The Bioaccessibility of Water-Soluble Vitamins
The Bioaccessibility of Water-Soluble Vitamins
The Bioaccessibility of Water-Soluble Vitamins
A R T I C L E I N F O A B S T R A C T
Keywords: Background: Water-soluble vitamins are indispensable organic molecules for growth, development, and body
Vitamin function. Epidemiological evidence often supports the link between sufficient dietary intake of water-soluble
Bioaccessibility vitamins and maintaining overall health. Knowing the bioaccessibility and bioavailability of water-soluble vi
Nutrition
tamins are important in terms of their usability in metabolism. There are many studies about the bioaccessibility
Daily intake
and bioavailability of food components, but studies about vitamins are limited.
Scope and approach: The purpose of this review was to evaluate the bioaccessibility of water-soluble vitamins and
identify the factors that may negatively affect the bioaccessibility. In this review, we focused on summarizing the
bioaccessibility of water-soluble vitamins. The influence of dietary fiber and its properties, temperature, pH,
grinding, inhibitors, antioxidants, polypeptides, polysaccharides, and vitamin-binding proteins on the bio
accessibility of vitamins was evaluated. However, the bioavailability values for some water-soluble vitamins
were also presented, but there is a limited study about the bioavailability of water-soluble vitamins.
Key findings and conclusions: Bioaccessibility may decrease significantly in vitamin C, folate, vitamin B1, and the
PL and PM forms of vitamin B6, which are more sensitive to temperature and acidity. Generally, decreases in pH-
sensitive vitamins may occur in the small intestine, where pH value is higher than the gastric phase. Also, the
presence of some metal ions, bonding with polypeptides and polysaccharides, digestive enzyme inhibitors, di
etary fiber, and binding proteins may negatively affect bioaccessibility. The numbers of studies conducted in this
field are limited. In conclusion, more studies are suggested to obtain more accurate information about the current
dietary nutrient intake.
1. Introduction reactions.
* Corresponding author. Department of Nutrition and Dietetics, Faculty of Health Sciences, İstanbul Sabahattin Zaim University, 34303, Küçükçekmece, Halkalı,
Istanbul, Turkey.
E-mail address: [email protected] (M. Yaman).
https://doi.org/10.1016/j.tifs.2021.01.056
Received 19 April 2020; Received in revised form 31 December 2020; Accepted 24 January 2021
Available online 30 January 2021
0924-2244/© 2021 Elsevier Ltd. All rights reserved.
M. Yaman et al. Trends in Food Science & Technology 109 (2021) 552–563
Therefore, vitamin C has essential biological functions regarding skin literally mimic the entire process of in vivo studies. Even so, the in vitro
health. However, it is not fully understood how some vitamins gastrointestinal digestion model provides essential data for estimating
contribute to the molecular and cellular reactions that enable physio the average requirement of individuals (Uğur et al., 2020).
logical processes to take place. When evaluating the health effects of While studies about the bioaccessibility and bioavailability of many
vitamins, the current scientific rationale is often based on theoretical nutrients in foods are available, studies about vitamins are limited.
biochemical principles and clinical features seen during obvious clinical Researchers may choose not to research vitamins because vitamin
deficiencies. Clinical observation of vitamin deficiencies is not very analysis is costly and requires a long extraction time, derivatization, and
common worldwide, especially in developed countries, but vitamin in purification requirements. In vitro studies cannot be used in place of in
sufficiencies are very common, and they vary by country, gender, and vivo studies, but they can be used as a screening, classification, and
age (Rippin, Hutchinson, Jewell, Breda, & Cade, 2017). However, ranking system for nutrients. The purpose of this review was to evaluate
although vitamin B deficiency is very rare today, symptoms related to the bioaccessibility of water-soluble vitamins from different studies and
folate and vitamin B12 deficiency are still observed (Ball, 2006; Combs & identify the factors that may negatively affect the bioaccessibility.
McClung, 2016).
2. Bioaccessibility of water-soluble vitamins
1.2. The importance of the bioaccessibility
The schematic description of bioaccessibility and bioavailability and
Many food composition databases or nutritional value calculation factors that negatively affect the bioaccessibility of water-soluble vita
tools contain nutritional component values of raw and cooked foods. mins are shown in Figs. 1 and 2, respectively. The bioaccessibilities of
Nutritionists or dieticians can calculate daily nutritional intake values water-soluble vitamins are summarized in Table 1.
