Functional Foods, Bioactive Food Components and Prevention of Chronic Disease

Functional Foods, Bioactive Food
Components and Prevention of Chronic

Disease
Elizabeth Jeffery,Department of Food
Science and Human Nutrition, University
of Illinois
Early to Mid 1900s:
Late 1900s:
% Avoidable
Percentage of Chronic Diseases Potentially

Preventable by Lifestyle Modification
(Willett WC. 2002 Science 296:695-8 )
(antioxidants)
Containing
components
that, at doses
found in the
diet, have
beneficial
health effects
Functional Foods ; Foods

that, by virtue of their
physiologically active
components, provide
health benefits which go
beyond
basic
nutrition
Not a legal term
Changes in
Regulations
Market
Opportunity
Technology
Advances
Increasing
Healthcare
Costs
Functional
Food
Consumer
Interest
Aging
Population
Research
Developing Functional Foods

Discover
y
Marketable
product
Improve public
health (hopefully)
NUTS and cardiovascular health:

The Nurses Health Study*
86,016 women (orig. 121,700 --> 34-59 yrs)
14 yrs of follow-up (1980-1994)
861 nonfatal MI & 394 fatal CHD
1.0
0.8
0.6
0.4
0.2
0.0
*Hu et al. N Engl JNever

Med. 337:1491-1499,
<1/wk1997 2-4/wk
>5/wk
Frequency of nut
consumption
Nuts are 80% fat BUT

the composition is like that of olive oil
Other components? Unstudied.
80
70
60
50
MUFA
% FA 40
PUFA
SFA
30
20
10
0
Almond Oil
Olive Oil
Are Cranberries an
effective functional
food?
Is protection from
urinary infection
an old wives tale?
Ericaceae Family:
cranberries, blueberries,
huckleberries, bilberries
(Coppola et. al. Methods to Detect Adulteration of Fruit-Juice Beverages. 1995; (1) 287-308. )
Clinical Trials of Cranberries in

Prevention of Urinary Tract Infection
Reference
Patient Group
Trial Design
Cranberry
Juice Dose
Outcome
Dignam et.al.
(1977)[27]
Elderly men and

women
538
Historical
Comparisons
6 capsules or
220 ml/day
Fewer UTIs
(P=0.001)
Avon et.al.
(1994)[25]
Elderly women
153
Placebocontrolled
300ml/day
Reduced
bacteriuria
(P=0.004)
Haverkorn and
Mandigers
(1994)[30]
Elderly men and

women
Crossover
(not blinded)
15 ml twice
daily
Fewer UTIs
(P=0.004)
Walker et.al.
(1997)[28]
Middle-aged
women
Crossover
(double-blind)
400 mg
capsules/day
Fewer UTIs
(P<0.005)
Foda et.al.
(1995)[29]
Children with
neuropathic
bladders
10
21
Crossover
(not blinded)
15 ml/kg/day
No
reduction in
prevalence
of UTI
A-Type Proanthocyanidin Trimers from Cranberry that Inhibit

Adherence of Uropathogenic P-Fimbriated Escherichia coli .
Foo et al,2000 J. Nat. Prod., 63: 1225- 1228
anti-adherence activity
(mg/mL)a
compound
2.4b 1.2 0.6
0.3 0.15
a Positive anti-adherence activity (+) is

measured as the ability of the compounds to
suppress agglutination of both human red blood
cells (A1, Rh+) and latex beads coated with
synthetic P receptor analogue following
incubation with P-fimbriated E. coli.b Dilution of
compounds 1-6 in PBS, neutralized with 1 N
NaOH.
Designing Functional Foods

Plant
Breeding
Efficacy
Studies
Discovery
NEW PRODUCTS
with increased
bioactivity
Marketable
product
Improve public health
Food
Processin
g
safety
studies
Dietary Supplement, as defined by the 1994

