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Food is Medicine - An introduction to Nutraceuticals

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Food is Medicine
-
An Introduction
to Nutraceuticals
Eng. Dr. Perkins Muredzi.

1
Food is Medicine
–
An Introduction
by Perkins Muredzi

to Nutraceuticals

2
 Food is Medicine –
An Introduction to
Nutraceuticals

Eng. Dr. Perkins Muredzi

School of Industrial Sciences & Technology; Harare Institute of
Technology Harare, Zimbabwe

3
 Dedicated to Mrs Dorothy Stembile Muredzi,
Sean Muredzi,
Sheldean Muredzi

and

In Loving Memory of:

Callisto Wunganayi Temba, Rudo Anastasia Bwanya
and John Tanjani

4
Contents
Chapter 1 .............................................................................................................................. 13
Understanding the concept of “Nutraceuticals” ...................................................................... 13
Historical Background ........................................................................................................... 13
Introduction .......................................................................................................................... 13
Nutraceuticals vs other Terminologies: .................................................................................. 15
Classification of Nutraceuticals ............................................................................................. 17
References: ........................................................................................................................... 25
Chapter 2 .............................................................................................................................. 29
Nutraceuticals and Diseases ................................................................................................... 29
2.0. Introduction .................................................................................................................... 29
Table 2.1. Nutraceuticals and Diseases................................................................................... 32
2.1. Cardiovascular Diseases ................................................................................................. 33
2.2. Current Status of Nutraceuticals in CVD ......................................................................... 35
2.3. Obesity........................................................................................................................... 35
2.4. Diabetes ......................................................................................................................... 36
2.5. Cancer ............................................................................................................................ 37
2.6. Immune Boosters and Anti-Inflammatory Agents ............................................................ 40
2.6.1. Immune Boosters ......................................................................................................... 40
2.6.2. Inflammatory Disorders ........................................................................................... 41
2.6.3. Osteoarthritis ........................................................................................................... 42
2.6.4. Allergy .................................................................................................................... 42
2.7. Degenerative Diseases .................................................................................................... 43
2.7.1. Macular Degeneration.............................................................................................. 43
2.7.2. Vision Improving Agents ......................................................................................... 44
2.7.3. Alzheimer's Disease................................................................................................. 44
2.7.4. Parkinson's Disease.................................................................................................. 45
2.8. Miscellaneous ................................................................................................................. 45
3.9. Metabolism, Bioavailability and Pharmacokinetics of Nutraceuticals - Metabolism Data.. 46
3.9.2. Pharmacokinetic Data .............................................................................................. 47
References: ........................................................................................................................... 48
Chapter 3 .............................................................................................................................. 50
Nutraceuticals from Seafood and Seafood By-Products.......................................................... 50
3.0. Introduction .................................................................................................................... 50
3.1. Marine Oils .................................................................................................................... 51
3.2. Omega-3 Concentrates .................................................................................................... 54
3.3. Structured Lipids ............................................................................................................ 55
3.4. Bioactive Peptides from Marine Resources...................................................................... 57
3.5. Chitin, Chitosan and Related Compounds........................................................................ 58

5
References ............................................................................................................................ 60
Chapter 4 .............................................................................................................................. 62
Nutraceutical Foods from Selected Asian Fruits and Fruit Products ........................................ 62
4.1. Annatto Fruits................................................................................................................. 62
4.2. Apples ............................................................................................................................ 63
4.3. Aronia Fruits .................................................................................................................. 64
4.4. Avocados ....................................................................................................................... 64
4.5. Bananas.......................................................................................................................... 65
4.6. Bilberries........................................................................................................................ 66
4.7. Black Prunes .................................................................................................................. 67
4.8. Cherimoyas .................................................................................................................... 68
4.9. Chinese Dates ................................................................................................................. 68
4.10. Red Dates: .................................................................................................................... 69
4.11. Black Dates: ................................................................................................................. 69
Citrus Fruits .......................................................................................................................... 69
4.12. Oranges ........................................................................................................................ 70
4.13. Red Tangerine .............................................................................................................. 71
4.14. Mandarin Oranges ........................................................................................................ 71
4.15. Kumquats ..................................................................................................................... 72
4.16. Pummelos..................................................................................................................... 72
4.17. Cranberries ................................................................................................................... 73
4.18. Durians......................................................................................................................... 74
4.19. Embalics....................................................................................................................... 74
4.20. Figs .............................................................................................................................. 75
4.21. Grapes .......................................................................................................................... 76
4.22. Guavas ......................................................................................................................... 77
4.23. Hawthorn Fruits............................................................................................................ 78
4.24. Indian Jujubes ............................................................................................................... 79
4.25. Jackfruits ...................................................................................................................... 80
4.26. Kiwifruits ..................................................................................................................... 80
4.27. Loquats ........................................................................................................................ 81
4.28. Longans........................................................................................................................ 81
4.29. Litchi............................................................................................................................ 82
4.30. Mangoes ....................................................................................................................... 83
4.31. Mangosteens................................................................................................................. 83
4.32. Mulberry ...................................................................................................................... 84
4.33. Papayas ........................................................................................................................ 85
4.34. Passion Fruits ............................................................................................................... 85
4.35. Persimmons .................................................................................................................. 86

6
4.36. Pineapples .................................................................................................................... 87
4.37. Pomegranates ............................................................................................................... 88
4.39. Sea Buckthorn Fruits .................................................................................................... 89
4.40. Santol Fruits ................................................................................................................. 90
4.41. Soursop Fruits .............................................................................................................. 90
4.42. Tamarinds .................................................................................................................... 91
4.43. Wolfberry ..................................................................................................................... 91
Chapter 5 .............................................................................................................................. 98
Selcted Fruits of African Origin – Nutraceutical Perspectives ................................................. 98
5.1. African Custard-Apple .................................................................................................... 98
5.2. The African Medlar ........................................................................................................ 99
5.3. African Moringa ........................................................................................................... 100
5.4. Aizen............................................................................................................................ 101
5.5. Balsam Apple ............................................................................................................... 102
5.6. Desert Date................................................................................................................... 103
5.7. Baobab ......................................................................................................................... 104
5.8. Butterfruit (Safou, Bush Mango) ................................................................................... 105
5.9. Carissa ......................................................................................................................... 105
5.10. Horned Melon ............................................................................................................ 106
5.11. Kei Apple ................................................................................................................... 107
5.12. Marula ........................................................................................................................ 108
5.13. Melon ......................................................................................................................... 109
5.14. Tamarind .................................................................................................................... 109
5.15. Watermelon ................................................................................................................ 110
Chapter 6 ............................................................................................................................ 111
Profiling Popular Foods and Herbs - Nutraceutical Perspectives ........................................... 111
6.1. Aloe Vera ..................................................................................................................... 111
6.1.1. References ............................................................................................................. 112
6.2. Apple Juice................................................................................................................... 113
6.2.1. References ............................................................................................................. 114
6.3. Beans ........................................................................................................................... 114
6.3.1. References ............................................................................................................. 115
6.4. Black Tea ..................................................................................................................... 115
6.4.1. References ............................................................................................................. 116
6.5. Cabbage ....................................................................................................................... 118
6.5.1. References ............................................................................................................. 118
6.6. Cacao ........................................................................................................................... 119
6.6.1. References ............................................................................................................. 119
6.7. Caffeine........................................................................................................................ 120

7
 6.7.1. References ............................................................................................................. 121
6.8. Chocolate ..................................................................................................................... 122
6.8.1. References ............................................................................................................. 124
6.9. Cocoa (Theobroma cacao) ............................................................................................ 124
6.9.1. References ............................................................................................................. 125
6.10. Coconut (Cocos nucifera) ........................................................................................... 126
6.10.1. References ........................................................................................................... 126
6.11. Coffee ........................................................................................................................ 127
6.11.1. References ........................................................................................................... 129
6.12. Garlic ......................................................................................................................... 131
6.12.1. References ........................................................................................................... 132
6.13. Ginseng ...................................................................................................................... 133
6.13.1. References ........................................................................................................... 134
6.14. Green Tea ................................................................................................................... 135
6.14.1. References ........................................................................................................... 136
6.15. Honey......................................................................................................................... 137
6.15.1. References ........................................................................................................... 139
6.16. Lemon ........................................................................................................................ 139
6.16.1. References ........................................................................................................... 140
6.17. Onions (Allium cepa Liliacae) .................................................................................... 141
6.17.1. References ........................................................................................................... 141
6.18. Red Wines .................................................................................................................. 143
6.18.1. References ........................................................................................................... 144
6.19. Rooibos Tea ............................................................................................................... 145
6.19.1. References ........................................................................................................... 146
6.20. Sorghum (Sorghum Vulgare) ...................................................................................... 147
6.20.1. References ........................................................................................................... 148
6.21. Soya Beans ................................................................................................................. 149
6.21.1. References ........................................................................................................... 150
6.22. Sweet Potatoes ............................................................................................................ 151
6.22.1. References ........................................................................................................... 152
6.23. Taurine ....................................................................................................................... 153
6.23.1. References ........................................................................................................... 154
6.24. Tomato ....................................................................................................................... 156
6.24.1. References ........................................................................................................... 157
Chapter 7 ............................................................................................................................ 159
Research and Technology Trends of Nutraceuticals – A Japanese Perspective ...................... 159
7.1. Introduction ................................................................................................................ 159
7.1.1. Needs of Prophylactic Medicine ........................................................................... 159

8
 7.1.2. Concept of Nutraceuticals ..................................................................................... 159
7.1.3. Procedure for Nutrigenomics ................................................................................ 161
7.2. Current Status of Nutraceuticals in Japan ..................................................................... 161
7.2.1. Food with Function Claims .................................................................................... 161
7.2.2.Nutraceuticals research in Japan.............................................................................. 164
7.2.2.1. Research on analysis and systematization of non-trophic functions of food .......... 164
7.2.2.2. Cooperative research with industries .................................................................. 165
7.2.2.3. Scientific evaluation in humans ........................................................................... 166
7.3. Nutraceuticals research in Europe ................................................................................. 167
7.3.1. Food valley in the Netherlands ............................................................................... 167
7.3.3.NIZO food research BV .......................................................................................... 170
7.3.4. NuGO; European nutrigenomics organization ........................................................ 170
7.3.5. UC Davis : disease prevention ............................................................................... 171
7.4. Reference ..................................................................................................................... 172
Chapter 8 ............................................................................................................................ 173
Analysis of Nutraceuticals – An Advanced and Comprehensive Perspective ......................... 173
8.0. Introduction .................................................................................................................. 173
8.1. Lipids ........................................................................................................................... 175
8.2. Fatty Acids ................................................................................................................... 178
8.3. Sterols .......................................................................................................................... 185
8.4. Terpenes....................................................................................................................... 186
8.5. Glycerolipids ................................................................................................................ 187
8.6. Sphingolipids................................................................................................................ 188
8.7. Vitamins....................................................................................................................... 191
8.8. Proteins, Peptides and Amino Acids.............................................................................. 195
8.9. Carbohydrates, Glycosides and Related Compounds...................................................... 196
8.10. Phenolic Compounds .................................................................................................. 202
Chapter 9 ............................................................................................................................ 227
Selected Nutraceutical and health Glossary of Terms and Concepts ..................................... 227
Chapter 10 .......................................................................................................................... 255
Current Status of the Global Nutraceuticals and Vitamins Industry – 2011 Review ............... 255
10.0. Status – 2011 .............................................................................................................. 255
10.1. Sector Growth and Challenges .................................................................................... 260

9
 Epigraph

"If you are planning for a year, sow

rice; if you are planning for a decade,
plant trees; if you are planning for a
lifetime, educate people."

Chinese Proverb

10
 PREFACE
Nearly two thirds of the world’s 6.1 billion people rely on the healing power of
plant based materials for many reasons to include: availability, affordability,
safety or their belief in traditional cures. Medical benefits of food have been
explored for thousands of years and it is considered that modern nutraceutical
industry began to develop in Japan during the 1980s.

The global nutraceutical market is predicted to account for growth of about 5%

(basing on 2011 data) during the next few years. Similar to the U.S. market, a
worldwide aging population, a rising prevalence of serious diseases and an
increasing trend for preventative medicine is spurring global growth. Industry
experts anticipate that omega-3 fatty acids, probiotics, and soy products will
help fuel growth in the marketplace. The nutraceutical market must overcome
challenges such as the strict regulatory environment and consumer scepticism of
alternative treatments. To maintain growth in the nutraceutical sector,
companies must focus on the scientific evidence backing the efficacy claims of
their products. Industry experts expect that in some cases, pharmaceuticals can
be replaced by naturally derived products to reduce side effects, eliminate
unfavourable drug interactions, and improve patient outcomes. A combination
of the words “nutrition” and “pharmaceutical,” the term nutraceutical
encompasses foods or food products that claim to prevent chronic diseases,
improve health, delay the aging process, and/or increase life expectancy.
Products in this category range from isolated nutrients, dietary supplements and
specific diets to genetically engineered foods, herbal products, and processed
foods such as cereals and beverages. This is an industry wrought with
controversy, beginning with the mere definition of the term nutraceutical to the
U.S. Food and Drug Administration’s minimal regulation over which products
display the nutraceutical designation on their labels. As a result, the market is
chock full of products with varying uses and effectiveness. Steady growth
during the upcoming years is expected to drive the global nutraceutical market
value to more than $180 billion in 2017. Factors that will contribute to this
growth include a globally aging population, increased prevalence of serious
diseases, and an enhanced concentration on preventative medicine. According
to World Health Organization (WHO) projections, by 2020 the number of
people 60 years old and older around the world will exceed 1 billion, with 700
million of them in developing countries. The industry will be widely influenced
in upcoming years by an aging population, particularly in developed countries;
access to healthy food in emerging countries; the evolving understanding of
food impact on health and the expectancy of more targeted foods and products
to address specific needs. Within the varied nutraceutical market, experts
predict strong performances from omega-3 fatty acids, probiotics, and soy.
The strict regulatory environment and consumer skepticism of alternative
treatments are challenges that the nutraceutical market must overcome. To

11
maintain growth in the nutraceutical segment, companies must concentrate on
the scientific evidence backing the efficacy claims of their products. Many
experts believe that in some instances, pharmaceuticals can be replaced by
naturally derived products to reduce side effects, eliminate unfavorable drug
interactions, and improve patient outcomes. Most chronic illnesses are linked to
long-term lifestyle and behavior choices. Experts are hopeful that the trend of
personalized health science nutrition will contribute to successfully preventing,
improving and treating acute and chronic medical conditions.

This first edition which introduces readers to nutraceuticals also attempts to

give an in depth understanding on the nature and efficacy of nutraceuticals
currently being marketed world wide and serves as a basic text for scholars
studying phamarcy, medicine or related courses.The book is also essential for
general readers wanting to have an understanding of the nature and efficacy of
nutraceuticals.

12
 Chapter 1
Understanding the concept of “Nutraceuticals”

Historical Background

The original idea in these concepts goes back three thousand years ago.
Hippocrates (460-377 BC), the well-recognized father of modern medicine,
stated “Let food be thy medicine and medicine be thy food” to predict the
relationship between appropriate foods for health and their therapeutic benefits.
The truth in this saying is widely recognised today. The concept of
nutraceuticals is not entirely new, although it has evolved considerably over
years. In the early 1900s, food manufacturers in the United States began adding
iodine to salt in an effort to prevent goiter, representing one of the first attempts
at creating a functional component through fortification. Today researchers
have indentified hundreds of compounds with functional qualities, and they
continue to make new discoveries surrounding the complex benefits of
phytochemicals (non-nutritive plant chemicals that have protective or disease
preventative properties) in foods. In Japan, England and other countries,
nutraceuaticals already have become part of the dietary landscape. Consumer
interest in the relationship between diet and health has increased the demand for
information on nutraceuticals. Rapid advances in science and technology,
increasing health care costs, changes in food laws affecting label and product
claims, an aging population and rising interest in attaining wellness through diet
are among the factors fueling U.S. interest in nutraceuticals. Credible scientific
research indicates many potential health benefits from food components. These
benefits could expand the health claims now permitted to be identified by the
Food and Drug Administration.

Introduction

About 2000 years ago, Hippocrates correctly emphasized “Let food be your
medicine and medicine be your food". Currently there is an increased global

13
interest due to the recognition that “nutraceuticals” play a major role in health
enhancement. The term "Nutraceutical" was coined by combining the terms
"Nutrition" and "Pharmaceutical" in 1989 by Dr Stephen DeFelice, Chairman of
the Foundation for Innovation in Medicine. “Nutraceutical” is a marketing term
developed for nutritional supplement that is sold with the intent to treat or
prevent disease and thus has no regulatory definition. Hence a “nutraceutical” is
any substance that may be considered a food or part of a food and provides
medical or health benefits, encompassing, prevention and treatment of diseases.
Such products may range from isolated nutrients, dietary supplements and diets
to genetically engineered "designer" foods, herbal products and processed foods
such as cereals, soups and beverages. Presently over 470 nutraceutical and
functional food products are available with documented health benefits.
“Nutraceuticals and functional foods have received considerable interest
because of their presumed safety and potential nutritional and therapeutic
effects”. The nutraceutical and functional food industry is in a unique position
to capitalize on consumers' interest. Be it a multinational pharmaceutical
corporation, a nutritional company, a large food multinational or a small
vitamin selling firm, all of them recognize the changing trends and are aware of
the more health-seeking consumer trend. There is, thus, a proliferation of these
value-added products aimed at not only keeping oneself healthy but also
prevention/treatment of various ailments ranging from heart diseases to cancer.
As mentioned earlier functional foods contain larger profit margins than
conventional foods (30 to 500 percent higher). The global market size is
estimated between 30 and 60 billion US$, with Japan, US, and Europe
occupying the biggest share. By 2010, the nutraceutical demand is forecast to
touch $197 billion. There is a lot of confusion regarding the terminologies like
“nutraceuticals”, “functional foods”, “dietary supplements” “designer foods”,
“medical foods”, “pharmafoods”, “phytochemicals” etc. There seems to be thin
dividing line in their interchangeable usage by different people on different
occasions. “Pharmaceuticals” may be considered as drugs used mainly to treat
diseases, while “nutraceuticals” are those that are intended to prevent diseases.
The above distinction between pharmaceuticals and nutraceuticals is cute, but
superficial and erroneous. Pharmaceuticals are substances which have (or have
had) patent protection as a result of expensive testing to conform to the
specifications of respective Governments. However, many nutrients may never
receive government approval since no one could justify the expense of testing
requirements for substances that cannot be protected by patent laws. Both
pharmaceuticals and nutrients can cure and prevent disease(s) but only
pharmaceuticals have governmental sanction. Many pharmaceuticals have their
origin in plants and animals and are no less "natural" than nutrients. Classic
example of nutrients is synthetic vitamins. Nutraceuticals sometimes referred as
“functional foods”, have caused heated debate because they blur the traditional
dividing line between food, and medicine. When food is being cooked or
prepared using "scientific intelligence" with or without the knowledge of how
or why it is being used, then the food is called as "functional food." Thus,
functional food provides the body with the required amount of vitamins, fats,
proteins, carbohydrates necessary for healthy survival. When functional food
aids in the prevention and/or treatment of disease(s)/disorder(s) other than

14
deficiency conditions like anemia it is called a “nutraceutical”. Thus, a
functional food for one consumer can act as a nutraceutical for another.
Examples of nutraceuticals include: fortified dairy products (milk as such is a
nutrient and its product casein is a pharmaceutical) and citrus fruits (orange
juice is nutrient and its constituent ascorbic acid is a pharmaceutical).

A dietary supplement is a product that is intended to supplement the diet that

bears or contains one or more ingredients like, vitamin, mineral, a herb, an
amino acid or a concentrate, metabolite, constituent, extract, or combinations of
these. “Medical foods” are a specific category of therapeutic agents that are
intended for the nutritional management of a specific disease. An example of
medical foods is formulations intended to manage patients with inborn errors in
amino acid metabolism. Newer medical foods are designed to manage
hyperhomocysteinemia, pancreatic exocrine insufficiency, inflammatory
conditions, cancer cachexia, and other diseases. The use of nutraceuticals, as an
attempt to accomplish desirable therapeutic outcomes with reduced side effects,
as compared with other therapeutic agents has met with great monetary success.
The preference for the discovery and production of nutraceuticals over
pharmaceuticals is well appreciated by the pharmaceutical and biotechnology
companies. Some popular nutraceuticals include glucosamine (for arthritis),
lutein (for macular degeneration), ginseng (for cold), echinacea (anti-immune),
folic acid, cod liver oil capsules, etc. The most popular functional food and
beverage products include omega-3 eggs, omega-3 enriched yoghurts, calcium-
enriched orange juice, green tea to mention a few.

Majority of the nutraceuticals do possess multiple therapeutic benefits, however

in the present review much effort has been devoted to decentralize them based
on their disease specific major indication. Nutraceuticals have been claimed to
have a physiological benefit or provide protection against the following diseases
(and/or found to act as):

• Cardiovascular agents
• Antiobese agents
• Antidiabetics
• Anticancer agents
• Immune boosters
• Chronic inflammatory disorders
• Degenerative diseases

Nutraceuticals vs other Terminologies:

There is a lot of confusion regarding the terminologies like nutriceuticals,

functional foods, dietary supplements, designer foods, medical foods,
pharmafoods, phytochemicals etc. “Pharmaceuticals” may be considered as
drugs used mainly to treat diseases, while “nutraceuticals” are those that are
intended to prevent diseases. Within European Medicines law a nutraceutical
can be defined as medicine for two reasons: It can be used for the prevention,

15
treatment or cure of a condition or disease or be administered with a view to
restoring, correcting or modifying physiological functions in human beings.
Both pharmaceuticals and nutrients can cure and prevent disease(s) but only
pharmaceuticals have governmental sanction. Drugs are subject to an approval
process prior to marketing. To be approved, a drug must demonstrate safety
and efficacy for its intended use. Nutraceuticals are not drugs simply because
they have not gone through an approval process. Many pharmaceuticals have
their origin in plants and animals and are no less “natural” than nutrients.
Classic example of nutrients is synthetic vitamins.

“Medical foods” are a specific category of therapeutic agents that are intended
for the nutritional management of a specific disease. An example of medical
foods is formulations intended to manage patients with inborn errors in amino
acid metabolism. Newer medical foods are designed to manage
hyperhomocysteinemia, pancreatic exocrine insufficiency, inflammatory
conditions, cancer cachexia, and other diseases. Food is generally recognized
as safe whereas Nutraceuticals may contain substances that are “natural” but
may not be generally recognised as safe.

Nutraceuticals sometimes referred as “functional foods”, have caused heated

debate because they blur the traditional dividing line between food, and
medicine. Nutraceuticals slightly differ from functional foods. When food is
being cooked or prepared using “scientific intelligence” with or without
knowledge of how or why it is being used, the food is called Functional food.
Thus, functional food provides the body with the required amount of vitamins,
fats, proteins, carbohydrates, etc needed for its healthy survival. When
functional food aids in the prevention and/or treatment of disease(s) and/or
disorder(s) other than anemia, it is called a Nutraceutical. (Since most of the
functional foods act in some way or the other as antianemic, the exception to
anemia is considered so as to have a clear distinction between the two terms,
functional food and nutraceutical.) Examples of nutraceuticals include fortified
dairy products (e.g. milk) and citrus fruits (e.g. orange juice) and vegetables.

The US Dietary Supplement Health and Education Act (DHSEA), defined

“dietary supplement” using several Criteria. A dietary supplement is a product
(other than tobacco) that is intended to supplement the diet that bears or
contains one or more of the following dietary ingredients: a vita-min, a mineral,
an herb or other botanical, an amino acid, a dietary substance for use by man to
supplement the diet by increasing the total daily intake, or a concentrate,
metabolite, constituent, extract, or combinations of these ingredients.

