Functional Foods & Nutraceutical

Phytochemicals
(Part 1)
Dr. Weiqun Wang
Department of Food, Nutrition, Dietetics &
Health

Kansas State University

Dr. Weiqun (George) Wang

Professor of Food Nutrition Dietetics
Director of Graduate Program
Kansas State University
Manhattan, KS 66506 USA

Phone: 1-785-532-5508
Email: wwang@ksu.edu

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 1. Functional Foods & Nutraceutical
Phytochemicals
2. Improving Healthy Quality of Cereal
Grains or Vegetable Fruits by
Increasing Phytochemicals
3. Antioxidant Phenolics & Colorectal
Cancer Prevention

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Outline
1. Chronic diseases and Dietary factors

2. Functional Foods & Nutraceuticals

3. Examples of Functional foods or

Nutraceuticals

4. Safety and Legal regulations

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US Leading Causes of Death in 2021

1. Heart disease: 695,547 (27%)
2. Cancer: 605,213 (23%)
3. COVID-19 416,893 (16%)
4. Accidents: 224,935 (9%)
5. Stroke: 162,890 (6%)
6. Chronic lower respiratory diseases: 142,342
(5%)
7. Alzheimer's disease: 119,399 (5%)
8. Diabetes: 103,294 (4%)
9. Liver disease: 56,585 (2%)
10.Influenza and Pneumonia: 54,358 (2%)
Mortality in the United States, 2021
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 Chronic Diseases

• Chronic diseases are diseases of long

duration and generally slow progression.
• Chronic diseases, such as heart disease,
cancer, chronic respiratory diseases,
diabetes, and Alzhimer are by far the leading
cause of mortality in the world, representing
60% of all deaths (~1.7 million people) in
2021.

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Causes of Chronic Diseases

• Genetic factors
• Environmental factors, such as
• unhealthy diet and excessive energy
intake
• physical inactivity
• tobacco use.

http://www.who.int/chp/chronic_disease_report/part2_ch1/en/inde
x12.html

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Human Chromosomes

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Lichtenstein et al. Environmental and Heritable

Factors in the Causation of Cancer: Analyses of
Cohorts of Twins from Sweden, Denmark, and
Finland. New England J Med 2000; 343:78-85.
Methods: Combined data of 44,788 pairs of twins in
order to assess the risk factors of cancer.

Conclusion: Inherited genetic factors make a

minor contribution to susceptibility to most of
types of neoplasms, indicating that the
environment has the principal role in causing
sporadic cancer.

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 Causes of Human Cancer
Diet 35% (20-60%)
Tobacco 30%
Genetic 15% (5-20%)
Reproduction 7%
Occupation 4%
Alcohol 3%
Geophysical 3%
Pollution 2%
Viruses 1% (1-10%)
Medical <1%

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• Diets or dietary factors are associated

with chronic diseases.
• Either causal or protective factors
• Protective factors make foods into
clinical practice as preventive medicine
(functional foods?)

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• “Let food be thy medicine and

medicine be thy food”
– 460 BC-370 BC by Hippocrates
• The philosophy of “food as medicine” was
changed in 19th century by the advent
modern medicine
• Since 1900s, however, the important role
of diet in chronic disease prevention and
health promotion were re-emphasized
– Chronic diseases: heart disease, cancer,
osteoporosis, diabetes and stroke, etc

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Diet, Nutrition & Health

• Diet plays a role for coronary heart disease
(CHD), certain types of cancer, stroke,
diabetes (type 2) and atherosclerosis
US Department of Health and Human Services
• Dietary cause pattern:
– Extra energy intake
– High in total and saturated fat, cholesterol, sodium
and refined sugars
– Low in unsaturated fat, grains, legumes, fruits and
vegetables
• However, accumulating data support dietary
prevention (functional foods) against chronic
diseases

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History of Dietary Guidelines for Americans

1980 2005 2010
1st Edition 2000
by DHHS 5th
& USDA edition

1985
2nd
1995
edition
4th
2015
edition

1990
National Nutrition
1990
Monitoring and
Related Research Act: 3rd
publication of the edition
Dietary Guidelines for
Americans every 5
years

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Summary of Dietary Guidelines

2020-2025
• Follow a healthy dietary pattern at every life
stage.
• Customize and enjoy nutrient-dense food and
beverage choices.
• Focus on meeting food group needs with
nutrient-dense foods and beverages, and stay
within calorie limits.
• Limit foods and beverages higher in added
sugars, saturated fat, and sodium, and limit
alcoholic beverages.

