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