Dietary Supplement Health and Education Act (DSHEA)
A product that is intended to supplement the

diet that bears or contains one of the following
[six] dietary ingredients: (A) a vitamin; (B) a
mineral; (C )an herb or other botanical; (D) an
amino acid; (E) a dietary substance for use by
man to supplement the diet by increasing the
total dietary intake; or (F) a concentrate,
metabolite, constituent, extract, or combination
of any ingredient described [above].
In the USA, dietary supplements are

regulated as foods: Implications for
safety and efficacy?
Foods
Drugs
Functional
Foods
Dietary
Supplement
s
In the USA, dietary supplements are

regulated as foods: Implications for
safety and efficacy?
Foods
Drugs
Functional
Foods
Regulated
Health
Claims
Generally
Regarded
as Safe
(GRAS)
Dietary
Supplement
s
Looselyregulated
structurefunction
claims
GRAS
Tightly
regulated
efficacy and
safety
Functional Food or Dietary

Supplement ? Benecol
Benecol, sold as a table
spread, contains sitosterols from pine
wood pulp. Slows
absorption of fats from
the intestine and
interrupts enterohepatic
recirculation of
cholesterol.
FDA ruling: Replaces butter or
other similar foods, therefore a
food, not a supplement to the diet.
Stanol Ester 1 year Trial
10.2% reduction
%
14.1% reduction
Total-C
LDL
HDL
TG
Miettinen et al. 1995
Stanol Ester Health Claim

Two to three
servings per day
with meals,
providing 3.4 grams
of Plant Stanol
Esters, with a diet
low in saturated fat
and cholesterol may
reduce the risk of
heart disease.
Benecol Spread
contains 1.7 g Stanol
Esters per serving.
Dietary supplement or Drug ?

Red Rice
Fermented product of rice on
which
red yeast (Monascus purpureus)
has
grown.
Contains:
* Mevinolin, known HMGCoA
reductase inhibitor, the
patented drug
lovastatin
ROLE OF SAFETY AND EFFICACY

DRUG DISCOVERY:
In vitro bioassays / structure-activity
lead to toxicology and pharmacokinetic
studies in animals
Lead to phase I and II clinical studies
Lead to full phase III clinical trial
Functional Foods, Dietary Supplement :

Epidemiological findings
(confirmation of mechanism/ effect/ safety)
(clinical trials)
MARKET
Phenotype
Plant
Genetics
Growing
Environment
BFC i.d.
i.d.
Formulation
formulation
Bioavailability
Bioavailability
Biomarkers
Biomarkers
Areas for Efficacy of Functional

Foods
Cancer prevention/ anticarcinogenesis/
antitumorigenesis
Cardiovascular Health/ Cholesterol
lowering/ antioxidants
Eye Health/ macular degeneration
Gut Health/ Pre- and pro-biotics
Bone Health/ anti-arthritics
General Health and Wellness/
Antioxidant / Anti-inflammatory /
Detoxification/ host defense
etc
Antioxidants may
protect against:
U.S.A.
Coronary Heart Disease

Arthritis
Alzheimers
Inflammation
Macular Degeneration
Cancer.
antioxidants
Foods rich in Antioxidants

What does this mean ?
Dark
Dark
Chocolate
Chocolate951951
mg/40g
mg/40 g
Milk
Milk
Chocolate
Chocolate394394
mg/40g
mg/40 g
HotHot
Chocolate
Chocolate45mg/240mL
45 mg/240 mL
Black
Black
TeaTea943mg/240mL
943 mg/240 mL
RedRed
Wine
Wine431mg/240
431 mg/240
mL mL
Polyphenolics Act as
Polyphenols can act as reducing agents
Antioxidants
e-,H+
OH
OH
OH
When ingested, they increase the
reducing capacity of plasma

Tea (green or black)
1996
Serafini et al.,
van het Hof et al., 1997

Red wine
Maxwell et al., 1994
Serafini et al., 1998
Duthie et al., 1998
Wine polyphenols
Carbonneau et al., 1997
Fruit juice (black currant/apple)Young et al., 1999
USDA Database for the Flavonoid Content

of Selected Foods 2003
www.nal.usda.gov/fnic/foodcomp/Data/Flav/flav.html
The database contains values for five subclasses of flavonoids :
FLAVONOLS: Quercetin, Kaempferol, Myricetin, Isorhamnetin
FLAVONES: Luteolin, Apigenin
FLAVANONES: Hesperetin, Naringenin, Eriodictyol
FLAVAN-3-OLS: (+)-Catechin, (+)-Gallocatechin, (-)-Epicatechin, (-)Epigallocatechin, (-)-Epicatechin 3-gallate, (-)-Epigallocatechin 3-gallate,
Theaflavin, Theaflavin 3-gallate, Theaflavin 3'-gallate, Theaflavin 3,3'
digallate, Thearubigins
ANTHOCYANIDINS: Cyanidin, Delphinidin, Malvidin, Pelargonidin, Peonidin,
Petunidin
Foods rich in Antioxidants