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What Are Functional Foods?

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 Concept of Functional Foods
• The concept of functional foods is based on
advanced knowledge of the nutrition
throughout 21st century
• During 1st half of 20th century, focus was on
undernutrition and nutritional deficiencies
• In 2nd half 20th century and 21st century,
focus shifted to overnutrition and nutrition-
associated public health problem
• In both situation, foods can be formulated to
have specific physiological or nutritional
effects that improve health

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Position of the Academy of Nutrition and

Dietetics
Functional food is defined as whole foods
along with fortified, enriched, or enhanced
foods that have a potentially beneficial effect
on health when consumed as part of a
varied diet on a regular basis at effective
levels based on significant standards of
evidence.
J. Acad. Nutr. Diet. 2013; 113: 1096-1103.

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Functional Foods
• The term functional foods was 1st
introduced in Japan in the mid-1980s as to
processed foods containing ingredients that
aid specific bodily function in addition to
being nutritious
• Japan has regulatory approval for functional
foods
• More than 1,000 products have been
licensed as Foods for Specified Health Use
(FOSHU) in Japan
• Functional foods category is not legally
recognized in the U.S.
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 What are functional foods?
• Any modified food or food ingredient that may
provide a health benefit beyond the traditional
nutrients it contains
National Academy of Sciences’ Food and Nutrition Board (IOM/FNB,
1994)
• Foods that , by virtue of the presence of
physiologically-active components, provide a
health benefit beyond basic nutrition
International Life Sciences Institute of North American, 1999
• Whole foods along with fortified, enriched, or
enhanced foods that have a potentially benefitcial
effect on health when consumed as part of a
varied diet based on significant standards of
evidence
American Dietetic Association, 2013

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Bioactive Nutraceuticals
• The ingredient(s) that aid specific function
called bioactive component(s) or
“Nutraceuticals”
• Nutraceuticals can be found or delivered in
foods  Functional Food
• Nutraceuticals can be purified or
concentrated as dietary supplements

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Defination of a Nutraceutical
• Any bioactive component that delivers a 
health benefit
Foundation for Innovation in Medicine, 1991

• Diet supplements that deliver a 
concentrated form of a presumed 
bioactive agents from food, presented in a 
nonfood matrix, and used to enhance 
health in dosages that exceed those that 
could be obtained from normal food
Zeisel, 1999

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 Nutraceuticals
• In plant foods (phyto-chemicals)

• In animal foods (zoo-chemicals)

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J Am Diet Assoc. 2009;109:735-46

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What is a Medical Food?

• “Is prescribed by a physician when a
patient has special nutrient needs in order
to manage a disease or health condition,
and the patient in under the physician’s
ongoing care”

• Label of product must clearly state that the

product is intended to be used to manage
a specific medical disorder or condition.

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 What is a Medical Food?
• These products are not meant to be
consumed by the general public
• They may NOT be available in stores or
supermarkets
• They are NOT foods included within a healthy
diet intended to decrease the risk of a specific
disease
– Low fat foods
– Low sodium foods
– Weight loss products

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Four Categories of Medical Foods

1. Nutritionally complete formulas (formulas
that can be used as sole-use nourishment)
2. Nutritionally incomplete formulas (modular
products of fat, protein, carbohydrate)
3. Formulas for metabolic disorders in patients
over 12 years of age
4. Oral rehydration products

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Medical Foods
Pediatric formulas
– Healthy full term infant formulas
– Premature infants
– Infants with inborn errors of metabolism
Adult formulas that meet special needs
HIV
Diabetic
Cancer
Renal disease
Pulmonary disease

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 Medical Foods for Selected Inborn
Errors of Metabolism
Disorder Products Manufacturer
PKU Lofenalac Mead-Johnson
PKU Maxamaid XP SHS
PKU Phenex-1 Ross Labs
MSUD MSUD 1 Mead-Johnson
MSUD MSUD SHS
Maximaid
MSUD Ketonex 1 Ross Labs
UCD OS 1 Mead-Johnson
UCD Cyclinex 1 Ross Labs

