spores survive the hygienisation process of heating to 700 C . The waste material is used as fertilizer spreading the spores in the environment. Grazing animals ingest such spores which evolve to toxins producing bacteria in the digestive tract. The spores are spread all over the landscape as dust transported by wind and are ingested by grazing animals. Dead birds of chicken farms and slaughterhouse waste are added to the raw material of biogas plants and are excellent growth conditions for Chlostridium. Carcasses should not be used as raws material but no regulation limits "unintentional" carcasses content of raw material for biogas plants. [128]
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Study found no Chlostridium botulinum in biogas plants and their wastes [129]
Gerhard Breves of the veterinary school Hannover believes that there is no great potential risk coming from biogas plants. He found no botulismus bacteria in biogas plant contents and waste. He says that he does not want to generalise his ndings, but he considers safety risk of biogas plants as small. Chicken dunghill at chicken farms: Feathers and carcasses of birds should not be added to chicken dunghill.
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Silage: Experts urge to keep dead wild birds, small wild animals and rats out of silage as it may increase the risk of growth of Chlostridium botulinum and death of livestock. Horses are very sensitive to botulismus toxins. Therefore silage is not used as feed for horses by some animal owners. It is being recommended to avoid fertilise grass eld with liquid manure and chicken dung shortly before harvest. Dry matter should not be below 30% to avoid noxious fermentation. [130]
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Brazilian Lupinus albus protein isolates lower blood cholesterol and reduce liver steatosis in hamsters [131]
Diets from lupin protein isolate and whole lupin seed promoted a signicant reduction of total cholesterol and non-HDL cholesterol in the plasma of hamsters, as compared to a control group fed with casein. The liver revealed that animals, fed on both lupin diets, present reduced steatosis (abnormal retention of fat within the liver cels) steatosis as compared to the ones fed on casein as protein diet. Fontanari et al. 2012, authors of the study, suggest that whole lupin and its protein isolate lowers serum cholesterol and reduces the risk of hepatic steatosis.
22.5.61
Lupin protein as feed for broiler produce better meas as compared to soybean feed [132]
Laudadio et al. 2011 report that dehulled-micronised lupin meal in diet for broiler chickens provides better lipid prole and quality, with no adverse eects on productive parameters as compared to defatted soybean meal diet. Micronised-dehulled lupin (Lupinus albus L. cv. Multitalia) diet did not result in lower growth rates of chickens, nore negative eect on carcass meat was noted. However, a reduction of abdominal fat content was reported. The lupin diet reduced fat content and increased the total collagen and water-holding capacity values of the meat of the birds. Saturated fatty acid content was reduced, while total PUFA and monounsaturated fatty acids levels were increased, improving heart disease prevention factors.
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White lupin based diet produced healthier meat as obtained with sunower meal [133]
Whole white lupin (Lupinus albus cv. Amiga) seed diet (WL) was found by Volek and Marounek 2011 to contain less saturated fatty acids and polyunsaturated fatty acids (PUFAs) but more monounsaturated fatty acids than sunower meal diet. The meat of rabbits fed with whole white lupin diet presented a signicant decreased saturated fats, reduced PUFAs content, and healthier PUFA n-6/PUFA n-3 ratio and saturation, atherogenic and thrombogenic indexes as compared to rabbits fed with the sunower meal. The authors
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concluded white lupin seed diet result in healthier meat as obtained with sunower meal diet for rabbits.
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Nutritional eects on fat composition of animal products [134]
Kouba and Mourot in a review in 2011 report healthy outcomes of fatty acid composition of eggs, milk and meat in response to feed containing sh meal or linseed. The eect of these diets are stronger in monogastrics such as pigs, poultry and rabbits than in ruminants, where dietary fatty acids are hydrogenated in the rumen. The authors stress that shortterm diet manipulation is sucient to increase PUFA content of the nal product. The linseed-supplemented diets is not needed to be maintained for a long time as PUFA content of the products increase promptly.
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Lupinosis [135]
Lupinosis is a mycotoxicosis caused by the ingestion of toxins produced by the fungus Diaporthe toxica (Phomopsis leptostromiformis) which grows on lupin plants. Allen and Randall 1993 found that in addition to being an hepatotoxicity, lupinosis also resulted in injury to muscle, kidney and adrenal cortex.
22.5.65
Isolation of phomopsin the poison of lupinosis [136]
Lupinosis was rst recognised in Germany in 1872 and is being reported in the United States of America, Poland, New Zealand, Australia and South Africa. Sheep are particularly susceptible and cause high economic losses. Two metabolites of P. leptostromijormis (phomopsins A and B) have been isolated as a crystalline mixture from a culture of the fungus on lupin seed. The mixture has been shown to be capable of inducing lupinosis in sheep and in young rats.
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Varieties of lupin [137]
Lupinus angustifolius breeding has been by far the major focus in Australia. Lupinus albus and Lupinus luteus have received more attention in Europe and the former USSR but breeding of Lupinus angustifolius is increasing. The most important disease of the narrow-leaf lupin (Lupinus angustifolius) in Victoria is brown leaf spot which is caused by the fungus Pleiochaeta setosa.
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Albus lupin variety Kiev [138]
The management of sheep grazing Albus lupin (Lupinus albus) stubble is similar to those grazing narrow leafed lupins. However, the seed is almost three times bigger and consequently sheep select and eat the seed much more quickly. Albus have a higher protein and
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energy content than narrow leafed lupins. In addition, Albus varieties such as Kiev are less prone to Phomopsis infection than narrow leafed lupins. Lupin stubble paddocks provide a valuable feed source. Careful management reduces the risk of lupinosis which can cause deaths, reduced twining and conception rates at joining, weight loss, poor wool growth and pregnancy toxaemia. An outbreak of natural lupinosis in lambs in Caceres, Spain was described by Soler Rodrigues et al. in 1991. [139] Lupinosis is a result of livestock grazing lupin stems or lupin seed infected by the fungus Diaporthe toxica, formerly known as Phomopsis leptostromiformis. New lupin varieties have some resistance to the fungus, however, danger still remains as favourable conditions are likely to result in the fungus being present in all varieties. The Western Australian Department of Agriculture and Food recommends to ensure there is other more digestible feed available and stocking rates are below 15 sheep per hectare to reduce grazing pressure. This reduces the need for sheep to graze lupin stems. Livestock are removed of the pasture when the grain falls below four grains per ten square centimetres and before the green weeds run out, as lupin stubbles on their own provide poor nutrition and the risk of Lupinosis greatly increases as the animals are more likely to graze the stems. [140]
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Weather [138]
Temperature, rainfall, humidity and dew all inuence the production of toxin by the fungus. Rainfall, high humidity or consistent dews when daily maximum temperatures are about 25 C create ideal conditions for toxin production in stubble. Lupinosis most commonly occurs in the rst few days following more than 10 mm of summer rain.
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Serine-Endopeptidase specicity to twin-arginine pairs in lupin seed may be associated with germination [141]
Magni et al. 2012 describe a novel serine-endopeptidase activity with cleavage specicity to twin-arginine pairs (-R-R-) in mature dry Lupinus albus seeds. The authors suggest that the activity of the novel endopeptidase is essential for degradation at germination and generates polypeptide fragments with specic biological activity.
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Prioritization of diseases of food-producing animals [142]
Humblet et al 2012 prioritized 100 animal diseases and zoonoses in Europe using 57 prioritization criteria. The method of disease prioritization has been dened as the "organization of listed diseases into a hierarchy, considering their respective impacts". Five aspects of a pathogen were considered: epidemiology, prevention/control, eects on economy/trade,
1556 zoonotic characteristics, and eect on society.
Prioritization of diseases has acquired major interest within the past few years, especially from a prevention point of view and in the sector of public health. Such a method is needed within the context of emerging diseases because it is not known how severe socioeconomic consequences of outbreaks will be. This study included zoonoses and transmissible diseases common to humans and animals and reportable animal diseases, and involves interdisciplinary work of animal and human epidemiologists; chief veterinary ocers; experts in agricultural economics, animal welfare, and biodiversity; and experts on societal aspects of diseases. The new model presented by the authors enables adaptations (vaccination becoming available, increased knowledge of a pathogen, viral mutations or genetic reassortments increasing host specicity). It may be applied to diseases aecting domestic (dogs, cats) pets or exotic pets (reptiles). Classication of 100 diseases of food-producing animals and zoonoses into 4 subgroups Classication and regression tree analysis showing grouping of diseases of food-producing animals and zoonoses into 4 subgroups by using overall weighted scores per disease as input, Europe. A) High importance and signicant importance. B) Moderate importance and relatively low importance. See the Classication tree: http://wwwnc.cdc.gov/eid/article/18/4/111151-f2.htm
Bibliography
[1] Wikipedia. Leptospirosis. http://en.wikipedia.org/wiki/Leptospirosis. [2] CDC. Leptospirosis. leptospirosis_t.htm. http://www.cdc.gov/ncidod/dbmd/diseaseinfo/
[3] Baliga KV, Uday Y, Sood V, and Nagpal A. Acute febrile hepato-renal dysfunction in the tropics: co-infection of malaria and leptospirosis. J Infect Chemother, 2 2011. http://www.ncbi.nlm.nih.gov/pubmed/21327689. [4] http://www.defra.gov.uk/news/latest/2007/animal-0301a.htm. More: Defra, UK: Bovine TB: pre-movement testing extended to younger animals. [5] http://www.defra.gov.uk/animalh/tb/premovement/index.htm. See also: Defra: Bovine TB pages. [6] http://www.fda.gov/fdac/features/2004/504_milk.html. US FDA: Got Milk? Make Sure Its Pasteurized. FDA Consumer Magazine; September-October 2004.
BIBLIOGRAPHY [7] Enzootic bovine leukosis (ebl). DEFRA, 1 2010. foodfarm/farmanimal/diseases/atoz/ebl/.
1557 http://www.defra.gov.uk/
[8] Corredor AG, St-Louis MC, and Archambault D. Molecular and biological aspects of the bovine immunodeciency virus. Curr HIV Res., 8(1):213, 1 2010. http: //www.ncbi.nlm.nih.gov/pubmed/20210777. [9] Immediate notication report. report reference: Ebl 2010, ref oie: 10089, report date: 23/12/2010 , country: Germany. OIE, 12 2010. http://www.oie.int/wahis/ reports/en_imm_0000010089_20101223_194802.pdf. [10] Wikipedia. Feline immunodeciency virus. Feline_immunodeficiency_virus. http://en.wikipedia.org/wiki/
[11] Smith TC. Can your pet dog make you sick? multiple sclerosis and canine distemper virus. april 29, 2010. Aetiology. http://scienceblogs.com/aetiology/2010/04/ can_your_pet_dog_make_you_sick.php. [12] C ceres sb: The long journey of cattle plague. Can Vet J, 52(10):1140, 10 2011. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3174515/. [13] de Swart RL, Duprex WP, and Osterhaus AD. Rinderpest eradication: lessons for measles eradication? Curr Opin Virol, 2(3):3304, 6 2012. http://www.ncbi.nlm. nih.gov/pubmed/22709518. [14] Jerey C, Mariner JC, House JA, Mebus CA, Sollod AE, Chibeu D, Jones BA Roeder PL, Admassu B, and van t Klooster GGM. Rinderpest eradication: Appropriate technology and social innovations. Science, 337(6100):13091312, 9 2012. http: //www.sciencemag.org/content/337/6100/1309. [15] Furuse Y, Suzuki A, and Oshitani H. Origin of measles virus: divergence from rinderpest virus between the 11th and 12th centuries. Virol J, 4(7):52, 3 2010. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2838858/. [16] "schmallenberg" virus: likely epidemiological scenarios and data needs. efsa 6 feb 2012. http://www.efsa.europa.eu/en/supporting/pub/241e.htm. [17] Evidence for presence of a new virus in cattle in germany. friedrich-loeerinstitut (i). press release 21 nov 2011. http://www.fli.bund.de/no_cache/en/ startseite/press-releases/presse-informationsseite/Pressemitteilung/ evidence-for-presence-of-a-new-virus-in-cattle-in-germany.html. [18] Efsa publishes report on likely scenarios for spread of "schmallenberg" virus in ruminants. efsa 8 feb 2012. http://www.efsa.europa.eu/en/press/news/120208.htm? WT.mc_id=EFSAHL01&emt=1.
1558
[19] Schmallenberg virus. current information on "schmallenberg virus". friedrich-loeer-institut.14th feb 2012. http://www.fli.bund. de/en/startseite/current-news/animal-disease-situation/ new-orthobunyavirus-detected-in-cattle-in-germany.html. [20] Schmallenberg virus: Distribution of virus samples, information on virus genome and protocol for genome detection. friedrich-loeer-institut (i). 10 jan 2012. http://www.fli.bund.de/fileadmin/dam_uploads/tierseuchen/ Schmallenberg_Virus/FLI_Information_Schmallenberg-20120110.pdf. [21] Gain: Schmallenberg virus found in cattle. 30 jan 2012. http://gain.fas.usda. gov/Recent%20GAIN%20Publications/Schmallenberg%20virus%20found%20in% 20cattle_The%20Hague_Netherlands%20EU-27_1-30-2012.pdf. [22] Information of the friedrich-loeer-institut on "schmallenberg virus" (european shamonda-like orthobunyavirus) 31 jan 2012. http://www.fli. bund.de/fileadmin/dam_uploads/tierseuchen/Schmallenberg_Virus/ Schmallenberg-Virus-Factsheet-20120131-en.pdf. [23] Risk assessment: New orthobunyavirus isolated from infected cattle and small livestock - potential implications for human health. european centre for disease, prevention and control. 22 dez 2011. http://ecdc.europa.eu/en/publications/ Publications/Forms/ECDC_DispForm.aspx?ID=795. [24] Homann B, Scheuch M, Hper D, Jungblut R, Holsteg M, Schirrmeier H, and et al. Novel orthobunyavirus in cattle, europe 2011. Emerg Infect Dis, 3 2012. http: //wwwnc.cdc.gov/eid/article/18/3/11-1905_article.htm. [25] Muskens J, Smolenaars AJ, van der Poel WH, Mars MH, van Wuijckhuise L, Holzhauer M, van Weering H, and Kock P. Diarrhea and loss of production on dutch dairy farms caused by the schmallenberg virus. Tijdschr Diergeneeskd, 137(2):1125, 2 2012. http://www.ncbi.nlm.nih.gov/pubmed/22393845. [26] van den Brom R, Luttikholt SJ, Lievaart-Peterson K, Peperkamp NH, Mars MH, van der Poel WH, and Vellema P. Epizootic of ovine congenital malformations associated with schmallenberg virus infection. 137(2):10611, 2 2012. http: //www.ncbi.nlm.nih.gov/pubmed/22393844. [27] Schmallenberg virus: Recommendations as endorsed by the oie scientic commission for animal diseases on 16 february 2012 (will be updated when relevant). http://www.oie.int/fileadmin/Home/eng/Our_scientific_expertise/ docs/pdf/A_Recommendations_Schmallenberg_virus.pdf. [28] European commission: Schmallenberg virus. http://ec.europa.eu/food/animal/ diseases/schmallenberg_virus/.
BIBLIOGRAPHY
1559
[29] Risk prole humaan schmallenbergvirus. national institute of public health and the environment, bilthoven, the netherlands. 21 dez 2011. http://www.rivm.nl/ dsresource?objectid=rivmp:60483&type=org&disposition=inline. [30] Schmallenberg virus. information for farmers and vets in great britain. animal health and veterinary laboratories agency. 3 2012. http://www.defra.gov.uk/ animal-diseases/a-z/schmallenberg-virus/. [31] Ducomble T, Wilking H, Stark K, Takla A, Askar M, Schaade L, and et al. Lack of evidence for schmallenberg virus infection in highly exposed persons. germany, 2012. Emerg Infect Dis, 8 2012. http://wwwnc.cdc.gov/eid/article/18/8/12-0533_ article.htm. [32] Efsa assesses impact of schmallenberg virus in eu. efsa press release 14 jun 2012. http: //www.efsa.europa.eu/en/press/news/120614.htm?WT.mc_id=EFSAHL01&emt=1. [33] Chen Z, Zhu Y, Li C, and Liu G. Outbreak-associated novel duck reovirus, china, 2011 [letter]. EID Journal, 18(7), 2012. http://wwwnc.cdc.gov/eid/article/18/ 7/12-0190_article.htm. [34] Dias MA, Oliveira RM, Giudice MC, Netto HM, Grigorio IM Jordao LR, Rosa AR, Amorim J, Nosanchuk JD, Travassos LR, and Taborda CP. Isolation of histoplasma capsulatum from bats in the urban area of so paulo state, brazil. Epidemiol Infect, pages 13, 12 2010. http://www.ncbi.nlm.nih.gov/pubmed/21205438. [35] Michael R, McGinnis, and Stephen K. Tyring. Introduction to mycology. medical microbiology. 4th edition.galveston (tx. University of Texas Medical Branch at Galveston, 1996. http://www.ncbi.nlm.nih.gov/books/NBK8125/#3919. [36] Dietrich PY, Bille J, Fontolliet C, and Regamey C. Disseminated histoplasmosis due to histoplasma capsulatum in a patient with acquired immunodeciency syndrome (aids). Schweiz Med Wochenschr, 117(35):128996, 8 1987. http://www.ncbi.nlm. nih.gov/pubmed/3313689. [37] Wuethrich M, Gern B, Hung CY, Ersland K, Rocco N, Pick-Jacobs J, Galles K, Filutowicz H, Warner T, Evans M, Cole G, and Klein B. Vaccine-induced protection against 3 systemic mycoses endemic to north america requires th17 cells in mice. J Clin Invest, 121(2):55468, 2 2011. http://www.ncbi.nlm.nih.gov/ pubmed/21206087. [38] http://www.ncbi.nlm.nih.gov/pubmed/20462164 http://www.dpi.nsw.gov.au/ __data/assets/pdf_file/0003/323049/Brucellosis-in-pigs.pdf. Cvetni Z, Spici S, Tonci J, Majnari D, Beni M, Albert D, Thibaud M, Garin-Bastuji B: Brucella suis infection in domestic pigs and wild boar in Croatia.Rev Sci Tech. 2009 Dec;28(3):1057-67.
1560
[39] CDC. Brucellosis. http://www.cdc.gov/nczved/divisions/dfbmd/diseases/ brucellosis/brucellosis_and_hoghunters.pdf. [40] http://e20.manu.edu.mk/prilozi/1pn.pdf. Nicoletti P: Brucellosis: Present and Future. Prilozi. 2010 Jul;31(1):21-32. Past,
[41] Reuter T, Xu W, Alexander TW, Gilroyed BH, Inglis GD, Larney FJ, Stanford K, and McAllister TA. Biocontained carcass composting for control of infectious disease outbreak in livestock. J Vis Exp, 6(39):pii 1946, 5 2010. http://www.jove.com/ Details.stp?ID=1946. [42] Guan J, Chan M, Grenier C, Brooks BW, Spencer JL, Kranendonk C, Copps J, and Clavijo A. Degradation of foot-and-mouth disease virus during composting of infected pig carcasses. Can J Vet Res, 74(1):404, 1 2010. http://www.ncbi.nlm. nih.gov/pmc/articles/PMC2801310/?tool=pubmed. [43] Sakar S, Yetilmezsoy K, and Kocak E. Anaerobic digestion technology in poultry and livestock waste treatmenta literature review. Waste Manag Res, 27(1):318, 2 2009. http://www.ncbi.nlm.nih.gov/pubmed/19220987. [44] van der Poel WH, Lina PH, and Kramps JA. Public health awareness of emerging zoonotic viruses of bats: a european perspective. Vector Borne Zoonotic Dis, 6(4):31524, 2006. http://www.ncbi.nlm.nih.gov/pubmed/17187565. [45] Klug BJ, Turmelle AS, Ellison JA, Baerwald EF, and Barclay RM. Rabies prevalence in migratory tree-bats in alberta and the inuence of roosting ecology and sampling method on reported prevalence of rabies in bats. J Wildl Dis, 47(1):6477, 1 2011. http://www.ncbi.nlm.nih.gov/pubmed/21269998. [46] Megali A, Yannic G, Zahno ML, Brgger D, Bertoni G, Christe P, and Zanoni R. Surveillance for european bat lyssavirus in swiss bats. Arch Virol, 155(10):165562, 10 2010. http://www.ncbi.nlm.nih.gov/pubmed/20803042. [47] Freuling C, Grossmann E, Conraths FJ, Schameitat A, Kliemt J, Auer E, GreiserWilke I, and Mller T. First isolation of eblv-2 in germany. Vet Microbiol, 131(12):2634, 9 2008. http://www.ncbi.nlm.nih.gov/pubmed/18424021. [48] Li L, Victoria JG, Wang C, Jones M, Fellers GM, Kunz TH, and Delwart E. Bat guano virome: predominance of dietary viruses from insects and plants plus novel mammalian viruses. 84(14):695565, 7 2010. http://www.ncbi.nlm.nih. gov/pubmed/20463061. [49] Rihtaric D, Hostnik P, Steyer A, Grom J, and Toplak I. Identication of sars-like coronaviruses in horseshoe bats (rhinolophus hipposideros) in slovenia. Arch Virol, 155(4):50714, 4 2010. http://www.ncbi.nlm.nih.gov/pubmed/20217155.
BIBLIOGRAPHY
1561
[50] Foley J, Cliord D, Castle K, Cryan P, and Ostfeld RS. Investigating and managing the rapid emergence of white-nose syndrome, a novel, fatal, infectious disease of hibernating bats. Conserv Biol, 2 2011. http://www.ncbi.nlm.nih.gov/pubmed/ 21284732. [51] Wong S, Lau S, Woo P, and Yuen KY. Bats as a continuing source of emerging infections in humans. Rev Med Virol, 17(2):6791, Mar-Apr 2007. http://www. ncbi.nlm.nih.gov/pubmed/17042030. [52] Kobinger GP, Leung A, Neufeld J, Richardson JS, Falzarano D, Smith G, Tierney K, Patell A, and Weingart HM. Replication, pathogenicity, shedding, and transmission of zaire ebolavirus in pigs. Journal of Infectious Diseases, 2011. http://jid.oxfordjournals.org/content/early/2011/05/12/infdis.jir077. [53] Otranto D and Dantas-Torres F. Canine and feline vector-borne diseases in italy: current situation and perspectives. Parasit Vectors, 3(2), 1 2010. http://www.ncbi. nlm.nih.gov/pubmed/21227500. [54] Beeler E, Abramowicz KF, Zambrano ML, Sturgeon MM, Khalaf N, Hu R, Dasch GA, and Eremeeva ME. A focus of dogs and rickettsia massiliae-infected rhipicephalus sanguineus in california. Am J Trop Med Hyg, 84(2):2449, 2 2011. http://www. ncbi.nlm.nih.gov/pubmed/21292893. [55] Beati L and Raoult D. New spotted fever group rickettsia rickettsia massiliae sp. nov., a new spotted fever group rickettsia. International Journal of Systematic Bacteriology, 43(4):839840, 1993. http://ijs.sgmjournals.org/cgi/reprint/43/4/ 839.pdf. [56] Dvorakov HM and Dvorckov M. Babesiosis, a little known zoonosis. Epidemiol Mikrobiol Imunol, 56(4):17680, 11 2007. http://www.ncbi.nlm.nih.gov/pubmed/ 18072299. [57] Irwin PJ. Canine babesiosis. Vet Clin North Am Small Anim Pract, 40(6):114156, 11 2010. http://www.ncbi.nlm.nih.gov/pubmed/20933141. [58] Ramharter M, Walochnik J, Lagler H, Winkler S, Wernsdorfer WH, Stoiser B, and Graninger W. Clinical and molecular characterization of a near fatal case of human babesiosis in austria. J Travel Med, 17(6):4168, 11-12 2010. http://www.ncbi. nlm.nih.gov/pubmed/21050324. [59] Hamaguchi K, Ike K, Yamazaki Y, Morita T, and Imai S. Inuence of zinc deciency to the mice infected with babesia microti. J Vet Med Sci, 19 2010. http://www. jstage.jst.go.jp/article/jvms/advpub/0/advpub_1010050346/_article. [60] Hamaguchi K, Ike K, Yamamoto R, Morita T, and Imai S. Inuence of zinc deciency to the rats infected with babesia rodhaini. J Vet Med Sci, 71(8):10858, 8 2009. http://www.jstage.jst.go.jp/article/jvms/71/8/71_1085/_article.
1562
[61] Zygner W, Baska P, Winiewski M, and Wedrychowicz H. The molecular evidence of babesia microti in hard ticks removed from dogs in warsaw (central poland). Pol J Microbiol, 59(2):957, 2010. http://www.pjm.microbiology.pl/archive/ vol5922010095.pdf. [62] Franke J, Meier F, Moldenhauer A, Straube E, Dorn W, and Hildebrandt A. Established and emerging pathogens in ixodes ricinus ticks collected from birds on a conservation island in the baltic sea. Med Vet Entomol, 24(4):42532, 12 2010. http://www.ncbi.nlm.nih.gov/pubmed/20868431. [63] Salvagni CA, Dagnone AS, Gomes TS, Mota JS, Baldani CD Andrade G AND, and Machado RZ. Serologic evidence of equine granulocytic anaplasmosis in horses from central west brazil. Rev Bras Parasitol Vet, 19(3):13540, Jul-Sep 2010. http: //www.ncbi.nlm.nih.gov/pubmed/20943015. [64] Hildebrandt A, Pauliks K, Sachse S, and Straube E. Coexistence of borrelia spp. and babesia spp. in ixodes ricinus ticks in middle germany. Vector Borne Zoonotic Dis, 10(9):8317, 11 2010. http://www.ncbi.nlm.nih.gov/pubmed/20420533. [65] Iori A, Gabrielli S, Calderini P, Moretti A, Pietrobelli M, Tampieri MP, Galuppi R, and Cancrini G. Tick reservoirs for piroplasms in central and northern italy. Vet Parasitol, 170(3-4):2916, 6 2010. http://www.ncbi.nlm.nih.gov/pubmed/20304560. [66] Howden KJ, Geale DW, Par J, Golsteyn-Thomas EJ, and Gajadhar AA. An update on bovine anaplasmosis (anaplasma marginale) in canada. Can Vet J., 51(8):http://www.ncbi.nlm.nih.gov/pubmed/20304560, 8 2010. http://www.ncbi. nlm.nih.gov/pmc/articles/PMC2905000/?tool=pubmed. [67] Aubry P and Geale DW. A review of bovine anaplasmosis:. Transbound Emerg Dis, 58(1):130, 2 2011. http://www.ncbi.nlm.nih.gov/pubmed/21040509. [68] Stuen. Anaplasma phagocytophilum - the most widespread tick-borne infection in animals in europe. Vet Res Commun, Suppl 1:7984, 8 207. http://www.ncbi.nlm. nih.gov/pubmed/17682851. [69] Oliveira JB, Montoya J, Romero JJ, Urbina A, Soto-Barrientos N, Melo ES, Ramos CA, and Arajo FR. Epidemiology of bovine anaplasmosis in dairy herds from costa rica. Vet Parasitol, 12 2010. http://www.ncbi.nlm.nih.gov/pubmed/21236580. [70] Katargina O, Geller J, Alekseev A, Dubinina H, Efremova G, Mishaeva N, Vasilenko V, Kuznetsova T, Jrveklg L, Vene S, Lundkvist A, and Golovljova I. Identication of anaplasma phagocytophilum in tick populations in estonia, european part of russia and belarus. Clin Microbiol Infect, 1 2011. http://www.ncbi.nlm.nih.gov/pubmed/ 21199155.
BIBLIOGRAPHY
1563
[71] Ismail N, Bloch KC, and McBride JW. Human ehrlichiosis and anaplasmosis. Clin Lab Med, 30(1):26192, 3 2010. http://www.ncbi.nlm.nih.gov/pubmed/20513551. [72] Woldehiwet Z. Anaplasma phagocytophilum in ruminants in europe. Ann N Y Acad Sci, 1078:44660, 10 2006. http://www.ncbi.nlm.nih.gov/pubmed/17114753. [73] Thomas S, Popov VL, and Walker DH. Exit mechanisms of the intracellular bacterium ehrlichia. PLoS One, 5(12):e15775, 12 2010. http://www.plosone.org/ article/info%3Adoi%2F10.1371%2Fjournal.pone.0015775. [74] Hayes EB. Looking the other way: preventing vector-borne disease among travellers to the united states. Travel Med Infect Dis, 8(5):27784, 9 2010. http://www.ncbi. nlm.nih.gov/pubmed/20971437. [75] Little SE. Ehrlichiosis and anaplasmosis in dogs and cats. Vet Clin North Am Small Anim Pract, 40(6):112140, 11 2010. http://www.ncbi.nlm.nih.gov/pubmed/ 20933140. [76] Scharf W, Schauer S, Freyburger F, Petrovec M, Schaarschmidt-Kiener D, Liebisch G, Runge M, Ganter M, Kehl A, Dumler JS, Garcia-Perez AL, Jensen J, Fingerle V, Meli ML, Ensser A, Stuen S, and von Loewenich FD. Distinct host species correlate with anaplasma phagocytophilum anka gene. J Clin Microbiol, 12 2010. http: //www.ncbi.nlm.nih.gov/pubmed/21177886. [77] Ravnik U, Tozon N, Smrdel KS, and Zupanc TA. Anaplasmosis in dogs: The relation of haematological, biochemical and clinical alterations to antibody titre and pcr conrmed infection. Vet Microbiol, 10 2010. http://www.ncbi.nlm.nih.gov/ pubmed/21112165. [78] Hornok S, Micsutka A, Fernndez de Mera IG, Meli ML, Gnczi E, Tnczos B, Mangold AJ, Farkas R, Lutz H, Hofmann-Lehmann R, and de la Fuente J. Fatal bovine anaplasmosis in a herd with new genotypes of anaplasma marginale, anaplasma ovis and concurrent haemoplasmosis. Res Vet Sci, 11 2010. http: //www.ncbi.nlm.nih.gov/pubmed/21094505. [79] Imai DM, Barr BC, Daft B, Bertone JJ, Feng S, Hodzic E, Johnston JM, Olsen KJ, and Barthold SW. Lyme neuroborreliosis in 2 horses. Vet Pathol, 2 2011. http://www.ncbi.nlm.nih.gov/pubmed/21285382. [80] Savi S, Vidi B, Lazi S, Lako B, Potkonjak A, and Lepsanovi Z:. Borrelia burgdorferi in ticks and dogs in the province of vojvodina, serbia. Parasite, 17(4):35761, 12 2010. http://www.ncbi.nlm.nih.gov/pubmed/21275243. [81] Tijsse-Klasen E, Jacobs JJ, Swart A, Fonville M, Reimerink JH, Brandenburg AH, van der Giessen JW, Hofhuis A, and Sprong H. Small risk of developing symptomatic tick-borne diseases following a tick bite in the netherlands. Parasit Vectors, 4(1):17, 2 2011. http://www.ncbi.nlm.nih.gov/pubmed/21310036.
1564
[82] Poland GA. Vaccines against lyme disease: What happened and what lessons can we learn? Clin Infect Dis, 52(suppl 3):s2538, 2 2011. http://www.ncbi.nlm.nih. gov/pubmed/21217172. [83] Shen AK, Mead PS, and Beard CB. The lyme disease vaccine-a public health perspective. Clin Infect Dis, 52(Suppl 3):s24752, 2 2011. http://www.ncbi.nlm.nih. gov/pubmed/21217171. [84] Nardelli DT, Munson EL, Callister SM, and Schell RF. Human lyme disease vaccines: past and future concerns. Future Microbiol, 4(4):45769, 5 2009. http://www.ncbi. nlm.nih.gov/pubmed/19416014. [85] Masters EJ, Grigery CN, and Masters RW. Stari or masters disease: Lone star tick-vectored lyme-like illness. Infect Dis Clin North Am, 22(2):36176,vii, 6 2008. http://www.ncbi.nlm.nih.gov/pubmed/18452807. [86] Vaughn MF, Sloane PD, Knierim K, Varkey D, Pilgard MA, and Johnson BJ. Practice-based research network partnership with cdc to acquire clinical specimens to study the etiology of southern tick-associated rash illness (stari). J Am Board Fam Med, 23:7207, Nov-Dec 2010. http://www.jabfm.org/cgi/content/full/23/6/ 720. [87] Southern tick-associated rash illness. Centers for Disease Control and Prevention CDC. http://www.cdc.gov/ncidod/dvbid/stari/. [88] Assous MV and Wilamowski A. Relapsing fever borreliosis in eurasia-forgotten, but certainly not gone! Clin Microbiol Infect, 15(5):40714, 5 2009. http://www.ncbi. nlm.nih.gov/pubmed/19489923. [89] Wikipedia. Tularemia. http://en.wikipedia.org/wiki/Tularemia. [90] Komitova R, Nenova R, Padeshki P, Ivanov I, Popov V, and Petrov P. Tularemia in bulgaria 2003-2004. J Infect Dev Ctries, 4(11):68994, 11 2010. http://www.ncbi. nlm.nih.gov/pubmed/21252445. [91] OConnell HA, Rose LJ, Shams AM, Arduino MJ, and Rice EW. Chlorine disinfection of francisella tularensis. Lett Appl Microbiol, 52(1):846, 1 2011. http://www.ncbi. nlm.nih.gov/pubmed/21189486. [92] Lo N, Beninati T, Sacchi L, Genchi C, and Bandi C. Emerging rickettsioses. Parassitologia, 46(1-2):1236, 6 2004. http://www.ncbi.nlm.nih.gov/pubmed/15305700. [93] Shapiro MR, Fritz CL, Tait K, Paddock CD, Nicholson WL, Abramowicz KF, Karpathy SE, Dasch GA, Sumner JW, Adem PV, Scott JJ, Padgett KA, Zaki SR, and Eremeeva ME. Rickettsia 364d: a newly recognized cause of eschar-associated illness in california. Clin Infect Dis, 50(4):5418, 2 2010. http://www.ncbi.nlm.nih.gov/ pubmed/20073993.
BIBLIOGRAPHY
1565
[94] Wikswo ME, Hu R, Dasch GA, Krueger L, Arugay A, Jones K, Hess B, Bennett S, Kramer V, and Eremeeva ME. Detection and identication of spotted fever group rickettsiae in dermacentor species from southern california. J Med Entomol, 45(3):50916, 5 2008. http://www.ncbi.nlm.nih.gov/pubmed/18533446. [95] Gern L, Lienhard R, and Pter O. Diseases and pathogenic agents transmitted by ticks in switzerland. Rev Med Suisse, 6(266):19069, 10 2010. http://www.ncbi. nlm.nih.gov/pubmed/21089555. [96] [97] Jskelinen AE, Tonteri E, Sironen T, Pakarinen L, Vaheri A, and Vapalahti O. European subtype tick-borne encephalitis virus in ixodes persulcatus ticks. Emerg Infect Dis, 17(2):3235, 2 2011. http://www.cdc.gov/eid/content/17/2/323.htm. [98] Jskelinen AE, Sironen T, Murueva GB, Subbotina N, Alekseev AN, Castrn J, Alitalo I, Vaheri A, and Vapalahti O:. Tick-borne encephalitis virus in ticks in nland, russian karelia and buryatia. J Gen Virol, (Pt 11):270612, 11 2010. http: //www.ncbi.nlm.nih.gov/pubmed/20660147. [99] Yun SM, Kim SY, Ju YR, Han MG, Jeong YE, and Ryou J. First complete genomic characterization of two tick-borne encephalitis virus isolates obtained from wild rodents in south korea. Virus Genes, 2 2011. http://www.ncbi.nlm.nih.gov/ pubmed/21286797. [100] WHO. Rift valley fever. fact sheet nr 207. WHO Media Centre, 2010. http://www. who.int/mediacentre/factsheets/fs207/en/. [101] Turell MJ, Dohm DJ, Geden CJ, Hogsette JA, and Linthicum KJ. Potential for stable ies and house ies (diptera: Muscidae) to transmit rift valley fever virus. J Am Mosq Control Assoc, 26(4):4458, 12 2010. http://www.ncbi.nlm.nih.gov/ pubmed/21290943. [102] Chapman DAG, Darby AC, Da Silva M, Upton C, Radford AD, and Dixon LK. Genomic analysis of highly virulent isolate of african swine fever virus. Emerg Infect Dis, 4 2011. http://www.cdc.gov/eid/content/17/4/pdfs/10-1283.pdf. [103] Scientic opinion on african swine fever. EFSA Journal, 8(3):1556(149pp.), 2010. http://www.efsa.europa.eu/en/efsajournal/pub/1556.htm. [104] Yeh JY, Kim HJ, Nah JJ, Lee H, Kim YJ, Moon JS, Cho IS, Choi IS, Song CS, and Lee JB. Surveillance for west nile virus in dead wild birds, south korea, 2005-2008. Emerg Infect Dis, 17(2):299301, 2 2011. http://www.cdc.gov/eid/content/17/ 2/299.htm.
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[105] Stock I. Chikungunya fever-expanded distribution of a re-emerging tropical infectious disease. Med Monatsschr Pharm, 32(17-26):1, 1 2009. http://www.ncbi.nlm.nih. gov/pubmed/19205134. [106] Ho K, Ang LW, Tan BH, Tang CS, Ooi PL, and James L. Epidemiology and control of chikungunya fever in singapore. J Infect, 2 2011. http://www.ncbi.nlm.nih. gov/pubmed/21315108. [107] Pleadin J, Vuli A, Persi N, and Vahci N. Clenbuterol residues in pig muscle after repeat administration in a growth-promoting dose. Meat Sci, 86(3):7337, 11 2010. http://www.ncbi.nlm.nih.gov/pubmed/20667663. [108] Wada seeks tainted beef info from china. 24.12.2011. China Post. http://www. chinapost.com.tw/china/national-news/2011/02/24/292293/WADA-seeks.htm. [109] Liu C, Ling W, Xu W, and Chai Y. Simultaneous determination of 20 beta-agonists in pig muscle and liver by high-performance liquid chromatography/tandem mass spectrometry. J AOAC Int, 94(2):4207, Mar-Apr 2011. http://www.ncbi.nlm. nih.gov/pubmed/21563674. [110] Eudmar Marcolino de Assis Junior, Ismael Malaquias dos Santos Fernandes, Caio Srgio Santos, Luciene Xavier de Mesquita, Rogrio Aparecido Pereira, Patrcio Borges Maracaj, and Benito Soto-Blanco. Brazil- toxicity of castor bean (ricinus communis) pollen to honeybees. Agriculture, Ecosystems and Environment, 141(1-2):221223, 4 2011. http://www.apinews.com/en/news/item/ 14684-brasil-toxicity-of-castor-bean--ricinus-communis--pollen-to-honeybees. [111] Honey containing gm needs approval before sale. european voice. 09.02.2011.. http://www.europeanvoice.com/article/2011/february/ honey-containing-gm-needs-approval-before-sale/70185.aspx. [112] Das deutsche gentechnikrecht. bundesministerium fr ernhrung, landwirtschaft und verbraucherschutz. http://www.bmelv.de/SharedDocs/Standardartikel/ Landwirtschaft/Pflanze/GrueneGentechnik/Gentechnikrecht.html. [113] Honig. unverkuich durch gen-tech-pollen? kotest. kotest. http://www. oekotest.de/cgi/index.cgi?artnr=10967;gartnr=90;bernr=04;co=. [114] Honey and food supplements containing pollen derived from a gmo are foodstus produced from gmos which cannot be marketed without prior authorisation. court of justice of the european union. press release no 79/11 luxembourg, 6 september 2011. http://curia.europa.eu/jcms/upload/docs/application/pdf/2011-09/ cp110079en.pdf.
BIBLIOGRAPHY
1567
[115] Eu bans gm-contaminated honey from general sale.07 sep 2011. bavarian beekeepers forced to declare their honey as genetically modied because of contamination from nearby monsanto crops. The Guardian. http://www.guardian.co.uk/ environment/2011/sep/07/europe-honey-gm. [116] Memo/11/451 date 24/06/2011 europa rapid press. pressReleasesAction.do?reference=MEMO/11/451. http://europa.eu/rapid/
[117] Wikileaks: Us targets eu over gm crops the guardian. 03 jan 2011. http://www.guardian.co.uk/world/2011/jan/03/ wikileaks-us-eu-gm-crops%20and%20http:/www.grist.org/article/ 2010-11-29-wikileaks-state-dept-wants-intel-on-african-acceptance-of-gmos. [118] Us asks turkey to change gmo regulation, daily says daily news 29 november 2011. http://www.hurriyetdailynews.com/n.php?n= us-asks-turkey-to-change-gmo-regulation-daily-says-2011-11-08. [119] The uk needs a labelling scheme for gm-free meat products. http://www.guardian. co.uk/environment/blog/2011/feb/10/labelling-gm-meat. [120] Peru bans gmo. http://www.capitalfm.co.ke/news/2011/11/ perus-congress-approves-10-year-gmo-ban/. [121] Gates foundation "swimming against a tide of informed opinion" 31 oct 2011. http: //www.gmfreeze.org/news-releases/170/. [122] Bhnel H, Schwagerick B, and Gessler F. Visceral botulism - a new form of bovine clostridium botulinum toxication. J Vet Med A Physiol Pathol Clin Med, 48(6):373 83, 8 2001. http://www.ncbi.nlm.nih.gov/pubmed/11554495. [123] Bhnel H, Behrens S, Loch P, Lube K, and Gessler F. Is there a link between infant botulism and sudden infant death? bacteriological results obtained in central germany. Eur J Pediatr, 160(19):6238, 10 2001. http://www.ncbi.nlm.nih.gov/ pubmed/11686509. [124] Fischer D, Freislederer A, and Jorch G. Sudden death of twins: botulism because of contamination by pap vegetables. Klin Padiatr, 216(1):315, Jan-Feb 2004. http: //www.ncbi.nlm.nih.gov/pubmed/14747969. [125] Bartram U and Singer D. Infant botulism and sudden infant death syndrome. Klin Padiatr, 216(1):2630, Jan-Feb 2004. http://www.ncbi.nlm.nih.gov/pubmed/ 14747968. [126] Lindstrm M, Myllykoski J, Sivel S, and Korkeala H. Clostridium botulinum in cattle and dairy products. Crit Rev Food Sci Nutr, 50(4), 4 2010. http://www. ncbi.nlm.nih.gov/pubmed/20301016.
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[127] Botulismus: Wie gefhrlich ist hhnertrockenkot? ndr 06 feb 2012. http://www. ndr.de/regional/botulismus115.html. [128] Botulismus krank durch biogas. ein gesprch mit dem tiermediziner und agrarwissenschaftler professor helge bhnel dradio. 09.06.2011. http://wissen.dradio.de/ botulismus-krank-durch-biogas.35.de.html?dram:article_id=10587. [129] Von biogasanlagen geht keine botulismus-gefahr aus. 13 dez 2011. Fleckvieh, 1, 12 2011. http://fleckvieh.agrarheute.com/tiergesundheit/von_ biogasanlagen_geht_keine_botulismus-gefahr_aus.html?redid=466592. [130] Botulismus. ballensilage. com. grundlagen_botulismus.html. http://www.ballensilage.com/dateien/
[131] Fontanari GG, Batistuti JP, da Cruz RJ, Saldivan PHN, and Are as JAG. Cholesterol-lowering eect of whole lupin (Lupinus albus) seed and its protein isolate, 132(3):15211526, 6 2012. http://www.sciencedirect.com/science/article/ pii/S0308814611017602. [132] Laudadio V and Tufarelli V. Dehulled-micronised lupin (lupinus albus l. cv. multitalia) as the main protein source for broilers: inuence on growth performance, carcass traits and meat fatty acid composition. J Sci Food Agric, 91(11):20817, 8 2011. http://www.ncbi.nlm.nih.gov/pubmed/21520452. [133] Volek Z and Marounek M. Eect of feeding growing-fattening rabbits a diet supplemented with whole white lupin (lupinus albus cv. amiga) seeds on fatty acid composition and indexes related to human health in hind leg meat and perirenal fat. Meat Sci, 87(1):405, 1 2011. http://www.ncbi.nlm.nih.gov/pubmed/20864262. [134] Kouba M and Mourot J. A review of nutritional eects on fat composition of animal products with special emphasis on n-3 polyunsaturated fatty acids. Biochimie, 93(1):13, 1 2011. http://www.ncbi.nlm.nih.gov/pubmed/20188790. [135] Allen JG and Randall AG. The clinical biochemistry of experimentally produced lupinosis in the sheep. Aust Vet J, pages 2838, 8 1993. http://www.ncbi.nlm. nih.gov/pubmed/8216093. [136] Culvenor CC, Beck AB, Clarke M, Cockrum PA, Edgar JA, Frahn JL, Jago MV, Lanigan GW, Payne AL, Peterson JE, Petterson DS, Smith LW, and White RR. Isolation of toxic metabolites of phomopsis leptostromiformis responsible for lupinosis. Aust J Biol Sci, 30(4):26977, 8 1977. http://www.publish.csiro.au/?act=view_ file&file_id=BI9770269.pdf. [137] Lupins.org:information resource portal for lupins. production/.
http://www.lupins.org/
BIBLIOGRAPHY
1569
[138] 13 lupinosis. http://www.agric.wa.gov.au/OBJTWR/imported_assets/content/ fcp/lp/lup/lupins/Lupinbulletinch13.pdf. [139] Soler Rodriguez F, Miguez Santiyan MP, Pedrera Zamorano JD, and Roncero Cordero V. An outbreak of lupinosis in sheep. Vet Hum Toxicol, 33(5):4924, 10 1991. http://www.ncbi.nlm.nih.gov/pubmed/1746145. [140] Lupinosis is a risk to stock. the rural 03 feb, 2011. http://www.therural.com.au/ news/local/news/general/lupinosis-is-a-risk-to-stock/2066118.aspx. [141] Magni C, Sessa F, Tedeschi G, Negri A, Scarafoni A, Consonni A, and Duranti M. Identication in lupin seed of a serine-endopeptidase activity cleaving between twin arginine pairs and causing limited proteolysis of seed storage proteins. Mol Plant, 1 2012. http://www.ncbi.nlm.nih.gov/pubmed/22217442. [142] Humblet MF, Vandeputte S, Albert A, Gosset C, Kirschvink N, Haubruge E, FecherBourgeois F, Pastoret PP, and Saegerman C. Multidisciplinary and evidence-based method for prioritizing diseases of food-producing animals and zoonoses. Emerg Infect Dis, 18(4), 4 2012. http://wwwnc.cdc.gov/eid/article/18/4/11-1151_ article.htm.
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Chapter 23 Colony Collapse Disorder (CCD)

Colony Collapse Disorder (CCD) is a poorly understood phenomenon involving the massive die-o of a beehive or bee colony. CCD is alternatively referenced as Vanishing Bee Syndrome (VBS). CCD was originally found only in colonies of the West honey bee in North America, but European beekeepers have recently claimed to be observing a similar phenomenon in Poland, Greece, Italy, Portugal and Spain, Switzerland and Germany. From 1971 to 2006 approximately half of the U.S. honey bee colonies have vanished. [1]
23.1
Causes of Colony Collapse Disorder
The cause (or causes) of the syndrome is not yet well understood and even the existence of this disorder remains disputed. Theories include environmental change-related stresses, malnutrition, unknown pathogens, mites (Varroa mites), pesticides such as neonicotinoids, emission from cellular phones or other man made devices, and genetically modied crops. This set of symptoms has in the past several decades been given many dierent names (disappearing disease, spring dwindle, May disease, autumn collapse, and fall dwindle disease).
23.1.1
No single factor or agent of Colony Collapse Disease found, researchers suggest a combination of parasites, pathogens and pesticides as primary cause [2]
No single factor or agent emerged as a denitive cause of the phenomenon. The best hypothesis is that particular virulent combination of parasites and pathogens may interact to produce lethal consequences to the colonies in an environmental context of chronic exposure to pesticides.
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CHAPTER 23. COLONY COLLAPSE DISORDER (CCD)
23.1.2
Network to study causes of CCD and genomic response of bees [3]
A network of eleven countries (BEE DOC) was created in 2010 to study the eects of multiple infections and pesticides at individual bee level and at colony level. will specically address sublethal and chronic exposure to pesticides and screen how apicultural practices aect colony health. It will tackle genomic responses towards the most important factors identied, help to prevent diseases emergence via disease resistance features, develop diagnostic tools including tools to be used at eld level and focus on innovative ways of prevention and control addressing the multi-factorial causes of colony death.
23.1.3
A sticky paper to ght varroa mite [4]
Je Pettisan entomologist from the USDA Agricultural research Service, Maryland says that varroa mite infestations have become such a serious problem that maintaining bee colonies without chemical treatment is virtually impossible. Apistana strip that contains the chemical tau-uvalinate is being used. Varroa, however, have begun to show resistance to the chemical. Pettisan, looking for alternatives, introduced a sticky paper which is located beneath the hive bottom. Mites get stick to the paper and can be removed from the hive. As safe and eective chemical controls continue to be researched and developed, the sticky paper will complement Apistan in assisting beekeepers with the control of invading varroa. Other causes of the Colony Collapse Disorder, according to Pettisan, may be an unknown virus, Bacteria, pesticides or a combination of these causes.
23.1.4
Genetic causes
The honey bee has a reduced number of genes which express resistance to toxics and diseases, compared with the genetic code of the fruit ies and ants. According to May Berenbaum from the University of Illinios this could make the bees more vulnerable to toxics and diseases. Berenbaum caled for improving genetic stocks of bees. He stressed the fact that supplies of animal-pollinated foods - most fruit, vegetable, and nut crops, which provide the bulk of vitamins and other necessary nutrients in our diets - may well be dramatically aected in case of further losses of hives. [5]
23.1.5
Decline of honeybee populations [6]
Honeybee decline is thought to be caused by a combination of factors like climate change, parasites (like the varroa mite), diseases, overexposure to pesticides and the loss of suitable habitat. Dr Dave Chandler examines naturally occurring fungi that kill the varroa mite. Varroa destructor, formerly V. jacobsoni feed on the circulatory uid of honey bee pupae
23.1. CAUSES OF COLONY COLLAPSE DISORDER
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and adult bees, activate and transmit diseases, reducing bee life expectancy and causing the colony to decline. Presently, the control of varroa is based on the use of chemical pesticides. To avoid growing mite resistance, biological control technologies, such as fungus which kill the varroa mite, could oer an alternative pest management strategy of varroa, but had a low impact on the bees and worked in the warm and dry conditions typically found in bee hives and nd the best ways of applying this weapon across the hive. This includes fungal footbaths at the main entrance to hives and powder spays.
23.1.6
Other mite control systems [7]
Fluvalinate (Apistan strips): Fluvalinate is the active ingredient of Apistan strips. It is a synthetic pyrethroid applied as a contact miticide. Coumaphos(CheckMite+ strips): Coumaphos is the active ingredient of CheckMite+ strips. The product is an organophosphate, applied as a contact miticide. Sugar esters: Sugar esters (Sucrocide) in spray application Formic Acid: Formic acid is eective against Varroa and tracheal mites (Acarapis woodi). Oxalic Acid: Oxalic acid (Oxalic acid dihydrate) should only be applied in late fall when the colony has no brood. Non Chemical Control: Traps and oils. Diana Cox-Foster and colleagues 2007 reported a correlation between colony collapse disease and the presence of Israeli acute paralysis virus (IAPV), a highly pathogenic virus. According to Cox-Foster infected bees present paralytic-type movements and die. The researcher say, however, that the virus may not be the the sole cause of CCD, and additional stresses are needed to trigger the disease. [8] A variety of environmental chemicals such as pesticides, found on pollen, wax, adult bees and brood may be such a trigger. [9]
23.1.7
Modied protein production found as primary cause of colony collapse disorder (CCD) [10]
Colony collapse disorder (CCD) made one third of US honey bees to disapear in late 2006. The researchers linked pathogens and other environmental stresses, including pesticides to the disease. However, a convincing causal relationship could not be presented. Berenbaum and colleagues 2009 studied the gene expression of bees sampled before CCD spread, and compared it with bees from CCD colonies. The researchers found 65 transcripts as potential markers for CCD status. The unusual ribosomal RNA fragments are possible remnants of picorna-like viral infection, including deformed wing virus and Israeli acute paralysis virus. Ribosomals are cell
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structures which produce proteins. The authors speculate that viruses invaded the ribosomes resulting in heavy alterations in protein synthesis in CCD colonies. Impaired protein production reduces resistance to pesticides, fungus or bacteria infections or even malnutrition. The authors propose that these unusual ribosomal fragments establish a link to other suggested causes of CCD. These RNA fragments are the primary cause which open the door to other factors of the disease. Ribosomal fragment abundance and presence of multiple viruses are being suggested by the authors as diagnostic markers of CCD.
23.1.8
Increasing toxicity of miticides [11]
According to Berenbaum and colleagues honey bee mortality may occur when tau-uvalinate and coumaphos are simultaneously present in the hive. Both varroa mite miticides the organophosphate coumaphos (Checkmite+), and the pyrethroid tau-uvalinate (Apistan) are lipoohilic and build up in wax structures of the hive. Honey bees may thus become exposed to both miticides as a result of repeated treatments. The authors found a large increase in the toxicity of tau-uvalinate in hives when coumaphos have been used before. This synergism was less accentuated whit treatment of coumaphos followed tau-fulvinate. The authors stress that the detoxication of the miticides is mediated by cytochrome P450 monooxygenase enzymes (P450s). A competition between both chemicals for access to detoxicative P450s may cause rising toxicity which would not be lethal when only one of the chemicals is present.
23.1.9
Symptoms of Colony Collapse Disorder [12]
Jerry Bromenshenk from Montana describes the signs of the disorder as follows: Colony Collapse Disorder (CCD) is the latest problem facing bee keepers today. Symtoms of CCD are: 1) In collapsed colonies The complete absence of adult bees in colonies, with no or little build up of dead bees in the colonies or in front of those colonies. The presence of capped brood in colonies. The presence of food stores, both honey and bee bread i.which is not immediately robbed by other bees ii.when attacked by hive pests such as wax moth and small hive beetle, the attack is noticeably delayed. 2) In cases where the colony appear to be actively collapsing
23.1. CAUSES OF COLONY COLLAPSE DISORDER An insucient workforce to maintain the brood that is present. The workforce seems to be made up of young adult bees. The queen is present.
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The cluster is reluctant to consume provided feed, such as sugar syrup and protein supplement. Jerry Bromenshenk is a member of a team of researchers studying the disorder. He developed a questionnaire, "National Bee Loss Survey" which can be found at http://www.beesurvey.com/
23.1.10
Nosemosis is one of the most widespread of the adult honey bee diseases [13]
The honeybee, Apis mellifera, is undergoing a worldwide decline. It is being suggest that the worldwide decline of honeybee colonies may caused by infectious diseases together with exposure to pesticides. Vidau et al. 2011 determined the sensitivity to sublethal doses of the insecticides pronil and thiacloprid of Nosema ceranae infected honeybee colonies. A signicant increase in honeybee mortality was observed when Nosema ceranae-infected honeybees were exposed to sublethal doses of insecticides. The authors concluded that the combination of increasing infections by Nosema ceranae together with high pesticide exposure may increase honeybee colony losses. Neonicotinoid insecticides linked to honeybee Colony Collapse Disorder [14] Bee populations are on decline, such phenomena is known as Colony Collapse Disorder. Goulson et al.2012 believes that neonicotinoid imidacloprid insecticides are linked to the decline as they occur at trace levels in the nectar and pollen of crop plants. The researchers exposed colonies of the bumble bee Bombus terrestris to neonicotinoid imidacloprid, observing reduced growth rate and an 85% reduction in production of new queens compared to control colonies. Imidacloprid insecticides are used worldwide to treat seeds such as rapeseed. During the growth of the plant, traces of the insecticide is carried to the owers of the plant. Bees get there in contact with the poison. Microsporidia Nosema spp. infections in Chinese bumblebees [13] Li et al 2012 report that 6,1% of Chinese bumblebees (Bombus spp.) were infected by microsporidia, notably Nosema bombi, Nosema ceranae, Nosema thomsoni, and four new putatively novel taxa: Nosema A, Nosema B-complex, Nosema C-complex and Nosema D-complex. Bumblebees are important pollinators of many economically important crops, and microsporidia infection is the most frequent disease of this important insect.
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Microsporidia are restricted to animal hosts, and all major groups of animals host microsporidia. Most infect insects, but they are also responsible for common diseases of crustaceans and sh. The distinguished species of microsporidia usually infect one specic host or a related group of hosts. Several species, most of which are opportunistic, also infect humans. [15] Energetic stress may explain Nosema spp. pathology in infected bees [16] According to Martn-Hernndez et al. 2011 Nosema ceranae is a relatively new parasite which causes a more virulent disease compared to Nosema apis infecting the honeybee for much longer. Both are obligate intracellular microsporidian parasites, consuming energy of the host. This causes an energetic stress increasing virulence observed. Caged bees, infected by Nosema ceranae presente higher mortality and sugar syrup consumption compared with those infected by Nosema apis. This was directly related to spore counts administered for infection. Dierences between both microsporidia depend on host-parasite interactions and increased energetic stress may even explain the changes in host behaviour, explained the authors. The authors report a higher prevalence of Nosema ceranae indicating advantage in the competition over Nosema apis. This may result of a better adaption to Spanish conditions. However both microsporidia may prevail in the dierent Spanish bioclimatic regions. [17] Sample size and time of collection aect results of Nosema diagnosis [18] Botas et al.2011 call for an accurate and reliable method to evaluate the presence of Nosema in honey bee. The authors stress that both sample size and the time of collection (month and day of sampling) notably aect the diagnosis. Traver, Williams and Fell 2011 studied honeybee colony infection by Nosema ceranae during the seasons. They found that all bees sampled were infected with Nosema ceranae, and colony infection levels were the highest in April-June and lowerest in the fall and winter. [19] Deformed Wing Virus and Varroa destructor causes honeybee losses during Winter in Switzerland [20] Dainat et al.2011 assessed the results of dierent pathogens as cause of winter losses of managed honey bee colonies in Zwitzerland. The authors found that Varoa destructor and deformed wing virus reduce the life span of winter bees, and can be considered as possible mechanism for honeybee colony losses. However, neither Nosema ceranae nor acute bee paralysis virus did correlated with longevity. Expression levels of the vitellogenin gene, as a biomarker for honey bee longevity gene expression, was signicantly positively correlated with acute bee paralysis virus and Nosema ceranae loads.
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Queen replacement to compensate for Nosema infection of a honeybee colony [21] Queen replacement reduces signicantly the rates of Nosema infection, comparable to fumagillin treatment, say Botas and colleagues 2011. The authors explain that younger queens lay high amount of eggs which compensates losses due to infections and production of not infected eggs. However, detrimental eects of stressors such as the queenless condition, lack of brood and high infection rates were noted. The ovaries and ventriculi of queens in infected colonies were not altered by Nosema infection. Honeybee glands as infection reservoirs of Nosema [22] Copley and Jabaji monitored the spore presence of Nosema ceranae and Nosema apis in dierent gland tissues (thoracic salivary, hypopharyngeal, mandibular glands, and venom sac and glands) of Canadian honeybees. The authors found both Nosema species present in all the glands as single or mixed species, and their seasonality in the dierent glands tightly followed the seasonal patterns in the honeybee guts. The authors concluded that these Nosema species are not tissue specic, and samples of honeybee glands may be used to determine the extent of disease in the colony. Honeybee glands are seen as an infection reservoir. Nosema ceranae is a microsporidian parasite known to infect Asian honey bee, Apis cerana, cross-infecting the European honey bee, Apis mellifera. Fries 2010 writes that the parasite seems to replace Nosema apis in some populations of European honey bees, despite their spores being less durable than those of N. apis, and its impact diers in dierent environments. [23] Nosema ceranae may cause honey bee Colony Collapse Disorder (CCD) in Spain [24] Higes and colleagues 2009 report that the depopulation in two Spanish colonies known as colony collapse disorder (CCD) were due to the infection by Nosema ceranae (Microsporidia), an emerging honeybee pathogen. No other signicant pathogens or pesticides (neonicotinoids) were detected and the bees had not been foraging in corn or sunower crops. The treatment with fumagillin avoided the loss of surviving weak colonies. The microsporidia are spore-forming unicellular parasites, infesting insects crustaceans, sh and vertebrates, including in humans. Some species produce deadly infections ans some are even used as biological control of insects pests. Colony collapse disorder (or CCD) is a phenomenon in which worker bees from a beehive colony abruptly disappear. Honeybees are important pollinators of crops. The eastern hive bee Apis cerana, were found to be infected by Nosema apis and the western hive bee Apis mellifera is susceptible to Nosema ceranae.
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According to Professor Fries Nosema ceranae diers in their ultrastructure and genetics from Nosema apis. Paxton writes that Nosema ceranae jumped host from Apis cerana to Apis mellifera within the last decade. It is found nowadays in the western honey bee in North and South America, the Caribbean, across Europe and Asia [25] Possible causes of CCD were cited such as Varroa mites and insect diseases including Nosema apis and Israel acute paralysis virus, environmental change-related stresses,malnutrition and pesticides, and migratory beekeeping. Other unproved causes were cited, such as cell phone radiation and genetically modied (GM) crops used to control pests. Some researchers suggest that the combination of many factors may naly be the cause of the disease.
23.1.11
Bee disease spreads to wild bumble bees [26]
Otterstatter and Thomson in 2008 suggests that a disease caused by Crithidia bombi (a trypanosome parasite) is being spread to wild bumble bees from commercially reared bumble bees used to pollinate greenhouse crops. The Colony Collapse Disorder (CCD) of commercial bees is somehow spreading to wild bumble bees which suer serious declines. Bees are important to pollinate greenhouse crops. Commercial bumble bees are used to pollinate tomato bell pepper, almond and a lot of berries. Infection with Crithidia bombi causes the bees to loose their ability to distinguish between owers that contain nectar and those that dont. They make many mistakes by visiting nectar scarce owers and in so doing, slowly starve to death. Commercially bred bees are used in greenhouses, to pollinate, for example, tomatoes and these bees typically harbour this parasite, while wild bees do not. It is believed that the commercial bees transmitted the parasite to wild populations in some cases. they escape from the greenhouses through vents and a simple mesh could help prevent their escape. [27] On a study in 2007 Otterstatter and Thomson found that within colonies, a bees rate of contact with infected nestmates emerged as the only signicant predictor of infection risk. The authors stress that the activity of bees, in terms of their movement rates and division of labour (e.g., brood care, nest care, foraging), do not inuence risk of infection. [28] The authors predict that the spread of C.bombi from the population of greenhouses will spread to all wild bumble bee species (Bombus spp.). A remarkably high degree of genetic diversity of C. bombi among infections was found by Schmid-Hempel and Funk 2004. The authors suggest that genetic diversication of the population of C.bombi results from strong genotypic host-parasite interactions. [29] To control the disease the authors suggest improved management of domestic bees, such as the reduction of the parasite loads and the contact with wild bees.
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23.1.12
High pathogen loads in collapsed honeybee colonies [30]
The winter of 2006/2007 and 2007/2008 were marked by large-scale unexplained losses of honey bee colonies. These losses of colonies were named Colony Collapse Disorder (CCD). Vanengelsdorp and colleagues 2009 believe that CCD involves an interaction between pathogens and other stress factors. The researchers found higher loads and greater number of pathogens in CCD colonies than in healthy populations. The authors write that an increased exposure to pathogens or a reduced resistance of bees toward pathogens may be the cause of the disease. Analysis of samples of adult bees, wax comb, pollen and brood the presence of parasites such as varroa and tracheal mites; infection by bacteria, viruses and fungi; pesticide levels; nutritional factors; and bee physiology could not specify a single factor as cause of CCD.
23.1.13
Pesticiddes
In this study no association between increased pesticide levels and CCD was found. In fact higher levels of the acaricide coumaphos and the pyrethroid insecticide Esfenvalerate were found in healthy colonies, compared with CCD-aected colonies. The authors suggest that the condition may be contagious or the result of exposure to a common risk factor impairing the immune systems of the bees. The higher pathogen loads are likely to have caused CCD symptoms, however, the cause of the high number of pathogens found in the aected colonies remains unknown causes the bees to become infected with so many pathogens is still not known. The authors add that it seems that pathogens play a secondary role in the development of the disease, with evidence that the condition is contagious or the result of exposure to a common risk factor. Further attention on monitoring parasite, pathogen and pesticide loads, as well as potential interactions among pesticide and pathogen loads are being suggested by the authors.
23.1.14
Bee Mortality and Bee Surveillance in Europe EFSA Report [31]
The EFSA in a 2009 report on Colony Collapse Disorder says that their review of relevant literature clearly highlights an absence of shared epidemiological indicators, common surveillance procedures and comparable populations. Trend analysis and mapping suggests some periods of higher colony loss rates, but these ndings should not be over interpreted. The FSA notes that there is a consensus amongst the scientic community that the causes of colony losses in Europe and in the United States are likely to be multifactorial (in the
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two aspects of this term: combination of factors at one place and dierent factors involved according to place and period considered). Factors implicated include beekeeping and husbandry practices (feeding, migratory beekeeping, treatments and so forth), environmental factors (climate, biodiversity, etc.), chemical factors (pesticides) or biological agents (Varroa, Nosema, etc.) which together create stress, weaken bees defense systems allowing pests and pathogens to kill the colony (e.g. one or several parasites, viruses, etc.). High concentrations of pesticides have rarely been identied in relation to colony losses (CCD in USA and winter colony losses in Europe) although acute events of pesticide toxicity are well described during the production season (and clearly dierentiated from CCD and winter colony losses). However, the questions of possible synergistic eects of various pesticides and the eect of chronic exposure to sublethal doses of pesticides remains, and requires further investigation. Biological agents such as parasites, viruses or bacteria, alone or in combination, have clearly been identied as important factors in colony losses. Nevertheless, there is still a lack of knowledge about the exact mechanisms and/or interactions involved, this must also be addressed. Even though the multifactorial origin of colony losses is well acknowledged, the respective role of each factor as a risk or causative agent is unknown, and no hierarchy of relative threat posed by each one has been established. There are many inconsistencies in the ways in which "colony losses" are dened, leading to confusions when reports not always refer to the same phenomenon.
23.1.15
European tool to monitor colony losses
The EFSA call for an appropriate tool to monitor colony losses at a European level which may provide accurate gures about colony mortality which, in turn could focus control and research activities. - Implementation of a sustainable European network for coordination and follow-up of surveillance, and research on colony losses to underpin monitoring programmes; - Strengthen standardization at European level by harmonization of surveillance systems, data collected and by developing common performance indicators; - Build on the examples of best practice found in existing surveillance systems on communicable and notiable diseases already present in some countries; - Undertake specic studies that build on the existing work in progress to improve the knowledge and understanding of factors that aect bee health (for example stress caused by pathogens, pesticides, environmental and technological factors and their interactions) using appropriate epidemiological studies (case control and longitudinal studies); - The set up of the coordination team at European level. This is a crucial issue and
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the coordination team should be organized in such a way so as to ensure its sustainability and to enable eective surveillance programme activities at the European level.
23.1.16
Viral infections of bees implicated in Colony Collapse Disorder [32]
Cox-Foster and colleagues 2010 found that native pollinators, like wild bees and wasps, are infected by the same viral diseases as honey bees and that these viruses are transmitted via pollen. The scientists suspect that RNA viruses are a major contributors to Colony Collapse Disorder (CCD). RNA viruses such as deformed wing virus, sacbrood virus and black queen cell virus were detected in pollen pellets collected by bees. The detection of RNA viruses in other pollinators, including bumble bees, solitary bees and wasps, suggests that viruses might have a deep impact on ecosystem health. The authors stress that pollen is currently being imported into many countries to feed honey bees used in agricultural pollination, increasing the risk of a wide spread of Colony Collapse Disorder.
23.1.17
Fly larvae causes honeybee colony losses in North America [33]
According to John Hafernik, y parasite Apocephalus borealis, found in honey bee hives in California and South Dakota, may be one cause of colony collapse disorder (CCD) and may easily spread to honey bee colonies throughout North America The y deposits its eggs into a bees abdomen which dies. After being parasitized by the y, the bees abandon their hives at night in search for lights, walking around in circles, often with no sense of direction unable to stand up on their legs and dies. About seven days the y larvae leaves the dead bee. The authors of the study stress that the fungus Nosema ceranae and the deformed wing virus can often also be found infecting both bees and ies. Other studies found that the fungus and the virus are implicated in CCD. Hive abandonment is the primary characteristic of the disorder. The authors write that the parasite may disturb the normal day-night rhythm of the bees, causing them to leave the hive at night. It is also possible that they are shunned by healthy hive mates because of a chemical signal allerting other bees. The y parasite Apocephalus borealis is also infecting bumblebees, suggesting that it may become a new threat to honey bees.
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Parasite develop complex behavioural and morphological adaptations to nd a host [34] Saul-Gershenz and Millar 2006 describe that larval aggregations of the blister beetle Meloe franciscanus, which parasitize nests of the solitary bee Habropoda pallida. The larvae agregate to a cluster formed like a female bee. Then, a chemical cue similar to the sex pheromone of the female bee is produced. Male bees are attracted by the larval aggregations, try to mate. Meanwhile the beetle larvae attach to the body of the bee, being transferred to female bees in following mating, and are then carried to the bee nest. Hafernik and Saul-Gershenz described for the rst time the cooperative behaviour and mimicry strategy in blister beetles. [35] Pollinator of rare and endemic plants growing on dunes under threat of parasites [36] Habropoda pallida builds single celled nests in sandy slopes along water-courses in the Mojave desert.The parasitized solitary bee Habropoda pallida is a ground-nesting bee and an important pollinator of Larrea tridentata and Astragalus lentiginosus var. borreganus at Kelso Dunes and other endemic rare and threatened plants such as Astragalus lentiginosus var. micans at Eureka Dunes, according to Saul-Gershenz. Such dune restricted plants are closely dependent on such pollinators.
Bibliography
[1] http://en.wikipedia.org/wiki/Colony_Collapse_Disorder. Wikipedia, the free enzyclopedia: Colony Collapse Disorder. [2] Europa: Animal health and welfare. bees research. http://ec.europa.eu/food/ animal/liveanimals/bees/research_en.htm. [3] Bees in europe and the decline of honeybee colonies bee doc. http://www.bee-doc. eu/. [4] http://www.ars.usda.gov/is/AR/archive/mar00/bees0300.htm. USDA United States Department of Agriculture : Screening Mites From Honey Bees. [5] http://www7.nationalacademies.org/ocga/testimony/Colony_Collapse_ Disorder_and_Pollinator_Decline.asp. Berenbaum, May R.: Colony Collapse Disorder and Pollinator Decline. Statement of May R. Berenbaum For Congress, 03/29/2007 110th Congress (First Session). [6] http://www2.warwick.ac.uk/fac/sci/whri/research/entomopathogenicfungi_ /varroa_/. Chandler, Dave; Prince, Gill; Ball, Brenda; Pell, Judith; Birchall, Caroline: Fungal biocontrol of the varroa mite.
BIBLIOGRAPHY [7] http://en.wikipedia.org/wiki/Varroa_mite. Wikipedia: Varroa mite.
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[8] http://www.ncbi.nlm.nih.gov/pubmed/17823314. Cox-Foster DL, Conlan S, Holmes EC, Palacios G, Evans JD, Moran NA, Quan PL, Briese T, Hornig M, Geiser DM, Martinson V, vanEngelsdorp D, Kalkstein AL, Drysdale A, Hui J, Zhai J, Cui L, Hutchison SK, Simons JF, Egholm M, Pettis JS, Lipkin WI.: A metagenomic survey of microbes in honey bee colony collapse disorder. Science. 2007 Oct 12;318(5848):283-7. Epub 2007 Sep 6. PMID: 17823314. [9] http://aginfo.psu.edu/news/2008/5/beeresearch.html. College of Agricultural Sciences: Researche continues as honey bee losses rise in U.S., Fall in Pa. [10] http://www.pnas.org/content/early/2009/08/21/0906970106. Reed M. Johnson, Jay D. Evans, Gene E. Robinson, May R. Berenbaum: Changes in transcript abundance relating to colony collapse disorder in honey bees (Apis mellifera). PNAS. August 18, 2009, 106 (33)Published online before print August 24, 2009, doi: 10.1073/pnas.0906970106. [11] http://www.ncbi.nlm.nih.gov/pubmed/19449624. Johnson RM, Pollock HS, Berenbaum MR.: Synergistic interactions between in-hive miticides in Apis mellifera. J Econ Entomol. 2009 Apr;102(2):474-9. [12] http://maarec.psu.edu/ColonyCollapseDisorder.html. Colony collapse disorder. CCD Working group:
[13] Li J, Chen W, Wu J, Peng W, An J, Schmid-Hempel P, and Schmid-Hempel R. Diversity of nosema associated with bumblebees (bombus spp.) from china. Int J Parasitol, 42(1):4961, 1 2012. http://www.ncbi.nlm.nih.gov/pubmed/22138016. [14] Whitehorn PR, OConnor S, Wackers FL, and Goulson D. Neonicotinoid pesticide reduces bumble bee colony growth and queen production. Science, 3 2012. http: //www.ncbi.nlm.nih.gov/pubmed/22461500. [15] Microsporidia. wikipedia. http://en.wikipedia.org/wiki/Microsporidia. [16] Martn-Hernndez R, Botas C, Barrios L, Martnez-Salvador A, Meana A, Mayack C, and Higes M. Comparison of the energetic stress associated with experimental nosema ceranae and nosema apis infection of honeybees (apis mellifera). Parasitol Res, 109(3):60512, 9 2011. http://www.ncbi.nlm.nih.gov/pubmed/21360094. [17] Martn-Hernndez R, Botas C, Bailn EG, Martnez-Salvador A, Prieto L, Meana A, and Higes M. Microsporidia infecting apis mellifera: coexistence or competition. is nosema ceranae replacing nosema apis? Environ Microbiol, 12 2011. http://www. ncbi.nlm.nih.gov/pubmed/22176602.
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[18] Botas C, Martn-Hernndez R, Meana A, and Higes M. Critical aspects of the nosema spp. diagnostic sampling in honey bee (apis mellifera l.) colonies. Parasitol Res, 12 2011. http://www.ncbi.nlm.nih.gov/pubmed/22193523. [19] Traver BE, Williams MR, and Fell RD. Comparison of within hive sampling and seasonal activity of nosema ceranae in honey bee colonies. J Invertebr Pathol, 11 2011. http://www.ncbi.nlm.nih.gov/pubmed/22085836. [20] Dainat B, Evans JD, Chen YP, Gauthier L, and Neumann P. Dead or alive: Deformed wing virus and varroa destructor reduce the life span of winter honeybees. Appl Environ Microbiol, 12 2011. http://www.ncbi.nlm.nih.gov/pubmed/22179240. [21] Botas C, Martn-Hernndez R, Das J, Garca-Palencia P, Matabuena M, Juarranz A, Barrios L, Meana A, Nanetti A, and Higes M. The eect of induced queen replacement on nosema spp. infection in honey bee (apis mellifera iberiensis) colonies. Environ Microbiol, 11 2011. http://www.ncbi.nlm.nih.gov/pubmed/22118366. [22] Copley TR and Jabaji SH. Honeybee glands as possible infection reservoirs of nosema ceranae and nosema apis in naturally infected forager bees. J Appl Microbiol, 112(1), 1 2012. http://www.ncbi.nlm.nih.gov/pubmed/22053729. [23] Fries I. Nosema ceranae in european honey bees (apis mellifera). J Invertebr Pathol, 103 Suppl 1:S739, 1 2010. http://www.ncbi.nlm.nih.gov/pubmed/19909977. [24] http://www3.interscience.wiley.com/journal/122204880/abstract?CRETRY= 1&SRETRY=0. Higes, Mariano; Martn-Hernndez, Raquel; Garrido-Bailn, Encarna; Gonzlez-Porto, Amelia V.; Garca-Palencia, Pilar; Meana, Aranzazu; del Nozal, Mara J. Mayo, R.; Bernal, Jos L.: Honeybee colony collapse due to Nosema ceranae in professional apiaries. Environmental Microbiology Reports, 2009; 1 (2): 110 DOI: 10.1111/j.1758-2229.2009.00014.x. [25] http://www.beesfordevelopment.org/portal/article.php?id=1131. Paxton, Robert J.: Nosema ceranae - a new threat to Apis mellifera honey bees. School of Biological Sciences, Queens University Belfast, UK (originally published in Bees for Development Journal 81). [26] http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone. 0002771. Otterstatter, Michael C.; Thomson, James D.: Does Pathogen Spillover from Commercially Reared Bumble Bees Threaten Wild Pollinators? PLoS ONE 3(7): e2771. 2008 doi:10.1371/journal.pone.0002771. [27] http://en.wikipedia.org/wiki/Crithidia. Wikipedia: Crithidia. [28] http://www.ncbi.nlm.nih.gov/pubmed/17713789. Otterstatter, Michael C.; Thomson, James D.: Contact networks and transmission of an intestinal pathogen in bumble bee (Bombus impatiens) colonies. Oecologia. 2007 Nov;154(2):411-21. Epub 2007 Aug 23.
BIBLIOGRAPHY
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[29] http://cat.inist.fr/?aModele=afficheN&cpsidt=16008790. Schmid-Hempel, P.; Funk, C. Reber: The distribution of genotypes of the trypanosome parasite, Crithidia bombi, in populations of its host, Bombus terrestris. Parasitology. 2004, vol. 129 (2), pp. 147-158. [30] http://www.plosone.org/article/info:doi/10.1371/journal.pone.0006481. Vanengelsdorp D, Evans JD, Saegerman C, Mullin C, Haubruge E, Nguyen BK, Frazier M, Frazier J, Cox-Foster D, Chen Y, Underwood R, Tarpy DR, Pettis J: Colony Collapse Disorder: A Descriptive Study PLoS One. 2009 Aug 3;4(8):e6481. [31] http://www.efsa.europa.eu/cs/BlobServer/External_Rep/027e.pdf? ssbinary=true. Bee Mortality and Bee Surveillance in Europe. Scientic Report submitted to EFSA 03.12.2009. [32] Rajwinder Singh, Abby L. Levitt, Edwin G. Rajotte, Edward C. Holmes, Nancy Ostiguy, Dennis vanEngelsdorp, W. Ian Lipkin, Claude W. dePamphilis, Amy L. Toth, and Diana L. Cox-Foster. Rna viruses in hymenopteran pollinators: Evidence of intertaxa virus transmission via pollen and potential impact on non-apis hymenopteran species. PLoS ONE, 5(12):e14357, 12 2010. http://www.plosone.org/article/ info%3Adoi%2F10.1371%2Fjournal.pone.0014357. [33] Hafernik j et al. a new threat to honey bees, the parasitic phorid y apocephalus borealis. PloS One, 1 2012. http://www.physorg.com/news/ 2012-01-deadly-parasite-honey-bees.html. [34] Saul-Gershenz LS and Millar JG. Phoretic nest parasites use sexual deception to obtain transport to their hosts nest. Proc Natl Acad Sci U S A, 103(38):1403944, 9 2006. http://www.pnas.org/content/103/38/14039.long. [35] Hafernik J and Saul-Gershenz L. Beetle larvae cooperate to mimic bees. Nature, 405(6782):356, 5 2000. http://www.nature.com/nature/journal/v405/n6782/ full/405035a0.html. [36] Mojave desert polllinators project. savenature.org. http://www.savenature.org/ content/save/research_fund.
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Part IV Bacteriology and Virology
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Chapter 24 General Bacteriology

24.1 General classication of bacteria related to food science
Great eorts were made to classify all living beings.There are three related elds of activities concerning taxonomy:
24.1.1
Nomenclature
Nomenclature provides names to the dierent groups. Identication Identication veries if an organism belongs to an already described group. Classication Classication tries to group bacteria on the basis of similarities or relationships. Bacteria are classied in[1]: Taxonomic rank Kingdom Division Class Order Family Genus 1589
1590 Species Subspecies
CHAPTER 24. GENERAL BACTERIOLOGY
intrasubspecic rank Subspecies may be divided into groups with special characters, the intrasubspecic ranks, which are very important in daily practical bacteriology but not part of the ocial nomenclature. Intrasubspecic ranks are: Biovar or biotype have special biochemical or physiological properties. Serovar or serotype have distinctive antigenic properties. Pathovar or pathotype have pathogenic properties for certain hosts. Phagovar or phagotype have ability to be lysed by certain bacteriophages. Morphovar or morphotype have special morphological features.
24.1.2
Sections
The Bergeys Manual of Determinative Bacteriology has grouped bacteria in dierent "sections" based on a few readily determined criteria. The binary nomenclature was introduced in 1735 by the Swedish scientist Carl von Linn containing usually informations about the genus and the species. It may be completed by the name of the author of the rst description followed by the year of the publication. New discoveries turn out to be necessary to change the position of bacteria in the classication what sometimes means to change their name. So it may come that in older books one germ is described under a dierent name as found in new books. For example the Escherichia coli was described in old publications under the name of Bacterium coli. The usual classication which is also used in "Our Food" follows the Bergeys Manual of Systematic Bacteriology vol I to IV. As many bacteria described in Bergeys Manual are not living any more and her description is still incomplete an international community made a general revision of the content of the manual and presented a list denominated as Approved List(Skerman et al.,1980).
24.1.3
Classication of important bacteria found in food
The sections of Bergeys Manual are:

24.1. GENERAL CLASSIFICATION OF BACTERIA RELATED TO FOOD SCIENCE 1591 Section 1 Spirochaeta Includes the genus Spirochaeta, Treponema, Borrelia and Leptospira. Section 2 Aerobic/microaerophilic, motile, helical, vibrioid, Gram- negative bacteria Includes the genus Campylobacter and Spirillum. Section 3 immobile (or rarely motile ), Gram-negative curved bacteria Section 4 Gram-negative aerobic rods and cocci Includes the family Pseudomonadaceae with the genus Pseudomonas and Xanthomonas, the family Azotobacteriaceae with the genus Azotobacter and Azomonas, the family Rhizobiaceae with the genus Rhizibium and Agrobacterium, the family Methylococcaceae with the genus Methylococcus and Methylomonas, the family Halobacteriaceae,with the genus Halobacterium and Halococcus, the family Acetobacteriaceae with the genus Acetobacter and Gluconobacter, the family Legionellaceae with the genus Legionella, the family Neisseriaceae with the genus Neisseria, Moraxella and Acinetobacter. In section 4 are also included the genus Flavobacterium, Alcaligenes and Brucella. Section 5 Facultatively anaerobic Gram-negative rods
Includes the family Enterobacteriaceae with the genus Escherichia, Schigella,Salmonella, Citrobacter, Klebsiella, Enterobacter, Erwinia, Serratia, Hafnia, Edwardsiella, Proteus, Providencia, Morganella and Yersinia, the family Vibrionaceae with the genus Vibrio,Photobacterium,Ae and Plesiomonas. Section 6 Anaerobic Gram-negative straight, curved and helical rods Section 7 Dissimilatory sulfate- or sulfur-reducing bacteria Section 8 Anaerobic Gram-negative cocci Section 9 The Rickettsias and Chlamydias Section 10 The Mycoplasmas Section 11 Endosymbionts Section 12 Gram-positive cocci Includes the family of Micrococcaceae with the genus Micrococcus, Stomatococcus, Planococcus, Staphylococcus. Section 12 includes also the genus Streptococcus, Enterococcus,Lactococcus, Leuconostoc, Pediococcus, Sarcina.
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Section 13 Endospores producing Gram positive rods and cocci Includes the genus Bacillus, Sporolactobacillus, Clostridium, Desulfotomaculum, Sporosarcina and Oscillospira. The genus Bacillus has only one aerobic form. This form is Bacillus anthracis which causes skin anthrax or if inhaled the serious form of pulmonary anthraxThe spores are oval
Bacillus anthracis This organism was seen hundred years ago in the blood of animals ill with anthrax. Robert Koch proved it to be the cause of the disease by inoculating pure cultures into susceptible cattle: Characteristics: Gram-positive rods, tending to form long chains, not motile. The vegetative form are destroyed by chemical and physical agents but the spores can survive for years in dust or soil and on other objects. The spores survive 5 minutes boiling and ordinary disinfectants.
Section 14 Gram-positive regular formed, not sporulated rods Includes the family Lactobacillaceae with the genus Lactobacillus, Carnobacter,Listeria and Erysopelothrix.
Section 15 Gram-positive, irregular formed, not sporulated rods Includes the genus Corynebacterium, Clavibacter, Aureobacterium, Arthrobacter, Propionibacterium, Actinomyces and Bidobacterium.
Section 16 Mycobacteria Includes the family Mycobacteriaceae with the genus Mycobacterium.
Section 24 Streptomyces and related genus Includes the genus Streptomyces. Streptomycetes are the source of an antibioticum Gibco BRL anti PPLO[2]it is Tyclocine and is sold under the name of Tylan. It has a good activity against PPLO from chicken, horses, human and pigs. In cell cultures it has an antiviral activity acting aswell against Meningopneumonitis from mouse and ornithosis. It is not toxic even in high concentrations. In vitro it is more bactericide than bacteriostatic.
24.1. GENERAL CLASSIFICATION OF BACTERIA RELATED TO FOOD SCIENCE 1593
24.1.4
Section 2
Detailed description of some important bacteria
Genus Spirillum The Genus Spirillum has a spiral form, is Gram-negative, aerophylic and microaerophylic. The Genus contains only one species the Spirillum volutans which is the greatest bacteria known. Its length goes up to 60 micrometers.It grows only in culture under microaerobic conditions. Oxidase and phosphatase are positive,catalase is negative.The germ inhabits water and feces of pigs.It produces volutin, a polyphosphate. Section 4 Family Pseudomonadaceae are straight, curved or ellipsoidal Gram-negative rods, monotrichous or polytrichous. The family is obligatory aerobic,catalase positive, and generally oxidase positive. The family grows from 4o C and below, up to 43o C . Its habit is water, plants, vegetable products and soil. Some species produce diseases on plants. The genus Pseudomonas can produce yellow-green, blue or red partially uorescent pigments.These pigments can diuse in the culture medium. The genus Pseudomonas is found in soil, water, other substrates and food producing deterioration due to proteases and lipases which decompose albumin and fatty acids with production of bad smell and mucus. The bacteria prefer a medium without carbohydrates. There are psychotropic species which are specialized in refrigerated products such as dairy products, meat, sh, poultry and eggs, spoiling these products even under good refrigeration. With 10.000 germs/g alterations of taste and smell starts. With 100.000 and more there is production of mucus in meat and sh. Pseudomonas grows only at high value of aw (water activity)(0,97 and higher). Pseudomonas uorescens and Pseudomonas aeruginosa are frequently found. They may produce alimentary poisoning.
24.1.5
Genus Xanthomonas
The genus Xanthomonas is closely related to the genus Pseudomonas and also belongs to the section 4. Xanthomonas has phytopathological species. It grows on agar plates as yellow colonies. This gave the name from Greek xanthos = yellow.
1594 Nitrates are not reduced.
Some variants of Xanthomonas campestris are used industrially to produce Xanthan.
24.1.6
Family Halobacteriaceae
The family Halobacteriaceae belongs to section 4. It has Gram-negative rods with various shapes or malformed cells. The family is characterized for necessitating a high concentration of around 15% of salt in the medium, as well as 0,1 to 0,5 mol of MG++ producing carotenoid yellow to strong red pigments. Its name comes from Greek halos=salt.The internal osmotic pressure corresponds to the pressure of the exterior medium turning mechanical supporting of the membrane of the cell unnecessary. These cells die when transfered to water or another medium with low content of salt. The family grows best at 20% to 30% of NaCl and 40o C to 50o C . Below 10o C there is no growth. The Halobacteriaceae family lives in salted lakes, in concentrated salt solutions, in meat, in sh, intestines and other salted food
24.1.7
Family Acetobacteraceae
(Aceto=vinegar, bacterion=rods) Recent cultures are Gram-negative,old cultures are Gramvariable. The germs are rigorously aerobic, generally catalase positive having oxidative activities. They oxidize ethylic acid in acetic acid. Acetobacter is used in industry to produce vinegar and acetic acid. The best temperature for growing is 25o C to 30o C the best ph is 5.4 to 6.3. The genus Acetobacter is undesired in the production of beer and wine because of the resulting acidity. Acetobacter xilinum causes great damage to non-alcoholic beverages growing in form of a white layer and supercial mucus. Acetobacter xilinum, Acetobacter aceti- and Acetobacter pasteurianus inhabits fruits and vegetables. The genus Gluconobacter with the old denomination of Acetomonas also belongs to the family of Acetobacteraceae. Gluconobacter oxidans is found in owers, fruits, vegetables, bakery yeast, beer, wine and soil. The germs are ellipsoid or in form of rods. They are Gram-negative weak Grampositive as they grow old. The germs are isolated, rarely in chain. Some strains produce
24.1. GENERAL CLASSIFICATION OF BACTERIA RELATED TO FOOD SCIENCE 1595 mucus and a water soluble brown pigment. Gluconobacter oxydans is obligatory aerophylic, catalase positive. Ethanol is oxidized to acetic acid and glucose to gluconic acid. This has given the name to the genus. Acetate and lactate are not oxidized because of absence of enzymes of the citric acid cycle. Growth is best at 25o C to 30o C and ph between 5.5 to 6.0.
24.1.8
Acetic acid bacteria [3]
The acetic acid bacteria are obligate aerobes that oxidise sugars, sugar alcohols, and ethanol with the production of acetic acid as the major end product. They are important in food and beverage production, as well as in the bioproduction of industrial chemicals, but they are also known to spoil food and beverages. The classication of acetic bacteria is being rearranged using 16S rRNA sequence analysis. Acetic acid bacteria belong to with polar agellation and no oxidation of acetate, the genus Acetobacter, and the genus Gluconacetobacter comprising G. liquefaciens and G xylinus. Vinegar is produced by conversion of carbohydrates of ethanol by yeasts, followed by the oxidation of ethanol to acetic acid by acetic acid bacteria, such as Acetobacter, Gluconacetobacter, and Gluconobacter. [4] Other uses of acetic acid bacteria are important in cocoa production, production of microbial cellulose. Bioproduction uses the enzymes such as 2-keto-L-gulonic acid for the production of vitamin C, the sweetener D-tagatose, and shikimate, an intermediate product for the synthesis of antibiotics. Macauley and colleagues 2001 evaluated the utility of the genus Gluconobacter in biotechnology and future industrial processes. [5] A pathogenic acetic acid bacterium was described, representing the tenth genus of acetic acid bacteria:
24.1.9
Granulibacter bethesdensis a new pathogenic acetic acid bacteria [6]
Granulibacter bethesdensis, was isolated from lymph nodes of chronic granulomatous disease patient. The genome of this pathogenic acetic acid bacteria includes the 967 ORFs important for virulence, adherence, DNA uptake, and methanol utilization. G. bethesdensis is a genetically diverse emerging human pathogen that may have recently acquired virulence factors new to this family of organisms.
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24.1.10
Grouping acetic acid bacteria by 16S rDNA sequence [7]
De Vero Luciana and Giudici Paolo 2008 developed a method for grouping acetic acid bacteria genera for preliminary screening acetic acid bacteria species used in vinegar production. The authors screened Acetobacter, Gluconobacter, Gluconacetobacter, Asaia, Neoasaia, Saccharibacter, Frateuria and Kozakia acetic acid babcteria strains focusing on 16S rDNA sequences. Using this method it is possible to group the species recovered from vinegar fermentation, being most frequently of the genera Acetobacter, Gluconobacter and Gluconacetobacter say the authors. Most prominent Gluconobacter genra are: Gluconobacter frateurii Gluconobacter thailandicus Gluconobacter oxydans Gluconobacter cerinus Gluconobacter albidus Gluconobacter kondonii
24.1.11
Gluconobacter japonicus [8]
Malimas and colleagues 2009 describe a cluster of ve strains. They were found to dier from the type strains of Gluconobacter frateurii, Gluconobacter thailandicus, Gluconobacter oxydans, Gluconobacter cerinus, Gluconobacter albidus and Gluconobacter kondonii. The authors propose the name Gluconobacter japonicus sp. Nov for the new cluster. Gluconobacter japonicus produces weakly dihydroxyacetone from glycerol, but not 2,5-diketod-gluconate or a water-soluble brown pigment from d-glucose and contained ubiquinone-10.
24.1.12
Intragenic structure of the Genus Gluconobacter using 16S rDNA and ITS sequences [9]
Taqkahashi and colleagues 2006 re-examined the species of the genus gluconobacter analysing The sequences of the 16S rDNA and 16S-23S rDNA internal transcribed spacer regions (ITS). Five cluster were identien which coorespond to Gluconobacter albidus, G. cerinus, G. frateurii, G. oxydans (type species), and G. thailandicus. The type strain of G. asaii, NBRC 3276T was included in the G. cerinus cluster. Gluconobacter cerinus, G. frateurii and G. oxydans clusters were heterogeneous. They contained clusters of other species. The authors stress that the species denition must be re-evaluated.
24.1.13
Gluconobacter sphaericus [10]
The strain NBRC 12467T was found by Malimas and colleagues 2008, applying 16S-23S rRNA gene ITS sequences, to form an independent cluster. The strain produced a watersoluble brown pigment and 2,5-diketo-D-gluconate from D-glucose, diering from the type strains of the eight Gluconobacter species. The authors propose the name of Gluconobacter sphaericus (Ameyama 1975) comb. nov.
24.1.14
Gluconobacter thailandicus [11]
Four strains of acetic acid bacteria were isolated from a ower of the Indian cork tree (Millingtonia hortensis) collected in Bangkok, Thailand by Tanasupawat and colleagues 2004. The researchers proposed the name of Gluconobacter thailandicus sp. nov.
24.1.15
Nitrogen xating bacteria [12]
To avoid or reduce the use of Nitrogen-fertilizers the use of plant growth-promoting bacteria, was proposed by Pedraza 2007. Promising genera include Azospirillum, Azotobacter, Herbaspirillum, Bacillus, Burkholderia, Pseudomonas, Rhizobium, and Gluconacetobacter and others. They are capable of promoting plant growth through dierent mechanisms including (in some cases), the biological nitrogen xation (BNF), the enzymatic reduction of the atmospheric dinitrogen (N(2)) to ammonia, catalyzed by nitrogenase. Well studied nitrogen-xing species are Gluconacetobacter diazotrophicus found in sugar plants, Gluconacetobacter johannae and Gluconacetobacter azotocaptans in coee plants from Mexico, and salt-tolerant bacterium named Swaminathania salitolerans in wild rice plants, which is salt-tolerant. In India Acetobacter peroxydans and Acetobacter nitrogenigens were found associated with rice plants and Kombucha tea as nitrogen-xing bacteria. According to Bhattacharjee and colleagues 2008 nitrogen-xing bacteria could signicantly reduce the use of the nitrogenous fertiliser which contributes to the green house emission (N2O) and underground water leaching. Non-leguminous plants like rice, sugarcane, wheat and maize were also found to be associated with nitrogen-xing bacteria. The authors stress the importance of nitrogen-xing bacteria in non-leguminous plants in face of a higher demand of these crops. [13]
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24.1.16
Gluconacetobacter diazotrophicus [14]
Gluconacetobacter diazotrophicus a nitrogen-xating bactera is important in low nitrogen fertilized sugarcane elds. Saravanan and colleagues 2007 discusses the survival and transmission of the bacterium. Other nitrogen xating Acetobacteraceae, such as Gluconacetobacter azotocaptans, Gluconacetobacter johannae and Swaminathania salitolerans, from coee, corn and rice and other plant-growth-promoting traits of this group of bacteria, such as phytohormone synthesis, P and Zn solubilization and biocontrol, are discussed by the authors. Munoz-Rojas and Caballero-Mellado 2003 studied the growth eect of Gluconacetobacter diazotrophicus on strains in the dierent sugarcane varieties. The authors found that the bacterial populations decreased drastically in relation to plant age. The inoculation of Gluconacetobacter diazotrophicus was found benecial for sugarcane plant growth, but depends on the bacteria genotype and the sugarcane variety. The authors stress the importance of the sugarcane variety for the persistence of the plant-bacteria interaction. [15] Inoculating sugarcane plants with Gluconacetobacter diazotrophicus and Herbaspirillum sp. was found by Muthukumarasamy and colleagues 2006 to increase nitrogen content in leaves of sugarcane of Co 86032 in South India. The authors found that the number of Herbaspirillum sp. remained stable with the age, but G. diazotrophicus were reduced in old plants. The authors report that total bio-mass and leaf N were higher in plants inoculated with G. diazotrophicus and Herbaspirillum sp. without fertilization than in plants fertilized with recommended dose of inorganic N (280 kg ha(-1)). This experiment showed that inoculation with these bacteria in sugarcane variety Co 86032 could mitigate fertilizer N application considerably in sugarcane cultivation. [16] Cocking, Stone and Darwey 2004 recommend the use of Gluconacetobacter diazotrophicus as a substitute of synthetic nitrogen fertilizers in maize, rice and wheat cropping systems for higher yields and environmental protection. The authors perform reseaches witch maize culture under4 zero nitrogen fertiliser input. [17] Fox and colleagues 2007 stress that the use of synthetic nitrogenous fertilizers, pesticides, and irrigation promoted by the "Green Revolution" doubled the grain production in the past, but crop yields are diminishing. The authors call for a common strategy to reduce dependence on nitrogenous fertilizers by rotating leguminous crops with nonleguminous crops. They point out that organochlorine pesticides, agrichemicals, and environmental contaminants inhibited or delay symbiosis of rhizobia bacteria with host plant roots, reducing overall plant yield. Synthetic chemicals compromise symbiotic nitrogen xation and increases dependence on synthetic nitrogenous fertilizer and reduces soil fertility. [18]
24.1.17
Biotechnology application of Gluconobacter strains [19]
Gluconobacter strains uses dehydrogenases connected to the respiratory chain located in the periplasmic space. Deppenmeier, Homeister and Prust 2002 explain that transport of substrates and products into, and out of, the cell is, therefore, not necessary. This turns Gluconobacter highly interesting for the production of L-sorbose (vitamin C synthesis), 6amino- L-sorbose (synthesis of the antidiabetic drug miglitol), dihydroxyacetone, gluconate and ketogluconates. Adachi and colleagues discusses the oxidative fermentation of Gluconobacter species. The authors highlight two dierent types of membrane-bound enzymes: The quinoproteins produce 5-keto- D-gluconate and L-sorbose from D-gluconate and D-sorbitol, respectively. The avoproteins D-gluconate dehydrogenase and D-sorbitol dehydrogenase were shown to produce 2-keto- D-gluconate and D-fructose. The quinate dehydrogenase is a new quinoprotein which produces 3-dehydroquinate from the oxidation of quinate. The quinate dehydrogenase can be used to produce shikimate entangled in the production of antibiotics, herbicides, and aromatic amino acids synthesis. [20]
24.1.18
Neisseriaceae
The family Neisseriaceae belongs to the section 4 and bears the genus Neisseria, Moraxella, Acinetobacter and Klingella. The genus Moraxella has isolated coccoid form or Gram-positive diplococcus. Oxidase and catalase are positive. Moraxella lacunata is psychotropic spoiling meat, sh and shrimp. The genus Flavobacterium (avus=yellow) is aerophylic or anaerophillic,Gram- negative rods and produces yellow or red pigments which are insoluble in water. Almost all species are psychophylic and proteolytic. They produce putrefaction and modication of color on sh, poultry, eggs, milk and butter.They are found in in fresh unheated milk, in vegetables, in water and in soil. Flavobacterium multiplies in the rst phase of sauerkraut.One species is pathogen. The genus Alcaligenes is obligatory aerophylic, Gram-negative rods, rarely coccoid. Its colonies are at, gray, yellow or brown. Some types are nitrate positive. They do not hydrolyze gelatine and casein. Carbohydrates are not transformed in acids. There is production of alkalinity from amides and other organic salts. This property has given the name to the genus. There are many species which are generally inhabitants of the intestines from vertebrates as saprophytes.They may act as opportunists on human infections.
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Alcaligenes may be present in milk, spoiled eggs and other food. The most common germ is Alcaligenes faecalis Achromobacter is an old denomination.Many species from this genus were included in the genus Alcaligenes. The genus Brucella was denominated in honor to Sir David Bruce. It has Gram-negative short rods or coccoid forms. The germs may present itself isolated or in chain.They are obligatory aerophylic, immobile, growing up to 40o C . The best ph is 6.6 to 7.4.Catalase is positive and nitrate is reduced to nitrite. Culture media for Brucella must contain peptons, liver extract, yeast extract and vitamins such as thiamin, biotin and nicotinic acid. Initial culture needs 5% to 10% CO2. Brucella causes brucellosis, an infection of animals which can be transmitted to man under the name of bang. The transmission is direct , very seldom the transmission is caused by contaminated milk and milk products. Brucella abortus and Brucella suis are old denominations which were included under the name of Brucella melitensis.
24.1.19 24.1.20
Section 5 Aeromonas
Aeromonas bacteria can be present in fresh waters, tap waters and food such as sh and other marine animals. It can cause infections in animals and man. That is why controlling water, faeces and food in general is of high importance.
24.2
Classication of Aeromonas spp.
Recent genetic studies have cleared some of the confusion in the classication of Aeromonas. The genus Aeromonas has Gram-negative rods is facultative anaerobic,is oxidase positive, catalase positive, resistant to 0/129 vibriostatic agent (2,4-diamino-6,7-diisopropylpteridine).The genus can show very easily two groups: Aeromonas salmonicida: psychrophilic, non-motile. Some species are pathogenic to frogs, sh and humans. Human disease is usually diarrhoea or bacterimia. Aeromonas hydrophila: motile The group Aeromonas hydrophila was according to Bergeys Manual of Systematic BacteOurFood Database of Food and Related Sciences Copyright 1998-2010 Karl H. Wilm. All rights reserved.
24.2. CLASSIFICATION OF AEROMONAS SPP.
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riology (1984) divided into three species, being increased today to 12 species. The three species of the classication of Bergeys are: Aeromonas hydrophila Aeromonas caviae Aeromonas sobria Table 24.1: Dierent Aeromonas species Aeromonas Esculin hydrolysis Gas from glucose Voges-Proskauer Acid from arabinose hydrophila + + + + caviae + + sobria + V -
24.2.1
Pathogenic Aeromonas in retail meat [21]
Aeromonas hydrophila was isolated from 6.8% of retail meat in Egypt, other isolate were Aeromonas caviae with 2.7% and Aeromonas sobria with 2.1% from the total meat samples. Three of seventeen meat isolates of Aeromonas hydrophila produced aerolysin toxin gene (aerA). Osman et al 2012 stress the health hazard to humans handling contaminated meat. Aeromonas hydrophila virulence factor described [22] According to Suarez et al 2012 Aeromonas hydrophila isolate 7966 possesses a functional repeat in toxin (RtxA) having an actin cross-linking domain (ACD) that contributes to the host cell apoptosis which may represent a virulence factor of Aeromonas hydrophila. However, only the full-length ACD of RtxA from Aeromonas hydrophila catalyses the covalent cross-linking of the host cellular actin and induces host cell apoptosis. The RtxA gene expression required host cell contact to be expressed. The RtxA contained six genes (rtxACHBDE) presenting similarities to the gene organization found for the Rtx of the Vibrio species. Aeromonas isolates from diseased sh, healthy controls and water environment in China [23] Hu et al. 2012 report that dead shes presented Aeromonas veronii and Aeromonas hydrophila as highest frequency of isolation in China. Aeromonas veronii was most the frequent in healthy sh and water samples. Aeromonas hydrophila isolates were signicantly more frequent from diseased sh than from healthy sh and presented the aerolysin (aer), cytotonic enterotoxin. (alt), cytotoxic enterotoxin (act), temperature-sensitive protease (eprCAI) and serine protease (ahp)
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genes These isolates were more virulent to zebrash comparing to the other genetic proles. The authors point to the fact that Aeromonas species in aquatic environmentsmay present virulence potential. They call for stringent epidemiological studies. Aeromonas hydrophila and outbreak of abortions and Infertility [24] Singh et al 2011 report that water-borne A. hydrophila were associated with equine abortions and infertility, and diarrhea in newborn foals. At an equine breeding farm near Hissar (Haryana-India), three mares aborted in their seventh month of pregnancy. The authors found risue samples, swabs and all water samples positive for Aeromonas hydrophila. Water should be included in the control system to avoid this bacteria.
24.3
Further classication of aeromonads
The phenotyping of Aeromonas has been for long time confused and is still not yet ready.
24.3.1
Historical classication of aeromonads
Bacillus punctatum, in 1890 classied by Zimmermann: bacillus Gram-negative not sporulated, motile found in tap water. Bacillus ranicida, classied by Ernst, isolated from frog with red leg disease.
24.3.2
Bacillus stereatothermophilus Donk 1920
The name of this bacterium is presumably intended to mean fat and heat loving. The most distinctive characters are capacity to grow at 65o C and a limited tolerance to acid. Bacillus strains capable of growing at temperatures of 65o C and above do not belong to a single species, it is however a useful diagnostic character. Bacillus stereatothermophilus occurs in soil, hot springs, desert sand, arctic waters, ocean sediments, foods and compost. The biochemical characteristics of bacillus stereatothermophilus are: Catalase = positive Voges-Proskauer test = negative Acid from D-glucose = positive Acid from L-arabinose = dier D-xylose = dier D-mannitol = dier Gas from glucose = negative
24.3. FURTHER CLASSIFICATION OF AEROMONADS Hydrolysis of casein = dier Hydrolysis of gelatin = positive Hydrolysis of starch = positive Utilization of citrate = dier Degradation of tyrosine = negative Desamination of phenylalanine = negative Nitrate reduced to nitrite = dier Formation of indole = negative Dihydroxiacetone = negative Sodium and potassium chloride required = negative Alantoin or urate required = negative
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Allen (1953) has pointed out that fresh isolates tend to diversity of characteristics. When maintained in culture for some times they are readily classiable. The bacterium has a vital importance for canning factories. Bacillus stereatothermophilus, together with Bacillus coagulans as well as other bacteria have high heat resistant spores. The temperature maximum where growth still takes place is 75o C . The best growth temperatures for Bacillus stereatothermophilus is 55 to 60o C . Bacillus stereatothermophilus is the bacterium whose spores can survive at temperatures higher than other bacteria. In hot springs bacteria may be found which resist temperatures higher than that.
24.3.3
D-value (Decimal reduction time)
The D-value is the time which is necessary at a specic temperature to reduce the initial population of a bacterium down to 10%. This means it kills 90% of the bacteria. It is measured in minutes. The temperature must always be cited. For Bacillus stereatothermophilus a D-value of D121,1C = 4 to 5 minutes are given.
24.3.4
D-values for other bacteria in order to draw a comparison
Clostridium botulinum type A and B D121,1C = 0,1 up to 0,2 minutes. Clostridium sporogenes D121,1C = 4 up to 5 minutes. Clostridium thermosoccharolyticum D D121,1C = 3 up to 4 minutes. Desulfotomaculum nigricans D121,1C 2 up to 3 minutes. For tropic conserves the sterilization has to be done carefully as Bacillus stereatothermophilus grows at storage temperatures higher than 37o . Below of that there is no growth. To kill its spores F121,1C = 15 to 30 minutes must be used in case of canned food. Another example of high temperature resistant spoilage of canned food is the mould Byssochlamiy nivea which is sometimes found in canned cucumber resisting up to 98degree centigrades in acid medium. Byssochlamis isolated from canned cucumber and cultivated on yeast chloramphenicol dextrose medium:
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Bacillus hydrophillus fuscus from the lymph of a frog with haemorrhagic septicaemia. In 1936 Kluiver and Van Niel created the genus Aeromonas. In 1943 Stanier grouped and rearranged all strains of Aeromonas under the sole species Aeromonas hydrophila. In 1984 Popo has included the genus Aeromonas under the family of Vibrionaceae under Section 5, facultatively anaerobic Gram-negative rods. He divided the group of A. hydrophila from Stainer in four species: Some bacteria from underheated food may turn it sour without gas. This is called "at sour spoilage". Only smell, taste and color may be changed. Deterioration with production of gas such as produced by Clostridium botulinum can easily be detected because of the pressure which is created inside.
24.4. THE CULTURE OF AEROMONADS
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Aeromonas hydrophila Aeromonas caviae Aeromonas sobria Aeromonas salmonicida Later studies using DNA-DNA hybridization has shown 12 genospecies of which 11 phenotypes were named: Aeromonas caviae predominates in sewage Aeromonas eucrenophila Aeromonas hydrophila found in all types of water, rivers, lakes and sewage. A.hydrophila can be isolated from faeces of warm-blooded animals and in man with up to 11,7%. Food such as sh, meat,milk , vegetables and tap water are very important place for A. hydrophila. Food can therefore be a source of human infection.In fresh unpolluted drinking waters Aeromonas hydrophila is predominant. Aeromonas jandei Aeromonas media Aeromonas schbertii Aeromonas sobria Aeromonas trota Aeromonas veronii Aeromonas salmonicida being found in sh but not in water. When found in water they are associated with sh. Aeromonas can be present in water with a ph from 5.2 to 9.8, growing by 10o C up to 45o C being 35o C the optimum. They can grow in water with very low organic matter as well in sewage with high content of organic matter. They are not found in sea water an they do not grow in vitro with 4 % of salt. They have been isolated from unchlorinated as well as from chlorinated water. A new family Aeromonadaceae, independent from Vibrionaceae is being proposed.
24.4
The culture of aeromonads
Aeromonads grow well on any complex medium such as Nutrient Agar or Trypticase Soy Agar as well as selective media for faecal forms such as McConkey Agar.The most common selective media for aeromonads use carbohydrates as the main carbon source.
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24.4.1
Pathogenesis in animals and human
Aeromonas hydrophila is being found in sh, reptiles and turtles. Under certain conditions it may cause infections of the host, such as the haemorrhagic septicemia and the red leg disease. Water is the principal source of Aeromonas infections in man.
24.4.2 24.4.3
History
Section 2 Campylobacter [25]
1886- Theodore Escherich discovered a non-culturable, spiral-shaped bacterium in stools of children and gave him the name of Vibrio felinus. Other classication followed such as: Vibrio fetus, Vibrio jejuni . 1963- All above micro-organism were united in the new genus of Campylobacter. 1973- Butzler and colleagues in Belgium isolated Campylobacter by ltration techniques from diarrheal stool. 1977- Skirrow in England using blood agar with antibiotics demonstrated that Campylobacter jejuni was responsible for human diarrhoea. 1989- The number of outbreaks caused by Campylobacter surpasses since 1989 the number of outbreaks caused by Salmonella. 1991- Vandamme proposed the following classication:
24.5
24.5.1
Family of Campylobacteraceae
Genus
Campylobacter: with 19 species and subspecies Arcobacter : with 4 species Helicobacter : 18 species
24.5.2
Description
Campylobacter are Gram-negative, slender spiral curved rods. They need a micro-aerobic atmosphere to grow. The pathogenic species grow at 42o C and 37o C .
24.5. FAMILY OF CAMPYLOBACTERACEAE
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24.5.3
Pathogenesis
Campylobacter may cause rare infections in disseminated systemic form. However Campylobacter are the most frequent agents of watery and bloody diarrhoea in the world. Campylobacterspecies can cause severe genital or intestinal disease in meat producing lifestocks and poultry. Genus Campylobacter has the following species : C.: is together with C.jejuni ssp. jejuni the most common cause of disease in human and in animals. Infection takes place during handling raw poultry or eating raw or undercooked poultry meat. [26] C.conscious C.curvus C.fetus ssp.fetus : important animal pathogen associated with abortions in sheep and cattle and human disease such as diarrhoea, meningitis, peritonitis, salpingitis, septic abortion, septicemia in older patients and in immune suppressed persons. C.fetus ssp.venerealis: causes infertility and embryonic death in cattle and abortion in infected cows. It does not infect man. C.hyointestinalis C.jejuni ssp.jejuni : It is together with Campylobacter the most common cause of disease in human and in animals such as diarrhoea in calves and abortion in sheep. In human it may cause septicemia, appendicitis and the Guillain- Barre syndrome (an acute inammatory polyneuropathy). C.jejuni ssp.doylei C.lari: isolated from human , dogs and cat outbreaks. C.mucosalis C.rectus C.sputorum biovar bubulus C.sputorum biovar fecalis C.sputorum biovar sputorum C.upsliensis: isolated from human, dogs and cat outbreaks. C.helveticus C.showae C.hyoillei C.gracilis Campylobacter jejuni: It is spiral formed, Gram-negative microaerophil rod. To cultivate it is necessary to reduce the oxygen between 5% to 7%. Campylobacter jejuni grows at 43o C but there is no growth at 25o C . The germ is very sensible to heat, chilling, and acids. The resistance to heat in skimmed milk = D 55o C is 1 to 3 minutes. Resistent to chilling temperatures: after 5 to 8 days there were no bacteria alive left from
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a population of 107 in skim milk at -20o C . Resistent to acids: At pH 5,0 all Campylobacter jejuni died after 24 hours. Campylobacter jejuni can be isolated from feces of children, animals water, beef, in particular poultry (chicken, duck, turkey), on vegetable,fruits and marine animals. An infection with Campylobacter jejuni is characterized with diarrhoea, fever and vomit. Campylobacter jejuni does not normally multiply outside the host. However the bacteria have the ability to survive a long time in the environment. It is very infectious. If one bird is infected the whole ock will be aected. For the production of Campylobacter free poultry rapid diagnostics are necessary to avoid the contamination to spread out. If poultry is infected nearly 100% will be bacterial carriers, therefore only a few birds in a ock need to be tested to ensure that the whole ock is Campylobacter free. Very few cells can produce an infection it is therefore important to enrich suspected material. The infectious level is 103 an 105 germs/g It is being told that even 50 bacteria can cause an infection. [27] Incubation is two to ve days.The onset of symptoms is sudden, often preceded with one or two days with fever and headache with sudden watery and sometimes bloody diarrhoea,abdominal cramps,fever and headache. After settling in the intestine Campylobacter produces a protein called "adesin" which acts as a glue between the germ and the wall of the mucosa causing the adhesion to the wall of the intestine which makes the invasion of the tissue possible. Campylobacter Jejuni, C. and C. lari produce an enterotoxin, in some cases Zytotoxin is reported.
24.5.4
Complications with Campylobacter infections
A possible complication with Campylobacter infections is an autoimmune disease called Guillain-Barre syndrome which results in weakening and paralysis. It seems that the similar surface of Campylobacter to the surface of the human nervous system can cause the production of antibodies that cross-react with the nervous tissue during an infection. The antibodies will attach to the peripheral nerves causing the disease.
24.5.5
Campylobacter infections decline in response to interventions aimed at poultry [28]
Campylobacter jejuni is the most common cause of acute enteritis in humans, with symptoms such as diarrhoea, fever and abdominal cramps. Beginning in the 1980s, New Zealand experienced rising annual rates of campylobacteriosis
1609
that peaked in 2006. Sears et al 2011 assessed the decline of campylobacteriosis incidence between 20072008, when voluntary and regulatory interventions to reduce Campylobacter spp. contamination of poultry were introduced. The authors report a reduction of 74% of cases attributed to poultry, compared with 2002-2006, a period before the introduction these interventions. Several foodborne pathways of campylobacteriosis (other than poultry) have been identied, including red meat and raw milk consumption. The contribution of these pathways to sporadic campylobacteriosis in New Zealand has been estimated to be notably less than that of poultry. The authors suggest that the data of their study may help other countries to control foodborne campylobacteriosis linked to specic food sources. The importance of collaboration between industry, food safety regulators, and public health researchers to control food borne diseases. According to Shaughnessy et al 2011 more than 90% of commercial chickens caecum is colonised asymtomatically by Campylobacter jejuni. The authors used chicken-specic 20K oligonucleotide microarrays to examine global gene expression in Campylobacter jejunichallenged birds. Increased gene expression of oxidative burst, endothelial cell activation and T cell mediated activity were found. The authors concluded that Campylobacter jejuni alters the global caecal gene expression and a protective intestinal T cell response takes place in the caecum of the chicken. [29] Conlan et al. 2011 stress that in commercial ocks of chickens are typically found to be Campylobacter free for the rst 14-21 days of life However, once detected Campylobacter jejuni spreads rapidly saturating the ock over the course of 2-3 days. Conlan and colleagues suggest that the mechanism of the so-called Campylobacter jejuni-free "lagphase" is based on the age-dependence of transmissibility between hosts, rather than their susceptibility to colonization. [30]
24.5.6
Identication and quantication of Campylobacter coli and Campylobacter jejuni [31]
Livestock animals are source of foodborne human contamination of Campylobacter jejuni and Campylobacter coli, especially in developing countries. Pigs are often colonized with Campylobacter coli, and their faeces contain high number of the pathogen. Leblanc-Maridor et al 2011 present a quantitative real-time PCR method for speciesspecic detection and quantication of Campylobacter coli and Campylobacter jejuni directly in faecal, feed, and environmental samples. The assay can be used for epidemiological studies of Campylobacter coli and C. jejuni by pigs from conventional herds and others.
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24.5.7
Campylobacter jejuni survival on packaged beef or pork [32]
According to Balamurugan et al. 2011 the number of Campylobacter jejuni decreased signicantly during storage under chilled, vacuum packaged and retail display conditions when inoculated on sterile meat. However, survival of Campylobacter jejuni on commercial vacuum packaged beef and pork was signicantly enhanced, decreasing only 1 log cfu cm(-2) reduction at the end of 6 weeks, and could still be detected after seven days of display in a retail case. The authors concluded that natural microora on vacuum packaged meat foster the survival of Campylobacter jejuni on beef or pork under refrigeration. Strict hygienic practices or the implementation of decontamination technologies are therefore necessary to reduce the risk of campylobacteriosis. In Denmark, the incidence of human campylobacteriosis cases, as well as the Campylobacter prevalence in broiler ocks, is highest during the summer months of July-August. Boysen et al. 2011 found that the occurrence of Campylobacter in broiler meat at retail increased in domestic chilled mead during summer. The prevalence of Campylobacter in broiler ocks may therefore be used as a predictor of this pathogen in broiler meat at retail, suggest the authors. [33]
24.5.8
Sources of infection
Infected poultry (up to 80% of broiler ocks), untreated water, cattle, pigs, pets, wild animals, birds, Fruits, marine animals.
24.5.9
Continuous air monitoring of Campylobacter for broiler ocks [34]
Campylobacteer is the most common case of diarrhoea in humans, and poultry counts for half of the infections. Olsen and colleagues 2009 assessed the detection of Campylobacter by PCR in feces, dust, and air samples in poultry houses, and found that the sensitivity of detection of Campylobacter in air is comparable to that in other sample materials. A low proportions of particles in the 0.5- to 2-m-diameter range and high proportions in the 2- to 5-m-diameter range was found. PCR detection of Campylobacter in air samples could also be performed at the hanging stage during the slaughter process but not at other places at the slaughterhouse. The researchers concluded that new detection technologies, allow continuous monitoring of colonization status.
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24.5.10
Detailed informations about Culture of Campylobacter
Enrichment broth is spread with a loop on specic agar and typical colonies are inoculated on Columbia Agar. Biochemistry, Latex agglutination and genetic methods like polymerase chain reaction (PCR)
24.5.11
Detection of Campylobacter jejuni
:Detection of Campylobacter is made using enrichment broth according to Wesley et al. 1983 or Blase and Wang (1979)or Campylobacter - selective - broth, under anaerobic atmosphere (5% O2, 10% CO2, 85% N2) at 42o C for 24 hours. The atmosphere is easily obtained with the Campylobacter - Gas Generation-Kit from Oxoid.
Table 24.2: Enrichment broth for Campylobacter jejuni Wesley,Swaminathan and Stadelman 1983 Composition/Liter ingredients Iron sulphate Sodium metabisult Sodium piruvate Bicine Haematin solution Rifampin Cefsulodin Polymyxin B amount 0,25 g 0,25 g 0,25 g 10 g 25 mg 6,25 g 20.000 IU
The enrichment broth according to Wesley can demonstrate up to less than 1 germ/g
Table 24.3: Enrichment broth for Campylobacter jejuni Blaser and Wang 1979,composition/liter ingredients Vancomycin Trimethoprim Polymyxin B Amphotericin amount 10 mg 5 mg 2500 IU 2 mg
1612 Selective Breeding
The enrichment has to be transfered to a selection such as selective medium according to Weslei 1983, Blaser and Wang (1979) or Campy BAP Agar and other. Incubate at 42o C for 48 hours under the atmosphere described above.
Biochemical conrm Suspicious colonies are examined under a phase contrast microscope searching for comma formed bacteria. No growth at 25o C under microaerophylic conditions. No growth under aerophylic conditions No growth with 3,5% NaCl. Resistant to cephalotin (30 microgram). Often sensible to nalidixic acid. (30 microgram) Catalase and oxidase positive Glucose negative H2S from TSI negative As basis for the biochemical reactions of Campylobacter jejuni use Brucella broth with 0,16% agar. Comparison of the methods of standard microbiological culture versus RFLP-PCR for the identication of Campylobacter was done by V. Atanassova and Ch. Ring. They found that 75.64% of swab samples collected from laying hens were tested positive by RFLP-PCR and only 33.33% by standard microbiological culture[35]. DNA based methods for the Campylobacter diagnostics DNA diagnostics of Campylobacter is the most specic and sensitive detection technique reducing the diagnostic time of 4 days with normal culture bacteriology to 4 hour with DNA techniques starting from intestinal content and faecal samples. This makes tests of poultry possible prior to slaughter in order to guarantee Campylobacter free products. The current DNA based tests are not able to distinguish living and dead microorganisms.
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The DNA based tests follow the way of separation from matrix, cell lysis, DNA purication and detection. System used are such as Genpoint AS Oslo, Norway.: The sample is added to a buer containing magnetic beads which are coated with a surface which absorbs bacteria. The bacteria are immobilized on the beads. The beads are pulled to the side of the tube by a magnet and the sample solution can be removed. Bacterial lysis and DNA immobilization follows so pure DNA is bound to the beads. This technique allows to isolate and detect several strains and species simultaneously using PCR amplication of the specic DNA labeling it with specic primers and followed by hybridization of the probes to oligonucleotide array giving a signal for the dierent bacteria in the sample.
24.5.12
Enhanced pathogen bacteria rapid detection systems
In a review in 2004 Stevens and Yaykus wrote that rapid detection technologies of small number of pathogen bacteria should be improved. Bacterial concentration may perhaps reduce or even eliminate the need for cultural enrichment prior to detection. However, methods such as centrifugation, ltration, and immunomagnetic separation were still not ideal and continued to be a stumbling block in the advancement of molecular methods for the detection of foodborne pathogens. [36] In this eld advances have been achieved, such as immuno-capture magnetic bead systems of Matrix MicroScience that selectively concentrates target microbial pathogens from complex food matrix. It uses paramagnetic beads coated with antibodies facilitates the rapid detection of target bacteria. Viable cultures are produced which enable full and detailed analysis, of any positive result to be carried out. These systems can be used to enhance the performance of other rapid methods such as PCR, lateral ow, ELISA, chromogenic media etc by signicantly reducing or eliminating the need for lengthy enrichment and/or selective enrichment steps. [37] Fukushima and colleagues 2007 developed a density gradient centrifugation method to separate bacteria from complex food matrices, as well as to remove compounds that inhibit rapid detection methods, such as PCR, and to prevent false-positive results due to DNA originating from dead cells. The combined separation and concentration methods and RTi-qPCR may conrme within 3 h the presence of 10 to 100 CFU/g of Salmonella and C. jejuni directly in naturally contaminated chicken and the presence of S. aureus. The author stresses the feasibility of rapid detection of pathogenic bacteria during outbreaks. [38]
1614
24.5.13
New Zealand produces update on work related to Campylobacter [39]
As concern around New Zealands high rates of campylobacteriosis continues, the New Zealand Food Safety Authority (NZFSA) has put together a a report "A Background to Campylobacter" [40] which sets out, in easy-to-understand terms, the scientic research that NZFSA has collated on Campylobacter in food and the practical measures currently in place to contain it, as well as an update on what is happening in this regard overseas. Campylobacter is naturally present throughout the environment, in water, on animals (including birds and pets) as well as being found on meat and food products. While dierent interventions may oer reductions in hazard levels at certain points in the farm-to-fork continuum, it is a combination of measures that is more likely to achieve the greatest reduction in risk to consumers. According Steve Hathaway, Director of NZFSA, the agency is considering some shortterm measures that will decrease contamination rates in poultry. However, the aim has always been to focus on not just removing the high levels of the pathogen from the food chain, but to nd ways to prevent it getting there in the rst place.
24.5.14
Genus Arcobacter
The genus Arcobacter is composed of Campylobacter - like bacteria. They were found associated with bovine and porcine abortion. They are aero tolerant,gram negative and are strongly motile. Arcobacter spp. has its habitat in animals like bovines,swine, primates and poultry;human beings are not excluded.
24.5.15
Occurrence of Arcobacter spp. in Food[41]:
Poultry 20% Red meat 0,5 - 5 %
24.5.16
Diseases caused by Arcobacter spp.
Acute diarrhea,appedicitis,septicemy and diarrhea in animals.
24.5.17
Culture of Arcobacter spp [42]
The Culture of Arcobacter spp. is made with enrichment broth and isolation medium followed by biochemical and serological identication.
24.6. HELICOBACTER
1615
24.5.18
Enrichment in Arcobacter-Selective-Broth (ASB)
Composition of the broth [42] 28 g Brucella broth powder (Difco) in 910 ml A.dest. After sterilization and cooling at about 50-60o C . Add 50 ml of lysated horse blood, 75 mg piperacillin (Sigma) dissolved in 10 ml Aqua dest., sterilized by ltration, 32 mg ceferoperazone (Sigma) dissolved in 10 ml Aqua dest., sterilized by ltration, 20 mg trimethoprim (Sigma)dissolved in 4 ml ethanol (96%) and 6 ml Aqua dest.sterilized by ltration, and 100 mg Cycloheximide (Serva) dissolved in 10 ml Aqua dest., sterilized by ltration. Final pH should be 7,0 +-0,2. Distribution should be made in 10 ml portions in tubes. Isolation medium for Arcobacter spp. Isolation is made using Arcobacter selective Medium ASM Composition 21 g Mueller-Hinton-Broth (Oxoid) and 2,5 g Agar Nr.3 (Oxoid) in 960 ml Aqua dest. After sterilization and cooling to 50o C add all substances cited under ASB medium with exception of blood.Final pH should be 7,4 +- 0,2. 20 g of product to be tested is homogenized in 180 ml physiological Na Cl solution. 1 ml of the suspension is added to 10 ml broth. Incubate 48 hours at 24o C . Identication:Spraying of Arcobacter spp. biochemical and serological identication. The genus Arcobacter has four species: Arcobacter cryaerophilus Arcobacter butzleri: was rst describe by Kielbauch et al. Later Vandamme et al. changed this classication to Arcobacter butzleri. These organisms could grow in presence of air and 30o C which made the distinction to Campylobacter and were found in diarrhoeas in blood and in peritonial uids. They were found also in not sucient cooked poultry, cattle, swine, ovine, equine,primates, sewage and water.The serotyping based on slide agglutination on living bacteria distinguishes between 73 serogroups and biotyping nds out 16 biotypes. Aerobacter nitrogilis Aerobacter skirowii
24.6
Helicobacter
The genus contains 16 species. The most important human pathogen are: Helicobacter pylori
1616
Helicobacter cinaedi Helicobacter fennelliae Adult animal pathogen, not found as human pathogen: Helicobacter mustelae: In 1980 Marshall and Warren cultured in campylobacter media a spiral bacteria from gastric biopsy. These bacteria were later denominated as Helicobacter pylori being responsible to gastritis and duodenal ulcers and are associated to gastric carcinome and gastric lymphoma. Claims of an association between Helicobacter pylori and atheroma leading to artheriosclerosis have become less credible, as the organism has not been detected directly from atheromatous lesions and 18 serological studies have failed to support the association [43]. It is being spread from person to person among the family. Cats may harbor the organism. The genus Helicobacter was created by Goodwin et al. in 1989 Helicobacter grows slowly on brain heart infusion BHI. Growth at 30o C . No growths at 25o C , optimum at 37o C . Colonies: non colored, translucents 1 - 2 mm mobility: rapid. Glycine: Growth with 0,5% Glycine and 0,04% triphenyltetrazolium chloride. NaCl: No growth with 3,5% NaCl. Catalase: positive Urea: positive H2S: negative on TSI and variable on lead acetate paper. Nitrate: Variable Hipurate: Variable Alkaline phosphatase: positive Gama-glutamyltranspeptidase: positive Leucine arylamidase: variable Susceptible to: penicillin, ampicillin, amoxicillin, erythromycine, gentamicin, kanamycin, rifampin, tetracycline. Resistant to: vancomycin, sulfonamides, and trimethoprim. Variable resistance: nalidixic acid, cephalothin, metronidazole and polymyxin. Isolation: from the gastric mucosa of primates and ferrets. Pathogenity: human gastritis and peptic ulcereation (gastric and duodenal) It includes two species: Table 24.4: Helicobacter mustelae and Helicobacter pylori Growth Growth Growth Growth at 42o C in 10% CO2 on PSD agar with 1% Glycine H. mustelae + d H. pylori + + -
24.6. HELICOBACTER Nitrate reduction Susceptible to Cephalothin 30 Causes type B gastritis and gastric and duodenal ulcers Causes gastritis and ulcers in adult animals Cellular fatty acids 3-OH 18:0 + - + +
1617
+ - +
PSD agar: Peptone-starch dextrose agar (Dunkelberg et al Appl.Microbiol. 19: 47-52 , 1970)
24.6.1
Suppression of Helicobacter pylori by green tea extracts
[44] Keiji Wakabayashi and colleagues 2003 assessed foodstus on its capability to suppress the urease enzyme of Helicobacter pylori which is is essential for its colonization. The authors found some tea such as green tea extracts and rosemary extracts inhibit H. pylori urease in vitro. Catechins, the hydroxyl group of 5-position were the active components inhibiting urease. H. pylori-infected Monglian gerbils responded to the administration of green tea extract with suppressed gastritis and the absence H.pilori. The authors concluded that tea and tea catechins may help to control H. pylori-associated gastroduodenal diseases, since H.pylori is getting resistant to antibiotics.
24.6.2
The eradication of Helicobacter pylori after gastric cancer cancer surgery [45]
Nicholas J. Talley wrote that the risk for regression of gastric cancer after gastric surgery was reduced after eradicating the bacteria Helicobacter pylori. Previous studies claimed that there was a relation between Helicobacter pylori infection and gastric cancer. [46] Despite being classied as carcinogen by the WHO, and the Asian-Pacic consensus conference in 2007 having recommended that population-based screening and antibiotic treatment of Helicobacter pylori in high-risk populations, this is not generally accepted. The author stresses therefore that eradication of this bacterium should be priority in regions with high incidence of gastric cancer. According to Kazutoshi Fukase and colleagues, 2008 the prophylactic eradication of Helicobacter pylori after endoscopic resection of early gastric cancer should be used to prevent the development of metachronous gastric carcinoma.[47] The study of Fukase contradicts previous studies which found no relation between the bacterium and stomach cancer. [48] [49]
1618
24.7
Transmission and sources of infection of Campylobacter
Enteritis cause by Campylobacter is a zoonosis, resulting from contact to poultry, cattle, raw milk, surface water and pets, following the faecal-oral route. The consumption of undercooked chicken is one major cause of outbreaks.
24.8
Avoid contamination of Campylobacter
To avoid contamination it is necessary to interrupt the chain of cross-contamination in kitchen caused by utensils, chopping-boards, hands and raw vegetables, handling poultry and red meats. Campylobacter were found in 5% of retail red meats and ground beef in USA and Canada and up to 23% in beef in UK. Important outbreaks were noted in Water and raw milk , especially in school children who drank raw milk. Pasteurization kills Campylobacter. A contamination after pasteurization however cannot be excluded. Nonchlorinated water can be contaminated with sewage, birds and animal faecal material, so that there were many outbreaks of Campylobacter caused by municipal waters in USA and Sweden. In England the ndings of Campylobacter in sea water and fresh water from rivers were always associated with Escherichia . The infection dose is very low: 2 bacteria/ml which turns the contamination through water very likely. The transmission from person to person is however very unlikely with exclusion in the case of mother/neonate. More likely is however the transmission from dogs and cats, birds or monkeys. The infections prevail in the summer, in the equatorial zone during the rain season. Campylobacter should always be presumed as a traveler risk. Campylobacter jejuni and C. are present in up to 100% in broiler chicken and as normal intestinal ora or domestic animals such as poultry and turkeys.
24.8.1
Prevention of infection with Campylobacter
General hygienic measures will prevent the spread of infection. Hand washing after contact with animal or their products, proper cooking and storage of food, pasteurization of milk
24.9. ISOLATION AND IDENTIFICATION and chlorination of water are important to prevent the disease.
1619
Irradiation of food should be allowed to reduce signicantly the number of food born pathogens.
24.9
Isolation and identication
Phenotyping of Campylobacter includes species identication, serotyping , biotyping, phagetyping. Molecular genotyping methods includes pulsed eld gel electrophoresis (PFGE) random amplied polymorphic DNA (RAPD) Selective medias such as charcoal media ltration techniques on media without antibiotics are used to grow Campylobacter which do not grow on media with antibiotics.
24.9.1
Enrichment broth
It is used only on food and water. Presumptive identication Gram-stain, wet mount for specic motility, oxidase test and hyppurate hydrolysis. Presumptive conrmation Commercial latex tests are avaliable: Campyslide (BBL) which identies the genus and Meritec-Campy (Meridian Diagnostics) to identify C.jejuni, C., and C. upsaliensis.The use of nalidixic acid as antibiotic to select Campylobacter is not reliable because the bacteria has developed resistance to quinolones Non-culturable forms: Campylobacter as well as Vibrio cholerae, Salmonella enteritides and enteropathogenic E.coli have developed Campylobacteroid forms to resist environmental conditions which do not grow on media. To recover these forms a passage in suckling mice is necessary. The polymerase chain reaction ( PCR ) has made possible to detect non-culturable forms by amplication of specic DNA sequences. PCR with a primer for the agellin gene is used to detect Campylobacter jejuni and Campylobacter coli in stools in chicken and in water. Indoxyl acetate hydrolysis test: Specication of Campylobacter which can be used as a simple test. Table 24.5: Biotyping scheme of Campylobacter by Lior C.lari C.jejuni spp.jejuni C.coli C.lari C.lari C.lari C.lari C.lari C.lari
1620 biotype I Test Hippurate hydrolises + Rapid H2S test DNA hydrolysis Serogroups 74 II + + 46 III + + 0 IV + + +
CHAPTER 24. GENERAL BACTERIOLOGY I II I II + +
- - + + -
24.9.2
Culture of Campylobacter spp using lter technique from the Veterinary department of Mnster,1998
20 ml or 20 g of the sample are minced with a scissors and tweezers. Mix without shaking (squeeze by hand) in 90 ml Preston-Broth and incubate at 42o C . Place a lter type DA, 0,65m, Fa Millipore, Kat Nr. DAW PO 4700 avoiding air bubbles. Distribute 300l from the enrichment broth on the lter paper. Incubate the Petry plate for 1 hour at room temperature.Remove the lter and incubated the medium at 42o C microaerophile for 48 hours
24.9.3
Escherichia Coli [50]
Escherichia coli is a normal inhabitant of the intestinal human and animal tract. His presence in food is considered to be an indicator of faecal contamination and causes deterioration. Some strains of Escherichia coli can however be pathogenic. The number of food born infections are increasing continuously.The outbreaks become greater by high shelf life of raw material and end products, increasing number of communal feeding and worldwide increasing distribution of food and animal food. In 1982 a great food born infection caused by underheated hamburger lead to the discovering of Enterohaemorrhagic Escherichia coli (EHEC). It was the E.coli O 157:H7 strain. In 1955 there was a great outbreak of EHEC-bacteria in Bavaria, Germany. EHEC are intestinal pathogenic bacteria producing watery and bloody diarrhoea with colical intestinal pain, the haemorrhagic colitis, HC. This infection can develop with life menacing complications in children under six years and in old people. First there are intestinal symptoms followed after three to twelve days after contamination by an haemolitic uraemic syndrome, (HUS) with damage of the kidneys with 10% of obit, another 10 to 30% develope a permanent kidney damage which makes a lifelong dialysis necessary. Neurological and artheroschlerotic complications may also occur.
24.9. ISOLATION AND IDENTIFICATION In Germany there are about 8.000 to 16.000 cases of EHEC each year.
1621
Most common places of infection are communal feeding, such as nurseries,kindergarten, old peoples home and restaurants, especially fast food. Most likely contaminated food are ground meat, underheated hamburgers, sausage,turkey sandwiches and underheated milk, all animal food, especially of ruminant origin as most important reservoir of EHEC and contaminated vegetables. Prophylaxis should be concentrated on proper instalation of toilets and hygienical conditions. Other important focus of infections are water, salads, vegetables, fresh appel juice and contamination by smear infection caused by diseased persons. Smear infection seams to have very great importance in infection with EHEC. The diagnostic of Enterohemorrhagic Escherichia coli EHEC is made by isolation of the germ using enterohemolisine-agar and using latex agglutination test. Escherichia coli strains may produce verotoxine. The strains of Escherichia coli which produce verotoxine are labeled as VTEC-bacteria. EHEC-strains are classied under the group of VTEC- strains.
24.9.4
Cucumber imported from Spain carrying the EHEC bacterium may be implicated in the actual outbreak of EHEC infections [51]
The EHEC infection outbreak of May 2011 in Germany has now spread to Denmark and other countries. Cucumber from Spain were found carrying the pathogen bacteria at an outlet in Hamburg. Scientists at the National Consulting Laboratory on Hemolytic Uremic Syndrome in Mnster compared the genetic code of previous EHEC cases in Germany with the actual strain which was identied HUSEC41, sequence type ST678 of the seroytpe Escherichia coli O104:H4. It is resistant to dierent antibiotics. Enterohaemorrhagic Escherichia coli (EHEC) are the pathogenic subgroup of Shiga toxin (Stx)-producing E. coli. EHEC can cause non-bloody and bloody diarrhoea, and the haemolytic uraemic syndrome (HUS) There are dierent serotypes of EHEC one of which is the E. coli O57:H7 known from other outbreaks. [52] Microbiologists suggest that the EHEC bacterium developed from the Escherichia coli which lives in the healthy gut of men and animals. Over a certain period genetic material from bacteriphages were introduced in the DNA of the E.coli which mutated to pathogen strains. The excessive use of antibiotics and toxic agrarian chemicals speeded this process.
1622
According to veterinary ocials the pathogen strains infects six per cent of cattle without producing disease. Manure containing these strains may contaminate directly vegetables and fruits or indirectly through aected irrigation water. Helge Karch of the Institute of Mnster developed a method to speed the identication of the bacteria. Further work is being done to determine if there are any genetic variations which dier from the original Husec 41 strain. According to Karch, the O104:H4 is not known to have caused an outbreak before. The laboratory is now sequencing the whole genome of HUSEC41. An important nding is that the strain lacks the eae gene which encodes the protein intimin. Intimin is a virulence factor (adhesin) of EHEC such as E. coli O127:H6 and EHEC such as E. coli O157:H7 Escherichia coli strains. It is an attaching and eacing protein which together with other virulence factors is responsible for enteropathogenic and enterohaemorrhagic diarrhoea. [53] Intimin is expressed on the bacterial cell surface. Together with Tir (Translocated intimin receptor) intimin is linked to infections of children. Its absence may explain the fact that mainly adult persons are aected from this outbreak.
24.9.5
The source of the Escherichia coli O104:H4 outbreak in Germany is still unkown [?]
The Escherichia coli O104:H4 outbreak in Germany has spread to Switzerland, Poland, the Netherlands, Sweden, Denmark, and the United Kingdom. All patients reported outside Germany had visited the country and were probably infected there. German ocials initially pointed to contaminated cucumbers originating in Spain as the source of the outbreak, but later recognised that Spanish cucumbers were not the source of the pathogenic strain which causes the epidemic. Meanwhile a great number of patients are hospitalised with Hemolytic-uremic syndrome (HUS) which requires urgent treatment. In Germany, 15 people have died and around 500 have been hospitalised with HUS. Presenting hemolytic anemia, acute renal failure (uremia) and a low platelet count. It predominantly but not exclusively aects children. Most cases are preceded by an episode of diarrhoea caused by an EHEC strain. The disease is acquired as a foodborne illness with a mortality of 5-10%. Health ocials recommend not to eat cucumber salad and fresh tomatoes.
24.9. ISOLATION AND IDENTIFICATION
1623
24.9.6
Characterisation of the Escherichia coli strain O104:H4 of the 2011 HUS epidemic [54]
The outbreak of the haemolytic uraemic syndrome and bloody diarrhoea caused by a virulent Escherichia coli strain O104:H4 in Germany counts fro 810 cases of the syndrome and 39 deaths since May, 2011. Karch et al. 2011 found that all isolates were of the HUSEC041 clone (sequence type 678). All shared virulence proles combining typical Shiga-toxin-producing E coli (stx2, iha, lpfO26, lpfO113 ) and enteroaggregative E coli (aggA, aggR, set1, pic, aap) loci and expressed phenotypes that dene Shiga-toxin-producing E coli and enteroaggregative E coli, including production of Shiga toxing 2 and aggregative adherence to epithelial cells. Isolates additionally displayed an extended-spectrum beta-lactamase phenotype absent in HUSEC041. The authors suggest that the high adherence of the strain to intestinal epithelium might facilitate the absorption of Shiga toxin and explain the HUS outcomes. The authors concluded that blended virulence proles in such pathogens may become extreme virulent.
24.9.7
Rapid next-generation technologies for whole genome characterization [55]
Karch et al. compared the whole genome sequence of the outbreak isolate of 2011 and a historic O104:H4 HUS isolate from 2001. The HUS-associated strains of both isolates carried genes typically found in two types of pathogenic E. coli, enteroaggregative E. coli (EAEC) and enterohemorrhagic E. coli (EHEC). The HUS-causing O104:H4 strains and the previously published sequence of the EAEC strain 55989 show a close relationship but are only distantly related to common EHEC serotypes. The outbreak strain diers from the 2001 strain in plasmid content and mbrial genes. The serotype O104:H4 had rarely been associated with HUS in the past. The authors suggest, therefore, that EAEC 55989 and EHEC O104:H4 strains evolved from a common EHEC O104:H4 progenitor. Stepwise gain and loss of chromosomal and plasmid-encoded virulence factors produced the highly pathogenic hybrid of EAEC and EHEC of the current outbreak.
24.9.8
Chinese/German cooperation unveiled the genetic code of the deadly German EHEC outbreak [56]
The Beijing Genomic Institute (BGI) in cooperation with the University Medical Center Hamburg-Eppendorf researchers, unveiled the genome of the EHEC strain. They report
1624
that the genome size is about 5.2 Mb. It is a new serotype of the 0104 Escherichia coli strain with 93 % sequence similarity with the EAEC 55989 E.coli strain from Central African Republic. Through horizontal gene transfer it acquired additional specic sequences of hemorrhagic colitis and hemolytic-uremic syndrome. Several antibiotic resistance genes, including resistance to aminoglycoside, macrolides and Beta-lactam antibiotics increase to deadly potential of this strain. The Chinese BGI sequenced the genome within three days using their technology. The BGI developes diagnostic kits to aid to control the European outbreak.
24.9.9
BGI and University of Lbeck cooperation [57]
German Chancellor Merkel and Chinese Prime Minister Wen Jiabao were present at the ceremony of the signing of the cooperation contract between Beijing Genomics Institute and University of Lbeck, strengthening the collaboration of the two institutions in the eld of genomic and structural analysis of new viruses. Many of these, such as the bird u virus H5N1 or the SARS coronavirus, have their origin in Southern China, from where they spread towards Europe (as presently is the case with H5N1) or Northern America (as with the SARS virus in 2003). Within the collaboration, the Beijing researchers will analyse the genetic material of the new viruses, whereas the Luebeck group will determine the three-dimensional structures of key components of the pathogens and develop antiviral drugs on this basis. Using such an approach, Professor Hilgenfeld had succeeded in presenting an anti-SARS compound in May 2003, only a few weeks after the discovery of the new virus and during the ongoing global SARS outbreak.
24.9.10
Chinese/German cooperation identied the EHEC bacteria, but will the source of the epidemic remain unidentied for ever? [58]
06.06.2011: Shiga toxin-producing E. coli (STEC) is a group of pathogenic Escherichia coli strains capable of producing Shiga toxins, with the potential to cause severe enteric and systemic disease in humans. The full serotype is usually dened by determining both O and H antigens. There are around 200 dierent E. coli O serotypes producing Shiga toxin, of which over 100 have been associated with human disease. Two major Shiga toxin types (Stx1 and Stx2) have been associated with strains causing human disease. While the serotype O157:H7 is considered as clinically the most important, it is estimated that up to 50% of STEC infections are caused by non-O157 serotypes. STEC is of public health concern because of the potential for outbreaks and the risk of serious complications. Haemolytic uremic syndrome (HUS) is considered as the most common cause of acute renal failure in European children.
1625
Transmission of STEC infection mainly occurs through contaminated food or water and contact with animals. Person-to-person transmission is also possible among close contacts (families, childcare centres, nursing homes, etc). A wide variety of food has previously been implicated in outbreaks as suspected sources, including raw (unpasteurised) raw milk and cheese, undercooked beef, a variety of fresh produce (e.g. sprouts, spinach, lettuce), unpasteurised apple cider, etc. Recently an outbreak of STEC O157 infections in Canada and the USA was linked to walnuts, thus new sources continue to be identied. Various types of animals, in particular cattle and other ruminants, can be healthy carriers of human-pathogenic STEC that can be spread to humans through faecal contamination. Secondary clusters of cases from person-to-person exposure may occur and thus personal hygiene messages are important. First diarrhoea cases were reported in early May 2011. On 22 May Germany informed the European Commissions Early Warning and Response System (EWRS) of a signicant increase in the number of patients with hemolytic uremic sysndrome (HUS) and bloody diarrhea caused by enterohemorrhagic Escherichia coli (EHEC). Four samples of cucumber tested positive for EHEC bacteria, but these germs were not the strain which causes the epidemic in Europe. Later on vegetable sprouts were thought to be implicated in the outbreak, but tests on batches from the Gaertnerhof organic sprouts farm in the northern German village of Bienenbuettel were negative.
24.9.11
Escherichia coli O157:H7 vaccine developed in China [59]
Escherichia coli O157 H7 causes bloody diarrhoea with kidney failure and death. The bacteria uses intimin for the adhesion in the rst step of interaction with the host and releases the Shiga toxins (Stxs), the poisons responsible for the sickening of the host. Gao and colleagues 2011 of the State Key Laboratory of Pathogens and Biosecurity, Beijing, China, report the production of a a novel SSI fusion protein that contains the critical toxin-antigens Stx2B and Stx1B, and the critical adhesion-antigen fragment Int281. The SSI induced Th2-mediated immune protection in a mouse model, triggering the production of antibodies against both Stx1 and Stx2 toxins, and produced a high level of anti-adhesion antibodies. The protein induced complete immune protection, with both anti-toxin and anti-adhesion eects.
24.9.12
Chinese/German cooperation [56]
The strain of STEC causing these illnesses, STEC O104:H4 is very rare. Beijing Genomic Institute (BGI) in cooperation with the University Medical Center Hamburg-Eppendorf researchers, unveiled the genome of the EHEC strain. They report that the genome size is
1626
about 5.2 Mb. It is a new serotype of the 0104 Escherichia coli strain with 93 % sequence similarity with the EAEC 55989 E.coli strain from Central African Republic. Through horizontal gene transfer it acquired additional specic sequences of hemorrhagic colitis and hemolytic-uremic syndrome. Several antibiotic resistance genes, including resistance to aminoglycoside, macrolides and Beta-lactam antibiotics increase to deadly potential of this strain. The Chinese BGI sequenced the genome within three days using their technology. The BGI is now developing diagnostic kits to aid to control the European outbreak.
24.9.13
WHO and EHEC alert [60]
The World Health Organization (WHO) conrms that a total of 1823 cases of STEC O104:H4 have been reported, including 520 cases of hemolytic uremic syndrome (HUS), a potentially life-threatening complication of the infection that can cause kidney failure. Twelve HUS cases were fatal, and 6 deaths were reported among non-HUS cases. Most infections have been reported in people in northern Germany (mainly Bremen, Hamburg, Lower Saxony, and Schleswig-Holstein) or in people who have recently travelled to these areas. Cases in travellers to northern Germany have been reported in Denmark, the Netherlands, Spain, Sweden, and the United Kingdom. German health authorities are investigating the outbreak but have not conrmed a source. They suspect that the source is contaminated food, possibly raw vegetables.
24.9.14
The functioning of epidemiology and global public health system is being questioned [61]
Dr. Michael Osterholm, director of the Center for Infectious Disease Research and Policy at the University of Minnesota calls "incompetence" the way the source of the epidemic is being investigated. However, the problem may be worse than just "incompetence". It seems that the food safety systems based on HACCP, Good Manufacturing Practice, ISO 9000 Certication failed to protect the consumer, resulting in over 20 fatalities up to present. The whole series of global food safety systems must be revised to avoid pathogens to enter the food chain without being detected by routine tests at farm, during processing, and at grocery stores.
24.9.15
EHEC bacterium enters water resources and environment [62]
Experts fear that the EHEC O104:h4 (Husec041) may spread to communal waters and drinking water reservoirs. If so, tap water is endangered as Escherichia coli bacteria are sporadically being found in drinking water samples, says Martin Exner, director of the Hygiene Institute of the Uni-Clinic Bonn and head of the drinking water commission of the German Federal Environmental Agency. The deadly bacterium strain has now been identied in water of a small river near Frankfurt, Germany. The possibility that this
1627
strain enters the drinking water systems has been underestimated. According to Helge Karch, director of the Institute of Hygiene of the university-clinic Mnster, there are many EHEC patients. They all egest high number of pathogen bacteria. It cannot be excluded that the deadly strain has found its place in the local environment and will cause more human infections through water. Call for stricter control of waterworks in Germany The drinking water commission of the German Federal Environmental Agency, on its last meeting, called for strict controls of faecal bacteria in water for overhead sprinkling systems and process water in vegetable ans sprouts production as well as water from small waterworks. Waterworks of great cities have their water tested on Escherichia coli often, however, small waterworks test only once a year. Before the EHEC epidemic started, ve per cent of tap water samples of small waterworks of Baden-Wuerttenberg tested positive for E.coli bacteria, and almost every second private well of this German region contained gut bacteria, reports the WHO. At this meeting the Drinking Water Commission called for stringent control
24.9.16
The French EHEC outbreak, sprouts and minced meat [63]
According to Professor Patrick Berche, head of the bacteriology department at Necker Hospital in Paris, the French outbreak of E Coli in Begles, a south-western French city of Bordeaux the strain type 0104 enterohaemorrhagic Escherichia coli (EHEC) was conrmed in two of seven diseased patients. Sprouts grown from rocket, fenugreek and mustard seeds that came from a British mail order seed and plant company. Ipswich-based Thomson &amp had been added to a soup which might have been the source of the infection. No EHEC bacteria on sprouts were found and a lot of sprouts and seeds of this company has been sold all over Europe without complaint. The outbreak comes days after an EHEC outbreak in a group of children in the northern city of Lille. That outbreak came from frozen supermarket beef burgers made in France, using minced meat originating from Germany, Belgium and The Netherlands.
24.9.17
European cattle herds are the primary source of the EHEC strain
All epidemiological investigations are failing to nd the source of the European EHEC epidemic. While concentrating on sprouts the real source is being neglected. Health ocials must concentrate their investigations on cattle, the primary source of the EHEC coli strain. All positive farms must be closed,sanitised and new EHEC breed introduced. All links point to cows manure which contaminates water resources.
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24.9.18
Source of the HUS bacterium [64]
EHEC can grow in temperatures ranging from from 70 C to 500 C , with an optimum temperature of 370 C . Some EHEC can grow in acidic foods, down to a pH of 4.4, and in foods with a minimum water activity (Aw) of 0.95. It is destroyed by thorough cooking of foods until all parts reach a temperature of 700 C or higher. E. coli O157:H7 is the most important EHEC serotype in relation to public health, however, other serotypes have frequently been involved in sporadic cases and outbreaks. WHO reports that in addition to Germany, EHEC cases have also been notied from: Austria 2, Czech Republic 1, Denmark 10, France 6, Netherlands 4, Norway 1, Sweden 28, Switzerland 2, United Kingdom 4.
24.9.19
Cows and camels breed the HUS bacterium says WHO [64]
Ruminants, particularly cows host dierent coli strains, including the EHEC bacterium without experiencing any harm. Their digestive tract is a real coli cloning laboratory which united the African strain with the local EHEC coli, resulting in the deadly HUS strain. The reservoir of this pathogen appears to be mainly cattle and other ruminants such as camels. It is transmitted to humans primarily through consumption of contaminated foods, such as raw or undercooked ground meat products and raw milk. Faecal contamination of water and other foods, as well as cross-contamination during food preparation (with beef and other meat products, contaminated surfaces and kitchen utensils), will also lead to infection. EHEC has also been isolated from bodies of water (ponds, streams), wells and water troughs, and has been found to survive for months in manure and watertrough sediments. Waterborne transmission has been reported, both from contaminated drinking-water and from recreational waters.
24.9.20
Italian EHEC case conrms hypothesis of oral-faecal infection route instead of a ruminant source [65]
Scavia et al 2011 report that a HUS case in Italy in 2009 by the STEC strain (ED-703) was found to have the same combination of virulence factors as the strain STEC O104 strain of the German and French epidemic in 2011. It presented identical Stx2 production and enteroaggregative adhesion genetic markers. The Italian strain of 2009 was positive for O104 and H4 antigen-associated genes, was agglutinated by an O104 antiserum and presented high degree of genetic similarity with the outbreak strain from Germany, but did not produce extended-spectrum -lactamases.
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This case reported a travel to Tunisia. No unpasteurized milk or dairy products, undercooked meat, or raw sprouts had been consumed and no direct exposure to ruminants or their manure had taken place. Scavia and colleagues suggest, therefore, that the infection was probably acquired through person-to-person transmission, and strains of STEC O104 strictly related to the epidemic strain in Germany had already caused sporadic infections in Europe. Such cases had been reported in 2001 in Germany, in 2004 in France, and in 2010 in Finland in a patient with diarrhoea who had travelled to Egypt from which the sprout seeds associated with both outbreaks could be traced The authors concluded that ruminants would not have had a specic role in the transmission of STEC O104:H4, as already suggested by the epidemiological features of the recent outbreaks. In fact, STEC O104 cannot be considered true STEC but rather EAEC strains that acquired the Stx2-coding phages by horizontal gene transfer, and EAEC is considered to be a human pathogen usually transmitted by the oralfaecal route
24.9.21
Enteric viruses in European recreational waters
Low concentrations of viruses were found in water of European rivers and at beaches. Their number may increase after heavy rain. Researchers recommend to include viruses in the monitoring of recreational waters The European Bathing Water Directive [66] establishes maximum levels for bacteria, in particular Escherichia coli and intestinal enterococcus, which must not be exceeded in order to maintain water quality, but does not include enteric viruses to monitore recreational waters. The EU Virobathe project is aimed at the rapid detection of viruses in recreational waters.Viruses which cause gastroenteritis in humans may be present in sewage-polluted bathing waters. Virobathe improves the molecular DNA technology to detect viruses in water and will contribute to the improvements in European bathing water quality. Virobathe Wyn-Jones et al. 2011 and other groups from the EU Virobathe project, determined the presence of adenoviruses and noroviruses in swimming water, both freshwater and seawater, in dierent European countries. The authors selected adenoviruses for their study, because these viruses are shed along the whole year and are resistant to environmental stress. Noroviruses are of importance as indicator of enteric viruses because they are widespread gastroenteritis agents. The authors detected enteric viruses in 39,2% of samples of water, adenoviruses in 36.4%, noroviruses in9.4%. More freshwater samples than marine water were found contaminated with viruses, and one-quarter remained infective. According to the authors the presence of infectious viruses in recreational waters are a threat to public health, and adenoviruses should be used as an indicator of bathing water quality. Virus numbers in bathing waters increase following heavy rains, and adenoviruses may dangerous levels Viruses take longer
1630
than bacteria to return to acceptable levels following heavy rains, and survive waste water treatment processes better than bacteria, and are more resistant to seawater. [67] According to Boll-Mas et al.2010 human adenoviruses in recreational water present a threat to the population. The authors found no relation between human adenoviruses and E. coli , intestinal enterococci or somatic coliphages concentrations. [68]
24.9.22
Importance for environmental microbiology of the prevalence of enteric viruses in wastewater [69]
La Rosa et al. 2010 point to the potential health risks of the release into the environment of enteric viruses in treated wastewaters, Using quantitative TaqMan real-time PCR (polymerase chain reaction) the authors determined the presence of adenoviruse,enteroviruses and noroviruses (GI and GII) in inuent and euent wastewaters of treatment plants at Rome, and compared the results to classical bacterial indicator of faecal contamination. The authors report a removal eciencies which ranged from 35% (enterovirus) to 78% (norovirus GI), while removal eciency for bacterial indicators was up to 99%. Infectivity assays conrmed potential public health risks through euent wasters of communal water treatment plants. Bacterial indicators were found inappropriate to monitor wastewater viral removal eciency.
24.9.23
Control and prevention methods
The prevention of infection requires control measures at all stages of the food chain, from agricultural production on the farm to processing, manufacturing and preparation of foods in both commercial establishments and the domestic environment. Available data are not sucient to enable the recommendation of specic intervention methods on the farm in order to reduce the incidence of EHEC in cattle. However, risk assessments conducted at national level have predicted that the number of cases of disease might be reduced by various mitigation strategies for ground beef (for example, screening the animals preslaughter to reduce the introduction of large numbers of pathogens in the slaughtering environment) Since a number of EHEC infections have been caused by contact with recreational water, it is also important to protect such water areas, as well as drinking-water sources, from animal wastes.
24.9.24
Recommendations to reduce the public health risk
To ensure that those who come directly or indirectly into contact with food are not likely to contaminate it with EHEC, food handlers should follow the Recommended International
24.9. ISOLATION AND IDENTIFICATION Code of Practice, General Principles of Food Hygiene. [70]
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Basic good food hygiene practice, as described in the WHO Five keys to safer food , can prevent the transmission of pathogens responsible for many foodborne diseases, and also protect against foodborne diseases caused by EHEC. Such recommendations should in all cases be implemented, especially "Cook thoroughly" so that at least the centre of the food reaches 700 C .
24.9.25
Specic recommendations to sprout producers
In recent years, the popularity of sprouted seeds has increased signicantly owing to their nutritional value. However, reports of foodborne outbreaks associated with such raw vegetable sprouts have raised concerns among public health agencies and consumers. Outbreak investigations have indicated that pathogens found on sprouts most likely originate from the seeds. The seed may be contaminated in the eld or during harvesting, storage or transportation. During the germination process in sprout production, low levels of pathogens present on seeds may quickly reach levels high enough to cause disease. Therefore specic care is needed. Guidance is available in the Codex Code of Hygienic Practice for Fresh Fruits and Vegetables, Annex for sprout production (document CAC/RCP 53-2003 of the Codex Alimentarius Commission. [71]
24.9.26
Seeds and sprouted seeds, health risks and recommendations of the EFSA [72]
The European Food Safety Authority (EFSA) assessed the risk of pathogenic bacteria that may contaminate seeds intended for sprouting and sprouted seeds (sprouts, shoots and cress) which are generally consumed raw or minimally processed. Pathogenic bacteria can contaminate seeds and grow during sprouting. Furthermore, preventing initial contamination during production, storage and distribution of seeds is of the foremost importance. The Germany and France sprout-associated outbreaks in 2011 had been preceded by large outbreaks in the EU and worldwide commonly caused by Salmonella and pathogenic E. coli (including STEC). Very low levels of the bacteria-as little as 4 bacteria/kg-in seeds intended for sprouting have been sucient to cause outbreaks. Other bacterial pathogens (e.g. Bacillus cereus, Listeria monocytogenes and Yersinia enterocolitica) have also been implicated in sprout-associated outbreaks, but very rarely. These pathogenic bacteria can contaminate the seeds intended for sprouting during production, storage and distribution through, for example, contaminated irrigation water and soil particles. The high temperature and humidity needed for the germination and sprouting of seeds are also favourable conditions for pathogenic bacteria to further grow and spread.
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24.9.27
Panel recommends additional safety measures for the sprouted seed production chain
Panel considers sprouted seeds as ready-to-eat foods and therefore recommends that general EU food safety hygiene rules should be applied across the whole chain from seed production to the nal sprouted product. Food safety systems such as Hazard Analysis and Critical Control Point (HACCP) principles, Good Hygiene Practices (GHP), Good Agricultural Practices (GAP) and Good Manufacturing Practices (GMP) should be applied. The Panel concludes that preventing initial contamination of seeds intended for sprouting is of particular importance, as there are currently no methods to ensure elimination of pathogens in all types of seeds used for sprouting. Suggested mitigation options include but are not limited to: identifying seed crops intended for sprout production before planting; safe use of fertilizers and irrigation water; minimizing contamination of seeds with soil during harvest and preventing mechanical damage of seeds; ensuring that workers harvesting and handling seeds follow hygiene and health requirements; ensuring that seeds are transported, processed and stored under conditions which will minimize the potential for microbial contamination; removing damaged seeds; and improving traceability and minimizing mixing of seed lots. Operators producing sprouted seeds should strive to implement additional food safety management measures across the whole sprout production chain. Stakeholders at all parts of the production chain and consumers, including also those practising home-sprouting, should be informed of the food safety risk posed by sprouted seeds.
24.9.28
French outbreak: First EHEC death conrms that the outbreak is still going on [73]
A patient at an hospital at Bordeux, Southwest o France die this morning suering hemolytic uremic syndrome. The deadly strain of Escherichia.coli which infected the women diered from the strain which caused the death of 48 people in Germany and one each in the United States and Sweden. Health experts suppose that contaminated Egyptian fenugreek seeds could be a n infection source, but again the source of the infection remains uncertain. Seven other patients hospitalised in Bordeaux were infected by the German strain EHEC O104:h4 (Husec041) and one patient has another strain, but also deadly as the German strain. This suggests that the EHEC bacteria is mutating quickly. It is known that deadly strains of Escherichia coli are bread by cattle and camels without doing harm to these animals. From the intensive farming of cattle in Europe the bacteria spread to the environment. Testing cattle at farms should be started to eliminate animals which shed the bacteria.
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Experts fear that the EHEC O104:h4 (Husec041) may spread to communal waters and drinking water reservoirs. If so, tap water is endangered as Escherichia coli bacteria are sporadically being found in drinking water samples, says expert. [74]
24.9.29
CDC renews raw sprout warning as outbreaks go on in 2011 [75]
Cook them or stay away to avoid salmonella, E. coli. The sprouts should be thoroughly cooked to kill the bacteria, and some people should stay away altogether, the Centers for Disease Control and Prevention said. Sprouted seed is a perfect vehicle for pathogens which cannot be washed o. Shiga toxin-producing E coli (STEC) have a low infectious dose, sprouts are a great vehicle. Sprouts have caused many outbreaks of illness. Since 1998, more than 30 outbreaks have been reported to the CDC, due to many dierent kinds of sprouts of alfalfa, bean, clover, and others. Sprouts can make even young and healthy people ill and can be particularly severe in vulnerable populations, such as young children, older adults, pregnant women, and people with compromised immunity. It can be hard for those who become ill to remember having eaten sprouts. People often do not remember having eaten them, because they are often just a garnish or just one of many ingredients in a food dish. It is not necessary to eat large quantities of sprouts to make a person sick. Raw produce can present a challenge, however, especially when it comes to salads, salsas, guacamoles or similar mixed dishes, and patients cant recall all the ingredients.
24.9.30
Genetic characterisation of Escherichia coli O 104 H4 of the HUS German and French outbreak 2011 [76] [77]
Weill et al 2011 suggest contaminated seeds of one type of sprouts to be the most probable source of the outbreak of bloody diarrhoea and haemolytic-uraemic syndrome caused by Shiga-toxin-producing Escherichia coli O104:H4 in France and Germany. The authors present microbiological data from the outbreak of the bloody diarrhoea and haemolyticuraemic syndrome, associated with consumption of sprouts that occurred in June-July, 2011 in Southwest of France. Bielaszewska et al 2011 presented the virulence prole of isolates from the German outbreak, and stress that blended virulence proles in enteric pathogens, may be fatal for susceptible populations. [78]
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The Serotype O104:H4AND has rarely been associated with HUS in the past. The HUSassociated strains carried genes typically found in two types of pathogenic E. coli, enteroaggregative E. coli (EAEC) and enterohemorrhagic E. coli (EHEC). Mellmann et al 2011 suggest that EAEC 55989 of 2001 and the actual EHEC O104:H4 strains evolved from a common EHEC O104:H4 progenitor, by stepwise gain and loss of chromosomal and plasmid-encoded virulence factors, creating the actual highly pathogenic hybrid of EAEC and EHEC. [79] The German and the French strain belong to the O104:H4 serotype serotype group B1. Extraintestinal virulence genes were found positive for irp2, fuyA and aerobactin genes. The extended-spectrum -lactamase phenotype was due to the blaCTX-M-15 gene. The Shiga-toxin-producing E coli virulence-factor genes were positive for the stx2 gene (stx2 a variant), whereas stx1, eae, and EHEC-hlyA genes were negative, Enteroaggregative E coli virulence factors was positive for aggR and pic, whereas astA was negative.
24.9.31
FDA Guidance for Industry to reduce microbial hazards from sprouted seeds [80]
It is dicult to grow "safe" sprouts. the US Food and Drug Administration developed guidance to help sprout growers reduce the risk for pathogen contamination in sprouts they produce and sell. The Food and Drug Administration recommends that producers soak the seeds in a calcium hypochlorite solution for 15 minutes. Many sprouts growers have implemented practices to decontaminate seeds before sprouting, but no available method has proved completely eective, because the contamination typically starts with the seed.
24.9.32
Idaho sprouts linked to outbreak of Salmonella Enteritidis sickening 25 people [81]
Epidemiological investigations linked an outbreak, which to alfalfa sprouts and spicy sprouts (a mix of alfalfa, clover and radish sprouts) grown by Evergreen Produce in Moyie, Idaho.
24.9.33
Investigating Foodborne Outbreaks [82]
If a larger number of people than expected appear to have the same illness in a given period and area, its called a cluster. When an investigation shows that ill persons in a cluster have something in common to explain why they all got the same illness, the group of illnesses is called an outbreak. Informations related to rising illness numbers are gathered by report systems. Laboratory testings include serotyping of markers on the surface of the bacteria, DNA ngerprinting identies the bacterias specic genetic pattern or DNA ngerprint. It can take 2 to 3 weeks from the day the person became ill to the day such
24.10. INTERNALISATION OF E.COLI AND SAMONELLA IN VEGETABLE PRODUCTS
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data are available. Identify mode of transmission such as food, water, or direct contact with an infected person or animal. Questionaire will help to clear this.
24.10
Internalisation of E.coli and Samonella in vegetable products
[83] The number of outbreaks of Salmonella spp. and Escherichia coli O157:H7 involving fresh produce, including leafy greens, fruits, and nuts is increasing. Salmonella spp. and Escherichia coli O157:H7 can internalize within a variety of plant tissues. Deering et al. 2011describes the various routes of internalization into the plant, survival following internalization, and interactions between internalized bacteria and the plant. There are numerous factors that can inuence the extent of internalization, such as greater demand, cross-country shipping and/or importation of fresh produce, increasing the time from harvest to consumption, more intensive use of land, and increasing demand by consumers for ready-to-eat fresh produce items. Deering and colleagues developed immunocytochemical techniques to localize internalized E. coli O157:H7 expressing green uorescent protein in germinated mung bean. The bacteria were found found in every plant tissue and cell type, particularly in cortical cells on the outside of the vascular bundles. Mung bean plants were found to support bacterial growth up to 10(7) CFU per plant keeping such high level of bacterial for more than 12 days. The authors remind that E. coli O157:H7 can be internalized in plant tissue following seed contamination. [84] Deering and colleagues also investigated internalisation of peanut seed with Salmonella. Their tests demonstrated a high internal contamination of the seeds with Salmonella after an external exposure to the bacterium. The researchers concluded that Salmonella Typhimurium can get into de cells of dierent plants and grow there. Washing or even rinsing with sanitizers will not eliminate the bacteria, while only cooking will be on the safe side. [85] Other pathogenic Escherichia coli strains are:
24.10.1
Escherichia coli enteroinvasiv (EIEC)
This group produces disenteria.It is similar to Schigella and may penetrate the cells of the mucous membrane and cause their death. The germs are none motile, they are gas negative and do not ferment lactose in 24 hours. Virulence of EIEC strains are due to the presence of the plasmids 120- until 140-kDA. These plasmids bear the code for dierent proteins of the cell membrane, being reponsible for the ability of invasion. Among these proteins there are lamentous brils with which the germ may xate to
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the host cells. EIEC has great anity to the small intestines.
24.10.2
Escherichia coli enterotoxic ETEC
Escherichia coli enterotoxic ETEC characterizes bacteria which produce thermolabile and or thermostable. The diarrhoeas caused by this group of bacteria are aqueous, accompanied by low fever and nausea. In acute cases they behave cholera accompanied by acute dehydration. Infection occurs by ingestion of food and water with faecal contamination. The ETEC group is responsible for most of the diarrhoea during travels (Travellers diarrhoea). To develop his toxic activities it is necessary to produce brils whose code is placed in the plasmids.With theses brils the germ can xate itself to the host cell and start the invasion. There is a small anity to the colon.
Enterotoxines thermolabiles (LT) There are toxins whose code is situated in the plasmids such as the serogroup (LT-I) with the toxins LTh and LTp. Less frequent is the enterotoxine of the serogroup II (LT-II) whose code is situated in the chromosomes.These toxins are similar to the toxin of cholera. The toxins are composed by part A and part B. Part A can be separated in the subunits A1 and A2 with trypsin. The subunit A1 is responsible for the toxic activity producing cyclic AMP (cAMP) which produces cholera similar diarrhoea. unit B is built of 5 identical parts. This subunit is responsible for the union of the toxins with the cell receptor gangliosides of the host as well as it is responsible for the union of the toxins with the enterocites (epitelial cells of the colon).
Enterotoxines thermostable (ST) The toxins ST from type A stay active even after heating at boiling point for about 15 to 30 minutes (stable up to 120o C ) and are stabil against many proteases. The toxin ST A is believed to activate the guanilateciclase stimulating thus the formation of GMP which produces loss of liquid similar to cAMP.
24.10. INTERNALISATION OF E.COLI AND SAMONELLA IN VEGETABLE PRODUCTS Sorbitol-fermenting EHEC O157:H- [86]
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According to Mellmann and colleagues 2010 Enterohemorrhagic Escherichia coli (EHEC) O157:H7 cause painful bloody diarrhea. Hemolytic uremic syndrome (HUS) develops in about 15% of infected children in around 1 week after the rst loose stool. Sorbitolfermenting (SF) E. coli O157:H- (nonmotile) strains cause about 20% of all cases of HUS. Unlike E. coli O157:H7, organisms within this clone can ferment sorbitol after overnight incubation on sorbitol MacConkey agar. Variations of the genome of enterohaemorrhagic Escherichia coli O157:H7 affects its adherence and virulence [87] In strain of enterohaemorrhagic Escherichia coli (EHEC) O157:H7 the Tellurite resistance (TelR ) is encoded by duplicate ter cluster in O islands (OI) 43 and 48, which also harbour iha, encoding the adhesin and siderophore receptor Iha. Bielaszewska et al 2011 described ve EHEC O157:H7 strains that dierentiate into large (L) colonies and small (S) colonies with high and low Tel minimal inhibitory concentrations (MICs) respectively. S colonies sustained large internal deletions within the TelR OIs via homologous recombination between IS elements and lost ter and iha. According to the authors, iha-negative phenotypes adhered less well to human intestinal epithelial cells and grew slower than did their iha-positive counterparts, and variations of TelR OIs aects EHEC O157 virulence concluded the authors
24.10.3
PulseNet
To identify reservoirs of EHEC O157:H7 infections and of other foodborne pathogens and to elucidate the molecular epidemiology of these pathogens in the United States, PulseNet was established in 1996. This US national molecular subtyping network for foodborne disease surveillance facilitates subtyping of bacterial foodborne pathogens for epidemiologic purposes. Multilocus variable number tandem repeat analysis (MLVA), used by PulseNet is a subtyping technique for characterizing human pathogenic bacteria such as enterohemorrhagic Escherichia coli (EHEC) O157. Multilocus variable number tandem repeat (VNTR) analysis (MLVA) is based on the characterization of dierent VNTR regions throughout the bacterial genome. Repeat regions are amplied by using PCRs, and resulting fragments are sized to determine the number of repeats. The combination of numbers of repeats of dierent VNTR loci results in an allelic prole known as the typing result. Mellmann and colleagues determined the phylogeny of epidemiologically unrelated EHEC
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O157:H7/H- clinical isolates through 8 MLVA loci obtained in Germany during 1987-2008. Specic MLVA proles with an evolutionary persistence were identied, particularly within sorbitol-fermenting EHEC O157:H-.These pathogens belonged to the same MLVA cluster.
24.10.4
Enteropathogenic Escherichia coli (EPEC)
Enteropathogenic Escherichia coli ( EPEC) causes diarrhoea dierent from that of Shigella and dierent from EIEC.They do not produce enterotoxines ETEC. Enteropathogenic Escherichia coli EPEC produces typical lesions. Especially dangerous are the serotypes O55, O111, O 127, O86 and others being found in babies. Diagnosis of outbreaks in nurseries is only possible through culture and identication of the germ using biochemistry and serology. Other diagnosis are done using hibridisated DNA sonde with the adherence factor (EAF) plasmid from the EPEC group. In milk and meat products VTEC- bacteria, but no EHEC strains were recently found in milk,yoghurt, cheese, meat products, ne salads and meals from great kitchens. The main danger is therefore unheated or underheated ground meat and milk. Heat treatment makes sausages safe if there is no reinfection after heating.
24.10.5
The Belgian E.coli outbreak report [88]
Eurosurveillance published a case occurred in October 2007, related to an outbreak of verocytotoxin-producing Escherichia coli (VTEC) O145 and E. coli O26 in ice cream in the province of Antwerp (Belgium). Five children, aged between two and 11 years, developed haemolytic uraemic syndrome (HUS). According to Eurosurveillance three VTEC O145 and one VTEC O26 infections were laboratory conrmed in three children. The infection was traced back ice cream leftovers, detected with PCR and PFGE in faecal samples taken from calves, and in samples of soiled straw from the farm at which the ice cream was produced. Contamination took place after the pasteurisation process. Verocytotoxin-producing Escherichia coli (VTEC), including E. coli O157:H7, O26, O145 and other E. coli serotypes, are important causes of gastrointestinal illness and haemolytic uraemic syndrome (HUS) in young children. This syndrome is characterised by haemolytic anaemia, thrombocytopenia and acute renal failure, a complication occurring in 5-14% of VTEC infections [89] [90]. HUS is a potential life-threatening disease and can induce hypertension, proteinuria and chronic renal failure in 5% of aected patients. The age group primarily aected are children under ve years.
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The Eurosurveillance authors stress that the incidence of VTEC in Belgium is probably underestimated, as most of the countrys clinical laboratories do not test for these micro-organisms in routine gastroenteritis samples. They point to the need to consider zoonotic transmission and to highlight the prevention measures in facilities where there is easy contact with farm animals and their environment. Moreover, in our case the presence of VTEC in cattle at the farm and the shared activities of food-handling are problematic, as these pathogens can survive for months on surfaces, cross-contamination is a signicant risk and there is the need to reinforce hygienic measures for food-handlers working at farms where food products are prepared.
24.10.6
Ways of infection with EHEC
The most important reservoir of the bacteria are ruminants.Unheated ground meat and unheated milk are the main source of infection.Human carrier of the bacteria are an important vector of the disease through smear infection of food and utensils as well as direct contact.Very important is the hygiene of communal toilets in kindergarten,in home and in homes for old people.
24.10.7
Measures to avoid contamination with EHEC
Heat food at at least70o C .The bacteria are killed at this temperature and their verotoxins are denaturated.This is most important in case of risk groups such as babies, children, old people and immune weakened persons. Avoid cross infection by keeping unheated food separated from heated food. Use careful hygiene in storage and handling of food. Infection with EHCE is bound to faecal contamination.Personal hygiene is most important, specially washing and disinfection of hands.About 90% of infections could be avoided with perfect handling of food.
24.10.8
A new, drug-resistant strain of E. coli is causing serious infectious diseases [91]
The ST131 Escherichia coli strain, was identied in serious antimicrobial-resistant infections in USA by James Johnson and colleagues 2010. Isolates of 2007 exhibited uoroquinolone or extended-spectrum cephalosporin resistance. The authors stress that the ST 131 strain has a high level of virulence together with an antimicrobial resistance. It is becoming almost untreatable, compared with older high virulent Escherichia coli which were known as susceptible, and other resistant strains which were less virulent.
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24.10.9
Antibiotic resistance gene NDM-1 from India and Pakistan [92]
Walsh and colleagues 2010 studied the carbapenem drug-resistant bacterial gene called NDM-1, or New Delhi metallo-beta-lactamase 1, rst identied in bacteria in India, Pakistan, and recently in UK. This may become a new global health problem. Most isolates carried the NDM-1 gene on plasmids. The authors assessed the prevalence of bla(NDM-1) carbapenem resistance gene, in multidrug-resistant Enterobacteriaceae in India, Pakistan, and the UK, using PCR and pulsed-eld gel electrophoresis of XbaIrestricted genomic DNA methods. Plasmids were analysed by S1 nuclease digestion and PCR typing. The authors report that NDM-1 was mostly found among Escherichia coli and Klebsiella pneumoniae, which were highly resistant to all antibiotics except to tigecycline and colistin. The NDM-1 gene produces an enzyme which breaks up the central ringed structure (beta-lactam), common to most of antibiotics. This structure halts bacteria replication. A beta-lactam ring has an heteroatomic ring structure, consisting of three carbon atoms and one nitrogen atom. [93]
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Carbapenems are a class of beta-lactam antibiotics with a broad spectrum of antibacterial activity. They have a structure that renders them highly resistant to beta-lactamases. The carbapenems are structurally very similar to the penicillins, but the sulfur atom in position 1 of the structure has been replaced with a carbon atom, and hence the name of the group, the carbapenems. [94] The NDM-1 gene renders bacteria also resistant to carbapenems, antibiotics of last reCopyright 1998-2010 Karl H. Wilm. All rights reserved. OurFood Database of Food and Related Sciences
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sort, and the gene can be transferred between dierent bacteria. Carbapenems resistance-conferring gene is spreading in India because of an irrational use of antibiotics. Due to an increasing tourism to India for cosmetic surgery the infection spreads to USA, Israel, Greece and Turkey.
24.10.10
High-risk clones disseminating antibiotic resistance [95]
Woodford et al. 2011 report that many bacterial species have a clonal structure which may be widespread. Some global clones are multiresistant and have disseminated from single foci, such as the KPC carbapenemase-positive Klebsiella pneumoniae ST258 from Greece to northwest Europe. The global ST131 Escherichia coli clone most often has CTX-M15 extended-spectrum beta-lactamase (ESBL). However there are also strains which do not depend on ESBLs or have dierent ESBL types. The authors describe clonal diversity Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii and Pseudomonas aeruginosa which presents the serotype O12/Burst Group 4 cluster presenting resistances variety from PSE-1 to VIM-1 beta-lactamases. These high-risk clones are entangled in spread of resistance presenting ability to accumulate and switch resistance. Carbapenem-resistant Enterobacteriaceae include strains of metallo-beta-lactamases (IMP, NDM or VIM) and non-metallo (KPC and OXA-48) enzymes, extended-spectrum betalactamase (ESBL) or AmpC enzyme with porin loss. Most strains with NDM-1 carbapenemase also have 16S rRNA methylases, conferring complete aminoglycoside resistance. Livermore et al. 2011 evaluated the activity of chloramphenicol, ciprooxacin, colistin, fosfomycin, minocycline, nitrofurantoin, temocillin and tigecycline against carbapenemresistant Enterobacteriaceae isolates. Acording to the authors the most important genes encoding carbapenem-destroying enzymes are KPCin the US and NDM, which is rapidly spreading internationally from India and Pakistan. [96] Livermore reports that NLX104 plus ceftazidime is particularly eective against Klebsiella pneumoniae strains carrying K. pneumoniae carbapenem (KPC) resistance genes. Combining NXL104 with the antibiotic aztreonam it becomes eective against a wide range of carbapenemase-producing strains, including those carrying the Verona imipenemase (VIM) and the recently identied New Delhi metallo-beta- lactamase (NDM). [97] [98]
24.10.11
Metallo-beta-lactamases [99]
According to Zhao and Hu 2011 metallo-beta-lactamases (MBLs) hydrolyze most betalactams including the carbapenems. VIMs families include 27 variants of metallo-beta lactamases found in Gram-negative bacilli found in more than 40 countries/regions. The authors report further that most of the bla (VIM)s are situated on a class 1 integron, which is a genetic platform able to acquire and express gene cassettes. The fact that integrons are positioned in transposons which are situated on plasmids, making them highly mobile.
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24.10.12
Reduction of antibiotic-resistant bacteria in municipal wastewater [100]
Diehl and LaPara studied the reduction of the quantity of antibiotic resistant bacteria in wastewater solids in anaerobic and aerobic digesters. The authors used lab-scale digesters at 22 0 C , 37 0 C , 46 0 C , and 55 0 C . ve genes encoding tetracycline resistance (tet(A), tet(L), tet(O), tet(W), and tet(X)) and the gene encoding the integrase (intI1) of class 1 integrons. A reduction of 99,9% of these genes were obtained with the anaerobic digester at 55 0 C . Aerobic digesters did not reduce gene quantities. The authors stress that bacteria produce methane gas that can be used to heat the reactor, reducing thus the heating costs. They conclude that high temperature anaerobic digestion of wastewater solids may eliminate various antibiotic resistance genes. This technology together with reduced use of antibiotics in human and veterinary medicine and other uses, such as aquaculture may decrease the risk of antibiotic- resistant strains.
24.10.13
Aztreonam resistance leaded by bla NDM-1 gene [101]
Aztreonam is a synthetic monocyclic beta-lactam antibiotic (a monobactam), with the nucleus based on a simpler monobactam isolated from Chromobacterium violaceum. [102] The CDC reported that during January-June 2010, three Enterobacteriaceae isolates carrying a newly described resistance mechanism, the New Delhi metallo-beta-lactamase (NDM1), were identied from three U.S. states. These isolates, which include an Escherichia coli, Klebsiella pneumoniae, and Enterobacter cloacae, were resistant to all beta-lactam agents except aztreonam Enterobacteriaceae containing blaNDM-1 are linked to patients which recived medical care in India and Pakistan.
24.10.14
Characterization of a new metallo-beta-lactamase gene, bla(NDM-1), and a novel erythromycin esterase gene from India isolates [103]
Young and colleagues 2009 describe a metallo-beta-lactamase gene, bla(NDM-1), and a n erythromycin esterase gene from Klebsiella pneumoniae 05-506 causing an urinary tract infection of a Swedish patient which travelled to Indian. The isolate was shown to possess a metallo-beta-lactamase (MBL) with three resistance-conferring regions: The rst contained bla(CMY-4) anked by ISEcP1 and blc. The second region contained gene cassettes arr-2, a new erythromycin esterase gene. The third region consisted of a new MBL gene, designated bla(NDM-1) which can hydrolyze all beta-lactams except aztreonam. The authors stress that In addition to K. pneumoniae 05-506, the bla(NDM-1) identied on the Klebsiella pneumoniae , was also found on a plasmid in an Escherichia coli isolated from the patients feces. Which rises worries that in vivo conjugation takes place.
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24.10.15
Antibiotic resistance genes transfer between lactic acid abcteria strains [104]
Toomey and colleagues 2009 describe the ability to transfer antibiotic resistance determinants (plasmid or transposon located) to other lactic acid bacteria. In vitro transfer experiments resulted in high transfer frequencies between all LAB pairs. In a rumen model transconjugants were detected but the frequencies of transfer was low and inconsistent The plant model using alfafa showed higher transfer rates. The authors concluded that lactic acid bacteria can act as a source of genetic elements encoding antibiotic resistance which can be transmitted to other lactic acid bacteria.
24.10.16
Chloramphenicol antibiotic found in German pigs[105]
In Bavaria, Germany 25 farms were closed o in mid January 2012 after urine of pigs tested positive for chloramphenicol, an important antibiotic. Ocials found that feed supplied to pig farms by the Bavarian dairy factory Ehrmann contained the antibiotic. Ehrman says that the laboratory of the quality management wrongly discarded the antibiotic. Choramphenicol is used in minimal amounts for selective culturing of moulds. Laboratory waste must be disposed properly or incinerated.
24.10.17
How much?
It is worth to look after details on how much chloramphenicol got into the production water, the so called white water. This production water contains a considerable amount of milk products and is used as feed in pig farms. To contaminate animals of 25 farms, over a period which made it possible to be detected by veterinary controls, implies considerable amount of antibiotics. Otherwise, the dilution factor of the white water would have turned laboratory residues undetectable.
24.10.18
Antibiotics in pig farms[106]
Antibiotics are commonly used in commercial swine production in the United States and around the world. They are used for disease treatment, disease prevention and control, and growth promotion. When used for growth promoting purposes, antibiotics are given at low concentrations for long periods of time given as feed and water additives which improve daily weight gain and feed eciency through alterations in digestion and disease suppression. Residues of Chloramphenicol, no matter how low, are of risk to humans. In humans chloramphenicol is being suspected to cause aplastic anemia, a condition where bone marrow does not produce sucient new cells to replenish blood cells. Other studies suggest that chloramphenicol is toxic to the embryo/foetus and reproduction system.
24.11. BACTERIOCINS IN FOOD INDUSTRY, VETERINARY USE AND IMPORTANCE FOR HUMAN HEALTH
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24.10.19
Chloranphenicol prohibited in animal breeding
Chloramphenicol is since 1994 prohibited in animal breeding for food, according to the EU regulation 2377/90, Annex IV [107], ammended by the regulation 37/2010 Table 2 (Prohibited substances) [108]. The directive 96/23 lays down measures to monitor the substances and groups of residues of toxicologic importance [109]. The directive 2003/181 setts the minimum required performance limits (MRPLs) of 0,3 microg/kg for Chloramphenicol [110]. Minimum required performance limit(MRPL) means minimum content of an analyte in a sample, which at least has to be detected and conrmed.
24.11
Bacteriocins in food industry, veterinary use and importance for human health
Bacteriocins are bacteriocidal toxins released by almost all bacteria. They may inhibit the growth of similar or closely related bacterial strains. They act somehow like yeast and paramecium killing factors. The use of bacteriocins in the food industry may reduce the addition of chemical preservatives as well as the intensity of heat treatments, resulting in foods that are more naturally preserved. The anti-infective potential of bacteriocins for inhibiting pathogens has been shown in various food matrices including cheese, meat, and vegetables, and are promising in treating infections in humans and animals, writes Hammami et al. 2012. [111]
24.11.1
Classication of bacteriocins [112]
Class I bacteriocins The class I bacteriocins are small peptide inhibitors and include nisin and other lantibiotics. Lantibiotics contain the amino acid Lanthionine as part of their structure. Class II bacteriocins The class II bacteriocins are small heat-stable proteins: The class IIa bacteriocins (pediocin-like bacteriocins) they have a Tyr-Gly-Asn-Gly-ValXaa-Cys sequence. This subgroup causes cell-leakage permeabilizing the target cell wall. This group is important in food preservation an medicine, with strong antilisterial activity. Most prominent bacteriocin of this subgroup is pediocin PA-1. The class IIb bacteriocins (two-peptide bacteriocins) require two dierent peptides for activity, such as the lactococcin G, which permeabilizes cell membranes for monovalent ions such as Na and K, but not for divalents ones. Class IIc bacteriocibs are cyclic. Enterocin AS-48 is the prototype of this group. Class IId are single-peptide bacteriocins, which do not have pediocin-like caracteristics, such as aureocin A53, stable under high acidity, is not aected by proteases and thermoresistant.
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Class Iie, are bacteriocins composed by three or four non-pediocin like peptides. Aureocin A70 is a four-peptides bacteriocin, highly active against L. monocytogenes, Class III bacteriocins Class III bacteriocins are large, heat-labile. Subclass IIIa comprises those peptides (bacteriolysins)that kill bacterial cells by cell-wall degradation, such as lysostaphin, hydrolises several Staphylococcus spp. cell walls, principally Staphylococcus aureus. Subclass IIIb, do not cause cell lysis, but disrupte the membrane potential. This causes ATP eux. Class IV bacteriocins Class IV bacteriocins are composed of an undened mixture proteins, lipids and carbohydrates. Examples of this class are Sublanicin and Glycocin F (GccF). Glvez et al. 2007 names the available commercial preparations of nisin and pediocin PA1/AcH, together with bacteriocins such as lacticin 3147, enterocin AS-48 or variacin. These bacteriocins provide news strategies for food biopreservation, reduce the use of chemical preservatives, turns it possible to rerduce heat treatments,use less acids and reduce salt content. Broad-spectrum bacteriocins focuses a wide area inhibition. Narrow-spectrum bacteriocins can be used specic pathogens like Listeria monocytogenes without aecting starter cultures. Bacteriocins are available concentrated form to be added to the food, or they can be produced by starter cultures. They may be integrated in the hurdle strategy. [113] Streptocuccus bovis HC5 cells as oral administration of bacteriocin found as safe Paiva et al 2012 suggest to add bacteriocin-producing bacteria to animal feeds to ruminant and monogastric animals aiming to reduce the use of antibiotics. The authors report that adding viable or heat-killed Streptococcus bovis HC5 cells to the feed of mice did not aect weight gain and general health condition of the animals. Streptococcus bovis may become a safe way to feed bacteriocin to livestock animals. Streptococcus macedonicus ACA-DC 198 important producer of bacteriocins [114] Georgalaki et al. 2013 describe the bacteriocin production of Streptococcus macedonicus ACA-DC 198. The bacterium produces two important lantibiotics: macedovicin and macedocin. Macedovicin was found to be identical to bovicin HJ50 of Streptococcus bovis and thermophilin 1277 produced by Streptococcus thermophilus. The authors report that macedovicin inhibits a broad spectrum of lactic acid bacteria,
1647
several food spoilage species such as Clostridium spp. and oral streptococci. Bovicin HJ50-like lantibiotics were also found to be encoded by Streptococcus suis strains SC84 and D12, Enterococcus columbae PLCH2, Clostridium perfringens JGS1721 and several Bacillus strains. The multiple bacteriocins of Streptococcus macedonicus improve bioprotection during food fermentation, according to the authors. Lantibiotics of Bacillus subtilis promising bacteriotricins for food production Members of the genus Bacillus produce bacteriocins, mostly lantibiotics some arer similar to the pediocin-like bacteriocins of the lactic acid bacteria. Bacillus bacteriocins have a broader spectra of inhibition as compared with lactic acid bacteria bacteriocins. Abriouel et al. 2011 discuss their applications in food preservation and in human, animal health as alternatives to conventional antibiotics. [115] Antimicrobial peptides produced by the genus Bacillus can be classied into two dierent groups based on whether they are ribosomally (bacteriocins) or nonribosomally (polymyxins and iturins) synthesized. These compounds may become important for applications in the food, agricultural, and pharmaceutical industries to prevent or control spoilage and pathogenic microorganisms. such as the ribosomally synthesized lantibiotic bacteriocins produced by members of Bacillus, where subtilin from Bacillus subtilis is a promising candidate. [116] Listeria and other foodborne pathogens resistance to nisin [117] Recently resistance to nisin and Class IIa bacteriocins among the foodborne pathogens were noted. Kaurs et al. 2011 assessed the mechanisms of bacteriocin resistance development among various foodborne pathogens which decrease the eciency of bacteriocins as biopreservatives, involving physiological activity prole of bacteria, alteration of cellenvelope lipid composition, and alteration of the antibiotic susceptibility/resistance prole of bacteria. Bacteriocin-like substances of Bidobacterium [118] Bidobacterial strains, isolated from humans have strain specic and not species-dependent antagonistic activity. Bidobacterium sp. 278 and Bidobacterium bidum 174 produced antimicrobial substances of the 4th class of bacteriocins with wide spectrum and have the highest antagonistic activity of all studied strains. The maximal bacteriocin production happens between 8-16 hours of cultivation, write Poltavska and Kovalenko 2012. Cronobacter in milk and infant formula [119] Cronobacter species are opportunistic pathogens, and a mortality rate of 40 to 80% is associated with infections resulting in meningitis, septicemia, necrotizing enterocolitis, and brain abscesses. Norberg et al. 2012 stress the risk of Cronobacter infections caused by
1648
powdered infant formula, creating immense problem for the powdered baby food industry. Norberg and colleagues refer to the ocial World Health Organization guidelines for preparation of powdered infant formula. [120] There are six genomospecies of Cronobacter spp. (Enterobacter sakazakii) being isolated from a wide variety of foods. According to Healy et al. 2010 Cronobacter spp has a high tolerance to osmotic stress and elevated temperatures improving its survival in dried foods such as powdered infant formula. Cronobacter spp. may survive in macrophage cells and may attach to and invade epithelial cell lines. Cronobacter produce biolm of exopolysaccharide and active eux pumps protect the bacteria of antimicrobial agents such as bile salts and disinfectants. [121] Bacteriocins inhibit Cronobacter sakazakii in milk and infant formula [122] Oshima et al. 201r report inhibition of Cronobacter sakazakii in milk and infant formula by bacteriocins and organic acids. Combination of these compound may improve the safety of infant milk formula. The antimicrobial activity were tested in reconstituted whole milk and in reconstituted powdered infant formula under low temperature of reconstitution of 40 and 500 C , and long storage or feeding times at ambient temperature. Propionic acid and monocaprylin (as POEM M-100) in combination inhibted Cronobacter sakazakii at concentrations of 0.1 to 0.2% in milk and formulas. Lactoperoxidase system (LPOS), combined with bacteriocins nisin or lacticin 3147, inhibited outgrowth of Cronobacter sakazakii at 370 C for 8 h, and 12 h when the infant formula was rehydrated at 40 or 500 C . Powdered milk and infant formulas must comply with the EU food safety criteria for readyto-eat food (EC 1441/2007) which establishes the absence in 25 g of Listeria monocitogenes and Salmonella, and absence of Enterobacter sakazakii in 25 g. [123] Bacteriocins of Enterococcus faecium [124] Banwo, Sanni and Tan 2012 studied nono, an African fermented milk. Enterococcus faecium CM4 and Enterococcus faecium 2CM1 were isolated from raw cows milk. The bacteriocin, entercin A, produced by these strains were active against Bacillus cereus DSM 2301, Bacillus subtilis ATCC 6633, Micrococcus luteus and Listeria monocytogenes. The bacteriocins were stable at pH 4-9, resisted heating of 1000 C for 10 min and treatment with lipase, catalase, -amylase and pepsin, but did not resist to other proteases. The authors concluded that Enterococcus faecium has probiotic activity, and may be interesting as starter culture, depending on safety studies.
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Nisin is eective against Staphylococcus aureus in dairy products, however, lysozyme is not [125] Sudagidan and Yemenicioglu report that 25 g/ml of nisin inhibited the growth of all strains and the biolm formation of Staphylococcus aureus isolated from raw milk and cheese. Lower concentrations, however, were ineective. Lysozyme tested at 5.0 mg/ml showed no inhibition. Strains of Staphylococcus containing both biolm-related protease genes (sspA, sspB, and aur) and active proteases were nisin resistant. The authors concluded that lysozyme do not reduce the risk of staphylococcus aureus growth in dairy products. Nisin can be used to control growth and biolm formation of foodborne Staphylococcus aureus as biopreservative. Possible formation of resistance must, however, be monitored.
24.11.2
Silver nanoparticles is an eective antibacterial and antifungal agent [126]
Silver is used in wound care products, dental work, catheters, in water disinfecting lters, in textiles, cosmetics, domestic appliances, as preservative cosmetic products, in the form of silica gel microspheres with silver thiosulfate complex mixed into plastics provides longlasting antibacterial protection. In this review Lara et al. 2011 state that silver nanoparticles bind with external membrane of lipid enveloped virus to prevent the infection with bacteria viruses and fungus. In particular silver nanoparticles have been studied in the inhibition of HIV infections. Interaction of silver nanoparticles with other viruses was, however, insuciently studied. Silver nanoparticles interact with disulde bonds of the glycoprotein/protein contents of microorganisms such as viruses, bacteria and fungi. Nanoparticles and silver ions change the three dimensional structure of proteins by interfering with S-S bonds and block the functional operations of the microorganism. The authors also stress that the size of nanoparticle is important, shape and morphology are important for best performance of the nanoparticles. Smaller silver nanoprticles than 3 nm are more citotoxic than particles with 25 nm.
24.11.3
Mechanism of bacteria swimming speed explained [127]
Boehm and colleagues 2010 stress that Escherichia coli moves by means of rotating agella that are powered by ion inux through membrane-spanning motor. The bacteria governs its swimming speed with the help of a molecular brake (YcgR) which binds around a messenger nucleotide, a cyclic dimeric GMP (di-GMP). In this bounded form the molecular brake YcgR interacts with the motor protein MotA on the base of the agella causing it to rotate. The authors found that at least ve signaling proteins are engaged in controlling the cellular concentration of cyclic di-GMP determining the swimming speed of the bacteria in response to variations of the environment.
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24.11.4
New method to study motility of bacteria [127]
Golding and colleagues 2009 describe a new method for studying the swimming of bacteria such as Escherichia coli bacteria. The researchers used optical traps with laser lights, microuidic chambers and uorescence microscopy to track pattern of movement of the organism and the response of a stimulus under a controlled environment. The optical traps conne individual cells without impeding their rotation or the movement of their agella. Movement of the bacterial cell alters the light from the laser informing about the direction of the movement, and uorescent markers improves visualization of the bacteria and their agella under a microscope. According to Golding Escherichia coli presentes three to six helical agella. If they all rotate in one direction the bacteria moves corkscrew-like in one direction. However, when one or more agella rotate in the opposite direction the bacteria seems to tumble. The authors determined long-term statistics of the run-tumble time series and changes in velocity and reversals of swimming direction of Escherichia coli.
24.11.5
Food spoiling [128]
Bacteria which may spoil mayonnaise, ketchup, sauces and salads are : Yeasts, molds, lactic acid bacteria such as Lactobacillus, Leuconostoc and Pediococcus. Salads with pH under 4.5: Lactic acid bacteria, yeasts and molds. Salads with pH over 4.5:Lactic acid bacteria, yeasts and molds, Enterobacteriaceen, Salmonella and coagulase positive Staphylococcus. Ketchup may be spoiled by: Bacillus coagulans, Bacillus stearothermophilus, yeast, molds lactic acid bacteria such as: Lactobacillus, Leuconostoc and Pediococcus, acetic acid, thermophilic Bacillus Sauces and dressings are spoiled by: Acid resistant microorganism such as yeasts, molds and lactic acid bacteria. Frozen Food: During the feezing of food water activity is reduced to a point where bacteria cannot divide and her biological activity is signicantly reduced. A part of the bacteria die during freezing. Another part is sublethal damaged so that special revival medias are necessary for further detection. A greater part of the bacteria remain alive and can start the activity as soon as temperatures rises. Important bacteria in frozen food are: Staphylococcus aureus coagulase positive Escherichia coli,Enterobacteriaceae,
24.11. BACTERIOCINS IN FOOD INDUSTRY, VETERINARY USE AND IMPORTANCE FOR HUMAN HEALTH Clostridium perfringens in precooked meat, Salmonella, especially in poultry, sh, crustaceans, eggs and milk,
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24.11.6
Salmonella serotype Enteritides in poultry and in Eggs
In live state, poultry is recognised as a major reservoir of various salmonella serotypes that can cause food poisoning and infection on man. The body temperature of poultry is 38o C allowing the germs to settel iheated n the intestinal trackt and breeding stock were eggs may be contaminated with Salmonella. To reduce the danger of contamination of entire ocks, feed should be heated at 85o for 12 minutes in the presence of 15% moisture.
24.11.7
Salmonella antibiotics-resistant strains should be declared as food adulterants, says CSPI [129]
Meats like chicken, ground beef, ground turkey, and pork are known to cause outbreaks from Salmonella strains Hadar, Heidelberg, Newport, and Typhimurium, presenting growing antibiotic-resistance. In a letter to USDA Secretary Vilsack, the CSPI urges the agency to declare these strains as adulterants. This could prevent meat contaminated with these pathogens to be placed at market. The USDA is considering increasing line speeds and reducing microbial testing in poultry facilities, which could make illnesses tied to chicken even more common. Undercooked meat can bear pathogens, improper handling after cooking allows bacteria to grow to dangerous levels. Keeping hot foods hot and cold foods cold can help limit your risk. Dont let cooked meat sit out for more than two hours. [130]
24.11.8
EU Regulation on the control of Salmonella and other zoonosis [131]
Salmonella spp. is one of the major causes of food borne illnesses in humans. According to the Community Summary Report on Trends and Sources of Zoonoses[1] a total of 192 703 cases of human salmonellosis were reported by 25 Member States in 2004. Pork, after eggs and poultry meat, is a major source of human food borne salmonellosis in the European Union (EU), although the participation of pork-associated salmonellosis in food borne salmonellosis varies between countries or is unclear as, for most Member States, data on the true contribution of pig/pork to human food borne salmonellosis are
1652 not available.
Regulation (EC) No 2160/2003 on the control of Salmonella and other specied zoonotic agents[2] provides for the setting of Community targets, for reducing the prevalence of Salmonella serovars with public health signicance in pig herds. The most frequently reported zoonotic diseases in humans are salmonellosis and campylobacteriosis. Listeria monocytogenes accounted for the highest number of reported fatalities (107 deaths) in 2004. According to EFSA, the report targets the reduction of Salmonella in laying hens in accordance with Article 4 of Regulation No 2160/2003 of the European Parliament and of the Council on the control of salmonella and other specied food-borne zoonotic agents. A nal report will be released in October 2006. Two main options exist for the implementation of monitoring schemes aimed at detecting/evaluating Salmonella prevalence and/or previous exposure to Salmonella in pig production. These options are based on bacteriological and immunological methods. When used appropriately, for specic purposes, each of these approaches is of benet. However, for monitoring purposes the results of immunological and bacteriological investigations cannot be compared directly, as they give dierent information. The choice between immunology and bacteriology, or their use in combination, therefore, will depend on the actual situation and the questions that have to be answered. Bacteriology can be of use when (a) isolation of the strain is necessary for identication, (b) information about all Salmonella infections (all serovars) is required, (c) antimicrobial sensitivity testing is required, (d) the current Salmonella status of individual animals is to be determined, (e) a description of the general diversity of infections with dierent Salmonellaserovars in a population is the purpose of the investigation, and (f) the evaluation of Salmonella-free status of herds is required. Immunology can be of use for the screening of large numbers of blood and other samples, for example, for monitoring the eectiveness of control programmes in endemic regions or establishing the current immunological status of a population (e.g. herd) and the prevalence of infection. Risk mitigation options were identied according to three lines of defence formulated by the World Health Organization (WHO): the rst line focuses on the control of Salmonella in the food producing animal (Pre-harvest control), the second line deals with improvement of hygiene during slaughter and further processing of meat (Harvest control) and the third line concentrates on measures during the nal preparation of the food and the education of the industry and the consumer concerning the application of eective hygienic measures (Post-harvest control). In general, the control of Salmonella is based upon the implementation of preventive actions throughout the whole production chain.
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More specically, measures should be addressed to (i) the prevention of introduction of Salmonella into the herd, (ii) the prevention of in-herd transmission, and (iii) the increase of the resistance to the infection. No universal mitigation option capable of eliminating Salmonella entirely from the harvest and post-harvest level was identied. A combination of measures aimed at the prevention of vertical and horizontal transmission is likely to be the most eective approach, as is the case with most other food borne pathogens. Reduction of the pathogen load in live pigs in each phase of the food chain, including the transportation phase, can be incrementally achieved by separation of batches, the implementation of Good Hygiene Practices (GHP) and hygiene management and optimisation of transport and lairage time. Slaughter and dressing has to be performed with a high level of hygiene, according to Hazard Analysis and Critical Control Points (HACCP) principles in association with GHP, and focusing on the avoidance of direct or indirect faecal/intestinal contamination of carcasses. Logistic slaughter is a further option for reducing the pathogen load on the carcasses of slaughtered pigs. Meat/carcass decontamination may be considered in specied situations, under the supervision of the competent health authorities. However decontamination should not be regarded as a substitute for any of the above mentioned recommendations. Risk mitigation during processing requires maintenance of the cold chain and the application of the so-called "hurdle concept" and the implementation of GHP and the principles of HACCP. At retail and consumer level mitigation includes hygienic handling and proper cooling or heating of pork and pork products. These options and procedures should be communicated to retailers and consumers. Monitoring at harvest level is of relevance in regard to both process hygiene evaluation purposes and evaluates the current Salmonella status of the entire food chain. For human exposure assessment, monitoring requires to be conducted at the pre-consumption level.
24.11.9
The EU Zoonose Directive
The Community system for monitoring and collection of information on zoonoses was established by Council Directive 92/117/ECC (The Zoonoses Directive).The new Zoonoses Directive 2003/99/EC was adopted by the Council and the European Parliament on 17 November 2003.
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This Directive setting rules for the Member States of European Union (EU) to collect, evaluate and report to the Commission, each year, data on specic zoonoses and zoonotic agents in animals, foodstus and feedingstus.
24.11.10
Summary Report of Zoonosis 2004 [132]
EFSAs First Community Summary Report on Trends and Sources of Zoonoses, Zoonotic Agents and Antimicrobial resistance in the European Union in 2004 was published in December 2005. The zoonoses, meaning infectious diseases transmissible from animals to humans, aected over 380,000 EU citizens in 2004. Often the human form of the disease is acquired through contaminated food. According to the report, the two most frequently reported zoonotic diseases in humans were Salmonella and Campylobacter infections. These bacteria were also commonly found in food and animals. The report includes information of 11 zoonoses, antimicrobial resistance in zoonotic agents as well as foodborne outbreaks. The ve most frequently isolated Salmonella species in the EU were, in descending order: Salmonella Enteritidis, Salmonella Infantis, Salmonella Typhimurium, Salmonella Mbandaka and Salmonella Livingstone. Data on Salmonella were reported for a wide range of foodstus. The majority of samples were collected from various types of meat and meat products. The lowest levels of contamination in poultry, pig, and bovine meat during the last ve-year period have been reported from Finland, Sweden and Norway. Salmonella was detected at all levels of the poultry meat production, with the highest rates of contamination observed at the slaughterhouse and processing plants. Proportions of positive samples in poultry meat were generally lower than 10%, with the lowest proportions reported in countries with control programmes in the poultry production. At retail Salmonella was reported in fresh poultry meat ranging from 2% to 18.5% positive samples. A general decreasing trend of Salmonella in table eggs was observed in those countries that had reported consistently. In pig meat, no clear trend was discernable, except for The Netherlands where a clear reduction was observed. Most countries reported Salmonella prevalences in pig meat below 10%. The contamination levels in bovine meat were generally considerably lower. Some Member States reported contamination of ready-to-eat-meat products at the same level as in fresh meat. Such products constitute a particular risk to human health. In milk and dairy products Salmonella was rarely reported. Several surveys covering spices and herbs revealed relatively high Salmonella contamination. Salmonellosis along with campylobacteriosis, are by far the most frequently reported food
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borne diseases in the EU. Both diseases are frequently caught through ingesting poultry and poultry products, such as eggs. On average about one in ve large scale commercial egg producers have laying hens infected with the Salmonella spp. pathogen. The testing did not nd the Salmonella spp. species in any large scale commercial egg producers in Luxembourg and Sweden. The maximum level was found in Portugal, where about 80 per cent of the holdings had at least one hen test positive for the pathogen. Salmonella Enteritidis and Salmonella Typhimurium were not found in Sweden, Ireland, Cyprus, Luxembourg, Latvia. Meanwhile, about 64 % per cent of the egg farms in the Czech Republic tested positive, followed by Poland, where 56 % had one or the other species of the pathogen, and Estonia, with 52 % testing positive. According to EFSA holdings having Salmonella enteritidis vaccinated ocks were less likely to test positive for the pathogen. However in eight countries with both vaccinated and unvaccinated ocks, there was no dierent in the proportion of laying hens infected with Salmonella enteritidis. At EU-level the presence of any Salmonella spp. was detected in about 31 per cent of the large-scale laying hen holdings surveyed. The number of positive samples in a holding varied between one and seven, with an important proportion of the holdings found positive on the basis of only one or two of the tested samples. Food-borne outbreaks were reported by eight new Member States. The Czech Republic reported proportionally more outbreaks than any other Member States in the EU, predominantly caused by Salmonella. The Czech Republic reported also 547 Campylobacter outbreaks (44% of the outbreaks) aecting 1,555 people with 90 hospitalisations. Hungary reported one large waterborne outbreak of campylobacteriosis. Lithuania and Poland recorded together 8 outbreaks of trichinellosis. With few exceptions, levels of Salmonella contamination in new Member States that reported testing for in food, were similar to that of the old Member States. Some higher prevalences were reported by Malta in fresh pig meat at slaughter (32.8% Salmonella positive) and by Cyprus in fresh broiler meat at processing (36.6% positive). New Member States also reported testing for Campylobacter in food, particularly in poultry meat. Considerable prevalences (30-40%) were recorded by the Czech Republic, Slovenia and Cyprus. Testing for Listeria monocytogenes in food was performed in all new Member States across a variety of foods. The level of contamination was in general similar to the level in the old Member States, although Estonia found 22.9% samples of shery products positive for L. monocytogenes. Seven new Member States reported testing for VTEC in food. Cyprus, Estonia and Slovenia did not detect any VTEC from the samples tested. Poland reported 8.3% of bovine meat samples were positive and Latvia reported 4.9% of pigs tested were positive.
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The new Member States reported lower incidence of brucellosis in humans and animals compared to the old Member States. This also applies to tuberculosis in cattle. Many of the new Member States are seeking to receive an ocially free status regarding these diseases in accordance with the EU legislation. The new Member States reported the majority of rabies cases in animals, where wildlife (especially foxes) were frequently infected. Estonia, Hungary, Latvia, Lithuania, Poland and Slovakia reported cases both in farm animals, pets and wildlife. Some new Member States reported ndings of parasites from slaughter animals. Lithuania, Poland and Slovakia found Trichinella in slaughter pigs, and Poland reported remarkable high Echinococcus ndings in sheep, goats and pigs. Data on antimicrobial resistance, primarily in Salmonella from humans, food and animals, was received from eight new Member States: Czech Republic, Estonia, Hungary, Lithuania, Latvia, Poland, Slovakia and Slovenia. In general, the prevalence of antimicrobial resistance reported by new Member States was similar to, or lower than, the prevalence reported by old Member States.
24.11.11
Unsafe EU food safety From Farm to Fork [133] [134]
UK Cadbury Schweppes pleads guilty for selling chocolate contaminated by a leaking waste water pipe with causing Salmonella montevideo strain outbreak According to the Birmingham City Council the company knew about the contamination but still sold the product, recalled the chocolate bars only after the UK Food Standards Agency. and the Health Protection Agency got envolved on the fact that 37 people were reported being infected by Cadbury chocolate products from January to June 2006. Cadbury is accused of not reporting positive private tests revealing the presence of salmonella strain in January last year alleging the levels present did not pose a danger. This is an infringement against article 19 (3) of the EU General Food Law. Food business operator is obliged to immediately inform the competent authorities if it considers or has reason to believe that a food which it has placed on the market may be injurious to human health. Cadbury Sweppes allege that the low level of Salmonella had been considered by them as harmless and will get through the loophole of the Food Law, which leaves up to the producer to decide whether or he responds to the deviation. [135] Dripping wate water contaminated the chocolate crumb (a mixture of sugar, milk and cocoa) during production at the plant in Marlbrook, Herefordshire. Poor layout of the factory and inadequate drainage and disinfection equipment. and not
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having the EU hygiene rules Hazard Analysis and Critical Control Point (HACCP) analysis in place are the cause of this scandal.
24.11.12
Salmonella reduction in poultry production at the primary production level [136]
Vandeplas et al.2010 describe preventive strategies to reduce the incidence of Salmonella colonization in broiler chickens at the farm level and additional preventive hygienic measures, such as feed and drinking water acidication with organic acids and immune strategies based on passive and active immunity, modication of the birds diet to reduce a birds susceptibility to Salmonella infection, in ovo feeding to accelerate small intestine development and enhances epithelial cell function. Feed additives such as antibiotics, prebiotics, probiotics, and synbiotics, the use of chlorate products and bacteriophages also being studied to reduce enteropathogens I broiler. Mulder 1997 stresses that safe poultry meat production begins with the live birds. Mulder calls therefore, for measures focused on the live bird an such critical control point approach of the HACCP concept should be considered. The capability of microorganisms to colonise the gastrointestinal tract is to be included use of vaccines, antimicrobials and competitive exclusion microoras as well as the implementation of new processing technology should be encouraged. [137]
24.11.13
Nonmotile Salmonella enterica variant bypassed safety procedures in France [138]
Le Hello et al 2012 report a food-related outbreak of salmonellosis in humans caused by a nonmotile variant of Salmonella enterica serotype Typhimurium in France in 2009 circulating in laying hens. This variant was not typed as Typhimurium escaping thus the European poultry ock regulations. The French Regulation has extended the target for reduction of prevalence of Salmonella spp. in poultry producers to include notication of monophasic (because of the recent emergence in humans) and nonmotile (because of this food poisoning) variants of Typhimurium after January 2010. This food poisoning outbreak also highlighted the need for a second selective enrichment media for Salmonella spp. detection not based on the motility in complement to the modied semisolid Rappaport-Vassiladis medium recommended as a single medium by the European Directive [139].
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24.11.14
Comparative risk assessment applied to pig slaughtering in Europe [140]
Fosse J, Seegers H, Magras present a calculation of the incidence and severity of human cases due to pork consumption in Europe together with the ratio of non-control (incidence of human cases divided by the prevalence of hazards on pork). Using these data highest incidence rates were determined for Salmonella enterica, Yersinia enterocolitica and Campylobacter spp. The highest severity scores were calculated for Listeria monocytogenes, Clostridium botulinum and Mycobacterium spp. The main high risk hazards presenting high non-control ratios were Y. enterocolitica, S. enterica and Campylobacter spp.. The authors stress that these risks cannot be detected by macroscopic examination of carcasses during meat inspection at slaughterhouse, which is based on an ante mortem clinical examination and a macroscopic post mortem examination of the carcass, including incision or palpation of lymph nodes and organs. New means of hazard control, such as presented here may improve the inspection at slaughterhouse.
24.11.15
Awareness of cross-contamination is of greater importance than undercooking [141]
Luber 2009 assessed epidemiological studies of Salmonella and Campylobacter infections from poultry meat and eggs Eorts to reduce the contamination of poultry meat or eggs faces the production. Information of the consumer regarding food preparation behaviour is another risk management tool, using messages such as "cook poultry meat and eggs thoroughly"or "wash your hands" to tackle cross-contamination events and undercooking. Reviewing available studies the authors concluded that cross-contamination due to the use of the same cutting board for chicken meat and salad without intermediate cleaning or spreading of pathogens via the kitchen environment seem to be of greater importance than the risk associated with undercooking of poultry meat or eggs.
24.11.16
Aected Cadbury products [142]
Cadbury Dairy Milk Turkish 250g; Cadbury Dairy Milk Caramel 250g; Cadbury Dairy Milk Mint 250g; Cadbury Dairy Milk eight chunk; Cadbury Dairy Milk 1kg; Cadbury Dairy Milk Button Easter Egg 105g; Cadbury Freddo 10p. According to bacteriologist Professor Hugh Pennington of Aberdeen University the fat in chocolate actually preserves the salmonella from the normal intestinal defences. Very few salmonellas cause an infection. The infection dose from chocolate is a thousand times smaller than eating it from traditional sources like meats.
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According to the Food Standards Agency the presence of salmonella in ready-to-eat foods such as chocolate is unacceptable at any level.
24.11.17
Serious situation of European food industry ethic
The responsible head of Cadbury Sweppes has overlook serious problems of the layout of the factory. This situation must have gone on for a long time. The head of the company has knowingly failed to report and recall contaminated products. This is a serious disruption commitment to ethic The company producing 97,000 tonnes of milk chocolate crumb every year placed nancial costs over food safety, selling chocolate with poisonous bacteria and disgusting waste water.
24.11.18
Serious situation of the ocial controls
The Food authority in UK not noticing poor layout of the Cadbury factory during normal check ups is an alarming loophole of the European food safety system and private certication auditings. Stronger surveillance by food authority of factories producing high fat and high sugar items are necessary. Carelessness in cleaning and disinfection is frequent with these produces because they do not present signs of spoilage. UK food authority surveillance is to be blame, at least in part, for the Cadbury Sweppes salmonella scandal.
24.11.19
Vibrio parahaemolyticus in sh and crustaceans
Is a Gram-negative mobile rod. It belongs to the family of Vibrionaceae being found in sh, mussels oysters and shrimps. It grows between 5o C and 44o C , it is halotolerant (it can grow at high content of salt), growing between 2% and 3% of salt and pH 4.8. Food with high contamination with Vibrio parahaemolyticus (1.000.000 /g) cause vomits, diarrohea and haemolysis positive at Wagatsuma-Agar = Kanagawa positive. Table 24.6: Vibrio parahaemolyticus Cytochromoxidase Motility Katalase L- Arginindihydrolase L-Lysinedecarboxylase Growth at 42o C Voges Proskauer TSI Agar + + + + + -
1660 inclined surface basic (red) bottom sour ( yellow ) gas negative H2 S negative Enriching culture
Demonstrate the presence or absence of Vibrio parahaemolyticus 100 ml or g food are mixed with Broth. Incubate at 37o C C for 18 +- 2 hours Inoculate the broth at TCBS-agar. Incubation and biochemical dierentiation.
Total count On TCBS-agar on surface, incubated at 37o C for 18 hours. Kanagawa reaction Point inoculum of dried Wagatsuma-agar. Incubate at 37o C for 18 hours +- 2 hours. Colonies with positive haemolysis are labeled as Kanagawa positive. MPN method MPN-method MPN= most probable number(using 3 tubes. This method is used for total count with very low contamination. Dilution Make dilutions with peptone-salt-broth (0,1% Peptone,3% Salt). 1 ml of the dilutions are added to 10 ml SPB-broth. Incubation 37o C for 18 +- 2 hours. Identication Inoculate the highest dilution on TCBS-agar. Incubate at 37o C for 18 hours. Typical colonies are 2 to 3 mm in diameter with green-blue center. Dierentiated in mediums with 2% to 3% NaCl. Table 24.7: TCBS-agar (Merck Art.Nr. 10263) gram per liter
24.11. BACTERIOCINS IN FOOD INDUSTRY, VETERINARY USE AND IMPORTANCE FOR HUMAN HEALTH Peptone from casein Peptone from beef Yeast extract Sodium citrate Sodium tiosulphate Dried bovine bile Sodiumcholate Saccharose Sodium chloride Iron III-citrate Thymolblue Agar-Agar 5,0 5,0 5,0 10,0 10,0 5,0 3,0 20,0 10,0 1,0 0,04 14,0
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24.11.20
Warning from untreated oysters [143]
A bacteria from the marine and and estuarine environments Vibrio vulnicus is being found in untreated oysters from the Gulf Coast. For people with compromise the immune system the bacteria is deadly for 50% of infections. The Vibrio vulnicus is a bacterium is present in seawater, sediments, plankton and shellsh (oysters, clams and crabs) in the Gulf of Mexico, the Atlantic Coast and the entire U.S. West Coast. As a member of the Vibrionaceae family, Vibrio vulnicus it is related to Vibrio cholerae and Vibrio parahaemolyticus which produce diarrhea. Vibrio vulnicus causes wound infections, gastroenteritis, or a syndrome known as primary septicemia. The CSPI says untreated oysters harvested from Gulf Coast waters from April to October should be subject to state bans and, meanwhile, consumers should avoid consuming such oysters. Raw shellsh northern regions are seen less dangerous as untreated shellsh from the Mexican Gulf because the water temperatures are lower than what is found in the Gulf. However, rising temperatures caused by the climate change will turn northern waters also a potential hazzard.
24.11.21
Action demanded to control deadly Vibrio vulnicus bacteria of raw oysters harvested from the Gulf Coast region [144]
The Center for Science in the Public Interest CSPI points out that eating raw oysters or other shellsh contaminated with deadly Vibrio vulnicus bacteria present a serious health risk. The contaminated oysters are mainly harvested from the Gulf Coast region, especially during the warmer summer months.
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The CSPI urges the FDA to set a performance standard for the shellsh industry to reduce this threat to consumers. An infection with Vibrio vulnicus presents symptoms of classic foodborne illness but for some consumers, it may develop to ulcerous skin lesions and septicemia, half of such cases die and those that survive can suer lifetime inrmities. At risk include consumers with diabetes, hemochromatosis (iron overload), compromised immune systems or liver disease. While the shellsh industry resisted a 2009 FDA attempt to require mandatory postharvest processing of contaminated oysters, the new food safety law signed by President Obama in January 2011 requires the FDA to set performance standards for signicant foodborne contaminants like Vibrio vulnicus. The CSPI stresses that the shellsh industry has a number of commercially viable methods of eliminating Vibrio, including four validated methods for pasteurizing oysters, or it could simply divert contaminated oysters to be cooked. Some restaurateurs and retailers, such as Legal Sea Food and Costco, only sell treated Gulf Coast oysters or oysters harvested from colder waters. Water and mussels were analysed by culture, using selective media including thiosulphatecitrate-bile salts-sucrose and modied cellobiose-polymixin B-colistin agar. Presumptive Vibrio colonies were identied using biochemical tests and PCR using primers based on anking sequences of the cytolysin, vvhA gene, pR72H DNA fragment and 16S-23S rRNA intergenic spacer region (ISR)
24.11.22
Vibrio bacteria in French mussels [145]
French mussels and marine and estuarine water was found by Hervio-Heath et al. 2002 to be contaminated with Vibrio alginolyticus, Vibrio parahaemolyticus, Vibrio vulnicus. Identied Vibrio cholerae were conrmed to be non-O1/non-O139. All 20 V. vulnicus isolates showed PCR amplication of the vvhA gene. The authors emphasise the health risk of Vibrio bacteria in French mussels.
24.11.23
Growth prediction model of Vibrio vulnicus stored at dierent temperatures. [146]
Dasilva et al 2012 developed a predictive model for Vibrio vulnicus stored at dierent temperatures. The Number of Vibrio vulnicus was slowly reduced at 5 and 10C, but increased at 15, 20, 25, and 30C. Using this model growth rate estimates of oysters stored at 25 and 30C were lower than Food and Agricultural Organization (FAO)/WHO model predictions. The model described by the authors may be implemented in food safety plans to reduce Vibrio vulnicus health risk in oysters. Prevalence in waters and shellsh is not associated to faecal indicator organisms. None
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of selective-dierential media developed for isolation of Vibrio spp., and specically for Vibrio vulnicus detection, are satisfying in sensitivity to low numbers and specicity to inhibit growth of other organisms. Harwood Gandhi and Wright 2004 stress, therefore, the importance of immunological and molecular protocols to detect and identify Vibrio vulnicus. [147]
24.11.24
PCR assay based on pilF gene to detect patogenic Vibrio vulnicus [148]
According to Baker-Austin et al. 2012 the bacterium Vibrio vulnicus, a leading cause of seafood-related mortality, has a genetically diverse nature, holds a variety of biotypes, and includes pathogenic as well as non-pathogenic variants hampering detection and enumeration by genetic methods. The researchers report the development of a real-time PCR assay for the detection of pathogenic Vibrio vulnicus strains based on a polymorphism in pilF, a gene associated with human pathogenicity, andmay detect biotype 2 and 3 strains.
24.11.25
Vibrio vulnicus phylogroup clade A [149]
According to Broza et al 2012 the biotype 3 group of the human pathogen Vibrio vulnicus emerged in Israel probably as a result of genome hybridization of two bacterial populations. Broza and colleagues studied the genetic relations between the biotypes 1,2 and 3 looking at 12 variable number tandem repeat (VNTR, also termed SSR) loci. They soon detected a new cluster which could not be associated to one of the three biotypes. Multilocus sequence typing (MLST) supports the creation of a new phylogroup called by the authors as clade A. Broza et al. call for caution as sh aquaculture environment, and possibly man-made ecological niches as a whole, may provide as a source of new pathogenic strains.
24.11.26
Sialic acid of mucous membranes can be catabolised by pathogen variants of Vibrio vulnicus [150]
Sialic or nonulosonic acids are sugars that are present in mucous membranes. Pathogen bacteria and commensal species of animals are able to digest sialic acids. Lubin et al. 2012 report that the sialic acid transport (SAT) and catabolism (SAC) region genes can catabolize sialic acid as a sole carbon source, and are found only in pathogenic Vibrio vulnicus. The tripartite ATP-independent periplasmic (TRAP) transporter was found to be essential for sialic acid uptake in this species. The authors concluded that the ability to catabolize and transport sialic acid is predominately lineage specic in Vibrio vulnicus.
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24.11.27
DNA array of the ISR regions may identify Vibrio species [151]
Kim et al 2012 note that the DNA sequences of the intergenic spacer regions (ISRs) in the groESL gene of 23 Vibrio spp. are variable in. ISR sequence length (41-85 bp). The authors suggest to use DNA array using ISR-specic probes to distinguish between Vibrio parahaemolyticus and Vibrio vulnicus from other species.
24.11.28
Severe epidemics of Vibrio cholerae in India due to faecal contamination of water [152]
Roy et al.2012 describe an outbreak of acute diarrhea occurred in Belgundi area in South India, in June 2010. The isolated Vibrio cholerae O1 El Tor was multiple drug resistant, corresponding to drugs used in empirical treatments. Water samples were found to be heavily contaminated with fecal coliforms. The authors stress that the complex of shortage of potable water, onset of monsoon rains and breakdown of sanitation systems leaded to the outbreak. Decline of the outbreak was attained changing the empirical treatment, chlorination, improvement in sanitation measures backed by information and education activities. The epidemic of cholera that occurred in Kashipur and Dasmantpur blocks of Orissa, reported during July-September 2007 were caused by Vibrio cholerae O1 Ogawa biotype El Tor positive for the ctxA and tcpA genes, according to Pal et al. 2010. [153]
24.11.29
Pathogenic bacteria in Brazilian coastal waters [154]
Ristori and colleagues 2007 analized oysters and estuarine water samples from coastal waters of So Paulo, Brazil., The authors found Aeromonas spp., Plesiomonas shigelloides, Vibrio cholerae O1, Vibrio parahaemolyticus, Vibrio vulnicus Salmonella, Shigella, Escherichia coli O157:H7 in oysters and in water samples too. The authors point out the Vibrio vulnicus was present in 10the samples, and Vibrio parahaemolyticus Kanagawanegative was detected in all oyster samples. The study highlight the true microbial hazard in the aquatic environment and oysters.
24.11.30
Vibrio bacteria in Brazilian oysters [155]
Vieira and colleagues 2010 analysed oyster samples from a coastal aquaculture in Euzebio, Cear, Brazil. The authors identied Vibrio parahaemolyticus. Vibrio carchariae and Vibrio vulnicus, stressing that oysters should never be eaten raw or undercooked becaause of the risk presented by Vibrio bacteria.
24.11. BACTERIOCINS IN FOOD INDUSTRY, VETERINARY USE AND IMPORTANCE FOR HUMAN HEALTH Vibrio vulnicus risk from untreated shellsh throughout the year [156]
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Ramirez and colleagues 2009 determined the occurrence of Vibrio vulnicus, in south Texas coastal waters. During this study Vibrio vulnicus was isolated at all sites throughout the year even with water temperature was down to 9.71 degrees C. However there was a correlations between concentrations of V. vulnicus and water temperature and dissolved oxygen, as well as between concentrations of V. vulnicus and enterococci. The authors concluded that the risk of infection of Vibrio vulnicus exists throughout the year. Monitoring of data such as water temperatur, dissolved oxygen and enterococciu count are being suggested to predict rising risk.
24.11.31
Treated and untreated marine products pose a health risk according to a German scientist [157]
Uwe Janssen, in a period from 1994 and 1996 examined various edible shery- and aquacultureproducts from the North Sea and the Atlantic Ocean, and several exotic species of sh from Africa and Southeast Asia. The incidence of Vibrionaceae was 43 % in the untreated products, and 11 % in the ready-to-eat foodstu. According to the author the high variety of pathogenic species found such as Plesiomonas shigelloides, Aeromonas hydrophila, Aeromonas caviae, Aeromonas sobria,Vibrio cholerae, Vibrio parahaemolyticus, Vibrio vulnicus, Vibrio mimicus, and Vibrio alginolyticus indicate a potential heath risk posed by Vibriuonaceae untreated as well as treated shery products, such as frozen, cooked, fermented, and cold-smoked products.
24.11.32
Vibrio vulnicus in German coastal waters [158]
Ruppert and colleagues 2004 reported two severe cases of Vibrio vulnicus wound infection with secondary septicemia in 2003 on the German island of Usedom in the southwestern Baltic Sea by wading in contaminated sea water. High concentrations of V. vulnicus in the sea water was found when water temperature exceeded 20 C for more than 2 weeks.
24.11.33
Vibrio vulnicus a pathogen in Gulf Coast oysters [159]
Limiting the Sale of Raw Oysters Harvested from the Gulf of Mexico The Center for Science in the Public Interest warns the consumers from Vibrio vulnicus, a deadly bacteria found in almost all Gulf Coast oysters harvested in warmer months. The Californian plan to reduce the risk of Vibrio vulnicus has proved to be eective, but it was binding only in this state [160]. The plan banned the sale of untreated Gulf Coast oysters reducing number of deaths from about ve a year to zero. This approach will now be adopted nationwide by a new FDA policy. The shellsh industry were opposed to the oyster treatment to kill the pathogen.
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The Department of Health Services (DHS) has amended California Code of Regulations (CCR), Title 17, Section 13675, [1ab]to prevent V. vulnicus illnesses and deaths associated with the consumption of raw Gulf oyster, restricting the sale of raw oysters harvested from the Gulf of Mexico during April 1 through October 31, unless the oysters are treated with a scientically validated process to reduce V. vulnicus to non-detectable levels. Raw Gulf oysters received during April through October that have not been processed to reduce V. vulnicus to non-detectable levels are considered adulterated.[161] Treatments to kill Vibrio vulnicus without aecting taste are cold pasteurization, hydrostatic pressure, cost of the processes are low and increase food safety. [162]
24.11.34
Post-Harvest Processed Oysters [163]
Freezing, heat-cool pasteurization, and high hydrostatic pressure are used commercially on oysters as post-harvest processes to kill spoilage bacteria and reducing Vibrio spp. bacteria to non-detectable levels.The treamtment increases the shelf life of the product. The organisation SafeOyster.org, however, stresses that not all bacteria and viruses may be killed. The organisation recommends high-risk patients not to eat oysters, even when they were post-harvest processed. As a safety measure, these patients should eat cooked oysters.
24.11.35
The Center for Science in the Public Interest (CSPI) says Gulf Cost oysters are not safe [162]
According to David W. Plunkett, a CSPI sta attorney, some Gulf oysters may be "safe" from oil contamination, but are not "safe" to eat. Plunkett contradicts several reassuring statements that seafood from the Gulf on the market is safe. Vibrio vulnicus contaminates Gulf oysters in the spring and summer. While it may cause mild illnesses in healthy individuals, it can kill people who have diabetes, liver disease, hemochromatosis or compromised immune systems, causing the death of 10 people last year. The Food and Drug Administration FDA arms on its website that shellsh harvested from areas unaected by the spill are safe to eat. [164] Plunkett remids that last year Mike Taylor, a Deputy of the FDA called Vibrio vulnicus a signicant hazard, and now FDA ignores the risk of the pathogen bacteria. The CSPI says that the FDA eventually backed down from its plans under pressure from Members of Congress who responded to industry posturing over potential job losses, and only California has implemented an eective control plan to protect its consumers.
24.11.36
Vibrio vulnicus infection [165]
Vibrio vulnicus is a bacteria which is present in marine environments such as estuaries, brackish ponds, or coastal areas, It causes an infection eating seafood, especially raw or
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undercooked oysters; the bacteria can also enter the body through open wounds when swimming or wading in infected waters, or via puncture wounds from the spines of sh such as tilapia. Symptoms include vomiting, diarrhea, abdominal pain, and a blistering dermatitis that is sometimes mistaken for pemphigus or pemphigoid. In people with compromised immune systems such as in chronic liver disease, a cut infected with Vibrio bacteria can quickly become worse and spread into the bloodstream. Severe symptoms and even death can then occur.
24.11.37
Vibrio illness in Florida [166]
Weis and colleagues 2010 report 834 vibrio infections in 825 individuals in Florida from 1998 to 2007. The incidence was Vibrio vulnicus 33%, V. parahaemolyticus 29%, and V. alginolyticus 16%, causing wound infections 45% and gastroenteritis 42%. Prevention is focused on oyster consumption. The authors call for educational messages focusing wound infections of high-risk populations.
24.11.38
Foodborne pathogens in oysters of South China food markets [167]
Chen and colleagues 2010 looking at the pathogens in shellstock Pacic oysters in the food markets in South China say that Vibrio vulnicus and Vibrio parahaemolyticus (89.3%) but no Listeria monototogenes could be detected in the samples. The authors concluded that Vibrio vulnicus and pathogenic Vibrio parahaemolyticus in oysters are a risk to public health in south China.
24.11.39
Temperature eects on the depuration of Vibrio parahaemolyticus and Vibrio vulnicus from oysters [168]
Chae, Cheney and Su 2009 investigated temperature eects on depuration for reducing Vibrio parahaemolyticus and Vibrio vulnicus in American oyster. Depuration of oysters at 22 degrees C had limited eects. Best reults were obtained with water temperature of 15 degrees C after 96 h of depuration at 15 degrees C. Depurations at 10 and 5 degrees C were less eective than at 15 degrees C.
24.11.40
Elektrolyzed water as sanitizer in food industry [169]
Hricova, Stephan and Zweifel 2008 report that electrolyzed water is obtained by electrolysing a dilute sodium chloride solution dissociating into acidic electrolyzed water (AEW) with a pH of 2 to 3, an oxidation-reduction potential of >1,100 mV, and an active chlorine content of 10 to 90 ppm, and basic electrolyzed water (BEW), which has a pH of 10 to 13 and an oxidation-reduction potential of -800 to -900 mV.
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AEW reduced bacteria in suspension > 6.0 log CFU/ml. However, surface type and the presence of organic matter reduce the eciency of AEW Applying BEW followed by AEW may lead to higher reductions than AEW only. The authors say electrolyzed water technology should be further discussed as industrial sanitization of equipment and decontamination of food products, but must be accompanied by good manufacturing and hygiene practices.
24.11.41
Electrolyzed oxidizing (EO) water treatment on reducing V. parahaemolyticus and V. vulnicus [170]
Holding vibrio contaminated oysters in electrolyzed oxidizing water containing 1% NaCl reduced the number of Vibrio parahaemolyticus and Vibrio vulnicus signicantly in 4 to 6 h, but exposure longer than 12 h in electrolyzed oxidizing water and chlorine levels over 30 ppm caused death of oysters. Ren and Su 2006, authors of the study, suggested to use electrolyzed oxidizing water treatment for 4 to 6 h as post-harvest treatment of oysters to reduce Vibrio contamination limited to 4 to 6 h to avoid death of oysters.
24.11.42
Weak acidic electrolyzed oxidizing water post-harvest treatment of oysters [171]
Quan and colleagues 2010 report that Vibrio vulnicus and Vibrio parahaemolyticus were killed with a treatment of 15 s and more of weak acidic electrolyzed oxidizing water (WAEW) containing an available chlorine concentration (ACC) higher than 20mg/L. The eect of the treatment was reduced, when the ACC of WAEW was less than 15mg/L. The authors stress that the bactericidal activity of WAEW was primarily aected by ACC rather than treatment time, and WAEW is more eective than sodium hypochlorite (NaClO).
24.11.43
Vibrio vulnicus resistance to bile and other stresses [172]
Chen, Oliver and Wong 2010 describe the adaptation of Vibrio vulnicus and an rpoS isogenic mutant to bile and other stresses. An in vitro tolerance of the bacterium to 10% bile was attained by the authors, The bile-tolerant strain was more resistant to high pH, heat, high salinity and detergents than the rpoS mutant which had a lower bile-adaption rate. The authors report further that production of GroEL was not markedly inuenced but DnaK was inhibited in the bile-adapted cells, and RpoS plays a signicant role in the response of Vibrio vulnicus to bile.
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24.11.44
The interaction between low salinity and other common stresses in V. vulnicus [173]
Wong and Liu 2006 studied the cross-protective response of sublethal heat-, acid-, or bileadapted Vibrio vulnicus against lethal low-salinity stress. The authors found that Vibrio vulnicus adapted to an acidity of pH 4.4 and 41 degrees C heat-adapted V. vulnicus died in 0.04% NaCl low-salinity environment. The bile-adapted bacteria were resistant to low salinity, however 0.12% NaCl low-salinity adaptation made them sensible to 12% bile stress.
24.11.45
Identication and subtyping of Vibrio parahaemolyticus and V. vulnicus targeting 16S-23S rRNA intergenic spacer regions [174]
Homann and colleagues 2010 developed rapid polymerase chain reaction (PCR)-based intergenic spacer (IGS)-typing system for vibrios based on the IGS regions located between the 16S and 23S rRNA genes of vibrios. The IGS-typing method demonstrated distinct IGS-typing patterns indicative of subspecies divergence in both populations making this technique equally useful for intraspecies dierentiation, as well. The authors concluded that the new method is useful to identify vibrios down to sub-species level, and may be applied in time saving epidemiological investigations. Gonzlez-Escalona, Jaykus and DePaola reported in 2006 that amplication of the 16S23S rDNA spacer region (ISR1) is a simple and rapid procedure for subtyping bacteria, especially those with several ribosomal operons including Vibrio vulnicus. V. vulnicus contains nine ribosomal operons with four or ve ISR1 classes that dier in size and sequence. Clinical isolates formed a single cluster containing ISR1 patterns I, V, XI, and XII all carrying the type B 16S rDNA (rrs) sequence associated with human illness. Shellsh isolates presented high variability in the ISR1 patterns. The dierent classes diered in their tRNA gene composition, allowing subtyping of Vibrio vulnicus. The authors suggest that ISR1 patterns are linked with the virulence of the bacteria. [175]
24.11.46
Two sh-pathogenic serovars of Vibrio vulnicus biotype 2 [176]
According to Fouz and colleagues 2010 Vibrio vulnicus biotype 2 is subdivided into serovar E, infecting sh and humans, and serovar A, infecting only sh, such as eel in brackish water. Serovar A caused infections of freshwater-cultured eels vaccinated against serovar E resulting in haemorrhagic intestine. Both serovars infect healthy eels, tilapia, sea bass and rainbow trout, but not sea bream, serovar A entering mainly by the anus and serovar E by
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the gills. The authors stress that serovar A form a new antigenic form of Vibrio vulnicus biotype 2 better adapted to fresh water than serovar E.
24.11.47
Vibrio vulnicus found in food and environmental samples of the Mediterranean area [177]
Caigral and colleagues 2010 found that samples of seawater, oyster and wastewater from a coastal area in Spain near the Mediterranean.were positive by real time PCR, and Vibrio vulnicus could be isolated from these samples. The authors stress that Vibrio vulnicus presents a risk to humans in the Mediterranean area.
24.11.48
Rapid detection of Vibrio vulnicus in shellsh and Gulf of Mexico [178]
Panicker and colleagues 2004 described the optimization of SYBR Green I-based real-time PCR parameters to detect the presence of vibrios in seafood or environmental samples, using vvh-specic oligonucleotide primers. The method is completed in 8 hours.
24.11.49
Other pathogens from shellsch [179]
Plesiomonas shigelloides is a Gram-negative, rod-shaped bacterium which has been isolated from freshwater, freshwater sh, and shellsh and from many types of animals. Infections from this organism cause gastroenteritis, followed by septicemia in immune decient patients. It is placed among the Enterobacteriaceae. Some Plesiomonas strains share antigens with Shigella sonnei, and cross-reactions with Shigella antisera occur. Plesiomonas can be distinguished from Shigella in diarrheal stools by an oxidase test: Plesiomonas is oxidase positive and Shigella is oxidase negative. Plesiomonas is positive for DNAse; this and other biochemical tests distinguish it from Aeromonas sp.
24.11.50
Other pathogenic microorganisms in Greece seafood [180]
Papadoupolou and colleagues 2007 report in Greece marine sh and shellsh the presence of Aeromonas hydrophilia, Klebsiella ozonae, Escherichia coli, Yersinia enterocolitica, Hafnia alvei, Enterobacter agglomerans, Citrobacter freundii, Proteus vulgaris, Proteus mirabilis, Morganella morganii, Pseudomonas uorescens, Pseudomonas putida, Plesiomonas shigelloides, Listeria innocua, Vibrio parahaemolyticus, Clostridium perfringens, Staphylococcus aureus and Candida quillermondi, Candida albicans, Penicillium oxalicum and Penicillium italicum.
24.12. CHLAMYDIA
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24.12
Chlamydia
The genus Chlamydia contains cocoid nonmotile from 0,2m to 1,5m organism which can reproduce only in the vacuoles near the host cell membrane. The reproduction follows a unique cycle. The development includes the passage through small elementary bodies up to larger reticulate bodies which can divide by ssion. At the end the reticulate bodies reorganize into new elementary bodies. These new bodies can survive out of the cells infecting other host cells using a special phagocytosis having no fusion of phagosomes of Chlamydia with the lysosomes. There is a gradual transition between the elementary and the reticulate form, existing intermediate forms. The morphology of the genus Chlamydia is very complex: Table 24.8: Properties of elementary bodies and reticular bodies Characteristics Diameter in m Density in g/cm Infectivity Intracellular Multiplication Intravenous mortality for nice. Immediate toxicity for cells in culture elementary bodies 0,2 - 0,4 1,21 + + + reticulated bodies 0,5 - 1,5 1,18 + -
There are 3 types of Chlamydia : Chlamydia psittaci Chlamydia trachomatis Chlamydia pneumoniae Chlamydia are Gram negative bacteria. They are nonmotile with reproduction intracellular. They cannot produce ATP so that they need other cells from eucariots as source of ATP.Artropodes are not hosts. The evolution comprehends two types of cells: The elementary infectious reticular corpuscules The reticular corpuscule with possibility of reproduction.
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After the intracellular reproduction in vacuoles in the cytoplasm of the cells of humans, other mammals or birds the reticular corpuscules which can reproduce itself are liberated and can be assimilated by new host cells [181] [182]. Within 8 to 12 hours the reticular corpuscules divide 10 to 12 times. At the end of this phase the reticular corpuscules are transformed again in elementary corpuscules.The elementary corpuscules can invade new cells. Chlamydia are susceptible to a series of antibiotic. In cases of infections from Chlamydia there are used tetracyclines, sulfonamides, erythroycine and rifampin. Chlamydia are resistant to aminoglicosides, bacitracin, vancomycin or ristocetin. Important species of Chlamydia are:
24.12.1
Chlamydia psittaci
This bacterium causes the ornithosis also known as psitacosis. Birds are the normal reservoir of Chlamydia together with other animals like cats, dogs and other mammals. Transmission from person to person is very rare. Ornithose looks like a pneumonia varying from not serious to mortal. Transmission is made through air.
24.12.2
Chlamydia trachomatis
Transmission from person to person is direct. The species have various serovares which can cause dierent symptoms.
24.12.3
Chlamydia trachomatis serotype A-K
Produces conjunctivitis by invading epithelial cells. it also invades the epithelial cells of the urinary tract, rectal mucous membrane and feminine genitals.
24.12.4
Chlamydia trachomatis serotype D-K
It is being transmitted through sexual contact. In women it may cause relapsing and chronical diseases resulting in tubal sterility. Infections during pregnancy may cause premature birth and transmission of the germ to the newborn during birth. Since 1995 the examination of secretions of pregnant to exclude a contamination with Chlamydia is provided by German regulations.
24.12. CHLAMYDIA
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24.12.5 24.12.6
Chlamydia pneumoniae Taxonomy
Analysis of gene sequence has led to a revision of the taxonomy of the family Chlamydiaceae. The species Chlamydia pneumoniae was reclassied to Chlamydophila pneumoniae[183].
24.12.7
Cell culture techniques for Chlamydia pneumoniae
Cell culture techniques are used for isolation of Chlamydia pneumoniae from clinical samples. The infection of a monolayer is achieved by centrifugation of the sample onto the monlayer and incubation at 37o C . Cells used for culture are HEp-2 cells and Chang cells with cycloheximide as antimetabolite [184] C. pneumoniae invade the epithelial layer of upper and lower respiratory tract. Many infections occur subclinical or after an incubation of 3 weeks as similar to ue infect. It is believed that 10 to 15% of treated pneumonia are caused by Chlamydia pneumoniae. Since 1989 Chlamydia pneumoniae is considered as pathogenic[185][186]. Transmission is made trough droplets. The possibility that amoebae may act as reservoir of Chlamydia is being discussed. According to seroepidemiological studies 80 percent of adults are infected by Chlamydia. Chlamydia pneumoniae has been detected in various cases of inammation of the myocardium and coronary tissue and blood vessels. This started the theory Chlamydia pneumoniae being the main cause of arteriosclerosis as a result of a respiratory infection during childhood[187][188][189][190]. Invasion of the body by Chlamydia is made through the respiratory tract. In vitro studies have shown that infections of macrophages result in elevation of the secretion of zitoquines such as the tumor-necrotic alfa factor (TNF) and interleukines (IL-1 and IL-6) The inammatory process is directly linked to the multiplication of the cells of the straight muscles as well as the stimulus of of coagulation. A high titer of antibodies in plasma shows that there had been a contact with the germ. Studies of Finland in 1988 have demonstrated the link between coronary diseases and the titer of the antibody. This has created the theory that Arteriosclerosis is caused by an old or a chronical infection with Chlamydia pneumoniae or Herpes simplex. It is still being discussed if they are the main cause or if they settle secondary on already existing lesions, accelerating the process. Chlamydia can infect macrophages and survive for long time in its interior. Macrophages play an important part in the etiology of arteriosclerosis. Macrophages are formed by the blood having the property to assimilate oxidized LDL
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particles and to transform itself in foam-cells. Macrophage may also be produced by the cells of the straight muscles of the blood vessels. Foam-cells are the basis of atheromes, which later on will turn out to arteriosclerosis. It is very likely that Chlamydia pneumoniae causes a local infection with lesions of the blood vessels. These lesions are the points where arteriosclerosis may start. Not always Chlamydia is found in case of arteriosclerosis causing false negative results. A lage amount of evidence has now accumulated demonstrating a positive association between chronic infection with Chlamydia pneumoniae and atheroma development[191]. Even being conrmed Chlamydia to have a leading role in the etiology of atherosclerosis the participation of nicotine, excess of body weight, hipercholesterinemia and hipertonia will not be denied. These risk factors will have to be treated or even eliminated at the same time.
24.12.8
Chlamydia and arteriosclerosis
There are an increasing number of scientic report about Chlamydia pneumoniae being responsible for arteriosclerosis. These reports bring up the discussion about reduction of fat, especially saturated fatty acids in the prevention of arteriosclerosis. The annual edition of "Ernhrungs-Umschau" 1998 has printed an interview with Prof.Dr. Wolfram, president of the "Deutsche Gesellschaft fr Ernhrung[192]. According to Dr. Wolfram there is no reason to modify the prevention of arteriosclerosis.Even in case that Chlamydia pneumoniae is proved to be the main cause of alterations of blood vessels the classic risks will not loose their validity. Helicobacter pylori is considered as being an agent of infections of the gastric mucous membrane. There are evidence that Chlamydia pneumoniae is responsible for the start of arteriosclerosis. The classic prevention such as reduction of weight, reduction of fat in food and increase of physical activity is now on doubt[193].
Heart infarcts, clinical reports Studies in Salt Lake ,Utah, USA[194] have demonstrated the presence of Chlamydia pneumoniae in 79% with coronary arteriosclerosis.Only 4% of the patients bearing Chlamydia had no coronary alterations. This study followed the comments of the studies of Finland and Sweden.The Authors believe that Chlamydia may elevate the level tissue-factors causing thrombosis and adheOurFood Database of Food and Related Sciences Copyright 1998-2010 Karl H. Wilm. All rights reserved.
24.12. CHLAMYDIA
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sion of plattlets causing coronary diseases. They admit however that the results of their studies only satisfy the rst postulate of Koch being more research necessary to conrm their theory.
24.12.9
Diagnostic of human infection caused by Chlamydia
Direct diagnostic of Chlamydia is very dicult starting from material of biopsis of blood vessels.The presence of Chlamydia is conrmed by PCR, immunoestequiometry, immunocitochemistry, electronic microscopy and culture of the germ. Indirect diagnostic can be made through a high titer of antibodies IgG and IgA from Chlamydia pneumoniae and specic immunocomplexes in the plasma of the patient. Chlamydia threatening the population on koala bears (Phascolarctos cinereus) in Australia [195] [196] Koala bears in Australia are being threatened by Chlamydia pecorum and Chlamydia pneumoniae. The concurrent infection with a retrovirus weakens the immune system of the animals. Fortunately, there is a vaccine available that seems to work on female koalas. Health professionals warn of getting in contact with koala bears infected with Chlamidia pneumoniae The disease can be transmited to humans. The urine of diseased Koala bears is also infectious. The Australian state of Queensland reports that the number of koals dropped from 60.000 down to 11.000 from 1990 to 2012. The chlamidia strain infecting up to 90% of the koalas is slightly dierent of the human strain. It is also transmitted through sexual contact and is more severe than the human strain. Symptoms include urinary tract infections and involuntarily bowel excretion, may cause infertility, blindness and death. Researchers from Queensland University of Technology mapped the koalas genome and are working to develop a vaccine. According to Professor Peter Timms the IFN-g genes were found to control chlamydia and Koala Retrovirus infections in humans and other animals. Chlamydophila pneumoniae formerly known as Chlamydia pneumoniae Chlamydia pneumoniae is widespread in humans. It causes acute upper and lower respiratory tract infections in addition to a range of other diseases in humans and animals. It is also infecting animals. Australian koalas are widely infected with Chlamydia, pecorum and Chlamydia pneumoniae. Other Chlamydia, such as Chlamydia psittaci and Chlamydia abortus, are known zoonotic pathogens. [197] Mathew et al. 2013 provide data on the role of two key cytokines, pro-inammatory tumour necrosis factor alpha (TNF) and anti-inammatory interleukin 10 (IL10), in koala bears infected with Chlamydia pecorum. According to the authors these data may be useful to develop a koala chlamydial vaccine. [198]
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Chlamydial vaccine in humans are built on the chlamydial major outer membrane protein (MOMP). Kollipara et al. 2013 report that koalas vaccinated with a MOMP-based Chlamydia pecorum vaccine developed strong antibody and lymphocyte proliferation responses to both homologous as well as heterologous MOMP proteins. The authors concluded that MOMP based Chlamydia pecorum vaccine may protect against a range of strains and vaccine is the best option to protect koalas. [199] Chlamydia trachomatis cause reproductive damage and infertility in many women. The lack of acute symptoms contributes to the high prevalence of chlamydial infection. [200] Chlamydophila pneumoniae infection was proposed as an agent of atherosclerosis, however, Joshi et al. 2013 found that negative clinical trials did not nd benets of antiChlamydophila drug therapy. The authors call for new paradigms in Chlamydophilaatherosclerosis research. [201]
24.12.10
Treatment of arteriosclerosis
Treating infarcts with azitomicin and roxitromicin could reduce the level of infection indicators. There were signicant reduction of the number of relapses. In patients with high levels of antibodies IgG azitomicin and roxitromicin reduced the signs of infection. There are however only a small number of cases under surveillance what does not justify an uncontrolled medication or prophylaxis of arteriosclerosis with these antibiotics. Even being promising, the use of azitomicin or roxitromicin in the treatment of arteriosclerosis may induce resistance to antibiotic in bacteria and loss of eect in the treatment of other infectious diseases.
24.12.11
Acetylsalicylic acid
Studies over 10 years have demonstrated that a group of patients with high level of Creactive protein using acetylsalicylic acid had less infarcts as a group with no protection with AAS. It is being suggested to continue these studies.
24.13. CLOSTRIDIUM PERFRINGENS
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24.12.12
Serum salicylic acid is related to fruit and vegetable consumption [202]
Spadafranca and colleagues 2007 studied the relationship between fruit and vegetable consume and and the amount of circulating salicylic acid, which is a natural phenolic compound present in fruits and vegetable, and is the active principle of aspirin. The authors found that the median salicylic acid serum concentration was 0.124 mumol/l, varying between 0.188 mumol/l for those who had more than 4.75 serving of fruits and vegetables the day before, and 0.112 for those who had only 2.3 servings. The authors stress that there is a low chronic salicylic acid exposure from vegetal food which may be responsible, at least in part, for the benecial eects of fruits and vegetable consume. Vitamin C and arteriosclerosis A study of Finland has established a link between a hypovitaminosis C and arteriosclerosis. It is believed that vitamin C protects against infectious diseases, especially of virotic origin and therefore also against Chlamydia. This theory is yet not conrmed.
24.12.13
Classical advises of arteriosclerosis prevention
Normalize body weight Avoid obesity Avoid hipercholesterinemia Avoid diabetes Avoid high arterial pressure
24.13
24.13.1
Clostridium perfringens
Clostridium perfringens:Merck Fluorocult TSC-Supplement
Clostridium perfringens is an anaerobic sporulating bacterium which is known in medicine causing gaseous gangrene, as well in food microbiology associated with dangerous toxins [203]. A rapid technique to detect Clostridium perfringens in food samples is done by using TSCAgar (Tryptose-Sult-Cycloserin Merck Nr. 1.11972) adding Fluorocult TSC-Supplement (Merck Nr. 1.04032). The supplement contains D-Cycloserin used to inhibit accompanying bacteria and a uorogen substrate (MUP) which acts as indicator of the specic acid phosphatase enzyme.
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24.13.2
Composition of Fluorocult TSC-Supplement
250 mg D-Cycloserin and 50 mg Methylumbelliferylphosphate disodium salt to be used in 500 ml TSC-Agar The supplement is diluted in water and added to the TSC-Agar. The sample is inoculated in pour plate and incubated under strict anaerobic conditions at 44o C for 18-24 hours. All under UV light uorescent colonies are Clostridium perfringens. Further biochemical reactions such as lactose, gelatine, nitrate, motility are unnecessary.
24.13.3
Refrigeration and shelf life
Refrigeration of food is used to increase shelf life. Food freezing made the transportation of perishable food over long distances possible. cooling and freezing food works against the activity of bacteria such as: Speed of biochemical reactions Temperature reduces the speed of biochemical reactions, the growing and the reproduction of bacteria. Drying At freezing point water is not available to bacteria. There are irreversible enzyme inactivations. This leads to refrigeration death. However a great part of bacteria, survive refrigeration and can get to new activity when the temperature rises again. The speed of enzymatic and biochemical reactions are highly temperature bounded. It is therefore obvious that low temperatures result in low biochemical activity. Even under low temperatures there may be enzymatic activity without increase of total number. Streptococcus lactis may produce lactic acid at 0o C but it does not multiplicate itself. As it grows older, the cells may die. As there are no new generations the total number of bacteria may decrease. Very often bacteriological counts from one laboratory do not compare with the counts of another laboratory when the samples are taken on dierent days. Proteolytical activity can take place even at -18o C . Lipolytical activity of Pseudomonas in butter is present at -10o C .
24.14
Diseases transmitted by water
Almost every pathogen agent can be transmitted through water. Normal safe supply of drinking water for the population of overcrowded areas is very important In disaster areas the supply of uncontaminated fresh water is crucial to avoid epidemics. In hospitals and nurseries sterilized water and milk is necessary to feed newborn, old,
24.14. DISEASES TRANSMITTED BY WATER
1679
sick and weakened persons. Strictest asepsis is necessary to prevent infections among these groups of patients.
24.14.1
Bacteria found in water
Water specic bacteria: Pseudomonas Flavobacterium : Cytophaga is in Bergeys Manual of Systematic Bacteriology included in the Flavobacterium-Cytophaga complex (side 355 volume 1984).Cytophaga are found in fresh sh. Water bacteria with contamination origin from sewage and other sources: Enterobacteriaceae Pseudomonas aeruginosa Enterococcus Clostridium Spirillum volutans Aeromonas Bacillus punctatum Aeromonas hydrophila Arcobacter butzleri Campylobacter jejuni Escherichia coli enterotoxic ETC Vibrio cholerae Leptospira Borrelia Legionella
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24.14.2
Legionella pneumophila
In 1976 Vietnam-veterans came together in a dilapidated hotel in Philadelphia. They contracted a lung disease of which 29 died. The disease was called "Veterans disease" and the isolated germ was labeled as Legionella. Legionella pneumonia is found in old water pipelines carrying warm water with often stand still. Moisture and water droplets from shower and air conditioning system with poor maintenance can bear the germs and make a lung infection possible. Old people and persons with reduced immunity are endangered.
24.14.3
Symptoms of Legionella infection
The symptoms of an infection caused by Legionella pneumophila are: High fever, Dry cough, Chest pain Headache and Diarrhoea. As these symptoms are unspecic the disease is often not diagnosed.Antibiotic medication is necessary. Sterilization of the warm water system can be done ushing the system with water at a temperature of at least 70o C . This temperature kills Legionella bacteria. Even the Buckingham-Palace in London was contaminated by Legionella pneumophila The water system of the palace was heated up to 70o C in December 1998 [204].
24.14.4
Test of Legionella pneumophila in water
The method to test the presence of Legionella pneumophila in water was published by the German Health Department: An inspection concerning the hygienic status of the system and his environment is important. Transportation to the laboratory should be made as soon as possible.If the sample has to be stored over night it should not be refrigerated, but left in dark and by room temperature.
24.14.5
Method for volumes from 100 ml to 1.000 ml
Membrane ltration with polycarbonate lter with pores from 0,4 to 0,45 milli micra should be used. Resuspend in 0,5 to 1 ml of the water of the sample with ultrasound using low power in order not to damage the cells of Legionella.
24.14. DISEASES TRANSMITTED BY WATER
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Add 0,5 ml of 0,2 ml-KCL/HCL buer mix and wait for 5 minutes. Inoculate the whole volume on the surface of several BCYE- Agar-Plate This culture media contains alfa-ketoglutarat,glycin, L-cysteine-hydrochloride and ironIII-pyrophosphate as well a antibiotic supplement. Incubate for seven days at 35 to 37o C in damp atmosphere.
24.14.6
Dierentiation
Inoculate about three typical colonies on a cysteine free culture media such as blood agar. Incubate two to three days at 35 to 37o C . If there is no growth, test identical colonies with Immunouorescent test using mono or polyvalent sera of Legionella pneumophyla.
24.14.7
Clear water samples expecting low number of Legionella
Membrane ltration should be made with "black" celulosenitrate lters. After ltration of the sample the lter should be covered with 10 ml 0,2-mol-KCl/HClbuer. After 5 minutes the buer should be ltered o and the lter should be washed with about 10 ml PBS (phosphate buer, pH 7,6). The lter should now be placed on a plate of blood-agar incubated and dierentiated as described above.
24.14.8
Method for small volumes of water sample
The water samples are inoculated directly using not more than 0,5 ml for each plate. Incubation and dierentiation as described above.
24.14.9
Legionella longbeachae, living in composted waste, causes lung infections and endocarditis [205]
Leggieri et al 2012 report a case of infectious endocarditis attributable to Legionella longbeachae. L. longbeachae is usually associated with lung infections. It is a facultative intracellular gram-negative bacillus, which is commonly found in composted waste wood products used in potting mixes. Legionella longbeachae should be regarded as an agent of infectious endocarditis, notably in the context of gardening involving handling of potting soils. The patient recently used only Australian potting mixes, which may contain Listeria longbeachae, although we were not able to cultivate Legionella longbeachae or other Legionella spp. from the potting mix.
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24.15
Enterobacteriaceae, culture methods
Culture methods for Enterobacteriaceae used in food bacteriology are: Ocial collection of methods according to the 35 of the Food Law in Germany (Amtliche Sammlung von Untersuchungsverfahren nach 35 LMBG) indicate under Methode L 05.00.5 the use of Violet Neutral Red bile Dextrose Agar (VRBD-Agar ) for the culture of Enterobacteriaceae in ne foods such as Mayonnaise emulsied sauces, could sauces ready to eat, ne salads, prime materials and quality control of the production. This medium is being used by commercial laboratories, by ocial laboratories of food control laboratories in Germany and with some small modications by a large number of quality control laboratories of the industry. This medium is also described by ISO/DIS 552 (1977), DIN 10164 and DIN 10172. Overlaying the plates with the same medium assures anaerobic conditions.Not fermenting gram negative bacteria will so be suppressed and fermentation of dextrose is increased. Enterobacteriaceae grow as 1-2 mm violet colonies having a precipitation around the colony.Not Enterobacteriaceae grow as colorless colonies. The Coli-Aerogenes - Group as possible indicator of feces contamination as great importance in the control of water but is of smaller signicance on food where the search for exact dened groups of bacteria. Enterobacteriaceae are considered to be a good indicator of failures by the manufacturing of foods using low heat. The VRBD-agar plate, Violet Red Bile Dextrose Agar gives positive colonies after 24 hours of incubation at 30 o C caused by the following bacteria:
24.15.1
Enterobacteriaceae
: Coliform bacteria Shigella which do not ferment lactose Escherichia coli Escherichia coli which can produce Enterotoxin.They are more resistant to heat than the apathogenic E.coli. Salmonella Citrobacter Klebsiella Other bacteria which grow on VRBD, not included in the group of Enterobacteriaceae Aeromonas Yersinia Pseudomonas, inhibited by overlay technique
24.15. ENTEROBACTERIACEAE, CULTURE METHODS Bacterium anitratum Achromobacter anitratus.
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The selectivity of VRBD reduces after 24 hours incubation.Some other not specied as Enterobacteriaceae bacteria can then grow. Table 24.9: Typical composition of VRBD-Agar Ingredient g/l Yeast extract 3,0 Pepton 7,0 Natrium chlorid 5,0 Bile salt Nr.3 1,5 Glucose 10,0 Neutral red 0,03 Violet red 0,002 Agar 12,0 pH 7,4+-0,2 VRBD- Agar is told to have a better recovery rate of Salmonella , Arizona and Shigella as with the lactose bearing VRB-Agar. Unfortunately it does not dierentiate between Coli and Salmonella/shigella.
24.15.2
Other media for Enterobacteriaceae
In food control laboratories using VRBD-agar there are often positive ndings with low number of Enterobacteriaceae. In order to make a decision about discarding or using the food further media could be used beside VRBD- agar examining food known to have problems , such as potatoes salad.In production of food with short shelf life it is impossible to wait for results of traditional bacteriology. To speed up nal results one or more of the following media could additionaly be used:
24.15.3
Detection of Coli-Aerogenes group in water,foods and dairy products with VRB-Agar; Violet Red Bile Agar
This medium is cited by DIN 10160, APHA 1985, FIL-IDF, Euroglace and the ocial methode according 35 LMBG L 00.00-21. It is not exclusive for Enterobacteriaceae, other bacteria such as Aeromonas and Yersinia spp. can produce similar reactions. Violet red and bile salt inhibit the growth of gram positive bacteria. The fermentation of lactose produces acid which makes the pH- indicator neutral red change its color to red and is responsible for the precipitation of bile salts. in the near surroundings of positive colony.
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Lactose positive bacteria grow as 0,5-2 mm (24 hours) purple colonies which may be surrounded by a purple zone.(Coliform bacteria grow as 1-2 mm colonies.The Coli-Aerogenes group Enterococcus and Klebsiella) grow as 0,5 mm small colonies after 24 hours at 30o C . Escherichia coli should be incubated at 44+-1o C Lactose negative bacteria grow as pale colonies which can be surrounded by a greenish zone. Table 24.10: Typical composition of VRB-Agar Ingredient g/l Yeast extract 3,0 Pepton 7,0 Natrium chlorid 5,0 Bile salt Nr.3 1,5 Lactose 10,0 Neutral red 0,03 Violet red 0,002 Agar 12,0 pH 7,4+-0,2 VRB-Agar is available under Art.-Nr. CM 107 from Oxoid and Ar.Nr. 1406 from Merck.
24.15.4
COLI ID, medium for the detection of coliforms and identication of E.coli
The medium COLI ID contains two chromogenic substrates which allows the direct recognition of coliforms and identication of Escherichia coli, without use of additional reagents. Table 24.11: Typical colonies of E.coli, coliforms and others Gram- on COLI ID rose blue colorless + + + Escherichia coli other coliforms other Gram(-) Coliforms on COLI ID, Citrobacter,Enterobacter or Klebsiella have blue color. Detection, enumeration and identication of E. coli and coliforms are made after 24-48 hours incubation at 37o C on pour-plate.E.coli colonies on COLI ID are of rose color with a rose zone around the colonies.Other Gram negative bacteria a on COLI ID are bight rose , small and have no surrounding zone. Gram positives and yeasts are inhibited.COLI ID is available under Ref 42017 from bioMrieux
Colony color beta-glucuronidase beta-galactosidase
24.15. ENTEROBACTERIACEAE, CULTURE METHODS
1685
24.15.5
Enrichment broth for total coliforms and Escherichia coli
Enrichment of total coliforms together with Escherichia coli can be made with Fluorocult LMX-broth according to Mana and Ossmer After 24 - 48 hours the broth will change its color to blue-green. Fluorocult LMX-broth is available under the number 1.10620. Positive cultures can be plated on Chromocult coliforms-agar.
24.15.6
Chromocult, coliforms agar
Chromocult, coliforms agar is a combination of two chromogene substrates Salmon-GAL and X-GLUC for the recognition of Escherichia coli, coliforms and other Enterobacteriaceae. The growth of Coliforms even sublethal damaged cells is granted due to use of peptone, pyruvate, sorbitol and a buer of phosphate. Gram(+) and some Gram (-) bacteria are inhibited by Tergitol 7. Coliform bacteria are beta-D-galactosidasepositive and ferment the substrate Salmon GAL turning pink/red. Escherichia coli is beta-D-glucuronidase positive and ferment the substrate Salmon GAL turning blue. The used substrate is X-Glucuronid.Escherichia coli ferments both Salmon-GAL and also X-Glucuronid turning blue-violet being easy to identify E. coli among other coliforms which turn pink-red. Tryptophane improves the indol reaction to conrm E. coli adding safety of the detection of the germ with Salmon-GAL and x glucuronid-reaction. To suppress Pseudomonas spp. and Aeromonas spp.add 5 mg Cefsulodin(such as Sigma)in 1 ml demineralised. water sterile ltered to 1liter of medium.
Inoculation As pour plate, as surface culture or as lter culture. Read the plate as follows:
Escherichia coli Deep blue-violet (Salmon-GAL reaction and x-glucuronid-reaction) To conrm E. coli the colonies may covered with one droplet of Kovacs indol solution. Red color of the solution after few seconds is positive for E.coli.
1686 Coliforms
:Pink-red colonies (Salmon-GAL reaction)(Citrobacter,Enterobacter, Klebsiella and some E.coli and deep blue-violet (E.coli). Some enterohaemorrhagic Escherichia coli ferment X-Gluc (Mug-) and behave like coliforms. To nd these bacteria use Fluorocult E.coli 0157:H7-agar . Other Enterobacteriaceae Pale colonies, with exception of some bacteria which have beta-glucuronidase activity. These Bacteria have bright blue turquoise colonies.
Table 24.12: Typical composition of Chromocult-Agar Ingredient g/l Pepton 3,0 Natrium chlorid 5,0 Sodium dihydrogen phosphate 2,2 di-sodium hydrogenphosphate 2,7 Sodium pyrovate 1,0 Sorbitol 1,0 Tryptophane 1,0 Agar-agar 10,0 Tergitol 7 0,15 Chromogen mixture 0,2 pH 7,4+-0,2 Chromocult Coliforms Agar is available under Number 1.10426 Merck.
24.15.7
EHEC, Enterohaemorrhagic Escherichia coli 0157:H7, culture
Verotoxin producing E. coli (VETC) and Escherichia coli 0157:H7 (EHEC) produce diarrhea, kidney failures in children and old patients and are also important in veterinary medicine. They can be detected on Fluorocult E coli 0157:H7-agar detected. e.coli 0157:H7 is sorbitol negative and has no beta-D-glucuronidase.This is used to distinguish him from not pathogen E.coli. The medium also distinguishes between Proteus and Shigella. Fluorescens of MUG is an important dierentiation between the dierent bacteria. Inhibition of Gram (+) bacteria is made by sodiumdesoxycholate.
24.16. FLUORESCENCE METHODS FOR DETECTION OF ESCHERICHIA COLI 1687 Table 24.13: Typical growth of bacteria on Fluorocult E.coli 0157:H7-agar
Bacteria colorprecipitationMUG Sorbitol E.coli 0157:H7 greenish E.coli yellow +Proteus mirabilis black-brown Enterobacter aerogenes yellow +Streptococcus faecalis no growth Fluorocult E.coli 0157:H7-agar is available under the number 1.04036
- + + - - +
24.16
Fluorescence methods for detection of Escherichia coli
: E. Meck, Darmstadt, Germany has various culture media to detect by means of uorescence, production of indol from tryptophan. The uorescence methode is done by adding MUG (4-Methylumbelliferyl-beta-D-glucuronid.) Best results on reading the cultures are at pH 9 to 10 under UV light of 366 nm.
Advantages of MUG (glucuronidase methode ) Glucuronidase -reaction is more sensitive compared with formation of gas from lactose. This increases diagnostic safety .
Reduced work and reduced costs
Reduced time, results are given in 24 to 48 hours compared with 96 to 144 hours.
Fluorogene substances are very sensitive. Activity of glucuronidase is a characteristic of 94% of all types of E.coli, Indol reaction is a characteristic 99% of all types of E.coli [203].
1688
To avoid false results please observe:
Glassware, other utensils and the material to be examinated should not have strong uorescence as this might overdo the reaction of MUG. Work always with control positive and control negative Alkaline pH brings strong uorescence.If the medium is acid add some droplets of 1N NaOH-solution to turn it alkaline Indol reaction has to be done after the reading of uorescence and not later than 24 hours. Fluorescence optical methods are cited in the following German DIN methods: DIN 10 110 : Determination on E.coli in meat and meat derivates. DIN 10 183 , part 3 : Determination of E.coli in milk, milk derivates, icecream, baby food based on milk. MUG can be added to almost any standard culture medium, however the usual media having MUG already added are available. Some examples are:
24.16.1
Merck Fluorocult Brila-broth (1.12587)
It is used as selective enrichment and enumeration from E. coli and other coliforms in titer test of water from swimming pools. Bile and brilliant green inhibit Gram positive bacteria. Reading of the cultures is done under 366 nm light. A pale blue uorescence of the tube stands for the presence of E.coli.
24.16. FLUORESCENCE METHODS FOR DETECTION OF ESCHERICHIA COLI 1689 To conrm the result the culture should be covered with approximately 5 mm with KOVACSindol reagent A cherry-red color of the reagent stands for the presence of E.coli and /or coliforms.
24.16.2
Merck Fluorocult DEV-lactose-peptone-broth (1.04037)
It is used as enrichment and titer of coliform bacteria in the examination of water. The presence of E. coli is demonstrated with uorescence under UV light, and the a positive indol reaction.
24.16.3
Merck Fluorocult ECD-Agar (1.04038)
The ECD agar (E.coli Direct Agar) is suitable to examine feces and food samples as well. It is cited under DIN 10 110 for the examination of meat and related material. The bile salt inhibits the not obligatory intestinal ora. The presence of E. coli is demonstrated with uorescence under UV light, and the a positive indol reaction.
24.16.4
Merck Fluorocult E.coli 0157:H7 Agar(1.04036)
It is a selective agar for the isolation and dierentiation of enterohaemorrhagic EHEC Escherichia coli 0157:H7 from food samples and from clinic material. This bacteria is sorbitol negative, glucuronidase negative, no uorescence. Sodium desoxicholat inhibits the concomitant Gram positive ora. Faecis are inoculated directly on plates and incubated for 14 to 24 hours at 37o C . Sorbitol negative colonies presenting no modication of the color of the medium have to be identied under UV light. E.coli o157:H7 grows as greenish and Proteus mirabilis as black/brown colonies. Fluorocult Lauryl-Sulfate-Broth (1.12588) This culture medium is determined to be a reference methode for E.coli in the examination of milk and derivates in DIN 10183, part 3. Lauryl-sulfate is added to inhibit the concomitant organism.
24.16.5
Merck Fluorocult LMX- Broth (Laurylsulfate-MUG-XGal)
This medium is used in the simultaneously detection or coliforms and E.coli. A rapid growth of coliform bacteria is granted due to the high nourishing properties of the medium and the presence of a phosphate buer. Lauryl-sulfate is added to inhibit the concomitant organism. The chromogen substrate
1690
X-Gal is being hydrolysed causing the change of color to blue-green. The booster substance IPTG intensifying the enzymatic activity of coliforms increasing the sensibility of the test. E. coli is conrmed with uorescence.
24.16.6
Merck Fluorocult MacConkey-Agar [1.04029]
This culture medium is used to isolate Salmonelleae Shigelleae and coliforms, especially Escherichia coli. Bile salts and violet red inhibit the Gram positive Flora. Lactose fermentation is demonstrated by the pH indicator neutral red. Escherichia coli colonies are uorescent under UV light. Lactose negative colonies are colorless,lactose positive red often with a turbid zone of precipitated bile.
24.16.7
Merck Fluorocult VRB-Agar(Fluorocult Violet Red Bile Agar 1.04030)
This selective culture medium is used to detect and to enumerate coliform bacteria, especially Escherichia coli.Violet red and bile salts inhibit the Gram positive Flora. Lactose positive bacteria turn red among them E.coli is uorescent under UV light. Lactose negative Enterobacteriaceae are colorless.
24.16.8
Merck Bactident E.coli, rapid test to identify Escherichia coli isolated on non selective media (1.13303)
[203] The result is available in about 30 minutes. There is no asepsis needed because the initial amount of bacteria is very high and growth of E. coli more rapid as concomitant bacteria. A colony on test is suspended in 200 microliter distilled water. A test stick is added and the tub is incubated by 37o C for 30 to 120 minutes. under ultra violet light of 366 nm uorescence is read (glucuronidase with MUG).Indol reaction is done by adding one droplet of KOVACS reagent. Red color of the suspension after some seconds is a positive reaction and conrms E.coli.
24.17
Thin layer chromatography with immunologic analysis to detect E.coli 0157:H7
Vip EHEC Thin layer chromatography with immunologic analysis to detect E.coli 0157:H7 is a rapid detection system for E.coli (EHEC) in food from BioControl Systems Inc.USA.
24.18. POLYMERASE CHAIN REACTION (PCR) IDENTIFYING MICROORGANISM
1691
This system is admitted by the AOAC. It makes EHEC specic antigens visible as a blue reaction line reacting with antibody linked to blue latex particle. To perform the test VIP EHEC Biotest Nr. 928 110 and further utensils are needed: - Sterile Pipette with 100 l volume - Stopwatch - 225 modied Casein peptone-Soy peptone-Broth with Novobiocin Table 24.14: Casein peptone-Soy peptone-Broth with Novobiocin ingredient Casein peptone-Soy peptone-broth bile salt Nor.3 K2 HPO4 Deionizated water Autoclavated and cool Novobiocin solution: Novobiocin (Na salt] 100 mg Deionized water 1,0 ml The novobiocine solution is to be sterile ltered an kept in dark a glass. The shelf life of the solution is several month at 4o C . quantity 30,0 g/l 1,5 g/l 1,5 g/l 1000 ml
24.17.1
Enrichment
25 g from the sample are incubated at 35-37o C during 18 hours in 225 ml modied Caseinpeptone-Soy peptone-Broth. 0,1 ml of the enrichment culture are place in the start eld. The test kit is then incubated for 10 minutes at room temperature. The reading of the test should be made after 10 minutes, after that false positive reactions can take place. Positive results should be conrmed inoculating the enrichment culture one a selective medium such as: Sorbitol-macConkey -Agar (Heipha Nr. 125e) , Bile-Chrysoidin -SorbitolAgar with MUG, (Heipha Nr 1052). After 24 hours of incubation the culture plates are read and suspected colonies are biochemicaly dierentiated and identied with specic serotypes.
24.18
Polymerase chain reaction (PCR) identifying microorganism
Tougher regulatory standards and the increased attention of the news media in relation to food contamination in restaurants, supermarkets and processing plants trigger higher
1692
priority on safety, shelf life and cleanliness. More stringent and rapid testing along the whole supply chain are being developed. PCR became one of the top laboratory methods for microbacterial detection in the food industry..It can detect small samples of contamination by amplifying the amount of DNA of the contaminant. Scientist of Campden and Chorleywood Food Researche have automated ribotyping for characterising microorganisms below the species level. The technique can be used for identication. To complement the technology the development of an identication system based on the capture of PCR-amplied DNA sequences onto DNA microarrays is being developed.
24.18.1
Microarray
A microarray is a solid surface as a microscope slide, onto which the amplied DNA is bond. The microarrays can be used to probe an unknown organism to see which of the DNA sequences on the array are also present in the organism. Microarray probes were designed for selected groups of bacteria, based on regions of the 16S ribosomal RNA. Campden and Chorleywood Food Researche (CCFRA) developed and has validated PCR protocols for Enterobacteriaceae, Pseudomonas, Bacillus and Clostridium species.
24.19
Impedance technologies for rapid detection and enumeration of bacteria
The impedance technology is being increasingly used in industrial microbiology.
24.19.1
Principle
Proteins and carbohydrates from the culture medium are electrically neutral or weakly ionized. Microorganisms transform these molecules into several smaller parts like amino acids, lactate etc which have greater charge and electrical motility. These modications can be measured between paired electrodes in the culture medium. Even very weak electrical variations of the medium can be measured and the presence of very few bacteria can be detected long before a colony is visible in culture. Making a curve of the percentage of electrical variation in relation to time there is an unexpected inection in the curve depending on the number and the metabolic activity of the bacteria being present.
24.19. IMPEDANCE TECHNOLOGIES FOR RAPID DETECTION AND ENUMERATION OF BACTERIA
1693
Detection time [206]: is the point of the inection of the curve, depending on the number and the metabolic activity of the bacteria being present.
24.19.2
Impedance
is the total resistance measured in a conductive medium.
24.19.3
Conductance
measures the bulk ionic strength in the growth medium.
24.19.4
Capacitance
is measured as the accumulation of electrical charges by increasing the ionic concentration around the electrodes. Measurement of capacitance is particularly adapted to detection of bacteria which release slightly ionized metabolites (yeasts, moulds and non-fermenting Gram negative organisms).
24.19.5
Sterility testing
a detection time at anytime during the test period signies a non sterile sample.
24.19.6
Screening or enumeration
the detection time enables samples to be accepted or rejected according to the specication level in a short period of time.
1694
Impedance technology provides results within hours. The more contaminated the sample, the quicker impedance technology detects it saving time. Automated impedance technology available as BACTOMETER from bioMrieux.This company also sells dehydrated culture media specially adapted to impedance technology: Total count BHI: Enumeration of total aerobic ora in food. Total count MPCA: Enumeration of total aerobic ora in food. Total count GPM: Sterility control and enumeration of total aerobic ora in milk, food, cosmetics, and pharmaceutical products. Total count GPM Plus: Sterility control and enumeration of total aerobic ora in milk, food, cosmetics and pharmaceutical products. The formula of the medium is enriched vitamins, amino acids etc to favor the growth of fastidious and/or stressed bacteria during the manufacturing process. Coliforms CM: Enumeration of coliforms in food. Enterobacteriaceae EM: Enumeration of Enterobacteriaceae in food. Yeasts/Moulds YMM: Detection of yeasts and moulds in fruit juice, milk, food, cosmetics and pharmaceutical products.
24.20
Lactic acid bacteria LM
Detection and enumeration of lactic acid bacteria in fruit juice, dairy products and food. The BACTOMETER impedance technology used for total count,sterility tests, coliforms Enterobacteriaceae, Yeasts and moulds as well as lactic acid bacteria can also be complemented with two other systems:
24.20.1
VITEK
Automated identication of Gram negative bacilli, Grampositive cocci, Bacillus, anaerobes, yeasts.
24.20.2
VIDAS
Automated detection using immunoanalysis of pathogenic bacteria, Listeria, Salmonella, Staphylococcal enterotoxins, E.coli O157, Campylobacter. The principle of VIDAS is based on a specic reaction between an antibody and an antigen. An antibody coated device captures the antigens of the organism being detected. After several washing procedures a second antibody will x the antigen using the sandwich technique. This second antibody is then conjugated with an enzyme, which will produce a uorescent
24.20. LACTIC ACID BACTERIA LM
1695
reaction with the substrate. The intensity of this reaction is measured and interpreted by the system.
24.20.3
The RABIT (Rapid Automated Bacterial Impedance Technique)
is a system developed by Don Whitley Scientic Limited,Shipley, West Yorkshire. Using the principles of the impedance technology RABIT detects and enumerates bacteria. High initial costs of the device still are a disadvantage of the impedance technique.
24.20.4
MALTHUS from Malthus Instruments
, Bury, UK measures electrical conductivity of culture media.It detects and enumerates specic bacteria such as Campylobacter, coliforms, Columbia, Enterobacteriaceae, Listeria monocytogenes, Salmonellae, TMA ( total count), Staphylococcus aureus.
24.20.5
Bioship to detect Listeria monocitogenes [207]
Bhunia and colleagues 2009 developed a biosensor to detect Listeria monocitogenes. Whioch could not easily be detected using antibodies. The researchers used heat shock protein 60 (Hsp60), a eukaryotic mitochondrial chaperon protein which is a receptor for Listeria adhesion protein (LAP) during Listeria monocytogenes infection. The authors concluded that Hsp60, immobilized on the surface of streptavidin-coated silicon dioxide biochip sensor platform may be used for the detection of Listeria monocytogenes. They report that the capture eciency of Listeria monocytogenes was 83 times greater than another Listeria receptor, the monoclonal antibody, mAb-C11E9.
24.20.6
BacTrac, impedance analytic
BacTrac is a system using Impedance technology to detect and to enumerate spoilage bacteria in beer, coliform, Salmonellae and Staphylococcus aureus and total bacterial count in milk powder. BcTrac system can scan three analytical methods: The Impedance of the medium (M-value) The Impedance at the Electrode (E-value) The indirect Measuring of the Gas Production (G-value) Measuring the three parameters at the same time a more rapid result is possible. The Impedance at the Electrode (E-Value) often reacts earlier as other values , permitting thus a rapid result. The E-value is relatively stable against variations of salt content. The Impedance of the Medium (M-value) is a conrmation of the E-value and increases the safety of the result.
1696
The biological activity of bacteria decompose big molecules (carbohydrates, proteins, peptides etc) of the medium in which they are growing. Smaller chemical compounds result which are dissociated and and increase conductivity. The electrical resistance is diminished. [208] There are 5 possible interaction of the bacteria with the substrate: The Impedance of the medium (E-value)
1. Molecules without charge and polar macromolecules are digested in smaller ions, increasing the conductivity of the medium.
2. Small molecules are digested in very small electrical charged parts which can move more easily increasing the conductivity.
3. Ions already existing in solution are united in great ions. The conductivity is diminished.
4. Small ions are united in electrical charged macromolecules. The conductivity is diminished.
5. Autolysis of cells: Due to autolytic activities of the cell often observed in yeasts, ions of the interior of the cell are liberated an increase the conductivity . This is not caused by growing number of alien bacteria.
To measure cultural media a metallic electrode of high-grade steel, platinum or gold is dipped into the solution. A layer of ions covers the surface of the electrode. Measuring the electrical resistance of the electrode the variations of this layer is recorded. The impedance of the electrode ZE acts as a capacitor with a parallel resistor. Cultural media or bacterial suspensions have ions and particles without charges which can also adhere to the electrode. A separate measure of the impedance of the electrode and the impedance of the medium is very useful to get earlier results:
24.20. LACTIC ACID BACTERIA LM
1697
The growth of Saccharomyces cerevisiae [208]is seen only after 15 hours measuring the impedance of the medium. Measuring the impedance of the electrode the result is already seen after 4 hours. When high amount of ions from the medium are already present new ions from the activity of microorganisms present no signicant modication of conductivity, conductance or resistance which is measured as Impedance of the Medium , M-value. Measuring the impedance of the Electrode E-value, there is a good result after a couple of hours. This is shown in the example of Zygosaccharomyces rouxii. Other toxigenic bacteria can be detected with the BacTrac system using the impedance technology. Such bacteria and other applications are: Listeria and Clostridium, total count, sterility test, shelf life, activity test of preservatives and antibiotic, activity of starter cultures. The impedance technology has been validated in DIN 10115 of the German standardization.
1698
24.20.7
Clostridium acetobutylicum
Clostridium acetobutylicum can digest whey, sugar, starch, lignin, cellulose ber, and other biomass directly into butanol, propionic acid, ether and glycerin. The bacterium is useful in the fuel production using organic waste.
24.21
Clostridium dicile Infection
[209] Clostridium dicile infections are related to food infections and 94% are healthcare contamination. The current epidemic strain of Clostridium dicile is the BI/NAP1/027, toxinotype III strain. This strain is more virulent than foregoing strains. It has an increased toxin A and B production, polymorphisms in binding domain of toxin B, and presents increased sporulation. The Centers for Disease Control and Prevention (CDC) outlined the 6 strategies that have the best chance of eradicating Clostridium dicile from healthcare. These strategies involve elements of antibiotic stewardship, testing for Clostridium dicile, isolation and infection control procedures, environmental cleaning, and communication. 1. Prescribe and use antibiotics carefully. About 50% of antibiotics that are given are not needed. 2. Test for C dicile when patients have diarrhea while taking antibiotics or within several months of taking them. 3. Isolate patients with C dicile immediately. 4. Wear gloves and gown when treating patients with C dicile, even during short visits. Hand sanitizer does not kill C dicile, and handwashing may not be sucient. 5. Clean room surfaces with bleach or another Environmental Protection Agency (EPA)approved spore-killing disinfectant after a patient with C dicile has been treated there. 6. When a patient transfers to another facility, notify the new facility if the patient has CDI.
24.21.1
Hand hygiene [210]
The alcohol-based (hand sanitizer) gels dont kill C dicile spores. Essentially, hand gels dont do anything to these spores, says Gerding et al. 2008. Handwashing, with soap, water, and friction, is better than alcohol-based hand sanitizers for Clostridium dicile, because of dilution and physical removal-getting the spores o of the hands. However, alcohol-based hand sanitizers are more eective than handwashing for a huge range of usual pathogens that do not form spores. Clostridium dicile is probably transmitted primarily between patients on the hands of healthcare personnel who are transiently contaminated after contact with symptomatic patients or their surrounding environment, therefore gloves are the rst and best line of defence.
24.21. CLOSTRIDIUM DIFFICILE INFECTION
1699
The data suggest that patients with Clostridium dicile infection can continue to shed organisms for up to 7 days after the cessation of diarrhoea. We know these patients will continue to shed; its the degree of shedding that is important. The important factor is diarrhoea. Most shedding occurs while the patient has diarrhoea. When diarrhoea resolves, shedding diminishes. Good physical cleaning should be accomplished, because this can lead to the physical removal of spores. This should be augmented with an EPA-approved spore-killing disinfectant, such as chlorine bleach. Standard EPA-registered hospital disinfectants are not eective against Clostridium dicile spores. CDC recommends telling patients to use a separate bathroom at home or make sure it has been cleaned before someone else uses it. SHEA/IDSA Practice Recommendation 2008: The organisations highlight practical recommendations designed to assist acute care hospitals in implementing and prioritizing their Clostridium dicile infection (CDI) prevention eorts. Hand hygiene and environmental disinfection is elucidated. [211] SHEA-IDSA Guidelines 2010: Clinical Practice Guidelines for Clostridium dicile Infection in Adults (2010). Update by the Society for Healthcare Epidemiology of America (SHEA) and the Infectious Diseases Society of America (IDSA). The revised guidelines of 2010 stress the need to advise visitors and Healthcare workers to wash hands with soap (or antimicrobial soap) and water after caring for or contacting patients with Clostridium dicile. [212] Glove use is the only Clostridium dicile infection prevention recommendation with the highest strength of recommendation. If gloves are removed properly to prevent hand contamination in the removal process, any potential benet of using soap and water over alcohol-based hand hygiene products is likely negated. Dubberke and Gerding in an update in 2011 conclude that although soap and water is superior to removing Clostridium dicile spores from hands of volunteers compared to alcohol-based hand hygiene products, there have been no studies in acute care settings that have demonstrated an increase in Clostridium dicile infections with alcohol-based hand hygiene products or a decrease in Clostridium dicile infections with soap and water. This is why preferential use of soap and water for hand hygiene after caring for a patient with Clostridium dicile infections is not recommended in non-outbreak settings. The recommendation to use soap and water preferentially in outbreak settings after caring for a patient with Clostridium dicile infections is based on expert opinion as there are no data that demonstrate preferential use of soap and water for hand hygiene after caring for a patient with Clostridium dicile infections in an outbreak setting is eective at preventing Clostridium dicile infections. [213]
1700
Dubberke 2012 stresses the importance of appropriate contact precautions, strict hand hygiene, eective environmental cleaning, identication and removal of environmental sources of Clostridium dicile, and antibiotic stewardship in the prevention of Clostridium dicile infections. [214]
24.21.2
Yoghurt or probiotics to reduce CDI risk
Although not a core CDC recommendation at this time, the idea of using yoghurt or probiotics to prevent CDI-associated diarrhoea makes a lot of sense. It has been studied, but the data dont fully say that the probiotics that are currently available are eective in preventing Clostridium dicile infection.
24.21.3
Over-the-counter drugs used to treat frequent heartburn increase risk of Clostridium dicile infection. [?]
The U.S. Food and Drug Administration (FDA) is informing the public that the use of stomach acid drugs known as proton pump inhibitors (PPIs) may be associated with an increased risk of Clostridium dicile-associated diarrhoea.
24.21.4
Chlostridium dicile prevention [215]
According to Badger et al 2012, Clostridium dicile may be found in the normal ora in some healthy individuals. Some persons, however, have selective risk factors which turns them susceptible to the morbidity and mortality of the diarrhoea caused by this bacteria. Toxigenic culture testing from anaerobic culture remains the gold standard, and together with real-time polymerase chain reaction (PCR) has a high specicity, however, both are time consuming. Enzyme immunoassay and common antigen (glutamate dehydrogenase) testing, are performed in a short time. A strategy for prevention and eradication of Clostridium dicile is being suggested by the authors. This strategy includes early disease recognition through appropriate surveillance, implementation of eective contact isolation strategies, adherence to environmental controls, judicious hand hygiene, evidence-based treatment, and management that includes antibiotic stewardship, continuous education of healthcare workers, and administrative support.
24.21.5
Clostridium dicile contamination of food [?]
Clostridium dicile infection is typically associated with exposure to health care settings, especially among patients who have taken antibiotics, however, it is increasingly recognized as a cause of diarrhoea in persons with no apparent health care contacts. Recent studies have isolated Clostridium dicile from retail beef, pork, turkey products
24.21. CLOSTRIDIUM DIFFICILE INFECTION
1701
and ground beef intended for human consumption in the United States, Canada, and Europe and from meat products intended for consumption by pets. Several studies found overlap among bovine, equine, porcine, canine, and human isolates. Toxinotype (TOX) V/PCR ribotype 078/PFGE type NAP7 or NAP8/REA type BK strains are the predominant strains in cattle and pigs in the United States and Europe and also a common pathogens in humans. The epidemic strain, NAP1/027/BI, aected crowded areas in the Netherlands, and human infections with ribotype 078 was concentrated in more rural areas where pigs are raised. Isolates from food animals were found to be very closely related to or indistinguishable from human isolates, however, it is unclear whether and how zoonotic transmission occurs. Clostridium dicile on contaminated meat originates from food animal hides, intestinal contents and human handling. Spore contamination may not be preventable during processing of meat. Unlike other bacterial contaminants of meat, cooking might not kill Clostridium dicile. Spores can survive in ground beef despite proper handling and adherence to recommended cooking temperatures.
24.21.6
Laboratory tests used to diagnose Clostridium dicile infection [216]
Clostridium dicile is a spore-forming, Gram-positive anaerobic bacillus that produces two exotoxins: toxin A and toxin B. It accounts for 15-25% of all episodes of antibioticassociated diarrhoea. Clostridium dicile infections cause nausea, fever, diarrhoea, and abdominal pain. Often, Clostridium dicile infections cause nausea, fever, diarrhea, and abdominal pain. The infections produce inammation of the colon. This bacterium is associated with the use of antibiotic therapies and long hospital stays. It can be life-threatenig among elderly and persons with weak immune systems or on prolonged antibiotic regimens. Clostridium dicile is the cause of 14,000 deaths in the US annually. The preferred test is the nucleic acid amplication test (NAAT), because it has the highest sensitivity. Many hospitals are still using enzyme immunoassay (EIA), which detects stool toxins A and B. These tests provide rapid results but have low sensitivity, which can lead to repeated testing, with the possibility of a false-positive result. Stools should be transported to the laboratory within 2 hours or refrigerated, because the toxins degrade rapidly at room temperature, resulting in a false-negative test result. Stool culture for Clostridium dicile: While this is the most sensitive test available, it is the one most often associated with false-positive results due to presence nontoxigenic Clostridium dicile strains. Isolates must be tested for toxin production (i.e. so called
1702 "toxigenic culture").
Molecular tests: FDA-approved PCR assays, which test for the gene encoding toxin B, are highly sensitive and specic for the presence of a toxin-producing Clostridium dicile organism. Antigen detection for Clostridium dicile: These are rapid tests (<1 hr) that detect the presence of Clostridium dicile antigen by latex agglutination or immunochromatographic assays. Antigen assays have been employed in combination with tests for toxin detection, PCR, or toxigenic culture in two-step testing algorithms. Toxin testing for Clostridium dicile: Tissue culture cytotoxicity assay detects toxin B only. It is recognized as less sensitive than PCR or toxigenic culture. Enzyme immunoassay detects toxin A, toxin B, or both A and B: There are increasing concerns about their relative insensitivity (less than tissue culture cytotoxicity and much less than PCR or toxigenic culture). AmpliVue(R) Clostridium dicile test: The US Food and Drug Administration approved the AmpliVue C. dicile test. The Clostridium dicile Assay is a time saving molecular test which is more sensitive than current traditional detection methods. According to the U.S. Company Quidel, the C. dicile test combines isothermal helicase dependent amplication with a molecular method that requires no nucleic acids extraction step and no expensive equipment. [217] Helicases: AmpliVue Clostridium test is based on helicases, which are often utilized to separate strands of a DNA double helix or a self-annealed RNA molecule by breaking of hydrogen bonds between annealed nucleotide bases. The helicase function is required for ecient and accurate replication, repair, and recombination of the genome. They also function to remove nucleic acid-associated proteins and catalyze homologous DNA recombination. Metabolic processes of RNA such as translation, transcription, ribosome biogenesis, RNA splicing, RNA transport, RNA editing, and RNA degradation are all facilitated by helicases. [218]
24.22
Corrosion caused by bacteria
Bilge water and standing water in ships,cooling water systems and water tanks may be contaminated by Desulfovibrio desulfuricans. This bacterium reduces sulfates to corrosive suldes producing mud which can make holes through iron plates of ten millimeters in a period of one year. A group of scientists of Palo Alto makes experiments experiments to change the bacterial layer (bio lm) of water systems to a population of oxygen consuming bacteria which due
24.22. CORROSION CAUSED BY BACTERIA
1703
to genetic modication can produce antimicrobial substances which act against sulfate reducing bacteria. [219] In the meantime maintenance of water systems is the best way to avoid damages caused by Desulfovibrio.
24.22.1
European standards for plastic pipelines for water and gas supply [220]
HD-PE pipes are increasingly used for water and also for gas distribution. These pipes are easy to install. They have high stability against corrosion, high resistance to mechanical damage, and are resistant to chemicals. The continuous improvement of the material originated three generations of HD-PE: PE 63, PE 80 and PE 100. The PE 100 has increased resistance.
24.22.2
Water pipes are regulated under Directive 89/106/EEC [221]
EU regulations classify water pipes as "construction products". These regulations dene technical specications and describe how to proceed if special specications applying for the product are unknown. The regulation 89/106/EEC comprises water pipes as well as gas pipes.
24.22.3
EN 12201 high density polyethylene (HDPE) for drinking water and gas pipes. 05.12.2003. [220]
This standard regulates the requirements be fullled by polyethylene pipelines (main and distribution for drinking water. The standard also species testing conditions for valves and other components, their welding among themselves or in combined with other material, These specications must be met under the following requirements: Maximal operational pressure not exceeding 25 bar. Reference temperature is 200 C . The colouring of tubes and additives are specied.
24.22.4
EN 1555-1 Plastics piping systems for the supply of gaseous fuels Polyethylene (PE). 2009. [222]
Usually pipe producers meet EN 12201 and EN 1555. The same material may thus be applied for both uses.
1704
24.22.5
US Regulations for water pipes
Food grade pipe must comply with the provisions of Title 21 of the United States FDA Code of Federal Regulations as being safe for use in food contact applications. [223] Pipe systems should also comply with the 3-A Sanitary Standard. [224]
24.22.6
Disinfection of drinking water [225]
Supply of drinking water may come from surface water or ground-water, from a river, a lake or a spring. As this water may be contaminated by bacteria or parasites it should be disinfected as follows:
24.22.7
Filtration
Filtration should be made using Berkefeld lters, Chamberlain-lters and others. Continuous detection of bacterial count is necessary to avoid overgrowing of the lter.
24.22.8
Disinfection of water using heat
Small amount of water can be boiled killing all bacteria. The taste of boiled water is not good enough because of the elimination of carbon acid and alkaline earth carbonates.
24.22.9
Ultraviolet radiation
Ultraviolet radiation is used in small quantities of water. It is to expensive for central communal distribution. Mercury low pressure lamps are used. Short waves producing ozone are often ltered out.
24.22.10 24.22.11
Chemical disinfection of drinking water Chlorine
is the most used chemical disinfectant of water. 0,2 to 1,0 g in 1 m3 kills all germs in water. Chlorine can combine with components such as lipoproteins and cell plasma of the cell of the bacteria.Chlorine can react with the unsaturated molecules. It can also act dehydrating. With water chlorine forms underchloric acid H2 O + Cl2 = HClO + HCl Underchloric acid decays in chloric acid and oxygen: 2 HCLO = 2 HCl + O2
1705
The oxygen in molecular form is an active part during disinfection killing bacteria. The resulting chloric acid is neutralized by earth alkaline carbonate generally present in complex media (E. Thofern and collaborators, 1958) According to drinking water regulations (German regulation) disinfection of water can be made with Chlorine, sodium-, calcium- and magnesium hypochloride, chlorine chalk and chlorine dioxide. Chlorine dioxide in 20% solution is widely used presenting low taste and low smell compared with chlorine.It has strong disinfectant activity and is used to brake down phenols in drinking water and waste water streams. [226] Drinking water should not have more than 0,3 mg/l active chlorine.If necessary, in case of highly contaminated water 0,6 mg/l are allowed. The disinfection of chlorinated water takes place in 30 minutes. the taste level of free chlorine is around 0,5 mg/l. The smell level of free chlorine is far below taste level. In case of resistant bacteria strong chlorination may be used.Excess of chlorine can be neutralized with natriumthiosulphate or ltering the water through granulate of calciumsulde (Katarsit) or charcoal. Charcoal lters out compounds of chlorphenol of chlorine reacted with natural phenoles of river water. Chlorination of drinking water was widely introduced in USA beginning with 1908.
24.22.12
Ozonization of drinking water
Ozone is created discharging two electrodes through a dried air stream. W.Siemens had built in 1857 an ozone glass tube where ozone could be produced. The modern equipment to generate ozone for the disinfection of drinking water have great capacity. Chlorine dioxide is used primarily for bleaching of wood pulp, our and disinfection of water. Its most common use in water treatment is as a pre-oxidant prior to chlorination of drinking water to reduce trihalomethanes which are a carcinogenic disinfection by-product associated with chlorination of naturally occurring organics in the raw water. [226] Chlorine dioxide is also used in conjunction with ozone disinfection of water to reduce the formation of bromates which are regulated carcinogens. Chlorine dioxide is also superior to chlorine when operating above neutral pH, when ammonia is present and for the control of biolms. [226]
1706
Chlorine dioxide is less corrosive than chlorine and superior for the control of legionella bacteria, viruses, bacteria and protozoa, including cysts of Giardia and the oocysts of Cryptosporidium. [226] It can also be used for air disinfection, and was the principal agent used in the decontamination of buildings in the United States after the 2001 anthrax attacs. After the disaster of 2007 of Hurricane Katrina in New Orleans, Louisiana and the surrounding Gulf Coast, chlorine dioxide has been used to eradicate dangerous mold from houses inundated by water from massive ooding. [226]
24.22.13
Chorine dioxide as disinfectant on produce, fresh fruits and vegetables [227]
An U.S. epidemic caused by spinach, contaminated with pathogenic Escherichia coli in September 2006 boosted the researches at the Purdue University of Indiana, concerning the use of chlorine dioxide gas as disinfectant on produce, fresh fruits and vegetables. The use of chlorine dioxide to sterilize processing equipment speeding up sterilisation and eliminating the heat energy needed for conventional sterilization is included in this study. According to Linton, leading author of the project, chlorine dioxide is highly eective at killing microbial pathogens but too much of it can cause a decrease of quality in the product, such as browning of leafy greens. To help to prevent future outbreaks like the spinach contamination in September 2006, Linton stresses the need to follow more stringent sanitary policies, as well as practicing better manure and water management.
24.22.14
High contamination of salad leaves found in United Arab Emirates [228]
According to Dr Dennis Russell mustard salad greens, known as arugula salad leaves, or jargeer greens (Eruca sativa) were found to be highly contaminated with faecal coliform cells and Escherichia coli bacteria after washing the leaves three times. These bacteria were found even after rinsing with diluted chlorine bleach. Some strains of these bacteria can be deadly. Dr Tibor Pal stressed that high levels indicated faecal contamination and risk of other serious diseases, such as viruses and parasites. The United Kingdom and Germany have limits of 100 E. coli bacteria per gram, and Switzerland has a limit of 10 per gram. Brazil has a limit of 100 viable faecal coliform per gram. Jargeer greens grown on United Arab Emirates (UAE) produce farms, are a favourite and popular part of the traditional Arab meal. The authors stress, however, that contamination on the farm, with raw or poorly composted manure, used as fertilizer, and untreated
1707
liquid manure for irrigation or as a foliage spray. Pose a risk of enteric disease outbreaks. High eorts to exclude disease organisms from farms growing irrigated lettuce and leafy vegetables at California were started following a deadly outbreak of Escherichia coli O157:H7 on August 2006 regarding fresh spinach, followed by several cases of hemolytic uremic syndrome (HUS) in September 2006. Contaminated surface water and vectoring by wildlife, most likely feral pigs are the most important sources of contamination. [229]
24.22.15
How Salmonella attach to salad leaves [230]
According to Professor Gadi Frankel, Dr. Rob Shaw and colleagues, Salmonella and E. coli O157 - a strain of E. coli can spread to salads and vegetables if they are fertilised with contaminated manure, irrigated with contaminated water, or if they come into contact with contaminated products during cutting, washing, packing and preparation processes. Some Salmonella bacteria use the long stringy appendages (agella) to attach themselves to salad leaves and other vegetables. The researchers found that Salmonella which were deprived of their agella could not attach themselves to the leaves, and the salad remained uncontaminated. Professor Frankel stresses that the agella play a key role in Salmonellas ability to contaminate salad leaves. He says that dierent types of salad leaves are aected and focuses his work on how to use the plant protection strategy to increase food safety. The authors fears that the number of infections will increase as people are eating more bagged salads, choosing organic produces ready to eat.
24.22.16
Chronic health eects of chlorine dioxide
Careful handling and use of chlorine dioxide is imperative because of possible chronic health eects. In the fact sheet about this gas, the National Pollutant Inventory (NPI) of the Australian Department of Environment states that the following chronic (long-term) health eects can occur at some time after exposure to chlorine dioxide and can last for months or years: irritate the lungs; repeated exposure may cause bronchitis to develop with cough, phlegm, and/or shortness of breath. Permanent lung damage may occur, especially with repeated exposure to the vapours. There is limited evidence that chlorine dioxide may damage the developing foetus. [231]
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24.23
24.23.1
Biolms
Interspecies bacterial amyloid biolms
Amyloid bre formation is responsible for several human diseases including Alzheimers, Huntingtons, and prion diseases. Polymerization of amyloidogenic proteins into ordered bers can be accelerated by preformed amyloid aggregates derived from the same protein in a process called seeding. Amyloid brilization is a multistep process characterized by an energetically unfavorable formation of nuclei (lag phase) followed by cooperative amyloid elongation. [232]
24.23.2
Curli, bacterial amyloid bres [233]
Curli are proteinaceous component of a complex extracellular matrix produced by many Enterobacteriaceae. Curli belong to a class of bers known as amyloids. Curli bers are involved in adhesion to surfaces, cell aggregation, and biolm formation, invasion and inammations.
24.23.3
Seeding accelerates polymerization of amyloidogenic proteins [234]
Zou et al 2012 describe the cross-seeding of bacterial functional amyloids. Curli are produced on the surface of many Gram-negative bacteria where they facilitate surface attachment and biolm development. Curli bers are composed of the major subunit CsgA and the nucleator CsgB, which templates CsgA into bers. The authors found that curli subunit homologs from Escherichia coli, Salmonella typhimurium LT2 and Citrobacter koseri were able to cross-seed in vitro. The polymerization of E. coli CsgA was also accelerated by bers derived from a distant homolog in Shewanella oneidensis that shares less than 30% identity in primary sequence. Interspecies ross-seeding of curli proteins was also observed in mixed colony biolms with other Enterobacteriaceae enhanced bacterial attachment to agar surfaces formed bacterial biolm formation.
24.24
The ten most dangerous diseases of the world
The WHO has listed the ten most dangerous diseases of the world.
Table 24.15: Ten most dangerous diseases
24.24. THE TEN MOST DANGEROUS DISEASES OF THE WORLD Disease Inuenza Tuberculosis Cholera Aids Malaria Measles Hepatitis-B Whooping cough Tetanus Dengue fever caused by Haemophilus inuenza Mycobacterium tuberculosis Vibrio cholerae Aids virus Plasmodium falciparum Measles virus Hepatitis-B virus Bortadella pertussis Clostridium tetani Flavivirus Million death/Y Respiratory system 3,7 Lung 2,9 Digestive tract 2,5 Immune system 2,3 Blood 1,5 lung and meninges 0,96 Liver 0,605 Respiratory system 0,41 Infections 0,275 Fever 0,14 aects
1709 trans mission Food (e.g. milk) food (e.g. water)
Food (e.g. water)
Three among ten of the most dangerous diseases are transmitted by food. This shows that food born diseases are of great importance. Other, more typical food born diseases like Campylobacter or Salmonella may have a local high incidence, but cause worldwide less casualties. Engineering and food hygiene must be improved to reduce this hazard.
24.24.1
Peanut butter Salmonella outbreak 2009 [235]
The outbreak strain of Salmonella typhimurium in late 2008 and January 2009 may have contributed to six deaths, according to the CDC. The FDA conrmed that the source of the outbreak is peanut butter and peanut paste made by the Peanut Corporation of America (PCA) at its Blakely, Ga., processing plant. The PCA peanut butter and the peanut paste is sold to institutions throughout the state to long-term care facilities, hospitals, schools, restaurants, delis, universities, cafeterias and bakeries. It is also sold to food manufacturers of products such as crackers, cookies, cakes, cereal, candy, and ice cream. The FDA advises consumers not to eat commercially prepared products containing peanut butter or peanut paste, or peanut butter served at institutions. Watch the list of ingredients at the label.
24.24.2
Hygiene and infections in ood catastrophe
Flood catastrophes cause enormous destructions, endange human life and cause a high risk of infections because of contaminated drinking water and food resources. Special care to avoid infections should be taken not only during but also long after the ood period.
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The role of Water during ood catastrophes During and long after ood catatrophes water of rivers,lakes, wells, ground-water and public water suply systems are contaminated by a high count of pathogen bacteria, virus and egs of parasitic worms due to faecal contamination and man to man infections. This is often caused by a breakdown of the sewage treatment systen of the region or even the destruction of the sewerage Another source of infection are deteriorating corpses of drowened animals. The contamination of the water due to urine of rat and mouses with Leptospirae should always be considered. Most frequent intestinal infections are typhoid and paratyphoid fever Coli-enteritis, Shigella infections and hepatitis A infections. Vacination of rescue and aid program groups All members of rescue or aid program groups should be vaccinated against typhoid fever and hepatitis A. Due to increased possibility of injuries tetanus vaccination should be included or if necessary old vaccinations should be freshed up.
24.24.3
Water quality for recreational waters [236]
According to the WHO guidelines for recreational waters contamination from agriculture and sewage treatment, sh and aquatic mammals and from animals grazing near rivers such as sheep, goats and deer produce inputs into rivers with very high concentrations of bacteria and viruses including a wide range of pathogenic organisms such as liver uke. In rivers used for swimming, safe levels of bacteria and viruses can be established based on risk assessment. Under certain conditions bacteria can colonise freshwaters occasionally making large rafts of lamentous mats known as sewage fungus, usually Sphaerotilus natans. The presence of such organisms is almost always an indicator of extreme organic pollution and would be expected to be matched with low dissolved oxygen concentrations and high BOD values. Escherichia coli is used to indicate the presence of recent human or animal faecal contamination.
24.24.4
Free-living microorganisms
Natural inhabitants of marine aquatic environments are also potential pathogens. Vibrio cholerae and other Vibrio species are natural inhabitants of marine aquatic environments. They cause gastrointestinal infections, wound and ear infections. The occurrence of vibrios does not correlate with the occurrence of the traditionally used bacterial faecal index organisms, except in case of disease outbreaks. Aeromonas spp. are present in surface fresh and marine waters with densities ranging from less than 1 to 1000 cells per ml. Sewage can also contain elevated numbers (106108
24.24. THE TEN MOST DANGEROUS DISEASES OF THE WORLD
1711
cells per ml) of aeromonads. Aeromonas causes gastroenteritis. wound infections pneumonia. Free-living amoebae of the members of the genus Acanthamoeba, Naegleria fowleri and Balamuthia mandrillaris infect humans. Some Acanthamoeba species are pathogenic to humans and cause two clinically distinct diseases aecting the central nervous system: granulomatous amoebic encephalitis (GAE) and inammation of the cornea (keratitis). Naegleria fowleri, which is found in thermal freshwater habitats worldwide, causes primary amoebic meningoencephalitis in humans, which is usually fatal, with death occurring in 310 days after exposure. Balamuthia mandrillaris encephalitis is largely a disease of the immunocompromised host.
24.24.5
No dierentiation between human and non-human faecal sources of pathogens [237]
Because faecal matter can be a major source of pathogens in ambient water, and because it is not practical or feasible to monitor for the full spectrum of all pathogens that may occur in water, water quality criteria are specied throughout the world in terms of faecal indicator organism densities. For decades, these faecal indicator organisms have served as surrogates for potential pathogens and subsequent health risks in both recreational and drinking waters. The EPA recommended recreational water quality criteria do not dierentiate between faecal sources of pathogens. Thus, EPAs regulatory premise concerning recreational water quality has been that nonhuman-derived human pathogens in faecally contaminated waters are as hazardous as their human-derived counterparts. Monitoring pathogens at recreation beaches [238] Beaches are monitored for faecal indicator bacteria (typically Escherichia coli) in order to protect the public from potential sewage contamination. The authors criticize that there is no universal standard for sample collection and analysis or results interpretation. Monitoring policies are developed by individual beach management jurisdictions, and applications are highly variable across and within lakes, states, and provinces.
24.24.6
Indicator microbes may predict pathogens and help to improve human protection at beaches [239]
Shah et al 2011 report an inverse correlation between moisture content of beach sand and most faecal indicator microbes. Some indicator microbes were found to be associated with pathogens such as nematode larvae, Candida yeasts and methicillin resistant Staphylococcus aureus. The authors suggest, therefore, that indicator microbes may be useful for
1712
monitoring sand of beaches to predict the presence of these pathogens and water quality to improve human health protection at recreational beaches.
24.24.7
Marine recreational water quality [240]
Shibata et al. 2004 tested the microbial status at two US beaches using enterococci, Escherichia coli, faecal coliform, total coliform and Clostridium perfringens as indicator microbes. The authors found that the results did not vary between one indicator microbe and another, and did not change between seasons with dierent rainfall, temperature, pH, and salinity. The shoreline points presented highest microbiological contamination which decreased at oshore points. Beach sands within the wash zone tested positive for all indicator microbes, suggesting that samples should be taken at this point. The authors stress further that concentrations of indicator microbes do not necessarily correlate with one another. The authors concluded that beach advisories, based on exceedance of water quality guidelines varies according the chosen indicator.
24.24.8
Cladophora algae mats in the Great Lakes are a shelter for pathogens [241]
According to Verhougstraete and colleagues 2010 the algae Cladophora form free-oating mats which may strand on recreational beaches of the Great Lakes. Pathogens such as Escherichia coli, enterococci, Shigella, Campylobacter, and Salmonella nd nutrients and shelter in Cladophora mats, aecting the water quality. The authors considers the traditional faecal indicators at beaches with Cladophora presence asinadequate to predicting the presence of faecal contamination.
24.24.9
Bacterial indicators and EPA water quality guidelines for recreational waters [242]
Wade et al. 2003 support the use of enterococci in marine water at U.S. Environmental Protection Agency guideline levels. They found, however, that in fresh water, Escherichia coli was better suited to predict gastrointestinal illness than are enterococci or other bacterial indicators. Indicators of viral contamination were considered by the authors as strong predictors of gastrointestinal illness in both fresh and marine water.
24.24.10
Faecal indicator bacteria monitoring and eect of tide [243]
Boehm et al. 2005 report that marine beach water quality is monitored in early morning once a week without respect to tidal condition. The authors assess the eect of tide on
1713
this monitoring system. They found that enterococci concentrations during spring tides were higher than data of neap tides. Spring-ebb tides yielded the highest enterococci concentrations. The authors concluded that tide should be considered in the design of beach monitoring programs.
24.24.11
Guide and warning standards for Foods
It is of great importance for industry, health service and trade agreements to have standards for limits of number of bacteria in foods.Some limits are already set by food regulations such as limits for milk or water. With growing importance of the global standards are becoming more important. The Deutsche Gesellschaft fr Hygiene und Mikrobiologie DGHM has compiled limits which are ocial regulations. They should be used as a help to dene Good Manufacturing Practice. The Standards can be downloaded under: http://www.unibonn.de/em-mibi The standards are divided in two parts: 1 - Guide limits: If the bacterial count is under or is equal to the guide limit changes are not necessary. If growth of bacteria exceeds guide limits but is under the warning limit weak points in storage, production transport and retail should be analyzed. Veterinary supervision should advice the companies which engaged in the production. 2 - Warning limits: If bacterial surpasses the warning limits error at hygiene during production must be eliminated. Veterinary control system may act against these foods.
24.24.12
The European Regulation on Microbiological Criteria for Foodstus [244]
The regulation 2073/2005 [244], amended by the Regulation 1441/2007 in December 2007 [123], lays down limits for specic bacteria in food. It was based on the following EU regulations: Regulation (EC) No 178/2002 [245]which lays down general food safety requirements, according to which food must not be placed on the market if it is unsafe. Food business operators have an obligation to withdraw unsafe food from the market. In order to contribute to the protection of public health and to prevent diering interpretations, it is appropriate to establish harmonised safety criteria on the acceptability of food, in particular as regards the presence of certain pathogenic micro-organisms. Microbiological criteria also give guidance on the acceptability of foodstus and their manufacturing, handling and distribution processes. The use of microbiological criteria should form an integral part of the implementation of HACCP-based procedures and other hygiene control measures.
1714
According to Regulation (EC) No 852/2004 [246], food business operators are to comply with microbiological criteria. This should include testing against the values set for the criteria through the taking of samples, the conduct of analyses and the implementation of corrective actions, in accordance with food law and the instructions given by the competent authority.
24.24.13
Conict and Emerging Infectious Diseases [247]
Instability of regions in Far East, Asia and Africa promote infectious diseases. Dr Michelle Gayerfrom the WHO, writing on detection, containment, and control of emerging infectious diseases in conict situations says that they are major challenges because of multiple risk factors that promote disease transmission and hinder control even more than those in many resource-poor settings. She stresses the moral imperative to alleviate the eects of these diseases on already vulnerable conict-aected populations. Risk Factors Enhancing Disease Emergence and Transmission in Conict Situations, according to Gayer, are: Population Displacement and Environmental Conditions Malaria epidemic due to Plasmodium falciparung was caused by massive population displacement to Afghanistan in 1992-1993. Emergence of Lassa fever in camps in non-disease-endemic areas has been documented and is probably related to the poor condition of dwellings and storage of grain rations in nonsecure canvas sacks, which attracts rodents. Unsanitary environmental conditions led to the proliferation of rats in postwar Kosovo and resulted in a tularemia outbreak among the displaced population from August 1999 through April 2000. Breakdown in Infection Control Poor infection control practices in healthcare facilities have enabled amplication of outbreaks of viral hemorrhagic fevers, several outbreaks of Ebola hemorrhagic fever (EHF) in Yambuku, in 1976, in Sudan in 1976 and 1979, in Kikwit, in 1995, and in Gulu, Uganda, in 2000. The outbreak of Marburg hemorrhagic fever in Angola from October 2004 through July 2005 was booted by healthcare centers reusing needles and syringes and using multidose vials in healthcare centers due to poor training in safe injection practice. An outbreak of Lassa fever occurred in Kenema District Hospital from January through April 2004 and was also caused by reuse of needles and syringes. Disruption of Disease Control Programs and Collapse of Health Systems Recurrence of the sleeping sickness (human African trypanosomiasis) in the 1990s, predominantly in conict-aected Angola, DRC, and Southern Sudan due to interruption of
24.24. THE TEN MOST DANGEROUS DISEASES OF THE WORLD the control measures. Inadequate Surveillance and Early Warning and Response Systems
1715
Surveillance systems are often weak in conict situations, which results in delays in detection and reporting of epidemics. Limited laboratory facilities and lack of expertise in specimen collection may delay conrmation of the causative organism. Outbreak investigation and implementation of control measures may be hampered by ghting, impeded access to populations, destroyed infrastructure, limited coverage of healthcare services, poorly trained health sta, and dicult logistics that prevent delivery of drugs. This resulted in the outbreak of Marburg hemorrhagic fever in Durba in northeastern DRC from October 1998 through September 2000. Impeded Access to Populations Ongoing conict can hamper access to populations for timely delivery of supplies and implementation of control measures during an outbreak. Access to populations to conduct vaccination campaigns may also be interrupted for months to years during protracted conict due to long-term inadequacies in cold chain and logistics or ongoing insecurity. Several outbreaks of pneumonic plague have been documented in Oriental Province in northeastern DRC, where war has hampered control eorts.
24.24.14
Development of Drug Resistance
Pathogen resistance to drugs can contribute to disease emergence. Resistance may develop more rapidly in conict situations because of inappropriate diagnoses or inappropriate drug regimens and outdated drugs. An outbreak of Shigella dysenteriae type 1 infection in a Rwandan camp for Burundian refugees eeing civil war in 1993, less than 50% of patients complied with their 5-day antimicrobial drug treatment. Refugee populations had higher anti-tuberculosis (TB) drug resistance rates than nonrefugee populations in northeastern Kenya.
24.24.15
Antibiotic resistance of strains of poultry [248]
Antimicrobials used for therapy, prophylaxis, and growth promotion in broiler chicken production have been associated with antimicrobial-resistant enteric bacteria. In February 2002 two U.S. poultry companies stopped the use of uoroquinolones for ockwide treatment. In 2003 Lance, Silbergeld and colleagues 2005 surveyed Campylobacter isolates on chicken products from these two companies together with two producers claiming total abstention from antibiotic use.
1716
The authors found that antibiotic-free brands were not more likely to be contaminated with Campylobacter. A high percentage of products from the two conventional brands were contaminated with FQ-resistant Campylobacter and these conventional brands had signicantly higher odds of carrying resistant strains compared with antibiotic-free products. The authors concluded that uoroquinolone resistance may persist in the commercial poultry environment in the absence of uoroquinolones-selective pressure and that these strains contaminate a larger proportion of foods than reported previously. Lance, Silbergeld and colleagues 2007 estimated the relative risk for carrying antimicrobialresistant E. coli among poultry workers compared with community referents. The authors found that poultry workers had 32 times the odds of carrying gentamicin-resistant E. coli compared with community referents. The poultry workers were also at signicantly increased risk of carrying multidrug-resistant E. coli. The researchers concluded that occupational exposure to antimicrobial-resistant E. coli from live-animal contact in the broiler chicken industry may be an important route of entry for antimicrobial-resistant E. coli into the community. [249]
24.24.16
Probiotics to phase out antibiotics in poultry breeding [250]
Antibiotics in poultry feed reduces Salmonella contamination and acts as a growth enhancer. Billy Hargis, director of the Poultry Health Research Laboratory at the University of Arkansas Systems Division of Agriculture develops probiotic bacteria to be added to feed or water to reduce Salmonella in either meat-type chicken houses or turkey houses before being transported to the processing plant and reduce the risk of cross contamination. The researchers are focused on Bacillus, a dened aerobic lactic acid bacterial culture which develops spores resistant to heat treatment of feed during pelleting. These probiotics may phase out the use of antibiotics in feed for poultry. However, the researcher notes that the lack of antibiotics means producers will have to give more feed to the birds to get the raise the same amount of meat. According to Hargis the price of grain is already going up to meet demand for biofuels, so the price of meats produced from small grains will also rise. With rising prices of grain due to high demand for biofuel it will be hard to phase out antibiotics in commercial poultry breeding.
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24.24.17
Bacteria are increasing their resistance to antibiotics [251]
Common bacteria have acquired resistance to multiple antibiotics. Most of these strains were conned to hospitals, however, some strains are now being found in free environment, such as methicillin-resistant Staphylococcus aureus and gram negative bacteria. To curb the use of antibiotics Gary Taubes advocates a switch from broad-to narrow-spectrum antibiotics and the reduction of the standard 7 to 10 days drug treatment, adopting a shorter use of antibiotics. Taubes cites the resistance of Clostridium dicile. [252] Eliot Marshall cites the resistance of Mycobacterium tuberculosis strains in Tomsk, Siberia, where Partners in Health (PIH) made some progress collaborating with local authorities which report that deaths have declined, but resistance to drugs remains high. [253] The authors claim that changes in natural ecosystems, including the release of large amounts of antimicrobials, might alter the population dynamics of microorganisms, including selection of resistance. Antibiotics in feed used to improve productivity of ocks are a one important door to high releases in the environment, aecting food safety. Martnez, Monk and Goeau. describe the evolution of antibiotic resistance genes in bacteria in natural environments and considers possible intervention in the expression of these genes. The authors strategies are based on improved diagnosis and indirect intervention via inhibition of the energy supply for drug eux as a way to develop of broad-spectrum fungicides. [254] [255]
24.24.18
Bacteria, such as Klesiella pneumoniae develop resistance to carbapenems [256]
Carbapenems, useful to treat infections caused by extended-spectrum beta-lactamase (ESBL)producing Gram-negative bacteria, is now getting ineective by bacteria developing enzymes called Klebsiella pneumoniae carbapenemases (KPCs), which inactivate them. KPCproducing organisms can spread inside hospitals as well as in the community setting. Treatment of KPCs often requires the use of tigecycline and the polymyxins. This epidemic of KPCs Gram-negative resistance reside on transferable plasmids and can hydrolyse all penicillins, cephalosporins, and carbapenems. Increased awareness and intensied infection control practices are the keys to curtail the spread of this terrifying antimicrobial resistance. The rst KPC-isolate was detected in 1995in isolates of Pseudomonas aeruginosa mutants [257]. KPC-resistace is most frequent in Klebsiella pneumoniae, and seems to have spread to the Enterobacteriaceae family, such as Proteus, Serratia, Salmonella, and Citrobacter.
1718
Antibiotic resistance of bacteria [258] Spzek and colleagues 2010 write that resistance to antibiotics and other antimicrobial compounds continues to increase and suggest protection strategies against pathogenic microorganisms. Such strategies should focus on new vaccines, use of specic bacteriophages, search for new antibiotics, sequencing microbial genomes to identify related genes and analysing DNA from the environment (metagenomics). Study explains antibiotic resistance mechanism of bacteria [259] Desai and Miller 2010 assessed the mechanisms used by bacteria to ght antibiotics. The authors used bromoacetate as an environmental threat to simulate antibiotics. In this study Escherichia coli produced protective proteins allowing its survival even at lethal concentration of bromoacetate. The authors identied nine genes from Escherichia coli whose overexpression aords survival in the presence of a normally lethal concentration of bromoacetate. Eight genes encode putative transporters or transmembrane proteins, while one encodes the enzyme UDP-N-acetylglucosamine enolpyruvoyl transferase (MurA), which is irreversibly inactivated by bromoacetate via alkylation of a critical active-site cysteine. Also 63 strains were found by the authors to be susceptible to bromoacetate. The techniques described allows to predict the resistance to specic antibiotics, identify the resistance mechanisms and may enable researchers to reverse the resistance to antibiotics.
24.24.19
Assessing the hygromycyn bacterial resistance [260]
Stogios and colleagues 2010 write that the aminoglycoside phosphotransferase APH(4)-Ia is one of two enzymes responsible for bacterial resistance to hygromycin B (hygB). The authors studied the crystal structure of APH(4)-Ia enzyme. The enzyme was found to form an hydrogen bond network with hygB primarily through polar and acidic side chain groups, and binding anity is spread across a distributed network. The APH(4)-Ia enzyme contains a cluster of hydrophobic residues which interact with hygromycin, and similar to APH(2") utilize either ATP or GTP for phosphoryl transfer, this pathway may be used to tailor new aminoglycoside antibiotics or inhibitors of this enzyme suggest the authors.
24.24.20
CmeG gene is linked to resistance to antimicrobials and oxidative defence [261]
Campylobacter jejuni presets rising resistance to antimicrobials. Jeon and colleagues studied the cmeG (Cj1375) gene in Campylobacter jejuni which encodes a putative eux transporter. The authors report that overexpression of the cmeGH operon in Campylobacter jejuni signicantly increased its resistance to uoroquinolones. The authors concluded that
1719
CmeG gene is a multidrug eux transporter involved in antibiotic resistance and oxidative defence of Campylobacter.
24.24.21
Peptide antibiotic bacterial resistance of Bacillus subtilis [262]
Staron, Finkeisen Mascher 2010 describe three peptide antibiotic sensing and detoxication modules in Bacillus subtilis consist of two-component system which induces the expression of an ABC transporter which removes the antibiotic from the bacterial cell wall resulting in resistance of the cell: BceRS-AB responds to bacitracin, plectasin, mersacidin and actagardine. YxdJK-LM is induced by a cationic antimicrobial peptide, LL-37. The PsdRS-AB system primarily responds to lipid II-binding lantibiotics, such as nisin and gallidermin. The authors suggest the PbceA and PpsdA promoters as novel whole cell biosensors for high-throughput screening.
24.24.22
Pan-resistant NDM1 bacteria [263]
NDM1 is an enzyme that confers resistance to one of the most potent classes of antibiotics, known as carbapenems. It is found in many dierent types of bacteria and one in 10 of these strains is resistant to all known antibiotics. For the moment there is no new antimicrobial being developed. The NDM enzyme genes that The NDM1 gene set has been found in Escherichia coli and can move easily from other bacteria. The WHO in its 2000 report "Overcoming antimicrobial resistance" called the rise of antimicrobial resistance a global crisis. In 2001 the organization released a global strategy and campaign which should be updated and rejuvenated. Of concern is selling for human use antibiotics over the counter in Asia,Africa Central and South America. Also of high concern is the use of antibiotics as growth promoters in animal feed and bee-hives. WHO calls on the responsibility of governments to regulate these isues, such as happened in the European Union where the use of antimicrobial growth promotion in livestock was banned.
24.24.23
Postgenomic strategies prot from foregoing activities of antibacterial drug development [264]
Brtz-Oesterhelt and Sasss 2010 stress that any use of antibiotics triggers bacterial resistance to the drug due to their short reproduction time leading to mutations and the
1720
exchange of genetic material with other strains. The authors call, therefore, for proper hygiene, skilful and restricted use of antibiotic treatment.
24.24.24
The classical strategy
discovered all currently used antibiotic classes by screening natural product extracts or synthetic compounds for their antibacterial activity.
24.24.25
The genomics strategy
New genetic discoveries initiated a "genomic" strategy replaced the classical strategy. However, research focused on synthetic quinolones class and synthetic low molecular weight compounds and bacterial genomic information faced a fruitless time. The High-Throughput Screening (HTS) strategy failed to produce signicant results.
24.24.26
The postgenomic strategy
now uses knowledge and libraries of foregoing researches and focuses on screening for new or underexploited natural products and structure-based drug design. Eorts to avoid bacterial resistance to antimicrobials should be further supported by alternative treatment options together with anti-virulence strategies and immunotherapeutic approaches
24.24.27
Alternatives to the emergence of carbapenemases in Enterobacter [265]
Looking for alternatives to the emergence of carbapenemases in Enterobacteriaceae Livermore and colleagues 2010 found that ACHN-490, a sisomicin derivative evades all plasmidmediated aminoglycoside-modifying enzymes. Carbapenem-resistant isolates are sensitive to ACHN-490, except those strains containing 16S rRNA methylases. Apramacin evades 16S rRNA methylases and is being suggested by the authors as a starting point for future aminoglycoside development.
24.24.28
Cervimycin C resistance in Bacillus subtilis described [266]
Krgel and colleagues 2010 report two mutations in the intergenic region preceding the ABC transporter gene bmrA in cervimycin C-resistant clones of Bacillus subtilis, The authors stress that the cumulative of these two mutations are responsible for ABC transporter confers antibiotic resistance by the cumulative eects of two mutations in the promoter region.
24.25. METHICILLIN-RESISTANT STAPHYLOCOCCUS AUREUS [MRSA]
1721
Mathematical model of drug resistance predicts variation in population of pathogen bacteria [267] Variation in the population of antibiotic non-resistant/resistant organisms such as methicillinresistant staphylococcus aureus can be predicted by a mathematical model developed by Friedman and colleagues 2010. The model predicts that antibacterial drugs initially decrease the load of the non-resistant bacteria, reaching a low level after 6 weeks. The load of drug-resistant bacteria will also decrease at rst but rise again to a high level later on. This level can be reduced with increasing drug dosis or decreased contact between health care workers and patients says the authors.
24.25
24.25.1
Methicillin-Resistant Staphylococcus aureus [MRSA]