A dietary supplement:

is intended for ingestion pill, capsule, tablet, or liquid form.

is not represented for use as a conventional food or as the sole item of a meal or
diet.
is labelled as a “dietary supplement.”

16
includes products such as an approved new drug, certified antibiotic, or licensed
biologic that was marketed as a dietary supplement or food before approval,
certification, or license.

Thus, nutraceuticals differ from dietary supplements in the following aspects:

Nutraceuticals must not only supplement the diet but should also aid in the
prevention and/or disorder.
Nutraceuticals are requested for use as a conventional food or as the sole item
of meal or diet.

A ray of “cure preference” in the mind of common patients revolves around

nutraceuticals because of their false perception that ‘all natural medicines are
good.” Also, the high cost of prescription pharmaceuticals and reluctance of
some insurance companies to cover the costs of drugs helps nutraceuticals
solidify their presence in the global market of therapies and therapeutic agents.

Classification of Nutraceuticals

Nutraceuticals classified on the basis of various chemical constituent present in

herbal plants. Table 1 shows list of various nutraceutical, their components,
source and their potential benefits.

Table 1 Classification of Nutraceuticals

Chemical constituent Source Potential Benefit

Carotenoids (Isoprenoids)
Lycopene Tomatoes, pink Antioxidant activity,
grapefruit, guava protects against against
papaya, formation of cancer
watermelon mainly prostate, bladder,
cervical, leukemia.
Lutin Corn, avocado, Anticancer activity (colon)
eggyork, spinach cataracts, protects the eyes
against development of
age related muscular
degeneration.
β-Carotene Carrots, various Antioxidant activity which
fruits and neutralizes free radicals,
vegetables protect cornea against UV
Carrots light. Antioxidants,
α-Carotene Orange and anticarcinogenic
α-Cryptoxanthin Tangerines Antioxidants, anticancer
Zeaxanthin Corn, avocado Protects eye from macular
Degeneration and cataracts
Dietary fibres

17
Solube fibre Legumes, oats, Anticancer, helpful in
barely, some fruits maintaining the digestive
tract
Insoluble fibre Whole grain foods Anticancer (colon), helpful
Wheat and corn in maintaining the
bran, nuts digestive tract
Polyphenolic compounds
Flavonones Citrus fruits Antioxidants, Anti cancer
Flavones Fruits, Vegetables, Antioxidants, Anti cancer
Soyabean
Flavonols Onions, apples, tea, Antioxidants
broccoli
Anthocyanins Blueberries, Anti-oxidants, counteracts
blackberries, black inflammation in the body,
raspberries Lower blood sugar levels
in people with diabetes
Phenolic acids Berries, legumes Phenolic acids reduce
oxidation of LDL
cholesterol.
Reduce formation of
cancer
Resveratrol Dark grapes, Lowers total serum
Raisins, berries, cholesterol increasing
peanuts HDL
Curcumin Turmeric root Strongly anti-
inflammatory and strongly
anti-oxidant, effective
anti-clotting agent
Fatty Acids
Omega 3 Fatty A cids (Poly Salmon, Flax seed Potent controllers of the
Unsaturated Fatty Acids) inflammatory processes,
Maintenance of brain
function, Reduce
cholesterol disposition
Monosaturated fatty acids Tree nuts Reduce risk of coronary
heart disease
Isothiocyanates Cauliflower, May enhance
Sulporaphane broccoli, cabbage, detoxification of
kale, Horseradish undersirable compounds
and bolster cellular
antioxidant defences
Phenols Apples, pears, May bolster cellular
Caffeic acid citrus fruits, some antioxidant defences:
Ferulic acid vegetables May contribute to
maintenance of vision and
heart health
Plant Stanols/Sterols Fortified table May reduce risk of

18
Stanol/sterol esters spreads, stanol coronary heart disease
ester dietary
supplements
Tocotrienol (Isoprenoids) Grains, Palm Oil Anticancer (breast cancer),
Promotes cardiovascular
health
Saponins Chickpeas and Lowers cholesterol level,
soybeans Anticancer activity (colon)
Probiotics/Prebiotics Yogurt, other dairy May improve
Lactobacilli, bifidobacteria and non dairy gastrointestinal health and
Applications systematic Immunity
Minerals Calcium, Food Important constituent of
selenium, potassium, zinc, balanced diets
copper
Polyols Sugar alcohols Fruits Reduces risk of dental
(xylitol, sorbital) caries
Sulphides/Thiols Cruciferous May contribute to
Dithiothiones vegetables maintenance of healthy
immune function
Gulcosinolates Cruciferous Anticancer (bladder
vegetables, cancer)
Cauliflower
Phytoestrogens
Isoflavanes (genistein, Soybeans, legumes Lowers LDL cholesterol
daidzein) antioxidant, anticancer
(prostate, breast, bowel)
Liganans Flaxseed, rye, Inhibit the development of
vegetables breast cancer and colon
cancer
Alkaloids
Quinine Cinchona Anti-malarial
Tropane alkaloids Solanaceous In treatment of heart
members: Deadly ailments
night shade, Datura
Morphine Opium poppy Antidepressant, pain killer
Ergot alkaloids Fungus: (Claviceps Abortifiacients
purpurea)
Vincristine Periwinkle Antineoplastic
Vinblastine Periwinkle Antineoplastic
Coumarin Fenugreek Hypoglycaemic
Scopoletin Fenugreek Hypoglycaemic
Fenugreekine Fenugreek Hypoglycaemic
Trigonelliine Fenugreek Hypoglycaemic
Non-carotenoid terpenoids
Perillyl alcohol Cherries and mints Anticancer
Saponins Legumes (Chicks, Reduces cholesterol levels
peas, fenugreek, all in blood

19
 pulse crops)
Terpenol Carrots Anticancer
Terpene Limonoids Peels and Anticarcinogenic
membranes of
citrus fruits
Anthraquinones
Senna Legumes and Purgative
pulses
Barbaloin Aloe Laxative, anti-helminthic
Hypericn St. John’s Wort Analgesic
Capsaicin Capsicum (hot Anticancer, anti-
peppers) inflammatory, anti-
apoptotic
Piperine Black peppers, Helps in digestion
jalapeno peppers
Terpenes
Menthol (Monoterpene) Plants of mint Topical pain reliever &
family anti-pyretic
Borneol (Monoterpene) Pine oil Disinfectant
Santonin (Sesquiterpene) Wormwood Photosensitizer
Gossypo 1 (Sesquiterpene) Cotton Contraceptive
Chemical constituent Source Potential Benefit
Carotenoids (Isoprenoids)
Lycopene Tomatoes, pink Antioxidant activity,
grapefruit, guava protects against against
papaya, formation of cancer
watermelon mainly prostate, bladder,
cervical, leukemia.
Lutin Corn, avocado, Anticancer activity (colon)
eggyork, spinach cataracts, protects the eyes
against development of
age related muscular
degeneration.
β-Carotene Carrots, various Antioxidant activity which
fruits and neutralizes free radicals,
vegetables protect cornea against UV
Carrots light. Antioxidants,
α-Carotene Orange and anticarcinogenic
α-Cryptoxanthin Tangerines Antioxidants, anticancer
Zeaxanthin Corn, avocado Protects eye from macular
Degeneration and cataracts
Dietary fibres
Solube fibre Legumes, oats, Anticancer, helpful in
barely, some fruits maintaining the digestive
tract
Insoluble fibre Whole grain foods Anticancer (colon), helpful
Wheat and corn in maintaining the

20
 bran, nuts digestive tract
Polyphenolic compounds
Flavonones Citrus fruits Antioxidants, Anti cancer
Flavones Fruits, Vegetables, Antioxidants, Anti cancer
Soyabean
Flavonols Onions, apples, tea, Antioxidants
broccoli
Anthocyanins Blueberries, Anti-oxidants, counteracts
blackberries, black inflammation in the body,
raspberries Lower blood sugar levels
in people with diabetes
Phenolic acids Berries, legumes Phenolic acids reduce
oxidation of LDL
cholesterol.
Reduce formation of
cancer
Resveratrol Dark grapes, Lowers total serum
Raisins, berries, cholesterol increasing
peanuts HDL
Curcumin Turmeric root Strongly anti-
inflammatory and strongly
anti-oxidant, effective
anti-clotting agent
Fatty Acids
Omega 3 Fatty A cids (Poly Salmon, Flax seed Potent controllers of the
Unsaturated Fatty Acids) inflammatory processes,
Maintenance of brain
function, Reduce
cholesterol disposition
Monosaturated fatty acids Tree nuts Reduce risk of coronary
heart disease
Isothiocyanates Cauliflower, May enhance
Sulporaphane broccoli, cabbage, detoxification of
kale, Horseradish undersirable compounds
and bolster cellular
antioxidant defences
Phenols Apples, pears, May bolster cellular
Caffeic acid citrus fruits, some antioxidant defences:
Ferulic acid vegetables May contribute to
maintenance of vision and
heart health
Plant Stanols/Sterols Fortified table May reduce risk of
Stanol/sterol esters spreads, stanol coronary heart disease
ester dietary
supplements
Tocotrienol (Isoprenoids) Grains, Palm Oil Anticancer (breast cancer),
Promotes cardiovascular

21
 health
Saponins Chickpeas and Lowers cholesterol level,
soybeans Anticancer activity (colon)
Probiotics/Prebiotics Yogurt, other dairy May improve
Lactobacilli, bifidobacteria and non dairy gastrointestinal health and
Applications systematic Immunity
Minerals Calcium, Food Important constituent of
selenium, potassium, zinc, balance diet
copper
Polyols Sugar alcohols Fruits Reduces risk of dental
(xylitol, sorbital) caries
Sulfides/Thiols Cruciferous May contribute to
Dithiothiones vegetables maintenance of healthy
immune function
Gulcosinolates Cruciferous Anticancer (bladder
vegetables, cancer)
Cauliflower
Phytoestrogens
Isoflavanes (genistein, Soybeans, legumes Lowers LDL cholesterol
daidzein) antioxidant, anticancer
(prostate, breast, bowel)
Liganans Flaxseed, rye, Inhibit the development of
vegetables breast cancer and colon
cancer
Alkaloids
Quinine Cinchona Anti-malarial
Tropane alkaloids Solanaceous In treatment of heart
members: Deadly ailments
night shade, Datura
Morphine Opium poppy Antidepressant, pain killer
Ergot alkaloids Fungus: (Claviceps Abortifiacients
purpurea)
Vincristine Periwinkle Antineoplastic
Vinblastine Periwinkle Antineoplastic
Coumarin Fenugreek Hypoglycaemic
Scopoletin Fenugreek Hypoglycaemic
Fenugreekine Fenugreek Hypoglycaemic
Trigonelliine Fenugreek Hypoglycaemic
Non-carotenoid terpenoids
Perillyl alcohol Cherries and mints Anticancer
Saponins Legumes (Chicks, Reduces cholesterol levels
peas, fenugreek, all in blood
pulse crops)
Terpenol Carrots Anticancer
Terpene Limonoids Peels and Anticarcinogenic
membranes of
citrus fruits

22
Anthraquinones
Senna Legumes and Purgative
pulses
Barbaloin Aloe Laxative, anti-helminthic
Hypericn St. John’s Wort Analgesic
Capsaicin Capsicum (hot Anticancer, anti-
peppers) inflammatory, anti-
apoptotic
Piperine Black peppers, Helps in digestion
jalapeno peppers
Terpenes
Menthol (Monoterpene) Plants of mint Topical pain reliever &
family anti-pyretic
Borneol (Monoterpene) Pine oil Disinfectant
Santonin (Sesquiterpene) Wormwood Photosensitizer
Gossypo 1 (Sesquiterpene) Cotton Contraceptive

Table 2. List of Marketed Nutraceuticals

Marketed Category Ingredients Manufacturer

Nutraceutical
Weight smart™ Nutritional Vitamins and trace Bayer
supplement elements corporation,
Morristown, NL,
USA
Omega woman Immune Antioxidants, Wassen,
supplement vitamins and ®Surrey, UK
phytochemicals
(e.g. lycopene, and
resveratrol
Rox® Energy drink Taurine, caffeine Rox American,
and Spartanburg, SA,
glucuronolactone USA
Proteinex® Protein Predigested Pfizer Ltd,
supplement proteins, vitamins, Mumbai, India
mineral and
carbohydrates
PNer plus™ Neuropathic pain Vitamin and other NeuroHelp, San
supplement natural supplement Antonio, Texas,
USA
Mushroom Immune Mushrooms, Jarrow formulas,
opitmiser™ supplement polysaccharides Los Angeles,
and folic acid CA, USA
Chaser™ Hangover Activated calcium Living essentials,
supplement carbonate and Walled lake, MI,
vegetable carbon USA
Calcirol D-3® Calcium Calcium and Cadilla

23
 supplement vitamins healthcare
limited,
Ahmedabad,
India
Appetite Appetite Caffeine, tyrosine Natrol,
Intercept™ suppressant and Phenylalanine Chatsworth,
CA,USA
Betafactor® Immune Beta-glucan Ameriden
capsules supplement international Inc,
USA
Tozal Eye Health Improved vision Omega 3 fatty Ameri Sciences,
formula acids, zinc, USA
antioxidants and
lutein
Snapple-a-day™ Meal Vitamins and Snapple
replacement minerals beverages group,
beverages USA
Brainspeed Brain health Blend of vitamins Natrol, USA
Memory® and minerals
Red bull® Energy drink Taurine, caffeine Austrain red bull
and Gmbh
Glucoronolactone,
b-group vitamins
5-Hour energy® Energy drink Vitamins, tyrosin, Living essentials,
Taurine, malicacid, USA
caffeine,
Glucuronoloctone,
WelLife® Amino acid Granulated-L- Daesang
supplement glutamine America Inc.,
Hackensach, NJ,
USA
Pediasure® Nutritional Protein, vitamin Abbott nutrition
supplement and other natural
supplement
Threptin® Protein Proteins and Raptakos, Brett
Diskettes supplements vitamin B & Co. Ltd.,
Mumbai, India
Olivenol Dietary Natural Cre Agri,
supplement antioxidant, Hayward, CA,
hydroxytyrosol USA
Beneflora® Maintain Lactobacillus Nupro, USA
probiotic gastrointestinal acidophilus,
health bifidobacterium
bifidum
Ferradol® Nutrition Carbohydrates, Pfizer Limited,
Powder supplement proteins, India
Niacinamide,

24
 calcium, iron, zinc,
vitamins
Muscle Meal Protein, vitamins, Jarrow formulas,
Optimeal® replacement dietary fibres, USA
drink mix xylitol and trace
elements
Revital® Daily health Ginseng, vitamins Ranbaxy
supplement and minerals
Becadexamine® Nutritional Multivitamins Glaxosmith kiln
supplement
Glowelle® Beauty drink Antioxidants, Nestle
vitamins and
botanical and fruit
extracts

References:

Brower V., Nutraceuticals: poised for a healthy slice of the healthcare market?,
Nat Biotechnology., 1998, 16, 728-731.

http://en.wikipedia.org/wiki/nutraceuticals.

http://www.aapspharmsci.org/ view.asp? Art=ps050325

Lockwood Brain, Nutraceuticals, second edition, Pharmaceutical press.

London, 2007, 60-65.

Hathcock J. Dietary supplements: How they are used and regulated. J.

Nutrition. 2001; 131: 1114-1117.

Allen LV. Nutritional Products, In: Covington TR, Berardi RR, Young LL, et
al. Editors. Handbook of Nonprescription Drugs. Washington DC: American
Pharmaceutical
Association; 1997.

Tyler VE, Foster F. Herbs and phytochemicals, In: Covington TR, Berardi
RR, Young LL et al. editors. Handbook of Nonprescription Drugs. Washington
DC:
American Pharmaceutical Association; 1996.

North Carolina Association for Biomedical Research, Nutraceuticals, www.

About
bioscience. Org; July 2007.

FCCI- Ernst & Young Study: Nutraceuticalscritical supplement for building

a healthy

25
India, health foods and dietary supplements association conference, Mumbai
sept10,2009.

www.pitt.edu/~super7/31011- 32001/31101.ppt

Kalioraa AC, Dedoussisa GVZ, Schmidtb H. Dietary antioxidants in

preventing atherogenesis. Atherosclerosis. 2006; 187: 1- 17.

http://www.globalregulatory.com /labclass/nutraceutical_consultants.cfm

Bass IS and Young AL. Dietary Supplement Health and Education Act. The
Food and Drug Law Institute, Washington DC,1996.

Ohama H, Ikeda H, Moriyama H. Health foods and Foods with health claims
in Japan.
Toxicology. 2006;221:95-111.

www.medind.nic.in/ibi/t03/i6/ibit03i6p363 .pdf

www.marketwatch.com/Nutraceuticals.

FICCI-Ernst & Young Study: Nutraceuticals- Critical supplement for

building a healthy India, Health Foods and Dietary Supplements Association
conferences, Mumbai. 10th
September, 2009.

Mandel S, Packer L, Youdim MBH and Weinreb O; Proceedings from the

Third Int.
Conf. Mechanism of Action of Nutraceuticals. J. Nutritional Biochem. 2005,
16, 513-520.

German JB and Walzem RL. The health benefit of wine. Annu Rev Nutr.
2000; 20:
561-593.

Hollman PCH, Feskens EJ, Katan MB. Tea flavonols in cardiovascular

disease and cancer epidemiology. Proc Soc Exper. Biol. Med. 1999;220: 198-
202.

Sirtori CR and Galli C. Fatty acids and the Omega 3. Biomedecine

&Pharmacotherapie.
2002; 56: 397-406.

Thomas B, Ghebremeskel K, Lowy C, et al. Nutrient intake of women with

and without gestational diabetes with a Specific focus on fatty acids. Nutrition.
2006; 22: 230-236.

26
Baljit S. Psyllium as therapeutic and drug delivery agent. Int J. Pharmaceutics.
2007; 334; 1-14
.
Daly PA, Khrieger DR and Dulloo AG. Ephedrine, caffeine and aspirin:
safety and
efficacy for treatment of human obesity. Int J Obes Relat Metab Disord. 1993;
17: 73-78.

Si-quan L, Zhang Q H. Advances in the development of functional foods from

buckwheat. Critical Reviews in Food Science and Nutrition. 2001; 41:451-464.

Bell SJ, Goodrick GK. A Functional Food Product for the Management of
Weight
Critical Reviews in Food Science and Nutrition. 2002; 42: 163-178.

Woodgate DE, Conquer JA. Prevalence of selftreatment with complementary

products and therapies for weight loss: A randomized, cross-sectional Study in
Overweight Obese Patients in Colombia. Current Therapeutic Research. 2003;
64: 248-262.

Kasbia GS. Functional foods and nutraceuticals in the management of obesity.

Nutrition and Food Science. 2005; 35:344- 351.

Frydoonfar HR, McGrath DR, Spigelman AD. The variable effect on

proliferation of a colon cancer cell line by the citrus fruit flavonoid Naringenin.
Colorectal Dis 2003; 5: 149- 152.

Limer JL and Speirs V. Phyto-oestrogens and breast cancer chemoprevention.

Breast Cancer Res. 2004; 6:119-127.

Mandel S, Packer L, You dim MBH, et al. Proceedings from the Third Int.
Conf. Mechanism of Action of Nutraceuticals. J. Nutritional Biochem. 2005;
16: 513-520.

Kucuk O, Sarkar FH, Sakr W, et al. Lycopene in the Treatment of Prostate

Cancer. Pure Appl. Chem. 2002; 74: 1443- 1450.

Gulcin I, Mshvildadze V, Gepdiremen A, et al. The antioxidant activity of a

triterpenoid glycoside isolated from the berries of Hedera colchica: 3-O-(B-
dglucopyranosyl)- hederagenin. Phytother Res. 2006; 20:130- 134.

Aggarwal BB, Kumar A, Bharti AC. Anticancer potential of curcumin:

preclinical and clinical studies. Anticancer Res. 2003; 23: 363-398.

Thanopolou E, Baltayiannis N, Lykogianni V. Nutritional aspects regarding

lung cancer chemoprevention. J Buon.2006; 11: 7-20.

27
Formica JV and Regelson W. Review of the Biology of Quercetin and
Related Bioflavonoids Food and Chemical Toxicology. 1995; 33:1061-1080.

Alarcon De La Lastra C, Martin MJ, Motilve V. Antiulcer and

gastroprotective effects of quercetin. Pharmacol. 1994; 48: 56-62.

Balch SA, Mckenney CB, Auld DL. Evaluation of gamma-linolenic acid

composition of evening primrose (Oenothera) species native to Texas. Hort
Science. 2003; 38:595-598.

Chidambara Murthy KN, Vanitha A, Rajesha J, et al. In vivo antioxidant

activity of carotenoids from Dunaliella salina - a green microalga. Life Sci.
2005; 76:1381-1390

Glenville M. Nutritional supplements in pregnancy: commercial push or

evidence based. Curr Opin Obstet Gynecol. 2006; 18: 642-647.

Latif S, Anwar F Ashraf M, et al. Moringa oleifera: a food plant with multiple
medicinal uses. Phytother Res.2007; 21: 17-25.

Brower V. A nutraceutical a day may keep the doctor away. EMBO reports.
2005; 8: 708- 711

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 Chapter 2
Nutraceuticals and Diseases

2.0. Introduction

About 2000 years ago Hippocrates correctly emphasized “Let food be your
medicine and medicine be your food". Currently there is an increased global
interest due to the recognition that nutraceuticals play a major role in health
enhancement. The term "Nutraceutical" was coined by combining the terms
"Nutrition" and "Pharmaceutical" in 1989 by Dr Stephen De Felice, Chairman
of the Foundation for Innovation in Medicine. Nutraceutical is a marketing term
developed for nutritional supplement that is sold with the intent to treat or
prevent disease and thus has no regulatory definition. Hence a nutraceutical is
any substance that may be considered a food or part of a food and provides
medical or health benefits, encompassing, prevention and treatment of diseases.
Such products may range from isolated nutrients, dietary supplements and diets
to genetically engineered designer foods, herbal products and processed foods
such as cereals, soups and beverages. Presently over 470 nutraceutical and
functional food products are available with documented health benefits.