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Examples of Functional foods

or Nutraceuticals

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Some Functional Foods

• Plant Sources
– Oats: soluble fiber -glucan to reduce
cholesterol, thereby CHD risk
– Soy
• Soy proteins to exert hypocholesterolemic effect
• Isoflavones and cancer prevention
• Soy and osteoporosis
– Flaxseed
• Omega-3 fatty acid or -linolienic acid and CHD
reduction
• Lignans and cancer prevention

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 Some Functional Foods
• Plant Sources
– Tomatoes
• Lycopene and cancer risk reduction
– Garlic 
• Sulfur‐containing elements and cancer prevention
• Garlic and antihypertensive properties (CHD reduction)
– Broccolis and other cruciferous vegetables
• Glucosinolates and cancer risk reduction
– Citrus fruits
• Limonoids and Anticancer activities

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Some Functional Foods

• Plant Sources
– Tea
• Polyphenols and cancer chemopreventive effects
• Flavonoids and CHD reduction
– Wine and Grapes
• Phenolics and reduced risk of CHD
• Resveratrol and cardiovascular
benefits/carcinogenesis inhibition

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Some Functional Foods

• Animal Sources
– Fish
• Omega-3 fatty acids & cancer/CHD reduction
– Dairy
• Calcium & osteoporosis prevention
• Probiotics & Anticarcinogenic and
hypocholesterolemic
• Lactic acid & Anti-colon cancer
– Beef
• Conjugated linoleic acid (CLA) & cancer
suppression
• CLA & weight-reduction

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 Functional Foods & Nutraceutical
Phytochemicals
(Part 2)
Dr. Weiqun Wang
Department of Food, Nutrition, Dietetics &
Health

Kansas State University

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Safety & Legal Regulation

• All substances are poison…the right dose
differentiates a poison from a remedy
Paracelsus’ 15th century doctrine
• FDA approves health claims of functional
foods based upon significant scientific
evidence (two dozen or more well-designed
clinical studies)
• Too often “emerging evidence (in vitro or
animal studies, uncontrolled human studies)
is the basis for marketing some functional
foods or nutraceuticals

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Law Act for Foods and Drugs

In the US, an act of government regulates the
sale and promotion of both food and drugs
is the Federal Food, Drug, and Cosmetic
Act (FD&C Act 1938)
In some other countries, there are separate
acts for food and drugs, mainly because
the definitions of food and drug are distinct

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 Difference Between Foods and Drugs
Definition:
Food is food for man or animals and chewing
gum (FD&C Act 1938)
A drug is any article intended for use in the
diagnosis, cure, mitigation, treatment or
prevention of disease in man or other animals
(FD&C Act 1938)
Label:
Foods: Nutrition Facts, Health Claims
Drugs: Principal Display Panel

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Good source >10%

Excellent source >20%

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Difference Between Foods and Drugs

(cont.)
Administration:
Foods: normally as oral
Drugs: oral, intravenous, etc

Preapproval Process:
Foods: No
Food Additives: Yes
Drugs: Yes

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 US Regulatory Approaches for Food or
Nutraceutical Phytochemical
Food or
Phytochemical

Taste or
Body cleansing or
Altering appearance Intended use? nutritive Food
value

Cosmetic Ingested to
Diagnose, cure Ingested to
affect supplement
Treat or
Function diet
prevent disease of body

Yes Intended use Dietary

Drug as drug? No supplement

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Regulatory Bodies Governing Nutrition

Health Claims
Country Regulatory Body

Australia Food Standards Australia New Zealand

Canada Health Canada
China State FDA
European Union European Food Safety Authority
Indonesia National Agency for Drug & Food Control
Japan Ministry of Health, Labor and Welfare
United Kingdom Joint Health Claims Initiative
USA FDA

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Functional Foods in Japan

• Japanese Foods:
1. "Food with Nutrient Function Claims,"
2. "Food for Specified Health Uses"
(FOSHU)
• FOSHU approval must tabulate both
published publications and internal reports
on the effectiveness of the product,
including in vitro metabolic and biochemical
studies, in vivo studies, and randomized
controlled trials on Japanese people