Pigs as Source of Methicillin-Resistant Staphylococcus aureus CC398 Infections in Humans [268]
Methicillin-resistant Stapylococcus aureus (MRSA) is becoming increasingly recognized among persons in the community without established risk factors. MRSA primarily causes human disease and animals have not, until now, been considered a source of infection. It has recently become apparent that animals, particularly pigs, can constitute a separate MRSA reservoir and be a source of a novel and rapidly emerging type of MRSA in humans; namely MRSA clonal complex (CC)398. According to Robert L. Skov and colleagues 2008 an emerging subtype of methicillinresistant Staphylococcus aureus (MRSA), clonal complex (CC) 398, was found in near 50 per cent in Danish pigs on 4 of 5 farms. The CC398 variant of the bacteria was found infecting humans. The study found that living or working on farms with animals was an independent risk factor for CC398. Based on microbiologic testing the authors stress that pigs are a source of CC398 in Denmark. The study reinforces results of studies in France, the Netherlands, and Canada that indicated that CC398 is transmissible from animals to humans.
24.25.2
Methicillin-Resistant Staphylococcus aureus carriage in Belgian swine farms [269]
Denis and colleagues 2009 found a prevalence of methicillin-resistant Staphylococcus aureus ST 398 (MRSA ST 398) carriage in 37,8% of persons working on Belgian pig farms. On farms with MRSA-colonized pigs the prevalence of carriage was 50% versus 3% on farms without colonized pigs. Swine, exposed farmers and veterinarians are thus high risk factors for carriage of MRSA from Belgian pig farms. Notably these MRSA strains are
1722
genetically unrelated to hospital- or community-acquired clones. The authors stress that risk factors for MRSA ST398 carriage was associated with being a farmer or farm co-worker, being male, having regular contact with animals (including goats, sheep, dogs, or cats) and, paradoxically, wearing gloves and apron and reporting occasional or regular hand disinfection with an antimicrobial product. This suggests that dierent animals could be MRSA ST398 reservoirs or vectors, at least on pig farms. The authors call for more studies to determine other routes of transmission such as airborne transmission and contact with contaminated surfaces and companion animals which apaerntly reduce the eectiveness of the protection of gloves and apron.
24.25.3 24.25.4
Methods used for Methicillin-Resistant Staphylococcus aureus ST 398 [269] Identication of MRSA ST398 according to Denis and colleagues 2009
Samples from anterior nares and skin lesions on hands or face of human participants were placed into Stuart transport medium (Copan, Italy), inoculated within 24 h into 7.5% NaCl brain-heart infusion enrichment broth, and subcultured after 24 h onto Chromagar MRSA (bioMrieux, Marcy lEtoile, France) and mannitol salt agar (Becton Dickinson, Heidelberg, Germany). S. aureus isolates were identied by coagulase test and PCR for 16S rRNA, mecA, and nuc genes.
24.25.5
Genotyping of MRSA ST398 used by Denis and colleagues 2009
Isolates were genotyped by pulsed-eld gel electrophoresis after SmaI macrorestriction, spa sequence typing (http://spaserver.ridom.de), and determination of staphylococcal cassette chromosome mec (SCCmec) type and accessory gene regulator (agr) polymorphism. Four MRSA isolates were further analyzed by multilocus sequence typing (www.mlst.net). Multiplex PCR was used to test for Panton-Valentine leukocidin, toxic shock syndrome toxin 1, and exfoliatin A and B genes.
24.25.6
Antimicribial drug susceptibility testing used by Denis and colleagues 2009
Antimicrobial drug susceptibility was tested by the Vitek2 system (bioMrieux). Multiplex PCR was used to test for resistance genes tetK, tetM, aac (6)-Ie + aph (2"), ant (4)-Ia, aph (3)-IIIa, ermA, and ermC.
24.25. METHICILLIN-RESISTANT STAPHYLOCOCCUS AUREUS [MRSA]
1723
24.25.7
Methicillin-resistant Staphylococcus aureus (MRSA) [270]
Deurenberg and Stobberingh 2008 stress that the resistance to methicillin and all other beta-lactam antibiotics is related to the mecA gene, situated on the staphylococcal cassette chromosome mec (SCCmec). Methicillin-resistant Staphylococcus aureus probably originated trough the transfer of SCCmec into a limited number of methicillin-sensitive lineages. According to the authors there are seven major variants of SCCmec, type I to VII. Two clones of MRSA had been identied, the hospital-associated (HA-MRSA), and the community-associated MRSA (CA-MRSA, which includes the SCCmec type IV, V or VII and is often associated with the toxin Panton-Valentine leukocidin (PVL). However, the distinction between HA-MRSA and CA-MRSA is vanishing.
24.25.8
Risk factors community-associated Staphylococcus aureus [271]
Golding and colleagues 2010 report that no signicant statistical dierences were found between the frequency of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) and community-associated methicillin-susceptible Staphylococcus aureus(CAMSSA) infections. The most common risk factors were overcrowding, previous antibiotic usage, existing skin conditions, household exposure to someone with a skin condition, scratches/insect bites, and exposure to healthcare workers. Standard hygienic measures and proper treatment guidelines for the control of both, CAMRSA and CA-MSSA, in remote communities were recommended.
24.25.9
Methicillin-resistant Staphylococcus aureus from pigs in humans [272]
Golding and colleagues 2010 stress a high prevalence of colonization with livestock-associated (LA) methicillin-resistant Staphylococcus aureus (MRSA) sequence type (ST) 398 among pigs and pig farmers are found in the Netherlands, in Canada and in the United States. However, no human or animal infections resulting from these strains were reported in North America. The authors identied a novel staphylococcal cassette chromosome (SCC) mecV subtype harboring clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated genes (cas) array in Staphylococcus aureus isolate 08 BA 02176.
1724
24.25.10
Canadian epidemic lineages of methicillin-resistant Staphylococcus aureus [273]
Christianson and colleagues 2007 pointed out that there is a high dissemination of Methicillinresistant Staphylococcus aureus (MRSA) throughout Canadian hospitals and communities. The authors found that the community-associated Canadian epidemic isolates (CMRSA7 and CMRSA10) contained one open reading frame (ORF) (SACOL0046) encoding a putative protein belonging to a metallo-beta-lactamase family. The hospital-associated Canadian epidemic isolates (CMRSA1 and CMRSA2) revealed additional factors including ORFs encoding potential virulence factors involved in capsular biosynthesis, serine proteases, epidermin, adhesion factors, regulatory functions, leukotoxins, and exotoxins. Semi-selective broth for detection of methicillin-resistant Staphylococcus aureus [274] Bcher and colleagues 2010 describe a new method for routine diagnostic screening of methicillin-resistant Staphylococcus aureus (MRSA). The use of a semi-selective enrichment broth containing cefoxitin and aztreonam (TSB-SSI) incubated overnight followed by plating on Columbia sheep blood (5%) agar (BA) and ChromID MRSA improved signicantly the detection of the bacteria, compared with non-selective enrichment broth (NB). Meticillin-resistant Staphylococcus aureus incidence doubles in UAE hospitals According to a study by UAE University carried out at Tawam Hospital, in Al Ain, found that the incidence of Meticillin-resistant Staphylococcus aureus (MRSA), doubled between 2003 and 2008. Sonnevend et al 2012 write in this study that the emergence of CA-MRSA clones with subsequent entry to and spread within the hospital has contributed to the increasing incidence of MRSA observed in Tawam Hospital. The study notes that 5.2 percent of analysed strains of Staphyllococcus aureus were resistant to meticillin in 2003 while this number rose to 12.3 percent in 2008. [275] In 2003, 61,5% of typical healthcare-associated (HA-MRSA) isolates were of genotypes ST239-MRSA-III, ST22-MRSA-IV and ST5-MRSA-II. Isolates of 2008 had changed to clonal types community-associated (CA) MRSA, representing 73.1% of the strains with ST80-MRSA-IV, ST5-MRSA-IV and ST1-MRSA. Non-typable SCCmec types were the most frequent. Community-associated (CA-) MRSA infections are acquired at home or at public places. About 75 percent of CA-MRSA are localized at skin and soft tissue where they usually can be treated eectively. But some CA-MRSA strains display enhanced virulence, spreading
24.26. LANTIBIOTICS AS NATURAL FOOD PRESERVATIVE AND BACTERIAL DISEASE PREVENTION 1725 more rapidly and causing illness much more severe than traditional healthcare-associated (HA-) MRSA hospital infections. They can aect vital organs and lead to widespread infection (sepsis), toxic shock syndrome, and necrotizing ("esh-eating") pneumonia. Dr Jens Thomsen of the Health Authority Abu Dhabi (Haad) stresses that there is an ongoing antimicrobial resistance data is currently still being compiled on a Pan-Emirate level. The bacteria are spread by a combination of lack of hand hygiene and direct contact from patient to patient or from a healthcare worker to a patient. Hygiene measures are therefore to be improved. Prescription of antibiotics must be controlled to reduce excessive use where it is not needed such as in case of a common cold. Such use brings a battery of bacteria in contact with antibiotics turning them resistant. [276]
24.26
Lantibiotics as natural food preservative and bacterial disease prevention
[277] The lantibiotics are becoming interesting as natural preservatives to prevent harmful bacteria in foods. They are easy to digest, nontoxic, do not induce allergies and are dicult for dangerous bacteria to develop resistance against. Lantibiotics are a class of antimicrobial peptides that are characterised by the presence of lanthionine and/or methyllanthionine residues. Lantibiotics are produced by Gram-positive bacteria such as Streptococcus and Streptomyces Bacillus, Bidobacterium and others. They are strong antimicrobials and may be usefull in food preservation.
24.26.1
Classication [278]
Type A lantibiotics: are long exible molecules - e.g. nisin, subtilin, epidermin. Subgroup AI includes mutacin II, subgroup AII includes mutacin I & III. Type A lantibiotics act by pore formation, Type B lantibiotics: are globular - e.g. mersacidin, actagardine, cinnamycin. type B lantibiotics inhibit peptidoglycan biosynthesis. Nisin and epidermin are members of a family of lantibiotics that bind to a cell wall precursor lipid component of target bacteria and disrupt cell wall production. The duramycin family of lantibiotics binds phosphoethanolamine in the membranes of its target cells and seem to disrupt several physiological functions.
24.26.2
List of known lantibiotics [279]
A description of all known lantibiotics and the producer organism is given in Bactibase database.
1726
24.26.3
Lantibiotic production in broth media [280]
Lee, Li and OSullivan 2011 report the production of lantibiotic from Bidobacterium longum DJO10A in agar culture but suppression of its expression in broth media. The authors found that the adding an agar culture extract to a broth cultures of B. longum DJO10A induces lan A gene expression of lantibiotic in liquid media. The transcription start analysis of lan A revealed a 284 bp 5 untranslated region to be involved in repression of transcription in broth culture. An inverted repeat structure located at -75 bp relative to the transcription start functions as a binding site for the two component response regulator. Better understanding of the regulation of lan A gene is important for the production of this lantibiotic in broth cultures.
24.26.4
Movement of Refugees and Aid Workers
International spread of infectious diseases from conict situations may occur through movement of refugees, relief workers, animals, goods, and private sector employees working in mining, oil, logging, or construction industries. An example of the outcomes of such conditions was the prolonged outbreak of hepatitis E virus in a camp in Darfur, Sudan, in May 2004. Also cited is the imported case of Lassa fever which was conrmed in Germany in July 2006, after a Sierra Leonean resident, ew from Freetown to Frankfurt through Abidjan and Brussels, 5 days after symptom onset. Aid workers and British soldiers have imported Lassa fever into the Netherlands (2000) and the United Kingdom (2000 and 2003) after postings in Lassa-endemic areas of Sierra Leone. Improving Detection and Control of Infectious Diseases in Conict Situations Gayer calls for a functional healthcare system for the detection and control of many emerging infectious diseases. In such settings, good hygiene and standard infection control precautions in health facilities are needed to reduce the potential for nosocomial transmission and amplication of disease. It is imperative that the technical capacity of all humanitarian health partners and ministries of health regarding disease surveillance, prevention, and control in conict-aected countries be enhanced to ensure eective implementation of infectious disease interventions. Data on disease incidence and trends are essential for prioritizing risks and planning interventions and should be obtained through disease surveillance and early warning and response systems. Several of these systems have been implemented in conict situations. Surveillance systems rely on close partnerships with NGOs, international organizations, and community groups and are built on resources and capacities of all organizations present.
24.27. INFECTIOUS DISEASES IN THE AMAZON REGION
1727
Epidemic preparedness measures to be taken should involve training sta to use surveillance tools and manage cases of epidemic-prone diseases and equipping them with reliable means of communication. Revised International Health Regulations of 2005 provide a global legal framework to guide response to public health events of international concern. Military forces are increasingly implementing aid programs for conict-aected populations. These programs have a crucial role and are a valuable resource.
24.27
Infectious diseases in the Amazon region
[281] Many of the tropical diseases of the region undergo epidemiologic changes in face of a growing population, environmental, and climate changes, and the incidence of some novel diseases increase. Important diseases are:
24.28
24.28.1
Flagellates
Malaria
It is caused by Plasmodium spp is the most important endemic disease in the region. It is naturally transmitted by mosquitoes of the genus Anopheles. Urbanisation contributes to malaria transmission in peripheral areas of Amazonian cities.
24.28.2
Tegumentary leishmaniasis
It is a high-incidence disease in the region. Multiple animal species serve as reservoirs for Leishmania spp. in the rainforest, as do the diseases primary vectors, insects of the genus Lutzomya.
24.28.3
Chagas disease Trypanosoma cruzi
The reservoir include armadillos, dogs, cats and rodents. Chagas disease is mainly a disease of children. It is characterized by svollen lymph nodes , fever and anemia. Cases may be acute and quickly fatal or milder and chronic.
24.29
Leishmaniasis
[282] Leishmaniasis is caused by protozoan parasites of the genus Leishmania. It is transmitted by the bite of sandies of the genus Phlebotomus.
1728
Only the female sandy transmits the parasites. Female sandies need blood for their eggs to develop, and become infected with the Leishmania parasites when they suck blood from an infected person or animal and the Leishmania can develop in the sany. Feeding blood from another animal or human the sandy inoculates the Leishmania, which can than mature. Sand ies within the genus Lutzomyia serve as the vectors for all species of the protozoan parasite Leishmania. Lutzomyia longipalpis was the predominant species collected within the Pacic plains region of western Nicaragua. Lutzomyia cruciata or Lutzomyia barrettoi majuscula were the species most frequently collected in the central highlands and Atlantic plains regions. [283] Leishmania protozoans which infect mamals are the Leishmania donovani complex with three species (L. donovani, L. infantum, and L. chagasi), the Leishmania mexicana complex with four species (L. mexicana, L. amazonensis, and L. venezuelensis), Leishmania tropica, Leishmania major, Leishmania aethiopica, and the subgenus Viannia with four important species (L. (V.) braziliensis, L. (V.) guyanensis, L. (V.) panamensis, and L. (V.) peruviana). The disease may cause cutaneous, mucocutaneous or visceral forms. Cutaneous leishmaniasis is the most common form. Visceral leishmaniasis is the most severe form, in which vital organs of the body are aected. The mucocutaneous form aects the nasopharyngeal tissues with lesions of this tissue. Dierention between the dierent species of Leishmania uses isoenzyme analysis, DNA sequence analysis, or monoclonal antibodies, because there is no dierence of morphology between the species. Cutaneous leishmaniasis is known to be endemic in south-central Texas. Wright et al.2008 report nine cases of cutaneous leishmaniasis in residents of north Texas. The authors warns that the disease may experience a northern spread. [284]
24.29.1
Leishmaniasis in Bolivia
In Bolivia, most cases of leishmaniasis are caused by Leishmania (Viannia) braziliensis. The parasite is transmitted zoonotically by several sandy species and, when transmitted to humans, may cause cutaneous leishmaniasis, and potentially, mucosal leishmaniasis.
24.29.2
A kind of a symbiosis between Leishmania and virus increasing severity of leishmaniasis [285]
The mucocutaneous form of leishmaniasis aecting the nasopharyngeal tissues was studied by Ives et al. 2011. The authors report that metastasizing parasites are highly infected by a virus, the Leishmania RNA virus-1 (LRV1). This virus interferes with the human immune system sensor protein called Toll-like receptor 3 (TLR3) localised in macrophages
24.30. MYCOSES
1729
of humans. The TLR3 protectve immune pathway is turned to produce proinammatory cytokines and chemokines triggered by the LRV1 virus.
24.29.3 24.29.4
Bacterial and micotic infection Leprosy
Bacterial infection caused by Mycobacterium Leprae. The lepromatous form of the disease is characterised by large, rm nodules in the skin of the face, hands and other exposed parts. These nodules are called lepromas contain high number of bacilli. The tuberculoid type of infections develop around peripheral nerves, leading to atrophy of the tissue, loss of sensation from sensory nerve, mutilations are therefore often not noted. Bacteria may leave or enter via the nares.
24.29.5
Suspected Brazilian purpuric fever
It is a Haemophilus aegyptius-caused febrile hemorrhagic illness of children that begins with conjunctivitis and has a case-fatality rate of 40%-90%.
24.29.6
Bartonella
Bartonella (formerly known as Rochalimaea) is a genus of Gram-negative bacteria. Facultative intracellular parasites, Bartonella species can infect healthy people but are considered especially important as opportunistic pathogens. Bartonella are transmitted by insect vectors such as ticks, eas, sand ies and mosquitoes. At least eight Bartonella species or subspecies are known to infect humans. Bartonella bacilliformis is found in Peru, Ecuador, and Colombia and causes the Carrions disease (Oroya fever, Verruga peruana)
24.30
24.30.1
Mycoses
Jorge Lobo disease
It is caused by Blastomyces loboi, are also characteristic of the region.
24.30.2
Adiaspiromycosis
It is a respiratory disease of humans and many animal species caused by the fungus Chrysosporium spp. and characterized by large, thick-walled spherules (adiaspores).
24.30.3
Intestinal parasites
Intestinal parasites high frequency of intestinal parasites are linked to contaminated food and water.
1730
24.30.4
Bacillus stearothermophilus
Bacillus stearothermophilus Donk, 1920 is presumably intended to mean fat and heatloving.In 2001 the name was chaged to Geobacillus stearothermophilus. The most distinctive diagnostic characters are capacity to grow at 65o C and a limited tolerance to acid. Bacillus strains capable of growing at temperatures of 65o C and above do not belong to a single species, it is however a useful diagnostic character. Bacillus stereatothermophilus occurs in soil, hot springs, desert sand, Arctic waters, ocean sediments, food and compost. The biochemical characteristics of Bacillus stearothermophilus are: Catalase= negative Voges-Proskauer test= negative Acid from D-glucose= positive hen Acid from L- arabinose= dier D-xilose= dier D-mannitol= dier Gas from glucose= negative Hydrolysis of casein= dier Hydrolysis of gelatin= positive Hydrolysis of starch= positive Utilization of citrate= dier Degradation of Tyrosine= negative Desamination of phenylalanine= negative Nitrate reduced to nitrite= dier Formation of indole= negative Dihydroxyacetone= negative Sodium and potassium chloride required= negative Alantoin or urate required= negative Allen ( 1953) has pointed out that fresh isolates tend to diversity of characteristics. When maintained in culture for some times they are readily classiable. This bacterium has a vital importance for canning factories. Bacillus stearothermophilus together with Bacillus coagulans as well as other bacteria have high heat resistant spores. The temperature maximum where growth still takes place is 75o C the best growth temperature for Bacillus stearothermophilus is 55 to 60o C . Bacillus stearothermophilus is the bacterium whose spores can survive at temperatures higher than other bacteria. In hot springs bacteria may be found which resist higher temperatures than that.
24.30. MYCOSES
1731
24.30.5
Biological indicator for sterilisation [286]
Geobacillus stearothermophilus is a spore biological indicators, which is used by the FDA. This biological indicator is used to verify the eectiveness of pasteurisation or sterilisation processes. The spores of the bacterium are enclosed in a glass vial, together with a culture media and an indicator. After the sterilisation process is nished the heated vial is incubated at 60o C , together with a similar unheated vial. Changing colour of the media in the unheated vial but no colour change in the heated vial demonstrates successful sterilisation.
24.30.6
Control strips
Autoclave control strips with 105 Geobacillus stearothermophilus ATCC 7953-Sporen (former Bacillus stearothermophilus), enclosed in plastic bags, are used for the validation of steam sterilisation and dry heat sterilisation After the heating process the strips are incubated in a Caso-Broth + Bromcresol purple (Tryptic Soy Broth + Bromcresol purple) at 55-60o C during 7 days. Daily control of growth seen by increasing turbidity and clour change from violet to yellow. A Gram-stain is made in case of growth. Gram-positive rods are Geobacillus, other forms are contaminants and are discarded.
24.30.7
D-value (Decimal reduction time)
The D-value is the time which is necessary at a specic temperature to reduce an initial population of a bacterium down to 10%. This means that it kills 90% of the bacterium. It is measured in minutes.The Temperature must be cited. For Bacillus stearothermophilus a D-value of D121,1 = 4 up to 5 minutes are given. D-values for other bacteria in order to draw a comparison: Clostridium botulinum type A and B D121,1 = 0,1 up to 0,2 min. Clostridium sporogenes D121,1 = 0,1 up to 1,5 min. Clostridium thermosaccharolyticum D121,1 = 3 up to 4,0 min. Desulfotomaculum nigricans D121,1 = 2 up to 3,0 min. For tropic conserves the sterilization has to be carefully done as Bacillus stearotermophilus grows at storage temperatures higher than 37o . Below of that there is no growth. To kill its spores F121,1 15 to 30 minutes must be used in case of canned meat.
1732
24.31
Tetrahymena protozoan and Samonella and resistance to sanitizers
[287] [288] Nondestructive ingestion by soilborne protozoa may enhance the environmental resiliency of important bacterial pathogens and may model how such bacteria evade destruction in human macrophages. Microbiologist Maria T. Brandl from the Agricultural Research Service (ARS) in the US have found that Salmonella enterica serovar Thompson may be ingested by the protozoan Tetrahymena. S. enterica cannot be digested by the protozoan which is expelled encased in miniature pouches called "food vacuoles." Other food pathogens such as Listeria monocytogenes, however, are destroyed and digested. Brandl found that twice as many Salmonella cells stayed alive in water if they were encased in expelled vacuoles than if they were not encased. Encased Salmonella cells were three times more likely than unenclosed cells to survive exposure to a 10-minute bath of two parts per million of calcium hypochlorite, the bleachlike compound often used to sanitise food and food-processing equipment being resistant to sanitising. Brandl found that some vacuoles held as many as 50 Salmonella cells. This dense clustering might safeguard the innermost ones from environmental stresses such as ultraviolet rays or harmful temperatures. Brandl concludes that the release of this human pathogen from Tetrahymena cells in highdensity clusters enclosed in a membrane may have important implications for public health. Brandl now wants to pinpoint genes that Salmonella bacteria turn on while inside the vacuoles. Those genes may be the ones that it activates when invading humans. [287]
24.31.1
Protozoa on leafy vegetables increases risk of enteric diseases [289]
Brandle and colleagues 2008 studied the protozoa Glaucoma sp., Tetrahymena pyriformis, Colpoda steinii, and Acanthamoeba palestinensis on spinach and lettuce and their interactions with S. enterica, Escherichia coli O157:H7, and Listeria monocytogenes. The authors found that vesicles production was observed during grazing on E. coli O157:H7 and S. enterica but not during grazing on L. monocytogenes, in vitro and on leaves. Also C. steinii and A. palestinensis did not produce vesicles, nor any of the enteric pathogens were trapped by both protozoa. The authors found that E. coli O157:H7 in expelled vesicles multiplied and escaped the expelled protozoan vesicles. They conclude that protozoa and their activity on leafy vegOurFood Database of Food and Related Sciences Copyright 1998-2010 Karl H. Wilm. All rights reserved.
24.31. TETRAHYMENA PROTOZOAN AND SAMONELLA AND RESISTANCE TO SANITIZERS 1733 etables with formation of vesicles may enhance the aggressivity of trapped enteric bacteria which can better resist food sanitation.
24.31.2
Phage potentiates antibiotic [290]
Steven Hagens found that specic bacteriophages, such as the lamentous phages Pf3 and Pf1 can make antibiotic-resistant Pseudomonas bacteria more susceptible, thus improving the attack on them by antibiotics. According to the author of the study phage DNA sequences code for membrane proteins that create channels in the bacteriums cell wall. Antibiotics are able to enter the cell through these gateways more quickly than it can dispose of them. Tests were performed in mice. The combination therapy using the antibiotic Gentamicin and the lamentous phages was eective against a strain of P. aeruginosa containing a gene for resistance to Gentamicin. Combination therapy using phages could then make progress when a bacterial strain was susceptible to a particular lamentous phage. Professor Martin Loessner of the Swiss Federal Institute of Technology Zurich (ETH) researches on the use of phages against Listeria monocytogenes in foods like soft cheeses. [291]
24.31.3
Potentials of phages in food industry [292]
The attempts to treat diseases including dysentery, typhoid and paratyphoid fevers, cholera and pyogenic urinary tract infections have not always succeeded due to the diculty to select the specic phage, incorrect identication of the bacterium or the mixture of bacteria which was causing the disease. Other problems were the gastric acidity which destroyed the phages, and sometimes deterioration of the patient following the release of endotoxin of the lyzed bacteria. Research on phages becomes new priority with the spreading of antibiotic resistant bacteria. Development of phage therapy is attractive oering low cost compared with antibiotics, can be used in food industry to reduce risk contamination with pathogenic bacteria during processing. Steven Hagens and Mark L. Oerhaus, both from EBI Food Safety in the Netherlands, working the application of phages in food industry, say that phages may be used to disinfect working surfaces and even food during processing. They stress, however, that the number of phages in a solution must be very high in order to get in contact with the bacterium to be eliminated.
1734
24.31.4
New phages to treat bacterial infections like multiple drug resistant strain of Staphylococcus aureus (MRSA) and Clostridium dicile [293]
A bacterial infection can be targeted using special bacteriophages which attack the exact strain of the pathogenic bacteria. Other benecial bacteria of the body are spared, according to Ana Toribio and colleagues. Excessive use of broad-spectrum antibiotics and their use in feed as growth promoter lead to resistant strains of pathogenic bacteria. The researchers used a cocktail of phages obtained from the River Cam to treat gut infections caused by Citrobacter rodentium in mice. Variety of phages are used to overcome bacterial mutations. The Tbilisi Bacteriophage Institute in Georgia already uses bacteriophages for the treatment of infections such as diabetic ulcers and wounds.
24.32
Meat "blown pack" spoilage
Gaseous spoilage of vacuum-packaged chilled meats were reported in Germany. Clostridium estertheticum was found to generate the gas with nauseating odour. Health ocials declared the phenomena as not health threatening. The aected meat had be destroyed. Clostridium estertheticum represents, therefore a nancial threat for chilled meat producers.
24.32.1
Clostridium estertheticum gaseous spoilage of chilled meats [294]
Collins and colleagues 1992 performed a taxonomic study of an unknown anaerobic Grampositive, spore-forming, psychrophilic bacterium isolated from spoiled vacuum-packed refrigerated beef and proposed it to be classied as a new species of the genus Clostridium, as Clostridium estertheticum sp. nov. The type strain is NCIMB 12511.
24.32.2
Contamination of vacuum-packed chilled meats with Clostridium estertheticum [295]
Clemens, Adam and Brightwell 2010 studied the contamination levels of Clostridium estertheticum spores causing gaseous spoilage of vacuum-packaged chilled meats, beef and lamb, stored at two dierent temperatures, -1.5 and 2 degrees C. The authors stress that onset of blown pack spoilage is delayed storing meat at -1.5 degrees C, compared with storage at 2 degrees C. To avoid the risk of "blown pack"spoilage,
24.32. MEAT "BLOWN PACK" SPOILAGE
1735
contamination with spores of Clostridium estertheticum must be reduced to a minimum by strict observance of hygienic handling of meat.
24.32.3
PCR amplication procedure to detect clostridia causing spoilage of vacuum-packed chilled meats [296]
Broda DM, Boerema JA, Brightwell 2009 determine preslaughter and processing sources of psychrophilic and psychrotolerant clostridia causing spoilage of vacuum-packed chilled meats using the polymerase chain reaction (PCR) amplication of specic 16S rDNA fragments. Clostridium gasigenes, C. estertheticum and C. algidicarnis/C. putrefaciens were commonly detected in farm, faeces, eece and processing environmental samples collected at the slaughter oor operations, but only 4 out of 26 cooling oor and chiller environmental samples were positive for all of them. Frequency of C gasigenes and C. estertheticum was low, and high frequency of C. algidicarnis/C. Putrefaciens was detected in boning room. Detection frequence of C. gasigenes and C. estertheticum was high, but low for C. algidicarnis and/or C. putrefaciens in samples of faecis. The authors concluded that control of meat spoilage by clostridia is best approached individually for each group.
24.32.4
Describing the bacteria isolated from blown packs of vacuum-packaged beef [297]
Yang, Gill and Balamurugan 2009 describe the bacteria recovered from the microora of blown packs of vacuum-packaged beef identied as Leuconostoc mesenteroides, Lactococcus lactis, Carnobacterium maltaromaticum, and Clostridium estertheticum, with Leuconostoc mesenteroides predominant. The authors stress that Clostridium estertheticum may predominate during the early stages of development of the spoilage microora of vacuum-packaged beef but will likely be inhibited by a falling pH later on.
24.32.5
Inhibition by Lactobacillus sakei of spoilage bacteria on vacuum-packed meat [298]
Jones 2009 and colleagues describe the abilities of ve Lactobacillus sakei strains and one Lactococcus lactis strain to retain inhibitory activity against target organisms on vacuumpackaged lamb and beef.
1736
Among others ndings, the authors report that in beef packs inoculated with Clostridium estertheticum spores and L. sakei strain 27, 44 or 63, the development of blown-pack spoilage was delayed by up to one week. The authors suggest a set of Lactobacillus sakei strains which may extended shelf life of minimally processed fresh beef and lamb.
24.32.6
Temperature and contamination level inuences onset of vacuum-packed meat spoilage [299]
Moschonas and colleagues 2010 examined the eect of storage temperature and inoculum level on the time of onset of "blown pack" spoilage caused by psychrotolerant bacteria in vacuum-packed meats. Clostridium estertheticum ssp. estertheticum presented at all inoculum levels/storage temperature combinations examined the earliest "blown pack" spoilage of all other bacteria in test. They stress the importance contamination level control and low storage temperature to delay the onset of "blown-pack" spoilage of meat.
24.32.7
Isolation and source of "blown pack" spoilage bacteria identication [300]
Moschonas and colleagues 2009 report that DNA-based techniques were the most ecient methods to determine the presence and distribution of blown pack spoilage at beef abattoirs of Clostridium estertheticum and Clostridium gasigenes, compared with culture-methods which presented poor results. The authors point out that hides and faeces were found to be the main reservoirs of "blown pack" spoilage clostridia in the abattoirs.
24.32.8
Glucose and lactose utilisation by Clostridium estertheticum
[301] According to Yang X, Balamurugan S, Gill 2009 blown pack spoilage of vacuum packaged beef is caused by the psychrophile Clostridium estertheticum, which grow exponentially on glucose with simultaneous hydrolysis of glycogen. Growth ceased when glucose in the media was depleted; but hydrolysis of glycogen continued at a reduced rate, and lactate was consumed rapidly. The authors suggest that reducing the availiability of glucose may limit the growth of Clostridium estertheticum and other gas generating bacteria on vacuum packaged beef. Lactate fermentation, however, will continue, even after growth ceases.
24.32.9
PCR detection of psychrophilic Clostridium spp. [302]
Broda, Boerema and Bell 2003 developed a practical molecular procedure that directly, without isolation, and specically detects the presence of clostridia which cause "blown pack" spoilage of vacuum-packed meat containing as few as 100 clostridial cells per gram. Clostridium gasigenes was conrmed as the causative agent of "blown pack" spoilage insome packages, and Clostridium estertheticum in others.
1737
The described procedure may also be used in in epidemiological trace back of "blown pack" spoilage incidents in meat processing plants.
24.32.10
Controlling "blown pack" spoilage in meat processing plants [303]
Broda and colleagues 2002 identied abattoir sources of psychrophilic clostridia causing "blown pack" spoilage of vacuum-packed chilled meats. Restriction fragment length polymorphism analysis of the 16S rDNA gene (PCR-RFLP) and 16S-23S rDNA internal transcribed spacer (ITS) analysis were used by the authors. The authors found that soil particles attached to hide or present in faeces are the primary reservoir of "blown pack" clostridia contaminating meat end products. The authors recommend strong dressing procedure hygiene to control the spread of psychrophilic Clostridium spp. in a meat plant.
24.32.11
Hygienic carcass dressing at abattoir is necessary to reduce blown pack spoilage of meat products [304]
Broda and colleagues 2009 assessed preslaughter and processing sources of psychrophilic and psychrotolerant clostridia causing spoilage of vacuum-packed chilled meats, using polymerase chain reaction (PCR) amplication of specic 16S rDNA fragments. Clostridium gasigenes, Clostridium estertheticum, Clostridium algidicarnis and Clostridium putrefaciens were detected in farm, faeces, eece, slaughter oor operations prior to eece removal. Clemens, Adam and Brightwell 2010 report that storage at -1.5 degrees C signicantly delays the onset of blown pack spoilage of meat in comparison with storage at 2 degrees C. The authors stress that one Clostridium estertheticum spore may initiate spoilage. They point out to the importance of hygienic carcass dressing to keep contamination to a minimum to improve shelf life of vacuum-packed chilled meat products. [305]
24.32.12
Description of Clostridium estertheticum subspp. laramiense and Clostridium estertheticum subsp. estertheticum growing in meat juice medium
[306] Recently two subtypes of Clostridium estertheticum were dened. Yang, Gill and Balamurugan 2010 presented further description of these subtypes: The fermentation products of both strains of Clostridium estertheticum subsp. laramiense and Clostridium estertheticum subsp. estertheticum were butyrate, acetate, and formate from gucose and 1butanol, ethanol, butyrate, and formate from the fermentation of lactate. Both organisms
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did not produce H2S. The optimum and maximum temperatures for growth of both were 10 degrees C, and 20 to 22 degrees C, respectively in a pH range for growth of 5.5 to 7.5. The authors expect blown pack spoilage of meat to be identical for both subtypes.
24.32.13
There is no epidemiological association of Staphylococcus aureus between isolates from cows and humans [307]
Hata and colleagues 2008 assessed the epidemiological association and bacteriological characteristics of human and animal Staphylococcus aureus isolates. Using pulsed-eld gel electrophoresis the authors found that pulsotypes of isolates from bulk milk diered from pulsotypes from human isolates. They concluded that there is no epidemiological association between isolates from these 2 sources, and that a number of factors play a role in the adaptation of Staphylococcus aureus isolates to specic hosts.
24.32.14
Hair-like protrusions on the surface of bacteria may turn them dangerous to premature babies [308]
Giovanna Marchini and colleagues 2009 found that Staphylococcus epidermis, a coagulasenegative staphylococci, which normally reside on the skin of healthy people can cause serious infections in premature babies, attaching to the childs skin and mucous membranes and cause serious infections. The researchers found hair-like protrusions on the surface of the bacteria which adhere the bacteria to the hosts cells. According to Marchini, an antimicrobial substance LL37 is found at the skin and lungs and inhibit the growth of the bacteria in older people. This may explain the human co-existence with certain microbes, such as intestinal bacteria which produces Vitamin K and others involved in the development of an immune system.
24.32.15
EFSA says cases of infections with Listeria monocitogenes are rising [309]
According to the EFSA 2008 updated opinion on Listeria monocytogenes risk the Pannel stresses that the number of infections are rising and gives advices to reduce the risk. In its advice to industry, the Panel identied the following as key areas for attention: food packaging and preparation practices in the food chain (such as the slicing of RTE meat products), storage temperatures, general industrial good hygiene practices and the education and training of food handlers. The lack of an eective HACCP system may pose another risk.
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24.32.16
Food poisoning outbreaks linked to cantaloup
Every growing season bacterial and viral outbreaks linked to cantaloupe are reported Cantaloupe-linked infections are top 5 of the list of fruits and vegetables for outbreaks. This is largely due to their growing conditions and the potential to support the growth of bacteria. Listeria monocytogenes contamination is known associated deli meat, unpasteurized cheese, raw milk, fresh-cut fruit, and fresh-cut vegetables. Reservoirs for Listeria monocytogenes include ruminant animals, such as cattle, goats, and deer, decaying vegetation, and cold, wet, and dicult to clean environments. CDC and food safety authorities publish advices to reduce the infection risk. Deadly bacteria or viruses can be pushed into the meat of the cantaloupe during slicing, Washing the cantaloupe before cutting is therefore highly recommended. Cantaloup has a very rough rind which rends the fruit prone to harbour and multiply pathogenic bacteria and viruses. A scrub brush should be used during washing under running water to keep bacterial number low. Cool cantaloupe and its slice in refrigerator. High incidence of outbreaks related to cantaloupe demonstrate the need to increase safety measures at farm, transportation, storage and in kitchen [310]: 1990 - 1991 two Salmonella outbreaks 1993 Escherichia coil O157:H7 outbreak 1997 Salmonella saphra and Escherichia coil O157:H7 outbreaks 1999 - 2003 Three Norovirus and seven Salmonella outbreaks 2005 - 2008 Five Salmonella outbreaks 2011 Linsteria monocitogenes
24.32.17
Invasive listeriosis, deadly cantaloupe outbreak in late 2011 [311]
CDC highlights the risk of listeriosis outbreak which started in July 2011 in Colorado, U.S.A. The disease spread over 28 states, 146 cases of invasive listeriosis were conrmed, 30 patients died and one miscarriage was reported until December. The source of this outbreak was tracked down to Jensen Farms cantaloupe. Cantaloupes have been linked to listeriosis illness caused by Listeria bacteria that contaminated the fruit while they were being stored and sorted in cold conditions after harvest. The U.S. Centers for Disease Control and Prevention is investigating the link between cantaloupe Listeria contamination and human sewage sludge that may have become airborne from a nearby farm.
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24.32.18
Infection incidence
An estimated 1,600 cases of invasive listeriosis and 260 related deaths occur annually in the United States. Listeria monocytogenes ranks third as a cause of death due to major known food born pathogens in the United States.
24.32.19
Groups at higher risk for invasive listeriosis
Higher-risk groups include older adults, patients undergoing transplants or receiving immunosuppressive medications, persons with immunocompromising conditions, patients with liver or kidney disease, diabetes and alcoholism. Pregnant women may suer foetal loss, premature labour, neonatal sepsis and meningitis.
24.32.20
Safety precautions
Listeria monocytogenes is able to grow at refrigeration temperatures. This means that storage times should be as short as possible, particularly for foods that are known to spread the disease such as soft cheeses, unpasteurized dairy products (including raw milk); deli and lunch meats, cold cuts, hot dogs, pa t, and meat spreads. Persons at higher-risk for invasive listeriosis should not eat deli and lunch meats, cold cuts, or hot dogs, unless they are heated to an internal temperature of 1650 F or until steaming hot just before serving. Persons at higher risk also should not eat soft cheeses unless they are labelled as made from pasteurized milk. No one should drink raw milk or eat un-aged cheeses or other products made from raw milk. In addition to Listeria monocytogenes, a wide variety of pathogens that are sometimes found in raw milk can make people sick.
24.32.21
Diagosis of listeriosis
Food products, such as smoked salmon, cheese, sandwiches, and lettuce/leafy greens, may be recalled because testing identied Listeria monocytogenes contamination, even without any associated case of illness. However, CDC says that no testing or treatment is indicated for an asymptomatic patient who ate a recalled product, unless symptoms appear within 2 months of eating the recalled product. According to CDC the diagnosis is conrmed only after isolation of Listeria monocytogenes from a normally sterile site, such as blood, or from amniotic uid or the placenta in the setting of pregnancy. Listeria monocytogenes can be isolated readily on routine media, but care must be taken to distinguish this organism from other Gram-positive rods, particularly diphtheroids. Selective enrichment media improve rates of isolation from contaminated specimens. Serological tests are unreliable, and not recommended at the present
24.32. MEAT "BLOWN PACK" SPOILAGE time.
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24.32.22
FDA performed an environmental assessment [312]
The environmental assessment including on-site visits to the farm, packing facility, and cold storage, and environmental and nished product sampling of cantaloup.
Growing environment Environmental samples collected in the growing elds such as soil, wild animal excreta, perimeter and furrow drag swabs, agricultural water, pond water, and cantaloupe were negative for Listeria monocytogenes. The environmental samples collected in the packing facility and cantaloupe collected in cold storage were positive for Listeria monocytogenes. The growing elds are not a likely means of contamination. However, FDA has determined that the growing environment cannot be eliminated as a potential contributor in the introduction of Listeria monocytogenes contamination. Specically, low-level sporadic Listeria monocytogenes contamination from the agricultural environment and incoming cantaloupes may have allowed for establishment of a harbourage or niche for Listeria monocytogenes in the packing facility and cold storage. There are a number of factors that are likely to have contributed to the introduction, growth, or spread of Listeria monocytogenes at Jensen Farms, such as facility and equipment design packing facility cold Storage and postharvest practices, free moisture or increased water activity of the cantaloupe rind from postharvest washing procedures.
Recommendations for prevention of Listeria monocytogenes contamination Fresh fruit and vegetable producers should employ good agricultural and management practices recommended for the growing, harvesting, washing, sorting, packing, storage, and transporting of fruits and vegetables sold to consumers in an unprocessed or minimally processed raw form. These practices are set forth in FDA and USDAs "Guidance for Industry - Guide to Minimize Microbial Food Safety Hazards for Fresh Fruits and Vegetables." [313] FDAs ndings regarding this particular outbreak highlight the importance for the industry to employ good agricultural and management practices in their packing facilities as well as in growing elds.Read "Tips for Fresh Produce Safety: Safe Handling of Raw Produce and Fresh-Squeezed Juices" [314] www.foodsafety.gov/keep/types/fruits/tipsfreshprodsafety.htm
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24.32.23
Listeria L-forms lost their membrane but are still highly pathogen [315]
Listeria (Listeria monocytogenes), a gram positive bacteria causes often fatal food-borne infections They were found in milk and soft cheese. Listeria can cross the blood-brain barrier and the placenta barrier. Loessner and colleagues 2009 report that listeria cells, usually in rod form, may loose their cell walls, being replaced by a thin cytoplasmic membrane. They become spherical and are small or greatly enlarged, the so called L-form. The stress regulating genes were found to be activated while metabolic and energy balance genes were downregulated in the L-form. L-form listeria bacteria form protoplast-like vesicles bearing daughter cells which are released when the vesicles bust. These L-forms can grow in milk but are dicult to cultivate under laboratory conditions and may remain undetected in milk.
24.32.24
Microbiological criteria [316]
Growth of L. monocytogenes is a function of the type of food, the storage time and the storage temperature. Microbiological criteria have been implemented in Europe according to the categories of ready-to-eat foods. Microbiological criteria will assist in controlling the levels of L. monocytogenes e.g. absence in 25 g or 100 cfu/g at the point of consumption.
24.32.25
The Codex alimentarius
Codex alimentarius document on microbiological criteria for L. monocytogenes in ready-toeat foods suggests a zero tolerance throughout the shelf life of the product for ready-to-eat foods in which growth of this microorganism can occur. Applying this criterion close to the end of shelf life could classify products as unsatisfactory, although they are of low risk. An additional option proposed in this Codex document is therefore to tolerate 100 cfu/g throughout the shelf life provided that the manufacturer is able to demonstrate that the product will not exceed this limit throughout the shelf life.
24.32.26
Recommendations EU Pannel
For ready-to-eat foods that support growth of L. monocytogenes, it is impossible to predict with high degree of certainty that the level will or will not exceed 100 cfu/g during the shelf life of these products. Thus, applying this option may result in accepting a probability that foods with more than 100 cfu/g will be consumed. The impact on public health would depend whether the levels markedly above 100 cfu/g are reached.
24.33. NEW PREDICTIVE MICROBIOLOGY TOOLS FOR LISTERIA MONOCITOGENES
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The Pannel recommends to investigate listeriosis cases more thoroughly and generate and analyse data on the consumption in the EU of ready-to-eat foods in which Listeria can be found. The Panel also advised that consumers should continue to observe recommended storage temperatures and keep food appropriately chilled at all times, and take note of the shelf-life of food in their refrigerators. Good food hygiene and preparation principles also play an important role in the prevention of Listeria and other food-borne infections.
24.33
24.33.1
New predictive microbiology tools for Listeria monocitogenes

The Pathogen Modeling Program (PMP) [317]
It is the most widely used predictive microbiology application software, and includes more than 35 models for 11 bacterial pathogens including L. monocytogenes. Download is free.
24.33.2
The ComBase [318]
It is a combined database of microbial responses to food environments. It is linked to the ComBase modelling toolbox, which includes : ComBase Predictor It is a set of 23 growth models and 6 thermal death models for food pathogenic and spoilage microorganisms including L. monocytogenes, Perfringens Predictor It is an application for predicting the growth of Clostridium perfringens during the cooling of meats. DMFit; It is a tting tool, for growth and inactivation curves. The access is free.
24.33.3
The Food Spoilage Predictor (FSP) and the Seafood Spoilage and Safety Predictor (SSSP) [319]
Include models for dierent seafood spoilage bacteria, and a model to predict the simultaneous growth of L. monocytogenes and spoilage microorganisms in sliced and vacuum packed cold-smoked salmon.
24.33.4
Symprevius [320]
Information from Symprevius is available on a commercial basis.

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24.33.5
The U.S. Food Protection Plan [321]
The FDA developed a new Food Protection Plan in late 2007 to address the changes in food sources, production, and consumption that we face in todays world. This plan is intended to cope with new infections like listeriosis. The Plan is based on three strings: Prevention of foodborne contamination It aims to promote increased corporate responsibility to prevent illness. It also seeks to identify and assess vulnerabilities and expand understanding and use of mitigation measures. Intervention at critical stages in the food supply chain This includes focus inspections and risk-based sampling, risk-based surveillance, and better detection of signals that indicate contamination has occurred. More rapid respond to problems This is aimed to reduce the impact, and improve its communication on risks to the public, industry, and other stakeholders.
24.33.6
Listeria in ice cream under aging and storage and distribution conditions [322]
Gougouli, Angelidis and Koutsoumanis 2008 simulated conditions of the aging process and of normal or abuse conditions during distribution and storage of commercial ice cream products to study the kinetic behaviour of Listeria monocytogenes. The bacteria was inoculated and the samples stored under static chilling (4 to 16o C ), static freezing (-5 to -33o C ) Under chilling conditions, L. monocytogenes grew well at all temperatures tested. Under freezing conditions, no signicant changes in the population of the pathogen were observed throughout a 90-day storage period, however freezing did not cause a severe stress in L. monocytogenes cells which were able to initiate growth within a very short time after a temperature upshift from freezing to chilling temperatures. The authors developed mathematical models, which can be used by the dairy industry as eective tools for predicting the behaviour of the pathogen during the manufacture, distribution, and storage of ice cream products
24.33.7
Changing genome sequence of yoghurt bacteria [323]
Van de Guchte and colleagues studying the genome sequence of Lactobacillus delbrueckii ssp. bulgaricus (L. bulgaricus) found that the sequence shows the signs of ongoing specialization, with a substantial number of pseudogenes and incomplete metabolic pathways and relatively few regulatory functions.
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The author point out signs of a rapid evolution of the genome: Exceptionally high numbers of rRNA and tRNA genes with regard to genome size, indicating recent phase of important size reduction. A much higher GC content at codon position 3 than expected The presence of a rare 47.5-kbp inverted repeat in the replication termination region The authors conclude that L. bulgaricus is in ongoing adaptation from a plant-associated habitat to the stable protein and lactose-rich milk environment, such as yoghurt,through the loss of superuous functions and protocooperation with Streptococcus thermophilus.
24.33.8
Genome sequence analysis of Lactobacillus delbrueckii [324]
Lactobacillus delbrueckii subsp. bulgaricus, together with Lactobazillus helveticus and Streptococcus thermophilus are part of starter cultures for fermented dairy products such as yoghurt, Swiss cheese and Italian cheese. The genome sequence of L.delbrueckii subsp bulgaricus is of interest for the dairy industry because strains must be resistant to bacteriophage, have stable fermentation properties, and consistently produce products with acceptable avour and texture attributes. A complete genome sequence analysis will provide the knowledge of the enzymes and metabolic pathways helping to enhance these strains. Lactobacillus delbrueckii species contains three subspecies, L. delbrueckii subsp. delbrueckii, L. delbrueckii subsp. lactis, and L. delbrueckii subsp. bulgaricus. L. delbrueckii subsp. Bulgaricus. The species are acid tolerant, cannot synthesize porphyrins, and possess a strictly fermentative metabolism with lactic acid as the major metabolic end product, and according to Axelsson, 1998, are part of the obligately homofermentative ("Group I") cluster, which produce D-lactic acid from hexose sugars via the Embden-Meyerhof pathway and are incapable of fermenting pentoses and, according to Hammes and Vogel, grow on a restricted number of carbohydrates and require pantothenic acid and niacin. [325] Hammes and Vogel found that the GC ratio of L. delbrueckii subsp. bulgaricus with 49-51%, is higher than that found among other species of this phylogenetic tree with 34 to 46%. [325] Its genome size is according to Leong-Morgenthaler 2.3 Mbp. [326]
24.33.9
Safety assessment for microorganisms added to food and feed [327]
EFSA introducted the use of Qualied Presumption of Safety (QPS) as a safety assessment tool for microorganisms added to food and feed.
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A wide variety of bacterial and fungal species are used in food and feed production, either directly or as a source of additives. Some of these have a long history of apparent safe use, while others are less well understood and may represent a possible risk for consumers. To capture important risk aspects without committing resources to thorough investigations of organisms known to be safe, there is a need for a tool for setting priorities within the risk assessment of microorganisms in the production of food and feed. In 2002/3 the introduction for selected microorganisms of a Qualied Presumption of Safety (QPS) was proposed. This concept shared some of the elements and purpose of the USA GRAS (Generally Recognised As Safe) system. In essence this proposed that a safety assessment of a dened taxonomic group (e.g. genus or group of related species) would be made independently of any particular pre-market authorisation process. If the taxonomic group did not raise safety concerns or, if safety concerns existed, but could be dened and excluded (the qualication) the grouping would be granted QPS status. Thereafter a strain of microorganism whose identity could be unambiguously established and assigned to a QPS group would be freed from the need for further safety assessment other than meeting any qualications specied. Microorganisms not considered suitable for QPS status would remain subject to a full safety assessment. Strains representing approximately 100 species of microorganisms have been or are expected to be referred to EFSA for a safety assessment (see Annex 1 for those already notied to EFSA). Individual species may be the subject of a single notication but more usually are found in several notications. This list includes both live organisms deliberately introduced into the food chain and those used as a source of food/feed additives. A large majority of these 100 species fall within four broad groupings:
1. Gram-positive non-sporulating bacteria (GPNS) 2. Bacillus species 3. Yeasts 4. Filamentous fungi
24.33.10
Antimicrobial drug-resistant Escherichia coli from humans and poultry products [328]
According to Johnson and colleagues 2007 the food supply, including poultry products, may transmit antimicrobial drug-resistant Escherichia coli to humans. Drug-resistant human isolates from US population were phylogenetic and virulence gene prole similar to
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poultry isolates, and drug-susceptible and drug-resistant poultry isolates were largely indistinguishable. Human-source drug-resistant fecal E. coli isolates more likely originated in poultry than in humans, whereas drug-resistant poultry isolates likely derive from drug-susceptible poultry isolates. However, avoidance of poultry consumption may not reliably provide personal protection.
24.33.11
Microbiology of raw milk is important for dairy product quality [329]
Hantsis-Zacharov and Halpern 2008 investigated milk spoilage during cold storage after milk collection. The source of the bacteria are the teat of the cow, the udder, milk equipment and the milking environment. They found that psychrotrophic bacteria and their extracellular proteases and lipases, even refrigerated at 7o C , contribute to the spoilage of dairy products. The heat-stable enzymes still aect the avour quality of milk and its products. Lipases release free fatty acids causing avour defects in the milk, and proteases may cause bitter avour. The authors classied the psychrotrophic isolates in seven classes:
24.33.12
The microbiologic isolates related to the seasons of the year
Gammaproteobacteria in spring and winter, Bacilli in summer, and Actinobacteria in autumn. The four minor classes were Alphaproteobacteria, Betaproteobacteria, Flavobacteria, and Sphingobacteria.
24.33.13
The enzymes
The dominant genera, Pseudomonas and Acinetobacter (Gammaproteobacteria) were lipolytic, Microbacterium (Actinobacteria) was lipolytic and proteolytic, and the lactic acid bacteria (Lactococcus and Leuconostoc) displayed had only minor enzymatic activity. Hantsis-Zacharov and Halpern stress that about 20% of the isolated bacteria were novel species and more studies are needed. They published the classication of a new species, the Chryseobacterium oranimense sp. Nov., which, together with two other novel bateria, Chryseobacterium haifense and Chryseobacterium bovis produce adverse eect on milk quality [330].
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The authors conclude that monitoring the dominant psychrotrophic species could become a sensitive and ecient quality control in the dairy industry.
24.33.14
Non-culture techniques to detect dicult to cultivate bacteria [331]
Uncultivated and dicult-to-cultivate bacteria, such as Fusobacterium nucleatum, Leptotrichia (Sneathia) spp., Bergeyella sp., Peptostreptococcus sp., Bacteroides spp., and a species of the order Clostridiales may have clinical relevance. Dr. Yiping W. Han and colleagues 2009 stress that 60% of the microbes present in cases of intra-amniotic inammation, leading to preterm birth, are missed with traditional culture testing. The authors compared the results of 16S rRNA-based culture-independent methods with standard culture testing. Two-thirds of the species detected by the culture-independent methods were not isolated by culture. These results correlated with increased amniotic uid levels of interleukin-6, histological chorioamnionitis, funisitis, and delivery of neonates with early-onset sepsis. The authors point to the fact
24.33.15
Pathogenicity of Bordetella hinzii [332]
According to Register and Kunkel 2009 Bordetella hinzii was believed to be non-pathogenic in poultry. However, recent studies say that the bacterium caused severe disease causing 100 percent morbidity in turkeys which was formerly attributed to Bordetella avium, a pathogenic bacterium that causes upper respiratory disease in poultry and wild birds. To distinguish between B. hinzii and B. avium DNA-based tests were used. [333] Register and Kunkle found four bordetella hinzii strains which were able to to grow and persist in the trachea and also caused clinical disease. The strains varied in severity, although none demonstrated 100 percent morbidity. Another study found that Bordetella hinzii is not pathogenic for chickens. Further researches will clarify how pathogenic strains dier from non-pathogenic once. And will look after the virulence factors aecting turkey poults.
24.33.16
Bordetella hinzii pathogenicity to humans [334]
Funke and colleagues 1996 highlight the importance of the genus Bordetella comprising species such as Bordetella pertussis and Bordetella parapertussis which are the causative agents of whooping cough in humans, Bordetella bronchiseptica is primarily a respiratory pathogen found in animals but may also cause pneumonia and bacteremia in humans. B.avium causes coryza in poultry but has never been described as causing infections in humans. Bordetella holmesii have been isolated from young adults with septicemia. Bordetella hinzii was proposed as the species of some strains isolated from poultry with resOurFood Database of Food and Related Sciences Copyright 1998-2010 Karl H. Wilm. All rights reserved.
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piratory disease. The authors report two isolates of Bordetella hinzii which, together with two other cases demonstrate that Bordetella hinzii can cause disease in humans. They caution, however, the role of Bordetella hinzii in human infections but is still not completely understood. Fry and colleagues 2007 describe a clinical isolate of Bordetella hinzii in the UK from a patient which had no known avian exposure, and the source of the organism remains unknown. The authors stress that human infection with Bordetella hinzii is rare. Genotypic methods, and the greater mutational variation of the ompA gene compared to other genes (e.g. 16S rRNA gene) is being suggested by the authors to dierentiate Bordetella hinzii from Bordetella avium and other non-classical Bordetella species. [335]
24.33.17
Raman spectroscopy to detect viruses [336]
A new rapid system for detecting and identifying viruses in near-real time is being developed by Tripp and colleagues. It is based on surface-enhanced Raman spectroscopy to measure the frequency of near-infrared laser light. It detects and classies microRNAs (miRNAs), which are regulators of gene expression during development and cell dierentiation as well as biomarkers of disease. miRNAs were rst described in 1993 by Lee and colleagues, and the term microRNA was only introduced in 2001. [337] The authors stress that the SERS-based sensor can detect extremely low number of viruses and provides its molecular ngerprint. The rapid response system can detect viruses from a nasal swab in one minute or less. A device which is now being developed can help to control disease outbreaks and bioterrorism, monitoring passengers at airports or speed up a diagnosis.
24.33.18
Fourier reection infrared spectroscopy (FTIR-ATR) detection of bacteria [338]
Li and Tripp 2008 used an alumina-coated ZnSe internal reection element (IRE) to detect spores of Bacillus globigii by attenuated total reection infrared spectroscopy (FTIR-ATR). The interaction between the carboxylate groups of the bacterium and the positively charged sites on the alumina modulates the adsorption which is highly dependent on pH having ist maximum value at pH 5 a detection limit of 10(7) spores per cm2 is reported by the authors.
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24.33.19
Multidrug-Resistant strains of Streptococcus pneumoniae [339]
Mingtao Zeng and colleagues 2009 report that Streptococcus pneumoniae 19A is resistant to all approved antimicrobial drugs for treatment of acute otitis media in children. Other S. pneumoniae isolates expressing 19A capsule were serotype 19A The authors describe the ST-2722 strain which belongs to a cluster which have 6 alleles of ST-156 expressing dierent capsular serotypes, such as 9V, 14, 11A, 15C, and 19F, They are antimicrobial resistant. The authors point out that such multidrug-resistant Streptococcus pneumoniae strains are of serious concern.
24.33.20
The use of seven-valent pneumococcal conjugate vaccine [340]
Dagan accentuates the reduction of penicillin-resistant Streptococcus pneumoniae carriage following the use of seven-valent pneumococcal conjugate vaccine (PCV7), However, a replacement by non-vaccine pneumococci serotypes was observed, with unknown impact on the disease. Penicillin-intermediate serotype 19A isolates increased with the use of the PCV7 vaccine. This serotype is found worldwide, is highly multidrug-resistant and cause invasive pneumococcal disease in children and the elderly after the use of vaccine. The author stresses that infections with serovar 19A increases also without vaccination in regions with heavy use of antibiotics which turn strategies to contain antibiotic resistance so important.
24.33.21
Routine use of vaccine [341]
Cohen 2009 reports that the Kaiser Pemanente study found a reduction of 7.8% of otitis after the introduction of the seven-valent vaccine (PCV7). In Israel a nine-valent PCV was used with a reduction of 17% in antibiotic use, and 41.9% less antibiotics treating acute otitis media were prescribed in USA and 10% less in France on account of vaccine PCV7. According to the author the penicillin-resistant pneumococci carriage reduced from 15.4% to 6.7% and penicillin-non-susceptible strains from 47.7% to 30.4%. Vaccine-serotype pneumococci carriage dropped from 44.3% to 28.9%. These studies, however, report a rise of carriage of non-vaccine serotypes from 9.6% to 15.8%. The serotype 19A increased from 8.6% to 12.6%, and highly penicillin-resistant strains decreased from 15.6% to 1.1%. Cohen points to the fact that supportive education on restricting the use of antibiotics should be part of an implementation of pneumococcal conjugate vaccine.
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24.33.22
Pneumonic plague in China worse than the svine u pandemic [342]
Yersinia pestis (formerly Pasteurella pestis) is a Gram-negative rod-shaped bacterium belonging to the family Enterobacteriaceae. It is a facultative anaerobe that can infect humans and other animals. Human Y. pestis infection takes three main forms: pneumonic, septicemic, and the notorious bubonic plagues. All three forms have been responsible for high mortality rates in epidemics throughout human history, including the Black Death (a bubonic plague) that accounted for the death of at least one-third of the European population in 1347 to 1353. Depending on circumstances, these forms may occur separately or in combination. Recently Y. pestis has gained attention as a possible biological warfare agent and the CDC has classied it as category A pathogen requiring preparation for a possible terrorist attack. Pneumonic plague erupted in the Chinese town of Ziketan in the Qinghai Province in July 2009. Three people died and ten others were also infected, all closely associated with the diseased. The Town was shut o in an eort to avoid the spread of the disease. The authorities tracked down people who came within germ-spreading distance of the infected people. A travel alert asked all visitors to keep an eye out for u-like symptoms of the pneumonic plague. [343] Symptoms of pneumonic plague [344] The rst signs are fever, headache, weakness, and rapidly developing pneumonia with shortness of breath, chest pain, cough, and sometimes bloody or watery sputum. The pneumonia progresses for 2 to 4 days and may cause respiratory failure and shock. Without early treatment, patients may die. Transmission The transmission is dierent for the three forms of plague. - Pneumonic plague Yersinia pestis infects the lungs. Infection spreads from person to person through the air in respiratory droplets from a person (or animal) with pneumonic plague. - Bubonic plague It is the most common form of plague. This occurs when an infected ea bites a person or when materials contaminated with Y. pestis enter through a break in a persons skin.
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Patients develop swollen, tender lymph glands (called buboes) and fever, headache, chills, and weakness. Bubonic plague does not spread from person to person. - Septicemic plague It occurs when plague bacteria multiply in the blood. It can be a complication of pneumonic or bubonic plague or it can occur by itself. When it occurs alone, it is caused in the same ways as bubonic plague; however, buboes do not develop. Patients have fever, chills, prostration, abdominal pain, shock, and bleeding into skin and other organs. Septicemic plague does not spread from person to person. Early treatment of pneumonic plague is essential To reduce the chance of death, antibiotics must be given within 24 hours of rst symptoms. Streptomycin, gentamicin, the tetracyclines, and chloramphenicol are all eective against pneumonic plague. Antibiotic treatment for 7 days will protect people who have had direct, close contact with infected patients. Wearing a close-tting surgical mask also protects against infection. A plague vaccine is not currently available for use in the United States. Rodents are the reservoir of Yersinia pestis in western North America, southern South America, southern Africa, the Middle East, and central Asia. Infected eas infect rats and man. [345]
24.33.23
New process explain the causes of the variability of individual cells in cell cultures [346]
Pelkmans and colleagues 2990 studied the causes of the causes of single-cell heterogeneity in cell adherent populations. They found that the properties of a cell population determine the dierent cell activities observed in cells of the same type, explaining that the reasons behind the dierent reactions seen in cells of the same type are certain causes that lead to predictable distribution patterns. The researchers developed a process aided by a image-based screening centre to observe the variability of individual cells in cell cultures, what they called as "heterogeneity signature". The process and the special computer program allow automatic quantication and description of the phenotypes of the cells, showing how individual cell properties develop and aect each other. The authors found that cell properties were predetermined by characteristics of the population of the cell culture, such as the size of the population, the local cell density, the size of an individual cell, whether the cell is on the edge of the cell culture. Also the progression of the infection by three dierent viruses were analysed with this method. The authors stress that their study may be important for the pharmaceutical industry
1753
studying eects of new substances, as many eects do not inuence the cell, but act on the population as a whole, which then inuences the individual cells.
24.33.24
Recombinant lactic acid bacteria protects against Yersinia pseudotuberculosis [347]
Daniel and colleagues 2009 report an immune response triggered by a recombinant Lactococcus lactis strain. It protected mice against both oral and systemic Yersinia pseudotuberculosis infections. The authors wrote that the Lactococcus strain secrets the Yersinia pseudotuberculosis low-calcium response V (LcrV) antigen which protects against the infection. The authors stress that recombinant lactic acid bacteria may provide an anti-Yersinia vaccination strategy.
24.33.25
Hydrogen from wastewater
[348] Bruce E. Logan of the Penn State Institutes of Energy and the Environment, in connection with the Napa Wine Company in Oakville developed a demonstration microbial electrolysis plant producing hydrogen from wastewater of the production of wine. Microbial electrolysis cells consist of one carbon anode and one stainless steel cathode in his system instead of platinum or gold electrodes. This keeps the cost low. The organic material of the are converted by the bacteria into electrical current which hydrolyses water into oxygen at the carbon electrode and hydrogen on the stainless steel cathode. The natural bacteria that work in the electrolysis cells can cope with wastewater composition such as high in sugar or shifting to remnants of the fermentation process.
24.33.26
Electromethanogenesis capturing CO2 as biofuel [349]
In their researches concerning the production of hydrogen Logan and colleagues 2009 found how to convert carbon dioxide in methan in a process called electromethanogenesis. This research shows that methanogenic microorganisms produce methane in marshes and dumps not by utilising hydrogen or organic materials, such as acetate, but it is carbon dioxide and water which is converted to methane. The researchers found that the Archaea may convert carbon dioxide and water to methane without any organic material, bacteria or hydrogen. The microorganism Archaeon, Methanobacterium palustre, can accept electrons directly, and use them to create methane in a twochambered cell with an anode immersed in water on one side of the chamber and a cathode in water, inorganic nutrients and carbon dioxide on the other side of the chamber. The authors stress that the system uses carbon dioxide as feed stock. Using solar energy or wind power to operate the system the produced methane would be carbon neutral.
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Methane is preferred over hydrogen because a large infrastructure of methane as fuel is already available.
24.33.27
Hero Baby brand baby milk contaminated with Enterobacter sakazakii [350]
Enterobacter sakazakii infection has been associated with the use of powdered infant formula, with some strains able to survive in a desiccated state for more than 2 years. The Kuwait Municipality has ordered the withdrawal of the Hero Baby brand of baby milk formula from co-operative societies. Traces of the potentially fatal entro bacter sakazakii bacteria were found in these products. This decision was based on similar moves made by the United Arab Emirates (UAE) and Saudi Arabia.
24.33.28
Mycoplasma [351]
Mycoplasma is a genus of bacteria which lack a cell wall. Without a cell wall, they are unaected by many common antibiotics such as penicillin or other beta-lactam antibiotics that target cell wall synthesis. They can be parasitic or saprotrophic. Several species are pathogenic in humans, including Mycoplasma pneumoniae, which is an important cause of atypical pneumonia and other respiratory disorders, and Mycoplasma genitalium, which is believed to be involved in pelvic inammatory diseases.
24.33.29
Mycoplasma contamination is a problem in cell culture
Mycoplasma species are often found in research laboratories as contaminants in cell culture. Mycoplasmal cell culture contamination occurs due to contamination from individuals or contaminated cell culture medium ingredients, such as serum or trypsin. Mycoplasma cells are physically small - less than 1 m - and cannot be eliminated by sterile ltration. Mycoplasmas may induce cellular changes, including chromosome aberrations, changes in metabolism and cell growth. Severe Mycoplasma infections may destroy a cell line. Detection techniques include PCR, plating on sensitive agar and staining with a DNA stain including DAPI or Hoechst. Mycoplasma pneumoniae reduced its genome size by discarding the complete anabolic and metabolic pathways acquiring an obligate parasitic lifestyle.
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24.33.30
Mycoplasma detection using PCR method validated according European Pharmacopoeia standards [352]
Zhi and colleagues 2010 report the completion of the validation of a nucleic acid amplication technique (NAT) for use in detection of mycoplasma contaminants in biologics drugs, meeting or exceeding European Pharmacopoeia compliance requirements. This method may replace or supplement the existing culture-based methods with a PCR-based method and will become important for the biopharmaceutical industry.
24.33.31
Mycoplasma detection in fermenters [353]
Asarnow and colleagues 2010 describe a method based on a simple extraction procedure followed by a qualitative "touchdown" (TD) PCR protocol with primers specic to the 16S rRNA gene. The method was developed and validated an assay to monitor rFVIII production fermenters for mycoplasma contamination. The method was validated according to The International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) guidelines, and may replace the culture-based mycoplasma detection.
24.33.32
Mycoplasma gallisepticum infection detection in chicken [354]
Kahya and colleagues 2010 compared a real-time PCR (rPCR) test to serology and culture for the detection of Mycoplasma gallisepticum infection in chicken breeder ocks. Agreements between serology and culture, and serology and rPCR were 83.9% and 90.3%, respectively. Based on the data of their study the authors advise the use of rPCR and/or culture for conrmation of serology results during screening infection of ocks.
24.33.33
Detection and eradication of mycoplasma in cell lines [355]
Molla Kazemiha and colleagues 2010 assessing the mycoplasma infection status of 200 cell lines using PCR assay with generic-specic universal primers found 20% of the cell lines contaminated with mycoplasma. Contaminating species were M. hyorhinis, M. fermentas, M. arginini, M. orale and A. laidlawii. Cell lines were treated with BM-Cyclin eradicating 100 % of the contamination. Mycoplasma removal agent eliminated 70% of mycoplasma, and Ciprooxacin 42%. The authors noted a regrowth after 4 month with 12% of BMCyclin treatment, 62.5% of mycoplasma removal agent and 82.5% Ciprooxacin.
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24.33.34
Genotyping of Mycoplasma pneumoniae [356]
Schwartz and colleagues 2009 stress the importance of Mycoplasma pneumoniae, accounting for up to 25% of community-acquired pneumonia. Mycoplasma pneumoniae are classied in type 1 and type 2 based on sequence variation within the gene encoding the major adhesion molecule P1. The authors present a real-time PCR assay that can distinguish between the two types using high-resolution melt-curve analysis with reference strains M129 (type 1) and FH (type 2). The authors claim that this assay is rapid, reliable and convenient.
24.33.35
A rapid and sensitive ow cytometric technique quantifying viable mycoplasma [357]
Mohammadpour and colleagues 2010 developed a rapid and sensitive ow cytometric method using a vital uorescent dye to enumerate viable Mycoplasma agassizii cells. This mycoplasma threatened desert tortoise of the Southwestern United States, causing upper respiratory tract disease. Detection of living Mycoplasma agassizii was performed using nonuorescent molecule 5-carboxyuorescein (5-CF) diacetate acetoxymethyl ester, which penetrates the cell membranes of the mycoplasma, and is converted in the cytoplasm to the uorescent molecule 5-CF by the action of intracellular esterases. Labelled mycoplasma cells can be counted in less than 1 h. The authors stress the importance of this technique in the eld of basic immunological, biochemical and pharmacological studies.
24.33.36
Brachyspira digestve infections in pigs and birds
Brachyspira pilosicoli, Brachyspira hyodysenteriae and Brachyspira intermedia indexBrachyspira hyodysenteriaeare helicoidal Gram negative, mobile and anaerobic bacteria. Brachyspira are responsible for diverse digestive infections in animals and humans, causing economic losses due to the delay of growth of the infected animals. These bacteria are responsible for the grey diarrhoea syndrome. It is estimated that 70% of the porcine breeding farms are aected by this syndrome.
24.33.37
Detection of Brachyspira [358]
The diagnostic is based on the microorganism isolation by culture followed by its biochemical characterisation, however, the results are not always conclusive. Molecular techniques (real time PCR) are the methods of choice for detecting the presence of the dierent Brachyspira after extraction and purication of the bacterial DNA. The molecular detection system Brachyspira Ceeram Tools uses real-time PCR with a detection limit is 5 genome copies. No cross-reaction was observed with other organisms
24.33. NEW PREDICTIVE MICROBIOLOGY TOOLS FOR LISTERIA MONOCITOGENES susceptible to infected pigs and in samples of the avian industry.
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La, Phillips and Hampson 2003 described a duplex PCR amplifying portions of the Brachyspira hyodysenteriae NADH oxidase gene and the B. pilosicoli 16S rRNA gene for the faecal detection of these spirochaetes. [359]
24.33.38
Comparing ordinary PCR with real time PCR methods to detect Brachyspira [360]
Akase and colleagues 2009 compared ordinary PCR with real time PCR methods to detect Brachyspira infections in swine dysentery cases. The authors found that real time PCR using nox primers was more eective than ordinary PCR and culture.
24.33.39
Genome sequence of Brachyspira hyodysenteriae [361]
Hampson and Ahmed 2009 stressed that the genus Brachyspira contains important gut pathogens of pigs, birds and other animal species, including human beings. The genome sequence of the pathogen Brachyspira hyodysenteriae is characterised by extensive genome adaptation to the environment of the colon. Comparing it with the genome sequences of other Brachyspira may explain their involvement in colitis and diarrhoea.
24.33.40
High prevalence of spirochetosis in cholera patients [362]
Spirochetes from the genus Brachyspira were identied in more than one third of cholera patients in Bangladesh by Nelson and colleagues. The authors recommend that spirochetosis be tracked in cholera outbreaks.
24.33.41
Pathogenicity of Brachyspira pilosicoli [363]
Studies on the physiology of Brachyspira pilosicoli are dicult because it is an anaerobic spirochete which requires a specialized culture, and its growth is slowly. To study the mechanism of colitis induced by Brachyspira pilosicoli Naresh and colleagues 2009 incubated strains of the bacterium with a human colonic adenocarcinoma cell line (Caco-2 cells). They found that the eect on the Caco-2 cells was an up-regulation of interleukin-1beta (IL-1beta) and IL-8 expression. B. pilosicoli sonicates caused signicant up-regulation of IL-1beta, TNF-alfa, and IL-6, but culture supernatants and non-pathogenic Brachyspira innocens did not alter cytokine expression. The authors concluded that B. pilosicoli is pathogenic.
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24.33.42
Human intestinal spirochetosis [364]
A histological diagnosis of human intestinal spirochetosis were performed inpatients with abdominal pain, bloody stools, diarrhea or bowel symptoms, and in patients which showed only occult fecal blood. PCR analysis found more patients infected with Brachyspira aalborgi than B. pilosicoli. Infestation with B. aalborgi was detected over a 6-year period. Sato and colleaguies 2010 suggest that these spirochetes may be harmless commensals in humans.
24.33.43
Antagonistic eect of gut bacteria on swine enteropathogens [365]
Klose and colleagues 2010 screened benecial strains from the animal gut to control pathogens related to dysentery in pig, such as Clostridium perfringens type A, various serovars of enterotoxigenic Escherichia coli and Salmonella enterica, as well as Brachyspira pilosicoli. The authors report that Enterobacteriaceae were eectively inhibited by Lactobacillus salivarius and Lactobacillus reuteristrains. Lactobacillus mucosae, Lactobacillus amylovorus and Bidobacterium thermophilum, were less eective and their eect was based on the production of organic acid. The Bacillus subtilis strain was found to have anti-clostridial and anti-Brachyspira pilosicoli eect and homofermentative lactobacilli and Bidobacterium thermophilum could suppress the growth of Brachyspira pilosicoli. Heterofermentative lactobacilli, such as Lactobacillus reuteri and Lactobacillus mucosae had no eect. Enterococcus faecium and L. amylovorus strain presented antagonism producing lactate and hydrogen peroxide. The authors call for more researches on gut bacteriia as antagonist in pig production.
24.33.44
Probiotic feed additive to inhibit Brachyspira hyodisenteriae which causes dysentery in swine [366]
Close and colleagues isolated strains of Bidobacterium thermophilum, Enterococcus faecium and Bacillus subtilis which may be used as probiotic feed additives for prevention of swine dysentery. Their characteristics are a well-established identity, antibiotic susceptibility and antagonistic activity against Brachyspira hyodisenteriae.
24.33.45
Probiotic inhibition of Brachyspira hyodisenteriae and Brachyspira pilosicoli [367]
Bernardeau and colleagues 2009 studied the inhibition activity of the probiotic Lactobacillus rhamnosus CNCM-I-3698 and Lactobacillus farciminis CNCM-I-3699 on Brachyspira
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hyodysenteriae and Brachyspira pilosicoli, agents of Swine Dysentery and Porcine Intestinal Spirochaetosis. The in vitro research demonstrated the trapping of spirochaetal cells in a physical network, and the inhibition of the motility of Brachyspira. The authors call for in vivo studies regarding the use of probiotic lactobacilli as feed addsitive for the prevention of Brachyspira hyodysenteriae and Brachyspira pilosicoli.
24.33.46
Human intestinal spirochetosis [368]
According to Tsinganou and Gebbers 2010 Brachyspira aalborgi and Brachyspira pilosicoli predominate in human intestinal spirochetosis. Rates of the disease are low where living standards are high, and common in poor populations. Invasion of spirochetes beyond the surface epithelium may be associated with gastrointestinal symptoms, but is asymptomatic invasion remains at the surface of gut epithelium. Rare cases of spirochetemia and multiple organ failure have been reported in critically ill patients with IS.
24.33.47
Brachyspira murdochii is low pathogenic for pigs [369]
Jensen, Christensen and Boye 2009 describe a Brachyspira murdochii catarrhal colitis in pigs, applying uorescent in situ hybridization and species-specic oligonucleotide probe targeting 23S rRNA. The bacterium was closely associated with the surface epithelium in diseased pigs. The authors concluded that high numbers of Brachyspira murdochii is low pathogenic for pigs.
24.33.48
Pathogenicity of Brachyspira among poultry [370]
Brachyspira intermedia and Brachyspira pilosicoli were found to be aect layer and breeder ocks in Europe and Australia. Myers and colleagues 2009 tested ocks of Pennsylvania for Brachyspira intermedia and Brachyspira pilosicoli using a duplex PCR and Brachyspira genus-specic PCR. The authors found colonization of layer ocks, older than 40 weeks of age, with pathogenic and call for further investigation.
24.33.49
Brachyspira intermedia and other indole-positive Brachyspira species [371]
Phillips and colleagues 2009 using the multilocus sequence typing assessed the population structure of Brachyspira intermedia isolates from pigs and chicken, and the relationship of the species to the other two indole-positive but strongly haemolytic Brachyspira species-B. hyodysenteriae and "B. suanatina". The results of sequence types, amino acid types and clonal complexes indicate that crossspecies may occur. Some isolates were found to be separated from others by large genetic distances and ongoing minor genetic change amongst isolates at the farm level are taking place. The authors conclude that their ndings concerning isolates of B. hyodysenteriae,
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and "B. suanatina", suggest that it will not be possible to classify all weakly haemolytic indole-positive Brachyspira isolates as Brachyspira intermedia.
24.33.50
Relations between strains of Spanish Brachyspira spp and isolates from Germany and Belgium [372]
Hidalgo and colleagues 2010 described the genetic and phenotypic diversity of Spanish Brachyspira hyodysenteriae, and conrmed the presence of tiamulin-resistant isolates in Spain. The PCR analysis was used for the identication of Brachyspira spp. and for the detection of the smpA/smpB gene. The combination of Random amplied polymorphic DNA (RAPD) and pulsed-eld gel electrophoresis (PFGE) protocol was used to determine the epidemiological relationships. The authors stress that indole-negative and tiamulin-resistant isolates of B. hyodysenteriae were found, and the genetic ndings indicated a relationship between Spanish isolates and strains of Germany and Belgium.
24.33.51
Understanding coral leaching and susceptibility to disease [373]
Low immunity response may increase the risk of coral leaching and its susceptibility to disease. Palmer, Bythell and Willis 2010 found an inverse correlation of the content of melanin, size of melanin-containing granular cells, and phenoloxidase activity, as well as concentrations of uorescent proteins to thermal bleaching and disease susceptibility, in hard (Scleractinia) and soft (Alcyonacea) corals. These indicators are known to be related to immunity in invertebrates. The authors stress that pheniloxidase activity, melanin-containing granular cell size, and uorescent proteins concentration are predictors of susceptibility and are important in coral immunity. The authors call for a holistic approach to study coral reef bleaching and disease susceptibility.
24.33.52
Wound healing properties of honey [374]
Salomon and colleagues 2010 describe the wound healing properties of honey. The high concentration of sugar constitute a hyperosmotic medium with antimicrobial properties. The authors also stress that dierent enzymes, including glucose-oxidase that generates hydrogen peroxide and gluconic acid in the presence of glucose and water. In addition,
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honey presents favourable viscosity and the hygroscopic qualities allowing spread on the wound bed. The authors concluded that honey is an ecient treatment of chronic wounds of the lower leg and also of abdominal wounds.
24.33.53
Bacteriostatic eects of honey [375]
Kwakman and colleagues 2010 described all bactericidal factors in a medical-grade honey. Bacillus subtilis, methicillin-resistant Staphylococcus aureus, extended-spectrum beta-lactamase producing Escherichia coli, ciprooxacin-resistant Pseudomonas aeruginosa, and vancomycinresistant Enterococcus faecium, were killed by 10-20% (v/v) honey, whereas more than 40% (v/v) of a honey-equivalent sugar solution was required for similar activity. Activity against all other bacteria tested depended on sugar, H2O2, methylglyoxal, and bee defensin-1, contributing to the eects of honey in medicine, whereas bee defensin-1 was the most active compound. According to Boukraa and Sulaiman 2009, honey, propolis, royal jelly and bee venom have a strong antibacterial activity, but considerably variability is found within the same product and its botanical origin. Propolis presents the strongest antibacterial activity based on its richness in avonoids. The authors stress that food quality of honey and royal jelly contain pollen and other particles which might cause allergies when used in wound care. Fine lters must therefore be used in the production of medical products. A safety issue of honey and their products for medical use is the presence of viable spores which includes clostridia. The growing number of licensed medical bee products will increase understanding of its use, which, however, should be limited to those which are safe and with certied antibacterial activities, say the authors. [376] Chernev and colleagues 2010 report benets of combined, noncontact, low-frequency ultrasound and topical application of medical honey in treatment of chronic and delayed healing wounds. [377]
24.33.54
No manuka honey resistant mutants found so far [378]
Cooper and colleagues 2010 report that honey-resistant bacteria have not been isolated from wounds treated with honey. However, bacteria isolated from wounds, exposed to sub-lethal concentrations of manuka honey presented a stepwise resistance training, but changes were not permanent and honey-resistant mutants were not detected. The authors concluded that high concentrations of honey will keep the risk of development of honey resistant mutants low.
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24.33.55
Antibacterial properties of tualang honey [379]
Mohd Nasir compared the properties of tualang honey with that of manuka honey in treatment of burn wounds. The authors found that tualang honey has a bactericidal as well as bacteriostatic eect, it is less sticky compared to Manuka honey. Tualang honey was less eective for Gram positive bacteria as silver-based dressing or medical grade honey dressing.
24.33.56
Classic treatment of burn wounds recommended instead of honey products [380]
Topical antimicrobials are employed for prophylaxis and treatment of burn wound infections. Glasser and colleagues 2010 point out that no dened susceptibility breakpoints exist and standards need to be established for topical antimicrobial. The authors recommend continuing to use silver products for prophylaxis against gram-negatives and mafenide acetate for treatment, and mupirocin for methicillin-resistant Staphylococcus aureus.
24.33.57
Susceptibility beakingpoints
Susceptibility beakingpoints are used to dene susceptibility and resistance to antibacterials. Depending on the testing method, they are expressed as either a concentration (in mg/liter or g/ml) or a zone diameter (in mm). Susceptibility breakpoints allow communication from the clinical laboratory to the prescriber regarding the likelihood that a particular antibacterial regimen will be clinically useful in the treatment of patients with infections. [381]
24.33.58
Fungal invasion pathway of plant and animal cells [382]
Kale and colleagues 2010 relate that special proteins from fungi and oomycetes, known as eectors are transferred to the interior of host cells suppressing its natural defences. This pathway may explain the Irish potato famine in the nineteenth century, actual soybean diseases and fatal infectious diseases in humans. The eector proteins bind a specic lipid molecule found on the cell surface, the lipid phosphatidylinositol 3-phosphate (PI3P), and can enter the cell using the lipid raft, a region of the cells outer membrane. The PI3P lipid acts as a bridge between the eector protein and the lipid raft. Bacteria puncture the host cells membrane and then inject their eectors into the host cells membrane with a needle-like structure. Fungi and oomycetes lack such an injection structure. They slip their eectors into plant cells by means of the PI3P found at the surface of plant cells, animal cells, and some human cells. The eector proteins N-terminal RXLR and dEER motifs enable oomycetes to bind with the PI3P to enter into host cells
24.34. BACTERIOLOGICAL METHODS
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via the lipid raft of the cells wall. Fungi, contain functional variants of the RXLR motif which may also enter human cells and may be targeted by new therapeutic measures, which act on the RXLR terminal or on the PI3P lipid of the cell, say the authors.
24.33.59
The lipid raft of cell walls [383]
The plasma membrane of cells is made of a combination of glycosphingolipids and protein receptors organized in glycolipoprotein microdomains termed lipid rafts. These specialized membrane microdomains compartmentalize cellular processes by serving as organizing centers for the assembly of signaling molecules, inuencing membrane uidity and membrane protein tracking, and regulating neurotransmission and receptor tracking. Lipid rafts are more ordered and tightly packed than the surrounding bilayer, but oat freely in the membrane bilayer.
24.34
24.34.1
Bacteriological methods
Bacteriological Analytical Manual (BAM) [384]
FDAs Bacteriological Analytical Manual (The BAM) is a collection of procedures preferred by analysts in U.S. Food and Drug Administration laboratories for the detection in food and cosmetic products of pathogens (bacterial, viral, parasitic, plus yeast and mould) and of microbial toxins. Methods development has always been driven by the demand for tests that are faster, cheaper, easier, and more accurate. Pressure for improved procedures is particularly apparent in microbial food safety, because traditional tests may involve many steps which take much time. Ways proposed to accelerate the procedure included, initially, improved media and compacted culturing. Then, automation began to replace manual execution. Also, indirect identication, i.e., by biochemical (e.g., fatty acid proles, nucleic acid sequences) or biophysical shortcuts (FT-IR) that reveal organisms pertinent biomarkers or genetic ngerprints, began to make the isolation of viable microbes not as necessary. These newer tests - known as "rapid methods" if they took hours rather than days and as "real-time" testing if they took minutes - have not yet, however, made traditional testing obsolete. There are good reasons why analysts should continue to have the traditional skills to resuscitate, enrich, isolate, and identify microorganisms. Often, some culturing is necessary before there is enough material for the application of a rapid method or real-time test. Then, too, foods may contain substances that interfere with biochemical/molecular test shortcuts. Furthermore, having a viable microbial isolate may still provide quantitative and infectivity information not otherwise available, or be mandatory because of regulatory
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requirements and legal issues, or be useful later for retrospective investigations such as the characterization of new biomarkers. And, since no two types of test have the same sensitivity, the old ones serve as convenient standards for false positive and false negative rates. Kit versions of rapid methods are interpreted dierently depending on whether the results are positive or negative: negative results are considered denitive but positive results require conrmation by another test. See index of Bacteriological Analytical Manual at: http://www.fda.gov/Food/ScienceResearch/LaboratoryMethods/BacteriologicalAnalyticalManualBAM
24.34.2
Aerobial plate count (APC) [385]
The aerobic plate count (APC) is intended to indicate the level of microorganism in a product. The FDA presents conventional plate count method for examining frozen, chilled, precooked, or prepared foods for a suitable colony counting range of 25-250. An automated spiral plate count method for the examination of foods and cosmetics, are also described at: http://www.fda.gov/Food/ScienceResearch/LaboratoryMethods/BacteriologicalAnalyticalManualBAM
24.34.3
Microbiology Laboratory Guidebook [386]
The Guidebook contains current protocols for analytical tests required by FSIS regulatory activities on meat, poultry and egg products. Specically, microbiological methods are presented for sample preparation, isolation and identication of the major foodborne pathogenic microorganisms and their toxins, meat tissue species identication, and the detection of extraneous materials and antimicrobial residues. Media and reagent formulations, and Most Probable Number Tables are contained in an appendix. See index of the Gudebook at: http://www.fsis.usda.gov/Science/Microbiological_Lab_Guidebook/index.asp
24.34.4
Genomics and Rapid Diagnostic Tests
Diagnostic medical bacteriology is based on microscopy, Gram stain, culture of microorganisms and antibiotic susceptibility testing. Molecular methods re evolving and genome sequencing has causes deep impact on the study of bacterial pathogens and tracing the source of epidemics,. Genomics may cause a revolution in diagnostic and public health microbiology. Says Pallen and Loman 2011. Genomic testing platforms will develop the rapid diagnoses of infectious. [387] Rapid Diagnostic Tests (RDTs) Some rapid diagnostic test have been developed to spare time and costs. However, accuracy must be determined to avoid false results. Accuracy involves sensitivity and specicity,
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positive and negative predictive values, or positive and negative diagnostic likelihood ratios. The Rapid Diagnostic Tests can be classied in 5 groups [388]: Antigen detection: This group includes enzyme immunoassay and immunoproteins like protein A and clumping factor from Staphylococcus aureus, and detection of PBP2a to identify Methicillin-resistant Staphylococcus aureus (MRSA) with low protein A. [389] Molecular detection: Molecular detection includes genomic testing methodologies, such as nucleic acid hybridization with RNA or DNA probes, amplication, polymerase chain reaction (PCR) technologies, or nucleic acid sequencing. Such PCR platforms were developed for detection of infections of MRSA, Clostridium dicile, and Neisseria gonorrhea.However, PCR is still costly and time-consuming. Rapid biochemical tests: This includes the famous urine dipsticks for nitrite and leukocyte esterase. Special stains: Stains for direct microscopy such as calcouor white stain, Gram stain for detection of gram-positive diplococcic (Streptococcus pneumoniae) in a sputum smear, gram-negative diplococcic (Neisseria gonorrhoea) in a urethral smear. The Ziehl- Neelsen for Mycobacteria Blood smears stained with acridine orange, and examined with a uorescence microscope reveal the presence of trypanosomes that cause sleeping sickness (Trypanosoma brucei) or Chagas disease (Trypanosoma cruzi).
24.34.5
Serologic testing
Immunoelectrophoresis: In the current era of advanced technology, it is very easy to disregard the value of basic light microscopy in the rapid diagnosis of infections. A Gram stain can conrm within minutes the presence of, or gram-negative rods in a spun specimen of urine. Mycobacteria can be identied rapidly by microscopy of specimens stained with Ziehl-Neelsen. Kinyoun, or rhodamine auromine stains. Are used to detct Giardia lamblia and Entamoeba histolytica in stuhl. India ink (nigrosin) wet mounts prepared from cerebrospinal uid (CSF) detects encapsulated cells of Cryptococcus species. Special culture media: selective and dierential solid media for the qualitative direct detection of VRE and MRSA Methicillin-resistant Staphylococcus aureus (MRSA) [390]
24.34.6
Specyc Rapid Diagnostic Tests (RDTs)
Herpes simplex virus: Real-time PCR is faster and more sensitive than previous technologies, such as cell cultures or immunouorescence microscopy, for detecting and genotyping herpes simplex virus (HSV) in clinical specimens. Septicemia: Molecular tests were developed to detect septicemia using whole blood specimens. Multiplex-PCR, a modication of PCR, is such a test. However, low sensitivity, diculties to identify bacteria involved and the inability to give antimicrobial susceptibility testing information makes the broth-based blood culture indispensable. Sutherland used Aymetrix array and multiplex tandem (MT)-PCR to evaluate transcriptional proles in circulating white blood cells applying a set of 42 molecular markers that had been identied
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a priori to predict sepsis. This molecular biomarker test can detect sepsis by monitoring molecular reaction of blood white cells in respond to a bacterial invasion. [391] Tuberculosis: Diagnosis includes culture of the organism, drug-susceptibility testing, using standard biochemical analyses, nucleic acid probes, or 16S rRNA gene sequencing. Real-time PCR assays that rapidly and specically detect Mycobacterium tuberculosis complex directly from acid-fast, smear-positive respiratory specimens and broth cultures are now routinely conducted in various reference laboratories, giving results within hours compared with the average of 2 weeks required for traditional susceptibility testing methods. Rapid tests for TB do not replace acid-fast smears or mycobacterial cultures. However, smear microscopy combined with most rapid tests improved diagnostic sensitivity from 75% (smear alone) up to 89% (smear plus rapid test) but also caused an unacceptable false positive rate of 42%. [392] DNA specic probes, hsp65 PRA and hsp65 gene sequencing are described by Esparcia et al 2011 to identify non-tuberculous mycobacteria. [393] Clostridium dicile: Available EIA and glutamate dehydrogenase tests are easy to perform and oer results within 2 hours, but lack sensitivity. Shetty, Wren and Coen 2011 report that the glutamate dehydrogenase test to detect Clostridium dicile, yields a specicity of 80-100% with a false positivity rate around 20%, detecting toxigenic and non-toxigenic strains of the organism, and test has high sensitivity and negative predictive value when combined with a test to detect toxin. [394] All real-time PCRs can be applied in screening for Clostridium dicile infections, but cannot be applied as stand-alone test, because of its low positive predictive value. However the test may be used to reduce the spread of the epidemic Clostridium dicile PCR ribotype 027. [395] Inuenza:Tests for inuenza include rapid antigen testing, reverse transcription-PCR, Real-time PCR, and immunouorescence assays that identify inuenza A and B viral nucleoprotein antigens in respiratory specimens. Outbreaks of H1N1 inuenza strains demonstrate the need for more sensitive RDTs to dierentiate between inuenza and other respiratory viruses. No one approach is applicable to all conditions, says Lee et al 2011, and a combination of dierent tests may be necessary. The authors stress that costs should not reduce quality of results on which clinical decisions depend on. [396] The real-time reverse transcription polymerase chain reaction (rRT-PCR) technique has been used as the reference technique for the diagnosis of pandemic (H1N1)2009 virus infections. Ciblak et al 2010 compared the sensitivity of the reference rRT-PCR technique with rapid inuenza diagnostics tests (RIDTs).The sensitivity of the rapid tests ranged from 31.7% to 50%, compared to 97.7% to 100% of the rRT-PCR technique.The authors stressed that available RIDTs are not sensitive enough and could lead to delay in treatment of patients. [397]
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Sexually transmitted infections: Culture of Treponema pallidum is not possible. All available syphilis RDT kits use T pallidum recombinant antigens to detect treponeme specic antibodies. Non-treponemal screening tests, such as the rapid plasma reagin (RPR) test does not look for antibodies against the actual bacterium, but rather for antibodies against substances released by cells when they are damaged by T. pallidum. Accurate detection of T pallidum antibodies is carried out using lateral-ow immunoassay. Syphilis lateral ow tests become available within 30 minutes and do not require a laboratory or other instrumentation. [398] The CDC proposed to test serum samples using a treponema-specic test and positive samples should be analyzed with a nontreponemal assay. Binnicker, Jespersen and Rollins 2011 compared the performance of dierent treponemal assays, uorescent treponemal antibody assay, Treponema pallidum particle agglutination, Trep-Sure enzyme immunoassay, Trep-Chek EIA , Trep-ID EIA, Treponema ViraBlot IgG, rapid plasma reagin (RPR) assay and a treponemal IgM Western blot assay. These techniques were compared to the FTA assay as the gold standard, and data may be used to decide between these tests. [399] MRSA and VRE: Currently, the standing screening method of detection of these pathogens is culture. Chromogenic media oer enhanced bacterial identication over tradition culture media through colour dierentiation. Nearly all studies that evaluated PCR (either conventional or real-time) have shown improved sensitivities for detecting VRE from faecal specimens compared with culture. Kilic and Basustaoglu 2011 developed and validated here a double triplex real-time PCR assay to simultaneously detect and identify Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus hominis, Staphylococcus haemolyticus and their methicillin resistance in a single reaction directly from Gram-positive cocci-in-clusters (GPCs)-positive blood culture bottles targeting tuf, nuc, mecA, atlE, gap and mvaA genes.The whole test is perfomed in 83 minutes. [400]
24.34.7
Rapid test using chemiluminescence dierentiates between bacterial or viral infection [401]
Antibiotics are ineective in treating viral infections. A new test based on the immune systems response to the infection, dierentiates between bacterial or viral infection allowing a clinical decisions promptly upon admission. Standard bacteriological methods need 24-48 hours to provide results which sometimes are not sucient for a diagnosis. The test adds luminol to a blood sample of the patient. The glow is measured. Luminol is a luminescent chemical substance used in crime scenes to locate traces of blood. Polymorphonuclear leukocytes or phagocytes, responding to infections, undergo functional changes that dier between bacterial or viral origin. These changes may be assessed by
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chemiluminescent byproduct reaction. Luminol: Luminol exhibits chemiluminescence, with a striking blue glow, when mixed with an appropriate oxidizing agent.Luminol is used by forensic investigators to detect trace amounts of blood left at crime scenes as it reacts with iron found in hemoglobin. It is used by biologists in cellular assays for the detection of copper, iron, and cyanides, in addition to the detection of specic proteins by Western Blot. [402] The authors claim that the method is timesaving, easy to perform and can be commercially available, and has predictive diagnostic value.
24.34.8
Bacteria from dog faeces are important source of airborne bacteria in cities [403]
Faecal bacteria from dog faecal material are important source of airborne bacteria in US cities, particularly in winter, says a new study. Airborne bacteria may impair human health, triggering allergic asthma and seasonal allergies. According to Bowers et al. 2011 airborne bacterial communities of Detroit and Cleveland were found to be similar to communities found in dog excrements which are an important source of bacteria at the atmosphere of both cities. Included in this study were Chicago, Cleveland, Detroit, and Mayville, Wis. The authors used high-throughput pyrosequencing to analyze bacterial present in the PM2.5 aerosol fraction (ne particulate matter <2.5 micro mm) and compared their data against a database of bacteria from leaf surfaces, soil, and human, cow and dog faeces. The authors stress that airborne bacteria community varied signicantly. In summer, airborne bacteria come from a variety of sources including soil, dust, leaf surfaces, lakes and oceans, however in winter, leaves drop and snow covers the ground. It is when airborne bacteria from dog faecal material predominate. The authors call for more studies to determine the types of bacteria in the air, how these bacteria vary by location and season, and where they are coming from.
Bibliography
[1] Krieg,Noel R.,Holt,John G.(et al.), Bergeys manual of Systematic bacteriology. Williams & Wilkins, Baltimore 1984,2. [2] Laborpraxis March 2000, Page 96: Streptomycetten gegen PPLO. [3] http://www.ncbi.nlm.nih.gov/pubmed/18568850. Raspor P, Goranovic D.: Biotechnological applications of acetic acid bacteria. Crit Rev Biotechnol. 2008;28(2):101-24.
BIBLIOGRAPHY
1769
[4] http://www.ncbi.nlm.nih.gov/pubmed/18199517. Yamada Y, Yukphan P.: Genera and species in acetic acid bacteria. Int J Food Microbiol. 2008 Jun 30;125(1):1524. Epub 2007 Dec 5. [5] http://www.ncbi.nlm.nih.gov/pubmed/11307843. Macauley S, McNeil B, Harvey LM.: The genus Gluconobacter and its applications in biotechnology. Crit Rev Biotechnol. 2001;21(1):1-25. [6] http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2168926. David E. Greenberg, Stephen F. Porcella, Adrian M. Zelazny, Kimmo Virtaneva, Dan E. Sturdevant, John J. Kupko, III, Kent D. Barbian, Amenah Babar, David W. Dorward, Steven M. Holland: Genome Sequence Analysis of the Emerging Human Pathogenic Acetic Acid Bacterium Granulibacter bethesdensis. J Bacteriol. 2007 December; 189(23): 8727-8736. doi: 10.1128/JB.00793-07. [7] http://www.biomedexperts.com/Abstract.bme/17919758. De Vero, Luciana; Giudici, Paolo: Genus-specic prole of acetic acid bacteria by 16S rDNA PCRDGGE. International journal of food microbiology 2008;125(1):96-101. [8] http://www.ncbi.nlm.nih.gov/pubmed/19244423. Malimas T, Yukphan P, Takahashi M, Muramatsu Y, Kaneyasu M, Potacharoen W, Tanasupawat S, Nakagawa Y, Tanticharoen M, Yamada Y: Gluconobacter japonicus sp. nov., an acetic acid bacterium in the Alphaproteobacteria. Int J Syst Evol Microbiol. 2009 Mar;59(Pt 3):466-71. [9] http://www.ncbi.nlm.nih.gov/pubmed/16960335. Takahashi M, Yukphan P, Yamada Y, Suzuki K, Sakane T, Nakagawa Y.: Intrageneric structure of the genus Gluconobacter analyzed by the 16S rRNA gene and 16S-23S rRNA gene internal transcribed spacer sequences. J Gen Appl Microbiol. 2006 Jun;52(3):187-93. [10] http://www.ncbi.nlm.nih.gov/pubmed/18802320. Malimas T, Yukphan P, Takahashi M, Muramatsu Y, Kaneyasu M, Potacharoen W, Tanasupawat S, Nakagawa Y, Tanticharoen M, Yamada Y. Gluconobacter sphaericus (Ameyama 1975) comb. nov., a brown pigment-producing acetic acid bacterium in the Alphaproteobacteria. J Gen Appl Microbiol. 2008 Aug;54(4):211-20. [11] http://www.ncbi.nlm.nih.gov/pubmed/15486825. Tanasupawat S, Thawai C, Yukphan P, Moonmangmee D, Itoh T, Adachi O, Yamada Y. Gluconobacter thailandicus sp. nov., an acetic acid bacterium in the alpha-Proteobacteria. J Gen Appl Microbiol. 2004 Jun;50(3):159-67. [12] http://www.ncbi.nlm.nih.gov/pubmed/18177965. Pedraza RO.: Recent advances in nitrogen-xing acetic acid bacteria. Int J Food Microbiol. 2008 Jun 30;125(1):2535. Epub 2007 Dec 5.
1770
[13] http://www.ncbi.nlm.nih.gov/pubmed/18600321. Bhattacharjee RB, Singh A, Mukhopadhyay SN.: Use of nitrogen-xing bacteria as biofertiliser for non-legumes: prospects and challenges. Appl Microbiol Biotechnol. 2008 Aug;80(2):199-209. Epub 2008 Jul 4. [14] http://www.ncbi.nlm.nih.gov/pubmed/17574542. Saravanan VS, Madhaiyan M, Osborne J, Thangaraju M, Sa TM.: Ecological occurrence of Gluconacetobacter diazotrophicus and nitrogen-xing Acetobacteraceae members: their possible role in plant growth promotion. Microb Ecol. 2008 Jan;55(1):130-40. Epub 2007 Jun 17. [15] http://www.ncbi.nlm.nih.gov/pubmed/14722690. Munoz-Rojas J, CaballeroMellado J.: Population dynamics of Gluconacetobacter diazotrophicus in sugarcane cultivars and its eect on plant growth. Microb Ecol. 2003 Nov;46(4):454-64. Epub 2003 Aug 14. [16] http://www.ncbi.nlm.nih.gov/pubmed/16765840. Muthukumarasamy R, Govindarajan M, Vadivelu M, Revathi G.: N-fertilizer saving by the inoculation of Gluconacetobacter diazotrophicus and Herbaspirillum sp. in micropropagated sugarcane plants. Microbiol Res. 2006;161(3):238-45. Epub 2005 Nov 14. [17] http://www.ncbi.nlm.nih.gov/pubmed/16512210. Cocking EC, Stone PJ, Davey MR.: Symbiosome-like intracellular colonization of cereals and other crop plants by nitrogen-xing bacteria for reduced inputs of synthetic nitrogen fertilizers. Sci China C Life Sci. 2005 Dec;48 Spec No:888-96. [18] http://www.ncbi.nlm.nih.gov/pubmed/17548832. Fox JE, Gulledge J, Engelhaupt E, Burow ME, McLachlan JA: Pesticides reduce symbiotic eciency of nitrogen-xing rhizobia and host plants. Proc Natl Acad Sci U S A. 2007 Jun 12;104(24):10282-7. [19] http://www.ncbi.nlm.nih.gov/pubmed/12436304. Deppenmeier U, Homeister M, Prust C.: Biochemistry and biotechnological applications of Gluconobacter strains. Appl Microbiol Biotechnol. 2002 Nov;60(3):233-42. Epub 2002 Oct 12. [20] http://www.ncbi.nlm.nih.gov/pubmed/12664142. Adachi O, Moonmangmee D, Toyama H, Yamada M, Shinagawa E, Matsushita K.: New developments in oxidative fermentation. Appl Microbiol Biotechnol. 2003 Feb;60(6):643-53. Epub 2002 Dec 18. [21] Osman K, Aly M, Kheader A, and Mabrok K. Molecular detection of the aeromonas virulence aerolysin gene in retail meats from dierent animal sources in egypt. World J Microbiol Biotechnol, 28(5):186370, 5 2012. http://www.ncbi.nlm.nih.gov/ pubmed/22806009. [22] Suarez G, Khajanchi BK, Sierra JC, Erova TE, Sha J, and Chopra AK. Actin crosslinking domain of aeromonas hydrophila repeat in toxin a (rtxa) induces host cell
BIBLIOGRAPHY
1771
rounding and apoptosis. Gene, 506(2):36976, 9 2012. http://www.ncbi.nlm.nih. gov/pubmed/22814176. [23] Hu M, Wang N, Pan ZH, Lu CP, and Liu YJ. Identity and virulence properties of aeromonas isolates from diseased sh, healthy controls and water environment in china. Lett Appl Microbiol, 6 2012. http://www.ncbi.nlm.nih.gov/pubmed/ 22725694. [24] Singh BR, Gulati BR, Virmani N, and Chauhan M. Outbreak of abortions and infertility in thoroughbred mares associated with waterborne aeromonas hydrophila. Indian J Microbiol, 51(2):2126, 6 2011. http://www.ncbi.nlm.nih.gov/pubmed/ 22654167. [25] Holt, John G. (et al.), Bergeys manual of determinative bacteriology. Williams & Wilkins, Baltimore 1994. [26] Campylobacter; World Food Law, november 1998 pg.17. [27] Knut Rudi Matforsk Food Research, Norway: Direct DNA Based Campylobacter Diagnostics: Rapid Methods Enable New Logistics in the Production of Campylobacter Free Poultry.; New Food 25 2001. [28] Sears A, Baker MG, Wilson N, Marshall J, Muellner P, Campbell DM, Lake RJ, and French NP. Marked campylobacteriosis decline after interventions aimed at poultry, new zealand. EID, 17(6). http://www.cdc.gov/eid/content/17/6/1007. htm?source=govdelivery. [29] Shaughnessy RG, Meade KG, McGivney BA, Allan B, and OFarrelly C. Global gene expression analysis of chicken caecal response to campylobacter jejuni. Vet Immunol Immunopathol, 4 2011. http://www.ncbi.nlm.nih.gov/pubmed/21605915. [30] Conlan AJ, Line JE, Hiett K, Coward C, Van Diemen PM, Stevens MP, Jones MA, Gog JR, and Maskell DJ. Transmission and dose-response experiments for social animals: a reappraisal of the colonization biology of campylobacter jejuni in chickens. J R Soc Interface, 5 2011. http://rsif.royalsocietypublishing.org/content/ early/2011/05/14/rsif.2011.0125.long. [31] Leblanc-Maridor M, Beaudeau F, Seegers H, Denis M, and Belloc C. Rapid identication and quantication of campylobacter coli and campylobacter jejuni by real-time pcr in pure cultures and in complex samples. BMC Microbiol, 11(1):113, 5 2011. http://www.biomedcentral.com/1471-2180/11/113. [32] Balamurugan S, Nattress FM, Baker LP, and Dilts BD. Survival of campylobacter jejuni on beef and pork under vacuum packaged and retail storage conditions: Examination of the role of natural meat microora on c. jejuni survival. Food Microbiol, 28(5):100310, 2011. http://www.ncbi.nlm.nih.gov/pubmed/21569945.
1772
[33] Boysen, Vigre H, and Rosenquist H. Seasonal inuence on the prevalence of thermotolerant campylobacter in retail broiler meat in denmark. Food Microbiol, 28(5):1028 32, 8 2011. http://www.ncbi.nlm.nih.gov/pubmed/21569948. [34] http://aem.asm.org/cgi/content/abstract/75/7/2074. Olsen, Katja N. ; Lund, Marianne; Skov, Julia; Christensen, Laurids S.; Hoorfar,Jerey Detection of Campylobacter Bacteria in Air Samples for Continuous Real-Time Monitoring of Campylobacter Colonization in Broiler Flocks. Applied and Environmental Microbiology, 2009; 75 (7): 2074 DOI: 10.1128/AEM.02182-08. [35] Atanassova, V. Ringh, Ch.: Campylobacter an important infectious agent; Fleischwirtschaft 5/2000 page 82. [36] http://www.ncbi.nlm.nih.gov/pubmed/15116760. Stevens, K.A.; Yaykus, L.A.: Bacterial separation and concentration from complex sample matrices: a review. Crit.Rev. in Microbiol. 2004;30(1):7-24. Review. PMID: 15116760 [PubMed - indexed for MEDLINE]. [37] http://www.matrixmsci.com/pdf/trix7.pdf. Matrix MicroScience: No.7-October 2006.- Rapid Isolation and Detection of Escherichia coli 0157:H7 in Fresh Produce. [38] http://aem.asm.org/cgi/content/abstract/73/1/92. Fukushima, H.; Katsube, K. Hata, Y.; Kishi, R.; Fujiware, S.: Rapid separation and concentration of foodborne pathogens in food samples prior to quantication by viable-cell counting and real-time PCR. Applied and Environmental Microbiology. 2007 Jan;73(1):92-100. doi:10.1128/AEM.01248-06. [39] http://www.nzfsa.govt.nz/publications/news-current-issues/ campylobacter.htm. NZFSA: New Zealand produces update on work related to Campylobacter. [40] http://www.nzfsa.govt.nz/consumers/food-safety-topics/ foodborne-illnesses/campylobacter/. NZFSA: Campylobacter. [41] Teufel, Prof.Dr.,Vortrag , Hygiene-Forum 9.-10.3.1999 Behrs Hamburg. [42] de Boer, A. et al.: Letters in appl. Microbiol. 23, 64-66, 1996. [43] Danesh J., Peto R. (1998). Risc factors for coronary heart disease and infection with Helicobacter pylori: metanalysis of 18 studies. BMJ 316: 1130-1132. [44] Matsubara, Satoshi; Shibata, Hideyuki; Ishikawa, Fumiyasu; Yokokura, Teruo; Takahashi, Mami; Sugimura, Takashi; Wakabayashi, Keiji: Suppression of Helicobacter pylori-induced gastritis by green tea extract in Mongolian gerbils. Biochemical and Biophysical Research Communications Volume 310, Issue 3, 24 October 2003, Pages 715-719 doi:10.1016/j.bbrc.2003.09.066.
BIBLIOGRAPHY
1773
[45] http://www.ncbi.nlm.nih.gov/pubmed/18675670. Talley, Nicholas J: Is it time to screen and treat H pilori to prevent gastric cancer? Lancet. 2008;372:350-352; 392-397. [46] http://www.ncbi.nlm.nih.gov/pubmed/17521398. Wang, Changcheng; Yuan, Yuhong; Hunt, Richard H.: The Association Between Helicobacter pylori Infection and Early Gastric Cancer: A Meta-Analysis. Am J Gastroenterol. 2007 Aug;102(8):1789-98. Epub 2007 May 23. [47] http://www.ncbi.nlm.nih.gov/pubmed/18675689. Fukase K, Kato M, Kikuchi S, Inoue K, Uemura N, Okamoto S, Terao S, Amagai K, Hayashi S, Asaka M; Japan Gast Study Group.Eect of eradication of Helicobacter pylori on incidence of metachronous gastric carcinoma after endoscopic resection of early gastric cancer: an open-label, randomised controlled trial. Lancet. 2008 Aug 2;372(9636):392-7. PMID: 18675689. [48] http://jama.ama-assn.org/cgi/content/abstract/291/2/187. Benjamin ChunYu Wong; Shiu Kum Lam; Wai Man Wong; Jian Shun Chen; Ting Ting Zheng; Rui E. Feng; Kam Chuen Lai; Wayne Hsing Cheng Hu; Siu Tsan Yuen; Suet Yi Leung; Daniel Yee Tak Fong; Joanna Ho; Chi Kong Ching; Jun Shi Chen Helicobacter pylori Eradication to Prevent Gastric Cancer in a High-Risk Region of China: A Randomized Controlled Trial. JAMA. 2004;291:187-194. [49] http://www3.interscience.wiley.com/journal/117987621/abstract. Fuccio, L.; Zagari, R.M.; Minardi, M.E.; Bazzoli, F.: Systematic review: Helicobacter pylori eradication for the prevention of gastric cancer (p 133-141). Alimentary Pharmacology & Therapeutics. Volume 25 Issue 2, Pages 133 - 141. 2008. Doi: 10.1111/j.13652036.2006.03183.x. [50] Ernhrungsinformation der CMA 11/97. [51] Spanische gurken als ehec-quelle identiziert. 26.05.2911. Spiegel Online. http: //www.spiegel.de/wissenschaft/medizin/0,1518,765020,00.html. [52] Karch HV Tarr PIV Bielaszewska MV. Enterohaemorrhagic escherichia coli in human medicine. Int.J.Med.Microbiol, 295(6-7):405418, 10 2005. http://www.ncbi.nlm. nih.gov/pubmed/16238016. [53] Menezes MA, Aires KA, Ozaki CY, Ruiz RM, Pereira MC, Abreu PA, Elias WP, Ramos OH, and Piazza RM. Cloning approach and functional analysis of antiintimin single-chain variable fragment (scfv). BMC Res Notes, 4:30, 2 2011. http: //www.biomedcentral.com/1756-0500/4/30. [54] Bielaszewska M, Mellmann A, Zhang W, Kck R, Fruth A, Bauwens A, Peters G, and Karch H. Characterisation of the escherichia coli strain associated with an outbreak
1774
CHAPTER 24. GENERAL BACTERIOLOGY of haemolytic uraemic syndrome in germany, 2011: a microbiological study. Lancet Infect Dis, 6 2011. http://www.ncbi.nlm.nih.gov/pubmed/21703928.
[55] Mellmann A, Harmsen D, Cummings CA, Zentz EB, Leopold SR, Rico A, Prior K, Szczepanowski R, Ji Y, Zhang W, McLaughlin SF, Henkhaus JK, Leopold B, Bielaszewska M, Prager R, Brzoska PM, Moore RL, Guenther S, Rothberg JM, and Karch H. Prospective genomic characterization of the german enterohemorrhagic escherichia coli o104:h4 outbreak by rapid next generation sequencing technology. PLoS One, 6(7):e22751, 2011. http://www.ncbi.nlm.nih.gov/pmc/articles/ PMC3140518/?tool=pubmed. [56] Bgi sequences genome of the deadly e. coli in germany and reveals new super-toxic strain. beijing genomic institute (bgi). 02.06.2011. http://www.genomics.cn/en/ news_show.php?type=show&id=644. [57] German chancellor dr. merkel and chinese prime minister wen jiabao witness signing procedure. university of lbeck. 23.05.2006. http://www. uni-luebeck.de/index.php?id=1334&tx_ttnews[tt_news]=324&cHash= 5f6ab77b876568d00cfbe28ac3e3e0b4. [58] European centre for disease prevention and control: Outbreak of stec in germany. 27.05.2011. http://www.ecdc.europa.eu/en/publications/Publications/1105_ TER_Risk_assessment_EColi.pdf. [59] Gao X, Cai K, Li T, Wang Q, Hou X, Tian R, Liu H, Tu W, Xiao L, Fang L, Luo S, Liu Y, and Wang H. Novel fusion protein protects against adherence and toxicity of enterohemorrhagic escherichia coli o157:h7 in mice. Vaccine, 2011. http: //www.ncbi.nlm.nih.gov/pubmed/21742003. [60] Who: Global alert and response (gar). 02.06.2011. http://www.who.int/csr/don/ 2011_06_02/en/index.html. [61] Germany: No proof sprouts caused e. coli outbreak 23 of 40 samples from suspected farm tested negative for toxic bacteria. june 2011. http://www.msnbc.msn.com/id/43285439/ns/health-food_safety/t/ germany-no-proof-sprouts-caused-e-coli-outbreak/. [62] Experten warnen vor ehec im trinkwasser. spiegel online. 26. juni 2011. epidemie. http://www.spiegel.de/wissenschaft/medizin/0,1518,770591,00.html. [63] E.coli bordeaux : une personne dans "un tat inquitant" le journale du dimanche weekly. 25.06.2011. http: //www.lejdd.fr/Societe/Sante/Actualite/Bacterie-E. coli-une-personne-dans-un-etat-inquietant-a-Bordeaux-339311/?from= headlines.
BIBLIOGRAPHY
1775
[64] Enterohaemorrhagic escherichia coli (ehec). who fact sheet nr 125 revised may 2005. http://www.who.int/mediacentre/factsheets/fs125/en/. [65] Scavia G, Morabito S, Tozzoli R, Michelacci V, Marziano ML, Minelli F, and et al. Similarity of shiga toxinproducing escherichia coli o104:h4 strains from italy and germany. Emerg Infect Dis, 10 2011. http://wwwnc.cdc.gov/eid/pdfs/ 11-1072-ahead_of_print.pdf. [66] Directive 2006/7/ec of the european parliamentand of the council of 15 february2006 concerning the management of bathing water quality and repealing directive 76/160/eec. http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=OJ:L: 2006:064:0037:0051:EN:PDF. [67] Wyn-Jones AP, Carducci A, Cook N, DAgostino M, Divizia M, Fleischer J, Gantzer C, Gawler A, Girones R, Hller C, de Roda Husman AM, Kay D, Kozyra I, LpezPila J, Muscillo M, Nascimento MS, Papageorgiou G, Rutjes S, Sellwood J, Szewzyk R, and Wyer M. Surveillance of adenoviruses and noroviruses in european recreational waters. Water Res, 45(3):102538, 1 2011. http://www.sciencedirect. com/science/article/pii/S0043135410007104. [68] Boll-Mas S, Calgua B, Clemente-Casares P, La Rosa G, Iaconelli M, Muscillo M, Rutjes S, Husman AMR, Grunert A, Grber I, Verani M, Carducci A, Calvo M, Wyn-Jones P, and Girones R. Quantication of human adenoviruses in european recreational waters. Food and Environmental Virology, 2(2), 2010. http://www. springerlink.com/content/e75q7m17k5731452/. [69] La Rosa G, Pourshaban M, Iaconelli M, and Muscillo M. Quantitative real-time pcr of enteric viruses in inuent and euent samples from wastewater treatment plants in italy. Ann Ist Super Sanita, 46(3):26673, 2010. http://www.iss.it/publ/anna/ 2010/3/463266.pdf. [70] Fao/who: Recommended international code of practice, general principles of food hygiene. http://www.fao.org/docrep/005/Y1579E/y1579e02.htm. [71] Codex Alimentarius. Code of hygienic practice for fresh fruits and vegetables. http: //www.codexalimentarius.net/download/standards/10200/CXP_053e.pdf. [72] Efsa assesses the public health risk of seeds and sprouted seeds.press release 15 nov 2011. http://www.efsa.europa.eu/en/press/news/111115.htm?WT.mc_id= EFSAHL01&emt=1. [73] France records rst e. coli death. arab news 02.07.2011. http://arabnews.com/ world/article465564.ece. [74] OurFood.com. Ehec bacterium enters water resources and environment. ourfood.com. 27.06.2011. http://www.ourfood-news.com/87.html.
1776
[75] Hold the raw sprouts, please. medscape news today. september 06.2011. http:// www.medscape.com/viewarticle/748566?src=mp&spon=17. [76] Mariani-Kurkdjian PAND Bingen EAND Gault GAND Jourdan-Da Silva NAND Weill F-X. Escherichia coli o104:h4 south-west france, june 2011. The Lancet Infectious Diseases, 11(10):732733, 10 2011. http: //www.thelancet.com/journals/laninf/article/PIIS1473-3099%2811% 2970266-3/fulltext?elsca1=ETOC-TLID&elsca2=email&elsca3=segment. [77] Gault G, Weill FX, Mariani-Kurkdjian P, Jourdan da Silva N, King L, Aldabe B, Charron M, Ong N, Castor C, Mace M, Bingen E, Noel H, Vaillant V, Bone A, Vendrely B, Delmas Y, Combe C, Bercion R, dAndigne E, Desjardin M, de Valk H, and Rolland P. Outbreak of haemolytic uraemic syndrome and bloody diarrhoea due to escherichia coli o104:h4,south-west france, june 2011. Euro Surveill, 16(26), 6 2011. http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=19905. [78] Bielaszewska M, Mellmann A, Zhang W, Kck R, Fruth A, Bauwens A, Peters G, and Karch H. Characterisation of the escherichia coli strain associated with an outbreak of haemolytic uraemic syndrome in germany, 2011: a microbiological study. Lancet Infect Dis, 11:671676, 2011. http://www.ncbi.nlm.nih.gov/pubmed/21703928. [79] Mellmann A, Harmsen D, Cummings CA, Zentz EB, Leopold SR, Rico A, Prior K, Szczepanowski R, Ji Y, Zhang W, McLaughlin SF, Henkhaus JK, Leopold B, Bielaszewska M, Prager R, Brzoska PM, Moore RL, Guenther S, Rothberg JM, and Karch H. Prospective genomic characterization of the german enterohemorrhagic escherichia coli o104:h4 outbreak by rapid next generation sequencing technology. PLoS One, 6(7):e22751, 2011. http://www.ncbi.nlm.nih.gov/pubmed/21799941. [80] Guidance for industry: Reducing microbial food safety hazards for sprouted seeds. fda oct 27 1999. page last updated: August 30. 2011. http://www.fda.gov/Food/GuidanceComplianceRegulatoryInformation/ GuidanceDocuments/ProduceandPlanProducts/ucm120244.htm. [81] Investigation update: Multistate outbreak of human salmonella enteritidis infections linked to alfalfa sprouts and spicy sprouts. http://www.cdc.gov/salmonella/ sprouts-enteritidis0611/070611/index.html. [82] CDC. Investigating foodborne outbreaks. investigations/investigating.html. http://www.cdc.gov/outbreaknet/
[83] Deering AJ, Mauer LJ, and Pruitt RE. Internalization of e. coli o157:h7 and salmonella spp. in plants: A review. Food Research International, 2011. http: //www.sciencedirect.com/science/article/pii/S0963996911004418. [84] Deering AJ, Pruitt RE, Mauer LJ, and Reuhs BL. Identication of the cellular location of internalized escherichia coli o157:h7 in mung bean, vigna radiata, by
BIBLIOGRAPHY
1777
immunocytochemical techniques. J Food Prot, 74(8):122430, 8 2011. http://www. ncbi.nlm.nih.gov/pubmed/21819647. [85] Deering AJ, Pruitt RE, Mauer LJ, and Reuhs BL. Examination of the internalization of salmonella serovar typhimurium in peanut, arachis hypogaea, using immunocytochemical techniques. Food Research International, 2011. http: //www.sciencedirect.com/science/article/pii/S0963996911000846. [86] http://www.cdc.gov/eid/content/16/4/610.htm. Christian Jenke, Dag Harmsen, Thomas Weniger, Jrg Rothgnger, Eija Hyyti-Trees, Martina Bielaszewska, Helge Karch, and Alexander Mellmann: Phylogenetic Analysis of Enterohemorrhagic Escherichia coli O157, Germany, 1987-2008. CDC: Emerging Infectious Diseases. Volume 16, Number 4-April 2010. [87] Bielaszewska M, Middendorf B, Tarr PI, Zhang W, Prager R, Aldick T, Dobrindt U, Karch H, and Mellmann A. Chromosomal instability in enterohaemorrhagic escherichia coli o157:h7: impact on adherence, tellurite resistance and colony phenotype. Mol Microbiol, 79(4):102444, 2 2011. http://www.ncbi.nlm.nih.gov/pmc/ articles/PMC3064760/?tool=pubmed. [88] http://www.eurosurveillance.org/edition/v13n07/080214_5.asp. K De Schrijver, Buvens, G.; Poss, B.; Van den Branden, D.; Oosterlynck, C.; De Zutter, L.; Eilers, K.; Pirard, D.; Dierick, K.; Van Damme-Lombaerts, R.; Lauwers, C.; Jacobs R.: Eurosurveillance: Outbreak of verocytotoxin-producing E. coli O145 and O26 infections associated with the consumption of ice cream produced at a farm, Belgium, 2007. Euro Surveill 2008;13(7). [89] Tarr PI, Gordon CA, Chandler WL.: Shiga-toxin-producing Escherichia coli and haemolytic uraemic syndrome. Lancet. 19 March 2005;365(9464):1073-86. [90] http://content.nejm.org/cgi/content/extract/333/6/364. Boyce, T.G.; Swerdlow, D.L.; Grin, P.M.: Escherichia coli O157:H7 and the haemolytic-uremic syndrome. N Engl J Med. 1995:333(6):364-8. [91] http://www.idsociety.org/Content.aspx?id=16864. Johnson J. et al: Emerging E. coli Strain Causes Many Antimicrobial-Resistant Infections in U.S. August 1, 2010 issue of Clinical Infectious Diseases. [92] http://www.ncbi.nlm.nih.gov/pubmed/20705517. Kumarasamy KK, Toleman MA, Walsh TR, Bagaria J, Butt F, Balakrishnan R, Chaudhary U, Doumith M, Giske CG, Irfan S, Krishnan P, Kumar AV, Maharjan S, Mushtaq S, Noorie T, Paterson DL, Pearson A, Perry C, Pike R, Rao B, Ray U, Sarma JB, Sharma M, Sheridan E, Thirunarayan MA, Turton J, Upadhyay S, Warner M, Welfare W, Livermore DM, Woodford N: Emergence of a new antibiotic resistance mechanism in India, Pakistan, and the UK: a molecular, biological, and epidemiological study. Lancet Infect Dis. 2010 Aug 10.
1778
[93] http://en.wikipedia.org/wiki/Beta_lactam. Wikipedia: Beta-lactam. [94] http://en.wikipedia.org/wiki/Carbapenems. Wikipedia: Carbapenem. [95] Woodford N, Turton JF, and Livermore DM. Multiresistant gram-negative bacteria: the role of high-risk clones in the dissemination of antibiotic resistance. FEMS Microbiol Rev, 2 2011. http://www.ncbi.nlm.nih.gov/pubmed/21303394. [96] Livermore DM, Warner M, Mushtaq S, Doumith M, Zhang J, and Woodford N. What remains against carbapenem-resistant enterobacteriaceae? evaluation of chloramphenicol, ciprooxacin, colistin, fosfomycin, minocycline, nitrofurantoin, temocillin and tigecycline. Int J Antimicrob Agents, 3 2011. http://www.ncbi.nlm.nih.gov/ pubmed/21429716. [97] Livermore DM, Mushtaq S, Warner M, Zhang J, Maharjan S, Doumith M, and Woodford N. Activities of nxl104 combinations with ceftazidime and aztreonam against carbapenemase-producing enterobacteriaceae. Antimicrob Agents Chemother, 55(1):3904, 1 2011. http://www.ncbi.nlm.nih.gov/pubmed/21041502. [98] Endimiani A, Hujer KM, Hujer AM, Pulse ME, Weiss WJ, and Bonomo RA. Evaluation of ceftazidime and nxl104 in two murine models of infection due to kpcproducing klebsiella pneumoniae. Antimicrobial Agents and Chemotherapy, 55(1):82, 2010. http://www.ncbi.nlm.nih.gov/pubmed/21041503. [99] Zhao WH and Hu ZQ. Epidemiology and genetics of vim-type metallo-bet-lactamases in gram-negative bacilli. Future Microbiol, 6:31733, 3 2011. http://www.ncbi.nlm. nih.gov/pubmed/21449842. [100] Diehl DL and LaPara TM. Eect of temperature on the fate of genes encoding tetracycline resistance and the integrase of class 1 integrons within anaerobic and aerobic digesters treating municipal wastewater solids. Environmental Science & Technology. http://pubs.acs.org/doi/abs/10.1021/es102765a. [101] http://www.ncbi.nlm.nih.gov/pubmed/20577157. Centers for Disease Control and Prevention (CDC): Detection of Enterobacteriaceae isolates carrying metallobeta-lactamase-United States, 2010. MMWR Morb Mortal Wkly Rep. 2010 Jun 25;59(24):750. [102] http://en.wikipedia.org/wiki/Aztreonam. Wikipedia: Aztreonam. [103] http://www.ncbi.nlm.nih.gov/pubmed/19770275. Yong D, Toleman MA, Giske CG, Cho HS, Sundman K, Lee K, Walsh TR: Antimicrob Agents Chemother. 2009 Dec;53(12):5046-54.: Characterization of a new metallo-beta-lactamase gene, bla(NDM-1), and a novel erythromycin esterase gene carried on a unique genetic structure in Klebsiella pneumoniae sequence type 14 from India.
BIBLIOGRAPHY
1779
[104] http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2681641/. Toomey N, Monaghan A, Fanning S, Bolton D: Transfer of Antibiotic Resistance Marker Genes between Lactic Acid Bacteria in Model Rumen and Plant Environments. Appl Environ Microbiol. 2009 May; 75(10): 3146-3152. [105] Antibiotika im tierfutter mastbetriebe bleiben gesperrt. sueddeutsche.de 23 jan 2012. http://www.sueddeutsche.de/gesundheit/ antibiotika-im-tierfutter-mastbetriebe-bleiben-gesperrt-1.1264097. [106] Subtherapeutic antibiotic use in swine. wikipedia. wiki/Subtherapeutic_antibiotic_use_in_swine. http://en.wikipedia.org/
[107] Council regulation (eec) no 2377/90 of 26 june 1990 laying down a community procedure for the establishment of maximum residue limits of veterinary medicinal products in foodstus of animal origin. http://eur-lex.europa.eu/LexUriServ/ LexUriServ.do?uri=CELEX:31990R2377:EN:HTML. [108] Commission regulation (eu) no 37/2010 of 22 december 2009 on pharmacologically active substances and their classication regarding maximum residue limits in foodstus of animal origin. http://eur-lex.europa.eu/LexUriServ/LexUriServ.do? uri=OJ:L:2010:015:0001:0072:EN:PDF. [109] Council directive 96/23/ec of 29 april 1996 on measures to monitor certain substances and residues thereof in live animals and animal products and repealing directives 85/358/eec and 86/469/eec and decisions 89/187/eec and 91/664/eec. http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri= CELEX:31996L0023:EN:HTML. [110] 2003/181/ec: Commission decision of 13 march 2003 amending decision 2002/657/ec as regards the setting of minimum required performance limits (mrpls) for certain residues in food of animal origin. http://eur-lex.europa.eu/LexUriServ/ LexUriServ.do?uri=OJ:L:2003:071:0017:0018:EN:PDF. [111] Hammami R, Fernandez B, Lacroix C, and Fliss I. Anti-infective properties of bacteriocins: an update. Cell Mol Life Sci, 2012. http://www.ncbi.nlm.nih.gov/ pubmed/23109101. [112] Savadogo A, Quattara CAT, Bassole IHN, and Traore SA. Bacteriocins and lactic acid bacteria - a minireview. African Journal of Biotechnology, 5(9):678683, 5 2006. http://www.ajol.info/index.php/ajb/article/viewFile/42771/26340. [113] Glvez A, Abriouel H, Lpez RL, and Ben Omar N. Bacteriocin-based strategies for food biopreservation. Int J Food Microbiol, 120(1-2):5170, 11 2007. http: //www.ncbi.nlm.nih.gov/pubmed/17614151.
1780
[114] Georgalaki M, Papadimitriou K, Anastasiou R, Pot B, Van Driessche G, Devreese B, and Tsakalidou E. Macedovicin, the second food-grade lantibiotic produced by streptococcus macedonicus aca-dc 198. Food Microbiol, 33(1):12430, 2 2013. http: //www.ncbi.nlm.nih.gov/pubmed/23122510. [115] Abriouel H, Franz CM, Ben Omar N, and Glvez A. Diversity and applications of bacillus bacteriocins. FEMS Microbiol Rev, 35(1):20132, 1 2011. http://www. ncbi.nlm.nih.gov/pubmed/20695901. [116] Lee H and Kim HY. Lantibiotics, class i bacteriocins from the genus bacillus. J Microbiol Biotechnol, 21(3):22935, 3 2011. http://www.jmb.or.kr/journal/download. php?Filedir=../submission/Journal/021/&num=4315. [117] Kaur G, Malik RK, Mishra SK, Singh TP, Bhardwaj A, Singroha G, Vij S, and Kumar N. Nisin and class iia bacteriocin resistance among listeria and other foodborne pathogens and spoilage bacteria. Microb Drug Resist, 17(2):197205, 6 2011. http: //www.ncbi.nlm.nih.gov/pubmed/21417775. [118] Poltavska OA and Kovalenko NK. Antimicrobial activity of bidobacterial bacteriocin-like substances. Mikrobiol Z, 74(5):3242, Sep-Oct 2012. http://www. ncbi.nlm.nih.gov/pubmed/23120984. [119] Norberg S, Stanton C, Ross RP, Hill C, Fitzgerald GF, and Cotter PD. Cronobacter spp. in powdered infant formula. J Food Prot, 75(3):60720, 3 2012. http://www. ncbi.nlm.nih.gov/pubmed/22410240. [120] Who: Guidelines for the safe preparation, storage and handling of powdered infant formula. http://www.who.int/foodsafety/publications/micro/pif_ guidelines.pdf. [121] Healy B, Cooney S, OBrien S, Iversen C, Whyte P, Nally J, Callanan JJ, and Fanning S. Cronobacter (enterobacter sakazakii): an opportunistic foodborne pathogen. Foodborne Pathog Dis, 7(4):33950, 4 2010. http://www.ncbi.nlm.nih.gov/pubmed/ 19958103. [122] Oshima S, Rea MC, Lothe S, Morgan S, Begley M, OConnor PM, Fitzsimmons A, Kamikado H, Walton R, Ross RP, and Hill C. Ecacy of organic acids, bacteriocins, and the lactoperoxidase system in inhibiting the growth of cronobacter spp. in rehydrated infant formula. J Food Prot, 75(10):173442, 10 2012. http://www.ncbi.nlm.nih.gov/pubmed/23043820. [123] http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=OJ:L:2007:322: 0012:0029:EN:PDF. Commission Regulation (EC) No 1441/2007 of 5 December 2007 amending Regulation (EC) No 2073/2005 on microbiological criteria for foodstus.
BIBLIOGRAPHY
1781
[124] Banwo K, Sanni A, and Tan H. Technological properties and probiotic potential of enterococcus faecium strains isolated from cow milk. J Appl Microbiol, 10 2012. http://www.ncbi.nlm.nih.gov/pubmed/23035976. [125] Sudagidan M and Yemenicioglu A. Eects of nisin and lysozyme on growth inhibition and biolm formation capacity of staphylococcus aureus strains isolated from raw milk and cheese samples. J Food Prot, 75(9):162733, 9 2012. http://www.ncbi. nlm.nih.gov/pubmed/22947470. [126] Lara HH, Garza-Trevino EN, Turrent LI, and Singh DK. Silver nanoparticles are broad-spectrum bactericidal and virucidal compounds. Journal of Nanobiotechnology, 9(30), 2011. http://www.jnanobiotechnology.com/content/9/1/30/ abstract. [127] http://www.ncbi.nlm.nih.gov/pubmed/20303158. Boehm A, Kaiser M, Li H, Spangler C, Kasper CA, Ackermann M, Kaever V, Sourjik V, Roth V, Jenal U: Second Messenger-Mediated Adjustment of Bacterial Swimming Velocity. Cell. 2010 Mar 18. Doi:10.1016/j.cell.2010.01.018. [128] Baumgart, Jrgen: Microbiologische Untersuchung von Lebensmitteln-Hamburg: Behr,1986. [129] Usda faulted for inaction on antibiotic resistant salmonella strains. may 16, 2013. http://cspi.net/new/201305161.html. [130] Risky meat: Will your meal send you to the hospital? hupost healthy living. 24 april 2013. http://www.huffingtonpost.com/michael-f-jacobson/ meat-foodborne-illness_b_3140117.html. [131] http://www.efsa.europa.eu/science/biohaz/biohaz_opinions/1430_en.html. European Food Safety Authority: Opinion of the Scientic Panel BIOHAZ related to Risk assessment and mitigation options of Salmonella in pig production; Adopted on 16 March 2006 (Question Nr. EFSA-Q-2005-019). [132] http://www.efsa.europa.eu/science/monitoring_zoonoses/reports/1277/ zoonoses2004-levels1-2-part11.pdf. European Food Safety Authority: The Community Summary Report on Trends and Sources of Zoonoses, Zoonotic Agents and Antimicrobial Resistance in the European Union in 2004, 21 December 2005; The EFSA Journal 2005- 310. [133] http://www.foodnavigator.com/news/ng.asp?n=77888&m=1fne704&c= nfuzqfgkdkribxo. FoodNavigator: Cadbury pleads guilty to all salmonella charges 04.07.2007. [134] http://news.bbc.co.uk/1/hi/uk/5112470.stm. BBC NEWS: Cadbury salmonella scare probed 24.06.2007.
1782
[135] http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=CELEX: 32002R0178:EN:HTML. Regulation (EC) No 178/2002 of the European Parliament and of the Council of 28 January 2002 laying down the general principles and requirements of food law, establishing the European Food Safety Authority and laying down procedures in matters of food safety OJ L 31, 1.2.2002, p. 1-24. [136] Vandeplas S, Dubois Dauphin R, Beckers Y, Thonart P, and Thwis A. Salmonella in chicken: current and developing strategies to reduce contamination at farm level. J Food Prot, 73(4):77485, 4 2010. http://www.ncbi.nlm.nih.gov/pubmed/ 20377971. [137] Mulder RW. Safe poultry meat production in the next century. Acta Vet Hung, 45(3):30715, 1997. http://www.ncbi.nlm.nih.gov/pubmed/9276991. [138] Le Hello S, Brisabois A, Accou-Demartin M, Josse A, Marault M, Francart S, Da Silva NJ, and Weill F-X. Foodborne outbreak and nonmotile salmonella enterica variant, france. Emerg Infect Dis, 18, 2012. http://wwwnc.cdc.gov/eid/article/18/1/ 11-0450_article.htm. [139] Commission regulation (eu) no 200/2010 of 10 march 2010 implementing regulation (ec) no 2160/2003 of the european parliament and of the council as regards a union target for the reduction of the prevalence of salmonella serotypes in adult breeding ocks of gallus gallus. http://eur-lex.europa.eu/LexUriServ/LexUriServ.do? uri=OJ:L:2010:061:0001:0009:EN:PDF. [140] Fosse J, Seegers H, and Magras C. Foodborne zoonoses due to meat: a quantitative approach for a comparative risk assessment applied to pig slaughtering in europe. Vet Res, 39(1), Jan-Feb 2008. http://www.vetres.org/articles/vetres/pdf/2008/ 01/v07149.pdf. [141] Luber P. Cross-contamination versus undercooking of poultry meat or eggs - which risks need to be managed rst? Int J Food Microbiol, 134(1-2):218, 8 2009. http: //www.ncbi.nlm.nih.gov/pubmed/19272666. [142] http://www.food.gov.uk/news/newsarchive/2006/aug/cadbury. UK Food Standards Agency: Cadbury recall update 1 August 2006. [143] http://cspinet.org/new/200907021.html. CSPI: Governors Urged to Block Sale of Untreated Gulf Coast Oysters. Deadly Vibrio Bacteria Common in Summer Months. 02.07.2009. [144] Fda urged to make oysters safe. cspi says agency should use new food safety law to protect consumers from deadly vibrio bacteria. cspi. 09 feb 2012. http://www. cspinet.org/new/201202091.html.
BIBLIOGRAPHY
1783
[145] Hervio-Heath D, Colwell RR, Derrien A, Robert-Pillot A, Fournier JM, and Pommepuy M. Occurrence of pathogenic vibrios in coastal areas of france. J Appl Microbiol, 92(6):112335, 2002. http://www.ncbi.nlm.nih.gov/pubmed/12010553. [146] Dasilva L, Parveen S, Depaola A, Bowers J, Brohawn K, and Tamplin ML. Development and validation of a predictive model for the growth of vibrio vulnicus in postharvest shellstock oysters. Appl Environ Microbiol, 78(6):16758, 3 2012. http://www.ncbi.nlm.nih.gov/pubmed/22247136. [147] Harwood VJ, Gandhi JP, and Wright AC. Methods for isolation and conrmation of vibrio vulnicus from oysters and environmental sources: a review. J Microbiol Methods, 59(3):300116, 12 2004. http://www.ncbi.nlm.nih.gov/pubmed/15488274. [148] Baker-Austin C, Lemm E, Hartnell R, Lowther J, Onley R, Amaro C, Oliver JD, and Lees D. pilf polymorphism-based real-time pcr to distinguish vibrio vulnicus strains of human health relevance. Food Microbiol, 30(1):1723, 5 2012. http: //www.ncbi.nlm.nih.gov/pubmed/22265278. [149] Broza YY, Raz N, Lerner L, Danin-Poleg Y, and Kashi Y. Genetic diversity of the human pathogen vibrio vulnicus: a new phylogroup. Int J Food Microbiol, 153(3):43643, 2 2012. http://www.ncbi.nlm.nih.gov/pubmed/22227412. [150] Lubin JB, Kingston JJ, Chowdhury N, and Boyd EF. Sialic acid catabolism and transport gene clusters are lineage specic in vibrio vulnicus. Appl Environ Microbiol, 2 2012. http://www.ncbi.nlm.nih.gov/pubmed/22344665. [151] Kim YR, Kim EY, Kim DG, Kim YO, Hossain MT, and Kong IS. Dna array with the groesl intergenic sequence to detect vibrio parahaemolyticus and vibrio vulnicus. Anal Biochem, 2012. http://www.ncbi.nlm.nih.gov/pubmed/22342881. [152] Roy S, Parande MV, Mantur BG, Bhat S, Shinde R, Parande AM, Meti R, Chandrasekhar MR, Kholkute SD, Saini A, Joshi M, and Gaonkar A. Multidrug resistant vibrio cholerae o1 in belgaum, south india. J Med Microbiol, 8 2012. http://www.ncbi.nlm.nih.gov/pubmed/22878247. [153] Pal BB, Khuntia HK, Samal SK, Kar SK, and Patnaik B. Epidemics of severe cholera caused by el tor vibrio cholerae o1 ogawa possessing the ctxb gene of the classical biotype in orissa, india. Int J Infect Dis, 14(5):e3849, 5 2010. http: //www.ncbi.nlm.nih.gov/pubmed/19781971. [154] http://www.ncbi.nlm.nih.gov/pubmed/17613090. Ristori, Christiane A.; Iaria, Sebastiao T.; Gelli, Dilma S.; Rivera, Irma N. G.: Pathogenic bacteria associated with oysters (Crassostrea brasiliana) and estuarine water along the south coast of Brazil. International Journal of Environmental Health Research, Volume 17, Number 4, August 2007 , pp. 259-269(11).
1784
[155] http://www.ncbi.nlm.nih.gov/pubmed/20428657. Vieira RH, de Sousa OV, Costa RA, Theophilo GN, Macrae A, Fonteles Filho AA, Rodrigues Ddos P: Raw oysters can be a risk for infections. Braz J Infect Dis. 2010 Feb;14(1):66-70. [156] http://www.ncbi.nlm.nih.gov/pubmed/19566724. Ramirez GD, Buck GW, Smith AK, Gordon KV, Mott JB.: Incidence of Vibrio vulnicus in estuarine waters of the south Texas Coastal Bend region. J Appl Microbiol. 2009 May 20. [157] http://elib.tiho-hannover.de/dissertations/96janssen-u.pdf. Janssen, Uwe: Investigations on Vibrionaceae in Wholesale- and Retail-Seafood, and their Importance for Human Health. [158] http://www.ingentaconnect.com/content/klu/10096/2004/00000023/ 00000012/art00009. Ruppert, J.; Panzig, B.; Guertler, L.; Hinz, P.; Schwesinger, G.; Felix, S.; Friesecke, S.: Two cases of severe sepsis due to Vibrio vulnicus wound infection acquired in the Baltic Sea. European Journal of Clinical Microbiology and Infectious Diseases, Volume 23, Number 12, December 2004 , pp. 912-915(4). [159] http://www.cspinet.org/new/200910191.html. FDA Acts to Protect Consumers from Vibrio in Oysters. CSPI October 19, 2009. [160] http://www.cdph.ca.gov/services/Documents/fdb%20Raw%20Gulf%20Oyst% 20Regs.pdf. Article 10.5. Raw Oysters. 13675. Raw Gulf Oysters: Labeling, Written Warnings and Additional Requirements. State of California. [161] http://www.co.el-dorado.ca.us/emd/envhealth/oyster.html. Environmental Health: Oysters:Limiting the Sale of Raw Oysters Harvested from the Gulf of Mexico. (Information from the California Department of Health Services). [162] http://www.cspinet.org/new/201006241.html. Gulf Coast Oysters Unsafe (But Not For the Reason You Think). Deadly Vibrio Vulnicus Bacteria, Not Oil, Contaminate Gulf Oysters Every Summer. CSPI Newsroom. June 24, 2010. [163] http://safeoysters.org/medical/prevention.html. SafeOysters.org-Health Care Providers. Vibrio vulnicus. Infection from Consumption of Raw Shellsh or Marine-Related Wounds. [164] http://www.fda.gov/Food/ucm210970.htm. FDA: Multi-government agency response to the Gulf of Mexico oil spill. Gulf of Mexico Oil Spill Update - June 14, 2010. [165] http://en.wikipedia.org/wiki/Vibrio_vulnificus. Wikipedia: Vibrio vulnicus. [166] http://www.ncbi.nlm.nih.gov/pubmed/20546636. Weis KE, Hammond RM, Hutchinson R, Blackmore CG: Vibrio illness in Florida, 1998-2007. Epidemiol Infect. 2010 Jun 14:1-8.
BIBLIOGRAPHY
1785
[167] http://www.ncbi.nlm.nih.gov/pubmed/20486433. Chen Y, Liu XM, Yan JW, Li XG, Mei LL, Mao QF, Ma : .Foodborne pathogens in retail oysters in south China. Biomed Environ Sci. 2010 Feb;23(1):32-6. [168] http://www.ncbi.nlm.nih.gov/pubmed/19323759. Chae MJ, Cheney D, Su YC: Temperature eects on the depuration of Vibrio parahaemolyticus and Vibrio vulnicus from the American oyster (Crassostrea virginica). J Food Sci. 2009 Mar;74(2):M62-6. [169] http://www.ncbi.nlm.nih.gov/pubmed/18810883. Hricova D, Stephan R, Zweifel C: Electrolyzed water and its application in the food industry. J Food Prot. 2008 Sep;71(9):1934-47. [170] http://www.ncbi.nlm.nih.gov/pubmed/16924906. Ren T, Su YC: Eects of electrolyzed oxidizing water treatment on reducing Vibrio parahaemolyticus and Vibrio vulnicus in raw oysters. J Food Prot. 2006 Aug;69(8):1829-34. [171] http://www.ncbi.nlm.nih.gov/pubmed/20004034. Quan Y, Choi KD, Chung D, Shin IS: Evaluation of bactericidal activity of weakly acidic electrolyzed water (WAEW) against Vibrio vulnicus and Vibrio parahaemolyticus. Int J Food Microbiol. 2010 Jan 1;136(3):255-60. Epub 2009 Dec 7. [172] http://www.ncbi.nlm.nih.gov/pubmed/20406715. Chen WL, Oliver JD, Wong HC: Adaptation of Vibrio vulnicus and an rpoS mutant to bile salts. Int J Food Microbiol. 2010 Jun 15;140(2-3):232-8. [173] http://www.ncbi.nlm.nih.gov/pubmed/17186660. Wong HC, Liu SH: Susceptibility of the heat-, acid-, and bile-adapted Vibrio vulnicus to lethal low-salinity stress. J Food Prot. 2006 Dec;69(12):2924-8. [174] http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2856557/?tool=pubmed. Homann M, Brown EW, Feng PC, Keys CE, Fischer M, Monday SR: PCR-based method for targeting 16S-23S rRNA intergenic spacer regions among Vibrio species. BMC Microbiol. 2010 Mar 23;10:90. [175] http://www.ncbi.nlm.nih.gov/pubmed/17883316. Gonzlez-Escalona N, Jaykus LA, DePaola A: Typing of Vibrio vulnicus strains by variability in their 16S-23S rRNA intergenic spacer regions. Foodborne Pathog Dis. 2007 Fall;4(3):327-37. [176] http://www.ncbi.nlm.nih.gov/pubmed/20158583. Fouz B, Llorens A, Valiente E, Amaro C: A comparative epizootiologic study of the two sh-pathogenic serovars of Vibrio vulnicus biotype 2. J Fish Dis. 2010 May;33(5):383-90. [177] http://www.ncbi.nlm.nih.gov/pubmed/20106642. Caigral I, Moreno Y, Alonso JL, Gonzlez A, Ferrs MA: Detection of Vibrio vulnicus in seafood, seawater and wastewater samples from a Mediterranean coastal area. Microbiol Res. 2010 Jan 25.
1786
[178] http://www.ncbi.nlm.nih.gov/pmc/articles/PMC342803/?tool=pubmed. Panicker G, Myers ML, Bej AK: Rapid detection of Vibrio vulnicus in shellsh and Gulf of Mexico water by real-time PCR: Appl Environ Microbiol. 2004 Jan;70(1):498-507. [179] http://en.wikipedia.org/wiki/Plesiomonas_shigelloides. siomonas shigelloides. Wikipedia: Ple-
[180] http://www3.interscience.wiley.com/journal/118520357/abstract?CRETRY= 1&SRETRY=0. Papadoupolou, C.; Economou, E.; Zacas, G.; Salamoura, C.; Dontorou, C.; Apostolou, J.: Microbiological and Pathogenic Contaminants of Seafood in Greece. Journal of Food Quality, Volume 30 Issue 1, Pages 28-42 Published Online: 23 March 2007. [181] Holt,John G. (et al.), Bergeys manual of determinative bacteriology. Williams & Wilkins, Baltimore 1994,351. [182] Krieg,Noel R.,Holt,John G.: Bergeys manual of determinative bacteriology,volume 1,1983,729. [183] Everett KD. Bush RM. Anderson AA. (1999): Emendet description of the order Chlamydiales , proposal of parachlamidiaceae fam. nov. and Simkaniaceae fam. nov. each containing one monotypic genus, revised taxonomy of the family chlamidiaceae, including a new genus and ve new species, and standards for the identication of organisms. Int J Syst Bacteriol 49 (pt2): 415-40. [184] Molestina RE, Dean D, Miller RD, Ramirez JA, Summersgill JT, (1998) Chraracterisation of a strain of Chlamydia pneumoniae isolated from a coronary atheroma by analysis of the omp 1 gene and biological activity in human endothelial cells. Infect Immun 66: 1370-1376. [185] Regnath,Th.; Hahn, H.: Infektionen durch Chlamydien - Stand des Wissens, RKI: Epidemiologisches Bulletin 18/97, 121 - 122. [186] Strobel, E.: Chlamydien-Infektionen nehmen weltweit zu. Fortschritte der Medizin 115 (1997), Nr. 33 , 43 - 44. [187] Marre, R.; Essig, A.: Chlamydia pneumoniae und Atherosklerose. Dtsch. Med.Wschr.122 (1997), 1092 - 1095. [188] Stille, W.; Just-Nbbling,G.: Ist die Arteriosklerose eine Infektionskrankheit durch Clamydia pneumoniae RKI: Epidemiologisches Bulletin 8/97, 51 - 52. [189] Ma, M.: Die Assoziation von Chlamydia pneumoniae-Infektionen und Arteriosklerose. RKI: Infektionsepidemiologische Forschung III/97, 1 - 6. [190] Mikrobiology Europe Volume 4 Number 4 July/August 1996, 6 : Chlamydia and Heart Disease.
BIBLIOGRAPHY
1787
[191] Dr S DArcy BSc,MBBS: Chlamydia pneumoniae and atherosclerosis: Association or causation; Culture Oxoid Volume 22 No 1 March 2001. [192] Das aktuelle Interview: Chlamidien und Arteriosclerose, Prof. Dr.med. G.Wolfram, Institut fr Ernhrungswissenschaft der Technischen Universitt Mnchen, Ernrungs-Umschau,Verlag Umschau Zeitschriftenverlag. [193] Brandis,H.: Eggers,H.J.Khler,W.:PulvererG. (Hrsg): Lehrbuch der Medizinische Mikrobiologie 7.Auage Gutav Fischer Verlag, Stuttgart 1994. [194] J.A.College Cardiol.27(7),1555-15561 (1996). [195] World-rst research will save koalas. qut science and engineering faculty. 09 april 2013. http://www.qut.edu.au/science-engineering/about/news/news? news-id=57452. [196] Polkinghorne A, Hanger J, and Timms P. Recent advances in understanding the biology, epidemiology and control of chlamydial infections in koalas. Vet Microbiol, 1(13):pii: S03781135, 2013. http://www.ncbi.nlm.nih.gov/pubmed/23523170. [197] Myers GS, Mathews SA, Eppinger M, Mitchell C, OBrien KK, White OR, Benahmed F, Brunham RC, Read TD, Ravel J, Bavoil PM, and Timms P. Evidence that human chlamydia pneumoniae was zoonotically acquired. J Bacteriol, 191(23):722533, 12 2009. http://jb.asm.org/content/191/23/7225.long. [198] Mathew M, Beagley KW, Timms P, and Polkinghorne A. Preliminary characterisation of tumor necrosis factor alpha and interleukin-10 responses to chlamydia pecorum infection in the koala (phascolarctos cinereus). PLoS One, 8(3):e59958, 2013. http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal. pone.0059958. [199] Kollipara A, Wan C, Rawlinson G, Brumm J, Nilsson K, Polkinghorne A, Beagley K, and Timms P. Antigenic specicity of a monovalent versus polyvalent momp based chlamydia pecorum vaccine in koalas (phascolarctos cinereus). Vaccine, 31(8):1217 23, 2 2013. http://www.ncbi.nlm.nih.gov/pubmed/23306372. [200] Darville T. Recognition and treatment of chlamydial infections from birth to adolescence. Adv Exp Med Biol, 764:10922, 2013. http://www.ncbi.nlm.nih.gov/ pubmed/23654060. [201] Joshi R, Khandelwal B, Joshi D, and Gupta OP. Chlamydophila pneumoniae infection and cardiovascular disease. N Am J Med Sci, 5(3):16981, 3 2013. http: //www.ncbi.nlm.nih.gov/pubmed/23626952. [202] http://www.ncbi.nlm.nih.gov/pubmed/17532866. Spadafranca A, Bertoli S, Fiorillo G, Testolin G, Battezzati A.Circulating salicylic acid is related to fruit and
1788
CHAPTER 24. GENERAL BACTERIOLOGY vegetable consumption in healthy subjects. Br J Nutr. 2007 Oct;98(4):802-6. Epub 2007 May 29.
[203] Fluorocult- Programm schneller und einfacher Nachweis von Bacterien und Hefen;information leaet of E.Merck, Darmstadt, Germany. [204] Todesbakterien bei der Queen;Bild 284/49 5.Dezember 1998. [205] Leggieri N, Gouriet F, Thuny F, Habib G, Raoult D, and Casalta J-P. Legionella longbeachae and endocarditis. Emerg Infect Dis, 1 2012. http://wwwnc.cdc.gov/ eid/article/18/1/11-0579_article.htm. [206] Automated impedance technology for rapid detection an enumeration.; leaet bioMrieux. [207] http://pubs.acs.org/doi/abs/10.1021/ac9000833. Koo, Ok Kyung; Liu, YiShao; Shuaib, Salamat; Bhattacharya, Shantanu; Ladisch, Michael R.;Bashir, Rashid; Bhunia, Arun K.: Targeted Capture of Pathogenic Bacteria Using a Mammalian Cell Receptor Coupled with Dielectrophoresis on a Biochip. Analytical Chemistry, 2009; 81 (8): 3094 DOI: 10.1021/ac9000833. [208] Futschik, Dr.K.: Impedanz-Splitting-Methode; leaet of Sy-lab, Purkersdorf, Austria. [209] Making health care safer: Stopping c. dicile infections. cdc. march 2012. http: //www.cdc.gov/vitalsigns/hai/. [210] Belmares J, Gerding DN, Tillotson G, and Johnson S. Measuring the severity of clostridium dicile infection: implications for management and drug development. Expert Rev Anti Infect Ther, 6(6):897908, 12 2008. http://www.ncbi.nlm.nih. gov/pubmed/19053902. [211] Dubberke ER et al. Strategies to prevent clostridium dicile infections in acute care hospitals. supplement: Shea/idsa practice recommendations. Infection Control and Hospital Epidemiology, 29(S1):S81S92, 10 2008. http://www.jstor.org/stable/ 10.1086/591065. [212] Cohen SH et al. Shea-idsa guideline 2010: Clinical practice guidelines for clostridium dicile infection in adults: 210 update by the society for healthcare epidemiology of america (shea) and the infectious diseases society aof america (idsa). Infection Control and Hospital Epidemiology, 31(5), 5 2010. http://www.jstor.org/stable/ 10.1086/651706. [213] Dubberke ER and Gerding DN. Rationale for hand hygiene recommendations after caring for a patient with clostridium dicile infection. http://www.shea-online. org/Portals/0/CDI%20hand%20hygiene%20Update.pdf.
BIBLIOGRAPHY
1789
[214] Dubberke ER. Strategies for prevention of clostridium dicile infection. J Hosp Med, Suppl 3:S147, 2012. http://www.ncbi.nlm.nih.gov/pubmed/22407995. [215] Badger VO, Ledeboer NA, Graham MB, and Edmiston CE Jr. Clostridium difcile: Epidemiology, pathogenesis, management, and prevention of a recalcitrant healthcare-associated pathogen. JPEN J Parenter Enteral Nutr, 5 2012. http: //www.ncbi.nlm.nih.gov/pubmed/22577120. [216] Frequently asked questions about clostridium dicile for healthcare providers. cdc. http://www.cdc.gov/hai/organisms/cdiff/cdiff_faqs_hcp.html#emergence. [217] Amplivue-clostridium dicile: A non-instrumented molecular test for the detection of toxigenic clostridium dicile bacterial dna. 18 dec 2012. http://www. ilexmedical.com/products.php?id=139. [218] Patel SS and Donmez I. Mechanisms of helicases. 281(27):182658, 7 2006. http: //www.jbc.org/content/281/27/18265.long. [219] Umweltbiotechnologie Biokorrosion schachmatt; UmweltMagazin;Februar 1999, S.8. [220] http://uk.ihs.com/document/abstract/CTKFDBAAAAAAAAAA. IHS: CEN EN 12201-2 Plastics piping systems for water supply - Polyethylene (PE) - Part 2: Pipes. [221] http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=CELEX: 31989L0106:EN:HTML. Council Directive 89/106/EEC of 21 December 1988 on the approximation of laws, regulations and administrative provisions of the Member States relating to construction products. [222] http://uk.ihs.com/document/abstract/EQNMEBAAAAAAAAAA. IHS: CEN EN 15551 Plastics piping systems for the supply of gaseous fuels Polyethylene (PE) Part 1: General. [223] http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm. FDA-CFR Title 21 Parts 170 to 199. [224] http://www.3-a.org/technical/papers/rubber.html. 3-A Sanitary Standard. [225] Schormller, Josef: Lehrbuch der Lebensmittelchemie, Springer-Verlag, Berlin. Gttingen. Heidelberg 1961 S. 660. [226] http://en.wikipedia.org/wiki/Chlorine_dioxide. Wikipedia, the free enzyclopedia: Chlorine dioxide. [227] http://news.uns.purdue.edu/html4ever/2006/061005LintonFood.html. due University news.
Pur-
1790
[228] Russell DJ, Abdul Majid S, and Tobias D. The presence of persistent coliform and e. coli contamination sequestered within the leaves of the popular fresh salad vegetable "jarjeer / rocket" (eruca sativa l.). Egypt. Acad. J. biolog. Sci., 2:18, 2 2010. http://microbiology.eajbs.eg.net/pdf/vol2.n2/1.pdf. [229] Crohn DM and Bianchib ML. Research priorities for coordinating management of food safety and water quality. Journal of Environmental Quality, 37(4):14111418. https://www.soils.org/publications/jeq/articles/37/4/1411. [230] http://www3.imperial.ac.uk/newsandeventspggrp/imperialcollege/ newssummary/news_3-9-2008-10-4-59?newsid=43294. How Salmonella bacteria contaminate salad leaves-its not rocket science. New research reveals secret to Salmonellas ability to contaminate salad-Imperial College London. News release 3.08.2008. [231] http://www.npi.gov.au/database/substance-info/profiles/21.html. NPI: Chlorine dioxide fact sheet: What eect might chlorine dioxide have on my health? [232] Jean L, Thomas B, Tahiri-Alaoui A, Shaw M, and Vaux DJ. Heterologous amyloid seeding: revisiting the role of acetylcholinesterase in alzheimers disease. PLoS One, 2(7):e652, 6 2007. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1920558/ ?tool=pubmed. [233] Barnhart MM and Chapman MR. Curli biogenesis and function. Annu Rev Microbiol, 60:13147, 2006. http://www.ncbi.nlm.nih.gov/pubmed/16704339. [234] Zhou Y, Smith D, Leong BJ, Brannstrom K, Almqvist F, and Chapman MR. Promiscuous cross-seeding between bacterial amyloids promotes interspecies biolms. J Biol Chem, 8 2012. http://www.ncbi.nlm.nih.gov/pubmed/22891247. [235] http://www.cdc.gov/salmonella/typhimurium/. phimurium. Update for January 21, 2009. CDC: Salmonella thy-
[236] Who: Recreational ("bathing") waters. http://www.who.int/water_sanitation_ health/bathing/en/. [237] Epa: Recreational: Water quality criteria. http://water.epa.gov/scitech/ swguidance/standards/criteria/health/recreation/index.cfm. [238] Whitman RL Nevers MB. Policies and practices of beach monitoring in the great lakes, usa: a critical review. J Environ Monit, pages 58190, 3 2010. http://www. ncbi.nlm.nih.gov/pubmed/20445845. [239] Shah AH, Abdelzaher AM, Phillips M, Hernandez R, Solo-Gabriele HM, Kish J, Scorzetti G, Fell JW, Diaz MR, Scott TM, Lukasik J, Harwood VJ, McQuaig S, Sinigalliano CD, Gidley ML, Wanless D, Agar A, Lui J, Stewart JR, Plano LR,
BIBLIOGRAPHY
1791
and Fleming LE. Indicator microbes correlate with pathogenic bacteria, yeast, and helminthes in sand at a subtropical recreational beach site. J.Appl Microbiol, 3 2011. http://www.ncbi.nlm.nih.gov/pubmed/21447014. [240] Shibata T, Solo-Gabriele HM, Fleming LE, and Elmir S. Monitoring marine recreational water quality using multiple microbial indicators in an urban tropical environment. Water Res, 38(13):311931, 7 2004. http://www.ncbi.nlm.nih.gov/pmc/ articles/PMC2548301/?tool=pubmed. [241] Verhougstraete MP, Byappanahalli MN, Rose JB, and Whitman RL. Cladophora in the great lakes: impacts on beach water quality and human health. Water Sci Technol, 62(1):6876, 2010. http://www.ncbi.nlm.nih.gov/pubmed/20595755. [242] Wade TJ, Pai N, Eisenberg JN, and Colford JM Jr. Do u.s. environmental protection agency water quality guidelines for recreational waters prevent gastrointestinal illness? a systematic review and meta-analysis. Environ Health Perspect, 111(8):1102 9, 6 2003. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1241558/?tool= pubmed. [243] Boehm AB and Weisberg SB. Tidal forcing of enterococci at marine recreational beaches at fortnightly and semidiurnal frequencies. Environ Sci Technol, 39(15):557583, 8 2005. ftp://ftp.sccwrp.org/pub/download/DOCUMENTS/ AnnualReports/2005_06AnnualReport/AR0506_263-276.pdf. [244] http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=OJ:L:2005:338: 0001:0026:EN:PDF. Commission Regulation (EC) No 2073/2005 of 15 November 2005 on microbiological criteria for foodstus. [245] http://eur-lex.europa.eu/pri/en/oj/dat/2002/l_031/l_ 03120020201en00010024.pdf. EU: Regulation (EC) No 178/2002 of the European Parliament and of the Council of 28 January2002 laying down the general principles and requirements of food law, establishing the European Food Safety Authority and laying down procedures in matters of food safety. [246] http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=OJ:L:2004:139: 0001:0054:EN:PDF. Commission Regulation Regulation (EC) No 852/2004 of the European Parliament and of the Council of 29 April 2004 on the hygiene of foodstus. [247] http://www.cdc.gov/EID/content/13/11/1625.htm. Gayer M, Legros D, Formenty P, Connolly MA. Conict and emerging infectious diseases. Emerg Infect Dis. 2007 Nov. [248] http://www.ehponline.org/members/2005/7647/7647.html. Price, Lance B.; Johnson, Elizabeth; Vailes, Rocio; Silbergeld, Ellen : Fluoroquinolone-Resistant Campylobacter Isolates from Conventional and Antibiotic-Free Chicken Products.
1792
CHAPTER 24. GENERAL BACTERIOLOGY Environ Health Perspect 113:557-560 (2005) . doi:10.1289/ehp.7647 (Online 2 February 2005).
[249] http://ehp.niehs.nih.gov/docs/2007/10191/abstract.html. Price, Lance B.; Graham, Jay P.; Lackey, Leila G.; Roess, Amira; Vailes, Rocio.; Silbergeld Ellen: Elevated Risk of Carrying Gentamicin Resistant Escherichia coli Among US Poultry Workers Environ Health Perspect: doi:10.1289/ehp.10191. (Online 4 September 2007]). [250] http://www.uark.edu/depts/fsc/news.current.htm. The Food Safety Consortium Newsletter: Probiotics: Live Organisms as Feed Supplements to Fight Salmonella. Vol. 18, No. 1 Winter 2008. [251] http://www.sciencemag.org/cgi/content/summary/sci;321/5887/355. Roberts, Leslie; Simpson, Stephen: Deadly Deance. Science 18 July 2008: Vol. 321. no. 5887, p. 355. Doi: 10.1126/science.321.5887.355. [252] http://www.sciencemag.org/cgi/content/summary/sci;321/5887/360. Taubes, Gary: Collateral Damage: The Rise of Resistant C. dicile. Science 18 July 2008: Vol. 321. no. 5887, p. 360 Doi: 10.1126/science.321.5887.360. [253] http://www.sciencemag.org/cgi/content/summary/sci;321/5887/362. Marshall, Eliot: Trench Warfare in a Battle With TB Science 18 July 2008, Vol. 321 (5887), 362. Doi: 10.1126/science.321.5887.362. [254] http://www.sciencemag.org/cgi/content/abstract/sci;321/5887/365. Martnez, Jos L.: Antibiotics and Antibiotic Resistance Genes in Natural Environments Science 18.July 2008. Vol. 321 (5887), 365. Doi: 10.1126/science.1159483. [255] http://www.sciencemag.org/cgi/content/abstract/sci;321/5887/367. Monk, Brian C.; Goeau, Andre: Outwitting Multidrug Resistance to Antifungals. Science 18 July 2008. Vol. 321 (5887), 367. Doi: 10.1126/science.1159746. [256] http://www.state.nj.us/health/phel/documents/teleconf/carbapenem_ powerpoint.ppt. Jean B. Patel: Emerging Carbapenem Resistance in GramNegative Bacilli. CDC Presentation. [257] http://www.ncbi.nlm.nih.gov/pubmed/8718600. Livermore DM.:Bacterial resistance to carbapenems. Adv Exp Med Biol. 1995;390:25-47. [258] http://www.ncbi.nlm.nih.gov/pubmed/21086099. Spzek J, Novotn J, Rezanka T, Demain AL: Do we need new antibiotics? The search for new targets and new compounds. J Ind Microbiol Biotechnol. 2010 Dec;37(12):1241-1248..
BIBLIOGRAPHY
1793
[259] http://www.pnas.org/content/early/2010/09/29/1007559107. Desai KK, Miller BG: Recruitment of genes and enzymes conferring resistance to the nonnatural toxin bromoacetate. Proceedings of the National Academy of Sciences, 2010; DOI: 10.1073/pnas.1007559107. [260] http://www.jbc.org/content/early/2010/11/17/jbc.M110.194266.long. Stogios PJ, Shakya T, Evdokimova E, Savchenko A, Wright GD.Structure and function of APH(4)-IA, a hygromycin B resistance enzyme. J Biol Chem. 2010 Nov 17. [261] http://www.ncbi.nlm.nih.gov/pubmed/21081547. Jeon B, Wang Y, Hao H, Barton YW, Zhang Q: Contribution of CmeG to antibiotic and oxidative stress resistance in Campylobacter jejuni. J Antimicrob Chemother. 2010 Nov 17. [262] http://www.ncbi.nlm.nih.gov/pubmed/21078927. Staron A, Finkeisen DE, Mascher T: Peptide antibiotic sensing and detoxication modules of Bacillus subtilis. Antimicrob Agents Chemother. 2010 Nov 15. [263] http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2971513/?tool=pubmed. Conly J: Antimicrobial resistance: revisiting the tragedy of the commons. Bull World Health Organ. 2010 November 1; 88(11): 805-806. Doi: 10.2471/BLT.10.031110. [264] http://www.futuremedicine.com/doi/full/10.2217/fmb.10.119. BrtzOesterhelt H, Sasss P: Postgenomic strategies in antibacterial drug discovery. Future Microbiology, October 2010, Vol. 5, No. 10, Pages 1553-1579 , DOI 10.2217/fmb.10.119. [265] http://www.ncbi.nlm.nih.gov/pubmed/21078604. Livermore DM, Mushtaq S, Warner M, Zhang JC, Maharjan S, Doumith M, Woodford N: Activity of aminoglycosides, including ACHN-490, against carbapenem-resistant Enterobacteriaceae isolates. J Antimicrob Chemother. 2010 Nov 14.. [266] http://www.ncbi.nlm.nih.gov/pubmed/21077936. Krgel H, Licht A, Biedermann G, Petzold A, Lassak J, Hupfer Y, Schlott B, Hertweck C, Platzer M, Brantl S, Saluz HP: Cervimycin C resistance in Bacillus subtilis is due to a promoter up-mutation and increased mRNA stability of the constitutive ABC-transporter gene bmrA. FEMS Microbiol Lett. 2010 Dec;313(2):155-163. doi: 10.1111/j.1574-6968.2010.02143.x. [267] http://www.ncbi.nlm.nih.gov/pubmed/21077707. Friedman A, Ziyadi N, Boushaba K: A model of drug resistance with infection by health care workers. Math Biosci Eng. 2010 Oct;7(4):779-92. doi: 10.3934/mbe.2010.7.779. [268] http://www.cdc.gov/eid/content/14/9/1383.htm?s_cid=eid1383_e. Lewis, Hannah C.; Molbak, Kare; Reese, Catrin; Aarestrup, Frank M.; Selchau, Mette; Sorum, Marit; Skov, Robert L.: Pigs as Source of Methicillin-Resistant Staphylococcus aureus CC398 Infections in Humans, Denmark. CDC Emerging Infectious Diseases. Volume 14, Number 9-September 2008.
1794
[269] http://www.cdc.gov/eid/content/15/7/1098.htm. Denis, Olivier; Suetens, Carl; Hallin, Marie; Catry, Boudewijn; Ramboer, Ilse; Dispas, Marc; Willems, Glenda; Gordts, Bart; Butaye, Patrick; Struelens, Marc J.: Methicillin-Resistant Staphylococcus aureus ST398 in Swine Farm Personnel, Belgium. CDC Emerging Infectious Diseases. Volume 15, Number 7-July 2009. [270] http://www.ncbi.nlm.nih.gov/pubmed/18718557. Deurenberg RH, Stobberingh EE: The evolution of Staphylococcus aureus. Infect Genet Evol. 2008 Dec;8(6):74763. Epub 2008 Jul 29. [271] http://www.ncbi.nlm.nih.gov/pubmed/20092664. Golding GR, Levett PN, McDonald RR, Irvine J, Nsungu M, Woods S, Horbal A, Siemens CG, Khan M, OfnerAgostini M, Mulvey MR; the Northern Antibiotic Resistance Partnership (NARP): A comparison of risk factors associated with community-associated methicillin-resistant and -susceptible Staphylococcus aureus infections in remote communities. Epidemiol Infect. 2010 Jan 22:1-8. [272] http://www.cdc.gov/eid/content/16/4/587.htm. George R. Golding, Louis Bryden, Paul N. Levett, Ryan R. McDonald, Alice Wong, John Wylie, Morag R. Graham, Shaun Tyler, Gary Van Domselaar, Andrew E. Simor, Denise Gravel, and Michael R. Mulvey: Livestock-associated Methicillin-Resistant Staphylococcus aureus Sequence Type 398 in Humans, Canada. CDC Emerging Infectious Diseases. Volume 16, Number 4-April 2010. [273] http://www.ncbi.nlm.nih.gov/pubmed/17428941. Christianson S, Golding GR, Campbell J; Canadian Nosocomial Infection Surveillance Program, Mulvey MR: Comparative genomics of Canadian epidemic lineages of methicillin-resistant Staphylococcus aureus. J Clin Microbiol. 2007 Jun;45(6):1904-11. [274] http://www.ncbi.nlm.nih.gov/pubmed/20130023. Bcher S, Middendorf B, Westh H, Mellmann A, Becker K, Skov R, Friedrich AW: Semi-selective broth improves screening for methicillin-resistant Staphylococcus aureus. J Antimicrob Chemother. 2010 Apr;65(4):717-20. [275] Sonnevend , Blair I, Alkaabi M, Jumaa P, Al Haj M, Ghazawi A, Akawi N, Jouhar FS, Hamadeh MB, and Pl T. Ch j clin pathol ange in meticillin-resistant staphylococcus aureus clones at a tertiary care hospital in the united arab emirates over a 5-year period. 65(2):17882, 2 2012. http://www.ncbi.nlm.nih.gov/pubmed/ 22039280. [276] [277] Cotter1 PD, Hill C, and Ross RP. Bacterial lantibiotics: Strategies to improve therapeutic potential. Current Protein and Peptide Science, 6:6175, 2005. http: //www.benthamscience.com/cpps/sample/cpps6-1/0007K.pdf.
BIBLIOGRAPHY [278] Lantibiotics. Wikipedia. http://en.wikipedia.org/wiki/Lantibiotic.
1795
[279] Bactibase database dedicated to bacteriocins. http://bactibase.pfba-lab-tun. org/bacteriocinslist.php?x_Class=lantibiotic. [280] Lee J-H, Li X, and OSullivan DJ. Transcription analysis of a lantibiotic gene cluster from bidobacterium longum djo10a. Appl. Environ. Microbiol. http://aem.asm. org/cgi/content/abstract/AEM.00571-11v1. [281] http://www.cdc.gov/eid/content/15/4/625.htm. Tauil, Pedro Luiz: The Status of Infectious Disease in the Amazon Region. Emerging Infectious Diseases. Volume 15, Number 4-April 2009. [282] World Heath Organisation. Leishmaniasis. http://www.who.int/leishmaniasis/ en/. [283] Raymond RW, McHugh CP, and Kerr SF. Sand ies of nicaragua: a checklist and reports of new collections. Mem Inst Oswaldo Cruz, 105(7):88994, 11 2010. http: //www.ncbi.nlm.nih.gov/pubmed/21120358. [284] Wright NA, Davis LE, Aftergut KS, Parrish CA, and Cockerell CJ. Cutaneous leishmaniasis in texas: A northern spread of endemic areas. J Am Acad Dermatol, 58(4):6502, 4 2008. http://www.ncbi.nlm.nih.gov/pubmed/18249464. [285] Ives A, Ronet C, Prevel F, Ruzzante G, Fuertes-Marraco S, Schutz F, Zangger H, Revaz-Breton M, Lye LF, Hickerson SM, Beverley SM, Acha-Orbea H, Launois P, Fasel N, and Masina S. Leishmania rna virus controls the severity of mucocutaneous leishmaniasis. Science, 331(6018):7758, 2 2011. http://www.sciencemag.org/ content/331/6018/775. [286] http://www.fda.gov/cdrh/ode/guidance/1320.pdf. Guidance for Industry and FDA Sta. Biological Indicator (BI) Premarket. Notication (510(k)) Submissions. Document issued on: October 4, 2007. The draft of this document was issued May 21, 2001. This document supersedes FDA Guide for Validation of Biological Indicator. Incubation Time, January 1, 1986. [287] http://www.ars.usda.gov/is/AR/archive/feb06/protozoa0206.pdf. Protozoa :The United States Department of Agriculture, Agricultural Research Service: The inside story; Are these tiny animals accidental allies of Salmonella?; Agricultural Research/February 2006:. [288] M. T. Brandl, B. M. Rosenthal, A. F. Haxo, and S. G. Berk enhanced Survival of Salmonella enterica in Vesicles Released by a Soilborne Tetrahymena Species Applied and Environmental Microbiology, March 2005, p. 1562-1569, Vol. 71, No. 3 00992240/05/08.00+0 doi:10.1128/AEM.71.3.1562-1569.2005.
1796
[289] http://aem.asm.org/cgi/content/abstract/74/8/2518. Gourabathini, Poornima; Brandl, Maria T.; Redding, Katherine S.; Gunderson, John H.; Berk, Sharon G.: Interactions between Food-Borne Pathogens and Protozoa Isolated from Lettuce and Spinach. Applied and Environmental Microbiology, April 2008, p. 2518-2525, Vol. 74, No. 8. doi:10.1128/AEM.02709-07. [290] http://www.ethlife.ethz.ch/e/articles/campuslife/filamentphage.html. Phage potentiateantibiotic. [291] Hagens, S., A. Habel & U. Blsi (2006): Augmentation of the Antimicrobial Ecacy of Antibiotics by Filamentous Phage. Microbiol. Drug Resistance, Vol. 12, Number 3. pp 164-168. www.ethlife.ethz.ch/e/articles/sciencelife/phagenundnahrung.html. [292] http://members.ift.org/NR/rdonlyres/2229BBEE-DED6-44AB-990C-841A555C5D2C/ 0/0408feat_safety.pdf. Hagens, Steven; Oerhaus, Mark L.: Bacteriphages - new weapons for food safety. April 2008, Volume 62, No. 4. [293] http://www.eurekalert.org/pub_releases/2007-09/sfgm-nvt082807.php. Society for General Bacteriology: New viruses to treat bacterial diseases My enemies enemy is my friend. EurekAlert, Public release date: 2-Sep-2007. [294] http://www.ncbi.nlm.nih.gov/pubmed/1383083. Collins MD, Rodrigues UM, Dainty RH, Edwards RA, Roberts TA: Taxonomic studies on a psychrophilic Clostridium from vacuum-packed beef: description of Clostridium estertheticum sp. Nov. FEMS Microbiol Lett. 1992 Sep 15;75(2-3):235-40. [295] http://www.ncbi.nlm.nih.gov/pubmed/20406381. Clemens RM, Adam KH, Brightwell G: Contamination levels of Clostridium estertheticum spores that result in gaseous spoilage of vacuum-packaged chilled beef and lamb meat. Lett Appl Microbiol. 2010 Jun 1;50(6):591-6. [296] http://www.ncbi.nlm.nih.gov/pubmed/19302329. Broda DM, Boerema JA, Brightwell G: Sources of psychrophilic and psychrotolerant clostridia causing spoilage of vacuum-packed chilled meats, as determined by PCR amplication procedure. J Appl Microbiol. 2009 Jul;107(1):178-86. Epub 2009 Mar 3. [297] http://www.ncbi.nlm.nih.gov/pubmed/19903404. Yang X, Gill CO, Balamurugan S: Eects of temperature and pH on the growth of bacteria isolated from blown packs of vacuum-packaged beef. J Food Prot. 2009 Nov;72(11):2380-5. [298] http://www.ncbi.nlm.nih.gov/pubmed/19835775. Jones RJ, Zagorec M, Brightwell G, Tagg JR: Inhibition by Lactobacillus sakei of other species in the ora of vacuum packaged raw meats during prolonged storage. Food Microbiol. 2009 Dec;26(8):876-81. Epub 2009 Jun 12.
BIBLIOGRAPHY
1797
[299] http://www.ncbi.nlm.nih.gov/pubmed/19659695. Moschonas G, Bolton DJ, Sheridan JJ, McDowell DA: The eect of storage temperature and inoculum level on the time of onset of blown pack spoilage. J Appl Microbiol. 2010 Feb;108(2):532-9. [300] http://www.ncbi.nlm.nih.gov/pubmed/19302293. Moschonas G, Bolton DJ, Sheridan JJ, McDowell DA: Isolation and sources of blown pack spoilage clostridia in beef abattoirs. J Appl Microbiol. 2009 Aug;107(2):616-24. [301] http://www.ncbi.nlm.nih.gov/pubmed/19027974. Yang X, Balamurugan S, Gill CO: Substrate utilization by Clostridium estertheticum cultivated in meat juice medium. Int J Food Microbiol. 2009 Jan 15;128(3):501-5. Epub 2008 Oct 31. [302] http://www.ncbi.nlm.nih.gov/pubmed/12588561. Broda DM, Boerema JA, Bell RG: PCR detection of psychrophilic Clostridium spp. causing blown pack spoilage of vacuum-packed chilled meats. J Appl Microbiol. 2003;94(3):515-22. [303] http://www.ncbi.nlm.nih.gov/pubmed/12392528. Broda DM, Bell RG, Boerema JA, Musgrave DR: The abattoir source of culturable psychrophilic Clostridium spp. causing blown pack spoilage of vacuum-packed chilled venison. J Appl Microbiol. 2002;93(5):817-24. [304] http://www.ncbi.nlm.nih.gov/pubmed/19302329. Broda, D.M., Boerema, J.A., Brightwell, G. (2009). Sources of psychrophilic and psychrotolerant clostridia causing spoilage of vacuum-packed chilled meats, as determined by PCR amplication procedure. J. Appl. Microbiol. July 2009, 107, 178-186. [305] http://www.ncbi.nlm.nih.gov/pubmed/20406381. Clemens RM, Adam KH, Brightwell G: Contamination levels of Clostridium estertheticum spores that result in gaseous spoilage of vacuum-packaged chilled beef and lamb meat. Lett Appl Microbiol. 2010 Jun 1;50(6):591-6. Epub 2010 Mar 17. [306] http://www.ncbi.nlm.nih.gov/pubmed/20615352. Yang X, Gill CO, Balamurugan S: Products of glucose and lactate fermentation, and utilization of amino acids by Clostridium estertheticum subspp. laramiense and estertheticum growing in meat juice medium. J Food Prot. 2010 Jul;73(7):1348-52. [307] http://jds.fass.org/cgi/content/abstract/91/2/564. Hata, E.; Katsuda,K.; Kobayashi, H.; Nishimori, K.; Uchida, I.; Higashide, M.; Ishikawa, E.; Sasaki, T.; Eguchi, M.: Bacteriological Characteristics of Staphylococcus aureus Isolates from Humans and Bulk Milk. Journal of Dairy Science. 2008 91: 564-569. [308] http://www.ncbi.nlm.nih.gov/pubmed/19390494. Nelson, Annika; Hultenby, Kjell; Hell, va; Riedel, Hilde M.; Brismar, Hjalmar; Flock, Jan-Ingmar; Lundahl, Joachim; Giske, Christian G.; Marchini. Giovanna: Staphylococcus epidermidis isolated from newborn infants express pilus-like structures and are inhibited by the cathelicidin-derived antimicrobial peptide LL37. Pediatric Research, 22 April 2009.
1798
[309] http://www.efsa.europa.eu/EFSA/Scientific_Opinion/biohaz_op_ej599_ listeria_en.pdf. EFSA: Request for updating the former SCVPH opinion on Listeria monocytogenes risk related to ready-to-eat foods and scientic advice on dierent levels of Listeria monocytogenes in ready-to-eat foods and the related risk for human illness. Scientic Opinion of the Panel on Biological Hazards (Question No EFSA-Q-2007-064) Adopted on 6 December 2007. [310] Cantaloupe. the international food safety network. foodsafety.ksu.edu. http://www. foodsafety.ksu.edu/articles/1183/cantaloupe_outbreaks_.pdf. [311] Multistate outbreak of listeriosis linked to whole cantaloupes from jensen farms, colorado. cdc centers for disease control and prevention. december 8, 2011. http://www. cdc.gov/listeria/outbreaks/cantaloupes-jensen-farms/120811/index.html. [312] Fda.environmental assessment: Factors potentially contributing to the contamination of fresh whole cantaloupe implicated in a multi-state outbreak of listeriosis. 10 2011. http://www.fda.gov/Food/FoodSafety/FoodborneIllness/ucm276247.htm. [313] Fda guidance for industry: Guide to minimize microbial food safety hazards for fresh fruits and vegetables. 10 1998. http://www.fda.gov/ Food/GuidanceComplianceRegulatoryInformation/GuidanceDocuments/ ProduceandPlanProducts/ucm064574.htm. [314] Tips for fresh produce safety: Safe handling of raw produce and fresh-squeezed juices. www.foodsafety.gov/keep/types/fruits/tipsfreshprodsafety.html. [315] http://www3.interscience.wiley.com/journal/122464707/abstract?CRETRY= 1&SRETRY=0. DellEra S, Buchrieser C, Couv E, Schnell B, Briers Y, Schuppler M, Loessner MJ.: Listeria monocytogenes L-forms respond to cell wall deciency by modifying gene expression and the mode of division. Molecular Microbiology, 73:306-322; Online: Jun 23 2009 DOI: 10.1111/j.1365-2958.2009.06774.x. [316] http://www.efsa.europa.eu/EFSA/efsa_locale-1178620753812_ 1178680093176.htm. EFSA: Request for updating the former SCVPH opinion on Listeria monocytogenes risk related to ready-to-eat foods and scientic advice on dierent levels of Listeria monocytogenes in ready-to-eat foods and the related risk for human illness - Scientic Opinion of the Panel on Biological Hazards . [317] http://www.ars.usda.gov/Services/docs.htm?docid=6786. Pathogen Modeling Program (PMP). [318] http://www.combase.cc/. The ComBase. [319] http://www.dfu.min.dk/micro/sssp/Home/Home.aspx. Danish Institute for Fisheries Researche: Seafood Spoilage and Safety Predictor (SSSP) software v. 2.0 .
USDA:
The
BIBLIOGRAPHY [320] http://www.symprevius.net/. Symprevius. [321] http://www.fda.gov/oc/initiatives/advance/food/plan.html. Protection Plan.
1799
FDA: Food
[322] http://jds.fass.org/cgi/content/abstract/91/2/523. Gougouli, M.; Angelidis, A. S.; Koutsoumanis, K.: A Study on the Kinetic Behavior of Listeria monocytogenes in Ice Cream Stored Under Static and Dynamic Chilling and Freezing Conditions. Journal of Dairy Science. 2008. 91:523-530. doi:10.3168/jds.2007-0255. [323] http://www.pnas.org/cgi/content/full/103/24/9274. M. van de Guchte, S. Penaud, C. Grimaldi, V. Barbe, K. Bryson, P. Nicolas, C. Robert, S. Oztas, S. Mangenot, A. Couloux, V. Loux, R. Dervyn, R. Bossy, A. Bolotin, J.-M. Batto, T. Walunas, J.-F. Gibrat, P. Bessires, J. Weissenbach, S. D. Ehrlich, and E. Maguin The complete genome sequence of Lactobacillus bulgaricus reveals extensive and ongoing reductive evolutionProc Natl Acad Sci USA 2006 Jun 13;103(24):9274-9. Epub 2006 Jun 5. [324] http://genome.jgi-psf.org/draft_microbes/lacde/lacde.home.html. Lactobacillus delbrkii subsp. Bulgaricus. JGI:
[325] Hammes, W.P. and R.F. Vogel. 1995. The genus Lactobacillus, pp. 19-54. In, B.J.B. Wood and W.H. Holzapfel (eds). The Genera of Lactic Acid Bacteria. Chapman & Hall, London. [326] Leong-Morgenthaler, P., C. Ruettener, B. Mollet, and H. Hottinger. 1990. Construction of a physical map of Lactobacillus bulgaricus. Proc. Third Symp. Lactic Acid Bact. A28. [327] http://www.efsa.europa.eu/EFSA/efsa_locale-1178620753812_ 1178620759439.htm. EFSA public consultation on the Qualied Presumption of Safety (QPS) approach for the safety assessment of microorganisms deliberately added to food and feed. [328] http://www.cdc.gov/eid/content/13/6/838.htm. Johnson JR, Sannes MR, Croy C, Johnston B, Clabots C, Kuskowski MA, et al.: Antimicrobial drug-resistant Escherichia coli from humans and poultry products, Minnesota and Wisconsin, 20022004. Emerg Infect Dis . 2007 Jun 6. [329] http://aem.asm.org/cgi/content/abstract/73/22/7162. Hantsis-Zacharov, Elionora; Halpern, Malka: Culturable Psychrotrophic Bacterial Communities in Raw Milk and Their Proteolytic and Lipolytic Traits. Applied and Environmental Microbiology, November 2007, p. 7162-7168, Vol. 73, No. 22.
1800
[330] http://ijs.sgmjournals.org/cgi/content/abstract/58/11/2635. HantsisZacharov, Elionora; Shakd, Tamar; Senderovich, Yigal; Halpern, Malka: Chryseobacterium oranimense sp. nov., a psychrotolerant, proteolytic and lipolytic bacterium isolated from raw cows milk. Int J Syst Evol Microbiol 58 (2008), 2635-2639; Doi 10.1099/ijs.0.65819-0. [331] http://jcm.asm.org/cgi/content/short/47/1/38. Han, Yiping W.; Shen, Tao; Chung, Peter; Buhimschi, Irina A.; Buhimschi, Catalin S.: Uncultivated Bacteria as Etiologic Agents of Intra-Amniotic Inammation Leading to Preterm Birth. J. Clin. Microbiol. 2009, 47: 38-47. [332] http://www.ncbi.nlm.nih.gov/pubmed/19432003. Register, K.B.; Kunkle, R.A.: Strain-specic virulence of Bordetella hinzii in poultry. Avian Dis. 2009 Mar;53(1):504. [333] http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool= pubmed&pubmedid=12682138. Register, K.B.; Sacco, R.E.; Nordholm, G.E.: Comparison of ribotyping and restriction enzyme analysis for inter- and intraspecies discrimination of Bordetella avium and Bordetella hinzii. J Clin Microbiol. 2003 Apr;41(4):1512-9. [334] http://www.pubmedcentral.nih.gov/picrender.fcgi?artid= 228927&blobtype=pdf. Funke, G,; Hess, T,; von Graevenitz, A,; Vandamme, P.: Characteristics of Bordetella hinzii strains isolated from a cystic brosis patient over a 3-year period. Journal of Clinical Microbiology, Apr. 1996, p. 966-969. [335] http://jmm.sgmjournals.org/cgi/content/full/56/12/1700. Fry NK, Duncan J, Edwards MT, Tilley RE, Chitnavis D, Harman R, Hammerton H, Dainton L.: A UK clinical isolate of Bordetella hinzii from a patient with myelodysplastic syndrome. J Med Microbiol. 2007 Dec;56(Pt 12):1700-3. [336] http://www.ncbi.nlm.nih.gov/pubmed/18799303. Driskell JD, Seto AG, Jones LP, Jokela S, Dluhy RA, Zhao YP, Tripp RA: Rapid microRNA (miRNA) detection and classication via surface-enhanced Raman spectroscopy (SERS). Biosens Bioelectron. 2008 Dec 1;24(4):923-8. Epub 2008 Aug 6. [337] http://en.wikipedia.org/wiki/MicroRNAs. Wikipedia: MicroRNA. [338] http://www.ncbi.nlm.nih.gov/pubmed/18801234. Li H, Tripp CP.: Detection of Bacillus globigii spores using a Fourier transform infrared-attenuated total reection method. Appl Spectrosc. 2008 Sep;62(9):963-7. [339] http://www.ncbi.nlm.nih.gov/pubmed/19331730. Xu Q, Pichichero ME, Casey JR, Zeng M.: Novel type of Streptococcus pneumoniae causing multidrug-resistant acute otitis media in children. Emerg Infect Dis. 2009 Apr;15(4):547-51. Doi: 10.3201/eid1504.071704.
BIBLIOGRAPHY
1801
[340] http://www.ncbi.nlm.nih.gov/pubmed/19366365. Dagan R.: Impact of pneumococcal conjugate vaccine on infections caused by antibiotic-resistant Streptococcus pneumoniae. Clin Microbiol Infect. 2009 Apr;15 Suppl 3:16-20. [341] http://www.ncbi.nlm.nih.gov/pubmed/19366366. Cohen R.: The need for prudent use of antibiotics and routine use of vaccines. Clin Microbiol Infect. 2009 Apr;15 Suppl 3:21-3. [342] http://en.wikipedia.org/wiki/Pneumonic_plague. Plague. Wikipedia: Pneumonic
[343] http://www.4to40.com/newsat4/index.asp?id=2864&news=Bubonic_plague. Outbreak of Pneumonic Plague in China. Chinese authorities recently announced an outbreak of the Pneumonic Plague, which could be worse than the current H1N1 virus that is threatening the world. Qinghai, China. 4To40.com. 8/7/2009. [344] http://www.bt.cdc.gov/agent/plague/factsheet.asp. Centers for Disease Control and Prevention CDC: Facts about Pneumonic Plague. [345] http://www.cdc.gov/ncidod/dvbid/plague/index.htm. Centers for Disease Control and Prevention CDC: CDC Plague Home Page. [346] http://www.nature.com/nature/journal/v461/n7263/full/nature08282.html. Snijder, Berend; Sacher, Raphael; Rm, Pauli; Damm, Eva-Maria; Liberali, Prisca; Pelkmans, Lucas: Population context determines cell-to-cell variability in endocytosis and virus infection. Nature, 2009; Doi: 10.1038/nature08282. [347] http://www.ncbi.nlm.nih.gov/pubmed/19135495. Daniel C, Sebbane F, Poiret S, Goudercourt D, Dewulf J, Mullet C, Simonet M, Pot B: Protection against Yersinia pseudotuberculosis infection conferred by a Lactococcus lactis mucosal delivery vector secreting LcrV. Vaccine. 2009 Feb 18;27(8):1141-4. Epub 2009 Jan 9. [348] http://www.environment.psu.edu/news/2009_news/sept_2009/logan_napa. asp. PSIEE: Renewable hydrogen production becomes reality at winery. September 29, 2009. [349] http://pubs.acs.org/doi/abs/10.1021/es803531g. Shaoan Cheng, Defeng Xing, Douglas F. Call and Bruce E. Logan. Direct Biological Conversion of Electrical Current into Methane by Electromethanogenesis. Environ. Sci. Technol. 2009, 43 (10), pp 3953-3958 Doi: 10.1021/es803531g. [350] http://www.kuwaittimes.net/read_news.php?newsid=NzkxMTE0NjY2. Order to withdraw of baby milk. Kuwait Times 03 February 2010. [351] http://en.wikipedia.org/wiki/Mycoplasma. Wikipedia: Mycoplasma.
1802
[352] http://www.ncbi.nlm.nih.gov/pubmed/20149967. Zhi Y, Mayhew A, Seng N, Takle GB: Validation of a PCR method for the detection of mycoplasmas according to European Pharmacopoeia section 2.6.7. Biologicals. 2010 Feb 9. [353] http://www.ncbi.nlm.nih.gov/pubmed/20149683. Asarnow D, Warford A, Fernandez L, Hom J, Sandhu G, Candichoy Z, Luna G, Goldman M, Rarich R. Validation and international regulatory experience for a mycoplasma touchdown PCR assay. Biologicals. 2010 Feb 9. [354] http://www.ncbi.nlm.nih.gov/pubmed/20149561. Kahya S, Temelli S, Eyigor A, Carli KT: Real-time PCR culture and serology for the diagnosis of Mycoplasma gallisepticum in chicken breeder ocks. Vet Microbiol. 2010 Jan 28. [355] http://www.ncbi.nlm.nih.gov/pubmed/20135349. Molla Kazemiha V, Shokrgozar MA, Arabestani MR, Shojaei Moghadam M, Azari S, Maleki S, Amanzadeh A, Jeddi Tehrani M, Shokri F: PCR-based detection and eradication of mycoplasmal infections from various mammalian cell lines: a local experience. Cytotechnology. 2010 Feb 6. [356] http://www.ncbi.nlm.nih.gov/pubmed/19392882. Schwartz SB, Thurman KA, Mitchell SL, Wol BJ, Winchell JM. Genotyping of Mycoplasma pneumoniae isolates using real-time PCR and high-resolution melt analysis. Clin Microbiol Infect. 2009 Aug;15(8):756-62. [357] http://www.ncbi.nlm.nih.gov/pubmed/20132436. Mohammadpour HA, Tracy CR, Redelman D, Dupre SA, Hunter KW: Flow cytometric method for quantifying viable Mycoplasma agassizii, an agent of upper respiratory tract disease in the desert tortoise (Gopherus agassizii). Lett Appl Microbiol. 2010 Jan 8. [358] http://www.ceeramtools.com/pdf/ceeram-tools.pdf. Fourrier A, Loisy-Hamon F, Guillaume J-M, Lebeau, B: CeeramTools molecular detection system for the detection of pathogens Brachyspira pilosicoli, Brachyspira hyodysenteriae and Brachyspira intermedia in pigs. Ceeram publication. [359] http://jcm.asm.org/cgi/content/full/41/7/3372. La T, Phillips ND, Hampson DJ: Development of a duplex PCR assay for detection of Brachyspira hyodysenteriae and Brachyspira pilosicoli in pig feces. J Clin Microbiol. 2003 Jul;41(7):3372-5. [360] http://www.ncbi.nlm.nih.gov/pubmed/19346708. Akase S, Uchitani Y, Sohmura Y, Tatsuta K, Sadamasu K, Adachi Y: Application of real time PCR for diagnosis of Swine Dysentery. J Vet Med Sci. 2009 Mar;71(3):359-62. [361] http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2680911. Hampson DJ, Ahmed N: Spirochaetes as intestinal pathogens: Lessons from a Brachyspira genome. Gut Pathog. 2009 May 1;1(1):10.
BIBLIOGRAPHY
1803
[362] http://www.ncbi.nlm.nih.gov/pubmed/19331734. Nelson EJ, Tanudra A, Chowdhury A, Kane AV, Qadri F, Calderwood SB, Coburn J, Camilli A: High prevalence of spirochetosis in cholera patients, Bangladesh. Emerg Infect Dis. 2009 Apr;15(4):5713. [363] http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2791440/. Naresh R, Song Y, Hampson DJ: The intestinal spirochete Brachyspira pilosicoli attaches to cultured Caco-2 cells and induces pathological changes. PLoS One. 2009 Dec 17;4(12):e8352. [364] http://www.ncbi.nlm.nih.gov/pubmed/20378723. Sato H, Nakamura SI, Habano W, Wakabayashi G, Adachi Y: Human intestinal spirochetosis in northern Japan. J Med Microbiol. 2010 Apr 8. [365] http://www.ncbi.nlm.nih.gov/pubmed/20226602. Klose V, Bayer K, Bruckbeck R, Schatzmayr G, Loibner AP: In vitro antagonistic activities of animal intestinal strains against swine-associated pathogens. Vet Microbiol. 2010 Feb 20. [366] http://www.ncbi.nlm.nih.gov/pubmed/19778354. Klose V, Bruckbeck R, Henikl S, Schatzmayr G, Loibner AP: Identication and antimicrobial susceptibility of porcine bacteria that inhibit the growth of Brachyspira hyodysenteriae in vitro. J Appl Microbiol. 2010 Apr;108(4):1271-80. [367] http://www.ncbi.nlm.nih.gov/pubmed/19356863. Bernardeau M, Gueguen M, Smith DG, Corona-Barrera E, Vernoux JP: In vitro antagonistic activities of Lactobacillus spp. against Brachyspira hyodysenteriae and Brachyspira pilosicoli. Vet Microbiol. 2009 Jul 2;138(1-2):184-90. [368] http://www.ncbi.nlm.nih.gov/pubmed/20200654. Tsinganou E, Gebbers JO: Human intestinal spirochetosis-a review. Ger Med Sci. 2010 Jan 7;8:Doc01. [369] http://www.ncbi.nlm.nih.gov/pubmed/20173181. Jensen TK, Christensen AS, Boye M: Brachyspira murdochii colitis in pigs.Vet Pathol. 2010 Mar;47(2):334-8. Epub 2009 Dec 31. [370] http://www.ncbi.nlm.nih.gov/pubmed/20095153. Myers SE, Dunn PA, Phillips ND, La T, Hampson DJ: Brachyspira intermedia and Brachyspira pilosicoli are commonly found in older laying ocks in Pennsylvania. Avian Dis. 2009 Dec;53(4):533-7. [371] http://www.ncbi.nlm.nih.gov/pubmed/19944544. Phillips ND, La T, Amin MM, Hampson DJ: Brachyspira intermedia strain diversity and relationships to the other indole-positive Brachyspira species. Vet Microbiol. 2009 Oct 29. [372] http://www.ncbi.nlm.nih.gov/pubmed/19480724. Hidalgo A, Carvajal A, Pringle M, Rubio P, Fellstroem C: Characterization and epidemiological relationships of Spanish Brachyspira hyodysenteriae eld isolates. Epidemiol Infect. 2010 Jan;138(1):76-85.
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[373] http://www.ncbi.nlm.nih.gov/pubmed/20124432. Palmer CV, Bythell JC, Willis BL: Levels of immunity parameters underpin bleaching and disease susceptibility of reef corals. FASEB J. 2010 Mar 10. [374] http://www.ncbi.nlm.nih.gov/pubmed/20455385. Salomon D, Barouti N, Rosset C, Whyndham-White C: Honey: from Noe to wound care. Rev Med Suisse. 2010 Apr 28;6(246):871-4. [375] http://www.ncbi.nlm.nih.gov/pubmed/20228250. Kwakman PH, te Velde AA, de Boer L, Speijer D, Vandenbroucke-Grauls CM, Zaat SA. How honey kills bacteria. FASEB J. 2010 Jul;24(7):2576-82. Epub 2010 Mar 12. DOI: 10.1096/fj.09-150789. [376] http://www.ncbi.nlm.nih.gov/pubmed/19673699. Boukraa L, Sulaiman SA: Rediscovering the antibiotics of the hive. Recent Pat Antiinfect Drug Discov. 2009 Nov;4(3):206-13. [377] http://www.ncbi.nlm.nih.gov/pubmed/19683834. Chernev I, Liguori PA, Senno SL, Peters KL, Bowers JM. Combined Noncontact, Low-Frequency Ultrasound and Medical Honey for the Treatment of Chronic Wounds: A Case Series. J Wound Ostomy Continence Nurs. 2010 Jun 20. [378] http://www.ncbi.nlm.nih.gov/pubmed/20549529. Cooper RA, Jenkins L, Henriques AF, Duggan RS, Burton NF: Absence of bacterial resistance to medical-grade manuka honey. Eur J Clin Microbiol Infect Dis. 2010 Jun 13. [379] http://www.ncbi.nlm.nih.gov/pubmed/20576085. Mohd Nasir NA, Halim AS, Banga Singh KK, Dorai AA, Muhammad Haneef MN: Antibacterial properties of tualang honey and its eect in burn wound management: a comparative study. BMC Complement Altern Med. 2010 Jun 24;10(1):31. [380] http://www.ncbi.nlm.nih.gov/pubmed/20542641. Glasser JS, Guymon CH, Mende K, Wolf SE, Hospenthal DR, Murray CK: Activity of topical antimicrobial agents against multidrug-resistant bacteria recovered from burn patients. Burns. 2010 Jun 7. [381] http://cmr.asm.org/cgi/reprint/20/3/391.pdf. Turnidge J, Paterson DL: Setting and revising antibacterial susceptibility breakpoints. Clin Microbiol Rev. 2007 Jul;20(3):391-408. [382] http://www.cell.com/retrieve/pii/S0092867410006628. Kale S, Gu B, Capelluto DGS, Dou D, Feldman E, Rumore A, Arredondo FD, Hanlon R, Fudal I, Rouxel T, Lawrence CB, Shan W, Tyler BM. External lipid phophatidylinositol 3-phosphate mediates entry of eukaryotic pathogen eectors into plant and animal host cells. Cell, 2010; DOI: 10.1016/j.cell.2010.06.008.
BIBLIOGRAPHY [383] http://en.wikipedia.org/wiki/Lipid_raft#T-cell_antigen_receptor_ signaling. Wikipedia: Lipid raft.
1805
[384] http://www.fda.gov/Food/ScienceResearch/LaboratoryMethods/ BacteriologicalAnalyticalManualBAM/default.htm. FDA: Bacteriological Analytical Manual. [385] http://www.fda.gov/Food/ScienceResearch/LaboratoryMethods/ BacteriologicalAnalyticalManualBAM/UCM063346. FDA: Bacteriological Analytical Manual. Chapter 3. Aerobic Plate Count. 11/10/2009. [386] http://www.fsis.usda.gov/Science/Microbiological_Lab_Guidebook/index. asp. USDA: Food Safety and Inspection Sevices: Microbiology Laboratory Guidebook. [387] Pallen MJ and Loman NJ. Will genomics transform medical microbiology? Genome Medicine, 3(53), 2011. http://genomemedicine.com/content/3/8/53/abstract. [388] Accuracy of diagnostic tests. http://www.rapid-diagnostics.org/accuracy.htm. [389] Oliveira AD, dAzevedo PA, de Sousa LB, Viana-Niero C, Francisco W, Lottenberg C, Martino MD, and Hing-Lima AL. Laboratory detection methods for methicillin resistance in coagulase negative staphylococcus isolated from ophthalmic infections. Arq Bras Oftalmol, 70(4):66775, 7-8 207. http://www.ncbi.nlm.nih.gov/pubmed/ 17906764. [390] Methicillin-resistant staphylococcus aureus (mrsa). detection and identication methods. http://www.rapidmicrobiology.com/test-methods/MRSA.php. [391] Sutherland A, Thomas M, Brandon RA, Brandon RB, Lipman J, Tang B, McLean A, Pascoe R, Price G, Nguyen T, Stone G, and Venter D. Development and validation of a novel molecular biomarker diagnostic test for the early detection of sepsis. Crit Care, 15(3):R 149, 6 2011. http://www.ncbi.nlm.nih.gov/pubmed/21682927. [392] Who: Laboratory-based evaluation of 19 commercially available rapid diagnostic tests for tuberculosis. http://apps.who.int/tdr/ publications/tdr-research-publications/diagnostics-evaluation-2/ pdf/diagnostic-evaluation-2.pdf. [393] Esparcia O, Espa nol M, Garrig M, Moreno C, Montemayor M, Navarro F, and Coll P. Use of dierent pcr-based techniques integrated into a non-tuberculous identication algorithm. Enferm Infecc Microbiol Clin, 9 2011. http://www.ncbi.nlm.nih. gov/pubmed/21924798. [394] Shetty N, Wren MW, and Coen PG. The role of glutamate dehydrogenase for the detection of clostridium dicile in faecal samples: a meta-analysis. J Hosp Infect, 77(1):16, 1 2011. http://www.ncbi.nlm.nih.gov/pubmed/21145132.
1806
[395] Knetsch CW, Bakker D, de Boer RF, Sanders I, Hofs S, Kooistra-Smid AM, Corver J, Eastwood K, Wilcox MH, and Kuijper EJ. Comparison of real-time pcr techniques to cytotoxigenic culture methods for diagnosing clostridium dicile infection. J Clin Microbiol, 49(1):22731, 1 2011. http://jcm.asm.org/cgi/content/full/49/1/ 227?view=long&pmid=20980562. [396] Lee BE, Mukhi SN, May-Hadford J, Plitt S, Louie M, and Drews SJ. Determination of the relative economic impact of dierent molecular-based laboratory algorithms for respiratory viral pathogen detection, including pandemic (h1n1), using a secure web based platform. Virol J. http://www.ncbi.nlm.nih.gov/pubmed/21645365. [397] Ciblak MA, Kanturvardar M, Asar S, Bozkaya E, Yenen OS, and Badur S. Sensitivity of rapid inuenza antigen tests in the diagnosis of pandemic (h1n1)2009 compared with the standard rrt-pcr technique during the 2009 pandemic in turkey. Scand J Infect Dis, 42(11-12):9025, 12 2010. http://www.ncbi.nlm.nih.gov/pubmed/ 20662619. [398] Yang H, Li D, He R, Guo Q, Wang K, Zhang X, Huang P, and Cui D. A novel quantum dots-based point of care test for syphilis. Nanoscale Res Lett, 5(5):8758, 3 2010. http://www.ncbi.nlm.nih.gov/pubmed/20672123. [399] Binnicker MJ, Jespersen DJ, and Rollins LO. Treponema-specic tests for serodiagnosis of syphilis: comparative evaluation of seven assays. J Clin Microbiol, 49(4):13137, 4 2011. http://www.ncbi.nlm.nih.gov/pubmed/21346050. [400] Kilic A and Basustaoglu AC. Double triplex real-time pcr assay for simultaneous detection of staphylococcus aureus, staphylococcus epidermidis, staphylococcus hominis, and staphylococcus haemolyticus and determination of their methicillin resistance directly from positive blood culture bottles. Res Microbiol, 9 2011. http://www.ncbi.nlm.nih.gov/pubmed/21925597. [401] Prilutsky D, Shneider E, Shefer A, Rogachev B, Lobel L, Last M, and Marks RS. Dierentiation between viral and bacterial acute infections using chemiluminescent signatures of circulating phagocytes. Analytical Chemistry, 83(11):4258, 2011. http: //pubs.acs.org/doi/abs/10.1021/ac200596f. [402] Luminol. Wikipedia. http://en.wikipedia.org/wiki/Luminol. [403] Bowers RM, Sullivan AP, Costello EK, Collett JL, Knight R, and Fierer N. Sources of bacteria in outdoor air across cities in the midwestern united states. Applied and Environmental Microbiology, 2011. http://aem.asm.org/cgi/content/abstract/ AEM.05498-11v1.
Chapter 25 Virology
Virology is the study of viruses and virus-like agents: their structure, classication and evolution, their ways to infect and exploit cells for virus reproduction, the diseases they cause, the techniques to isolate and culture them, and their use in research and therapy. Virology is often considered a part of microbiology or of pathology.
25.0.9
The International Committee on Taxonomy of Viruses (ICTV) [1]
The International Committee on Taxonomy of Viruses (ICTV) develops an internationally agreed taxonomy for viruses, develops internationally agreed names for virus taxa, including species and subviral agents, and maintains an Index of virus names. Study Groups are responsible for proposing new species or higher taxa in their families by submitting taxonomic proposals to the appropriate Subcommittee. Subcommittees of the ICTV are: Viruses of Vertebrates, Viruses of Plants, Viruses of Insects, Viruses of Prokaryotes, Viruses of Fungi. Meetings of the ICTV process the taxonomic proposals and include them in the virus taxonomy database. [2]
25.1
25.1.1 25.1.2
Diseases caused by viruses