Concept of Nutraceuticals
“Nutraceuticals and functional foods have received considerable interest
because of their presumed safety and potential nutritional and therapeutic
effects”. The nutraceutical and functional food industry is in a unique position
to capitalize on consumers' interest. Be it a multinational pharmaceutical
corporation, a nutritional company, a large food multinational or a small
vitamin selling firm, all of them recognize the changing trends and are aware of

29
the more health-seeking consumer trend. There is a proliferation of these value-
added products aimed at not only keeping oneself healthy but also
prevention/treatment of various ailments ranging from heart diseases to cancer.
As mentioned earlier functional foods contain larger profit margins than
conventional foods (30 to 500 percent higher). The global market size is
estimated between 30 and 60 billion US$, with Japan, US, and Europe
occupying the biggest share. By 2010 the nutraceutical demand is forecast to
touch $197 billion. There is a lot of confusion regarding the terminologies like
nutraceuticals, functional foods, dietary supplements, designer foods, medical
foods, pharmafoods, phytochemicals etc. There seems to be thin dividing line in
their interchangeable usage by different people on different occasions.
Pharmaceuticals may be considered as drugs used mainly to treat diseases,
while nutraceuticals are those that are intended to prevent diseases. The above
distinction between pharmaceuticals and nutraceuticals is cute, but superficial
and erroneous. Pharmaceuticals are substances which have patent protection as
a result of expensive testing to conform to the specifications of respective
Governments. However, many nutrients may never receive government
approval since no one could justify the expense of testing requirements for
substances that cannot be protected by patent laws. Both pharmaceuticals and
nutrients can cure and prevent disease but only pharmaceuticals have
governmental sanction. Many pharmaceuticals have their origin in plants and
animals and are no less natural than nutrients. Classic example of nutrients is
synthetic vitamins. Nutraceuticals sometimes referred as functional foods, have
caused heated debate because they blur the traditional dividing line between
food, and medicine. When food is being cooked or prepared using "scientific
intelligence" with or without the knowledge of how or why it is being used, then
the food is called as "functional food." Thus, functional food provides the body
with the required amount of vitamins, fats, proteins, carbohydrates necessary for
healthy survival. When functional food aids in the prevention and/or treatment
of disease/disorder other than deficiency conditions like anemia it is called a
nutraceutical. Thus, a functional food for one consumer can act as a
nutraceutical for another. Examples of nutraceuticals include fortified dairy
products (milk as such is a nutrient and its product casein is a pharmaceutical)
and citrus fruits (orange juice is nutrient and its constituent ascorbic acid is a
pharmaceutical). A dietary supplement is a product that is intended to
supplement the diet that bears or contains one or more ingredients like, vitamin,
mineral, herb, amino acid or a concentrate, metabolite, constituent, extract, or
combinations of these. Medical foods are a specific category of therapeutic
agents that are intended for the nutritional management of a specific disease. An
example of medical foods is formulations intended to manage patients with
inborn errors in amino acid metabolism. Newer medical foods are designed to
manage hyperhomocysteinemia, pancreatic exocrine insufficiency,
inflammatory conditions, cancer and other diseases. The use of nutraceuticals,
as an attempt to accomplish desirable therapeutic outcomes with reduced side
effects, as compared with other therapeutic agents has met with great monetary
success. The preference for the discovery and production of nutraceuticals over
pharmaceuticals is well appreciated by the pharmaceutical and biotechnology
companies. Some popular nutraceuticals include glucosamine (for arthritis),

30
lutein (for macular degeneration), ginseng (for cold), echinacea (anti-immune),
folic acid, cod liver oil capsules, etc. The most popular functional food and
beverage products include omega-3 eggs, omega-3 enriched yoghurts, calcium-
enriched orange juice, green tea to mention a few. Majority of the nutraceuticals
do possess multiple therapeutic benefits, however in the present review much
effort has been devoted to decentralize them based on their disease specific
major indication.

Table 2.0. List of Nutrients and their Relevance

S. Nutrients Health benefit

No
1 Vitamin A Antioxidant, essential, for growth and development and
in the treatment of certain skin disorders
2 Vitamin E Antioxidant, helps form blood cells, muscles, lung and
nerve tissue, boosts the immune system
3 Vitamin K Essential for blood clotting
4 Vitamin C Antioxidant for healthy bones, gums, teeth and skin, in
wound healing, prevent common cold and attenuate its
symptoms
5 Vitamin B1 Helps to convert food in to energy, essential in
neurologic functions
6 Vitamin B2 Helps in energy production and other chemical
processes in the body, helps maintain healthy eyes, skin
and nerve function
7 Vitamin B3 Helps to convert food in to energy and maintain proper
brain function
8 Vitamin B6 Produce the genetic material of cells, formation of
RBCs, maintenance of central nervous system and
synthesize amino acids and metabolism of fats, protein
and carbohydrates
9 Folic acid Produce the genetic materials of cells, in pregnancy for
preventing birth defects, RBCs formation, protects
against heart disease.
10 Calcium Bones and teeth and maintaining bone strength
important in nerve, muscle and glandular functions
11 Iron Energy production, carry and transfer oxygen to tissues
12 Magnesium Healthy nerve and muscle function and bone formation,
may help prevent premenstrual syndrome (PMS).
13 Phosphorous Strong bones and teeth, helps in formation of genetic
material, energy production and storage
14 Chromium With insulin helps to convert carbohydrates and fats into
energy
15 Cobalt Essential component of vitamin B12, but ingested cobalt
is metabolized in 16vivo to form the B12 coenzymes.
16 Copper Essential for hemoglobin and collagen
production,healthy functioning of the heart,energy

31
 production, absorption of iron from digestive tract.
17 Iodine Essential for proper functioning of the thyroid

Table 2.1. Nutraceuticals and Diseases

Types of Diseases Nutraceuticals Used

Cardiovascular Anti-oxidants, Dietary fibres, Omega-3 poly unsaturated
diseases fatty acids, Vitamins, minerals for prevention and
treatment of CVD. Polyphenol(in grape) prevent and
control arterial diseases Flavonoids (in onion, vegetables,
grapes, red wine, apples, and cherries) block the ACE and
strengthen the tiny capillaries that carry oxygen and
essential nutrients to all cells.
Diabetes Ethyl esters of n-3 fatty acids may be beneficial in diabetic
patients. Docosahexaenoic acid modulates insulin
resistance and is also vital for neurovisual development.
Lipoic acid, an antioxidant, for treatment of diabetic
neuropathy. Dietary fibres from psyllium have been used
for glucose control in diabetic patients and to reduce lipid
levels in hyperlipidemia.
Obesity Herbal stimulants, such as ephedrine, caffeine, ma huang-
guarana, chitosan and green tea help in body weight loss.5-
hydroxytryptophan and green tea extract may promote
weight loss, while the former decreases appetite, the later
increases the energy expenditure. A blend of glucomannan,
chitosan, fenugreek, G sylvestre, and vitamin C in the
dietary supplement signifi cantly reduced body weight.
Conjugated linoleic acid (CLA), capsaicin, Momordica
Charantia (MC) possesses potential anti obese properties
Cancer Flavonoids which block the enzymes that produce estrogen
reduce of estrogen-induced cancers. Prevent prostate/breast
cancer a broad range of phyto-pharmaceuticals with a
claimed hormonal activity, called “phytoestrogens” is
recommended . Soy foods source of isoflavones, curcumin
from curry and soya isoflavones possess cancer chemo
preventive properties. Lycopene concentrates in the skin,
testes, adrenal and prostate where it protects against
cancer.
Anti- Curcumin (diferuloylmethane) which is a polyphenol of
inflammatory turmeric possesses anticarcinogenic, antioxidative and
activities anti-inflammatory properties. Top of Form Beet roots,
cucumber fruits, spinach leaves, and turmeric rhizomes,
were reported to possess anti-tumour activity. Gamma
linolenic acid (found in green leafy vegetables, nuts,
vegetable oils i.e. evening primrose oil, blackcurrant seed
oil and hemp seed oil, and from spirulina, cyanobacteria)

32
 are used for treating problems with inflammation and auto-
immune diseases. Glucosamine and chondroitin sulphate
are used against osteoarthritis and regulate gene expression
and synthesis of NO and PGE2. Cat’s claw has 17
alkaloids, along with glycosides, tannins, flavonoids, sterol
fractions, and other compounds and work as potent
antiinflammatory agent.
Alzheimer’s β-carotene, curcumin, lutein, lycopene, turmerin etc may
disease exert positive effects on specific diseases by neutralizing
the negative effects oxidative stress mitochondrial
dysfunction, and various forms of neural degeneration
Parkinson’s Vitamin E in food may be protective against Parkinson’s
disease disease. Creatine modifies Parkinson’s disease features as
measured by a decline in the clinical signs.

2.1. Cardiovascular Diseases

Worldwide, the burdens of chronic diseases like cardiovascular diseases,

cancers, diabetes and obesity is rapidly increasing. In 2001, chronic diseases
contributed approximately 59% of the 56.5 million total reported deaths in the
world and 46%of the global burden of disease. Cardiovascular diseases (CVD)
is the name for the group of disorders of the heart and blood vessels and include
hypertension (high blood pressure), coronary heart disease (heart attack),
cerebrovascular disease (stroke), heart failure, peripheral vascular disease, etc.
In 1999 CVD alone contributed to a third of global deaths and by 2010 it would
be the leading cause of death in developing countries. Majority of the CVD are
preventable and controllable. It was reported that low intake of fruits and
vegetables is associated with a high mortality in cardiovascular disease. Many
research studies have identified a protective role for a diet rich in fruits and
vegetables against CVD. This apart, nutraceuticals in the form of antioxidants,
dietary fibres, omega-3 polyunsaturated fatty acids (n-3 PUFAs), vitamins, and
minerals are recommended together with physical exercise for prevention and
treatment of CVD. It has been demonstrated that the molecules like polyphenols
present in grapes and in wine alter cellular metabolism and signalling, which is
consistent with reducing arterial disease. Optimal nutrition, nutraceuticals,
vitamins, antioxidants, minerals, weight reduction, exercise, cessation of
smoking, restriction of alcohol and caffeine plus other lifestyle modifications
can prevent, delay the onset, reduce the severity, treat, and control hypertension.
Nutrients and nutraceuticals with calcium channel blocking activity (thus
antihypertensive activity) include α-Lipoic acid, magnesium, Vitamin B6
(pyridoxine), Vitamin C, Nacetyl cysteine, Hawthorne, Celery, ω-3 fatty acids
etc. Flavonoids are widely distributed in onion, endives, cruciferous vegetables,
black grapes, red wine, grapefruits, apples, cherries and berries. Flavanoids in
plants available as flavones (containing the flavonoid apigenin found in
chamomile); flavanones (hesperidin - citrus fruits; silybin- milk thistle flavonols
(tea: quercetin, kaempferol and rutin grapefruit; rutinbuckwheat; ginkgo

33
flavonglycosides - ginkgo), play a major role in curing the cardiovascular
diseases. Flavonoids block the angiotensin-converting enzyme (ACE) that raises
blood pressure; by blocking the "suicide" enzyme cyclooxygenase that breaks
down prostaglandins, they prevent platelet stickiness and hence platelet
aggregation. Flavonoids also protect the vascular system and strengthen the tiny
capillaries that carry oxygen and essential nutrients to all cells. Flavonoids
block the enzymes that produce estrogen, thus reducing the risk of estrogen-
induced cancers. Polyphenols are simple phenolic molecules to highly
polymerized compounds with molecular weights of greater than 30,000 Da.
Stilbenes, anthocyanins, condensed tannins (proanthocyanidins), in grape and
wine, tetrahydro-β-carbolines, dietary indoleamines, melatonin, and serotonin,
in different plant foods are hypothesized to impart health benefits, associated
with Mediterranean dietary style. Hesperidin is a flavanone glycoside which is
classified as a citrus bioflavonoid. Sweet oranges (Citrus sinensis) and tangelos
are the richest dietary sources of hesperidin. The peel and membranous parts of
lemons and oranges have the highest hesperidin concentrations. Therefore,
orange juice containing pulp is richer in the flavonoid than that without pulp.
Hesperidin, in combination with a flavone glycoside called diosmin, is used for
the treatment of venous insufficiency and hemorrhoids. Hesperidin, rutin and
other flavonoids are reported to possess analgesic and anti-inflammatory
activity.

Flavonoid intake was significantly inversely associated with mortality from

coronary heart disease and the incidence of myocardial infarction. Flavonoids in
regularly consumed foods may reduce the risk of death from coronary heart
disease in elderly men. Ginger, the rhizome of Zingiber officinalis, one of the
most widely used species of the ginger family, is a common condiment for
various foods and beverages. Ginger has a long history of medicinal use dating
back 2500 years. Some pungent constituents present in ginger and other
zingiberaceous plants have potent antioxidant and anti-inflammatory activities,
and some of them exhibit cancer preventive activity. The anticancer properties
of ginger are attributed to the presence of certain pungent vallinoids, viz. [6]-
gingerol and [6]-paradol. Animal studies provide provides sound mechanistic
basis for the use of ginger in hypertension and palpitations. . Ginger has some
antiemetic properties but clinical evidence beyond doubt is only available for
pregnancy-related nausea and vomiting. Preclinical safety data do not rule out
potential toxicity, especially following ginger consumption over longer periods.
Cholesterol has long been implicated as a significant risk factor in
cardiovascular disease. Sterols occur in most plant species and are called as
phytosterols. Although green and yellow vegetables contain significant
amounts, their seeds concentrate the sterols. Phytosterols compete with dietary
cholesterol by blocking the uptake as well as facilitating its excretion from the
body. Phytosterols in diet have the potential to reduce the morbidity and
mortality from cardiovascular disease . Fagopyrum esculentum Moench
(common buckwheat or sweet buckwheat), originated in Asia. Buckwheat seeds
possess proteins, flavonoids, flavones, phytosterols, thiamin-binding proteins
etc. Buckwheat proteins are beneficial in constipation and obesity and more
importantly lower cholesterol and high blood pressure. Dietary fibre preparation

34
from defatted rice bran has laxative and cholesterol-lowering ability with
attendant benefits towards prevention or alleviation of cardiovascular disease,
diabetes, diverticulosis and colon cancer. It has been suggested that rice bran is
a good fibre source (27%) that can be added to various food products. Milk and
eggs are the important animal sources of nutraceuticals like proteins and
polyunsaturated fats or essential fatty acids (EFAs). EFAs are required for
production and rebuilding of cells, to reduce blood pressure, lower cholesterol
and triglycerides, reduce the risk of blood clots, help prevent many diseases
including arthritis, arrhythmias, and other cardiovascular diseases. Nutritional
value of egg is increased because of added gamma linolenic acid (GLA) which
has many benefits, including prevention and management of CVD like
hypertension. Fatty acids of the omega-3 series (n-3 fatty acids) present in fish
are well established dietary components affecting plasma lipids and the major
cardiovascular disorders, such as arrhythmias. Octacosanol is a 28-carbon chain
alcohol. This nutraceutical is present in fruit, leaves and skin of many plants and
whole grains. It has gastroprotective and lipid lowering effects. Since it has no
side effects further studies may be undertaken to prove the claims.

2.2. Current Status of Nutraceuticals in CVD

Because of the extremely long history of CVD, the causal relationship of

nutrition/physical exercise on major CVD events is still difficult to assess
prospectively. The relationship between calcium and risk of hypertension is
inconsistent and inconclusive, and the relationship between calcium and risk of
pregnancy-induced hypertension and preeclampsia is highly unlikely. Treatment
with beta carotene, vitamin A, and vitamin E may increase mortality. The
potential roles of vitamin C and selenium on mortality need further study. There
are possibilities to develop nutraceuticals to prevent and manage thrombosis
risk in women with thrombophilic gene mutations.

2.3. Obesity

Obesity, defined as an unhealthy amount of body fat, is a well-established risk

factor for many disorders like angina pectoris, congestive heart failure,
hypertension, hyperlipidemia, respiratory disorders, renal vein thrombosis,
osteoarthritis, cancer, reduced fertility etc. Obesity is now a global public health
problem, with about 315 million people are estimated to fall into the WHO-
defined obesity categories. One of the primary causes this rapid rise in obesity
rates is the increased availability of high-fat, energy dense foods. Excessive
consumption of energy-rich foods (snacks, processed foods and drinks) can
encourage weight gain, which calls for a limit in the consumption of saturated
and trans fats apart from sugars and salt in the diet. Caloric restriction and
increased physical activity has been shown to be only moderately successful in
managing obesity. Thus many health care practitioners and obese individuals
are seeking the help of pharmaceuticals and nutraceuticals to treat obesity. A
tolerable and effective nutraceutical that can increase energy expenditure and/or
decrease caloric intake is desirable for body weight reduction. Herbal

35
stimulants, such as ephedrine, caffeine, mahuang-guarana, chitosan and green
tea have proved effective in facilitating body weight loss. However, their use is
controversial due to their ability to cause undesired effects. Buckwheat seed
proteins have beneficial role in obesity and constipation acting similar to natural
fibres present in food. 5-hydroxytryptophan and green tea extract may promote
weight loss, while the former decreases appetite, the later increases the energy
expenditure. Current status of nutraceuticals in obesity A blend of
glucomannan, chitosan, fenugreek, G sylvestre, and vitamin C in the dietary
supplement significantly reduced body weight and promoted fat loss in obese
individuals. Further studies are needed to establish a long term efficacy and
adverse effect potential. There is a very high prevalence of obesity globally and
hence nutrition and exercise play a key role in its prevention and treatment.
Nutraceutical interventions are currently being investigated on a large-scale
basis as potential treatments for obesity and weight management. Nutraceuticals
like conjugated linoleic acid (CLA), capsaicin, Momordica Charantia (MC) and
Psyllium fibre possess potential antiobese properties.

2.4. Diabetes

Diabetes mellitus is characterized by abnormally high levels of blood glucose,

either due to insufficient insulin production, or due to its ineffectiveness. The
most common forms of diabetes are type 1 diabetes (5%), an autoimmune
disorder, and type 2 diabetes (95%), which is associated with obesity.
Gestational diabetes occurs in pregnancy. Globally the total number of people
with diabetes is projected to rise from 171 million in 2000 to 366 million in
2003. Diabetes, like most chronic health conditions, not only places substantial
economic burdens on society as a whole but also imposes considerable
economic burdens on individual patients and their families. In US alone an
estimated the expenditures for health care for people with diabetes totalled
$85.7 (11.9% of total health care expenditures) in 1992. Diet therapy is the
cornerstone for the management of gestational diabetes mellitus. Although there
is widespread use of herbal dietary supplements that are believed to benefit type
2 diabetes mellitus, few have been proven to do so in properly designed
randomized trials. Isoflavones are phytoestrogens; they have a
structural/functional similarity to human estrogen and have been consumed by
humans world-wide. Of all phytoestrogens, soy isoflavones have been studied
most. A high isoflavone intake (20–100 mg/day) is associated with lower
incidence and mortality rate of type II diabetes, heart disease, osteoporosis and
certain cancers. Omega-3 fatty acids have been suggested to reduce glucose
tolerance in patients predisposed to diabetes. For the synthesis of the long chain
n-3 fatty acids, insulin is required; the heart may thus be particularly susceptible
to their depletion in diabetes. Ethyl esters of n-3 fatty acids may be potential
beneficial in diabetic patients49. Docosahexaenoic acid modulates insulin
resistance and is also vital for neurovisual development. This is especially
important in women with gestational diabetes mellitus which foster the
recommendation for essential fatty acids during pregnancy. Lipoic acid is a
universal antioxidant, now used in Germany for the treatment of diabetic

36
neuropathy. It is possible that lipoic acid may be more effective as a long-term
dietary supplement aimed at the prophylactic protection of diabetics from
complications. Dietary fibres from psyllium have been used extensively both as
pharmacological supplements, food ingredients, in processed food to aid weight
reduction, for glucose control in diabetic patients and to reduce lipid levels in
hyperlipidemia. Good magnesium status reduces diabetes risk and improves
insulin sensitivity; chromium picolinate, calcium and vitamin D appear to
promote insulin sensitivity and improve glycemic control in some diabetics;
extracts of bitter melon and of cinnamon have the potential to treat and possibly
prevent diabetes. However it has been suggested that nutraceuticals with
meaningful doses of combinations may substantially prevent and presumably
could be marketed legally.

2.5. Cancer

In the year 2000, malignant tumors were responsible for 12 per cent of the
nearly 56 million deaths worldwide from all causes. According to the World
Cancer Report the cancer rates there would be 15 million new cases in the year
2020 i.e. a rise in 50%. Cancer has emerged as a major public health problem in
developing countries, matching the industrialized nations. A healthy lifestyle
and diet can help in preventing cancer. People who consume large amount of
lutein-rich foods such as chicken eggs, spinach, tomatoes, oranges and leafy
greens experienced the lowest incidence of colon cancer. Chronic inflammation
is associated with a high cancer risk. At the molecular level, free radicals and
aldehydes, produced during chronic inflammation, can induce deleterious gene
mutation and posttranslational modifications of key cancer-related proteins.
Chronic inflammation is also associated with immune suppression, which is a
risk factor for cancer. Ginseng as an example of an antiinflammatory molecule
that targets many of the key players in the inflammation-to cancer sequence.
Recently, attention has been on phytochemicals that possess cancer-preventive
properties. Besides chemo preventive components in vegetables and fruits,
some phytochemicals derived from herbs and spices also have potential
anticarcinogenic and antimutagenic activities, among other beneficial health
effect. A broad range of phyto-pharmaceuticals with a claimed hormonal
activity, called "phyto-estrogens", is recommended for prevention of
prostate/breast cancer. Flavonoids found in citrus fruit appear to protect against
cancer by acting as antioxidants59. Soy foods are a unique dietary source of
isoflavones, the polyphenolic phytochemicals exemplified by epigallocatechin
gallate from tea, curcumin from curry and soya isoflavones possess cancer
chemo preventive properties. The main soybean isoflavones, genistein,
daidzein, biochanin inhibits prostate cancer cell growth. Carotenoids are a
group of phytochemicals that are responsible for different colours of the foods.
Recent interest in carotenoids has focused on the role of lycopene in human
health. Because of the unsaturated nature of lycopene it is considered to be a
potent antioxidant and a singlet oxygen quencher. Lycopene prevents cancer,
cardiovascular disease, and gastrointestinal tract. It concentrates in the skin,
testes, adrenal and prostate where it protects against cancer. The linkage

37
between carotenoids and retinoids and the prevention of cancer coronary artery
diseases, and advanced age-related macular degeneration heightened the
importance of value-added fruits in human diet. Recently, it was reported that
lycopene containing fruits and vegetables exert cancer-protective effect via a
decrease in oxidative and other damage to DNA in humans66. Lycopene is one
of the major carotenoids in western diets and is found almost exclusively in
tomatoes, water melon, guava, pink grapefruit and papaya. Beta-carotene, the
important precursor of vitamin A has anti-oxidant properties and help in
preventing cancer and other diseases. Among the carotenes, beta carotene is the
most active as antioxidants. Alpha carotene possesses 50 % to 54 % of the
antioxidant activity of beta carotene, whereas epsilon carotene has 42 % to 50
% of the antioxidant activity. Alpha and beta carotenes, along with gamma
carotene and the carotenes lycopene and lutein which do not convert to vitamin
A, seem to offer protection against lung, colorectal, breast, uterine and prostate
cancers. β- Carotene is the more common form and can be found in yellow,
orange, and green leafy fruits and vegetables. These can be carrots, spinach,
lettuce, tomatoes, sweet potatoes, broccoli, cantaloupe, oranges, and winter
squash. Saponins are reported to possess antitumor and antimutagenic activities
and can lower the risk of human cancers, by preventing cancer cells from
growing. Saponins are phytochemicals which can be found in peas, soybeans,
and some herbs with names indicating foaming properties such as soapwort,
soapbark and soapberry. They are also present in spinach, tomatoes, potatoes,
alfalfa and clover. Commercial saponins are extracted mainly from Yucca
schidigera and Quillaja saponaria. The non-sugar part of saponins has also a
direct antioxidant activity, which may result in other benefits such as reduced
risk of cancer and heart diseases. Tannins also called proanthocyanidins,
detoxify carcinogens and scavenge harmful free radicals . Tannins in
cranberries also protect against urinary tract infections. It is present in
blackberries, blueberries, cranberries, grapes, lentils, tea and wine. Ellagic acid
is a proven anti-carcinogen is used in alternative medicine and to prevent
cancer. It is present in strawberries, cranberries, walnuts, pecans, pomegranates
and the best source, red raspberry seeds. Pectin is a soluble fibre found in
apples. A new form of citrus pectin called modified citrus pectin (MCP) has
been shown to prevent prostate cancer metastasis by inhibiting the cancer cells
from adhering to other cells in the body. Several studies have also shown pectin
to have positive influences in decreasing serum cholesterol levels, without
effecting serum triglyceride levels. Pectin also has the ability to reduce the rise
of blood sugar when combined with meal73. Naturally occurring phenolic acid
derivatives are reported to possess potential anticancer properties. Phenolics
such as ferulic, caffeic, gallic acids and curcumin are reported to possess
anticancer activity. Glucosinolates are found in cruciferous vegetables including
the Brassica crops—Brussels sprouts, broccoli, cauliflower, cabbage,
watercress, oilseed rape, and mustard and are powerful activators of liver
detoxification enzymes. Glucosinolates and their hydrolysis products, including
indoles and isothiocyanates, and high intake of cruciferous vegetables has been
associated with lower risk of lung and colorectal cancer They also regulate
white blood cells and cytokines. White blood cells are the scavengers of the
immune system and cytokines act as "messengers," coordinating the activities

38
of all immune cells. Bio-transformation products of glucosinolates include
isothiocyanates, dithiolthiones and sulphoraphane. They block the enzymes that
promote tumour growth, particularly in the breast, liver, colon, lung, stomach
and oesophagus. The sulphur compounds, in garlic were found to kill bacteria
and parasites, boost the immune system and reduce atherogenesis and platelet
stickiness. All members of the cruciferous family” broccoli, cauliflower,
cabbage, bok choy, Brussels sprouts, collards, cress, kale, kohlrabi, mustard”
contains a group of closely related sulphur compounds known as glucosinolates.
Sulforaphane rich in broccoli is a potent phase 2 enzyme inducer. It produces
Dglucarolactone, a significant inhibitor of breast cancer. Sulphoraphane is an
antioxidant and stimulator of natural detoxifying enzymes. Sulforaphane has
been reported to reduce the risk of breast cancer and prostate cancer.
Thiosulfonates an organosulfur phytochemical is present in garlic and onions
(Allium cepa). Onions are rich in two chemical groups that have perceived
benefits to human health, which include anticarcinogenic properties, antiplatelet
activity, antithrombotic activity, antiasthmatic and antibiotic effects. Curcumin
(diferuloylmethane) is a polyphenol derived from the plant Curcuma longa,
commonly called turmeric. Curcumin, an active yellow pigment of turmeric
reported to possesses anticarcinogenic, antioxidative and anti-inflammatory
properties. The anticancer potential of curcumin stems from its ability to
suppress proliferation of a wide variety of tumour cells. Top of Form Beet roots,
cucumber fruits, spinach leaves, and turmeric rhizomes, were reported to
possess anti-tumour activity. Non-prescription antioxidants and other nutrients
(patients using beta-carotene; vitamins A, C, and E; selenium; cysteine; B
vitamins; vitamin D3; vitamin K3; and glutathione as single agents or in
combination.) do not interfere with therapeutic modalities for cancer. Current
status of nutraceuticals in cancer Approximately 20-30% of Americans
consume multivitamin supplements daily, indicating high public interest in the
prevention of cancer and other chronic diseases through a nutrition-based
approach. Because epidemiologic studies generally evaluate foods rather than
specific bioactive food components, a systematic approach to determining how
combinations of vitamins and minerals may interact to ameliorate cancer risk is
necessary to further our understanding of the potential benefits and risks of
supplement use. Increasing consumption of vegetables and fruits elevates the
levels of antioxidative components, for example, selenium, vitamin E, vitamin
C, lycopene, cysteine-glutathione and various phytochemicals. These
detrimental processes of heme catalysis of oxidative damage hypothesized here
are not well recognized. More investigative studies in this field to be done.
Large scale clinical trials suggest that some agents such as selenium, lycopene,
soy, green tea, vitamins D and E, anti-inflammatory and inhibitors of 5a-
reductase are effective in preventing prostate cancer. In order to demonstrate
clinical benefit with the minimum adverse effects. Appropriate selection of
agent(s), trial design and end points is critical in selecting the most promising
regimens to accomplish these goals. Cancer was not prevented by beta-carotene,
alphatocopherol, retinol, retinyl palmitate, N-acetylcysteine, or isotretinoin in
smokers. On-going trials may help define new avenues for chemoprevention.
The concept of chemoprevention in lung cancer is still in its infancy, but in the
future it may have a significant impact on the incidence and mortality of lung

39
cancer. Several studies have demonstrated the improvement in quality of life
and the value of complementary medicine as an adjuvant to chemotherapy or
radiotherapy. Complimentary therapy might serve as a valuable and useful
supportive measure for prostate cancer patients89. Majority of the studies
indicate a preventive role of nutraceuticals in cancer, however more elaborate
randomized double blind studies are needed.