using these data. It is essential to calculate the daily nutritional intake
values precisely to guide individuals properly (Grande & Vincent, 2020). 2.1. Bioaccessibility of vitamin C
Currently, it is difficult to reach the vitamin values of many cooked
foods. When calculating a diet’s nutritional values containing cooked Vitamin C has two biologically active forms, L-ascorbic acid (Fig. 3)
foods, an estimated value using the nutrient loss rates of similar cooking and L-dehydroascorbic acid (Travica et al., 2017), and is an essential
methods is generally used (Greenfield & Southgate, 2003). Although it is nutrient for many metabolic functions (Lykkesfeldt & Tveden-Nyborg,
thought that an adequate and balanced diet rich in nutritious foods such 2019). L-Ascorbic acid is easily oxidized to L-dehydroascorbic acid,
as fruits, vegetables, grains, legumes, meats, and dairy products can which can be reduced back to L-ascorbic acid. Vitamin C acts as a
provide the necessary amount, vitamin losses occur during the pro reducing agent or antioxidant in many biochemical reactions (Smirnoff,
cessing and cooking of foods. These losses vary depending on the tem 2018). The daily vitamin C requirement is 90 mg in adult males and 75
perature, pH, and presence of oxygen and light. Vitamin C, thiamine, mg in adult females (FNB, 1998a). Broccoli, brussel sprouts, cauliflower,
and folate are the most unstable and prone to degradation among the red and green peppers, tomato, kiwi, strawberry, cherry, mango,
water-soluble vitamins (Ball, 2004). However, a limited number of papaya, watermelon, and melon are the best sources of vitamin C
studies report vitamin losses for cooked foods compared with raw foods (TURKOMP, 2020; USDA, 2020). Ascorbic acid quickly oxidizes to the
(Lešková et al., 2006). L-dehydroascorbic acid form at neutral or alkaline pH. This form
On the other hand, when vitamin intakes are calculated in daily non-reversibly oxidizes to the 2,3-diketogulonic acid form (Pathy,
diets, these vitamins’ bioavailability is not fully predicted because of 2018). Oxygen, light, crushing, cutting, chopping, washing, cooking,
their unknown bioaccessibility in the gastrointestinal system. Therefore, canning, and the presence of metal ions such as Cu2+ and Fe3+ can cause
the possibility of determining potential health effects is not well known. significant vitamin C losses (El-Ishaq & Obirinakem, 2015). In addition
The bioaccessible amount of water-soluble vitamins in the gastrointes to removing free radicals, vitamin C plays an essential role in growth,
tinal tract, which includes the mouth, stomach, and small intestine, can bone health, and against viral infections (Uğur, Eker, Çatak., & Yaman,
vary depending on the pH, temperature, bonds with polypeptides and 2020). It has been reported that vitamin C levels decrease in some viral
polysaccharides, and the presence of metal ions and digestive enzymes infections, and 6 g/day vitamin C supplementation to improve immune
inhibitors (Ball, 2006). Bioaccessibility is the amount of nutrients response reduces symptoms associated with the common cold (Hume
released from the food matrix before absorption from the small intestine et al., 1973). However, it is thought that vitamin C may give effective
(Heaney, 2001). The bioaccessibility of foods is generally determined results in SARS-CoV-2 infection. In a trial conducted by Carr (2020), 140
using in vitro digestion methods with simulated gastric and small in patients were given 24 g/day vitamin C for 7 days, and clinical findings
testinal conditions, and sometimes using Caco-2 cells, if a cell culture are expected to be reported. It also plays an important role in the ab
laboratory is available (Courraud, Berger, Cristol, & Avallone, 2013). sorption of iron and the synthesis of collagen, catecholamine, choles
Bioavailability is the utilization of the nutrients in metabolism and in terol, amino acids, and carnitine (Akbari, 2016; Travica et al., 2017). In
cludes digestion with gastrointestinal enzymes, absorption from the vitamin C deficiency, collagen synthesis is disrupted, and wound healing
small intestine, metabolism, tissue distribution, and bioactivity (Benito can be delayed (FNB, 1998a; Li & Schellhorn, 2007). Folate deficiency
& Miller, 1998). The in vitro bioaccessibility may not be the same as in can cause anemia, but vitamin C may reduce folate deficiency because
gastric and intestinal conditions. Also, the utilization of nutrients in vitamin C prevents folate oxidation (FAO, 2001, pp. 235–247; Tardy,
metabolism is not the same for each individual. Accordingly, bio Pouteau, Marquez, Yilmaz, & Scholey, 2020). Vitamin C also prevents
accessibility and bioavailability values of foods may differ between in the oxidation of low-density lipoprotein, which may reduce the inci
vitro methods and gastrointestinal conditions or between the in dence of cardiovascular diseases (Honarbakhsh & Schachter, 2008).
dividuals. In vivo studies provide more specific bioavailability informa Brandon et al. (2014) studied the bioaccessibility of fortified vitamin
tion, but they are time-consuming and have high costs and ethical C in dietary supplements, infant formula, and fortified foods using an in
restrictions. Therefore, a few in vivo studies are conducted, and vitro model. Compared with multi-supplements (0.1–44%), vitamin C
bioavailability is usually described as the fraction of a given compound bioaccessibility was higher in mono-supplements (49–99%). Vitamin C
in circulation (Thakur et al., 2020). Alternatively, the in vitro methods bioaccessibility was very low (0.3–1.4%) in infant formulas and
developed are used extensively to determine nutrient bioaccessibility (0.4–6%) in fortified foods compared to other vitamin supplements. The
(Failla, Huo, & Thakkar, 2008). In vitro gastrointestinal digestion model authors thought that lower bioaccessibility in the multi-supplements
is considered useful for estimating preabsorption phase such as bio and other fortified foods was that other food ingredients and encapsu
accessibility and stability of nutrients released from food matrix. Despite lation might affect the vitamin C bioaccessibility in the gastrointestinal
their extensive applicability and potential, in vitro models cannot system (Brandon et al., 2014). Rodríguez-Roque, Rojas-Graü,
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Elez-Martínez, and Martín-Belloso (2013) reported vitamin C bio ascorbic acid is slowly oxidized by oxygen. Alkaline pH, temperature,
accessibility in both gastric and small intestinal conditions in blended and enzyme activity increase vitamin C oxidation or complexing with
fruit juice. Vitamin C was reduced by 17% compared with the other nutrients or chemicals. Jeney-Nagymate and Fodor (2008) indi
non-digested sample. However, the ascorbic acid amount was reduced cated that vitamin C decays at pH > 4. Therefore, there was more loss of
by 39% in the small intestine compared with the gastric phase. In vitamin C in the small intestinal phase than the gastric phase because the
another in vitro studies, vitamin C was reduced by 7% in broccoli in acidity of the small intestine was around neutral in Rodríguez-Roque
florescences (Vallejo, Gil-Izquierdo, Pérez-Vicente, & García-Viguera, et al. (2013). Vitamin C degradation also occurs by forming metal
2004) and by 29% in pomegranate juice (Pérez-Vicente, Gil-Izquierdo, & complexes with ascorbic acid (Ball, 2006). Rodriguez-Roque et al.
García-Viguera, 2002). Thus, gastric conditions affect vitamin C con (2015) reported that fruit juice containing soymilk has higher bio
centration less than the small intestinal condition. It may be because the accessibility (20.5–23.2%) than fruit juice containing milk
acidic gastric condition prevents vitamin C oxidation chemically and (10.9–13.1%) and water (11.1–14.2%). The authors indicated that the
enzymatically. Ascorbic acid is completely protonated at low pH; hence, higher bioaccessibility of fruit juice containing soymilk might be due to
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Table 1
Bioaccessibility of water-soluble vitamins.