What does this mean ? : Polyphenolics
Dark
Dark
Chocolate
Chocolate951951
mg/40g
mg/40 g
Milk
Milk
Chocolate
Chocolate394394
mg/40g
mg/40 g
HotHot
Chocolate
Chocolate45mg/240mL
45 mg/240 mL
Black
Black
TeaTea943mg/240mL
943 mg/240 mL
RedRed
Wine
Wine431mg/240
431 mg/240
mL mL
C hocolate
Red W ine
B lack Tea
Orange
Garlic
Red
Onion
S pinach
B roccoli
160
140
120
100
80
60
40
20
0
B eet
Total P henols D W (umol/g)
Total
Phenolics
Vinson et al. J Agric Food Chem 1999 47(12) 4821 & 1998 46(9) 3630
Oxygen Radical Absorbance Capacity

(ORAC) of a water extract correlates with
estimate of total polyphenols (22 broccoli
genotypes)
Not validated for any bioassay of antioxidant

activity
Eberhardt et al, 2005
ORAC Assay
DCFH Assay
DCFH-DA
Fluorescein
DCFH-DA
Antioxidant
Blank
esterase
ROS
DCFH
DCF-
AUCantioxidant
AUCblank
Antioxidant Capacity = AUCantioxidant - AUCblank
In vitro/
BROCCOLI
-carotene
lutein
Carotenoids
-Toc
In culture
HEPATOCYTE
-Toc
Tocopherols
ORAC-L
DCFH-L
ORAC-H
DNA-L
DCFH-H
DNA-H
TR-L
QR-L
TR-H
QR-H
Polyphenolics
The relationship between biomarkers using the

lipophilic (-L) and hydrophilic (-H) fractions.
Significant correlations are shown by the joining
Eberhardt et al, 2005
Polyphenolics are more than just

antioxidants:
prevent cardiovascular disease,
inflammation and
cancer
Inhibit COX enzymes
Inhibit Cytochrome P450
Induce phase II detoxification enzymes
Estrogenic/ Antiestrogenic
Induce apoptosis in vitro in transformed
Fruits, Vegetables & Cancer

Prevention
Variety or Category
Vegetables
Fruits
Raw vegetables
Cruciferous Vegetables
Allium Vegetables
Green vegetables
Carrots
Tomatoes
Citrus Fruit
% Positive
80% (59/74)
64% (36/56)
87% (40/46)
69% (38/55)
77% (27/35)
77% (68/88)
81% (59/73)
71% (36/51)
66% (27/41)
The 1997 World Cancer Research Fund and the American Institute for Cancer Research (WCRF/AICR) report:
Food, Nutrition and the Prevention of Cancer: a global perspective, p442. by John D Potter and other panel members
Diet and Prostate cancer risk: do

diets rich in lycopene and/or
tomato lower risk for prostate
cancer ?
How Much Tomato Offers Cancer

preventon ?
1 serving of tomato = 1/2 cup of raw tomato or juice
Cancer
Prostate
Prostate
Prostate
Prostate
Servings
Decreased Risk
>3.5 vs <1/wk
41%
>5 vs <1/wk
40%
>5 vs <1/wk
36%
>4 vs <1.5/wk
22%
Reference
Schuman et al.
Mills et al.
Jain et al.
Giovannucci et al.
5 or more tomato product servings a week

provides better cancer prevention than
consuming only 2 servings a week!
Bosetti et al. 2000
Is Lycopene the Magic