J. Nutr 2008; 138:1192S-8S

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 1,000
Transition of FOSHU items

2018

Yamada K et al. J. Nutr. 2008;138:1192S-1198S

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Regulation of Food with Health Claim in Japan

Yamada K et al. J. Nutr. 2008;138:1192S-1198S

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Functional Foods in China

• 4 main rules for functional food assessment
in China:
– functional assessment procedures
– standard toxicological assessment
– regulations on nutrient supplements
– standard analytical methods for functional
components

J. Nutr 2008; 138:1199S-205S

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US Legal Problems for Functional Foods
• There is not a legal category for functional
foods or nutraceuticals in the US.
• Legally a functional food or nutraceutical
may make a health claim as foods, food
fortification, or dietary supplements that are
regulated in the Code of Federal
Regulations (CFR)
• Those pertaining to foods and dietary
supplements are published in Title 21 CFR
Parts 1-199

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Legal Problems for Functional Foods

• Those pertaining to meats are published in
Title 9 CFR
• These are under the regulatory authority of
the FDA as administered by the Secretary
of Health and Human Services (HHS).
• All the legal documentation is available in
electronic format on the FDA home page at
http://www.fda.gov

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US Agencies Related to Foods

• FDA  Food (all processed), drug, dietary
supplements, cosmetics, medical devices,
bottled water, seafood, wine <7% alcohol
• USDA  Raw vegetables, raw fruit, meats,
poultry, eggs
• EPA (Environmental Protection Agency) 
Drinking water, pesticide residues
• FTC (Federal Trade Commission) 
Advertising
• BATF (Bureau of Alcohol, Tobacco & Firearms)

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 Foods Are Reviewed by FDA as:
• Conventional Foods
• Special Dietary Foods
• Medical Foods
• Dietary Supplements

No categories for “Functional Foods” or

“Nutraceuticals”

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Federal Food & Nutrition Law

More than 350 federal policies exist:

• Food Safety and Regulation
• Food Fortification
• Dietary Supplements

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Key US Laws related to Functional Foods

• 1906 Pure Food and Drug Act
• 1906 Federal Meat Inspection Act
• 1938 Food, Drug and Cosmetic Act (FD&C)
• 1958 Food Additives Amendment
• 1960 Color Additives Amendment
• 1973 Nutrition Labeling Regulations
• 1990 NLEA
• 1990 US Organic Foods Production Act
• 1994 DSHEA
• 1996 Food Quality and Protection Act
• 1997 Food Modernization Act

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 Key US Laws related to Functional Foods
(cont.)
• The Federal Food Drug and Cosmetic Act
of 1938 (FD&C Act)
• 1958 Food Additives Amendment
• The Nutritional Labeling and Education Act
of 1990 (NLEA)
• The Dietary Supplement and Health
Education Act of 1994 (DSHEA)
• 1997 FDA Food Modernization Act (Health
Claims)

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Health Claims
The definition of health claim in the US as
part of the Nutrition Labeling and
Education Act (NLEA) is:
• A health claim is any claim made on the
label that either expressly or through
implication characterizes the relationship
between any substance to a disease or
health related condition

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1997 FDA Modernization Act

• All health claims must undergo review by

FDA through a petition process
• All unqualified health claims must meet
the significant scientific agreement

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 Scientific Ranking for Health Claims

• In July 10, 2003, FDA announced a

guidance for industry:
– Interim Evidence-based Ranking
System for Scientific Data

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Six Steps to Evaluating the Strength by FDA

1. A proposed relationship between a substance
and a disease is identified.
2. Individual studies are identified.
3. Individual studies are classified according to
study design type.
4. Individual studies are assigned according to
the quality.
5. The strength of the scientific evidence in
support of the substance/disease relationship
is given a rank.
6. The rank is reported

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Scientific Ranking for Qualified Health Claims

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 Health Claims

• Up to 12 food health claims have been

approved by FDA
• https://www.fda.gov/food/food-labeling-
nutrition/authorized-health-claims-meet-
significant-scientific-agreement-ssa-standard

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Approved Health Claims

• Calcium, Vitamin D, and Osteoporosis (21
CFR 101.72)
• Dietary lipids (Fat) and Cancer (21 CFR
101.73)
• Sodium and Hypertension (21 CFR 101.74)
• Dietary Saturated Fat and Cholesterol and
Risk of Coronary Heart Disease (21 CFR
101.75)
• Fiber-containing Grain Products, Fruits,
Vegetables and Cancer (21 CFR 101.76)

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Approved Health Claims (cont.)