2.6. Immune Boosters and Anti-Inflammatory Agents

2.6.1. Immune Boosters

Various nutrients in the diet play a crucial role in maintaining an “optimal”

immune response, on the organism’s immune status and susceptibility to a
variety of disease conditions. a broad range of phytopharmaceuticals with a
claimed hormonal activity, called “phyto-estrogens”, is recommended for
prevention of various diseases related to a disturbed hormonal balance. In this
respect, there is a renewed interest in soy isoflavones (genistein, daidzein,
biochanin) as potential superior alternatives to the synthetic selective estrogen
receptor modulators (SERMs), which are currently applied in hormone
replacement therapy. Phytochemicals integrate hormonal ligand activities and
interfere with signalling cascades; their therapeutic use may not be restricted to
hormonal ailments only, but may have applications in cancer chemoprevention
and/or certain inflammatory disorders as well63. Nutraceuticals that belong to
the category of immune boosters and/or anti-viral agents are useful to improve
immune function and accelerate wound-healing. They include extracts from the
coneflowers, or herbs of the genus Echinacea, such as Echinacea purpurea,
Echinacea angustfolia, Echinacea pillida, and mixtures thereof; extracts from
herbs of the genus Sambuca, such as elderberries; and Goldenseal extracts. The
coneflowers in particular are a popular herbal remedy used in the central United
States, an area to which they are indigenous. The extract derived from the roots
contains varying amounts of unsaturated alkyl ketones or isobutylamides.
Goldenseal is an immune booster with antibiotic activity, and includes
compounds like berberine and hydrastine, which stimulate bile secretion and
constrict peripheral blood vessels respectively. Astragalus membranaceous,
Astragalus mongolicus, and other herbs of the genus Astragalus are also
effective immune boosters in either their natural or processed forms. Astragalus
stimulates development and transformation of stem cells in the marrow and
lymph tissue to active immune cells. The effect of plant and bacteria on
systemic immune and intestinal epithelial cell function has led to new credence
for the use of probiotics and nutraceuticals in the clinical setting. The probiotics
have been found to effective in conditions like in infectious diarrhoea in
children and recurrent Clostridium difficile induced infections. Evidence is
being acquired for the use of probiotics in other gastrointestinal infections,
irritable bowel syndrome and inflammatory bowel disease90. The dietary
approach to allergy has evolved to include active stimulation of the immature
immune system in order to support the establishment of tolerance.
Supplementation with probiotics may provide maturational signals for the

40
lymphoid tissue and improve the balance of pro- and anti-inflammatory
cytokines. Enteral polymeric feeding is effective in Crohn's disease. Dietary
nucleotides may improve growth and immunity, optimize maturation, recovery
and function of rapidly dividing tissue. Usage of probiotics (live viable
microbial organisms) in the treatment of specific diseases has evolved into an
extremely valuable option. The ability to reduce antibiotic use, the apparently
very high index of safety, and the public’s positive perception about “natural”
or “alternative”therapies. These products manipulated the intestinal microflora
to maintain the normal balance between pathogenic and non-pathogenic
bacteria. Therapeutic effects of most commercial preparations are
unsubstantiated. Certain probiotics will be effective in the treatment or
prevention of certain conditions. Lactobacillus GG has been shown to be
effective in the treatment or prevention of a number of problems including acute
diarrhoea in children, travellers’ diarrhoea in adults, Crohn’s disease, and
reduction of the incidence of antibiotic-associated diarrhoea in infants. Most
probiotic preparations are comprised of one or more lactic acid bacteria (LAB).
Within this group, strains of Lactobacillus, Bifidobacterium sp. And
occasionally Streptococcus are most commonly used. A supplementary use of
oral digestive enzymes and probiotics is also an anticancer dietary measure
towards decreasing the incidence of breast, colon-rectal, prostate and
bronchogenic cancer.

2.6.2. Inflammatory Disorders

Inflammation is the response of body tissues to injury or irritation, characterized

by pain and swelling and redness and heat. Arthritis is a general term that
describes inflammation in joints. Some types of arthritis associated with
inflammation include: rheumatoid arthritis shoulder tendinitis or bursitis gouty
arthritis and polymyalgia rheumatica. Micronutrients for which preliminary
evidence of benefit exists include vitamin C and vitamin D. In addition,
numerous nutraceuticals that may influence osteoarthritis pathophysiology,
including glucosamine, chondroitin, Sadenosylmethionine, ginger and
avocado/soybean unsaponifiables, have been tested in clinical trials. These
products are safe and well tolerated, but interpretation of the collective results is
hampered by heterogeneity of the studies and inconsistent results. Cat’s claw is
a potent anti-inflammatory agent. The two known species of cat’s claw are
Uncaria guianensis, used traditionally for wound healing, and Uncaria
tomentosa, which has numerous medicinal uses and is most commonly found in
supplements. Cat’s claw is a rich source of phytochemicals: 17 alkaloids, along
with glycosides, tannins, flavonoids, sterol fractions, and other compounds.
Scientists previously attributed the efficacy of cat’s claw to compounds called
oxindole alkaloids; more recently, however, water-soluble cat’s claw extracts
that do not contain significant amounts of alkaloids were found to possess
strong antioxidant and anti-inflammatory effects are independent of their
alkaloid content. Resveratrol is present in the fruits of bilberry (Vaccinium
myrtillus), the lowbush "wild" blueberry (Vaccinium angustifolium), the
rabbiteye blueberry (Vaccinium ashei Reade), and the highbush blueberry
(Vaccinium corymbosum). Although blueberries and bilberries were found to

41
contain resveratrol, the level of this chemo protective compound in these fruits
was <10% that reported for grapes. Resveratrol shows the strongest sirtuin-like
deacetylase action of any known phytochemical. Sirtuins have been shown to
extend the lifespan of yeast and fruit flies. It acts as an anti-inflammatory agent,
antifungal and inhibits cyclooxygenase-1 enzyme. Other beneficial health
effects include anti-cancer, antiviral, neuroprotective, anti-aging and life-
prolonging effects. The omega-3 and omega-6 series play a significant role in
health and disease by generating potent modulatory molecules for inflammatory
responses, including eicosanoids (prostaglandins, and leukotrienes), and
cytokines (interleukins) and affecting the gene expression of various bioactive
molecules. Gamma linolenic acid (GLA, all cis 6, 9, 12-Octadecatrienoic acid,
C18:3, n-6), is produced in the body from linoleic acid (all cis 6,9-
octadecadienoic acid), an essential fatty acid of omega-6 series by the enzyme
delta-6- desaturase. Preformed GLA is present in trace amounts in green leafy
vegetables, nuts, vegetable oils, such as evening primrose (Oenothera biennis)
oil, blackcurrant seed oil, borage oil and hemp seed oil, and from spirulina,
cyanobacteria. It is a nutraceutical used for treating problems with inflammation
and auto-immune diseases. The most significant source of GLA for infants is
breast milk. GLA is further metabolized to dihomogamma linlenic acid (DGLA)
which undergoes oxidative metabolism by cyclooxygenases and lipoxygenases
to produce anti-inflammatory eicosanoids. Phytoconstituent gentianine present
in Gentian root is an effective anti-inflammatory agent. Anti-inflammatory
herbal nutraceuticals and anti-inflammatory nutraceutical compounds derived
from plants or herbs may also be used as anti-inflammatory agents. These
include bromolain, a proteolytic enzyme found in pineapple; teas and extracts of
stinging nettle; turmeric, extracts of turmeric, or curcumin, a yellow pigment
isolated from turmeric.

2.6.3. Osteoarthritis

Osteoarthritis (OA), a debilitating joint disorder, is the most common form of

arthritis in the United States, where it affects an estimated 21 million people. In
2004, the direct and indirect health care costs associated with all forms of
arthritis were approximately 86 billion dollars. Joint discomfort from OA and
other joint disorders may reduce physical activity in individuals experiencing
this condition, resulting in energy imbalance and weight gain. Increased weight
can exacerbate existing problems, through additional stress on joints.
Glucosamine (GLN) and chondroitin sulphate (CS) are widely used to alleviate
symptoms of OA. These nutraceuticals have both nutrient and pharmaceutical
properties and seem to regulate gene expression and synthesis of NO and PGE2,
providing a plausible explanation for their anti-inflammatory activities.

2.6.4. Allergy

Allergy is a condition in which the body has an exaggerated response to either a

drug or food. Quercetin (QR) belongs to a group of polyphenolic substances
known as flavonoids. QR is a member of the class of flavonoids called

42
flavonols. It is widely distributed in the plant kingdom in rinds and barks.
Especially rich sources of QR include onions, red wine and green tea. QR is a
natural antihistamine and opposes the actions of the histamine in the body.
Histamines are responsible for allergic and inflammatory reactions. It can help
reduce the inflammation that results from hay fever, bursitis, gout, arthritis, and
asthma1. QR inhibits some inflammatory enzymes, such as lipid peroxidases,
and decreases leukotriene formation. QR has anti-inflammatory, antiviral,
immunomodulatory, anticancer and gastroprotective activities. QR blocks an
enzyme that leads to accumulation of sorbitol, which has been linked to nerve,
eye, and kidney damage in those with diabetes. QR also possesses potent
antioxidant properties. It protects LDL cholesterol from becoming damaged.
QR prevents damage to blood vessels by certain forms of cholesterol and other
chemicals produced by the body. LDL cholesterol is an underlying cause of
heart disease. QR also works as an antioxidant by scavenging damaging
particles in the body known as free radicals. People with diabetes are at higher
risk of blood vessel damage from free radicals.

2.7. Degenerative Diseases

2.7.1. Macular Degeneration

The prevalence and effects of age-related macular degeneration (AMD) are

increasing dramatically as the proportion of elderly in our population continues
to rise. A combination of vitamin C, vitamin E, beta-carotene, and zinc (with
cupric oxide) is recommended for AMD. Healthy lifestyle with a diet
containing foods rich in antioxidants, like lutein and zeaxanthin, n-3 fatty acids,
appears beneficial for AMD. Herbs or herbal extracts, such as garlic, (which
contain allicin), green tea (containing catechins and bioflavonoids such as QR,
hesperidin, rutin) are effective antioxidants. Bioactive components of food,
which are of special interest, include the Vitamins E and C, polyphenols,
carotenoids— mainly lycopene and β-carotene, and coenzyme Q10 possess
antioxidant properties. High content of polyphenolic flavonoids in
nutraceuticals and functional foods had been ascribed to possess
antioxidant/radical scavenging activity. Antioxidant therapy is supposed to be
effective in the early stages of atherosclerosis by preventing LDL oxidation and
the oxidative lesion of endothelium. Astaxanthin is an important naturally
occurring molecule and the most abundant carotenoid in the marine world. It
can be found in many of our favourite seafood such as salmon, trout, sea bream
and shrimps. Natural astaxanthin is produced from Haematococcus pluvialis
microalgae. Unlike β-carotene, astaxanthin has no pro-vitamin A activity. It has
a number of essential biological functions in aquatic animals such as protecting
against oxidation process, protecting against UV light effects, immune response
and pigmentation. It is also a very potent anti-oxidant and it has ten times more
powerful antioxidant activity than any other carotenoids. For more than ten
years, astaxanthin’s role in enhancing the immune system and preventing
oxidative stress has been the subject of international research. It offers powerful
protection for the eyes and prevents macular degeneration. Prevents heart

43
disease due to oxidative damage, boosts immune system function, protects the
nervous system from degenerative diseases like Alzheimer's disease. It is used
in drug delivery for medicines that are insoluble in water. In vivo antioxidant
activity of carotenoids from green microalgae (Dunaliella salina) was reported.

2.7.2. Vision Improving Agents

Lutein is one of the carotenoids, found in many fruits and vegetables including
mangoes, corn, sweet potatoes, carrots, squash, tomatoes and dark, leafy greens
such as kale, collards and bok choy. Lutein dipalmitate is found in the plant
Helenium autumnale. Lutein also known as helenien is used for the treatment of
visual disorders. Zeaxanthin is used in traditional Chinese medicine mainly for
the treatment of visual disorders. Food sources of zeaxanthin, include corn, egg
yolks and green vegetables and fruits, such as broccoli, green beans, green peas,
brussel sprouts, cabbage, kale, collard greens, spinach, lettuce, kiwi and
honeydew. Lutein and zeaxanthin are also found in nettles, algae and the petals
of many yellow flowers. In green vegetables, fruits and egg yolk, lutein and
zeaxanthin exist in non-esterified forms. They also occur in plants in the form
of mono-or diesters of fatty acids. A new source of these carotenoids, a
crystalline lutein product, is an extract from the marigold flower (Tagetes
erecta) that contains approximately 86% by weight of the carotenoids lutein and
zeaxanthin.

2.7.3. Alzheimer's Disease

Alzheimer's disease (AD) is characterized by progressive dementia with

memory loss as the major clinical manifestation. In 1996, approximately 4
million people in the United States were clinically diagnosed with AD; which is
expected to triple in the next 50 years118. Women are more affected than men
at a ratio of almost 2:1 due in part to the larger population of women who are
over 70119. Several lines of evidence strongly suggest that oxidative stress is
etiologically related to a number of neurodegenerative disorders including
Alzheimer's disease. Nutraceutical antioxidants like β-Carotene, curcumin,
lutein, lycopene, turmerin etc. may exert positive effects on specific diseases by
neutralizing the negative effects oxidative stress, mitochondrial dysfunction,
and various forms of neural degeneration. A great deal of research has pointed
to deleterious roles of metal ions in the development of Alzheimer's disease, by
the augmentation of oxidative stress by metal ion. The growing trend in
nutraceutical intake is in part a result of the belief that they postpone the
development of dementias such as Alzheimer's disease. However, pathogenic
events centred on metal ions are expected to be aggravated by frequent
nutraceutical intake.

44
2.7.4. Parkinson's Disease

Parkinson’s disease is a brain disorder that results from nerve damage in certain
regions of the brain causing muscle rigidity, shaking, and difficult walking,
usually occurring in mid to late adult life. Canadian researchers indicated that
vitamin E in food may be protective against Parkinson's disease. Creatine
appeared to modify Parkinson’s disease features as measured by a decline in the
clinical signs. Researchers have also studied glutathione to determine its effect
on nerve and its power as an antioxidant. The appropriate long-term dosing,
side-effects and the most effective method of administration are not yet clear.
Nutritional supplements have shown some promising results in preliminary
studies, it is important to remember that there is not sufficient scientific data to
recommend them for Parkinson's disease at present. The patients should be
cautioned that over-the-counter medications do have side-effects and
interactions with other drugs and are also expensive .

2.8. Miscellaneous

In our modern society women can be over-fed, but undernourished which can
lead to nutrient deficiencies with adverse impact on the pregnancy outcome.
Good quality nutritional supplements (combinations rather than isolated single
nutrients) can play a valuable role in the health of the pregnant mother and the
baby though emphasis must always be on eating a good diet. There is also
insufficient evidence to identify adverse effects and to say that excess multiple-
micronutrient supplementation during pregnancy is harmful to the mother or the
foetus. Angiogenesis is an enzymatic process involved in almost all classes of
enzymes. It is a process that is generally down regulated in healthy individuals.
Antiangiogenic compounds are selective against newly formed blood vessels
while sparing existing ones may not lead to side effects even after prolonged
exposure. Available indirect evidences suggest that antiangiogenic compounds
may prevent diseases involving degenerative process like, arthritis, multiple
sclerosis, Alzheimer's, Parkinson's, osteoporosis, diabetes and cancer. Many
inhibitors of angiogenesis are being isolated from functional foods. Naturally
occurring bioactive compounds are speculated to be potentially effective and
safe anti-angiogenic compounds. Such compounds include catechins, flavins,
Curcumin, Isoflavones, Resveratrol, proanthocyanidins, flavonoids, Saponins,
terpenes, Chitin, chitosan, Vitamins B3, Vitamin D3, Fatty acids, peptides and
amino acids (alpha 2-macroglobulin, arginine, phenylalanine etc. Psyllium, a
dietary fibre is valuable in the management of irritable bowel syndrome,
inflammatory bowel disease-ulcerative colitis, colon cancer, constipation.
Moringa oleifera Lam (Moringaceae) has an impressive range of medicinal uses
with high nutritional value. Different parts of this plant contain a profile of
important minerals, and are a good source of protein, vitamins, beta-carotene,
amino acids and various phenolics. It provides a rich and rare combination of
zeatin, QR, beta-sitosterol, caffeoylquinic acid and kaempferol. With water
purifying powers and high nutritional value. Various parts of this plant such as
the leaves, roots, seed, bark, fruit, flowers and immature pods act as cardiac and

45
circulatory stimulants, possess antitumor, antipyretic, antiepileptic, anti-
inflammatory, antiulcer, antispasmodic, diuretic, antihypertensive, cholesterol
lowering, antioxidant, antidiabetic, hepatoprotective, antibacterial and
antifungal activities, and are being employed for the treatment of different
ailments in the indigenous system of medicine, particularly in Asia.

3.9. Metabolism, Bioavailability and Pharmacokinetics of Nutraceuticals -

Metabolism Data

Metabolites play very important role in activity of particular nutraceutical.

Dietary level have impact on physiological level .e.g. except for food containing
Q10,Carnitine,soy there is little chance of dietary supplement increasing
physiological level. Some nutraceuticals do not show physiological level but
consumption with other specific food e.g.-lycopene, tea or soy, increased
physiological level.

Table 2.2. : Metabolism Data of Selected Nutraceuticals

Nutraceuticals Physiologic Dietary Metabolite

al Level
Level
Glucosamine - - Glucosaminic acid
Methylsulfonylmetha 4mg/person minimal Methionine
ne
Methylsulfonylmetha 4mg/person minimal Coenzyme Q9
ne
Coenzyme Q10 0.5micro 3-5mg/day 6-(5’,8’,6’)carboxylated
gm/ml derivatives
Coenzyme Q10 0.5micro 3-5mg/day 6-hydroxymelatonin
gm/ml
Carnitine 9mg/L 3- acetylcarnitine
97mg/100g
m meat
Carnitine 9mg/L 3- Butyrobetaine
97mg/100g
m meat
Flax lignans Diet Diet SDG-enterolactone
dependent dependent
Resveratrol - 0.1-2.3 Piceartanol
mg/L
Resveratrol - 0.1-2.3 Piceartanol plus another

46
 mg/L tetra
hydroxystilbene
Resveratrol - 0.1-2.3 dihydroresveratrol
mg/L
Grape seed - - Catechin/proanthrocyani
din
metabolites
Lycopene - 2-5 mg/day 5,6 dihydroxy 5,6
dihydrolycopine
Lycopene - - Lycopene epoxide
Soy isoflavones - 15- 18-demethylated
20mg/day

Table 2.3. : Bioavailability Data of Selected Nutraceuticals

Nutraceutical Dose Bioavailability Increased

serum level
Glucosamine 7.5gm 26%,44% -
incorporation into
globulin
Co-enzyme Q 10 30 mg - 3.5% increase in
serum level at 6
hours
Co-enzyme Q 10 30 mg - 2.7-6 times
normal level
Carnitine 2gm/12 hr 14-16 % -
Carnitine 0.5-0.6 gm 14-18 % 43%
Resveratrol 50gm/Kg 38% -

3.9.2. Pharmacokinetic Data

It is important to know about optimum dosage levels and frequency of

administration of nutraceuticals.

Table 2.4. : Pharmacokinetic Data of Selected Nutraceuticals

Nutraceutical No of Dose Cmax t1/2 AUC

dose
Glucosamine 8 beagles 1500 mg 12.7 μg/ml 1.52 17.8μg.hr/ml
Co-enzyme Q 9 180mg 1.03μg/ml - 57.67μg.hr/ml
Caritine 15 2gm 12.4 μg/ml 0.79 377Pg.hr/ml
every 12
hr

47
Flax lignans 12 0.9 - 4.4 280μg.hr/ml
gm/kg

References:

Brower V., Nutraceuticals: poised for a healthy slice of the healthcare market?,
Nat Biotechnol., 1998, 16, 728-731.

Cindy S. Oliveri, Nutraceuticals, Phytochemicals, and Antioxidants-What Are

They All About, OSU Extension Fact Sheet, 2003, 5051-5098.

Lockwood Brain, Nutraceuticals, second edition, Pharmaceutical press.