Vitamin Food/processing type Bioaccessibility (%) Factors affecting bioavailability Reference
Vitamin C Dietary supplements-mono, -multi and 49–99%, 0.1–44%, 0.3–1.4% Other food ingredients and encapsulation Brandon et al. (2014)
fortified foods
Blended fruit juice (gastric, small 83%, 51% Gastric and small intestine pH Rodríguez-Roque et al.
intestine) (2013)
Broccoli inflorescences 93% Gastric and small intestine pH Vallejo et al. (2004)
Pomegranate juice 71% Gastric and small intestine pH Pérez-Vicente et al.
(2002)
Fruit juice-soymilk, -milk, -water (20.5–23.2%), (10.9–13.1%), Binding with proteins, vitamins and metal Rodriguez-Roque et al.
(11.1–14.2%) ions (2015)
Fruit beverages 16.3–56.0% No difference with the addition of milk Cilla et al. (2011)
Fruit beverages-whole milk, -skim milk, 70.17%, 62.41%, 12.58% Emulsion with milk increases BAC Cilla et al. (2012)
-soy milk
Orange segments, homogenized orange 54%,38% Homogenization Aschoff et al. (2015)
segments
Vitamin B1 Hard and soft red spring wheat brans 79.1%, 94.6%, (h) Dietary fiber Omaye et al. (1982)
Fortified wheat breads 69.1–91.2% Particle size of dietary fiber Kurek et al. (2017)
Durum wheat aleurone fractions 86–99% Particle size Zaupa et al. (2014)
Dry and -wet milled maize bran 2.33%, 1.70%, (h) Particle size and milling process Yu and Kies (1993)
Plant and animal-based foods 73%, 94%, (a) Roth-Maier et al. (1999)
Baby foods (gastric pH 1.5 and 4) 81%, 65% Gastric pH Akça et al. (2019)
Different breads 45–75% Content of beta-glucan Yaman (2019)
Vitamin B2 Fortified wheat breads 40.9–50.2% Particle size of dietary fiber Kurek et al. (2017)
Enriched milk, spinach meal 60%, 65%, (h) Dainty et al. (2007)
Baby foods (gastric pH 1.5 and 4) 66–97%, 46–85% Particle size, dietary fiber, polypeptides, and Akça et al. (2019)
gastric pH
Vitamin B3
Cereal, non-cereal samples rat 17%–111%, 46%–118%, (a) Bonding with polysaccharides and Carter and Carpenter
glycopeptides (1982)
Cooked wheat bran extract and -alkali- 24%, 62%, (h) Bonding with polysaccharides and Carter and Carpenter
treated glycopeptides (1982)
Fortified wheat breads 60.2–70.2% Particle size of dietary fiber Kurek et al. (2017)
Durum wheat aleurone fractions 10%–55% Particle size Zaupa et al. (2014)
Nicotinic, Baby foods (gastric pH 1.5, pH 4) 39%–51%, 33%–41% Bonding with polysaccharides and Akça et al. (2019)
nicotinamide glycopeptides, gastric pH
Vitamin B6
PNG Pyridoxine-5 ́-β-D-glucoside (PNG), 58 ± 13%, (h) PN-glucoside form Gregory et al. (1991)
administered orally
PL, PN, PM Cereal-based baby foods (gastric pH 1.5 53%–38%, 76%–67%,50%–36% Gastric pH, dietary fiber, bonding with Yaman and Mızrak
and 4) polypeptides, stability (2019)
PN Fortified wheat breads 27%–34% Particle size of dietary fiber Kurek et al. (2017)
PN Whole wheat bread, peanut butter 75%, 63%, (h) PN-glucoside form Kabir et al. (1983)
PL, PN, PM Different breads 56%–67% Stability of PN, PM and PL, beta-glucan Yaman (2019)
PL, PN, PM Different foods 41%–89%, 14%–98%, 26%–91%, Stability difference and heat treatment Roth-Maier et al. (2002)
(a)
Folate
Folic acid, 5-methyl- Fortified UHT and pasteurized milk, no 58%–61%, 71% Folate binding proteins Verwei et al. (2003)
THF FPB added
Folic acid, 5-methyl- Fortified UHT and pasteurized milk FPB 44%–51%, 72% Folate binding proteins Verwei et al. (2003)
THF added
5-methyl-THF Fortified yogurt with FBP added 82% Folate binding proteins Verwei et al. (2003)
Folic acid Fortified yogurt with FBP added 34%–57% Folate binding proteins
Folic acid Fortified baby foods (gastric pH 1.5 and 63%, 47% Folate binding protein, gastric pH Yaman et al. (2019)
4)
Folic acid Fortified French-type bread 100% Neves et al. (2019)
Folic acid Dietary supplements, fortified baby 24%–100%, 11% Brandon et al. (2014)
foods
Folate Cereal based fermented foods 23–81% Stability, food matrix Bationo et al. (2020)
Vitamin B12 Vitamin B12, oral intake (0.5, 5, and 70%, 28%, 1%, (h) Absorption efficiency or a limited number of Herbert (1987)
100 μg) receptor
Vitamin B5 Two types of average American diets 40%–61%, (h) Alkaline intestinal environment, enzyme Tarr et al. (1981)
activity
Wet and dry milled maize brans 48.69%, 54.33%, (h) Particle size of maize Yu and Kies (1993)
Wheat, potatoes, boiled pork, beef meal 65%–81%, (a) Roth-Maier et al. (2000)
Vitamin B7 Wheat, fed maize 12%, 100%, (a) Food matrix Bryden et al. (1991)
Soybean meal, barley, and maize 55%, 5%, 22%, (a) Complexing with indigestible protein Sauer et al. (1988)
h
, in vivo human study.
a
, in vivo animal study.