Arboviruses Oropouche virus
It is a tropical viral infection, a zoonosis similar to dengue fever, transmitted by biting midge (species Culicoides paraensis) and mosquitoes from the blood of sloths to humans. It occurs mainly in the Amazonic region, the Caribbean and Panama. 1807
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CHAPTER 25. VIROLOGY
25.1.3
Venezuelan equine encephalitis virus
It is a mosquito-borne viral pathogen that causes Venezuelan equine encephalitis or encephalomyelitis (VEE) can aect all equine species, such as horses, donkeys, and zebras. After infection, equines may suddenly die or show progressive central nervous system disorders. Humans also can contract this disease. Healthy adults who become infected by the virus may experience u-like symptoms, such as high fevers and headaches. People with weakened immune systems and the young and the elderly can become severely ill or die from this disease.
25.1.4
Dengue virus [3]
Dengue is a mosquito-borne infection that causes a severe u-like illness, and sometimes a potentially lethal complication called dengue haemorrhagic fever. Dengue is transmitted by several species of mosquito within the Aedes genus, principally Aedes aegypti which acquired the virus an infected persons or monkeys. There is no vaccine. Prevention concentrates on reducing the habitat and the number of mosquitoes and limiting exposure to bites. The incidence of dengue has grown dramatically around the world in recent decades. Some 2.5 billion people, two fths of the worlds population, are now at risk from dengue. Laboratory diagnosis Laboratory diagnosis methods for conrming dengue virus infection may involve detection of the virus, viral nucleic acid, antigens or antibodies, or a combination of these techniques. After the onset of illness, the virus can be detected in serum, plasma, circulating blood cells and other tissues for 4-5 days. During the early stages of the disease, virus isolation, nucleic acid or antigen detection can be used to diagnose the infection. At the end of the acute phase of infection, serology is the method of choice for diagnosis. Diagnostic methods Virus isolation, genome detection, NS1 detection, serology IgM, serology IgG, haematological tests (Platelets and haematocrit values). There are four serotypes of dengue virus (DENV-1 to 4) causing dierent symptoms, such as Dengue haemorrhagic fever. Lima et al 2011 investigate the usefulness of NS1 capture tests as an alternative tool to detect DENV in tissue specimens from dengue fatal cases occurred in 2002 in Brazil. The authors evaluated three tests for NS1 antigen capture: rst generation Dengue Early ELISA, Platelia NS1 and the rapid test NS1 Ag Strip. The NS1 Ag Strip achieved the best results of all three tests. The authors concluded that DENV NS1 capture assay is a rapid and valuable approach to postmortem dengue conrmation in dierent tissues. [4]
25.1. DISEASES CAUSED BY VIRUSES Polyclonal antibodies against Dengue virus Protein expressed in E.coli [5]
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The non-structural 1 (NS1) protein plays an important role in dengue diagnosis. It is present as serum antigen in both primary and secondary infections. Alonso and colleagues 2011 describe a polyclonal antibody produced from the properly folded E. coli recombinant NS1 (rNS1) protein which could detect 100% of the Dengue virus 2 (DENV2) in infected patients. The study demonstrates the correctly folding rNS1 that maintains its structural and immunogenic properties, enabling an early diagnosis. Testing saliva for Dengue antibodies in early phase of regions with secondary infections [6] Yap and colleagues 2011 used an antigen capture anti-DENV IgA (ACA) ELISA technique to test saliva samples for Dengue antibodies. The sensitivity within 3 days from fever onset was over 36% in primary dengue infections, and 100% in secondary infections,within 1 Day after fever onset. Testing saliva is much cheaper then performing tests on venous blood. The authors suggest that saliva should be tested to detects dengue virus (DENV)-specic immunoglobulin A (Ig A) early in the phase of a dengue infection. The Asian tiger mosquito, a new vector of Dengue and tropical diseases in Europe French researchers are watching the Asian tiger mosquito (Aedes albopictus), capable of spreading dengue fever and other tropical diseases in temperate Europe. Traps are to survey mosquitoes laying their eggs. The mosquito is black-and white tiger-like striped. It is able to spread many kinds of viruses, such as dengue, West Nile virus, St. Louis encephalitis and chikungunya, a disease of the joints. The researchers warn that the insect may spread the tropical diseases brought in by infected passengers arriving from tropical countries where such diseases are endemic. The mosquito was rst spotted in Albania in 1979, caused an outbreak of chikungunya in Italy in 2007, and ten cases of dengue in Croatia and two cases of both diseases on south France in 2010. It is spreading north and west in Europe. Entomologists in 20 European countries,including Germany, Belgium and the Netherlands are monitoring the mosquito. According to the French entomologist Jean-Baptiste Ferre, the danger of spreading tropical diseases is low, however, the risk will increase if the number of mosquitoes rises.
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Picture: CDC: Aedes albopictus female mosquito obtaining a blood meal from a human host. http://phil.cdc.gov/phil/details.asp?pid=4487 http://phil.cdc.gov/phil/details.asp?pid=1866 The report of Iia phase test of dengue vaccine CYD-TDV The dengue vaccine CYD-TDV of the French drugmaker Sano SA, in Phase IIa proved only 30 per cent eective instead of the predicted 70 per cent. Thailand is heavily aected by the mosquito-borne disease, also known as "breakbone fever" which is also spreading in the Dominican Republic. It is being believed that the mixed dengue vaccine containing four dierent virus strains can produce uneven results, indermining the hopes of the researchers. However, the ongoing nal-stage phase 3 study with a high number of participants seem to produce much better results. Findings of IIa phase test [7] Ecacy was 30.2% (2,8 per cent of vaccinated children had Dengue fever and 4,4 per cent of not vaccinated children became ill), and diered by serotype. Dengue vaccine was well tolerated, with no safety signals. The authors of the study commented that the data of protected participants were not signicant. Ongoing large-scale phase 3 studies in various epidemiological settings will provide more data for the CYD dengue vaccine of Sano. There are four serotypes of Dengue virus. The ecacy of the vaccine varied between 60 to 90 per cent against the Dengue virus Serotype DNV 1, DNV 3 and DNV 4. Only the serotype DNV 2Dengue was resistant to the vaccine. Scott B Halstead, who wrote an accompanying commentary on the study in The Lancet, said it was possible that a vaccine against three out or four virus strains might still combat dengue eectively, since severe disease is caused by a second infection. however, more research is needed. [8] Jonas Schmidt-Chanasit, a German expert of viral diagnostics of the Bernhard-NochtInstitute for Tropical Medicine (BNI) in Hamburg, Germany, warns for high expectations on the outcomes of the vaccine CYD-TDV. The initial goal had been to tackle all four serotypes. To control only three serotipes is not enough to eradicate the disease. [9] Live vaccines require up to three doses of the vaccine be given over a 12-month period of time. The DENV vaccine is being developed to achieve immune protection when given over the course of a few months, writes Durbin and Whitehead 2011. The DENV vaccine is a live attenuated chimeric vaccine The researchers are also working on DNA vaccines, recombinant adenovirus vectored vaccines, alphavirus replicons, and sub-unit protein vaccines. [10]
25.2. VIRAL HEPATITIS
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25.1.5
Yellow fever
It is also endemic. Nonhuman primates are the principal reservoirs of the disease during its sylvatic cycle. Vaccination is an essential means of protection against yellow fever for both the local population and visitors. Aedes aegypti mosquitoes in Amazonian urban centers pose an ever-present risk for yellow fever transmission and are also responsible for the high incidence of dengue.
25.2
Viral hepatitis
It is an acute liver disease with varying severity caused by the hepatitis A virus (HAV), contamination by fecal matter and ingestion of contaminated food or drinks.
25.2.1
Hepatitis A virus
The delay of incubation oh hepatitis A virus is around thirty days. The severity of the clinical signs vary from asymptomatic case in children younger than 6 years old with cases of acute or fulminant hepatitis. Fecal-oral parental, sexual, salivary or urinary transmissions are reported. There is no specic curative treatment but a vaccine is available. Hepatitis A virus can resist to dierent physical and chemical treatments, and can survive in dierent kind of environment for a long period. The diagnostic by cellular culture or ELISA is not adapted to the detection of Hepatitis A virus in environmental or food samples. Molecular techniques (real time RT-PCR) are the methods of choice for Hepatitis A detection after extraction and viral RNA purication from the sample.
25.2.2
Hepatitis B virus (HBV)
Contamination by contact with infectious blood, semen, and other body uids from having sex with an infected person, sharing contaminated needles to inject drugs, or from an infected mother to her newborn. Ancient hepatitis B virus found in mummy of the 16th-century An ancient hepatitis B virus (aHBV)-DNA sequences was isolated of the liver of a mummied Korean child dated of the 16th-century. The DNA is 3,000 to 100,000 years ago old. Its genetic sequence, compared with actual viral genomes show changes which may have their origin in immunologic, environmental and pharmacologic mutations an environmental pressures acting during milleneans. The complete genome of 3,215bp is a unique aHBV genotype C2 sequence of Southeast Asia which diers from actual HBV/C2 DNA sequences along four open reading frames.
1812 [11]
Bar-Gal et al. 2012 write that the aHBV/C2 genome may be used as basis for further researches on the evolution and spread of chronic hepatitis B from China and Japan to Korea and Australia, causing cirrhosis and liver cancer. The disease causes the death of 600.000 people per year. Hepatitis B is endemic in Africa, China and other parts of Asia, as well in the Amazon and the southern parts of eastern and central Europe. Hepatitis B vaccine is 95% eective in preventing infection and its chronic consequences, and is the rst vaccine against a major human cancer. [12] Two distinct subtypes of hepatitis B virus-related acute liver failure [13] Dao et al. 2012 describes the imunological dierenciation of the acute HBV infection (AHBV-ALF) and the exacerbation of chronic HBV infection (CHBV-ALF) , both processes may end in Hepatitis B virus (HBV)-related acute liver failure (HBV-ALF). The authors found that measurements of immunoglobulin M (IgM) anti-hepatitis B core antibody (anti-HBc) titers and of HBV viral loads (VLs) might allow the separation of AHBV-ALF from CHBV-ALF. The researchers conclude that AHBV-ALF and CHBVALF dier markedly in IgM anti-HBc titers, in HBV VLs, and in prognosis.
25.2.3
Vaccination, screening of migrants and injecting drug users [14]
Hatzakis et al. 2011 report that worldwide, the hepatitis B virus (HBV) and the hepatitis C virus (HCV) cause, respectively, 600,000 and 350,000 deaths each year. Viral hepatitis is the leading cause of cirrhosis and liver cancer, and is the third cause of cancer death worldwide. The authors point out that the most eective means of prevention against HBV is vaccination, and screening of migrants and injecting drug users (IDU) is eective and potentially cost-eective. The authors call for a concerted eort of the members of the EU to implement lasting, eective policies and programmes and increase the public health activities to face viral hepatitis
25.2.4
Hepatitis C virus (HCV)
Contamination by contact with the blood of an infected person, primarily through sharing contaminated needles to inject drugs.
25.2.5
Hepatitis D (HDV) virus
Contamination by contact with infectious blood, similar to how HBV is spread.

25.3. VIRAL INFECTIONS
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25.2.6
Hepatitis E virus (HEV)
Contamination by ingestion of fecal matter, even in microscopic amounts; outbreaks are usually associated with contaminated water supply in countries with poor sanitation.
25.2.7
Kaposi sarcoma-associated herpesvirus ( HHV-8)
It is the eighth human herpesvirus. It causes Kaposis sarcoma, a cancer commonly occurring in AIDS patients, as well as primary eusion lymphoma and some types of multicentric Castlemans disease.[15]
25.3
Viral infections
The cause of infectious diarrhoea were usually told to be bacterial or parasitic. Only recently, beginning with the 70 decade of 2000 better diagnostic methods have proved that food-borne diseases caused by virus are very frequent. The most important agents of these diseases are: Mouth and foot disease virus: is present in all kind of tissues of cattle and swine (Hepatitis A-virus, Hepatitis E-virus phage).
25.3.1 25.3.2
The name of viruses Animal viruses
Viruses which attack animals were named based on the disease which they caused followed by the word virus, such as inuenza virus,poliovirus, human immunodeciency virus (HIV).
25.3.3
Viruses living on plants
They are named according to the plant they live on, followed by the main symptoms of the disease which they cause, such as tobacco mosaic virus (TMV) tomato bushy stunt virus (TBSV), raspberry ringspot virus. However, plant viruses may infect a variety of other plants, such as the cucumber mosaic virus (CMV)may cause up to 80 sets of symptomn in various host plants.
25.3.4
Bacterial viruses
Bacterial viruses are named by code letters or by a system of letters such as phage , Q , T2, X174. These names of bacterial viruses do not follow any rules, and were given by the laboratories which were studying the virus such as the virus MS2 so called because it was the second isolate of a virus infecting male specic strains of E. coli.
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25.4
Inuenza viruses
They can be divided in three types: A, B and C. Especially the type A undergoes genetic variation. That is the reason why often new strains of inuenza arise. These strains are called serotypes because they can be distinguished by serological agglutination tests. Inuenza-A-virus: is found in lung of swine. It is the most common type of inuenza outbreaks in humans.
25.4.1
Avian inuenza A and Newcastle disease
Both aect avian species.Criteria for contengy plans in case of both diseases are found Annexe IV of Council Directive 92/40/EEC of 19.5.1992 and Directive 92/66/EEC introducing Community measures for the control of both diseases, involving poultry producers,operators of slaughterhouses and rendering plants,veterinarians, and diagnostic laboratories. The Directive 92/40/EEC lays down Community measures to eradicate and prevent the spread of avian inuenza on poultry farms should an outbreak occur and prohibits removal of the poultry and poultry products from specied areas such as protection or surveillance zones. Avian inuenza has a high mortality and a rapid spread. Infection occurs through direct contact between the animals or vectors such as man,birds, utensils,transport devices such as packaging materials such as egg trays. Avian inuenza (Subtype H7N7)which has caused an epidemic spread in the Netherlands in February 2003 is not infectious to mankind. There are 15 inuenza virus A subtypes that can infect poultry. Vaccination is therefore not possible as there is no cross-immunity. Inuenza vaccination is not eective against H5N1 virus. It is intended to avoid H5N1 to cross with human inuenza types and become highly infective for humans. The Incubation period is 8 days and quarantine 21 days.
25.4.2
Bird ue H5N1 becomes more easily transmissible, fear scientists [16]
Chen, 39, a Chinese bus driver tested positive for the H5N1 bird u virus. He died on December 31, 2011 at the city of Shenzhen near Hong Kong, where more than 19.000 birds were slaughtered and imports and sales of live poultry were banned for three weeks following a positive test for H5N1 at a chicken carcass. Chen had no contact with poultry. The H5N1 virus rarely infects humans which come into close contact with diseased poultry. However, the mortality among infected people is nearly 60 percent. Scientists fear that the virus is becoming more easily transmissible from human to human. About 120 people had contact with Chen, however, no one become sick so far.
25.4. INFLUENZA VIRUSES
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WHO says globally there have been 336 human deaths from 573 conrmed bird u cases since 2003. Of these, 40 cases were in China, 26 of which were fatal. Chinas last case of H5N1 was reported in June 2010 when a women died after exposed to sick and dead poultry.
25.4.3
Avian inuenza H5N1 animal- human [17]
The highly pathogenic avian inuenza A H5N1 viruses poses a risk to humans because of the endemicity in poultry populations in several countries, such as Asia and Egypt. A reassortment with the H1N1 pandemic strain is possible. Transmission of the H5N1 virus from poultry to humans is rare, and is attributed to contact with infected blood or bodily uids of infected poultry via food preparation practices, touching and caring for infected poultry, consuming uncooked poultry products, exposure to H5N1 via swimming or bathing in potentially virus laden ponds; and exposure to H5N1 at live bird markets. Environmental contamination may also occur by inhalation, ingestion, conjunctival or intranasal inoculation of contaminated water, mud, cleaning poultry areas, removing faeces, gathering eggs, using poultry waste/scrap as fertilizer, etc. Inhalation of virus at LBM, or in village/household where poultry have been recently sick or died. Occasional limited human-to-human transmission occur. The authors stress the importance of collaboration between human and animal health sectors for surveillance, case investigation, virus sharing, and risk assessment is essential to monitor for potential changes in circulating H5N1 viruses Rabinowitz et al 2010 suggest that direct contact with sick birds is not the only means of human exposure to avian inuenza H5N1 virus. The authors stress ther necessity to study the environmental virus persistence, the shedding of virus by asymptomatic poultry and disease pathophysiology in dierent avian species relative to human zoonotic risk, as well as specic modes of zoonotic transmission, should be determined. [18]
25.4.4
Bird migration routes and risk for pathogen dispersion
Jourdain et al. 2007 analysed the inuence of wild bird migration routes and risk for pathogen dispersion. Birds can move fast over large distances, such as the the arctic tern (Sterna paradisaea), which travels u p to 50,000 km between Antarctica and northern Scandinavia during a period of one year. During their migration birds carry pathogens that can be transmitted between species at breeding, wintering, and stopover places. [19] The authors considered the area of the Camargue (southern France) as an example to assess the transmission risk for birdborne diseases in the western Mediterranean wetlands, focusing on avian inuenza and West Nile viruses because birds play an important role in the epidemiology of these viruses.
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Bird abundance, migration, geographic origin, and interspecies mingling are highlighted in this study, which analyses the role of birds ying north coming from the sub-Saharan Africa, heading south coming from northern areas of Tundra and Taiga, and birds coming from the continental Europe.
25.4.5
Birds Coming from sub-Saharan Africa
The risk for introduction of African pathogens in Mediterranean wetlands would be highest during spring migration and breeding from March to July. Introduction in Africa of pathogens originating from the north occurs in autumn. Although birds migrating from sub-Saharan regions do not play a major part in the epidemiology of AI viruses, it might explain why an outbreak occurred in 2000 in the Camargue.
25.4.6
Birds Coming from Northern Areas of Tundra and Taiga
AI viruses may be introduced into Mediterranean wetlands by birds coming from northern areas of Scandinavia and Siberia. The risk would be higher from September to December, but WNV activity has never been reported in Scandinavia and Siberia, probably because the transmission cycle cannot be maintained in these northern biotopes.
25.4.7
Birds Coming from Continental Europe
The transmission of bird pathogens originating from continental Europe would be most likely in autumn and in winter. Aquatic birds, which need unfrozen ponds to feed, show variations in their movements, depending on climatic conditions. Surveys of have shown that AI viruses are frequently associated with wild waterbirds in continental Europe which may therefore spread the virus in the Camargue.
25.4.8
Risk for Bird-to-Bird Transmission of Pathogens
The risk for bird-to-bird transmission depends on bird abundance or density, bird diversity, species receptivity and sensitivity to pathogens, interspecies interactions, and environmental conditions. Human activities such as legal or illegal trade of wild and domestic birds or bird products are also spreading bird-carried pathogens. The pathogenic AI strain H5N1 was isolated in Belgium from crested hawk-eagles (Spizaetus nipalensis) smuggled by air travel, and this virus was spread in Asia at live-poultry markets and by the international trade of birds, bird products, or contaminated equipment. The authors suggest to include mathematical modelling, databases of long-term records to unveil bird-pathogen relationships in natural conditions. These data should focus on hosts, their migration, population age, behaviour, and other informations. Host-pathogen interactions should be described by using data such as antibody prevalence in dierent
1817
age classes, frequency of virus isolation, and characterization of the strains involved, to understand the hosts, pathogens, predators, competitors relationship. Cui et al 2011 studied the inuence of wild birds in the spread of H5N1 virus in Qinghai Lake area, which is an important breeding and stopover site for aquatic birds along the Central Asian Flyway. The authors determined the high-risk species to be of the family Anatidae, order Anseriformes (9/14 in spring, 11/15 in fall). The authors found that species from family Anatidae accounted for over 39% and over 91% of the total risk at spring and fall migration periods, respectively. [20]
25.4.9
Passerines are more important avian ue transmitter than aquatic birds [21]
Waterfowl are linked with avian inuenza, however, Fuller and colleagues 2010 emphasizes that 22 species of song birds and perching birds are also reservoirs of inuenza. The authors point out that the inuenza prevalence in passerines is high. These birds share the same habitat as poultry and are more eective transmitters of the disease to humans than aquatic birds. Cloacal samples indicate that the prevalence of inuenza in passerines is greater than the prevalence in eight other avian orders. Data of this study identies the Great Plains and the Pacic Northwest as high-risk areas for Avian inuenza virus. The authors also stress that the amount of harvested cropland are highly signicant predictors of Avian inuenza virus, because of the reduction of natural habitat available to avian migrants, This is also valid for the rst day of the year when a county is snow free and birds may move in.
25.4.10 25.4.11
WHO urges consumer to maintain precautions against avian u [22] [23] New cases in China in January 2009
Chinese health authorities are worried with a third case of bird u. No abnormality was found in poultry farms or agriculture markets where the child where the last case had been in contact with. Health ocials say if there is no avian u outbreak in poultry and yet there are human cases, a change in the virus might have happened, so that chicken do not get sick, but the H5N1 virus remains deadly to humans. Another possibility of "silently infected chickens" carrying the virus or transmitting the disease without bird u-like symptoms.
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25.4.12
Precaution
WHO urges consumer to maintain normal precaution against avian inuenza, such as ensuring all poultry is well cooked and always washing hands after contact with raw meat.
25.4.13
New case in Egypt
A new human case of avian inuenza A(H5N1) virus infection was hospitalized on 10 January 2009 and is currently in a stable condition. The patient had contact with sick and dead poultry. Of the 52 cases conrmed to date in Egypt, 23 have been fatal. [24]
25.4.14
Vaccination against avian inuenza of H5 and H7 subtypes in domestic poultry and captive birds [25]
Control measures of the HPAI strain of H5N1 are based on eradication of infected ocks, but increasingly more countries supplement these measures by the use of vaccination which is becoming important to control and prevent the propagation of the disease. The opinion of the European Scientic Panel on Animal Health and Welfare is intended to support the Commission in the further developments of a vaccination policy and was adopted on 11 May 2007. According to this opinion, the current EU authorised AI vaccines for poultry such as chickens and ducks meet the relevant quality standards and are thus, safe and eective to be used. However, for other poultry and captive bird species the level of eectiveness of current AI vaccination is not suciently known and therefore additional data on the immunogenicity and eectiveness of current and future AI vaccines should be generated. In general, the use of AI vaccines in poultry should be dened in advance dependant on the epidemiological situation, geographical area and overall risk perception as a preventive, emergency or in endemic situations. Vaccination may also reduce transmission of AI virus amongst captive and wild birds, having also major benets for animal welfare as vaccination will prevent them from contracting the disease, death and from being culled during eradication measures. Silent spread of AI viruses can occur after vaccination, and therefore serological monitoring with DIVA based strategies will be required to detect AI virus transmission after vaccination (shedding of the virus without presenting symptoms of the disease). Vaccination programmes using vaccines authorised by the competent authority may reduce the potential for human and other mammalian cases of HPAI, where the disease may become endemic. The use of EU authorised vaccines per se is recommended because is safe
25.4. INFLUENZA VIRUSES and has no negative eect on poultry products for consumers.
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On the evaluation of laboratory testing methods for surveillance of vaccinated ocks (in particular DIVA strategy), it is concluded that to date only conventional inactivated and recombinant live-vectored vaccines are available for use and can be coupled with a suitable companion diagnostic test. An intrinsic problem of the DIVA principle is that infections with all AI subtypes (including non H5 and H7) may interfere. The "DIVA" (Dierentiating Infected from Vaccinated Animals) a control strategy for avian inuenza infections in poultry is based on the use of an inactivated oil emulsion vaccine containing the same haemagglutinin (H) subtype as the challenge virus, but a dierent neuraminidase (N). [26] The "ad hoc" serological test based on the detection of specic anti-N1 antibodies. "DIVA" control strategy may represent a tool for the control of avian inuenza infections in poultry to dierentiate between vaccinated and naturally infected birds. [26]
The H7N9 avian ue virus outbreak is responsible for already 18 deaths in China [27] China has sent a specime of the H7N9 avian u virus to Taiwan which is trying to cooperate in the production of a vaccine and further research on diagnosis of this new strain of ue virus, reports the Taiwanese Centers for Disease Control (CDC). The virus is responsible for already 18 deaths and infected dozens in China. Taiwan fears the strain may cross the strait which separates it from the mainland. Measures to reduce the risk of a spread of the virus to Taiwan include temperature checks at airports on Chinese passengers and more than 100 birds smuggled from the mainland and seized by the coastguard have been destroyed. A ban on the slaughtering of live poultry at traditional wet markets to be implemented by the Council of Agriculture since there are enough certied poultry slaughterhouses to meet the local market demand. In terms of intensied surveillance for the H7N9 virus in animals, the Council of Agriculture has increased the sample size and frequency of farm inspections, covering live poultry, pet birds, pigs and wild-bird droppings. Thus far, no inuenza A (H7N9) antibody or virus has been detected in any of the specimens.
1820 The dierent strains of avian ue [28]
Humans are rarely infected with avian inuenza viruses, with the exception of highly pathogenic avian inuenza A(H5N1) viruses, which have caused 634 infections and 371 deaths as of 12 March 2013. A few isolated cases of human infection with viruses of the H7N2, H7N3, and H7N5 subtypes have been reported, but none were fatal. In 2003, in the Netherlands, 89 people were infected with an inuenza virus of the H7N7 subtype that caused conjunctivitis and one fatality. Kageyama et al. 2013 present the sequences of the avian inuenza A(H7N9) viruses that caused fatal human infections in China. The authors stress that these viruses possess several characteristic features of mammalian inuenza viruses, which are likely to contribute to their ability to infect humans and raise concerns regarding their pandemic potential. When compared with A(H5N1) viruses, animal-to-human transmissibility seems to be higher for inuenza A(H7N9). The new virus is a reassortant virus based on an haemaglutinin antigen A(H7) to which most humans will not have been exposed. Therefore, if human-to-human transmission starts, population immunity cannot be presumed. [29]
25.4.15
Reassortment or point mutations of H9N2 inuenza virus is predicted to become a new pandemic, says University of Maryland researcher [30] [31]
The avian N9N2 is endemic and presents occasional transmission to humans and pigs Perez and colleagues 2009 in an article in the Proceedings of the National Academy of Sciences of the United States of America report how the current swine inuenza strain formed. The authors write that avian, swine, and human-like viruses combined in a pig to make the new virus. It then mutated to be able to spread by human respiratory. The infection of avian inuenza viruses from birds to humans may cause a serious disease, however, the spread from human to human is rare. A pig can host both avian and human-like viruses where they can combine and form hybrid avian-human viruse. These viruses can infect humans. The immune system is not prepared to ght them because the surface proteins are new. This type of virus can easily mutate to spread quickly and potentially cause a human pandemic. The authors reverse genetics mutated the H9N2 inuenza virus, creating a hybrid humanavian virus. The new hybrid had internal human u genes and surface avian u genes from the H9N2 virus. The combination avian and human inuenza virus under laboratory conditions was similar to the origin of the swine u virus H1N1 of the actual outbreak. Ferrets were infected with the virus created by the researchers. The mutated virus was able to spread by respiratory droplets.
1821
Only two mutations were necessary to make the hybrid H9N2 transmissible. A human pandemic of this virus is predictable. Perez suggests that the H1N1 swine u virus mutated in a similar form as shown with the H9N2 in his research. The two genetic mutations took place in the lab strain, one on the HA surface protein enabled respiratory transmission between mammals and the other mutation was the site where human antibodies would bind but is dierent from actual vaccine stocks. The H9N2 is therefore a new candidate for a pandemic. The authors concluded that the reassortant virus expressing only the hemaglutinin HA and the neuraminidase (NA) of the ferret-adapted virus was able to account for the transmissibility. The currently circulating avian H9N2 viruses require little adaptation to turn pandemic. Aerosolized respiratory transmission may also be caused by others then by the current human H1, H2, and H3 inuenza subtypes.
25.4.16
Reassortment may increased pathogenicity of pandemic (H1N1) [32]
Schrauwen and colleagues 2011 report that three inuenza A viruses (seasonal (H3N2), seasonal (H1N1), and pandemic (H1N1) 2009) were found to be circulating during the swine ue pandemic which started in 2009. The authors are concerned with the possibility of genetic reassortment between these viruses. The resulting strains my present increased pathogenicity. The authors tested four reassortant viruses determining their replication kinetics in vitro and pathogenicity and transmission in ferrets. Pandemic (H1N1) 2009 with neuraminidase of seasonal (H3N2) virus resulted in increased virus replication and produced severe pulmonary lesions, while pandemic (H1N1) 2009 viruses containing basic polymerase 2 alone or in combination with acidic polymerase of seasonal (H1N1) virus were attenuated in ferrets. The authors concluded that pandemic (H1N1) 2009 virus has the potential to reassort with seasonal inuenza viruses, which may increase its pathogenicity and maintains the abillity of transmission through the aerosols or respiratory droplets.
25.4.17
Mutations which may aect oseltamivir resistance of inuenza A pandemic (H1N1) [33]
Hurt et al 2011 report that I117V mutation in pandemic H1N1 is rare, and was detected in only one isolate from Australia. It confers only a mild resistance to oseltamivir, but combined with H275Y it exerts a synergistic eect of both mutations, increasing the resistance to the drug. The mutation I117M does not confer oseltamivir resistance.
1822
The eect of I117V appears to be mainly caused by an internal cavity of the mutation, which could increase exibility of neighbouring residues such as E119, R118, and V116 that form part of the drug-binding framework. The authors stress that functional drug resistance should be considered when studying novel mutations, rather than substitution of aminoacids at the same residue.
25.4.18
Swine-originated inuenza A virus known as pandemic (H1N1) 2009 [34]
A novel swine-originated inuenza A virus known as pandemic (H1N1) 2009 was rst isolated from humans in Mexico in April 2009, the worldwide pandemic resulted in more than 18,000 deaths. Swine, turkeys, ferrets, cats, and cheetahs, were found to have been infected. Transmission from humans to pigs were reported. In August 2010, the World Health Organization stated that the pandemic caused by this virus had ended. Swine inuenza A virus (SIV) belongs to the family Orthomyxoviridae and is a causative agent of respiratory disease in pigs. Three subtypes of inuenza viruses are circulating in the swine population globally: H1N1, H3N2, and H1N2. Pigs can be simultaneously infected with avian inuenza viruses and human inuenza viruses. The inuenza viruses can exchange genes between both viruses and produce new variants in pigs. The inuenza viruses. Pandemic (H1N1) 2009 is such a triple hybrid that contains swine, human, and avian virus gene segments becoming dangerous for humans. Yan et al. 2012 describe an outbreak of pandemic (H1N1) 2009 virus in a pig farm in Guangxi Province/China in January 2011, with severe respiratory problems and a death rate of 22%. The virus had high identities to a pandemic strains A/California/04/2009 (H1N1) . The sequencing of a partial genome of the HA gene found 10 strains of subtype H1N1 inuenza virus, 5 strains of classic swine H1N1, 3 strains of Eurasian avianlike H1N1, and 2 strains of pandemic (H1N1) 2009 virus. Several samples tested positive for HI titers in the serology for pandemic (H1N1) 2009 and others had positive HI titres for SIV (H1N1). Cross-reactivity of pandemic (H1N1) 2009 virus between H1 subtype viruses has been reported , but the higher rate was positive for pandemic (H1N1) 2009 virus. The data of Yan and colleagues demonstrate that growing and fattening pigs are susceptible to infection of pandemic (H1N1) 2009 virus, no gene reassortment occurred yet, the pandemic virus is currently circulating in swine populations in southern China. Increasing serological surveillance of pigs for prevention and better control of pandemic inuenza is urgently needed in China.
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25.4.19
Human H3N2 inuenza A virus (IAV) infections in swine populations in Argentina 2008 [35]
Cappuccio et al. 2011 reports that the virus isolate in 2008 in Argentina shared nucleotide identities of 96-98% with H3N2 IAVs that circulated in humans from 2000 to 2003. The authors stress the importance of two-way transmission of H3N2 inuenza A virus (IAV) and swine inuenza viruses (SIVs) between pigs and humans, and call for enhanced inuenza surveillance in the pig population worldwide.
25.4.20
A new variant of u virus H3N2v was detected by CDC researchers [36]
CDC reports the detection in humans of the virus H3N2v, which is a variant of the HaN2 virus having genes from avian, swine, and human inuenza viruses. The new virus had acquired acquired the matrix (M) gene from the 2009 H1N1 pandemic virus. CDC writes that the M gene plays a role in viral assembly and replication, but its role in illness severity or transmissibility in humans is uncertain. The H3N2 variant with the 2009 H1N1 pandemic M gene was detected in US swine as early at 2010. August 2011, however, was the rst time this virus was found in a person. Human infection following contact with swine, as well as limited human-to-human transmission are known, but most illness associated with this virus has been mild and selflimited. The CDC cautions that all inuenza viruses have the capacity to change, and certain people are likely at greater risk for serious complications from infection, cases of severe illness, even deaths, resulting from infection with H3N2v could occur. CDC is recommending that clinicians consider the possibility of infection with one of these variant viruses when seeing patients with febrile respiratory illness in cases of exposure to pigs and/or if the patient is a young child in a state where infections with variant inuenza viruses have occurred. The seasonal u vaccine is unlikely to protect against u viruses that normally circulate in swine.
25.4.21 25.4.22
Evaluation of Rapid Inuenza Diagnostic Tests (RIDTs) for Inuenza A (H3N2)v Novel Inuenza A Virus claims one death. New variant with matrix gene H1N1 of 2009 found [37]
The CDC reports a total of 296 infections with inuenza A (H3N2) variant (H3N2v) viruses July 12 through September 6, 2012 in U.S.A. The rst death caused by the virus occurred in the last week of August.
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The CDC also reports three infections with inuenza A (H1N2) variant (H1N2v) virus in Minnesota. The patients became ill after contact with swine. One patient was hospitalized, but all have recovered from their illness. All three patients were infected with the H1N2v which includes the matrix gene (a so called "M" gene) from the pandemic 2009 H1N1. This gene codes for matrix proteins in the viral shell, and may improve the ability of the H3N2v virus to spread among humans. The CDC stresses the importance of early identication and investigation of human infections with novel inuenza A viruses in order to evaluate the extent of the outbreak and possible human-to-human transmission. The CDC calls vor increased eorts to detect all new cases of H3N2v infections. However, it should be kept in mind that the sensitivity of Rapid Inuenza Diagnostic Tests (RIDTs) which used to detect H3N2v virus infection varies. A negative RIDT should not be considered evidence of lack of infection. [38] Only four of seven RIDTs were found by the authors of a CDC study (Directigen, Soa, Veritor, and Xpect) to nd all inuenza A (H3N2)v viruses. BinaxNOW detected ve of seven, and QuickVue detected three of seven. FluAlert detected only one of seven.
25.4.23
Outbreaks at a county fair -Indiana July 2012 [39]
Two days after the swine fair held on July 8-14 was closed, four persons became ill. All four persons were swine exhibitors or members of their families, with close contact with swine. All four tested positive for inuenza A (H3N2) (H3N2v) virus with the inuenza A (H1N1)pdm09 virus M gene. Inuenza viruses that circulate in swine are called swine inuenza viruses when isolated from swine, but are called variant viruses when isolated from humans. A variant virus (human isolate) might or might not have the M gene from the inuenza A (H1N1)pdm09 virus, along with other genetic changes. The antigenic and genetic constitution of H3N2v viruses dier from swine inuenza A (H3N2) viruses. Nelson et al. 2012, identied 34 swine inuenza viruses (termed rH3N2p) with the same combination of H3, N2, and pM segments as the H3N2v viruses isolated from humans. The authors write that the rH3N2p viruses are a reassortment of H3N2 viruses and the pM segment in swine. The N2 segment of all H3N2v viruses found in humans is derived from N2 lineage circulating in swine after a reassortment with human H3N2 viruses in 2001-2002. [40] No vaccine exists , however A vaccine virus specic for A (H3N2)v has been developed and could be used to produce an H3N2v vaccine, if needed. [41]
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25.4.24
Subtype H1N2 inuenza viruses in Guandong/China [42]
In China H3N2 and H1N1 swine inuenza viruses have been circulating for many years, and in january 2010, one subtype H1N2 inuenza viruses was isolated by Kong et al.in Guandong. The complete genome was determined and the strain was called A/swine/Guangdong/1/2010(H1N The PB2 and PAsegments were close to avian origin, but NA and PB1 were close to human origin. Kong and colleagues underline the interspecies transmission of avian inuenza viruses to pigs. Swine inuenza virus (SIV) surveillance is, therefore, important in association with food and mouth diseases in pigs.
25.4.25
Warning about new swine u virus strain H3N2v [43]
The CDC reports new cases of swine u virus strain H3N2v in Indiana, Ohio, and Hawaii. The virus contains genes from the H1N1 u virus, which made headlines as it spread. Most of the cases were associated with exposure to swine before the onset of symptoms, and exposure to swine while at fairs. The majority of the cases have occurred in children. Symptoms of H3N2v swine inuenza include basic "u" symptoms, including fever, cough, runny nose, sore throat, and muscle aches. All cases of the H3N2v virus have recovered, including the three cases that required hospitalization.
25.4.26
Recommended precautions
The CDC recommends frequent handwashing especially when handling animals, avoiding eating and drinking around animals, and watching animals closely for signs of illness. Children under 5 years of age, people over the age of 65, and those who are pregnant or who have other major medical conditions should practice special care, as they are greater risk of complications if the contract the u. CDC recommended precautions when interacting with pigs or their environments at fairs. In case of getting sick after a contact with swine its good to talk to a doctor and maybe be tested for this virus. The CDC stresses that the u is not transmissible through properly cooked and prepared pork food products. Its not a food borne disease.
25.4.27
The H3N2v virus variant [44]
The CDC speculates that inclusion of the H1N1 gene in the H3N2v virus may contribute to easier transmissibility to humans. The 2009 outbreak of the H1N1 swine inuenza virus resulted in over 14,000 deaths worldwide, 12,000 of which were in the United States. The CDC On July 21, 2012 completed the partial genome sequencing of the H3N2v virus with the inuenza A (H1N1)pdm09 virus M gene found in four persons with respiratory
1826
illness. All four persons were swine exhibitors or family members of swine exhibitors and had close contact with swine.
25.4.28
Swine origin inuenza viruses (SOIV) [45]
Swine inuenza viruses (SIV) have been recognized as important pathogens for pigs and occasional human infections with swine origin inuenza viruses (SOIV) and A(H1N1) have been reported. in the United States. Shu et al. 2012 assessed SOIV subtypes of samples from human cases and identied these samples as triple reassortant (tr-SOIV) containing genes from classical swine, avian and human inuenza viruses. These tr-SOIV, were of A(H1N1), A(H1N2), and of A(H3N2) subtype. These SOIVs were closely related to inuenza viruses circulating in pigs but distinct from inuenza viruses circulating in humans. Shu and colleagues write that a continued surveillance of the animal-human interchange of these viruses is important.
25.4.29
The 2009 pandemic H1N1 (pH1N1) evolved in pigs by cross reactivity [46]
Nfon et al. found pH1N1 virus several times in Canadian pigs in 2009, together with H1N1 with human genes, the TRIG cassette and an oseltamivir-resistance marker. The authors stress the possibility of reassortment between the NS gene of one of these seasonal human-like SIV (shSIV) H1N1 isolates and the pH1N1 NS virus as both were hound to be homologous. Antigenic cross-reactivity was observed between pH1N1 and conSIV but not with shSIV H1N1. The authors suggest that pH1N1 in pigs were built by reassortment because it had not found before May 2009. A close monitoring is necessary to avoid further epidemics of new strains.
25.4.30
Swine inuenza virus antibodies in humans suggest serologic cross-reactivity with antigenically distinct viruses [47]
Serologic studies for swine inuenza viruses (SIVs) in humans in Luxembourg were performed by Gerlo et al. 2011. Higher levels of neutralizing antibodies against pandemic (H1N1) 2009, avian-like enzootic subtype H1N1 SIV, and 2007-08 seasonal subtype H1N1 viruses were found in persons whose profession involved contact with swine than controls with no exposures to swine. The authors, solving the puzzle of positive serology for SIVs in controls not exposed to swine, explain that sequential exposure to variants of seasonal inuenza (H1N1) viruses may have created serologic cross-reactivity with antigenically distinct viruses and do not correlate with infection.
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25.4.31
Newcastle disease or infectious bronchitis
It is caused by a Virus of the family Paramyxoviridae, genus Rubulavirus. The disease does not pose a risk to human health. Poultry and egg products are safe to consume. Human infection with Newcastle disease virus is extremely rare, and usually occurs only in people who have close direct contact with infected birds The virus causes only mild, short-term conjunctivitis or inuenza-like symptoms. The use of Newcastle disease virus as a treatment for cancer has been suggested. Avian inuenza virus infections are widespread in wild birds, especially ducks, migrating waterfowl are a signicant source of avian inuenza viruses. That is why poultry should not be kept outdoors to avoid contact with wild birds in epidemic regions. Disinfection with normal detergents and disinfectants is sucient. Heating and drying inactivates the virus. Heating of contaminated houses for several days is eective. Organic material and manure must be disposed properly as it can protect the virus from disinfectants allowing them to survive for over 100 days. To date, a large number of human infections with the H5N1 virus have been linked to the home slaughter and subsequent handling of diseased or dead birds prior to cooking. These practices represent the highest risk of human infection and are the most important to avoid. People working or living in close contact with poultry, such as poultry farm workers, or family with household poultry breeding are at high risk if diseased animals are present. The virus is found in secretions of the respiratory tract, and most of all in manure. Human infection occurs mainly by inspiration of dust particles containing viruses, and handling infected animals omitting handwashing.
25.4.32
Avian inuenza A viruses infecting humans since 1997

Table 25.1: Human infections with avian inuenza A Cases Infection occurred in both poultry and humans. It was the rst detected direct avian inuenza transmission from birds to humans.Six persons died. 18 cases were reported. 1.5 million chickens were killed in order to control the epidemic China and Hong Kong, 1999 Two children were infected. They recovered.Several human H9N2 infections from mainland China were reported in 1998-99
Virus Occurrence) H5N1 Hong Kong, 1997
H9N2
1828 H7N2 Virginia,USA, 2002
CHAPTER 25. VIROLOGY One person had positive serological reaction to H7N2 following an outbrake of H7N2 in the Shenandoah Valley area China and Hong Kong, 2003 Two case occurred among travellers from Hong Kong to China. One Person died. Another death due to respiratory illness from the travellers group was not serologicallyly cleared. Netherlands, 2003 Outbrakes of inuenza A (H7N7) in poultry pigs and humans. 89 were infected by H7N7in association with the poultry outbrake. One death of a veterinarian who visited an infected far was reported. Three possible transmissions from poultry workers to family members occurreded. Since that time no other infection was reported Hong Kong, 2003 One child was infected by H9N2. It recovered. New York, 2003 One patient was medicated in relation to an infection with H1N1. In March 2004 further tests has showned that it had been H7N2 Thailand and Vietnam, 2003 Highly pathogenic inuenza A (H5N1) was reported. Human cases are still happening there. Canada, 2004 Human infections among poultry workers were due to an outbreak of H7N3 in poultry.The illness consists of eye infections. Asia,Thailand Avian inuenza in Turkey,Romania and Russia
H5N1
H7N7
H9N2 H7N2
H5N1 H7N3
H5N1
25.4.33
The signs of avian inuenza
Detectable antibody titre to AI. AI, respiratory, enteric, reproductive or nervous system disease, decreased food consumption and drops in egg production, coughing, sneezing, rufed feathers, swollen heads, nervous signs like depression, and diarrhoea. There are three pathotypes of Newcastle disease viruses (NDVs)known:lentogenic, mesogenic, and velogenic. The Velogenic Newcastle disease is the most severe of Newcastle Diseases.
25.4.34
Clinical signs
Respiratory and/or nervous signs: gasping and coughing,drooping wings, dragging legs, twisting of the head and neck, circling, depression, inappetence, complete paralysis. Partial or complete cessation of egg production. Greenish watery diarrhoea. Swelling of the tissues around the eyes and in the neck.
25.5. WHO RECOMMENDATIONS REGARDING AVIAN INFLUENZA
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25.4.35
Clinical signs of human infection
Symptom may appear up to two weeks after infection. They are similar to a serious cold: Fever head- and throat pain, cough, respiratory complaints, pneumonia, additional stomach and gut complaints, and abnormal liver test results, bloodcells and platelets count decreases. Some patients kidney failure.
25.5
WHO Recommendations Regarding Avian Inuenza
WHO recommends that travellers to areas experiencing outbreaks of highly pathogenic H5N1 in poultry should avoid contact with live animal markets and poultry farms. Large amounts of the virus are known to be excreted in the droppings from infected birds. Populations in aected countries are advised to avoid contact with dead migratory birds or wild birds showing signs of disease. Direct contact with infected poultry, or surfaces and objects contaminated by their droppings, is considered the main route of human infection. Exposure risk is considered highest during slaughter, defeathering, butchering, and preparation of poultry for cooking. There is no evidence that properly cooked poultry or poultry products can be a source of infection. Countries located along migratory routes need to be vigilant for signs of disease in wild and domestic birds. Recent events make it likely that some migratory birds are now implicated in the direct spread of the H5N1 virus in its highly pathogenic form.[48] To avoid any contact of poultry with wildlife birds all poultry farms must keep their poultry indoors. In animals, avian inuenza is most commonly transmitted through direct contact with wild birds, especially asymptomatic waterfowl, and contacts with infected poultry and poultry products. There are also common indirect routes, e.g. through contaminated clothing, footwear, vehicles and equipment, as well as contaminated feed, water, manure and litter. Insects, rodents, cats and dogs can also act as vectors and transmit the disease.[49] In several countries in Asia, rural families keep small free-range ocks and up to 80% of poultry are raised at small-household village level. This poses a challenge for controlling outbreaks of highly pathogenic avian inuenza (HPAI) in poultry. Poultry and humans often share the same environment in Asia. Poultry are present in almost all villages and are generally marketed as live animals. In these conditions, the disease can spread quickly between the many small ocks. The practice of home slaughtering means that human exposure to the virus can easily occur in aected areas. Outbreaks in Hong Kong and the Neatherlands in 2003 could be controlled by culling of infected ocks, quarantine, bans on the movement of animals, and compensation schemes for aected farmers because the aected areas were characterised by industrial production conditions.
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25.6
Avian Inuenza and food safety
According to WHO, there is a recent concern over the possibility that the avian inuenza in addition to direct contact with live infected animals could spread through contact with contaminated poultry products. To date there is no epidemiological information to suggest that the disease can be transmitted through contaminated food or that products shipped from aected areas have been source of infection in humans. Reports indicate that in addition to chicken, pigs and ducks have also been infected. Infected chicken ocks rapidly develop symptoms and should be destroyed before having any possibility to enter the food-chain. Ducks have been reported to be asymptomatic carriers and duck products such as frozen duck meat could be contaminated with the H5N1 virus. The further processing would inactivate the virus. In general, good hygiene practices during handling of raw poultry meat and usual recommended cooking practices for poultry products would lower any potential risk to insignicant levels. Eggs from infected poultry could also be contaminated with the virus and therefore care should be taken in handling shell eggs or raw egg products. Freezing and refrigeration does not substantially reduce the concentration or virulence of viruses on contaminated meat. Proper cooking kills such viruses. In general, WHO recommends that food s should be cooked to reach an internal temperature of 700 C.[49]
25.6.1
Nutraceuticals as preventatives of H5N1 virus infection [50][51]
Professor Edzard Ernst, professor of complimentary medicine at the University of Exeter, said in February 2006 that olive leaf extract, garlic, oregano oil, bee pollen, cayenne pepper, garlic colloidal silver, aloe vera, Echinacea, kimchi (Korean sauerkraut), cranberry juice, honeysuckle and green tea present no scientic evidence to support claims such as to protect against avian u. Dr. Damien Downing, president of the British Society for Ecological Medicine, and medical director of the Alliance for Natural Health called the statement of Professor Ernst irresponsible and a danger to public health. He pointed out the importance of zinc and vitamin C when it comes to ght infections being then essential for the immune system. However, less than ten per cent of adults in the UK have sucient levels of zinc in their diet. The point of view of Dr. Dowing was countered by Dr. Ron Cutler from the School of Biosciences at the University of East London saying that the H5N1 virus is said to stimulate the immune system, llilng the lungs with blood causing death. Any supplement boosting the bodys immune system would be of no help at that time.
25.6. AVIAN INFLUENZA AND FOOD SAFETY
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25.6.2
New outbreak of avian ue in Bavaria, Germany
The H5N1 virus has been conrmed at a poultry farm at Wachenroth, Erlangen-Hchstadt in Erlangen, Bavaria, Germany. According to Ursula Huber from the German agricultural ministry, 160.000 animals were culled, and the farm was sealed o. About 400 geese had died on the 24.of August 2007. Farmers are ordered to keep poultry indoors. The health ocials advice the public not to eat food products containing raw eggs, as already 190 death were caused worldwide by the virus H5N1 since 2003. With this new outbreak in Germany heavy nancial losses come over the poultry business.
25.6.3
Avian inuenza in Brandenburg, near Berlin [52]
New cases of avian inuenza by H5N1 virus were conrmed in various locations in Brandenburg, in 27.12.2007, near Berlin. Health ocials disposed a quarantine zone around the aected farms. All birds were culled. Cats and dogs should be kept indoor to avoid contact dead wild bird bearing H5N1 virus. The European Unions Standing Committee on the Food Chain and Animal Health issued the following recommendations for areas where H5N1 has been conrmed in wild birds: - Sick or dead cats and dogs should not be touched and the veterinary authorities should be informed, so that post-mortem examination and further testing can be performed. - Contacts between domestic pets, particularly cats, and wild birds should be prevented, i.e. cats should be kept indoors and dogs should be kept on a leash or otherwise restrained, and kept under control by the owner. - All pet owners are advised to stay alert to reports of H5N1 infections in either migratory waterfowl or domestic poultry in their local area and the possible need to quarantine dogs and cats accordingly. The U.S. Department of Health and Human Services (HHS) is oering a guidebook for families and households to plan for infectious disease. HHS Secretary Michael Leavitt released Pandemic Inuenza Planning: A Guide for Individuals and Families January 6. [53] A specic vaccine for humans that is eective against avian inuenza has not yet been approved. Based upon limited data, the Centers for Disease Control ave suggested that the anti-viral medication Oseltamavir (brand name-Tamiu) may be eective in preventing or treating avian inuenza. Please see the State Departments publication "Meeting the Challenge of Bird Flu" for more background on the U.S. commitment, the science and response to bird u. [54]
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25.6.4
New outbreak2007 of H5N1 virus in UK
In UK a new outbreak of H5N1 virus avian ue was noted on the 27.01.07 and conrmed on the 03.02.07 in the English, province of Suolk, Upper Holton in a farm for turkeys for meat production. Three zones were declared around the Infected Premises to reduce the spread of disease. These are the Protection Zone (3km), the Surveillance Zone (10km) and a wider Restricted Zone, encompassing wider areas of Suolk and Norfolk. UK loses its status as "disease free" country (06-02-07) and Ireland, Russia, Hong Kong, South Africa, South Korea and Japan and India impose ban on UK poultry meat, live birds and hatching eggs. The chief veterinary ocer in charge, Fred Landeg, conrmed that about 159,000 turkeys have been culled. 10.02.07: The H5N1 virus of the farm is identical to the virus of recent outbreaks in Hungary according to a statement on 10.02.2007 of the ocial veterinary ocer in charge. The company has poultry farms and production sites all over UK Germany and Hungary and transports fresh meat from one side to another. The veterinary investigators believe that the virus was on this way imported from Hungary.
25.6.5
Inuenza H5N1 virus conrmed in wild birds in Dorset [55]
According to UK Defra laboratory test has conrmed highly pathogenic H5N1 avian inuenza in wild swans in Dorset. A 3km Control Area and a 10 km Monitoring Area has been established around the location. UK, Poland, Hungary, Germany and the Czech Republic are European countries where bird ue outbreaks took place.
25.7
[56]
Still human death cases caused by H5N1 avian ue virus
25.7.1
Egypt
One teenage girl tested positive for the H5N1 avian u died on April 10, 2007 at a hospital in Cairo despite Tamiu medication. The total number of H5N1 deaths in Egypt are 14.
25.7. STILL HUMAN DEATH CASES CAUSED BY H5N1 AVIAN FLUE VIRUS 1833
25.7.2
Nigeria
In the city of Lagos, Nigeria, 11 contact persons were tested for H5N1 virus, having symptoms of the disease in early April 2007. One women died on February after slaughtering a chicken without wearing gloves or a mask and probably spread the virus to their contacts.
25.7.3
Reported deaths due to H5N1 virus (WHO 11.04.2007) [57]

5 7 15 14 63 2 2 1 17 4 42 172
Azerbaijan Cambodia China Egypt Indonesia Iraq Laos Nigeria Thailand Turkey Viet Nam Total
25.7.4
Preparedness plans for a global u epidemic
The U.S. Department of Health and Human Services gives advices and preparedness plans for a global epidemic. Please look at http://www.avianu.gov/plan/individual/index.html
25.7.5
Intensive animal food production systems [58]
According to Food and Agriculture Organization of th United Nations (FAO), global animal food production is undergoing a major transformation that could lead to a higher risk of disease transmission from animals to humans. The risk of disease transmission from animals to humans will increase in the future due to human and livestock population growth, dynamic changes in livestock production, the emergence of worldwide agro-food networks and a signicant increase in the mobility of people and goods. Excessive concentration of animals in large scale industrial production units should be avoided and adequate investments should be made in heightened biosecurity and improved disease monitoring to safeguard public health.
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25.7.6
How humans can protect themelves from bird u
A healthy lifestyle with plenty of exercise to keep immune levels high, making sure to wash hands regularly is recommended. Avian u virus strains are widely distributed within the bodies of diseased chickens and turkeys, as well as in sub-clinically infected species like ducks. Chickens, for instance, have the highest viral load at the end of the incubation period, just before the bird becomes ill. The viruses are expelled from the body in the feces during the acute stage of the disease and may end up contaminating food and water. Human infections have generally resulted from direct and intensive contact with infected poultry. Particularly high risk has been associated with slaughtering, defeathering, butchering or preparing sick birds for consumption, with exposure to infected droplets as well as feces being possible sources of infection. A third of the cases reported in Vietnam had no direct exposure to poultry and the source of the infection remains unknown. Two conrmed cases have followed consumption of raw duck blood pudding. Another case may have been linked to swimming in a canal frequented by infected ducks. EFSA74 According to the French Food Standards Agency keeping birds indoors will not eliminate the risk of infection, since the virus could be carried in mud containing wild bird feces, or in feathers, litter or food. The agency calls for strict biosecurity measures on farms.
25.8
Avian inuenza and industry
The current bird u scenario should not cause panic and fear; instead it calls for rational and immediate action to ght the disease at its origin - that means in animals.
25.8.1
Pigs and poultry
Globally, pig and poultry production are the fastest growing and industrializing livestock sub-sectors. As a consequence, in the industrialized countries, the vast majority of chickens and turkeys are now produced in houses with 15 000 to 50 000 birds. This business is being introduced in Asia, South America and Africa. Industrial pig and poultry production relies on a signicant movement of live animals. In 2005, for example, nearly 25 million pigs, more than two million pigs per month, were traded internationally. According to FAO the highly pathogenic H5N1 virus is currently of major global concern,
25.8. AVIAN INFLUENZA AND INDUSTRY
1835
however, the "silent" circulation of inuenza A viruses (IAVs) in poultry and swine should also be closely monitored internationally. A number of IAVs are now fairly widespread in commercial poultry and to a lesser extent in pigs and could also lead to emergence of a human inuenza pandemic. FAO called upon meat producers to apply basic biosecurity measures. Production sites should not be built close to human settlements or wild bird populations; farms should be regularly cleaned and disinfected; the movements of sta and vehicles should be controlled and employees should be trained in biosecurity.
25.8.2
Swine Inuenza A (H1N1) virus mutation is resistant to antiviral drugs [59]
The virus found in pigs infected humans. Now the subtype of the inuenza virus which caused the death of 20 to 50 million people in 1918 can travel from person to person. [60] In 2005 a virus laboratory regained the plasmid of the 1918 epidemic using samples of human corpses which had been buried in Arctic permafrost. About 1000 are hospitalized in Mexico city and 18 already died. California report 6 cases of the new H1N1 virus which is resistant to Tamiu antiviral drug. In California 6 persons and two in Texas were tested positive for H1N1.
25.8.3
Recommendations
CDC recommends: There are everyday actions people can take to stay healthy - Cover your nose and mouth with a tissue when you cough or sneeze. Throw the tissue in the trash after you use it. - Wash your hands often with soap and water, especially after you cough or sneeze. Alcoholbased hands cleaners are also eective. - Avoid touching your eyes, nose or mouth. Germs spread that way. Try to avoid close contact with sick people. - Inuenza is thought to spread mainly person-to-person through coughing or sneezing of infected people. - If you get sick, CDC recommends that you stay home from work or school and limit contact with others to keep from infecting them. Other eective measures to avoid infection Avoid handshaking Avoid kissing Use surgical mask
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25.8.4 25.8.5
Antiviral drugs resistance [61] Oseltamivirn (Tamiu)
Concern about H5N1 bird u caused the development of the Tamiu drug the new u causing concern is a pig virus, of a family known as H1N1. The antiviral drug Tamiu, also known as Oseltamivir blocks the H5N1 enzyme Neuraminidase, and was known to be ecient against inuenza viruses A and B. The H1N1 mutated the expression of the enzyme and became resistant to these antiviral drugs. Health ocial advice, therefore, not to use Oseltamivir any more, or when, give it together with Amantadine (Relenza), which is an uncoating inhibitor.
25.8.6
Amantidine (Symmetrel)
In Europe infections with H1N1 are about 10% of ue cases, and H3N2-Viruses are more common. H3N2 viruses are resistant to Amantadine, but sensitive to Oseltamivir, which is also ecient against inuenza B viruses.
25.8.7
Zanamivir [Relenza]
According to Patrick Hollstein 2009 there is no resistance of H1N1 to the second neuraminidase inhibitor Zanamivir (Relenza ) reported. It is useful against inuenza viruse A and B.
25.8.8
Rimatidine (Flumadine)
It is active only against inuenza A viruses.
25.8.9
Doubts on the eect on Tamiu to treat swine u [62]
Prof. Bernd Mhlbauer, director of the Institute of Pharmacology at the Clinical Centre Bremen, Germany calls for human studies on the eectiveness of Tamiu before million of Euro are being spent to built a stock sucient for 20 percent of the population, as demanded by the German National Pandemic Plan. Up to date only laboratory studies were conducted to verify the eect of the drug on swine inuenza virus. Mhlbauer says that other inuenza drugs reduce u only by the average of one day. He fears that the drug is prescribed too often in an irresponsible manner. The German pharmacology expert says that the drug should be stocked only for risk patients, medical personal, police and reman. Only such groups should receive prophylactic drugs in case of a pandemic.
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25.8.10
H1N1 inuenza may present atypical Symptoms [63]
According to Fatima S. Dawood the H1N1 virus causes common inuenza signs of fever, cough, and sore throat, additional diarrhea and vomiting may also occur in one fourth of cases. The CDC recommends, therefore, to look after an association of signs of seasonal inuenza and atypical gastrointestinal signs. A wide clinical spectrum similar to that seen among persons infected with earlier strains of swine-origin inuenza viruses are reported.
25.8.11
Two groups of H1 virus have evolved from the 1918 pandemic inuenza virus [64] [65]
The present H1 viruses is derived from Eurasian rather than North American swine u lineages. Other sporadic human inuenza cases caused by triple-reassortant viruses occurred before the current outbreak and appeared to be transmitted from pigs to humans. CDC cautions that sporadic cases of triple-assortment inuenza infections in humans who have had contact with pigs may be sentinels for a larger outbreak. The 2 groups of viruses dier in their infective potential. They evolved from viruses from 1918 and have subsequently evolved. Dr. Robert Beshe says that infections are caused by remnants of the 1918 pandemic inuenza virus. In case of u signs the CDC stresses to consider recent history of exposure to pigs, domesticated fowl, or wild birds, especially when human u viruses are not in circulation in the community.
25.8.12
WHO Increases Pandemic Alert Level to Phase 6 [66] [67]
On 11 June 2009 The World Health Organisations director-general Dr. Margaret Chan has ocially declared the swine u to have entered the pandemic phase 6.
25.8.13
Phase 6
the pandemic phase, is characterized by community level outbreaks in at least one other country in a dierent WHO region. Designation of this phase will indicate that a global pandemic is under way. Dr. Chan pointed to the fact that actually the swine u pandemic coexists with the H5N1 avian u in phase 3 pandemic alert status. This is considered to be an extremely unusual situation. She pointed out that pregnant women are at increased risk for complications, and the virus preferentially infects younger age groups, under age 25 years.
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Although there have not been large numbers of severe cases in USA so far, severity may increase toward fall. H1N1 immunization campaign should therefore start in late September. Swine Flu virus A/1H1N is a super u that consists of 3 known swine u strains, 3 known bird u strains and a human u virus. The combination of these strains makes the A/1H1N Swine Flu an unusual strain of the u with unknown outcomes. If you had contact with persons which may be suering from this new hybrid strain of Swine Flu, in special travellers from USA and Mexico, seek immediate medical advice. WHO recommends a measured fever over 100, along with either cough or sore throat an also has an underlying condition, whether you have asthma, diabetes, or are pregnant, or an infant under the age of 2, see your doctor right away to see if you should be treated for inuenza with antiviral medication.
25.8.14
Swine u, a seasonal u, CDC says school closing is rarely indicated [68]
CDC Director Thomas R. Frieden, MD reported that closure of schools is rarely indicated, even if u is in the school. Health and Human Services Secretary Kathleen Sebelius pointed out that the disease caused by swine u is not more severe than disease caused by seasonal u.
25.8.15
The new CDC Swine Flu Rules for Schools
CDC recommends not closing schools during a wave of pandemic swine u, and follow the advices:
25.8.16
Stay home when sick
If youve had the u, dont go back to school until 24 hours after your fever goes away.
25.8.17
Separate ill students and sta
Students and sta who appear ill should be sent to a room separate from others until they can be sent home. They should wear surgical masks if possible; those that care for them should wear masks, too.
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25.8.18
Wash hands, observe cough/sneeze etiquette
Frequent and thorough hand washing will be more important than ever. So will covering each cough or sneeze with a disposable tissue (or shirtsleeve or elbow if tissues arent available).
25.8.19
Routine cleaning
School sta should clean areas that students and sta touch often. Use normal cleaners; bleach and special cleansers arent necessary.
25.8.20
Early treatment of at-risk students and sta
People at high risk of severe swine u disease - for example, those who are pregnant, have asthma or diabetes, neuromuscular diseases, or immune deciency - should see a health provider as soon as they become ill. Early antiviral treatment is very important for them. If swine u becomes more severe:
25.8.21
Active screening
Students and sta should be checked for fever and other u symptoms every morning; those with these symptoms should be sent home. Throughout the day, students and sta should be on the lookout for people who appear ill.
25.8.22
High-risk students/sta should stay home
Students and sta with conditions that put them at high risk of severe u disease - such as pregnancy, chronic asthma, or heart disease - should stay home from school "when a lot of u is circulating in the community." Schools should immediately start planning for the continued education of such students.
25.8.23
Students with ill family members should stay home
Students should stay home for ve days starting from the rst day their household member got sick. This is the time they are most likely to get sick themselves.
25.8.24
If sick, stay home longer
Stay home for at least seven days even if you feel better before then. If you still feel ill after seven days, stay home for 24 hours after your symptoms nally go away.
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25.8.25
Consider school closure
If its deemed necessary to close a school, the school should remain closed for ve to seven calendar days and then consider whether to reopen.
25.8.26
Travel restrictions immediately needed
The WHO says that it continues to put no restrictions on travel. The reason of WHO hesitation to impose travel restrictions may result from pressure of USA who fears economic losses. However, the pandemic spreads worldwide by travellers coming from USA and Mexico. WHO must undergo criticism for the lapse of not imposing travel restrictions. There are worldwide about 300.000 cases of swine u human infection known of which 13.000 in USA.
25.8.27
Facemasks are not eective protection from H1N1 virus [69]
The FDAlabeled as surgical, laser, isolation, dental or medical procedure masks are a loose-tting and do not protect against viral infections. A facemask is eective in blocking large-particle and droplets but is ineective to block very small particles emitted by coughs or sneezes.
25.8.28
N95 Respirators for Use by the Public
An N95 respirator is a device which achieves a very close facial t and blocks at least 95% of very small test particles. However, they are not appropriate for children or people with facial hair. FDA has cleared the following N95 respirators for use by the general public in public health medical emergencies: 3M T M Particulate Respirator 8670F 3M T M Particulate Respirator 8612F Pasture Tm F550G Respirator Pasture Tm A520G Respirator
25.8.29
Fitted N95 Respirators Recommended to Protect Healthcare Workers
N95 respirators cleared by FDA for use in the healthcare setting are called surgical N95 respirators
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25.8.30
The Institute of Medicine IOM recommends the use of tted N95 respirators for healthcare Workers to protect against H1N1 infection [70]
A report of the IOM stresses that ltration and t of medical masks are insucient to to avoid small particles to overcome the barrier of the mask and inadequate t do not oer an eective protection against airborne transmission. The IOM recommends therefore, the use of N95 respirators which lter out at least 95% of particles 0.3 m or larger blocking the inuenza virus.
25.8.31
Face masks and N95 respirators are not reusable [71]
The N95 respirator is the least expensive and the most widely available respirator for protecting healthcare workers and the public against airborne infection. However, disposable N95 respirators cannot be eectively cleaned or disinfected and should therefore be discarded after each use.
25.8.32
Origin of the swine u virus described [72]
Andrew Rambaut and colleagues 2009 showed that the H1N1 virus is a mixture of other viruses that had been circulating in pigs and includes human and avian-like genetic sequences. The initial transmission to humans occurred several months before recognition of the outbreak. The authors say that movement of live pigs between Eurasia and North America seems to have facilitated the mixing of diverse swine inuenza viruses and the lack of systematic swine surveillance allowed for the undetected evolution for many years. Analysing the molecular structure of the virus, the authors dated their appearance between 9.2 and 17.2 years ago and remained undetected for about a decade. The pork industry protested against the use of the term "swine u" and exerted pressure on the WHO to use the generic designation of "inuenza A(H1N1)" fearing pork prices to be aected.
25.8.33
Inuenza threat of the North American swine [73]
Gerardo Nava and colleagues 2009 reported that their genetic analysis also pointed to North American swine as a potential source of the new virus. The researchers call for a systemic surveillance system which integrates phylogenetic information of inuenza viruses circulating in humans and livestock. Meanwhile entire poultry ocks are slaughtered to control outbreaks of avian inuenza, no action is take in face of outbreaks of swine u. Pork farmers wait out outbreaks among
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their ocks because the infection rarely kills the animals. According to Nava and colleagues this may permit the virus to recombine in the pig and elaborate new sequences, new genes. Nava and colleagues said that ocials focused on avian u and ignored the new threat coming from pigs and the people who work with them. The authors point to the fact that the United States invested 3.8 billion dollars to prevent and contain the foreign threat of Asian avian u, neglecting the inuenza threat that the North American swine population presents. Protecting itself from foreign avian u USA neglected to protect the world from the swine u whose origin is now being tracked to be the North American swine.
25.8.34
Collecting specimen for H1N1 swine inuenza testing [74]
Nasopharyngeal swab as respiratory specimes, sera for cases or contacts of cases with conrmed swine inuenza. Specimens should be collected within the rst 24-72 hours of onset of symptoms and no later than 5 days after onset of symptoms. The specimens should be kept refrigerated at 40 C and sent on cold packs if they can be received by the laboratory within ve days of the date collected. If samples cannot be received by the laboratory within ve days, they should be frozen at -700 C or below and shipped on dry ice.
25.8.35
Laboratory testing
Throat smear taken by health ocials are sent to a lab performing the tests: 1 - The US Flu Rapid Antigen testing: This test is not specic. Its sensitivity is unknown. A negative result does not exclude a diagnosis of swine inuenza A and should be submitted to PCR and subtyping. 2 - The CDC under the Emergency Use Authorization (EUA) procedure authorized diagnostic tests called "diagnostica reverse-transcriptase polymerase chain reaction (RT-PCR) swine inuenza panel", the "rapid inuenza antigen" and the "immunouroscence". All three can detect the new swine inuenza virus, but they only identify probable cases because they cannot distinguish between seasonal inuenza A and swine inuenza, which is a subtype of A. 3 - The RT-PCR can conclusively conrm a case of swine inuenza. 4 - Culture of the virus in cell cultures and chicken eggs. This takes much time. Active infection with swine inuenza can only be conrmed by polymerase chain reaction (PCR) assays, including subtyping and further characterization by other special PCR assays
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25.8.36
Laboratory safety precautions
Rapid antigen testing or PCR) can be performed under BSL-2 conditions. All sample manipulations should be done inside a biosafety cabinet. (BSC). Viral isolation on clinical specimens from patients who are suspected cases of swine inuenza A (H1N1) virus infection should be performed in a BSL2 laboratory with BSL3 practices (enhanced BSL2 conditions).
25.8.37
Safety precautions during specimen collection
Personnel collecting clinical specimens should wear a t-tested N95 respirator, goggles, disposable gown, and disposable gloves. When completed, place all personal protective equipment in a biohazard bag for appropriate disposal. Wash hands thoroughly with soap and water or alcohol-based hand gel.
25.8.38
Egypt culls swines to prevent swine inuenza pandemic [75]
The Health Minister of Egypt ordered the culling of Egypts 400,000 pigs. Pigs are seen as unclean, Haram by muslims. The culling should help to protect against swine u. Egypt had been hit by the last H5N1 avian inuenza and fears another u pandemic. There are no infections of swine u reported yet, a pandemic u strain could, however, spread quickly through the heavy crowded region. A member of the Cabinet called the conditions of the swine farms in Egypt as unhealthy, being a hazard in themselves, even without the swine u. A compensation of 120 per pig were oered, but the farmers doubt that the money will ever be payed and they claim the loss of their livelihood. They say that the pigs are feeding from 6,000 tonnes of organic rubbish produced in he region every day and they do not know how the food scraps should be handled otherwise.
25.8.39
The UN food experts say pork meat is safe
The UN food experts call the culling decision a mistake, stressing that the newly mutated H1N1 virus is not found in pigs. The animals can be the vessels for the "genetic reassortment" that produces new strains, but pork meat is safe to eat, because it must be cooked anyhow.
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25.8.40
Canadian swine herd infected with H1N1 by farme worker returning from Mexico [76]
Pigs in Alberta were infected with H1N1 by a farm worker who fell ill after returning from Mexico. Pigs can be infected by u virus from human and avian virus. The pig is able to mix its own u virus with the human and the avian type. The result is a dangerous pandemic form of inuenza.
25.8.41
Import restrictions on pork
Russia and China imposed an import ban of pork from USA, Canada and Mexico.
25.8.42
German IT company "ExploSYS" developed an InuenzaPandemic-Planning-Simulator InuSim [77] [78] [79]
The epidemiologist Prof Dr. Martin Eichner, from the German city Tbingen, together with the mathematician Markus Schwehm developed an "Inuenza-Pandemic-PlanningSimulator InuSim" which will support decision makers at airports, medical centres, health departments and governments to nd the best measures to counter pandemics. The simulator received input from the German Robert Koch Virus institute and will be distributed by ExploSYS. The developers say that simulation shows that even closing the borders to a country with disease cases, the pandemic will get through, because no border can be absolutely leak proof. For such events the pandemic simulator shows where the rst cases are expected to turn up.
25.8.43
Inuenza A H1N1 avian u virus continues to spread [80] [81]
The WHO on its report of May 4, 2009 sees the virus moving south, but no communitylevel transmission is being reported right now. WHO pandemic alert level is being maintained at phase 5. An increase to phase 6 will take place when community-level transmission is occurring in more than 1 WHO region. Currently, such outbreaks are taking place only in North America. The spectrum of illness varies from very mild to fatal cases occurring in young, healthy people infected by the inuenza viruis H1N1. Severe pneumonia, 40% to 50% of patients developing diarrhoea are some signs of the disease. WHO says that the incubation of a regular inuenza is about 5 days. With H1N1 there is uncertainty about whether it is 6, 7, or 8 days. Dr. Besser from the CDC expects all states to have conrmed cases, ongoing hospitalizations and additional deaths.
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25.8.44
The big H1N1 hype of Roche
Now that tension concerning swine u in media revives, some conclusions become evident. Marketing department of leading pharmaceutical corporations performed a spectacular job heating up media and politics. Nobody dared to argue about the necessity of a vaccine and stockpiles of Tamiu. CNBC on his morning business ticker of 23.07.2009 reported a net prot of 4.05 Billion Swiss francs at Swiss drugmaker Roche on account of H1N1 vaccine. [82] Global sales of the antiinuenza medicine Tamiu (oseltamivir) rose 203% to 1.0 billion Swiss francs in the rst half-year. Sales to governments and corporations for pandemic stockpiling amounted to 653 million francs (609 million francs in the second quarter of 2009 compared with 49 million francs in the second quarter of 2008). Roche, working with the World Health Organization (WHO) and national governments, started in May 2009 to supply Mexico and 71 other countries with the stocks of Tamiu, and by the start of 2010 Roche will be able to supply up to 400 million packs annually. Oseltamivir will also be produced for China, India. [83] Germanys health ministers on 21.07.2009 agreed on a plan to order some 50 million units of u vaccine units. Thats enough to immunize 25 million people against the H1N1 swine u - a person has to be injected twice in order for the vaccine to be eectiveThe vaccines will provide protection for 30 percent of the German population. In Germany 727 cases of swine u have been reported, none were fatal. Authorities fear a mutation of the swine u virus, could prove deadly. The H1N1 hype continues, boosted by governments and the WHO which warned that the spread of swine u was unstoppable [84].
25.8.45
Mutation
Flu viruses mutate continuously. That is why vaccination of "common" cold is considered ineective. Brazilian Adolfo Lutz Bacteriological Institute identied a new strain of the H1N1 called A/So Paulo/1454/H1N1 and compared it with samples of the A(H1N1) swine u from California. According to Terezinha Maria de Paiva (June 16, 2009) the mutation comprised alterations in the Hemagglutinin protein which allows the virus to infect new hosts. However, it was not yet known whether the new strain was more aggressive than the current A(H1N1) virus. [85]
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25.8.46
Severity is of no concern, says WHO [86]
At this time, WHO considers the overall severity of the inuenza pandemic to be moderate. This assessment is based on scientic evidence available to WHO, as well as input from its Member States on the pandemics impact on their health systems, and their social and economic functioning. The moderate assessment reects that: Most people recover from infection without the need for hospitalization or medical care. Overall, national levels of severe illness from inuenza A(H1N1) appear similar to levels seen during local seasonal inuenza periods, although high levels of disease have occurred in some local areas and institutions.
25.8.47
Vaccination for H1N1 unnecessary
Looking at the costs and the results, it immediately becomes clear that there were rare global cases of death. Comparing with death tolls of other contagious diseases such as tuberculosis, malaria, viral hepatitis, early summer meningocephalitis and others, H1N1 is of no concern. Note hat Germany having diagnosed more than 3.000 cases had no even one single fatal case. Swine u is thus a mild, often asymptomatic disease. The risk of adverse eects of vaccination is high, compared with u risk. Contact with the swine u trains the immune system building up barriers against u viruses. WHO and German health ocials in an last eort to hide the wrong decision stress that mutation of the actual mild H1N1 virus may mutate to a more virulent variant. The pharmaceutical industry awaits hopefully this hype to be spread by the media.
25.8.48
Contagious period of swine inuenza H1N1 [87]
De Serres and colleagues 2010 report that, according to their data, persons infected with pandemic (H1N1) 2009 virus, a minimum of 8% of outpatients shed replicating virus on day 8. The authors conclude that self-isolation only until fever abates appears insucient to limit transmission. They call for a self-isolation at the household, for a week and caution that some patients may shed infectious virus for a longer period. Some studies with seasonal inuenza state that virus shedding after day 7 is rare, but clinical studies have shown that shedding may persist beyond that period in some populations, such as elderly persons, immunocompromised patients, and children.
25.8.49
Contagiousness
According to the authors, contagiousness depends on viral load and depends on the spread of droplets (such as coughing, rhinorrea, or sneezing), the number and proximity of contacts
25.8. AVIAN INFLUENZA AND INDUSTRY between a case-patient and a susceptible person.
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25.8.50
CDC recommend outpatients to extend the reclusion 1 day after end of fever
CDC recommends that people with inuenza-like illness remain at home until at least 24 hours after they are free of fever (37.80 C ). [88]
25.8.51
Duration of isolation precautions for hospitalized patients
CDC says that the recommended duration of isolation precautions for hospitalized patients is longer than that recommended for other populations because duration of virus shedding is likely to be longer than for outpatients with milder illness. De Serres, however, calls to extend the precautionary measures of hospitalized patients also to outpatients. Isolation precautions for patients who have inuenza symptoms should be continued for the 7 days after illness onset or until 24 hours after the resolution of fever and respiratory symptoms, whichever is longer, while a patient is in a healthcare facility. Because some patients with inuenza may not have fever but may be shedding inuenza virus, patients with any respiratory symptoms should follow hand and respiratory hygiene recommendations. [89] With pandemic (H1N1) 2009, fever generally persists 1-4 days and may be absent in 6%11% of patients. In our study, of the 32 pH1N1 PCR-positive household members who had been symptomatic for less than 7 days, 78% had fever at any time since onset of their illness, but only 34% were still febrile on the day they tested positive. Nonetheless, 97% of specimens obtained from these patients were positive by cell culture. Before policy implications can directly follow from these ndings, the association of selfisolation with substantial social impact needs to be carefully weighed against the possible benets of reducing community transmission. In the general population, a 1-week selfisolation period seems more likely to prevent transmission than does isolation until fever has resolved. However, given that 8%-13% of patients may still shed infectious virus on day 8, longer periods of self-isolation for persons expected to come into contact with vulnerable persons (e.g., pregnant women, newborns, or immunocompromised persons) also may be prudent.
25.8.52
Infectious viral shedding
Ling and colleagues 2010 write that virus shedding in pandemic (H1N1) 2009-infected patients in Singapore, treated with oseltamivir, were still PCR positive by 37% of the patients
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on day 7 of their illness and 9% on day 10. The authors also note that oseltamivir, prescribed during the rst 3 days of illness, shortened the duration of viral shedding. [90] According to Li and colleagues 2010, oral oseltamivir medication initiated 2 day or earlier, suppresses infectious viral load of nasopharyngeal aspirate of pandemic 2009 inuenza A(H1N1) more eectively compared with patients with an onset of medication after 2 days, and was signicantly lower, compared with nontreated. No viral load was determined at day 6 of medication. [91] Highest viral load in respiratory samples, stool and urine occurred on the day of onset of symptoms. Eight days after onset of symptoms the RT-PCR 8 and after 5 days the were negative with only one exception. Younger age was associated with prolonged respiratory tract and stool shedding was observed in younger people. [92]
25.8.53
Quick test for H1N1 [93]
Louie and colleagues 2010 say that diagnose inuenza at the point of care, using commercial rapid enzyme immunoassay, are unable to dierentiate between inuenza A virus subtypes and the sensitivity varies between 40% and less, up to 90%, compared with PCR and culture methods. The authors compared the QuickVue Inuenza test (Quidel Corp., San Diego, CA, USA) with PCR and culture methods, and found that the test had suboptimal sensitivity and specicity for the detection of pandemic (H1N1) 2009. Their results should be conrmed with PCR. The authors call for the development of more accurate rapid tests.
25.8.54
H1N1 now in the post-pandemic period (Disease activity at seasonal levels) [94]
10 August 2010 - WHO Director-General, Dr Margaret Chan announced that the H1N1 inuenza virus has moved into the post-pandemic period. However, localized outbreaks of various magnitudes are likely to continue. WHO says that the world is no longer in phase 6 of inuenza pandemic alert. The new H1N1 virus has largely run its course. The WHO recommends monitoring for unusual events, such as clusters of severe respiratory illness or death, and monitoring the H1N1 2009 virus for important genetic, antigenic or functional changes, such as antiviral drug sensitivity. [95]
25.8.55
Costs of exaggerated panic of advising instituts in Germany [96]
The Rober Koch Institute was responsible for advices to the Health Departments regarding vaccination of German population. The institute spread panic informations, leading to the order of 34 Million H1N1 vaccines. Only 4,17 Mio units were used following a restricted
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number of illness and mild disease. 336 Million EURO of unused vaccines must be paid by taxpayers.
25.8.56
The blue ear disease [97]
Chinese ocials say million pigs are dying in China killed by the epidemic on Porcine Reproductive and Respiratory Syndrome (PRRS), or blue ear disease , which is caused by a virus in the arterivirus family. This disease is known as post-weaning multisystemic wasting syndrome PMWS in Europe, and as the porcine circovirus associated disease PCVAD in USA. It is a very common pig disease known for many years in Europe and USA in the mid 80s, from were it spread to other countries, such as to the Cape. China is being seriously hit by the disease, because pork is a staple food and meat is lacking on the markets and the government wants to release frozen stocks. [98] The mortality is known to be up to 50% caused by the porcine circovirus type 2 (PCV2), but has declined now to 1-2% in the nursery due to hygiene strategy and the porcine circovirus type 2 vaccine, but it is still up to 9% in nisher.
25.8.57
Human infectivity of blue ear disease [99]
According to Albert Osterhaus, a virology expert at the Erasmus University Medical Centre in Rotterdam, an international centre for blue ear disease, there are no indications that spread to humans can happen. Many viral infections that do occur in certain animal species are restricted to that particular species. A mutation to a variety which could be infectious to human, so as feared about the H2N5 virus of avian inuenza, however, is highly unlikely.
25.8.58
Symptomatic
The virus causes still-births, fever, loss of appetite, diarrhoea, redness of the skin and mortality rates of up to 50 percent on some farms. The ears of aected pigs turn blue. The virus invades and multiplies in the white blood cells which die later on in the lung tissue of the pigs. Up to 40% of the macrophages are destroyed reducing the defence mechanism and allows bacteria and other viruses to proliferate. The virus mutates quickly turning the production of vaccines dicult, but vaccination in Guangdong will start soon.
25.8.59
Rules for pig slaughterhouses in China
According to Chinas Ministry of Commerce the draft rules for pig slaughterhouses demands for a slaughterhouse to be licensed and approved by local governments and environmental
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bureaux, and must be located away from drinking water supplies, residential districts and public areas, the said on its Web site.
25.8.60
Transmission
Direct pig to pig transfer is not common; the transmitting agent is Hematopinus suis, the swine louse. The diagnosis is the Virus isolation The control of the disease is the elimination of lice and hygiene measures. Chinese ocials believe that carcasses thrown into rivers may have been responsible for the spread of the disease to the surrounding areas. Infected pigs were raised by individual rural farmers applying poor hygiene measures rather than industrialized pig farms. Endemic areas include Africa (South of the Sahara), Spain, and Portugal. The outbreaks in the Dominican Republic, Haiti, and Cuba have beenn reported. In China the desease appeared in the mid-90s, and actually in the Cape Flats.
25.8.61
The blue ear disease virus not to be compared with the avian ue H5N1 and H7N1 virus [100]
Despite the economical impact, the blue ear virus does not menace mankind so as the H5N1 virus of the avian inuenza does. China reports a new case of human infection with the H5N1 virus which was conrmed on the 30.05.2007. There had been no contact with sick birds prior to becoming unwell. Close contacts have been placed under medical observation and all remain well. Of the 25 cases conrmed to date in China, 15 have been fatal. In UK two human infections with the less deadly variant of H7N1 were reported.
25.8.62
Evolution of drug resistance in H5N1 avian ue [101]
Governments and organizations stockpile antiviral drugs such as oseltamivir (Tamiu) to be prepared to control a possible inuenza A H5N1 pandemic. Hill and colleagues 2008, however, warn that lineages of H5N1 are becoming resistant to adamantane derivatives, and a few lineages are resistant to oseltamivir. The authors stress that the rise of resistance to adamantanes, including the nonprescription drugs amantadine and rimantadane, is linked to Chinese farmers adding the drugs to chicken feed as a u preventative. If Tamiu is ever used in the manner of adamantanes, similar drug resistance may evolve. According to the study, H5N1 drug resistance to adamantanes arose through novel genetic mutations rather than an exchange of RNA segments within cells, a process known as re-assortment.
25.9. NOROVIRUS
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The authors developed phylogenetic methods, which, added to molecular evolutionary analyses, and geographic visualization using Google Earth, provided a framework for analysis of globally distributed genomic data that can be used to monitor the evolution of drug resistance.
25.8.63
China increases blue-ear vaccine production in 2008
According to Jia Youling, Chinas chief veterinary ocer blue-ear pig disease also known as Porcine Reproductive and Respiratory Syndrome. has been brought under "preliminary control" through vaccinations and mass culls of infected pigs. In 2007 the disease had infected 257,000 pigs in 26 Chinese provinces, of which 68,000 died and 175,000 were destroyed. The highly pathogenic disease can be fatal for pigs, but the vaccinated pigs will no longer be infected by the disease. [102] The Harbin Veterinary Research Institute has recently donated blue-ear disease vaccines for 800,000 pigs to ve snow-hit provinces. The Institute increased its production of the vaccine in a bid to prevent the potential outbreak after the recent blizzard since spring is the season of a high occurrence in the blue-ear disease. Blue-ear disease was rst discovered in the United States in 1987 and spread to China in mid 1990s. China rst spotted a more virulent form of the pig disease in the summer of 2006 and identied it as a mutated highly pathogenic strain in January of 2007. [103]
25.9
Norovirus
Norovirus should replace the designation "u-like", "Norwalk-like","Norwalk- and Norwalklike viruses (Caliciviruses)", "bug". Noroviruses are the most common viral agents of acute gastroenteritis in humans. Many studies on the epidemiological and genetic characteristics of Noroviruses outbreaks point to their importance in food safety. Rapid analytical methods were developed to identify the source of epidemics.
25.9.1
Norwalk- and Norwalklike gastroenteritis virus
are leading causes of foodborn diseases:Norwalk virus is part of a family which is not well dened It causes stomach and intestinal illness. It was rst identied in 1972 in the city of Norwalk (Ohio). The group of these viruses are recently called Noroviruses. They are included in the genus Norovirus, family Caliciviridae. They are single stranded RNA, nonenveloped. They spread by person-to-person contact from the stool of infected persons and its symptoms are vomiting and diarrhoea.Special care is needed to avoid spreading of the disease such as:
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Avoid food or water which has been contaminated by stool from infected persons, raw shellsh, oysters, clams, ice, eggs, salads and other food contaminated by sick food handlers or water which has been contaminated by sewage of cities or disposals of boats. Incubation is 1 to 2 days. Illness is not severe, but rehydration may be necessary. Recovery in 2 to 3 days. People with the virus are contagious skin to skin for 3 days after symptoms have disappeared. The stool remains infectious for 2 to 3 weeks after symptoms are gone. Strict handwasching and use of disinfectants are very important to avoid spreading of the virus. People can be reinfected and have the disease several times in life because there are many strains and a strong mutagenic activity. Food should be served in restaurants authorised persons only instead of self-serving service. Hotels should carefully clean bed clothes and pillow cases. Refrigerators and icemachines should be thawed and cleaned periodically. As disinfectant chlorine water solution should be used. Viral gastroenteritis outbreaks caused by caliciviruses have been associated with eating contaminated shellsh, particularly oysters (Crassostrea virginica), implicating sewage from oyster harvesting vessels as the probable cause of contaminated oysters.
25.9.2
Special measures
Special care is needed to avoid spreading of the disease. Avoid food or water which has been contaminated by stool from infected persons, raw shellsh, oysters, clams, ice, eggs, salads and other food contaminated by sick food handlers or water which has been contaminated by sewage of cities or disposals of boats. Strict hand washing and use of disinfectants are very important to avoid spreading of the virus. Only authorised persons should be allowed to serve food instead of self-serving service in restaurants. Hotels should carefully clean bed clothes and pillow cases. Refrigerators and ice machines should be thawed and cleaned periodically. Chlorine water solution should be used as disinfectant Paper towels should be used instead of textile towels. Sterilise hands with sterilisation solution after drying hands. Cutting boards and knives must be washed with hot water and soap when changing food.
25.9. NOROVIRUS Fruits and vegetables must be washed carefully before processing.
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Meat, poultry and sh must be cooked. After maximum of 2 hours after cooking all food must be refrigerated.
25.9.3
Norovirus in oysters
If shellsh such as fresh oysters infected with norovirus are eaten, acute gasterointestitis may occur. Vomiting, stomach ache, diarrhoea and fever may result. Available measures to ght Norovirus in oysters is to provide sterile water and use chlorinebased germicides. However, sterile cultivation is costly and the Norovirus is resistant to chlorine-based germicide and sterilising alcohol. The use of high chlorine concentrations will make shellsh unpalatable. Researches made by IEMT/AIST with micro-bubbles which are ultra-ne gas water bubbles (less than 50 micrometers in size) containing low concentration ozone to inactivate norovirus in live oyster under cultivation as well as unshelled oysters. These micro-bubbels are concentrated oxygen and 2 per cent ozone. As the bubbles are suspended in water, the bubble size shrinks spontaneously to the level of nanometer inactivating the virus. The oxygen/ozone micro-bubbles also suppress legionella bacteriain a circulating bath system as well as carp herpes virus.
25.9.4
Norovirus GII.4 leading global cause of viral gastroenteris [104]
According to Said, Perl and Sears 2008 the Noroviruses are a leading global cause of viral gastroenteritis and a major contributor to food-borne illness. According to the authors the GII.4 strain of the virus dominates in epidemics by antigenic drift evading thus the immune system.
25.9.5
Norovirus NoV frequent agent of gastroenteritis in an older population [105]
Rosenthal and colleagues 2010 assessing outbreaks infections in an older population found that 70% were caused by Noroviruses, with a case-fatality rate of 0.5%. GII.4 strains accounted for 84% of Noroviruses outbreaks and had a mean duration of 33 hours versus 24 hours of non-GII.4 infections.
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25.9.6
GAP, GMP and HACCP improves microbiological safety of ready to eat vegetables [106]
De Giusti and colleagues 2010 report that GAP, GMP and HACCP improves the microbiological safety of ready to eat vegetables compared with dierent preventive strategies, such as use of chlorine disinfection at a second washing step, or using a physical microbial stabilization. The aerobic mesophilic count and Escherichia coli were quantied, and the presence of Salmonella spp, Listeria monocytogenes, E. coli O157:H7, hepatitis A virus and Norovirus were determined. The authors found that GAP, GMP and HACCP presented better microbiological quality than those processed with chemical or physical stabilization.
25.9.7
Water purication systems are unable to remove Norovirus from bivalve moluscs [107]
The ecacy of the water depuration systems in the presence of Norovirus contamination of bivalve moluscs, Mussels, Manila clam and Pacic oyster were examined by reverse transcriptase-polymerase chain reaction before and after depuration. Viral RNA was detected non-depurated samples as well in depurated samples indicating that the purifying systems in place were not able to remove Norovirus contamination from the live bivalve molluscs, write Savini and colleagues 2009.
25.9.8
Removal of Norovirus during a coagulation-ceramic microltration of drinking water [108]
Shirasaki and colleagues 2010 assessed the removal performance as particles during a coagulation-ceramic microltration process using recombinant NV virus-like particles (rNVVLPs), and the bacteriophages Qbeta and MS2, similar to Noroviruses. More than 4log removal of rNV-VLPs with a 1.08 mg-Al/L dose of polyaluminium chloride in the coagulation-ceramic MF process was found . The removal ratios of Qbeta and MS2 were smaller than the ratio of rNV-VLPs. The authors concluded that both bacteriophages are appropriate surrogates for native Noroviruses in the coagulation-ceramic MF process. They suggest the use of Qbeta as surrogate.
25.9.9
Review of Calicivirus studies [109]
Catpally and colleagues reviewed the current studies of Noroviruses which had been hampered by the lack of animal model and tissue culture system. The authors report that recent advances in protein expression systems and the development of a mouse norovirus animal model have brought a rapid growing knowledge about these viruses.
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25.9.10
New Porcine Calicivirus in US Swine [110]
Wang and colleagues 2011 report that new St-Valerien-like porcine caliciviruses are prevalent in up to 80% in nisher pigs in North Carolina. One strain, NC-WGP93C, shares over 89 genomic nucleotide identity with Canadian strains. The authors could not say whether these strains are pathogenic for animals or humans or may aect food safety. The caliciviruses have been found in humans, cattle, pigs, cats, chickens, reptiles, dolphins and amphibians.Viruses in the family Caliciviridae are nonenveloped, polyadenylated, single-stranded, positive-sense RNA viruses with 5 genera (Norovirus, Sapovirus, Vesivirus, Lagovirus, and Nebovirus). The nonhuman primate Tulane virus and the porcine St-Valerien-like viruses, may become a new genera in the Caliciviridae family. St-Valerien-like viruses have been detected in Canada, the United States, and Italy. In order to support the classication of St-Valerien-like viruses as a member of Casliciviridae it is important to demonstrate the presence of the virus in other regions and determine the genetic dierences between strains. St-Valerien-like viruses are close to Tulane virus and human noroviruses, and more data may may help to clear if an interspecies transmission may take place, and nd the best way to control the spread of the new viruses.
25.9.11
Wastewater and crop contamination by Norovirus and Ascaris lumbricoides [111]
Mara and Sleigh 2010 estimate norovirus and Ascaris infection risks to urban farmers in developing countries using wastwater for crop irrigation. To achieve a tolerable disease burden of 1 percent of the diarrhoeal disease a norovirus reduction of 1-2 log units and an Ascaris egg reduction to 10-100 eggs per litre are required. The authors stress that such reductions are easily achieved by minimal wastewater. A sequential batch-fed three tank/pond system are being suggested, in addition to education and regular deworming in farming regions. The authors reminds that reductions of 4-6 log units can be achieved using settling basins (1-log unit), pathogen die-o (1-2 log units), produce washing in cold water (1 log unit) and produce disinfection (3 log units). [112]
25.9.12
Small Round Structured Viruses (SRSVs) [113]
SRSV infections are generaly short-lived illness, sometimes referred to as winter vomiting disease, which rarely need medication, however, they are the commonest cause of epidemic viral gastroenteritis. There was little known about these viruses before 1990 when the rst sequencing of their DNA was reported. SRSVs infection causes projectile vomiting and short and less severe diarrhoea as noted with Norwalk virus. Headache and fever may occur in some patients.
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Transmission: Transmission occur by person-to-person contact, food-borne associated with restaurants and receptions, outbreaks associated with potable water were reported in the USA. Water as source of an SRSV sudden outbreak should always be considered. Actual techniques are insuciently sensitive to detect SRSV in water. Environmental and epidemiological investigations, based on examination of faeces of diseased must be used to determine the source. Food-borne outbreaks of SRSVs: Bivalve molluscs (oysters, cockles and mussels) are the only type of food implicated in such outbreaks. Shellsh beds are often located in estuarine waters polluted with human sewage. Bivalve molluscs are lter feeders and concentrate low number of viruses of the sea water. Depuration process applied to oysters is eective in removing bacterial pathogens, but has almost no eect on these viruses. A poor correlation of levels of bacterial indicator organisms and viral contamination is being reported. Eorts are being undertaken to replace the inecient depuration by relaying in biologically cleaner water before cleansing, to do so, the EU suggests a period of eight weeks for some areas and shellsh beds should be classied to use less hazardous locations. Contamination from food handles: Food may be contaminated by an infected food handle. SRSVs are destroyed above 600 C . Known outbreaks are related to eating shellsh raw or not cooked after handling. An infected food handler sheds SRSVs few hours before onset of illness and continues two to three days. Incubation time is 24-72 hours. [114] Diagnostic detection systems using RT-PCR are available to determine the importance of SRSVs and investigate the point source outbreaks of non-bacterial gastroenteritis.
25.9.13
Rapid Concentration and Detection of Enteric Viruses [115]
Butot, Putallaz and Snchez 2006 developed a method to detect enteric viruses such as hepatitis A virus, norovirus and rotavirus from berries, vegetables and frozen products. The viruses were extracted from the food surface by a direct elution method in a glycineTris (pH 9.5) buer containing 1% beef extract and concentrated by ultraltration. PCR inhibitors were eliminated with pectinase treatment. The concentration method was combined with real-time reverse transcription-PCR (RT-PCR) using specic primers. The authors write that the procedure is suitable to detect and quantify enteric viruses within 6 h and can be applied for surveillance of enteric viruses in fresh and frozen products.
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25.9.14
Control for losses of target virus [116]
To control for losses of target virus during concentration and extraction, samples are spiked prior to processing with a dene amount of a process control virus. The Mengo virus strain VMCO in known concentration is used in the CEERAM Kit. Mengo virus strain MC0 is a recombinant virus, non pathogenic and culturable. This virus has structural and physicochemical properties close to those of hepatitis A virus. It has resistance properties in environment close to those of targeted viruses By adding a known quantity of mengo virus in each sample prior any processing, it is possible to dene an extraction eciency for each sample after amplication by real time RT-PCR and comparison with an equal quantity of Mengo virus puried from cell culture.
25.9.15
Hepatitis A virus [116]
Incubation of hepatitis A virus is around thirty days. Clinical signs of the infection vary from asymptomatic case in children younger than 6 years old to acute hepatitis. Fecal-oral parental, sexual, salivary or urinary transmissions are reported. There is no specic curative treatment but a vaccine is available. Hepatitis A virus can resist to dierent physical and chemical treatments, and can survive in dierent kind of environment for a long period. The diagnostic by cellular culture or ELISA is not adapted to the detection of Hepatitis A virus in environmental or food samples. Molecular techniques (real time RT-PCR) are the methods of choice for Hepatitis A detection after extraction and viral RNA purication from the sample.
25.9.16
Purication of Norovirus RNA from human stool samples [117]
Magnetic-particle technology are used for rapid purication of nucleic acids. The magneticparticle technology, used for rapid purication of nucleic acids, combines the speed and eciency of silica-based nucleic acid purication with the convenient handling of magnetic particles and enables purication of high-quality nucleic acids that are free of proteins, nucleases, and other impurities. The puried nucleic acids are ready for direct use in downstream applications, such as amplication or other enzymatic reactions. It can be used to purify nucleic acids from viruses.
25.9.17
Norovirus genotype proles may help to nd origins of outbreaks [118]
Noroviruses are members of the family Caliciviridae and recognized as major pathogens in outbreaks of gastroenteritis worldwide. They can survive in the environment, can use dierent transmission routes, and have a low infective doses. Transmission occurs through
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contact with shedding persons; food contaminated during processing, preparation or serving; sewage-contaminated water used for consumption, cultivation or irrigation of food; contaminated aerosols resulting from vomiting; and environmental contamination. Verhoef and colleagues 20101 described six genotype proles of Norovirus outbreaks: A) food or B) humans; C) person-borne outbreaks; D) food handler-borne outbreaks; E) outbreaks with an unknown mode of transmission; and F) routine monitored bivalve mollusks. Their study may help to detect the sources of the foodborne outbreaks resulting from infected food handlers and those resulting from food contaminated early in the food chain. The authors stress that dierentiating between person-borne or food handler-borne outbreaks is of public health interest because dierent control measures are applicable, such as prevention measures during the production process, detection should enable containment of viral foodborne infection and thus prevent further spread and the consequent potential for large numbers of human infections. The authors urge, however, that genotyping data need to be interpreted with care, and continuous updating of the database remains necessary.
25.9.18
Norovirus genogroup I and II [116]
There is no cell culture system available for the multiplication of human noroviruses. The detection by ELISA is not recommended due to norovirus genetic diversity and its lack of sensitivity. Molecular techniques (real time RTPCR) are the methods of choice for Norovirus detection after extraction and viral RNA purication from the sample.
25.9.19
Bottled water: Attachment of Enteric Viruses to Bottles [119]
Butot and colleagues 2007 developed an internationally accepted virus detection methods for bottled water, facing some doubts concerning its safety due to the reported nding of norovirus sequences in 33% of commercially available water samples sold in Switzerland. [120] However, this could not be conrmed by other studies. A standard method therefore was welcome: Storage of water that was deliberately contaminated with enteric viruses in polyethylene terephthalate (PET) bottles led to a rapid decrease of the apparent viral load, due to adhesion adsorbed norovirus, and rotavirus on bottle walls. This was also observed with glas bottles. The virus retention on PET bottle walls after 62 days reached an average level of up to 95% of the recovered inoculum of norovirus, hepatitis Elution of the virus from bottle walls using the described method on 294 commercially available water bottles obtained from 25 dierent countries did not give any positive result.
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The authors concluded that the sources used for bottled water are free from enteric viruses and support the theory that bottled water is not a vehicle for viral diseases.
25.9.20
Reo virus
infects intestines, lung, kidneys, liver and spleen of cattle and swine.
25.9.21
Rotavirus
in the intestines of cattle and swine. Rotaviruses belong to the group of the reovirus. The particles of rotavirus contain 11 segments of double-stranded RNA. They are 70 nm in diameter and resemble wheels with a central axis and radiating spokes. Rotaviruses are the major agent of non-bacterial diarrhoeal diseases with great risk to infants and young children. The large majority of gastroenteritis are due to group A rotavirus. Transmission occurs commonly through water.
25.9.22 25.9.23
Astro virus Adenovirus
is found in intestines, lung, kidneys of cattle and swine
25.9.24
Canine parvovirus
The members of the group of the parvoviruses are roughly spherical with a diameter of about 24 nm. Canine parvovirus causes enteritis and miocarditis in dogs.
25.9.25
Coxsackie virus
It is found in the intestines and lung of swine.
25.9.26 25.9.27
ECHO viruses Corona virus
infects the intestines of cattle.
25.9.28 25.9.29
Newcastle virus Norwalk virus
from infected mussels