• Fruits, Vegetables and Grain Products that
contain fiber, particularly Soluble fiber, and
Risk of Coronary Heart Disease (21 CFR
101.77)
• Fruits and Vegetables and Cancer (21 CFR
101.78)
• Folic Acid and Neural Tube Defects (21 CFR
101.79)
• Dietary Non-cariogenic Carbohydrate
Sweeteners and Dental Caries (21 CFR
101.80)

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 Approved Health Claims (cont.)
• Soluble Fiber from Certain Foods and
Risk of Coronary Heart Disease (21 CFR
101.81)
• Soy Protein and Risk of Coronary Heart
Disease (21 CFR 101.82)
• Stanols/Sterols and Risk of Coronary
Heart Disease (21 CFR 101.83)

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Health Claims for Dietary Supplements (cont.)

• Consumption of omega-3 fatty acids may

reduce the risk of coronary heart disease.
FDA: although there is scientific evidence
supporting the claim, the evidence is not
conclusive  B

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Health Claims for Dietary Supplements (cont.)

• Selenium may reduce the risk of certain

cancers.
FDA: this evidence is limited and not
conclusive  C

• Phosphatidylserine may reduce the risk of

dementia in the elder.
FDA: there is little scientific evidence
supporting this claim  D

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 How to Develop A Functional
Food Product?

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Good Manufacturing Practices (GMP)

• GMP should ensure if a structure function
claim is made:
– The product is not adulterated
– It is not misbranded at least with respect
to the claim
– The effective substance is present and
safe
– The effective substance lasts through
processing procedure
– The product is labeled with an expiration
date
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Criteria
1. identification of a plant/crop with biological
activity
2. identification and characterization of the
active principle(s) in the plant
3. variation in content of the active principle(s)
4. examination of biological activity and efficacy
of a natural product or its active
component(s)
5. toxicity of natural product or active
principle(s)
Modified from Stephen AM, Functional Foods, 1998, p421

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 Examination of Biological Activity & Efficacy
1. In vitro experiments
2. Animal experiments
3. Human Studies

In vitro and animal studies are valuable for

detailed mechanistic aspects of the action
of a product
however, these must be supplemented
with human studies.

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How Much Evidence Is Required for

A Health Claim?

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Preliminary Requirements for a

Health Claim under NLEA
1. The substances are associated with a
disease for which the US population is at
risk.
2. The substances are a food.
3. The substances are safe

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 FDA uses Human Studies to Evaluate
the Scientific Evidence
• present data and adequate descriptions of
the study design and methods
• are available in English
• include estimates, or enough information to
estimate dietary intake
• include direct measurement of biological
markers for disease
• are conducted in persons who represent
the general U.S. population

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FDA uses Human Studies to Evaluate

the Scientific Evidence (cont.)

• Functional foods that have a FDA-approved

health claim generally are supported by two
dozen or more well-designed published
clinical trials

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Costs of Making Health Claims

• The major costs:
– Chemical analysis
– Human studies
• A considerable financial commitment can
be incurred in human studies
• Shared funding between industry and
government may be able to address the
high costs of trials
• However, the burden of proof for dietary
supplement under DSHEA is transferred to
FDA
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 Regulation Process vs. Functional Foods
$33B

adults taking
58% of US
Nutraceuticals Functional foods

$152 B
$8B

1938 1979 1984 1990 1994 2012 2018 2021

Food & Drug Act Nutrition labeling Dietary Supplement & Health
& Education Act Education Act
Health claims for food
products are supported Claims for supplements without
by scientific evidence FDA approval as long as stated:
It is not intended to diagnose,
cure, treat or prevent diseases,
& has not been evaluated by FDA

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 Conclusions
• No doubt that increasing interest in
functional foods will continue
• The health of consumers is dependent on
such products being safe, and having the
effects
• Government health agents should ensure
the health of consumers is not at risk by
these products
• Those developing and promoting products
with health benefit must recognize the
responsibility they take

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