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Functional Foods, Bioactive Food Components and Prevention of Chronic Disease

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Title: Functional Foods, Bioactive Food Components and Prevention of Chronic Disease


1
Functional Foods, Bioactive Food Components and
Prevention of Chronic Disease
  • Elizabeth Jeffery,Department of Food Science and
    Human Nutrition, University of Illinois

2
Early to Mid 1900s
Nutrient Deficiency Prevention
3
Late 1900s
Chronic Disease Prevention
4
Percentage of Chronic Diseases Potentially
Preventable by Lifestyle Modification
Avoidable
(Willett WC. 2002 Science 296695-8 )
5
Flavonoids
(antioxidants)
6
PLANT FOODS AS FUNCTIONAL FOODS
Containing components that, at doses found in the
diet, have beneficial health effects
7
Functional Foods Foods that, by virtue of their
physiologically active components, provide
health benefits which go beyond basic
nutrition
Not a legal term
8
Increasing Healthcare Costs
Changes in Regulations
Market Opportunity
Consumer Interest
FunctionalFood
Technology Advances
Aging Population
Research
9
Developing Functional Foods
Discovery
Marketable product
Improve public health (hopefully)
10
NUTS and cardiovascular health
  • The Nurses Health Study
  • 86,016 women (orig. 121,700 --gt 34-59 yrs)
  • 14 yrs of follow-up (1980-1994)
  • 861 nonfatal MI 394 fatal CHD
  • Hu et al. N Engl J Med. 3371491-1499, 1997

1.0 0.8 0.6 0.4 0.2 0.0
Frequency of nut consumption
Never lt1/wk 2-4/wk gt5/wk
11
Nuts are 80 fat BUT the composition is like
that of olive oil Other components? Unstudied.
12
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. )
13
Clinical Trials of Cranberries in Prevention of
Urinary Tract Infection
14
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 anti-adherence activity (mg/mL)a anti-adherence activity (mg/mL)a anti-adherence activity (mg/mL)a anti-adherence activity (mg/mL)a
compound 2.4b 1.2 0.6 0.3 0.15
1 - - - - -
2 - - - - -
3 - - - -
4 -
5 -
6 - -
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.
15
Designing Functional Foods
Food Processing
Plant Breeding
Discovery
NEW PRODUCTS with increased bioactivity
safety studies
Efficacy Studies
Marketable product
Improve public health
16
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.
17
In the USA, dietary supplements are regulated as
foods Implications for safety and efficacy?
Foods
Drugs
Dietary Supplements
Functional Foods
18
In the USA, dietary supplements are regulated as
foods Implications for safety and efficacy?
Foods
Drugs
Dietary Supplements
Functional Foods
Loosely-regulated structure-function claims
Tightly regulated efficacy and safety
Regulated Health Claims
Generally Regarded as Safe (GRAS)
GRAS
19
Functional Food or Dietary Supplement ? Benecol
Benecol, sold as a table spread, contains
ß-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.
20
Stanol Ester 1 year Trial
10.2 reduction

14.1 reduction
Total-C LDL HDL TG

Miettinen et al. 1995
21
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.
22
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 9 other
HMGCoA reductase inhibitors
23
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
24
Safe
Effective Dose
Phenotype
Plant Genetics
Growing Environment
BFC i.d. Formulation
Bioavailability Biomarkers
Bioavailability Biomarkers
i.d. formulation
25
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

26
Antioxidants may protect against Coronary
Heart Disease Arthritis Alzheimers Inflammatio
n Macular Degeneration Cancer.
U.S.A.
antioxidants
27
Foods rich in Antioxidants
What does this mean ?
Dark Chocolate 951 mg/40g Milk Chocolate 394
mg/40g Hot Chocolate 45mg/240mL Black Tea
943mg/240mL Red Wine 431mg/240 mL
Dark Chocolate 951 mg/40 g Milk Chocolate
394 mg/40 g Hot Chocolate 45 mg/240 mL
Black Tea 943 mg/240 mL Red Wine 431
mg/240 mL
28
Polyphenolics Act as Antioxidants
  • Polyphenols can act as reducing agents
  • When ingested, they increase the reducing
    capacity of plasma
  • Tea (green or black) Serafini et al., 1996
  • 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