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25.9.30
Herpes virus
It infects lung liver spleen, milk and muscles of cattle and lung and muscles of swine.
25.9.31
Other entero viruses
Infection occurs through fecal contamination of food, water and air. Personal hygiene, communal hygiene such as sewage treatment and isolation of diseased persons from food processing are the most important measures to avoid food born diseases. The contamination can be of primary or secondary nature. The primary contamination of food occurs when the animal which is going to be killed has already a virus disease. Meat and organs may then carry the virus. Fish and oysters near the estuary of sewage carrying rivers may bear hepatitis viruses. The secondary contamination of food occurs during processing, transportation and storage through dirt and smear infections. Virus carrier of hepatitis - A virus may contaminate food handling food in restaurants. Water which bears viruses is the most common cause of contamination when used in the production of food or used in cleaning of tools and equipment. Enteroviruses are the most important group of water-borne viruses.
25.9.32
Food poisoning from mussels, oysters and clams
Bivalves are important vehicles for the transmission of enteric diseases when eaten raw or undercooked. Vibrio species, are abundant in bivalve tissue. According to Carla Pruzzofrom the University of Genova, immunity in bivalves is carried out by circulating haemocytes and soluble haemolymph factors that act in a co-ordinated way to kill microorganisms. Studying the physiology of the Mediterranean Mytilus galloprovincialis, the scientists identied a rage of factors that are important in determining the fate of vibrio cholerae within the bivalve host. These are bacterial surface ligands, soluble hemolymph components and the ability of bacteria to inuence distinct signalling pathways responsible for the haemocyte immune response. [121]
25.9.33
Hepatitis A - virus
The HAV is a heat resistant RNS from the family of the Picornaviridae.
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25.9.34
Hepatitis E - virus
The HEV is supposed to be a member of the Calici - group. It is a RNS - virus, its incubation is about 40 days. It causes a high mortality between pregnant by rst infection. It is very frequent in India and Mexico.
25.9.35
Denition of virus
Viruses are obligate intracellular parasites, they can only multiply inside living cell. Denition according to S.E. Luria and James Darnell (1967): "Viruses are entities whose genomes are elements of nucleic acid that replicate inside living host cells using the cellular synthetic machinery and causing the synthesis of specialised elements (virus particles) that transfer the virus genome to other cells." This denition should be added by 5 characteristics enumerated by A. Lwo (1957): Viruses are extremely small microorganism ( 15 - 300 nm which can pass normal bacterial lters). 1. They contain only DNA or RNS 2. There is no division. Reproduction occurs by only means of nucleic acid. 3. There is no growth in the extracellular latent phase. 4. There are no metabolic enzymes 5. Replication by means of the ribosomes of the host cells
25.9.36
Groups of viruses
Viruses are generally divided into animal viruses, plant viruses and bacterial viruses. The division of viruses in to groups is important as they do not cross the boundaries as they are specialised to the biology of their hosts. Only a few viruses , however can do that. This is the case of the rhabdovirus group
25.9.37
Animal viruses
are viruses which infect vertebrates, including human viruses of medical importance and those of veterinary importance.
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The name of animal viruses are based on the disease caused on the principal host followed by the name virus.
25.9.38
invertebrate viruses
especially insect viruses.
25.9.39
Plant viruses
such as mosaic virus of tobacco and viruses of owering plants. The name of plant viruses are given according to the major host of plant and the main symptoms of disease caused such as tobacco mosaic virus (TMV), tomato bushy stunt virus (TBSV)raspberry ringspot virus (RRV). (On regard of the problems of classication please refer also to "Phytopathology"
25.9.40
Bacterial viruses
are also known as pages, bacteriophages. Well known are the phages which infect Escherichia coli. Bacterial viruses are named by code letters or by a system of letters and numbers Bacterial infections may be a lytic infection such as caused by phage T2 or T4 infecting Escherichia coli causing it to burst which is called lyse. The phages infection of bacteria may be lysogenic, infected cells of bacteria show no signs of infection but retain the ability to produce infective virus particles.
25.9.41 25.9.42
Nipah virus and Hendra virus [122] cite
Hendra Both viruses are member of the family of Paramyxoviridae both are included in the genus of Henipavirus. They are known to be able to infect a wide rage of hosts ( pigs, horses,cats, dogs and guinea pigs). The natural host of the Nipah virus are certain species of fruit bats (Megachiroptera such as Pteropus vampyrus) which are infected without being ill themselves. Though Nipah and its closely related zoonotic Hendra virus ( formerly called Equine morbilli virus EMV) are not known to be transmitted by food there are cases known of transmissions from pigs and horses to mankind.So breeders and abattoir workers should take special care to avoid infection leading with sick pigs with Nipah virus infections.Sick horses with severe respiratory disease were reported to be the source of infection with Hendra virus in Australia. Once infected the death rate in humans is higher than 50%. There is no medication against the viruses. Only ribavirin can reduce the severity of the disease. It is recommended that close contact with body uids and infected tissues should be
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avoided if Nipah infection is suspected. Respiratory secretions of diseased humans and animal contain the viruses. In an Malaysian outbreak in Nipah infected pigs were the cause of human disease. The virus carries therefore this name. Incubation time is between 4 and 18 days in some cases up to twelve months and is in most cases sub-clinical with inuenza-like symptoms, high fever and muscle pains.Inammation of the brain,drowsiness, disorientation, convulsions and coma.
25.9.43
Menangle virus
Menangle virus, a member of the Paramyxovirus family causes a disease in pigs with stillborns and deformed piglets and inuenza-like illness in humans. Its host are fruit bats.
25.9.44
Tioman virus
Tioman virus is a member of the Paramyxovirus family and of the genus Rubulavirus. It is related to Menangle virus.
25.9.45
Newcastle Disease in pigeons in Germany [123]
Friedrich-Loeer Institute in Germany conrmed the outbreak of paramyxovirus-1 Newcastle Disease in pigeons at the border of Bavaria with Austria. on 22.4.2008. The veterinarian Dr. Barbara Hohhmann reported 33 cases at a farm in Rottal-Inn Bayerbach. The applied control measures were quarantine, movement control inside the country, zoning and disinfection of infected premises. Chickens, turkeys, pigeons and ducks may be aected. In ducks the disease is rarely diagnosed but causes production drops and fertility problems. Mammals may be occasionally aected, such as conjunctivitis in man. [124]
25.9.46
Other viruses
they infect protozoa, algae,lamentous fungi and yeasts. They are not so well known.
25.9.47
Structure of virus particles
The structure of virus particles can be determined with electron microscopy and X-ray crystallography. In 1939 a tobacco mosaic virus TMV was seen for the rst time using an electron microscope. Virus particles are transparent in the electron beam, special staining is therefore necessary:
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25.9.48
Shadow casting
Metals such as gold are vaporized and sprayed over the virus particle, forming a thin lm over the object. The resulting shadows are used to analyse the three-dimensional structure of the particle.
25.9.49
Negative staining
Heavy metal salts are used as negative stains such as potassium phosphotungstate or uranyl acetate. These compound ll the gaps between particles giving rise to the image of the details of the particle against a dark background.
25.9.50
R-ray crystallography
X-ray Crystallography can be used whenever the virus particles can be isolated in crystalline form. This method was used with viruses such as: Polio virus and tobacco mosaic virus. The external morphology is made by a protein shell called capsid. Capsids are composed of subunits called capsomeres The capsomeres may contain several proteins such as the capsomeres of the particles of poliovirus.These proteins are called virion proteins VP Polioviruses have virion proteins VP1, VP2, VP3, VP4. According to the morphology the viruses may be classied:
25.9.51
Icosahedral symmetry
They are small and infect animals such as poliovirus, plants such as turnip yellow mosaic virus (TYMV) and bacteria. Their morphology resembles an icosahedron.
An icosahedron is a regular three-dimensional body with 20 triangular faces, 12 pointed corners called vertices and 30 edges with a special symmetry called 5:3:2 rotational symmetry: Fivefold axis symmetry Has the same symmetry when the particle is rotated on-fth of a complete rotation. Threefold axis symmetry The symmetry repeats every third of a complete rotation. Twofold axis symmetry The symmetry repeats every half rotation.
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25.9.52
Helical symmetry
Viruses which are rod shaped and have helical arrangement of their subunits are called helical symmetry viruses. Rod shaped viruses can be rigid as seen by the tobacco mosaic virus or exible as found with the potato virus X and mumps virus.
25.9.53
Enveloped virus
Enveloped viruses have a lipid-rich outer coat forming a regular phospholipid bilayer similar to the cell membranes of eucariotic cells. The shape can vary, being called pleomorphic particles. Some glycoprotein structures emerge from the lipid coat. These structures are called peplomers or spikes, such as seen in inuenza virus Some viruses have haemaglutining spikes HA which stick to the surface of red blood cells causing clumping of blood. The envelope is essential for the infection process. Treatment with detergents or organic solvents such as chloroform or ether damages the lipoprotein layer and inactivates the virus.
25.9.54
Complex virus particles
There are two types of complex virus particles known: Poxvirus and Phages
25.9.55
Poxviruses
They have a central nucleoid core of DNA covered by a lipoprotein membrane with spikes. Poxvirus particles can be brick shaped such as smallpox or ovoid as in orf which is a poxvirus of lamb and kid goats
25.9.56
Phages
Are virus particles with a head of icosahedral symmetry and a tail of helical symmetry. Examples of phages are the T2, T4 and T6.
25.9.57
Genetic variations of viruses
Genetic variation of viruses modify their reaction to specic antibodies giving place to new strains of viruses. One distinguishes antigenic drifts and antigenic shifts.
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25.9.58
Antigenic drifts
The mutation of the genes may be very small. They are point mutations, changing simple aminoacids of the HA and the N proteins. These small antigenic drifts explain the appearance of mild epidemics such as inuenza being only of local importance.
25.9.59
Antigenic shifts of viruses
The changes of the genetic code is very great and new strains of viruses appear. They are responsible for world-wise inuenza epidemics.
25.9.60
Virus infection due to contaminated water
Contaminated surface water can be the cause of virus epidemic diseases when chemical disinfectants without slow ltration through sand or occulation is used. Concentration of chemical disinfectants may be sucient to destroy Escherichia coli but not enough to inactivate viruses. Despite a negative coli test contamination with viruses are still possible. Some viruses found in water are: Enteroviruses causing diseases of the intestines, meninges, repiratory system and heart muscle and cause poliomyelitis and infectious hepatitis Adenoviruses, causing diseases or the respiratory system and conjunctiva. Rotaviruses, causing diarrhoea, being serious diseases of infants. The amount of virus particles in contaminated water can be very low , the water still remaining infectious for humans. New laboratory method are being applied to control virus contamination of water. These methods are DNA and RNA sondes and control of specic nucleic acid sequences with hybrid techniques as well as the polymerase chain reaction Food may be contaminated by food preparers or handlers who have viral gastroenteritis, especially if they do not wash their hands regularly after using the bathroom. Shellsh may be contaminated by sewage, and persons who eat raw or undercooked shellsh harvested from contaminated waters may get diarrhoea. Drinking water can also be contaminated by sewage and be a source of these viruses. Viral gastroenteritis outbreaks can occur in schools, child care facilities, nursing homes, banquet halls, cruise ships, dormitories, and campgrounds Rotavirus infection can be diagnosed by laboratory testing of a stool specimen. Tests to
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detect other viruses that cause gastroenteritis were not in routine. Genetic ngerprinting technology using PCR methods, can now identify many common foodborne illnesses and nd their origin with great accuracy. Infection of the most of the viruses occurs through faecal contamination of water food and air.
25.9.61
Vaccination reduces severity of rotavirus infections [125]
Pitzer and colleagues developed a mathematical modelling based on changing patterns of rotavirus transmission in the United States. The model includes regional birth rates and predicted vaccination levels and eectiveness. It says that when 80 percent or more of children in a given population are vaccinated, annual epidemics may occur on a less regular basis and more unvaccinated children will be protected. The study explains the timing of rotavirus epidemics dependent on the birth rate in the population because newborns infants have an untrained immune system. With the introduction of vaccination the rotavirus outbreaks may become less frequent and less pronounced as it was before vaccination. Pitzer stresses that despite uncertainties in the demographic dierences and unpredictable conditions the introduction of vaccination in the developing world will decrease rotavirus death rates which is high in children under 5 years in developing countries.
25.9.62
Measures to avoid food born viral diseases
Personal hygiene, communal hygiene such as sewage treatment, isolation of diseased persons from food processing. The contamination can be of primary or secondary nature. The primary contamination of food occurs when the animal which is going to be killed has already a virus disease. Meat and organs may then carry the virus. Fish and oysters near the estuary of sewage carrying rivers may bear hepatitis viruses. The secondary contamination of food occurs during processing, transportation and storage through dirt and smear infections. Virus carriers of hepatitis-A virus may contaminate food in restaurants. Water which bears viruses is the most common cause of contamination when used in the production of food or used in cleaning of tools and equipment or rinsing vegetables. Enteroviruses are the most important group of water-borne viruses. The human pathogens in these groups have been poorly studied since for the most part, they do not grow in culture. They have been grouped on the basis of their appearance. Recently, nucleotide sequences of members of each group have been determined, allowing genome organisation to be used as a basis for future classication. In the past, the cause of food poisoning could not be found. Health ocials named a
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particular food product or brand not until many people became ill because of recourse. Sometimes they acted to fast removing a product from the market which were not contaminated, damaging the reputations of innocent food growers, manufacturers, and vendors. This happened with Birkel noodle in Germany. The company was blamed to have used spoiled eggs for here products. The company proved its innocence but almost went into bankruptcy.
25.10
Reoviruses
Respiratory Enteric Orphan viruses, i.e. infect the human respiratory and intestinal tracts, usually without disease symptoms. There are 150 species in the family Reoviridae. They are a diverse group, infecting invertebrates, vertebrates and plants, but are unied by their most unique feature, the composition of their genome.
25.10.1
Bluetongue virus
Bluetongue is an insect transmitted, viral disease of domestic(cattle and sheep) and wild ruminants that is caused by bluetongue virus (BTV). Human infection are unknown, and there is no risk of the disease being contracted or spread through meat or milk. The Bluetongue virus is a member of the genus Orbivirus and Reoviridae family. There are 24 serotypes. It is transmitted by a midge Cullicoides imicola and other culicoid species. In August 2006 cases of bluetongue were found in the Netherlands, then Belgium and Germany. Major signs are high fever, excessive salivation, swelling of the face and tongue and cyanosis of the tongue. Swelling of the lips and tongue gives the tongue its typical blue appearance, though this sign is conned to a minority of the animals. Recovery is very slow.
25.10.2
Report on Epidemiological analysis of the 2006 bluetongue virus serotype 8 epidemic in north-western Europe updated in June 2007 [126]
Bluetongue (BT) is an arthropod-borne viral disease caused by the BTV-serotype 8 (BTV8) It aects domestic and wild ruminants, particularly certain breeds of sheep. It is a severe clinical disease, including mortality which rapidly spread in north-western Europe in 2006 . It aected cattle and sheep holdings in Belgium, Germany, France, Luxembourg, and The Netherlands.
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25.10.3
The main ndings reported by the EFSA bluetongue working group
Statistical modelling showed that the initial infection occurred in the area close to Maastricht. The source of the introduction of BTV-8 could not be identied and the exact origin and route of the introduction of BTV-8 thus far remains unknown. However, the absence of legal import of ruminants from outside the EU into the Area of First Infection and the absence of BTV-8 from southern Europe suggest that the introduction of the BTV-8 infection into north-western Europe is likely to have occurred via a other than through import of infected ruminants. Specically, the potential for Culicoides to be imported along with or independently of the import of animals, plants or other materials merits further study.
25.10.4
Blutongue virus serotype 8 reemerges in Germany [127]
Martin Beer and colleagues 2008 report that bluetongue virus (BTV) is a double-stranded RNA virus of the genus Orbivirus. BTV is transmitted to its hosts by the bite of Culicoides spp. midges. It causes a noncontagious, arthropod-borne disease of domestic and wild ruminants and camelids; disease can be serious, particularly in sheep. BTV had never been reported in any European country north of the Alps until August 2006, when outbreaks of BTV serotype 8 (BTV-8) were almost simultaneously discovered in the Netherlands, Belgium, Germany, and France. In 2006, a total of 893 cases were detected in Germany, but the source of initial virus introduction remains unknown. Subsequently, BTV-8 overwintered in the region, spread over most of the country, and led to almost 21,000 new cases in 2007 in Germany. BTV-8 infections spread to additional European countries, e.g., the United Kingdom, Switzerland, the Czech Republic, Denmark, and Spain. In February 2008 bluetongue virus serotype 8 (BTV-8) was detected in Germany in an export heifer. According to the authors reemergence was conrmed by retesting the samples, experimental inoculation, ngerprinting analysis, and virus isolation. The authors stress that overwintering of BTV-8 and continuous low-level infections are assumed.
25.10.5
Monitoring
Sheep ocks should be monitored by a system based on clinical signs, as PCR in aected sheep is often negative. Cattle monitoring system based on serological surveillance is being recommended.
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25.10.6
Culicoides as a vector of BTV
The BTV-8 virus was found to be present in vectors (Culicoides species) which are endemic to north-western Europe. C. imicola, which is thought to be responsible for at least 90% of BTV transmission in the Mediterranean Basin, was not found in the aected region. Indigenous Culicoides found to be PCR-positive were C. dewul (a species breeding exclusively in the dung of cattle and horses) and C. obsoletus/C. scoticus. In all likelihood this persistent activity of adult Culicoides owes much to the mild temperatures that have continued to prevail across northern Europe during the winter of 2006/2007. Local spread was modelled and found to occur at a rate of about 2 km per day or approximately 15 km per week and equals the ight distances covered by Culicoides. Wind may aect spread over long distances. In particular, the density of the observed wind events contributed, at least in part, to explaining the spread of BTV. In conclusion, changes in climatic conditions coupled with increased worldwide trac might increase the risk in the appearance and the establishment of diseases in parts of Europe that were thus far exotic to those regions.
25.11
Rotaviruses
Rotaviruses belong to the group of the reoviruses. They resemble wheels with a central axis and radiating spokes (Rota=Wheel) Rotaviruses are the most common cause of severe diarrhoea worldwide. In developing countries, rotavirus infection may cause up to one million deaths each year. Clean water and improved sanitation are seldom available in developing countries. Rotavirus particles remain active on human hands for at least 4 hours, on hard dry surfaces for 10 days, and on wet areas for weeks. The large majority of gastroenteritis are due to group A rotavirus. Adsorbed on particles, they can survive in dierent kind of environment for a long period. Food can be contaminated by a food-handler during the various stages of food production or via the environment. Thanks to their structural properties, rotaviruses can persit to dierent food processes. The consumption of contaminated food can lead to outbreaks in population. The diagnostic by cellular culture or ELISA is not adapted to the detection of rotavirus in environmental or food samples. Molecular techniques (real time RT-PCR) are the methods of choice for rotavirus detection
25.12. ASTROVIRUSES
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after extraction and viral RNA purication from the sample. Although the rotavirus and the Norwalk family of viruses are the leading causes of viral infects other viruses can also cause diarrhoea. [116]
25.12
Astroviruses
Astroviruses are the cause of most frequent viral gastrointestinal infections and are a signicant cause of diarrhoea in developing countries. They are clinically similar to caliciviruses. Astroviruses have been isolated from birds, cats, dogs, pigs, sheep, cows and man. There are at least 7 human astrovirus serotypes. Outbreaks in UK, in Mexico and food borne astrovirus infection in Japan involving thousands of children and adults.
25.13
Adenoviruses
Adenoviruses most commonly cause respiratory illness; however, depending on the infecting serotype, they may also cause various other illnesses, such as gastroenteritis, conjunctivitis, cystitis, and rash illness. Adenoviruses are unusually stable to chemical or physical agents and adverse pH conditions, allowing for prolonged survival outside of the body. Transmission occurs by direct contact foecal-oral transmission, and occasionally by water. Shedding can occur for months or years.
25.13.1
An adenovirus deadly for monkeys deadly was found to infect Humans [128]
The UCSF Viral Diagnostics and Discovery Center identied a new adenovirus (titi monkey adenovirus TMAdV) infecting New World titi monkeys and two humans, jumping between the animals and humans. TMAdV caused an upper respiratory illness which progressed to pneumonia and a death rate of 83% of the monkeys at the Center. Adenoviruses are known to infect humans and many animals like monkeys and rodents. In humans, the adenoviruses cause diseases associated with cold-like symptoms, diarrhoea or pneumonia. The authors report that the new virus is the rst adenovirus which is able to cross the human-monkey species barrier. Crossig the species barrier is known for inuenza and corona viruses, but had been unknown for adenoviruses. The monkeys and researcher and two members of his family tested positive for antibodies to the TMAdV virus. The UCSF used for this study the pan-viral microarray platform Virochip has the capacity
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to detect all known viruses as well as novel variants on the basis of conserved sequence homology, identifying novel viruses, such as the SARS corona virus, a novel rhinovirus clade, XMRV (a retrovirus linked to prostate cancer), avian bornavirus (the cause of a wasting disease in parrots), and a novel cardiovirus in children with respiratory and diarrheal illness. [129] The new virus shares only 56 percent of its DNA to its closest viral relative and is very deadly to titi monkeys. The authors suggest therefore that these monkeys are not the primary host of the virus which is still unknown, but might have its origin in Old World monkeys deducing from a positive test for TMAdV antibodies for one monkey with Old World origin.
25.13.2
Novel coronavirus
Coronaviruses are a large family of viruses that includes viruses that may cause a range of illnesses in humans, from the common cold to SARS (severe acute respiratory syndrome) with 8 000 deseases and 800 death caused by the SARS epidemic in 2003. No SARS cases were reported since 2004. Viruses of this family also cause a number of animal diseases. Novel coronavirus This particular strain of coronavirus has not been previously identied in humans. This novel coronavirus is not the same coronavirus that caused SARS. The CDC reported on 14 May 2013 that a total of 34 people in Saudi Arabia, Qatar, Jordan, the United Kingdom (UK), the United Arab Emirates, and France were conrmed to have respiratory illness caused by a novel (new) coronavirus, twenty people died. [130] The health organizations recommend surveillance for severe acute respiratory infections (SARI). Health care providers are advised to be vigilant among recent travellers returning from areas aected by the virus who develop severe SARI. The WHO and CDC see no need for travelers to change their travel plans because of these cases of the novel coronavirus. However, travelers to countries in or near the Arabian Peninsula should monitor their health and see a doctor right away if they develop fever and symptoms of lower respiratory illness, such as cough or shortness of breath. [131] How to avoid u like diseases [132] Taking these everyday actions can help prevent the spread of germs and protect against colds, u, and other illnesses: Wash your hands often with soap and water. If soap and water are not available, use an alcohol-based hand sanitizer. Avoid touching your eyes, nose, and mouth. Germs spread this way. Avoid close contact with sick people. Be sure you are up-to-date with all of your shots. The disease is associated with symptoms of lower respiratory illness, such as cough
25.14. PARVOVIRUSES
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or shortness of breath, within 10 days after travelling from countries in or near the Arabian Peninsula.
25.14
Parvoviruses
Parvoviruses are associated with human gastroenteritis. Shellsh have been implicated in illness caused by a parvo-like virus. Although foods are not analysed in routine for these viruses, it may be possible to apply current immunological procedures to detect viruses in clinical specimens. Gene probes and PCR detection methods are currently being developed. In near future a better surveillance of these epidemics will increase food safety. Quality assurance programs in slaughterhouses should reduce fecal contamination of carcasses and meat should be chilled rapidly. Monitoring trends of indicator organisms, e.g. Enterobacteriaceae and Standard Plate Count should indicate deviations from quality standard A general method for E.coli detection i.e. for non-pathogenic and potentially pathogenic strains, is also useful as levels of all types of E.coli should be minimised in food production. Any increase of normal levels or indicators should trigger an active investigation of the reasons for the increased levels. Eective process control of all cooking / pasteurisation stages is essential to ensure that the correct heating temperatures and times are achieved.
25.15
SARS Severe Acute Respiratory Syndrome
SARS coronavirus (SARS-CoV) type causes an epidemic of a respiratory disease which spreads in Guangdong and other provinces of Chin, Canada, the United States. The virus may remain on hands and surfaces for several hours. Strict hand-hygiene be enforced among food handlers and within the food processing industry. This should be done very carefully after using the restroom and after sneezing or coughing. In addition, food workers should not handle ready-to-eat foods, such as sandwiches, vegetables and cut fruits, with bare hands, but should use gloves or utensils for an extra level of protection. The SARS global outbreak of 2003 was contained; however, it is possible that the disease could re-emerge. Proper hand washing continues to serve as a vital and necessary public health practice
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to eliminate the spread of food borne illnesses in retail food stores and food service. Contamination factors common in retail and food service environments inhibit the eectiveness of alcohol-based hand sanitizers when used in place of hand washing. Corona viruses are named for their corona-like appearance. The corona or halo is due to an array of surface projections on the viral envelope, one of which is the E2 glycoprotein, the viral attachment protein. Corona viruses are second only to rhinoviruses as a cause of the common cold and pneumonia.
25.15.1
Oral zinc formulations reduce duration of cold symptoms in adults [133]
According to Michelle Science et al. 2012 oral zinc formulations reduce the duration of cold symptoms in adults, but not in children. The authors conducted a systematic review and meta-analysis to evaluate the ecacy and safety of oral zinc as a single agent for the treatment of the common cold. Additional zinc formulation, as zinc acetate, but not zinc gluconate or zinc sulfate, were found to reduced the duration of symptoms. Adverse events, such as bad taste and nausea were more frequent in patients which received zinc. The authors call for large high-quality trials enrolling adults and children as uncertainty remains regarding the ecacy and adverse eects were common.
25.15.2
High daily dose exceeding 75 mg, but not low-dose of zinc lozenges reduce duration of common cold [134]
Harri Hemil 2011 reports that high-dose, but not low-dose, zinc lozenges shorten the duration of the common cold. Many studies found diverging results related to the eect of zinc lozenges on the common cold. The trials using a total daily zinc dose of less than 75 mg found no eect on common cold duration, trials using zinc acetate in daily doses exceeding 75 mg showed a 42% reduction in the duration of colds. The trials using zinc salts other than acetate in daily doses exceeding 75 mg, showed a 20% reduction in the duration of colds. Zinc lozenges caused bad taste and constipation in some cases, but no long term harm was reported No adverse eects were reported with zinc acetate, even at daily dose of 92 mg. No harm is expected treating the common cold for a week with high doses of zinc in the form of lozenges.
25.15.3
Infectious Laryngotracheitis in poultry
Infectious Laryngotracheitis is a viral infection of the respiratory tract of chickens, pheasants and peafowl. It can spread rapidly among birds and causes high death losses in poultry
25.15. SARS SEVERE ACUTE RESPIRATORY SYNDROME
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that are susceptible. The disease is not a human health risk. Turkeys, ducks and geese do not get the infection but could spread the virus.
25.15.4
Mycoplasmosis
Mycoplasma gallisepticum is associated with chronic respiratory disease (CRD)/air sac syndrome in chickens and turkeys and infectious sinusitis of turkeys; Mycoplasma meleagridis is associated with airsacculitis in turkeys; and Mycoplasma synoviae is the cause of infectious synovitis in chickens and turkeys. Mycoplasma are bacterial-like organisms.
25.15.5
Mareks Disease
Mareks is a member of the herpesvirus family of viruses. It causes internal tumours. The most common Mareks in chictumoursre eye, visceral, and nerve versions. The turkevisceralon is Herpes Virus Turkey. The waterfowl version is known as Duck Virus Enteritis. All three are from the same family of viruses.
25.15.6
Vaccination in China [135]
Using a technique called reverse genetics, scientists at the Key Laboratory of Animal Inuenza, aliated to Harbin Veterinary Research Institute, altered the genome sequence of the virus to construct a vaccine that is believed to be safe to both poultry and mammals. The vaccine will be administered to fowls in the countrys key water areas, including rivers and lakes. Laboratory tests show the vaccine enables ducks and geese to ght H5N1, the highly lethal strain of bird u, three weeks after the ocks were vaccinated, the statement claimed. The new vaccine also provides at least 10 months of protection for chickensfour months longer than the existing bird u preventive drugs. China developed advanced bird u virus test technology (RT-PCR reagent kit) last April. This can detect H5, H7 and H9 subgroups of the bird u simultaneously in several hours. Vaccination is a must for water fowls and poultry farms in Chinese regions at high risk, according to a national tele-conference in bird u prevention on January 28 in Beijing. Apart from the encouraging laboratory test results, eld tests also indicate that upon receiving two shots of the vaccine, ducks and geese can each produce antibodies eective for 10 months and three months, respectively. According to the ministry statement the vaccination thus makes it impossible for ducks and geese to become the load of H5 subgroup bird u virus. Therefore, it can cut a key link for the highly pathogenic avian inuenza to spread.
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German ocials , however say, vaccination is not the solution of the problem. In Italy nobody can say if poultry is free of H5N1 because some ocks were vaccinated using an attenuated virus H7N3. Imunity against all H7 (Hafez) Vaccinated poultry cannot be exported. Under European law, any vaccinated birds would face restrictions on movement which would prevent export and allow them only to be transported to a slaughterhouse. Britain continues to oppose the vaccination programme on grounds of both cost and eectiveness, as do Germany, Austria, Denmark and Portugal. Vaccinated birds could incubate the disease without showing symptoms, allowing low-level spread among ocks and increasing the likelihood of its mutation into a form transmissible to people. Neuraminidase is the protein which gives the number to N. There are only two laboratories which can type the N number. One is located at the island Riems (Germany) and the other is the EU reference laboratory located in England. In Germany researches on a vaccine is being done at the Bundesforschungsinstitutes fr Tiergesundheit, Im Friedrich-Loeer-Insitut (FLI) Thomas Mettenleiter says they are working on recombinant serum which can be sprayed instead of having to be injected on every bird. They could have a marker eect which could be easily detected. A vaccine which will take two to three years to be ready to use. New epidemic of highly pathogenic avian inuenza virus of subtype H5N1 in Germany [136] An epidemic of highly pathogenic avian inuenza virus of subtype H5N1 Asia (HPAIV H5N1) broke out again in mid February 2013 in a farm of Bandenburg, On 16.Febr. 2013 14.500 ducks had to be culled. Germany had been free of avian inuenza virus for three years. Germany. Veterinarians say that there is no danger for humans, however the H5N1 virus threatened poultry holdings worldwide since 1997. According to the Friedrich-Ler-Institut the actual epidemic is caused by a not high pathogenic variant of the virus, says Alrun Kaune-Nlein, speaking for the Health Department of Potsdam, Germany. Because of its signicant zoonotic potential this virus is also able to infect humans after direct, close contact with infected birds. The detection of HPAIV H5N1 in wild bird populations as well as in several poultry holdings in Germany in 2006 and 2007 highlighted the problems and dangers of such outbreaks. [137] The concerned poultry farm has been isolated by 1 kilometre of a prohibited area for 21 days to avoid spreading of the epidemic. People which had been in contact with the
25.15. SARS SEVERE ACUTE RESPIRATORY SYNDROME animals were told to report immediately any symptoms of disease.
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Signs of the disease in poultry are marked by paranormal position of the head, discharges at eyes and beak, refusal of feed, sneezing. Most human infections with avian inuenza A viruses have occurred following direct contact with infected poultry. Human clinical illness from infection with avian inuenza A viruses has ranged from eye infections (conjunctivitis) to severe respiratory disease (pneumonia) to death. Avianin57668 Avian inuenza A virus strains are further classied as low pathogenic (LPAI) or highly pathogenic (HPAI) on the basis of specic molecular genetic and pathogenesis criteria that require specic testing. Most avian inuenza A viruses are LPAI viruses that are usually associated with mild disease in poultry. In contrast, HPAI viruses can cause severe illness and high mortality in poultry. More recently, some HPAI viruses (e.g., H5N1) have been found to cause no illness in some poultry, such as ducks. LPAI viruses have the potential to evolve into HPAI viruses and this has been documented in some poultry outbreaks. [138]
25.15.7
EU measures to limit the spread of avian inuenza
The European Commission measures designed to limit the disease are approve member states individual surveillance plans for avian inuenza and to provide up to 50 per cent co-funding for these programmes. The measures include a three km "protection zone" around the place where the birds with H5 infection were found for at least 30 days along with a 10 km "surveillance zone" for the next three weeks. Within the protection zone poultry must be kept indoors. All movement of poultry, excluding direct transportation to a slaughterhouse is banned. No meat may be transported outside the protection zone. In both the protection and surveillance zone farm biosecurity measures must be strengthened and the hunting of wild birds is banned. All bird markets and exhibitions are banned. Early warning measures are in place in all member states to ensure quick detection of the disease, both in domestic and wild birds. Contingency plans call for the rapid control and eradication of avian inuenza should it occur in poultry farms. Indonesia vaccinated 114 million poultry against avian u with traditionally made vaccine in 2004. India last week conrmed the presence of avian u and has started a mass culling of poultry.
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In February 2006 the French government ordered all domestic birds indoors. Wild birds with highly pathogenic avian inuenza have been detected in France, Slovakia, Slovenia, Italy, Greece, Austria, Hungary and Germany, in addition to the accession countries Bulgaria and Romania and Turkey. Aected EU member states are implementing strict protection and surveillance zones around the location where H5N1 infected wild birds have been found. In addition, the EU has approved the vaccination of bird ocks in certain areas of the Netherlands and France. Vaccination is being permitted in selected southern areas of France that are believed to be at risk from avian inuenza. The free-range ducks and geese in this region are not easy to put "indoors" and are therefore at risk of contact with wild birds that may be carrying the virus, according to an European Commission report. The vaccination programme will begin immediately and will continue until 1 April 2006. Sentinel birds, which are unvaccinated control birds, will be used as part of the monitoring for avian inuenza. Vaccinated poultry, their hatching eggs and day-old chicks cannot be exported or moved to any third country, including countries in the EU. There are strict conditions on the movement of vaccinated birds within France. Fresh meat and meat products from vaccinated poultry will be able to be sold in the EU, provided the safety conditions have been complied with by the farm. Indonesia vaccinated 114 million poultry against avian u with traditionally made vaccine in 2004. India last week conrmed the presence of avian u and has started a mass culling of poultry. The Food and Agriculture Organisation (FAO) has warned that the virus could become entrenched in the Black Sea, Caucasus and Near East regions through trade and movement of people and animals and it could be further spread by migratory birds particularly coming from Africa in the spring. According to FAO ghting the avian inuenza virus in animals is the most eective and cost-eective way to reduce the likelihood of H5N1 mutating or reassorting to cause a human u pandemic. Containing bird u in domestic animals-mostly chickens and ducks-will signicantly reduce the risk to humans. Avian inuenza should not only be considered as a human health issue, but as a human and animal health issue.
25.15.8
Extraordinary collective eort to address avian u
According to a study of Anna Thorson and colleges the veried human cases of highly pathogenic avian inuenza in Vietnam may represent only a selection of the most severely
25.16. VACCINE AGAINST H5N1 FOR HUMANS ill patients.
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Epidemiological data are consistent with transmission of mild, highly pathogenic avian inuenza to humans and suggest that transmission could be more common than anticipated, though close contact seems required. However, the virus is more widespread than thought[139] According to Ko Annan, Secretary-General, United Nations (2005), a threat like a u pandemic cannot be addressed by one organisation, one group of countries, one sector or one profession. It presents us with an extraordinary collective challenge, and it calls for an extraordinary collective eort. On 29 November 2005, the Commission adopted a communication calling for the strengthening of EU-wide coordination in tracking and responding to avian u.
25.16
Vaccine against H5N1 for humans
[140] In March 2005, Sano Pasteur, the French vaccine manufacturer, released the rst vaccine made for humans directed against the avian inuenza A H5N1 virus for testing and evaluation by virology laboratories. Tests showed it was eective, but in a much higher than usual dose. The Sano Pasteur H5N1 avian u vaccine is unlikely to be of much use against the virus because the u virus is always changing. While vaccination is our best hope of avoiding catastrophe, it is pretty certain that none will be available when the rst wave of the pandemic spreads across the globe.
25.16.1
Low dose vaccine against H5N1
A 10 mg vaccine that contains a modied version of the whole H5N1 virus plus adjuvant was tested in China in 2006. This vaccine is eective at low doses allow more people to be immunised. [141]
25.16.2
Vaccine using fertilized eggs
Vaccine production using fertilized eggs takes 6 to 8 months under the best of circumstances, it has been more dicult than usual with the H5N1 strain because it is so lethal that it kills chicken embryo before there is enough time raise a good yield of vial particles. This type of vaccine requires two high doses, one month apart. Research is looking for a vaccine that requires much smaller doses so that manufacturers can rapidly produce more vaccine doses. For this new methods of producing vaccines are discussed:
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25.16.3
Vaccine with aluminium adjuvant
An adjuvant such as aluminium or gold particles attached to the vaccine can boost the immune response. By increasing the immune response, smaller doses of vaccine may be used, helping the manufacturers to produce more doses. The administration of the vaccine would be easier using air pistols instead of injection by needls.
25.16.4
EFSA Advises on the Safety of Aluminium in Food [142]
Europes food safety watchdog established a Tolerable Weekly Intake (TWI) of 1 milligram of aluminium per kilogram of body weight. The mean dietary exposure of adults varied from 0.2 to 1.5 mg/kg bw/per week. In children and young people, the highest exposures ranged from 0.7 to 2.3 mg/kg bw/per week. The TWI of 1 mg/kg bw/week is therefore likely to be exceeded in a signicant part of the European population. Children generally have higher food intake than adults when expressed on a body weight basis, and therefore represent the group with the highest potential exposure to aluminium per kg body weight. Large individual variations in dietary exposure to aluminium can occur. In children and young people the potential estimated exposure at the 97.5th percentile ranged from 0.7 mg/kg bw/week for children aged 3-15 years in France to 2.3 mg/kg bw/week for toddlers (1.5-4.5 years) and 1.7 mg/kg bw/week for those aged 4-18 years in the UK. Cereals and cereal products, vegetables, and beverages appeared to be the main contributors (>10%) to the dietary aluminium exposure in the general population. The major source of exposure to aluminium in foods originates from its natural occurrence, from the use of food additives containing aluminium and from the presence of aluminium in food contact materials such as pots, pans and foil. The main contributors to aluminium intake from the diet are cereals and cereal products (such as bread, cakes, biscuits and pastries) vegetables (such as mushrooms, spinach, radish and lettuce), beverages (such as tea and cocoa) and some infant formulae. Drinking water is a minor source of exposure. Additional exposure may arise from pharmaceuticals and consumer products containing aluminium compounds. The Panel based its evaluation on the combined evidence from a number of animal studies showing adverse eects on testes, embryos and the developing and mature nervous system following dietary administration of aluminium compounds. Aluminium has shown neurotoxicity in patients undergoing dialysis and thereby chronically exposed to high concentrations of aluminium. It has also been suggested that aluminium is associated with Alzheimers disease and other neurodegenerative diseases in humans; however, based on the available scientic data, the Panel did not consider exposure to aluminium through food to present a risk for developing Alzheimers disease.
25.16. VACCINE AGAINST H5N1 FOR HUMANS
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Under normal and typical conditions the contribution of migration from food contact materials would represent only a small fraction of the total dietary intake. However, the Panel noted that in the presence of acids and salts, the use of aluminium-based pans, bowls, and foils for foods such as apple puree, rhubarb, tomato puree or salted herring could result in increased aluminium concentrations in such foods. Also, the use of aluminium vessels and trays for convenience and fast food in might moderately increase the aluminium concentrations, especially in foods that contain tomato, dierent types of pickles, and vinegar.
25.16.5
Aluminium in infant formulae
In infants aged 0-3, 4-6, 7-9 and 10-12 months, potential dietary exposures from infant formulae and other foods manufactured specially for infants were estimated to be respectively 0.10, 0.20, 0.43 and 0.78 mg/kg bw/week. Potential exposure to aluminium in 3-month infants from a variety of infant formulae was estimated by the Panel. At the mean it was up to 0.6 mg/kg bw/week for milk-based formulae and was 0.75 mg /kg bw/week for soya-based formulae; at high percentiles of exposure it was up to 0.9 mg/kg bw/week for milk-based formulae and was 1.1 mg /kg bw/week for soya-based formulae. The Panel noted that in some individual brands of formulae (both milk-based and soyabased) the aluminium concentration was around 4 times higher that the mean concentrations estimated above, leading to a 4 times higher potential exposure in brand-loyal infants. Potential exposure in breast-fed infants was estimated to be less than 0.07 mg/kg bw/week.
25.16.6
High-dose, but not low-dose of zinc lozenges reduce duration of common cold [143]
Harri Hemil 2011 reports that high-dose, but not low-dose, zinc lozenges shorten the duration of the common cold. Many studies found diverging results related to the eect of zinc lozenges on the common cold. In this review Hemil separated the low-dose zinc and high-dose zinc trials. The trials using a total daily zinc dose of less than 75 mg found no eect on common cold duration, trials using zinc acetate in daily doses exceeding 75 mg showed a 42% reduction in the duration of colds. The trials using zinc salts other than acetate in daily doses exceeding 75 mg, showed a 20% reduction in the duration of colds. In several trials, the zinc lozenges caused bad taste and constipation, but none of the trials reported long term harm. These adverse eects may have been caused by the specic lozenge composition and are not related to zinc ions per se. No adverse eects were reported with zinc acetate, even at daily dose of 92 mg. No harm is expected treating
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the common cold for a week with high doses of zinc in the form of lozenges. The author concluded that benet is observed with high doses of zinc (daily doses exceeding 75 mg) but not with low doses.
25.16.7
Reverse genetics technique
Reverse genetics uses only specic parts of the genetic code of the viruses. This enables to make a generic vaccine with all of the 15 variations from H1 to H15.
25.17
Researches on HIV and antiretroviral drugs strategies, the HPTN 035 Study
A retrovirus is an RNA virus that is replicated in a host cell via the enzyme reverse transcriptase to produce DNA from its RNA genome. The DNA is then incorporated into the hosts genome by an integrase enzyme. The virus thereafter replicates as part of the host cells DNA. Retroviruses are enveloped viruses that belong to the viral family Retroviridae. The virus itself stores its nucleic acid in the form of a +mRNA (including the 5cap and 3PolyA inside the virion) genome and serves as a means of delivery of that genome into cells it targets as an obligate parasite, and constitutes the infection. Once in the hosts cell, the RNA strands undergo reverse transcription in the cytosol and are integrated into the hosts genome. The HIV virus is the most prominent retrovirus. Antiretroviral drugs are medications for the treatment of infection by retroviruses, primarily HIV. Dierent classes of antiretroviral drugs act at dierent stages of the HIV life cycle. [144]
25.17.1
Genetic engineered plant production of a complex HIV drug unites eciency and low production cost [145]
Sexton and colleages 2009 describe a fusion protein molecule which may be useful as HIV microbicide. It is the combination of the HIV-neutralizing mAb b12 expressed in transgenic plants. This substance has gp120 binding activity and HIV-neutralizing activity in vitro. A combinational protein, also obtained by genetically modifying the plant, unites the mAb b12 with cyanovirin-N, both microbicides act synergistically to control the HIV virus. The fusion protein molecule is predicted to have four binding sites for HIV gp120. The authors stress that genetic engineering of plant can make the drug aordable for developing countries and turn the production of high quantities possible. Its eciency was only tested in vitro. The authors deplore the high legislation barriers for new drugs, meanwhile no regulations are set regarding new food supplements to be put on market.
25.17. RESEARCHES ON HIV AND ANTIRETROVIRAL DRUGS STRATEGIES, THE HPTN 035 STUDY 1883
25.17.2
Microbicide gel to prevent HIV infection of women [146]
Sharon Hillier and colleagues 2009, leading the HPTN 035 study reports the prevention of HIV infections in women using a vaginal 0.5% microbicide gel preventing the HIV virus from attaching to cells in the genital tract. The authors claim that the gels was 30% eective. Several candidate microbicides are being tested in clinical trials, although none is yet approved or available for use. Condoms are very eective to prevent HIV infection, but are often not accepted by the male partner. Applying the gel, women could protect themselves. Infection male to female is more frequent as the infection of men. The study was conducted in Africa an in the USA during 2005 - 2008, assessing the effectiveness of BuerGel and 0.5% PRO 2000/5 Gel (P) in preventing the following among women at risk for sexually-transmitted HIV infection: bacterial vaginosis, chlamydia infection, genital ulcer disease, gonorrhea infection, herpes simplex virus-2 infection, pregnancy, syphilis infection, trichomoniasis. HPTN 035 tested two candidate microbicides with dierent mechanisms of action: BuerGel and PRO 2000 (0.5% dose). BuerGel is designed to boost the natural acidity of the vagina in the presence of seminal uid. Semen reduces the acidity of the vagina making it more receptive for pathogens that cause sexually transmitted infections, such as HIV. PRO 2000 is an entry/fusion inhibitor that is designed to hamper HIVs ability to attach to and infect healthy cells. Although the participants in the PRO 2000 study arm had a 30 percent lower rate of HIV infection compared with the Buer gel, tha placebo gel and a no-gel group. However, 33 percent eectiveness would have been needed to considered the results statistically signicant. The authors call therefore for more studies whether PRO 2000 prevents HIV infection in women. [147]
25.17.3
Mathematical models predict higher protection rate in men than women using vaginal microbicides [148]
Results of mathematical models of 2008 simulating clinical trials and population-level transmission of HIV, found that if HIV-positive women using microbicides may develop drugresistant strains of HIV that are then less likely to be transmitted to men. In the high-risk scenario, the mathematical models predict for the use of microbicides prevention of infection of 21% for women and 27% for men. In the low-risk scenario, the microbicide would be 17% and 18% respectively. Sally Blower, professor of psychiatry and biobehavioral sciences said that vaginal microbicides are being developed to provide direct protection to women in case of non-acceptance
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of condom use by men. However, there are also concerns that microbicides could lead to drug resistance if they are used by HIV-positive women.
25.17.4
Impact of climate change on viral pathogens in water [149]
Viroclime project tries to determine the eects of climate change on the dispersal of pathogenic viruses in rivers,lakes and at beaches, and resulting viral water-related diseases. Studies will be performed in Sweden, Spain, Hungary, Greece and Brazil which are vulnerable to climate change (principally rainfall events), and changes in exposure under dened conditions will be estimated. Bacterial faecal indicator analysis will permit the determination of relationships between virus levels and water quality standards, and also between changes in virus concentration in water and risk to public health activities, such as bathing in polluted water or consumption of shellsh. The Virocline project stresses the importance of gastro-intestinal disease caused by viruses related to climate change. Human-derived viruses are present in sewage and waste water and and have a strong survival in the environment. The project aims to develop tools for routine and quantitative virological monitoring of the environment, and provide baseline virological data from dierent environments to predict the inuence of climate change on virus population and their impact on disease burden.
25.18
Hantavirus
Hantaviruses are enveloped RNA viruses which may infect humans through rodent bites, urine, saliva or contact with rodent waste products. Some hantaviruses cause potentially fatal diseases in humans, hemorrhagic fever with renal syndrome (HFRS) in the Old World and hantavirus pulmonary syndrome (HPS), but others have not been associated with human disease in the Americas. [150]
25.18.1
Hanta virus in Germany [151]
From October 2011 to April 2012, 852 human hantavirus infections were notied in Germany, 68% of which occurred in Baden-Wrttemberg. The early rise could be due to a beech mast year in 2011, followed by an early and massive reproduction of the reservoir bank vole populations during winter 2011 and spring 2012. Puumala virus is the predominant human pathogenic hantavirus species in western, central and northern Europe, and is transmitted by exposure to excreta of bank voles (Myodes
25.18. HANTAVIRUS
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glareolus), a small rodent. Picture: Bank Vole. Author=Evan James hymo Date=2010-04-12 http://en.wikipedia.org/wiki/Bank_Vole Incubation period is two to four weeks followed by fever, headache, back pain and gastrointestinal symptoms. Renal involvement is prominent and manifests initially as oliguria and later as marked polyuria (nephropathia epidemica). Only 30% present typical clinical signs. The disease is therefore under-reported. There is no specic antiviral treatment available, avoidance of exposure and inhalation of contaminated dust is therefore recommended, says Eurosurveillance. The bank vole, the striped eld mouse (Apodemus agrarius) and the eld mouse (Microtus arvalis) may be infected. The live in forests and human dwellings. It is therefore being recommended to avoid undergrowth when walking throug a forest or a park, and keep the garage and attic tidy.
25.18.2
Preventing Hantavirus Pulmonary Syndrome (HPS) [152]
Rodent control in and around the home remains the primary strategy for preventing hantavirus infection.says the CDC. Eliminate or minimize contact with rodents in your home, workplace, or campsite. Seal up holes and gaps in your home or garage. Place traps in and around your home to decrease rodent infestation. Clean up any easy-to-get food. Some people who became ill reported that they had not seen rodents or rodent droppings at all. The CDC recommends, therefore, if you live in an area where the carrier rodents are known to live, try to keep your home, vacation place, workplace, or campsite clean. Signs and symptoms for Hantavirus Pulmonary Syndrome (HPS) may develop between 1 and 5 weeks after exposure to fresh urine, droppings, or saliva of infected rodents.
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Symptoms of HPS
Early symptoms include fatigue, fever and muscle aches, especially in the large muscle groups thighs, hips, back, and sometimes shoulders, headaches, dizziness, chills, and abdominal problems, such as nausea, vomiting, diarrhea, and abdominal pain. Late symptoms are noted 4 to10 days after the initial phase of illness, the late symptoms of HPS appear. These include coughing and shortness of breath as the lungs ll with uid. The disease has a mortality rate of 38%.
25.18.4
Emerging viral diseases in Europe [153]
Lbermann et al 2012 report that due to climate changes, insucient vaccination, and travel of man and goods may become a new health risk due to emerging viral infections of low incidence in Europe. Dengue, Sindbis, or Chikungunya virus, tick-born encephalitis (TBE), Toscana, or West Nile virus, Crimean Congo and Hanta virus.
25.18.5
Diseases transmitted by animal food are responsible for 2.2 million people [154]
Flores Castro 2010 stresses that international trade in animals, products and sub products, as well as the intense travel of people around the world, represent risks of emerging and reemerging zoonotic diseases, such as anthrax, rabies, tuberculosis, brucellosis, cysticercosis, echinococcosis, hanta virus, Hendra and Nipah virus and leptospirosis, the widest spread zoonotic disease in the world.
Bibliography
[1] The international committee on taxonomy of viruses (ictv), the international code of virus classication and nomeclature. http://www.ictvonline.org/ codeOfVirusClassification_2002.asp. [2] Current ictv virus taxonomy database. http://ictvonline.org/virusTaxonomy. asp. [3] Who: Dengue guidelines for diagnosis, treatment, prevention and control 2009. http: //whqlibdoc.who.int/publications/2009/9789241547871_eng.pdf. [4] Lima Mda R, Nogueira RM, Schatzmayr HG, de Filippis AM, Limonta D, and Dos Santos FB. A new approach to dengue fatal cases diagnosis: Ns1 antigen capture in tissues. PLoS Negl Trop Dis, 5(5):e1147, 5 2011. http://www.plosntds. org/article/info%3Adoi%2F10.1371%2Fjournal.pntd.0001147. [5] Allonso D, da Silva Rosa M, Coelho DR, da Costa SM, Nogueira RM, Bozza FA, Santos FB, de Barcelos Alves AM, and Mohana-Borges R. Polyclonal antibodies
BIBLIOGRAPHY
1887
against properly folded dengue virus ns1 protein expressed in e. coli enable sensitive and early dengue diagnosis. J Virol Methods, 5 2011. http://www.ncbi.nlm.nih. gov/pubmed/21569796. [6] Yap G, Sil BK, and Ng LC. Use of saliva for early dengue diagnosis. PLoS Negl Trop Dis, 5(5):e1046, 5 2011. http://www.ncbi.nlm.nih.gov/pubmed/21572982. [7] Sabchareon A, Wallace D, Sirivichayakul C, Limkittikul K, Chanthavanich P, Suvannadabba S, Jiwariyavej V, Dulyachai W, Pengsaa K, Wartel TA, Moureau A, Saville M, Bouckenooghe A, Viviani S, Tornieporth NG, and Lang J. Protective ecacy of the recombinant, live attenuated, cyd tetravalent dengue vaccine in thai schoolchildren: a randomised, controlled phase 2b trial. www.thelancet.com published online september 11, 2012. 9 2012. http://www.thelancet.com/journals/ lancet/article/PIIS0140-6736%2812%2961428-7/abstract. [8] Halstead SB. Dengue vaccine development: a 75% solution? the lancet, early online publication, 11 september 2012. The Lancet, 9 2012. dx.doi.org/10.1016/ S0140-6736(12)61510-4. [9] Die welt: Neuer impfsto wirkt gegen dengue-eber. 11 sept 2012. http://www. welt.de/print/die_welt/wissen/article109134213/Wissen-Kompakt.html. [10] Durbin AP and Whitehead SS. Next-generation dengue vaccines: novel strategies currently under development. Viruses, 3(10):180014, 10 2011. http://www.ncbi. nlm.nih.gov/pmc/articles/PMC3205382. [11] Bar-Gal GK, Kim MJ, Klein A, Shin DH, Oh CS, Kim JW, Kim TH, Kim SB, Grant PR, Pappo O, Spigelman M, and Shouval D. Tracing hepatitis b virus to the 16(th) century in a korean mummy. Hepatology, 5 2012. http://www.ncbi.nlm.nih.gov/ pubmed/22610996. [12] Who hepatitis b fact sheet nr. 204 july 2012. http://www.who.int/mediacentre/ factsheets/fs204/en/index.html. [13] Dao DY, Hynan LS, Yuan HJ, Sanders C, Balko J, Attar N, Lok AS, Word RA, and Lee WM; Acute Liver Failure Study Group. Two distinct subtypes of hepatitis b virus-related acute liver failure are separable by quantitative serum immunoglobulin m anti-hepatitis b core antibody and hepatitis b virus dna levels. Hepatology, 55(3):67684, 3 2012. http://www.ncbi.nlm.nih.gov/pubmed/21987355. [14] Hatzakis A, Wait S, Bruix J, Buti M, Carballo M, Cavaleri M, Colombo M, Delarocque-Astagneau E, Dusheiko G, Esmat G, Esteban R, Goldberg D, Gore C, Lok AS, Manns M, Marcellin P, Papatheodoridis G, Peterle A, Prati D, Piorkowsky N, Rizzetto M, Roudot-Thoraval F, Soriano V, Thomas HC, Thursz M, Valla D, van Damme P, Veldhuijzen IK, Wedemeyer H, Wiessing L, Zanetti AR,
1888
CHAPTER 25. VIROLOGY and Janssen HL. The state of hepatitis b and c in europe: report from the hepatitis b and c summit conference. J Viral Hepat, 18(Supl 1):116, 9 2011. http: //onlinelibrary.wiley.com/doi/10.1111/j.1365-2893.2011.01499.x/full.
[15] http://en.wikipedia.org/wiki/Chlorine_dioxide. Wikipedia, the free enzyclopedia: Chlorine dioxide. [16] Chinese man dies in rst bird u case since 2010. time healthland 31 dec 2011. http://healthland.time.com/2011/12/31/ chinese-man-dies-in-first-bird-flu-case-since-2010/#ixzz1iQMKFMC0. [17] Van Kerkhove MD, Mumford E, Mounts AW, Bresee J, Ly S, Bridges CB, and Otte J. Highly pathogenic avian inuenza (h5n1): pathways of exposure at the animal-human interface, a systematic review. PLoS One, 6(1):e14582, 1 2011. http: //www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0014582. [18] Rabinowitz P, Perdue M, and Mumford E. Contact variables for exposure to avian inuenza h5n1 virus at the human-animal interface. Zoonoses Public Health, 57(4):227 38, 6 2010. http://www.ncbi.nlm.nih.gov/pubmed/19486500. [19] Jourdain E, Gauthier-Clerc M, Bicout DJ, and Sabatier P. Bird migration routes and risk for pathogen dispersion into western mediterranean wetlands. Emerg Infect Dis, 13(3):36572, 3 2007. http://wwwnc.cdc.gov/eid/article/13/3/06-0301_ article.htm. [20] Cui P, Hou Y, Xing Z, He Y, Li T, Guo S, Luo Z, Yan B, Yin Z, and Lei F. Bird migration and risk for h5n1 transmission into qinghai lake, china. Vector Borne Zoonotic Dis, pages 56776, 5 2011. http://www.ncbi.nlm.nih.gov/pubmed/20925522. [21] http://www.biomedcentral.com/1471-2334/10/187. Trevon L Fuller, Sassan S Saatchi, Emily E Curd, Erin Toelmier, Henri A Thomassen, Wolfgang Buermann, David F DeSante, Mark P Nott, James F Saracco, C J Ralph, John D Alexander, John P Pollinger, Thomas B Smith. Mapping the risk of avian inuenza in wild birds in the US. BMC Infectious Diseases, 2010; 10 (1): 187 DOI: 10.1186/1471-2334-10187. [22] http://www.upi.com/Science_News/2009/01/19/Third_case_of_bird_flu_in_ China/UPI-28011232418672/. UPI.com: Third case of bird u in China. [23] http://www.who.int/csr/don/2009_01_19/en/index.html. WHO: 19 January 2009. The Ministry of Health in China has reported 3 new cases of human infection with the H5N1 avian inuenza virus. [24] http://www.who.int/csr/don/2009_01_14a/en/index.html. Avian inuenza - situation in Egypt - update 14 January 2009.
BIBLIOGRAPHY
1889
[25] http://www.efsa.europa.eu/etc/medialib/efsa/science/ahaw/ahaw_ opinions/ej489_ai_vaccines.Par.0002.File.dat/ahaw_op_ej489_AI_ Vaccination_summary_en.pdf. Opinion of the Scientic Panel on Animal Health and Welfare on a request from the Commission related with the vaccination against avian inuenza of H5 and H7 subtypes in domestic poultry and captive birds. Published 6 June 2007. [26] http://www.ncbi.nlm.nih.gov/sites/pubmed/12745380. Capua, I.; Terregino, C.; Cattoli, G.; Mutinelli, F.; Rodrigues, J.F.: Development of a DIVA (Dierentiating Infected from Vaccinated Animals) strategy using a vaccine containing a heterologous neuraminidase for the control of avian inuenza. Avian Pathol. 2003. Febr.32(1) 47-55. [27] 4th meeting held by central epidemic command center for inuenza a (h7n9) passes ban on slaughtering of live poultry at traditional wet markets beginning june 17, 2013 ( 2013-04-18 ) . taiwanese centers for disease control (cdc). http://www.cdc.gov.tw/english/info.aspx?treeid= EE0A2987CFBA3222&nowtreeid=D3C5BBCF8E60CF3D&tid=21D026116A44C562. [28] Kageyama T, Fujisaki S, Takashita E, Xu H, Yamada S, Uchida Y, Neumann G, Saito T, Kawaoka Y, and Tashiro M. Genetic analysis of novel avian a(h7n9) inuenza viruses isolated from patients in china, february to april 2013. Euro Surveill, 18(15):pii: 20453, 4 2013. http://www.eurosurveillance.org/ViewArticle. aspx?ArticleId=20453. [29] Nicoll A and Danielsson N. A novel reassortant avian inuenza a(h7n9) virus in china - what are the implications for europe. Euro Surveill, 18(15):pii: 20452, 4 2013. http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=20452. [30] http://www.newsdesk.umd.edu/scitech/release.cfm?ArticleID=1878. University of Maryland - UM Newsdesk: Avian Flu Research Sheds Light on Swine Flu Outbreak. April 28, 2009. [31] http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool= pubmed&pubmedid=19380727. Sorrell, Erin M.; Wan, Hongquan; Araya, Yonas; Song, Haichen; Perez Daniel R.: Minimal molecular constraints for respiratory droplet transmission of an avian-human H9N2 inuenza A virus. Proceedings of the National Academy of Science U S A. pnas.0900877106. Published online 2009 April 17. doi: 10.1073/pnas.0900877106. [32] Schrauwen EJA, Herfst S, Chutinimitkul S, Bestebroer TM, Rimmelzwaan GF, and Osterhaus ADME et al. Possible increased pathogenicity of pandemic (h1n1) 2009 inuenza virus upon reassortment. Emerg Infect Dis, 2 2011. http://www.cdc.gov/ eid/content/17/2/200.htm?source=govdelivery.
1890
[33] Hurt AC, Leang SK, Speers DJ, Barr IG, and Maurer-Stroh S. Mutations i117v and i117m and oseltamivir sensitivity of pandemic (h1n1) 2009 viruses. Emerg Infect Dis, 12 2011. http://dx.doi.org/10.3201/eid1712.111079. [34] Yan J-H, Xiong Y-O, Yi C-H, Sun X-X, He Q-S, and Fu W et al. Pandemic (h1n1) 2009 virus circulating in pigs, guangxi, china (letter). Emerg Infect Dis, 18(2), 2 2012. http://dx.doi.org/10.3201/eid1802.111346. [35] Cappuccio JA, Pena L, Dibrbora M, Rimondi A, Pin eyro P, Insarralde L, Quiroga MA, Machuca M, Craig MI, Olivera V, Chockalingam A, Perfumo CJ, Perez DR, and Pereda A. Outbreak of swine inuenza in argentina reveals a non-contemporary human h3n2 virus highly transmissible among pigs. J Gen Virol, 92(Pt12):28718, 12 2011. http://www.ncbi.nlm.nih.gov/pubmed/21849519. [36] Cdc conrms detection of a dierent inuenza a variant virus. 23 dec 2011. http: //www.cdc.gov/media/haveyouheard/stories/Influenza_A_Variant.html. [37] Cdc uview: 2011-2012 inuenza season week 35 september 1, 2012. http://www. cdc.gov/flu/weekly/. [38] Evaluation of rapid inuenza diagnostic tests for inuenza a (h3n2)v virus and updated case count - united states, 2012. centers for disease control and prevention (cdc). MMWR Morb Mortal Wkly Rep, 61:61921, 8 2012. http://www.cdc.gov/ mmwr/preview/mmwrhtml/mm6132a4.htm. [39] Notes from the eld: Outbreak of inuenza a (h3n2) virus among persons and swine at a county fair - indiana, july 2012. centers for disease control and prevention (cdc). MMWR Morb Mortal Wkly Rep, 61:561, 7 2012. http://www.cdc.gov/mmwr/ preview/mmwrhtml/mm6129a5.htm. [40] Nelson MI, Vincent AL, Kitikoon P, Holmes EC, and Gramer MR. Evolution of novel reassortant a/h3n2 inuenza viruses in north american swine and humans, 2009-2011. J Virol, 86(16):88728, 8 2012. http://www.ncbi.nlm.nih.gov/pubmed/22696653. [41] Antibodies cross-reactive to inuenza a (h3n2) variant virus and impact of 201011 seasonal inuenza vaccine on cross-reactive antibodies - united states. centers for disease control and prevention (cdc). MMWR Morb Mortal Wkly Rep, 61(14):23741, 4 2012. http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6114a1.htm. [42] Kong WL, Huang LZ, Qi HT, Cao N, Zhang LQ, Wang H, Guan SS, Qi WB, Jiao PR, Liao M, and Zhang GH. Genetic characterization of h1n2 inuenza a virus isolated from sick pigs in southern china in 2010. Virol J, 13(8):469, 10 2011. http: //www.ncbi.nlm.nih.gov/pmc/articles/PMC3221723/?tool=pubmed. [43] Cdc issues new warning about swine u. http://www.capitolcolumn.com/news/ cdc-issues-new-warning-about-swine-flu-video/.
BIBLIOGRAPHY
1891
[44] Centers for disease control and prevention (cdc): Notes from the eld: Outbreak of inuenza a (h3n2) virus among persons and swine at a county fair - indiana, july 2012. MMWR Morb Mortal Wkly Rep, 61:561, 2012. www.ncbi.nlm.nih.gov/ pubmed/22832938. [45] Shu B, Garten R, Emery S, Balish A, Cooper L, Sessions W, Deyde V, Smith C, Berman L, Klimov A, Lindstrom S, and Xu X. Genetic analysis and antigenic characterization of swine origin inuenza viruses isolated from humans in the united states, 1990-2010. Virology, 422(1):15160, 1 2012. http://www.ncbi.nlm.nih. gov/pubmed/22078166. [46] Nfon CK, Berhane Y, Hisanaga T, Zhang S, Handel K, Kehler H, Labrecque O, Lewis NS, Vincent AL, Copps J, Alexandersen S, and Pasick J. Characterization of h1n1 swine inuenza viruses circulating in canadian pigs in 2009. J Virol, 85(17):866779, 9 2011. http://www.ncbi.nlm.nih.gov/pubmed/21697484. [47] Gerlo NA, Kremer JR, Charpentier E, Sausy A, Olinger CM, Weicherding P, Schuh J, Van Reeth K, and Muller CP. Swine inuenza virus antibodies in humans, western europe, 2009. Emerg Infect Dis, 17(3):40311, 2011. http://www.ncbi.nlm.nih. gov/pubmed/21392430. [48] WHO Epidemic and Pandemic Alert and Response (EPR) - Disease Outbreak newsAvian inuenza - new areas with infection in birds - update 34- 13 October 2005. [49] WHO Food safety-Avian inuenza (H5) in rural areas in Asia: food safety considerations. [50] http://www.foodnavigator-usa.com/news/ng.asp?n= 66062-bird-flu-vitamin-c-zinc. Stephen Daniells: Dietary supplements and bird u - the debate. Food Navigator.com USA 2/24/2006. [51] http://www.guardian.co.uk/birdflu/story/0,,1714320,00.html#article_ continue. Sarah Boseley: Warning over worthless remedies ; The Guardian Tuesday February 21, 2006. [52] http://www.mluv.brandenburg.de/cms/detail.php/lbm1.c.279974.de. Ministerium fr Lndliche Entwicklung, Umwelt und Verbraucherschutz (MLUV): Vogelgrippe in Brandenburg. [53] http://www.pandemicflu.gov/plan/pdf/guide.pdf. Guidelines for families and households to plan for infectious disease. [54] http://usinfo.state.gov/gi/img/assets/5096/120105_birdflu_2.pdf. CDC: Meeting the challenge of bird ue.
1892
[55] http://www.defra.gov.uk/animalh/diseases/notifiable/disease/ai/index. htm. Defra, UK: Avian Inuenza H5N1 conrmed in wild birds in Dorset. January 12, 2008 18:37. [56] http://www.cdfa.ca.gov/exec/pa/birdflu/. Latest Bird Flu World News 8-14. April 2007. [57] http://www.who.int/csr/disease/avian_influenza/country/cases_table_ 2007_04_11/en/index.html. WHO: Cumulative Number of Conrmed Human Cases of Avian Inuenza A/(H5N1) Reported to WHO 11 April 2007. [58] http://www.fao.org/newsroom/en/news/2007/1000660/index.html. Food and Agriculture Organization of the United Nations: Dramatic changes in global meat production could increase risk of diseases. Livestock producers should invest more in biosecurity and disease monitoring. 17 September 2007, Rome. [59] http://www.cdc.gov/swineflu/investigation.htm. uenza Investigation. April 25, 2009. CDC: Human Swine In-
[60] http://muse.jhu.edu/login?uri=/journals/bulletin_of_the_history_of_ medicine/v076/76.1johnson.html. Johnson, Niall P. A. S. / Mueller, Juergen D. pdating the Accounts: Global Mortality of the 1918-1920 Spanish nuenza Pandemic, Bulletin of the History of Medicine Volume 76, Number 1, Spring 2002, S. 105-115. DO1:10.1353/bhm.2002.0022. [61] http://www.apotheke-adhoc.de/index.php?m=1&s=5&showPage=4&id=5749. Hollstein, Patrick: Apotheke ad Hoc: H1N1 resistent gegen Tamiu. 11.03.2009. [62] http://www.spiegel.de/wissenschaft/mensch/0,1518,623867,00.html. Spiegel Online: Schweinegrippe, Pharmakologe zweifelt an Wirksamkeit von Tamiu. 10.05.2009. [63] http://content.nejm.org/cgi/reprint/NEJMoa0903810.pdf. Fatimah S. Dawood et al: Emergence of a Novel Swine-Origin Inuenza A (H1N1) Virus in Humans. This article (10.1056/NEJMoa0903810) was published at NEJM.org on May 7, 2009. N Engl J Med 2009;361. [64] http://content.nejm.org/cgi/content/full/NEJMoa0903812?query=TOC. Vivek Shinde et al: Triple-Reassortant Swine Inuenza A (H1) in Humans in the United States, 2005-2009. Published at www.nejm.org May 7, 2009 (10.1056/NEJMoa0903812). [65] http://content.nejm.org/cgi/content/full/NEJMe0903995. [4] Belshe, Robert B.: Implications of the Emergence of a Novel H1 Inuenza Virus. Published at www.nejm.org May 7, 2009 (10.1056/NEJMe0903995).
BIBLIOGRAPHY
1893
[66] http://www.who.int/csr/disease/avian_influenza/phase/en/index.html. WHO: The Current WHO phase of pandemic alert. [67] http://hygimia69.blogspot.com/2009/06/usa-cdc-press-briefing-transcripts-june_ 12.html. A Times Memory: USA. CDC Press Brieng Transcript June 11, 2009. [68] http://flu.gov/plan/school/toolkit.html. CDC: Preparing for the Flu: A Communication Toolkit for Schools (Grades K-12). 08.08.2009. [69] http://www.fda.gov/MedicalDevices/ProductsandMedicalProcedures/ MedicalToolsandSupplies/PersonalProtectiveEquipment/ucm055977.htm. FDA: Masks and N95 Respirators. [70] http://www.iom.edu/Object.File/Master/72/970/H1N1%20report%20brief% 20FINAL%20for%20web.pdf. Institute of Medicine. September 3, 2009. Respiratory protection for healthcare workers in the workplace against novel H1N1 inuenza A: A letter report. Washington, DC: The National Academies Press. [71] http://www.iom.edu/Object.File/Master/34/212/Face%20Masks%20for% 20web.pdf. Institute of Medicine (IOM): Reusability of Facemasks During an Inuenza Pandemic: Facing the Flu. Report April 2006. [72] http://www.ncbi.nlm.nih.gov/pubmed/19516283. Smith GJ, Vijaykrishna D, Bahl J, Lycett SJ, Worobey M, Pybus OG, Ma SK, Cheung CL, Raghwani J, Bhatt S, Peiris JS, Guan Y, Rambaut A.: Origins and evolutionary genomics of the 2009 swine-origin H1N1 inuenza A epidemic. Nature. 2009 Jun 11. [73] http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=19228. Nava, G. M.; Attene-Ramos, M. S.; Ang, J. K. Escorcia, M.: Origins of the new inuenza A(H1N1) virus: time to take action. Rapid communications. Eurosurveillance, Volume 14, Issue 22, 04 June 2009. [74] http://ww2.cdph.ca.gov/programs/vrdl/Pages/TestingforSwineInfluenzaA(H1N1) .aspx. California Department of Public Health. [75] http://www.timesonline.co.uk/tol/news/world/africa/article6193785.ece. Times Online: Egyptian Christians riot after swine u cull. April 29, 2009. [76] http://ca.news.yahoo.com/s/afp/090502/canada/health_flu_canada_pigs_1. Canadian pigs infected with H1N1 virus: ocial. [77] http://www.netzeitung.de/wissenschaft/367288.html. Netzeitung: Pandemie im Computer. Tbinger Wissenschaftler simulieren die Ausbreitung von Grippewellen. Ihr Programm soll als Entscheidungshilfe bei der Bekmpfung einer drohenden Pandemie dienen. 11.11.2005.
1894
[78] http://www.bioregio-stern.de/node/253. Bio Regio Stern: ExploSYS Simulation biologic Systems. [79] http://www.uni-tuebingen.de/modeling/Mod_Pub_Software_en.html. Modelling group at the Department of Medical Biometry, University of Tbingen: Software. [80] http://www.who.int/csr/disease/swineflu/en/. WHO: Swine u. [81] http://www.pandemicflu.gov/. One-stop access to U.S. Government H1N1, avian and pandemic u information: Pandemic Flu.gov. [82] http://www.cnbc.com/id/32096080/site/14081545. CNBC: Roche Prot Misses Forecasts, but Ups Guidance. 23.07.2009. [83] http://www.roche.com/media/media_releases/med-cor-2009-07-23.htm. Roche Global Website: Pharmaceuticals Division growth twice as fast as market. Media release 23.07.2009. [84] http://www.dw-world.de/dw/article/0,,4486961,00.html. Deutsche Welle.de: Germany plans to order 50 million swine u vaccination units. 14.07.2009. [85] http://www.ial.sp.gov.br/gripe/gripe.html. Instituto Adolfo Lutz: Nota Tecnica. [86] http://www.who.int/csr/disease/swineflu/frequently_asked_questions/ levels_pandemic_alert/en/index.html. World Health organisation: What about severity? [87] http://www.cdc.gov/eid/content/16/5/783.htm. De Serres, G; Rouleau, I; Hamelin,M-E; Quach, C; Skowronski, D; Flamand, L; Boulianne, N; Li, Y; Carbonneau, J; Bourgault, A-M; Couillard, M; Charest, H; Boivin, G: Contagious Period for Pandemic (H1N1) 2009. EID Journal. Volume 16, Number 5-May 2010. [88] http://www.cdc.gov/h1n1flu/guidance/exclusion.htm. Centers for Disease Control and Prevention. Recommendations for amount of time persons with inuenza-like illness should be away from others. October 23, 2009. [89] http://www.cdc.gov/h1n1flu/guidelines_infection_control.htm. Centers for Disease Control and Prevention. Interim Guidance on Infection Control Measures for 2009 H1N1 Inuenza in Healthcare Settings, Including Protection of Healthcare Personnel. March 10, 2010. [90] http://www.ncbi.nlm.nih.gov/pubmed/20180701. Ling LM, Chow AL, Lye AC, Tan AS, Krishnan P, Cui L, et al.: Eects of early oseltamivir therapy on viral shedding in 2009 pandemic inuenza A (H1N1) virus infection. Clin Infect Dis. 2010;50:963-9.
BIBLIOGRAPHY
1895
[91] http://www.ncbi.nlm.nih.gov/pubmed/20061398. Li IW,Hung IF, To KK, Chan KH, Wong SS, Chan JF, Cheng VC, Tsang OT, Lai ST, Lau YL, Yuen KY: The natural viral load prole of patients with pandemic 2009 inuenza A(H1N1) and the eect of oseltamivir treatment. Chest. 2010 Apr;137(4):759-68. Epub 2010 Jan 8. [92] http://www.ncbi.nlm.nih.gov/pubmed/19950247. To KK, Chan KH, Li IW, Tsang TY, Tse H, Chan JF, Hung IF, Lai ST, Leung CW, Kwan YW, Lau YL, Ng TK, Cheng VC, Peiris JS, Yuen KY: Viral load in patients infected with pandemic H1N1 2009 inuenza A virus. J Med Virol. 2010 Jan;82(1):1-7. [93] http://www.cdc.gov/eid/content/16/5/824.htm. Louie, J K; Guevara, H; Boston, E; Dahlke, M; Nevarez, M; Kong, T; Schechter, R; Glaser, CA, Schnurr, DP: Rapid Inuenza Antigen Test for Diagnosis of Pandemic (H1N1) 2009. EID Journal. Volume 16, Number 5-May 2010. [94] http://www.who.int/mediacentre/news/statements/2010/h1n1_vpc_ 20100810/en/index.html. H1N1 in post-pandemic period. WHO 10.08.2010. [95] http://www.who.int/csr/disease/swineflu/notes/briefing_20100810/en/ index.html. WHO recommendations for the post-pandemic period. WHO 10.08.2010. [96] http://www.spiegel.de/wissenschaft/medizin/0,1518,711246,00.html. Schweinegrippe-Impfstoe: Bund und Laender streiten ueber Millionenkosten. Spiegel Online 11.08.2010. [97] http://www.cdc.gov/eid/content/13/9/1434.htm. Tong G-Z, ZhouY-J, Hao XF, Tian Z-J,An T-Q, Qiu HJ: Porcine reproductive and respiratory syndrome in China. EID Volume 13, Number 9-September 2007. [98] http://www.capegateway.gov.za/eng/pubs/news/2004/jun/76376. The cape gateway: Blue ear disease in pigs: Possible source further investigation. [99] http://www.thepigsite.com/pighealth/article/142/ porcine-reproductive-and-respiratory-syndrome-prrs. Porcine Reproductive and Respiratory Syndrome (PRRS). [100] http://www.who.int/csr/don/2007_05_30/en/index.html. uenza, Situation in China, Update 2 30.05.2007. The pig site.com: WHO: Avian In-
[101] http://www.ncbi.nlm.nih.gov/pubmed/19022400. Hill, A.W; Guralnick, R.P.; Wilson, M.J.; Habib, F.; Janies, D.: Evolution of drug resistance in multiple distinct lineages of H5N1 avian inuenza. Infect Genet Evol. 2008 Oct 30. [102] http://news.xinhuanet.com/english/2007-08/20/content_6571588.htm. www.chinaview.cn: China brings blue-ear pig disease under preliminary control 2007-08-20 20:17:58.
1896
[103] http://news.xinhuanet.com/english/2008-02/23/content_7652514.htm. www.chinaview.cn: Blue-ear disease vaccines sent to 5 snow-stricken provinces. 2008-02-23 14:38:20. [104] http://www.ncbi.nlm.nih.gov/pubmed/18808354. Said MA, Perl TM, Sears CL: Healthcare epidemiology: gastrointestinal u: norovirus in health care and long-term care facilities.Clin Infect Dis. 2008 Nov 1;47(9):1202-8. [105] http://www.ncbi.nlm.nih.gov/pubmed/20412611. Rosenthal NA, Lee LE, Vermeulen BA, Hedberg K, Keene WE, Widdowson MA, Cieslak PR, Vinj J: Epidemiological and genetic characteristics of norovirus outbreaks in long-term care facilities, 2003-2006. Epidemiol Infect. 2010 Apr 23:1-9. [106] http://www.ncbi.nlm.nih.gov/pubmed/20408920. De Giusti M, Aurigemma C, Marinelli L, Tu D, De Medici D, Di Pasquale S, De Vito C, Boccia A: The evaluation of the microbial safety of fresh ready-to-eat vegetables produced by dierent technologies in Italy.J Appl Microbiol. 2010 Mar 22. [107] http://www.izs.it/vet_italiana/2009/45_4/pdf.gif. Savini G, Casaccia C, Barile NB, Paoletti M, Pinoni C: Norovirus in bivalve molluscs: a study of the ecacy of the depuration system. Vet Ital. 2009 Oct-Dec;45(4):535-9. [108] http://www.ncbi.nlm.nih.gov/pubmed/20389000. Shirasaki N, Matsushita T, Matsui Y, Urasaki T, Oshiba A, Ohno K: Evaluation of norovirus removal performance in a coagulation-ceramic microltration process by using recombinant norovirus virus-like particles. Water Sci Technol. 2010;61(8):2027-34. [109] http://www.ncbi.nlm.nih.gov/pubmed/20376611. Katpally U, Smith TJ: The Caliciviruses. Curr Top Microbiol Immunol. 2010 Apr 1. [110] Wang Q, Scheuer K, Zhang Z, Gebreyes WA, Molla BZ, Hoet AE, and Saif LJ. Characterization and prevalence of a new porcine calicivirus in swine, united states. EID, 17(6), 2011. http://www.cdc.gov/eid/content/17/6/1103.htm?source= govdelivery. [111] http://www.ncbi.nlm.nih.gov/pubmed/20375486. Mara D, Sleigh A: Estimation of norovirus and Ascaris infection risks to urban farmers in developing countries using wastewater for crop irrigation. J Water Health. 2010 Sep;8(3):572-6. Epub 2010 Mar 9. [112] http://www.ncbi.nlm.nih.gov/pubmed/20009246. Mara D, Sleigh A: Estimation of norovirus infection risks to consumers of wastewater-irrigated food crops eaten raw. J Water Health. 2010 Mar;8(1):39-43. [113] Caul EA. Viral gastroenteritis: small round structured viruses, caliciviruses and astroviruses. part i. the clinical and diagnostic perspective. J Clin Pathol,
BIBLIOGRAPHY
1897
49(874-880), 1996. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC500824/ pdf/jclinpath00248-0010.pdf. [114] Brugha R, Vipond IB, Evans MR, Sandifer QD, Roberts RJ, Salmon RL, Caul EO, and Mukerjee AK. A community outbreak of food-borne small round-structured virus gastroenteritis caused by a contaminated water supply. Epidemiol Infect, 122(14554):1, 2 1999. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2809600/pdf/ 10098798.pdf. [115] http://aem.asm.org/cgi/content/abstract/73/1/186. Butot, S.; Putallaz, T.; Snchez G.: Procedure for Rapid Concentration and Detection of Enteric Viruses from Berries and Vegetables. Appl. Environ. Microbiol. 2007 73: 186-192. doi:10.1128/AEM.01248-06. [116] http://www.ceeramtools.com/pdf/ceeram-tools.pdf. CeeramTools. [117] http://www1.qiagen.com/literature/render.aspx?id=103727. User-Developed Protocol: For purication of Norovirus RNA from human stool samples using the BioSprint 96 workstation. BioSprint publication 25 June 2008. [118] http://www.cdc.gov/eid/content/16/4/617.htm. Verhoef, Linda; Vennema, Harry; van Pelt, Wilfrid; Lees, David; Boshuizen, Hendriek; Henshilwood, Kathleen; Koopmans, Marion, on behalf of the Food-Borne Viruses in Europe Network. Use of Norovirus Genotype Proles to Dierentiate Origins of Foodborne Outbreaks. CDC Emerging Infectious Diseases. Vol. 16, No. 4. April 2010. [119] http://aem.asm.org/cgi/content/full/73/16/5104. Butot, S.; Putallaz,T.; Croquet, C.; Lamothe, G.; Meyer, R.; Joosten, H.; Snchez, G.: Attachment of Enteric Viruses to Bottles. Appl. Environ. Microbiol. 2007 73: 5104-5110. [120] http://aem.asm.org/cgi/content/full/68/4/1925. Beuret, C.; Kohler, D.; Baumgartner,A.; Lthi, T. M.: Norwalk-like virus sequences in mineral waters: oneyear monitoring of three brands. Appl. Environ. Microbiol. 2002. 68:1925-1931. [121] Pruzzo, Carla; Gallo, Gabriella; Canesi, Laura: Persistence of vibrios in marine bivalves: the role of interactions with haemolymph components pp761-772(12). [122] Chua KB, Bellini BJ, Rota PA et al (2000): Nipah virus: A recent emerging deadly paramyxovirus; Science 288:1432-1435. [123] http://www.oie.int/wahid-prod/reports/en_imm_0000006996_20080423_ 123207.pdf. OIE: Immediate Notication: Report reference: ND in pigeons-2008, Ref OIE: 6996, Report Date: 23/04/2008 , Country: Germany 23.04.2008. [124] http://www.thepoultrysite.com/diseaseinfo/111/ newcastle-disease-paramyxovirus-1. ThePoultrySite Quick Disease Guide: Newcastle Disease (Paramyxovirus-1).
1898
[125] http://www.ncbi.nlm.nih.gov/pubmed/19608910. Pitzer VE, Viboud C, Simonsen L, Steiner C, Panozzo CA, Alonso WJ, Miller MA, Glass RI, Glasser JW, Parashar UD, Grenfell BT:.Demographic variability, vaccination, and the spatiotemporal dynamics of rotavirus epidemics. Science. 2009 Jul 17;325(5938):290-4. [126] http://www.efsa.europa.eu/en/in_focus/bluetongue/bluetongue_report_ s8.html. European Food Safety Authority: Report on Epidemiological analysis of the 2006 bluetongue virus serotype 8 epidemic in north-western Europe. [127] http://www.cdc.gov/EID/content/14/9/1421.htm http://www.cdc.gov/eid/ content/14/9/1421.htm?s_cid=eid1421_e. Homann, Bernd; Sasserath, Michael; Thalheim, Sabine; Bunzenthal, Claudia; Strebelow, Gnther; Beer, Martin: Bluetongue virus serotype 8 reemergence in Germany, 2007 and 2008. Emerg Infect Dis. 2008 Sep. Available from. [128] Chen EC, Yagi S, Kelly KR, Mendoza SP, Maninger N, Rosenthal A, Spinner A, Bales KL, Schnurr DP, Lerche NW, and Chiu CY. Cross-species transmission of a novel adenovirus associated with a fulminant pneumonia outbreak in a new world monkey colony. PLoS Pathogens, 7(7):e1002155, 2011. http://www.plospathogens. org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1002155. [129] Chen EC, Miller SA, DeRisi JL, and Chiu CY. Using a pan-viral microarray assay (virochip) to screen clinical samples for viral pathogens. J Vis Exp, 50:pii:2536, 4 2011. http://www.ncbi.nlm.nih.gov/pubmed/21559002. [130] Novel (new) coronavirus in the arabian peninsula. cdc 14 may 2013. http://wwwnc. cdc.gov/travel/notices/watch/coronavirus-arabian-peninsula.htm. [131] Novel coronavirus infection update. who 12 may 2013. http://www.who.int/csr/ don/2013_05_12/en/index.html. [132] Interim surveillance recommendations for human infection with novel coronavirus. who 18 march 2013. http://www.who.int/csr/disease/coronavirus_ infections/InterimRevisedSurveillanceRecommendations_nCoVinfection_ 18Mar13.pdf. [133] Science M, Johnstone J, Roth DE, Guyatt G, and Loeb M. Zinc for the treatment of the common cold: a systematic review and meta-analysis of randomized controlled trials. CMAJ, 5 2012. http://www.cmaj.ca/content/early/2012/05/07/cmaj. 111990. [134] Hemil H. Zinc lozenges may shorten the duration of colds: A systematic review. The Open Respiratory Medicine Journal, 5:5158, 2011. http://www.ncbi.nlm. nih.gov/pmc/articles/PMC3136969/pdf/TORMJ-5-51.pdf.
BIBLIOGRAPHY
1899
[135] http://www.chinadaily.com.cn/english/doc/2005-02/07/content_415649. htm. China Daily: New bird u vaccine capable of prevention; By Zhao Huanxin Updated: 2005-02-07 02:00. [136] Vogelgrippe-virus in brandenburg: 14.500 enten eines mastbetriebs gettet. spiegel online. 16 febr 2013. http://www.spiegel.de/wissenschaft/medizin/ vogelgrippe-virus-in-brandeburg-500-enten-eines-mastbetriebs-getoetet-a-883874. html. [137] Unger F, Harder T, Conraths FJ, Teuert F, Staubach C, Globig A, Grund C, Beer M, and Mettenleiter TC. Klassische gegelpest h5n1. rckblick und aktuelle synopsis der globalen situation unter besonderer bercksichtigung des geschehens in deutschland. friedrich-loeer-institut, bundesforschungsinstitut fr tiergesundheit, insel riems und wusterhausen. Tierrztl Prax, 36(G):5 13, 2008. http://tpg.schattauer.de/en/contents/archive/issue/special/ manuscript/9404/download.html. [138] Cdc: Inuenza viruses. http://www.cdc.gov/flu/avian/gen-info/flu-viruses. htm. [139] Anna Thorson, MD, PhD; Max Petzold, PhD; Nguyen Thi Kim Chuc, PhD; Karl Ekdahl, MD, PhD: Is Exposure to Sick or Dead Poultry Associated With Flulike Illness? A Population-Based Study From a Rural Area in Vietnam With Outbreaks of Highly Pathogenic Avian Inuenza. Arch Intern Med. 2006;166:119-123. [140] http://en.wikipedia.org/wiki/Flu_vaccine. Wikipedia, the free enzyclopedia: Flu vaccine. [141] http://www.thelancet.com/journals/lancet/article/ PIIS0140673606692945/fulltext. The Lancet: Early trial shows H5N1 vaccine safe and eewctive in humans at low doses. [142] http://www.efsa.europa.eu/EFSA/efsa_locale-1178620753812_ 1178720563452.htm. EFSA Advises on the Safety of Aluminium in Food. EFSA press release 15.07.2008. [143] Hemil H. Zinc lozenges may shorten the duration of colds: A systematic review. The Open Respiratory Medicine Journal, 5:5158, 2011. http://www.ncbi.nlm. nih.gov/pmc/articles/PMC3136969/pdf/TORMJ-5-51.pdf. [144] http://en.wikipedia.org/wiki/Retrovirus. Wikipedia:Retrovirus. [145] http://www.fasebj.org/cgi/content/abstract/fj.09-131995v1. Sexton, Amy; Harman, Sarah; Shattock, Robin J.; Ma, Julian K.-C.: Design, expression, and characterization of a multivalent, combination HIV microbicide. The FASEB Journal, 2009; DOI: 10.1096/fj.09-131995.
1900
[146] http://www.hptn.org/research_studies/hptn035.asp. HIV Prevention Trials Network: HPTN 035 Phase II/IIb Safety and Eectiveness Study of the Vaginal Microbicides BuerGel and 0.5% PRO2000/5 Gel (P) for the Prevention of HIV Infection in Women. [147] http://www3.niaid.nih.gov/news/QA/HPTN_035_qa.htm. National Institute of Allergy and Infectious Diseases: The HPTN 035 Study of Two Candidate Microbicides, BuerGel and PRO 2000 (0.5% dose). February 9, 2009. [148] http://www.ncbi.nlm.nih.gov/pubmed/18606986. The paradoxical eects of using antiretroviral-based microbicides to control HIV epidemics. Wilson DP, Coplan PM, Wainberg MA, Blower SM. Proc Natl Acad Sci U S A. 2008 Jul 15;105(28):9835-40. Epub 2008 Jul 7. [149] Viroclime virology water and climate change: Impact of climate change on the transport, fate and risk management of viral pathogens in water. http://www.viroclime. org/. [150] Artois M, Cochez C, Van Mele R, and Heyman P. Genetic evidence of puumala and tula hantaviruses in rodents in the jura region, france - preliminary results. Euro Surveill, 12(26):pii 3226, 2007. http://www.eurosurveillance.org/ViewArticle. aspx?ArticleId=3226. [151] Boone I, Wagner-Wiening C, Reil D, Jacob J ANDRosenfeld UM, Ulrich RG, Lohr D, and Pfa G. Rise in the number of notied human hantavirus infections since october 2011 in baden-wrttemberg, germany. Euro Surveill, 17(21):pii 20180, 2012. http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=20180. [152] Cdc: Hantavirus. http://www.cdc.gov/hantavirus/. [153] Lbermann M, Grtler LG, Eichler-Lbermann B, and Reisinger EC. Emerging viral diseases in europe. Dtsch Med Wochenschr, 137(17):9005, 4 2012. http: //www.ncbi.nlm.nih.gov/pubmed/22511281. [154] Flores Castro R. Current situation of the most frequent zoonosis in the world. Gac Med Mex, 146(6):4239, Nov-Dec 2010. http://www.ncbi.nlm.nih.gov/pubmed/ 21384639.
Part V Poisonous Chemicals in Food
1901
Chapter 26 Dioxin
26.0.6 Ongoing dioxin scandal in Germany
[1] The high levels of dioxins that have shown up in small amounts of German produce have been traced to a single fats manufacturer, Harles and Jentzsch. Another feed producer based in Damme/Germany has now been traced more than 15 days the begin of investigations. The company had tried to conceal his connections with Harles Jentzsch. Now, about 900 farms have to be closed and wait for dioxin tests. Dioxin source Hans Schenkel, a professor of agricultural chemistry of the University of Stuttgart, said the pattern of dioxins in the fat were similar to dioxins found in kaolin which might be involved in the latest food poisoning. Kaolin can be used up to 3% in animal feed to improve the ow during pumping when moving the animal feed from one store to another and caused a dioxin scandal in 1999. Kaolin is also used to sort out spoiled potatoes and potatoes unsuitable for French fries. The speculations of professor Schenkel were dissipated by investigations of the ocials of Mnster/Germany. The chemical and veterinary investigations oce of Mnster came to the conclusion that residues of the Biodiesel oil production were responsible for the ongoing dioxin contamination of European food chain. The oce found that the pattern of the dioxins found in fat, feed and eggs was similar to samples of the Biodiesel rening byproducts. Some dioxin food scandals 1976 - The Seveso accident. 1999 - Dioxin contaminated feed from Belgium June 1999 - German kaolin with high level of dioxin had also been added to animal feed in Austria and Germany. 1903
1904
CHAPTER 26. DIOXIN
2003 - Backery waste of Thuringia/Germany with high dioxin levels was used as feed. 2004 - Several farms were closed in Germany because of dioxin in feed using industrial potato peeling contaminated with poisoned kaolin. [2] 2008 - Irish pork with high dioxin levels September until December 2008 about 4000 Tonnes exported to Germany due to feed contaminated with discarded foods which were dried using fuel with high dioxin content. Dioxin levels of some samples of Irish pork exceeded the WHO-TEQ by 2500 times. 2010 - May 2010: Organic eggs were contaminated with dioxin from feed using maize from Ukraine. April/December 2010 - High dioxin in eggs, poultry, liquid egg yolk made of these eggs were used for bakery products and mayonnaise. Contaminated feed has also sold for dairy cattle farms. Organic eggs in Germany tainted with dioxin-like PCB [3] Shortly before the eastern feast, in early April 2012, news were spread that organic eggs are tainted by dioxin. The chicken farm in North Rhine-Westphalia/Germanywith 25.000 laying hens was closed by veterinary authorities. The dioxin-like Polychlorinated Biphenylen (PCB) content was found to be three to six times of the permitted levels. The source of the contamination is unknown. Animal feed was to be free of dioxin. This case revives the scandal of dioxin in German eggs in 2011 when highly contaminated feed had been sold to hen and pig farms. Eggs, poultry meat and pork had to be discarded. It seems that all safety measures are not sucient to avoid dioxi and dioxin-like tainted food. The health-conscious consumer which buys organic food is mislead by the tainted eggs sold by supermarkets. The Ministry says there is no immediate health risk if tainted eggs are consumed, however, eaten over long time health problems cannot be ruled out, such as disorders of the immune system, skin diseases, airways and thyroid gland, digestive tract disfunction. German dioxin scandal December 2010 discredits certication and the HACCP safety concept of the food industry German food safety is discredited by the failure of the HACCP concept and failure of certication. Thilo Bode from Foodwatch accuses the German government to have no interests to impose further burdens on feed mills in order to avoid impairments on the export of German meat products. [4]
1905
26.0.7
Dioxin-like PCB poison in German eggs rises question about safety of eggs and chicken meat
The dioxin scandal in European eggs in early 2011 is being followed by new dioxin-like PCB tainted eggs found in Germany. The source of the 2011 poison was tracked back to fatty acids of the production of bioDiesel which were illegally added to the feed of hens. However, no source is known which might have caused the 2012 PCBs which poisoned organic eggs of North Rhine-Westphalia/Germany and conventional free range farms in Lower Saxony/Germany. PCBs levels in eggs were found to be six times the permitted limit. For the time being all samples of feed, water and local soil were found not to be the source of the contamination. Dioxins and PCBs are of industrial origin and may be found in eggs and meat oll over the world.
Dioxin in free-range eggs [5] Lin, Hsu and Liao 2012 report that the levels of dl-PCBs in the free-range samples were 5.4 times higher than those in caged eggs. The dl-PCB levels in the free-range eggs were highly correlated with elevated levels of 17 polychlorinated dibenzo-p-dioxins and dibenzofurans, indicating a coexposure scenario in free-range hens. As the consumption of free-range eggs is becoming more popular worldwide, risk of cancer caused by dioxins and PCBs will increase. The bioavailability of PCBs in contaminated soil in vicinity of a former re involving treated wood was assessed by Fournier et al. 2012. The sandy soil contained 709g indicator PCBskg(-1) dry matter. The concentration of indicator PCBs in yolk in abdominal fat and liver linearly increased with the amount of indicator PCB ingested, conrming the bioavailability of these compounds. [6] Combustion of fossil fuels and biofuels increase environmental poisoning, being spread as dust and dioxin particulates. Bio fuels of rst, second and third generation are based on carbon combustion producing dioxins and PCBs. The energy strategy for the next century should therefore be based on solar and wind energy which is carbon combustion free. Schrter- Kermani et al. 2005 report that seabirds are top predators which accumulate persistent chemicals, such as PCDDs, PCDFs, and dioxin-like PCBs including several POPs like DDT, HCH, and HCB which can be found in high concentrations in their eggs. In the framework of the German Environmental Specimen Bank eggs of herring gulls are collected since 1988 from two North Sea islands and since 1993 from one Baltic Sea island, to monitore the industrials and agrochemicals environmental contamination. [7]
1906
CHAPTER 26. DIOXIN
Inuence of dioxin in soil and their accumulation in egg yolk of organic eggs [8] De Vries, Kwakkelz and Kijlstra 2006 reviewed studies related to dioxin in organic eggs in the Netherlands, Germany and other EU countries. The authors found that eggs are responsible for about 4 percent of the intake of dioxin in humans, organic eggs contain more dioxin than conventional eggs, and the organic eggs of a signicant number of farms exceed the EU standards. The authors analysed the inuence of dioxin in soil and their accumulation in egg yolk. Aside of feed as source of dioxin in eggs, the authors stress the importance of ingestion of worms, insects, grass, herbs and soil by hens. Hens on conventional and free-range farms spend less time in the outdoor run, compared with hens of organic farms.
Flock Size and measures to reduce dioxin in eggs [8] De Vries and colleagues stress also that mall ocks were found to be outside most of the time whereas large ocks tend to remain inside. This explains why almost none of the larger layinghen farms (more than 1500 laying hens) in the Netherlands have problems maintaining their egg dioxin level below the EU standard of 3 pg TEQ. Shortening the time hens spend ranging in the outdoor run, reduce the size of the outdoor run and covering the soil in the outdoor run are being proposed to reduce dioxin intake. Improving the general health status may prevent the hens from ingesting soil. The maximum residue limit for dioxins in chicken eggs is set at 3 picograms WHO-PCDD/F-TEQ/g fat. [9]
Dioxin in German eggs, the burden of past environmental delicts [10] Lower Saxony, North Rhine-Westphalia and other parts of Germany had been closed in April 2012 by German food authorities because of elevated PCBs and Dioxin contamination. Non-dioxin-like PCBs contamination in eggs of a organic farm at the district of Oldenburg/Germany were recently found in May. Some ot these eggs were sold at dierent places and were already consumed. Food authorities say there is no acute health risk for those who have eaten such eggs, however. PCBs are known to cause health impairments if contaminated foods are eaten over a long period. In the district of Duisburg dioxin was found, while non-dioxin-like PCBs were found in eggs of other farms. Authorities believe that there is no common source like feed or water, tests in Lower Saxony were all negative. However, soil samples of a hen free run of the conventional part of the hen farm were found to have elevated contamination of PCB. This, however does not explain why organic eggs were contaminated while the soil of the organic part of the farm was negative tested.
1907 Brominated ame retardant in eggs of free-range hens [11] According to Fournier et al 2012, high concentrations of hexabromocyclododecane (HBCD), a brominated ame retardant, are sometimes recorded in eggs of free-range hens. The source of the contamination is the ingestion of soil. The gama-HBCD isomer is the most prevalent in soil. It is rapidly biotransformed and eliminated, and partly isomerized into the more persistent alpha-HBCD. The carry-over rate of ingested gama-HBCD to egg yolk is 1.2% and its half-life is 2.9 days in egg yolk, 13 days in abdominal fat, and 0,41 days in liver. Three main stereoisomers, alpha, beta, and gamma, comprise roughly 10, 10, and 80% of the mixture, respectively. The major stereoisomer found in wildlife and human tissues including breast milk and blood of humans is the alfa-HBCD isomer, despite its low percentage of the re retardant mixtures, suggesting the bioaccumulation of this isomer. [12]
26.0.8
European denition of egg types
The EU- Directive 1999/74 denes and species the standards for the protection of laying hens, dening the barn egg, the free range egg and the organic egg. [13] All newly built or rebuilt systems of production or brought into use for the rst time must be equipped in such a way that all laying hens have: EU regulations require commercially sold eggs to be stamped with an indication of the method of rearing and the country of origin. 0 is a "Bio" egg, 1 a free range egg, 2 a barn egg, and 3 a cage egg (battery eggs). The European Union has banned battery cages as of 2012. Barn egg production: 250 cm of littered area per hen. The littered area has to be a minimum of one third of the oor surface area. 9 hens/m usable area, of at least 30 cm width, oor slope must not exceed 14% or 80 and headroom must be at least 45 cm. The levels must be so arranged as to prevent droppings falling on the levels below. 120 hens/m2 group laying nest or 7 hens/single nest. 15 cm perch/hen- perches must not be installed above the littered area, the horizontal distance between the perches has to be at least 30 cm, horizontal distance between perch and wall at least 20 cm. 10 cm of linear feeders/hen. 10 hens/drinking nipple. Free range production: Production must additionally comply with the following standards: The pop holes have to be at least 35 cm high and 40 cm wide; 200 cm of total opening width for every 1000 hens. Shelter in the free-range area. Organic production: Additional standards for the production, processing and marketing of organic eggs are established in the EU-Eco-regulation [14]. In 1999 it was supplemented by regulation (EC) Nr 1804/1999 [15], which regulates the raising, labelling and inspection of the most relevant animal species (i.e. cattle, sheep, goats, horses and poultry).
1908 The German way to transform bad foods to good foods
CHAPTER 26. DIOXIN
[16] The chairman of the veterinarians of the German Association of Animal Welfare, Prof. Thomas Blaha, says that eggs and meat with high levels of dioxin do not need to be discarded. They may be made t for human consumption mixing it with eggs or meat with low dioxin levels. So high dioxin levels come down to the permissible range of contamination. This is absolutely against Good Manufacturing Practice and HACCP basic principles and contravenes ethics of clean and sound foods from farm to fork. Professor Blaha is director for epidemiology of the Veterinary University of Hannover and reects the careless way German veterinary and food authorities handle safety issues. This supports the accusations of Foodwatch against the German government and the German food safety certication systems. Certication system [16] DEKRA, a food certication system, recently certied the Harles und Jentzsch company which was responsible for selling industrial fats and feed with high dioxin levels. The certier examining the ow chart of the production should have noted the lacking of a Control Point (CP) of raw ware and its safety. A series of food scandals, primarily linked to the origin of raw ware point to the serious failure of German certication systems. Where dioxin goes [17] [18] German dioxin eggs were used for the production of liquid egg yolk for bakery products. In UK. Tesco recalled its cakes produced with German egg yolk. EU Commissioner says that the German eggs were sold to the Netherlands for the production of egg yolk which went to mayonnaise and cake production. [19] Mayonnaise and sauces have a high content of egg yolk and are therefore products which should be avoided by the consumer. Due to a shelf life of 6 month or more, these products will remain hazardous for a long period. According to a spokesman for Agriculture Minister Ilse Aigner there are indications of high level of illegal activity. European poultry, eggs and pork industry is to be blamed for closing eyes on safety issues. The consumer and the export partners cannot trust any more on German and European food, unless serious failures of the safety system are removed. Playing down the 2010 dioxin scandals More laws will be of no help at all Harles and Jentzsch began selling the dioxintainted fat in March, and continued the shipping despite being aware of high dioxin analysis results of tests. The contamination in Germany was discovered in December 2010 by local government inspectors randomly testing food.
1909 Poison to food using the mixing phenomenon [20] According to the European Commission health spokesman, Frederic Vincent, some eggs had been found to contain up to ve times the legal European Union limit for dioxin, which can cause cancer, but those levels would not pose a risk to human health, other tests found eggs with 77 times the legal limit for dioxin. The UK Food Standards Agency (FSA) was not concerned with the consumer safety, because German dioxin-eggs had been mixed with noncontaminated eggs to make pasteurized liquid egg in the Netherlands and sold in the UK. The Mixing brought the poison in the liquid egg down to levels allowed by law. [21] Such statements of the UK FSA, together with German veterinary ocial Prof. Thomas Blaha undermine the premise that food products should be made of suitable raw materials and should not be made of diluted poisons, such as happened in 1999 where discarded motor oil was use as feed in Belgium, or sewage sludge in French animal feed. Dioxin and other poisons accumulate in human body throughout decades. Mixing foods high in aatoxins is also considered "legal" in nuts and cereals to get toxins down to limits. Every eort to keep such poisons out of food should be of top priority in any Good Manufacturing Practice system. Such mixing may be considered "legal" but does not correlate with the perceptions of the consumer. More laws and restrictions do not remedy carelessness of safety systems These criminal activities cannot be avoided with more laws and restrictions. It is a matter of integrity of the directors of food businesses which deliberately use loopholes to introduce poisonous material not intended for food production. The directors of the whole European food production chain should be blamed for maintaining a low surveillance of their suppliers and the failure of their own safety GPM and HACCP system related to this matter. A mayonnaise producer, as an example, must control his supplier of liquid egg yolk to see if he controls eggs used for his production. With such a conscious self-monitoring system dioxin eggs should have been detected earlier than 9 month. Dioxin, the endless story Dioxin is since long time known as one of the strongest poisons which man is able to produce. It causes cancer of liver and lung, interferes in the immune system resulting in a predisposition to infectious diseases and embrional misgrowth. Dioxins comprise polychlorinated dibenzo-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs). Environmentally persistent dioxins and dioxin-like compounds include 29 congeners of dioxins, furans and polychlorinated biphenyls (PCB) with similar toxic effects, their quantication commonly expressed as toxic equivalent units according to their
1910
CHAPTER 26. DIOXIN
varying potency. While the amount of those compounds in the environment has declined since the late 1970s, there is a continued concern because of their accumulation in the food chain, particularly in animal fat. In 2002 the European Commission prescribed a list of actions to further reduce the presence of dioxins and dioxin-like PCBs and later introduced action and maximum levels [22] At the beginning of the 20th century the production of chlorine splitting sodium chloride by Dow Chemical Midland,USA free chlorine could be used for many new compounds like pesticides, plastics such as PVC,chlorine bleaching of paper and many other sources. Dioxins are also built as unwanted side reactions during the production of chlorinated products. When these new compounds are burned as waste, chlorine atoms combine with carbon resulting dioxins. Dioxin is also originated during combustion, mainly by heat below 780o C It is therefore found in the atmosphere and in the fallout in rain. A main source of dioxin is used discarded motor oil and in some geological formations like kaolinite. In the press dioxin was cited in relation to the accident at the chemical plant of Homann-LaRoche in Seveso, Italy. Due to an explosion a great amount of 2,3,7,8 TCDD dioxin was spread over the city of Seveso in 1976. Limits for dioxin expressed as tolerable daily intake are given in picogram 1 pg=1012 g : Germany 1 picogram (1012 g) per Kg body weight Netherland4 pg (4X1012 g) per Kg body weight Canada 10 pg (10X1012 )g per Kg body weight FDA from USA 0,03pg (0,03X1012 g) per Kg body weight Environmental administration EPA from USA 0,006pg (0,006X1012 g) per Kg body weight Please note that sometimes dioxin values are expressed in nanograms. One nanogram=109 g. Today emission of smoke stacks has been reduced from 400g i-TE/year in 1988 down to 2g i-TE/year.According to German regulations emission of smoke stacks over 5000 m3 /h the emission should be reduced to 0,1 ng i-TE/ m3 . Sludge from industrial wastewater should not exceed 100 ng i-TE/kg of dry matter according to German regulation. Soil of playground for children should not exceed 100 ng i-TE/kg of dry matter. Soil of residential neighborhood should be kept under 1000 ng i-TE of dry matter according to the List of Berlin 1996.
1911 The role of Dioxins in cancer People who have been exposed to high levels of dioxin have developed chloracne, a skin disease marked by severe acne-like pimples. Studies have also shown that chemical workers who are exposed to high levels of dioxins have an increased risk of cancer. Other studies of highly exposed populations show that dioxins can cause reproductive and developmental problems, and an increased risk of heart disease and diabetes. More research is needed to determine the long-term eects of low-level dioxin exposures on cancer risk, immune function, and reproduction and development. Dioxins produce cancer acting through the aryl hydrocarbon receptor (AhR) gene in conjunction with the receptors binding partner, aryl hydrocarbon receptor nuclear translocator (ARNT). This gene produces a protein which interrupts the signal transmission by the AhR by competing with the ARNT for binding to the arylhydrocarbon receptor. TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin) activates the aryl hydrocarbon receptor (AHR) modifying its gene expression and toxicity. The AHR repressor (AHRR) inhibits AHR signaling through a mechanism described by Evans and colleagues 2008. The authors describe a mechanism of AHRR action involving "transrepression" of AHR signaling through protein-protein interactions. [23] The aryl hydrocarbon receptor repressor (AHRR) contains tumor suppressor genes. Zudaire and colleagues 2008 report that in case of cancers of colon, breast, lung, stomach, cervix, and ovary downregulation of The AHRR mRNA is downregulated with DNA hypermethylation as the regulatory mechanism of AHRR gene silencing. [24] The AHR regulates responses to environmental chemicals. Hahn and colleagues 2009 describe how AHR may repress AHRR transcription, resulting in unbridled AHR activity, and the way how the AHRR may exert AHR-independent eects.and AHR-regulated malignancy. [25] Immune suppression induced by TCDD [26] According to Nancy and colleagues 2007, the aryl hydrocarbon (Ah) receptor responds to environmental stress such as oxygen partial pressure, light intensity, and pollutants such as tetrachlorodibenzodioxin (TCDD) which is the most potent Ah receptor suppressor. TCDD has immunosuppressive eects. Activation of the Ah receptor by TCDD leads to profound immune suppression involved in the generation of regulatory T cells.
26.0.9
Chemical structure of dioxins
There are about 210 dioxins and related compounds called furanes. They are classied in two classes of chemical compounds: The class of the polychlorinated dibenzo-p-dioxins and the class of the dibenzofuranes. The dierence between dioxins and furanes is that some
1912
CHAPTER 26. DIOXIN
compounds have an oxigen bridge, others dont. Both classes of compounds are usually called dioxins. The most poisoning dioxin is 2,3,7,8-TCDD (tetrachlorodibenzo-p-dioxin)(described by Sandemann et all. in 1957) therefore equivalents are calculated in relation to this compound as only 17 of the 210 dioxins and furanes have a chlorine atom at the position 2,3,7 and 8 being therefore strongly toxic and are expressed as Toxicity Equivalence (TE) TCDD is classied as carcinogenic class I which is the highest step in the classication of the IARC (International Agency of Research of Cancer). 1 ng TE means that there is a mixture of PCDD and PCDF present which corresponds to 1 nanogram of 2,3,7,8 TCDD. Dioxins accumulate in liver an fat tissue and it takes about 10 years for the body to reduce half of the amount of once stored dioxins. Other dioxins furanes and related compounds presenting toxicity: PCDDs (Polychlorinated dibenzodioxin) PCDFs (Polychlorinated dibenzofurans) PCBs (Polychlorinated biphenyls) Dioxins are very dicult to be analysed. PCB Polychlorated biphenil are most all the time present together with dioxins. PCBs are much more easy and is does not take so much time to analise as dioxins. Therefore PCB control with GC/MSD or HRGC/HRMS is used as indicator for dioxins. In milk a contamination of 100 ng/g of PCB in fat is an indicator of high dioxin values. In egg yolk a maximum of 60 ng/g in fat stands for tolerable values of Dioxins The most toxic compound is 2,3,7,8-tetrachloro-dibenzo-p-dioxin (TCDD). It is used as a reference of the toxicity of other dioxins. The liver microsomal P4501A1 enzyme oxygenates dioxins. The enzyme is encoded by the CYP1A1 gene. Expression of CYP1A1 is increased by the cytosolic aryl hydrocarbon receptor (AhR) together with hydrocarbon nuclear translocator (ARNT) and xenobiotic responsive element (XRE) Foetuses and infants are most sensitive to dioxins. [27] Dioxins activate the aryl hydrocarbon receptor (AhR), which is linked to tissue-specic toxicity phenotypes. Dioxins are involved in developmental or tissue regeneration processes, impaired prostate development and hydronephrosis in mouse, reduced midbrain blood ow and malformation in zebrash embryos and adult zebrash, and signaling by receptors for inammatory cytokines have been implicated in tissue-specic endpoints of dioxin toxicity. [28] Burns and colleagues 2010 found that blood serum levels of dioxins and PCBs were inversely associated with height z scores and height velocity (cm growth/year). The authors concluded that dioxins and PCBs are associated with reduced growth during the peripubertal period and compromise adult body mass, stature, and health. [29]
1913 Dioxins, heavy metals and environmental contaminants in foodstus report of German food authorities [30] The research project "Foodborne exposure to environmental contaminants" (LExUKon) of the German Federal Institute for Risk Assessment (BfR) have calculated the amounts of cadmium, lead, mercury, dioxins and polychlorinated biphenyls (PCBs) which consumers usually absorb with foods. According to the study, the main sources for cadmium intake are vegetables and cereals. Lead is primarily absorbed by consumers via beverages and cereals. Methylmercury is mainly contained in sh, whereas dairy products and meat are determining for dioxins and PCBs. The intake of environmental contaminants through foodstus was determined for the general population, taking into account dierent consumption habits as well as individual lifestyles. It turned out, for instance, that consumers eat more sh as they grow older and hence absorb, amongst other things, more methylmercury than younger people. Cadmium Eating more vegetables and cereal increases the intake of cadmium which is short over 1,5 microg/kg bodyweight/week, which corresponds to 58% of the Tolerable Weekly Intake (TWI) of 2,5 microg/kg bodyweight. People with high vegetable and cereals eating habits have an intake of 2,35 microg cadmium /kg bodyweight, which is near the upper rage of the TWI set by the European Food Safety Authority. Lead intake and margin of exposure (MoE) Beverages and vegetables are responsible for high intake of lead, which is calculated to be 3,7 microg/kg bodyweight for the average consumer, and 5,1 microg/kg bodyweight/week for people with high consume of this food group, corresponding to 1,2 and 0,9 MoE, respectively, for kidney toxicity, and 2,8 and 2,1 MOE respectively for systolic blood pressure. Mercury Intake of methylmercury is related to sh and milk products. The intake of mercury and methylmercury is calculated to be 0,49 microg/kg bodyweight for the average consumer, and 0,9 microg/kg bodyweight/week for people with high consume of this food group, which is 21% and 37%, respectively, of the limit value of 2,4 microg/kg bodyweight set by JECFA. Dioxins and PCBs in dairy and meat Dairy products and meat are responsible for the exposition to PCDD/F and dioxi-like PCB (dl-PCB). Dioxin and dl-PCB intake is calculated to be 12,7-16,9 picog/kg bodyweigh/weekt for the average consumer, which is 90-121% of the limit value of 14 picog/kg
1914
CHAPTER 26. DIOXIN
bodyweight set by SCF. Not dioxin-like PCB (ndl-PCB) exposition is 15-21,7 nanog/kg bodyweight of average consumer. This is 75-109% of the TDI of 20 nanog/kg bodyweight set by the WHO. Conclusions of the report Specic population groups and high consume of special food groups reach, or exceed intake of toxicological limits. The report stresses that dietary supplements may increase the calculated intake of cadmium, lead,mercury dioxins and PCB. Waste incinerators are source of dioxins in agricultural soils [31] Deng and colleagues 2010 found polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans (PCDD/F) in agricultural soils near two municipal solid waste incinerators in Shanghai ranging from 71.32 to 3,881.44 pg g(-1), whereas the highest concentrations were found approximately 1,000 m from the incinerators. The authors stress that the PCDD/F pollutions in soil result from emissions of the municipal solid waste incinerators. Reduction of dioxins in sh oils [32] Ortiz and colleagues 2010 developed a silicon-based and carbon-based solid adsorbent system to reduce dioxins from sh oils. The authors report a reduction of dioxins ranging from 99% to 10% without aecting nutritional properties. Dioxins in German eggs in 2010: Is the poultry feed industry careless or is it criminal? [33] Eggs and poultry meat of German farms were found contaminated with dioxin in late December 2010. Veterinary authorities suspect that technical oil such as discarded engine lubricating oil was included in poultry feed sold by a company in Schleswig-Holstein, the northernmost state of Germany with border to Denmark. Around 1000 farms raising egg-laying chicken, pigs and turkey were closed after double the permitted levels of dioxin in eggs and chicken were found in North Rhine-Westphalia (Germany). More than 8,000 laying hens had to be culled. German animal feed manufacturer Harles & Jentzsch bought the dioxin contaminated oil from a Dutch supplier. The oil was delivered by Petrotech AG, a plant in Emden (Germany) which produces bio-Diesel from palm oil, soy oil, rape oil and used deep-frying fats. The incident of Ukrainian organic maize used in organic poultry feed in April-May highly contaminated with dioxins is now topped by technical oil used as feed ingredient in Germany. This demonstrates that European animal feed industry fails to follow basic safety rules. Veterinary authorities do not cope with their obligations to supervise the "farm to fork" chain. [34]
1915
26.0.10
The Belgian scandal of dioxin
In June 1999 Europe was confronted by the news of the scandal of dioxin in Belgian animal feed. Eggs, meat of hen, pigs and beef were not safe. Belgian animal feed had been enriched with old used engine oil with high level of dioxin. As Belgic exported the contaminated meat as animal feed all over Europe was to be considered as bearing PCBs and dioxins. Later on Swiss animal feed was also found to be contaminated by dioxins. This was caused by certain charges containing kaolinite from Germany. Kaolinite is part of earth which is used in the production on porcelain. As 3% in animal feed it is used to improve the ow during pumping when moving the animal feed from one store to another. German kaolin with high level of dioxin had also been added to animal feed in Austria and Germany. In June 1999 animal feedings with added kaolinite were found to have 1,5 to 30 pg i-TE/g resulting in a contamination of German turkeys of 30,6 pg i-TE/g fat. According to German regulation from 9.6.99 a maximum of Dioxin equivalents should be observed in following foods: Eggs maximum of 4 pg i-TE/g fat Poultry maximum of 5 pg i-TE/g fat Milk maximum of 3 pg i-TE/g fat Beef maximum of 6 pg i-TE/g fat Pork maximum of 2 pg i-TE/g fat French animal feed now found to carry dioxins tells that there is still very much wrong. Everything is being used to feed animals. As calcium is needed to feed cows, calcium oxide from washing industrial smoke stack combustion gases had been added to citric pellets from Brazil which were fed to German cows. Great amount of milk had to be discarded because of high level of dioxin. Even sewage sludge resulting from industrial waste water treatment is being added to animal feed, often without separation between the waste water and the normal sewage system. In 1991 the use of sewage sludge from industrial waste water for animal feed was forbidden by the EU but this has not always been followed. In 1998/1999 French knackeries and gelatine factories as well as Dutch companies had sewage sludge from industrial waste water mixed with animal feed. Pigs and chicken fed with it were also sold in Germany. Sewage sludge concentrates heavy metals, dioxin, antibiotics and resistant bacteria. [35] Sewage sludge is still being used in France (November 1999) as ingredient to animal feed disregarding EU regulation of 1991. This conrms the deep distrust of the consumer condence on public institutions.
1916
CHAPTER 26. DIOXIN
26.0.11
High dioxin levels in German organic eggs, failure of incoming controls?
[36] Dioxins increase the risk of cancer. Levels above the EU standard of 3 pg TEQ were found in May 2010 in German organic eggs by the Association for controlled alternative husbandary, which maintains the label: "Controlled by KAT". The whole production chain did not comply with the HACCP and ISO 9000 principles, questioning organic eggs and their seals of approval. Investigations found that the organic feed from the Dutch Harreveld facility of ForFarmers were the source of the dioxin. Organic corn for the production of the feed imported from the Ukraine could be traced as the primary source of the contamination. Incoming controls have failed. It is a sign of failure of the quality system when toxic food is found at the end of the chain and hazzards are not identied with incoming controls of the Ukrainian corn. Organic eggs are continuously on the headlines of food scandals. [37]
26.0.12
Belgian dioxin crisis related to chicken feed in 1999
[38] In 1999, Belgium had a dioxin crisis caused by dioxin-contaminated feed being fed to livestock. The source of the contamination was a Belgian at-rendering company, where transformer oil with high levels of polychlorinated biphenyls (PCBs) and dioxins was used to manufacture animal foods sale of Belgian poultry and eggs and all food items containing more than 2% egg product
26.0.13
Dioxin levels are higher in eggs of free-ranging chickens than chickens kept inside
DeVriesDioxininEggs2006 De Vries and colleagues 2006 found that dioxin levels are higher in eggs from free-ranging chickens than in eggs from chickens kept inside. Free-ranging chickens ingest soil and eat insects and worms, all of which contain environmental dioxins. Flock size inuences the behaviour of the animals. Small ocks are outside most of the time whereas large ocks tend to remain inside. The uptake of dioxin-contaminated soil or insects taken up varies accordingly. The authors say that large Dutch farms with more than 1500 laying hen have egg dioxin levels below the EU standard of 3 pg TEQ, while organic farms with small ocks present unacceptably high egg dioxin levels because the animals spend most of the time outside. In Lower Saxony state, 28% of all free-range eggs produced in the last two years were above European Union limits for dioxin levels, because hens were allowed to roam on land contaminated with the chemicals. [39]
1917
26.0.14
EFSA report on dioxin levels in food and feed, July 2010
[22] Dioxin and furan congeners comprised between 30% and 74% of the total concentrations depending on food or feed group, while mono-ortho PCBs comprised between 15% and 45% of the dioxin-like PCBs. The highest mean levels of dioxins and dioxin-like PCBs in food expressed on fat basis were observed for "liver and products thereof from terrestrial animals" and on whole weight basis for "sh liver and products thereof". In feed the highest levels were found in "sh oil". An overall 8% of the samples exceeded dierent maximum levels and a further 4% exceeded some action levels. European animal feed directive Forbidden Industrial waste water sludge is forbidden as animal feed. All components of sewage remain are not allowed to be added to animal feed even if they were submitted to any technological procedure. Exception Allowed is process Water which come out of closed circuits and which does not contain substances which are not allowed for animal feed. In 1999 faeces were found in French animal feed with added sewage. Recycled oils and fats are allowed as animal feed by way of exception under the control of an HACCP system. Unfortunately many industrial waste water sludges are being declared as process water evading the European directive.
26.0.15
Unilever Chairman pleas for an EURO- FDA
To conter the loss of the consumers condence and to restore the ability of the public veterinary and food control to do their job Antony Burgmanns Chairman of Unilever NV, Rotterdam says ( 14.11.99) that the creation of an European Control System like the US FDA will be necessary[40].
26.0.16
Dioxin in foods
Low levels of dioxin from environment are present in vegetables and all other kind of foods. The amount of environmental dioxin is not relevant, excluding the region of Seveso and some parts of Serbian. Eggs, milk, beef and sh all over Europe can have high amount of dioxin when animal feed with dioxin had been fed. As dioxin accumulates in fatty tissue it is possible to reduce the intake of dioxin by eating less greasy fatty food. Therefore veterinary ocials claim analytical checks on dioxin and PCBs when the food bears more than 2% of fat on exports from Belgium. Despite the criminal procedures on the scandal of dioxin contaminated animal feed from
1918
CHAPTER 26. DIOXIN
Belgium the WHO reports decreasing levels of dioxins in worldwide human blood plasma. This is told to be a result of eorts to reduce dioxin in environment. So mothers milk in Germany being reported in 1985 as average of 29,6 ng i-TE/kg fat has decreased to an average of 15,9 ng i-TE/kg fat in 1994. BSE problems in Great Britain, dioxin in Belgian foods caused gigantic nancial losses to the involved industry and commerce. It disregarding laws and good manufacturing practice does not bring wealth. It soon or later ends in scandals. It should be a lesson to all who want to earn easy money without regarding safety and public health. Industry,great retailers and last but not least the consumer should help to keep food safe paying appropriate prices to their suppliers avoiding price battles which end on outlaw practices. The WHO Consultation of May 25-29, in Geneva, Switzerland regarding the health risk of Dioxins[41] shows that the most important amount of dioxins intake resulting from food (90% of total human exposure to dioxins) has been reduced about half of the former values due to increased emission reducing activities. Food born dioxins are found mainly in animal fat. That is why vegetarian food becomes more attractive. But remember: Supplementation of vegetarian diets with B12 vitamin from drugstore is important to avoid undersupply. According to the consultation of WHO the contamination of food is primarily caused by deposition of emissions from various sources (like waste incineration and production of chemicals) on farmland and waterbodies followed by bioaccumulation up terrestrial and aquatic food chains. Other sources may include contaminated feed for cattle, chicken and farmed sh so what has happened lately with Belgian animal feed, improper application of sewage sludge, ooding of pastures, waste euents and certain food technologies.
26.0.17
Tolerable daily intake (TDI)
The WHO in December 1990 in the Netherlands established a tolerable daily intake (TDI) of 10 pg/kg by weight for TCDD. The consultation concerning health risk of dioxins in May 1998, Geneva re-evaluated the TDI as an upper range of the TDI of 4 pg TEQ/kg by weight should be considered a maximal tolerable intake on a provisional basis and that the ultimate goal is to reduce human intake levels below 1 pg TEQ/kg bw/day. In Germany the human exposure to TCDD is supposed to be only 45% of the limit of 1 pg TEQ/kg bw/day. The consultation however recommended that every eort should be made to limit environmental releases of dioxin and related compounds to the extent feasible in order to reduce their presence in the food chains, thereby resulting in continued reduction in human body burdens. Eorts to reduce the exposure of more highly exposed sub-populations should be undertaken. These eorts bear their price and this should be honored by commerce and by the consumer. Someone has to pay for it. So honest prices for good honest raw materials to reduce risk in food.
1919
26.0.18
Toxic Equivalents (TEQ) and Toxicity equivalency factors (TEF)
The European Centre for Environment and Health of the World Health Organization (WHO-ECEH) and the International Programme on Chemical Safety (IPCS) the toxic equivalency (TEQ) concept. To arrive at a TDI expressed as TEQ, a composite uncertainty factor of 10 was recommended. By applying this uncertainty factor a TDI range of 1-4 pg TEQs/kg body weight was established. [42] The presence of dioxins and dioxin-like PCBs is expressed as toxic equivalents (TEQ) after multiplication of congener-specic concentration levels with toxicity equivalency factors (TEF) developed based on their relative toxicity compared to 2,3,7,8-TCDD. The current European legislation is based on TEFs set by the World Health Organisation (WHO) in 1998 with the results expressed as TEQW HO98 . New TEFs were suggested in 2005 with the results expressed as TEQW HO05 . [22]
26.0.19
Accidental exposure to dioxin
Accidental exposures had taken place in Seveso and res in PCB lled electrical equipment, that is why PCBs are being changed in such equipments. Some foods were also accidently contaminated such as an edible oil Yusho (Japan) and Yu-Cheng (Taiwan). Other heavy exposure to dioxins took place in Vietnam resulting from aerial spraying of forests with agent orange (TCDD) contaminating airforce personal and inhabitants of Vietnam.
26.0.20
Maximum Dioxin levels for specic contaminants in foodstus
Three important regulation apply from 1 March 2007: Regulation (EC) 1881/2006 sets maximum levels for specic contaminants in foodstus. [43] Regulation 1882/2006 sets out the methods testers must use in sampling and analysis for the control of nitrate levels in lettuce and spinach. [44] Regulation 1883/2006, deals with sampling and analysis methods for determining the levels of dioxins and dioxin-like PCBs in specic foodstus.[45] Much attention is given to mycotoxins, such as setting limits on deoxynivalenol and zearalenone, including cereal bran marketed for direct human consumption and for germination. The limits of lead in cows milk is extended to sheep and goat milk and their products like cheese. The maximum level of lead in sh was risen from 200 mg/kg to 400 mg/kg to comply with the value of the Codex Alimentarius. The limit on levels of cadmium found in the liver and kidney has been extended to include horse meat.
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CHAPTER 26. DIOXIN
26.0.21
Specic aspects of health-related environmental protection
[46] The naturally occurring mercury content of sh in the worlds oceans, a source of food for humans, is so low that it does not pose a health risk. This does not apply, however, to species on top of the food chain such as swordsh, the Atlantic halibut or certain species of shark which are exposed to high concentrations, mature slowly and have a long life. These sh may show a rather high mercury content under "natural" conditions. Therefore, in Germany maximum levels of 1mg/kg were laid down for mercury concentrations in sheries products as early as 1975 to protect consumers health. Corresponding provisions at EU level were stipulated in 1993. Since April 2002, maximum levels for lead and cadmium in various foodstus such as cereals, vegetables, fruits, additives, meat and sheries products have been applied EU-wide to protect human health. These maximum levels are also stipulated in Regulation (EC) 1881/2006 [43]. When lead, cadmium and mercury levels were determined in the course of the annual food monitoring, only a small share of food samples exceeded the maximum levels for the heavy metals listed above. Dioxins and polychlorinated biphenyls (PCBs) are also environmental contaminants. Dioxins are unwanted and unavoidable by-products which must be minimised. They are mainly released through certain industrial thermal or combustion processes, in particular from sintering installations, metal production and residential replaces or woodstoves. Dioxins were not and are not produced intentionally. In contrast, PCBs were manufactured for a specic purpose, mainly as non-burning, non-conductive viscous liquids in transformers and hydraulics. Pollution legacies are the main source of dioxin and PCB emissions. Some compounds of these unwanted substances are chemically very stable, particularly toxic and persistent. Both groups of substances accumulate in human and animal fatty tissue. People generally absorb these harmful substances by eating food containing animal fat. In order to protect consumers, mandatory maximum levels (limit values) for PCBs in various foodstus produced from animals were already adopted in 1988. These national limit values were supplemented in 2002 by Europe-wide mandatory maximum levels (limit values) and voluntary action values for dioxins and, since 2006, for dioxin-like PCBs in various foodstus.
26.0.22
The perpetrator, not the tax payer must pay for environmental cleanup
[47] The U.S. Environmental Protection Agency (December 2009) reduces the need for federal taxpayers to fund the cleanup of environmental releases. The agency has identied three additional industry sectors for which it will begin the regulatory development process for any necessary nancial assurance requirements: the chemical manufacturing industry;
1921 the petroleum and coal products manufacturing industry, which primarily includes reneries and not coal mines; and the electric power generation, transmission, and distribution industry. Already included in this program is the hard-rock mining industry. Financial assurance requirements help ensure that owners and operators of facilities are able to pay for cleanup of environmental releases and help reduce the number of sites that need to be cleaned up by federal taxpayers through the Superfund program, following Section 108(b) of the Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA). Additional classes of facilities that require further regulations: waste management and remediation services, wood product manufacturing, fabricated metal product manufacturing, electronics and electrical equipment manufacturing, and facilities engaged in the recycling of materials containing CERCLA hazardous substances.
26.0.23
Dioxins
Farmed game are excluded from the limits of dioxins and dioxin-like PCBs set for meat and meat products. The limits set for liver, derived products, and fat is now restricted to bovines, sheep, poultry, pigs.
26.0.24
Swiss thickening agent Guar Gum with dioxin
[48] According to the European Commission of an edible thickening agent called guar gum (E412), used in a variety of pre-prepared foods,may contain dioxin and pentachlorophenol contamination. Member States were asked to test all batches of guar gum imported Indian. High levels of dioxin had been found on the 13.07.2007 in a Swiss-made thickening agent Unipektin branded VIDOCREM with levels of up to 156 picograms of dioxin per gram of fat in additives have been found (Maximum allowed= 6 picograms) . Ocial issues claim that there is no immediate health risk to consumers, but as these chemicals have the potential for a range of toxic eects such as high risk of cancer, people shouldnt be exposed to them unnecessarily. Consumer should avoid products which have thickening agent guar gum in their ingredient list. The contaminated guar gum had been exported by the India Glycols Limited company.
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CHAPTER 26. DIOXIN
26.0.25
Dioxin-like PCBs in pork from Ireland
[49] Dioxins and polychlorinated biphenols (PCBs) are chemicals that get into our food from the environment. Foods high in animal fat, such as milk, meat, sh and eggs are the main source of dioxins and PCBs although all foods contains at least low levels of these chemical. Dioxins may be formed as unwanted by-products in a variety of industrial and combustion processes, including household res. PCBs have been used since the early 1930s, mainly in electrical equipment, however, their production was stopped in the 1970s. According to the latest information from the European Rapid Alert System, levels of up to 292 mug/kg polychlorinated biphenyls (PCBs) have been detected in pork products from Ireland in December 2008. As this constitutes a major exceeding of the maximum admissible levels in the samples examined, the Irish government has recalled these foods. The food industry is therefore required to recall from the market all Irish (Republic) pork products produced from pigs slaughtered in Ireland. This includes all raw and cooked pork products e.g. pork, ham, sausages, bacon, gamon steaks etc. Irish beef is also aected by dioxin scandal [50] Irelands Food Safety Authority (FSAI) has conrmed that feed contaminated with dioxins has been fed to some cattle in Ireland. Dr Andrew Wadge, FSA Chief Scientist, said that the risk from dioxin in beef is signicantly lower than in pork. Cattle consume a wider variety of feeds and the way their bodies process the feed is dierent which makes the risk of contamination much lower. Republic of Ireland Agriculture Minister Brendan Smith said the levels of dioxins found in the beef were two to three times above safe limits, compared with 200 times for the pig meat. The risk consuming Irish beef is low and therefore beef products are not removed from shelves. Losses with beef are expected to be less serious because there is better traceability in the beef sector than the pork sector. Isolating the aected meat will be easier.
26.0.26
Pesticide in guar gum detected
[51] The Czech Agricultural and Food Inspection (CAFIA) detained one 10 ton guar gum batches (E412) destined for the market in October 2008. The detained guar gum contained 0.046 mg/kg - ppm pentachlorophenol, a pesticide and wood preservative. It is toxic to liver interferes in reproduction, development and rises body temperature. Since 5 May 2008 all charges of guar gum and guar gum products have to be tested by the Indian
1923 authorities, or by food operators to enter the EU [52]. Guar gum producing plants are cultivated in India and Pakistan, producing up to 85 per cent of global demand. Very low levels of pentachlorophenol in contaminated indoor and outdoor air, food, drinking water and soil are present as a result of uninhibited use of the chemical in the past. In August 2007 and March 2008 dioxin had been detected in guar gum charges and resulted in import safety regulations of testing guar gum. The high dioxin levels were linked to contamination of the guar gum with pentachlorophenol (PCP). Although there was no immediate risk to health, large numbers of food products, including yoghurts and fruit drinks, were withdrawn from sale all over Europe. [53] Early Detection method for Prion Diseases Infectious prions can be present decades before symptons appear, an early detection method is needed for early treatment to stop the spread of the Creutzfeldt-Jakob disease in humans. Prion diseases are dicult to diagnose, untreatable and ultimately fatal. Brain tissue dies out and sponge-like holes are formed in the brain. Real time quaking induced conversion assay, or RT-QuIC prion detection method [54] Infectious prions are also found outside the brain, in saliva, blood, breast milk, urine and the nasal and cerebral spinal uids, however, their concentrations in these bodily uids are to low to be measured with available methods. A new prion detection method, called real time quaking induced conversion assay, or RT-QuIC was has been developed by by Byron Caughey. Using this technique the small amounts of infectious prions are leaded to convert large amounts of normal prion protein into an abnormal form which enables their detection. The test detected high levels of prions in nasal uids of hamsters, pointing to such uids as possible sources of contagion in various prion diseases. RT-QuIC related applications might also be used to diagnose similar neurodegenerative protein diseases, such as Alzheimers, Huntingtons and Parkinsons diseases. William and colleagues 2010 estimate the relative amount of prions using the RT-QuIC prion detection method. [55] Quantitative N-terminal amino acid proling (N-TAAP) for TSE diagnosis [56] Gielbert and colleagues 2009 report a method to identify dierences between bovine spongiform encephalopathy (BSE), the classical scrapie and experimental transmissible spongiform encephalopathy strains.
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CHAPTER 26. DIOXIN
Diagnosis of TSE is based on the detection of the abnormal protease-resistant prion protein (PrP(Sc)). Proteolysis by proteinase K (PK) generates protease-resistant products (PrP(res)) with partially variable N-termini.The N-terminal aminoacid proles (N-TAAPs) is , and can be determined with the method developed by Gilbert and colleagues Fluorescence Spectroscopy of the Retina for Diagnosis to detect mad cow disease [57] Fluorescence spectra of the eye for diagnosis of transmissible spongiform encephalopathies (TSEs) may become a new diagnostic tool analysing dierences in the uorescence intensity and spectroscopic signatures. It is based on the accumulation of lipofuscin in the retina. The detection of infectious prion diseases in animals could help prevent the disease from spreading in the food supply.
Bibliography
[1] Dioxinherkunft klar. land und forst. 21.01.2011. http://www.landundforst.de/ bund-futterhersteller-dioxin-verdacht-erst-entdeckt?redid=384453. [2] Dioxin in futtermitteln aus der kartoelverarbeitung. bundesministerium zieht zwischenbilanz. 12.11.2004. http://www.bfr.bund.de/cm/208/kaolinit_in_der_ lebensmittelherstellung_dioxin_in_kartoffeln.pdf. [3] Nrw: Dioxin in bio-eiern gefunden - hof gesperrt. spiegel online 04 apr 2012. http: //www.spiegel.de/wirtschaft/service/0,1518,825644,00.html. [4] Foodwatch. Der foodwatch futtermittel-report (04/2005) schwaechen der kontrolle durch das qs-system pp 67. http://foodwatch.de/foodwatch/content/e10/e11/ e1283/foodwatchFuttermittelreportkomplett0405_ger.pdf? [5] Lin C, Hsu JF, and Liao PC. Coexposure of dioxin-like polychlorinated biphenyls and polychlorinated dibenzo-p-dioxins and dibenzofurans in free-range hens and implications derived from congener prole analysis. J Agric Food Chem, 60(8):196372, 2 2012. http://www.ncbi.nlm.nih.gov/pubmed/22309676. [6] Fournier A, Feidt C, Travel A, Bizec BL, Venisseau A, Marchand P, and Jondreville C. Relative bioavailability to laying hens of indicator polychlorobiphenyls present in soil. Chemosphere, 3 2012. http://www.ncbi.nlm.nih.gov/pubmed/22386460. [7] Schrter-Kermani C, Schmolz E, Herrmann T, and Ppke O. Pcdd, pcdf, and dioxinlike pcb in herring gull eggs from the north sea and baltic sea: Levels, patterns and, temporal trends. Organohalogen compounds, (67):12951299, 2005. http://www. umweltprobenbank.de/de/documents/publications/11898.
BIBLIOGRAPHY
1925
[8] De vries m and kwakkelz rp and kijlstra a: Dioxin in organic eggs. a review. NJAS, pages 542, 8 2006. http://orgprints.org/10175/1/NJAS_54-2_207-222.pdf. [9] Frequently asked questions on dioxins in food. the federal institute for risk assessment (bfr) faq, 10 january 2011. http://www.bfr.bund.de/en/frequently_asked_ questions_on_dioxins_in_food-69876.html#topic_69851. [10] Pcb und dioxin in eiern: Weiterer fall in niedersachsen. verbraucherzentrale thringen. 22 may 2012. http://www.vzth.de/UNIQ133768321807512/ dioxin-in-eiern-drei-nrw-betriebe-gesperrt. [11] Fournier A, Feidt C, Marchand P, Vnisseau A, Le Bizec B, Sellier N, Engel E, Ratel J, Travel A, and Jondreville C. Kinetic study of -hexabromocyclododecane orally given to laying hens (gallus domesticus). "transfer of hbcd in laying hens". Environ Sci Pollut Res Int, 19(2):4407, 2 2012. http://www.ncbi.nlm.nih.gov/pubmed/21808974. [12] Szabo DT, Diliberto JJ, Hakk H, Huwe JK, and Birnbaum LS. Toxicokinetics of the ame retardant hexabromocyclododecane alpha: eect of dose, timing, route, repeated exposure, and metabolism. Toxicol Sci, 121(2):23444, 6 2011. http://www.ncbi. nlm.nih.gov/pubmed/21441408. [13] Council directive 1999/74/ec of 19 july 1999 laying down minimum standards for the protection of laying hens. http://eur-lex.europa.eu/LexUriServ/LexUriServ. do?uri=OJ:L:1999:203:0053:0057:EN:PDF. [14] Regulation eec nr 2092/91. eu-eco-regulation on organic production of agricultural products and indications referring thereto on agricultural products and foodstus. http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=OJ:L:1991: 198:0001:0015:EN:PDF. [15] Regulation (ec) nr 1804/1999. http://eur-lex.europa.eu/LexUriServ/ LexUriServ.do?uri=OJ:L:1999:222:0001:0028:EN:PDF. [16] Neue dioxin-funde, neue vorwuerfe: Immer neue dioxin-funde heizen die debatte um den verbraucherschutz in deutschland an. dabei geraet auch die rolle der bundesregierung ins blickfeld. news.de 09.01.2011. 1 2011. http://www.news.de/ vermischtes/855107742/neue-dioxin-funde-neue-vorwuerfe/1/. [17] Dioxin threat eggs from germany baked in uk cakes. bbc news uk. 7 january 2011. 1 2011. http://www.bbc.co.uk/news/uk-12133402. [18] Tesco recalls sponge cakes over egg fear. 08.01.2011. Herald ie, 1 2011. http://www.herald.ie/national-news/ tesco-recalls-sponge-cakes-over-egg-fears-2489037.html.
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[19] Zahl gestiegen: Rund 4700 betriebe gesperrt. zahl gestiegen: Rund 4700 betriebe gesperrt. in ganz deutschland ist die zahl der gesperrten hoefe wegen des dioxinskandals gestiegen. allein niedersachsen sperrte 4468 betriebe. hamburger abendblatt 06.01.2011. Hamburger Abendblatt, 1 2011. http://www.abendblatt.de/hamburg/ article1748671/Zahl-gestiegen-Rund-4700-Betriebe-gesperrt.html. [20] New York Times:. Germans fear dioxin has contaminated small farms. 07.01.2011. http://www.nytimes.com/2011/01/08/world/europe/08dioxin.html. [21] FSA:. Update on dioxin contamination of pig and poultry feed in germany. 06.01.2011. http://www.food.gov.uk/news/newsarchive/2011/jan/dioxinupdate. [22] Results of the monitoring of dioxin levels in food and feed. European Food Safety Authority (EFSA), 6 2010. http://www.efsa.europa.eu/en/scdocs/doc/1385.pdf. [23] Evans BR, Karchner SI, Allan LL, Pollenz RS, Tanguay RL, Jenny MJ, Sherr DH, and Hahn ME:. Repression of aryl hydrocarbon receptor (ahr) signaling by ahr repressor: role of dna binding and competition for ahr nuclear translocator. Molecular Pharmacology, 73(2):38798, 2008. http://molpharm.aspetjournals.org/content/73/2/ 387.long. [24] Zudaire E, Cuesta N, Murty V, Woodson K, Adams L, Gonzalez N, Martnez A, Narayan G, Kirsch I, Franklin W, Hirsch F, Birrer M, and Cuttitta F:. The aryl hydrocarbon receptor repressor is a putative tumor suppressor gene in multiple human cancers. J Clin Invest., 118(2):64050, 2 2008. http://www.ncbi.nlm.nih.gov/pmc/ articles/PMC2157559/?tool=pmcentrez. [25] Hahn ME, Allan LL, and Sherr DH:. Regulation of constitutive and inducible ahr signaling: complex interactions involving the ahr repressor. Biochem Pharmacol, 77(4):48597, 2 2009. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2701375/ ?tool=pubmed. [26] Kerkvliet NI and Funatake CJ:. Possible role for the ah receptor in the generation of regulatory t cells. NIEHS, 3 2007. http://www.niehs.nih.gov/research/ supported/sep/2005/Ah-Tcell.cfm. [27] Marinkovic N, Pasalic D, Ferencak G, Grskovic B, and Rukavina AS. Dioxins and human toxicity. Arh Hig Rada Toksikol, 61(4):445453, 12 2010. http://www.ncbi. nlm.nih.gov/pubmed/21183436. [28] Yoshioka W, Peterson RE, and Tohyama C. Molecular targets that link dioxin exposure to toxicity phenotypes. J Steroid Biochem Mol Biol, 12 2010. http: //www.ncbi.nlm.nih.gov/pubmed/21168493.
BIBLIOGRAPHY
1927
[29] Burns JS, Williams PL, Sergeyev O, Korrick S, Lee MM, Revich B, Altshul L, Del Prato JT, Humblet O, Patterson DG Jr, Turner WE, Needham LL, Starovoytov M, and Hauser R. Serum dioxins and polychlorinated biphenyls are associated with growth among russian boys. Pediatrics, 12 2010. http://www.ncbi.nlm.nih. gov/pubmed/21187307. [30] BFR:. Aufnahme von umweltkontaminanten ber lebensmittel (cadmium, blei, quecksilber, dioxine und pcb) ergebnisse des forschungsprojektes lexukon. bfr january 2011. 1 2011. http://www.bfr.bund.de/cm/238/aufnahme_von_umweltkontaminanten_ ueber_lebensmittel.pdf. [31] Deng YY, Jia LJ, Li K, Rong ZY, and Yin HW. Levels of pcdd/fs in agricultural soils near two municipal waste incinerators in shanghai, china. Bull Environ Contam Toxicol, 12 2010. http://www.ncbi.nlm.nih.gov/pubmed/21161505. [32] Ortiz X, Carabellido L, Mart M, Mart R, Toms X, and Daz-Ferrero J. Elimination of persistent organic pollutants from sh oil with solid adsorbents. Chemosphere, 12 2010. http://www.ncbi.nlm.nih.gov/pubmed/21190713. [33] Radio Hamburg. Dioxin in eiern und eisch. jetzt auch in hamburg der dioxin-skandal weitet sich jetzt unter anderem auf hamburg und niedersachsen aus. http://www.radiohamburg.de/Hamburg/Nachrichten/2010/Dezember/ Dioxin-in-Eiern-und-Fleisch-Jetzt-auch-in-Hamburg. [34] NDR. Dioxin-fette kommen von rma aus emde. ndr 3.01.2011. 2011. http://www. ndr.de/regional/niedersachsen/Dioxin101.html. [35] EU prft Produktion von Tierfutter in Deutschland; vwd/24.8.99/br. [36] http://pressemitteilung.ws/node/208328. Rhein-Wied-News: Lidl nimmt dioxinverseuchte Bio-Eier aus dem Handel - auch ein Legehof in RLP geschlossen! Pressemitteilung WS 07.05.2010. [37] http://www.presseportal.de/pm/73754/1608864/verein_fuer_kontrollierte_ alternative_tierhaltungsformen_e_v_kat. Sofort umfangreiche Untersuchungen eingeleitet. Keine Bio-Eier mit erhoehtem Dioxingehalt im Verkauf. Na-Presseportal 05.05.2010. [38] http://www.cdc.gov/ncidod/eid/vol8no1/01-0129.htm. Vellinga A, Van Loock F: The Dioxin Crisis as Experiment To Determine Poultry-Related Campylobacter Enteritis. [39] http://news.bbc.co.uk/2/hi/science/nature/4182029.stm. Dioxin found in German eggs. Germany has called for higher environmental standards on farms after free-range eggs were found to contain the cancer causing chemical dioxin. BBC News 17 January 2005.
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[40] Lebensmittelzeitung: Unilever-Chairman fordert Euro-FDA;LZ42 22.11.99. [41] http://www.who.int/home/whatsnew.html. Executive Summary, Assessment of the health risk of dioxins: re-evaluation of the Tolerable Daily Intake (TDI), WHO Consultation May 25-29 1998, Geneva, Switzerland. [42] van Leeuwen FX, Feeley M, Schrenk D, Larsen JC, Farland W, and Younes M:. Dioxins: Whos tolerable daily intake (tdi) revisited. Chemosphere, 40(9-11):1095101, 2000. http://www.ncbi.nlm.nih.gov/pubmed/10739051. [43] http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=OJ:L:2006:364: 0005:0024:EN:PDF. Commission Regulation (EC) No 1881/2006 of 19 December 2006 setting maximum levels for certain contaminants in foodstus. [44] http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=CELEX: 32006R1882:EN:NOT. Commission Regulation (EC) No 1882/2006 of 19 December 2006 laying down methods of sampling and analysis for the ocial control of the levels of nitrates in certain foodstus. [45] http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=CELEX: 32006R1883:EN:NOT. Commission Regulation (EC) No 1883/2006 of 19 December 2006 laying down methods of sampling and analysis for the ocial control of levels of dioxins and dioxin-like PCBs in certain foodstus. [46] http://www.umweltministerium.de/english/food_safety/general_ information/doc/5720.php. Specic aspects of health-related environmental protection. German Federal Environment Ministry. 2010. [47] http://yosemite.epa.gov/opa/admpress.nsf/652d9edd5cf71a2585257359003f5343/ a8c0942a295468338525769c00689c70. EPA Identies Three Industries for Financial Obligations in Cleanup of Environmental Releases Action is a rst step to ensure owners of these facilities, not taxpayers, foot bill for the cleanup of environmental releases. December 30.2010. [48] http://www.foodstandards.gov.uk/news/newsarchive/2007/aug/guargum. Food Standards Agency: Guar Gum Inverstigation. UK
[49] http://www.bfr.bund.de/cd/template/index_en. German Federal Institute for Risk Assessment: Dioxin-like PCBs in pork from Ireland. [50] http://www.food.gov.uk/news/newsarchive/2008/dec/irishupdate. Standards Agency: Update on Irish beef. 9.12.2008. UK Food
[51] http://www.szpi.gov.cz/eng/news/article.asp?id=63053&cat=2215&ts=2ec6. Czech Agriculture and Food Inspection Authority: Analyses detected a consignment of guar gum originating from India containing higher levels of pentachlorophenol. 3 Oktober 2008.
BIBLIOGRAPHY
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[52] http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=OJ:L:2008:117: 0042:0044:EN:PDF. 2008/352/EC: Commission Decision of 29 April 2008 imposing special conditions governing guar gum originating in or consigned from India due to contamination risks of those products by pentachlorophenol and dioxins (notied under document number C(2008) 1641). [53] http://www.food.gov.uk/news/newsarchive/2008/mar/gum. FSA: New EC measures on guar gum. 10.03.2008. [54] National Institute of Allergy and Infectious Diseases (NIAID):. Nih study suggests that early detection is possible for prion diseases. 02.10.2010. http://www.niaid. nih.gov/news/newsreleases/2010/Pages/prionCaughey.aspx. [55] Wilham JM, Orr CD, Bessen RA, Atarashi R, Sano K, Race B, Meade-White KD, Taubner LM, Timmes A, and Caughey B:. Rapid end-point quantitation of prion seeding activity with sensitivity comparable to bioassays. PLoS Pathog, 6(12):e1001217, 12 2010. http://www.plospathogens.org/article/info%3Adoi% 2F10.1371%2Fjournal.ppat.1001217. [56] Gielbert A, Davis LA, Sayers AR, Hope J, Gill AC, and Sauer MJ:. High-resolution dierentiation of transmissible spongiform encephalopathy strains by quantitative nterminal amino acid proling (n-taap) of pk-digested abnormal prion protein. J Mass Spectrom, 44(3):38496, 3 2009. http://www.ncbi.nlm.nih.gov/pubmed/19053160. [57] Adhikary R, Mukherjee P, Krishnamoorthy G, Kunkle RA, Casey TA, Rasmussen MA, and Petrich JW:. Fluorescence spectroscopy of the retina for diagnosis of transmissible spongiform encephalopathies. Analytical Chemistry, 82(10):4097, 2010. http://www. ncbi.nlm.nih.gov/pubmed/20411920.
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CHAPTER 26. DIOXIN
Chapter 27 Food Poisoning

27.0.27 Food contaminants are a special risk to children [1]
According to Vogt et al. 2012, food contaminants are of concern for all ages, but specially for children. The authors stress that children are in developing phase. The intake of food and uids relative to the bodyweight is greater as that of adults. The type of food the amount and the frequency of their intake, preparation of the meal, processing and even packaging inuence the exposure to toxic chemicals. Vogt and colleagues assessed food contamination of arsenic, lead, mercury, pesticides, dioxin, DDT, dieldrin, chlordane, acrylamide, hormones and antibiotics. These compounds are linked to diseases like cancer, asthma, lead poisoning, neurobehavioural disorders, learning and developmental disabilities, and birth defects in children. Many studies of dietary exposure to toxic substances look at isolated chemicals. There is a need to consider all contaminants of a food as a whole, on a daily basis throughout the life span. Pregnancy and childhood are crucial developmental periods which should be included in these considerations. The authors calculated the toxic risk and estimated benchmark levels for cancer risk and non cancer health risks. The intake exceeded safe benchmark levels in acrylamide, arsenic, lead and chlordane (children only), dieldrin, 1,1 dichloro-2,2-bisethylene and polychlorinated dibenzo-p-dioxins. The calculated threat to children was greater than calculated for adults for all compounds. Exposure to pesticides were linked to tomatoes, peaches, apples, peppers, grapes, lettuce, broccoli, strawberries, spinach, dairy, pears, green beans, and celery. The exposure to most of these environmental toxic components are preventable. Prevention strategies should be focused on compounds, consume of organically produced dairy and selecting fruits and vegetables to reduce agrochemicals, consuming less animal foods to reduce persistent organic pollutants, such as DDT and others. Very important for children is to reduce the consumption of chips, cereals, crackers and other processed carbohydrate foods such as French fries to reduce acrylamide. 1931
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CHAPTER 27. FOOD POISONING
27.1
27.1.1
Algal Toxins
Algae
Algae may present variable morphology. Species are known being unicellular, other algae may grow up to 20 to 30 meters of length. Algae serve as food for marine animals, they may be used as ingredients such as the production of agar agar, used in food, in drugs, as basis for bacteriological medias and is used in many other ways. Chlorophyll is often hidden by yellow, brown,blue and red pigments.This gave the origin to a classication of algae in Xantophyceae, Cyanophyceae or Rodophyceae. Algae produce starch, mannite, leucosine and oil. Algae are generally inhabitants of water. Algae adapted to life in contact with air are found on the surface of rocks, on the bark of trees and at soil. In extreme cases they may survive at 70o C (Cyanophyceae). Algae are an important factor of regeneration of water and treatment of drinking water. Microscopical identication of algae is used in the characterisation of quality of water. Algae are important part of marine plankton serving as food for a variety of aquatic animals. Chlorella pyrenoidosa, unicellular alga was studied as a possible food. Rodoceae are industrially used to obtain natural carotene. In reduce amount dehydrated algae are used as food in Japan.
27.1.2
Classication of alga
[2] Classications are often not up to date but some are didactical and will still be used even when there is a new classication proposed so this is why the present classication proposed by Strasburger is used here: The plant kingdom is divided in 7 great divisions : 1. Bacteriophyta containing bacteria 2. Cyanophyta containing the blue-green Alga 3. Phycophyta containing all other alga 4. Mycophyta containing mushrooms 5. Bryophyta containing the mosses 6. Pteridophyta containing ferns 7. Spermatophyta containing plants with seeds Alga which produce toxins are settled in division 2 Cyanophyta and division 3 Phycophyta.
27.1. ALGAL TOXINS
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27.1.3
Division 2: Cianophyta
The division contains the following orders:
Chrooccocales generally unicellular, forming jelly on rocks. Hormogonales laments
27.1.4
Division 3: Phycophyta:
This division contains algae organised as Flagellatae with the following orders: Chrysomonadales Heterochloridales Cryptomnonadales Dinoagellatae Euglenales Protochloridales Volvocales The Flagellatae have subdivision Chlorophytina includes the green algae (Chlorophyceae).They live mainly in fresh water as plankton and form the green coating on rocks and on the bark of trees. The Chlorophyceae contain Chlorella pyrenoidosa and Chlorella vulgaris. The latter can live in symbiosis with other individuals. Pyrrhophytina Euglenophytina Phaeophytina Rhodophytina Cyanophyta
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27.1.5
[3]
Classication of microorganism according Streble
1. Phylum Bacteriophyta(Bacteriae) Order Eubacteriales Order Actinomycetales Order Chlamydobacteriales 2. Phylum Cyanophyta(Blue algae) Order Chroococcales Order Pleurocapsales Order Chamaesiphonales Order Stigonematales 3. Order Chrysophyta(Yellow algae) Class Chrysophyceae(Gold algae) Order Chrysomonadales Order Rhizochrysidales Order Chrysocapsales Class Bacillariophyceae, Diatomae ( Diatom ) Order Centrales Order Pennales Class Xanthophyceae (Yellow-green algae) Order Heterogloeales (Heterocapsales) Order Heterococcales Order Heterosiphonales 4. Euglenophyta Order Euglenales Order Peranematales 5. Phylum Dinophyta Class Dinophyceae Order Peridiniales 6. Phylum Cryptophyta 7. Phylum Chlorophyta(Green Algae) Class Chlorophyceae Order Volvocales Order Tetrasporales Order Chlorococcales Order Ulotrichales Order Ulvales Order Prasiolales Order Microsporales
27.1. ALGAL TOXINS Order Chaetophorales Class Oedogoniophyceae Class Bryopsidophyceae Order Cladophorales ivermectin Order Sphaeropleales Class Conjugatophyceae Order Mesotaeniales Order Gonatozygales Order Desmidiales Order Zygnemales 8. Phylum Rhodophyta(Red algae) Order Banglales Order Nemalionales Order Cryptonemiales 9. Phaeophita(Brown algae) Order Ectocarpales 10. MycophytaOrder Archimycetes Order Phycomycetes Order Ascomycetes Order Basidiomycetes Order Fungi imperfecti
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27.1.6
Algal toxins
Beside useful algae there are many single cell algae which produce toxins. These species develop rapidly under favourable conditions forming algae carpets in seawater killing sh in Mexico gulf and North Sea (such as Microcystis). Marine animals such as oysters,Crustaceae and dierent types of sh may eat the toxic algae storing the toxins. This can lead to serious poisoning. According to the species of algae the symptoms of poisoning are[4]: 1. Damage of the nervous system (Paralytical Shellsh Poisoning)(PSP) 2. Loss of memory(Amnesic Shellsh Poisoning)(ASP) 3. Neurotoxic phenomenons(Neurotoxic Shellsh Poisoning) 4. Sodium channel blocking in nervous cells(Tetrodotoxin)(TTX) In the summer the temperature of seawater rises causing high growth of algae. In the Netherlands the harvest of oysters are stopped at this time of the year or the oysters are transfered to unpolluted water tanks to regenerate.
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The alga Fibrocapsa japonica was found in the German Bay. This alga produces a toxin which is associated with the death of seals. According to Ursula Siebert from the Forschung und Technologie Zentrum , Bsum, Germany, was found in samples of the German Bay for the rst time in 1995. How the toxin of Fibrocapsa japonica acts and if it can harm humans is unknown[5]. In USA and Canada the maximum tolerable value of saxitoxin is 0,8 mg/Kg of mollusc meat. In Germany absence of liposoluble DSP is provided by regulations. Water soluble PSP should not exceed 400 micrograms/Kg of mollusc meat. The maximum tolerable amount of dominoic acid in Germany is 20 mg DA/kg mollusc meat.
27.2
27.2.1
Algal blooms at eutrophic estuarine and water sheds