the presence of antioxidants that could decrease vitamin C degradation B12), and metal ions (Fe, Cu, and Zn) that interact with vitamin C (Ball,
because soymilk contains appropriate amounts of phenols and iso 2006). The bioaccessibilities of eight fruit beverages were between 16.3
flavones. On the other hand, the low vitamin C bioaccessibility in the and 56.0% (Cilla et al., 2011), and no difference was found with or
milk-based fruit juice may be due to the presence of some without the addition of skim milk. However, in a study conducted by
vitamin-binding proteins (Claeys et al., 2013), vitamins (B1, B2, and Cilla et al. (2012), the vitamin C bioaccessibility in whole milk-fruit
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beverages, skim milk-fruit beverages, and soy milk-fruit beverages were thiamine pyrophosphate (TPP), is a coenzyme in many metabolic
70.17, 62.41, and 12.58%, respectively. In fact, the bioaccessibility of pathways in living tissues. The phosphorylated forms of thiamine are
vitamin C is very low in original fruit juices. Ascorbic acid degradation hydrolyzed to free thiamine in the intestinal lumen by different phos
occurs during digestion due to the presence of oxygen and the pH of the phatases such as alkaline phosphatase. In living tissues, over 90% of
small intestine (Cilla et al., 2011; Pérez-Vicente et al., 2002). Thus, thiamine is in the phosphorylated form, primarily as TPP. As a coen
higher vitamin C bioaccessibility in whole and skim milk-based fruit zyme, TPP is found in the structure of the pyruvate dehydrogenase
juice was reported. The author thought that the combination of milk and enzyme complex and is involved in the conversion of pyruvate to Acetyl-
fruit juice produced an emulsion that prevented contact with oxygen. CoA. TPP is involved in the tricarboxylic acid cycle, pentose phosphate
Aschoff et al. (2015) compared the vitamin C bioaccessibility in two pathway, and oxidative decarboxylation of branched-chain α-keto acids
prepared orange segments and found 54% in orange segments but 38% via keto acid dehydrogenase (Ball, 2004). The best sources of vitamin B1
in homogenized orange segments. It is thought that in addition to other are yeast, wheat germ, oat bran, wheat, durum, lamb, loin, nuts, eggs,
vitamin C oxidation factors, homogenized orange segments are more vegetables, and fruits (TURKOMP, 2020; USDA, 2020). The recom
affected by oxygen than orange segments. mended thiamine requirements are between 0.9 and 1.2 mg for males
and females. The requirement increases to 1.4 mg in the pregnancy and
2.2. Bioaccessibility of B group vitamins lactation periods (FNB, 1998b). Most vitamin B1 is lost during milling;
therefore, thiamine enrichment in foods is utilized in many countries
2.2.1. Bioaccessibility of vitamin B1 (Ball, 2004, 2006). Lack of vitamin B1 causes anorexia, weight loss,
As a water-soluble vitamin, thiamine can be found in biological tis central neuropathy, muscle weakness, mental changes, Wernick
sues as thiamine monophosphate (TMP), thiamine diphosphate (TDP), e–Korsakoff syndrome, and beriberi. Thiamine loss occurs in increased
thiamine triphosphate (TTP), and in free form (Fig. 3). TDP, also called pH and temperature. Most importantly, thiamine is the most heat-labile
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vitamin of the B group vitamins (Ball, 2006). Hoyumpa (1986) studied higher activity in lower gastric pH (below 2) (Li-Chan & Nakai, 1989). It
the effects of alcohol on thiamine absorption in rats. Ethanol reduces the is thought in this study that thiamine was released less from the proteins
absorption of thiamine and reduces the elimination of cellular thiamine at gastric pH 4. Therefore, higher gastric pH causes the low bio
by decreasing the basolateral Na+–K+-ATPase activity. The accessibility of thiamine. It was also mentioned in that study (Akça et al.,
Ca2+/calmodulin second messenger system regulates thiamine absorp 2019) that stability, temperature, and dietary fiber content might affect
tion, but inhibition of this system affects thiamine bioavailability the bioaccessibility. The bioaccessibility of vitamin B1 in different
(Laforenza, Gastaldi, & Rindi, 1993). breads was studied by Yaman (2019). The lowest bioaccessibility was in
As anti-thiamine factors, thiaminases reduce the bioavailability oat bread (45%), whereas the highest bioaccessibility was whole wheat
during food storage, preparation, and through the gastrointestinal tract. bread (75%). In this study, the author indicated that beta-glucan content
Besides, polyphenols such as caffeic acid, chlorogenic acid, tannin, and in oat bread might reduce the bioaccessible amount of vitamin B1.
quercetin act as anti-thiamine factors (Yang & Pratt, 1984). Some foods
show high anti-thiamine activity, for instance, tea, coffee, blueberries, 2.2.2. Bioaccessibility of vitamin B2
black currents, beetroot, red cabbage, and brussel sprouts (Hilker & As a water-soluble vitamin, riboflavin can be found in foods and
Somogyi, 1982). Taungbodhitham (1995) detected low levels of vitamin biological tissues as free riboflavin (Fig. 3), and the phosphorylated
B1 in plasma from people who consumed vegetables containing high forms; riboflavin-5′ -phosphate (FMN) and riboflavin-5′ adenosyl
anti-thiamine activity. An in vitro study found that ascorbic acid prevents diphosphate (FAD) (Combs & McClung, 2016). The rich sources of
thiamine modification by tannic acid. Cysteine and reduced glutathione riboflavin in foods are yeast extract, liver, eggs, chicken meat, chick
also prevent thiamine modification. Vimokesant, Kunjara, Run peas, cheese, cow milk, and green leafy vegetables (USDA, 2020). The
gruangsak, Nakornchai, and Panijpan (1982) found low levels of the flavin coenzymes, FMN, and FAD, are bound non-covalently to proteins
active form of vitamin B1 in subjects who drank tea and chewed fer in foods (Merrill, Lambeth, Edmondson, & McCormick, 1981). FAD and
mented tea leaves. Also, both caffeinated and decaffeinated coffees show FMN are released from the proteins at low gastric pH and then hydro
anti-thiamine activity and decrease the plasma vitamin B1 level in lyzed to free riboflavin by brush-border enzymes (FMN phosphatase and
subjects. FAD pyrophosphatase) in the upper small intestine (Akiyama, Selhub, &
Omaye, Chow, and Betschart (1982) studied the bioavailability of Rosenberg, 1982). Absorption is increased by the presence of bile salt in
thiamine in hard red spring (HRS) and soft white winter (SWW) wheat two ways. First, bile salts both increase the solubility of riboflavin in the
brans using an in vitro gastrointestinal system. HRS and SWW wheat small intestine and the permeability of the brush-border to riboflavin.