London, 2007, 60-65. pdfcast.org/search/all/nutraceutical-ppt

Kalra E.K., Nutraceutical--definition and introduction", AAPS Pharm Sci ,

2003, 5, 27- 28.

Hardy G., Nutraceuticals and functional foods: introduction and meaning,

Nutrition, 2000, 16,

Ahmad, M.F., Ashraf S.A., Ahmad F.A., Ansari J.K., and Siddiquee
M.R.A., Nutraceutical market and its regulation., Am. J. Food Technol., 2011,
6, 342-347.

Imanaga Y., Yoshifuji K,, Monose N., Metabolism of D-glucosamine, Koso.,

Kagaku Shimpoijuma, 1960,14,183-189.

Ely A, Lock Wood B., What is evidence for the safety and efficacy of dimethyl
sulphoxide and methylsulphonylmethane., pailief. Pharm J, 2002, 269,685-687.

Grunler J, Dallner G., Investigation of regulatory mechanism in co-enzyme Q

metabolism, Method Enzymol.,2004,3-17

Evans AM, Fornasini G., Pharmacokinetics of L-carnitin, Clin.

Pharmacokinet., 2003, 42, 941-967.

Alhassane Touré , Xu Xueming, Flaxseed lignan source Biosynthesis,

Metabolism, Antioxidant Activity, Bio-Active Components, and Health
Benefits, Comprehensive Reviews in Food Science and Food Safety, 2010,9
(3),261-269.

Zhu Y,Chiang H,Zhou J,Kissinger PT., In vitro metabolism study of

resveratrol and identification and determination of its metabolism piceatanol by
LC/EC and LCMS., Curr separation, 2003,20,93-96.

48
Ward Nc, Croft KD, Puddey IB, Hodgson JM., Supplement with grape seed
polyphenols result in increased urinary excretion of 3- hydroxyphenyl propionic
acid,. J Agric Food Chem, 2004, 52, 5545-5549.

Barclay T.S., Tsourounis C. and McCart G.M., Glucosamine, The Annals of

Pharmacotherapy, 1998, 5, 574-579.

Anderson J.W., Nicolosi R.J., Ozelleca J.K., Glucosamine effect in human: a

review of effects on glucose metabolism, side effect, safety consideration and
efficacy, Food Chem. Toxicol , 2005, 43,187-201.

Majithia V. Geraci S.A., Rheumatoid arthritis Dietary fat Cancer Dietary

saturated fat and cholesterol Coronary heart disease Sodium High blood
pressure Swati Chaturvedi et al /Int.J. PharmTech Res.2011,3(1) 448 diagnosis
and management, Am. J. Med, 2007, 120, 36-939.

Deal C.L., Moskowitz R.W., Nutraceuticals as therapeutic agent in

asteoarthritis, Osteoarthritis, 1999, 25,379.

Jonathan Cluett , What are glucosamine and chondroitin? Orthopedics,

2010,1-2.

McAlindon T.E., La Valley M.P., Gulin J.P., Glucosamine and chondroitin

for treatment of osteoarthritis: a systematic quality assessment and meta-
analysis. JAMA. 2000; 283:1469- 1475.

Horton D., Wander J.D., The Carbohydrates, New York: Academic

Press,1980,IB,28

Kim LS., Axelrod L.J., Howard P., Buratovich N., Waters R.F., Efficacy of

methylsulfonylmethane (MSM) in osteoarthritis pain of the knee: a pilot clinical

trial, Osteoarthritis Cartilage, 2006, 14, 286–94.

Zeisel S.H., Regulation of Nutraceutical, Science, 1999, 285,185-186.

Kaushik Deepak., Kaushik Nisha., Nutraceuticals Regulation In India,

Pharma info.net, 2009,7,45-46.

Dr Bhaskaran K., Nutraceuticals, Health Administrator, 2002, 1&2, 76-77.

49
 Chapter 3
Nutraceuticals from Seafood and Seafood By-Products

3.0. Introduction

Marine foods have traditionally been used because of their variety of flavor,
color, and texture. More recently, seafoods have been appreciated because of
their role in health promotion arising primarily from constituent long-chain
omega-3 fatty acids, among others. Nutraceuticals from marine resources and
the potential application areas are varied, as listed in Table 3.0. Processing of
the catch brings about a considerable amount of by-products accounting for 10
to 80% of the total landing weight. The components of interest include lipids,
proteins, flavorants, minerals, carotenoids, enzymes, and chitin, among others.
The raw material from such resources may be isolated and used in different
applications, including functional foods and as nutraceuticals. The importance
of omega-3 fatty acids in reducing the incidence of heart disease, certain types
of cancer, diabetes, autoimmune disorders, and arthritis has been well
recognized. In addition, the residual protein in seafoods and their by-products
may be separated mechanically or via a hydrolysis process. The bioactive
peptides so obtained may be used in a variety of food and nonfood applications.
The bioactives from marine resources and their application areas are generally
diverse.

Table 3.0. Nutraceutical and Bioactive Components from Marine

Resources and Their Application Area

Component (source) Application Area

Chitin, chitosan, glucosamine Nutraceuticals, agriculture, food,
water purification, juice clarification,
etc.

50
Carotenoids, carotenoproteins Nutraceuticals, fish feed
Omega-3 fatty acids Nutraceuticals, foods, baby formula,
etc.
Biopeptides Nutraceuticals, immune enhancing
agents
Minerals (Calcium, etc.) Food, nutraceuticals
Algae (Omega-3, minerals, Nutraceuticals
carotenoids)
Chondroitin sulfate Arthritic pain relief
Squalene Skin care
Specialty chemicals Miscellaneous

3.1. Marine Oils

The long-chain omega-3 polyunsaturated fatty acids (PUFA) are of considerable
interest because of their proven or perceived health benefits. These fatty acids
are found almost exclusively in aquatic resources (algae, fish, marine mammals,
etc.) and exist in varying amounts and ratios. While algal sources also provide
minerals, such as iodine, as well as carotenoids and xanthophylls, fish body oil
contains mainly triacylglycerols, and fish liver oils serve as a source of vitamin
A, among others. In addition, liver from other aquatic species, such as shark,
contain squalene and other bioactives. Another source of long-chain omega-3
fatty acids is the blubber of marine mammals which contains eicosapentaenoic
acid (EPA) and docosahexaenoic acid (DHA), similar to fish oils, as well as
docosapentaenoic acid (DPA). It is worth noting that myristic acid is present in
much smaller levels in the blubber oil from marine mammals than algal or fish
oils; this is a definite advantage when considering the atherogenic properties of
myristic acid. In humans, DHA accumulates at a relatively high level in organs
with electrical activity, such as retinal tissues of the eye and the neural system
of the heart. While DHA and other long-chain omega-3 fatty acids may be
formed from alpha linolenic acid (ALA) (Figure 10.1), the conversion
efficiency for this transformation is very limited in healthy human adults and is
approximately 3 to 5%. In adults with certain ailments, the conversion of ALA
to DHA is less than 1%.

As shown in Figure 3.0, DHA may be retroconverted to DPA and EPA. Human
feeding trials have indicated a retro conversion of DHA to EPA of about 10%.
The beneficial health effects of marine oils in reducing the incidences of
coronary heart disease (CHD) have been attributed to their omega-3 fatty acid
constituents.Omega- 3 fatty acids are known to reduce the incidence of CHD by
lowering the level of serum triacylglycerols and possibly cholesterol and also to
lower the blood pressure in individuals with high blood pressure as well as to
decrease the ventricular arrhythmias, among others. In addition, omega-3 fatty
acids are known to relieve arthritic swelling and possibly pain, relieve type II
diabetes, and enhance body immunity. However, omega-3 fatty acids may
increase fluidity of the blood, and hence their consumption by patients on blood
thinners such as coumadin and aspirin should be carefully considered in order to
avoid any unnecessary complication due to vasodilation and possible rupture of

51
capillaries. The omega-3 fatty acids, especially DHA, are known to dominate
the fatty acid spectrum of brain and retina lipids and play an essential role in the
development of fetus and infants as well as in the health status and body
requirements of pregnant and lactating women. Consideration of the three-
dimensional structures of unsaturated fatty acids demonstrates that bending of
the molecules increases with an increase in the number of double bonds in their
chemical structures, and this is further influenced by the position of the double
bonds (i.e., omega-3 vs. omega-6). These structural features in the
triacylglycerol molecules as well as the location of the fatty acids in the glycerol
molecule (i.e., sn-1, sn-2, and sn-3) may have a major effect on the
bioavailability of fatty acids involved and their potential health benefits.

Figure 3.0. Essential fatty acids of the omega-6 and omega-3 families.
Symbols are: LA, linoleic acid; GLA, gamma linolenic acid; DGLA,
dihomo-gamma linolenic acid; AA, arachidonic acid; DPA,
docosapantaenoic acid; ALA, “alpha linolenic acid; EPA, eicosapentaenoic
acid; and DHA, docosahexaenoic acid.

52
Two important sources of omega-3 fatty acids, namely menhaden oil (MO) and
seal blubber oil (SBO) were considered in our work. Table 3.1 summarizes the
fatty acids of MO, SBO, cod liver oil, and a commercial algal oil known as
DHASCO (docosahexaenoic acid cell oil). While omega-3 fatty acids,
especially DHA, are primarily located in the sn-2 position in menhaden oil, they
are mainly in the sn-1 and sn-3 positions of seal blubber oil.

Table 3.1. : Major Fatty Acids of Omega-3 Rich Marine and Algal Oils

Fatty Acid Seal Blubber Cod Liver Menhaden Algal

(DHASCO)
14:0 3.73 3.33 8.32 14.9
16:0 5.58 11.01 17.4 9.05
16:1 T7 18.0 7.85 11.4 2.20
18:0 0.88 3.89 3.33 0.20
18:1 T9+T11 26.0 21.2 12.1 18.9
20:1 T9 12.2 10.4 1.44 -
20:5 T3 6.41 11.2 13.2 -
22:1 T11 2.01 9.07 0.12 -
22:5 T3 4.66 1.14 2.40 0.51
22:6 T3 7.58 14.8 10.1 47.4

Note: Units are weight percentages of total fatty acids. DHASCO =

docosahexaenoic acid single cell oil.

These differences undoubtedly have a definite influence on their assimilation,

absorption, and health benefits as well as reactions in which they are involved.
Regardless of the source of long-chain omega-3 fatty acids, such oils must
undergo appropriate processing in order to provide a bland-tasting product
devoid of contaminants. Therefore, refining, bleaching, deodorization, and
addition of appropriate antioxidant stabilizers must be practiced in order to
allow their use in food formulations

Table 3.2: Distribution of Long-Chain Omega-3 Fatty Acids in Menhaden

and Seal Blubber Oils

Fatty Seal blubber Menhaden

acid sn-1 sn-2 sn-3 sn-1 sn-2 sn-3
EPA 8.36 1.60 11.2 3.12 17.5 16.3
DPA 3.99 0.79 8.21 1.12 3.11 2.31
DHA 10.5 2.27 17.9 4.11 17.2 6.12

Note: Units are weight percents of total fatty acids. EPA = eicosapentaenoic
acid; DPA = docosapentaenoic acid; and DHA = docosahexaenoic acid.

53
3.2. Omega-3 Concentrates

For therapeutic purposes the natural sources of omega-3 fatty acids, as such,
may not provide the necessary amounts of these fatty acids and hence
production and use of concentrates of omega-3 fatty acids may be required. The
omega-3 fatty acid concentrates may be produced in the free fatty acid, simple
alkyl ester and acylglycerol forms. To achieve this, physical, chemical, and
enzymatic processes may be employed for concentrate production. The
available methods suitable for large-scale production include low-temperature
crystallization, fractional or molecular distillation, chromatography,
supercritical fluid extraction, urea complexation, and enzymatic splitting.
Among the simplest methods for concentrate production is fractional
crystallization, which takes advantage of the existing differences in the melting
points of different fatty acids, as neat compounds or in different solvent
systems. The more saturated fatty acids have higher melting points and may
crystallize out of the mixtures and hence leave behind, in the liquid form, the
more unsaturated fatty acids. Obviously, the free fatty acids and simple alkyl
esters are more amenable to provide a higher concentration of omega-3 fatty
acids than acylglycerols. This is because the latter mixtures consist of fatty
acids with varying chain lengths and degrees of unsaturation in many different
combinations in the triacylglycerol molecules. Fractional distillation is another
facile process for separation of mixtures of fatty acid esters under reduced
pressure (0.1 to 1.0 mm Hg) . However, due to sensitivity of more highly
unsaturated fatty acids to oxidation, one may use a spinning band column,
which does not impose such limitations. While fractional distillation of
menhaden oil ethyl esters increased the content of EPA from 15.9 to 28.4%, and
DHA from 9.0 to 43.9%, molecular distillation afforded DHA with 90% parity.
Reverse phase chromatography has been used by Nakahara to produce a DHA
and DPA concentrate from marine microalgae. Teshiman used a silver nitrate-
impregnated silica gel column to separate EPA and DHA from squid liver oil
fatty acid methyl esters. The yield of the process for these fatty acids was 39
and 48%, respectively, with 85 to 96% EPA and 95 to 98% DHA purity. Similar
studies on a variety of other oils have recently appeared in the literature using
highperformance liquid chromatography. More recently, centrifugal partition
chromatography (CPC) has gained attention for production of omega-3
concentrates. Wanasundara Shahidi used a CPC technique to produce highly
concentrated fatty acids such as EPA and DHA with a near quantitative yield.
Supercritical fluid extraction (SFE) is a relatively new process, which is
desirable for separation of PUFA. Since this method is based on separation of
compounds based on their molecular weight and not their degree of
unsaturation, a prior concentration step may be required in order to concentrate
the omega-3 PUFA. Thus omega-3 fatty acids have been concentrated by SFE
from fish oil and seaweed.

Fish oil esters were fractionated by SFE to obtain an oil with 60 to 65% DHA.
Another possibility for concentration of omega-3 fatty acids is urea
complexation. The natural acylglycerols are hydrolyzed to their fatty acid
constituents in ethanol and the resultant components are allowed to crystallize

54
in the presence of urea. The highly unsaturated fatty acids, which deviate more
and more from a near linear shape, are not included in the urea crystals and
remain in the liquid form, referred to as nonurea complexing fraction (NUCF).
Meanwhile, saturated fatty acids and, to a lesser extent, mono- and
diunsaturated fatty acids may be included in the urea to afford the urea
complexing fraction (UCF). In this manner, depending on the variables
involved, e.g., the amount of solvent, urea, and time and temperature, optimum
conditions may be employed for the preparation of concentrates. If necessary,
the urea complexation process may be repeated in order to enhance the
concentration of certain fatty acids in the final products. We have used such
techniques to prepare concentrates dominated by DHA, EPA, or DPA. The total
omega-3 fatty acids in one such preparation from seal blubber oil was 88.2%
and this was dominated by DHA (67%) Finally, enzymatic procedures may be
used to produce concentrates of omega-3 fatty acids. Depending on the type of
enzyme, reaction time, temperature, and the concentration of the reactants and
enzyme, it is possible to produce concentrates in different forms, e.g., as free
fatty acids or as acylglycerols. Thus, processes such as transesterification,
acidolysis, alcoholysis, and hydrolysis as well as esterification of fatty acids
with alcohols or glycerol may be employed. Wanasundara and Shahidi have
shown that enzymes might be used to selectively hydrolyze saturated and less
unsaturated lipids from triacylglycerols, hence concentrating the omega-3 fatty
acids in seal blubber and menhaden oils in the acylglycerol form. In this
manner, the omega-3 PUFA content was nearly doubled. Furthermore,
following urea complexation, omega-3 concentrates obtained may be subjected
to esterification with glycerol to produce concentrated acylglycerols. Upon
glycerolysis of specialty alkyl esters from seal blubber oil, we found that
monoacylglycerols (MAG), diacylglycerols (DAG), and triacylglycerols (TAG)
were formed simultaneously. The amount of MAGs decreased continuously
while that of TAGs increased Depending on the structural characteristics of
final products, the stability of acylglycerols was found to be better than that of
their corresponding ethyl esters. Possible loss of natural antioxidants during
processing may also affect the stability of products involved. Therefore, it is
important to stabilize the modified oils using any of the recommended synthetic
antioxidants or preferably natural stabilizers. Thus, TBHQ (tertiary-
butylhydroquinone) at 200 ppm was able to inhibit oxidation of menhaden oil at
60°C over a 7-day storage period. Meanwhile, the inhibition effects were 32.5%
for mixed tocopherols (500 ppm), 18.0% for alphatocopherol (500 ppm), 39.8%
for mixed green tea catechins (200 ppm), 45.1% for EC (epicatechin), 48.2%
for ECG (epicatechin gallate), 51.3% for EGC (epigallocatechin), and 50% for
EGCG (epigallocatechin-3 gallate). For seal blubber oil, the best protection of
56.3% was rendered by TBHQ at 200 ppm and 58.6% by ECG (200 ppm).

3.3. Structured Lipids

Structured lipids (SL) are triacylglycerols containing combinations of short-

chain fatty acids (SCFA), medium-chain fatty acids (MCFA) and long-chain
fatty acids (LCFA) located in the same glycerol molecule, and these may be

55
produced by chemical or enzymatic means. SLs are developed to fully optimize
the benefits of their fatty acid varieties in order to affect metabolic parameters
such as immune function, nitrogen balance and lipid clearance from the
bloodstream. These specialty lipids may be produced via direct esterification,
acidolysis, and hydrolysis or interestification. MCFA are those with 6 to 12
carbon atoms and are often used for production of SLs. As mentioned earlier,
MCFA are highly susceptible to oxidation.

These fatty acids are not stored in the adipose tissues and are often used in the
diet of patients with maldigestion and malabsorption. They have also been
employed in total parenteral nutrition and formulas for preterm infants.
Production of SLs via acidolysis of blubber oil with capric acid was recently
reported. Lipozyme-IM from Mucor miehei was used as a biocatalyst at an oil
to fatty acid mole ratio of 1:3 in hexane, at 45°C for 24 h and 1% (w/w) water.
Under these conditions, a SL containing 2.3% EPA and 7.6% DHA at 27.1%
capric acid (CA) was obtained. In this product, CA molecules were primarily
located in the sn-1 and sn-3 positions, thus serving as a readily available source
of energy to be released upon the action of pancreatic lipase. Incorporation of
CA into fish oil TAG using immobilized lipase from Rhizomucor miehei (IM-
60) was also reported.

Table 3.3. Enzymatic Modification of Seal Blubber Oil with Capric Acid

Fatty acid Unmodified Modified Sn-1 & Sn-3

10:0 - 27.1 85.1
14:0 3.4 2.7 48.1
14:1 1.0 0.8 58.3
16:0 5.0 3.7 46.8
16:1T7 15.1 11.9 55.5
18:1T9 and T11 26.4 19.3 56.1
18:2T6 1.3 1.7 66.7
20:T9 15.0 9.1 72.5
20:5T3 5.4 2.3 31.9
22:1t11 3.6 1.9 52.6
22:5t3 4.9 3.0 76.7
22:6T3 7.0 7.6 82.1

Note: Percentage of modified fatty acid in sn-1 and Sn-3 positions. Units are
percentages of total fatty acids. The enzyme used was lypozyme-IM from Mucor
miehei

After a 24 h incubation in hexane, 43% CA was incorporated into fish oil while
the content of EPA and DHA in the product was reduced to 27.8 and 23.5%,
respectively. Similar results were obtained upon acidolysis of seal blubber with
lauric acid. In an effort to produce specialty lipids containing both omega-3
PUFA and gamma linolenic acid (GLA), preparation of such products under
optimum conditions was reported.

56
GLA is found in relatively large amounts in borage oil (20 to 25%), evening
primrose oil (8 to 10%) and blackcurrant oil (15 to 18%). Using borage oil, urea
complexation process afforded a concentrate with 91% GLA under optimum
reaction conditions. Lipase-catalysed acidolysis of seal blubber oil and
menhaden oil with GLA concentrate, under optimum conditions of GLA to
TAG mole ratio of 3:1, reaction temperature of 40°C over 24 hrs and 500 units
enzyme per gram oil afforded products with 37.1 and 39.6% GLA
incorporation, respectively. Of the two enzymes tested, lipase PS-30 from
Pseudomonas sp. served better in the acidolysis process than Mucor miehei
Incorporation of GLA was in all positions and its content in the sn-2 position of
both seal blubber oil and menhaden oil was 22.1 and 25.7%, respectively. Thus,
PS-30 served in a nonspecific manner in the acidolysis process. The structured
lipids containing GLA, EPA, and DHA so produced may have health benefits
above those exerted by use of their physical mixtures. Production of structured
lipids containing GLA, EPA, and DHA may also be achieved using borage and
evening primrose oils as sources of GLA and either EPA or DHA or their
combinations. The products so obtained, while similar to those produced by
incorporation of GLA into marine oils, differ in the composition and
distribution of fatty acids involved.

Table 3.4. Fatty Acids of Seal Blubber Oil (SBO), Menhaden Oil (MO) and
Their Acidolysis Products with Gamma linolenic Acid (GLA, 18:3T6)

SBO MO
Fatty Unmodified Modified Sn-1 Unmodified Modified Sn-1
acid and and
Sn-3a Sn-3a

14:0 3.36 2.40 58.3 8.18 4.55 53.3

16:0 5.14 3.04 51.1 19.89 8.78 53.5
18:1T9 22.6 14.1 46.6 9.86 4.24 53.7
18:3T6 0.59 37.1 77.9 0.43 39.6 74.3
20:1T9 17.3 8.30 55.4 1.62 0.83 20.0
20:5T3 5.40 3.80 84.6 12.9 11.0 65.9
22:5T3 5.07 2.99 78.0 2.48 2.07 66.7
22:6T3 7.73 4.36 79.2 10.0 6.56 77.4

3.4. Bioactive Peptides from Marine Resources

Protein hydrolysis leads to the formation of peptides with different numbers of

amino acids as well as free amino acids. Depending on reaction variables as
well as the type of enzyme, the degree of hydrolysis of proteins may differ
considerably. The peptides produced from the action of a specific enzyme may
be subjected to further hydrolysis by other enzymes. Thus, the use of an enzyme
mixture or several enzymes in a sequential manner may be advantageous. The
peptides so obtained may be subjected to chromatographic separation and then

57
evaluated for their amino acid sequence as well as their antioxidant and other
activities.