Harmful Algal Blooms (HAB)
Harmful Algal Blooms (HAB) is a natural disaster which has attracted global attention in recent decades since it threatens greatly public health, causes economic damage to sheries and tourism. Fibrocapsa japonica is one of HAB causative organisms which caused significant loss to coastal sheries in Japan. From the 1990s it was also reported frequently in European coastal waters. In a work of the University of Oldenburg, the toxicity of Fibrocapsa japonica algal cells was rst established by Artemia salina biotest. Fibrocapsins was screened step by step through Artemia salina biotest, bioluminescence inhibition biotest and erythrocyte lysis assay methods, isolated then in HPLC. The chemical natures of brocapsins 1, 2 and 3 were determined nally as 6,9,12,15octadecatetraenoic acid, all-cis-5,8,11,14,17-eicosapentaenoic acid and all-cis-5,8,11,14-eicosatetraenoic acid by HPLC-MS, IR, GC-(HR)MS, NMR experiments and biotest. The toxins are unsaturated fatty acids. (Isolation and characterisation of toxins from Fibrocapsa japonica (Raphidophyceae) / Meng Fu. - 2003. - V, 85 Bl. - Oldenburg, Univ., Diss., 2003)
27.2.2
Euglenophycin from microalgae is toxic to sh and presents anticancer properties
[6] In the summer of 2002 striped bass were killed by toxins of the freshwater microalgae Euglena sanguinea and Euglena granulata according to a report of Zimba and colleagues in 2004 [7].
27.2. ALGAL BLOOMS AT EUTROPHIC ESTUARINE AND WATER SHEDS
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Cyanoprokaryotic algae, diatoms, haptophytes, dinoagellates, euglenoids, and rhaphidophytes are known to produce algal toxins. However, according to the authors, euglenophycin from Euglena sanguinea presents potentials to treat cancer. The authors seek patent protection on ndings of the toxin. The toxic compounds is an alkaloid similar in structure to re ant venom.
27.2.3
Dried Euglena viridis enhance the immune system of sh
[8] Das, Pradhan and Sahu in 2009 assessed the eect of dietary doses of Euglena viridis on the immune response and disease resistance of Labeo rohita ngerlings, a sh of the carp family found commonly in rivers and freshwater lakes in Asia. The results demonstrate that sh fed with Euglena showed increased levels of superoxide anion production, lysozyme, serum bactericidal activity, serum protein and albumin compared with the control group. Following challenge with the bacterial pathogen Aeromonas hydrophila, less survivability was observed in the control group without supplementation with Euglena, compared with the group fed with 0.5 g Euglena viridis kg(-1) dry diet. The authors concluded that Euglena stimulates the immunity system of sh.
27.2.4
Blue-green alga Microcystis aeruginosa and aquatic environment
Microcystis small algal cells which organize into colonies with a light blue-green coloration, or dark due to optical eects of gas-lled vesicles. These vesicles provide the buoyancy necessary for Mycrocystis aeruginosa to stay near the surface of the water. In may 2007 an outbreak of Microcystis caused great troubles at the water works of Wuxi city (China). More than 2 million people without drinking water for a week. Concentrations of microcystin, the poison produced by the alga, were higher in summer and autumn than in other seasons Concentration up to 15.6 mug L-1 were measured in the the water of the lake Taihu, from which water is being taken for the Wuxi city. [9] Stone 2011 reports that eorts to reduce eutrophication of the lake shows rst results, The author also refers to eorts to reduce the pollution of Lake Erie. [10]
27.2.5
Microcystis blooms in Lake Erie
[11] Monitoring of nutrient loads and zebra mussel distribution must be intensied to improve the ecosystem of Lake Erie. Microtoxins of algal bloom of Microcystis aeruginosa have caused the death of sh and birds. The U.S. and Canada signed the 1972 Great Lakes Water Quality Agreement aiming a
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coordinated eort to reduce phosphorus inputs to the Great Lakes, including Lake Erie. This reduced to amount of algae., such as the alga Aphanizomenon os-aquae. Blooms Microcystis aeruginosa become most evident during calm periods when the cells oat to the surface and form a scum. Blooms of Microcystis are poor food for zooplankton which serve as food for larval sh. The microcystin toxin of algae may damage the liver of animals which come in contact with it. It is also an issue for water works, but water treatment is believed to remove the toxin from water. Algal blooms in western Lake Erie, however, are linked to nutrient loading, nutrient releases by zebra mussels, and selective feeding by zebra mussels andd its connection to Microcystis. Zebra mussels were found to selectively lter and reject phytoplankton of Microcystis but digest other algae leading to Microcystis blooms. Various massive blooms of the cyanobacteria Microsystis aetuginosa formed in western Lake Erie surface scums of Microcystis with high concentrations of the toxin microcystin resulted in foul-smelling, rotting, algal mats, rending beaches unusable and sport shing was adversely aected.
27.2.6
Eect of chlorination on microalgae
[12] The eect of chlorination of source water containing toxic cyanobacterial cells were determined by Zamyadi et al. 2011. The authors found that the treatment cause cell damage, toxin release and disinfection by-products (DBP) formation. Microalgae included in the study were Anabaena circinalis, Microcystis aeruginosa, Cylindrospermopsis raciborskii, and Aphanizomenon issatsckenka. Chlorine <4.0 mg min/L made more than 60% of cells release their toxins. Saxitoxin was the easiest to be oxidize by chlorine, followed by cylindrospermopsin and microcystin-LR. Concentrations of chlorination by-products (trihalomethanes and haloacetic acids and N-nitrosodimethylamine) were lower than the guideline values. However, the disinfection by-products (DBP) concentrations, during a bloom were over the guideline values.
27.2.7
Disinfection Byproducts
[13] Disinfection byproducts are formed when disinfectants used in water treatment plants react with bromide and/or natural organic matter. Disinfection byproducts found in drinking water, including trihalomethanes, haloacetic acids, bromate, and chlorite. Trihalomethanes (THM): Trihalomethanes are chloroform, bromodichloromethane, dibromochloromethane, and bromoform. EPA established a maximum allowable annual average level of 80 parts per billion of THM. Haloacetic Acids (HAA5): Haloacetic acids, known as HAA5, are: monochloroacetic acid, dichloroacetic acid, trichloroacetic acid, monobromoacetic acid, and dibromoacetic acid. EPA established a maximim allowable annual average of 60 parts per billion of
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HAA5 in water. Bromate: Bromate is formed when drinking wateris disinfected using bomide. EPA established a maximum allowable annual level of 10 parts per billion in drinking water for bromate. Chlorite: Chlorite is a byproduct formed when chlorine dioxide is used to disinfect water. EPA regulates chlorite at a monthly average level of 1 part per million in drinking water.
27.2.8
Nitrogen and Microcystis aeruginosa in aquatic ecosystems
[14] The last two centuries, with the introduction of the agrarian chemical, most of all, nitrogen and phosphorous, inuenced the aquatic ecosystems. Chen et al.2011 investigated the eects of nitrite and the cyanobacterium Microcystis aeruginosa on population growth in the rotifer Brachionus calyciorus. Brachionus calciorus is a hatchery food for larval sh and is used as model organism in aquatic toxicology and evolutionary ecology. The authors report that a high tolerance of Brachionus calyciorus to nitrite levels may be due to the absence of specic respiratory structures and pigments. However, an increased toxicity of nitrite in combination with Microcystis aeruginosa was observed, caused by an increased production of microcystin suggesting a synergistic way between nitrite and Microcystis aeruginosa in causing toxicity.
27.2.9
Phosphorous and Microcystis blooms
[15] Cyanobacteria blooms caused by species such as Microcystis have become commonplace in many freshwater ecosystems. Phosphorus (P) typically limits the growth of freshwater phytoplankton populations. However, Microcystis uses eciently organic phosphorous to form blooms. Harke et al. 2011 examined genes involved in P acquisition in Microcystis including two high-anity phosphate-binding proteins (pstS and sphX) and a putative alkaline phosphatase (phoX). The authors found three genes (phosphate-binding proteins (pstS and sphX) and an alkaline phosphatase (phoX)) strongly upregulated under low inorganic phosphorous conditions in Microcystis aeruginosa. The expression of phoX was not identied in Microcystis wesenbergii. High levels of organic phosphorus sources conditions did not leaded to high expression of the three genes. Microcystis dominates phytoplankton blomms in summer under low levels of inorganic phosphorous and grow rapidly under high organic phosphorous relying on pstS, sphX, and phoX to handle inorganic and organic phosphorous.
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27.2.10
Paralytic shellsh toxins from cyanobacterial blooms in Brazilian water reservoir
[16] Clemente and colleagues 2009 studied the eect of cyanobacterial blooms -PST producers) at the Alagados Reservoir (Brazil), an important source for the supply of water and shery. The authors monitored biomarkers in sch and water. The authors found paralytic shellsh toxins 5.15, 43.84, and 50.78 ng equiv Saxitoxin/L concentrations in water in the spring, summer and autumn, respectively. Gonyautoxins (GTX) were found in water samples and sh muscle, and GTX 5 was the major analogous found in muscle. Alterations in the sh gills and liver were found in all samples, varying according to season. The authors stress that farming activities and to the contaminants bioavailability during the year may also be envolved.
27.2.11
Coral species are menaced by the black band disease
[17] Richardson and colleagues 2007 wrote that black band disease (BBD) is a disease of coral caused by cyanobacterias such as Geitlerinema and Leptolyngbya sp. It is a sulde-rich microbial mat that moves across coral colonies lysing coral tissue. The pathogenicity is related to the production of sulde, however, the cyanotoxin microcystin may also be envolved. The gene mcyA from the microcystin synthesis complex was detected in both species. Microcystin, however was not detected in samples of other regions. The authors propose a regional specicity for microcystin in the cause of black band disease.
27.2.12
Testing microcystin in water using carbon nanotubes
[18] Microcystin is a poison from blue-green algae Cyanobacteria. Microcystin-LR is one of over 80 known toxic variants and is the most studied by biologists and ecologists. Microcystin containing blooms are a problem worldwide, including China, Australia, the United States and much of Europe. Once ingested, microcystin travels to the liver, via the bile acid transport system, where most is stored; though some remains in the blood stream and may contaminate tissue. Microcystin binds covalently to protein phosphatases thus disrupting cellular control processes. [19] Wang and colleagues 2009 at the University of Michigan developed a biosensor based on single-walled carbon nanotubes to test for microcystin in water. This test is rapid and simple to perform. The researchers plan to adapt the test to detect a variety of other toxins in water and food by replacing the antibodies. The test measures the electrical conductivity of the nanotubes located on a paper strip. The nanotubes are put in contact with a dispersion of antibody to the microcystin-LR turning the paper conductive. The antibody in contact with the toxin changes the width
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of nanotube-nanotube tunneling gap changing the conductivity of the paper which can be measured. It takes less than 12 minutes to perform the test which may replace the dicult ELISA method. The limit of detection was reported to be 0.6 nmol/L (0.6 ng/mL) and may be used to control compliance which the WHO standard for microcystin-LR content in drinking water (1 ng/mL).
27.2.13
Agrochemicals and fertilisers impacts on aquatic systems
[20] Hapeman and colleagues 2002 summarising the "Agrochemical and Nutrient Impacts on Estuaries" symposium of the American Chemical Society stresses that expanding urbanization and agricultural activity can result in increased particulate and chemical loads, such as nutrients and pesticide loads, resulting in decreased light penetration and degraded aquatic habitats. The authors urge to develop more eective agricultural and land management strategies and sound science-based regulations.
27.2.14
Non-point source pollution
[21] Non-point source pollution refers to diuse contamination that does not originate from a single discrete source. Non-point source pollution is often accumulative eect of small amounts of contaminants from a large area. Scott andf colleagues 1999 stressed that agricultural non-point source runo may result in signicant discharges of pesticides, suspended sediments, and fertilizers into estuarine habitats adjacent to agricultural areas or downstream from agricultural watersheds. The authors emphasise that integrated pest management (IPM), best management practices (BMP), and retention ponds (RP) as risk management to reduce the contaminant risk of agricultural runo into estuarine ecosystems. In sites not included in the agricultural management the authors found elevated levels of P-glycoprotein in gravid female grass shrimp populations. P-glycoprotein is a multidrug resistance protein, which may transport various pesticides across cellular membranes. The authors concluded that their data clearly support an integrated risk reduction strategy (BMP, IPM, and RP) to reduce agricultural pesticide runo.
27.2.15
Ammonium nitrate is an environmental stress to frog larval
[22] Ortiz-Santaliestra and colleagues 2010 found that sublethal eects of toxicants, such as ammonium nitrate impairs behavioural responses to predators. Detection of predators and
1942
mobility may be reduced following the eect of pollution. Tadpoles may be hampered to escape from predators. The authors noted that tadpoles exposed to ammonium nitrate were consumed by crayshes faster than controls. According to the study nitrogenous fertilizers can impair larval defensive behaviours. Tadpoles may be hampered to escape from predators. The authors write that environmental stresses should not be neglected while performing toxicological studies on amphibians. The eects of pollution on amphibians are increased when combined with stress by other environmental factors such as water salinity. In another study in 2010, the same authors report that embryos of frogs exposed to ammonium nitrate and water salinity were up to 17% smaller than controls. Mortality rate due to predators was increased facing a single stress and further increased under the eect of two stressors. Embryos could develop a natural adaptation to salinity and mortality was then not increased. The authors concluded that multiple stressors should be considered when testing environmental pollution eect on amphibians. [23]
27.2.16
Harmful algae blooms buoy
Dr. Phil Culverhouse from the University of Plymouth developed the HAB (harmful algae blooms)-Buoy. This project was funded by the European Union. The buoy is a swimming microscope coupled natural object recognition software. It can image and recognise harmful algae. It will be operated either underwater suspended from a buoy or on a musselproducing raft, or in the laboratory to monitor algae. The relevant specimens which are scanned from ltered water will be further analysed to decide on their species label. This enables shell shery sta to have advance warning that HAB species are present. Tests are instruments will be located in Galicia in Spain, Galway in Ireland, and the Gulf of Trieste in Italy. Table 27.1: Shellsh poisoning Poisoning Amnesic Shellsh poisoning ASP Ciguatera Fish Poisoning CFP Diarrhetic Shellsh Poisoning DSP neurologic shellsh poisoning NSP Symptoms Amnesia, vomit, diarrhoea Parestesia, muscle pains, numbness of limbs reversal of hot/cold temperature sensation Vomit, diarrhoea Paresthesia, vomit, diarrhoea Toxins Domoic acid
Ciguatoxins maitotoxin Ocada acid derivate dynophysistoxin Brevetoxin
27.2. ALGAL BLOOMS AT EUTROPHIC ESTUARINE AND WATER SHEDS paralytic shellsh poisoning PSP Palytoxin poisoning Paresthesia, numbness of limbs, paralysis Haemolysis, rhabdomyolysys, muscle cramps Saxitoxin Palytoxin
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27.2.17
Damage of the nervous system (Paralytical Shellsh Poisoning)(PSP)
They are caused by toxins produced by Dinoagelata such as Alexandrium spp. The PSP toxins are water soluble.
27.2.18
Damage of the digestive tract (Diarrhetic Shellsh Poisoning)(DSP)
Toxins of Diarrhetic Shellsh Poisoning (DSP) are okada acid (okadaic acid) the Dinophysis toxin, the pectenotoxins and yessotoxin which are liposoluble causing strong diarrhoea.
27.2.19 27.2.20
Analytical methods Mouse-Bioassay
A biological test giving immediate informations about the activity of the toxins in whole. To study the dierent paralytic toxins chromatography methods are necessary, such as the use of the ionicpair chromatography with RP-C18 and a step gradient making possible to separate PRP toxins. At the beginning there were only biological tests in rats and mice, the Bioassays and immunological tests, the immunoassays. Modern HPLC methods with derivatization before column with uorescence marker using a uorescence detector can detect very small amounts of toxins. Using HPLC/MS coupling with Atmospheric Pressure/Electrospray Ionisation (API/ESI)Interfaces better results may be achieved.
27.2.21
DSP: Diarrhoeic Shellsh Poisoning (A colorimetric phosphatase inhibition assay)
[24] To detect DSP toxins, a colorimetric phosphatase inhibition assay was developed using a highly puried recombinant human PP2A C-subunit, which is produced by a recombinat Baculovirus. The assay is very sensitive, fast, easy,accurate, reproducible and inexpensive to detect DSP toxins (OA group) in the shellsh. The intensity of the color is proportional to the enzyme activity and the absorbance is measured at 405 nm. The lowest detectable concentration of OA is 0.1 g/g in shellsh digestive glands,which comprise about 10-30%
1944 of all the soft tissue of the shellsh by weight.
The DSP Rapid Kit was developed following the studies of Takai and Mieskes 1991, and Tubaro and colleagues 1996 which proposed the assay as routine assessment of okadaic acid shellsh contamination, stressing that it is sensitive, rapid and does not require expensive equipment. [25] [26]
27.2.22
DSP Rapid Kit (Diarrheic Shellsh Poison Test)
[27] The DSP Rapid Kit is based on the inhibition of the protein phosphatase (PP2A) by DSP toxins (okadaic acid and dinophysistoxin: OA and DTXs). According to Sceti bioscience Export, the producer of the test kit, it has high sensitivity, and eliminates cross reaction and non-specic reaction seen with EIA and ELISA methods. The assay comprises one step which takes only 30 minutes as incubation time. The producer of the DSP Rapid Kit explains that PP2A can hydrolyze a colourless articial substrate, p-nitrophenyl phosphate (p-NPP), and produces the yellow colour of p-nitrophenol (p-NP) in the alkaline solution. The intensity of the colour is proportional to the enzyme activity and the absorbance is measured at 405 nm.
27.2.23
Loss of memory (Amnesic Shellsh Poisoning)(ASP)
A poisoning with ASP in Canada aecting about 100 persons was related in 1987. These persons had eaten meat of mollusks which were intoxicate with ASP. The survivals had amnesia. This gave the name of the poisoning which is caused by the dominoinic acid of the alga Nitzschia pungens. This alga is found also in Europe turning oysters poisonous. The maximum tolerable amount of dominoic acid in Germany is 20 mg DA /Kg mollusc meat.
27.2.24
Analytical methods
HPLC is used as analytical method of ASP using an RP-C18 column without derivatization. Dominoinic acid down to 1,0 mg/kg mollusc meat can be detected with this method. Making derivatization of dominoinic acid before the column using uorenilmetoxicarbonylchlorid. Amounts below 1 mg/Kg can be detected.
27.2.25
Neurotoxic phenomenons(Neurotoxic Shellsh Poisoning)
The NSP toxins are produced by Gymnodinium breve, also denominated as Ptychodiscus brevis. This alga has several times caused death to sh in the Gulf of Mexico.
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APS toxins may be classied in to types: Brevetoxin A and Brevetoxin B. They are a group of polyethers.
27.2.26
Analytical methods
HPLC and immunoassays and HPLC with MS coupling.
27.2.27
Sodium channel blocking in nervous cells (Tetrodotoxin)(TTX)
Tetrodotoxin is also called fugu-toxin. It may be produced by some sh of the family of Tetradontidae (Takifugu sp.). This ball-sh is being consumed in Japan causing sometimes severe poisoning. The toxin TTX blocks the sodium channel of nervous cells acting neurotoxic. This toxin has no absorbtion of ultra violet light and is not uorescent. HPLC is used with derivatization before column, producing a uorescent derivate with sodium hydroxide. The HPLC/MS coupling with an API/ESI interface is used with good results and in some cases chromatography with mass spectrometry recheck.
27.2.28
Saxitoxin
Saxitoxin is an algal toxin of the PSP type, being water soluble. More 20 derivates of saxitoxin are produced by Dinoagelata such as Alexandrium spp.
27.2.29
Analytical method to determine Saxitoxin
[28] Summary Saxitoxin is an algal toxin which is extracted in acid solution. After extraction the toxin is puried with periodic acid in alkaline medium. Saxitoxin is then read uorimetricaly against a standard curve. The food to be analysed is triturated in trichloracid 1 N and hydrochloric acid 0,2N in equal parts. After 20 minutes heating it is ltered, taken to pH 5.2 +-0.1 with potassium hydroxide 1 mol/l and centrifugated and transfered to a column with ion exchange resin in ME+ form 50 to 100 mesh to purify the saxitoxin. The column is then washed with 100 ml buer of potassium acetate at a pH of 5.2+-0.1 followed with 50 ml distilled water. Saxitoxin is then eluated with sulfuric acid 0,5N until 20 ml are obtained in a volumetric ask. The velocity of elution should not exceed 3 ml/minute. 2 ml of the elution are mixed with 2 ml NH4 OH 1,2 N and 100 microliter of periodic acid 0.1 ml/l. After 15 Minutes 200 microliter of glacial acetic acid are added to the solution and read against a blank containing the same components as before having periodic acid
1946
changed with water. Standard solution: Saxitoxin dissolved in acetic acid 0,1 ml/l. Further dilution are made with sulfuric acid in a way that 2 ml of the dilutions are added to 2 ml NH4 OH 1,2 N and 100 microliter of periodic acid. Reading is made at 388 nm. The blank should be subtracted from the value of the sample. Before using purifying column the resins must be suspended three times in 50 ml chloridric acid 3N and washed with distilled water until reaction is neutral. Again the resin must be suspended 2 times in 50 ml acetic acid 2mol/l. The upper layer is then exchanged by 150 to 200 ml acetic acid and the pH is adjusted to 5.2+-0.1 with acetic acid. The resin can be kept until use under a buer solution of potassium acetate 0,2 mol/l at an pH of 5.2+-0.1 adjusted with acetic acid. The column of 1 cm diameter is charged with approximately 5 g resin which gives a length of 5 cm.
27.3
European regulatory limits for marine biotoxins not eective to protect consumer
[29] European Food Safety Authority (EFSA) in a paper on marine biotoxins in shellsh concluded that the current EU regulatory limit values for okadaic acid (OA) and analogues, azaspiracid (AZA)-group toxins, saxitoxin (STX)-group toxins and domoic acid (DA), are not suciently protective for high consumers. Only the limits et for yessotoxin (YTX)-group toxins, pectenotoxin (PTX)-group toxins were found to be sucient protective. For actual regulatory limits for marine biotoxins see Regulation (EC) No 853/2004. [30]
27.3.1
Shortcomings of the ocial reference method for lipophilic biotoxins
The Panel on Contaminants in the Food Chain (CONTAM Panel) also reported that the mouse bioassay has shortcomings and is not considered an appropriate tool for control purposes because of the high variability in results, the insucient detection capability and the limited specicity. Alternatives to the reference methods for the determination of the marine biotoxins with lower limits of detection (LOD) are being developed. For ocial reference methods for biotoxins see Regulation (EC) No 2074/2005. [31]
27.3. EUROPEAN REGULATORY LIMITS FOR MARINE BIOTOXINS NOT EFFECTIVE TO PROTECT CONSUMER
1947
27.3.2
Health regulations related to bivalve molluscs and other marine species
[32] Health concerns related to shellsh, live bivalve molluscs and other aquatic animals contaminated with coli, salmonella or other bacteria or viruses as well as algal toxins are of public concern. Actual global warming may spur micro organisms in water turning and turn it necessary to tighten safety control on molluscs. The Council Directive 91/492/EEC of 15 July 1991 lays down the health conditions for the production and the placing on the market of live bivalve molluscs. It dene production areas from which molluscs can bet gathered for direct human consumption, or from which they have to be puried or relayed. It is primarily the responsibility of the producers to ensure that the bivalve molluscs are produced and placed on the market in compliance with the health requirements prescribed; whereas the competent authorities must, carry out checks and inspections, to ensure that producers comply with those requirements do not contain microorganisms and toxic substances in quantities which are considered to be dangerous to human health. Live bivalve molluscs from purication areas must not exceed the limits of a ve-tube, three-dilution MPN-test of 6 000 faecal coliforms per 100 g of esh or 4 600 E. Coli per 100 g of esh in 90% of samples. Live bivalve molluscs from areas where they do not exceed the limits of a ve-tube, threedilution MPN-test of 60 000 faecal coliforms per 100 g of esh.can be collected but placed on the market only after relaying over a long period (at least two months).
27.3.3
Requirements concerning live Bivalve Molluscs intended for immediate consumption
1. The possession of visual characteristics associated with freshness and viability, including shells free of dirt, an adequate response to percussion, and normal amounts of intravalvular liquid. 2. They must contain less than 300 faecal coliforms or less than 230 E. Coli per 100 g of mollusc esh and intravalvular liquid based on a ve-tube, three-dilution MPN-test or any other bacteriological procedure shown to be of equivalent accuracy. 3. They must not contain salmonella in 25 g of mollusc esh. 4. They must not contain toxic or objectionable compounds occurring naturally or added to the environment such as those listed in the Annex to Directive 79/923/EEC. [33]
1948
5. The upper limits as regards the radionuclide contents must not exceed the limits for foodstus as laid down by the Community. 6. The total Paralytic Shellsh Poison (PSP) content in the edible parts of molluscs (the whole body or any part edible separately) must not exceed 80 microgrammes per 100 g of mollusc esh in accordance with the biological testing method - in association if necessary with a chemical method for detection of Saxitoxin - or any other method recognized in accordance with the procedure laid down in Article 12 of this Directive. If the results are challenged, the reference method shall be the biological method. 7. The customary biological testing methods must not give a positive result to the presence of Diarrhetic Shellsh Poison (DSP) in the edible parts of molluscs (the whole body or any part edible separately). 8. In the absence of routine virus testing procedures and the establishment of virological standards, health checks must be based on faecal bacteria counts.
27.3.4
Algal toxins, new detection methodes
[34] Algal toxins may be present in shellsh, molluscs and other marine and fresh water inhabitants. Global warming may spur algal blooms which highlights the importance of algal toxins detection. Maximum levels and Detection methods are described in the Decision 2002/225 EEC. (1) Chapter V, point 7, of the Annex to Directive 91/ 492/EEC provides that the customary biological testing methods must not give a positive result to the presence of diarrhetic shellsh poisoning (DSP)in the edible parts of molluscs(the whole body or any part edible separately). (2) It has been scientically proven that certain marine biotoxins such as those of the diarrhetic shellsh poisoning (DSP)complex (okadaic acid (OA)and dinophysistoxins (DTXs)) and also yessotoxins (YTXs), pectenotoxins (PTXs)and azaspiracids (AZAs), pose a serious hazard to human health when present above certain limits in bivalve molluscs, echinoderms, tunicates or marine gastropods. (3) In the light of recent scientic studies it is now possible to establish maximum levels and methods of analysis for those biotoxins.
1949
This Decision lays down the maximum levels for the marine biotoxins of the diarrhetic shellsh poisoning (DSP)complex (okadaic acid and dinophysistoxins), yessotoxins, pectenotoxins and azaspiracids and the methods of analysis to be used for their detection. It applies to bivalve molluscs, echinoderms, tunicates and marine gastropods that are intended for immediate human consumption or for further processing before consumption. Maximum levels Okadaic acid, dinophysistoxins and pectenotoxins together Yessotoxins Azaspiracids
160 g of okadaic acid equiv./kg. 1 mg of yessotoxin equivalent/kg. 160 g of azaspiracid equivalents/kg.
27.3.5
The EU EFSA Panel recommends reduction of EU Okadaictoxin limit
[35] Okadaic acid (OA) and its analogues, the dinophysis toxins (DTX1, DTX2, and DTX3), together form the group of OA-toxins. These toxins are lipophilic and heat stable, are produced by dinoagellates and can be found in various species of shellsh, mainly in lter-feeding bivalve molluscs such as oysters, mussels, scallops, and clams. OA-group toxins cause Diarrhoeic Shellsh Poisoning (DSP), which is characterized by symptoms such as diarrhoea, nausea, vomiting and abdominal pain. These symptoms may occur in humans shortly after consumption of contaminated bivalve molluscs such as mussels, scallops, oysters or clams. Inhibition of serine/threoninephosphoprotein phosphatases is assumed to constitute the mode of action of OA-group toxins. According to the Panel OA appears to be not mutagenic per se, but induces changes at the chromosome level and is aneugenic in vitro. The Panel noted that these eects may be related to cytotoxicity of OA. The Panel concluded that a lowest-observed-adverse-eect-level (LOAEL) for human illness is in the region of 50 microgram OA equivalents/person, this approximates to 0.8 microgram OA equivalents/kg bodyweight (b.w.) for adults. An uncertainty factor of three was applied to extrapolate this LOAEL to a no-observed-adverse-eect-level (NOAEL) which resulted in an ARfD of 0.3 microgram OA equivalents/kg b.w. Based on data provided by ve Member States, the Panel identied 400 g of shellsh meat as the high portion size to be used in the acute risk assessment of marine biotoxins.
1950
It was noted that a 400 g portion of shellsh meat containing OA-group toxins at the current EU limit of 160 microgram OA equivalents/kg shellsh meat would result in a dietary exposure of 64 microgram toxin. For a 60 kg adult this is equivalent to approximately 1 microgram/kg b.w. This gure exceeds the ARfD by approximately 3-fold. The Panel concluded that in order for a 60 kg adult to not exceed the ARfD, a 400 g portion of shellsh should not contain more than 18 microgram toxin, i.e. 45 microgram OA equivalents/kg shellsh meat. The mouse and the rat bioassay are the ocially prescribed reference methods in the EU for the detection of OA-group toxins. The Panel called for a validation of the phosphoproteinphosphatase assays and liquid chromatograph-mass spectrometry (LC-MS) to replace actual methods.
27.3.6
Detection methods
Detection methods are described in the Decision 2002/225 EEC. Biological methods: Use mice or rats. The tests involve the death of the animals.
27.3.7
Alternative detection methods
A series of methods such as high performance liquid chromatography (HPLC)with uorimetric detection, liquid chromatography (LC)-mass spectrometry (MS), inmunoassays and functional assays such as the phosphatase inhibition assay can be used as alternative or complementary methods to the biological testing methods, provided that either alone or combined they can detect at least the following analogues, that they are not less eective than the biological methods and that their implementation provides an equivalent level of public health protection: - okadaic acid and dinophysistoxins: an hydrolysis step may be required in order to detect the presence of DTX3, - pectenotoxins: PTX1 and PTX2, - yessotoxins: YTX, 45 OH YTX, homo YTX, and 45 OH homo YTX, - azaspiracids: AZA1, AZA2 and AZA3.
27.3.8
On market available kits for the detection of algal toxins
Saxitoxin (STX) is a neurotoxin found in marine dinoagellates (algae). It is a selective sodium channel blocker. It is so strong that it is known as "TZ" chemical weapon by the U.S. military with the Lct50 of 5 mg . min/m3 . [36] The medical importance is in relation to red tide in shellsch because of the paralytical shellsh poisoning (PSP) food poisoning. The blocking of the sodium channel produces a accid paralysis that leaves its victim calm and conscious through the progression. Death is caused by respiratory failure. [36] A Saxitoxin (PSP) algal toxin immunoassay ELISA kit is now commercially available
1951
among others: The Direct ELISA Enzyme Linked Immunosorbent Assay (ELISA) has proved to be a sensitive and rapid method for phycotoxin detection, such as:
27.3.9
Yessotoxin (YTX)
Yessotoxin and its analogues produced by marine algae, in particular Protoceratium reticulatum and Gonyaulax polyedra. YTX is known to accumulate in shellsh meat and is regarded as hepatotoxic and cardiotoxic when ingested above a certain level. The yessotoxins have previously been included in the diarrhetic shellsh poison (DSP) group, but the YTX chemistry and toxicology dier distinctly from the DSP toxin family. The European Commision recently placed the yessotoxins in a separate phycotoxin group, and implemented a maximum permitted level (MPL) of 1 mg YTX eqvivalents/kg shellsh intended for human consumption (Directive 2002/225/EC). [37]
27.3.10
Microcystins / nodularins and its congeners detection kit
It responds to a broad range of the toxic microcystin congeners, as well as the structurally related nodularin toxins.The ELISA is derived from antibodies recognizing 6E-ADDA,the common structural feature present in the toxic congeners of microcystins and nodularins. [38]
27.3.11
Dominoic acid
The amnesic shellsh poison (ASP) toxins, domoic acid (DA) and DA isomers are watersoluble neurotoxins produced by a number of marine algae, in particular by the microalgae of the genus Pseudo-nitzschia. Blooms of Pseudo-nitzschia spp. may lead to the accumulation of DA in shellsh lter feeders and other marine species. Ingestion of DA contaminated shellsh may lead to amnesic shellsh poisoning (ASP) by aecting the central nervous system, and has caused the death of both animal and human consumers in severe cases. The European Commission Directive 2002/226/EC implemented a maximum permitted level (MPL) of 20 mg DA/kg shellsh intended for human consumption. This MPL is adopted by the regulatory authorities in most other countries. This quantitative DA EIA kit detects DA in water samples shellsh and algal extracts The assay is primarily intended for use in routine monitoring of DA levels in bivalve molluscs to comply with the regulatory MPL, but is also applicable for DA quantication in the marine matrixes. [39]
27.3.12
Cylindrospermopsin
It is a naturally produced toxin of several cyanobacterial strains and has been found in fresh water throughout the world. Certain strains of Cylindrospermopsis raciborskii (Australia, Hungary, United States), Umezakia natans (Japan), Aphanizomenon ovalisporum (Australia, Israel) have been found to produce cylindrospermopsin.
1952
The production of cylindrospermopsin seems to be strain specic and not species specic. The antibody binds Cylindrospermopsin The assay sensitivity allows the determination of Cylindrospermopsin in a range of environmental samples (water, sh tissue, sh plasma, etc.). [40]
27.3.13
Microcystine ELISA Test
Microcystins and the structurally related nodularins are toxins produced by cyanobacteria (blue-green algae). Acute poisoning in humans and animals can be caused by these toxins and in several cases has led to death. These toxins inhibit liver function and might act as tumor promoters. Many dierent structural variants (congeners) are found, with the most common variant being microcystin-LR. To protect public health, the WHO has proposed a provisional upper limit for microcystin-LR of 1 ppb in drinking water. [41]
27.4
Bacterial poisoning
Bacteria can settle on food. Due to industrialisation and globalization they can be widespread turning: endemic[42] The spread of a disease is called endemic when there are continuously a certain number of infections left in a region. epidemic The spread of a disease is called epidemic when there is an increase of the normal number of infections in a region. pandemic The disease is told to be pandemic when an epidemic is spread over many countries. The bacteria present in food can: Spoil the food causing o-taste and o-smell. Produce toxins under favourable conditions of growth, causing acute poisoning or subacute but very harmful alterations such as cancer. Be infectious causing diarrhoea and other serious diseases Be opportunists[43] Facultative pathogenic bacteria may be harmless to people with strong immunological system. Small children and people with weak immunological system can be attacked by the opportunists. They generally cause isolated cases and very rarely epidemics.
27.4. BACTERIAL POISONING
1953
27.4.1
Examples of microorganism which spoil food
Molds, yeasts, Escherichia coli, Proteus etc.
27.4.2
Examples of microorganism producing toxins
The microorganism cited below can produce toxins when present in food and having sucient time during storage under appropriate temperatures. In this case the microorganisms dont necessarily need to be alive when reaching the nal consumer.:
27.4.3
Laboratory diagnosis
Sometimes the microorganism which spoiled the food are dead because the food was sterilised after deterioration. In this case chemical analysis may bring the evidence of undesired microbiological activity, such as the rise of ergosterol or rise of acidity in salads or succinic acid in egg yolk. Bacillus cereus produces endotoxin about which there is little known. Bacillus cereus produces hemolysin and lecithinase which is not toxic and is a phospholypase. Campylobacter jejuni produces endo- and enterotoxin. Clostridium botulinum produces exotoxins from type A, B, C, D, E and F. They are the strongest toxins which are known and act as neurotoxins. They inhibit the excretion of acetylcholine avoiding thus the transmission of signals from the nerve to the muscle causing paralysis comparable to the eect of curare, the poison of South American Indians. The endotoxins which are thermo unstable are formed in canned food with a pH higher than 4.5 and about 6 month of storage. This toxin is destroyed when food is cooked before serving. Clostridium perfringens produces an enterotoxin formed in bad refrigerated precooked food. Escherichia coli produces an enterotoxin under bad hygienic conditions. Listeria monocytogenes produces listeriolysine. Salmonella enteritides produces a heat unstable exotoxin mainly in ground meat, in eggs, in poultry, in milk powder, in chocolate and ne salads. Salmonella typhimurium produces a heat unstable exotoxin. Shigella dysenteriae and Shigella sonnei produce endotoxin or heat unstable exotoxins.
1954
Shigella dysenteriae, Shigella sonnei and Staphylococcus aureus, produce thermostable toxins. The toxins produced by Staphylococcus aureus can be classied serologically as toxin A, B, C1, C2, D, E and F. About 19% of Staphylococcus aureus are toxin producing strains. The toxin A and B are resistant to very high temperatures and may resist even to 20 minutes at 121,1o C . Often there are no sensory changes in food with staphylocoxin. In the production of industrialised food all eorts should be made to avoid a contamination of food with Staphylococcus aureus, paying great attention to avoid handling of food by person with suppurative focuses. Streptococcus faecalis, produces thermostable toxins Vibrio cholerae produce enterotoxin. Vibrio parahaemolyticus produces exotoxin. Yersinia enterocolytica produces enterotoxin.
27.4.4
Examples of microorganism causing infections
: All microorganism cited as producer of toxins of the above paragraph are able to cause infections. The microorganism must be alive and in sucient number to cause an infection.
27.4.5
Staphylococcus aureus penicillin resistant
Staphylococcus aureus has experienced increasing resistance to antibiotics. The rst reports from penicillin-resistant isolate, type 80/81, came from Australia and Canada in 1953, causing skin lesions, sepsis and pneumonia in children and young. The hospital and community acquired infections were treated in the 1960s with meticillin
27.4.6
Community-acquired MRSA (ca-MRSA)
Emerging infections with community-acquired MRSA (Ca-MRSA) picked up in public places is resistant to meticillin antibiotic. It is believed that the strain of Staphylococcus aureus may have evolved from the 80/81. Key regions in genes of community-acquired MRSA are identical to the genes of the 80/81 strain. It is therefore believed that the cMRSA strain has developed from this strain through several intermediate steps. The total genetic code diers from the hospital form. One important toxin of cMRSA Staphylococcus aureus is Panton-Valentin-Leukozidin (PAL), responsible for the necrosis of wounds, abscesses and pustules and is determined by the gene lucks-Luke.
1955
The Ca-MRS strain was described in USA and Canada in 1994. The germ has a specic gene "lucks-Luke" which produces a necrotic toxin causing deep necrotic wounds. These wounds must be surgically drained. Sometimes amputations becomes necessary. German, French and Swiss samples of cMRSA are resistant to fusidin acid. This indicates the formation of a new strain of Staphylococcus aureus. Intercontinental spreading of the cMRSA is demonstrated by the nding of the MLST-Type STr with the element SCCmec type IVa in USA as well in Germany. [44][45] There are nasal carriers which may spread the bacteria causing what is called a skin and soft tissue infection SSTI. Contamination occurs during body contact, smears by hand contact, crowded living conditions. Insucient personnel hygiene.
27.4.7
Avoiding cMRSA
Strict personnel hygiene, Hexachlorophene Hexachlorophene should be used for hand disinfection. Avoiding crowded living conditions. Football and wrestling being a sport with body contact should take precautions on these matters.[46] An undersupply of vitamin complex B due to a food insuciency or single-sided nutrition may lower immunity regarding pustules. Yeast extract or food supplement of complex B vitamines may be useful to bodys defence, and may in some cases even avoid infection.
27.4.8
Examples of microorganism which can act as opportunists
Candida albicans can cause infections of mouth and digestive tract by persons with weak immunological system. Yeasts being found in food should be controlled in regard of the presence of Candida albicans.
27.4.9
Mycotoxins
Mycotoxins are poisonous metabolites of certain moulds which can cause pathological changes in human and animals. The most important species which produce mycotoxins are Aspergillus, Penicillium and Fusarium. Intoxication takes place through ingestion of contaminated food more seldom by inhalation or skin resorption. Mycotoxins unlike the bacterial or algal toxins generally do not produce acute intoxication but they are known as strong carcinogenic, teratogenic with chronic activity.
1956
27.4.10
Contamination with mycotoxins
Direct contamination with mycotoxins can take place when moulds grow on the food. Indirect contamination can take place mycotoxins contaminated feed is ingested by cattle and pork. Milk, eggs and meat are examples of indirect contamination of food caused by spoiled feed containing Aatoxins Ochratoxin A and some of the Fusaria toxins. The direct contamination caused by on food growing moulds is of great importance on cereals, oil seeds, coee, fruits, vegetables, spices some types of cheese like Roquefort cheese and meat products.
27.4.11
Aatoxins
Aatoxins are mycotoxins which are exclusively produced by the mould Aspergillus avus and Aspergillus parasiticus. Of importance are the aatoxins B1 , G1 and G1 .
27.4.12
Aatoxin B1
Aatoxin B1 is the strongest carcinogenic compound known. It causes liver cancer. In food aatoxin M1 is sometimes present and is almost as poisoning as aatoxin B1
1957
In animal feed the most frequent aatoxin is B1 being often found together with Aatoxin B 2 , G 1 G2
27.4.13
Mycotoxins and food chain
[47] According to a review by Bryden 2007 mycotoxins are secondary fungal metabolites that can be produced in crops and other food commodities both pre- and post-harvest. Around 25 per cent of the worlds crops are aected by moulds. Low levels of mycotoxins may produce chronic conditions with reduced growth and development, immunosuppression and cancer are chronic eects in many developing countries. Bryden calls for a mycotoxin reduction which includes eorts of farmers, government agencies, food processors and scientists. However, a signicant impact on the cost of food production is being expected.
27.4.14
Ochratoxin A on surface of dry sausages
[48] Iacumin and colleagues assessed the moulds as a seasoning for sausage and aatoxines such as ochratoxin A on the surface of sausages from northern Italy. The most frequently isolated mould strains from sausage casings were Penicillium nalgiovense, Penicillium oxalicum, Eurotium amstelodami, Penicillium olsonii, Penicillium chrysogenum, Penicillium verrucosum, Penicillium viridicatum, and Eupenicillium crustaceum. Aspergillus ochraceus. Ochratoxin A was found in 45 per cent of the samples, ranging from 3 and 18 microg/kg. The authors report that ochratoxin A concentration was reduced to below the limit of detection by brushing and washing the sausages prior to sale. They concluded that there is no health risk for the consumer, since ochratoxin A was found only on the casings and not inside the dry meat.
27.4.15
Ergot in cereals
[49] The term ergot refers to fungal structures from Claviceps species replacing kernels on grain ears or seeds on grass heads, being visible as large discoloured sclerotia. These sclerotia contain dierent classes of alkaloids, the most prominent being ergometrine, ergotamine, ergosine, ergocristine, ergocryptine and ergocornine and their related -inines. Ergot alkaloids (ergolines) exert toxic eects in all animal species, and the most prominent toxic signs can be attributed to the interaction of ergot alkaloids with adrenergic, serotinergic and dopaminergic receptors. Typical clinical symptoms are vasoconstriction that may progress into vaso-occlusion and gangrenous changes, but also into abortions.
1958
The neurotoxic signs comprise feed refusal and dizziness but also convulsions. Typical dopaminergic eects are agalactia accompanied with insucient nursing of suckling animals such as piglets and foals. Available data indicate that adverse eects may occur in agricultural animalsparticularly in pigs after intake of feed contaminated with ergot at levels close to the current EU limit. Data on the toxicity of individual ergot alkaloids are scarce, as under eld conditions animals are exposed to the complex mixtures with a varying composition of ergot alkaloids depending on the fungal strain, the host plant and on environmental factors. Systematic analyses of common grains and forage grasses will be necessary to establish a correlation between exposure to ergot alkaloids and adverse eects in individual animal species. There are reports on human intoxications and on ergot poisoning of farm animals in particular cattle, horses, sheep, pigs, chicken and even wild animals. EFSA carried out a risk assessment on ergot alkaloids as undesirable substance in animal feed in 2005. [50] Analytical methods have only recently been developed to measure simultaneously the most prominent ergot alkaloids in cereals intended for human consumption or animal feeding by liquid chromatographyuorescence detection (LC-FLD) and liquid chromatographytandem mass spectrometry (LC-MS/MS). [51] [52]
27.4.16
Post-harvest control strategies to reduce risk of mycotoxins in grain storage
[53] Magan and Aldred in a review of 2007 stress that contamination of cereal by moulds and mycotoxins results in dry matter, quality, and nutritional losses and represents a hazard to the food chain. According to the authors very small amounts of dry matter loss due to mould activity can be tolerated. A dry matter loss <0.5% is a signal of visible moulding, mycotoxin contamination and downgrading of lots. Important moulds contaminating dried grain are Penicillium verrucosum (ochratoxin) in damp cool climates of Northern Europe, and Aspergillus avus (aatoxins), A. ochraceus (ochratoxin) and some Fusarium species (fumonisins, trichothecenes) on temperate and tropical cereals. To control the growth of moulds during grain storage modied atmospheres, fumigation with sulphur dioxide and ammonia and CO2 of >75% were tried. Also preservatives based on aliphatic acids, essential oils and anti-oxidants have been used storing dried grains for
27.4. BACTERIAL POISONING feed.
1959
The authors concluded that an eective post-harvest management requires clear monitoring criteria, hygiene and the implementation of key critical control points during harvesting, drying and storage stages in the cereal production chain to minimise mycotoxin contamination during storage.
27.4.17
Micotoxins in African grains
[54] According to Wagacha and Muthomi 2008 the factors that contribute to mycotoxin contamination of food and feed in Africa include environmental, such as high humidity and temperatures favour fungal proliferation, and a low socio-economic status of the majority of inhabitants of sub-Saharan Africa predisposes them to consumption of mycotoxin contaminated products. This exposes the polpulation to increased risk of immuno-suppression, impaired growth, various cancers and death depending on the type, period and amount of exposure. The authors accentuate the synergistic eect between mycotoxin and some diseases such as malaria, kwashiorkor and HIV/AIDS. In 2004 Africa registered the greatest fatal mycotoxinpoisoning outbrek caused by contaminated maize. The authors call for intervention strategies such as early harvesting, proper drying, sanitation, proper storage and insect management, biological control, chemical control, decontamination, breeding for resistance as well as surveillance and awareness creation. Ecient, cost-eective sampling and analytical methods suitable in developing countries are needed.
27.4.18 27.4.19 27.4.20 27.4.21 27.4.22 27.4.23 27.4.24
Ochratoxins Fumonisins Trichothecens Zearalenon Citrinin Patulin Fusaria toxins
[55] Fusaria toxins is a generic term for the so called fade-toxin produced by Fusaria moulds which produce wrinkling of plant parts. Moulds which produce fusaria toxins are: Fusaria sporotrichiella
1960
Fusarium tricinctum Fusaria diverisporum Gibberella zeae There are not enough ocial data related to fumonisin available in order to dene limits of fusaria toxins in food. There is currently no ocial limit for fumosins in food, however,the EU has proposed a limit of 500 microgrammes per kilogram [56].The following results of tests are published:
27.4.25
Maize our, polenta, maize semolina
290 samples were analysed with following results: 58% below 30 mug/Kg 23% from 30 to 500 mug/Kg 17% >500mug/Kg The highest result was 9818 mug/Kg. The group of maize products has therefore the highest concentration of fusaria toxins of all food on test. Fumonisin was found over all in Italian maize and over 1000 mug/Kg in biological maize cultures.
27.4.26
Extruded products, Breakfast cereals
The content of fumonisin of these products is much lower as found in maize: About 25% below 30 mug/Kg 74 % from 30 to 500 mug/Kg 1% > 500 mug/Kg up to 1600 mug/Kg
27.4.27
Sweet corn
Fumonisin content found in sweet corn was very low. More than 85% had not detectable amounts of fumonisin. 5% from 100 to 500 mug/Kg
27.4.28
Baby food
. From 149 samples only 2 samples were positive to fumonisin with a maximum concentration of 55 mug/Kg. According to the German Institute of Consumer Health Protection and Veterinary Medicine (Bundesinstitut fr gesundheitlichen Verbraucherschutz und Veterinrmedizin BgVV in Berlin the contamination of cereals with Fusaria is increasing resulting in higher content of fusaria toxins in baby Food containing cereals. The Fusaria moulds grow on the cereal stalk and transfer their toxin to the grain. The most important of these toxins are desoxynivalenol (DON)also known as vomitoxinVomitoxin), and fumonisin. They damage cells und interfere in the immune system. In wheat and maze products there were found up to 600g/kg food.
1961
Desoxynivalenol may coexist with Zeralenone. Desoxynivalenol causes growth depression and suppression of the immune system. 1 ppm limit in the sole feeding should not be exceeded. Zearalenone may cause fertility disturbances on the oestrogen production in pigs. Consuming one or several meals with 20 g of fusaria contaminated cereals the tolerable daily intake (TDI) of 1g will be surpassed. All eort should be made to discard batches of wheat, maize, and cereals with fusaria toxins. The control of the raw material should be intensied in order to guarantee low levels of fusaria toxins.
27.4.29
Wheat, beer, oil seeds and spices
640 samples were analysed with no positive ndings.
27.4.30
U.S. bio ethanol industry result in threefold mycotoxins contamination in feed
[57] High levels of mycotoxins in maize-based ethanol co-products up to three times compared with grains, are expected by Wu and Munkvold 2008. The co-products are mostly dried distillers grain and solubles or wet distillers grains which are fed to livestock. The authors estimate that the mycotoxins from dried distillers grain and solubles, mainly fumonisins, may result in loss of up to 293 million USD/y to the swine industry from weight gain reduction. Other stakeholders are also aected if mycotoxin contamination in both preand postharvest maize. will not be controlled. The toxicity of the fumonisins, fumonisin B1 (FB1), fumonisin B2 (FB2), and fumonisin B3 (FB3), produced by Fusarium moniliforme to poultry was studied by Henry and Wyatt. The authors found that the 50% lethal dose for FB1, when injected into the air cell of embryonating chicken eggs, was 18.73 microg per egg. [58]
27.4.31
Synergistic eect of fumonisins on the toxicity of fusaric acid
[59] Fusaric acid, only moderately toxic to the chicken egg, was found by Bacon, Porter and Norred 1995 to have its toxicity increased due to the synergistic eect of fumonisin B1 and other fusaria toxins found on corn and other cereals. The authors concluded that fusaric acid might play a role in enhanced and unpredicted toxicity in mammalian systems if it is consumed with other mycotoxins.
1962
27.4.32
Fumonisins in quail rations
[60] Butkeraitis and colleagues 2004 found that exposure to FB 1 at concentrations equal or more than 50 mg/kg could adversely aect quail performance. The authors stress the importance of controlling fumonisin contamination of quail rations. Human tolerable Daily Intake is 800 ng/kg bw/day of FB1.
27.4.33
FDA sees fumonisins residues from meat and eggs not of public health concern
[61] The FDA concluded in residue Studies in 2000 that fumonisins are poorly absorbed orally in all species tested to date. Oral bioavailability averaged about 4% in swine and 0.7% in laying hens. Most of the ingested FB1and FB2 is excreted in the feces unchanged. The FDA believes fumonisin residues in meat, milk and eggs will likely not be a public health concern.
27.4.34
Exposure Assessment by the Australian FSA
[62] Maize is the only commodity that contains signicant amount of fumonisins (IPSC, 2000). Estimated mean dietary intakes of fumonisin B1 based on regional diets and published distributions of concentrations of fumonisin B1 in maize, indicating a mean intake of fumonisin B1 ranging from 0.2 44g/kg bw/day in European-type diet to 2.4 g/kg bw/day in the African diet (WHO, 2001c). Fumonisin B1 is not well absorbed by poultry and should not contribute signicantly to human dietary exposure.
27.4.35
Risk Characterisation
The FSA Australia says that secondary exposure to fumonisin B1 through consumption of poultry meat products derived from poultry fed fumonisin B1-containing feed, presents a negligible risk to the consumer
27.4.36
Fusarium sporotrichoides
This mould grows in the surroundings of the Baykal sea and other parts of east Siberia, in the north of China and North Korea. It grows on cereals producing toxins which cause the Kaschin-Beck-disease which is a chronic osteoarthrose which begins in early childhood resulting in heavy disorder of growth, deformation of the extremities.The toxins of Fusarium sporotrichoides contract the vascular system which serves the epiphysic cartilage and metaphysis resulting in disorder in the growth of cartilage which can be observed not only
1963
in humans but also in dogs and rats which had been fed with corn covered by Fusarium sporotrichoides.
27.4.37
Other Fusarium:Fusarium poae, Fusarium lateratium
, Alternaria and Cladosporium fagi can produce toxins resulting in the toxic aleukie. The moulds grow on cereals specially on millet left during the winter on elds. The disease develops in two phases : First there is a burning feeling in mouth and throat,nausea,gastroenteritis,vomit and diarrhoea.After these signs there is a leucopenia within two month which may result in sepsis. Additionally there comes to trombopenia and aplasie of red marrow. The mortality is high.The toxins are not inactivated by cooking. There are three toxins known: Sporofusariogenin, epicladosporic acid and fagicladosporic acid .
27.4.38
Ochratoxin A
Ochratoxin A [63] is a mycotoxin produced by moulds of genus Penicillium and Aspergillus. It is a water soluble cumarin derivate
It is found in cereals,coee, spices and other foods. The growth of moulds and production of ochratoxin A is speeded by high temperatures and high moisture during: Harvest, handling, drying, storage and transport. The daily intake of ochratoxin A in Europe is 0,7 to 4,6 ng/Kg/day. In Germany the daily intake of ochratoxin A is estimated 0,9 ng/Kg/day.
1964
Sources of ochratoxin A are: Cereals with 0,5 ng/Kg, coee with 0,2 ng/Kg and beer with 0,2 ng/Kg. Ochratoxin A is carcinogenic and genotoxic in mice and rats. Recommended limits of ochratoxin A are: Cereals and their derivates maximum 3 micrograms/kg Ingredients for baby foods maximum 0,3 micrograms Coee green or roasted maximum 3 micrograms/kg. Mixing of dierent charges of coee to reduce the content of ochratoxin A is not allowed.
27.5
Ochratoxin and aatoxins in spices
Ochratoxin A (OTA) is a mycotoxin produced by several fungal species of the genera Penicillium and Aspergillus. Contamination of food commodities, including cereals andcereal products, pulses, coee, beer, grape juice, dry vine fruits and wine as well as cacao products, nuts and spices, has been reported from all over the world. In addition, contamination of animal feeds with OTA may result in the presence of residues in edible oal and blood serum, whereas the OTA contamination in meat, milk and eggs is negligible. Despite efforts to reduce the amount of this mycotoxin in foods as consumed, a certain degree of contamination seems unavoidable at present. The Expert Panel of the European Food Safety Authority reported that the dietary exposures of adult European consumers to OTA ranged from 15 to 60 ng OTA per kg bodyweight per week. Tolerable Weekly Intake (TWI) of 120 ng/kg b.w. for OTA was derived by the Panel. [64] Spices and paprika are often contaminated by aatoxinx and ochratoxin. Aatoxins are the only mycotoxins with legal limits for spices in the European Union. A limit for ochratoxin A is expected to be adopted soon. Limits set up by EC No. 1881/2006 regulation are 5 g/kg for aatoxin B1 and 10 microgram/kg for total aatoxins, but no legal limit for ochratoxin A exist. [65] According to Hernandez-Hierro and colleagues using a new method to analyse aatoxins B1, B2, G1, G2 and oxratoxins based on the methoide of Rafael J. Garcia-Villanova 2004. found that aatoxins were below these legal limits. Ochratoxin A was found with a mean of 11.8 microgram/kg. A maximum level between 10 and 20 microgram/kg is generally used in commercial transactions. [66] [67]
27.5.1
Past ndings of aatoxin and ochratoxin in spices
Portugal, aatoxins in paprika with amounts from 1 - 20 microgram/kg aatoxin B1. Hungarian paprika, in 2004, with amounts up to 66.2 microgram/kg of aatoxin B1.
27.5. OCHRATOXIN AND AFLATOXINS IN SPICES
1965
Red pepper from Turkey (2005) with amounts from 1.1 to 97.5 microgram/kg aatoxins. Paprika from bazar of Turkey with amounts from 0,5 - 116,4 microgram/kg aatoxins.
27.5.2
Inactivation of ochratoxin and other mycotoxins in cereals
Heating during cooking and backing does not inactivate ochratoxin.Stored cereals can be decontaminated with an atmosphere of 2% NH3 at 20 degrees during 4 to 6 month. Regarding cost and danger which this decontamination can bear it should always tried to avoid initial contamination of food storing the cereals under proper conditions of humidity and temperature and reducing the storage time.
27.5.3
Harmful chemicals in hatcheries
Residues of drugs "to prevent diseases" are found in sh meat up to 6 months after administration of the drug. Feed with animal origin with BSE material fed to routs, salmon and eels. Fish of hatcheries being fed with prion contaminated meat is a possible source of human CJD disease. Antibiotics and hormones to speed weight gain are of general concern. Drugs to combat worms are found in samples of sh meat from hatcheries.
27.5.4
Addictive drugs
Some vegetable substances and their derivates are toxic and create addiction, such as excessive consumption of alcohol, smoking or taking drugs.
27.5.5
Alcohol classied as carcinogenic substance
A German commission of the German association of research (Deutsche Forschungsgemeinschaft (DFG) [68]classifying ingredients of working materials has recently classied alcohol as carcinogenic substance[68]. As alcohol is used as cleaning agent such as window cleaning product, disinfection agent in health care and in many other working materials the recent publication has given ground to many discussions about toxicity and addiction. As the commission was designated to classify working materials she was not allowed to extend their results to food ingredients. It is obvious that the lobby of beverage industry makes everything possible to avoid the extension of the classication of alcohol in food as carcinogenic and addictive drug. According to the commission alcohol is transformed in the body to acetaldehyde which on his turn damages the genotype. The commission of the DFG created a new classication of cancerogenic substances, including alcohol in the " class of substances whose activity is so small that below a maximum
1966
concentration on working place (Maximale Arbeitsplatzkonzentration) (MAK) there is no signicant risk of cancer expected." This classication includes however also formaldehyde, styrol, lindan and hexachlorbenzol at a concentration below MAK. The former rule that any cancerogenic substance should be avoided because even a single molecule is able to start cancer is now discarded. Toxicologists on their turn argue that alcohol is a part of the normal metabolism. They say: "Resulting cancerogenic activity of normal metabolism is unavoidable. A small increase of the normal level of alcohol due to a limited amount of external origin does not signicantly increase the cancer risk." Heavy drinking does signicantly increase the risk.
27.5.6
Acetaldehyde in alcohol beverages and other foods increases cancer risk
[69] Lachenmeier, Kanteres and Rehm, 2009 point out that acetaldehyde, occurs naturally in in alcoholic beverages and is the main cause of "hangover". It is also produced by the body while metabolising alcohol. There are limited evidences that acetaldehyde is an independent risk factor for cancer during alcohol consumption. The authors identied alcohol consumption as a direct source of acetaldehyde exposure. Together with other sources such as food avourings, tobacco and air pollution must be reduced to reduce cancer risc. The authors recommend to re-classify acetaldehyde with respect to cancer, risks assessments should consider all sources of expousure to acetaldehyde reduce the acetaldehyde content in alcoholic beverages as low as technologically possible, and to restrict its use as a food avour additive.
27.5.7
Carcinogenicity of acetaldehyde
[70] Acetaldehyde was classied as reasonably anticipated to be a human carcinogen based on the carcinogenicity in animals. There is inadequate evidence for the carcinogenicity of acetaldehyde in humans. However, three case control studies found cancers following heavy alcohol intake, demonstrating an increased risk of these cancer in individuals with genetic polymorphisms in enzymes involved in the metabolism of acetaldehyde; these polymorphisms were associated with higher blood concentration of acetaldehyde following alcohol intake. [71] [72] [73] The main source of human exposure to acetaldehyde is through the metabolism of alcohol. Other sources include food and other lesser extent, the air (IPCS 1995). Principal human exposure occurs with inhalation of ambient air from urban areas. Other sources of acetaldehyde are cheese, heated milk, cooked beef, cooked chicken, and
27.5. OCHRATOXIN AND AFLATOXINS IN SPICES rum. It is a synthetic avoring ingredient in processed foods, especially margarine.
1967
Acetaldehyde has been detected in emissions from power plants that burn fossil fuels, wood, or trash. Acetaldehyde also occurs in gasoline exhaust (1.4 to 8.8 mg/m3) and diesel exhaust (0.05 to 6.4 mg/m3) (IARC 1985).
27.5.8
Alcohol as addictive drug
Le Monde presented at the 17.of June 1998 the report of the professor of pharmacy Bernard Roques concerning the risk of addictive drugs[74]. Bernard Roques had been appointed by Kouchner (state minister for health of the Ministry for Work and Solidarity of France ) to name a commission to screen the international scientic literature related to addictive drugs. Bernhard Rouques is head of a section of of the National Institute for Health and Medical Research (Inserm). The report was made under his direction. It is based mainly on medical molecularbiological knowledge. It does not consider historical, psychological and cultural aspects of the consumption of addictive drugs. Some drugs are still not suciently known, such as ecstasy which is feared to produce heavy damage of the nervous system. Should this fear proof to be true, ecstasy must be inserted in the rst group of the very hard addictive drugs. Having some weak points, however, the Roques - Report is in his basic message correct and represents the trend towards the classication of alcohol as addictive drug.
27.5.9
Endomorphins control the pathway of drug and alcohol addiction
[75] Dzung Anh Le and colleagues 2009 found that alcohol releases endogenous opioid peptides such as endorphins, enkephalins and dynorphins in the midbrain/Ventral Tegmental Area (VTA) region. Low to moderate levels of alcohol alter beta-endorphin release in the VTA region, producing the pleasant eects that likely reinforce alcohol consumption. The euphoric or rewarding eects of alcohol is triggered by the stimulation of the natural opioid peptides in the VTA pathway, which consequently activates dopamin involved in drug and alcohol addiction. Alcohol does not release other families of endogenous opioid peptides such as enkephalins and dynorphins. Like morphine, endogenous opioid peptides can induce analgesia and a mild euphoric effect, reduce anxiety, and may lead to a general feeling of well being.
1968
Naltrexone [76] is currently used as treatment of alcoholism blocking opioids not specically [77]. The authors, however, suggest to target specically the endorphins in the VTA beta-endorphin pathway in treatment of alcohol abuse and craving. Le and colleagues stress that low to moderate but not high doses of alcohol increase the release of beta-endorphin in the VTA region mediating some of the rewarding eects of alcohol. High doses of alcohol, however, induce sedative and hypnotic eects, and often increase rather than decrease anxiety and depression. The authors, therefore, recommend to stop drinking should the pleasant eects of alcohol not be experienced, otherwise negative eects may appear.
27.5.10
Health risks of dierent addictive drugs, according Rouques - Report

Cocain weak strong,changing strong strong very strong yes
Table 27.2: First category of dangerous substances according the Rouques - Report Harm Heroin(opiate) Alcohol Physical addiction very strong very strong Psychic addiction very strong very strong Neurotoxic weak strong General toxicity strong strong Social danger very strong strong Treatment chances yes yes
Table 27.3: Second category of dangerous substances according the Rouques - Report Harm Ecstasy psychostimulants Physical addiction very weak weak Psychic addiction no informations middle Neurotoxic very strong strong General toxicity very strong strong Social danger weak weak Treatment chances no no ***Cancer benzodiazepine middle strong 0 very weak weak no research tobacco weak very strong 0 very strong*** 0 yes
Table 27.4: Third category of dangerous substances according the Rouques - Report Harm Cannabinoides Physical addiction weak Psychic addiction weak Neurotoxic 0 General toxicity very weak
27.5. OCHRATOXIN AND AFLATOXINS IN SPICES Social danger weak Treatment chances no research
1969
27.5.11
The use and abuse of alcohol in pharmacy
Alcohol is used in many medicaments mainly as solvent and preservative of herb extracts, tinctures, antitussives, tonics, sedatives and many other traditional pharmaceutical preparations and last but not least it is used to improve the taste of certain medicaments. The above mentioned publications are a great challenge to pharmacy to reduce the use or ban alcohol in their preparations because of following reasons: 1. Alcohol, even in small doses is carcinogenic Alcohol was classied as carcinogenic substance by a German commission of scientists of DFG classifying ingredients of working materials. 2. Alcohol is an addictive drug of rst category The Rouque - Report has classied the dangerousness of alcohol as strong. 3. Alcohol should not be taken together with certain medicaments. Alcohol is listed in the incompatibility list of medicaments such as antibiotics, neuroleptics and many other. Patients under antibiotics have to avoid tonics or other additional medicaments because of their content of alcohol.
27.5.12
Light and moderate alcohol consumption reduces cardiovascular mortality
[78] Light and moderate alcohol consumption was found by Mukamal and colleagues 2010 to reduce cardiovascular mortality, compared with complete abstention. Data of heavy drinking was inconclusive. The authors stress, however, that there are uncertainties related to coronary heart disease (CHD) and stroke; inclusion of former or occasional drinkers with long-term abstainers as a referent category; generalizability to the adult US population; and the importance of drinking patterns such as regular light drinking or occasional binge drinking. They also remind that drinking above recommended limits, 3 or more compared with 2 drinks/drinking day, causes a higher risk. Klatsky 2010 reminds, however, that the risk of breast cancer in women is increased with even moderate drinking and that youthful drinking can often be hazardous [79].
27.5.13
Heavy alcohol consumption
[80] Klatsky in 2009 reminds that there are substantial medical risks of heavy alcohol drinking
1970
and a less harmful or safe drinking limit may be valid. Heavy drinking is dened as 3 or more standard drinks per day. Alcohol-mortality risk is highest for heavy drinkers, lowest for light drinkers and intermediate for abstainers. A number of non-cardiovascular and cardiovascular problems contribute to the increased mortality risk of heavier drinkers. Wine is more protective against CHD than liquor or beer, probably due to non-alcohol benecial components in red wine, a healthier pattern of drinking or more favourable risk traits in wine drinkers.
27.6
Pesticides
The term "pesticides" covers insecticides, acaricides, herbicides, fungicides, plant growth regulators, rodenticides, biocides and veterinary medicines. Pesticides are chemical compounds used to: Kill, repel or control pests to protect crops before and after harvest. Inuence the life processes of plants. Destroy weeds or prevent their growth. Preserve plant products. [81] Pesticides are regulated in the European Community by the Regulation (EC) No 1107/2009. [82] The EU Pesticides database provides extensive informations on plant and animals and the allowed pesticides. [83]
27.6.1
Dioxin in milk
[84] The great demand of orange juice has cause intensive farming of orange trees in Brazil. Derivates of this farming are orange oil and the peel which is dried as pellets used as cattle fodder in Germany. These Brazilian orange peel pelletsmainly exported by "Coimbra Frutesp" company together with calcium of combustion exhaust washer was responsible to an increase of dioxin levels in milk, butter, cream and meat in Germany. The average level of dioxin in milk was 0,5 Picogramm in one gram fat. In August 1998 this level was three times as high as four month ago. In Sd Baden (Germany) milk with 4,83 Picogramm had to be destroyed as special garbage. The orange peel pellets from Brazil used as fodder had 147 picogram dioxin per gram. According to Abecitrus this contamination comes from the use of perchloretylene containing mineral oil used to dry the pellets. Chalk used to wash combustion gases from smokestacks had also been added to the bovine fodder. The real origin of the dioxin in the citrus pellets therefore could not be found.
27.6. PESTICIDES
1971
27.6.2
Dioxin in feed
In the beginning of 2006 pig, poultry and rabbit farms in Europe were supplied with dioxin contaminated feed. The Netherlands and Belgium announced that some of the meat from contaminated farms was sold in shops over the last two months, but no serious risk to public health was expected. Tessenderlo, a feed ingredients company was the source of the contamination, blaming an inadequate PCB test which was not suited for testing dioxins as the cause had of the error. The rst alert came from pig fat originating from Belgium with 25 times the maximum permitted concentration in pork fat. Two defective lters at Tessenderlo Chemicals caused an error in the treatment of hydrochloric acid which was then used by PB Gelatin to extract pig fat from the process of making gelatin at PB Gelatins, a unit of Tessenderlo, a Belgian chemical company. The extracted fat was later distributed to animal feed producers such as Leroy and Algoet, it said. The level of toxicity equivalent, or TEQ, in the contaminated fat was 400 picograms per one gram of fat. The maximum acceptable level is 2 picograms. Dioxin contaminated feed was then distributed to pork farms in Belgium, Germany and The Netherlands.The dioxin was no longer present in subsequent batches of extracted fat at PB Gelatins [85] Recent meat pollution: 1999 dioxins in pigs and chicken 2002 illegal hormone given to pigs in the Netherlands. 2004 dioxin in pork due to dioxin contaminated Dutch potato feed.
27.6.3
Maximum levels of sum of dioxins and dioxin-like PCBs
The European Commission has adopted in 03.02.2006 new implementing legislation setting maximum levels for the sum of dioxins and dioxin-like Polychlorinated Biphenyls (PCBs) in food and feed. Maximum levels for dioxins in food of animal origin and all animal feed have been applicable since July 2002. However, due to lack of sucient data and scientic information at the time, no levels were set for dioxin-like PCBs. Since 2002, new data on dioxin-like PCBs has become available, and the legislation adopted today lays down mandatory limits for the combined level of dioxins and dioxin-like PCBs.
1972
From November 2006, any food or feed in which the sum of dioxins and dioxin-like PCBs exceeds these maximum levels will not be allowed to be marketed in the EU. [86]
27.6.4
EU report says that 8 per cent of foods transgress dioxin specications
[87] The European Food Safety Authority (EFSA) published data concerning dioxins and similar compounds, such as dioxin-like polychlorinated biphenyls (PCBs) in samples collected between 1999 and 2008. Overall, 8 per cent of the samples exceeded the dierent maximum levels set out in EU legislation. The highest levels of dioxins and dioxin-like PCBs, related to fat, were found in liver and liver products from animals. The highest levels in relation to total product weight were for sh liver and products derived from sh liver. In animal feed, the highest average levels were found in sh oil. The EFSA explains that dioxins are formed by res, such as waste incineration, forest res and industrial processes. Dioxins are found at low levels in many foods, and longterm exposure to high levels of dioxins may cause a range of eects, including cancer. They are very persistent and accumulate in the food chain, notably in animal fat. The report concludes that no clear trend can be established as there were increases in some categories but decreases in others and some uncertainties could not be ruled out. Toxicity values for dierent types of dioxins recommended by the World Health Organisation (WHO) in 1998 were used in this report. However, current method for measuring overall dioxin levels, based on WHO recommendations from 2005, downgraded the relative toxicity of certain types of dioxins. The new values would reduce overall dioxin levels by 14 per cent [88]. More specications are found at the ocial Codex Standard CAC/RCP 62 of 2006 [89]. The EFSA report 2010 recommends continuous random testing of a sucient number of samples in each food and feed group to ensure accurate assessments of the presence of dioxins and dioxin-like PCBs.
27.6.5
Guar gum thickening agent contaminated with high levels of dioxin
[90] In 2007 after high levels of the dioxin pentachlorophenol (PCP) were discovered in Indian guar gum shipments. India is leading guar gum producer, counting for 80 to 90% of the world production.
27.7. ORGANOCHLORINE COMPOUNDS
1973
The latest inspection mission of the EU in 2009 discovered serious serious deciencies of the Indian control measures to prevent contamination of guar gum with pentachlorophenol (PCP) and dioxins. With availability of sodium pentachlorophenolate and its use in the guar gum industry, and with a largely self regulated industry, there are inadequate controls in place to ensure that this contamination does not occur again. [91] To avoid further risks of dioxins in Indian guar gum the European Commission introduce a compulsory inspection system of 5% of imports. Food industry says that these inspections will increase price pressure on European food producers. Under EU Regulation (EU) 258/2010, which came into force on April 15 2010 and updates earlier restrictions, consignments of Indian guar gum, or compounds containing at least 10 per cent of the substance, must have an appropriately authorised health certicate certifying they do not contain more than 0.01 mg/kg pentachlorophenol (PCP). [90] India published in July 2010 updated restrictions in its regulations, demanding that guar gum exports to European Union, intended for animal or human must bear a Health Certicate by authorized representative of Ministry of Commerce & Industry, Government of India.
27.7
27.7.1
Organochlorine compounds
Pentachlorophenol (PCP)
[92] Pentachlorophenol (PCP) is an organochlorine compound. In the past, PCP has been used as a herbicide, insecticide, fungicide, algaecide, disinfectant and as an ingredient in antifouling paint. Some applications were in agricultural seeds (for nonfood uses), leather, masonry, wood preservation, cooling tower water, rope and paper mill system. Its use has been signicantly declined due to the high toxicity of PCP and its slow biodegradation.
27.7.2
Chlorothalonil harms the environment
The fungicide chlorothalonil (Daconil and Bravo) is used on peanuts, tomatoes, potatoes, lawns, turf, and roses. It is the second most widely used agricultural fungicide in the U.S. It is classied as a probable human carcinogen by EPA. It has been found in groundwater in the air approximately a mile from chlorothalonil-treated elds, and in Bering Sea fog and seawater samples. Chlorothalonil is very highly toxic to sh, shrimp, frogs, benecial microorganisms, and earthworms. In plants it causes a variety of eects, including reductions in yield. [93]
1974 Chlorothalonil should be re-evaluated
McMahon et al. 2012 report that the fungicide chlorothalonil increases the mortality of amphibians, gastropods, zooplankton, algae and a macrophyte, reduces decomposition, water clarity, dissolved oxygen and net primary productivity. All this promotes algal blooms. The authors stress the need to re-evaluate the safety of chlorothalonil and its risks to the ecosystem. [94] Picture: http://en.wikipedia.org/wiki/Chlorothalonil
During the production chlorothalonil is contaminated with the carcinogen hexachlorobenzene. Chlorothalonil reduces fungal intracellular glutathione molecules to alternate forms which cannot participate in essential enzymatic reactions. Chlorothalonil-containing products are sold under the names Bravo, Echo, and Daconil. Mozzachio et al 2008 have not found any strong evidence for an association between chlorothalonil and human cancers. However, animal studies suggest chlorothalonil to be associated with renal cancer. The authors used data from the Agricultural Health Study, a prospective cohort of licensed pesticide applicators in Iowa and North Carolina. [95]
27.8. IN UTERO EXPOSURE TO PESTICIDES
1975
27.8
27.8.1
In utero exposure to pesticides

Organic foods reduce organophosphorous pesticides exposure
Lu et al 2006 reported that organic diet provides a dramatic and immediate protective eect against exposures to organophosphorus pesticides through their diet. [96] The conclusions of Lu and colleagues are heavily countered by Robert et al. 2006 alleging that specic health risks have never been associated with such miniscule insecticide exposures found in the study of Lu. Neurotoxicity has not been observed in the population who consumes food that sometimes contains OP pesticides or OP metabolite residues exposures are well below the experimental lowest observed adverse eect level (LOAEL), the no observed adverse eect level (NOAEL), and the regulatory reference dose (RfD) for neurotoxicity of any OP insecticide used in crop protection are also well below established limits. Robert and colleagues concluded that the research of Lu et al. is misrepresented with respect to its relevance to risk reduction. [97] Reduction in organophosphorus insecticide exposures [98] Dialkylphosphate (DAP) is a urinary metabolite of organophosphorous insecticides. Clune et al. 2012 report that human exposure to these insecticides, measured as urinary DAP, decreased by more than half 20032004. Reductions of about 50%-90%. The authors, however, are not certain that the reduction was caused by US EPA actions in response to the The Food Quality Protection Act of 1996. Infants may be especially vulnerable to pesticides-exposure [99] In utero exposure to organophosphate pesticides may be linked to adverse birth outcomes and neurodevelopment. Huen et al. 2012 measured organophosphate pesticide metabolites in mothers and in cord plasma of a population living in an agricultural area. Chlorpyrifos levels in maternal and in cord plasma ranged from 0-1,726 ng/mL, diazinon levels were 00.5 ng/mL, which is slightly higher than found in other populations. Increased detoxifying PON1 levels were associated with decreased odds of chlorpyrifos and diazinon detection. Notably newborns had lower levels of PON1 than found in the plasma of their mothers. The authors conclude that infants may be especially vulnerable to organophosphate pesticide exposures. In boys, prenatal exposure to chlorpyrifos was associated with lower scores on short-term memory tests compared with girls exposed to similar amounts. The brain of boys seems to be more vulnerable to some chemical exposures, however, boys benet more from a nurturing environment than females. [100]
1976
The Study of the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS study) assessed the paraoxonase 1 (PON1) genotypes and enzymes which detoxie oxon derivatives of some organophosphate (OP) pesticides. The Center also found that maternal urinary concentrations of dialkyl phosphate (DAP) metabolites a marker of OP pesticide exposure, were related to poorer mental development and pervasive developmental disorder (PDD) in 2-year-old children. Eskenazi et al, authors of the present study, found that children with the PON1(-108T) allele had poorer Mental Development Index scores and somewhat poorer Psychomotor Development Index scores. PON1 was, therefore, associated with child neurobehavioral development, however further studies are important. [101] Eskenazi et al.2008 report a negative mental development of neonates which had been exposed to organochlorine pesticides in utero. This association was found in prenatal but not postnatal organophosphate pesticide exposure. [102] Breast milk of urban and agricultural regions present considerable levels of pesticides Weldon et al 2011 measure non-persistent and persistent pesticides and polychlorinated biphenyl (PCBs) in human milk samples from women residing in the agricultural region between 2002-2007 in California. Urban samples presented lower levels compared milk of agricultural women. Pesticides present in human milk were chlorpyrifos, cis-permethrin, trans-permethrin, hexachlorobenzene, -hexachlorocyclohexane, DDT, DDE, dacthal, and PCBs. The authors stress that neonates and young children may be exposed to persistent and non-persistent pesticides and PCBs via breast milk. [103] Neonate exposure to pesticides in mother milk in the Turkish city of Mersin PCB 153 showed the highest concentration, followed by PCB 138 and 180. For the dioxinlike PCBs, PCB 118 was the dominant. Naphthalene, phenanthrene, pyrene and uoranthene were the major PAHs among the 16 PAHs detected. The estimated daily intakes of DDTs, PCBs, HCHs and HCB did not exceeded the tolerable daily intake (TDI) proposed by the Health Canada Guideline. However, these data indicate that the neonates of Mersin city are exposed to these persistent organic pollutants. The exposure of neonates in other regions is even higher as those found in Mersin city considering organochlorine pesticides and polychlorinated biphenyls (PCBs) levels in breast milk, write Cok et al 2012, authors of the study. [104] Pesticides in maternal milk of Hong Kong residents exceeds Canadian Guidelines Studying the burdens of persistent organic pollutants in residents of Hong Kong, Tsang et al. 2011 found that the estimated daily intakes of DDTs by infants indicated that 7 out of
1977
29 of the human milk samples exceeded 20 ng g-1 day-1, the tolerable daily intake (TDI) proposed by the Health Canada Guideline in terms of DDTs levels. [105]
27.8.2
Consumer should avoid products with thickening agent guar gum E412
The call for low prices on detriment of food safety cannot be justied. The consumer can da his own safety inspection reading the ingredient list and ban those products bearing guar gum.
27.8.3
A call for cost reductions disastrous for pork meat in Ireland
[106] In December 2008 pig farms were blocked as meat of their livestock were found contaminated with polychlorinated biphenyls (PCBs) at levels up to 200 pg WHO-TEQ / g fat in pig meat originating in Ireland. The use of feed containing contaminated bread crumbs produced from bakery waste was identied to be the source. The contamination was due to a cost ecient direct heating process whereby chimney stack combustion gases came in direct contact with the material to dry and whereby an inappropriate fuel was used. The toxic responses to dioxins include dermal toxicity, immunotoxicity, carcinogenicity, reproductive and developmental toxicity. The toxicity of dioxins is related to the amount accumulated in the body during a lifetime, the so-called body burden. A tolerable weekly intake (TWI) of 14 pg WHO-TEQ/kg body weight (b.w.) has been established by the Scientic Committee on Food (SCF) in 2001. The term "dioxins" refers to a group of chemically and structurally related halogenated aromatic hydrocarbons, including 75 polychlorinated dibenzo-p-dioxin (PCDD) and 135 polychlorinated dibenzofuran (PCDF) congeners. Dioxins are widely distributed contaminants formed as unwanted by-products in a number of anthropogenic activities, involving incomplete combustion processes, both industrial and natural. They also occur as contaminants during various industrial processes, e.g. the chemical manufacture of some chlorinated compounds and chlorine bleaching of paper pulp.
27.8.4
Mineral oil hydrocarbons (MOH) [107]
According to the European Food Safety Authority (EFSA) human exposure through the diet to a diverse group of mixtures known as "mineral oil hydrocarbons" (MOH) are food contaminants with health impact.
1978
These highly complex mixtures of unknown chemical composition are derived mainly from crude oil but are also produced synthetically from coal, natural gas and biomass. Their composition varies from batch to batch. Specications are often expressed in terms of viscosity, or "thickness", as related to the applications of the products and not in terms of chemical composition, the EFSA .distinguishes between "Aromatic" MOH and "Saturated" MOH. They have a wide variety of industrial and domestic uses. Sources of MOH in food:are mainly food packaging materials, food additives, processing aids and environmental contaminants such as lubricants.
27.8.5
"Aromatic" MOH
The "aromatic" MOH may act as genotoxic and carcinogens. No ADIs could be set because of lack of sucient data on exposure and toxicology. Exposure to this type of MOH is of potential concern and limits should be set.
27.8.6
"Saturated" MOH
Some "saturated" MOH, as food contaminants, can accumulate in human tissue and may cause adverse eects in the liver. However, new information on the lack of toxicological relevance for humans of previous animal studies, makes a revision necessary of the Acceptable Daily Intakes (ADIs) of some "saturated" MOH present in specic food products. Low levels of saturated MOH are present in all the food groups included with some high levels found in "Bread and rolls" and "Grains for human consumption" due to their use, respectively, as release/non-sticking agents and spraying agents (used to make grains shiny). The presence of both saturated and aromatic MOH in dry foods including "pudding" dessert mixes and noodles may be partially attributed to the use of recycled paper/cardboard packaging. Exposure to saturated MOH through the diet was higher among younger consumers than for adults and the elderly. There may be a potential concern for some customers who are brand loyal or who often buy the same food product from the same shop may be exposed on a regular basis to food with higher levels of MOH. Mineral oil saturated hydrocarbons (MOSH) consist of linear and branched alkanes, and alkyl-substituted cyclo-alkanes, whilst mineral oil aromatic hydrocarbons (MOAH) include mainly alkyl-substituted polyaromatic hydrocarbons. Technical grade MOH contain 15 35 % MOAH, which is minimised in food grade MOSH (white oils). Estimated MOSH exposure ranged from 0.03 to 0.3 mg/kg b.w. per day, with higher exposure in children. Specic production practices of bread and grains may provide additional MOSH exposure. Except for white oils, exposure to MOAH is about 20 % of that of MOSH. Absorption of alkanes with carbon number above C35 is negligible. Branched and cyclic alkanes are less eciently oxidised than n-alkanes. MOSH from C16
1979
to C35 may accumulate and cause microgranulomas in several tissues including lymph nodes, spleen and liver. Hepatic microgranulomas associated with inammation in Fischer 344 rats were considered the critical eect. The no-observed-adverse-eect level for induction of liver microgranulomas by the most potent MOSH, 19 mg/kg b.w. per day, was used as a Reference Point for calculating margins of exposure (MOEs) for background MOSH exposure. MOEs ranged from 59 to 680. Hence, background exposure to MOSH via food in Europe was considered of potential concern. Foodborne MOAH with three or more, non- or simple-alkylated, aromatic rings may be mutagenic and carcinogenic, and therefore of potential concern. Revision of the existing acceptable daily intake for some food grade MOSH is warranted on the basis of new toxicological information. [108]
27.8.7
Food poisoning
Food may contain toxins originated by a biological activity such as mycotoxins, pollutants resulting from pollution of the environment such as dioxins and poisons resulting from human activities such as antibiotics, hormones, antihelmintica and other pesticides (lindane, carbendazim and chlopyrifos) resulting from animal breeding, mercury in sh from industrial sewage,PAC (polycyclic aromatic carbon) resulting from smoke used in food,dioxin (Polychlorated dibenzodioxin PCDD) , dibenzofuran (PCDF), Heavy metals such as arsenic, lead, cadmium, Japan had two great food poisoning: 1954 - contaminated sh with cadmium causing the "Itai-Itai disease. 1968 - contaminated sh with mercury in Minamata, resulting from industrial sewage. Mercury is found in mediteranean sh, such as tuna in concentrations up to 1 mg/Kg. Fish is the most important poison source for mercury.
27.8.8
Mercury in food
[109] The EFSA reported in 2004 that methylmercury toxicity has been demonstrated at low exposure levels, and therefore exposure to this compound should be minimised. However, it also noted that sh constitutes an important part of a balanced diet. EFSA has also provided advice on the safety and nutritional contribution of wild and farmed sh in 2005. The CONTAM Panel assessed the health risks related to human consumption of wild and farmed sh, including an overall risk assessment related to the consumption of Baltic herring. EFSAs advice concentrated on the most relevant metals and persistent organic contaminants, namely methylmercury, dioxins and dioxin-like PCBs. It also reviewed the nutritional value and benets from consuming sh. Mercury is an environmental contaminant that is present in sh and seafood products largely as methylmercury. Food sources other than sh and seafood products may contain mercury, but mostly in the form of inorganic mercury. Based on the available data the contribution to methylmercury exposure from these foods is considered to be insignicant.
1980
Inorganic mercury in food is considerably less toxic than methylmercury. Methylmercury is highly toxic particularly to the nervous system, and the developing brain is thought to be the most sensitive target organ for methylmercury toxicity. The JECFA established a Provisional Tolerable Weekly Intake (PTWI) of 1.6 microg/kg body weight based on two epidemiological studies that investigated the relationship between maternal exposure to mercury and impaired neurodevelopment in their children. A previous evaluation by the (U.S.) National Research Council (NRC) established an intake limit of 0.7 microg/kg body weight per week. Given that the average intake estimates of methylmercury for European consumers are below but at times rather close to the PTWI established by the JECFA (1.6 microg/kg body weight) and some intake estimates exceed the limit established by the US-NRC (0.7 microg/kg body weight per week). Taking into account the important nutritional contribution that sh makes to the diet, EFSA recommends that women of childbearing age (in particular, those intending to become pregnant), pregnant and breastfeeding women as well as young children select sh from a wide range of species, without giving undue preference to large predatory sh such as swordsh and tuna. Due to their place in the food chain, these sh are likely to contain higher levels of methylmercury than other sh species.
27.8.9
Mercury and selenium contamination of sh caused by coal-red power plants
[110] Sackett and colleagues 2010 report that sh in lakes located at least 30 kilometres from a coal-red power plant had mercury levels more than three times higher than sh in lakes that are within 10 km of a plant. An inverse picture was found for selenium. The species used for this study were predators at the top of the food chain and are also consumed by humans. Coal-red power plants are the leading source of mercury and selenium air emissions. A signicant amount of both contaminants settles out of the air within 10 km of a smokestack of a power plant. In this study sh within 10 km of a coal-red power plant showed selenium levels three times higher than samples taken from sh located further away. Selenium is known to have an antagonistic relationship to mercury. Despite the reduction of mercury uptake caused by selenium, high concentrations of this contamination presents a serious hazard to the environment, say the authors. Filters of coal-red stacks should be improved to reduce the emission of mercury and other important global contaminants.
27.9. CHANGING ECOLOGY AND TOXIC FOODS
1981
27.9
27.9.1
Changing ecology and toxic foods

The Minamata disease in Japan
The disease was rst known in Japan where 1,500 citizens of the small village Kumamoto on the shore of the Minamata bay contracted symptoms in the 1950s after an industrial release of mercury in the waters of the Minamata Bay. The Japanese victims had eaten the mercury contaminated sh.
27.9.2
The disease in Tapajs region
Minamata disease has been found in the shing communities of the Tapajs River in Brazils Amazon basin. It causes serious damage to the nervous system, resulting in uncontrollable shaking and muscle wasting. It also produces deformities in the children of osprings.
27.10
Origin of mercury in the Amazon region
A research team analysing the problem includes specialists in cytogenetics, ethnobotany, biogeochemistry, sociology, the environment, and forestry from the Amazonian Federal University of Par(UFPa) in Belm, the UFPa outreach campus in Santarm, the Federal University of Rio de Janeiro, UQAM, and the Grupo do Defencia do Amazona in Santarm. Their work is supported by the International Development Research Centre (IDRC).
27.10.1
Gold mining
Gold-mining activity was blamed to be responsible for the presence of mercury in the Tapajs. Independent miners mixe elemental mercury with river sediments and soil in order to extract the gold. It has been calculated that only 68 tonnes mercury/year due to poorly conducted amalgamation practice by volatilisation during amalgam distillation are liberated in the environment and is left there in the metal form. This is a small amount compared with the size of the problem. The Minamata cases involve soluble methyl mercury, and the suerers live hundreds of kilometers from the nearest mine.
1982
27.10.2 27.10.3
The ecology Slash and burn
In addition, "slash and burn" agricultural practices, leading to large-scale deforestation and erosion of soil heavily laden with natural mercury, are a major source of mercury pollution. The mercury content in wood is about 0.1 to 0.5 ppm. Slash an burn liberates this mercury. Heavy agricultural activities such as cattle pastures, soybean, maize and cotton plantations will promote further erosion of soil which will increase mercury in the rivers of the Amazon region. Fish from reservoirs in Northern Manitoba showed high Hg levels. Forest res may be expected to mobilise Hg contained in biomass and redistribute it into the atmosphere either as vapor or attached to particulates.
27.10.4
Wild forest res and wood combustion
Wild forest res are estimated to release 20 tonnes of Hg to the atmosphere, which is less than 1% of natural emissions. Intentional wood combustion represents 60 to 300 tonnes of Hg about 5% of all man-made emission.
27.10.5
Deforestation
The deforestation by res in the Amazon liberate about 75 tonnes of mercury in the atmosphere every year. The land is generally used for pasture and reburned in a cycle between 2 to 7 years. Cerrado vegetation, which is mainly grass and bush, covers wide area of Brazil takes up mercury from soil and deposition by rain. Only 10% of the biomass burnt is from the deforestation and 90% is from cerrado burning.
27.10.6
Emission from vegetation
The formation of methylmercury called methylation, in the Amazon region diers from temperate regions due to specic sediments, oating macrophyte mats and ooded soils, together with the unique aquatic and semi-aquatic systems of the Amazon and the high mercury content of organic soils. This favorises the methylation of mercury in the region. Mercury is present as an environmental contaminant in foods, notably in sh and seafood in the form of methylmercury. Vulnerably groups in particular select sh from a wide rage of species without consuming too much large predatory sh that tend to contain higher levels of methylmercury, such as swordsh and tuna.
27.10. ORIGIN OF MERCURY IN THE AMAZON REGION
1983
The provisional tolerable weekly intake (PTWI) of methylmercury established by FAO/WHO and Food Additives (JECFA) is 1.6 microg/kg body weight. The US National Researche Council has set a maximum of 0.7 g/kg body weight per week.
27.10.7
Fish as local food
Predator sh contain the highest mercury levels because it has an upper place in the food chain. Eating herbivorous sh and choosing low mercury species the intake of this metal can decrease. The local population, however, eat what they can get and this is most often the predator sh.
27.10.8
Flooded soil
Bacteria living in oxygen-starved conditions in river sediments are believed to convert inorganic mercury into the dangerous methylated form. Flooded soils and semi aquatic sediments had higher Hg-methylation potentials than river sediments. The high net Hgmethylation potentials found in newly ooded soils are interesting, because vast areas of the Amazon are ooded in annual cycles. As we know how dreadful the poisoning with mercury in the bay of Minamata (Japan) was all eorts should be made to avoid a total poisoning of the Amazon region. Gold mining using elementary mercury, deforestation and agriculture causing leaching of mercury should be prohibited.
27.10.9
Formation of Methylmercury in the North Paci Ocean
[111] Sunderland and colleagues 2009 report that mercury levels of samples of water from the Pacic Ocean in 2006 were approximately 30 percent higher than those measured in the mid-1990s. The authors found that algae from the surface fall to deeper water when they dye. There they settle, forming the particulate organic carbon which is decomposed by bacteria. Together with mercury II brought down from the surface methylmercury is produced. Tuna from the Pacic ocean is a predator which accumulates methylmercury, accounting for 40% of the mercury ingested by humans. Marine sh and shell sh account for 75 percent of human exposure to mercury. Pregnant women who consume mercury can harm their children. Mercury gets into the atmosphere by emissions from land-based combustion facilities. InCopyright 1998-2010 Karl H. Wilm. All rights reserved. OurFood Database of Food and Related Sciences
1984
creasing mercury content of the water of the ocean results from fallout near the Asian coasts and is transported on long range by strong circulating currents.
27.10.10
Researchers warn from eating large quantities of certain shes because of mercury
[112] Valera and colleagues 2009 report mercury levels to be more than 50 nmol/L in Nunavik Inuit men and women of northern Quebec, whereas levels in the general US population in the National Health and Nutrition Examination Survey (NHANES) study were found to be 4 nmol/L. The high sh and marine mammals in the traditional Inuit diet is the source of methylmercury in this population. According to the authors every 1% increase in blood mercury levels was associated with a 0.02-mm-Hg increase in systolic BPX. An association with diastolic BP was also documented but was not signicant. The authors tress the eect of omega-3s and selenium and the eects of mercury in blood pressure which should always be considered together. The American Heart Association (AHA) warns from eating large quantities of species containing a high mercury content and low omega-3s such as big predator sh tuna, swordsh, marlin, sharks, may not benecial to health. However, the AHA, still recommends people eat oily sh two times per week to achieve the health benets of omega-3 fatty acids, including canned light tuna, which is signicantly lower in mercury than white tuna. Children and nursing mothers should avoid high mercury sh (shark, swordsh, king mackerel, or tilesh). The US Food and Drug Administration ( FDA) stresses that the benets of sh consumption outweigh the mercury risks in middle-aged and older men, plus postmenopausal women. [113]
27.10.11
Methylmercury from sh does not increase heart disease
[114] Methylmercury exposure from sh ingestion has been linked to increase cardiovascular disease risk. The eects, if any, of methylmercury exposure on CVD risk may be partially oset by benecial eects of sh consumption and by selenium intake. Fish intake has been inversely associated with the risk for CHD, especially fatal CHD, and ischemic stroke. Mozaarian et al.2011 present a study which included a total of 173.229 persons for whom toenail clippings had been analysed and 3427 incident cases of CVD were reported. as CHD and ischemic stroke. In the case patients, median toenail mercury concentrations were 0.23 microg/g vs 0.25 microg/g in the control participants. The risk for CVD was not higher in participants with higher mercury exposures. The authors suggest that higher mercury levels were related to higher eating of sh and resulting increase of benecial seOurFood Database of Food and Related Sciences Copyright 1998-2010 Karl H. Wilm. All rights reserved.
27.11. CHEMICAL CONTAMINANTS lenium counterbalancing the eect of mercury.
1985
The authors concluded that mercury exposure from sh consume does not cause coronary heart disease, stroke, or total cardiovascular disease in U.S. Adults.
27.10.12
PCB in sh from the North Sea
According to the Belgian Ministry of Health in June 2000 the amount of PCB ( polychlorinated biphenyl) in sh from the North Sea is in some cases as high as 500 Nanogram in one gram fat.In 30% the upper limit for meat of 200 Nanogram PCB in 1 g fat is surpassed. The Belgian Health Ministry urges the European Commission to establish an upper limit for PCB in sh.The limit used for meat does not apply for sh because of the low fat content of sh compared to meat. The upper limit for PCB in sh is therefore expected to be set much higher as 200 Nanogramm /g fat.
27.10.13 27.10.14
Poison of heated foods HAA, Heterocyclic Aromatic Amines
They are cause by heating protein rich foods.They are carcinogenic. PAK Polycyclic Aromatic Carbon and PAH Polycyclic Aromatic HydrogenThy are formed when fat drips from grill foods and are brought back with smoke and ames contaminating the foods which are done.They are carcinogenic. To avoid heterocyclic and polycyclic aromatic toxic compounds one should take care not to overheat foods, discard burned parts and refuse smoked food.such as smoked ham.
27.10.15
Hydrocyanic acid
Hydrocyanic acid HCN is a strong poison which is present in certain foods, cigarette smoke and exhaust gases from cars. Hydrocyanic acid in food is present as hydrocyanic glycoside, nitrilosid or cyanoside. These compound can liberate hydrocyanic acid. Acute intoxication can be cause by intake of great amount of bitter almonds and some kernels of apricots, cherry, peaches, poppy seed, lima beans and millet. A chronic intoxication can be caused by manioc.
27.10.16
Denitions
27.11
Chemical contaminants
: "Contaminant" means any substance not intentionally added to food which is present in food as a result of the production (including operations carried out in crop husbandry and
1986
veterinary medicine), manufacture, processing, preparation,treatment, packaging, transport or holding of such food, or as a result of environmental contamination. Extraneous matter, such as, for example, insect fragments, animal hair etc are not covered by this denition (Codex).
27.11.1 27.11.2
Denition of residues limits in food NOAEL
No Observed Eect Level. It is determined on the most sensitive animal and gender, being the level where no adverse eect is found.
27.11.3
ARfD
Acute Reference Doses (ARfD in units mg/kg body weight) uses short-term studies for the evaluation. If the ARfD exceedes even for once only, an acute impairment of human health make take place.
27.11.4
ADI
Acceptable daily intake or ADI is a measure of the amount of a specic substance that can be ingested over a lifetime without an appreciable health risk. ADIs are expressed in milligrams per kilograms of body mass per day. The ADI is determined from toxicity studies in which chronic endpoints are examined. These are often carcinogenicity, reproduction or multigeneration studies. The no observed adverse eect level established from the relevant studies is then divided by a so-called (un)certainty factor which should take into account both inter-species dierences (i.e. between animals and humans) as well as intra-species dierences (i.e. between individuals). The factor 100 is normally used for this. There is no immediate harm if the ADI is exceeded for once, or even for a limited time, because this limit is calculated for a lifelong exposion.
27.11.5
Pesticides
Pesticides are substances which are used to prevent, destroy, repel, or mitigate any pest. This includes herbicides, insecticides, fungicides, fumigants and algaecides.
27.11.6
Other contaminants of food
Chemicals of environment Chemicals of industrial origin

27.11. CHEMICAL CONTAMINANTS Chemicals of warfare such as Agent Orange They are found in food, water and environment.
1987
27.11.7
Regulations for pesticides
: Important regulations in EU are the Directive 90/642/EC setting Maximum Residue Levels (MRLs) for pesticides on raw agricultural products. According to Directive 97/41/EC Maximum Residue Levels on processed products should be derived of the MRLs for the raw materials.
27.11.8
Important herbicides
:Herbicides are the most widely used pesticides in agriculture. Table 27.5: Important Herbicides Herbicide Atrazine: member of steriazine group Use as growth control Weed in crops of corn, soybeans and sorghum. Inhibit photosynthesis Possible harm Possible carcinogen. Harm aquatic microorganism. Slight tendency to bioaccumulate Possible carcinogen. Moderate toxic to sh. It does not bioaccumulate.
Metachlor: member of chloracetamides
Grasses and weeds in crops beans,corn, cotton, peanuts, peas, potatoes, saower, sorghum, soybeans sunowers. Perturbe protein synthesis
Alachlor member of chloracetamides
Grasses and many broadleaf Restrict use because of weeds in crops of beans, corn, groundwater contamination cotton, milo, peanuts, peas Toxic to saltwater sh and water soybeans and sunower. plants. Perturbe protein synthesis. Toxic to shes and aquatic invertebrates. Because these compounds contain chlorine, they may change to dioxin.
2,4-D Agrotect Stimulates plant growth member of the hormones (auxin), causing Chlorophenoxy uncontrolled cell proliferation acetic acid Because these compounds
1988 herbicides
CHAPTER 27. FOOD POISONING contain chlorine, they pose a risk for dioxin formation Grasses and broadleaf weeds in a variety of tree fruit, nuts vegetables and grain crops such as soybeans, alfalfa and cotton. Nitrosamine in some technical products. Harmful to sh and aquatic life. Practically non-toxic to man. The enzymatic process that is disrupted in plants is dierent enough from that of humans and animals that the later experience no eects from the chemicals. Glyphosate is probably not a carcinogen, group E. Possibility for toxicity when glyphosate is applied to aquatic environments. According to Myriam Fernandez of the Semiarid Prairie Agricultural Researche
Triuralin Member of the Dinitroaniline herbicides
Glyphosphate Member of the Organophosphate herbicides(nonnitrogen based herbicides
Inhibits synthesis of essential aminoacids and promotes destruction of photosynthetic pigments in foliage a) Isopropylamine salt, control of weeds in broadleaf and grasses.
Centre in Swift Current b) Sodium salt, growth regulator Saskatchewan, glyphosatefor peanuts and sugar cane. treated wheat appeared to have higher levels of Fusarium head c) Monoammonium salt, control blight (a toxic fungal disease) of weeds in tea plantation, that wheat elds where on orchards, rubber, plantation glyphosate had been applied. corn, sugarcane and forests. Dicamba Member of the benzoic acid and and analogue herbicides Cyanazine and simazine Members of the s-triazine Broadleaf weeds, Chickweed, mayweed and bindweed in cereals and other related crops Dicamba is not carcinogenic
Grasses and broadleaf weeds in cereals, cotton, maize, onions peanuts, peas, potatoes, soybeans, sugar cane and wheat
Cyanazine: Cancer-causing potential in experimental animals and possible risks to humans. The rat strain used was
27.11. CHEMICAL CONTAMINANTS herbicides fallow predisposed to develop the mammary tumours observed. Practically nontoxic.
1989
2,4,5-T Member of the chlorinated phenoxyalkanoic aciherbicideses acid herbicides
Stimulate plant growth May lead to teratogenic eects hormones (auxin), causing in mammals. uncontrolled cell proliferation Because these compounds contain chlorine, they pose a risk for dioxin formation Table 27.6: Important Insecticides
Insecticide groups Organophosphates
Insecticide
Breakdown
Remarks
Malathion Ethylparathion Diazinon
Easy
No residues in crops, not stored in animal tissue. These pesticides aect the nervous system by disrupting the enzyme that regulates acetylcholine, a neurotransmitter. Most organophosphates are insecticides. They were developed during the early 19th century, but their eects on insects, which are similar to their eects on humans, were discovered in 1932. Some are very poisonous (they were used in World War II as nerve agents). However, they usually are not persistentin the environment.
Organosulfurs Carbamates
Tetradifon Carbaryl Degradade They are a danger to many useful rapidly in the insects, especially honeybees. environment They aect the nervous system
1990
CHAPTER 27. FOOD POISONING by disrupting an enzyme that regulates acetylcholine, a neurotransmitter. The enzyme eects are usually reversible. There are several subgroups within the carbamates
Formamidines Dinitrophenols
Amitzaz 2,4 Dinitrophenol Cyhexatin Permethrin Pyrethroid Pesticides were developed as a synthetic version of the naturally occurring pesticide pyrethrin, which is found in chrysanthemums. They have been modied to increase their stability in the environment. Some synthetic pyrethroids are toxic to the nervous system
Organotins Pyrethroids
Nicotinoids
Imidacloprid (Gaucho) Acetaprimid Fipronil Chlorofenapyr Tebufenpyrad Pyridaben No residues in crops, not stored in animal tissue Persistence Accumulate in the fat tissue. Harms
Fiproles Pyrroles Pyrazoles Pyridazinones
Chlorinated
27.11. CHEMICAL CONTAMINANTS hydrocarbons (DDT) or organo chlorines(Such as DDT, HCC, Dieldrin, Toxophene its resistance to breakdown in the environment is enormous shes, earthworms, and robins. They were commonly used in the past, but many have been removed from the market due to their health and environmental eects and their persistence (e.g. DDT and chlordane
1991
Table 27.7: Natural Insecticides Botanicals (Plant extracts) Insecticide Extracted from
Pyrethrum
Pyrethrum
Flowers of a Chrisanthenum. Kenia and Ecuador Tobacco Legumes Citrus peel
Nicotine Rotenone Limonene
Nicotine Rotenone Limonene
Table 27.8: Fumigants Fumigants Insecticide Remarks
(They become gas above 40C and contain the halogens Cl, Br or F Ethylene dichloride Phosphine gas (PH3 )
Methylbromide
The most frequent used fumigants
Ethylene dichloride Phosphine gas (PH3 )
Insect repellents Before a more edied approach to insect olfaction and behaviour was developed, it was assumed that if a substance was repugnant to humans it would likewise be repellent to insects. Table 27.9: Insect Repellents
1992 Repellent Registration Agent
CHAPTER 27. FOOD POISONING Remarks
Benzyl benzoate Indalone Rutgers 612 Dibutyl phtalate MGK repellent 326
Registration Registration Registration Registration
lost lost lost lost Dipropyl isocinchomeronate It is used to expand the repellency of DEET, MGK 264, pyrethroids, and other active ingredients. Repellent for military clothes Dimethylcarbamate N,N-Dimethyl-metatoluamide DEET is used worldwide for biting ies and mosquitos.No harm if used as labelled.
Registration lost Potential cancer risk.New analysis of risk
N-butyl acetanilide
Registration lost
Dimelone DEET, Delphene(r)
Registration lost Still registrated
27.11.9
EU Regulation of maximum residue levels of pesticides
[115] Regulation (EC) No 396/2005 establishes the maximum residue levels MRLs of pesticides permitted in products of animal or vegetable origin intended for human or animal consumption. The Regulation is applicable since September 2008.
27.11.10
The EFSA suggestion on some Pesticide MRLs
[116] EFSA calles for lower MRLs where safety concerns were identied and also for substances where data available were not sucient to substantiate the safety of the current MRL. According to the EFSA the MRLs of active substances not authorised in the European Union should be set at the lowest level which can be measured through routine monitoring.
Table 27.10: EFSA proposes the change of the MRL of pesticides