brans contain dietary fiber. The bioavailability of thiamine was Second, bile salt retards gastric emptying and enhances the dephos
decreased in both samples (79.1%, 94.6%), and the authors hypothe phorylation time of FMN and FAD to riboflavin in the small intestine.
sized that thiamine interacts with dietary fiber either covalently or Free riboflavin is found in circulation as approximately 50% of total
physically, resulting in low bioaccessibility. In another study conducted flavins. The liver is the primary storage site for vitamin B2, where
by Kurek, Wyrwisz, Karp, and Wierzbicka (2017) the thiamine bio 70–90% is stored as FAD. Riboflavin in cells converts to FMN by fla
accessibility was between 69.1 and 91.2% in wheat breads containing vokinase and undergoes a reversible reaction to FAD by FAD synthetase.
6.17–6.20 g/100 g dietary fiber. The authors thought decreasing the FAD and FMN function as coenzymes in many biochemical reactions, for
particle size of dietary fiber in wheat bread influenced the thiamine example, decarboxylation of pyruvate to Acetyl-CoA, α-ketoglutarate to
bioaccessibility negatively because more hydroxyl groups arise with succinyl-CoA in the Krebs cycle, beta-oxidation of fatty acids, and
decreasing dietary fiber particle size, and hydroxyl groups could interact oxidation of succinate to fumarate. FAD transfers the electrons to
with thiamine and reduce the bioaccessibility. Zaupa et al. (2014) re nicotinamide adenine dinucleotide (NAD) to form NADH as an electron
ported the effects of particle size of industrial durum wheat aleurone carrier. The symptoms of riboflavin deficiency are a sore throat and
fractions on thiamine bioaccessibility. The particle size of the inner and lesions of the lips, mucosa of the mouth, and seborrheic dermatitis (Ball,
outer parts of aleurone were <100 μm and 300–425 μm, respectively. 2004). The recommended daily riboflavin requirements are between 0.9
The bioaccessibility of thiamine increased with decreasing particle size and 1.3 mg for males and females, and the requirement increases to 1.6
of durum wheat fractions. Yu and Kies (1993) studied the bioavailability mg in the pregnancy and lactation periods (FNB, 1998b). The stability of
of different maize brans. The bioavailability was estimated using the riboflavin increases with increasing acidity. Riboflavin is stable between
amount of urinary thiamine excretion. In this study, subjects who pH 2.0 and 5.0 and in heat (up to 120 ◦ C). Destruction of riboflavin
received dry milled maize bran had higher bioavailability (2.33%) than occurs at alkaline pH. Riboflavin, FMN, and FAD are very sensitive to
those who received wet-milled maize bran (1.70%). This report sug light. In a study about photodegradation of riboflavin in milk, 85% of the
gested that the particle size and milling process influences dietary riboflavin degraded in a glass bottle (Eitenmiller, Landen, & Ye, 2016).
thiamine absorption. The bioavailability of riboflavin is higher in animal-based foods than
Roth-Maier, Wild, Ehrhardt, Henke, and Kirchgessner (1999) esti plant-based foods (Ball, 2004). Excessive alcohol consumption inhibits
mated the prececal digestibility of thiamine in some foods in male pigs. the FMN phosphatase and FAD pyrophosphatase (Pinto, Huang, & Riv
In that study, the male pigs were fed for 12 days with boiled eggs, ba lin, 1984). Kurek et al. (2017) studied riboflavin’s bioaccessibility in
nanas, white cabbage, corn, milk powder, stewed fish, barley, boiled fortified wheat bread. The bioaccessibility was between 40.9 and 50.2%.
soybeans, boiled rice, wheat bran, and feedstuff containing free thia The author suggested that the decreasing particle size of dietary fiber
mine. Then, the digesta of pigs were collected twice a day during the last content negatively influenced bioaccessibility. More hydroxyl groups
five days of the experiment. The bioaccessibility of thiamine was arise with decreasing dietary fiber particle size, and hydroxyl groups
comparatively high both in foods containing natural thiamine and could interact with riboflavin and reduce the bioaccessibility. Ahmed &
enriched with free thiamine and ranged between 73% in stewed fish and Ayres (2006) reported the bioavailability of riboflavin in different sizes
94% in boiled soybeans. Comparing the bioaccessibility, plant-based of a gastric retention formulation. When comparing the large-sized
foods and animal-based foods have relatively equal bioaccessibility. capsules to small sizes, large capsules were retained for enough time
Akça, Sargın, Mızrak, and Yaman (2019) determined thiamine’s bio to release the contents and allow absorption in the gastric and intestinal
accessibility in cereal-based baby foods in different gastric pH envi conditions. In a clinical study, twenty healthy women aged between 18
ronments (pH 1.5 and 4). The bioaccessibility was 81 and 65% at pH 1.5 and 65 y were fed a riboflavin-enriched milk or spinach meal. It is stated
and 4, respectively. As seen, the thiamine bioaccessibility decreased that 60–65% of riboflavin was absorbed, and no difference was reported
with increasing gastric pH. In food, phosphorylated forms of thiamine between riboflavin-enriched milk and spinach (Dainty et al., 2007). The
are more often bound non-covalently to proteins (Ball, 2004). Pepsin bioaccessibility of riboflavin was studied in commercially available
breaks down the proteins in the gastric environment. Pepsin shows cereal-based baby foods (Akça et al., 2019). The riboflavin
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bioaccessibility was between 66 – 97% and 46–85% in gastric pH 1.5 Kurek et al. (2017). This reduction may be due to the binding of niacin to
and 4, respectively. As seen from that study, the highest decrease was polypeptides. This hypothesis was confirmed by Akça et al. (2019). In
reported at gastric pH 4. As mentioned above, the flavins are bound that study, nicotinic and nicotinamide’s bioaccessibility was 39% and
non-covalently to proteins. The author also indicated that most of the 51% at gastric pH 1.5 and 4, respectively. However, increasing gastric
flavins are bond to polypeptides, and therefore fewer flavins are released pH decreased both nicotinic acid and nicotinamide bioaccessibility to 33
from the proteins at higher gastric pH. As we evaluate the bio and 41%, respectively. The reason for the decreases may be a reduction
accessibility of riboflavin, particle size, dietary fiber, and gastric pH in the release of nicotinic acid and nicotinamide from the polypeptides
affect the release and absorption rate of riboflavin. as gastric pH increased.