In a study on capelin protein hydrolyzates, four peptide fractions were separated

using Sephadex G-10. While one fraction exerted a strong antioxidant activity
in a beta-carotene- linoleate model system, two fractions possessed a weak
antioxidant activity and the fourth one had a prooxidant effect. Two-
dimensional HPTLC (high performance thin layer chromatography) separation
showed spots with both pro- and antioxidative effects. Meanwhile, protein
hydrolysates prepared from seal meat were found to serve as phosphate
alternatives in processed meats and reduced the cooking loss considerably.
Furthermore, Alaska pollock skin hydrolysate was prepared using a
multienzyme system in a sequential manner. The enzymes used were in the
order of alcalase, pronase E, and collagenase. The fraction from the second
step, which was hydrolysed by pronase E, was composed of peptides ranging
from 1.5 to 4.5 kDa and showed a high antioxidant activity. Two peptides were
isolated, using a combination of chromatographic procedures, and these were
composed of 13 and 16 amino acid residues

Table 3.5. Antioxidative Peptides from Gelatin Hydrolysate of Alaska

Pollock Skin in Comparison with that of Soy Conglycinin

Peptide Amino acid sequence

Alaska Pollock Skin
P1 Gly-Glu-Hyp-Gly-Pro-Hyp-Gly-Pro-Hyp-Gly-Pro-Hyp-Gly-Pro-
Hyp-Gly
P2 Gly-Pro-Hyp-Gly-Pro-Hyp-Gly-Pro-Hyp-Gly-Pro-Hyp-Gly
Soy Conglycinin
P1 Val-Asn-Pro-His-Asp-His-Glu-Asn
P2 Leu-Val-Asn-Pro-His-Asp-His-Glu-Asn
P3 Leu-Leu-Pro-His-His
P4 Leu-leu-Pro-His-His-Ala-Asp-Ala-Asp-Tyr
P5 Val-Ile-Pro-Ala-Gly-Tyr-Pro
P6 Leu-Glu-Ser-Gly-Asp-Ala-Leu-Arg-Val-Pro-Ser-Gly-Thr-Tyr-
Tyr

3.5. Chitin, Chitosan and Related Compounds

Chitin may be recovered from processing discards of shrimp, crab, lobster, and
crayfish following deproteinization and demineralization. The chitin so obtained
may then be deacetylated to afford chitosan. Depending on the duration of the
deacetylation process, the chitosan produced may assume different viscosities
and molecular weights. The chitosans produced are soluble in weak acid
solutions, thus chitosan ascorbate, chitosan acetate, chitosan lactate, and
chitosan malate, among others, may be obtained and these are all soluble in
water. Chitosan has a variety of health benefits and may be employed in a
number of nutraceutical and health-related applications. Chitosan derivatives

58
may also be produced in order to obtain more effective products for certain
applications. However, to have the products solubilized in water without the use
of acids, enzymatic processes may be carried out to produce chitosan oligomers.
Due to their solubility in water, chitosan oligomers serve best in rendering their
benefits under normal physiological conditions and in foods with neutral pH.
Furthermore, depending on the type of enzyme employed, chitosan oligomers
with specific chain length may be produced for certain applications. Chitosans
with different viscosities were prepared and used in an experiment designed to
protect both raw and cooked fish against oxidation as well as microbial
spoilage. The content of propanal, an indicator of oxidation of omega-3 fatty
acids, was decreased when chitosan was used as an edible invisible film in
herring.

Table 3.6. Characteristics of Three Different Kinds of Chitosans Prepared

from Crab Shell Waste

Properties Chitosan
I II III
Deacetylation 4 hrs 10 hrs 20 hrs
timeb
Moisture (%) 4.50 ± 0.30 3.95 ± 0.34 3.75 ± 0.21
Nitrogen (%) 7.55 ± 0.10 7.70 ± 0.19 7.63 ± 0.08
Ash (%) 0.30 ± 0.03 0.25 ± 0.02 0.30 ± 0.00
AVa (cps)d 360 57 14
DAc (%) 86.3 ± 2.1 91.3 ± 1.2 94.5 ± 1.3
Mvc (dalton) 1,816,732 963,884 695,122
a
Results are expressed as mean ∀ standard deviation of three determinations.
b
Deacetylation for chitosan I, II and III was achieved using 50% NaOH at
100°C.
c
Mv = viscosity molecular weight; AV = apparent viscosity; and DA = degree
of deacetylation.
d
cps = cycles per second.

TABLE 3.7. Content of Propanal mg/kg (dwb) in Headspace of Chitosan-

Coated Herring Samples Stored at 4°Ca

Chitosan Storage Period (days)

0 2 4 6 8 10
Uncoate 12.6±4a 23.7±4.2 29.9±4.2 34.3±1.9c 44.1±4.0 46.3±2.4
b c c c
d
14cps 13.8±2.1. 18.3±2.1 24.6±1.2 30.9±2.9b 33.0±0.8 39.7±0.9
a a b c b b

57cps 12.6±3.0a 15.5±2.1 19.7±2.6 24.9±1.6a 22.8±1.9 24.2±1.9

a a a a

360cps 14.2±2.4a 15.7±2.6 17.6±2.2 20.2±1.4a 18.3±2.4 22.7±1.3

a a a a

59
a
Results are expressed as mean standard deviation of three determinations.
Values with the same superscripts within each column are not significantly
different (P<0.05).

Furthermore, the effects were more pronounced as the molecular weight of the
chitosan increased . In addition, inhibitory effects of chitosan coatings in the
total microbial counts for cod and herring showed an approximately 1.5 and 2.0
log cycles difference between coated and uncoated samples, respectively, after
10 days of refrigerated storage (results not shown). The monomer of chitin, N-
acetylglucosamine, has been shown to possess anti-inflammatory properties.
Meanwhile, glucosamine, the monomer of chitosan, prepared via HCl
hydrolysis, is marketed as glucosamine sulfate. This formulation is prepared by
addition of ferrous sulfate to the preparation. Glucosamine products may also be
sold in formulation containing chondroitin 4- and chondroitin 6-sulfates. While
glucosamine helps to form proteoglycans that sit within the space in the
cartilege, chondroitin sulfate acts like a liquid magnet. Thus, glucosamine and
chondroitin work in a complementary manner to improve the health of the joint
cartilage. The by-products in chitin extraction process from shellfish include
carotenoids/carotenoproteins and enzymes.52–54 These components may also
be isolated for further utilization in a variety of applications.

References

Alasalvar, C., Taylor, T. Eds., Springer, Berlin and New York, NY, 2002, pp
157–174

Chen, H-M., Muramoto, K., Yamauchi, F. Structural analysis of antioxidative

peptides from soybean β-conglycinin. J. Agric. Food Chem. 1995, 43, 574–578.
Corley, D.G., Zeller, S.G., James, P., Duffin, K. Process for Separating a
Triglyceride Comprising a Docosahexaenoic Acid Residue from a Mixture of
Triglycerides. International Patent PCT/US so/04166, 2000.

Hayashi, K., Kishimura, H. Preparation of n-3 PUFA ethyl ester concentrates

from fish oil by column chromatography on silicic acid. Nippon Suisan
Gakkaishi 1993, 59, 1429–1435.

He, Y., Shahidi, F. Enzymatic esterification of T-3 fatty acid concentrates from
seal blubber oil with glycerol. J. Am. Oil Chem. Soc. 1997, 74, 1133–1136.

J.W. Eds., ACS Symposium Series 778, American Chemical Society,

Washington, D.C., 2001, pp.

Jeon, Y-J., Kamil, J.Y.V.A., Shahidi, F. Chitosan as an edible invisible film

for quality preservation of herring and Atlantic cod. J. Agric. Food Chem. 2002,
50, 5167–5178.

60
Kamil, J.Y.V.A., Jeon, Y-J., Shahidi, F. Antioxidative activity of different
viscosity chitosans in cooked comminuted flesh of herring (Clupea harengus).
Food Chem. 2002, 79, 69–77.

Kim, S-K., Kim, Y-T., Byun, H-G., Nam, K-S., Joo, D-S., Shahidi, F.
Isolation and characterization of antioxidative peptides from gelatin hydrolyzate
of Alaska pollack skin. J. Agric. Food Chem. 2001, 49, 1984–1989.

Shahidi, F., Synowiecki, J. Protein hydrolysates from seal meat as phosphate

alternatives in food processing applications. Food Chem. 1997, 60, 29–32.

Shahidi, F., Arachchi, J.K.V., Jeon, Y-J. Food application of chitin and
chitosans. Trends Food Sci. Technol. 1999, 10, 37–51.

Shahidi, F., Kamil, J., Jeon, Y-J., Kim, S-K. Antioxidant role of chitosan in a
cooked cod (Gadus morhua) model systems. J. Food Lipids 2002, 9, 57–64.

Shahidi, F. Role of chemistry and biotechnology in value-added utilization of

shellfish processing discards. Can. Chem. Neur. 1995, 10, 25–29.

Shahidi, F., Kamil, Y.V.J. Enzymes from fish and aquatic invertebrates and
their application in the food industry. Trends Food Sci. Technol. 2001, 12, 435–
464.

Simopoulos, A.P. Omega-3 fatty acids in health and disease and growth and
development. Am. J. Clin. Nutr. 1991, 54, 438–463.

Shahidi, F., Wanasundara, U.N. Concentration of omega-3 polyunsaturated

fatty acids of seal blubber oil by urea complexation: Optimization of reaction
conditions. Food Chem. 1999, 65, 41–49.

Wanasundara, U.N., Shahidi, F. Positional distribution of fatty acids in

triacylglycerols of seal blubber oil. J. Food Lipids 1997a, 4, 51–64.

Wanasundara, U.N., Wanasundara, J., Shahidi, F. Omega-3 fatty acid

concentrates: a review of production technologies. In: Seafoods: Quality,
technology and nutraceutical applications.
Wanasundara, U.N., Shahidi, F. Structural characteristics of marine lipids and
preparation of omega-3 concentrates. In: Flavor and lipid chemistry of seafoods.
Shahidi, F., Cadwallader,

Wanasundara, U.N., Shahidi, F. Lipase-assisted concentration of T-3

polyunsaturated fatty acids in acylglycerol forms from marine oils. J. Am. Oil
Chem. Soc. 1998, 75, 945–951.

61
 Chapter 4
Nutraceutical Foods from Selected Asian Fruits and Fruit
Products

4.1. Annatto Fruits

The annatto ( Bixa orellana L.) is cultivated in many tropical countries in Asia.
The fruits inside are generally found in cavities containing 10 to 50 small seeds,
about the size of grape seeds. The seeds are covered with a thin, highly colored,
orange to red resinous layer from which the natural color is obtained. The main
application of annatto fruits is for coloring cheese and other dairy products such
as ice cream, butter mixes, yogurt, meat (sausages), fish margarine, snacks,
dressings, sauces, and confectionery. Among the naturally occurring colorants,
annatto colorant ranks second in economic importance after caramel. Around
80% of the carotenoids in annatto consist of bixin, a diapocarotenoid that
contains 24 carbon atoms in the skeleton and a (Z)-double bond. Also norbixin,
the corresponding dicarboxylic acid with the (all- E )-configuration has been
isolated. It is well established that the carotenoids possess a wide range of
biological activities, with potential health benefits. Some minor carotenoids in
annatto and some 15 minor compounds have been identified recently.

62
4.2. Apples

Apples ( Malus sylvestris ) are grown in China, Korea, Japan, and India. Most
of apples are eaten fresh. Fresh apples can be made into puree, then dried and
grounded into powder. Apple powder is a special product used mainly in the
treatment of infant diarrhea. Apple pectin in apple powder has a strong
bacteriostatic action on Staphylococcus aureus ,Streptococcus faecalis,
Pseudomonas aeruginosa , and Escherichia coli. Eberhardt et al. suggested that
the strong inhibition of tumor-cell proliferation in vitro could be due to apples’
combination of phytochemicals (phenolic acids and flavonoids), as these are
natural antioxidants. Apple pectin inhibits azoxymethane (AOM)-induced colon
carcinogenesis. Therefore, apple pectin may be expected to have a strong
influence on the intestinal microflora and bacterial enzyme activities. The same
intestinal bacteria may reportedly play a significant role in the pathogenesis of
colon cancer because their enzymes are important in the metabolism of
procarcinogens, and the production of tumor promoters in the colon. Apple
pectin has a stronger bacteriostatic action against pathogenic bacteria than citrus
pectin. The induction of colon neoplasia by AOM is dose-dependently inhibited
by apple pectin. Fecal tryptophanase activity tends to decrease in the apple
pectin group compared with that in the control group. The reduced level of
tryptophan metabolites in the colon might be related to the inhibitory effect of
apple pectin on colon carcinogenesis. Apple pectin exerts an antitumor effect
and prevents cancer metastasis and carcinogenesis by modifying host immune
function, and altering the intestinal flora. The inhibition of hepatic metastasis by
oral administration of apple pectin (apple powder) suggests it may be effective
for the prevention of hepatic metastasis and residual cancer cells remaining after
surgery.

63
4.3. Aronia Fruits

Aronia ( Aronia melanocarpa Michx.) trees are organically grown as a hardy

plant, and aronia berries are not attacked by insects. Aronia trees grow as high
as 6 feet, and the darkcolored berries are picked in late August or early
September. Aronia berries contain one of the highest concentrations of
anthocyanin pigments of any cultivated plant. The pigment is located
throughout the berry. The majority of the anthocyanin pigment remains with the
pomace when the juice is squeezed. Thus, this waste product is an excellent
source of anthocyanin pigments. Aronia berries contain four kinds of
anthocyanins. All of the anthocyanins identified are 3-substitued
monoglycosides and they are present in the following percentages, galactose
(68%), arabinose (28%), glucose (1.5%), and xylose (2.5%). Only two of these
compounds (galactose and arabinose) account for more than 95% of the
material. The anthocyanins obtained from aronia provide one of the least
complex mixtures found in the plant kingdom. Aronia fruits (chokeberry)
provide a healthy fruit beverage and are a natural colorant. Aronia berry juice
has an astringent taste, very similar to that of cranberry and black currant.
Aronia berry is rich in vitamins, minerals, antioxidants, and other health-
beneficial materials. Aronia juice concentrate is attractive to consumers. The
aronia beverage is high in flavonoids, specifically condensed tannins and
anthocyanins, and is considered beneficial to human health.

4.4. Avocados

64
Avocados ( Persea Americana Mill.) are commercially grown in the
Philippines, Hawaii, and Israel. People usually prefer the avocado fruits
sweetened with sugar, or combined with other fruits such as pineapples,
oranges, grapefruits, dates, and bananas. Avocados have a high lipid content of
5 to 25%. Among the saturated fatty acids the myristic level may be 0.1%,
palmitic 14 to 21%, and stearic 0.6 to 1.7%. The oil in the flesh is rich in
Vitamins A, B, G, E. The fruit peel is considered as an antibiotic for vermifuge
and a remedy for dysentery.

4.5. Bananas

Bananas ( Misa acuminate Colla.) are grown in the humid tropical regions and
constitute one of the largest fruit crops of the world. India is the leading banana
producer in Asia. Other producers are Taiwan, Indonesia, and the Philippines.
Most of bananas are eaten fresh. Some are dried in various forms such as
banana powder and some are made into puree. Diced banana products are used
as raisin substitutes in food ingredients. They can be eaten as a snack food or
used in making fruit cake and bakery products. Banana puree is by far the most
important processed product from the pulp of ripe fruits. The puree has a
creamy white to golden yellow colour, free from musty or off-flavors. Banana
puree is an important infant food. Puree canned in drums by the aseptic canning
process is a new product for the baking and ice cream industry. All parts of
banana fruits, peel and flesh, have medicinal applications. Banana pulp soup is
taken to control dysentery and diarrhea and also used for treating malignant
ulcers. Antifungal and antibiotic principles are found in the peel and pulp of
ripe bananas. Norepinephrine, dopamine, and serotonin are also present in the
ripe bananas, which give bananas a functionality in elevated blood pressure and
inhibiting gastric secretion and stimulating the smooth muscle of intestines.

65
4.6. Bilberries

The bilberry ( Vaccinium myrtillus L.) is a low-growing shrub native to Asia

and northern Europe. The small dark blue fruit is eaten fresh or made into juice
and preserves. The dried berries can be used as snacks. Bilberries can be used as
a colorant for several food products. Bilberry juice is one of the most
antimutagenic fruit products and is effective in reducing mutagenicity caused by
the polycyclic aromatic hydrocarbons. Gallic acid, an astringent, and an unusual
phenolic acid, melilotic acid are identified in bilberry fruits and leaves. Other
phenolic compounds are also found in the plant. Bilberry fruits contain
flavonoids (quercitrin, isoquercitrin, hyperoside, avicularin, meratine, and
astragaline), catechin tannis, oligomeric proanthocyanidins, iridoid
monoterpenes (asperuloside and monotropein), phenolic acids (chlorogenic,
salicylic, and gentisic), quinolizidine alkaloids (myrtine, epimyrtine and
occasionally arbutine), and some pectin. Bilberries have a wide range of fiber
values on a fresh weight basis: insoluble dietary fiber 1.9 to 3.2%, soluble
dietary fiber 0.4 to 1.1%, total dietary fiber 2.3 to 3.9%. Bilberry fruit and
leaves are used for a variety of medical conditions. The functional components
of bilberry products appear to be the phenolic compounds, particularly the
anthocyanins. Several anthocyanins are found in the fruits. The pigments are
located primarily in the skin of the berries. Morazzoni and Bombardelli
reviewed the history of medical uses for bilberries from the Middle Ages to the
present. Surveys of 1,994 cases found 183 products containing bilberry extract
as an ingredient. Bilberry anthocyanins also reduce platelet aggregation in vitro.
Anthocyanin extracts inhibit porcine elastase in vitro. The fruits of bilberry are
used to treat many conditions resulting from diabetes. The high levels of
glucose in the blood of diabetics trigger many deteriorative events in the body.
Bilberry extract is believed to help improve eyesight, particularly night vision.
This health benefit is the primary reason for the product’s popularity in Japan
and Korea. Anthocyanins are important for regeneration of visual purple.
Bilberry extracts appear to benefit vision in several ways: improving night
vision by enhanced regeneration of retinal pigments, increasing circulation

66
within the capillaries of the retina, inhibiting of Maillard reactions in the lens to
reduce cataract formation, and protection from ultraviolet light. The antioxidant
properties of bilberry extracts may be responsible for these health benefits.
Antioxidants have been suggested to retard oxidation in the lens and slow
retinal angiopathy that occurs in age-related macular degeneration and diabetic
retinopathy. Tannins in bilberry are considered to be responsible for their ability
to treat acute diarrhea and mild inflammations of the mouth and throat.

4.7. Black Prunes

The black prune ( Prunus armeniace , Thunb.) is also known as the Japanese
apricot. The fruit is sour and tart to taste. Major chemical components are
glucoside prudomenin, malic acid, and succinic acid. Some of its medicinal
functions are to act as an astringent, antipyretic, and vermicidal, to stimulate
contraction of the muscles of intestinal parasites and gallbladder, and to cause
relaxation of the bile duct. It is also an antimicrobial agent. People usually use it
for the treatment of chronic diarrhea and dysentery, feverish thirst, achlorhydria,
no appetite, residue coughing, chronic malaria, biliary ascariasis, hookworms,
abdominal pain, cholecystitis, and gallstones. The fruits are commonly
preserved as snack foods, or made into a beverage or wine. Carambolas The
Carambola (Averrhoa carambola L.) is originated in Sri Lanka. The common
name is “star fruit” due to its shape when cut in cross section. The major
production areas are in East Asia, including Indonesia, Malaysia, Sri Lanka,
Taiwan, the southern part of China, and Vietnam. There are two distinct
cultivars: sweet and sour cultivars. The sour cultivar is rich in flavor, with more
oxalic acid. The sweet cultivar is mild flavoured, rather bland, with less oxalic
acid. The sweet cultivar is used for fresh consumption and juice processing,
while the sour cultivar is processed into jam, jelly, canned fruits, sweetened
nectar, or other preserves. Juice products are by far the most important
processed commodities of carambola fruits. Fermented carambola juice is a
traditional health drink in China and India. It is served as a cooling beverage,
and good for smoothing some uncomfortable body conditions, such as to
quench thirst, increase the salivary secretion, and allay fever. The fruit pulp is
considered to allay biliousness and diarrhea, and relieve a hangover from

67
excessive indulgence in alcohol. In India, the ripe fruit is used to halt
hemorrhages and to relieve bleeding hemorrhoids. Carambola is recommended
as a diuretic in kidney and bladder complaints, and is believed to have a
beneficial effect in the treatment of eczema.

4.8. Cherimoyas

Cherimoya (A nnona cherimola Mill.) is growing in the Philippines, India, and

Sri Lanka. The flesh of ripe cherimoya fruits is most commonly eaten out of
hand. Fruits also can be made into juice and salad, or fermented into alcoholic
beverage, or dried into powder. The cherimoya fruit’s powder is used to kill lice
and is applied on parasitic skin disorders, and also to relieve pneumonia.

4.9. Chinese Dates

Chinese dates ( Zizyphus vulgaris var. spinosa) are grown in the Hunan,
Shandong, Zhejiang, and Shanxi provinces of China. Chinese dates are dried in
the sun, or by dryers depending on the technique used for drying, the final dried

68
dates products have different names: “red dates” and “black dates.” The final
products have moisture levels of 18 to 20%.

4.10. Red Dates:

Fully ripe Chinese dates are blanched and dried as whole fruits by the sun. The
product has a dark-red color, golden-yellow meat, elastic texture, and sweet
taste.

4.11. Black Dates:

Fully ripe Chinese dates are selected, blanched, then dried and fumed at 60 to
70°C for 20 to 24 hrs. The product has a dark-violet color, wrinkled surface,
sweet taste, and elastic texture. Chinese date products have a special function in
invigorating blood circulation according to Chinese traditional medicine. Some
major medicinal functions are to strengthen the spleen and stomach, moisturize
the heart and lungs, and regulate various medications. Chinese dates products
are used for treatment of weak stomach and spleen, anemia, inadequate energy
(fatigue), and salivation. Dates and rice cooked into gruel is nutritious.

Citrus Fruits
Citrus fruits are widely known to contain various types of chemopreventers
such as -limonene, limonoids and their glucosides, flavonoids, and carotenoids.
Levels of auraptene vary from high (408 to 585 mg/kg fresh wt.) in the peels of
natsumikan and hassaku oranges, moderate (101 to 120 mg/kg fresh wt.), and
absent (<1 mg/kg fresh wt.) in the peels of the Satsuma mandarin (tangerine),

69
Valencia orange, navel orange, lemon, and lime. The auraptene content in the
sarcocarps of the above fruits is similar to that in the peels. Commercial juices
from natsumikan and hassaku oranges showed higher contents of auraptene
(0.87 to 1.80 mg/L). Auraptene, a citrus coumarin, is an effective cancer
chemopreventer. These characteristics together with high chemopreventive
potency make it an appropriate source substance for the creation of
physiologically functional foods. The citrus juices have hypocholesterolemic
effects in heart disease.

4.12. Oranges

The juice of oranges ( Citrus sinensis ) grown in China, India, and Japan has a
deep orange color. Orange juice concentrate is prepared from either freshly
extracted and pasteurized single-strength juice or from a storage and pasteurized
singlestrength juice. Spraying and drum drying produce dehydrated orange
juice. The final powder has less than 0.6% moisture and maintains its quality
when stored at room temperature. Orange products are traditionally taken to
allay fever and catarrh. The roasted pulp is prepared as a poultice for skin
diseases. The immature fruits are also made into infusion (or tea) to relieve
stomach and intestinal complaints.

70
4.13. Red Tangerine

Red tangerine ( Citrus reliculata Blanco.) peels are the redcolored external
layer of the pericarp. The major chemical components are citral, geraniol,
linalool, methylanthranilate, stachydrine, putrescine, apyrocatechol, and
glucosides (naringin, poncirin, hesperidin, neohespiridin, and nobiletin). Some
of the medicinal functions are to correct energy circulation, strengthen the
lungs, and resolve phlegm. Red tangerine peels are used for treatment of
fullness in chest and indigestion, eliminating sputum and coughing. People use
it as a tea, or prepare a red tangerine peel gruel made by decocting and cooking,
in which the ingredients include red tangerine peel and bitter apricot kernel. The
red tangerine peels can also be steamed with chicken and wine.

4.14. Mandarin Oranges

Mandarin orange ( Citrus reticulate ) is considered a native of southeastern Asia

and the Philippines. It is now abundantly grown in China, Japan, and India.
Mandarin oranges are eaten fresh, or used in fruit salads, gelatins, puddings, or
cakes. The essential oil from the peel is produced commercially as a flavoring
ingredient. Mandarin orange peels are dried peels that are bitter and acrid to
taste. Major chemical components are bitter-tasting flavone glycosides
(neohesperidin and naringin, neohesperidose), nonbitter flavonoids (hesperidin,
rutoside, sinensetin, nobiletin, and tangeratin), 1 to 25 essential oils (limonene),

71
and pectin. Some medicinal functions are to correct energy circulation,
strengthen the spleen, counteract excessive moisture in the body, and resolve
phlegm. People often use it for easing of fullness in chest and abdomen,
regurgitation and vomiting, chest and abdominal pains, poor appetite,
productive coughing, indigestion, and diarrhea. It also can be used as a popular
dish called mandarin orange peels beef, or as preserved fruit products to
enhance the digestive system and blood circulation.