27.11. CHEMICAL CONTAMINANTS Pesticides Existing MRL EFSA proposed (mg/Kg) MRL (mg/Kg) 0,02 ADI 0,04mg/Kg bw/d ARfD 0,05 mg/Kg bw/d to be maintained 10,0 0,20 0,10 0,10 0,20 0,20 1,00 0,10 0,10 3,00 Remarks
1993
Tetraconazole
In apricots
Clomazone Mandipropamid Lambda-cyhalothrin Indoxacrab Trioxistrob Thiram Fluroxypyr Teubenzuron Azoxystrobin Azoxystrobin Fludioxonil
0,01 0,01 0,01 0,02 0,10 0,05 0,50 0,05 -
In rice In currant Passion fruits, Kenia In bananas In leek In pepper In passion fruit Kenya In turnips Pomegranades, USA
27.11.11
MRLs of concern
[116] The EFSA found the MRLs of concern for the active substances and suggests signicant reduction of the actual MRLs: Vinclozolin, procymidone, pirimiphos-methyl, oxydemetonmethyl, methomyl and thiodicarb, methamidophos, fenarimol, carbendazim, fenamiphos, ethephon, benfuracarb and carbosulfan, methomyl and thiodicarb,
27.11.12
Reaction of food industry
[117] Food manufacturers say serious problems will arise from a tightening of pesticides regulations. According to the Food and Drink Federation (FDF) the reduced MRLs, the ban of some chemicals and the tighter management of pesticides may cause a reduction of 20 to 30 per cent in yields. A range of fruit and vegetables will be unable to grow in UK. Food and Drink Federation (FDF) says that the the legislation had no scientic or practical basis.
27.11.13
Study complains about high pesticide MRLs in fruit juices
[118] Study from Juan F. Garcia-Reyes and colleagues 2008, says that pesticide MRLs in fruit juices are hundreds of times higher as those for water and mineral water.
1994
Juices and fruit-based soft drinks produced in Spain and UK were found by the authors to have the highest levels of pesticides like carbendazim, thiabendazole, imazalil and malathion, compared with products from Russia and United States which had the lowest pesticide residues in the trial. This justies actions of the EFSA facing a reduction of pesticide levels. Fruit juices promoted as very healthy for kids need to be strongly regulated. The authors present a new methodology to analyse pesticide residues in juices and fruitbased beverages.
27.11.14
Carbendazim in orange juice [119]
Carbendazim is being found in orange juice in USA. It is believed that this fungicide is present in orage juices sold worldwide. The Coca Cola Company reported for the rst time the nding of Carbendazim in its orange juice Minute Maid and Simply Orange and in competitor products. Probably also aected is Pepsico Inc.s Tropicana brand Analyse values, however, were very low and FDA ocials said that these values are of no health risk. Carbendazim is a fungicide used to control plant diseases in cereals and fruit, including citrus, bananas, strawberries, pineapples, and pome. It is also controversially used in Queensland, Australia on macadamia plantations. It is widely used in Brazilian orange plantations. Studies have found that high doses of carbendazim cause infertility and destroy the testicles of laboratory animals. Carbendazim was included in a biocide ban proposed by the Swedish Chemicals Agency and approved by the European Parliament on January 13, 2009. Carbendazim is also not approved in USA for use on citrus.
27.11.15
The pesticide clothianidin is responsible for dying of German bees at the Rhine valley
[120] The German Federal Institute for Risk Assessment BVL has stopped the use of the insecticide PONCHO with the chemical clothianidin widely used to ght the corn borer, following analyses of dead bees which were positive for the insecticide. The use of clothianidin to treat corn seed and rape seed was stopped by the BVL on 16.05.2008. According to the German Minister of Agriculture Peter Haug chlothianine plays an important role in the death of bees. The Julius-Khn Institute, the federal research institute for cultivated plants conrmed the presence of clothianidin in all dead bees which were examined. Experts say that special seed pneumatic machines loosened the insecticide from the corn seeds during sawing. This
27.12. PESTICIDE RISK ASSESSMENT
1995
may be the way the insecticides was liberated and then spread by the local wind. The Institute says that it is unclear if honey of the region is contaminated or not with the pesticide which is extreme water soluble. [121] The trademarks of the chlothianidin containing products are: [122] Antarc 4674-00 Chinook 4672-00 Cruiser 350 FS 4914-00 Cruiser OSR 4922-00 Elado 5849-00 Faibel 4704-00 Mesurol liquid 3599-00 Poncho 5272-00
27.12
Pesticide risk assessment
The EFSA assessed the risk of several pesticides and presented its conlusions
27.12.1
Abamectin
[123] According to the EFSA,Abamectin is a mixture of avermectins, containing more than 80% avermectin B1a and less than 20% avermectin B1b. These two components, B1a and B1b have very similar biological and toxicological properties. The avermectins are insecticida or antihelmitic compounds derived from the soil bacterium Streptomyces avermitilis as a fermentation product. It is used to control insect and mite pests. [124] The acceptable daily intake (ADI) and acceptable operator exposure level (AOEL) are 0.0025 mg/kg bw/day based on the short term dog studies, whereas the acute reference dose (ARfD) is 0.005 mg/kg bw based on the acute neurotoxicity study. The EfSA concluded that a safe use with respect to aquatic invertebrates is demonstrated only for the use in lettuce in the eld (pond scenario) and the use in lettuce and tomatoes in glasshouses (ditch). For all the other uses and scenarios the risk is not acceptable without sucient risk mitigation measures (for example no-spray buerzones varying from 14 (stream scenario) - 18 m (ditch scenario) for applications in citrus and 2 m for the applications in tomatoes and lettuce. The relevant regulatory endpoint for the acute risk assessment for sh was the mean HC5 based on LC50-values (= 3.08 g a.s./L) with a safety factor of 10 = 0.31 g a.s./L. Based on this value the use in citrus needs a buerzone of minimal 10 m. For the other uses no additional buerzones are necessary. For the chronic risk assessment to sh an HC5 of 0.22 g a.s./L was agreed upon. For the use in citrus a buer zone of minimal 15 m is needed to get an acceptable o-eld risk. For the eld uses in lettuce and tomatoes this buer zone should be 5 m.
1996
27.12.2
Fluazinam
[125] The representative formulated product for the evaluation was "Fluazinam 500SC", a suspension concentrate containing 500 g/L uazinam. Fluazinam is the technical grade active ingredient of Allegro 500F. It is used for the control of late blight on potatoes and is temporary registered under Section 17 of the Pest Control Products (PCP) Regulations of Canada. In the acute studies, uazinam was harmful by inhalation, severely irritating to the eyes and skin sensitizer. The liver was the target organ in repeat dose studies with rats, mice and dogs. Some haematological changes were also observed in dogs, and the increased vacuolation of white matter in brain and spinal cord observed at high doses was demonstrated to be directly related to one impurity. The acceptable daily intake (ADI) is 0.01 mg/kg bw/day, the acute reference dose (ARfD) 0.07 mg/kg bw and the acceptable operator exposure level (AOEL) 0.004 mg/kg bw/day. Fish was the most sensitive aquatic organisms.
27.12.3
Metazachlor
[126] Metazachlor is neither a skin nor an eye irritant. It was proposed to be classied as skin sensitiser. The relevant NOAELs for subacute and subchronic exposure in rats are 110 mg/kg bw/day and 21 mg/kg bw/day. Metazachlor did not show any genotoxic potential. Liver adenomas and thyroid tumours occurred in the rat, while the mouse showed slight increases in bladder transitional cell tumours at high dose levels. Since there was no genotoxicity and clear no- eect levels for tumour development were seen in all tests, it was apparent that tumour development could be considered to involve a threshold mechanism. A classication as "Limited evidence of a carcinogenic eect" was proposed. An ADI of 0.08 mg/kg bw/day was derived for metazachlor. A possible transfer of soil residues to rotational crops has been identied, but under usual rotation practices with rape seed no measurable residue level above the analytical limit of quantication is expected in food commodities from rotational crops. There is a low exposure of livestock to residues present in feeding stu but their transfer to edible animal commodities is not expected to reach analytically measurable levels.
27.12.4
Fenpropimorph
[127] Fenpropimorph is rapidly and almost completely absorbed, largely distributed, extensively metabolised and without bioaccumulation in the body. In the acute toxicity studies, the compound was shown to be harmful if swallowed and irritating to the skin. In the short term studies, the liver was the target organ and the body weight was decreased in all species.
1997
No eects on the reproductive parameters were observed in a multigeneration study in rats, but teratogenic ndings in rats and rabbits led to the proposed classication "Possible risk of harm to the unborn child". The agreed ADI (acceptable daily intake) was 0.003 mg/kg bw/day.
27.12.5
Mepiquat
[128] In mammalian toxicity tests, mepiquat-chloride is harmful to rats after oral exposure and is proposed for classication with R22 "Harmful if swallowed" (LD50 464 mg/kg bw, equivalent to 270 mg/kg bw mepiquat). The dermal LD50 of mepiquat-chloride in rats is >2000 mg/kg bw; mepiquat-chloride is proposed for classication as "Harmful by inhalation". The ADI is 0.2 mg/kg bw/day based on the NOAEL of 19.9 mg/kg bw/day.
27.12.6
Buprofezin (NNI-750)
[129] The Acceptable Daily Intake of 0.01 mg/kg bw/day. Target organs in subchronic and chronic studies are liver and thyroid, showing increased weights and histological and clinical chemistry ndings. A potential transfer of residues to rotational crops has been noted. In soil under aerobic conditions NNI-750 exhibits medium to high persistence. NNI-750 is as very toxic to aquatic organisms. Buer zones of 20 m are required for use in citrus to identify low risk.
27.12.7
Imidacloprid (Condor, Gaucho) risk to bees
[130] Imidacloprid is almost completely absorbed by oral administration, does not bioaccumulate and is excreted mainly by the urine. Showing a high acute oral toxicity in mice but a low toxicity after dermal or inhalative exposure. The acceptable daily intake (ADI) was 0.06 mg/kg bw/day No risk for the consumer has been identied under acute or chronic exposure to residues resulting from the representative uses of imidacloprid. The representative uses are spray application in apples (northern Europe and southern Europe) and tomatoes (southern Europe) indoors and outdoors and seed treatment of sugar beet. Overall it is concluded that the spray applications of imidacloprid pose a high risk to bees. Risk mitigation is required for the use in orchards. The risk to bees is considered to be low if the product is not applied during owering and if owering weeds are removed/mown before the application. However it should be noted that bees potentially foraging in the o-crop area would still be exposed via spray drift and hence not be protected by the suggested risk mitigation measure. Flowering tomato plants are visited by honey-bees and other pollinators. The risk mitigation suggested for orchards is not an option for the use in tomato since the tomato plants ower almost continuously.
1998
The spray application of imidacloprid will cause severe impacts on non-target arthropods in the ineld and o-eld area. However in semi-eld and eld studies it was demonstrated that recolonisation of the in-eld area is possible. The available data suggest that ageing of residues of 273 days is required in order not to be hazardous to larvae of Poecilus cupreus. A high risk to soil dwelling arthropods cannot be excluded for the seed treatment use. The available semi-eld test with P. cupreus was conducted at too low concentrations of imidacloprid to allow a conclusion on the risk from the representative use in sugar-beet.
27.12.8
Tralkoxydim
[131] Based on increased incidences of Leydig cell tumours in male rats and increases in ovarian tumours in the carcinogenicity study in female hamsters a classication as "Limited evidence of a carcinogenic eect" is proposed. Based on adverse eects on gonads observed in hamster, dog and rat in subchronic and chronic studies a classication as "Possible risk of impaired fertility" is proposed. Based on postimplantation loss and malformations observed in rats and abortions and reduced litters in rabbits, a classication as "Possible risk of harm to the unborn child" is proposed. Based on these classications the tralkoxydim metabolite R173642 was considered relevant according to the EU guideline Sanco/221/2000-rev.10. The acceptable daily intake (ADI) and the acceptable operator exposure level (AOEL) have been set at 0.005 mg/kg bw/d based on the eects observed in the 90- day and the 1-year dog study applying a safety factor of 100. The acute reference dose (ARfD) of 0.01 mg/kg bw has been derived from a rat developmental study. Risk mitigation comparable to 5 m buer zones are required to protect non- target plants outside the treated eld.
27.12.9
Napropamide
[132] The acceptable daily intake (ADI) is set at 0.3 mg/kg bw/day.
27.12.10
Epoxiconazole
[133] The liver has been identied as the main target of toxicity. Epoxiconazole increased liver tumours and the classication as "Harmful; Limited evidence of a carcinogenic eect" was proposed. Based on the eects on reproduction seen in a two- generation study in rats (dystocia, impaired fertility, prolonged gestation and vaginal haemorrhages) it was concluded to propose a classication with "Harmful; Possible risk of impaired fertility". Based on developmental eects such as increases in number of resorptions, skeletal variations and malformations observed in relevant studies in rats and rabbits also a classication with "Harmful; Possible risk of harm to the unborn child" was proposed. The acceptable daily intake (ADI) is 0.008 mg/kg bw/d.
1999
27.12.11
Bromuconazole (Granit)
[134] In mammals, bromuconazole oral LD50 is 328 mg/kg bw. Classication as "harmful if swallowed" was proposed. The acute toxicity by dermal and inhalation route is low (LD50>2000 mg/kg bw and LC50>5 mg/L). Hepatocellular and cholangiocellular carcinomas in rats and hepatocellular carcinoma in mice. In both rats and mice, the tumours were likely caused by liver toxicity and subsequent cell renewal. Overall, it was agreed that bromuconazole does not have carcinogenic potential relevant to humans. Based on a dose-dependent increase of placental weight and ossication delays or supernumerary bones in a number of skeletal structures it was proposed to be classied as "May cause harm to unborn child". The ADI of 0.01 mg/kg bw/day.
27.12.12
Flutolanil
[135] During the mammalian toxicology studies, utolanil was shown to be orally absorbed up to 70% and rapidly excreted. Its acute toxicity was low, it was not irritating and did not cause skin sensitization. In short term studies, the target organ was the liver in the dierent species. The acceptable daily intake (ADI) is 0.09 mg/kg bw/day based on the 2-year rat study.
27.12.13
Benuralin
[136] Benuralin has a low acute toxicity, but showed irritating and sensitizing properties. Main target organs in short term and long term studies were the liver and kidneys. Classication as "limited evidence of a carcinogenic eect" was proposed based on neoplastic changes observed in the liver of rats and mice and thyroid tumours in rats upon long term exposure. The acceptable daily intake (ADI) is set at 0.005 mg/kg bw/day.
27.12.14
Risk assessment of Plant Protection Products on bees [137]
The Scientic Panel on Plant Protection Products and their Residues (PPR Panel) of EFSA published an opinion on the risk assessment of Plant Protection Products on bees (Apis mellifera, Bombus spp. and solitary bees) to dene safety tests demanded by the Regulation (EC) 1107/2009. The methodology dened by the opinion is of great importance in the wake of the complexity of the honeybee Colony Collapse Disorder (CCD). It is primarily important to dene what to protect, where to protect it and over what
2000
time period. Specic protection goals based on ecosystem services were suggested according to the methodology outlined in the Scientic Opinion of EFSA (2010). [138] Specic options to access ecosystem protection regarding honeybees and solitary bees are given, and existing test guidelines were evaluated and suggestions for improvement and further research needs were listed. The opinion also suggests a tool to study the cumulative eects of single pesticides using mortality data. Special attention was given to eect of repeated and simultaneous exposure and synergism. A special risk assessment schemes for honey bees, as well as a risk assessment for bumble bees and solitary bees are discussed. A method to detect cumulative toxicity is proposed based on Habers law. The opinion will be the scientic basis for the development of a Guidance Document which should provide guidance for notiers and authorities in the context of the review of Plant Protection Products and their active substances under Regulation (EC) 1107/2009.
27.12.15
Regulation on plant protection products (EC) No 1107/2009 [82]
The purpose of this Regulation is to ensure a high level of protection of both human and animal health and the environment and at the same time to safeguard the competitiveness of Community agriculture. The precautionary principle should be applied. The industry is obliged to demonstrates that substances produced or placed on the market do not have any harmful eect on human or animal health or any unacceptable eects on the environment.
27.12.16
Plant protection products and honeybees safety
The Regulation (EC)1107/2009 stipulates that an active substance, safener or synergist shall be approved only if it is established following an appropriate risk assessment on the basis of Community or internationally agreed test guidelines, that the use under the proposed conditions of use of plant protection products containing this active substance, safener or synergist: - will result in a negligible exposure of honeybees, or - has no unacceptable acute or chronic eects on colony survival and development, taking into account eects on honeybee larvae and honeybee behaviour.
27.12.17
Bananas and chemicals
United Fruit Company used pesticides like Counter and Mocap (Nematicide-Insecticide). They are being sprayed by crop planes. Honduras and Costa Rica are strongly aected by the way United Fruit handles pesticide programs and social aairs.
2001
27.12.18 27.12.19
Chemicals used in Water treatment Algaecides
Chelated Complex Copper Algaecide in 9 percent formulation for very eective control of a broad range of planktonic, lamentous and macro algae. Copper sulfate is also used as bactericide.
27.12.20 27.12.21
Other aquatic herbicides Fluridone
It is a systemic herbicide that kills the entire plant and is generally nonselective since most submersed plants will be killed or aected by a whole lake treatment. It inhibits the formation of carotene, chlorophyll without the protection of carotene is then degraded by sunlight. The contact time between the plant and Fluridone must be maintained for many weeks, otherwise the plant can regenerate. There are no swimming, shing or drinking water restrictions for the application of Fluridone. It is moderately persistent in water of ponds and lakes. Average half-life in pond water is 21 days and 90 days in sediments, being degraded by sunlight and bacteria. Residues may persist longer depending on the amount of sunlight and the water temperature. Fluridone is not considered to be a carcinogen or mutagen and is not associated with reproductive or developmental eects in test animals. Treated water should not be used for irrigation for thirty days because some terrestrial plants may be damaged, even by low concentrations of Fluridone.
27.12.22
Glyphosate for aquatic use
It is the same active ingredient of Roundup. It has been formulated for safe aquatic use. It is very eective for emerged aquatic weed control and shoreline vegetation.
27.12.23
Granular 2,4-D and liquid 2,4-D Amine
It is eective for control of many submerged, emerged and oating aquatic weeds. 2,4-D kills the entire plant, what is called to be a systemic herbicideindexHerbicide, systemic, acting as stimulant of plant stem elongation. It generally targets the broad-leaved plants (dicots) such as milfoil. Most other aquatic plants are monocots (grass-like) which are not aected by 2,4-D.
2002
27.12.24
Cutrine
It is a chelated copper which stays in solution to continue controlling a broad range of algae long after application. There are no water use restrictions after application. Cutrine is used to control planktonic and lamentous algae, Phythophora, diatoms Chara, Nitella and Hydrilla verticillata. It was used in trout raceways and irrigation canals and is the favourite algaecide for sh farms.It is also being used to reduce secondary bacterial or fungal infections by reducing the phytoplanctonic irritants exposing the gill surface of the sh.
27.12.25
Diquat dibromide
It is a quarternary ammonium herbicide for watermilfoil, Parrot Feather (Myriophyllum), Hydrilla, Water Hyacinth, Water Lettuce, Giant Salvinia and Brazilian Elodea. Diquat is often used to dessicate potato vines to make harvesting of underground tubers easier. It also promotes peridem formation in the tubers. Diquat should not be applied to potatoes if the soil is very dry, because under such conditions, the water may move from the shoots to the tubers via xylem instead of the normal opposite direction. Tubers, close to the surface become green, treated with Diquat, they may be damaged. Diquat is nonselective, any plant can be damaged when light and chlorophyl is present.
27.13
Toxicity of Roundup weed-killer and Monsanto NK 603 corn long-time study
[139] The Monsanto GM corn NK 603 is authorized by the EU Commission to be grown and fed to animals in Europe. French scientists leaded by Gilles-Eric Sralini of the University of Caen report in September 2012 that rats developed mammary tumours and multiple organ damage if fed on the Monsantos corn or exposed to its weed killer Roundup (0.1 ppb Roundup in water) at levels permitted in the USA. The researchers said 50 percent of male and 70 percent of female rats died prematurely, compared with only 30 percent and 20 percent in the control group. GM soybean, tolerant to the Roundup weed-killer dominates global cultivation and is a major animal feed worldwide. Monsanto spokesman Thomas Helscher points to a series of feeding studies, which conrmed the safety of corn NK 603, however, no long time data exist. Many chemicals and drugs had proven in retrospect to be unsafe. The latest study of Sralini et al. on Roundup and GM revives the discussion on its safety and is a setback in USA where GM food is highly accepted by the consumer, while Europe does not accept such foods.
27.13. TOXICITY OF ROUNDUP WEED-KILLER AND MONSANTO NK 603 CORN LONG-TIME STUDY 2003 Critics on the study note lacking data on how much the rats were given to eat, or what their growth rates were. Rats used in the study are prone to mammary tumors when food intake is not restricted. The statistical methods used by the authors of the study are also being criticised as unconventional, studys control comprised only 10 rats of each sex, most of which also got tumours.
27.13.1
Foregoing studies
The study of Sralini et al. Is a long-time study on rats conrmed a series of previous studies rising concerns on the safety of the weed-killer and the GM corn from Monsanto. Only three-month long feeding trials with rats performed by Monsanto The most detailed regulatory tests on the GMOs are three-month long feeding trials of laboratory rats. The study was not independently conducted. The test data and the corresponding results are kept in secret by the companies. The Sralini team in 2009, reported possible liver and kidney toxicities when testing maize NK 603, MON 810, and MON 863 at conditions cited by Monsanto. [140] Impact of Monsanto Roundup on biodiversity and ecosystem [141] Clair et al. 2012 report that Roundup() has an inhibitory eect on microbial growth and a microbicide eect at lower concentrations than those recommended in agriculture. The toxic eects of glyphosate were less intense. Glyphosate is the main active component of Roundup. According to the authors, the toxicity of Glyphosate is being amplied by adjuvants of the commercial formulation of Roundup. The toxic eects were noted on Geotrichum candidum, Lactococcus lactis subsp. cremoris and Lactobacillus delbrueckii subsp. Bulgaricus, used by the dairy industry as starters for milk products. Their work may explain the oss of microbiodiversity and microbial concentration observed in raw milk, note the authors. Extensive cell tests in 2009 performed by Benachour and Sralini have shown that the adjuvants in Roundup formulations are not inert the mixtures available on the market may cause cell damage and even death around residual levels to be expected, especially in food and feed. [142] The endocrine and toxic eects of Roundup adjuvants enhances glyphosate bioavailability and/or bioaccumulation according to Richard et al 2005. [143] Glyphosate residues and toxic breakdown products are present in GM plants. Sralini et al. 2012 looked at the combined eects of Cry1Ab and Cry1Ac Bt toxins on human
2004
embryonic cells. Modied Bt toxins are not inert on human cells. They may present combined side-eects with other residues of pesticides specic to GM plants. Combined eect of Cry1Ab and Cry1Ac reduce caspases 3/7 activations induced by Roundup delaying the activation of death of test cells. [144] Glyphosate-based herbicides residues are frequent pollutants in the environment. Up to 400 ppm of their residues are accepted in some feed. However, cytotoxic eects on human liver HepG2 cells were found by Sralini et al. to start at 10 ppm, and DNA damages at 5 ppm. Gasnier et al. 2009 urged to include real cell impact of glyphosate-based herbicides residues in food, feed or in the environment in safety considerations. [145] The glyophosate-based pesticides with adjuvants have an endocrine impact at very low environmental doses, but only a high contamination appears provoke an acute rat testicular toxicity. The chronic toxicity is insuciently tested says a study of Clair et al. 2012. [146]
27.14
27.14.1
Inorganic Insecticides
Sulfur
Sulfur is the oldest known, eective insecticide. Sulfur and sulfur candles were burned in the past for every purpose. Sulfur is used in integrated pest management programs targeting specic pests. Sulfur dusts are especially toxic to mites of every variety, such as chiggers and spider mites, and to thrips and newly-hatched scale insects. Sulfur dusts are also used as fungicides, such as powdery mildews.
27.14.2
Very toxic.
Mercury
27.14.3
Boron
Boric acid is being used against cockroaches and other crawling household insects.
27.14.4
Sodium borate
It is being used to treat lumber and other wood products to control decay by fungi, termites and other wood infesting pests.
27.15. MISCELLANEOUS COMPOUNDS
2005
27.14.5 27.14.6
Thalium Arsenics
Copper arsenate, Paris green, lead arsenate and calcium arsenate. The arsenicals uncouple oxidative phosphorylation, inhibit certain enzymes that contain suldryl (-SH) groups and coagulate protein by causing the shape or conguration of proteins to change.
27.14.7 27.14.8
Antimony Fluoride
Sodium uoride, barium uosilicate, sodium silicouoride and cryolite are used as insecticides. Cryolite is a relative safe fruit and vegetable insecticide used in integrated pest management programs.
27.14.9
Silica gels or silica aerogels
Silica dusts are light, white, uy and are used in combination with pyrethrum in household insect control.
27.15
27.15.1
Miscellaneous compounds
Pyriproxyfen
It is a pyridine.
27.15.2
Buprofezin
It is a thiadiazine. Both are used to control the whity complex, a universal problem in cotton farming.
27.15.3
Clofentezine
It is a member of the group of the tetrazines, used as an acaricide/ovocide for fruits, citrus, cotton, cucurbits, vines and ornamentals,inhibiting mite growth.
27.15.4
Enzone(r) sodium tetrathiocarbonate
It is used only on grapes and citrus applied as a water application and irrigated into the soil. It breaks down in the soil to form carbon disulde, which acts rapidly, decomposes quickly being active against nematodes, soil insects and soil borne diseases.
2006
27.15.5
Clandosan(r)
It is dried, powdered, chitin protein isolated from crustacean exoskeletons and blended with urea. It stimulates growth of benecial soil microorganisms that control nematodes, but does not have a direct adverse eect on nematodes as such.
27.16
Other contaminants
The Regulation 466/2001/EC sets maximum for other contaminants in foodstus. Relevant for palmoil is the maximum level of lead in fats and oils for human consumption of 0,1 mg/KG. The regulation 2375/2001/EC sets maximum levels for dioxinsin fats and oils meant for human consumption. In this regulation the limit for dioxin is set at 0,75 pg/g for all vegetable oils.
27.16.1
Copper
Various copper salts, including basic copper sulfate, coppersulfatechloride, -carbonate, hydroxide and -oxychloride are able to cause serious intoxication Ingestion of food, water and beverages,contaminated with copper have been related. Soft drinks like orange juice dispensed in contact with chromium plated copper tubes have caused intoxication. The acid of juices can cause migration of copper from the tube as soon as the chromium surface is corroded, leaving free the copper to react.
27.16.2
Lead
Lead is found in the ice of Greenland dated back to the Romans and the Greeks 2000 years ago. Layers or permafrost ice are a kind of deposition of almost every environmental contaminant. In order to reduce the consumption of lead contaminated food, it is useful to avoid the use of glazed pottery and pewter dishes to serve or store food, to avoid the storage of beverages in leaded decanters, to keep the home clean and as dust free as possible, to eat a variety of foods and to eat foods rich in calcium, iron and vitamin C so the body will absorb less lead from specic food sources that have been exposed to lead Lead absorption is increased with iron and calcium deciency and nutritional deciency. Old paint is the most important source of contamination of the environment. Lead water pipes are even more dangerous when they transport hot water. Tin-coated lead foil capsules on wine bottles were banned in 1996. According to a study of the Bureau of Alcohol, Tobacco and Firearms 3 to 4 percent of wines were being contaminated during pouring from lead residues deposited on the mouth of the bottle by the
27.16. OTHER CONTAMINANTS
2007
foil capsule. Lead-soldered food cans were banned in 1996. Some countries still use lead-soldered cans for food and are still sold in ethnic grocery stores. Lead was banned from house paint in 1978, and phaseout of lead in gasoline was completed in 1995. Lead in drinking water should not exceed 5 ppb. This is the detection limit of general available methods for water analysis.
27.16.3
Lead in food
[147] EFSA assesses health implications of lead in food in 2010. Lead is an environmental contaminant that occurs naturally and, to a greater extent, from anthropogenic activities such as mining and smelting and battery manufacturing. Human exposure to lead can occur via food, water, air, soil and dust. Food is the major source of exposure to lead. Cereals, vegetables and tap water to were found to contribute most to dietary exposure to lead for most Europeans. Non-dietary exposure to lead was considered to be of minor importance to adults, although house dust and soil can be important sources of exposure for children. The Panel identied reduced intelligence quotient (IQ) levels in young children, and high blood pressure in adults, as the key health eects on which to base its assessment. Following a review of the available data, the Panel considered that the PTWI (provisional tolerable weekly intake) was no longer appropriate. A new guidance level could not be established, as there was no clear threshold below which the Panel was condent that adverse eects would not occur. The Panel therefore compared current exposure estimates for dierent groups of the population to levels above which adverse eects may occur. As a result, the Panel concludes that in particular there is a potential concern for neurodevelopmental eects in foetuses, infants and children.
27.16.4
Lead limits
[147] Lead dietary exposure for average adult consumers in 19 European countries ranged from 0.36 to 1.24 microg/kg body weight (b.w.) per day (lower bound for country with lowest average exposure - upper bound for country with highest average exposure) and from 0.73 to 2.43 microg/kg b.w. per day for high consumers, respectively. Overall, cereals, vegetables and tap water were the most important contributors to lead exposure in the general European population. More specically, the following food groups were identied as the major contributors to lead exposure: cereal products, followed by potatoes, cereal grains (except rice), cereal-based mixed dishes and leafy vegetables and tap water.
2008
Lead levels in breast milk are highly variable but exposure of infants is estimated to be 0.21 microg/kg b.w. per day on average or 0.32 microg/kg b.w. per day for high consumers. For infants fed with ready-to-consume infant formula, the average exposure estimates range from 0.27 to 0.63 microg/kg b.w. per day, based on lower bound and upper bound assumptions, respectively; for high consumers, lead exposure estimates range from 0.40 to 0.94 microg/kg b.w. per day. For children aged 1-3 years mean lead dietary exposure estimates range from 1.10 to 3.10 microg/kg b.w. per day based on lower bound and upper bound assumptions, respectively; for high consumers, lead exposure estimates range from 1.71 to 5.51 microg/kg b.w. per day. For children aged 4-7 years mean lead dietary exposure estimates range from 0.80 to 2.61 microg/kg b.w. per day based on lower bound and upper bound assumptions, respectively; for high consumers, lead exposure estimates range from 1.30 to 4.83 microg/kg b.w. per day. Breast-fed 3-month old infants are predicted to have a lead exposure that is below the BMDL01 intake value of 0.50 microg/kg b.w. per day for neurodevelopmental eects. Estimated exposure in children up to age seven exceeds the BMDL01 intake level of 0.50 microg/kg b.w. per day for neurodevelopmental eects. Blood lead levels of children in France [148] Low-level lead exposure is associated with intellectual decits and behavioural problems. Oulhote et al. 2013 studied the contribution of residential sources of lead to childrens blood lead levels. Lead-contaminated oor dust was the main source of lead in blood. The steepest increase in blood lead occurred at the lowest levels of lead-contaminated oor dust (blood lead levels increased by 65% to 5% when environmental lead content increased from 25th percentile to 95th percentile, respectively). The authors recommend, therefore that lead contamination should be kept as low as possible, and standards for lead levels in residential dust, soil and water be set low. With the lower levels of exposure, it is becoming more dicult to identify lead sources and new approaches may be required for preventive action. Oulhote et al. 2011 found lead isotope ratios useful for identifying sources of lead using data of French children aged from six months to six years with blood lead levels 25 g/L. [149] Metabolomics of urine to determines exposure to biomarker-lead [150] Metabolomics analysis of overnight void urine was found by Beckmann et al. 2013 may be used to determine exposure biomarker-lead in a population. Dietary intake is linked to the health of a specic population. Conventional observational epidemiological studies are sometimes inconclusive because of the diculty in measuring food intake. Urine biomarkers using non-targeted metabolomics may be used to unveil exposure to specic foods and increases reliance of nutritional data.
27.16. OTHER CONTAMINANTS Dietary axseed oil reduces lead-induced nephrotoxicity [151]
2009
Lead is nephrotoxic. Flaxseed oil, a rich source of omega-3 fatty acids and lignans, has been shown to prevent/reduce the progression of certain types of cardiovascular and renal disorders. lead acetate (PbAc)-induced renal damage. Rats were pre-fed with axseed oil presented improved antioxidant defense mechanism and improving brush border membrane integrity and energy metabolism, when challenged with lead acetate. Various serum parameters were improved compared with rats which also received lead acetate but no axseed oil. Herb extract reduces lead-induced infertility [152] Oxidative stress has been proposed as a possible mechanism involved in lead toxicity that causes reproductive system failure in both human and animals. Dorostghoal et al. 2013 report that Fumaria parviora L., used in Persian folk medicine, mayprotect the male rats against lead-induced testicular oxidative stress. Administration of ethanolic extract of Fumaria parviora improved signicantly reproductive parameters in lead-treated rats. The authors concluded that extract of the leaves of Fumaria parviora restores suppressed reproduction and reduces lead-induced testicular toxicity in rats. High blood lead levels linked to ischemicheart disease [153] Ghiasvand et al. 2013 report an association of high blood lead level (lead<=40 mg) with diastolic blood pressure but not with triglyceride, fasting blood sugar, and high density lipoprotein-cholesterol, low density lipoprotein-cholesterol and cholesterol. The authors recommend obsevation of health policies, working place changes and periodic medical examinations rigarding diastolic blood pressure in lead exposed workers. Blood lead reduces walking speed in women, but not in men [154] According to Ji et al. 2013 walking speed may be used to measure adverse health events in older people, including falls, disability, hospital admissions, and mortality. Lead is linked to vascular and neurological human systems ailments. adverse aects on human health, particularly on the vascular and neurological systems. The authors found that walking speed decreased with increasing quintiles of blood lead in women (0.11 ft/s slower for women with blood lead concentrations in the highest versus lowest quintile). No association with walking speed was found in men. The authors concluded that their data underline the negative eects of lead exposures.
27.16.5
Lead in food, conclusions
[147] Compared to dietary exposure, non-dietary exposure to lead is likely to be of minor importance for the general population in the European Union (EU). House dust and soil can
2010
be an important source of exposure to lead for children. In humans, the central nervous system is the main target organ for lead toxicity. In adults, lead-associated neurotoxicity was found to aect central information processing. There is considerable evidence demonstrating that the developing brain is more vulnerable to the neurotoxicity of lead than the mature brain. In children, an elevated blood lead level is inversely associated with a reduced Intelligence Quotient (IQ) score and reduced cognitive functions up to at least seven years of age. The CONTAM Panel concluded that the provisional tolerable weekly intake (PTWI) of 25 microg/kg b.w. set by the Joint FAO/WHO Expert Committee on Food Additives (JECFA) and endorsed by the Scientic Committee of Food is no longer appropriate and that as there was no evidence for a threshold for a number of critical endpoints including developmental neurotoxicity and nephrotoxicity in adults, it would not be appropriate to derive a PTWI. The CONTAM Panel does consider it appropriate to calculate margins of exposure to support the risk characterisation. Estimates of dietary exposure to lead based on lower bound assumptions and upper bound assumptions for the level of reporting for average adult consumers in Europe are lower than the limit of the benchmark dose BMDL intake value for eects on systolic blood pressure (SBP) (1.50 microg/kg b.w. per day), but vary from above to below the BMDL intake value for eects on the prevalence of chronic kidney disease (0.63 microg/kg b.w. per day). The respective margins of exposure (MOEs) range from 1.2 to 4.2 and from 0.51 to 1.81, respectively. Hence, if exposure were closer to the upper bound estimates, the possibility of an eect on some consumers cannot be excluded. The Panel concluded that current levels of exposure to lead pose a low to negligible health risk for most adults but there is potential concern over possible neurodevelopmental eects in foetuses, infants and children.
27.17
Integrated Pest Management (IPM)
IPM represents an alternative to chemical poisoning of nature promoting minimised pesticide use, enhanced environmental stewardship and sustainable systems. A public-private partnership resulted in The National Integrated Pest Management Network (NIPMN). It provides the latest informations on IPM on the World Wide Web. IPM research develops alternatives to pesticides, using integrated management tactics such as:
Attractants
27.17. INTEGRATED PEST MANAGEMENT (IPM) Biopesticides Transgenic plants
2011
Cultural practices(such as altered row spacings that reduce weed populations, alternative rotation patterns and physical barriers such as mulches) Host resistance Pheromone mating disruptors Host plant resistance (Enhanced host plant resistance either by traditional breeding methods or genetic engineering techniques.) Pesticide resistance management (Greater knowledge of natural and articial selection increasing pest resistance to pesticides to design IPM systems to avoid the development of such resistance) Application technology (Application of minimum amount of pesticides necessary to control the pest and reducing adverse impacts on non-target organism.) Forecasting movement and dispersal (Forecast of aerial movement of pests and their natural enemies) Decision support systems (Systems assisting growers in pest management decisions and educational programs.) Table 27.11: Volatile chemicals with environmental impact Chemicals hazard
Benzene Carbon Tetrachloride Chlorobenene Toluene Vinyl chloride
Freshwater, life, salt water Aquatic life, cancer risk Aquatic life, cancer risk Aquatic life, cancer risk Packaging
Table 27.12: Non-volatile chemicals with environmental impact Chemicals hazard
Pentachlorphenol Acrylamide
Aquatic life, Human consumptin Human consumption
2012
Polychlorinated Biphenyls 2,3,7,8-TCD (dioxin)
Aquatic life, human consumption, cancer risk
Aquatic life, human consumption, cancer risk
27.18
Herbicides in rainfall
Agricultural practices in the United States require extensive use of herbicides for producing three principal row crops-corn, soybeans, and grain sorghum. Approximately 140 of the 218 million kilograms of herbicides used at the beginning of the 90th were mainly atrazine and Alachlor applied in the upper Mississippi River drainage basin, the Corn Belt of USA which is parts of Illinois, Indiana, Iowa, Ohio, Minnesota, and Nebraska. They came into the atmosphere by volatilisation and entrainment on dust particles. Winds transported them to the region of the Great Lakes. The rainfall in this region contained atrazine and Alachlor as most frequent herbicide. The degradation of atrazine in water is about only 1 % per year.Therefore this herbicide accumulates in the lakes.
27.18.1
Eect of herbicide Atrazine on sh reproduction
[155] Atrazine is the most frequent pesticide detected in streams in agricultural areas like the Corn Belt states, and is known for its eects on the hypothalamus-pituitary-gonad axis in certain vertebrate species, Tillitt and colleagues 2010 looked at the eects on sh reproduction at concentrations of 0, 0.5, 5.0, and 50mug/L of atrazine. The authors found that total egg production, due to reduced numbers of spawning events, was lower under Atrazine exposure compared to Antrazine free breeding. Gonad abnormalities and alteration of nal maturation of oocytes were also observed. The authors call for more studies to evaluate the atrazine risk on shes.
27.18.2
Pesticide Action Network (PAN)
The Pesticide Action Network (PAN) Pesticide Database is a one-stop location for toxicity and regulatory information for pesticides. [156]
27.19. BIOPESTICIDES
2013
27.19
Biopesticides
Biopesticides are certain types of pesticides derived from natural materials.
27.19.1 27.19.2
Classes of biopesticides Microbial pesticides
They consist of a microorganism, such as bacteria, fungus, virus or protozoans as the active ingredient. Important microbial pesticides are strains of Bacillus thuringiensis which produce mixtures of proteins killing specicly one or a few related species of insect larvae. While some Bts control moth larvae found on plants, other Bts are specic for larvae of ies and mosquitoes. The target insect species are determined by whether the particular Bt produces a protein that can bind to a larval gut receptor, thereby causing the insect larvae to starve.
27.19.3
Plant-Incorporated-Protectans (PIPs)
They are pesticidal substances that plants produce from genetic material that has been added to the plant, such as genes from Bacillus thuringiensis. Those who deny genetic engineering do not use plant-integrated-protectans.
27.19.4
Biochemical pesticides
Biochemical pesticides are substances, such as insect sex pheromones, that interfere with mating, as well as various scented plant extracts that attract insect pests to traps by nontoxic mechanisms. Conventional pesticides, by contrast, are generally synthetic materials that directly kill or inactivate the pest.
27.20
27.20.1
Conventional pesticides
Atrazine
It is the most widely used pesticide, controlling broadleaf and grassy weeds. It was registered in December 1958. Its estimated production is 76 to 85 million pounds annually. It is used in the culture of corn, sugarcane, residential lawns, sorghum, guava, hay, macadamia nuts, pasture, winter wheat and on non-agricultural sites. Atrazine is not likely to be carcinogenic to humans, however, it has been associated with imbalances in hormone levels in laboratory animals, possibly disrupting reproductive and developmental processes.
2014
27.20.2
Azinphos-methyl
It is an organophosphate insecticide used on fruits and vegetables. It is a risk to children ages of one to six years and agricultural workers. It can over stimulate the nervous system causing nausea, dizziness, confusion, and at high exposures, respiratory paralysis and death.
27.20.3
Desert Locust
[157] Yemen is facing its worst Desert Locust outbreak since 1993, FAO warned on 6 June 2007. An intensive survey and aerial control campaign using helicopters needs to be mounted to avoid massive locust infestations and serious damage to food crops. If locust infestations are not controlled in time, agricultural crops in Wadi Hadhramaut and other areas including the Sanaa highlands will be at risk. Locusts are migratory grasshoppers that often travel in vast swarms. A Desert Locust lives about three to ve months. The life cycle comprises three stages: egg hopper and adult. Eggs hatch in about two weeks, hoppers develop in ve to six stages over a period of about 30-40 days, and adults can mature within three weeks. Swarms can travel from 5 to 130 kilometres or more in a day with the wind. A Desert Locust adult can consume roughly its own weight in fresh food per day about two grams. A very small part of an average swarm eats the same amount of food in one day as about 500 people.
27.20.4
Contaminants in food
[158] The European Commission noted on the 7. June 2007 what has been undertaken to reduce contaminants in food. According to the denition adopted by the EU, contaminants are substances that have not been intentionally added to food. These substances may be present in food as a result of the various stages of its production, packaging, transport or holding. They also might result from environmental contamination. Some contaminants have already studied by food safety authorities, such as mycotoxins (aatoxins, ochratoxin A, fusarium-toxins, patulin), metals (cadmium, lead, mercury ,inorganic tin), dioxins and PCBs, polycyclic aromatic hydrocarbons (PAH), 3-MCPD and nitrates Ongoing investigations are:
27.20. CONVENTIONAL PESTICIDES
2015
Acrylamide - The Commission will collect data concerning surveys of acrylamide made by member states over three years between 2007 and 2009. [159] Organotins - chemicals which can be found in water systems due to their presence in paints as anti-biofouling agents e.g. used on the hulls of ships and marine apparatus. The European Food Safety Authority (EFSA) has issued an opinion on the health risks to consumers associated with exposure to organotins in foodstus. Scientic Committee on Health and Environmental Risks (SCHER) has recently adopted an opinion on the risks to health and the environment associated with the use of 4 organotin compounds. In this opinion food and non-food exposure routes were assessed. More informations are available at the EFSA opinion, SCOOP Report. [160]
27.20.5
Low-level environmental contaminant exposures prenatally can alter behaviour in infants [161]
According to Sagiv et al 2012 eating sh with even low levels of mercury while pregnant can increase the risk for attention-decit/hyperactivity disorder (ADHD) in ospring at the age of 8 years. Mean peripartum maternal hair mercury level was 0.45 g/g. The ADHD risk is associated with maternal mercury levels of at least 1 g/g. The authors, however, stress that consumption of 2 sh servings weekly of several other types of sh during pregnancy may protect against the disorder. The authors recommend pregnant women to avoid shark, fresh tuna, and swordsh. Haddock, salmon, and ounder should be preferred because of their low levels of mercury and their nutritional value. The study also assess a possible link between exposure to polychlorinated biphenyls (PCBs) and neurodevelopment. Low levels of prenatal organochlorine exposure is linked to ADHD [162] Organochlorines are environmentally persistent contaminants which may cross the placenta and pose a risk to fetuses. Sagiv et al 2010 found that prenatal polychlorinated biphenyl (PCB) and p,p-dichlorodiphenyl dichloroethylene (p,p-DDE) levels were linked to behaviors associated with attention decit hyperactivity disorder (ADHD) in children of mothers living near a PCB-contaminated harbour in New Bedford, Massachusetts. The median umbilical cord serum level of the sum of 4 prevalent PCB congeners ranged between 0.01- 4.41 ng/g serum. Higher risk for ADHD-like behaviours were found at higher levels of PCBs and p,p-DDE. These results support the association between low-level prenatal organochlorine exposure and ADHD-like behaviours in childhood. Winneke 2012 [163] focuses on attention-decit hyperactivity disorder (ADHD) in children in relation to environmental exposure to lead, mercury and aluminium in school
2016
children in Romania. Lead, but not Hg or Al, was associated with ADHD. Low-level exposure to lead contributes to this neurodevelopmental disorder. Polychlorinated biphenyls (PCBs) are persistent environmental pollutants still present in harmful concentrations. The study demonstrates that ADHD is aected by low environmental Pb in blood even below 10mug/dl, but not by other neurotoxic trace metals. Winneke concludes that pre- and early postnatal exposure to PCBs and lead is associated with decit or retardation of mental and/or motor development caused by an interference with the thyroid metabolism during brain development. [164] Only boys aected by PCBs induced neuropsychological decits [165] In 2012 Sagiv et al report the associations between PCBs and neuropsychological decits for children but only among boys. These results support an association between organochlorines (mainly PCBs) and neuropsychological measures of attention among boys only. Sexspecic eects should be considered in studies of organochlorines and neurodevelopment. Prenatal exposure to low levels of PCBs impairs foetal growth [166] Govarts et al 2012 compared birth weight and the concentration of cord serum PCB-153 ranging from 20 to 484 ng/L and that of p,p-DDE ranging from 50 to 1.208 ng/L. They found that prenatal exposure to PCB-153 decreased birth weight by 150 g per 1-g/L increase in PCB-153. Contrary, a 1-g/L increase in p,p-DDE was associated with a 7g increase in birth weight. Overweight caused by prenatal environmental contaminants [167] Valvi et al 2012 report that prenatal exposure to endocrine-disrupting chemicals such as Organochlorine compound (OC) concentrations (polychlorinated biphenyls (PCBs), dichlorodiphenyldichloroethylene (DDE), and dichlorodiphenyltrichloroethane (DDT) increase the risk of overweight at at 6.5 years of age, with strongest impact in girls. DDT was associated with overweight only in boys.
27.20.6
Ethyl carbamate
It is a compound that can naturally occur in fermented foods and beverages. It often occurs in alcoholic beverages (in particular stone fruit brandies). Ethyl carbamate is formed by ethanol and certain precursors in the fruit mash under the inuence of light during the distillation process. EFSA is currently collecting data on the presence of ethyl carbamate.
27.20.7
Urea in sugar cane distilled spirits
[168] Labanca and Gloria 2008 detected 500 to 5,100 microgram/L urea in 69 per cent of analOurFood Database of Food and Related Sciences Copyright 1998-2010 Karl H. Wilm. All rights reserved.
2017
ysed samples of Brazilian sugar cane distilled spirits. The authors found no signicant correlation between the levels of urea and ethyl carbamate. The authors used a spectrophotometric quantication at 540 nm which uses a reaction of urea with 1-phenyl-1,2propanodione-2-oxime.
27.20.8
Copper II, iron II and Iron III oxidise cyanate to form ethyl carbamate
[169] Aresta, Boscolo and Franco assessed the role of copper(II) species in the oxidation of inorganic cyanide to cyanate and in the conversion of cyanate or urea into ethyl carbamate. According to the authors urea has a minor role in the formation of ethyl carbamate in brazilian sugar cane distilates, being the oxydation of cyanade and its complexation to Cu II the main pathway of the formation of ethyl carbamate. Lachenmeier and colleagues 2009 analysed Brazilian sugar cane distilled spirits and found a relatively high incidence for ethyl carbamate contamination. The authors report that 56 per cent were above 0.15 mg/l considered of public health relevance. [170] Lachenmeier and colleagues 2005 reported that measures to reduce ethyl carbamate in cherry, plum or mirabelle (yellow plum) spirits, which include destoning are used in many distilleries. However, some small distilleries could not minimize the content of ethyl carbamate yet. [171]
27.20.9
Ethyl carbamate in UK spirits
[172] According to the FSA a mean concentration of 29 microgram/l of ethyl carbamate was found in the 205 samples of UK whiskies. Values ranged from not detectable to 239 microgram/l.
27.20.10
In In [173] In In In
Maximum levels of ethyl carbamate
table wines 30 ppb fortied wines 100 ppb distilled spirits 150 ppb fruit brandies and liqueurs 400 ppb sake 200 ppb
2018
27.20.11
Special yeast strains to reduce residual urea during fermentation
[173] Tim Paterson suggests the use of yeast strains from Phyterra Yeast that are genetically enhanced to greatly reduce residual urea. The genetic code of the yeast was rearranged by moving the promoters within the genes to a place which activated the expression of degrading urea instead of using other nitrogen sources. The company which supplies this yeast claims that it is genetic enhanced, and such a genetic rearrangement is not being considered as genetic modication by the European legislation. A promoter signal is a start signal for the cell to start the activity of the gene such as the production of a specic protein. Most of the promoters which are being used were derived from the Cauliower Mosaic Virus (CaMv) called 35S promoter.
27.20.12
FDA Ethyl Carbamate Preventive Action Manual
[174] Ethyl carbamate preventive action manual: 1997 of the U. S. Food and Drug Administration presented suggestions to reduce the formation of ethyl carbamate in wine. This strategy is mainly built in reduction of excessive nitrogen fertilization in the vineyard, monitoring of grape juice and vine nitrogen status, use of cultivars and rootsstocks which take up less nitrogen, avoid of nitrogen and urea as supplements, choosing the wine yeasts and malolactic with known characteristics. And avoiding elevated temperatures during storage and transport.
27.20.13
Furan
Furan has been identied in a number of foodstus that undergo heat treatment such as canned and jarred foodstus. A report on provisional ndings on furan in food has been compiled by EFSA. [175] EFSA is currently collecting more data on furan .e.g. on its mode of formation, levels in food and toxicity. [176]
27.20.14
Furan in heat treated foods
[177] Furan was found by the FDA in a number of foods that undergo heat treatment, such as canned and jarred foods. The presence of furan is listed in the Department of Health and Human Services Report on Carcinogens and is considered possibly carcinogenic to humans by the International Agency for Research on Cancer.
2019
27.20.15
Furan, a cancerogen in food
[178] The European Food Safety Authority (EFSA) has issued a report updating results of monitoring on the levels of furan found in food in heat-treated commercial food products. Furan is an organic compound formed during heat-treatment which has been shown to be carcinogenic in animal laboratory studies. The ve coee categories showed the highest furan content in comparison to the other food groups, with mean values equal to 104 microg/kg for "coee ready-to-drink", 602 microg/kg for "coee instant", 1,807 microg/kg for "coee roasted ground", 1,855 microg/kg for "coee non specied" and 3,611 for "coee roasted bean". The maximum value was found in "coee roasted ground" with 6,900 microg/kg. In the non-coee categories mean values ranged between 3.2 microg/kg for "infant formula" and 40 microg/kg for certain "baby food" categories. The highest maximum concentrations for the non-coee categories were found in "baby food" with 224 microg/kg and "soups" with 225 microg/kg. In all coee subcategories the upper bound mean furan content was lower in the beverage coee samples than in the raw coee samples. There is obviously a dilution eect in preparing the coee. The mean furan content in infant formulae was 3.2 microg/kg. The mean furan content in the dierent baby food categories ranged from 5 microg/kg for baby food containing only fruits to 40 microg/kg for baby food containing either meat and vegetables or vegetables only. Maximum values exceeding a level of 100 microg/kg were found in cereal products like pued rise, in sh products like mackerels and sardines in tomato sauce, in meat products like canned duck with lentils or rabbit with prunes, in soups like tomato soup and in gravy. Milk based processed food showed low mean furan content (6 microg/kg), but interestingly a maximum furan content of 80 microg/kg was found in sweetened condensed milk. EFSA recommends that future testing for furan should provide a detailed analysis of samples before and after cooking, with a precise indication of cooking time, temperature and handling. The EFSA also stresses that the reduction of furan formation in food is more difcult compared to the reduction of acrylamide, since furan formation is closely connected with the taste and smell of foods. It can be concluded that furan is present in a variety of heat-treated commercial foods for adults and infants.
27.20.16
Soybean oil and sunower oil in starch- based emulsion developed cancerogenous furan
[179] Owczarek-Fendor and colleagues 2010 found that furan, was formed during sterilisation heating process in starch-based emulsions of Soya bean oil and sunower oil, when the
2020
oils were oxidised. No furan or very low amounts were created using fresh, not oxidised soybean oil and sunower oil, and only minor amounts of furan formation were found in food-relevant systems containing fresh lipids. Emulsions of olive, linseed, and rapeseed oils developed only after a storage of 11 and 22 days an increase in furan content which, however, was much lower than the soybean and olive oil based emulsions. Soyabean oil and sunoweroil were rich in omega-3 unsaturated alfa-linolenic acid. These faty acids were associated with the generation of furan if the oils were oxidized. However, high-oleic sunower oil did not generated furan when heated and oxidised. Para-anisidine values could not be related to the amount of generated furan. The authors concluded that both fatty acid composition and oxidation status of oil seem to determine furan generation upon heating.
27.20.17
Mechanisms of Formation
The primary source of furans in food is thermal degradation and rearrangement of organic compounds, particularly carbohydrates. A variety of experimental systems, including heating of sugars in the presence of amino acids or protein and thermal degradation of vitamins produced furans in food. Furan producing systems are: Thermal degradation of glucose; thermal degradation of glyceraldehydes, D-Erythrose, pentosans, hexoses, and polysaccharide; and a lactose-casein browning system. The specic mechanism that produce furan are unknown. Among the model systems studied, ascorbic acid had the highest potential to produce furan, followed by glycolaldehyde/alanine > erythrose > ribose/serine > sucrose/serine > fructose/serine > glucose/cysteine. [180] Intake of dioxins and furans can take place through breathing contaminated air, drinking contaminated water or eating contaminated food. About 90% of exposure to dioxins and furans is from eating contaminated food. Dioxins and furans can build up in the fatty tissues of animals. This means that eating beef, pork, poultry, sh as well as dairy products can be a source of exposure.
27.20.18
Recommendations EPA
[181] The U.S. EPA has set a limit of 0.00003 micrograms of 2,3,7,8-TCDD per liter of drinking water (microg/L). The Food and Drug
2021
Administration recommends not eating sh and shell sh with more than 50 parts per trillion (50 ppt) of 2,3,7,8-TCDD.
27.20.19
Foods which may contain furan
[182] During heat treatment furan may be formed in foods rich in carbohydrates such as babyfoods with banana or potatoes, other foods likee fruits, vegetable juices, canned vegetables, coee cocoa, bread, grilled meat and smoked foods. Furan is present in the smoke of cigarettes in concentration of 8,4 microgram in 40 ml breath (Egle et al. 1979) Furan is the 1,4 -Epoxy-1,3-butadien, it is also called Furfuran, Oxol, Tetrol, Divinylenoxid, Oxacyclopentadien. Furan is not dibenzo-furan which is part of a group of dioxin-like substances called furane.
27.20.20
The CONTAM Panel Report on furan
[183] Taking into account all the presently available data on the mode of action of furan, the Panel concluded that the weight of evidence indicates that furan-induced carcinogenicity is probably attributable to a genotoxic mechanism. However, chronic toxicity with secondary cell proliferation may indirectly amplify the tumour response. From the presently available data it appears that there is a relative small dierence between possible human exposures and the doses in experimental animals that produce carcinogenic eects, probably by a genotoxic mechanism. However, a reliable risk assessment would need further data on both toxicity and exposure.
27.20.21
Control of locusts
[184] The Desert Locust is a dicult pest to control. Early warning and preventive control is the strategy adopted by locust aected countries in Africa and Asia to try to stop locust plagues from developing and spreading .FAOs Desert Locust Information Service (DLIS) in Rome, Italy monitors the weather, ecological conditions and the locust situation on a daily basis. Results and warnings are available on the FAOs Locust Watch web site. FAO also provides information. An ecological method to control Desert Locust is with natural enemies. These include predatory anand parasitic wasps and ies, predatory beetle larvae, birds and reptiles, but are not sucient to control great swarms Another old African method is by putting poisonous or aromatic plants next to the crop they are trying to protect.
2022
27.20.22
Organophosphate insecticides
[184] At present the primary method of controlling desert locust infestations is with organophosphate insecticides applied in small concentrated doses by vehicle-mounted and aerial sprayers. The insecticide must be applied directly to the insect.
27.20.23
Biological control of locusts
Biopesticides include fungi, bacteria, neem extract and pheromones. The eectiveness of many biopesticides equals that of conventional chemical pesticides. They are usually harmless to other creatures and the environment.
27.20.24
Biological control of locusts
[184] A biological control product is Green Muscle. It is based on a naturally occurring entomopathogenic fungus which is a fungus which infects fungus Metarhizium anisopliae var. acridum This fungus infects many groups of insects. It is harmless to humans and other mammals and birds. It is recommended for use mainly against hoppers, the wingless early stages of locusts. it allows the natural enemies of locusts and grasshoppers to continue their benecial work. Biopesticides are also safer to use in environmentally sensitive areas such as national parks or near rivers and other water bodies. Green Muscle was developed under the LUBILOSA project Pathogens have the advantage that they can be produced in articial culture in large quantities and be used with ordinary spraying equipment. The fungal spores are sprayed in oil. Oil-based formulations allow the application of fungal spores under dry conditions such as found in deserts. Most insects living near the soil have evolved natural defenses against entomopathogenic fungi like M. anisopliae. This fungus is therefore locked in an evolutionary battle to overcome these defenses, which has led to a large number ofstrains that are adapted to certain groups of insects. Some strains are so specic that they have attained variety status, like Metarhizium anisopliae var. acridum, which almost exclusively infects grasshoppers. The use of Metarhizium anisopliaein the control of malaria mosquitos coating mosquito nets or cotton sheets attached to the wall with them.is under investigation. [185]
27.21
Antimicrobial agents
Antimicrobial agents are substances used to destroy or suppress the growth of harmful microorganisms whether bacteria, viruses, or fungi on inanimate objects and surfaces.
27.22. PESTICIDES
2023
More than 8000 antimicrobial products, containing about 300 dierent active ingredients, are sold as sprays, liquids, concentrated powders, and gases, ending in the environment.
27.22
27.22.1
Pesticides
Chromated Copper Arsenate
This denomination is used for mixtures consisting of three pesticidal compounds (arsenic, chromium, and copper) which are registered for wood preservative uses. The majority of the wood used outdoors is pressure-treated with this wood preservative to protect it from rot and decay. Heavy contamination of the soil of playgrounds with arsenic (up to 177 ppm) coming from wood treatment with chromated copper arsenate.The standard of risk for residential cleanup is 7.6 parts per million according to the Michigans Department of Environmental Quality. Arsenic is a known human carcinogen. A substitution for chromated copper arsenate should be developed. Sealants which stop the arsenic from coming out of the wood are not a good alternative, because arsenic remains in the environment.
27.22.2
Arsenic in food, juices and drinking water [186]
The juice sold by any one company can be made from concentrate that is literally sourced throughout the world, including U.S. domestic sources. For example, Asia and South America are major suppliers of apple juice concentrate. Even if a company buys concentrate from only one supplier in a country, such as Argentina, that supplier may be getting juice from a dozen or more dierent farms within Argentina. Some juice may have higher amounts of arsenic than others because of dierent amounts of arsenic in orchard soils. FDA has not set any standard for arsenic in fruit juice. The FDA states that arsenic contamination of apple juice is almost always very low. The maximum level of arsenic allowed in bottled water is 10 micrograms in one litre of bottled water or 10 parts per billion (ppb). Arsenic is present in the environment as a naturally occurring substance or as a result of contamination from human activity. It is found in water, air, food and soil in organic and inorganic forms. Arsenic contamination of groundwater is a problem that aects millions of people across the world, especially in the Ganges area and Bangladesh. George et al 2012 suggests to test drinking water of Bangladesh households in the eld by trained village workers using the Hach EZ kit, using an extended reaction time of 40 min. This might enable residents to use a low-arsenic well in the proximity of their home. [187]
2024
Picture: Author: Benutzer:Matze6587, Nov 2005 http://en.wikipedia.org/wiki/Arsenic_contamination_of_groundwater There are two types of arsenic: organic and inorganic. The inorganic forms of arsenic are the harmful forms, while the organic forms of arsenic are essentially harmless. Because both forms of arsenic have been found in soil and ground water, small amounts may be found in certain food and beverage products, including fruit juices and juice concentrates. Some scientic studies have shown that two forms of organic arsenic found in apple juice, dimethylarsinic acid (DMA) and monomethylarsinic acid (MMA), may also be a health concern.
27.22.3
Arsenic in rice and rice products, actual data and recommendation of FDA
The Food and Drug Administration (FDA) monitors foods and beverages for harmful substances. Concerns arise about the presence of inorganic arsenic in rice and rice products.Arsenic is a chemical that under some circumstances has been associated with longterm health eects. [188] According to the FDA arsenic levels can vary greatly from sample to sample, even within the same product. The agency published on 19 Sep 2012 average levels of inorganic arsenic in micrograms (one millionth of a gram): - Rice (other than Basmati rice): 6.7 per 1 cup (cooked) - Rice cakes: 5.4 per 2 cakes - Rice beverages: 3.8 per 240 ml (some samples not tested for inorganic arsenic) - Rice cereals: 3.5 per 1 cup - Basmati rice: 3.5 per 1 cup cooked
27.22. PESTICIDES Recommendation
2025
The FDA is not recommending that consumers change their consumption of rice and rice products at this time, but that people eat a balanced diet containing a wide variety of grains. More data are being compiled to determine whether additional recommendations are necessary. Particular attention targets rice and rice products consumed by children, as well as consumers like Asian-Americans and those with coeliac disease who may consumer higher levels of rice. Origin of arsenic in foods Arsenic is a chemical element distributed in the Earths crust. It is released from volcanoes and from the erosion of mineral deposits. It is found throughout the environment some foods and beverages. Human arsenic input include burning coal, oil, gasoline and wood, mining, and the use of arsenic compounds as pesticides, herbicides and wood preservatives. Rice comes from all over the world and is grown very dierently from region to region, which may greatly vary the levels of arsenic within the same kind of product. There are no evidence of a change in total arsenic levels over the last 20 years.
27.22.4
Arsenic-based pesticides [189]
Arsenic-based pesticides were commonly used in United States agricultural production up until 1970, when more eective substances became available, trace levels of organic and inorganic forms of arsenic can be detected in soil and in certain foods and beverages. Arsenic was used in various agricultural insecticides, such as lead hydrogen arsenate , monosodium methyl arsenate (MSMA) and disodium methyl arsenate (DSMA) have replaced lead arsenate in agriculture.
27.22.5
Arsenic wood preservative [190]
In the 1950s a process of treating wood with chromated copper arsenate (also known as CCA or Tanalith) was invented, and for decades this treatment was the most extensive industrial use of arsenic. An increased appreciation of the toxicity of arsenic resulted in a ban for the use of CCA in consumer products; the European Union and United States initiated this process in 2004.CCA remains in heavy use in other countries however, e.g. Malaysian rubber plantations. Arsenic is still added to animal food, in particular in the U.S. as a method of disease prevention and growth stimulation. One example is roxarsone, which is used as a broiler starter by about 70% of the broiler growers since 1995. The Poison-Free Poultry Act of 2009 proposes to ban the use of roxarsone in industrial swine and poultry production. Copper Chromated Arsenic (CCA): In 2003, the United States was the worlds largest consumer of arsenic, with an apparent demand of 21,600 metric tons. In 2005, the Unites
2026
States was still the worlds largest consumer of arsenic, mainly for CCA. Production of wood preservatives, primarily CCA, CrO3.CuO.As2O5, accounted for >90% of domestic consumption of arsenic trioxide prior to 2004. In 2005, about 65% of domestic consumption of arsenic trioxide was used for the production of CCA. The remainder was used for the production of agricultural chemicals, including herbicides, and insecticides.
27.22.6
Disposal of arsenic and its products
Wastes containing arsenic are considered hazardous wastes, and as such, their treatment, storage, and disposal are regulated by law (see Chapter 8). CCA-treated wood is classied as nonhazardous waste under the Federal Resource Conservation and Recovery Act (RCRA). CCA-treated wood is disposed of with regular municipal trash (i.e., municipal solid waste, not yard waste). It should not be burned in open res, stoves, residential boilers, or re places and should not be composted or used as mulch. Treated wood from commercial or industrial applications may only be burned in commercial or industrial incinerators in accordance with state and federal regulations.
27.22.7
Biomethylation of arsenic [187]
Inorganic arsenic and its compounds, upon entering the food chain, are progressively metabolised through a process of methylation. For example, the mould Scopulariopsis brevicaulis produce signicant amounts of trime thylarsine if inorganic arsenic is present. The organic compound arsenobetaine is found in some marine foods such as sh and algae, and also in mushrooms in larger concentrations. The average persons intake is about 1050 g/day. Values about 1000 g are not unusual following consumption of sh or mushrooms. But there is little danger in eating sh because this arsenic compound is nearly non-toxic.
27.22.8
Arsenic in drinking water
Widespread arsenic contamination of groundwater has led to a massive epidemic of arsenic poisoning in Bangladesh and neighbouring countries. Large part of the world population is drinking groundwater with arsenic concentrations elevated above the World Health Organizations standard of 10 parts per billion. However, a study by Lamm et al 2006 report high lung and bladder cancer rates in Taiwan suggesting that signicant increases in cancer mortality appear only at levels above 150 parts per billion. [191] A dose-dependent connection between chronic arsenic exposure and various forms of cancer, in particular when other risk factors, such as cigarette smoking were found by Ferreccio and Sancha 2006, persisting below 50 parts per billion of arsenic. The authors advise the Chile authorities to follows the World Health Organizations recommendation of 10 microg/L using the conventional coagulation process using iron. [192]
27.22. PESTICIDES
2027
27.22.9
Chinese limit for arsenic on surface of buildings and facilities at cooking plants [193]
China has set a level of 4.02 g/100 cm(2) of arsenic on surface of buildings and facilities at cooking plants at which health risk are expected. Liao et al. 2012 report that wipe samples of surfaces ranged from 0.01 to 23.90 g/100 cm(2). 20.2% of the samples exceeded the level considered as safe. Highest levels were found on the surface of bricks, and coking zone.
27.22.10
Increased prevalence of diabetes mellitus in population exposed to arsenic in drinking water at Chile [194]
Palacios, Roman and Cifuentes 2012 exposed male and female rats to drinking water from Antofagasta city/Chile with total arsenic of 30 ppb and lead of 53 ppb for 3 months. Treated male rats become insulin resistant, while females remained sensitive to insulin. The intestinal Na+/glucose cotransporter in male rats increased indicating increased glucose absorption. Palacios and colleagues also report that the total cholesterol and LDL cholesterol increased in treated male rats, and triglyceride increased in treated female rats, compared animals receiving deionised water. The authors concluded that low levels of arsenic and lead in drinking water induce insulin resistance in male subjects.
27.22.11
Small brown rice high in arsenic exceeds WHO limits in 29% of rural population of Bengal [195]
According to Halder et al 2012 the average accumulation of arsenic in rice grain increases with decrease of grain size. The authors stress that in rural villages mostly low cost brown coloured short-bold type of rice is consumed, and therefore the total daily intake of inorganic arsenics in 29% of the population exceeds the WHO recommended provisional tolerable daily intake value (2.1 g day-1 kg-1 BW).
27.22.12
Arsenic from rice consumption in Brazil is 10% of TDI [196]
A mean level of total arsenic in Brazilian rice of 222.8 ng g(-1) was reported by Batista et al. 2011.The daily intake of inorganic arsenic from rice consumption is 10% of the Provisional Tolerable Daily Intake (PTDI) with a daily ingestion of 88 g of rice. According to the authors, the percentages of total arsenic were 38.7; 39.7; 3.7 and 17.8% for dimethylarsinic acid (DMA), As(3+), monomethylarsinic acid (MMA) and As(5+), respectively. Rice of the state of Rio Grande do Sul presented highest levels of arsenic than rice of Minas Gerais or Gois,
2028
27.22.13
Arsenic in rice and their products
[197] Richard Stone reported in June 2008 that rice and products such as rice bran and rice crackers have elevated arsenic levels which increase cancer risk. Rice elds are recently extended to regions where arsenic pesticides had been used in cotton plantations. Rice accumulates arsenic ten-fold compared with wheat and other cereals. The World Health Organisation stipulates a maximum level of 10 g/litre of arsenic for water. China regulates arsenic in food, setting levels (0.15 g/kg). In relation to shellsh US FDA recommends a tolerable daily intake of inorganic arsenic of 130 g. In 2007 high levels of arsenic were found in in a rice porridge sold in UK supermarkets for weaning infants, exceeding 150 g of inorganic arsenic/kg. Rice bran from Japan and USA was also found to have high levels of arsenic. The FSA, however, wrote in May 2008 that the organic form of arsenic is less harmful but the inorganic form is known to cause cancer. While the concentration of total arsenic in rice is low, about 50% of it is present as inorganic arsenic. Recent studies compare intakes of arsenic from baby food with standard of drinking water. It must be decided which level of arsenic in food should be accepted. In this case the FSA believes the amounts of arsenic found are of no concern, because the arsenic is naturally present, it is likely to have always been present in rice and recent studies show that the intake levels are not increasing. Currently, the Agency does not feel that these reports require any changes in consumption of rice or rice products for either adults or children. [198]
27.22.14
Arsenic in food
[199] The European Food Safety Agency (EFSA) reports that arsenic is a widely-occurring contaminant which occurs both naturally and as a result of human activity. Foodstus are the main source of exposure for the general population in Europe. The EFSA recommended that exposure to inorganic arsenic should be reduced. The main sources of inorganic arsenic intake are cereal grains and cereal based products, food for special dietary uses (e.g. algae), bottled water, coee and beer, rice and rice-based products, sh and vegetables. The highest total arsenic levels were measured in the following food commodities: sh and seafood, food products or supplements based on algae, especially hijiki, and cereal and cereal products, with particularly high concentrations in rice grains and rice-based products, and bran and germ. Values for inorganic arsenic are 0.03 mg/kg in sh and 0.1
27.22. PESTICIDES mg/kg in seafood.
2029
The EFSA estimates that the national inorganic arsenic exposures from food and water range from 0.13 to 0.56 microg/kg body weight (b.w.) per day for average consumers, and from 0.37 to 1.22 microg/kg b.w. per day. High consumers of rice in Europe, such as certain ethnic groups, are estimated to have a daily dietary exposure of inorganic arsenic of about 1 microg/kg b.w. per day, and high consumers of algae-based products can have dietary exposure of inorganic arsenic of about 4 microg/kg b.w. per day. Children under three years of age are the most exposed to inorganic arsenic. Exposure estimates reported in two dierent studies show an inorganic arsenic intake ranging from 0.50 to 2.66 microg/kg b.w. per day. The Panel noted that, since the provisional tolerable weekly intake (PTWI) of 15 microg/kg b.w. was established by the Joint FAO/WHO Expert Committee on Food Additives (JECFA), new data had established that inorganic arsenic causes cancer of the lung and urinary tract in addition to skin, and that a range of adverse eects had been reported at exposures lower than those reviewed by the JECFA. Therefore the CONTAM Panel concluded that the JECFA PTWI of 15 microg/kg b.w. is no longer appropriate and, in its assessment, focussed on more recent data showing eects at lower doses of inorganic arsenic than those considered by the JECFA. The main adverse eects reported to be associated with long term ingestion of inorganic arsenic in humans are skin lesions, cancer, developmental toxicity, neurotoxicity, cardiovascular diseases, abnormal glucose metabolism, and diabetes. There is emerging evidence of negative impacts on foetal and infant development, particularly reduced birth weight. The CONTAM Panel therefore concluded that the overall range of BMDL01values of 0.3 to 8 microg/kg b.w. per day should be used instead of a single reference point in the risk characterisation for inorganic arsenic. Of the organic forms of arsenic, arsenobetaine, which is the major form in sh and most seafood, is widely assumed to be of no toxicological concern. For other organoarsenic compounds no human toxicity data are available. The CONTAM Panel recommended that dietary exposure to inorganic arsenic should be reduced.
27.22.15
Arsenic in animal feed
[200] Regions with high geological occurrence of inorganic arsenic have been identied in particular in Asia and other non-European countries. Drinking water many contain signicant
2030
amounts of inorganic arsenic and upper limits have been set in most countries. Seafood and sh have been identied as major source of arsenic in the human diet, and in animal feed materials that contain products derived from sh or other marine organisms. In seafood and sh, arsenic is present predominantly in the organic forms of arsenobetaine and arsenocholine, which are virtually non-toxic. Data on total arsenic in feed materials do not indicate arsenic levels of concern in materials others than sh-derived products. Food derived from terrestrial animals contributes only insignicantly to human exposure.
27.22.16
Arsenic in groundwater in India
[201] High arsenic content of water and some crops of rice are of local relevance. According to Dr.Ashok Ghosh there are regions of four districts of India facing heavy contamination of ground water and irrigation water with arsenic. The districts are Patna, Bhojpur, Vaishali and Bhagalpur. Bihar has is experiencing the highes contamination of its ground water. Hand pump water was found with up to 1861ppb arsenic. This justies the need for expanding the study area to the remaining area of Bihar state, says Dr.Ghosh. Serious skin diseases and other ailmernts due to high arsenic in water, symptons of arsenicosis, were reported from the aected regions. [202]
27.22.17
Genetic engineering of rice to reduce arsenic in foods
Zhu Yong-Guan of the Research Center for Eco-environmental Sciences in Beijing, China to investigate ways in which farm practices could be changed, for instance by growing paddy rice in raised beds or engineering rice plants to shed arsenic. Other studies include aquaglyceroporins which are proteins which transport arsenic and other metals across cell membranes. A transgenic rice with modied aquaglyceroporins settings or inclusion of bactzerial enzime, arsenite S-adenosyl-methyltransferase, may reduce nal arsenic content of rice. Other strategies are being suggeste, like blending high arsenic rice with low arsenic rice from other regions of the world is being suggested. Researchers suggest to grow upland rice on dry land which absorbs far less arsenic from the soil, or to grow rice aerobically in raised beds to reduce the mobilisation of soil arsenite.
27.22.18
Antitumor eect of low levels of arsenic in treatment of brain cancer and leukemia
[203] Arsenic is a known carcinogen, however, used as drug it has therapeutic eect in the treatment of leukemia and interferes in the cellular signaling cascade, the Hedgehog pathway. Aberrant Hedgehog pathway activation is linked to cancers of diverse tissues and organs,
27.22. PESTICIDES and the tumor growth-inhibiting eects of pathway antagonists.
2031
Beachy and colleagues 2010 found that low levels of arsenic trioxide, use in treating patients with acute promyelocytic leukemia, block one of the last steps of the Hedgehog pathway, unlike cyclopamine, which acts near the beginning of the signaling cascade. Because only the tail end of the pathway is aected, a cancer cell has fewer opportunities to acquire resistance to arsenic. Cyclopamine binds to a protein on the surface of the cell called Smoothened, blocking its ability to transmit the Hedgehog signal. Arsenic trioxide acts at the end of the Hedgehog pathway blocking the ability of the Gli2 protein to induce gene transcription in the nucleus. It stops Gli2 from moving into the cells primary cilium, a communication hub, where many of the events of Hedgehog signaling take place. Without Gli2 in the cilium, the Hedgehog message is interrupted. Certain type of brain tumor, medulloblastoma which depends on Hedgehog signaling, responded to the treatment with arsenic trioxide combined with cyclopamine in cultured cells. The authors conclude that arsenic might be useful to treat some types of cancers in combination with other drugs that act at dierent levels of the Hedgehog pathway, in resistant diseases or when cyclopamine resistance take place.
27.22.19
High levels of arsenic interferes in Hedgehog pathway increasing the risk of cancer of lung, skin and bladder
[204] Karagas and colleagues 2010 point out that arsenic act as co-carcinogen activating the Hedgehog pathway, alterating its signaling and targets a transcription factor. High levels of arsenic exposure are associated with high levels of Hedgehog activity. Hedgehog protein is a signaling pathway of cancer. Exposure to arsenic increases the risk of cancer of lung, skin and bladder. Karagas and colleagues explain that arsenic activates the Hedgehog signaling by decreasing the stability of the repressor form of GLI3, which is one of the transcription factors that regulate Hedgehog activity. These ndings are important to understand the aetiology of arsenic-induced disease. Millions of people worldwide who are exposed to environmentally relevant arsenic levels, such as found in Taiwan, Bangladesh, Argentina and United States where arsenic concentrations are above the current maximum contaminant level of 10 microg/L often found in private, unregulated drinking water systems.
27.22.20
Vitamines protect from bladder cancer
[205] Brinkman and colleagues 2010 report that higher total intakes of carotenoids, vitamin D,
2032
thiamin, niacin, and vitamin E were inversely related to bladder cancer risk among older individuals. Future studies should focus on high risk groups such as heavy smokers and older individuals. This study supports the importance of diet rich in fruits, vegetables and vitamin E rich oils.
27.22.21
Increase of lung cancer at lower levels of arsenic exposure
[206] Heck and colleagues 2010 report a higher risk of small-cell and squamous-cell lung cancer induced by low levels of arsenic exposure for toenail arsenic concentration > or = 0.114 microg/g, versus < 0.05 microg/g. Other lung diseases, such as bronchitis, chronic obstructive pulmonary disease, or brosi were found associated with increased lung cancer with toenail arsenic > or = 0.05 microg/g , compared with persons with low toenail arsenic and no history of lung disease. The authors concluded that there are indications that low to moderate levels of concentrations of arsenic (< 100 microg/L) in drinking water. increase lung cancer risk, and recommend further large scale studies.
27.22.22
High-level environmental arsenic exposure reduce risk of bladder death, says the New Hampshire study
[207] Bladder cancer patients who have been exposed to high levels of environmental arsenic may have a lower risk of death compared with those exposed to low levels, according to Andrew and colleagues 2009. High toenail arsenic levels was associated with longer overall survival, the association with drinking water levels and the trend observed for bladder cancer-specic deaths were not statistically signicant. The authors also found that the protective eect of high levels of arsenic exposure applied to smokers but not to non-smokers. Arsenic exposure may be related to the survival of patients with bladder cancer. Bajorin, Halabi and Small 2009, however, reported that the use of arsenic trioxide at a dosage of 0.3 mg/kg for ve days every 28 days in patients with recurrent urothelial cancer did not reduce mortality and was associated with substantial toxicity. The authors suggest that arsenic treatment post-diagnosis is not eective. The longer survival observed in the New Hampshire study may be explained by chronic arsenic exposure inducing development of less aggressive tumor type. [208]
27.23
Agent Orange
Approximately 20 million gallons of the herbicide Agent Orange was used in Vietnam from 1962 to 1971 to defoliate trees under which the enemy was hiding or some killed crops to deprive Viet Cong and North Vietnamese troops of food. It was a mixture of:
27.23. AGENT ORANGE
2033
2,4,5-trichlorophenoxyacetic acid (2,4,5-T), contaminated with dioxin, 2,4-dichlorophenoxyacetic acid (2,4-D), cacodylic acid and picloram. 2,4-D and 2,4,5-T were developed during World War II for destruction of the enemies crop but came not in use. With the beginning of its production in 1940 it was used in large scale by farmers, foresters and homeowners to control weed and brush. A byproduct of the industrial production of 2,4,5-T was a dioxin which was the toxic cancer causing component of the Agent Orange.
27.23.1
Eects of Agent Orange on mangrove Trees
Besides the cancer causing eect of Agent Orange the herbicide killer about 36% of the mangrove trees in the Southern part of South Vietnam were killed because of their high sensitivity to it. The mangrove trees will not return without extensive reseeding. Persons exposed to herbicides similar to Agent Orange or some of its components have a high risk of Chronic LymphocyticLeukaemiaa,Diabetes, Hodgkins disease, multiple myeloma, prostate cancer, lung cancer. Highest use was in the period 1962-1971 for agricultural purposes, on lawns and turf, along rights-of-way, on private forests, to kill aquatic plants, and for other purposes. Almost everyone all over the world was in contact with this poison, a careless lack of knowledge. Other herbicides were sprayed in Vietnam varying according the season, dierent vegetation and environment.
27.23.2
Other chemicals used for military activity
During 2000, the US Congress planned to use the fungus Fusarium as a biological control agent to kill coca crops in Colombia and another fungus to kill opium poppies in Afghanistan. These plans were dropped because the rest of the world could see it as unilateral biological war. Sanho Tree is the director of the Drug Policy Project at the Institute for Policy Studies, Washington DC says the US has supplied tens of thousands of gallons Roundup to the Colombian government for use in aerial fumigation of coca crops by crop dusters to dump glyphosate over hundreds of thousands of acres in one of the most delicate and bio-diverse ecosystems in the world.
2034
27.23.3
Late sequelae of agent orange defoliant herbicide in Vietnam made by Monsanto and Dow
[209] The Vietnamese Association of Victims of Agent Orange/Dioxin (VAVA) will launch their appeal at a federal court opening on 18 June 2007 in New York against 37 US companies that produced Agent Orange, a poisonous defoliant that the US army showered forests and rice paddies with during its war against Vietnam. VAVA presented a claim against 37 companies who produced Agent Orange, among them being Dow Chemical and Monsanto, in January 2004. The claim species that the production of dioxin and other toxic substances used as weapons by US military forces against Vietnam has a direct link with extreme health problems and deformities of three millions of people in this country. In 2005, VAVAs initial case was rejected as the court determined there were no legal grounds for the trial. The US has compensated its own army veterans who have developed certain cancers since serving in Vietnam, but little has been done for the Vietnamese. In 1999, 20,000 South Koreans led a lawsuit in Korea and in January 2006, the Korean Appeals Court ordered Monsanto and Dow to pay $62 million in compensation to about 6,800 Koreans. Hai Bluhm a Vietnamese person seeking asylum in Potsdam, Germany is heavily signed by agent orange. He is one of the witnesses which will be heard by the court. The appeal is launched against the chemical factories of the defoliant because the constitution of the united States of America does not allow in this case action lawsuit to be been led against the US Government. [210]
27.23.4
Reduction of input of pesticides
The government of Ontario launched a pesticide reduction program in 1982 based on rotation of the elds between corn and soybeans. The use of pesticides went down by 40 percent. At the same time the use of pesticides in USA increased by 10 percent. More eort should be spent in order to reduce the use of pesticides developing farming knowledge.
27.24
Pollutants in milk and dairy products
Pesticides in milk have their origin in animal feed. There is much being done in Europe regarding safety of feed. The fat soluble pesticides like polychlorated hydrocarbons can contaminate easily milk. Pesticides such as insecticides, fungicides, herbicides, hexachlorobenzene (HCB) and isoOurFood Database of Food and Related Sciences Copyright 1998-2010 Karl H. Wilm. All rights reserved.
27.25. USE OF DDT FOR INDOOR SPRAYING
2035
mers of hexachloro cyclohexane (HCH) are used in agriculture or are found on the elds. Low concentration of pesticides in animal feed store in the body of animals and can be detected in the milk in high level.
27.24.1
Polychlorated biphenyl(PCB)
Chlorated hydrocarbon such as Polychlorated biphenyl (PCB) were used in the past in transformers, refrigerators, in hydraulic oil and as all round chemicals. Its level in milk has decreased after the use of PCB has been reduced. Other chlorated hydrocarbons such as polychlorated dibenzodioxine ( PCDD ) and polychlorated dibenzofurane ( PCDF ) are also present in the human milk and in the milk of cows, but not as high as Chlorine hydrocarbons ( HCB, DDT and PCB ). The identication of polychlorinated dibenzodioxins and dibenzofurans requires expensive equipment. Many countries with low budge neglect the surveillance of these contaminants.
27.25
Use of DDT for indoor spraying
[211] In September 2006 WHO issued a clear statement outlining their position on indoor spraying with long-lasting insecticides such as DDT, specifying where and how spraying will be implemented in accordance with WHO guidelines, and how they will provide all possible support to accelerate and manage this intervention eectively. According to Dr Arata Kochi, Director of WHOs Global Malaria Programme, one of the best tools against malaria is indoor residual house spraying DDT. Indoor residual spraying is the application of long-acting insecticides on the walls and roofs of houses and domestic animal shelters in order to kill malaria-carrying mosquitoes that land on these surfaces. The Presidents Malaria Initiative (PMI) is a ve-year initiative to control malaria in Africa. Announced by President Bush on June 30, 2005, it is a collaborative U.S. Government effort led by USAID The PMI used initially pyrethroids, however, Anopheles funestus developed resistance to this insecticide and the indoor residual spraying moved to DDT. Only Mozambique refused the use of DDT and accepted the use of carbamates such as Bendiocarb and Propoxu. [212]
2036
27.25.1
Insecticide-treated mosquito nets
The use of bed nets has long been encouraged by WHO, the recent development of "longlasting insecticidal nets" (LLINs) has dramatically improved their usefulness. Unlike their predecessors, the long-lasting nets need not be re-dipped in buckets of insecticide every six months as they remain eective for up to ve years without retreatment.
27.25.2
Uganda and DDT
[211] The health minister of Uganda Jim Muhwezi has told the Parliamentary Committee on Social Services that government will soon start indoor spraying of DDT. Uganda is proposing that DDT is only used indoors, and not outdoors. It will be sprayed onto the inside walls of houses and is expected to dramatically reduce the number of mosquitoes in residential accommodation. Consequently the incidence of malaria in Uganda should fall dramatically. However outdoor spraying of DDT was halted in Europe and America in the 1960s after it was discovered that it can accumulate in the food chain. The one proviso should be that government puts in place strict safeguards to ensure that no outdoor spraying of DDT takes place in Uganda. If this happened and was detected by the European Union, exports of agricultural and horticultural products could be banned.
27.26
Chlorpyrifos
The indoor exposure of young children to the semivolatile pesticide chlorpyrifos is higher than previous estimations. Gurunathan and colleagues found that the pesticide continues to accumulate on childrens toys and hard surfaces 2 weeks after spraying. [213] [214] According to a joint agreement between the U.S. EPA and the registrants of chlorpyrifosbased products Chlorpyrifos and products based on in 1997, a number of indoor uses of the pesticide, including broadcast spraying and direct uses on pets will be phased out. While crack and crevice treatment of insects (such as cockroaches and termites) by chlorpyrifos will still continue, it appears prudent to explore other insect control options, including the use of baits, traps, and insect sterilants and growth regulators.
27.26.1
The pesticide Chlorpyrifos produces brain anomalies in babies [?]
Rauth et al 2012 report that prenatal exposure to chlorpyrifos, measured in umbilical cord blood, is associated with neurobehavioural decits in humans and animals. Aected are, alertness, emotions, control of impulse and social relationship. Rauth and colleagues found
27.26. CHLORPYRIFOS
2037
in their study more than 4,39 Pikogramm Chlorpyrifos/gram umbelical blood., which is even rather low, compared to samples of the blood bank of Cincinnati whhich present an average 9,9 Pikogramm pro Gramm. High chlorpyrifos exposure was found in this study to be associated with enlargement of superior temporal, posterior middle temporal, and inferior postcentral gyri bilaterally, and enlarged superior frontal gyrus, gyrus rectus, cuneus, and precuneus along the mesial wall of the right hemisphere. Other anatomic deformations of the brain found in highly exposed babies, are consistent with deformations reported in animal models. The authors concluded that prenatal exposure to chloropyrifos, at standard use levels,causes structural changes in the developing human brain. Dow AgroSciences, the producer of Chlorpyrifos, says that the organophosphate pesticide is one of the most widely used crop protection products in the world. The company writes that chlorpyrifos is registered in about 100 countries worldwide, including the U.S., Canada, the United Kingdom, Spain, France, Italy, Japan, Australia, New Zealand, and most other developed nations. More than 50 crops, many of which are dietary staples for entire nations, are protected from insect infestation with chlorpyrifos products. [?] Foregoing studies came to the conclusion that Chlorpyrifos has neurological eects in fetuses and children even at very small amounts and inhibit their mental activity. Chlorpyrifos is being used in Germany, rst and foremost, in the production of fruits and in viticulture, but is also used for home and garden products. Hans Drexler, Director of the environmental medicine institute of the University of Erlangen says that many pregnants and small childrens in rural areas are exposed to high doses of this pesticide. Residues on agrarian products are spread to the entire population. [?] The crops with the most intense chlorpyrifos use are cotton, corn, almonds, and fruit trees including oranges and apples.
27.26.2
Mycotoxines (aatoxins)
Aatoxins such as aatoxin B1 may be present in ground peanuts or cotton seeds come in through animal feed. The cows changes the aatoxin B1 to aatoxin M1. This is why animal feed should be protected against deterioration. Feed with mould should be discarded.
27.26.3
Heavy metals
Heavy metals such as lead, cadmium and mercury are of small importance because their concentration in milk is low due to their low solubility. All eorts should be made to avoid
2038
contamination because milk is used to feed children and dairy products such as cheese or yoghurt are consumed in large scale. Concentration in human fat depot takes place.
27.26.4
Cadmium in food
[215] establishing a new Tolerable Weekly Intake level (TWI). Foodstus are usually the main source of cadmium intake for the non-smoking general population. The Panel reduced the TWI for cadmium to 2.5 micrograms per kilogram of body weight (microg/kg b.w.), based on analysis of new data. The current average dietary exposure to cadmium for adults is around this level and exposure for certain subgroups, such as vegetarians and smokers, may be higher. However, the risk of adverse eects even for groups that have exposure at levels above the TWI is very low because the TWI is not based on actual kidney damage, but on an early indicator of changes in kidney function suggesting possible kidney damage later in life. Cadmium is a heavy metal which enters the environment from natural sources, such as volcanic emissions and the weathering of rocks, as well as from industry and agriculture. It is found in the air, soil and water and can subsequently accumulate in plants and animals. Cadmium is primarily toxic to the kidney, but can also cause bone demineralisation, and has been classied as carcinogenic to humans by the International Agency for Research on Cancer. Foodstus are the main source of cadmium exposure for the non-smoking population. Cereals and cereals products, vegetables, nuts and pulses, starchy roots and potatoes as well as meat and meat products contribute most to human exposure. High levels were also found in some other foodstus (e.g. seaweed, sh and seafood, food supplements, mushrooms, chocolate) but as they are consumed to a lesser extent, they were no major contributors to exposure. The Panel concluded that the risk of adverse eects even for groups that have exposure at levels above the TWI was very low because the TWI was not based on actual kidney damage, but on an early indicator of changes in kidney function suggesting possible kidney damage later in life. The Panel also analysed data on levels of cadmium in food from 20 dierent countries, alongside national dietary surveys and EU-wide consumption data collected by EFSA. This information indicated that average and high-level exposure were 2.3 microg/kg bw and 3.0 microg/kg bw per week respectively. Vegetarians-who eat relatively high amounts of foods containing cadmium, including cereals, nuts, oilseeds and pulses - were estimated to have an average weekly exposure of up to 5.4 microg/kg bw. The Panel also stated that locally-produced food in highly contaminated areas may lead to higher exposure levels. Furthermore, dietary exposure could be higher for children than adults, due to the greater amount of food consumed by children
27.26. CHLORPYRIFOS in relation to their bodyweight.
2039
The Panel also stated that smoking can contribute to a similar internal exposure as the diet, and that house dust can be an important source of overall exposure to cadmium for children.
27.26.5
Cadmium in animal feed
[216] Dietary cadmium exposure aects the absorption of trace elements, particularly that of copper resulting in an apparent copper deciency in ruminants. In turn, high copper supplementation of feeds for pigs was considered to comprise the risk of an undesirable cadmium accumulation in the liver and kidneys, whereas zinc supplementation of feed reduces cadmium bioavailability. Within the EU maximum levels have been set for trace elements in animal diets, including copper and zinc (Commission Regulation (EC) 1334/2003). If these permissible levels are not exceeded, the overall tissue burden of cadmium is unlikely to exceed the maximum levels set for foods from animal origin under the conditions of current agricultural practice. Ruminants and horses, however, may be exposed during their entire lifespan to cadmium present in pastures. In distinct regions, this may result in an undesirable cadmium accumulation particularly in kidneys. The frequent consumption of kidney tissue from older animals (cattle and horses), as well as the frequent consumption of liver and kidneys from wildlife may thus contribute signicantly to the overall human exposure.
27.26.6
Contagious diseases
Foods bearing pathogenic bacteria viruses or other agents of diseases like BSE should be avoided through rigorous epidemiological measures. Contaminated or spoiled food should not be fed to animals. Often spoiled food and cereals are given to the production of animal feed in order to get rid of them.
27.26.7
Radioactive pollution of milk
In Europe the nuclear accident of Chernobyl had caused a considerable increase of radioactivity in milk and milk products in 1986. The amount of radioactive material which was liberated into the atmosphere was several times the amount liberated by the Hiroshima bomb in 1945. Immediately after the accident due to west bounded winds there were the following radionuclides found in West Europe: Iodine-131, cesium-134 and cesium-137 and a small amount of Strontium-90.
2040
Strontium-90 is still very high in Brazil nuts of the Amazon region originated from nuclear bomb test in Nevada, in the forties. The radioactive pollution was carried through the Stratosphere and came down as fall-out in the rain forest. These incidents show how carefully radioactivity should be handled. In milk the nuclides are concentrated in the whey and remain there. That is why whey powder was highly contaminated causing headlines. The contamination with Strontium 90 in butter was low. In whey powder due to the concentration, radioactivity can increase from 200 Bq/liter to 7.200 Bq/kg. In 1986 500 tons of whey powder were discarded in Germany having high radioactivity resulting from the concentration of cesium. In cheese the remaining cesium amount is very low. After some weeks only cesium -134 and cesium -137 were left. Low levels of radioactivity are told to increase the eciency of the DNA repair-system increasing the activity of the immune system. This is not valid for nuclide in food because they are deposited in bones and organs and with the time this material is being concentrated in the body. Damage of cells is than possible. Therefore radioactivity in food must be kept as low as possible. Pollutants in milk and dairy products in Bavaria,(South of Germany): The pollutants in milk and dairy products are being controlled over 25 years by the laboratory MUVA Kempten (Veterinary medical analytical oce of Kempten). This laboratory has monitored the organochlor-pesticides, PCB, halogenated solvents and heavy metals. The results of these analyses made it possible to nd the cause of the contamnation and helped to reduce it. At the moment most of the former pollutants of organochlor-pesticides have fallen below detection level in milk from Bavaria. Only lindan is still increased. This is an example of handling the environment problems making long term monitoring of food with the cooperation of the laboratory, the agriculture and the industry. One important concern of the laboratory is the contamination of food caused by migration of packing components into the food, such as styrol from polystyrol, dioxines from cardboard, plasticiser, heavy metals, nitrosamines from rubber, and (Bisphenyl-Adiglycidilether), problems which come from coating of tin cans. About 70% of canned food were found to be contaminated with BADGE and BFDGE (Bisphenol-A-diglycidilether) according to the French magazine "test achat". Heavy contamination was found in cans containing sh and foods with high amount of acid like lemon, vinegar or tomatoes.
27.26.8
Tolerable Daily Intake (TDI) for Bisphenol A [217]
EFSA completed its full risk assessment of BPA in 2006 and set a Tolerable Daily Intake (TDI) of 0.05 mg/kg body weight/day for this substance. EFSA has updated its scientic
27.26. CHLORPYRIFOS
2041
advice on BPA several times since 2006, reconrming the TDI in 2008, 2010 and 2011. The TDI is an estimate of the amount of a substance, expressed on a body weight basis, that can be ingested daily over a lifetime without appreciable risk. EFSA also evaluated intakes of BPA through food and drink, for adults, infants and children and found that they were all well below the TDI. In recent years, eorts have been made to reduce exposure to BPA, particularly for vulnerable population groups such as infants, children and pregnant women, and baby bottles made of BPA-containing polycarbonate plastics have been banned. EFSA will launch a call for data from Member States to provide an up-todate indication of the occurrence of BPA in food as well as the amount of BPA residue that migrates from food contact materials into food. Some multidisciplinary working groups are porforming further studies on the hazard characterisation of BPA (concerning its toxicological eects) and on exposure to BPA (how and how much BPA is absorbed by the human body). An EU cooperation with experts of USA related to BPA will improve knowledge concerning its risks.
27.26.9
Uranium in foodstus
[218] Uranium is a naturally occurring radioactive metal, which can be found in varying concentrations in the environment, water and foodstus. The Panel did not identify any new data which would have called for a revision of the TDI for uranium of 0.6 microg/kg b.w. per day established by the World Health Organisation (WHO), and therefore it endorsed this TDI. The Panel concluded that average dietary exposure to uranium for the general population and high consumers across Europe is currently below the TDI. In specic areas where uranium concentrations in drinking water are high, the exposure estimates are close, but still below the TDI. For infants fed with infant formula made up with water containing uranium, the Panel noted that exposure in relation to body weight may be up to three times higher than for adults, and concluded that such exposure should be avoided. This opinion focuses on uraniums chemical toxicity, while the radiological risk will be addressed by another Group of Experts of the European Atomic Energy Community (EURATOM). Uranium (U) is a silvery-white metal occurring in a number of minerals such as uraninite, carnotite and pitchblende. Uranium is also a naturally occurring radioactive element. Uranium can be present in water, air, food and feed in varying concentrations through leaching from natural deposits such as soil or rocks, emission from nuclear industry, nuclear weapons, dissolution in fertilizers and combustion of coal and other fuels. Tap and bottled water had mean concentrations of uranium of slightly above 2 microg/L
2042
while soft drinks had concentrations less than half of this. Concentrations in food are less representative since they are reported only from one country and there are few samples in selected categories only. The overall lower- and upper-bound uranium exposure estimates varied between 0.05 and 0.28 microg/kg body weight (b.w.) per day. For infants, the exposure scenario included mean and high consumption of infant formula reconstituted with water containing both average and high levels of uranium. The lowerand upper-bound uranium exposure estimates varied between 0.18 and 1.42 microg/kg b.w. per day, for both bottled and tap water. Toxicity of ingested uranium is related to the solubility of the uranium compound; the higher the oral uranium compound solubility is, the greater its toxicity is expected to be. The kidney is recognized as the primary target organ for uranium both in experimental animals and humans. Kidney damage results from the accumulation of uranium in the renal tubular epithelium, where it can cause cell necrosis and atrophy of the tubules, leading to a compromised tubular secretion of organic anions and reabsorption of ltered glucose and amino acids. Besides nephrotoxicity, reproductive and developmental alterations (e.g. decreased pup growth and internal/external malformations), diminished bone growth and neurotoxicity have been documented in animal models but only at higher doses. The World Health Organization (WHO) has established a tolerable daily intake (TDI) for soluble uranium of 0.6 microg/kg b.w. per day, based on the lowest-observed-adverseeect-level (LOAEL) for uranium nephrotoxicity of 0.06 mg/kg b.w. per day from a 91-day study in male rats. The Panel on Contaminants in the Food Chain (CONTAM Panel) noted that no new data were identied that would require a revision of this TDI and endorsed it. The CONTAM Panel noted that for all exposure scenarios evaluated for infants fed with infant formula reconstituted with water containing uranium, the exposure may be up to 3 times higher than the uranium exposure of adults on the body weight basis. The CONTAM Panel concluded that such exposure in infants should be avoided.
27.26.10
BADGE / BFDGE
The European Commission has completed in early 1999 a study concerning the safety of BADGE. According to this study there is no danger coming from BADGE. Therefore the Commission decided to rise the maximum allowed amount of BADGE in foods from 20 microgram in one kilogram up to 1 milligram in one kilogram food. This is intended only for tin cans coated with plastics. As there are no limits established for coatings with clear varnish, many countries use this high value also for varnished cans. The toxicology of BADGE and the catabolic products of BADGE and BFDGE are still unknown. Discarding the immersion brine can reduce Badge and BFDGE of canned foods.
27.26. CHLORPYRIFOS
2043
The cooperation between ocial supervision of food, agriculture and industry has brought good results in research and improvements since repressive supervision had been changed to open discussion and mutual good will of all parts engaged in the long way from farming to the consum.
27.26.11
Levels of dioxins and environmental pollutants PCBs in UK food
According to the survey of 2001 the total amount of dioxins in the diet has fallen by around 50 per cent for all age groups since the last survey in 1997. Exposure to dioxins in food has fallen by around 85 per cent over the last 20 years and continues to fall steadily. Polychlorinated biphenyls (PCBs) tend to accumulate particularly in foods containing fat, such as milk, meat, sh and eggs. Any potential health risks will only come from long term exposure to dioxins and dioxin-like PCBs at the highest levels found in foods.
Table 27.13: PCBs PCBs WHO TEQ/kg bw/day 1997 WHO TEQ/kg bw/day 2001 UK Tolerable Daily Intake (TDI)WHO TEQ/kg bw/day2001
average adult Children
1,8pg 1,6-5,1pg
0,9pg 0,7-2,3pg
2pg Source: FSA UK
Only 1 per cent of adults are now estimated to exceed the TDI for dioxins from the average diet, falling from 35 per cent in 1997. The percentage of schoolchildren likely to exceed the TDI for dioxins from an average diet has also fallen considerably - from 62 per cent in 1997 to 10 per cent in 2001. The percentage of toddlers likely to exceed the TDI for dioxins is now 37 per cent, falling from 97 per cent in 1997.
27.26.12
Dioxin and dioxin-like PCBs in sh oil supplements
The FSA controlling 33 products of sh oil, found a wide range of concentration of dioxins. According to the FSA, exposure to dioxins has decreased by 75 per cent over the past 20 years. Consumers should not avoid sh oils as a result of the survey, since the benets of the product far outweighed the potential risks if taken in the right amounts.
2044
27.26.13
The Food Standards Agency reviews sh advice on account of sustainability
[219] The FSA says that it is reviewing its advice on eating sh in relation to the sustainability of some types of sh to cope with the concern about the sustainability of sh stocks and the wider environmental impact of shing and sh farming. The Agencys current nutritional advice remains that consumers should be eating more sh and should be aiming to eat at least two portions of sh a week, one of which should be oily. There may be low levels of pollutants in oily sh that can build up in our bodies, so pregnant and breastfeeding women, girls and women who one day may have a baby should not eat more than two portions of oily sh a week. Others can eat up to four portions a week.
27.26.14
Organohalogens and vitamin A metabolism
Contamination of foods by organohalogens, in particular dioxins (PCDD and PCDF) and dioxin-like PCBs (polychlorinated biphenyls) PCBs are of concern. The most toxic dioxin is TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin). Dioxins and dioxin-like PCBs aect the skin, the liver, and the nervous system but also have some eect on cancer development, disturbance in the immune system and on the growth and development of the foetus. Dr. Abraham Brouwer at the Institute for Environmental Studies in Amsterdam, leading an EU project, concluded that organohalogens disturbed processing of retinoid-controlled pathways. The organohalogens cause a functional hyper-vitaminosis A with increased concentrations in plasma, liver and kidney, which can result in developmental abnormalities resembling the symptoms of excessive vitamin A intake.
27.26.15
Contaminants in baby foods
In baby food phthalat DBP and DEHP were found.They have endocrinous activities, hormone disruption.Milk used as ingredient for these products was the source of these plasticisers.(Bavaria, MUVA Kempten) Use of Phthalates as Plasticiser: Table 27.14: use of Phthalate as Plasticiser Phthalates Abbreviation
27.27. PLASTICISERS AS POSSIBLE CANCER-CAUSING AGENTS
2045
Dietylhexylphthalate DEHP Dibutylphthalate DBP Diisodecylphthalate DIDP Butylbenzylphthalate BBP Bisphenol A BPA Diisononyl phthalate DINP In Western Europe, about one million tonnes of phthalates are produced each year, of which approximately 900,000 tonnes are used to plasticise PVC (polyvinyl chloride). All eorts should be made to reduce or even to avoid the possibility of contamination of the milk on its origin.
27.27
Plasticisers as possible cancer-causing agents
BPA is a synthetic resin used in food packaging and polycarbonate plastic products. and BBP is a widely used plasticiser used in food wraps and cosmetics. These compound can leach out of the plastic and migrate into the food when plastic is heated, old or scratched According to Fox Chase Cancer Center in Philadelphia, BPA and BBP are environmental estrogens capable of aecting gene expression in the mammary glands of young female laboratory rats exposed to the compounds through their mother milk. The changes of the gene expression prole of mammary tissue changes occording to the age. The decrease of the expression of the GADI gene is one of these changes. The GADI gene encodes a key enzyme of the GABA-ergic system, which could be involved in hormonal regulation and breast cancer development. GADI has consistently been overexpressed in primary breast cancer. BBP exposure modies the genomic expression of the mamary gland, more studies are therefore necessary to see wether these estrogens can lead to cancer and its implications to human kind.[220].
Canned and plastic packaged foods increase Urine levels of BPA and DEHP metabolites Bisphenol A (BPA) and bis(2-ethylhexyl) phthalate (DEHP) exposures were substantially reduced when canned and packaged food diets were changed to "fresh foods" that were not canned or packaged in plastic, says a study of Rudel et al 2011. BPA and DEHP are used in plastics and resins for food packaging and are linked to endocrine disruption in animals and human studies. [221]
2046
No consistent conclusion of environmental exposure such as BPA link to ADHD Genetic and environmental factors are linked to attention-decit/hyperactivity disorder (ADHD). Environmental factors include heavy metals and chemical exposures, nutritional, lifestyle factors. Exposure to phthalates, bisphenol A (BPA), tobacco smoke, polycyclic aromatic hydrocarbons (PAHs), polyuoroalkyl chemicals (PFCs) and alcohol. Results of studies are not consistent. Most studies on ADHD focused on exposure to tobacco smoke, found an association, but few studies assessed the impact of phthalates, BPA, PFCs, PAHs and alcohol and do not lead to a consistent conclusion. [222] Inammation and allergy amplifying eect of phthalate esters Phthalate esters, di-(2-ethylhexyl) phthalate (DEHP) has been widely used for exible polyvinyl chloride products including vinyl ooring and wall covering and are found in the environment of houses. Tanaka et al 2012 assessed the exposure to DEHP on allergen (ovalbumin)-induced peritonitis in mice. DEHP synergistically increased the ovalbuminrelated neutrophilic inammation and allergy-related molecules (cytokines). [223] Consumer products contain complex mixtures of endocrine disruptors and asthma-associated chemicals, including parabens, phthalates, bisphenol A (BPA), triclosan, ethanolamines, alkylphenols, fragrances, glycol ethers, cyclosiloxanes, and ultraviolet (UV) lters. Dodson et al 2012 call for toxicological studies of these mixtures raising concern about the interaction of co-ocurring chemicals. The authors stress the need of a labelling of substances which some consumer try to avoid. [224]
27.28
Growth stimulating hormones in beef
Growth stimulating hormones and other chemicals are present in animal feed, beef and related products in Brazil and other developing countries. The most impportant are:
27.28.1
Dietylstilbestrol
It is a growth stimulating hormone. Zeranol (6-(6, 1C-dihydroxyundecyl) -resorcylic acid -2lactone) Non-hormonal anabolic agents for use as implants in several countries of the American continent. It is sold under the commercial brand-name of Ralgro.
27.28.2
Nortestosterone
Nortestosterone is a hormone that helps to increase protein synthesis, decrease protein breakdown, and increase workout intensity, increasing muscle size. Trembolone Trembolone acetate is a steroid having a short half life, probably no more than a day or two, though it is an extraordinarily potent AAS, being about three times as eective as testosterone esters.
27.28. GROWTH STIMULATING HORMONES IN BEEF
2047
27.28.3
Hexestrol
Is a diethylstilbestrol derivative having the uses of estrogen. Dinestrol It is an estrogen hormone.
27.28.4
Estradiol
Estradiol is the most active of the estrogens, the female sex hormones, and is responsible for the development of female sex organs and characteristics. Testosterone Testosterone is the most important representative of the male sex hormones collectively called androgens.
27.28.5
Medroxyprogesterone
It is a growth stimulating hormone. Salbutamol It is a beta sympathomimetics.
27.28.6
Clenbuterol
It promotes muscle gains as well as fat loss and weight loss.
27.28.7
Eects of Low oral doses of bisphenol A on male rats
He, Paule and Ferguson 2012 studied the eects of pre- and post-natal treatment with low bisphenol A (BPA) doses on rats. Their data indicate that BPA can have sex-specic eects on the increase of the volume of sexually dimorphic nucleus of the preoptic area (SDN-POA) in males. This eect, however, was not found in females. The authors write that BPA might lead to organizational changes within sexually dimorphic neuroendocrine pathways and alter the reproductive physiology and socio-sexual behaviour in adult rats. [225]
27.28.8
Estrogen-like Bisphenol A (BPA) found in paper and paper products [226]
Bisphenol A (BPA) is used in the production of plastics such as water bottles. It is also used to coat the inside of tin cans and is found in a in a variety of paper products, including napkins, toilet paper, tickets, food wrappers, newspapers, and printer paper. Liao and Kannan 2011 report that some paper products, such as thermal receipt papers contain very high levels of up to 13,9 mg/g BPA as colour developer. BPA levels in paper, found by the authors, were 100 to 1 million times higher in paper than amounts detected in canned and packaged foods. Their recycling is supposed to be the source of BPA in all kind of paper products. The authors estimated a daily intake (DI) of BPA through dermal absorption handling
2048
paper products of 17.5n g for the general population and 1300 ng/day for occupationally exposed individuals. Thermal receipt papers contribute over 98%) of the exposures. People like cashiers or printers who have continuously to touch a lot of BPA-tainted paper as part of their jobs are at immediate risk.
27.28.9
Biodegradation and detoxication of bisphenol A [227]
A facultative anaerobic bacterial strain, Bacillus sp. GZB, was found by Li et al. 2012 to completely degrade bisphenol A (BPA) under anaerobic and aerobic conditions. During the biodegradation seven metabolites are formed. These metabolites also present estrogenic activity which increase during the degardation process, but declines later on.
27.28.10
Alternative to bisphenpl A does not improve safety of baby bottles [228]
Bisphenol S is often used as a substitute for the production of babybottles in response to a 2011 restriction of the use of bisphenol A in Europe. Bisphenol A has a weak estrogenic activity. Bisphenol S was now found by Grignard, Lapenna and Bremer 2012 to have a comparable estrogenic-like potency.
27.28.11
Environmental estrogens genistein and bisphenol A and uterine tumorigenesis [229]
Greenhouse et al 2012 report that genistein, a soy phytoestrogen, and the plasticizer bisphenol A induce genomic estrogen receptor signaling in the uterus. However, only genistein caused estrogen-responsive genes in the adult uterus to become hyperresponsive to hormone, whereas bisphenol A repressed estrogen-responsive genes Developmental reprogramming by genistein increasing tumor incidence and multiplicity, whereas bisphenol A did not. The authors conclude that environmental estrogens have distinct nongenomic eects related with the epigenetic regulator enhancer of zeste homolog 2 (EZH2), decrease levels of the repressive epigenetic histone H3K27, and promote uterine tumorigenesis.
27.28.12
The BPA National Health and Nutrition Examination Survey (NHANES)
[230] According to Calafat and colleagfues 2008 BPA is used in the manufacture of polycarbonate plastics and epoxy resins (BPA) and nonionic surfactants (tOP) . The authors measured the total urinary concentrations of BPA and tOP in the 2003-2004 National Health and Nutrition Examination Survey. BPA and tOP were detected in 92.6% and 57.4% of the persons, respectively.
2049
The authors concluded that urine concentrations of total BPA diered by race/ethnicity, age, sex, and household income. The study should help guide public health research priorities, including studies of exposure pathways, potential health eects, and risk assessment.
27.28.13
BPA: Bisphenol A (BPA; 2,2-bis(4-hydroxyphenyl)propane)
BPA is used in the manufacture of polycarbonate plastic and epoxy resins, which can be used in impact-resistant safety equipment and baby bottles, as protective coatings inside metal food containers, and as composites and sealants in dentistry. Exposure to BPA is thought to result primarily from ingestion of food containing BPA. [231] [232].
27.28.14
tOP: 4-tertiary-octylphenol (tOP; 4-(1,1,3,3-tetramethylbutyl)ph
tOP is both a degradation product of and an intermediate in the manufacture of octylphenol ethoxylates, which are nonionic surfactants used in detergents, pesticide formulations, and other applications. Exposure to tOP may occur from contact with personal care products, detergents, water, and food containing tOP. BPA and tOP are of concern to environmental public health because of the high potential for exposure of humans to these phenols and their demonstrated animal toxicity. Exposures to tOP can result in developmental and reproductive alterations in aquatic species and in laboratory animals. At high doses, BPA demonstrates estrogen-like eects on uterine and prostate organ weights in experimental animals. At doses below the putative lowest observed adverse eect level, exposure to BPA has reportedly resulted in decreased sperm production, increased prostate gland volume, altered development and tissue organization of the mammary gland, altered vaginal morphology and estrous cycles, disruption of sexual dierentiation in the brain, and accelerated growth and puberty.
27.28.15
BPA in drinking bottles
[233] Hoa H. Le and colleagues evaluated the migratio of BPA into water stored in new or used high-quality polycarbonate bottles used by consumers. they found migration rates ranging from 0.20 ng/h to 0.79 ng/h. At room temperature the migration of BPA was independent of whether or not the bottle had been previously used. Exposure to boiling water (100o C ) increased the rate of BPA migration by up to 55-fold. The authors concluded that the amounts of BPA found to migrate from polycarbonate drinking bottles should be considered as a contributing source to the total "EDC-burden" to which some individuals are exposed.
2050
27.28.16
BPA and nonylphenol (NP) pollution a consequence of human domestic and industrial waste discharge
[234] Hodaka Kawahata and colleagues analyzed endocrine disrupters nonylphenol (NP) and bisphenol A (BPA) levels at various sites in Okinawa and Ishigaki Islands, Japan. Riverwater samples showed low to undetectable concentrations of NP and BPA, but appreciable amount of NP and BPA were detected in sediments at one coral reef site and in river sediment. The authors stress that the inuence of endocrine disrupters may have already begun on adjacent coral reefs and conclude that NP and BPA pollution is a consequence of human waste discharge, both domestic and industrial, and not by agricultural activities.
27.28.17
Sewage treatment plant euents cannot be the only sources for tech.-4-NP found in the river water in Germany
[235] Four small freshwater streams in the region known as Hessisches Ried in Germany were investigated with respect to the temporal and spatial concentration variations of the endocrine disruptors bisphenol A (BPA), 4-tert-octylphenol (4-tert-OP), and the technical isomer mixture of 4-nonylphenol (tech.-4-NP). Quednow and Pttmann 2007 found that BPA levels concentration were decreasing due to the European Directive 2003/53/EG which restricts the marketing and the use of nonylphenols [236]. Results from the analysis of additionally collected water samples from sewage treatment plant euents indicate that these euents cannot be the only sources for tech.4-NP found in the river water. The European Directive 2003/53/EG [236] aims to protect the environment and in particular the soil, when sewage sludge is used in agriculture, establishing a concentration limit value for NP and NPE in sewage sludge that is to be spread on land. In order further to protect the environment, the placing on the market and the use of NP and NPE should be restricted for specic uses which result in discharges, emissions or losses to the environment. Nonylphenol C6H4(OH)C9H19 and Nonylphenol ethoxylate (C2H4O)nC15H24O may not be placed on the market or used as a substance or constituent of preparations in concentrations equal or higher than 0,1 % by mass for the following purposes: (1) industrial and institutional cleaning except:
2051
- controlled closed dry cleaning systems where the washing liquid is recycled or incinerated, - cleaning systems with special treatment where the washing liquid is recycled or incinerated; (2) domestic cleaning; (3) textiles and leather processing except: - processing with no release into waste water, - systems with special treatment where the process water is pretreated to remove the organic fraction completely prior to biological waste water treatment (degreasing of sheepskin); (4) emulsier in agricultural teat dips; (5) metal working except: - uses in controlled closed systems where the washing liquid is recycled or incinerated; (6) manufacturing of pulp and paper; (7) cosmetic products; (8) other personal care products except:- (9) spermicides; (10) co-formulants in pesticides and biocides.
27.28.18
Meat from USA and Australia with ractopamine refused by China
Ractopamine is a beta-agonist like Clenbuterol. It is a feed additive to promote leanness in pigs raised for their meat.It was approved by the FDA in 1999 and also in countries like Australia, Brazil, Canada, Mexico, and Thailand. The EU did not approve it yet. China refused 18 tons of US kidneys of pork, and 24 tons of Canadian cutlets because of traces of Ractopamine. Only a trace amount of ractopamine need be added for a marked increase in protein and decrease in fat accretion in animals, in particular swine. For the last 90 pounds of live weight gain, a mere 18.5 grams of ractopamine added to a ton of feed (20 ppm) will increase protein by 24% and decrease fat by 34%. [237] When fed at the maximum rate (18g/ton), RAC can increase the amount of lean removed from the carcass from 51.8 to 57.5% (Schinckel et al., 2002). Schinckel found that ractopamine has a positive impact on barrows and gilts with substantially dierent genetic potentials for lean growth and carcass lean percentage, according to Schinkel. [238]
2052
27.28.19
Suspended cyclist says clenbuterol must have come from meat he eat
[239] Alberto Contador was suspended after a World Anti-Doping Agency lab in Germany found low levels of clenbuterol in probe A and B in his urine sample on July 21 at the 2010 Tour of France. Contador denied doping and insists that contaminated meat was to blame for the positive result. Clenbuterol, a beta-2-symphatomimetic, is used by athletes to strip fat and enhance muscle size, increase aerobic capacity and is a short-term stimulant. People with chronic breathing disorders such as asthma use this as a bronchodilator to make breathing easier. Clenbuterol is sometimes given illegally to cows, pigs and other animals to increase their growth rate. Should it come true that the hormone came from ingested meat concerns about food safety would rise, as consumed for a long time negative eects on human are expected, and food control system would be ineective
27.29
International trade of Pesticides
The Rotterdam Convention on for Certain Hazardous Chemicals and Pesticides in International Trade text was agreed by governments in Rotterdam in September 1998. It requires 50 ratications before it will come into force, and so far 20 governments have done so. Growth in internationally traded chemicals during the 1960sand 1970s led to increasing concern over pesticides and industrial chemical use, particularly in developing countries that lacked the expertise or infrastructure to ensure their safe use. Therefore the following organisations were founded: International Code of Conduct for the Distribution and Use of Pesticides by the Food and Agriculture Organisationn (FAO) London Guidelines for the Exchange of Information on Chemicals in International Trade by the United Nations Environment Programme (UNEP). Rotterdam Convention on the Prior Informed Consent (PIC) Procedure for Certain Hazardous Chemicals and Pesticides in International Trade September 1998. The convention covers the export and import of hazardous chemicals and, by implication, their use and regulation.In both instances, less-advantaged importing countries often lack the means to manage hazards chemicals throughout their life cycle, from importation through use and safe disposal.
27.30. LIST OF THE ROTTERDAM CONVENTION ON THE PRIOR INFORMED CONSENT OF BANNED OR SEVERELY RESTRICTED CHEMICALS 2053 Many countries also face the problem of huge quantities of unused chemicals, dumped illegally or forgotten in unsafe storage areas, which can contaminate soil, water and air. Eective disposal systems for hazardous chemicals rarely exist. This was the case of the nitrofen scandal in animal feed in Germany where a warehouse, formerly used as nitrofen storage contaminated large quantities of feed grain.
27.30
List of the Rotterdam Convention on the Prior Informed Consent of banned or severely restricted chemicals
The list covers 29 of the most hazardous chemicals, most of them pesticides. The most important are:
27.30.1
Binapacryl
It is toxic to the liver, kidney and nervous system, especially among workers in hot environments. Can cause toxic psychosis and convulsions.
27.30.2
Ethylene dichloride
Eects range from liver and kidney damage to death from pulmonary oedema. Shown to cause stomach, lung, breast and other types of cancer in animals.
27.30.3
Ethylene oxide
Exposure results in respiratory tract irritation, sleeplessness, muscular weakness, diarrhoea, nausea, conjunctivitis and neurological disorders.
27.30.4
Toxaphene
Severe poisoning provokes convulsive seizures and coma. In some cases, it leads to hyperthemia, rapid heartbeat and death.
27.30.5
Granox TBC
In July 2000, sixteen farmers in Senegal died due to intoxication with Granox TBC and Spinox T, used to protect newly planted groundnut seeds against fungus and insects.
2054
27.30.6 27.30.7 27.30.8 27.30.9 27.30.10 27.30.11
Spinox T Parathion Tetraethyl lead Tetramethyl lead Tributyltin oxide Monocrotophos
It is an insecticide that is applied in many developing countries, particularly in Asia, to control insects and spider mites and weedkiller.
27.30.12
DNOC
It is a fungicide which is highly toxic to humans.
27.30.13
.
All forms of asbestos
27.31
Annex III - Chemicals Subject To The Prior Informed Consent Procedure - Category Pesticide
2,4,5-T Aldrin Captafol Chlordane Chlordimeform Chlorobenzilate DDT Dieldrin Dinoseb and dinoseb salts 1,2-dibromoethane (EDB) Fluoroacetamide HCH (mixed isomers) Heptachlor Hexachlorobenzene Lindane Mercury compounds, Pesticide including inorganic mercury compounds, alkyl mercury
27.31. ANNEX III - CHEMICALS SUBJECT TO THE PRIOR INFORMED CONSENT PROCEDURE - CATEGORY PESTICIDE compounds and alkyloxyalkyl and aryl mercury compounds Pentachlorophenol.
2055
27.31.1
Heptachlor in feed with shmeal
[240] According to the EFSA Scientic Panel on Contaminants in the Food Chain heptachlor was commercially introduced as a non-systemic contact insecticide in 1945. It was also a major constituent (about 10%) of technical chlordane. Heptachlor was used for agricultural purposes, soil and seed treatment, wood protection and termite- and household insect control. It has been banned for use in the European Union since 1984 and in most other countries worldwide because of the persistency in the environment of the two break-down products heptachlor epoxide and photoheptachlor. All these compounds are lipophilic and particularly heptachlor epoxide and photoheptachlor tend to accumulate in the food chain.
27.31.2
Toxicity
Heptachlor shows moderate acute toxicity and heptachlor epoxide and photoheptachlor are more toxic than heptachlor. In mammals, the main target organs are the nervous system and the liver, but also the reproductive and the immune system are aected. Heptachlor and heptachlor epoxide cause liver tumours in mice, but are not genotoxic. Heptachlor is classied by IARC as possibly carcinogenic to humans (group 2B). Heptachlor is moderately or highly toxic to sh exposed via water, but no data from oral studies have been found.
27.31.3
Food chain
Amongst the species studied, the domestic hen is the most sensitive species and egg production and hatchability are the critical endpoints. Total heptachlor (sum of heptachlor and heptachlor epoxide) is not frequently found in feed commodities. When present, it is mostly in sh derived products and only very infrequently in feed materials of plant origin. Heptachlor epoxide is the predominant contaminant.
27.31.4
Human exposure to heptachlor
The present dietary exposure of the adult population to total heptachlor is below 1 ng/kg b.w. per day, which is two to three orders of magnitude below the tolerable daily intake of 0.0001 mg/kg b.w. as established by WHO in 2006.
2056
27.31.5
Recommendations
To reduce human exposure to heptachlor Scientic Panel on Contaminants in the Food Chain recommends to increase surveillance of feed: - the Besides heptachlor and heptachlor epoxide, the analyses of feed samples, especially of marine origin, should also include the determination of photoheptachlor. - In the clean-up of samples, treatment with sulfuric acid must be avoided in order to prevent the decomposition of the analytes. - Inter-comparisons performed on biological samples revealed large discrepancies in the performance of laboratories, indicating scope for improvement of the analytical methods. - Toxicity and kinetic studies in sh exposed to heptachlor and heptachlor epoxide via the diet are lacking and should be conducted. - The Members States are requested by the Commission to report the results of their monitoring programmes on undesirable substances in animal feed. - Special attention should be paid to the control of feed materials coming from areas of the world where heptachlor has recently been or still is used.
27.32
Category Severely hazardous
Methamidophos
27.33
Category Severely hazardous pesticide formulation
Monocrotophos Phosphamidon Methyl-parathion Parathion
27.34
Category Industrial
Crocidolite Polybrominated biphenyls (Hexa-, Deca-, Octa-) Polychlorinated biphenyls (PCB) Polychlorinated terphenyls (PCT) Tris (2,3-dibromopropyl) phosphate
27.35. NON DIOXIN-LIKE POLYCHLORINATED BIPHENYLS (PCB) IN FEED AND FOOD 2057
27.35
Non dioxin-like polychlorinated biphenyls (PCB) in feed and food
[241] Polychlorinated biphenyls (PCB) cover a group of 209 dierent PCB congeners which can be divided into two groups according to their toxicological properties. One group, consisting of 12 congeners, show toxicological properties similar to dioxins, is therefore termed "dioxin-like PCB" (DL-PCB), and these have been included in the "Risk Assessment of Dioxins and Dioxin-Like PCBs in Food" performed by the EU Scientic Committee on Food (SCF). The other PCB, referred to as "non dioxin-like PCB" (NDL-PCB), have not been previously evaluated by the SCF or EFSA. Both groups of PCB, NDL-PCB as well DL-PCB, are usually found in feed and food. PCB were widely used in a number of industrial and commercial applications. It is estimated that more than 1 million tons of technical PCB mixtures were produced world-wide since their rst commercial use in the late 1920s. Although produced by comparable production processes, technical PCB mixtures contain both DL and NDL-PCB and may vary considerably with respect to their congener composition due to dierences in the amount of chlorine and the reaction conditions applied. Moreover, technical PCB mixtures contain other dioxin-like compounds as impurities, such as polychlorinated dibenzofurans (PCDF). The dierent compositions as well as the presence of toxicologically relevant impurities may have a signicant impact on the results of toxicological studies with technical PCB mixtures. Although the manufacture, processing and distribution of PCB has been prohibited in almost all industrial countries since the late 1980s, their entry into the environment still occurs, especially due to improper disposal practices or leaks in electrical equipment and hydraulic systems still in use. PCB are highly persistent and are globally circulated by atmospheric transport and thus are present in all environmental media. Data on the occurrence of NDL-PCB in food and feed have been reported in dierent ways: 1. as the sum of three PCB congeners (PCB 138, 153 and 180) 2. as the sum of six PCB congeners (PCB 28, 52, 101, 138, 153, 180) often referred to as indicator PCB. The sum of these six indicator PCB represent 50% of total NDL-PCB in food, and is being used by the EU Scientic Committee on Food (SCF) 3. as the sum of seven (sum of six indicator PCB plus PCB 118).
2058
27.35.1
Accumulation of NDL-PCB and carry-over
Following exposure of farm animals, NDL-PCB will accumulate in meat, liver and particularly in fat tissues. PCB 138 and 153, both with six chlorine atoms, show the highest carry-over into milk and eggs, in the order of 50-60%. After cessation of exposure, levels in eggs and milk initially decrease rapidly to about 50%, followed by a slower elimination phase. In fattened animals like calves, piglets, and poultry, and also farmed sh, no steady state is obtained, due to the fact that these animals are slaughtered at a young age.
More than 90% of the NDL-PCB exposure in the general population is via food. Average daily dietary intakes of total NDL-PCB can be estimated to be in the range of 10-45 ng/kg body weight (b.w.) per day. Limited exposure data for young children, up to six years of age, indicates that the average intake (breastfeeding excluded) of total NDL-PCB is about 27-50 ng/kg b.w. per day. However, where data on both adults and children within a specic population were available, in general children had exposure levels 2.5 fold higher than adults. In specic subpopulations with high dietary PCB exposure such as Baltic Sea shermen the daily intake from sh of the sum of the six NDL-PCB could be about 40 ng/kg b.w., corresponding to an intake of total NDL-PCB of 80 ng/kg b.w. per day before taking into account the rest of the diet. Breastfed infants are a group of high NDL-PCB intake which might be two orders of magnitude higher than adult exposure. Other routes of exposure such as ambient and indoor air, dust and soil, do not usually contribute signicantly to the body burden of the general population. However, there are situations in which contribution from contaminated indoor air could be considerable. Technical PCB mixtures used in toxicity studies contain both NDL-PCB and dioxin-like compounds such as DL-PCB. These mixtures exert a variety of toxicological eects such as eects on liver, thyroid, immune function, reproduction and behaviour as well as carcinogenicity. The adverse eects reported in laboratory animals following exposure to individual NDL-PCB were eects on the thyroid, liver and brain biochemistry, as well as immunotoxicity, oestrogenicity, and reproductive and neurodevelopmental eects. The latter eects are particularly found in the ospring of rodents following in utero exposure. However, these eects are not all specic for NDL-PCB but are also to be seen following exposure to polychlorinated dibenzo-p-dioxins, polychlorinated dibenzofurans, and DL-PCB. Several NDL-PCB congeners are metabolised to hydroxy-PCB and/or methylsulfonyl-PCB. Some of these metabolites may contribute to hormone-like eects seen with PCB. Results of in vitro and in vivo genotoxicity studies indicate that PCB are not mutagenic at the gene or chromosome level. Some NDL-PCB, in particular the lower chlorinated congeners, caused DNA damage, probably resulting from the formation of reactive oxygen species. In two-stage initiation-promotion studies, technical PCB mixtures containing
27.35. NON DIOXIN-LIKE POLYCHLORINATED BIPHENYLS (PCB) IN FEED AND FOOD 2059 NDL-PCB as well as DL-PCB promote liver carcinogenesis in rats, following initiation with genotoxic carcinogens. Data from animal experiments with several technical mixtures (Aroclor 1016, 1242, 1254 and 1260) indicate that PCB can cause liver and thyroid neoplasms in rats. The International Agency for Research on Cancer (IARC) classied PCB in Group 2A (probably carcinogenic to humans), based on limited evidence in humans and sucient evidence in animals. Evaluation of the cancer studies in rats with technical PCB mixtures, and comparison with data obtained with TCDD, indicate that the dioxin-like components in technical PCB mixtures are likely to be responsible for the carcinogenic response of these mixtures. No peer reviewed data are available on the carcinogenicity of individual NDL-PCB congeners. Occupational exposures to PCB have been reported to be associated with an increased risk of cancer of the digestive system and possibly other sites. Some studies suggest that environmental PCB exposure may be linked to the development of breast cancer, although perhaps only in certain vulnerable sub-groups. The most sensitive eects seen in studies with individual NDL-PCB congeners in experimental animals were liver and thyroid toxicity. Considering that the "lowest observed adverse eect level" BB for the most sensitive eects (liver, thyroid) were 10 times higher than the NOAEL BB (400, 800, and 1,200 microg /kg b.w. for PCB 28, 128, and 153, respectively), the Panel chose an overall body burden of 500 microg /kg b.w. as a representative conservative body burden at the NOAEL (NOAEL BB) for all individual NDL-PCB and for the sum of NDL-PCB occurring in human tissues. Based on the median total concentration of all NDL-PCB measured in human milk sampled in European countries of about 240 nanog/g fat, and assuming 20% fat content in the human body, a median human body burden of about 50 g/kg b.w. was estimated. Consequently the overall NOAEL MoBB is about 10. During the nursing period, breastfed infants may have daily intakes, on a body weight basis, of NDL-PCB estimated to be about two orders of magnitude higher than the average adult intake. This elevated intake by the infants is related to the mothers long-term intake of NDL-PCB with food. However, the subtle neurodevelopmental eects that were reported in some studies of human infants were mainly associated with exposure to a mixture of NDL-PCB, DL-PCB, and polychlorinated dibenzo-p-dioxins/polychlorinated dibenzofurans, and any causal role of NDL-PCB is unclear. The Panel noted that in many other studies of infants, breastfeeding was associated with benecial eects, in spite of the contaminants present in human milk.
2060
27.35.2
Conclusion
In conclusion, no health based guidance value for humans can be established for NDLPCB because simultaneous exposure to NDL-PCB and dioxin-like compounds hampers the interpretation of the results of the toxicological and epidemiological studies, and the database on eects of individual NDL-PCB congeners is rather limited. There are however indications that subtle developmental eects, being caused by NDLPCB, DL-PCB, or polychlorinated dibenzo-p-dioxins/polychlorinated dibenzofurans alone, or in combination, may occur at maternal body burdens that are only slightly higher than those expected from the average daily intake in European countries. Because some individuals and some European (sub)-populations may be exposed to considerably higher average intakes, a continued eort to lower the levels of NDL-PCB in food is warranted.
27.35.3
Dichlorovos
[242] Dichlorvos is an organophosphate insecticide that acts by inhibiting acetylcholinesterase (AChE), which results in a disturbance of nerve signal transmission and induces rapid respiratory failure in most insects. The same mechanism is responsible for the acute toxicity in mammals, including humans. Dichlorvos is highly toxic by oral, dermal and inhalatory exposure (oral LD50 is 80 mg/kg b.w., dermal LD50 is 120 mg/kg b.w. and LC50 is 0.083 mg/l). It was also demonstrated to be a skin sensitizer. The only use of dichlorvos supported by one applicant is against ower bulb pests during storage. Dichlorvos has been evaluated for carcinogenicity in ve long-term studies in mice and in six long-term studies in rats. The substance was administered orally via the diet in the drinking water or by gavage, or by inhalation (one study in rats). Most of the studies provided no evidence for the induction of neoplasia and only in two gavage studies, one in F344/N rats and the other in B6C3F1 mice, was there some evidence for neoplastic responses. In these studies, increases in the incidence of mononuclear cell leukaemia in male rats, mammary broadenomas combined with adenomas in female rats, pancreatic acinar adenomas in male rats and forestomach tumours in male and female mice were reported. After considering all of the available data the PPR Panel concluded that with the exception of tumours of the forestomach in mice, there was no convincing evidence for a compound-related increase in tumour incidence. The response on mouse forestomach was a consequence of local, rather than systemic, exposure.
27.36. TRYPTOPHAN AND EOSINOPHILIA-MYALGIA-SYNDROME (EMS)
2061
The PPR Panel concluded that the available data clearly demonstrate that dichlorvos is an in vitro mutagen, and that there is some limited evidence that dichlorvos is a site-ofcontact in vivo mutagen but that the mechanism of this eect is unclear; the evidence for alkylation of DNA in vivo, a possible mechanism, is very weak. The Panel was of the opinion that the weight of evidence suggests that this would not occur at the levels of exposure that would be encountered by the proposed use of the compound. In addition severe systemic toxicity would occur before any concentration in tissues other than in the forestomach is reached that would induce the tumourigenic eect.
27.36
Tryptophan and eosinophilia-myalgia-syndrome (EMS)
Tryptophan became popular in the 1970s as a safe, nonaddictive treatment for insomnia, premenstrual syndrome and depression. [243] Tryptophan had been produced for many years using non-genetically engineered bacteria convert nutrients into L-tryptophan. In the late 1980s the company Showa Denko decided to introduce a new, genetically engineered bacterium called Strain V.to accelerate and increase the eciency of tryptophan production. The product was released without primary tests and sold in 1988. It caused the deaths of 37 people and caused 1500 more to be permanently disabled. EMS is a debilitating disease characterized by severe muscle and joint pain, weakness, swelling of the arms and legs, fever, skin rash, and an increase of eosinophils in blood. EBT (1-1-ethylidenebis tryptophan), was identied as a dimerization product of tryptophan. The high yields of tryptophan using the GM method made it possible for these compounds to react with themselves, generating the toxin. The activated charcoal used in ltering the tryptophan was reduced from 20 to 10 kilograms per batch to reduce costs. The desire to increase productivity and failing to comply with safety tests resulted in this catastrophe. Studying samples of lots which caused the EMS epidemic outbreak in 1989 using RPHPLC, six contaminant peaks were traced. Further contaminants could be classied as tryptophan metabolites, non-physiological oxidation compounds or carbonyl condensation compounds. The authors stress the fact that knowledge of the identity and formation conditions of these contaminants may help to prevent their formation in a prospective manufacturing
2062
practice to comply strict demands on purity by licensing authorities and the etiologic agent of EMS is still not been identied beyond all shadow of doubt. Simat and colleagues conclude that biotechnological processes require high purication process of the end-product because of side reactions of the fermentation. The purication process causes price dierence between tryptophan for feed or for infusion quality. The purity criteria that must be complied with, set by the European Pharmacopoeia is 400 ppm of substances which are detected at 220 nm and includes all contaminants which might be responsible for EMS disease. [244]
27.36.1
Chloropropanol in Soy sauce and vegetable hydrolyses
Chloropropanols were found in surveys of acid hydrolysed vegetable protein (acid HVP) and some soy sauces and related products. The chloropropanols are 3-monochloropropane-1, 2-diol (3-MCPD) and 1, 3-dichloro-2-propanol (1, 3-DCP). Both are suspected carcinogens. All sauces with high chloropropanols had been produced using an acid hydrolysis process. Soy sauces manufactured using only a traditional fermentation process did not give rise to the chloropropanols. It seems that acid hydrolysis was introduced to cut costs in the production of soy sauce, whereas the traditional process of fermentation was much expensive but the safe way. 3-MCPD (3-monochloropropane-1,2-diol) is a chemical which may be formed in foods by the reaction of chloride with lipids. It is the most commonly found member of a group of chemical contaminants known as chloropropanols. More recent evaluations by the European Commissions Scientic Committee on Food (SCF) and other expert committees have concluded that there is a lack of evidence of in vivo genotoxicity and proposed a provisional TDI level of 2 microg/kg body weight/day for the amount of 3-MCPD.
27.36.2
Chloropropanols in food
[245] The European Commission, in the Regulation No 1881/2006 [65], xed the limit on the level of 3-MCPD in soy sauce and acid hydrolysed vegetable protein at 20 g kg-1. This limit is for a liquid product containing 40% dry matter, corresponding to a maximum level of 50 g kg-1 in dry matter. The level needs to be adjusted according to the dry matter content of the product. It also sets the tolerable daily intake (TDI) at 2 g kg-1 bw (bodyweight). There is no EU regulation for the other chloropropanols. For 1,3-DCP, the general agreement is that its level should be kept as low as reasonably possible. 3-MCPD also represents a challenge in the production of paper towels using resin containing epichlorhydrin resulted in a high loading of 3-MCPD in the nal paper towel. Epichlorhydrin can also aect food
2063
when it is present in coating materials and 3-MCPD migrating into the food may occur such as sausage casings, tea bags, coee lter and others.
27.36.3
Deep frying palm oil contaminants increase risk of benign tumour and kidney damage
[246] The German kotest journal reports contaminants in French fries which increase risk of benign tumour and kidney damage, such as 3-MCPD-Ester and carcinogen glycidylester. Palm oil used for deep frying of the potato products is the source of these contaminants which are formed during rening of palm oil and can be found in foods containing this fat, such as margarine and fried products. The German Institute for Risk Assessment (BfR) in a report of 2009 warn of these contaminants [247]. Palm oil is also considered as unhealthy because of its high amount of saturated fatty acids. Buhrke and collegues 2011 [248] compared dierent analysing methods of these contaminants. They report that glycidyl esters is present only in rened, but not in crude or native, fats and oils. Palm oil and palm oil-based fats had highest concentrations on glycidyl esters, varying according to dierent deodorization parameters, temperature, and time, while 3-MCPD ester concentration was relatively constant. The authors suggest that formation of glycidyl esters, but not 3-MCPD may be reduced by optimizing rening parameters.
27.36.4
Dietary exposure to 3-MCPD
[249] 3-Mono-chloropropane-1,2-diol (3-MCPD) is a contaminant that occurs in food in its free (diol) form as well as in an esteried (with fatty acids) form. Seefelder et al. 2008 found that the yield of 3-MCPD from a 3-MCPD monoester was high, but the release from the diesters was slow. The slow release of 3-MCPD from 3-MCPD diesters, and the mono- to diesters ratio suggest that 3-MCPD esters may in fact contribute only marginally to the overall dietary exposure to 3-MCPD.The authors call for more research on the bioavailability, metabolism and possible toxicity of these chloroesters.
27.36.5
Formation of MCPD and glycidyl esters
[250] Haines and colleagues 2011 reports that. MCPD monoesters were not found in any oil samples. MCPD diesters were found only in samples containing palm oil, and were not present in all palm oil samples. Glycidyl esters were found in a wide variety of oils. Monochloropropanediol (MCPD) and MCPD esters were known to form from glycerol released from triacylglycerols treated with hydrochloric acid. Baer et al 2010 stress the concern related to the carcinogenic properties of 3-MCPD the contaminants regardless of low levels as it it found in a variety of foodstus. To minimize the formation of 3-MCPD the authors suggest to raising the pH of high moisture content
2064
food, reduce the processing temperature and salt content of the food, avoid low-water/hightemperature treatments, limit the amount of glycerol produced in the food during process and storage, avoid the use of partial glycerides as additives, use spice extract instead of native spices, or reducing the microbial load via thermal treatment, conrm the purity of food additives, Inactivation of lipases/esterases and screen food contact materials for 3-MCPD precursors. [245]
27.36.6
The International Life Sciences Institute (ILSI) report on 3-MCPD esters
[251] According to a report from the International Life Sciences Institute, ILSI 3-MCPD esters are formed at high temperatures during the rening of edible fats and oils, mainly during the deodorisation step, in presence of chloride ions, glycerol, tri-, di- or monoacylglycerides, depending on temperature and time. According to a 2009 report from the International Life Sciences Institute (ILSI), high levels of 3-MCPD esters are being found in rened edible fats, such as margarine and oils, and in fat-containing foods including infant formula and human milk. The major chloropropanol is 3-chloro-1,2-propanediol (3-MCPD). It is formed when fat- and salt-containing foods are processed at high temperatures during production. The 3-MCPD esters are formed in all rened oils and fats during the rening, mainly during the deodorisation procedure in presence of chloride ions, glycerol, tri-, di- or monoacylglycerides, depending on temperature and time. Rened palm oil contains 4.5-13 mg/kg 3-MCPD esters, together with other thermally processed foods like French fries, toasted bread, bread crust, donuts, salty crackers, roasted coee, roasted chicory (coee surrogate), roasted barley, roasted dark malt and coee creamer, and in fermented foods like pickled herring and sausage, whose levels of free 3-MCPD vary between 0.2 and 6.6 mg/kg. Soy sauce and soy-sauce based products are the main source of 3-MCPD. The European Commission, therefore, limited the maximum allowed content of 3-MCPD in hydrolysed vegetable protein and soy sauce to 20 g/kg of product . Some other foods eaten in large quantities, such as bread and noodles, also contributed signicantly to intake because of high consumption of these foods.
27.36.7
Conotoxins
[252] A conotoxin, discovered in venom from the sh-eating cone snail Conus magus or magicians cone, made it possible to develop a pain treatment medicine, Prialt. Cone shells are carnivorous; they eat other mollusks, worms, or sh. Cone shells are predominantly nocturnal, burrowing in the sand and coral during the daytime. The cone
2065
shells injects paralytic and lethal oligopeptide toxins in its preys,The venom mixture is specic to each cone shell species, containing 30-200 conotoxin peptides. alfa-conotoxin attacks acetylcholine receptors at nerves and muscles. delta-conotoxin inhibits the inactivation of voltage-dependent sodium channels. kappa-conotoxin inhibits potassium channels. -conotoxin inhibits voltage-dependent sodiumm ion channels in muscles. omega-conotoxin inhibits N-type voltage-dependent calcium channels. Because Ntype voltage-dependent calcium channels are related to algesia (sensitivity to pain)in the nervous system, omega-conotoxin has an analgesic eect: the eect of omegaconotoxin M VII A is 100 to 1000 times that of morphine. Therefore omega-conotoxin M VII A is used as an analgesic drug named ziconotide; it is marketed under the brand name Prialt. [253] According to Michael McIntosh, a new alpha conotoxin OmIA isolated from a cone snail species named Conus omaria was discovered. The conotoxin blocs nicotinic acetylcholine receptors. It activates production of the hormone dopamin which is decient in Alzheimer patients. Conotoxins will be a useful tool in designing new medicines for a variety of brain disorders, including Alzheimers and Parkinsons diseases, depression, nicotine addiction and perhaps schizophrenia.
27.36.8
Novel Class of Nicotinic Receptor Antagonists from snail Conus
[254] The venoms of predatory marine snails (Conus spp.) contain diverse mixtures of peptide toxins with high potency and selectivity for a variety of voltage-gated and ligand-gated ion channels. The authors describe the chemical and functional characterization of three novel conotoxins alfa D-VxXIIA, alfa D-VxXIIB, and alfa D-VxXIIC which are potent inhibitors of nicotinic acetylcholine receptors (nAChRs).
27.36.9
What to eat and drink in case of food poisoning
Food poisoning may be cause by chemicals (pesticides, heavy metals ...), bacteria (Salmonella, Shigella...)or their poisons (Staphylococcin...). Appropriate medication is necessary. See your doctor. Mineral water cannot harm. Eat as little as possible. Take the food you have appetite for. Follow the diet given by your doctor.
2066
27.36.10
Pyrrolizidine alkaloids as undesirable substances in animal feed
[255] The European Food Safety Authority released an opinion concerning pyrrolizidine alkaloids (PAs), a group of more than 350 individual compounds that share as a basic structure one of the four necine bases platynecine, retronecine, heliotridine, or otonecine. PAs are produced as secondary metabolites of more than 6000 plant species, belonging to the families of Boraginaceae, Compositae (Asteraceae) and Leguminosae (Fabaceae) and occur worldwide. Basic alkaloids seem to accumulate in the seeds, whereas the respective N-oxides dominate in the green parts of a plant. In farm animals, however, acute intoxications caused by PAs are rare, as animals avoid PA containing plants if other feed is available. However, this recognition fails in preserved forages such as silage and hay.
27.36.11
PAs intoxication in animals
Acute intoxications: hepatotoxicity and hemorrhagic liver necrosis. Long-term exposure: hepatic megalocytosis, veno-occlusion in liver and to a lesser extent in the lungs, proliferation of the biliary tract epithelium, fatty liver degeneration and liver cirrhosis.
27.36.12
PAs intoxication in humans
In humans, PAs cause primarily hepatic veno-occlusive disease (VOD). Toxicological concerns about the potential human exposure to PAs were based on the results of extensive rodent studies indicating a carcinogenic potential of this class of compounds, and on the in vitro investigations that convincingly demonstrated that the dehydropyrrolic metabolites of PAs can form DNA-adducts, DNA-cross links and DNA-protein cross links, and result in genotoxicitiy and mutagenicity in a variety of bioassays conducted in rodent models.
27.36.13
PAs carry over in food
PAs are excreted with milk of dairy cows (and lactating sheep) albeit at a low rate, varying between 0.04 and 0.08% of the ingested dose. Analyses in Australia indicated the presence of certain PAs in eggs. No residues have been found in other animal tissues. The contribution of the residues in animal derived tissues to human exposure is low; however, honey, in which PA residues are regularly found, deserves special attention.
27.37. VETERINARY MEDICINE RESIDUES IN EGGS AND POULTRY MEAT 2067
27.37
27.37.1
Veterinary medicine residues in eggs and poultry meat

Nicarbazin in eggs
[256] According to a report from the UK Food Standards Agency into the possible causes of nicarbazin residues in chicken. Nicarbazin is a medicated feed additive used to treat a debilitating poultry disease called coccidiosis. Nicarbazin is a coccidiostat used to treat a protozoan disease, coccidiosis, that can be debilitating or even fatal to poultry. It is used as a feed additive to control the disease at a critical period of the birds lives but should not be used within ve days of the birds slaughter. This ensures no appreciable residues of it remain in chicken for human consumption. It is combined in equal amounts with another coccidiostat, narasin, in the only UK-licensed product that contains nicarbazin, Maxiban. Residues can be found in poultry meat but are more common in poultry liver. Neither is a signicant food safety risk at the levels found, but can be avoided with good farm practice. A UK action level for residues has been set at 200 g/kg based on international Joint FAO/WHO Expert Committee on Food Additives (JECFA) considerations. Residues over 1000 g/kg are investigated on-farm by Animal Health, as this amount suggests a possible failing in feed management. This recent investigation considered all detectable residues, including those below 200 g/kg, which greatly increased the amount of data available to assess risk factors.
27.37.2
Nicarbazin application as an infertility agent
[257] Nicarbazin was tested in 2004 in eld studies on its ecacy to support its registration by the Environmental Protection Agency (EPA) as a reproductive control agent for Canada geese. As a reproductive inhibitor for Canada geese in baits with contraceptive doses it reduces hatchability of eggs about 51 per cent. This is intended to reduce the population of at airports and resorts
27.37.3
Nicarbazin testing
[258] According to Andrew Cannavan and colleagues 1999 nicarbazin is a mixture of 4,6-dimethyl2-hydroxypyrimidine (DMHP) and 4,4A-dinitrocarbanilide (DNC) It is licensed for use as a feed additive, at concentrations of 100-125 mg kg, in broiler chickens up to a maximum age of 28 days. The treatment must be withdrawn for at least 9 days prior to slaughter. Nicarbazin is not licensed for use in commercial egg-laying chickens in the UK, and
2068
consequently eggs should be free from nicarbazin residues. A joint FAO/ WHO Expert Committee recommended the use of DNC alone as the marker residue for nicarbazin, and xed a maximum residue limit (MRL) of 200 mg kg21 in broiler chicken tissues. Cross-contamination of feed of mill production lines can cause unwanted residues in eggs and broiler chickens. The authors describe a method for the determination of nicarbazin in feeds using liquid chromatography-electrospray mass spectrometry (LC-ESI-MS).
27.37.4
Testing method of Eggs and meat
[259] Huet and colleagues 2005 write that accidental cross-contamination of feed can lead to residues of these compounds in eggs and/or muscle. They developed an ELISA method to screen for halofuginone and for dinitrocarbanilide (marker residue for nicarbazin) in eggs and meat.
27.37.5
Halofuginone hydrobromide in chicken and turkeys
[260] Halofuginone hydrobromide is a non-ionophoric plant-derived quinazolinone compound that is authorised as a coccidiostat feed additive for use in chickens for fattening, chickens reared for laying up to 16 weeks of age, and turkeys up to 12 weeks of age at a minimum-maximum concentration of 2-3 mg/kg in complete feed (Regulation (EC) No 2004/C 50/01). Despite the requirements set for feed business operators in Regulation (EC) No 183/2005, it is generally acknowledged that under practical conditions during the production of mixed feeds, a certain percentage of a feed batch remains in the production circuit and these residual amounts can contaminate the subsequent feed batches. This cross-contamination may result in the exposure of non-target animal species, and hence the potential health risks for non-target animal species as well as the potential residue deposition in foods derived from these non-target animal species have been evaluated. Accidental ingestion of feed intended for chickens or turkeys containing halofuginone at the maximum authorised level of 3 mg/kg feed, could present a health risk for several nontarget animal species, including rabbits, geese, partridges and quails, which might react with feed refusal and decreased body weight gain. This dose could also cause mortality in partridges. The Panel on Contaminants in the Food Chain (CONTAM Panel) conclude that adverse health eects in non-target animals are unlikely to occur as a result of cross-contamination of feed up to a hypothetical level of 10% of the maximum authorised level of halofuginone in feed for target animals.
27.37. VETERINARY MEDICINE RESIDUES IN EGGS AND POULTRY MEAT 2069 No kinetic or occurrence data were available to estimate the amount of halofuginone hydrobromide residues in milk, meat or oal from non-target animal species. Hence, consumer exposure was estimated using data from eggs and kinetic data from chickens for fattening at practical zero withdrawal time. The data were extrapolated to a concentration of 0.3 mg/kg feed to correspond to feed cross-contaminated with halofuginone at a level of 10% of the maximum authorised level. Using a food basket approach for foodstus of animal origin, the maximum human exposure level was estimated to be 0.1 g/kg b.w. from eggs and 0.29 g equivalents/kg b.w. for a 60 kg person) from liver, kidney, muscle and skin/fat. Due to the unknown nature and toxicity of the residues in avian species, the CONTAM Panel could not reach conclusions on the potential impact for consumers of such exposure.
27.37.6
Bitter apricot kernel warning
[261] The German Federal Institute for Risk Assessment says that bitter apricot kernels can lead to poisoning. These kernels are being sold increasingly on the Internet. In some cases it is claimed that they can help to ght cancer.[262] However, there is no scientic evidence to back this claim. [263] [264] According to the German Federal Institute for Risk Assessment bitter apricot kernels have a high natural level of amygdalin. During digestion hydrocyanic acid is released from the glycoside which can lead to severe, acute poisoning. At high doses it can even prove fatal. Hence, bitter apricot kernels may involve health risks. Eating just a few kernels can already lead to the onset of acute poisoning symptoms. [261] Consumers should not, therefore, eat more than one or two bitter apricot kernels a day or even none at all for precautionary reasons. Unsubstantiated health claims, which could encourage desperate sick people to buy them, are irresponsible. [261] Amygdalin (called here vitamin B17)has been studied by FDA in USA and found useless to ght cancer. [265] The claim cancer cells have within them an enzyme which unlocks the poison in the amygdalin, and in this way the cancer cells are destroyed. Normal, healthy cells do not have this enzyme. Is not backed by any study. [264] Acute cyanide intoxications may arise from eating apricot kernels, choke cherries, and other stone fruit kernels with high concentrations of cyanogenic glycosides. Inadequately prepared cassava, when constituting the major part of the diet, may be hazardous. Amygdalin is also present in some sorts of cassava. [265]
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27.37.7
Fresh salat contaminated with poisonous groundsel
[266] The German Federal Institute for Risk Assessment (BFR) found owers and leaves from the common groundsel (Senecio Vulgaris L) in fresh salad ready too eat mix of radicchio, frisee and lambs lettuce. Groundsel is a poisonous plant which recently grows together with radicchio and other lettuce types because some herbicides which control groundsel were prohibited. The plant produces senecionin and riddelin , which belong to the group of unsaturated pyrrolizidin alcaloids (PA). These alcaloids were found to be carcinogenic and mutagenic. Producer and consumer should wash carefully lettuce and discard all pieces of extraneous plants. Photography of Senecio Vulgaris L.: http://wisplants.uwsp.edu/scripts/detail.asp?spcode=SENVUL
27.37.8
Nitrofurans in Shrimps from Bangladesh
[267] Import of frozen shrimp and sh from from Bangladesh are threatened because of high contents of nitrofurans . The EU introduced strict laws against the presence of nitrofurans in food and rejected food with nitrofurans above zero level. The United States admits hat is 0.3 parts per billion as permissible level for nitrofurans. Imports of sea food may be stopped as the Bangladesh government does not pay attention to the matter. The problems with nitrofurans are known since 2005.
27.37.9
UK FSA response to nitrofurans in shrimps
[268] Test results have been received on warm water prawns and shrimps from SE Asia. The test results revealed that 16 out of the 77 samples of tested positive for illegal and unacceptable residues of nitrofuran drugs. These drugs are no longer permitted in the European Union for use in food producing animals. This is because of concerns including a possible increased risk of cancer in humans through long-term consumption. The shrimps and prawns that were found to contain these residues are from Thailand, Vietnam, Indonesia, India and Bangladesh. Most of the samples with residues were tiger prawns and king prawns and not the cold water types which are used in the UK to make sandwiches and prawn cocktails. The aected batches are being recalled.
27.37.10
Illegal use of nitrofurans in Portugal
[269] Although nitrofurans in food production are forbidden in the EU illegal use may still continue. According to a report from Antunes, Machado and Peixe 2006 indiscriminate
27.37. VETERINARY MEDICINE RESIDUES IN EGGS AND POULTRY MEAT 2071 use of nitrofurans might be implicated in the emergence in Portugal of two multiresistant Salmonella Typhimurium and of Salmonella Enteritidis in poultry industry. These bacteria presented a decreased susceptibility to nitrofurantoin.
27.37.11
Drugs contaminate US drinking weater from California to New York
[270] According to an investigation of Associated Press published by the Washington Post on March 10, 2008 pharmaceuticals such as antibiotics, anti-convulsants, mood stabilizers, acetaminophen Carbamazepine, Monensin (antibiotic administered to cattle), Sulfamethoxazole (antibiotic used in humans and animals), ibuprofen, chemotherapy drugs, and sex hormones (such as used in the anti-baby pill) are found in the US drinking water supplies. Water authorities say that the water is safe because it is far below the levels of a medical dose. However, scientists are worried about long-term consequences to human health. The article explains that pills and medicine taken all over the country is almost entirely eliminated by the body and is ushed down the toilet. Wastewater treatment does not eliminate these drugs and they are discharged into reservoirs, rivers or lakes and return as tap water. According to Benjamin H. Grumbles, assistant administrator for water at the U.S. Environmental Protection Agency EPA recognizes this contamination as a growing concern.
27.37.12
Peruorinated chemicals may reduce human fertility
[271] Fei, McLaughlin, Lipworth and Olsen found peruorooctanoate (PFOA) and peruorooctane sulfonate (PFOS) to be hormonal disruptors. Both belong to the group of peruorinated chemicals (PFCs), and are used in food packagings, such as grease-resistant packaging for microwave popcorn bags and pizza boxes, other applications are in the eld of pesticides, clothing, carpets and personal care products, industrial surfactans emulsiers and products like Teon. PFOS may be concentrated in the food chain. According to the study, women who had higher levels of peruorooctanoate (PFOA) and peruorooctane sulfonate (PFOS) in their blood took longer to become pregnant than women with lower levels. If the ndings of Fei and colleagues will be reproduced by other studies, the compound will have to be added to the list of risk factors for infertility. The authors say that Mens sperm may also be aected by PFCs and contribute to the associations between PFC levels and time to pregnancy, however, however, data on PFC eects in fathers are not available yet.
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The biological mechanisms by which exposure to PFOS and PFOA might reduce fertility are unknown, but interference in menstrual period indicate a possible pathway. The authors concluded that exposure to PFOS and PFOA at levels plasma levels common in the general population in developed countries may reduce fecundity.
27.37.13
Greaseproong chemicals used in wrapping materials and popcorn bags are source of contaminants in food
[272] Deon and Mabury 2010 write that polyuoroalkyl phosphate esters (PAPs) are chemicals used in food wrappers and microwave popcorn bags. These chemicals migrate to the food and digestion breaks them down forming peruorinated carboxylic acids (PFCAs), such as peruorooctanoic acid (PFOA). PAPs are found in kitchen pans, clothing and food packagings like pop-corn bags, used as greaseproong agents. In this study the authors demonstrated that PAPs are the major source of human PFCA exposure, resulting from food contact applications. Findings of PFOS in the environment should not divert the attention from packaging material as an important source of these contaminants, say the authors. In this study data of PAP concentrations in human blood, together with the PAP and PFCA data from experiments with rats were used to calculate human PFOA exposure from PAP metabolism. Reacting to the results of latest studies, the government of Canada, the United States and Europe begin monitoring programs for these chemicals and their use in packaging materials.
27.37.14
Peruorinated compounds in environment, biota and humans
[273] Peruorinated compounds such as peruorooctane sulfonate (PFOS) and peruorooctane acid (PFOA) are environmental pollutants of global importance. Suja, Pramanik and Zain 2009 describe distribution, bioaccumulation and toxic eects of PFOS and PFOA in the tap and surface water. PFOS and PFOA were detected globally in the tissues of sh, bird and marine mammals and humans, demonstrating a global bioaccumulation in the ecosystem. The authors write that atmospheric transport of these compounds might explain the worldwide distribution of these compounds.
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27.37.15
Data remain controversial
[274] Negri and colleagues, in a 2008 review found that research on health eects of peruoroalkylcompounds (PFOA) on possible endocrine disruption, thyroid and liver carcinogenicity, and development alteration remain controversial. Environmental Protection Agency (EPA) established in 2006 that every PFOA emission will be eliminated before 2015.
27.37.16
EFSA calls for more studies on PFOS and PFOA
[275] According to an opinion of the European Safety Agency in 2008, that sh seem to be an important source of human exposure to PFOS and also contribute to human exposure to PFOA. The agency, however, stresses that ndings may be inuenced by an overrepresentation of studies from polluted areas. The Panel of the EFSA concluded that the general population in Europe is unlikely to suer negative health eects from PFOS and PFOA, but high consumers of sh might slightly exceed the TDI for PFOS. The Panel called for further research on contamination of foods and feeding stus of these compounds.
27.37.17
Thiacloprid in strawberries
[276] Bayer CropScience B.V made an application to modify the existing MRL for the active substance thiacloprid in strawberries, raising the existing MRL in strawberries from 0,5 mg/kg to 1,0 mg/kg. Residue eld trials indicate that a higher EC MRL of 0,7 mg/kg for strawberries would be necessary to accommodate the intended use of thiacloprid. EFSA concluded that no signicant residues are expected provided that thiacloprid is applied according to the intended use. Residues in commodities of animal origin were not assessed in the framework of this application since the crop under consideration is not a livestock feeding item. Therefore the EFSA proposes the EC MRL of 0,7 mg/kg of thiacloprid in strawberries.
27.37.18
EPA Moves to Terminate All Uses of Insecticide Endosulfan to Protect Health of Farmworkers and Wildlife
[277] Endosulfan, a highly controversial organochlorine insecticide and acaricide. It is registered since the 1950s. It is used also is used on vegetables, fruits, cotton, ornamental shrubs,
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trees, and herbaceous plants. The U.S. Environmental Protection Agency (EPA) is taking action to end all uses of the insecticide in the United States, causing an unacceptable neurological and reproductive risks to farmworkers and wildlife and can persist in the environment. According to EPA the new data show that the risks are greater than previously known for farmworkers, aquatic and terrestrial wildlife, as well as to birds and mammals that consume aquatic prey which have ingested endosulfan. Endosulfan is used on a very small percentage of the U.S. food supply and does not present a risk to human health from dietary exposure. Makhteshim Agan of North America, the manufacturer of endosulfan, is in discussions with EPA to voluntarily terminate all endosulfan uses. The WHO estimates that the worldwide production of endosulfan is 12,800 tons per year. Due to its acute toxicity, potential for bioaccumulation, and role as an endocrine disruptor it was banned in more than 62 countries, including the European Union and several Asian and West African nations. It is still used extensively in many other countries including India, Brazil, and Australia. It is produced by Bayer CropScience, Makhteshim Agan, and Government-of-India-owned Hindustan Insecticides Limited among others. Because of its threats to the environment, a global ban on the use and manufacture of endosulfan is being considered under the Stockholm Convention. [278]
27.37.19
Bayer will terminate all uses of Aldicarb in USA by 2018
[279] According to a new risk assessment conducted by the U.S. Environmental Protection Agency aldicarb, an N-methyl carbamate insecticide may pose unacceptable dietary risks, especially to infants and young children. Aldicarb is registered for use as a systemic insecticide and nematicide on agricultural crops. The Agency and Bayer CropScience reached an agreement on 17.August 2010 to end use of the pesticide aldicarb sold in the United States under the name of Temik by Bayer. Bayer will rst end aldicarb use on citrus and potatoes and will adopt risk mitigation measures for other uses to protect groundwater resources. New measures to protect shallow drinking water wells in vulnerable areas of the southeastern U.S. coastal plain and lower application rates will be immediately added to product labels for use on cotton, soybeans, and peanuts. The production of aldicarb will be phased out by December 31, 2014. All remaining aldicarb uses will end no later than August 2018.
27.37. VETERINARY MEDICINE RESIDUES IN EGGS AND POULTRY MEAT 2075 Aldicarb at levels higher than those typically found in food has the potential to cause various eects such as sweating, nausea, dizziness and blurred vision, abdominal pain, vomiting, and diarrhea. Aldicarb is registred in more than 50 countries including Australia, Brazil, Latin America, South Africa and USA. Essential uses status in European Union.
27.37.20
Human Biomonitoring rises concerns about exposure to certain plasticisers
[280] Human biomonitoring surveys investigate public exposure to chemicals and other harmful environmental impacts detrimental to public health, provides data on which substances are absorbed by the human body and at what levels, whether there are certain population groups which are particularly aected and whether chemical policy regulations have led to the desired decrease in exposure. Federal Environment Minister Norbert Roettgen noted at the Conference at Berlin 2628.09.2010: "Human biomonitoring is an excellent early warning system to detect pollutants harmful to the public at an early stage. It gives us the opportunity to monitor the successes of our chemicals policy and to determine those areas where action is most needed. The need of strengthening of international cooperation in the eld of biomonitoring to prevent an exposure of public health to numerous environmental chemicals which are used on a global scale by refusing to approve the use of problematic substances in products. The Ministry says that exposure to chemicals such as lead cadmium, DDT and dioxins has considerably dropped in Germany. However, concerns remain about the elevated exposure of children to certain plasticisers extensively used in plastic manufacturing. Some of the detected chemicals include Lead Mercury Arsenic Perclorate Triclosan Persistent organic pollutants Dioxins Furans Organochlorine pesticides DDT and DDE Peruorinated compounds Bisphenol A (BPA) Polybrominated diphenyl ethers (PBDE) Polybrominated biphenyls (PBBs) Phthalates Oxybenzone (Benzophenone-3)
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27.37.21
Cancerogenous and allergenic substances in Bubble tea sold in Germany in August 2012 [281]
Bubble tea is a Taiwanese iced tea beverage lled with chewy globules of tapioca which is being launched in Europe was found to be contaminated with chemicals which may cause cancer and allergies. Scientists of the Institute of Hygiene and Environmental Medicine of the University Aachen examined nine varieties of bubble-tea on sell at a restaurant chain. In all varieties styrol, acetophenon and bromated substances were found in signicant concentrations. The researchers explain that these poisons develop during unclean production process of aroma compounds in Taiwan and are used as ingredients of the tapioca bubbles. According to McDonalds McCafe the company launched June 2012 a bubble-tea line in German restaurants. The bubble tea is a Taiwanese iced tea beverage lled with chewy globules of tapioca. [282]
27.37.22
High content of sugar in Bubble Tea [283]
There are also concerns about the high sugar content of bubble tea varieties. The Mango Bubble Tea, for instance, has 90 grams of sugar in a 500 ml cup. The WHO advices not to consume more than 50g sugar/day/adult person.
27.37.23
Phthalates in Bubble-Tea in Taiwan 2011 [284]
Also plasticizer Di(2-ethylhexyl) phthalate (DEHP) has been detected in the products of manufacturers of food and drinks that unknowingly used the tainted Taiwan emulsier that is commonly used in fruit jelly, yogurt mix powder, juices and other drinks. Products are being recalled. Investigations show that the tainted emulsier products were either produced by Yu Shen Chemical Co or came from intermediaries supplied by the company. Some of the tainted ingredients and products were believed to have been exported overseas.
27.37.24
Phenylbutazone
Residues of phenylbutazone in horsemeat is of low concern for consumers, says EFSA [285] The European Food Safety Authority (EFSA) and the European Medicines Agency (EMA) considers the illegal presence of residues of phenylbutazone in horsemeat to be of low concern for consumers due to low exposure and low likelihood toxic eects. The level of phenylbutazone that could be considered safe in food of animal origin could not be evaluated by EMA in 1997 and a maximum residue limits (MRLs) in food products
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could not be established. Therefore animals treated with phenylbutazone are not allowed to enter the food chain. The use of phenylbutazone in the food chain should remain prohibited. The EFSA and the EMA recommend to further reduce the risk of this substance entering the food chain, focusing on measures to strengthen traceability. At focus are a reliable identication system for horses and other so-called solipeds, harmonising checks of phenylbutazone, improving the reporting of monitoring data for its possible presence in foods, and report data on the presence of residues of veterinary medicines in live animals. Beef products had been found adulterated with horsemeat. Some horse carcasses illegally entering the food chain contained the anti-inammatory drug phenylbutazone. Toxicity of phenylbutazone Phenylbutazone is used in human medicine for the treatment of patients with severe rheumatoid arthritis and has been linked to rare occurrence of a blood disorder, aplastic anemia. Genotoxicity of phenylbutazone can not be excluded but is considered unlikely. The risk of carcinogenicity is of very low concern given the estimated infrequency of consuming horsemeat and low exposed through the diet.
Bibliography
[1] Bennett D Vogt AND, Cassady D, Frost J, Ritz B, and Hertz-Picciotto I. Cancer and non-cancer health eects from food contaminant exposures for children and adults in california: a risk assessment. Environ Health, 11(1):83, 11 2012. http: //www.ncbi.nlm.nih.gov/pubmed/23140444. [2] Strasburger,E.; Noll,F; Schenk,H; Schimper,A.F.W: Lehrbuch der Botanik fr Hochschulen.28.Auage Gustav Fischer Verlag,Stuttgart,1965. [3] Streble,Heinz;Krauter, Dieter: Das Leben im Wassertropfen, Mikroora und Mikrofauna des Ssswassers. Ein Bestimmungsbuch.7.Auage,Stuttgart;Franksche Verlagshandlung (Kosmos Naturfhrer). [4] Luckas,B.: Einsatz Chromatographischer Verfahren mit selektiver Detection zur Kontrolle von Seafood auf Algentoxine,GIT Labor-Fachzeitschrift 5/98 page 482. [5] Seehunde an giftige Alge gestorben?; Jeversches Wochenblatt Nummer 114, 19.05.99, page 8.
2078
[6] http://www.ncbi.nlm.nih.gov/pubmed/19615398. Zimba PV, Moeller PD, Beauchesne K, Lane HE, Triemer RE: Identication of euglenophycin-A toxin found in certain euglenoids. Toxicon. 2009 Jul 15. [7] http://www3.interscience.wiley.com/journal/118768872/abstract. Zimba, P. Zimba, P. V., Rowan, M. and Triemer, R.E. 2004. Identication of euglenoid algae that produce ichthyotoxin(s). J. Fish Diseases 27:115-117. Doi: 10.1046/j.13652761.2003.00512.x. [8] http://www.ncbi.nlm.nih.gov/pubmed/19345266. Das BK, Pradhan J, Sahu S: The eect of Euglena viridis on immune response of rohu, Labeo rohita (Ham.). Fish Shellsh Immunol. 2009 Jun;26(6):871-6. Epub 2009 Apr 3. [9] Xu Q, Chen W, and Gao G. Seasonal variations in microcystin concentrations in lake taihu, china. Environmental Monitoring and Assessment, 145(1-3):7579. http: //www.springerlink.com/content/46205p34m2798374/. [10] Stone R. Ecology: China aims to turn tide against toxic lake pollution. Science, 333(6047):12101211, 9. http://www.sciencemag.org/content/333/6047/1210. summary. [11] Detroit river-western lake erie basin indicator project. indicator: Algal blooms in western lake erie. epa. http://www.epa.gov/med/grosseile_site/indicators/ algae-blooms.html. [12] Zamyadi A, Ho L, Newcombe G, Bustamante H, and Prvost M. Fate of toxic cyanobacterial cells and disinfection by-products formation after chlorination. Water Res, 7 2011. http://www.ncbi.nlm.nih.gov/pubmed/21820143. [13] Epa: Disinfection byproducts. http://www.epa.gov/envirofw/html/icr/gloss_ dbp.html. [14] Harke MJ, Berry DL, Ammerman JW, and Gobler CJ. Molecular response of the bloom-forming cyanobacterium, microcystis aeruginosa, to phosphorus limitation. Microb Ecol, 2011. http://www.ncbi.nlm.nih.gov/pubmed/21720829. [15] Chen W, Liu H, Zhang Q, and Dai S. Eects of nitrite and toxic microcystis aeruginosa pcc7806 on the growth of freshwater rotifer brachionus calyciorus. Bull Environ Contam Toxicol, 86(3):2637, 3 2011. http://www.ncbi.nlm.nih.gov/pubmed/ 21290099. [16] http://www.ncbi.nlm.nih.gov/pubmed/19778550. Clemente Z, Busato RH, Oliveira Ribeiro CA, Cestari MM, Ramsdorf WA, Magalhaes VF, Wosiack AC, Silva de Assis HC: Analyses of paralytic shellsh toxins and biomarkers in a Southern Brazilian reservoir. Toxicon. 2009 Sep 21. Doi:10.1016/j.toxicon.2009.09.003.
BIBLIOGRAPHY
2079
[17] http://www.ncbi.nlm.nih.gov/pubmed/17506829. Richardson LL, Sekar R, Myers JL, Gantar M, Voss JD, Kaczmarsky L, Remily ER, Boyer GL, Zimba PV.: The presence of the cyanobacterial toxin microcystin in black band disease of corals. FEMS Microbiol Lett. 2007 Jul;272(2):182-7. Epub 2007 May 16. [18] http://pubs.acs.org/doi/abs/10.1021/nl902368r. Libing Wang, Wei Chen, Dinghua Xu, Bong Sup Shim, Yingyue Zhu, Fengxia Sun, Liqiang Liu, Chifang Peng, Zhengyu Jin, Chuanlai Xu, Nicholas A. Kotov: Simple, Rapid, Sensitive, and Versatile SWNT-Paper Sensor for Environmental Toxin Detection Competitive with ELISA. Nano Letters, 2009; 9 (12): 4147 DOI: 10.1021/nl902368r. [19] http://en.wikipedia.org/wiki/Microcystin. Wikipedia: Microcystin. [20] http://www.ncbi.nlm.nih.gov/pubmed/12105974. Hapeman CJ, Dionigi CP, Zimba PV, McConnell LL:Agrochemical and nutrient impacts on estuaries and other aquatic systems. J Agric Food Chem. 2002 Jul 17;50(15):4382-4. Review. [21] http://www.ncbi.nlm.nih.gov/pubmed/10188203. Scott GI, Fulton MH, Moore DW, Wirth EF, Chandler GT, Key PB, Daugomah JW, Strozier ED, Devane J, Clark JR, Lewis MA, Finley DB, Ellenberg W, Karnaky KJ Jr: Assessment of risk reduction strategies for the management of agricultural nonpoint source pesticide runo in estuarine ecosystems. Toxicol Ind Health. 1999 Jan-Mar;15(1-2):200-13. [22] http://www.ncbi.nlm.nih.gov/pubmed/20493565. Ortiz-Santaliestra ME, Fernndez-Benitez MJ, Marco A, Lizana M: Inuence of ammonium nitrate on larval anti-predatory responses of two amphibian species. Aquat Toxicol. 2010 May 19. [23] http://www.ncbi.nlm.nih.gov/pubmed/19800720. Ortiz-Santaliestra ME, Fernndez-Benitez MJ, Lizana M, Marco A: Adaptation to osmotic stress provides protection against ammonium nitrate in Pelophylax perezi embryos. Environ Pollut. 2010 Mar;158(3):934-40. Epub 2009 Oct 3. [24] http://www.sceti.co.jp/medical/PdfFiles/dsp_rapid_kit_english.pdf. DSP Rapid Kit: Diarrhoeic Shellsh Poisoning (A colorimetric phosphatase inhibition assay). [25] http://www.biochemj.org/bj/275/bj2750233.htm. Takai A, Mieskes G.: Inhibitory eect of okadaic acid on the p-nitrophenyl phosphate phosphatase activity of protein phosphatases. Biochem J. 275:233-9, 1991. [26] Tubaro, Aurelia; Florio, Chiara; Luxich, Elena; Sosa, Silvio; Della Loggia, Roberto; Yasumoto, Takeshi: A protein phosphatase 2A inhibition assay for a fast and sensitive assessment of okadaic acid contamination in mussels. Toxicon 34(7):743-52, 1996.
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[27] Sceti Bioscience Export:. Dsp rapid kip (diarrheic shellsh poison test.). http://sceti.jp/export/news/2009/08/ dsp-rapid-kit-diarrhoeic-shellfish-poisoning-test-1.html. [28] Untersuchung von Lebensmitteln: Bestimmung des Gehaltes an Algentoxinen in Muscheltieren und Muscheltiererzeugnissen,Fluorimetrisches Verfahren Paragr.35 LMBG, Beuth Verlag. [29] http://www.efsa.europa.eu/cs/BlobServer/Scientific_Opinion/contam_op_ ej1306_summaryopinionregulatedmarinebiotoxins_en.pdf?ssbinary=true. EFSA: Marine biotoxins in shellsh - Summary on regulated marine biotoxins. Question number: EFSA-Q-2009-00685. Adopted: 13 August 2009. [30] http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=OJ:L:2004:139: 0055:0205:EN:PDF. Regulation (EC) No 853/2004 of the European Parliament and of the Council of 29 April 2004 laying down specic hygiene rules for food of animal origin2 establishes maximum levels for marine biotoxins in live bivalve molluscs. [31] http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=OJ:L:2005:338: 0027:0059:EN:PDF. Commission Regulation (EC) No 2074/2005 of 5 December 2005 laying down implementing measures for certain products. This regulation establishes the testing methods for detecting marine biotoxins. [32] http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=CELEX: 31991L0492:EN:HTML. Council Directive 91/492/EEC of 15 July 1991 laying down the health conditions for the production and the placing on the market of live bivalve molluscs. [33] http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=CELEX: 31979L0923:EN:HTML. Council Directive 79/923/EEC of 30 October 1979 on the quality required of shellsh waters. [34] http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=OJ:L:2002:075: 0062:0064:EN:PDF. European Commission: (2002/225/EC) Decision of 15 March 2002 laying down detailed rules for the implementation of Council Directive 91/492/EEC as regards the maximum levels and the methods of analysis of certain marine biotoxins in bivalve molluscs, echinoderms, tunicates and marine gastropods (notied under document number C(2002) 1001). [35] http://www.efsa.europa.eu/EFSA/efsa_locale-1178620753812_ 1178682985887.htm. EFSAMarine biotoxins in shellsh - okadaic acid and analogues - Scientic Opinion of the Panel on Contaminants in the Food chain. Adopted date: 27/11/2007. Question number: EFSA-Q-2006-065A Publication date: 31/01/2008. [36] http://en.wikipedia.org/wiki/Saxitoxin. Wikipedia: .Saxitoxin.
BIBLIOGRAPHY
2081
[37] http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2525482/. Paz B, Daranas AH, Norte M, Riob P, Franco JM, Fernndez JJ. Yessotoxins, a group of marine polyether toxins: an overview. Mar Drugs. 2008 May 7;6(2):73-102. [38] http://www.ncbi.nlm.nih.gov/pubmed/11775161. Fischer WJ, Garthwaite I, Miles CO, Ross KM, Aggen JB, Chamberlin AR, Towers NR, Dietrich DR. Congenerindependent immunoassay for microcystins and nodularins. Environ Sci Technol. 2001 Dec 15;35(24):4849-56. [39] http://www.ncbi.nlm.nih.gov/pubmed/17760339. Kleivdal H, Kristiansen SI, Nilsen MV, Goksyr A, Briggs L, Holland P, McNabb P. Determination of domoic acid toxins in shellsh by biosense ASP ELISAa direct competitive enzyme-linked immunosorbent assay: collaborative study. J AOAC Int. 2007 Jul-Aug;90(4):1011-27. [40] http://ntp.niehs.nih.gov/ntp/htdocs/Chem_Background/ExSumPdf/ Cylindrospermopsin.pdf. Masten S, Carlson B. Cylindrospermopsin (CASRN 143545-90-8). Review of Toxicological Literature. Integrated Laboratory Systems 2000. [41] http://www.oandhs.org/articles/article/218. Pliski Marcin P, Hanna M-M, Justyna K, Lisa S, Jussi M. Cyanobacterial hepatotoxins, microcystins and nodularins, in fresh and brackish waters of the Pomeranian Province, northern Poland. Ocean. Hydrob. Studies, 2008, 37(4): 3-21. [42] Duden-Lexikon in drei Bnden,Dudenverlag, 1965. [43] Mller, Gunther und Weber, Herbert: Mikrobiolopgie der Lebensmitel, Grundlagen, Behr Verlag, Hamburg 8.Auage 1996 s.216. [44] Vandenesch F, Naimini T, Enright MC, Lina G, Nimmo GR, Heernan H, Liassine N, Bes M, Greenland T, Reverdy ME, Etienne J: Community-acquired methicillinresistant Staphylococcus aureus carrying Panton-Valentine leukocidin genes; worldwide emergence. EID 2003:9:978-984. [45] Robert Koch Institut:Epidemiologisches Bulletin 11.Mrz 2005/Nr. 10;Ausbruch von Furunkeln durch lukS-lukF-positive Staphylococcus aureus in einem Dorf in Brandenburg 2002-2004. [46] Centers for Disease Control and Prevention (CDC): Nguyen, Dao M; Mascola, Laurene; and Bancroft, Elisabeth: Recurring Methicillin-resistant Staphylococcus aureus Infections in a Football Team; Current Issue Volume 11, No.4 April 2005. [47] http://www.ncbi.nlm.nih.gov/pubmed/17392084. Bryden, W.L.: Mycotoxins in the food chain: human health implications. Asia. Pac J Clin Nutr. 2007;16 Suppl 1:95-101.
2082
[48] http://www.ncbi.nlm.nih.gov/pubmed/19028307. Iacumin, L.; Chiesa. L; Boscolo. D; Manzano. M; Cantoni. C; Orlic. S; Comi, G: Moulds and ochratoxin A on surfaces of artisanal and industrial dry sausages. Food Microbiol. 2009 Feb;26(1):6570. Epub 2008 Aug 22. [49] http://www.efsa.europa.eu/EFSA/efsa_locale-1178620753812_ 1178620762803.htm. EFSA - Opinion of the Scientic Panel on Contaminants in the Food Chain related to ergot alkaloid as undesirable substance in animal feed. [50] http://www.efsa.europa.eu/en/contam201001/docs/ cfpefsacontam201001cfp.pdf. Call for proposals CFP/EFSA/CONTAM/2010/01: Survey on ergot alkaloids in cereals intended for human consumption and animal feeding. [51] http://www.ncbi.nlm.nih.gov/pubmed/18415090. Krska R, Subbings G, MacArthur R and Crews C, 2008: Simultaneous determination of six major ergot alkaloids and their epimers in cereals and foodstus by LC-MS-MS. Analytical and Bioanalytical Chemistry, 391, 563-576. [52] http://www.springerlink.com/content/203l41u0580237g6/. Ruhland M and Tischler J, 2008. Determination of ergot alkaloids in feed by HPLC. Mycotoxin Research, 24, 73-79. [53] http://www.ncbi.nlm.nih.gov/pubmed/17764773. Magan N, Aldred D.: Postharvest control strategies: minimizing mycotoxins in the food chain. Int J Food Microbiol. 2007 Oct 20;119(1-2):131-9. Epub 2007 Jul 31. [54] http://www.ncbi.nlm.nih.gov/pubmed/18258326. Wagacha JM, Muthomi JW.: Mycotoxin problem in Africa: current status, implications to food safety and health and possible management strategies. Int J Food Microbiol. 2008 May 10;124(1):1-12. Epub 2008 Jan 24. [55] Fusarien-Toxine Abschtzung der Fumosinaufnahme des Verbrauchers z. Zt. nicht mglich; Der Lebensmittelbrief 10. Jahrgang 1+2/1999,S 21. [56] http://www.agbioworld.org/newsletter_wm/index.php?caseid= archive&newsid=1797. AgBioWorld:Organic Toxic Maize. 7.10.2003. [57] http://pubs.acs.org/cgi-bin/abstract.cgi/jafcau/2008/56/i11/abs/ jf072697e.html. Wu, Felicia; Munkvold, Gary P. : Mycotoxins in Ethanol Coproducts: Modeling Economic Impacts on the Livestock Industry and Management Strategies. Journal of Agricultural and Food Chemistry. Volume 56, Number 11, Pages 3900-39011 doi:10.1021/jf072697e.
BIBLIOGRAPHY
2083
[58] http://ps.fass.org/cgi/content/abstract/80/4/401. Henry, M. H.; Wyatt, R. D.: The toxicity of fumonisin B1, B2, and B3, individually and in combination, in chicken embryos. Poultry Science, Vol 80, Issue 4, 401-407. [59] http://cat.inist.fr/?aModele=afficheN&cpsidt=3597478. Bacon, C. W.; Porter, J. K.; Norred, W. P.; Toxic interactions of fumonisin B1 and fusaric acid measured by injection into fertile chicken egg. Mycopathologia. 1995, vol. 129, nr 1, pp. 29-35 (47 ref.). [60] http://www.ingentaconnect.com/content/tandf/cbps/2004/00000045/ 00000006/art00010. Butkeraitis, P.; Oliveira, C.A.F.; Ledoux, D.R.; Ogido, R.; lbuquerque, R. A; Rosmaninho, J.F.; Rottinghaus, G.E.: British Poultry Science. Volume 45, Number 6, December 2004 , pp. 798-801(4). [61] http://www.cfsan.fda.gov/~dms/fumonbg2.html. FDA: Background Paper in Support of Fumonisin Levels in Animal Feed. June 6, 2000. [62] http://www.foodstandards.govt.nz/_srcfiles/P282_Poultry%20_%20DAR% 20Attach3.pdf. FSA Australia New Zealand: Scientic Assessment of the Public Health and Safety of Poultry Meat in Australia Food Standards Australia New Zealand November 2005. [63] Mathiaschk G,Weber berlegungen zur Festsetzung von Ochratoxin A- Hchstmengen fr Lebensmittel.Bundesgesundhbl 10(1998 443-444);Der Lebensmittelbrief 10. Jahrgang 1+2/1999,S 21. [64] http://www.efsa.europa.eu/EFSA/efsa_locale-1178620753812_ 1178620762138.htm. EFSA: Opinion of the Scientic Panel on contaminants in the food chain (CONTAM) related to ochratoxin A in food Question number: EFSA-Q-2005-154 Adopted 04.04.2006. [65] http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=OJ:L:2006:364: 0005:0024:EN:PDF. Commission Regulation (EC) No 1881/2006 of 19 December 2006 setting maximum levels for certain contaminants in foodstus. [66] http://pubs.acs.org/cgi-bin/abstract.cgi/jafcau/asap/abs/jf073002c. html. Hernndez Hierro,J.Miguel; Garcia-Villanova, Rafael J.: Torrero,Puricacin Rodrguez, Toruno Fonseca, Ivania M.: Aatoxins and Ochratoxin A in Red Paprika for Retail Sale in Spain: Occurrence and Evaluation of a Simultaneous Analytical Method. J.Agric. Food Chem. ASAP Article10.1021/jf073002c Web Release Date: January 19, 2008. [67] http://pubs.acs.org/cgi-bin/abstract.cgi/jafcau/2004/52/i24/abs/ jf048882z.html. Rafael J. Garcia-Villanova, Carlos Cordn, Ana M. Gonzlez Params, Aparicio, P.; Garcia Rosales, M. Eugenia: Simultaneous Immunoanity Column Cleanup and HPLC Analysis of Aatoxins and Ochratoxin A in
2084
CHAPTER 27. FOOD POISONING Spanish Bee Pollen. J.Agric. Food Chem.Web Release Date: October 28, 2004. Doi:10.1021jf048882z.
[68] Schuh,Hans: Klarer Blick , Schnaps sei Dank:eine neue Kategorie kanzerogener Stoe; Die Zeit, Nr. 29 vom 9.7.98. [69] http://www3.interscience.wiley.com/journal/122265507/abstract. Lachenmeier, D.W., Kanteres, F., Rehm, J. Carcinogenicity of acetaldehyde in alcoholic beverages: risk assessment outside ethanol metabolism. Addiction, 2009; 104 (4): 533 DOI: 10.1111/j.1360-0443.2009.02516.x. [70] http://ntp.niehs.nih.gov/ntp/roc/eleventh/profiles/s001acet.pdf. Report on Carcinogens. 11th
[71] http://catalogue.nla.gov.au/Record/244625. IARC. 1985. Allyl Compounds, Aldehydes, Epoxides, and Peroxides. IARC Monographs on the Evaluation of Carcinogenic Risk of Chemicals to Humans, vol. 36. Lyon, France: International Agency for Research on Cancer. 369 pp. [72] http://monographs.iarc.fr/ENG/Monographs/suppl7/index.php. IARC Supplement No. 7 Overall Evaluations of Carcinogenicity: An Updating of IARC Monographs Volumes 1 to 42 1987; 440 pages ISBN 92 832 1411 0. [73] http://monographs.iarc.fr/ENG/Monographs/vol71/index.php. IARC Volume 71 Re-evaluation of Some Organic Chemicals, Hydrazine and Hydrogen Peroxide. 1999; 1589 pages; ISBN 92 832 1271 1. [74] Schuh,Hans: Alkohol - Opium frs Volk;Die Zeit Nr. 28; 2.juli 1998, page 31. [75] http://www.eurekalert.org/pub_releases/2009-03/ace-ltm031209.php. Dzung Anh Le, Ph.D. : Low to moderate, not heavy, drinking releases feel-good endorphins in the brain. [76] http://ncadi.samhsa.gov/govpubs/BKD268/28c.aspx. NCADI: Naltrexone and Alcoholism Treatment. [77] http://en.wikipedia.org/wiki/Bupropion/naltrexone. pion/naltrexone. Wikipedia: Bupro-
[78] http://www.ncbi.nlm.nih.gov/pubmed/20338493. Mukamal KJ, Chen CM, Rao SR, Breslow RA: Alcohol Consumption and Cardiovascular Mortality Among U.S. Adults, 1987 to 2002. J Am Coll Cardiol. 2010 Mar 30;55(13):1328-1335. [79] http://content.onlinejacc.org/cgi/content/long/55/13/1336. Klatsky: Alcohol and Cardiovascular Mortality: Common Sense and Scientic Truth J Am Coll Cardiol.2010; 55: 1336-1338.
BIBLIOGRAPHY
2085
[80] http://www.ncbi.nlm.nih.gov/pubmed/20045009. Klatsky AL: Alcohol and cardiovascular health. Physiol Behav. 2009 Dec 31. [81] Health and consumer: Pesticides european commission. http://ec.europa.eu/ food/plant/plant_protection_products/index_en.htm. [82] Regulation (ec) no 1107/2009 of the european parliament and of the council of 21october 2009 concerning the placing of plant protection products on the market and repealing council directives 79/117/eec and 91/414/eec. http://eur-lex.europa. eu/LexUriServ/LexUriServ.do?uri=OJ:L:2009:309:0001:0050:EN:PDF. [83] Eu pesticides database. http://ec.europa.eu/sanco_pesticides/public/index. cfm. [84] Der Spiegel 33/1998: Dioxin in Kraftfutter. [85] http://www.cha.state.md.us/ophpr/pdf/2006/BT06-04_WK04.pdf. Maryland Department of Health and Mental Hygiene February 2, 2006 Bioterrorism Bulletin: 2006:04: Reporting for the week ending 01/28/06 International Disease Reports: Dioxin, Animal Feed (Belgium). [86] http://europa.eu.int/comm/agriculture/newsdigest/2006/141.htm#cnt7. Maximum levels set for dioxins and PCBs in feed and food. [87] http://www.efsa.europa.eu/en/press/news/datex100331.htm. EFSA publishes European overview of dioxin levels in food and feed. EFSA 31.03.2010. [88] http://www.who.int/ipcs/assessment/tef_update/en/. WHO: Project for the re-evaluation of human and mammalian toxic equivalency factors (TEFs) of dioxins and dioxin-like compounds. [89] http://www.codexalimentarius.net/download/standards/10693/CXP_062e. pdf. CAC/RCP 62: Code of Practice for the Prevention and Reduction of Dioxin and Dioxin-like PCB Contamination in Food and Feeds. Codex Alimentarius 2006. [90] http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=OJ:L:2010:080: 0028:0031:EN:PDF. Commission Regulation (EU) No 258/2010 of 25 March 2010 imposing special conditions on the imports of guar gum originating in or consigned from India due to contamination risks by pentachlorophenol and dioxins, and repealing Decision 2008/352/EC. [91] http://ec.europa.eu/food/food/chemicalsafety/contaminants/dioxins_en. htm. Dioxins in guar gum from India. [92] http://en.wikipedia.org/wiki/Pentachlorophenol. tachlorophenol.
Wikipedia:
Pen-
2086
[93] Cox C. Fungicide factsheet. journal of pesticide reform/ winter 1997. 17(4):14 20, 1997. http://www.pesticide.org/get-the-facts/pesticide-factsheets/ factsheets/chlorothalonil. [94] McMahon T, Halstead NT, Johnson S, Rael TR, Romansic JM, Crumrine PW, and Rohr JR. Fungicide-induced declines of freshwater biodiversity modify ecosystem functions and services. Ecol Lett, 15(7):71422, 7 22012. http://www.ncbi.nlm. nih.gov/pubmed/22587750. [95] Mozzachio AM, Rusiecki JA, Hoppin JA, Mahajan R, Patel R, Beane-Freeman L, and Alavanja MC. Chlorothalonil exposure and cancer incidence among pesticide applicator participants in the agricultural health study. Environ Res, 108(3):4003, 11 2008. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2936501/. [96] Lu C, Toepel K, Irish R, Fenske RA, Barr DB, and Bravo R. Organic diets signicantly lower childrens dietary exposure to organophosphorous pesticides. Environ Health Perspect, 114:260263, 2006. http://www.ncbi.nlm.nih.gov/pmc/ articles/PMC1367841/. [97] Robert I, Krieger, James J, Keenan, Yanhong Li, and Helen M. Vega. Op pesticides, organic diets, and childrens health. Environ Health Perspect, 114(10):A572, 10 2006. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1626419/. [98] Clune AL, Ryan PB, and Barr DB. Have regulatory eorts to reduce organophosphorus insecticide exposures been eective? Environ Health Perspect, 120(4):521525, 4 2012. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3339465/. [99] Huen K, Bradman A, Harley K, Youse P, Boyd Barr D, Eskenazi B, and Holland N. Organophosphate pesticide levels in blood and urine of women and newborns living in an agricultural community. Environ Res, 117:816, 8 2012. http://www.ncbi. nlm.nih.gov/pubmed/22683313. [100] Horton MK, Kahn LG, Perera F, Barr DB, and Rauh V. Does the home environment and the sex of the child modify the adverse eects of prenatal exposure to chlorpyrifos on child working memory? Neurotoxicol Teratol, 34(5):53441, 9 2012. http://www. ncbi.nlm.nih.gov/pubmed/22824009. [101] Eskenazi B, Huen K, Marks A, Harley KG, Bradman A, Barr DB, and Holland N. Pon1 and neurodevelopment in children from the chamacos study exposed to organophosphate pesticides in utero. Environ Health Perspect, 118(12):177581, 12 2010. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3002199/. [102] Eskenazi B, Rosas LG, Marks AR, Bradman A, Harley K, Holland N, Johnson C, Fenster L, and Barr DB. Pesticide toxicity and the developing brain. Basic Clin Pharmacol Toxicol, 102(2):22836, 2 2008. http://www.ncbi.nlm.nih.gov/ pubmed/18226078.
BIBLIOGRAPHY
2087
[103] Weldon RH, Barr DB, Trujillo C, Bradman A, Holland N, and Eskenazi B. A pilot study of pesticides and pcbs in the breast milk of women residing in urban and agricultural communities of california. J Environ Monit, 13(11):313644, 11 2011. http://www.ncbi.nlm.nih.gov/pubmed/22009134. [104] Cok I, Mazmanci B, Mazmanci MA, Turgut C, Henkelmann B, and Schramm KW. Analysis of human milk to assess exposure to pahs, pcbs and organochlorine pesticides in the vicinity mediterranean city mersin, turkey. Environ Int, 40:639, 4 2012. http://www.ncbi.nlm.nih.gov/pubmed/22280929. [105] Tsang HL, Wu S, Leung CK, Tao S, and Wong MH. Body burden of pops of hong kong residents, based on human milk, maternal and cord serum. Environ Int, 37(1):14251, 1 2011. http://www.ncbi.nlm.nih.gov/pubmed/20828823. [106] http://www.efsa.europa.eu/en/efsajournal/doc/contam_ej_911_dioxins_ rev2.pdf?ssbinary=true. Statement of EFSA on the risks for public health due to the presence of dioxins in pork from Ireland (Question No EFSA-Q-2008-777) Issued on 10 December 20081. [107] Mineral oil hydrocarbons: Efsa publishes opinion on these complex compounds. efsa 06 jun 2012. http://www.efsa.europa.eu/en/press/news/120606.htm?WT. mc_id=EFSAHL01&emt=1. [108] Scientic opinion on mineral oil hydrocarbons in food. EFSA Journal, 10(6):2704(185pp.), 2012. http://www.efsa.europa.eu/en/efsajournal/pub/ 2704.htm. [109] http://www.efsa.europa.eu/en/scdocs/scdoc/34.htm. Opinion of the Scientic Panel on contaminants in the food chain [CONTAM] related to mercury and methylmercury in food. Question number: EFSA-Q-2003-030. 24 February 2004. [110] http://www.ncbi.nlm.nih.gov/pubmed/20848188. Sackett DK, Aday DD, Rice JA, Cope WG, Buchwalter D. Does proximity to coal-red power plants inuence sh tissue mercury? Ecotoxicology. 2010 Sep 17. [111] http://www.agu.org/pubs/crossref/2009/2008GB003425.shtml. Sunderland, Elsie M.; Krabbenhoft, David P.: Moreau, John W.; Strode, Sarah A.; Landing, William M.: Sunderland et al. Mercury sources, distribution, and bioavailability in the North Pacic Ocean: Insights from data and models. Global Biogeochemical Cycles, 2009; 23 (2): GB2010 DOI: 10.1029/2008GB003425. [112] http://hyper.ahajournals.org/cgi/content/abstract/HYPERTENSIONAHA. 109.135046v1. Valera B, Dewailly E, Poirier P. Environmental mercury exposure and blood pressure among Nunavik Inuit adults. Hypertension 2009; DOI:10.1161/HYPERTENSIONAHA.109.135046.
2088
[113] http://americanheart.mediaroom.com/index.php?s=43&item=835. American Heart Association: Mercury in sh seems to raise blood pressure in spite of nutrients Press release October 5, 2009. [114] Mozaarian D, Shi P, Morris JS, Spiegelman D, Grandjean P, Siscovick DS, Willett WC, and Rimm EB. Mercury exposure and risk of cardiovascular disease in two u.s. cohorts. N Engl J Med, 364(12):111625, 3 2011. http://www.ncbi.nlm.nih.gov/ pubmed/21428767. [115] http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=OJ:L:2005:070: 0001:0016:EN:PDF. Regulation EC 396/2005 of the European Parliament and of the Council of 23 February 2005 on maximum residue levels of pesticides in or on food and feed of plant and animal origin and amending Council Directive 91/414/EEC. [116] http://www.efsa.europa.eu/EFSA/efsa_locale-1178620753812_Opinions498. htm. EFSA Opinion on some pesticides. 27.11.2008. [117] http://www.panna.org/files/EurActivToughNegotiationsAheadAsMEPsBackBans20081006. pdf. EurActiv: Pesticides: Tough negotiations ahead as MEPs back bans . Published: Thursday 6 November 2008. [118] http://pubs.acs.org/doi/abs/10.1021/ac8012708. Juan F. Garcia-Reyes, Bienvenida Gilbert-Lopez and Antonio Molina-Diaz, Amadeo R. Fernandez-Alba: Determination of Pesticide Residues in Fruit-Based Soft Drinks. Anal. Chem., 2008, 80 (23), pp 8966-8974 Doi: 10.1021/ac8012708 Publication Date (Web): November 4, 2008. [119] Fungicide in orange juice: Coca-cola alerted fda about fungicide sprayed on brazilian orange trees. http://www.huffingtonpost.com/2012/01/12/ fungicide-orange-juice-coca-cola_n_1201787.html. [120] http://www.spiegel.de/wissenschaft/natur/0,1518,553814,00.html. Spiegel Online: Bienensterben im Rheintal Behrde nimmt Insektengift vom Markt. 17.05.08. [121] http://idw-online.de/pages/en/news?id=260637. Julius-Khn Institut: Mit Clothianidin gebeiztes Saatgut ist nach Untersuchungen des Julius Khn-Instituts Ursache fr aktuelle Bienenschden in Baden-Wrttemberg. Dr. Gerlinde Nachtigall, Pressestelle 16.05.2008. [122] http://www.bvl.bund.de/. BVL: BVL ordnet das Ruhen der Zulassung fr Saatgutbehandlungsmittel an. 16.05.2008. [123] http://www.efsa.europa.eu/EFSA/efsa_locale-1178620753812_ 1211902028558.htm. EFSA: Conclusion regarding the peer review of the pesticide risk assessment of the active substance abamectin. F inalised: 29 May 2008.
BIBLIOGRAPHY [124] http://en.wikipedia.org/wiki/Abamectin. Wikipedia: Abamectin.
2089
[125] http://www.efsa.europa.eu/EFSA/efsa_locale-1178620753812_ 1211902028566.htm. Conclusion regarding the peer review of the pesticide risk assessment of the active substance uazinam. 26.03.2008. Publication date 29.07.2008. [126] http://www.efsa.europa.eu/EFSA/efsa_locale-1178620753812_ 1211902028580.htm. Conclusion regarding the peer review of the pesticide risk assessment of the active substance metazachlor. 14.04.2008. Publication date: 29.07.2008. [127] http://www.efsa.europa.eu/EFSA/efsa_locale-1178620753812_ 1211902028594.htm. Conclusion regarding the peer review of the pesticide risk assessment of the active substance fenpropimorph 14.04.2008. Publication Date: 29.07.2008. [128] http://www.efsa.eu.int/EFSA/efsa_locale-1178620753824_1211902024449. htm. EFSA: Conclusion regarding the peer review of the pesticide risk assessmtent of the active substance mepiquat. 14.04.2008. Publication Date: 28.07.2008. [129] http://www.efsa.europa.eu/EFSA/efsa_locale-1178620753812_ 1211902014630.htm. EFSA: Conclusion regarding the peer review of the pesticide risk assessment of the active substance buprofezin (notied active substance). [130] http://www.efsa.europa.eu/EFSA/efsa_locale-1178620753812_ 1211902024633.htm. EFSA: Conclusion regarding the peer review of the pesticide risk assessment of the active substance imidacloprid. 29.05.2008. Publication Date: 28.07.2008. [131] http://www.efsa.europa.eu/EFSA/efsa_locale-1178620753812_ 1211902024649.htm. EFSA: Conclusion regarding the peer review of the pesticide risk assessment of the active substance tralkoxydim. 26.03.2008 PublicationDate: 28.07.2008. [132] http://www.efsa.europa.eu/EFSA/efsa_locale-1178620753812_ 1211902024663.htm. EFSA: Conclusion regarding the peer review of the pesticide risk assessment of the active substance napropamide. Publication Date 28.07.2008. [133] http://www.efsa.europa.eu/EFSA/efsa_locale-1178620753812_ 1211902024675.htm. EFSA: Conclusion regarding the peer review of the pesticide risk assessment of the active substance epoxiconazole. 26.03.2008. Publication Date: 28.07.2008.
2090
[134] http://www.efsa.europa.eu/EFSA/efsa_locale-1178620753812_ 1211902024689.htm. EFSAConclusion regarding the peer review of the pesticide risk assessment of the active substance bromuconazole. 26/03/2008 Published: 28/07/2008. [135] http://www.efsa.europa.eu/EFSA/efsa_locale-1178620753812_ 1211902024722.htm. EFSA: Conclusion regarding the peer review of the pesticide risk assessment of the active substance utolanil. 03/03/2008 Published: 28/07/2008. [136] http://www.efsa.europa.eu/EFSA/efsa_locale-1178620753812_ 1211902024736.htm. EFSA: Conclusion regarding the peer review of the pesticide risk assessment of the active substance benuralin. 03/03/2008 Published: 28/07/2008. [137] Scientic opinion on the science behind the development of a risk assessment of plant protection products on bees (apis mellifera, bombus spp. and solitary bees). efsa journal 2012. 10(5):2669(275pp.). http://www.efsa.europa.eu/en/efsajournal/ pub/2668.htm. [138] Scientic opinion on emerging toxins: Efsa panel on contaminants in the food chain (contam). http://www.aesan.msssi.gob.es/en/CRLMB/web/soporte_ cientifico/seccion/opiniones_cientificas.shtml. [139] Sralini G, Clair E, Mesnage R, Gress S, Defarge N, Malatesta M, Hennequin D, and Spiroux de Vendmois J. Long term toxicity of a roundup herbicide and a roundup-tolerant genetically modied maize. Food and Chemical Toxicology, 9 2012. http://research.sustainablefoodtrust.org/wp-content/ uploads/2012/09/Final-Paper.pdf. [140] de Vendmois JS, Cellier D, Vlot C, Clair E, Mesnage R, and Sralini G. Debate on gmos health risks after statistical ndings in regulatory tests. Int J Biol Sci, 6(6):5908, 10 2010. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2952409/. [141] Clair E, Linn L, Travert C, Amiel C, Sralini G, and Pano JM. Eects of roundup and glyphosate on three food microorganisms: Geotrichum candidum, lactococcus lactis subsp. cremoris and lactobacillus delbrueckii subsp. bulgaricus. Curr Microbiol, 64(5):48691, 5 2012. http://www.ncbi.nlm.nih.gov/pubmed/22362186. [142] Benachour N and Sralini G. Glyphosate formulations induce apoptosis and necrosis in human umbilical, embryonic, and placental cells. Chem Res Toxicol, 22(1):97105, 1 2009. http://www.ncbi.nlm.nih.gov/pubmed/19105591. [143] Richard S, Moslemi S, Sipahutar H, Benachour N, and Sralini G. Dierential eects of glyphosate and roundup on human placental cells and aromatase. Environ Health
BIBLIOGRAPHY
2091
Perspect, 113(6):71620, 6 2005. http://www.ncbi.nlm.nih.gov/pmc/articles/ PMC1257596/. [144] Mesnage R, Clair E, Gress S, Then C, Szkcs A, and Sralini G. Cytotoxicity on human cells of cry1ab and cry1ac bt insecticidal toxins alone or with a glyphosatebased herbicide. J Appl Toxicol, 2 2012. http://www.ncbi.nlm.nih.gov/pubmed/ 22337346. [145] Gasnier C, Dumont C, Benachour N, Clair E, Chagnon MC, and Sralini G. Glyphosate-based herbicides are toxic and endocrine disruptors in human cell lines. Toxicology, 262(3):18491, 8 2009. http://www.ncbi.nlm.nih.gov/pubmed/ 19539684. [146] Clair E, Mesnage R, Travert C, and Sralini G. A glyphosate-based herbicide induces necrosis and apoptosis in mature rat testicular cells in vitro, and testosterone decrease at lover levels. Toxicol In Vitro, 26(2):26979, 33 2012. http://www.ncbi. nlm.nih.gov/pubmed/22200534. [147] http://www.efsa.europa.eu/en/scdocs/scdoc/1570.htm. EFSA assesses health implications of lead in food. 18.03.2010. [148] Oulhote Y, Tertre AL, Etchevers A, Bot BL, Lucas JP, Mandin C, Strat YL, Lanphear B, and Glorennec P. Implications of dierent residential lead standards on childrens blood lead levels in france: Predictions based on a national cross-sectional survey. Int J Hyg Environ Health, pages pii: S14384639(13)000345, 3 2013. . [149] Oulhote Y, Le Bot B, Poupon J, Lucas JP, Mandin C, Etchevers A, Zmirou-Navier D, and Glorennec P. Identication of sources of lead exposure in french children by lead isotope analysis: a cross-sectional study. Environ Health, 10:75, 8 2011. . [150] Beckmann M, Lloyd AJ, Haldar S, Fav G, Seal CJ, Brandt K, Mathers JC, and Draper J. Dietary exposure biomarker-lead discovery based on metabolomics analysis of urine samples. Proc Nutr Soc, 1:110, 5 2013. http://www.ncbi.nlm.nih.gov/ pubmed/23632011. [151] Rizwan S, Naqshbandi A, and Khan F. Dietary axseed oil supplementation mitigates the eect of lead on the enzymes of carbohydrate metabolism, brush border membrane, and oxidative stress in rat kidney tissues. Biol Trace Elem Res, 4 2013. http://www.ncbi.nlm.nih.gov/pubmed/23613149. [152] Dorostghoal M, Seyyednejad SM, and Jabari A. Protective eects of fumaria parviora l. on lead-induced testicular toxicity in male rats. Andrologia, 4 2013. http://www.ncbi.nlm.nih.gov/pubmed/23611729. [153] Ghiasvand M, Aghakhani K, Salimi A, and Kumar R. Ischemic heart disease risk factors in lead exposed workers: research study. J Occup Med Toxicol, 8(1):11, 4 2013. http://www.ncbi.nlm.nih.gov/pubmed/23607481.
2092
[154] Ji JS, Elbaz A, and Weisskopf MG. Association between blood lead and walking speed in the national health and nutrition examination survey (nhanes 1999-2002). Environ Health Perspect, 4 2013. http://www.ncbi.nlm.nih.gov/pubmed/23603014. [155] http://www.ncbi.nlm.nih.gov/pubmed/20471700. Tillitt DE, Papoulias DM, Whyte JJ, Richter CA: Atrazine reduces reproduction in fathead minnow (Pimephales promelas). Aquat Toxicol. 2010 Apr 22. [156] The pesticide action pesticideinfo.org/. network (pan) pesticide database. http://www. FAO:
[157] http://www.fao.org/newsroom/en/news/2007/1000590/index.html. Yemen is facing worst locust outbreak in nearly 15 years.
[158] http://ec.europa.eu/food/food/chemicalsafety/contaminants/index_en. htm. EU Commission, Food Safety from Farm to Fork: News Archive: Contaminants of food. 07.06.2007. [159] http://ec.europa.eu/food/food/chemicalsafety/contaminants/ciaa_ acrylamide_toolbox.pdf. Commission Recommendation of 3 May 2007 on the monitoring of acrylamide levels in food (notied under document number C(2007) 1873). [160] http://assets.panda.org/downloads/fact_sheet___organotins_food.pdf. EFSA opinion, SCOOP Report Assessment of the dietary exposure to organotin compounds of the population of the EU Member States. [161] Sagiv SK, Thurston SW, Bellinger DC, Amarasiriwardena C, and Korrick SA. Prenatal exposure to mercury and sh consumption during pregnancy and attentiondecit/hyperactivity disorder-related behavior in children. Arch Pediatr Adolesc Med, 8:19, 10 2012. http://www.ncbi.nlm.nih.gov/pubmed/23044994. [162] Sagiv SK, Thurston SW, Bellinger DC, Tolbert PE, Altshul LM, and Korrick SA. Prenatal organochlorine exposure and behaviors associated with attention decit hyperactivity disorder in school-aged children. Am J Epidemiol, 171(5):593691, 3 2010. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2842227/. [163] Winneke G. Developmental aspects of environmental neurotoxicology: lessons from lead and polychlorinated biphenyls. J Neurol Sci, 308(1-2):915, 9 2011. http: //www.ncbi.nlm.nih.gov/pubmed/21679971. [164] Nicolescu R, Petcu C, Cordeanu A, Fabritius K, Schlumpf M, Krebs R, Krmer U, and Winneke G. Environmental exposure to lead, but not other neurotoxic metals, relates to core elements of adhd in romanian children: performance and questionnaire data. Environ Res, 110(5):47683, 6 2010. http://www.ncbi.nlm.nih.gov/pubmed/ 20434143.
BIBLIOGRAPHY
2093
[165] Sagiv SK, Thurston SW, Bellinger DC, Altshul LM, and Korrick SA. Neuropsychological measures of attention and impulse control among 8-year-old children exposed prenatally to organochlorines. Environ Health Perspect, 120(6):9049, 20126. http://www.ncbi.nlm.nih.gov/pubmed/22357172. [166] Govarts E, Nieuwenhuijsen M, Schoeters G, Ballester F, Bloemen K, de Boer M, Chevrier C, Eggesbo M, Guxens M, Krmer U, Legler J, Martnez D, Palkovicova L, Patelarou E, Ranft U, Rautio A, Petersen MS, Slama R, Stigum H, Toft G, Trnovec T, Vandentorren S, Weihe P, Kuperus NW, Wilhelm M, Wittsiepe J, Bonde JP, OBELIX, and ENRIECO. Birth weight and prenatal exposure to polychlorinated biphenyls (pcbs) and dichlorodiphenyldichloroethylene (dde): a meta-analysis within 12 european birth cohorts. Environ Health Perspect, 120(2):16270, 2 2012. http: //www.ncbi.nlm.nih.gov/pmc/articles/PMC3279442/. [167] Valvi D, Mendez MA, Martinez D, Grimalt JO, Torrent M, Sunyer J, and Vrijheid M. Prenatal concentrations of polychlorinated biphenyls, dde, and ddt and overweight in children: a prospective birth cohort study. Environ Health Perspect, 120(3):4517, 3 2012. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3295349/. [168] http://pubs.acs.org/doi/abs/10.1021/jf800520e. Labanca, Renata A.; Glria, M. Beatriz A.: Spectrophotometric Determination of Urea in Sugar Cane Distilled Spirits. J. Agric. Food Chem., 2008, 56 (13), pp 5211-5215 Doi: 10.1021/jf800520e. [169] http://www.ncbi.nlm.nih.gov/pubmed/11409971. Aresta M, Boscolo M, Franco DW.: Copper(II) catalysis in cyanide conversion into ethyl carbamate in spirits and relevant reactions. J Agric Food Chem. 2001 Jun; 49(6):2819-24. [170] http://www.getcited.com/pub/103462187. Lachenmeier, Dirk W; Kuballa, Thomas; Lima, Maria CP; Nbrega, Ian CC, Kerr-Correa, Florence; Kanteres, Fotis; Rehm, Jrgen: Ethyl carbamate analysis in German fruit spirits and Brazilian sugarcane spirits: Improved sample cleanup with automated parallel evaporation. Deutsche Lebensmittel-Rundschau, 105(8), 507 - 512. 2009. [171] http://www.ingentaconnect.com/content/tandf/tfac/2005/00000022/ 00000005/art00001. Lachenmeier, Dirk W.; Schehl, Beatus; Kuballa, Thomas; Frank, Willi; Senn, Thomas: Retrospective trends and current status of ethyl carbamate in German stone-fruit spirits. Food Additives and Contaminants, Volume 22, Number 5, May 2005 , pp. 397-405(9). [172] http://www.food.gov.uk/science/surveillance/fsis2000/2whisky. Food Standards Agency UK - Survey of Ethyl Carbame in Whisky (Number 02/00). 1 May 2000. [173] http://findarticles.com/p/articles/mi_m3488/is_2_90/ai_n31414084/. Patterson, Tim: New Methods to limit urea: genetically enhanced yeasts reduce probable carcinogen: Wines & Vines, Feb, 2009.
2094
[174] http://www.foodsafety.gov/~frf/ecaction.html. Butzke, Christian; Bisson, Linda: Ethyl Carbamate Preventive Action Manual: 1997. indexU. S. Food and Drug Administration, Center for Food Safety and Applied Nutrition. [175] http://www.efsa.europa.eu/en/science/contam/contam_documents/760.html. EFSA Report of the CONTAM Panel on provisional ndings on furan in food. 22 December 2004. [176] http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=CELEX: 32007H0196:EN:NOT. Recommendations on the monitoring of the presence of furan in foodstus. [177] http://www.cfsan.fda.gov/~lrd/fr040510.html. FDA: Federal Register: May 10, 2004 (Volume 69, Number 90) Furan in Food, Thermal Treatment; Request for Data and Information. [178] http://www.efsa.europa.eu/en/press/news/datex100730b.htm. data on furan in food. News 30 July 2010. EFA updates
[179] http://pubs.acs.org/doi/abs/10.1021/jf101671u. Owczarek-Fendor A, De Meulenaer B, Scholl G, Adams A, Van Lancker F, Yogendrarajah P, Uytterhoeven V, Eppe G, De Pauw E, Scippo ML, De Kimpe N: Importance of fat oxidation in starch-based emulsions in the generation of the process contaminant furan. J Agric Food Chem. 2010 Aug 6. [180] http://pubs.acs.org/cgi-bin/abstract.cgi/jafcau/2004/52/i22/abs/ jf0490403.html. Carolina Perez and Varoujan Yaylayan: Origin and Mechanistic Pathways of Formation of the Parent Furan-A Food Toxicant J. Agric. Food Chem 2004, 52, 6830-6836. Doi:10.1021/jf0490403. [181] http://www.epa.gov/wastemin/factshts/dioxfura.pdf. EPA: Dioxins and Furans. [182] http://www.bfr.bund.de/cm/232/furan_in_lebensmitteln_nach_acrylamid_ ein_weiteres_herstellungsbedingtes_toxin.pdf. Bundesanstalt fr Risikobewehrtung: Furan in Lebensmitteln - Nach Acrylamid ein weiteres herstellungsbedingtes Toxin ? Dr. H. Klake, 16.03.2005, Berlin. [183] http://www.efsa.europa.eu/EFSA/efsa_locale-1178620753812_ 1178620772979.htm. EFSA: Report of the CONTAM Panel on provisional ndings on furan in foods. 07/12/2004. [184] http://en.wikipedia.org/wiki/Desert_locust. Wikipedia, the free enzyclopedia: Desert locust. [185] http://en.wikipedia.org/wiki/Metarhizium_anisopliae. Wikipedia, the free enzyclopedia: Metarhizium anisopliae.
BIBLIOGRAPHY [186] Fda: Apple juice and arsenic. 12 2011. ResourcesForYou/Consumers/ucm271595.htm.
2095 http://www.fda.gov/Food/
[187] George CM, Graziano JH, Mey JL, and van Geen A. Impact on arsenic exposure of a growing proportion of untested wells in bangladesh. Environ Health, 11(1):7, 2 2012. http://www.ncbi.nlm.nih.gov/pubmed/22353180. [188] Fda looks for answers on arsenic in rice. 19 sep 2012. ForConsumers/ConsumerUpdates/ucm319827.htm. http://www.fda.gov/
[189] Arsenic. wikipedia. http://en.wikipedia.org/wiki/Arsenic. [190] Arsenic, production, import/export, use and disposal. "arsenic. section 5.3, p. 310". agency for toxic substances and disease registry. http://www.atsdr.cdc.gov/ toxprofiles/tp2-c5.pdf. [191] Lamm SH, Engel A, Penn CA, Chen R, and Feinleib M. Arsenic cancer risk confounder in southwest taiwan data set. Environ Health Perspect, 114(7):107782, 7 2006. http://www.ncbi.nlm.nih.gov/pubmed/16835062. [192] Ferreccio C and Sancha AM. Arsenic exposure and its impact on health in chile. J Health Popul Nutr, 24(2):16475, 6 2006. http://www.ncbi.nlm.nih.gov/pubmed/ 17195557. [193] Liao XY, Yan XL, Wang YZ, Li P, and Ma D. Environmental risk presented by arsenic contamination of building and facility surfaces in a coking plant. Bull Environ Contam Toxicol, 2 2012. http://www.ncbi.nlm.nih.gov/pubmed/22358118. [194] Palacios J, Roman D, and Cifuentes F. Exposure to low level of arsenic and lead in drinking water from antofagasta city induces gender dierences in glucose homeostasis in rats. Biol Trace Elem Res, 2 2012. http://www.ncbi.nlm.nih.gov/pubmed/ 22354675. [195] Halder D, Bhowmick S, Biswas A, Mandal U, Nriagu J, Guha Mazumdar DN, Chatterjee D, and Bhattacharya P. Consumption of brown rice: a potential pathway for arsenic exposure in rural bengal. Environ Sci Technol, 2012. http: //www.ncbi.nlm.nih.gov/pubmed/22352724. [196] Batista BL, Souza JM, De Souza SS, and Barbosa F Jr. Speciation of arsenic in rice and estimation of daily intake of dierent arsenic species by brazilians through rice consumption. J Hazard Mater, 191(1-3):3428, 7 2011. http://www.ncbi.nlm.nih. gov/pubmed/21601359. [197] http://www.sciencemag.org/cgi/content/full/321/5886/184. Stone, Richard: Food Safety: Arsenic and Paddy Rice: A Neglected Cancer Risk? Science 11 July 2008: 184-185. DOI: 10.1126/science.321.5886.184.
2096
CHAPTER 27. FOOD POISONING FSA: Arsenic in
[198] http://www.fsascience.net/2008/05/01/arsenic_in_rice. rice. May 1st 2008 in Science, safety and health.
[199] http://www.efsa.europa.eu/en/scdocs/scdoc/1351.htm. Scientic Opinion on Arsenic in Food. Question number: EFSA-Q-2008-425. Question number: EFSA-Q2008-425. 12 October 2009. [200] http://www.efsa.europa.eu/en/scdocs/doc/180.pdf. Opinion of the Scientic Panel on contaminants in the food chain [CONTAM] related to Arsenic as undesirable substance in animal feed. Question number: EFSA-Q-2003-031. 31.January 2005. [201] http://ghosh51.tripod.com/id15.html. Ashok Ghosh: Arsenic - The Slow Poison Threatening Bihar. [202] http://phys4.harvard.edu/~wilson/arsenic/conferences/2007_RGS/S5. 3NBose.pdf. Bose, Nupur; Ghosh, Ashok K.; Roy, N.P.; Upadhyay, Ajay; Siingh, Amardeep; Siingh, Sushantt K.: Vulnerability of population exposed to arsenic contamination in the mid Ganga plain of Bihar, India. [203] http://www.pnas.org/content/early/2010/07/08/1006822107. Kim J, Lee JJ, Kim J, Gardner D, Beachy PA: Arsenic antagonizes the Hedgehog pathway by preventing ciliary accumulation and reducing stability of the Gli2 transcriptional eector. Proc Natl Acad Sci U S A. 2010 Jul 12. [204] http://www.aacr.org/home/public--media/aacr-press-releases.aspx?d= 1768. American Association for Cancer Research: Arsenic Exposure Activates an Oncogenic Signaling Pathway; Leads to Increased Cancer Risk. [205] http://www.ncbi.nlm.nih.gov/pubmed/20043202. Brinkman MT, Karagas MR, Zens MS, Schned A, Reulen RC, Zeegers MP: Minerals and vitamins and the risk of bladder cancer: results from the New Hampshire Study. Cancer Causes Control. 2010 Apr;21(4):609-19. Epub 2009 Dec 31. [206] http://www.ncbi.nlm.nih.gov/pubmed/20049123. Heck JE, Andrew AS, Onega T, Rigas JR, Jackson BP, Karagas MR, Duell EJ: Lung cancer in a U.S. population with low to moderate arsenic exposure. Environ Health Perspect. 2009 Nov;117(11):171823. [207] http://www.ncbi.nlm.nih.gov/pubmed/19834714. Kwong RC, Karagas MR, Kelsey KT, Mason RA, Tanyos SA, Schned AR, Marsit CJ, Andrew AS: Arsenic exposure predicts bladder cancer survival in a US population. World J Urol. 2009 Oct 16. [208] http://www.ncbi.nlm.nih.gov/pubmed/19815484. Bajorin DF, Halabi S, Small E: Arsenic trioxide in recurrent urothelial cancer: a cancer and leukemia group B phase II trial (CALGB 99903). Clin Genitourin Cancer. 2009 Oct;7(3):E66-70.
BIBLIOGRAPHY [209] http://www.thanhniennews.com/features/?catid=10&newsid=28991. Thanhnien News: Public support raised for Agent Orange lawsuit.
2097
[210] http://www.spiegel.de/panorama/justiz/0,1518,488299,00.html. Spiegel Online: Todesregen, Prozessut und ein Tropfen Honung. Marina Mai. 14.06.2007. [211] http://www.newvision.co.ug/D/8/14/495628. New Vision Online: Indoor spraying of DDT is Ok. 27th April, 2006. [212] http://www.fightingmalaria.gov/technical/index.html. Malaria Initiative. The presidents
[213] Devra Lee Davis and A. Karim Ahmed: Exposures from Indoor Spraying of Chlorpyrifos Pose Greater Health Risks to Children than Currently Estimated. [214] http://www.ehponline.org/docs/1998/106p9-16gurunathan/abstract.html. Somia Gurunathan, Mark Robson, Natalie Freeman, Brian Buckley, Amit Roy, Roy Meyer, John Bukowski, and Paul J. Lioy : Accumulation of Chlorpyrifos on Residential Surfaces and Toys Accessible to Children. Environmental Health Perspectives Volume 106, 9-16, Nr. 1, 1998. [215] http://www.efsa.europa.eu/en/press/news/contam090320.htm. EFSA sets lower tolerable intake level for cadmium in food. EFSA Press Release 20 March 2009. [216] http://www.efsa.europa.eu/en/scdocs/scdoc/72.htm. Opinion of the Scientic Panel on contaminants in the food chain [CONTAM] related to cadmium as undesirable substance in animal feed. Question number: EFSA-Q-2003-033. 2 June 2004. [217] Bisphenol a: Efsa launches full re-evaluation focussing on exposure and possible low dose eects 24.04.2012. http://www.efsa.europa.eu/en/press/news/120424. htm?WT.mc_id=EFSAHL01&emt=1. [218] http://www.efsa.europa.eu/en/scdocs/scdoc/1018.htm. Uranium in foodstus, in particular mineral water. Question number: EFSA-Q-2007-135. 25 March 2009. [219] http://www.food.gov.uk/news/newsarchive/2008/feb/fish. Agency: Agency to review sh advice. 06.02.2008. Food Standards
[220] Moral, Raquel: Fox Chase Cancer Center Researchers: Two compounds in Plastic Packaging Act as an Environmental Estrogen and Can Alter Genes in Breast Tissue; Anaheim, Calif., April 18, 2005. www.fccc.edu/news/2005/plastic-PackagingEstrogens-04-18-05.html. [221] Rudel RA, Gray JM, Engel CL, Rawsthorne TW, Dodson RE, Ackerman JM, Rizzo J, Nudelman JL, and Brody JG. Food packaging and bisphenol a and bis(2ethyhexyl) phthalate exposure: ndings from a dietary intervention. Environ Health
2098
CHAPTER 27. FOOD POISONING Perspect, 119(7):91420, 7 2011. http://www.ncbi.nlm.nih.gov/pmc/articles/ PMC3223004/.
[222] Polaska K, Jurewicz J, and Hanke W. Exposure to environmental and lifestyle factors and attention-decit / hyperactivity disorder in children - a review of epidemiological studies. Int J Occup Med Environ Health, 10 2012. http://www.ncbi. nlm.nih.gov/pubmed/23086631. [223] Tanaka M, Inoue KI, Momoi T, and Takano H. In vivo immunoamplifying eects of di-(2-ethylhexyl) phthalate on cytokine response. Immunopharmacol Immunotoxicol, 10 2012. http://www.ncbi.nlm.nih.gov/pubmed/23098214. [224] Dodson RE, Nishioka M, Standley LJ, Perovich LJ, Brody JG, and Rudel RA. Endocrine disruptors and asthma-associated chemicals in consumer products. Environ Health Perspect, 120(7):935943, 7 2012. http://www.ncbi.nlm.nih.gov/pmc/ articles/PMC3404651/. [225] He Z, Paule MG, and Ferguson SA. Low oral doses of bisphenol a increase volume of the sexually dimorphic nucleus of the preoptic area in male, but not female, rats at postnatal day 21. Neurotoxicol Teratol, 4 2012. http://www.ncbi.nlm.nih.gov/ pubmed/22507915. [226] Liao C and Kannan K. Widespread occurrence of bisphenol a in paper and paper products: implications for human exposure. Environ Sci Technol, 45(21):93729, 11 2011. http://www.ncbi.nlm.nih.gov/pubmed/21939283. [227] Li G, Zu L, Wong PK, Hui X, Xiong J Lu AND, and An T. Biodegradation and detoxication of bisphenol a with one newly-isolated strain bacillus sp. gzb: Kinetics, mechanism and estrogenic transition. Bioresour Technol, 2012. http://www.ncbi. nlm.nih.gov/pubmed/22507902. [228] Grignard E, Lapenna S, and Bremer S. Weak estrogenic transcriptional activities of bisphenol a and bisphenol s. Toxicol In Vitro, 4 2012. http://www.ncbi.nlm.nih. gov/pubmed/22507746. [229] Greathouse KL, Bredfeldt T, Everitt JI, Lin K, Berry T, Kannan K, Mittelstadt ML, Ho SM, and Walker CL. Environmental estrogens dierentially engage the histone methyltransferase ezh2 to increase risk of uterine tumorigenesis. Mol Cancer Res, 10(4):54657, 4 2012. http://www.ncbi.nlm.nih.gov/pubmed/22504913. [230] http://www.ehponline.org/docs/2007/10753/abstract.html. Calafat, Antonia M.; Ye, Xiaoyun; Wong, Lee-Yang; Reidy,John A.; Needham, Larry L.: Exposure of the U.S. Population to Bisphenol A and 4-tertiary-Octylphenol: 2003-2004. EnvironmentalHealth Perspectives, Volume 116, Number 1, January 2008.
BIBLIOGRAPHY
2099
[231] Kang JH, Kondo F, Katayama Y. 2006. Human exposure to bisphenol A. Toxicology 226:79-89. doi:10.1016/j.tox.2006.06.009. [232] Vandenberg LN, Hauser R, Marcus M, Olea N, Welshons WV. 2007. Human exposure to bisphenol A (BPA). Reprod Toxicol 24:139-177 doi:10.1016/j.reprotox.2007.07.010. [233] Le, Hoa H.; Carlson, Emily M.; Chua, Jason P.; Belche, Scott M.: Bisphenol A is released from polycarbonate drinking bottles and mimics the neurotoxic actions of estrogen in developing cerebellar neuronns Toxicology Letters. Volume 176, Issue 2, 30 January 2008, Pages 149-156 Doi:10.1016/j.toxlet.2007.11.001. [234] Kawahata, Hodaka; Ohta, Hidekazu; Inoue, Mayuri; Suzuki, Atsushi: Endocrine disrupter nonylphenol and bisphenol A contamination in Okinawa and Ishigaki Islands, Japan-within coral reefs and adjacent river mouths. Chemosphere, Volume 55, Issue 11, June 2004, Pages 1519-1527 doi:10.1016/j.chemosphere.2004.01.032. [235] Quednow, Kristi; Pttmann, Wilhelm: Endocrine disruptors in freshwater streams of Hesse, Germany: Changes in concentration levels in the time span from 2003 to 2005 Environmental Pollution, In Press, Corrected Proof, Available online 15 August 2007 Doi:10.1016/j.envpol.2007.05.032. [236] http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=OJ:L:2003:178: 0024:0027:EN:PDF. Directive 2003/53/EC of the European Parliament and of the Council of 18 June 2003 amending for the 26th time Council Directive 76/769/EEC relating to restrictions on the marketing and use of certain dangerous substances and preparations (nonylphenol, nonylphenol ethoxylate and cement). [237] http://en.wikipedia.org/wiki/Ractopamine. Wikipedia: Ractopamine. [238] http://jas.fass.org/cgi/content/abstract/80/E-Suppl_2/E85. Schinckel, A. P., B. T. Richert, and C. T. Herr. 2002. Variation in the response of multiple genetic populations of pigs to ractopamine. J. Anim. Sci. 80(E. Suppl. 2): E85-E89. [239] http://www.newsdaily.com/stories/tre68t1yf-us-cycling-contador/. tador suspended as doping charges rock cycling. News Daily 30.09.2010. Con-
[240] http://www.efsa.europa.eu/en/science/contam/contam_opinions/ej478_ heptachlor.html. EFSA: Opinion of the Scientic Panel CONTAM related heptachlor as an undesirable substance in animal feed. Published 5 June 2007. [241] http://www.efsa.eu.int/science/contam/contam_opinions/1229_en.html. European Food Safety Authority: Opinion of the CONTAM panel related to the presence of non dioxin-like polychlorinated biphenyls PCB) in feed and food; Adopted on 8 November 2005. Question Nr EFSA-Q-2003-114).
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[242] http://www.efsa.eu.int/science/ppr/ppr_opinions/1452_en.html. European Food Safety Authority; PPR Opinions: Opinion of the Scientic Panel PPR related to the evaluation of dichlorvos in the context of Council Directive 91/414/EEC. 20 April 2006. [243] Simat, Thomas J.; Eulitz, Klaus D.;Steinhat, Hans: Undesirable contaminants in biotechnologically manufactured L-Tryptophan.GIT Fachz. Lab. 4/96 339-344. [244] http://www.food.gov.uk/multimedia/pdfs/tryptophanconresponseng.pdf. UK FSA: Summary of responses to the 2 March 2005 consultation on tryptophan in food regulation 2005. [245] Baer I, Beatriz de la Calle, and Philip Taylor. 3-mcpd in food other than soy sauce or hydrolysed vegetable protein (hvp). Anal Bioanal Chem, 396(1):44356, 1 2010. http://www.ncbi.nlm.nih.gov/pubmed/19841911. [246] Pommes frites, backofen. oekotest. 5 2011. http://www.oekotest.de/cgi/index. cgi?artnr=97689;bernr=04;seite=00;co=. [247] Erste einschtzung zur bewertung der in ranierten panzlichen fetten nachgewiesenen gehalte von glycidol-fettsureestern. stellungnahme nr. 007/2009 des bfr vom 10. mrz 2009. http://www.bfr.bund.de/cm/343/erste_einschaetzung_ von_glycidol_fettsaeureestern.pdf. [248] Buhrke T, Weisshaar R, and Lampen A. Absorption and metabolism of the food contaminant 3-chloro-1,2-propanediol (3-mcpd) and its fatty acid esters by human intestinal caco-2 cells. Arch Toxicol, 2 2011. http://www.ncbi.nlm.nih.gov/pubmed/ 21327620. [249] Seefelder W, Varga N, Studer A, Williamson G, Scanlan FP, and Stadler RH. Esters of 3-chloro-1,2-propanediol (3-mcpd) in vegetable oils: signicance in the formation of 3-mcpd. food addit contam part a chem anal control expo risk assess. 25(4):391 400, 4 2008. http://www.ncbi.nlm.nih.gov/pubmed/18348037. [250] Haines TD, Adlaf KJ, Pierceall RM, Lee I, Venkitasubramanian P, and Collison MW. Direct determination of mcpd fatty acid esters and glycidyl fatty acid esters in vegetable oils by lc-tofms. J Am Oil Chem Soc, 88(1):114, 1 2011. http://www. ncbi.nlm.nih.gov/pmc/articles/PMC3022155/?tool=pubmed. [251] Ilsi europe report series: 3-mcpd esters in food products. summary report of a workshop held in february 2009 in international life sciences institute, brussels, belgium. http://www.ilsi.org/europe/publications/final%20version% 203%20mcpd%20esters.pdf. [252] http://www.eurekalert.org/pub_releases/2006-08/uou-ant081806.php. A new tool against brain disease: Snail toxin may spur new meds for Alzheimers, Parkinsons, depression.
BIBLIOGRAPHY
2101
[253] http://en.wikipedia.org/wiki/Conotoxins. Wikipedia, the free enzyclopedia: Conotoxin. [254] http://www.jbc.org/cgi/content/abstract/281/34/24745. Marion Loughnan, Annette Nicke, Alun Jones, Christina I. Schroeder, Simon T. Nevin, David J. Adams, Paul F. Alewood, and Richard J. Lewis: Identication of a Novel Class of Nicotinic Receptor Antagonists: Dimeric conotoxins VxXIIA, VxXIIB, and VxXIIC from Conus vexillum. J. Biol. Chem., Vol. 281, Issue 34, 24745-24755, August 25, 2006 doi:10.1074/jbc.M603703200. [255] http://www.efsa.europa.eu/en/science/contam/contam_opinions/ej447_ pyrrolizidine.html. EFSA: Opinion of the Scientic Panel CONTAM related to pyrrolizidine alkaloids as undesirable substances in animal feed. Last update 25 May 2007. [256] http://www.food.gov.uk/news/newsarchive/2008/may/nicarbazin0508. Food Standards Agency: Report issued on nicarbazin residues in chicken. 12 May 2008. [257] http://www.aphis.usda.gov/ws/researchreports/report07.pdf. USDA: Development of Nicarbazin for Application as an Infertility Agent. Wildlife Services FY 2004. [258] http://www.rsc.org/ej/AN/1999/a904557k.pdf. Cannavan, Andrew; Ball, Glyn ; Kennedy, D. Glenn: Determination of nicarbazin in feeds using liquid chromatography-electrospray mass spectrometry. Analyst, 1999, 124, 1431-1434. [259] http://cat.inist.fr/?aModele=afficheN&cpsidt=16654236. Huet A.-C.; Mortier L.; Daeseleired E.; Fodey T.; Elliott C.; Delahaut P.: Screening for the coccidiostats halofuginone and nicarbazin in egg and chicken muscle: development of an ELISA. Food Additives & Contaminants. Volume 22, Issue 2 February 2005, pages 128 - 134. Doi: 10.1080/02652030500038041. [260] http://www.efsa.europa.eu/EFSA/efsa_locale-1178620753812_ 1178701242025.htm. Opinion of the Scientic Panel on Contaminants in the Food chain on a request from the European Commission on cross-contamination of non-target feedingstus by halofuginone hydrobromide authorised for use as a feed additive, The EFSA Journal (2008) 657, 1-31. [261] http://www.bfr.bund.de/cd/template/index_en. German Federal Institute for Risk Assessment BfR: Bitter apricot kernels can lead to poisoning. [262] http://www.apricotkernels.org/main.htm. CEM Food.C. Ltd. [263] Bertsche T, Schulz M; 2003. Amygdalin - ein neues altes Krebsmittel?, Pharmazeutische Zeitung. www.pharmazeutische-zeitung.de/leadmin/pza/2003-24/pharm4.htm.
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[264] http://www.cancer.gov/cancertopics/pdq/cam/laetrile/ healthprofessional. National Cancer Institute, USA, 2005. [265] http://whqlibdoc.who.int/publications/2004/9241530618.pdf. WHO: Hydrogen Cyanade and Cyanides: Human Health Aspects. [266] http://www.bfr.bund.de/cd/template/index. BFR: Salatmischung mit Geiskraut verunreinigt. [267] http://www.newagebd.com/2006/sep/15/busi.html. NewAgeBusiness: Govt inaction hurts shrimp exports 15.09.2006. [268] http://www.food.gov.uk/multimedia/faq/51434/. FSA: Nitrofurans in shrimps and prawns. Question and Answers 15.01.2008. [269] http://www.ingentaconnect.com/content/bsc/clm/2006/00000012/00000011/ art00001? Antunes, P.; Machado, J.; Peixe, L.: Illegal use of nitrofurans in food animals: contribution to human salmonellosis? Clinical Microbiology and Infection, Volume 12. Number 11, November 2006, pp.1047-1049(3) DOI: 10.1111/j.1469-0691.2006.01539.x. [270] http://www.washingtonpost.com/wp-dyn/content/article/2008/03/10/ AR2008031000621_pf.html. Washinton Post: AP Probe Finds Drugs in Drinking Water. By Je Donn, Martha Mendoza and Justin Pritchard. The Associated Press Monday, March 10, 2008; 9:17 AM. [271] http://www.oxfordjournals.org/eshre/press-release/freepdf/den490.pdf. Fei,Chunyuan; McLaughlin, Joseph K.; Lipworth, Loren; Olsen, Jorn: Maternal levels of peruorinated chemicals and subfecundity. Human Reproduction, Vol.1, No.1 pp. 1- 6, 2009 doi:10.1093/humrep/den490. [272] http://ehp03.niehs.nih.gov/article/info%3Adoi%2F10.1289%2Fehp.1002409. Deon JC, Mabury SA: Exploring Indirect Sources of Human Exposure to Peruoroalkyl Carboxylates (PFCAs): Evaluating Uptake, Elimination and Biotransformation of Polyuoroalkyl Phosphate Esters (PAPs) in the Rat. Environmental Health Perspectives, 2010; DOI: 10.1289/ehp.1002409. [273] http://www.ncbi.nlm.nih.gov/pubmed/19759456. Suja F, Pramanik BK, Zain SM: Contamination, bioaccumulation and toxic eects of peruorinated chemicals (PFCs) in the water environment: a review paper. Water Sci Technol. 2009;60(6):1533-44. [274] http://www.ncbi.nlm.nih.gov/pubmed/18700679. Negri, S.; Maestri, L.; Esabon, G.; Ferrari, M.; Zadra, P.; Ghittori, S.; Imbriani. M.: Characteristics, use and toxicity of uorochemicals: review of the literature G Ital Med Lav Ergon. 2008 JanMar;30(1):61-74.
BIBLIOGRAPHY
2103
[275] http://www.efsa.europa.eu/EFSA/efsa_locale-1178620753812_ 1211902012171.htm. EFSA: EFSA opinion on two environmental pollutants (PFOS and PFOA) present in food. [276] http://www.efsa.europa.eu/en/scdocs/doc/1498.pdf. Reasoned opinion of EFSA: Modication of the existing MRL for thiacloprid in strawberries. EFSA 02.02.2010. [277] http://www.epa.gov/pesticides/reregistration/endosulfan/ endosulfan-cancl-fs.html. EPA to Terminate All Uses of Insecticide Endosulfan To Protect Health of Farmworkers and Wildlife. June 08, 2010. [278] http://en.wikipedia.org/wiki/Endosulfan. Wikipedia: Endosulfan. [279] http://www.epa.gov/oppsrrd1/REDs/factsheets/aldicarb_fs.html. Agreement to Terminate All Uses of Aldicarb. EPA:
[280] http://www.umweltministerium.de/english/current_press_releases/pm/ 46511.php. Federal Environment Minister Roettgen and Environment Agency President Flasbarth: Data on human exposure to pollutants urgently needed. Human Biomonitoring is an important instrument of health related environmental protection. Ministry for Environment, Nature Conservation and Nuclear Safety. No. 145/10 Berlin, 27.09.2010. [281] Forscher entdecken in bubble-tea gefhrliche stoe. berliner morgenpost 23 aug2012 ppg 9. [282] Mcdonalds launches bubble tea line in german restaurants (video) huingtonpost. 2012/06/11. http://www.huffingtonpost.com/2012/06/11/ mcdonalds-bubble-tea-germany_n_1587833.html. [283] Im bubble tea blubbert es gefhrlich. zeit online 29.08.2012. http://www.zeit.de/ wissen/gesundheit/2012-08/bubbletea-schadstoffe. [284] Pearl bubble milk tea from taiwan is considered a louis vuitton product in the international market. 08.01.2011. http://taiwanreview.nat.gov.tw/fp.asp?xItem= 172531&ctNode=1354. [285] Eu agencies consider phenylbutazone detected in horsemeat of low concern for consumers; recommend improved horse traceability and monitoring of veterinary medicinal residues. 15. efsa. april 2013. http://www.efsa.europa.eu/en/press/news/ 130415.htm.
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Chapter 28 Radioactivity and Food