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B6 in infants is most likely affected because the gastric pH of infants is deconjugation to monoglutamyl forms (Butterworth, Baugh, & Krum
higher than in adults (Nagita et al., 1996). Cereal baby foods contain a dieck, 1969). The optimum activity of conjugase enzymes occurs in pH
suitable amount of dietary fiber. Kurek et al. (2017) reported that adding 6.7–7.0, and it is activated by Zn2+ (Gregory 3rd, Ink, & Cerda, 1987).
small sized dietary fiber to bread reduces (27–34%) the bioaccessibility The liver takes up 10–20% of the reduced folate, and the remaining
of the pyridoxine form of vitamin B6. Yaman and Mızrak (2019) folate is transferred to extrahepatic tissues. Glutamate residues are
mentioned that decreases in the bioaccessibility of the PNG form are added to THF by folylpolyglutamyl synthetase for the intracellular
related to the dietary fiber content of cereal-based baby foods. In addi activation of folate. Folic acid is also reduced to THF by DHFR. The
tion to this knowledge, the author concluded that the bioaccessibility of folate is responsible for transferring the one-carbon units (methyl and
the forms of vitamin B6 is influenced by stability, temperature, pH of the formyl groups) in metabolism (Steinberg, 1984). The THF can be con
gastrointestinal tract, and dietary fiber, as well as bonding to poly verted to 5-methyl-THF by 5,10-methylenetetrahydrofolate reductase
saccharides and polypeptides. (MTHFR). The primary function of 5-methyl-THF is to transfer methyl
Plant-based foods have lower bioavailability than animal-based groups to homocysteine forming methionine by methionine synthase. In
foods because plant-based foods mostly contain the low bioavailable this reaction, 5-methyl-THF is converted to THF. The folate plays an
PN-glucoside form. Kabir, Leklem, and Miller (1983) studied the essential role in DNA synthesis as well as glycine and serine metabolism.
bioavailability of vitamin B6 in eight men. The findings showed the The deficiency of folate leads to megaloblastic anemia, neural tube de
vitamin B6 bioavailability was 75% in whole wheat bread and 63% in fects, and certain types of cancer. Clinical studies show that increased
peanut butter. Yaman (2019) studied the bioaccessibility of vitamin B6 homocysteine levels in plasma lead to cardiovascular diseases (Ball,
in white, whole wheat, bread with bran, and oat breads. The vitamin B6 2004). The recommended daily allowance for folate is 300–400 μg for
bioaccessibility ranged between 56 and 67% for the PL, PN, and PM males and females. This requirement increases to 600 μg during preg
forms. The highest bioaccessibility was observed for the PN form nancy and lactation (FNB, 1998b). The bioavailability of folic acid is
whereas the lowest bioaccessibility was found for the PL and PM forms. higher than naturally available folate, and the conversion factor of 1.7 is
The author stated the reason for the low bioaccessibility of the PL and used for converting folic acid to dietary folate equivalent (Greenfield &
PM forms might be that the PL and PM forms are less stable than PN. The Southgate, 2003). Spinach, dried beans, lentils, chickpeas, broccoli,
lowest bioaccessibility of vitamin B6 was found in oat bread compared to eggs, and breakfast cereal are good folate sources (TURKOMP, 2020;
other breads. Kurek et al. (2017) reported that the dietary fiber content USDA, 2020). The synthetic form of folate is more stable than other
and small particle size of dietary fiber in foods decreases the bio folate derivatives, and it is stable at 100 ◦ C and in pH 5.0–12.0. All fo
accessibility of the pyridoxine form of vitamin B6. As seen from that lates, including synthetic forms, are susceptible to photochemical
study, the dietary fiber content in foods influences the bioaccessibility of degradation. On the other hand, some reducing agents, including
vitamins. When we compare the type of dietary fiber content in breads, ascorbic acid and dithiothrietol, stabilize folates. However, folates can
only oat bread contains beta-glucan. Many studies show that be lost in the presence of metals (Fe2+). The stability of natural folates
beta-glucan decreases the bioavailability or bioaccessibility of many decreases with decreasing pH and increasing temperature. The addition
nutrients in foods such as glucose, cholesterol, and free fatty acids. of sodium nitrite to cured products can cause the degradation of folates.
Roth-Maier, Kettler, and Kirchgessner (2002) studied in vitro bio Comparing the stability of folates, THF is less stable than other folates
accessibility of the PL, PN, and PM forms of vitamin B6 in pigs fed (Eitenmiller et al., 2016).
different food sources. The bioaccessibility of PL, PN, and PM forms Unprocessed and pasteurized milk contains appropriate amounts of
ranged between 41% from rye and 89% from stewed fish, 14% from corn folate binding proteins (FBP) to prevent bacterial uptake of folate. FBP
and 98% from white cabbage, and 26% from boiled eggs and 91% from also prevents folate destruction by binding and carrying folate to the
bananas, respectively. Overall, when we evaluate the bioaccessibility of intestinal mucosa, increasing the bioavailability of folate (Swiatlo,
vitamin B6, the PN form has higher bioaccessibility than other forms. O’Connor, Andrews, & Picciano, 1990). As a whey protein, FBP contains
This may be because the PN form is more stable in alkali environments eight disulfide bridges, making it resistant to degradation and digestive
and heat treatment. enzymes such as pepsin and proteases (Verwei et al., 2004). The esti
mated ratio of FBP to folate is 1:1. The affinity of FBP to folic acid is
2.2.5. Bioaccessibility of folate 100-fold higher than 5-methyl-THF (Nygren-Babol, Sternesjö, Jägerstad,
Naturally available folates are found in the structure of pterin asso & Björck, 2005). The folate releases from FBP with decreasing gastric pH
ciated with methylene bridges to p-aminobenzoic acid, which binds to ˂ 4.5. The amount of FBP in milk is very sensitive to heat treatment.