4.15. Kumquats

Kumquats ( Fortunella margarita ), also called “Golden Orange” in China,

originated in Northern China, and are produced primarily in China and the
Philippines, with limited production in other areas of the world such as in
Southeast Asia and Japan. Kumquats are eaten fresh or are candied or cured
whole, and are unique in that the entire fruit, including the peel, is generally
eaten. The cured products have a golden colour, translucent texture, dry surface
without sugar particles, and strong fresh flavour. The cured kumquat products
are usually used as confections to improve appetite.

4.16. Pummelos

Pummelos ( Citrus maxima Merr.) are the largest citrus fruit, native to
southeastern Asia, and are grown in China, India, Indonesia, Japan, Malaysia,
Thailand, Taiwan, and the Philippines. People like to eat the juicy pulp, which
is used for salads, desserts, or made into preserves. Pummelo juice makes an
excellent beverage. The pulp and peel have a sedative effect in cases of

72
epilepsy, chorea, and convulsive coughing. Pummelo juice is taken as a
febrifuge in the Philippines and Southeast Asia.

4.17. Cranberries

Cranberry ( Vaccinium macrocarpon A.) products as dietary supplements are

widely available in a variety of food and beverage forms. Cranberry fruits
contain phytochemicals, which include flavonoids and phenolic acids with
antioxidant and other physiologically beneficial activities. Classes of cranberry
flavonoids include anthocyanins, flavonols, flavan-3-ols, and
proanthocyanidins. Each of these classes of compounds has interesting
physiological activities. Anthocyanins are the pigments that give cranberries
their rich, red color. Cranberry fruits also contain ellagic acid, which has been
shown to have a broad range of anticarcinogenic activities. Cranberries and
cranberry products have long been associated with a variety of health benefits.
Cranberries appear to have a relatively unique menu of components that have
interesting value in human nutrition, particularly in maintaining health and
wellness. Cranberries, and particularly cranberry juice products have long
enjoyed a folk reputation as a treatment for urinary tract infections. Although
the low pH of the fruit is considered as the antimicrobial agent, fructose and
high molecular weight phenolic compounds have been found to prevent the
adhesion of Escherichia coli cells in vitro . Fructose and polyphenols prevent
mamnnose-resistant adhesions on certain P-fimbriated E. coli isolated from
attaching epithelial tissues in the urinary tract. Purified cranberry
proanthocyanidins are reported to possess antiadherence properties in an in vitro
assay. It is said that cranberries can dress wounds and prevent inflammation,
and were used aboard ships to help prevent scurvy, although their level of
vitamin C is well below that of most citrus fruits. Cranberries are thought to
help relieve the symptoms of urinary tract infections, even prevent their
occurrence. Much anecdotal information is responsible for the medical myth
that surrounds the fruits and their products.

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4.18. Durians

Durians ( Durio zibethinus L.) are large fruits covered with hard, hexagonal,
stubby spines. It is a heavy fruit reaching the size of a honey melon. Skin of the
ripened fruit turns from brown to bright yellow. Durian is a delicious tropical
fruit and well known throughout Southeast Asia, Thailand, Malaysia, and South
Vietnam; the southern Philippines are important producers of durians. Durian
flesh is mostly eaten fresh but is also canned in syrup, or dried, or made into
paste. Durian is a good source of iron, B vitamins, and ascorbic acid. The thick,
pudding-like texture of the aril is due to gums, pectin, and hemicellulose. The
flesh of durian is said to serve as a vermifuge. Durian flesh is also widely
considered an aphrodisiac in Thailand. In India, durian products are marketed to
provide energy, to keep the body vigorous and tireless, the mind alert with
faculties undimmed and spirit youthful.

4.19. Embalics

Embalics ( Phyllanthus emblica L.), native to Southeastern Asia, are grown in

tropical Asia such as Bangladesh, Cambodia, India, Malaysia, Pakistan, Sri
Lanka, Southern China, Thailand, Vietnam, and the Philippines. Both ripe and
halfripe fruits can be canned or made into jam and juice. Embalics can be
combined with other fruits in making chutney and pickles. The embalics are
important in Asian traditional medicine as an antiscorbutic and in the treatment
of diverse ailments, especially with the digestive organs. Embalic’s are often
considered diuretic and laxative. The embalics pulp and juice, especially after

74
fermentation, are helpful for indigestion, anemia, jaundice, dyspepsia, coughs,
nasal congestion, retention of urine, and some cardiac problems. The embolic
powder is an effective expectorant as it stimulates the bronchial glands.

4.20. Figs

Figs ( Ficus carica L.) are believed to be indigenous to Western Asia, and
grown in mild temperate climates, and have been commercially produced in
most of the countries bordering the Mediterranean Sea. Fig flesh is usually
eaten out of hand, but the fruits are also cooked in pies, cakes, bread, cookies,
or ice cream. Fruits also can be prepared into jam, marmalade, and paste. They
are usually sun-dried, but dehydration is also practiced to produce low-moisture
fig products. Turkey is one of the most important fig-producing countries. Dried
figs are eaten as a snack, or used as cake fillings. Dried figs are a good nutrient
and energy source because of their carbohydrate content. Figs are an especially
good source of fibre, which aids in the anticonstipation process. Dried figs
contain 5.6% fiber. In addition, the potassium salts of organic acids in figs help
maintain acid-alkaline balance in the body by neutralizing the excess acids
present. Dried figs exert a positive effect on the alkaline reserves in the body.
Figs and fig extracts have been used for medicinal purposes such as in the
treatment of Ehrlich sarcoma. Dried figs have long been appreciated for their
laxative action. The latex is widely used for treating warts, skin ulcers and
sores, and taken as a purgative and vermifuge. A decoction of the fruits is
gargled to relieve sore throat. The fig fruits are used as poultices on tumors and
other abnormal growths.

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4.21. Grapes

Grapes (Vitis vinifera) are processed primarily into wine, juice, raisins, and
brandy. Other products include grape-seed oil, grape pomace, hydrocolloids,
and anthocyanins. The components of grapes and grape products play a
significant role in preventing or delaying the onset of diseases including cancer
and cardiovascular diseases. Phenolic compounds and other health-promoting
compounds are secondary plant metabolites that significantly contribute to the
flavour and color characteristics of grapes, grape juices, and wines. The
phenolic compounds of grapes include phenolic acids, anthocyanins, flavonols,
flavan-3-ols, and tannins. The flavonoids (C6 -C3-C6), which include the
amthocyanins, flavonols, and flavan-3-ols, are powerful antioxidants, and are
found in high concentration in grapes and grape products. These compounds
exhibit a wide range of biochemical and pharmacological effects, including
anti-inflammatory and antiallergic effects. Other grape flavonoids such as
quercetin, kaempferol, and myricetin also inhibit carcinogen-induced tumors.
Grape is rich in anthocyanins, which have known pharmacological properties
and are used by humans for therapeutic purposes. Applied orally or by
intravenal or intramuscular injection, pharmaceutical preparations of
anthocyanins reduce capillary permeability and fragility.35 This anti-
inflammatory activity of anthocyanins accounts for their significant antiedema
properties and their action on diabetic microangiopathy. It has also been
reported that anthocyanins possess antiulcer activity, and provide protection
against UV radiation. Ellagic acid and resveratrol are two important
components to reduce the risk of cancer and coronary heart diseases. Ellagic
acid (C14H6O8) is an acid hydrolytic product of ellagitannin found in grape
juice. Resveratrol (3,4,5-trihydroxystilbene), a naturally occurring phytoalexin
produced in response to injury, has drawn much attention as a functional
component. It is found in large quantities in grapes, and its presence in wine is
thought to be responsible for the low mortality from coronary heart disease in

76
wine-drinking populations. Resveratrol is reported to be a cancer
chemopreventive agent having shown activity in assays representing three
stages of carcinogenesis. It is also shown to be an antioxidant, inhibiting
lipopolysaccharide or phorbol esterinduced superoxide radical and hydrogen
peroxide production by macrophages. In muscadine grapes, the skins have the
highest concentration of resveratrol.

4.22. Guavas

Guavas (Psidium guajava L.) are grown in Malaysia, Indonesia, India, Vietnam,
Thailand, South China, and the Philippines. Guava flesh is often eaten fresh as
dessert and salads. Many commercial products use guava flesh in pies, cakes,
puddings, sauce, ice cream, juice, nectar, jam, jelly, marmalade, chutney, relish,
and other products, which may frequently be seen on the markets in India,
Pakistan, and Indonesia. The products made from immature fruits are
commonly used to halt gastroenteritis, diarrhea, and dysentery throughout the
tropical area. It contains several glucosides including avicularin, guaijavarin,
and amritoside, and their hydrolyzed genin, quercetin. Fruits of Fan Shi Liu
exhibit antidiarrheal and antibacterial effects, which are spasmolytic, chiefly
from the effect of the glucosides and their genin and quercetin. The fruit has a
slight antihyperglycemic effect.The water-based extract also exerts an
antimutagenic activity and can counteract the mutagenicity of the direct action
of mutagens. The fruit is used to treat dysentery and acute gastrointestinal
inflammation.

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4.23. Hawthorn Fruits

Hawthorn fruits (Crataegus pinnatifida Bge.) are grown in China. Hawthorn has
long been used to make candies in China. It can be consumed as a snack food
such as hawthorn cookies and hawthorn cake. Hawthorn fruits have a sweetsour
taste, and a fresh flavour. The dish of sweet and sour pork with hawthorn is
considered a medicinal food, in which hawthorn and licorice are first cooked. It
is also used as a sauce for deep-fried pork. The fruit contains chlorogenic acid,
caffeic acid, phlobaphene, L-epicatechol, choline, choline acetate, (β)-sitosterol,
sorbitol, vitamin C, crategolic acid, hyperin, tartaric acid, citric acid, and certain
chromones. Hawthorn is a rich source of the flavan-3-ol (α)-epicatechin and
proanthocyanidins related to (α)-epicatechin, e.g., epicatechin- (4β→8)-
epicatechin (procyanidin B2). This fruit has also long been used in Chinese
herbal medicine to provide one of the best tonic remedies for the heart and
circulatory system, and for treating swelling. Hawthorn fruits are said to control
blood stasis, relieve pains associated with swelling, promote digestive function,
and mitigate other conditions, especially in reducing blood pressure. Some of
the pharmacological activities, e.g., the hypotensive effects, have been
attributed to the chromones. They act in a normalizing way upon the heart,
depending on the need, stimulating or depressing its activity. The major
medicinal functions are to help digestion, stimulate blood circulation, stop
diarrhea, lower blood cholesterol, smooth the surface of the atherosclerotic area,
increase blood flow in heart, increase the myocardial contractibility, and lower
blood pressure.Hawthorn products are usually used for treatment of indigestion,
infantile marasmus, menstrual cramps, diarrhea, dysentery, hernia, hyperchole
sterolemia, angina pectoris, and hypertension. It is often used as a cardiac tonic,
and the blossoms are also effective. Recently a study on 104
hypercholesterolemic patients demonstrated that a daily dose equivalent to 46 g
of the fruit for 45 days caused normalization of cholesterol value in 75% of the
patients, with an additional 15% of the patients experiencing a 20
milligrams/deciliter (mg/dl) reduction. Daily supplementation of an extract of
the fruit (equivalent to 15 g fresh fruit daily) for 12 weeks in 16 coronary artery

78
patients with angina led to outstanding improvement in the conditions of most
of the patients, including normalization of exertional electrocardiogram and
resting electrocardiogram. There were also substantial reductions in serum
triglycerides and cholesterol. Oral supplementation of extracts of the fruit
showed effectiveness in lowering blood pressure in hypertensive patients. In
addition to these human studies, many animal studies also demonstrated that the
hawthorn fruits and their extracts can reduce heart muscle fatigue, strengthen
the heart muscles, contraction amplitude and pumping power, dilate the
coronary artery, and enhance blood supply to the heart muscles. Extracts of
hawthorn fruits are now sold in world markets as a health food or cardiac tonic.

4.24. Indian Jujubes

Indian jujubes (Zizyphus mauritiana Mill.), with other names such as Indian
plum, Indian cherry, and Malay jujube, are grown in India, Indonesia, Malaysia,
Southern China, Thailand, and the Philippines. The ripe fruits are usually eaten
raw, or stewed. Some canned products, juice, and dried powder are also
available in the markets. The fruits are traditionally used for cuts and ulcers, for
pulmonary ailments and fevers. The dried fruit powder is a mild laxative.
Sometimes the fruit pulps are blended with salt and chili for indigestion and
biliousness.

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4.25. Jackfruits

Jackfruits (Artocarpus heterophyllus L.) are produced in the Philippines,

Malaysia, Thailand, Cambodia, Laos, and Vietnam. Fruit flesh can be made into
ice cream, chutney, jam, jelly, paste. Firm types of jackfruits are preferred for
canning. Products more attractive than the fresh pulp are called ‘vegetable
meat.’ The fruits also can be dried. The Chinese consider jackfruit pulp a
nutritious tonic, cooling and nutritious, and effective in overcoming the
influence of alcohol in humans.

4.26. Kiwifruits

Kiwifruits (Actinidia chienesis Planch.), with a Chinese name “gooseberry” or

“Yang Tao,” are grown in the Yangtze River valley. Kiwifruits are rich in
Vitamin C and usually eaten fresh, or used as appetizers, in salads, pies,
pudding, and cakefilling. Quinic acid predominates in young fruits, then
disappears with the formation of ascorbic acid. Kiwifruits contain the
proteolytic enzyme actinidin that is said to aid digestion. Kiwifruit flesh is also
rich in folic acid, potassium, chromium, and Vitamin E. Kiwifruit juice of

80
optimal flavor is produced from ripe fruits of sound quality. With other fruit
juice, a sparkling kiwifruit juice can be made by carbonation. In China, the fruit
juice is valued for promoting expulsion of the kidney or gallstone.

4.27. Loquats

Loquats (Eriobotrya japonica Lindl.), also called Japanese plums, probably

originated in China, and are adapted for a subtropical to mild-temperate climate.
Today China, India, Israel, and Japan are the leading producers of loquats.
Loquats are usually eaten fresh. Japan, Taiwan, and Israel have exported canned
loquats in syrup to the world markets. Canned loquats are consumed largely as
dessert fruits. Canned products retain a golden color and fresh flavor. The fruits
are also used in gelatin desserts, as pie-filling, or chopped and cooked as a
sauce. The loquat products are traditionally considered to act as a sedative and
are taken to halt vomiting, quench thirst, or relieve coughing.

4.28. Longans

Longan (Euphoria longan Lour.) fruits are produced in Southern China,

Taiwan, India, Thailand, Cambodia, Laos, Vietnam, Malaysia, and the
Philippines. Longans are mostly eaten fresh. The dried products are black,
leathery, and smoky in flavour. They are mainly used in the making of infusion
beverages. The main chemical components in Longans are vitamin B, glucose,

81
sucrose, and tartaric acid. The fruit products can be administered as a
stomachic, febrifuge, and vermifuge, and are regarded as an antidote for poison.
A decoction of the dried flesh is traditionally taken as a tonic and treatment for
insomnia and neurasthenic neurosis. Some major medicinal functions are to
nourish the spleen, cultivate the heart, and supplement the intellect.
Traditionally the fruit products are used for anemia, hyperactive mental activity,
and forgetfulness.

4.29. Litchi

Litchi or lychee (Litchi chinensis Sonn.) originates in the Guangdong province

of China and has been grown in China for more than 4,000 years. The
Guangdong and Fujian provinces in southern China remain the largest
producers of litchi, followed by Vietnam, Thailand, India, Burma, Japan, the
Philippines, Taiwan, Pakistan, and Bangladesh. Dried lichi fruits, frequently
referred to as “lychee nuts,” or “lichi nut,” offer interesting opportunities in
domestic and foreign markets. During drying, the pericarp or outer skin
gradually loses its original color and becomes cinnamon-brown and brittle,
while retaining its shape. The pulp turns dark-brown to nearly black as it
shrivels around the seed and becomes very pleasant in flavour and raisin-like in
texture. Lichi are most relished fresh. Pureed lichi are added to ice cream and
hot milk. Canned lichi in sugar syrup has been exported from China and India
for many years. Ingested in moderate amounts, lichi are traditionally taken to
relieve coughing and have beneficial effects on gastralgia, tumors and
enlargements of glands. Fermented lichi are also used in the Chinese medicine.

82
4.30. Mangoes

Mangoes (Mangifera indica L.) are originally from the Indo- Malaysian region.
The earliest growing area was Northeastern India and Burma eastward to
Indochina. The production of mangoes later extended into many Asian countries
and regions such as Southern India, the Philippines, Indonesia, China, Thailand,
Malaysia, Sri Lanka, and Israel. India, the Philippines, Pakistan, and Thailand
are the leading exporters of processed mango products. Most people enjoy
eating mango flesh as appetizers or dessert. The ripe flesh may be spiced and
preserved in jars or canned in syrup, or made into jam, marmalade, jelly, or
nectar. Dried mangoes are utilized commercially as a substitute for the mangoes
used in chutney manufacture. Dried slices are prepared from ripe fruits. The
peeled or unpeeled slices of raw mango are dried in the sun or in a cabinet
dryer, then turned into powder used as a souring agent in Indian cuisine. Mango
juice has a red-yellow colour, and high in fresh like flavour. Mango juice
powder is used in infant and invalid foods. Mango products have the medicinal
properties of a laxative, diuretic and a fattening agent according to traditional
medicine. Mango juice has a cooling effect and is used during hot weather in
the North Indian region. It is also alleged to help cure cholera and plague. Dried
mango peel and flowers, containing up to 15% tannins, can be used as
astringents in cases of diarrhea, chronic dysentery, catarrh of the bladder, and
chronic urethritis resulting from gonorrhea.

4.31. Mangosteens

83
Mangosteens (Garcinia mangostana L.) are grown in Burma, India, Malaysia,
Sri Lanka, Thailand, the Philippines, and Vietnam. The mangosteen flesh is
often eaten fresh as dessert. The flesh amounts to 31% of the fruits. The fruit
flesh contains phytin up to 0.68% on a dry basis. The flesh is canned, or made
into jam in Malaysia and the Philippines. The dried fruit powder is used to
overcome dysentery in traditional medicine, and is also applied on eczema and
skin disorders, to relieve chronic diarrhea, cystitis, gonorrhea, and gleet, it is
sometimes used for astringent lotion.

4.32. Mulberry

Mulberry (Morus alba L.) is grown in subtropical areas. Mulberry is sour and
tart, yet has a pleasant taste. Some chemical components such as morin,
dihydromorin, dihydromorin, dihydrokaempterol, 2,4,4′,6-
tetrahydroxybenzophenone, maclurin, mulberrin, mulberrochromene, and
cyclomulberrochromene have been isolated from mulberry. Major medicinal
functions are to strengthen kidneys, aid vision, and nourish blood. People use it
for treatment of agitation and insomnia, deafness and blurred vision, white
patches in hair and beard, hot intestines and constipation, pain in back and
knees, and stiffness of muscles and joints. Famous mulberry gruel is made with
mulberry fruits, rice, chicken, and other ingredients, including red jujubes, lotus
seeds, and pine seeds. The congee is very effective for bronchitis, sinusitis, and
asthma. It is said to strengthen the lungs and is used as an antitussive. Mulberry
is also processed into fruit beverage.

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4.33. Papayas

Papayas (Carica papaya L.) are grown in Hawaii, India, Malaysia, Sri Lanka,
Thailand, and the Philippines. Ripe papayas are most eaten fresh. The ripe flesh
is usually made into sauce, or pickled, or preserved as marmalade and jam.
Papaya flesh is rich in carotenoids. The major carotenoid is cryptoxanthin.
Papaya flesh is also prepared into juice, puree, and nectar. Papaya juice is
extracted, then prepared into nectar, a ready-to-drink beverage. Papaya juice has
a deep, rich orange color, and contains papain. It is also high in vitamin A and
C, and is considered a “health food.” Papaya juice concentrate is commonly
sold to hospitals and health food stores in the Philippines.

4.34. Passion Fruits

Passion fruits (Passiflora edulis Deg.) are grown in Southern Asia. Passion fruit
juice, due to its unique intense flavor, high acidity, and yellow/orange pulp, has
been described as a natural concentrate. Passion fruit juice makes a highly
palatable beverage when sweetened and diluted. India, Sri Lanka, Indonesia,
Thailand, Malaysia, Taiwan, and the Philippines are important sources of
passion fruit products in the world market. The yellow flesh has less ascorbic
acid than that in the purple flesh, but is richer in total acid (mainly citric acid)

85
and carotene content. Carotenoids in the flesh are 0.6 to 1.16%. The flesh is a
good source of niacin and riboflavin. The juice can be sweetened, and then
diluted with water or other fruit juices, to make cold drinks. Passion fruit juice
can be concentrated, then used in the making of sauces, gelatin desserts, candy,
ice cream, sherbet, cake filling, meringue or chiffon pie, cold fruit soup, and
cocktails. The frozen juice can be kept for 1 year, and is a very appealing
product. The juice can also be dehydrated using a freeze-dryer or vacuumdryer
process. According to Chinese traditional medicine, passion fruits (or dried
powder) can be prescribed for insomnia, convulsions, nervous breakdown,
menopause, fevers, tension, and high blood pressure. It is rich in the nutrient
complexes, especially calcium and magnesium. The juice is taken as a digestive
stimulant, and used in treatment for gastric cancer. There is currently a revival
of interest in the pharmaceutical industry in the use of glycosides as sedatives or
tranquilizers.

4.35. Persimmons

Persimmons (Diospyros kaki L.) are grown all over Asia. Japan is the largest
producer and Kaki is its popular name in Japan. Other persimmon-producing
countries are China, Israel, the Philippines, Indonesia, India, Burma, Vietnam,
and Korea. The fully ripe persimmons are usually eaten fresh. The flesh may be
added to salads, blended with ice cream, yogurt, cakes, cookies, desserts,
puddings, jam, or marmalade. The Japanese dry large quantities of persimmons,
which are used as confection or food. Dried persimmon products have white
“persimmon sugar” on the surface, with a soft texture, and a sweet taste. Large
quantities of persimmons are preserved by drying in the sun. The dried products
are flattened into form by pressing, sugar crystals then appear on the surface. In
Indonesia, ripe fruits are stewed until soft, then pressed flat and dried in the sun.
In Israel, the intestinal compaction from consumption of persimmons has been
eliminated by drying the fruits before marketing, and some dried fruits are now

86
being exported to Europe. A decoction of the calyx and fruit products is
traditionally taken to relieve hiccups, coughs, and labored respiration in Asian
countries.

4.36. Pineapples

Over the past 100 years, pineapple (Ananas comosus Merr.) has become one of
the leading commercial tropical fruits in the world. Major producing areas are
Malaysia, Hawaii, Taiwan, the Philippines, and Thailand. Field ripe fruits are
best eaten fresh. The flesh of pineapples is cut in pieces and eaten fresh as
dessert, in salads, or cooked in pies, cakes, puddings, or made into sauces or
preserves. In Malaysia, pineapples are used in curries and meat dishes. In the
Philippines, the fermented pineapple pulp is made into a popular sweetmeat
called nata de pina. Much of the Asian-grown pineapples are canned and are an
important value-added product in world markets. The chief sources of the
world’s canned pineapple and pineapple juice are Bangladesh, India, Malaysia,
Taiwan, Thailand, and the Philippines. Thailand is the leading producer and
exporter in the world canned pineapple product market. There is a growing
demand for pineapple juice. Pineapple juice, nectar, and concentrate are now
commercially prepared. Pineapple juice as syrup is used in confections and
beverages, or made into powder. Pineapple juice is traditionally taken as a
diuretic and to expedite labor, also as a gargle in cases of sore throat and as an
antidote for seasickness.