Radioactivity is the property of atomic nucleus to change spontaneously to another nucleus by itself, without the inuence from outside, releasing energy in form of particles and/or electromagnetic rays. The parent nucleus is called the emitting nucleus which changes its atomic number and becomes the nucleus of a dierent element being called daughter nucleus or decay product.
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Ionizing radiation
Ionising radiation is produced by a beam of electrons striking a target, by cosmic radiation, radioactivity and nuclear reactions, which release energetic photons (gamma rays, x-rays) and/or particles. Ionizing radiation penetrates living organisms and alters cells, which then send signals to initiate various defensive responses.
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Mass number of an atom
is the sum of neutrons and proton. It is given as a small number high up in front of the symbol of the element.
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Atomic number
is the sum of protons of an atom. It is given as a small number down in front of the symbol of the element. Every atom has a central, positively charged nucleus made of protons and neutrons. Nuclei are unaected by chemical reactions. Protons and neutrons are collectively referred to as nucleons
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Isotopes
Two atoms which have the same number of protons but dierent numbers of neutrons are called isotopes of each other. Isotopes have identical chemical properties and cannot be 2105
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separated by chemical methods. The isotopes of hydrogen are: 1 Hydrogen (1 H ) 2 Deuterium (1 D) 3 Tritium (1 T ) The particles of the nucleus are held together by one of the four fundamental forces: Strong interaction, also called nuclear force. This force is very strong. Electromagnetic force. Weak interaction. Gravitational force. Atomic warfare and atomic bomb tests in Nevada, Bikini and Soviet Union are responsible for high levels of strontium 90 fall out which caused high levels of strontium 90 in Brazil nuts growing in the rain forest of the Amazon region. Nuclear energy is an important part of electrical power supply. It was considered to be clean energy.The disaster of Harrisburg and Chernobyl have demonstrated the danger of nuclear power stations. The fallout from Chernobyl made the killing and disposal of Norwegian reindeer. Rising radioactivity of the Arctic region and its food chain is a product of uncontrolled nuclear handling. The disposal of radioactive waste is unsolved problem for future generations. The salt mine of Gorleben in Germany is unsafe for disposal of nuclear waste.
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Contamination of foods and feedstus by nuclear accidents
The accident of Chernobyl provided a lot of knowledge on contamination of the food chain. These information can now be applied in the actual Japan nuclear disaster. It is important to avoid milk of cattle which received grass and fodder of the contaminated region. As most of the radioactive particles end up in the ocean it is imperious to avoid sea foods of any kind. Do not drink tap water. More personal protection measures are described below. The food chain safety will be compromised in the next decades by the situation in Fukushima. Primarily drinking water in Japan and Pacic sh and seafood will bear an increased load of radionuclides.
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Japan prohibits the sell of shiitake-mushrooms [1]
In the region of Fukushima shiitake-mushrooms (Lentinus edodes Sing) with high radiation were found. A total of 16 cities and towns are compromised. The ban was imposed on mushrooms cultivated outdoors. Mushrooms grown in greenhouses are safe and may be sold, according to Kyodo News. The local department of health reports a 1,55 times
2107 of the maximum permitted content of Iodine 131 and 1,78 times for Caesium in shiitakemushrooms. On April 1, shiitake mushrooms from the city Iwaki had a level of radioactive cesium of 890 becquerels per kilogram against the limit of 500 becquerels, reports Kyodo News.
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Radionuclides in the food chain [2]
The exposure may result from direct inhalation of contaminated air or ingestion of contaminated water, or from a less direct pathway, the ingestion of contaminated food products. The exposure may result from direct inhalation of contaminated air or ingestion of contaminated water, or from a less direct pathway, the ingestion of contaminated food products. The the contamination of the milk of the cow is a typical example to the incorporation of radionuclides in the food chain resulting of the ingestion of contaminated pasture, the so called the pasture-cow-milk exposure route. Mushrooms from Bavaria, Germany, are still contaminated with radiating Caesium from the disaster of Chernobyl. German wild boars even after 25 years after Chernobil disaster are excluded from food market because they exceed the German limit on 600 Becquerel/Kg in meat. Wild boars like mushrooms which are highly contaminated by radionuclides. [3] The contamination of mushrooms with radionuclides depends on the type of mushroom and on the type of soil they grow on. The Cs-137 nuclides can highly be absorbed from forest soil where it is free available for plant roots. In agricultural areas the radionuclides are tightly bound to soil particles and their absorption is diminished. Sweet chestnuts and birch bolete are plant products with highest contamination. [4] Schwaiger et al. 2004 report that in 2002, the ingestion dose of radionuclides from the accident of Chernobyle in Austria amounts to 2.24 microSv (adult), or 0.88 microSv (5year infant) respectively, which is less than 0.5% of the ingestion dose of the rst year and amounts to 0.7% of the ingestion dose from natural radionuclides. [5]
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Soil type important for prediction of food-chain contamination [6]
According to Bell and Shaw 2005 initial studies and advices of the UK Ministry of Agriculture, Fisheries and Food, following the Chernobyl accident, were based on agricultural soils, with high clay and low organic matter contents where the radioiodine decayed and the radiocaesium became immobilised by attachment to clay particles. Other soils, low in clay and high in organic matter, such as the wet and acidic uplands, however favour mobility and bioavailability of the radionuclides. Radiocaesium entered the food chain. Sale of sheep had to be banned over areas of upland. Bans will continue in some cases for some years to come.
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The authors stress the importance of a fundamental understanding of biogeochemical pathways in dierent ecosystems to predict the impact of radionuclides fall-out.
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Root uptake of radionuclides in organic soils [7]
Rigol, Vidal and Rauret 2002 report that high 137CS soil-to-plant transfer persists in organic soils over years, which may be related to the low solid-liquid distribution coecient resulting of the low clay content and high NH4+ concentration in the soil solution, and the low K+ availability, which enhances root uptake. Chiang et al. 2010 studied the sorption of Caesium and Strontium of soils around nuclear facilities in Taiwan. The amounts of pyrophosphate extractable Fe (Fe(p)) clay minerals and increased temperatures were correlated signicantly with the Cs and Sr sorption capacities. The authors concluded that short-range ordered sesquioxides especially Al- and Fe-oxides complexed with organics inuence Cs and Sr sorption. [8]
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Chernobyl contamination data [9]
Leoniak et al. 2006 report that the air at Chernobyl had been contaminated with about 5300 PBq radionuclide activity, including 1760 PBq (131)I and 85 PBq (137)Cs. The contaminated areas presented 37 kBq/m(2)of (137)Cs. The highest mean radiation dose per year for the whole body in the rst year after the accident was in Poland 932 microSv, in Bulgaria 760 microSv, in Austria 670 microSv and Greece 590 microSv), The lowest radiation dose was observed in Portugal (1.8 microSv) and Spain (4.2 microSv). Actual radiation dose in Poland is close to the limited dose permitted of 1 mSv/year.
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Body radiation burden of the population of Sweden [10]
Rf and colleagues 2006 present data of human body burden resulting from fallout from nuclear weapons tests (only (137)Cs) and Chernobyl debris (both (134)Cs and (137)Cs)The authors found that the committed eective dose over a 70 y period for the urban Swedish population is 20-30 microSv/kBq m(-2), reindeer herders 700 microSv/kBq m(-2), hunters in the counties dominated by forest vegetation 100 microSv/kBq m(-2), rural non-farming populations living in sub-arctic areas 40-150 microSv/kBq m(-2), and farmers 50 microSv/kBq m(-2).
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Eating behaviour of population of the contaminated areas
According to Rf eating behaviour is an important pathway of the fall-out radioniclides to man. Contamination takes place by ingesting foodstus of the region. This can be
2109 reduced by meticulously following the recommendations of the authorities.
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Maximum permitted levels for foodstus and feedstus of European Regulation [11] Iodine administration to reduce damage caused by radiation following a nuclear accident [12]
28.0.38
Iodine- 131 is concentrated in the thyroid gland. It is one of the most carcinogenic nuclear ssion products. If people are expected to be exposed to a signicant amount of environmental radioactive iodine (iodine-131 in fallout), they should take non-radioactive potassium iodide tablets. The typical adult dose is one 130 mg tablet per 24 hours, supplying 100 mg (100,000 micrograms) iodine, as iodide ion. Typical daily dose of iodine to maintain normal health is of order 100 micrograms. By ingesting this large amount of non-radioactive iodine, radioactive iodine uptake by the thyroid gland is minimized. KI can protect only the thyroid from radioactive iodine, not other parts of the body. KI cannot reverse the health eects caused by radioactive iodine once damage to the thyroid has occurred. KI cannot protect the body from radioactive elements other than radioactive iodine. Tablets approved by FDA come in two strengths, 130 milligram (mg) and 65 mg. Each milliliter (mL) of the oral liquid solution contains 65 mg of KI. According to the FDA, the following doses are appropriate to take after internal contamination with radioactive iodine: - Adults should take 130 mg (one 130 mg tablet. Women who are breastfeeding should take the adult dose of 130 mg. - Children between 3 and 18 years of age should take 65 mg (one 65 mg tablet OR 1 mL of solution). Children who are adult size (greater than or equal to 150 pounds) should take the full adult dose, regardless of their age. - Infants and children between 1 month and 3 years of age should take 32 mg (1/2 of a 65 mg tablet OR 1/2 mL of solution). This dose is for both nursing and non-nursing infants and children. - Newborns from birth to 1 month of age should be given 16 mg (1/4 of a 65 mg tablet or 1/4 mL of solution). This dose is for both nursing and non-nursing newborn infants. Frankfort, Roos and Franssen 2003 recommend 100 mg non- radioactive iodine to block the absorption of radioactive iodine by the thyroid gland after a nuclear accident. The authors stress the problem of a well-regulated distribution and thorough protocols that sta of hospitals are familiar with. The solution of both problems are not guaranteed. [13]
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Measures to reduce radioactivity in drinking water, agriculture and food [14]
Smith et al. 2001 suggest that reduction of radioactivity in drinking water should focus on water treatment and distribution. Other measures to reduce human exposition to radionuclides is to ban consumption of sh. Deboning of sh may reduce strontium. Lake liming may reduce radiostrontium in sh, however, it is ineective for radiocaesium. The authors stress the importance of the provision of accurate information of the public. Agricultural countermeasures used between 1986-2006 to mitigate the consequences of the Chernobyl accident in Belarus, Russia and Ukraine averted 30-40% of the internal collective dose that would have been received by the residents of aected regions without the use of countermeasures, according to a study of Fesenco and colleagues 2007. This is not comforting as nearly 40% of all Europe and parts of Asia were compromised. [15]
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Deposition of radionuclides and decontamination of vegetables [16]
Tschiersch et al. 2009 studied the dry deposition of radionuclides to leafy vegetables under controlled greenhouse conditions, and the eect of washing of these vegetables. The authors found that the deposition depends on the leaf area, stomatal aperture, and plant morphology. Iodine deposition was signicantly higher compared to the particulate caesium deposition. Washing of contaminated vegetables ecient for iodine ut performed better for caesium.
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Contaminated area and foodstus will be dangerously radioactive for the next three centuries [17]
In many European countries levels of I-131, Cs-134/137, Sr-90, and other radionuclides in milk, dairy products, vegetables, fruits, grains, meat, and sh increased as much as 1,000fold immediately after the catastrophe. Incorporated Cs-137 and Sr-90 in the heavily contaminated territories increased from 1991 to 2005. The contaminated areas will be dangerously radioactive for roughly the next three centuries, say Nesterenko and colleagues 2009.
28.0.42
Chernobyl contamination of atmosphere, water and soil [18]
Yablokov et al.2009 report that the air particulate activity over all of the Northern Hemisphere was up to 1 million times higher than before the Chernobyl accident, producing ionic, aerosol, and gas structure of the surface air measured by electroconductivity and air
2111 radiolysis. The radionuclides are still being transported by forest res over hundreds of kilometres, and washout contaminates freshwater ecosystems The radionuclides concentrate in sediments, water, plants, and animals. Plants with deep roots bring the radionuclides back to the surface increasing actual values of internal irradiation among the population of the contaminated area.
28.0.43
Anti-nuclear movements in Japan [18]
Little was known related to the impact of the atomic bombings of Hiroshima and Nagasaki in August 1945 due to the US censorship on public information on radionuclides. The hydrogen bomb test by the US in the Bikini atoll on March 1, 1954 exposed the crew of the Japanese shing wessel "Lucky Dragon No.5" to radiation and Mr Aikichi Kuboyama died of the causes of the exposure. This incidence brought the danger of radionuclides at headlines. As a result of public petition, the Atomic Energy Basic Law established in December 1955 forbids the use of atomic energy for military projects. Table 28.1: Dairy products Isotopes of strontium (Sr-90) Isotopes of iodine (I-31) Alfa-emittinng isotopes of plutonium and transplutonium (Pu-239 Am-241) All other nuclides of half-life greater than 10 days (Cs-134, Cs-137) Dairy products 125 500 Other 750 2.000
20
80
1.000
1.250
Table 28.2: Other foodstus and liquid foodstus [19] Baby foods 75 150 Dairy products 125 500 Other foodstus 750 2.000 Liquid Foodstus 125 500
Isotopes Strontium, Sr-90 Isotopes of iodine, I-131 Alpha-emitting isotopes of plutonium and transplutonium elements, notably Pu-239, Am-241 All other nuclides of half-life greater than 10 days,
20
80
20
2112 notably Cs-134, Cs-137 400 1.000
CHAPTER 28. RADIOACTIVITY AND FOOD 1.250 1.000
28.0.44
Maximum permitted levels are set too high [20]
Green MEPs believe the maximum permitted levels of radioactive contamination are set far too high and would leave the European public exposed to unacceptably high doses of radioactive contamination. Strontium-90 is absorbed by bone, which leads to bone cancer and leukemia, caesium-137 spreads throughout the body but favours muscle tissue, plutonium is primarily toxic when inhaled and causes lung cancer and thyroid cancer broke among children in Chernobyl which drank milk which was iodine-131 contaminated.
28.0.45
Minor Foodstus [21]
For the minor foodstus given in the Annex of Regulation 944/89, the maximum permitted levels to be applied are 10 times those applicable to other foodstus except minor foodstus xed in the Regulation No 3954/87. Minor foodstus are those of minor dietary importance which make only a marginal contribution to food consumption by the population. List of minor foodstus Garlic, truels, capers (fresh, chilled, dried or as powder), manioc, arrowroot, salep, Jerusalem artichokes, sweet potatoes and similar roots and tubers with high starch or inulin content, fresh or dried, sago pith, peel of citrus fruit, curry and other spices, natural gums, agar-agar and other mucilages and thickeners, fats and oils and their fractions of sh or marine mammals, cocoa, yeasts baking powders, vitamins, essential oils.
28.0.46
Information to the public in case of a nuclear accident [22]
In case of a nuclear accident the public should be provided with the following informations. - Information on the type of emergency which has occurred and, where possible, its characteristics (e.g. its origin, extent and probable development). .- The various types of radiological emergency covered and their consequences for the general public and the environment. Basic facts about radioactivity and its eects on human beings and on the environment. - Emergency measures envisaged to alert, protect and assist the general public in the event of a radiological emergency. - Appropriate information on action to be taken by the general public in the event of a radiological emergency. - An invitation to the population concerned to tune in to radio or television, subsectionAdvice on personal protection Have iodine supplementation. Do not go outside,
2113 stay indoors. Close windows and make the house airtight. Do not turn on ventilators. Hang laundry indoors. Use wet cloth to breath through. Change often cloth. Use waterproof clothing to go outside. Wash hands often. Do not drink milk. Eat canned food. Avoid to drink tap water. Avoid seafood.
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Export ban of foods and feedstus which exceed maximum radiation levels [23]
It is not acceptable to allow products with contamination levels in excess of the maximum permitted levels relating to products for consumption in the Community to be exported to third countries.
28.0.48
Maximum permitted levels of radionuclides for feedstus [24]
Maximum permitted levels of radioactive contamination of feedstus following a nuclear accident or any other case of radiological emergency: Feedstus Table 28.3: Feedstus for Pigs Poultry, lamb, calves Others max Bq/Kg 1.250 2.500 5.000
28.0.49
Maximum allowed radiation levels [25]
The International Atomic Energy Agency said after Tuesdays blast that radiation dosages of up to 400 millisieverts per hour had been recorded at the site. Exposure to over 100 millisieverts a year is a level which can lead to cancer, according to the World Nuclear Association. 4.000 mSv (short exposure) causes 50% death rate. 7.000 mSv (short exposure causes death 1.000 mSv/hour radiation level near Fukushima power plant 16.03.2011 250 mSv (short exposure) causes radiation sickness (nausea, vomiting headache) 100 mSv (exposure during 1 year) causes 1% cancer
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2,4 mSv (cosmic radiation of 1 year according UN)
28.0.50
Australian nuclear waste dump at Muckaty Station [26]
Australia hosts one of the worlds rst nuclear research reactors. It was place of British nuclear weapons tests at Maralinga, and is an important supplier of uranium to the world.
28.0.51
Disposal of nuclear waste is becoming crucial [26]
Minister Martin Ferguson announced in February 2010 his plans to dump nuclear waste at Muckaty Station, 120km north of Tennant Creek, in the Northern Territory. Australian nuclear waste is currently stored at numerous sites around the country. Some Australian radioactive waste is also stored in Scotland and France. Federal Resources Minister Martin Ferguson said that the storage facility needed to be established before Australian waste was brought back from Scotland and France in 2014 and 2015. Australia has total holdings of around 4 300 cubic metres of radioactive waste which is not as much compared to other countries, such as Canada with a total holdings of more than 1.8 million cubic metres of low level waste alone. [27]
28.0.52
Will Muckaty Station become a global repository of nuclear waste? [28]
Senator Bob Brown says it is only a matter of time before Australias rst nuclear waste dump stores high level waste from overseas. Senator Brown calls for nuclear waste to be stored where it is produced, such as Lucas Heights in Sydney. He reasons that nuclear waste must be stored at its origin and not dumped somewhere. The former ALP prime minister Bob Hawke referred to the moral, nancial and environmental responsibility of Australia to assess a nuclear waste industry. Gareth Evans, says Australia should back all waste derived from the uranium it sells. [29] According to The Environmenter Centre Northern Territory there is a very real chance that in the future it will be expanded to take high level radioactive waste from nuclear reactors in Europe, Asia and North America, including reprocessed spent fuel rods which are amongst the most highly dangerous radioactive materials produced by the nuclear industry anywhere in the world. This waste remains dangerous to people, wildlife and the environment for thousands of years. There is a growing global crisis in high level waste disposal and many overseas companies and governments are looking to Australia to dump their waste. [30] World Nuclear Association director-general John Ritch said that Australians had nothing to fear from accepting radioactive waste. Thousands of years of radiation sounds like a
2115 long time, but there are many places on earth that have been geologically stable for many millions of years, he argued. [28]
28.0.53
History of radioactivity
1895 Roentgen rays (X rays) were discovered by Rntgen. 1896 Radioactivity was discovered by H.Becquerel working with uranium at the Ecole Polytechnique in Paris. 1898 Discovery of radioactivity of thorium by C.G. Schmidt at the same time with Madame Marya Curie. In the same year Madame Curie isolated from pitchblende (uraninite) polonium and radium. 1899 Discovery of actinium by Debierne, collaborator of Madame Curie. Actinium is a very rare element. 1934 The rst articial atomic nucleus was created by J. and Irne Joliot. This discovery opened the way to further studies in modern particle accelerators. 1963 FDA approves the use of irradiation in food to control insects in wheat and wheat our. Another application of irradiation which was approved by the FDA was the inhibition of sprouting of potatoes. 1980 The Food and Agriculture Organization (FAO), the International Atomic Energy Agency (IAEA) and the World Health Organization (WHO)concluded that the irradiation of food up to a maximum dose of 10 kilo Grays is considered to be safe . 1983 FDA approves the irradiation of spices and seasonings. 1985 FDA approves irradiation of pork to control trichina. 1990 FDA approves the irradiation of packaged fresh or frozen unheated poultry. 1992 FDA based on a review data and information concluded that irradiated food is safe and nutritionally adequate. 1997 FDA approves the irradiation of red meats.
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Dierent types of rays Electron beams X rays
Radiation was used in many ways as X rays in medical use and industrial purposes.
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Radiation of uranium
Radiation of uranium includes alfa- beta- and gama rays.

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Alfa rays
are positive charged particles of helium nuclei(two protons and two neutrons). Alfa rays are heavy and are stopped by a piece of paper. They are therefore not interesting for technological irradiation of food. Alpha particles are the most energetic form of radiation produced by radioactive decay. As they are charged and move relatively slowly ( 6% of the velocity of light], they produce high ionization, loosing their energy over a short distance producing considerably ionization. An alfa decay of a nucleus takes place when the nucleus loses four nucleons, two of them are protons. Uranium-238 decays by alfa-emission to thorium 234. The mass number decreases by 4. The atomic number decreases by 2.
28.0.59
Beta rays
are negative charged very fast electrons with near light velocity.Beta particles are emitted by nuclei which have to many neutrons to be stable. One neutron changes then into a proton and an electron which is emitted as beta particle. The mass number does not change. The atomic number increases by 1. Beta rays are used for irradiation of food because of their high penetration. The radioactivity of carbon can be use to date archaeological samples. As an example suppose that an archaeological sample has an activity of 7,5 disintegrations per minute, and that an equal mass of carbon from a living plant has an activity on 15 disintegrations per minute. The activity of the sample is one half that of the present day level and therefore its age is equal to the half-life of C 14. The sample is therefore 5.730 years old.
28.0.60
Gama rays
are electromagnetic waves which are very short and bear high energy. In comparison with alfa and beta particles they produce very little ionization and are very penetrating
28.0.61
Radiation of cobalt-60
Irradiation of food is practiced most frequently with cobalt-60 as radiation source with emission of gama and beta. The technology of the future will probably be the irradiation with X-rays which penetrate the food more eectively than gama rays of cobalt 60 does. X-rays can be switched o when the rays are not needed. Cancer cells can be destroyed by gama-radiation from cobalt 60.
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Irradiation of food
Irradiation of food can prolong shelf-life, reduce spoilage, reduce the menace of pathogens, delay ripening of fruits and vegetables avoiding the sprouting of potatoes [31]. The acceptance of irradiated food is very low because safe foods can be produced without radiation. The problems of Salmonella in poultry must be handled by monitoring the poultry feed, by hygienic measures of poultry stables and last but not least hygienic measures in kitchen. It is not known if radiolytic products and free radicals which are created by irradiation are harmless or toxic and essential nutrients such as vitamin E are reduced by radiation. Foods with high fat content such as oily sh and some dairy products , develop o-odors even with low dosis. Other technologies of food processing may cause more damage to the food as radiation does. The problem of the disposal of useless cobalt-60 units still unsolved. Germany has decided to exit atomic energy programs in order to reduce radiation garbage.
28.0.63
Irradiation detection tests
Lipids from not cooked foods under ionising rays form a cyclic compound 2-alkyl-cyclobutone. Hydrocarbons of irradiated lipid-rich foods can also be detected. Damage of the DNA caused by radiation may also be detected on unheated foods. Cell membrane damage may cause changes of the physical properties of irradiated foods such as: electrical impedance, viscosity, electrical potential, electron spin resonance (ESR) and thermal and nearinfraread analysis as well as thermoluminescence. Minerals trapp in their crystals free radicals originated by irradiation. These crystals are responsible for theroluminescence which can be used for the detection of irradiation of vegetables, fruits, grains and spices because all contain minerals. The same phenomena takes place in bone bearing foods where ESR may be used to detect irradiated food such as chicken with bones. Boneless chicken, liquid egg nd certain fruits are analysed by mass spectrometric detection of 2-alkylcyclobutanones after gaschromatgraphic separation.
28.0.64
Low body exposure to radiation
Low fractionated body exposure to radiation can activate immunological resistance. This is being used in tumor therapy. That is why short rest in certain radioactive caves are being used in the treatment of some sanitariums and mineral water with low radioactivity is being sold in Brazil. High dosis of radioactivity are responsible for a decrease of immunity because of the reduction of lymphocytes causing an increase of infections and cancer risk [32].
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Natural radioactive exposure Radon
Radon and its decay products which are present trapped air in rooms can be reduced with fresh air[33]. Radon endangers lung.
28.0.67
Air pollution from coal power plant
All minerals have a low natural radioactivity, so does coal. As it is being burned the radioactive part concentrates in the ash and through exhaust gases it comes to the atmosphere and causes fallout of isotopes of uranium, polonium and lead.
28.0.68
Air travel
Cosmic radiation is very high. The atmosphere is a natural shiel against this radiation. Air trac at high altitude is exposed to increased radiation because of a thin atmosphere leading to 5 microSievert/hour (0,5 millirem/hour). This is very important for aircraft crews who are due to their profession exposed to this radiation.
28.0.69
Phosphate fertilizer
Phosphate fertilizer are being utilized in great amount in modern agriculture. As phosphate fertilizer contain radioactive parts increase the natural exposure of people engaged in storage an handling including an increase of radiation of fertilized plants. This leads to an exposure of 40 millirem/year [34].
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Mineral water
Drinking 60 liters of mineral water in a year leads to 300 millirem/year.
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Cigarette smoke
Tobacco has lead-210 and Polonium 210 as natural isotopes. Smoking during 25 years leads to an exposure of 20 000 millirem. Life has been always submitted to natural radiation. A low level of radioactivity can cause small damage to DNA. The body can repair this by itself. It triggers th immune system. As the radioactive contamination caused by civilization rises, it becomes dangerous because of deposition in bones and organs concentrates radioactive material. The only way out of this dilemma is to reduce growing industrialization, reduce trac, is to return to small ecological limited populations and to be satised with a normal life avoiding the destruction of earth.
2119
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Radiation sensitivity of Women and unborn child
[35] According to Prof. Dr. Wolfgang-Ulrich Mller, radiation sensitivity of the unborn child is particularly high, while radiation sensitivity of women appears to be twice as high as that of men. Furthermore, radiation sensitivity of the eye lens is higher than previously assumed. Research in this eld must be continued and intensied, and lowering the limit value for the eye lens must be investigated as a matter of urgency.
28.0.73
Half-life period of radioactive material
The half-life period is the time in which half of a certain amount of radioactive material will decay. An element with 1600 years as half-life period has after 1600 years half of its material still active. After another 1600 years half of this amount is still active, one-fourth of the initial amount from 3200 years ago. It takes another 1600 to reduce it to one-eighth of the initial amount of 4800 years ago. Some examples demonstrate the necessity to handle radioactivity with great care as radioactive garbage will remain as burden for thousands of generations to come: Element
238
Half-life
Uranium-238 (92 U ) 4 510 000 000 years 235 Uranium-235 (92 U ) 704 000 000 years 234 Uranium-234 (92 U ) 247 000 years 226 Radium-226 (88 Ra) 1 600 years 222 Radon-222 (86 Rn) 3,82 days 214 4 Polonium-214 (84 P o) 1.6 X 10 seconds 218 Polonium-218 (84 P o) 3.05 minutes
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Radiation hazards
The extend of the harm caused to cells by radiation depends on the nature of the rays, the part of the body exposed to radiation and the dose received. Nature of rays: Alfa- particles are absorbed in the dead surface layers of the skin and are therefore not dangerous. If the source however is taken into the body through food, water or dust. Alfa rays can cause great damage.
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Radiation dose
Radiation doses the energy absorbed by a unit of mass. It is measured in gray (GY) units ( 1 Joule is absorbed by 1 Kg mass). 1 GY = 1 Jkg old writings used 1 Gy = 100 rad Unied atomic mass unit ( u ) 1 u = 1.660 X 1027 kg 1 u = 931 MeV
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Relative biological eectiveness ( RBE-Values)
In order to take account of the dierent biological eects of the dierent radiations it is useful to dene the eective dose as : Eective dose = Radiation dose X RBE The RBE values are given below: Radiation X rays Beta, gama and X High Speed neutrons Alpha rays RBE 1 1 10 20
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Measuring radiation dosage [36]
There is a relationship between radiation dose and its eect on the body. Radiation dosing can be thought of as an amount of energy absorbed by the body.
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The rad
The rad is a unit of absorbed radiaton dose dened in terms of the energy actually deposited in the tissue. One rad is an absorbed dose of 0.01 joules of energy per kilogram of tissue.
28.0.79
RBE
To accurately assess the risk of radiation, the absorbed dose energy in rad is multiplied by the relative biological eectiveness (RBE) of the radiation to get the biological dose equivalent in rems. The RBE is a "quality factor," often denoted by the letter Q, which assesses the damage to tissue caused by a particular type and energy of radiation. For alpha particles, Q may be as high as 20, so that one rad of alpha radiation is equivalent to 20 rem. The Q of neutron radiation depends on their energy. However, for beta particles, x-rays, and gamma rays, Q is taken as one, so that the rad and rem are equivalent for those radiation sources
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The jungle of units
The eective dose is labeled as Sievert (Sv) An old unit for eective dose had been the rem (rntgen equivalent man) 1 rem = 1 rad times RBE 1 Millirem ( mrem ) = 0.001 Sievert 1 Sv = 100 rem The unit of the activity of radioactive material is Becquerel (Bq): 1 Bq = 1 decay/second. The old unit of activity replaced by Bq, is Curie (Ci): 1 Ci = 3,7 X 1010 decays/second = 3,7 X 1010 Bq.
28.0.81
Energy dose
The rays of radiation have an interaction with the mass of the body which is being irradiated. This is called energy dose. The unit is Gray (Gy) , which means that 1 joule is absorbed by 1 kg of body. 1 Gray (Gy) = 1 J/Kg The old unit of energy dose was Rad (Radiation absorbed dose)RadRadiation absorbed dose 1 Gray (Gy) = 100 Rad
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The mass-energy relation of Einstein
According to the theory of relativity mass is equivalent to energy in accordance to: E = mc2 where c is the speed of light (3 X 108 m )s1
28.0.83
Mass-energy during an atomic ssion
When 1 kg of uranium-235 undergoes ssion the energy released is 80 000 000 000 000 J corresponding to a decrease in mass of 0,9 gram. This is a signicant loss of mass and can be measured.
28.0.84
Mass-energy during a chemical reaction
Chemical reactions release relatively small amounts of energy and the decrease in mass is to small to be measured. When 1 kg of petrol is burned the energy released is only 50 000 000 J corresponding to a decrease in mass of only 0,000 005 500 gram. This is to small to be measured and is omitted in chemical stoichiometry.
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Natural exposures Cosmic radiation
The atmosphere protects against cosmic radiation. As the air gets thinner, radiation rises. Free protons as primary rays from outer space collide with the upper layers of the terrestrial atmosphere reacting with other particles. This causes a mixture of rays, like mesons which passes meter of concrete and weak rays such as electrons,positrons and gama rays. Some examples demonstrate the growing exposition to radiation resulting growing air trafc. Passengers and crew of airlines are submitted to considerable high cosmic radiation. To spare fuel air trac takes place at 10 000 o 20 000 meters over sea level: Altitude(meters) sea level 1 500 3 000 4 000 Air trac Cosmic radiation (mrem/year) 30 60 140 200
0,5 mrem/ight hour (4 320 mrem/year) A crew member with 80 ight-hours per month is exposed to 480 mrem/year, this is twelve times the exposure of a profession at sea level.
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Exposition to radon
The lung of inhabitants in cold climates are exposed to radiation of radon which emanates from soil and concentrates in poor change of air. This may lead to an exposition of the air tract and lungs of: exposition to radon = 400 to 1 300 mrem/year The radiation of radon (86 Rn) is signicant because it consists of alfa particles which cause great damage to surface cells. The volume of air which passes the lungs is very high. Intake of radon is therefore relevant. Keep rooms well aerated to get rid of radon.
220
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Lung cancer caused by radioactive radon in living spaces [35]
The latest ndings on the risk of lung cancer from radon exposure were discussed at the International Commission on Radiological Protection (ICRP) Berlin, 19 June 2007. According to Dr. Margot Tirmarche, the risk of radon-related lung cancer in habitations increases by around 8% per 100 Becquerel per cubic metre (Bq/m3 ).
2123
Additional cases of cancer are already observed at between 100 and 200 Bq/m3 . Every year in Germany around 1,800 people die due to radon - one person every four hours. Radon may also play a role in child leukaemia. There is an urgent need for action to reduce radon exposures. The target value for new buildings is 100 Bq/m3 , a guideline value for remediation work in existing buildings is 200 Bq/m3 .
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Articial radioactivity
Radioactive nuclides which do not occur in nature can be produced by bombarding natural occurring nuclides inside a nuclear reactor with atomic particles such as neutrons.
28.0.90
Nuclear reactor
Nuclear reactors provide electric energy with the claim of clean energy. Today Germany tries to get rid of the atomic industry as it proved to be unsafe and there is no solution for the disposal of nuclear waste.
28.0.91
Nuclear ssion
is the disintegration of a heavy nucleus into two lighter nuclei with release of energy because the binding energy per nucleon of the ssion products is greater than that of the parents. 235 A classic example of ssion is the bombardment of uranium-235 (92 U ) by slow neutrons 236 and the formation of 92 U which is unstable and undergoes ssion. 235 1 236 141 92 1 U + (0 n)-> 92 U -> 56 Ba + 36 Kr + 30 n + energy 92 Nuclear reaction make use of controlled ssion reactions to provide energy. The atom bomb makes use of an uncontrolled ssion reaction.
28.0.92
Nuclear fusion
is the combining of two light nuclei to produce a heavier nucleus and energy. A classic example of nuclear fusion is the fusion of two deuterium nuclei to produce helium 3. 2 2 3 1 H + 1 H ->2 He + 0 n + energy 1 This is the source of energy of the sun. The high pressure and high temperature which is necessary to overcome the mutual electrostatic repulsion in the hydrogen bomb is provided by an atom bomb.
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The thermal reactor
Uranium-236 being bombarded by neutrons undergoes a ssion and releases about 2,5 neutrons which can bombard other uranium-236 atoms turning to a chain reaction.
2124

235 238
In natural uranium only about 1 atom is a 92 U atom. All other atoms are 92 U which can 235 only be ssioned with very fast neutrons. To produce ssion of 92 U atom slow neutrons are 235 238 necessary. Therefore the neutrons released by 92 U atom are to slow to cause ssion of 92 U 235 atom and to fast for a 92 U atoms. Therefore they must be slowed down by moderators ( graphite, water or heavy water D2 .). According to the material of the moderator the reactors are called:
28.0.94
Graphite-moderated reactor
Control rods of boron coated steel are used to keep the rate of production of neutrons to the requiredrods level by capturing the necessary proportion before they can initiate ssion. The produced energy is removed with a coolant such as carbon dioxide or water though the reactor, passing through an heat exchanger producing steam to drive turbines.
28.0.95
Cycle of the fuel rods of nuclear power plants
Uranium is being won from ore in 99,3% U-238 and 0,7% U-235. This mixture is tranformed in gas as Uranium hexa uorid (UF6 ) in the special enrich plant. The amunt of U-235 is risen to 3,5% which is necessary for the function of light water reactors. Here the Uranium is formed to rods which arre then forwarded to the nuclear power plants. The fuel rods once exhauted are stored until the separation of Uranium and Plutonium and other materials can take place. Waste of recycling is stored being protected by a glas layer.
28.0.96
Cancers in nuclear power plant workers [35]
According to Dr. Elisabeth Cardis) speaking at the Conference of the International Commission on Radiological Protection (ICRP) Berlin, 19 June 2007, the impact of low exposures has been underestimated in the past in two respects. The relative radiation risk in the area of occupational radiation exposure is denitely comparable to that of high exposures. Increased rates of cancer are already observed in the case of occupational lifetime doses which comply with the limit values currently in force. Lowering the limit values must be investigated as a matter of urgency.
28.0.97
Leukemia in children living near nuclear power plants [37]
The German Federal Agency for Radiation Protection says that there is an increased leukemia risk for children living in the proximity of 5 kilometres from a nuclear power
2125 station. The risk increases inversely to the distance to the plant. A research study leaded by Dr. Maria Blettner , analysed all leukemia cases in the proximity of 16 German nuclear power plants from 1980 to 2003. The researchers found 37 new cases while only 17 had been statistically expected. One member of the team said that the results were underrated. He says the area of concern is to increase to 50 kilometres around nuclear power plants. The study says that the emission of radiation of the nuclear power plants is not sucient to cause to increase the risk of cancer, also other concurrent causes could not explain the association of increased leukemia risk with inverse distance to the nuclear power plant. Worldwide studies conrm increased risk of leukemia in children under 5 years. The study of Dr. Blettner was done at The Institute of Medical Statistics, Epidemiology and Informatics (IMBEI) at the Clinical Centre of Mainz University. The study rises high doubts on the veracity of foregoing studies which deny any increased cancer risk related to nuclear power plants. The Federal Minister for the Environment Sigmar Gabriel asked the Radiation Protection Commission to assess the study, which is part of the German Children Cancer Register.
28.0.98
Japanese nuclear power plants are not earthquake safe [38]
The Japanese Nuclear power plant in Kashwazaki was seriously damaged by the 6,8 heavy earthquake on the 16. July 2007. The earthquake was 2,5 stronger as the plant was built for. Radioactive liquid was released at the site which is going through repair works for one year. There are another 17 nuclear power plants with the same guidelines used for the Kashwazaki plant.
28.0.99
Uranium-238 and ammunition in warfare
Uranium-238 is a waste of the production of fuel cells for nuclear power plants. As waste it is forwarded to the arms industry which uses it for hard core projectiles, mines and grenades. Depleted uranium-238 (DU) projectiles were used to bust tanks in the desert of Kuwait and Iraq. From the 24.2.1991 to the 28.2.1991 around 315.000 kg of radioactive uranium red against Sadams soldiers are now scattered all over the region. Later, in the war against Milosewich in Kosovo almost the same amount of depleted uranium-238 was used and is still distributed all over the territory. This material is highly radioactive with a half-life of 4,5 billions of years. All eorts should be done to avoida growing contamination of nature as there alternatives to uranium (density=18,7 Kg/dm3 with traces of plutonium which can be replaced by tungsten (density=19,3 Kg/dm3 ).
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20 years after Chernobyl [39]
The accident of Chernobyl in 1986 is still responsible for sheep at the farms in Cumbria, Scotland and Wales in April 2006 to still contain levels radioactivity above safety limits. Their meat is not allowed to enter the food chain. The particular chemical and physical properties of the peaty soil types of these regions makes the radiocaesium-137 to pass from soil to grass, accumulating in sheep. The levels of radioactivity have fallen in some of the aected areas but a number of farms are still under restriction and will not have their restrictions lifted in the near future. According to FEPA only sheep that have less than the maximum limit of 1,000 becquerels per kilogram of radiocaesium are allowed to enter the food chain.
28.0.101
Incorporation of radionuclides from the disaster of Chernobyl are increasing. Protective measures will be necessary for many generations [40]
Nesterenko and colleagues 2009 report that radiation levels for individuals in Belarus, Ukraine, and Russia have been increasing steadily since 1994 due to internal absorption. To reduce levels of incorporated radionuclides in food and meat production food additives are used, such as ferrocyanides, zeolites, lime/Ca as an antagonist of Sr-90, K fertilizers as antagonists of Cs-137, and phosphoric fertilizers that form a hard, soluble phosphate with Sr-90, disk tillage and replowing of hayelds, cleaning cereal seeds, processing potatoes into starch, processing carbohydrate-containing products into sugars, and processing milk into cream and butter. Forestry operations to create "a live partition wall," to regulate the redistribution of radionuclides into ecosystems are discussed. The authors conclude that these protective measures will be necessary in Europe for many generations.
28.0.102
Contamination of food and people [41]
In many European countries levels of I-131, Cs-134/137, Sr-90, and other radionuclides in milk, dairy products, vegetables, grains, meat, and sh increased drastically after the catastrophe. Some foodstus from Europe exceeded permissible levels of Cs-137 in 2007. From 1995 to 2007, up to 90% of the children from Belarus had levels of Cs-137 accumulation higher than 15-20 Bq/kg, with maximum levels of up to 7,300 Bq/kg in Narovlya District, Gomel Province. Average levels of incorporated Cs-137 and Sr-90 in the heavily contaminated territories increased from 1991 to 2005. According to Nesterenko these areas will remain dangerously radioactive for the next three centuries.
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28.0.103
Preventive Protective Action Guidelines [42]
The Protective Action Guides are 5 mSv (0.5 rem) for committed eective dose equivalent or 50 mSv (5 rem) committed dose equivalent to an individual tissue or organ, whichever is more limiting. These correspond to the "intervention levels of dose" consensus values set by international organizations. Intervention levels of dose are radiation doses at which introduction of protective actions should be considered (ICRP 1984b). Limit Responder Exposure - 5 rem (or greater), sheltering - 1 to 5 rems. Evacuation 1 to 5 rems. Relocation - 2 rems in rst year, 500 mrem/yr in subsequent years, food Interdiction - 500 mrem/yr, drinking Water - 500 mrem/yr. The US EPA response levels for preventive Protective Action to Land Contamination Guides (PAGs) are 3 Ci/m2 (111 kBq/m2) while levels for emergency PAGs are set at 30 Ci/m2 (1,110 kBq/m2) for infants and 50 Ci/m2 (1850 kBq/m2) for adults. Inhaled Cesium-137 commits to humans a 50-year committed eective dose equivalent (CEDE50) of 8.63 X 10-9 sievert per becquerel while its specic activity is 3.26 X 1012 becquerel per gram. [43] The mean contamination of Cs-137 in Germany after Chernobyl was 2000-4000Bq/m2 , some parts in the south even 10 times higher. This corresponds to a contamination of 1mg of Cs-137 per square kilometer or around 500g Cs-137 deposited all over Germany.
28.0.104
Fallout of Chernobyl aected Europe, Asia and Emirates [44]
Fall out of the Chernobyl meltdown aected 40% of Europe (including Austria, Finland, Sweden, Norway, Switzerland, Romania, Great Britain, Germany, Italy, France, Greece, Iceland, Slovenia) and wide territories in Asia (including Turkey, Georgia, Armenia, Emirates, China), northern Africa, and North America. Radioactivity exposure at a level higher than 4 kBq/m(2) (0.11 Ci/km(2)) from April to July 1986 happened. The consequences of radioactive contamination are therefore not conned to Belarus, Ukraine, and European Russia.
28.0.105
Interference level for radiation protection and decorporation of radionuclides [45]
Due to local food consumption the annual individual dose limits in Belarus, Ukraine, and European Russia exceed 1 mSv/year in 2007, and for eective radiation protection the interference level for children at should be set at 30% of the ocial dangerous limit (i.e., 15-20 Bq/kg), says Nesterenko.
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Pectin food additives from apples, currants grapes and seaweed, 5 g twice a day, reduced radionuclides in children by 30 to 40%, report the authors.
28.0.106
Radiological impact in Europe [46]
According to Leoniak, Zonenberg and Zarzycki 2005 the air at Chernobyl had been contaminated with about 5300 PBq radionuclide activity, and surface 137Cs activity was 37 kBq/m(2). The highest mean radiation dose per year for the whole body in the rst year after the accident was in Bulgaria (760 microSv), Austria (670 microSv), Greece (590 microSv), and Poland 932 microS, while the lowest radiation dose was observed in Portugal (1.8 microSv) and Spain (4.2 microSv).
28.0.107
Persistent contamination with 137 Cs of Alpine lakes sediments [47]
Rezzoug and colleagues 2006 found that the region of the alpine lake Boron at the southeast of France was contaminated with 137Cs fallout of the Chernobyl accident with at least 3.5 Bqcm(-2), more probably the double. The lake sediments still undergo a rather strong contamination by 137Cs and the external exposure impact was evaluated at 2 mSvy(-1) for 2002. Transuranics and ssion products 90Sr, 137Cs, 238Pu, 239/240Pu and 241Am have been measured in Boron lake sediment samples. These data enable future determination of the mass balances of the radiopollutants. Schertz and colleagues 2005 stress that this area is in a recreational area used by urban population. [48]
28.0.108
Fish of Finnish lakes with high uptake of 137Cs [49]
Saxn and Ilus report continuously high concentrations of 137Cs in sh of two Finnish lakes due to a prolonged stay of caesium at a relatively high level in the water. There were dierences between the two lakes found which was explained by a slow sedimentation rate, deciency of potassium in water, a low pH and a swampy soil type of the catchment resulting in a higher content of 137 Cs of the water and its uptake by shes in the lake Lake Siikajarvi compared with the Lake Vehkajarvi.
28.0.109
Radionuclides in North Sea, a result of anthropogenic activities [50]
According to a report of Ried and Kanisch 2011 dumping nuclear waste into the North Sea is not allowed any more, however, a high amount of drums, lled with, once dumped at deep sea, are now corroding and release polonium and other nuclides which are detected in water, sh and plants of the North Sea. The fuel rod reprocessing plants of La Hague (France) und Sellaeld (GB) still discard
2129 million litres of low radioactive sewage water, adding to the contamination with nuclides of past nuclear experiments during the Cold War and fall out of Chernobyl. Nuclides of Strontium, Caesium, Uranium and Plutonium accumulate in organs and bones.
28.0.110
Radionuclides released by oil and natural gas production and mining
A considerable amount of radioactivity in the North Sea has its origin in oil and natural gas. Their natural content of Radium-226, Radium-228, Lead-210 and Polonium-210 are a product of the decay of Uranium and Thorium. They are bound in the underground and released during the production of oil and natural gas. The nuclides get to the sea as run-o and contaminate seafood. All mining and other activities which bring deep stratums to the surface and release hazardous materials which were safely deposited there for millions of years. Articial nuclides in the North Sea released by La Hague und Sellaeld have decresed in last years. The German BSH reported in 2004 for the German bight 1,4 to 6,1 Bq/m3 of Cs-137, 1,7 to 3,7 Bq/m3 of Sr-90, 8,5 to 26,1 mBq/m3 of Pu-239/240 and 3,5 to 21,8 mBq/m3 of Am-241. Cs-134 was not detected any more in North Sea water. The distribution of the trans-uranium elements Pu-239,240, Pu-238 und Am-241 in the German bight and the activity relationship between both Plutonium nuclides provide evidence that the plutonium comes from the plants in Sellaeld and La Hague. [51]
28.0.111
Radionuclide transfer to wood and food from forests [52]
Radionuclide transfer varies in space and time depending on deposition processes, soil type, land use, and resulting contamination in food products, the radionuclide transfer through food chains. Calmon and colleagues 2001 assessed the transfer of radionuclides of radiocaesium and radiostrontium to trees in forests which vary between T(ag) 10(3)m(2)kg(-1) (dry weight). Tree foliage was usually 2-12 times more contaminated than trunk wood. The transfer of radionuclides to mushrooms varies from T(ag) 10(-3) to 10(1)m(2)kg(-1) (dry weight), for berries, typical values are around 0.01-0.1 m(2)kg(-1) (dry weight). Transfer of radioactive caesium to game animals, reindeer, moose birds and waterfowl reect the soil and pasture conditions at individual locations. In wild boar the caesium activity concentration shows no decline because of its special feeding habits.
28.0.112
Wild animals in Germany cannot be sold as food because of high levels of radioactive caesium-137 [53]
The south of Germany was heavily aected by fall out of the Chernobyl accident on April 26, 1986. German wild boar present high levels of contamination with caesium-137 in
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2010. According to the Environment Ministry, the average contamination for boar shot a forested region on the Bavarian border with the Czech Republic, was 7,000 becquerel per kilogram. According to food law any animals showing contamination levels higher than 600 becquerel per kilogram must be disposed of. Germanys Atomic Energy Law, which regulates the use of nuclear energy in the country, mandates that the government in Berlin pay compensation to hunters who harvest contaminated animals. Wild boar have a predilection for mushrooms and trues, which are particularly high in radioactivity. Experts say that the contamination of mushrooms and trues will remain high and may even rise slightly. German government compensation payments to hunters are part of a 238 million euro recompense for damages relating to Chernobyl accident. Radioactivity in wild boar will likely remain that way for at least the next 50 years.
28.0.113
Radionuclides from soil to fruits [54]
Carini 2001 in a 2001 review writes that the transfer of radionuclides from soil to fruit is nuclide specic, depends on the type of soils and fruit plant species. Caesium has a higher transfer rate to fruits of woody trees and the transfer from soil to fruits of shrubs is higher for strontium in temperate areas. Caesium is higher in subtropical and tropical fruits and strontium, plutonium and americium, in the same fruits, are lower because of dierent soil characteristics, says the author.
28.0.114
Japan prohibits the sell of shiitake-mushrooms [1]
In the region of Fukushima shiitake-mushrooms (Lentinus edodes Sing) with high radiation were found. A total of 16 cities and towns are compromised. The ban was imposed on mushrooms cultivated outdoors. Mushrooms grown in greenhouses are safe and may be sold, according to Kyodo News. The local department of health reports a 1,55 times of the maximum permitted content of Iodine 131 and 1,78 times for Caesium in shiitakemushrooms. On April 1, shiitake mushrooms from the city Iwaki had a level of radioactive cesium of 890 becquerels per kilogram against the limit of 500 becquerels, reports Kyodo News.
28.0.115
Meat of cows from Fukushima entered the food market [55]
Meat of cows from Fukushima were sold all over Japan. The radioactive meat could reach consumers through shops or be digested by restaurant goers. Caesium levels in the hay fed
2131 to cattle were 520 times above norm. Meat samples presented a contamination of radioactive cesium, measuring 2,300 becquerels per kilogram, against the provisional ceiling of 500 becquerels, according to the local government. More than 400 cows of Fukushima were sold and entered retail, including Tokyo, between March 28 and July 6. The Aeon supermarket chain admitted that 320 Kg of contaminated meat had been sold in end of April to early June. The cows had been fed with contaminated with high radiation levels.
28.0.116
Bluen tuna with Fukushima radiation in California waters [56]
According to Madigan, Baumann and Fischer 2012, caesium-137 and caesium-134 of the Fukushima Daiichi accident on 11 march 2011 were detected in bluen tuna caught in Californian waters near San Diego in August 2011. Bluen tuna were found to contain 4 becquerels per kilogram of caesium-134 and 6.3 becquerels per kilogram of caesium-137. A study of 2008 had found no evidence of of caesium-134 which has its origin in nuclear power plant or nuclear weapons. The 2008 study had found normal environmental levels of caesium 137 while caesiium 134 was not detectable. The data of August 2011 are 10 times higher as those of years before, but are of no immediate health risk for environment and people. Japan has a safety limit of 100 becquerels per kilogram in food. The authors stress that bluen tuna had carried the radioactive materials across the Pacic ocean faster than those conveyed by wind or water. Researchers are therefore worried about the fact that some sh can cross the ocean without eliminating the radionuclides during their journey. Radionuklides Cs(134) and (137)Cs of the Fukushima accident contaminated waters 30-600 km oshore, mostly carried by the near-shore eddies and the Kuroshio Current Radionuclides originated from Fukushima were also found in zooplankton and mesopelagic sh, The data of a study of Buzesseler et al 2012 support higher estimates of the magnitude of Fukushima fallout and direct releases of dierent other authors in 2011. The authors stress, however, that public health and marine biota, despite being 10-1,000 times over levels before the accident, marine animals and humans are not at risk because the actual levels are below the level of natural radiation level.[57]
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28.1
Conversion of Becquerel to millisievert
The contamination of soil, food and water is given in Becquerel/sq.metre or Becquerel/Kg or litre. [58]
28.1.1
Becquerel
Becquerel (Bq) means one disintegration per second. The Becquerel (Bq) measures the activity of radioactive substances, whereas the Sievert (Sv) evaluates the eects of radiation on the body.
28.1.2
Dose Equivalent
A measure of the biological damage to living tissue as a result of radiation exposure. Also known as the " biological dose," the dose equivalent is calculated as the product of absorbed dose in tissue multiplied by a quality factor and then sometimes multiplied by other necessary modifying factors at the location of interest.
28.1.3
Sievert
The dose equivalent, measured in sievert, dened as the dose of absorbed radiation that has the same biological eect as a dose of one joule of gamma rays absorbed in one kilogram of tissue. In the United States the roentgen equivalent man (rem), equal to 0.01 sievert, is still in common use, although regulatory and advisory bodies are encouraging transition to sieverts
28.1.4
Conversion Becquerel/Sievert and Sievert/Becquerel
1 Bq = 0,0125 microsievert 1 microsievert = 80 Becquerel
28.1.5
Examples
Eating an amount of food with 80.000 Becquerel Caesium 137 is equivalent to approximately one millisievert. Eating 200 g mushrooms contaminated with 4.000 Becquerel Caesium 137/Kg s equivalent to 0,01 Millisievert.
28.1.6
Radiation exposure
The radiation exposure considers how long the exposure took place. It is given in Millisievert/year. Example; The natural radiation exposure in Germany is 2,1 Millisievert/year
28.1. CONVERSION OF BECQUEREL TO MILLISIEVERT
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(0,24 Microsievert/hour) another 2Millisievert are added as articial radiation (mainly medical devices)
28.1.7
Radiation limits for food
Food radiation should not exceed 500 Becquerel/Kg Baby food radiation should not exceed 400 Becquerel/Kg for Caesium and 100 Becquerel for iodine.
28.1.8
Radionuclides in the food chain [2]
The exposure may result from direct inhalation of contaminated air or ingestion of contaminated water, or from a less direct pathway, the ingestion of contaminated food products. The exposure may result from direct inhalation of contaminated air or ingestion of contaminated water, or from a less direct pathway, the ingestion of contaminated food products. The the contamination of the milk of the cow is a typical example to the incorporation of radionuclides in the food chain resulting of the ingestion of contaminated pasture, the so called the pasture-cow-milk exposure route. Mushrooms from Bavaria, Germany, are still contaminated with radiating Caesium from the disaster of Chernobyl. German wild boars even after 25 years after Chernobil disaster are excluded from food market because they exceed the German limit on 600 Becquerel/Kg in meat. Wild boars like mushrooms which are highly contaminated by radionuclides. [3] The contamination of mushrooms with radionuclides depends on the type of mushroom and on the type of soil they grow on. The Cs-137 nuclides can highly be absorbed from forest soil where it is free available for plant roots. In agricultural areas the radionuclides are tightly bound to soil particles and their absorption is diminished. Sweet chestnuts and birch bolete are plant products with highest contamination. [4] Schwaiger et al. 2004 report that in 2002, the ingestion dose of radionuclides from the accident of Chernobyle in Austria amounts to 2.24 microSv (adult), or 0.88 microSv (5year infant) respectively, which is less than 0.5% of the ingestion dose of the rst year and amounts to 0.7% of the ingestion dose from natural radionuclides. [5]
28.1.9
Soil type important for prediction of food-chain contamination [6]
According to Bell and Shaw 2005 initial studies and advices of the UK Ministry of Agriculture, Fisheries and Food, following the Chernobyl accident, were based on agricultural soils, with high clay and low organic matter contents where the radioiodine decayed and the radiocaesium became immobilised by attachment to clay particles. Other soils, low in clay and high in organic matter, such as the wet and acidic uplands, however favour
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mobility and bioavailability of the radionuclides. Radiocaesium entered the food chain. Sale of sheep had to be banned over areas of upland. Bans will continue in some cases for some years to come. The authors stress the importance of a fundamental understanding of biogeochemical pathways in dierent ecosystems to predict the impact of radionuclides fall-out.
28.1.10
Root uptake of radionuclides in organic soils [7]
Rigol, Vidal and Rauret 2002 report that high 137CS soil-to-plant transfer persists in organic soils over years, which may be related to the low solid-liquid distribution coecient resulting of the low clay content and high NH4+ concentration in the soil solution, and the low K+ availability, which enhances root uptake. Chiang et al. 2010 studied the sorption of Caesium and Strontium of soils around nuclear facilities in Taiwan. The amounts of pyrophosphate extractable Fe (Fe(p)) clay minerals and increased temperatures were correlated signicantly with the Cs and Sr sorption capacities. The authors concluded that short-range ordered sesquioxides especially Al- and Fe-oxides complexed with organics inuence Cs and Sr sorption. [8]
28.2
Chernobyl contamination data
Leoniak et al. 2006 report that the air at Chernobyl had been contaminated with about 5300 PBq radionuclide activity, including 1760 PBq (131)I and 85 PBq (137)Cs. The contaminated areas presented 37 kBq/m(2)of (137)Cs. [9] The highest mean radiation dose per year for the whole body in the rst year after the accident was in Poland 932 microSv, in Bulgaria 760 microSv, in Austria 670 microSv and Greece 590 microSv), The lowest radiation dose was observed in Portugal (1.8 microSv) and Spain (4.2 microSv). Actual radiation dose in Poland is close to the limited dose permitted of 1 mSv/year.
28.2.1
Body radiation burden of the population of Sweden [10]
Rf and colleagues 2006 present data of human body burden resulting from fallout from nuclear weapons tests (only (137)Cs) and Chernobyl debris (both (134)Cs and (137)Cs)The authors found that the committed eective dose over a 70 y period for the urban Swedish population is 20-30 microSv/kBq m(-2), reindeer herders 700 microSv/kBq m(-2), hunters in the counties dominated by forest vegetation 100 microSv/kBq m(-2), rural non-farming populations living in sub-arctic areas 40-150 microSv/kBq m(-2), and farmers 50 microSv/kBq m(-2).
28.2. CHERNOBYL CONTAMINATION DATA
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28.2.2
Eating behaviour of population of the contaminated areas
According to Rf eating behaviour is an important pathway of the fall-out radioniclides to man. Contamination takes place by ingesting foodstus of the region. This can be reduced by meticulously following the recommendations of the authorities.
28.2.3
Undeclared irradiated supplements [59]
Dried aromatic herbs, spices and vegetable seasonings are the only foods that may be irradiated inside and outside Member States of the EU and sold freely within the EU. Imported irradiated food must comply with EU labelling and documentation rules. They must have been irradiated at a facility approved by the European Commission. There are only few approved facilities outside the EU: three in South Africa, one in Turkey and one in Switzerland. Testing food supplements the FSA found in 2003 that 50 per cent of food supplements in the UK had been irradiated or contain an irradiated ingredient, but are not labelled as such. Publication of the results was deferred until 2006 pending enforcement action by local authorities. The Food Safety Authority of Ireland (FSAI) found that 25 per centre of dried noodle products contained ingredients that had been irradiated. They had not been labelled as such. The US, South Africa, the Netherlands, Thailand and France, followed by about 50 adopted irradiation technology and use it on 60 products. Currently regulations on food irradiation in the European Union: EU: Directive 1999/2/EC establishes a framework for controlling irradiated foods, their labelling and importation. Directive 1999/3 establishes an initial positive list of foods which may be irradiated and traded freely between member states, which includes only dried aromatic herbs, spices and vegetable seasonings. Belgium, France, the Netherlands and the UK allow other foods to be irradiated. Denmark, Germany and Luxembourg remain opposed to irradiation. UK allow 7 categories of foods to be irradiated.
28.2.4
WHO Technical Report on Irradiation of Food
A World Health Organisation scientic report in 1999 found that irradiation posed no risk to human health:
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Overall chemical change, as reected either in the formation of a stable compound or the loss of a particular constituent, is quantiable and relatively minor, requiring sensitive techniques to discern that a product had been irradiated. In summary, the macronutrients - proteins, fats and carbohydrates - are not signicantly altered in terms of nutrient value and digestibility by irradiation treatment. Among the micronutrients, some of the vitamins are susceptible to irradiation to an extent very much dependent upon the composition of the food and on processing and storage conditions. From a nutritional viewpoint, irradiated foods are substantially equivalent or superior to thermally sterilized foods. On the basis of the extensive scientic evidence reviewed, the report concludes that food irradiated to any dose appropriate to achieve the intended technological objective is both safe to consume and nutritionally adequate. The experts further conclude that no upper dose limit need be imposed, and that irradiated foods are deemed wholesome throughout the technologically useful dose range from below 10 kGy to envisioned doses above 10 kGy." [60]
28.3
Irradiated foods in EU
[61] The irradiation of dried aromatic herbs, spices and vegetable seasonings is authorised in the EU (Directive 1999/3/EC of the European Parliament and of the Council of 22 February 1999 on the establishment of a Community list of food and food ingredients treated with ionising radiation In addition, 6 Member States have notied that they maintain national authorisations for certain foods in accordance with Article 4(4) of Directive 1999/2/EC. Under Article 6 of Directive 1999/2/EC, any irradiated food or any irradiated food ingredient of a compound food must be labelled with the words "irradiated" or "treated with ionising radiation".
28.3.1 28.3.2
Approved food irradiation facilities in EU Belgium
IBA Mediris S.A. Irradiating shrimps, frog legs, herbs, frozen vegetables, cheese, eggs, poultry/game, meat, sh, dried fruit, starch, plasma, prepared dishes, total 5,8 Tons in 2004
28.3. IRRADIATED FOODS IN EU
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28.3.3
Czech Republic
Dried aromatic herbs, spices and vegetable seasonings, egg white, total 460 tons in 2004.
28.3.4
Germany: In 2004
there were four approved irradiation facilities in Germany: Gamma Service Produktbestrahlung GmbH, Radeberg irradiating dried vegetables, herbs and seasonings, other foodstus ( guarana seeds), Total of 342 Tons in 2004. Beta-Gama Service GMBH&Co.KG, Whiel, irradiating granulated slippery jack mushrom, plant raw materials (parsley, dill, cilantro), powdered spinach powdered celery, horse radish, parsley. Total of 24 Tons in 2004. Total of 429 Ton in 2004. Isotron Deutschland GmbH, Allershausen irradiating seasonings, herbs total 429 Tons in 2004. Gama-Service GMBH&Co KG, Bruchsal. No food products were irradiated in the facility in 20034
28.3.5
Spain
There were two facilities approved for the irradiation of food. No information concerning activities in 2004 were given.
28.3.6
France
There were seven facilities approved for irradiation of food. In 2004 the following foods were irradiated: Herbs, spices and vegetable seasonings, frozen herbs, dried vegetables and fruits, gum arabic, casein, caseinates, mechanically recovered poultry meat, oal of poultry, frozen frog legs, shrimps, total of 1.800 Tonns.
28.3.7
Hungary
In 2004 there was one facility. No informations were given.
28.3.8
Italy
In Italy here was one facilty. No information was given.
28.3.9
The Netherlands
There were two facilities. One in Ede and one in Etten-Leur. Irradiated foods in 2004 were: Spices and herbs, dehydrated vegetables, poultry meat (frozen) frog parts, egg white (cooled), Foods intended for export to third countries. Total in 2004 4 768 Tons.
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28.3.10
Poland
There were two approved facilities: Institute of Nuclear Chemistry and technology, Warsaw, irradiated were spices, Herbs, dehydrated vegetables, and dried mushrooms, total in 2004 of 680 Tons. Institute of Applied Radiation Chemistry Technical university of Lodz. Spices in 2004 total of 47,8 Tons.
28.3.11
The United Kingdom
It has one facility approved. No food was irradiated in 2004.
28.3.12
Labelling
The Neatherlands reports that a total of 430 samples had been taken in the marketplace and analysed for irradiation. Of these 430 samples, 45 dietary supplements and spices proved to be irradiated. Only 2 of the irradiated samples were correctly labelled as such. No indication of the origin of the positive samples was given. The information submitted shows that during 2004, 3,9% of samples were irradiated and not correctly labelled. The infringements are unevenly distributed over product categories. Products imported from Asia, especially Asian-type noodles and dried prepared noodles, are particularly concerned. In addition, it should be noted that in 2004, there were no facilities in Asia approved by the European Community. Dierences between Member States regarding the results of controls could partly be explained by the choice of the samples and the performance of the analytical methods used. No reports from 2005 and 2006 are available.
28.3.13
Adhesion and internalization of pathogens in fresh produces reduce ecacy of sanitizers [62]
Lynch, Tauxe and Hedberg 2009 explain that widespread food borne outbreaks have their cause in the increasing consumption of fresh produce, changes in production and distribution. Adhesion of pathogens to surfaces and internalization of pathogens reduce the eciency of conventional processing and chemical sanitizing methods. At the surface of fruits pathogens can build biolms which protects them from sanitizers, or they invade the
28.3. IRRADIATED FOODS IN EU interior of the plants where they cannot be harmed.
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To reduce these risks the authors suggest to improve the prevention of the contamination on the farm, during packing or processing. A terminal such as irradiation may improve safety of fresh produce. The authors call for more investigations on the causes of outbreaks to develop improved prevention strategies. Noah 2009, commenting this article stresses that the worldwide transport of fruits and vegetables may distribute pathogens over large areas. [63]
28.3.14
Irradiation of fruits and Vegetables [64]
Arvanitoyannis and colleagues 2009 emphasizes that central processing of fresh fruits and vegetables turns irradiation technology interesting. The authors stress that gamma irradiation restrain potato sprouting, kills pests in grain, extends shelf life of fruit and vegetable shelf life. To avoid high irradiation doses the "hurdle technology" may be useful. This strategy applies more than one technology to improve quality and shelf life. Furthermore, various methods for detection of irradiated foods, such as EPR, TL and Comet assay are discusses. The impact and eectiveness of irradiation dose on the shelf life and microora and sensory and physical properties of sh, shellsh, molluscs, and crustaceans were assessed by Arvanitoyannis and colleagues. The authors looked also at the synergistic eect of irradiation in conjunction with other techniques such as salting, smoking, freezing, and vacuum packaging. Again, methods to detect irradiation of sh and seafood are assessed. [65]
28.3.15
Irradiation of spinach aects nutrients [66]
FDA approved the irradiation of fresh iceberg lettuce and spinach to kill E. coli 0157:H7 and Salmonella enteric. Doses of irradiation up to 4kGy had been considered not to impact the nutrients of spinach. Lester and colleagues 2010 assessing the eect of gamma-irradiation or electron beams on spinach found that concentrations of vitamins B(9), E, and K and neoxanthin were little or not changed by irradiation. However, total ascorbic acid (vitamin C), free ascorbic acid, lutein/zeaxanthin, violaxanthin, and beta-carotene all were signicantly reduced at 2.0 kGy and lesser doses. Dihydroascorbic acid increased with increasing irradiation due to the formation of oxidative radicals. The authors report that packaging atmosphere had little eect, however, spinach irradiated under N2 presented an increase of dihydroascorbic acid levels, compared to air.
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28.3.16
Irradiated foods are free of risks, but consumer is still insecure [67]
No scientic study demonstrating that consumption of irradiated food might pose a risk to consumers were found by Rossi and colleagues 2009. All studies conclude that food irradiation at the appropriate dose required to reduce contamination is safe and does not aect its nutritional value, however the technology is not accepted by a broad part of the consumers. In an eort to demonstrate the potential benets, the authors compared food irradiation with the risk of infection with E. coli 0157: H7, and concluded that up to date no risk of irradiated foods are known, but death cases from bacterial pathogens are known.
28.3.17
Escherichia coli internalized on lettuce leaves [68]
Gomes and colleagues 2009 assessed the ecacy of irradiation of leaves of iceberg, Boston, green leaf, and red leaf lettuces contaminated with a cocktail mixture of two isolates of Escherichia coli, and subjected to a vacuum perfusion process locate the bacteria on crevices and into the stomata. Gamma irradiation was applied at 0.25-1.0-kGy. Calculated D(10)-values varied between 48 and 62%. No signicant dierence was noted between the lettuce varieties. Irradiation up to 1.0-kGy resulted in 3-4-log reduction of internalized E. coli on the lettuce leaves. The authors concluded that ionizing irradiation may be used to reduce the risk of food disease outbreaks by reducing internalized pathogens. The eect is dose-dependent,
28.3.18
Irradiation compared with chlorination for elimination of Escherichia coli O157:H7 [69]
Niemira 2008 comparing the eect of irradiation with that of chlorination found that pathogenic bacteria penetrate the leaf tissues and are protected against chlorination. In rhis study E. coli inoculated leaves of boston, green leaf, and red leaf lettuce were treated with a 3-min wash with sodium hypochlorite solution (0, 300, or 600 ppm) or various doses of ionizing radiation (0.25 to 1.5 kGy). The reduction obtained with chlorine solutions was less than 1 log, while irradiation reduced pathogenic E. coli 5 logs on iceberg lettuce treated with 1.5 kGy. The variety of lettuce inuences the specic results. The author concluded that irradiation is able to eectively reduce viable E. coli O157:H7 cells internalized in lettuce.
28.3. IRRADIATED FOODS IN EU
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28.3.19
Irradiation of food, an emerging technology [70]
In a review in 1998 Farkas suggests the irradiation of food ranging from 2 to 7 kGy, depending on the variety of food, to eliminate potentially pathogenic. The author recommends irradiation of poultry and red meat, egg products, and shery products, irradiation can be performed in frozen state. According to the author fumigation of herbs and enzyme preparations may be replaced irradiation using doses of 3-10 kGy. Radiation treatment at doses of 0.15-0.7 kGy are being suggested for the control of foodborn parasites. The author stresses that microorganisms surviving radiation treatment are more sensitive subsequent food processing treatments than not irradiated bacteria. The author concluded that irradiation of food is an emerging technology with increasing number of clearances on radiation decontaminated foods.
28.3.20
Improved safety and quality of poultry and other irradiated meat [71]
OBryan and colleagues 2009 emphasize that currently permitted levels of irradiation are insucient to control pathogenic viruses, while gram-negative spoilage organisms are very sensitive to irradiation. The reduction of spoilage bacteria increased the shelf life and, on the other hand, did not provide a competitive growth advantage for other food pathogens, weakened by irradiation. The authors stress that most of the antimicrobials and antioxidants produce an increased lethality of irradiation. Thus, the combinations of dosage, temperature, dietary and direct additives, storage temperature and packaging atmosphere can improve quality of meat.
28.3.21
Irradiation as food preservation method [72]
Andrews and colleagues 2008 stresses the use of irradiation in fruits and vegetables as an insect control as an alternative to less eective methods. For grains such as rice and wheat, irradiation has been used to control infestation by fumigation resistant insects. For spices irradiation doses of 10 kGy were recommended to extend shelf life. Safety of meat may be improve with irradiation, so as it is happening with seafood products such as shrimps for the Asian and European markets
28.3.22
Electron spin resonance (ESR) detection of irradiated food [73]
Electron spin resonance (ESR) may detect the radiation-induced radicals which persist, even after most of the radicals have decayed within days or weeks. Dodd 1995 calls it the most specic for the detection of irradiated food. Later, in 2008, Yu and Cheng provided a review of the use of this method used in nutraceutical and food research, microstructure
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change, phase transition and viscosity related properties during food formulation, processing, and storage. [74] Electron paramagnetic resonance EPR method to detect irradiation of soybean [75] The gamma radiation dose in the 0.25 to 1.0 kGy range irradiation is permitted to control insect infestation of food. Sanyal and Sharma 2009 developed an electron paramagnetic resonance (EPR) spectrum method. The authors detected cellulose and phenoxyl radicals in the skin part of irradiated soybean. The authors suggest that that progressive saturation and thermal characteristics of induced radicals may be used to distinguish low doses irradiated soybean from thermally treated one. This method is applicable also in case of long storage, say the authors.
28.3.23
Relaxation behaviour of the radicals may be used to detect irradiation of cashew nuts [76]
In 2008 Sanyal and Sajilata assessed the electron paramagnetic resonance (EPR) spectrum of free radicals formed during irradiation and compared it with those caused by conventional thermal treatment of cashew nuts. These signals found at irradiated cashew nuts were related to cellulose and CO 2 (-) radicals. An increase of the intensity of the central line (g = 2.0045) was found to be similar to that of thermal treated cashew nuts. The authors report, however, that irradiation of cashew nuts could be demonstrated by measuring the dierent relaxation and thermal behaviours of the free radicals, compared with those of roasted cashew nuts.
28.3.24
Radiation accidents emergency plan for Kuwait [77]
The Ministry of Health presented a radiation accidents emergency plan for Kuwait to deal with any radioactive pollution accidents. Levels of radiation are monitored by 15 xed and two mobile radiation detection stations. . Actual level of radiation in Kuwait ranges between 84 and 266 nanosievert (nSv) per hour which means that the average is 130 nSv/h. (Radiation in Germany varies between 50-60 nSv/h). A strategic reserve of drugs for radiation-related illnesses, including up to 60 million doses of non-radioactive iodine for various radioactive categories and 18,000 bottles of medicine in syrup form for infants aged under three were provided to be ready for any nuclear accident.
BIBLIOGRAPHY
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28.3.25
New genetic mapping technique shows an evolutionary response to rapid climate change on mosquito [78]
Scheiner, Bradshaw and colleagues 2010, analysed the genome of the pitcher plant mosquito, Wyeomyia smithii. using Restriction-site Associated DNA (RAD) sequencing technique. This mosquito lives within the water-lled leaves of the purple pitcher plant, Sarracenia purpurea, also known as the side-saddle ower, growing at the eastern seaboard of the U.S., the Great Lakes and southeastern Canada. Using the RAD-Tag approach, the scientists have demonstrated that post-glacial populations of Wyeomyia smithii originated from a southern Appalachian Mountain refugium after recession of the Laurentide Ice Sheet some 22,000 to 19,000 years ago. The results of this study increases understanding of the genetic mechanism underlying photoperiod response to rapid climate change, responsible for the correct timing of dormancy, migration, development and reproduction in temperate organisms such as blood-feeding in mosquito vectors of dengue, encephalitis and malaria. According to the authors the RAD-Tag protocol has increased the resolution of genetic relatedness among populations and may be used in elds from ecology and evolution to human behaviour and medicine, and may predict patterns of invasion of species during rapid climate change, and to correlate gene-based illnesses with susceptible human populations on a local or worldwide scale.
Bibliography
[1] Government bans shipments of some shiitake mushrooms near nuclear plant. kyodo news. 13.04.2011. http://english.kyodonews.jp/news/2011/04/85133.html. [2] Dinis ML and Fiza A. Models for the transfer of radionuclides in the food chain. iaeacn-145/205p. http://curem.iaea.org/envrad2007/content/rsrc/Envrad2007/ 205P/205P-Dinis-S1formatted.pdf. [3] BR Online. Jger messen wildbret auf csium-belastung. 03.01.2011. http://www.br-online.de/bayern1/mittags-in-mainfranken/ regionalnews-frankenmagazin-caesiumtest-wildfleisch-ID1291199214738. xml. [4] BR Online. Tschernobyl ist nicht pass. 03.09.2010. http://www. br-online.de/ratgeber/ernaehrung/pilze-sammeln-DID1195676901904970/ pilze-strahlung-pilze-schwammerl-ID67119567686849892.xml. [5] Schwaiger M, Mueck K, Benesch T, Feichtinger J, Hrnecek E, and Lovranich E. Investigation of food contamination since the chernobyl fallout in austria. Appl Radiat Isot, 61(2-3):35760, Aug-Sep 2004. http://www.ncbi.nlm.nih.gov/pubmed/15177371.
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[6] Bell JN and Shaw G. Ecological lessons from the chernobyl accident. Environ Int, 31(6):7717, 8 2005. http://www.ncbi.nlm.nih.gov/pubmed/16005971. [7] Rigol A, Vidal M, and Rauret G. An overview of the eect of organic matter on soil-radiocaesium interaction: implications in root uptake. J Environ Radioact, 58(23):191216, 2002. http://www.ncbi.nlm.nih.gov/pubmed/11814166. [8] Chiang PN, Wang MK, Huang PM, Wang JJ, and Chiu CY. Cesium and strontium sorption by selected tropical and subtropical soils around nuclear facilities. J Environ Radioact, 101(6):47281, 6 2010. http://www.ncbi.nlm.nih.gov/pubmed/19038481. [9] Leoniak M, Zonenberg A, and Zarzycki W. The radiological situation before and after chernobyl disaster. Endokrynol Pol, 57(1):4552, Jan-Feb 2006. http://www.ncbi. nlm.nih.gov/pubmed/16575762. [10] Rf CL, Hubbard L, Falk R, Agren G, and Vesanen R. Transfer of 137cs from chernobyl debris and nuclear weapons fallout to dierent swedish population groups. Sci Total Environ, 367(1):32440, 8 2006. http://www.ncbi.nlm.nih.gov/pubmed/ 16504249. [11] Council regulation (euratom) no 3954/87 of 22 december 1987 laying down maximum permitted levels of radioactive contamination of foodstus and of feedingstus following a nuclear accident or any other case of radiological emergency. http://eur-lex. europa.eu/LexUriServ/LexUriServ.do?uri=CELEX:31987R3954:EN:HTML. [12] Cdc emergency preparednes and response: Potassium iodide (ki). http://www.bt. cdc.gov/radiation/ki.asp. [13] Frankfort SV, Roos JC, and Franssen EJ. Iodine prophylaxis to prevent radiation damage following nuclear disasters. Ned Tijdschr Geneeskd, 47(34):16414, 8 2003. http://www.ncbi.nlm.nih.gov/pubmed/12966630. [14] Smith JT, Voitsekhovitch OV, Hakanson L, and Hilton J. A critical review of measures to reduce radioactive doses from drinking water and consumption of freshwater foodstus. J Environ Radioact, 56(1-2):1132, 2001. http://www.ncbi.nlm.nih. gov/pubmed/11446114. [15] Fesenko SV, Alexakhin RM, Balonov MI, Bogdevitch IM, Howard BJ, Kashparov VA, Sanzharova NI, Panov AV, Voigt G, and Zhuchenka YM. An extended critical review of twenty years of countermeasures used in agriculture after the chernobyl accident. Sci Total Environ, 383(1-3):124, 9 2007. http://www.ncbi.nlm.nih.gov/pubmed/ 17573097. [16] Tschiersch J, Shinonaga T, and Heuberger H. Dry deposition of gaseous radioiodine and particulate radiocaesium onto leafy vegetables. Sci Total Environ, 407(21):5685 93, 10 2009. http://www.ncbi.nlm.nih.gov/pubmed/19640563.
BIBLIOGRAPHY
2145
[17] Nesterenko AV, Nesterenko VB, and Yablokov AV. 12. chernobyls radioactive contamination of food and people. Ann N Y Acad Sci, 1181:289302, 11 2009. http://www.ncbi.nlm.nih.gov/pubmed/20002056. [18] Yablokov AV, Nesterenko VB, and Nesterenko AV. 8. atmospheric, water, and soil contamination after chernobyl. Ann N Y Acad Sci, 1181:22336, 11 2009. http: //www.ncbi.nlm.nih.gov/pubmed/20002050. [19] Council regulation (euratom) no 2218/89 of 18 july 1989 amending regulation (euratom) no 3954/87 laying down maximum permitted levels of radioactive contamination of foodstus and of feedingstus following a nuclear accident or any other case of radiological emergency. http://eur-lex.europa.eu/LexUriServ/LexUriServ.do? uri=CELEX:31989R2218:EN:HTML. [20] Radioactive foodstus: Eu rules on radioactive contamination of foods need to be strengthened, ep wants greater say. the greens 13.01.2011. http://www.greens-efa. eu/cms/pressreleases/dok/367/[email protected]. [21] Commission regulation (euratom) 944/89 (oj l101, p17, 13/04/1989) of 12 april 1989 laying down maximum permitted levels of radioactive contamination in minor foodstus following a nuclear accident or any other case of radiological activity. http: //www.fsai.ie/uploadedFiles/Commission_Regulation_Euratom_944_89.pdf. [22] Council directive (euratom) 89/618 (oj l357, p31, 07/12/89) of 27 november 1989 on informing the general public about health protection measures to be applied and steps to be taken in the event of a radiological emergency. http://www.fsai.ie/ uploadedFiles/Council_Directive_Euratom_89_618.pdf. [23] Council regulation (eec) no 2219/89 of 18 july 1989 on the special conditions for exporting foodstus and feedingstus following a nuclear accident or any other case of radiological emergency. http://eur-lex.europa.eu/LexUriServ/LexUriServ. do?uri=CELEX:31989R2219:EN:HTML. [24] Commission regulation (euratom) no 770/90 of 29 march 1990 laying down maximum permitted levels of radioactive contamination of feedingstus following a nuclear accident or any other case of radiological emergency. http://eur-lex.europa.eu/ LexUriServ/LexUriServ.do?uri=CELEX:31990R0770:EN:HTML. [25] Bbc news: Radiation fears after japan blast. 15.03.2011. http://www.bbc.co.uk/ news/world-12740843. [26] http://news.brisbanetimes.com.au/breaking-news-national/ nuclear-waste-dump-is-a-duty-ferguson-20100303-pj8c.html. waste dump is a duty: Ferguson. Brisbane Times. 03.03.2010.
Nuclear
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[27] http://www.ecnt.org/html/cur_other_toxics_nukedump.html. Why we oppose the proposed Commonwealth radioactive waste dump in the Northern Territory. The Environmenter Centre Northern Territory. 27. April 2006.
[28] http://www.theaustralian.com.au/news/nation/store-nuclear-waste-in-australia-gare story-e6frg6nf-1225783120360. Store nuclear waste in Australia: Gareth Evans. The Australian 06.08.2010. [29] http://www.abc.net.au/news/stories/2010/08/04/2972925.htm. Store nuclear waste at source, not in NT: Brown. ABC News 04.08.2010. [30] http://www.aph.gov.au/library/pubs/online/radioactivewaste.htm. Parliament of Australia Parliamentary Library: Radioactive waste and spent nuclear fuel management in Australia. 01.01.2006. [31] Food and feedstu analysis, Preserving food by irradiation;Lab Plus international, November 2000; volume 14,nr5,page16-17. [32] Altmann,H.;Tuschl,H.: DNA-repair in lymphocytes of persons living in elevated natural background radiation areas (Badgastein). Late biological eects of ionizing radiation. Vol I, IAEA, Wien, 1978. [33] Feinendegen L. E.: Strahlenschutz Radioaktivitt und Gesundheit; Bayerisches Staatsministerium fr Landesentwicklung undUmweltfragen; 3.Auage-September 1986. [34] Bundesminister des Innern: Umweltradioaktivitt und Strahlungbelastung in den Jahren 1981 und 1982. September 1984. [35] http://www.bmu.de/english/current_press_releases/pm/39542.php. Federal Ministry for the Environment, Nature Conservation and Nuclear Safety: Gabriel: New ndings on the eects of radiation on humans should be given greater consideration. Press release No. 176/07 Berlin, 19 June 2007. [36] http://www.ij-healthgeographics.com/. Study details catastrophic impact of nuclear attack on U.S. cities Writer: Sam Fahmy, 706/542-5361, [email protected]. [37] http://www.bfs.de/de/bfs/presse/aktuell_press/Studie_Kernkraftwerke. html. Pressemitteilung 011 vom 08.12.2007 Krebsrisiko fr Kinder in der nahen Umgebung von Kernkraftwerken: Neue Studie im Auftrag des Bundesamtes fr Strahlenschutz bringt erstmals belastbare Ergebnisse. [38] http://portal.1und1.de/de/themen/nachrichten/panorama/vermischtes/ 4536592-Japans-Atomkraftwerke-sind-offenbar-nicht-erdbebensicher,cc= 000003112500045365921TGej6.html. Portal 1und1: Japans Atomkraftwerke sind oenbar nicht erdbebensicher. 26.08.2007.
BIBLIOGRAPHY
2147
[39] http://en.wikipedia.org/wiki/Chernobyl_disaster_effects. Wikipedia, The Free Enzyclopedia: Chernobyl desaster eects. [40] http://www.ncbi.nlm.nih.gov/pubmed/20002058. Nesterenko AV, Nesterenko VB.: Protective measures for activities in Chernobyls radioactively contaminated territories. Ann N Y Acad Sci. 2009 Nov;1181:311-7. [41] http://www.ncbi.nlm.nih.gov/pubmed/20002056. Nesterenko AV, Nesterenko VB, Yablokov AV: Chernobyls radioactive contamination of food and people. Ann N Y Acad Sci. 2009 Nov;1181:303-10. [42] http://www.epa.gov/rpdweb00/docs/er/400-r-92-001.pdf. EPA: Manual of Protective Action Guides and Protective Actions for Nuclear Incidents. [43] http://www.armscontrol.info/reports/authors/liolios/cesium-137% 20dirty%20bomb%20occasional%20paper.pdf. [44] http://www.ncbi.nlm.nih.gov/pubmed/20002040. Yablokov AV, Nesterenko VB: Chernobyl contamination through time and space. Endokrynol Pol. 2006 JanFeb;57(1):45-52. [45] http://www.ncbi.nlm.nih.gov/pubmed/20002057. Nesterenko VB, Nesterenko AV: Decorporation of Chernobyl radionuclides. Ann N Y Acad Sci. 2009 Nov;1181:5-30. [46] http://www.ncbi.nlm.nih.gov/pubmed/16575762. Leoniak M, Zonenberg A, Zarzycki W.: The radiological situation before and after Chernobyl disaster. J Environ Radioact. 2006;85(2-3):369-79. Epub 2005 Aug 15. [47] http://www.ncbi.nlm.nih.gov/pubmed/16102877. Rezzoug S, Michel H, Fernex F, Barci-Funel G, Barci V: Evaluation of 137Cs fallout from the Chernobyl accident in a forest soil and its impact on Alpine Lake sediments, Mercantour Massif, S.E. France. J Environ Radioact. 2006;85(2-3):380-8. Epub 2005 Sep 16. [48] http://www.ncbi.nlm.nih.gov/pubmed/16150519. Schertz M, Michel H, BarciFunel G, Barci V: Transuranic and ssion product contamination in lake sediments from an alpine wetland, Boron (France). J Environ Radioact. 2006;85(2-3):380-8. Epub 2005 Sep 16. [49] http://www.ncbi.nlm.nih.gov/pubmed/18313103. Saxn R, Ilus E: Transfer and behaviour of 137Cs in two Finnish lakes and their catchments. J Environ Radioact. 2009 Sep;100(9):757-66. Epub 2008 Dec 18. [50] Rieth U and Kanisch. Atomtests, sellaeld, tschernobyl und die belastung der meere. woher kommen radioaktive stoe in schen? von thnen-institut, institut fr schereikologie, report 1/2011. http://www.vti.bund.de/fileadmin/dam_uploads/ vTI/Presse/PDFs/PM_pdf_2011/FoReport_1-11_Rad-Fische.pdf.
2148
[51] Mursys- nordsee retrospectiv. bundesamt fr seeschiahrt und hydrographie, zusammenfassung der meereschemischen verhltnisse im 2. halbjahr 2004. http: //www.bsh.de/de/Meeresdaten/Beobachtungen/MURSYS-Umweltreportsystem/ Mursys_031/seiten/nozuch01.jsp. [52] http://www.ncbi.nlm.nih.gov/pubmed/19100665. Calmon P, Thiry Y, Zibold G, Rantavaara A, Fesenko S: Transfer parameter values in temperate forest ecosystems: a review. J Environ Radioact. 2001;52(2-3):237-79. [53] http://www.spiegel.de/international/zeitgeist/0,1518,709345,00.html. A Quarter Century after Chernobyl. Radioactive Boar on the Rise in Germany Spiegel Online 30.07.2010. [54] http://www.ncbi.nlm.nih.gov/pubmed/11202699. Carini F: Radionuclide transfer from soil to fruit. J Environ Radioact. 2001;52(2-3):237-79. [55] Excess level of radioactive caesium found in meat of fukushima cow. the mainichi daily news- 9 july 2011. http://mdn.mainichi.jp/mdnnews/news/ 20110709p2g00m0dm011000c.html. [56] Tuna contaminated with fukushima radiation found in california. the guardian. 29 may 2012. http://www.guardian.co.uk/world/2012/may/29/ tuna-contaminated-radiation-fukushima-california. [57] Buesseler KO, Jayne SR, Fisher NS, Rypina II, Baumann H, Baumann Z, Breier CF, Douglass EM, George J, Macdonald AM, Miyamoto H, Nishikawa J, Pike SM, and Yoshida S. Fukushima-derived radionuclides in the ocean and biota o japan. Proc Natl Acad Sci U S A, 109(16):59848, 5 2012. http://www.ncbi.nlm.nih.gov/pmc/ articles/PMC3341070/?tool=pubmed. [58] Nuclear regulatory commission. "nrc regulations: 34.3 denitions". united states government. http://www.nrc.gov/reading-rm/doc-collections/cfr/part034/ part034-0003.html. [59] http://www.food.gov.uk/news/newsarchive/2006/feb/irradexercise. UK Food Standards Agency: Irradiated food supplements enforcement exercise published; Wednesday 01 February 2006. [60] http://www.who.int/foodsafety/publications/fs_management/en/irrad.pdf. Report of a Joint FAO/IAEA/WHO Study Group: High-Dose Irradiation Wholesomeness of Food Irradiated with Doses Above 10 kGy (WHO technical report series: 890). [61] http://europa.eu.int/comm/food/food/biosafety/irradiation/approved_ facilities_en.pdf. Report from the commission on Food Irradiation for the year 2004 ( 2006/C 230/08).
BIBLIOGRAPHY
2149
[62] http://journals.cambridge.org/action/displayAbstract?fromPage= online&aid=3650384. Lynch, M.F.; Tauxe, R.V.; Hedberg, C.W.: The growing burden of foodborne outbreaks due to contaminated fresh produce: risks and opportunities. Epidemiology and Infection, 2009; 137 (3): 307-315 Doi: 10.1017/S0950268808001969. [63] Noah, Norman: Food poisoning from raw fruit and vegetables. Epidemiology and Infection, 137, pp 305-306. (2009). Doi:10.1017/S0950268808001957. [64] http://www.ncbi.nlm.nih.gov/pubmed/19399670. Arvanitoyannis IS, Stratakos ACh, Tsarouhas P: Irradiation applications in vegetables and fruits: a review. Crit Rev Food Sci Nutr. 2009 May;49(5):427-62. [65] http://www.ncbi.nlm.nih.gov/pubmed/18949599. Arvanitoyannis IS, Stratakos A, Mente E: Impact of irradiation on sh and seafood shelf life: a comprehensive review of applications and irradiation detection. Crit Rev Food Sci Nutr. 2009 Jan;49(1):68-112. [66] http://www.ncbi.nlm.nih.gov/pubmed/20329797. Lester GE, Hallman GJ, Perez JA: Gamma-Irradiation Dose: Eects on Baby-Leaf Spinach Ascorbic Acid, Carotenoids, Folate, alpha-Tocopherol, and Phylloquinone Concentrations. J Agric Food Chem. 2010 Mar 24. [67] http://www.ncbi.nlm.nih.gov/pubmed/19802398. Rossi L, Watson D, Escandarani S, Miranda A, Troncoso A: Radiation on the dining table. Rev Chilena Infectol. 2009 Aug;26(4):318-30. Epub 2009 Sep 23. [68] http://www.ncbi.nlm.nih.gov/pubmed/19733930. Gomes C, Da Silva P, Moreira RG, Castell-Perez E, Ellis EA, Pendleton M: Understanding E. coli internalization in lettuce leaves for optimization of irradiation treatment. Int J Food Microbiol. 2009 Nov 15;135(3):238-47. Epub 2009 Aug 27. [69] http://www.ncbi.nlm.nih.gov/pubmed/18577002. Niemira BA: Irradiation compared with chlorination for elimination of Escherichia coli O157:H7 internalized in lettuce leaves: inuence of lettuce variety. J Food Sci. 2008 Jun;73(5):M208-13. [70] http://www.ncbi.nlm.nih.gov/pubmed/9851599. Farkas J: Irradiation as a method for decontaminating food. A review. Int J Food Microbiol. 1998 Nov 10;44(3):189-204. [71] http://www.ncbi.nlm.nih.gov/pubmed/18464033. OBryan CA, Crandall PG, Ricke SC, Olson DG : Impact of irradiation on the safety and quality of poultry and meat products: a review. Crit Rev Food Sci Nutr. 2008 May;48(5):442-57. [72] http://www.ncbi.nlm.nih.gov/pubmed/9414630. Andrews LS, Ahmedna M, Grodner RM, Liuzzo JA, Murano PS, Murano EA, Rao RM, Shane S, Wilson PW: Food preservation using ionizing radiation. Rev Environ Contam Toxicol. 1998;154:1-53.
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[73] http://www.ncbi.nlm.nih.gov/pubmed/8660399. Dodd NJ: Free radicals and food irradiation. Biochem Soc Symp. 1995;61:247-58. [74] http://www.ncbi.nlm.nih.gov/pubmed/18080243. Yu LL, Cheng Z: Application of electron spin resonance (ESR) spectrometry in nutraceutical and food research. Mol Nutr Food Res. 2008 Jan;52(1):62-78. [75] http://www.ncbi.nlm.nih.gov/pubmed/19799676. Sanyal B, Sharma A: A new electron paramagnetic resonance method to identify irradiated soybean. J Food Sci. 2009 Oct;74(8):N57-64. [76] http://www.ncbi.nlm.nih.gov/pubmed/18767862. Sanyal B, Sajilata MG, Chatterjee S, Singhal RS, Variyar PS, Kamat MY, Sharma A: Identication of irradiated cashew nut by electron paramagnetic resonance spectroscopy. J Agric Food Chem. 2008 Oct 8;56(19):8987-91. Epub 2008 Sep 4. [77] http://www.kuwaittimes.net/read_news.php?newsid=ODQ0MDAwODYw. MoH develops radiation accidents emergency plan. Kuwait Times 30.08.2010. [78] http://www.nsf.gov/news/news_summ.jsp?cntn_id=117577&org=NSF&from=news. Genetic Structure of First Animal to Show Evolutionary Response to Climate Change Determined. National Science Foundation. August 24. 2010.
Part VI Food Industry
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Chapter 29 Hygienemonitoring
To achieve safety on regard of disease agents and to secure shelf-life are the central concern of hygiene of every food processing. Continuous training of the people which are engaged with handling and processing of food is vital importance. To guarantee safe foods it is necessary to control the raw material which is being used. Check the processing, the packaging, the end product and last but not least necessary to keep samples of all charges until expiring date. Example of wood as bacterial contamination is demonstrated by a splinter of wood cul-
tivated on plate count agar: Hygiene monitoring tries to avoid the contamination caused by raw materials, not sterile packagings, the inuence of the environment and wrong behavior of the sta. Hygienemonitoring is a part of the HACCP Program which was introduced in the European community by law The hygiene may be supervised by: Traditional methods such as contact cultures of surfaces of utensils and parts of machines,and culture of swabs of places to be dicultly reached,nal results taking 2 to 2153
2154 3 days.
CHAPTER 29. HYGIENEMONITORING
quick methods based upon ATP-Bioluminescence nal results taking about 2 minutes
29.1
ATP-Bioluminescence
ATP-Bioluminescence is used to supervise cleaning in food industries and other industries where perfect cleaning is necessary. ATP nds also increased use in special methods of detection and counting of bacteria.
29.1.1
Bioluminescence in environmental and food science
[1] Waidman and colleagues 2011 in a review of studies on Bioluminescence , say that luciferases are used in molecular biology as autoinducer-1 activity assays, promoter test assays, imaging of bacterial infections in live animals, in vivo activity assays genes involved in host response and disease and monitoring of bacterial contaminations of food products. Of more than 700 species carrying bioluminescence systems over 80% have been isolated are of marine origin. The authors note that frequent used bioluminescent reporter systems are the luciferase of a North American rey (Photinus pyralis), the lux operon of Photorhabdus luminescens, an enteric pathogen of nematodes, the luciferase of the sea pansy (Renilla reniformis), and Luciferase from the marine copepod Gaussia princeps. The lux systems are best known as bacterial luciferase systems encoded by the luxCDABE operon. Target-specic phages harbouring all genes required for bioluminescence, such as the LuxI and LuxR, are used to infect target bacteria which turns them luminescent. This is used to detect enterobacteria or Listeria monocytogenes. genes in food and environmental samples.
29.1.2
Firey luciferase
[2] Inouve 2010 reports that rey luciferase is a member of the acyl-adenylate/thioesterforming superfamily of enzymes, and is also involved in the synthesis of fatty acyl-CoA from fatty acids. The author says that the rey luciferase has its origin in a fatty acyl-CoA synthetase in insects because such genes are found in rey, Drosophila, and non-luminous click beetles. According to Hosseinkhani 2011, the light emitter of the rey luciferase is the excited singlet state of OL(-) ((1)(OL(-))*), and light emission from (1)(OL(-))*] is modulated by the polarity of the active-site environment at the phenol/phenolate terminal of the benzothiazole fragment in oxyluciferin. [3] According to Hirano et al 2009 the light emitter is the excited singlet state of OL(-) [(1)(OL(-))*], and light emission from (1)(OL(-))* is modulated by the polarity of the
29.2. HYGIENEMANAGEMENT IN FOOD INDUSTRY
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active-site environment of a luciferase and the degree of covalent character of the O8...H bond between (1)(OL(-))* and a protonated basic moiety in the active site. [4]
29.1.3
Bioluminescence in clinical applications
[5] Minekawa et al 2011 developed enhancers for bioluminescence reactions to reduce the rapid decay in light emission. In normal systems the light emission decrease to 42% after 5 seconds. With the described enhancers coenzyme A, inosine5-triphosphate sodium salt, sodium tripolyphosphate and potassium pyrophosphate light emission was improved to 89, 83, 87 and and 82% after 5 seconds. The authors used these enhancers in a bioluminescent enzyme immunoassay (BLEIA) for hepatitis B virus surface antigen (HBsAg) that employed rey luciferase as a labeling enzyme. The authors suggest that using such enhancers bioluminescence may become more suitable for clinical applications. According to de Almeida, Rappard and Wu 2011 bioluminescence imaging (BLI) is useful for monitoring the physiology of cell survival to gene expression to complex molecular processes, monitor stem cell therapy in vivo. Bioluminescence is also used in semi-quantitative measurements of gene expression in vivo to optimize drug and gene therapies and therapeutic interventions on the outcome of cardiac injuries. [6]
29.1.4
ATP bioluminescence rapid method for enumerating TVC in soy sauce
[7] The adenosine triphosphate (ATP) bioluminescence rapid determination method is used for enumerating the total viable count (TVC) in food and beverages for sanitation. Yan et al 2011 describe an ATP bioluminescence method to obtain total viable count of soy sauce samples within 4 hours, compared to 48 h required for the conventional aerobic plate count (APC) method. The authors report that they have eliminated interfering factors such as ingredients of soy sauce and found a high correlation coecient between total aerobic plate counts and ATP bioluminescence after ltration and resuscitation with special medium.
29.2
Hygienemanagement in food industry
In the production of food quick methods are important to check the quality of cleaning. During the cleaning of utensils and machines it is important to remove from the surfaces as much organic material as possible to insure a later disinfection and to avoid protein failure and to withdraw organic material for further growth of bacteria.
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The ATP-luminescence measures the ATP (Adenosine tri phosphate) from animal and from vegetable cells as well as living or dead bacteria. It shows in this manner how much impurities have been left after cleaning.
29.2.1
Principle of the ATP-bioluminescence-method
The ATP taken up with a swab from approximately 100 cm2 of the surface to be tested is put together with a luciferin/luciferase system of commercially available kits. There is light emitted which is proportional to the amount of ATP being present. This light is measured with a luminometer as "Relative Light Units RLU" . The light being emitted during this method is proportional to the amount of ATP being present on the surface to be examined. In order to achieve a better supervision of the hygiene it is advisable to use both system: The ATP luminescence method showing how much residues are left after cleaning, and the normal method of contact cultures telling what kind of bacteria are present, As the ATP-method gives the total amount of organic material left, it is necessary to determine for every place how much residues are still being considered as "good", and "bad". To determine the maximum RLU being accepted for these two points proceed as following: Measure for about 1 week the RLU of all relevant places of the production line and list the results for each place and note as: Good cleaning: Sum total of RLU measured during one week divided by the number measures for each place. Bad cleaning: 2 times the "Good Cleaning" point. In order to determine the standard of hygiene which can be obtained during normal production proceed as follow: Determine the RLU after "normal" cleaning. Continue the cleaning by hand using dierent detergents and determine the RLU after "rigorous cleaning". This is considered as being the best achievable cleaning. The best reference data are those values of "normal cleaning"which are as close as possible to the values of "rigorous cleaning". After one to two month repeat the determination of the reference points "good" and "bad". It is very likely that these points will be reduced because cleaning is growing better as a result of the continuous supervision. The checks may be "horizontal" being made on the same specic critical places of all machines. It is good to change from time to time to "vertical" checks from isolated machines checking all their parts.
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29.2.2
Understanding cleaning of food process plants
[8] Liu and colleagues assessed the removal of food fouling deposits during the cleaning of process plants. According to the authors deposits form by adhesion to the surface and cohesion between elements of the deposit. Cleaning can result from either or both adhesive and cohesive failure. The authors measured the adhesive/cohesive strength of deposits in terms of the work required to remove them from the surface, using a range of coated surfaces They found that tomato concentrate, bread dough and egg albumin deposits have a lower adhesive than cohesive strength, whilst others (whey protein) have a lower cohesive than adhesive strength. The researchers present a simple model to analyse the results in terms of the work required to remove the deposit per unit surface area and volume.
29.2.3
[9]
Manual dishwashing for restaurants
29.2.4
FDA recommendation for manual dishwashing in restaurants
The FDA recommends restaurants to follow a three-step process when washing dishes, scrub in soapy hot water at an uncomfortable 110 degrees Fahrenheit (44o C ), rinse with clean water, and then soak in sanitizer.
29.2.5
Low temperatures found to be sucient for dishwashing in restaurants
Melvin Pascall and colleagues 2007 assessed the sanitization eciency of the manual cleaning dishwashing procedure. Pascall and colleagues found that using a combination of low washing temperatures of 75o F (24o C ) and and minimal sanitizer concentration (150 ppm) of quaternary ammonium compounds the FDA recommended bacteria reduction greater than 5-log bacterial reductions were achieved. The stress, however, that dierent material of the utensils and dierent food residues, like milk may have dierent survival opportunities for various bacteria. The authors recommend to wash dishes right away before food dries. It saves washing time and gets rid of problematic places, like gaps between prongs of forks,where bacteria might be able to survive washing and drying. This is valid for restaurants as well as for home kitchen.
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29.2.6
DNA based pathogen detection system from Lumora
[10] The food safety diagnostics company Lumora developes a detection system which identies and measures food borne pathogens such as Salmonella, E. coli O157 and Listeria by means of a version of a luciferase gene. Specic bacteria in contact with this gene emit light which is identied by a sensor. In this way the precise amount of contamination can be determined within hours. The system will be available soon. The system may also detect small quantities of genetic modied material in foods and may enhance the traceability of ingredients.
29.2.7
Hygienic training of the sta
The Hygiene rule 93/43/EWG demands also for a training of the sta. To train your sta show the bacterial count made on Plate count Agar Base. Bad cleaning and disinfection resulting in food spoilage: innumerous bacteria on the surface of a table. Good cleaning and disinfection gives low bacterial count of the surface of the table. On Plate Count Agar Base there are no colonies grown. A good shelf life of food is the result.
29.2.8
Cleaning with CO2 in food industry
[11] The main concern of cleaning in food industry is: Remove the coatings of rest of product and dirt. Reduce the number of bacteria an the surface of machines and utensils, preparing the eld for a following disinfection. Cleaning must be made very carefully. It is expensive, produces great amount of wastewater, chlorine and other disinfectants. Cleaning with pellets of carbon dioxide can be an alternative to conventional cleaning methods. CO2 pellets are mixed with an air jet and directed against the surface to be cleaned under high pressure at about 20 bar. The reduction of the surface temperature due to sublimation of the carbon dioxide hardens the layers to be removed and cracks are formed. The undesired material starts to peel o. An abrasive action takes place. The cracks formed on the surface of product layers due to very low temperatures allows carbon dioxide pellets to get under and between the undesired material. As the pellets sublimate they enlarge their volume about 700 times removing thus foreign material like organic rest, dirt and bacteria. The DIL (Deutsches Institut fr Lebensmitteltechnik) has tested this technique with good results in cleaning and reduction of the number of surface bacteria.
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29.2.9
Cleaning and disinfection, Standard method
(According Codex Alimentarius) Good hygiene includes the following steps Cleaning of building, of tools and equipment and the transportation system. Important is the complete removal of food rests and garbage from the rooms where production takes place. Disinfection using an appropriate disinfectant. Sometimes the cleaning step is combined with the disinfection. This is ecient because organic material inhibits the disinfection agents or built a protective layer around microorganism. The cleaning and disinfection method before being included in the daily work should be discussed and authorized by: Veterinary authorities in charge Production management Engineering management and Supplier of cleaning and disinfection agents. The cleaning and disinfection method should be written and be available to the personal engaged in the daily work and to the production management. Cleaning instructions should include the handling of cleaning equipment such as disinfection of scrub brushes an buckets. The production management should continuously supervise cleaning and disinfection in order to make sure the work is being done according instructions observing the prescribed intervals. All persons engaged in cleaning and disinfection should be instructed regarding the caution in handling chemicals such as: Alkaline solutions should not be put together with acid solutions. Hypochlorite solutions should not be put together with acid solutions because chlorine gas can be generated. All chemical containers must be labeled so that everyone can know its content. They must be kept separate from food and packing material. Handling strong concentrated chemicals the use of gloves, safety goggles and protective clothes are necessary. Good cleaning and disinfection results: a low bacterial count is found at the surface of the equipment
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Bad cleaning and disinfection results: a high bacterial count is found at the surface of the equipment
29.2.10
Cleaning methods
Cleaning methods should remove the main part of food and other materials from the surfaces with could or hot water. Cleaning agents should remove strongly adherent rests. Clear water should wash the cleaning agents away. Abrasive substances or acid solutions should not interfere with surface. Cleaning can be made by
29.2. HYGIENEMANAGEMENT IN FOOD INDUSTRY hand using brushes,
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Cleaning in place (CIP method): This method is being used in large scale to clean pipe systems, tanks and machines without disassemble them.The system must be appropriated for CIP cleaning. The Flow of water and cleaning solutions should be over 1,5 meter per second having ushing character. Flushing with low pressure using much water: This method uses much water under 6,8 bar (100 psi) pressure and great amount with chemicals. Flushing with high pressure and little water: High pressure up to 68 bar (1.000 psi) is used. Foam cleaning: The cleaning agents are integrated in the foam sticking on the surfaces to be cleaned for about 15 to 20 minutes. They are then washed away. Openly accessible surfaces can easily be cleaned and disinfected with foaming and disinfecting cycles. Wash machines: Small parts, buckets an other utensils can be washed and disinfected Cleaning agents There may be necessary to use heat in order to get good cleaning results. Sometimes cold solutions are sucient. Mineral salts may deposit scale. Small amount of scale can be detected with ultraviolet light. After all cleaning agents have been washed away disinfection can follow.
29.2.11
Disinfection
Disinfection are the methods to reduce the number of bacteria living on the surfaces. Disinfection can be made using:
29.2.12
Heat
The most common way of disinfection is to rise the temperature of the surfaces to a minimum of 70o C (160o F). The surfaces to be disinfected should be clean having no rests of product left, otherwise protein would coagulate building insoluble layers.
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29.2.13
Disinfection with hot water
IndexHot water as disinfectant This method is widely used. Machines and parts to be disinfected are immersed in hot water at 80o C (176o F) for at least two minutes. Water to rinse o disinfectants in mechanical dish washers should have this temperature.
29.2.14
Steam as disinfectant
Steam can be used to disinfect tanks, pipes and other parts which are not easily reached. Steam must be applied long enough to heat up the surfaces to temperatures which can kill bacteria. Steam can be unsuitable for machines and systems containing plastic materials or gaskets which are destroyed by high temperatures. Steam kills bacteria even when they are located behind gaskets. Chemical disinfectants does have the same property as seen from the disinfection using steam. Steam disinfection can give origin to condensing water which can collect in in pipes and tank drain giving chance to bacteria to grow. Therefore it is important to repeat steam disinfection after a standstill for more then one day.
29.2.15
Chemical disinfection
Chemical disinfectants are reduced in their activity in presence of dirt and other residues of food. Disinfectants are useless when the amount of residues are to high. Therefore disinfection should always be preceded by a cleaning procedure. High temperatures increases the activity of chemical disinfectants.There is however a limit of temperature for every disinfectant. The technical informations of the suppliers of the chemical must be observed. Iodophores give iodine free which can corrode metal, so as chlorine producing corrosion coming from hot hypochlorite solution. All chemical disinfectants need time to kill bacteria. This time diers from one disinfectant to another according to the technical informations. The concentration of the disinfection solutions must be made according to the informations of the supplier. They should not be mixed with cleaning agents or other disinfectants because of loss of activity. The most important chemical disinfectants are:
29.2.16
Chlorine and their compounds
Chlorine and products on basis of Chlorine such as hypochlorite-compounds are the best chemical disinfectants. Commercial products have 100 to 120 gram chlorine per liter being active against a great number of bacteria. They have low prices compared with other chemical disinfectants. Working solutions should have 200 to 250 mg of active chlorine/Kg. Chlorine disinfection is being substituted by other disinfectants because of environment. Chlorine reacts with organic residues forming AOX compounds. . Chlorine produces corrosions and turns inactive in presence of residues of food and dirt.
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29.2.17
Whey permeate as alternative to chlorine solutions for preserving fresh-cut vegetables
[12] A chlorine 120 ppm (pH 8) solution is widely used in the washing treatmen as sanitizing agent prolonging the shelf-life of fresh-cut fruits and vegetables. The use of chlorine in food processing plants is being reduced due to the possible formation of carcinogenic chlorinated compounds in water. In a study leaded by Anabelen Martin-Diana whey permeate solution was used as antimicrobial agent to control total bacteria counts during washing step of fresh cut vegetables as an alternative to chlorine. The whey permeate from Glanbia, Ireland was used in the following solutions: 0.5% (pH 3.84) 1.5% (pH 3.53) 3% (pH 3.45) Fresh-cut lettuce and carrot packages stored at 4o C were monitored over 10 days. Whey permeate at 3% resulted in equivalent or better microbial load reduction than chlorine. Although lower concentration of whey permeate produced minor initial reduction, microbial counts at the end of the storage of 10 days at 10o C were below the recommended levels (108 CFU/g) for safety of fresh-cut vegetables. According to the researchers the anti-microbial activity is most likely due to the pH of the wash solutions, or the presence of bio-active peptides. These results suggest that whey permeate could be a promising alternative to chlorine for sanitizing fresh-cut vegetables.
29.2.18
Iodophore
Iodophores may be used in combination with acid cleaning agents. They need a short time of contact with the surfaces, killing a broad spectrum of bacteria. Working solutions should have a concentration of 25 to 50 milligram/liter of active iodine using a pH <4. iodophores are inactivated in presence of food residues and dirt. They have yellow color when active iodine is still present. Loss of color indicates the loss of activity. They can be corrosive, being necessary to ush away the iodophores with clean water.
29.2.19
Ammonium quarternairy-compounds
Theses substance have good cleaning activity and have low corrosive activity. They are not toxic. Their taste is bitter. These compounds tend to settle on the surfaces, therefore it is important to rinse with clear water carefully after disinfection. They should be used
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in 200 to 1200 milligrams per liter solution. Using hard water high concentrations must be used. They should not be used together with soaps and anionic cleaning agents. Their activity against Gram negative bacteria are smaller as found by chlorine.
29.2.20
Surfactants (amphotheric surface active substances)
Surfactants are old disinfection agents being made out of active agents with cleaning and bactericide activity. They are low toxic, tasteless and have little corrosive activity.Organic rests inactivate surfactants.
29.2.21
Strong acids and basic agents
Strong acids and basic reacting agents have cleaning and disinfectant activities. They can easily contaminate food. They should be handled with great care.
29.2.22
Control of the activity of cleaning
The control of the cleaning and disinfection activity of the system being used should be made using bacteriological methods described above.
29.3
Improving CIP technology
[13] Eorts of reduction of environmentally harmful and cost-intensive resources for CIPcleaning installations include per acetic acid sensor systems, chlorine-dioxide disinfection.
29.3.1
Chlorine-dioxide disinfecting procedures
[13] Chlorine-dioxide disinfecting procedures are designed for drinking water disinfection, removal of odour and taste substances (phenols, algae, algae decomposition products), and reduction of organo-chlorine formations (AOX) Chlorine-dioxide is used for the purication of water in CIP-installations, usage water, cooling water and waste water, in llers, process water, and in washing maschines.
29.3.2
Per acetic acid
[13] Per acetic acid is being used in CIP processes for disinfection. Its spectrum includes bacteria, yeasts, algae and viruses, breaking down to oxygen and traces of acetic acid. No rinsing of the plant is therefore necessary.
29.4. ORIGIN OF CONTAMINATION OF FOOD WITH PATHOGEN BACTERIA 2165
29.4
Origin of Contamination of food with pathogen bacteria
is originated by: 1. Contaminated raw material e.g. water, meat, cereals. 2. Handling e.g.unclean devices, bacteria bearing surfaces of machines etc. 3. Environment e.g. dust, unclean rooms, polluted air from air conditioning systems. 4. Personal e.g.sick persons handling food. To avoid contamination wash hands before starting work, after visiting toilet and before starting with a new work. Disinfection solution should be used after washing. There are lots of bacteria on ngers as shown
by ngerprints on nutrient media:
29.4.1
Clean room technology
Clean room technology is being used in the microelectronic, micro optics, in hospitals, pharmaceutical industry, cosmetic industry, research laboratories and many other branches. To guarantee a clean environment of a room the air must be ltered. Today air lters are available which can lter particles 0,12 micro m. Clean air, correct temperature humidity and pressurization of the room are fundamental parts of clean room technology. The outlets of the air system should be located over the places where handling takes place, such as: Cutting machines, Can openers, Mixer, Bowl-choppers.
2166
In this way processing heat,from sta contaminated air and microorganism which may multiply in standing air or humidity are driven away by the sterile air ow of the air conditioning system. To avoid not ltered air to get into the clean room through doors and other outlets it important to create a pressure high enough to overcome atmospheric variations. Laminar airow is often used to achieve safety at doors. The airow should be always against the sta and never from the sta to the product which is being handled as contamination of living beings is unavoidable. This type of clean room is called island solution and is much cheaper as what is being described for clean rooms in VDI- guideline 2083 or US-FS 209 E for the RR-class demanding the ltration of particles down to 0,5micro m. In food processing the aim is to avoid bacterial contamination. As these microorganisms are generally linked to particles between 0,12 and 100 micro m. The lter should be from the class 14 and better. One important factor of a product contamination is the sta which produces particles down to 0,5 micro m. Most of the contamination results from breathing, talking, coughing and movements. Microorganism isolated from the skin,nose, mouth and bowl are Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Candida albicans and Enterobacteriaceae like Salmonella and Shigella. People with clinical signs like boils and suppurating wounds, diarrhea and strong cough should report this to the management and be released from working with unpacked food or send home for medication. The personal which works in a clean room must b e dressed with special headdress to avoid bacteria from hairs to contaminate air. An overall should cover all the part of the body, shoes should be changed before entering the clean room. There should be a ood gate entering the clean room.in front of this ood gate there should be a device to clean shoes, gloves. This outt should be changed daily. In the clean room personal belongings are not allowed. Eat and drink in the clean room is not allowed. Private food and drink should not be taken into the clean room. A high motivation of the sta is necessary. This can only be achieved when the environment of the clean room has been put in accordance to hygienic rules like the disposal of trash, tiled walls and oor, machines and other devices made of stainless steel without rusty parts.
29.4.2 29.4.3
European regulations on hygiene of foodstus Regulation (EC) No 852/2004 of the European Parliament and of the Council of 29 April 2004 on the hygiene of foodstus.
[14]
29.4. ORIGIN OF CONTAMINATION OF FOOD WITH PATHOGEN BACTERIA 2167
29.4.4
Corrigendum to Regulation (EC) No 852/2004 of the European Parliament
EU regulation No 853/2004, part of the package of hygiene laws that came into eect on 1 January, provides a legal basis to permit the use of a substance other than potable water to remove surface contamination from products of animal origin. Previously, such a legal basis did not exist in the blocs legislation for red meat and for poultry meat. [15]
29.4.5
Regulation (EC) No 854/2004 of the European Parliament and of the Council of 29 April 2004 laying down specic rules for the organisation of ocial controls on products of animal origin intended for human consumption.
[16]
29.4.6 29.4.7
Other EU Regulations with hygiene relevance Commission Regulation (EC) No 2073/2005 on microbiological criteria for foodstus
Specic rules for testing and sampling and food safety criteria determining limits of bacteria in foods. [17]
29.4.8
Commission Regulation (EC) No 2074/2005
The regulation introduces the food chain information, and lays down the obligations on food business operators and competent authorities. [18]
29.4.9
It lays down specic rules on ocial controls for Trichinella in meat. [19]
29.4.10
It lays down transitional arrangements. [20]
29.4.11
Regulation (EC) No 882/2004
This regulation lays down the ocial controls to ensure the verication of compliance with feed and food law, animal health and animal welfare rules. [21]
2168
29.4.12
Regulation (EC) No 1174/2002
Regulation laying down health rules concerning animal by-products not intended for human consumption. 3 October 2002. [22]
29.4.13
Microorganisms as indicators of on-farm hygiene practices
[23] On-farm hygiene related to the cowsudder and teats, the milking equipment or the storage tank inuence quality and quantity of bacteria in freshmilk. Bacterial mastitis can also lead to poor raw milk quality. Total viable counts (TVCs) are not always giving a true measure of on-farm hygiene during milking. Hutchison and colleagues compared total viable counts, Escherichia coli, coliforms, Bacillus spp., Bidobacteria spp., and Pseudomonas spp. with results of dairy farm hygiene audits. They investigated the possible reasons for the low correlations between on-farm hygiene and bacterial indicator counts in raw milk. The authors concluded that despite some problems, total viable count was best suited as indicator of on-farm hygiene. There were no other marker bacteria with higher correlation with audits. Somatic cell count reect any possible mastitis in the herd.
29.4.14
Health rules for milk in Europe
[24] The Council Directive 92/46/EEC of 16 June 1992 lays down the health rules for the production and placing on the market of raw milk, heat-treated milk and milk-based products. This directive was repealed by the Hygiene Package which entered in force in 2006.
29.4.15
RABIT (Rapid Automated Bacterial Impedance Technique)
[25] [26] Impedance microbiology is a rapid method for both quantitative and qualitative studies with bacteria, yeasts and moulds. Unlike the standard plate methods which only measure microbial activity at a single point in time, RABIT monitors real time activity and thereby produces two signicant benets. Results are determined in a signicantly shorter time frame compared to conventional microbiology. Impedance can be simply dened as the resistance to ow of an alternating current as
29.4. ORIGIN OF CONTAMINATION OF FOOD WITH PATHOGEN BACTERIA 2169 it passes through a conducting material. When two metal electrodes are immersed in a conductive medium the test system behaves as a resistor and capacitor in series. Microbial metabolism usually results in an increase in both conductance and capacitance causing a decrease in impedance and a consequent increase in admittance, it is the admittance which is plotted against time by the RABIT system. Bacteria metabolise the nutrients of the media, producing a change of conductivity and resistance. When a bacteria arrive a concentration of log 5/ml it will cause a change of these parameters.A large initial population of bacteria will make the time to make this change will be shorter than a food with less concentration of bacteria. In the same food system, the number of the initial population of the food can be estimated by the detection time.
29.4.16
Infections in German hospitals causes 15 000 deaths per year
[27] According to ocial data of 2011, up to 15 000 patients die of hospital-infections yearly. More than 600.000 of such infections per years are known. They must be treated causing enormous high costs. Better hygiene conditions at hospitals are to reduce infections. The German Federal Assembly approved a series of regulations which demand an increase of hospital sta and improvement in hygiene. The following important changes will be introduced in the German Infection Protection act: -Hospitals must increase infection protection and medical sta must include a specialist in hygiene which control the hygiene status of the organisation. -Sta costs are estimated to amount up to 76 Million Euro. - Improved notication of epidemic outbreaks. The primary rules to avoid such infections in hospitals are known to be sterilisation of tables,disinfection of hands of nursing sta an doctors.
29.4.17
FDA assesses the Dirty 22 common pest species to reduce the risk of food borne diseases [28]
Twenty two common pest species called by the FDA the "Dirty 22" are the spreaders of foodborne diseases. The presence of lth and extraneous materials and any one of these species in food indicates unsanitary conditions in food processing and storage facilities, says the FDA. Sulaiman et al 2011 classied the 22 species in four groups: Group I including four cockroach species, the group II has two ant species, the group III has 12 y species, and IV includes four rodent species.
2170
To identify remains and even small pieces of body parts of insects, which cannot be determined by microscopy, the authors described a two-step nested PCR protocol to determine the cockroach species of the group I which include Blattella germanica, Blatta orientalis, Periplaneta americana, and Supella longipalpa.The authors stress that data related to food contamination by insects are important for regulation and prevention of foodborne pathogens.
Bibliography
[1] Waidmann MS, Bleichrodt FS, Laslo T, and Riedel CU. Bacterial luciferase reportersthe swiss army knife of molecular biology. Bioeng Bugs, 2(1):816, 1 2011. http://www.landesbioscience.com/journals/biobugs/WaidmannBBUGS2-1.pdf. [2] Inouye S. Firey luciferase: an adenylate-forming enzyme for multicatalytic functions. Cell Mol Life Sci, 67(3):387404, 2 2010. http://www.ncbi.nlm.nih.gov/pubmed/ 19859663. [3] Hosseinkhani S. Molecular enigma of multicolor bioluminescence of rey luciferase. Cell Mol Life Sci, 68(7):116782, 4 2011. http://www.ncbi.nlm.nih.gov/pubmed/ 21188462. [4] Hirano T, Hasumi Y, Ohtsuka K, Maki S, Niwa H, Yamaji M, and Hashizume D. Spectroscopic studies of the light-color modulation mechanism of rey (beetle) bioluminescence. Luminescence, 131(6):239596, 2 2011. http://www.ncbi.nlm.nih. gov/pubmed/19159303. [5] inekawa T, Ohkuma H, Abe K, Maekawa H, and Arakawa H M. Practical application of bioluminescence enzyme immunoassay using enhancer for rey luciferin-luciferase bioluminescence. Luminescence, 26(3):16771, 5 2011. http://www.ncbi.nlm.nih. gov/pubmed/21681909. [6] de Almeida PE, van Rappard JR, and Wu JC. In vivo bioluminescence for tracking cell fate and function. Am J Physiol Heart Circ Physiol, 6 2011. http://www.ncbi. nlm.nih.gov/pubmed/21666118. [7] Yan SL, Miao SN, Deng SY, Zou MJ, Zhong FS, Huang WB, Pan SY, and Wang Q. Atp bioluminescence rapid detection of total viable count in soy sauce. Luminescence, 6 2011. http://www.ncbi.nlm.nih.gov/pubmed/21674749. [8] Liu,W.; Fryer, P.J.; Zhang, Z.; Zhao, Q.; Liu, Y.: Identication of cohesive and adhesive eects in the cleaning of food fouling deposits. Inovative Food Science and Emerging Technologies. Volume 7, Issue 4, December 2006, Pages 263-269. Doi:101016/j.ifset.2006.02.006.
BIBLIOGRAPHY
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[9] http://fsrio.nal.usda.gov/news_article.php?article_id=4112. Lee, Jaesung; Cartwright, Richard; Grueser, Tom; Pascall, Melvin A. 2007. Eciency of manual dishwashing conditions on bacterial survival on eating utensils. Journal of Food Engineering, 80 (3): 885-891. [10] http://www.lumora.co.uk/downloads/pdf/webpress.pdf. Lumora Press Release 17 July 2006: Cambridge biotech company Lumora announces key licensing deal with French diagnostics company bioMrieux. [11] Knoch,Achim: Einsatz der CO2 - Reinigung in der trie.Jahresbericht 1996 Deutsches Institut fr Lebensmittel. Lebensmittelindus-
[12] A.B. Martin-Diana, D. Rico, J. Frias, J. Mulcahy, G.T.M. Henehan and C. BarryRyan:Whey permeate as a bio-preservative for shelf life maintenance of fresh-cut vegetables; Innovative Food Science and Emerging Technologies (Vol. 7, pp. 112-123) doi:10.1016/j.ifset.2005.08.002. [13] http://www.loehrke.com. Jrge Lrthke GmbH: The operational areas of Lhrke Chlorine- Dioxide Disinfecting Procedures. [14] http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=OJ:L:2004:139: 0001:0054:EN:PDF. Commission Regulation Regulation (EC) No 852/2004 of the European Parliament and of the Council of 29 April 2004 on the hygiene of foodstus. [15] http://europa.eu.int/eur-lex/lex/LexUriServ/site/en/oj/2004/l_226/l_ 22620040625en00220082.pdf. Corrigendum to Regulation (EC) No 853/2004 of the European Parliament and of the Council of 29 April 2004 laying down specic hygiene rules for food of animal origin (OJ L 139, 30.4.2004) 32004R0853R(01) Ocial Journal L 226, 25/06/2004 P. 0022 - 0082. [16] http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=OJ:L:2004:139: 0206:0320:EN:PDF. Regulation (EC) No 854/2004 of the European Parliament and of the Council of 29 April 2004 laying down specic rules for the organisation of ocial controls on products of animal origin intended for human consumption. [17] http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=OJ:L:2005:338: 0001:0026:EN:PDF. Commission Regulation (EC) No 2073/2005 of 15 November 2005 on microbiological criteria for foodstus. [18] http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=OJ:L:2005:338: 0027:0059:EN:PDF. Commission Regulation (EC) No 2074/2005 of 5 December 2005 laying down implementing measures for certain products. This regulation establishes the testing methods for detecting marine biotoxins. [19] http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=OJ:L:2005:338: 0060:0082:EN:PDF. Commission Regulation (EC) No 2075/2005 of 5 December 2005 laying down specic rules on ocial controls for Trichinella in meat.
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[20] http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=OJ:L:2005:338: 0083:0088:EN:PDF. Commission Regulation (EC) No 2076/2005 of 5 December 2005 laying down transitional arrangements. [21] http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=OJ:L:2004:165: 0001:0141:EN:PDF. Regulation (EC) No 882/2004 of the European Parliament and of the Council of 29 April 2004 on ocial controls performed to ensure the verication of compliance with feed and food law, animal health and animal welfare rules. [22] http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=CONSLEG: 2002R1774:20070724:EN:PDF. Regulation (EC) No. 1174/2002 Regulation laying down health rules concerning animal by-products not intended for human consumption. [23] M. L. Hutchison, D. J. I. Thomas, A. Moore, D. R. Jackson, and I. Ohnstad: An Evaluation of Raw Milk Microorganisms as Markers of On-Farm Hygiene Practices Related to Milking; Journal of Food Protection: Vol. 68, No. 4, pp. 764-772. [24] http://europa.eu/scadplus/leg/en/s84000.htm#PAQUETHYGIENE http: //europa.eu/scadplus/leg/en/lvb/l12036a.htm. Europa: Summaries of Regulations: Hygiene package. [25] http://www.dwscientific.co.uk/template.php?pagename=impedsys.html. Don Whitley Scientic Limited Impedance systems. [26] http://members.ift.org/NR/rdonlyres/3BFC8CDD-2B46-4C84-8E4D-CBE65B528F77/ 0/crfsfsv01n1p013017ms20001206.pdf. Rapid methods and automation in microbiology.Comprehensive Reviews in Food Science and Food Safety.Vol. 1, 2002. [27] Ehec-epidemie behoerde verbietet arzneien mit bockshornsamen. 08 jul 2011. Spiegel Online, 7 2011. http://www.spiegel.de/wissenschaft/medizin/0,1518, druck-773217,00.html. [28] Sulaiman IM, Anderson M, Khristova M, Tang K, Sulaiman N, Phifer E, Simpson S, and Kerdahi K. Development of a pcr-restriction fragment length polymorphism protocol for rapid detection and dierentiation of four cockroach vectors (group i "dirty 22" species) responsible for food contamination and spreading of foodborne pathogens: Public health importance. J Food Prot, 74(11):188390, 11 2011. http: //www.ncbi.nlm.nih.gov/pubmed/22054189.
Chapter 30 Avoiding Food Scandals

Food borne diseases and food poisoning have always threaten humanity. Old writings report a high ranking food poisoning in India. According to these reports Buddha Gautama died after eating spoiled meat during his stay as a guest at the house of the metal-worker Cunda at Pava, a village near Magadha capital Rajagraha [1]
30.1
The cause of food scandals
The cause of a scandal is not the scandal in its itself, it is rather the fact that no necessary conditions were consciously provided to avoid it. Lack of knowledge and low level of ethics are the causes of food scandals. Even nowadays food scandals cause high costs and loss of condence of the consumer such as scandals with organics, BSE threat and contaminants in food. Due to heavy industrial processing some danger arise when precautionary activity fails to protect the consumer. Caustic sodium hydroxide used to clean and sanitize manufacturing equipment was left in Vanilla soymilk in White Wave Silk Brand cartons being recalled in early 2004 is an example of heavy losses due to technical failure. Food processors are responsible to provide the conditions to avoid food poisoning and to control its eectiveness. 2173
2174
CHAPTER 30. AVOIDING FOOD SCANDALS
Example of wrong location of level sensor resulting in cleaning agent leftover
No leftover in the storage tank Transboundary plant pests and animal diseases such as BSE and avian ue are of growing economic and scientic complexity and consequently warrants priority attention. Government are responsible to provide conditions to avoid transboundary pests and diseases [2].
30.2. THE COMBASE DATABASE
2175
30.1.1
Increasing Food Safety with Predictive Microbiology
[3] [4] The main sources of food scandals are caused by pathogenic bacteria. Predictive Microbiology is a new tool for food producers to predict safety and shelf life of new products. The common database can become an important step to avoid food scandals.
30.2
The ComBase Database
The ComBase Database is a combined database for predictive microbiology and is an outcome from the Common Database for Predictive Microbiology which was launched in June 2003 creating a virtual environment for every food and every bacteria and should contribute to a more rapid understanding of food safety and quality. Its purpose is to make data and predictive tools on microbial responses to food environments freely available via web-based software. The ComBase Database is an international collaboration between: FSA: www.food.gov.uk IFR: www.ifr.ac.uk USDA-ARS-ERRC: www.ars.usda.gov Australian Food Safety Centre of Excellence: www.foodsafetycentre.com.au Everyone can create an environment by entering data such as the temperature, pH and salt content - all the parameters relevant to his food product during processing, distribution, storage and sale. The database consists of thousands of microbial growth and survival curves that have been collated in research establishments and from publications. They form the basis for numerous microbial models presented in ComBase Predictor.
30.2.1
[5]
Dierent use of ComBase Browser and Combase Predictor
ComBase database The ComBase Browser searches a database of kinetics of spoilage organisms and pathogens in broth and food. The data come from the scientic literature or were produced by miscellaneous institutions.
2176
ComBase Predictor The ComBase Predictor gives predictions from models based on selected data of the ComBase database as a function of environmental factors such as temperature, pH and water activity in broth.
30.3
ComBase Predictor
[6] ComBase Predictor is a tool for industry, academia and regulatory agencies. They can be used in developing new food technologies while maintaining food safety; in teaching and research; in assessing the microbial risk in foods or setting up new guidelines. The Internet version of the ComBase Predictor, developed by IFR, was launched in February 2006. ComBase Predictor web-edition is a modied and improved version of the Growth Predictor programme. It comprises a set of twenty three growth models and six thermal death models for predicting the response of many important foodborne pathogenic or spoilage microorganisms to environmental factors, including temperature, pH and salt concentration. Some of the models also include an additional fourth environmental factor, such as the concentration of carbon dioxide or acetic acid.
30.3.1
The Pathogen Modelling Program (PMP)
[7] ComBase has developed a new set of predictive models known as ComBase-PMP, which will produce predictions based on all the data on the site. The Pathogen Modelling Program (PMP) is available at http://ars.usda.gov/Services/docs.htm?docid=6786. The PMP is a package of models that can be used to predict the growth and inactivation of foodborne bacteria, primarily pathogens, under various environmental conditions.
30.3.2
[8]
Other microbiologocal sites
Seafood Spoilage Predictor Software, Danish Institute for Fisheries Research www.dfu.min.dk/micro/ssp/ Microbial Risk Assessment of meat product-an output of the SMAS project smas.chemeng.ntua.gr/miram/ European Union Risk Analysis Information Network www.eu-rain.com
30.3. COMBASE PREDICTOR Food risk analysis clearing house www.foodriskclearinghouse.umd.edu SymPrevius (an integrated database and predictive software, in French) www.symprevius.net Physical Properties of Food Database www.nelfood.com
2177
30.3.3
[8]
Links of interest
CEMMI - The ERRC Center of Excellence in Microbial Modeling & Informatics (CEMMI) brings together researchers with diverse and complementary talents to advance the science of microbial modeling. Center for Food Safety & Applied Nutrition - FDA CIFSAN - ensuring the security of our countrys food supply. Foodsafe Archives - USDA / FDA Foodborne Illness Education Information Center. Food Safety Network - The agri-food risk management and communications web site. Food Safety Risk Analysis Clearinghouse - The aim of this site is to assist those professionals involved with any of the many aspects of risk analysis as it pertains to the safety of our food. Joint Institute for Food Safety and Applied Nutrition - JIFSAN - a program of dynamic partnerships. MEDLINE - A large database of scientic, technical, medical, and other scholarly content. Search through 20 million citations and 10 million abstracts from over 30,000 journals. Medscape - Oers a large amount of information about medical information and education tools. National Food Safety Database - An informative website providing food safety information for consumers, educators and the food industry. ProMED - Global monitoring of emerging diseases. The Microbiology Network - The Microbiology Network serves as a communication resource for the microbiologist. The objective of this service is to encourage communication within the microbiology and biotechnology community.
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30.4
Sea water and irrigation water as cause of food born diseases
There is a growing concern linked to spread of agents through vegetables contaminated with enterovirus and bacterial pathogens as Shigella from low-standard irrigation water, parasites on tropical fruits and berries, and Vibrio cholera, other enteric bacteria and enteroviruses from sea-foods harvested in polluted sea water. Sea-food: Polluted water is of public concern. The government of bordering states and international organizations are responsible to issue warnings and to initiate measures to eliminate the causes of the pollution. Vegetables: Intervention must be on the communal level, a general improvement of hygiene and pollution control.
30.5
30.5.1
Animal product health threats

Husbandry
[9] Many of the scandals of food safety in Europe the last decades have been linked to this intensive husbandry system seen in Northern Europe. As there has also been incidents caused by chemical pollution of feed (Belgium) or direct contamination of food (cooking oil in Spain), most of the diseases in man have been caused by agents either transferred to man from animals to man through animal products or agents form man spread through vegetables contaminated by polluted irrigation water. Due to the very low prevalence of many foodborne microbiological hazards in Norwegian products, an increased import of some foods to Norway from countries outside the Nordic area will represent a potential Public Health risk.
30.5.2
Food trade
US CDC , analising concludes that certain aspects of food trade represent a considerable public health hazard. At the same time, the western consumer is today probably less exposed to some environmental pollutants than some years ago. A main pattern is that the main hazards are linked to animal products from the subsidized, industrialized western agriculture and some seafood and vegetables from poor/tropical countries.
30.5. ANIMAL PRODUCT HEALTH THREATS
2179
As a last comment, it is worth reminding that the main food item traded is various forms of grains, where trade represents a minor if any health hazard. It is also

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OurFood Database of Food and Related Sciences

Karl H. Wilm [email protected] July 6, 2013

OurFood Database of Food and Related Sciences

iv 7.7 7.8 7.9 7.10 7.11 7.12

. . . . . . . . . . . . . . . . . and the Codex Alimentarius . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Copyright 1998-2010 Karl H. Wilm. All rights reserved.

921 921 923 923 928 931 933

OurFood Database of Food and Related Sciences

Copyright 1998-2010 Karl H. Wilm. All rights reserved.

OurFood Database of Food and Related Sciences

Food Related Diseases

Copyright 1998-2010 Karl H. Wilm. All rights reserved.

CONTENTS 22.5 Zoonoses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1530 Bibliography . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1556

Bacteriology and Virology

Copyright 1998-2010 Karl H. Wilm. All rights reserved.

xi 1732 1734 1743 1763 1768

Poisonous Chemicals in Food

1931 1932 1936 1946 1952 1964 1970 1973 1975

OurFood Database of Food and Related Sciences

xii 27.9 27.10 27.11 27.12 27.13

Copyright 1998-2010 Karl H. Wilm. All rights reserved.

OurFood Database of Food and Related Sciences

Copyright 1998-2010 Karl H. Wilm. All rights reserved.

OurFood Database of Food and Related Sciences

xvi 35.5 35.6 35.7

Copyright 1998-2010 Karl H. Wilm. All rights reserved.

Agriculture and Ecology

Copyright 1998-2010 Karl H. Wilm. All rights reserved.

xix 2972 2978 2985 2994 3001 3006 3015 3027

43 Nutritional Genomics 3255 43.1 The beginning of nutritional genomics . . . . . . . . . . . . . . . . . . . . 3255

OurFood Database of Food and Related Sciences

Copyright 1998-2010 Karl H. Wilm. All rights reserved.

General information Why a database on food ?

Evolving food systems are dominated by nancial interests

Globalization of trade and industry

Copyright 1998-2010 Karl H. Wilm. All rights reserved.

OurFood Database of Food and Related Sciences

4 Archer Daniels Midland Danone USA 16 14

OurFood Database of Food and Related Sciences

Copyright 1998-2010 Karl H. Wilm. All rights reserved.

OurFood wishes you success on your researches.

Copyright 1998-2010 Karl H. Wilm. All rights reserved.

OurFood Database of Food and Related Sciences

OurFood Database of Food and Related Sciences

Copyright 1998-2010 Karl H. Wilm. All rights reserved.

Chapter 2 Food, what is it?

The very big international dairy food producers [1]

CHAPTER 2. FOOD, WHAT IS IT?

Bio availability of calcium

Daily calcium intake [5]

CHAPTER 2. FOOD, WHAT IS IT?

Pollutants in milk and dairy products

Radioactive pollution of milk

CHAPTER 2. FOOD, WHAT IS IT?

mg/Kg 86 180 225 72 - 1.416 2.000 - 4.000 up to 2.300

Cheese Camembert Brie Emmentaler Cheddar Cheddar Roquefort

Whey protein concentrates

Whey protein concentrates

Dietary polyamines [8]