glutamic acid(s) by peptide bonds. All folates are found predominantly Wigertz, Svensson, and Jagerstad (1997) reported that the amount of
in polyglutamate forms, containing five to seven glutamate residues FBP in pasteurized milk, ultrahigh temperature treated milk, skim milk
with the peptide linkage. Folic acid, also called pteroylglutamic acid powder, whey, and hard cheese are 211, 14, 1960, 97, and 13 nmol/L,
(Fig. 3), is not found naturally in foods, and unlike natural forms, it respectively. There is limited study regarding how the FBP affects the
contains only one glutamic acid (Ball, 2006; Combs & McClung, 2016). folate bioaccessibility in milk. The bioaccessibility of folic acid and
Natural forms of folates are largely present in foods bound to proteins 5-methyl-THF in fortified ultra-high temperature processed (UHT) and
(Baugh, Krumdieck, Baker, & Butterworth, 1971) and polysaccharides pasteurized milk were tested by the addition of FBP (Verwei et al.,
(Cerná, & Káš, 1983) and predominantly found in the form of tetrahy 2003). The folic acid bioaccessibility was 58–61%, while 5-methyl-THF
drofolate (THF), 5-methyl-THF, and 10-formyl-THF (Gregory, 1984). was 71%. On the other hand, the addition of FBP into fortified milk
The synthetic form of folates, which is folic acid, is most commonly used decreased the folic acid bioaccessibility to 44–51%, but 5-methyl-THF
in food fortification because it is more stable and more bioavailable than bioaccessibility was not changed (72%). This result indicated that folic
natural forms (Cuskelly, McNulty, & Scott, 1996). The poly acid was strongly bound to FBP during the gastrointestinal passage,
lpolyglutamate structure is large and is highly electronegative, and reducing bioaccessibility. Arkbage, Verwei, Havenaar, & Witthöft
therefore cannot enter into cells. All folates are deconjugated to mono (2003) reported that the bioaccessibility of both fortified-folic acid and
glutamate forms by the brush-border conjugase folylpoly-γ-glutamyl 5-methyl-THF in yogurt was 82%. In that study, inactivated FBP (ther
carboxypeptidase (EC 3.4.12.10). Some foods such as tomatoes, orange mal processing, 90 ◦ C for 5 min) was added to folic acid and 5-meth
juice extract, and organic acid can inhibit conjugase enzyme activity and yl-THF fortified yogurt, and folic acid bioaccessibility decreased to
can reduce the folate bioavailability in the human diet. 5-methyl-THF is 34% while 5-methyl-THF decreased to 57%. Yaman, Mızrak, Çatak, and
found in plasma and can convert to THF by the enzyme dihydrofolate Sargın (2019) reported the folic acid bioaccessibility was 63% at gastric
reductase (DHFR) in the liver, which is the active form of folate (Ball, pH 1.5 and 47% at gastric pH 4 in fortified baby foods formulated milk
2006). The polyglutamate can be absorbed by up to 50–75% after and milk products. In this research, the author indicated that the low
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bioaccessibility of folic acid suggested that less folic acid was released proteins might bind to vitamin B12 and increase its absorption.
from the FBP at higher gastric pH than lower gastric pH. The retention of
folic acid in fortified French-type bread was 61% after baking, and the 2.2.7. Bioaccessibility of vitamin B5
remaining folic acid bioaccessibility was 100% after the in vitro phase Vitamin B5, also called as pantothenic acid (Fig. 3), is found in a
(Neves et al., 2019). Brandon et al. (2014) reported the folic acid bio bound form in the structure of coenzyme A (CoA) and an acyl carrier
accessibility was between 24 and 100% in dietary supplements, while on protein (ACP) and also can be found in the free form in biological tissues
average, it was 11% in fortified baby foods. The fortified baby foods (Gonthier, Fayol, Viollet, & Hartmann, 1998). CoA is involved in many
generally are formulated with milk and milk products. We discussed biochemical reactions such as energy metabolism, and Acetyl-CoA re
above that milk contains FBP. As can be seen from this study, folic acid is leases the energy from carbohydrates, fats, and amino acids. ACP is part
less bioaccessible in fortified baby foods than dietary supplements. FBP of fatty acid synthase and responsible for the biosynthesis of fatty acids
might reduce folic acid bioaccessibility. The total folate loss was (Ball, 2004). Liver, egg, peanuts, and beans are the primary dietary
20–59% during debranning, soaking, and wet-milling in cereal-based sources of vitamin B5, but meat, potatoes, and green leafy vegetables
fermented foods consumed by young children in West Africa. The contain smaller amounts of vitamin B5 (USDA, 2020). Humans can also
folate bioaccessibility was between 23 and 81% in vitro. The author obtain vitamin B5 from a bacterial source provided from the normal
thought that the loss of bioaccessibility might be due to the stability of microflora of the large intestine. However, the contribution level of the
folate and the rate of release of folate from the food matrix (Bationo bacterial source to the vitamin requirement of the body has not been
et al., 2020). precisely defined (Said, 2011b). The recommended daily dietary intake
is 19–50 mg for both males and females (FNB, 1998b). Due to the
2.2.6. Bioaccessibility of vitamin B12 ubiquitous distribution of pantothenic acid, no known case of deficiency
Vitamin B12 also called as cyanocobalamin (Fig. 3), is an essential has been noticed in humans. CoA is hydrolyzed to pantothenic acid by
water-soluble vitamin because humans cannot synthesize it, and it must non-specific phosphatases and pantetheinase, secreted from the intes
be obtained from the diet. Vitamin B12 deficiency is common in people tinal mucosa (Shibata, Gross, & Henderson, 1983) and is carried in the
who consume a low dietary intake of animal-source foods. Malabsorp form of pantothenic acid in the circulation. Pantothenic acid is stable