Compound in Tomatoes?
Rats were fed a 10% tomato powder (13 mg
lycopene/ kg diet) or lycopene (161 mg
lycopene beadlets/ kg diet), or control diet
Hazard ratio P value
95% CI
Tomato
vs. Control
0.74
0.01
0.59-0.93
Lycopene
vs. Control
0.91
0.63
0.61-1.35
Boileau et al. 2003
Diet and Prostate cancer risk:

rats were implanted with a rat
prostate tumor and fed diets of
lycopene, tomato, broccoli or a
How Much Broccoli provides

protection from prostate cancer?
1 serving of crucifers = 1 cup of fresh = cup frozen
Prostate Cancer:
>3 servings
RR = 0.54
Cohen et al
3-5 servings of broccoli a week provides

better cancer prevention than
consuming one serving or less a week!
Effect of Sulforaphane on Incidence of DMBA/TPAinduced Papillomas in mice

Schedule A - One Week Before Initiation to End
DMBA/TPA
1 Mol SF
p<0.001
5 Mol SF
10 Mol SF
Gills, Jeffery, Pezzuto et al, 2005
p<0.001
p<0.001
Sulforaphane is formed from the glucosinolate

glucoraphanin, when broccoli is crushed
Glucosinolates break down to ITC

when plants are crushed or
chewed
Myrosinas
e
ITC
Isothiocyanate
Anticarcinogen
Glucosinolates break down to ITC

when plants are crushed or
chewed
O
S
C6H11O5
C
N O
Glucoraphanin
SO3-
Myrosinas
e
O
ITC
S
N
Sulforaphane
C S
Isothiocyanate
Anticarcinogen
Effect of Bioactive Food Components

like Sulforaphane on Detoxification
and Carcinogenesis
Chemicals
Radiation
Virus
Sulforaphane
Induce Phase II
Detoxification Enzymes
Inhibit P450 Activation

Preventing DNA Adducts
Sulforaphane
Initiation
Promotion
Progression
Inactivation/ excretion
Sulforaphane
Arrest Cell Cycle
Apoptosis

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Functional Foods, Bioactive Food

Components and Prevention of Chronic

Early to Mid 1900s:

Percentage of Chronic Diseases Potentially

(Willett WC. 2002 Science 296:695-8 )

Functional Foods ; Foods

Developing Functional Foods

NUTS and cardiovascular health:

*Hu et al. N Engl JNever

Nuts are 80% fat BUT

Clinical Trials of Cranberries in

Elderly men and

Elderly men and

A-Type Proanthocyanidin Trimers from Cranberry that Inhibit

2.4b 1.2 0.6

a Positive anti-adherence activity (+) is

Designing Functional Foods

Improve public health

Dietary Supplement, as defined by the 1994

A product that is intended to supplement the

In the USA, dietary supplements are

In the USA, dietary supplements are

Functional Food or Dietary

Stanol Ester 1 year Trial

Stanol Ester Health Claim

Dietary supplement or Drug ?

ROLE OF SAFETY AND EFFICACY

Functional Foods, Dietary Supplement :

Areas for Efficacy of Functional

Coronary Heart Disease

Foods rich in Antioxidants

When ingested, they increase the

reducing capacity of plasma

van het Hof et al., 1997

USDA Database for the Flavonoid Content

Foods rich in Antioxidants

Total P henols D W (umol/g)

Oxygen Radical Absorbance Capacity

Not validated for any bioassay of antioxidant

Antioxidant Capacity = AUCantioxidant - AUCblank

The relationship between biomarkers using the

Eberhardt et al, 2005

Polyphenolics are more than just

Fruits, Vegetables & Cancer

Diet and Prostate cancer risk: do

How Much Tomato Offers Cancer

5 or more tomato product servings a week

Is Lycopene the Magic

Diet and Prostate cancer risk:

How Much Broccoli provides

3-5 servings of broccoli a week provides

Effect of Sulforaphane on Incidence of DMBA/TPAinduced Papillomas in mice

Gills, Jeffery, Pezzuto et al, 2005

Sulforaphane is formed from the glucosinolate

Glucosinolates break down to ITC

Glucosinolates break down to ITC

Effect of Bioactive Food Components

Inhibit P450 Activation