29
  • 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

30
Foods rich in Antioxidants
What does this mean ? Polyphenolics
Dark Chocolate 951 mg/40g Milk Chocolate 394
mg/40g Hot Chocolate 45mg/240mL Black Tea
943mg/240mL Red Wine 431mg/240 mL
Dark Chocolate 951 mg/40 g Milk Chocolate
394 mg/40 g Hot Chocolate 45 mg/240 mL
Black Tea 943 mg/240 mL Red Wine 431
mg/240 mL
31
Total Phenolics
Vinson et al. J Agric Food Chem 1999 47(12)
4821 1998 46(9) 3630
32
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
33
ORAC Assay
DCFH Assay
esterase
ROS
Antioxidant Capacity AUCantioxidant - AUCblank
34
The relationship between biomarkers using the
lipophilic (-L) and hydrophilic (-H) fractions.
Significant correlations are shown by the joining
arrows.
Eberhardt et al, 2005
35
  • 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 cells

36
Fruits, Vegetables Cancer Prevention
Variety or Category

Positive
Vegetables
80 (59/74)
Fruits
64 (36/56)
Raw vegetables
87 (40/46)
Cruciferous
Vegetables
69 (38/55)
Allium
Vegetables
77 (27/35)
Green vegetables
77 (68/88)
Carrots
81 (59/73)
Tomatoes
71 (36/51)
Citrus Fruit
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
37
Diet and Prostate cancer risk do diets rich in
lycopene and/or tomato lower risk for prostate
cancer ?
38
How Much Tomato Offers Cancer preventon ?
1 serving of tomato 1/2 cup of raw tomato or
juice
Cancer Servings Decreased
Risk Reference Prostate gt3.5 vs lt1/wk 41
Schuman et al. Prostate gt5 vs lt1/wk
40 Mills et al. Prostate gt5 vs lt1/wk
36 Jain et al. Prostate gt4 vs
lt1.5/wk 22 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
39
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 Lycopene vs. Control
0.74
0.01
0.59-0.93
0.91
0.63
0.61-1.35
Boileau et al. 2003
40
Diet and Prostate cancer risk rats were
implanted with a rat prostate tumor and fed diets
of lycopene, tomato, broccoli or a mix.
41
How Much Broccoli provides protection from
prostate cancer?
1 serving of crucifers 1 cup of fresh ½ cup
frozen
Prostate Cancer gt3 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!
42
Effect of Sulforaphane on Incidence of
DMBA/TPA-induced Papillomas in mice Schedule A -
One Week Before Initiation to End
DMBA/TPA
1 ?Mol SF
plt0.001
plt0.001
5 ?Mol SF
plt0.001
10 ?Mol SF
Gills, Jeffery, Pezzuto et al, 2005
43
Sulforaphane
Sulforaphane is formed from the glucosinolate
glucoraphanin, when broccoli is crushed
44
Glucosinolates break down to ITC when plants are
crushed or chewed
Myrosinase

ITC Isothiocyanate Anticarcinogen
45
Glucosinolates break down to ITC when plants are
crushed or chewed
Glucoraphanin
Myrosinase

ITC Isothiocyanate Anticarcinogen
Sulforaphane
46
Effect of Bioactive Food Components like
Sulforaphane on Detoxification and Carcinogenesis
Chemicals Radiation Virus
Sulforaphane
Sulforaphane
Induce Phase II Detoxification Enzymes
Inhibit P450 Activation
Initiation ? Promotion ? Progression
Preventing DNA Adducts
Inactivation/ excretion
Sulforaphane
Arrest Cell Cycle
Apoptosis
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