tion caused by atrophic gastritis or Helicobacter pylori infection, pa between pH 4.0 and 5.0, but it is degraded into pantoic acid and
thology of the pancreas and small intestine, and gastric acid-reducing β-alanine under acidic and basic conditions. Tarr et al. (1981) reported
drugs are likely to contribute to the deficiency (Park & Johnson, 2006). that the bioavailability of pantothenic acid in the American diet ranged
Vitamin B12 deficiency or reduced intake can cause irreversible com from 40% to 61%. The bioavailability of vitamin B5 depends on the
plications such as disturbances in cell division and the nervous system, activity of enzymes involved in the release of pantothenic acid from CoA
megaloblastic anemia, and neuropathy (Truswell, 2007). The recom in the intestinal lumen before absorption. Because the alkaline intestinal
mended vitamin B12 requirements are between 1.8 and 2.4 μg for males environment can affect pantothenic acid, bioaccessibility may also be
and females. The requirement increases to 2.6 μg in the pregnancy and low (Ball, 2004). In another study (Yu & Kies, 1993), the bioavailability
lactation periods (FNB, 1998b). Animal-based products are the primary of vitamin B5 was higher in dry-milled coarse maize bran (54.33%) than
sources of vitamin B12 and contain adenosyl- and hydroxocobalamin wet-milled coarse maize bran (48.69%). This difference may be due to
forms together with methylcobalamin. Milk predominantly contains the the particle size because less vitamin B5 is liberated from larger particle
hydroxocobalamin form. The synthetic form, cyanocobalamin, is the sizes. In another study (Roth-Maier, Wauer, Stangl, & Kirchgessner,
most stable form of the vitamin and commonly used in food fortification 2000), the bioavailability of pantothenic acid was 65–81% in wheat,
and supplementation (Ball, 2004). Although vitamin B12 is resistant to potatoes, boiled pork, and beef meal in pigs. The highest bioavailability
heat treatment, some losses are reported in milk products from boiling was in the wheat diet, whereas the lowest was in the beef diet. However,
(30%) and pasteurization (7%), and increasing cooking temperature there was no statistical difference between the samples.
increases the losses. Vitamin B12 is bound to proteins and is released
from the proteins by pepsin and hydrochloric acid in the gastric phase. 2.2.8. Bioaccessibility of vitamin B7
Vitamin B12 deficiency increases in the elderly because the production of Vitamin B7, which is also called biotin (Fig. 3), occurs in nature in the
hydrochloric acid and digestive enzymes required to break down the d-(+)-biotin form. Biotin can be found in animal- and plant-based tissue
protein-bound vitamin B12 is reduced (Park & Johnson, 2006). After as free biotin and biocytin, which is the biologically active form. Bio
release from proteins, vitamin B12 binds to haptocorrin and intrinsic cytin is an amide formed between the amino group of a lysine residue
factors to prevent possible degradation in the gastrointestinal system. and the carboxyl group of biotin. It is covalently linked to the structure
The haptocorrin has a higher affinity than the intrinsic factor for vitamin of biotin-dependent carboxylase enzymes in animal- and plant-based
B12. Vitamin B12 is released from haptocorrin by the pancreatic pro tissues. Carboxylase enzymes such as pyruvate carboxylase, Acetyl-
teases before absorption in the jejunum region of the small intestine. CoA carboxylase, and propionyl-CoA carboxylase transfer the carboxyl
Unlike haptocorrin, intrinsic factors are more resistant to proteolytic group to substrates in metabolism, and they are involved in a variety of
enzymes. Vitamin B12-bound intrinsic factors are thought to be absorbed metabolic reactions, including fatty acid biosynthesis, gluconeogenesis,
and released by intestinal cells through a receptor called cubilin. and catabolism of specific amino acids and fatty acids. Proteolytic en
Vitamin B12 is mostly bound to the transcobalamin protein, which is zymes secreted from the pancreas do not release the biotin from the
plasma haptocorrin in circulation. The role of plasma haptocorrin is to protein-bound structure. Biotinidase, which is secreted from the intes
prevent the filtering of vitamin B12 by the kidney. Plasma beta globulin tinal mucosa, liberates the biotin from the biocytin. Nevertheless, the
and transcobalamin II transfer the vitamin B12 into the cell (Ball, 2004; biocytin can also be absorbed from the intestinal mucosa (Ball, 2006;
Seetharam & Alpers, 2010). Methionine synthase requires the methyl Combs & McClung, 2016). About 81% of total biotin is found in the free
cobalamin coenzymes, which involves the conversion of homocysteine form in plasma, but the remaining bound form is liberated by biotinidase
to methionine. L-methylmalonyl-coenzyme A (CoA) mutase requires (Mock & Malik, 1992). The egg white contains avidin, and it binds to
adenosylcobalamin to convert succinyl-CoA (Ball, 2004). In a study biotin. As long as the egg is not cooked or denaturized, the gastroin
conducted by Herbert (1987), increasing the vitamin B12 content in the testinal tract cannot release the biotin from the avidin. Biotin is stable to
diet decreases the absorption of vitamin B12. In that study, about 70% of heat treatment and alkaline environments. Hoppner and Lampi (1993)
vitamin B12 was absorbed in 0.5 μg of intake, 28% was absorbed in 5 μg reported between 88 and 95% of biotin retention during different
of intake, and the lowest absorption was 1% at 100 μg of intake. Tucker cooking times in dried legumes. Biotin undertakes a role in regulating
et al. (2000) reported that cyanocobalamin bioavailability in milk is the oncogene’s expression and the cellular level of the second messenger
higher than in other animal-based foods. The author thought that some cGMP (Scheerger & Zempleni, 2003; Spence & Koudelka, 1984).
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