87
4.37. Pomegranates

The pomegranate (Punica granatum L.) is a subtropical fruit native to the

Middle East. It has long been cultivated in the Middle East, the Mediterranean
region, and other areas in Asia. The most important pomegranate growing
regions are China, Afghanistan, Pakistan, Bangladesh, Iran, Iraq, India, Burma,
and Saudi Arabia. There are some commercial orchards in Israel on the coastal
plain and in the Jordan Valley. People like sucking the fruit sacs from the fresh
pulp of pomegranates. In some countries, pomegranate juice is a very popular
beverage. An attractive colored juice (purplish red), large juicy grains, mild
acid-sweet taste, and tannin content of not more than 0.25% are the qualities
desired in the fruits used for the juice processing. For beverage purposes, the
juice is usually sweetened. In Saudi Arabia, the juice sacs may be frozen intact
or the extracted juice may be concentrated and frozen for future use.
Pomegranate juice is widely made into grenadine syrup for use in mixed drinks.
It is also made into thick syrup for use as a sauce. Pomegranate is a source for
antioxidants considered to be antiatherogenic. The juice is rich in citric acid and
sodium citrate, which can be used for pharmaceutical purposes. Pomegranate
juice has been used for treating dyspepsia, and is considered beneficial in
leprosy. Recent in vitro studies demonstrated a significant dose-dependent
antioxidant capability of pomegranate juice against lipid peroxidation in plasma
(by up to 33%), in low-density lipoprotein (by up to 43%), and in highdensity
lipoprotein (by up to 22%). Pomegranate juice not only inhibited low-density
lipoprotein oxidation, but also reduced two other related modifications of the
lipoprotein, i.e., its retention to proteoglycan and its susceptibility to
aggregation. The antioxidative effects of pomegranate juice against lipid
peroxidation in whole plasma and in isolated lipoproteins have been also shown
in vivo in humans. Pomegranate juice consumption by humans increases the
activity of their serum paraoxonase, which is high-density lipoprotein-
associated esterase that acts as a potent protector against lipid peroxidation.

88
4.39. Sea Buckthorn Fruits

Sea buckthorn (Hippophae rhamnoides L.) is distributed widely throughout the

Himalayan regions in Asia, and usually on river banks and coastal dunes along
the Baltic Coast and on the Western coast along the Gulf of Bothnia. Sea
buckthorn is a unique and valuable plant species currently being domesticated
in various parts of the world. Sea buckthorn fruits are yellow or orange berries,
rich in carbohydrates, protein, organic acids, amino acids, and vitamins. The
contents of these components vary with fruit maturity, fruit size, species, and
geographic locations. Medicinal uses of sea buckthorn are well documented in
Asia. The most important pharmacological functions attributed to sea buckthorn
oil include: anti-inflammatory, antimicrobial, pain relief, and the promotion of
tissue regeneration. Sea buckthorn oil is also recommended as a treatment for
oral mucositis, rectum mucositis, vaginal mucositis, cervical erosion, radiation
damage, burns, scalds, duodenal ulcers, gastric ulcers, chilblains, skin ulcers
caused by malnutrition, and other skin damage. Sea buckthorn oil extracted
from seed is popular in cosmetic preparations, such as facial cream. According
to the recent report from China, in a study with 350 patients, beauty cream
made with sea buckthorn oil had positive therapeutic effects on melanosis,
senile skin wrinkles, and freckles. More than 10 different functional foods have
been developed from sea buckthorn fruits in Asia such as liquids, powders,
plasters, films, pastes, pills, liniments, suppositories, and aerosols. Other
products made from sea buckthorn include beverages and jam from fruits and
fermented pulp products.

89
4.40. Santol Fruits

Santol fruits (Sandoricum koetjape Merr.) are grown in Cambodia, India,

Indonesia, Laos, Malaysia, Thailand, Vietnam, and The Philippines. The fruits
are abundant in the local markets. The fruits are usually eaten fresh, sometimes
with spices in India. The fruits are also made into jam, jelly, marmalade, or
canned, after removing the seed and peeling. The preserved pulp is used for
medicinal purposes as an astringent.

4.41. Soursop Fruits

Soursop (Annona muricata L.) fruits are the largest tropic fruits, and are very
common in the markets of Malaysia, Thailand, the Philippines, and Southeast
Vietnam. Soursop fruits are eaten fresh, or in refreshing juices throughout the
tropical area. The pulp is made into tarts, jelly, syrup, and nectar. The strained
and frozen pulp and canned vacuumconcentrated juice are commercial products
in the Philippines. The juice of the ripe soursop fruits has a diuretic function and
is considered a remedy for hematuria and urethritis. It is also believed that juice
can relieve liver ailments and leprosy.

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4.42. Tamarinds

Tamarind (Tamarindus indica L.) fruits are grown in Cambodia, India, Laos,
Malaysia, the Philippines, and Vietnam. The pulp is rich in calcium,
phosphorous, iron, thiamine, riboflavin, and niacin. The fully ripe fresh fruits
are relished and eaten fresh. The tender, immature, and sour pulp is cooked as
seasoning with rice, fish, and meats in India. The acid-sweet pulp is also
blended with sugar to make into confection, sauce, jam, or nectar. In Southeast
Asia, some people use the tamarinds to counteract the ill effects of an overdose
of false chaulmoogra. Tamarind pulp is considered useful in the restoration of
sensation in cases of paralysis.

4.43. Wolfberry

Wolfberry (Lycium Chinense Miller.) is grown in subtropical areas. Wolfberry

is pleasant to taste. Major chemical components are betaine, zeaxanthin,
physalein, and vitamins (carotene, nicotinic acid, and vitamin C). Major
medicinal functions are to strengthen the kidneys, restore semen, nourish the
liver, and clear vision. People usually use it for treatment of nutritional
deficiency, eye diseases, diabetes, inadequate liver and kidney function, and
seminal emission. A dish called pork kidney with wolfberry (other ingredients
include squid and lycium bark) can energize the body and supplement the
blood. It can be a mild treatment for diabetes and vision defects. Wolfberry can
also be cooked with chicken or rice. It can be decocted as a tea for drinking.

91
References

GB Block, B Patterson and A Subar. Fruit, vegetables, and cancer

prevention: a review of the epidemiological evidence, Nutr. Cancer. 18:1–29.
1992.

World Cancer Research Fund and American Institute for Cancer

Research. Food, Nutrition and the Prevention of Cancer: A Global Perspective.
AICR, Washington, D.C., 1997.

AZ Mercadant, A Steck, H Pfander. J. Agri. Food Chem., 45:1050–1055,

1997.

K Tazawa, H Yamashita, I Ohnishi, Y Saito, T Okamoto, M Masuyama, K

Yamazaki, K Takemori, S Saito, and M Arai. Anticarcinogenic and/or
antimetastatic action of apple pectin in experimental rat colon carcinogenesis
and on hepatic metastasis rat model. In: Functional Foods for Disease
Prevention, Vol 1, Fruits, Vegetables, and Teas.

Metastasis Rat Model, Functional Foods for Disease Prevention, Vol 1,

Vegetables, and Teas. Chapter 9, 96–103, 1997.

MV Eberhardt, CY Lee, RH Liu. Antioxidant activity of fresh apples.

Nature, 405:903–904, 2000.

H Ohkami, K Tazawa, I Yamashita, Y Ohnishi, K Kobashi, M Fujimaki.

Jpn. J. Cancer Res. 86:523, 1995.

GC Schloemer, G Kaczmarowicz, J Niedworok. Anthocyanin products from

aronia melanocarpa. In: Natural colorants for food, nutraceuticals, beverages,
confectionery and cosmetics: proceedings of the third international symposium,
Princeton, SIC Publishing Company, 1998, pp 309–313.

JF Morton. Fruits of Warm Climates. Media, Incorporated, Winterville, NC

1987.

ME Camire. Bilberries and blueberries as functional foods and

pharmaceuticals. In: Functional Foods: Herbs, Botanicals and Teas, G. Mazza,
B.D. Oomah, Eds. Technomic Press, Lancaster, PA, 2000.

J Gruenwald, T Brendler, C Jaenicke. Vaccinium myrtillus, Physicians Desk

Reference for Herbal Medicines, 1st ed., Medical Economics, Montvale, NJ, pp
1201–1202, 1998.

92
SP Plami, JT Kumpulainen, RL Tahvonen. Total dietary fiber contents in
vegetables, fruits and berries consumed in Finland, J. Sci. Food Agric.
59(4):545–549, 1992.

P Morazzoni, E Bombardelli. Vaccinium myrtillus L., Fitoterapia. 67(1):3–

29, 1996.

W Kalt, S MacEwan, G Miner. Vaccinium Extract in Pharmaceutical

Products. Report to the Wild Blueberry Association of North America and the
Wild Blueberry Producers Association of Nova Scotia, 1994.

F Zaragoza, I Iglesian, J Benedi. Estudio comparativo de los efectos

antiagregantes de los antocianosidos y otros agents Archiv. Farmacol. Toxicol.
11(3):183–188, 1985.

W Kalt, D Dufour. Health functionality of blueberries, Hort- Technol.

7(3):216–222, 1997.

R Alfieri, P Sole. Influence des anthocyanosides administers par voie oro-

perlinguale sur l’adapto-electroretinogramme(AERG) en lumiere rouge chez
l’Homme, Comptes Rendus des Seances de la Societe de Biologie et des Ses
Filiales. 160(8):1590–1593, 1996.

JR Trevithick, KP Mitton. Antioxidants and diseases of the eye. In:

Antioxidant Status. Diet, Nutrition, and Health, AM Pappas, Ed. CRC Press,
Boca Raton, FL, pp 545–565, 1999.

VE Tyler. Herbs of Choice, Haworth Press, Binghampton, NY, pp 51–54,

1994.

YW Huang, CY Hung. Traditional Chinese functional foods. In: Asian Foods,

Science and Technology. CYM Ang, K Lui, YW Huang. Eds. Technomic
Publishing Co. Inc., 1999.

KC Huang. The Pharmacology of Chinese Herbs. CRC Press, Inc., Boca

Raton, FL, 1993.

ST Chow. Fruit Processing and Storage. 2nd ed., Beijing Scientific Press,
China, 1991.

A Murakami, Y Wataru, H Takahashi, T Yonei, H Tanaka, K Makita, N

Wada, M Ueda, Y Haga, Y Nakamura, Y Ohto, OK Kim, H Ohigashi, K
Koshimizu. Auraptene, an Alkyloxylated coumarin from citrus natsudaidai
HAYATA, inhibits mouse skin tumor promotion and rat colonic aberrant crypt
foci formation. Functional Foods for Disease Prevention, Fruits, Vegetables,
and Teas, 8:86–95, 1997.

93
A Chiralt, X Martinez-Monzo, M Chafer, P Fito. Limonene from citrus. In:
Functional Foods: Processing and Biochemistry Aspects, J. Shi, G. Mazza, M.
Le Maguer, Eds. CRC Press, New York, 2002.

I Ofek, J Goldhar, D Zafriri, H Lis, R Adr, N Sharon. Anti- Escherichia coli

adhesin activity of cranberry and blueberry juices, New Engl. J. Med.
324(22):1599, 1991.

I Ofek, J Goldhar, N Sharon. Anti-Escherichia coli adhesion activity of

cranberry and blueberry juices. In: Toward Anti- Adhesion Therapy for
Microbial Diseases, Itzhak Kahane and Itzhak Ofek, Eds. Plenum Press, New
York, 179-183, 1996.

AB Howell, A Der Marderosian, LY Foo. Inhibition of the adherence of P-

fimbriated Escherichia coli to uroepithelial-cell surfaces by proanthocyanidin
extracts from cranberries, New Engl. J. Med. 339(15):1085–1086, 1996.

PW Martin. Durian and mangosteen, tropical and subtropical fruits, S Nagy,

PE Shaw, Eds. AVI, Westport, CT, 1980.

CV DeWhalley, SM Rankin, RS Hoult, W Jessup, DS Leake. Flavonoids

inhibit the oxidative modification of low-density lipoproteins by macrophages,
Biochem. Pharmacol., 39:1743–1748, 1980.

EN Frankel, J Kanner, JE Kinsella. Inhibition in vitro of oxidation of human

low-density lipoproteins by phenolic substances in wine, Lancet, 341:454–457,
1993. Functional Foods from Fruit and Fruit Products 337

MGL Hertog, PCH Hollman, MB Katan, D Kromhout. Intake of potentially

anticarcinogenic flavonoids and their determinants in adults in the Netherlands,
Nutr. Cancer, 20:21–29, 1993.

J Kanner, E Frankel, R Granit, B German, JE Kinsella. Natural

antioxidants in grapes and wines, J. Agric. Food Chem., 42:64–69, 1994.

H Wei, L Tye, E Bresnick, DF Birt. Inhibitory effect of apigenin, a plant

flavonoid, on epidermal ornithine decarboxylase and skin tumor promotion in
mice. Cancer Res., 50:499–502, 1990.

EE Deschner, J Ruperto, G Wong and HL Newmark. Quercetin and rutin as

inhibitors of azoxymethanol-induced colonic neoplasia, Carcinogenesis,
7:1193–1196, 1991.

E Middleton, C Kandaswami. Effects of flavonoids on immune and

inflammatory cell functions, Biochem. Pharmacol., 43:1167–1179, 1992.

94
H Wagner. New plant phenolics of pharmaceutical interest, Ann. Proc.
Phytochem. Soc. Eur., Vol. 15. cf. Van Sumere and PJ Lea, Oxford
UK:Clarendon Press. pp 409–425, 1985.

R Boniface, M Miskulin, L Robert, AM Robert. Pharmacological properties

of Myrtillus anthocyanosides: correlation with results of treatment of diabetic
microangiophathy, In: Flavonoids and Bioflavonoids. L Farkas, M Gabor, F
Kally, Eds. Amsterdam: Elsevier. pp 193–201, 1986.

E Kano, J Miyakoshi. UV protection effect of keracyanin an anthocyanin

derivative on cultured mouse fibroblast L. cells, J. Radiat. Res., 17:55–65, 1976.

JL Maas, GI Galletta, GD Stoner. Ellagic acid, an anticarcinogen in fruits,

especially strawberries: a review, HortScience, 26:10–14, 1991.

M Jang, L Cai, GO Udeani, KV Slowing, CF Thomas, CWW Beecher,

HSnFong, NR Farnsworth, AD Kinghorn, RG Mehta, RC Moon, JM
Pezzuto. Cancer chemopreventive activity of resveratrol, a natural product
derived from grapes, Science, 275:218–220, 1997.

T Okeda, K Yokotsuka. Trans-resveratrol concentrations in berry skins and

wines from grapes grown in Japan. Am. J. Enol. Vitic., 47:93–99, 1996.

AM Rimando, W Kalt, JB Magee. Resveratrol in vaccinium species and

muscadine grapes, Proceedings of Pre-Congress Internet Conference. pp 186–
188, 2001.

MA Morales, J Tortoriello, M Meckes, D Paz, X Lozoya. Calciumantagonist

effect of quercetin and its relation with the spasmolytic properties of Psidium
guajava L. Arch. Med. Res., 25 (1):17–21, 1994.

R Roman-Ramos, JL Flores-Saenz, FJ Alarcon-Aguilar. Antihyperglycemic

effect of some edible plants. J. Ethnopharmacology, 48:25–32, 1995.

IS Grover, S Bala. Studies on antimutagenic effects of guava (Psidium

guajava) in Salmonella typhimurium. Mutation Res., 300:1–3, 1993.

YH Lee. Home-Cook Nutritional Recipes. Haibin Publishing, Hong Kong,

1990.

D Potterton, Ed. Culpepers Color Herbal. Sterling Publishing, New York,

1983.

Shen Yang Army Hospital. Medical Data Base. Vols. 1 and 2 (in Chinese),
1975.

Disease Prevention Center. Tieh Ling Medicine 2:33–36, 1972.

95
AN Liao Ling See Fung Chau An, County Health Survey. County Health
Department. Database on Canton Medicines. 11, 44–49, 1977.

DB Zhang. Fruit and Vegetable Processing Technology. China Light Industry

Press, Beijing, China, 1994.

WC Chen. Chinese Herb Cooking for Health. Chin-Chin Publishing, Taipei,

Taiwan, 1997.

RN Adsule, NB Patil. Pomegranate. In: Handbook of Fruit Science and

Technology, Salunkhe DK, Kadam SS, Eds., Marcel Dekker, New York, 1995.

M Aviram, L Dornfeld, M Rosenblat, N Volkova, M Kaplan, T Hayek, D

Presser, B Fuhrman. Pomegranate Juice Consumption Decreases Oxidative
Stress, Low-Density Lipoprotein Modifications and Atherosclerosis: Studies in
the Atherosclerotic Apolipoprotein E-Deficient Mice and in Humans,
Proceedings of Pre-Congress Internet Conference. 151–152, 2001.

M Aviram, L Dornfeld, M Rosenblat, N Volkova, M Kaplan, T Hayek, D

Presser, B Fuhrman. Pomegranate juice consumption reduces oxidative stress,
low-density lipoprotein modifications and platelet aggregation: studies in the
atherosclerotic apolipoprotein in E deficient mice and in humans. Am. J, Clin.
Nutr., 71:1062–1076, 2000.

SE Kudritskaya, LM Zagorodskaya, EE Shishkina. Carotenoids of the sea

buckthorn, variety obil’naya. Chem. Natural Compounds 25:724–725, 1989.

W Franke, H Muller. A contribution to the biology of useful plants. 2.

Quantity and composition of fatty acids in the fat of the fruit flesh and seed of
sea buckthorn. Angewandre Botanik 57:77–83, 1983.

J Bernath, D Foldesi. (Hippophae rhamnoides L.): a promising new medicinal

and food crop. J. Herbas, Spices, Medicinal Plants, I:27–35, 1992.

WL Su. Oriental Herbal Cook Book for Good Health (1). Shun An Tong
Corp., Flushing, NY, 1993.

Beijing Medical College Chinese Herbal Medicine Research Group. J.

Beijing Medical College 1:104. 1959, (in Chinese).

R I S Lin. Phytochemicals and antioxidants. In: Functional Foods, Designer

Foods, Pharmafoods, Nutraceuticals. I Goldberg Ed. Chapman & Hall, New
York, 1994.

The Wealth of India. A Dictionary of Indian Raw Materials and Industrial

Products; Raw Materials; C. S. I. R.: New Delhi; vol. 3 pp 168–170, 1952.

96
PG Sur, DK Ganguly, Y Hara, Y Matsuo. Antitumor activity of Emblica
officinalis Gaertn fruit extract, In: Functional Foods for Disease Prevention 1.
Fruits, Vegetables, and Teas. Chapter 10, p. 104, 1997.

H Matsuda, M Higashono, W Chen, H Tosa, M Iinuma, M Kubol. Studies

of cuticle drugs from national sources. III. Inhibitory effect of Myrica rubra on
melanin biosynthesis. Biol. Pharm. Bull., 18:1148–1150, 1997.

S Gatner JL Wolfender, S Mavi, K Hostettmann. Antifungal and

antibacterial chalcones from Myrica serrata. Planta Med., 62:67–69, 1996.

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 Chapter 5
Selcted Fruits of African Origin – Nutraceutical Perspectives

5.1. African Custard-Apple

Annona senegalensis, commonly known as African custard-apple, wild custard

apple, and wild soursop, is a species of flowering plant in the custard apple
family, Annonaceae. The specific epithet, senegalensis, translates to mean "of
Senegal", the country where the type specimen was collected. A traditional food
plant in Africa, the fruits of A. senegalensis have the potential to improve
nutrition, boost food security, foster rural development and support sustainable
land care. Well known where it grows naturally, it is largely unheard of
elsewhere. The primary use of this versatile plant is for food, but it has
applications in numerous aspects of human endeavour, and every part of the
plant has unique properties and uses. The flowers, leaves and fruit are edible
and culinary: white fruit pulp has a mild, pineapple-like flavour. Flowers are
added to spice or garnish meals; leaves are eaten by humans as vegetables, or
browsed by livestock. Leaves are also part of the diet of the West African
giraffe. The leaves are also used to create a general health tonic, in the treatment
of pneumonia, and as mattress and pillow stuffing. Specific to Sudan, leaves are
boiled in the making of perfume. Bark can be processed to produce yellow-
brown dye, insecticide, or medicine for treating a wide array of ailments,
including worms parasitic on the intestines or flesh (notably guinea worms),
diarrhoea, gastroenteritis, lung infections, toothaches, and even snakebites.

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Natural gum in the bark is used to close open wounds. Roots are also used
medicinally in treating a gamut of conditions, from dizziness and indigestion to
chest colds to venereal diseases. Suckering shoots provide binding fibers, and
the malleable, pale brown to white wood is used to carve tool handles, or
fashioned into poles. Wood ash is an admixture to chewing tobacco and snuff,
and also in soap production as solvent. The essential oils in the fruits and leaves
are valued for their organic chemical constituents: car-3-ene[clarification
needed] (in fruit) and linalool (from leaves). Certain parts of A. senegalensis are
used in treating skin or eye disorders. Many South Africans believe the roots
can cure insanity. Some Mozambicans feed them to infants to wean them from
their mother's breast.

5.2. The African Medlar

The African medlar (Vangueria infausta) is a species of plant in the family

Rubiaceae, which is native to the southern and eastern Afrotropics. The specific
name infausta alludes to the misfortune believed to result from its use as
firewood. This shrub or small tree occurs in abundance in woodlands, scrub,
valleys, stony kopjies, or sandy dunes throughout much of Southern and East
Africa, including Madagascar. In Africa it is native to Uganda, Kenya,
Tanzania, Malawi, Mozambique, Zimbabwe, Namibia, Botswana and South
Africa. It may be found from 350 to 1,330 m above sea level.The African
medlar is a traditional food plant in Africa. This little-known fruit has the
potential to improve nutrition, boost food security, foster rural development and
support sustainable land care. The fruit are consumed raw or the pulp may be
dried and stored for later use, while the seeds may be roasted. Goats and game
browse on the leaves, while other animals may consume the fruit in the tree, or
after they are shed on the ground. The roots and leaves are used by traditional
healers.

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5.3. African Moringa

Moringa stenopetala is often referred to as the African Moringa Tree because it

is native only to Ethiopia and northern Kenya. Though it does grow in many
other parts of the old- and new-world tropics, it is not as widely known as its
close relative, Moringa oleifera.

Much of the plant is edible by humans or by farm animals. The leaves are rich
in protein, vitamin A, vitamin B, vitamin C and minerals. One hundred grams of
fresh Moringa leaves have: 2 times the protein of 100 gm yogurt (Moringa 8.3
g, yogurt 3.8 g); 4 times the calcium of 100 gm milk (Moringa 434 mg, whole
cow milk 120 mg); the same potassium as 100 gm banana (Moringa 404 mg,
banana 376 mg); the same vitamin A as 100 gm carrot (Moringa 738 mcg,
carrot 713 mcg); 3 times the vitamin C of 100 gm orange (Moringa 164 mg,
orange 46.9 mg.

All parts of the tree except the wood are edible, providing a highly nutritious
food for both humans and animals. The flowers are a good nectar source for
honey and the seeds are a rich oil source for cooking and lubricant uses. Many
parts of the plant have been used in medicinal preparations. Whole plants have
been used as living hedges, fences, and windbreaks. The wood is very soft;
useful for paper but makes low-grade firewood and poor charcoal. Attracting
attention in recent decades is the use of the dried, crushed seeds as a coagulant
similar to the chemical alum. Even very muddy water can be cleared when
crushed seeds are added. Solid matter and some bacteria will coagulate and then
sink to the bottom of a container. The cleaned water can then be poured off and
boiled. Use 100 milligrams (about 1 to 1 ½ seeds) of crushed seed to clean 1
liter (1 quart) of muddy water.

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5.4. Aizen

Boscia senegalensis or Aizen, is a member of the family Capparaceae. The

plant originated from West Africa. Still a traditional food plant in Africa, this
little-known fruit has potential to improve nutrition, boost food security, foster
rural development and support sustainable landcare. Fruits are a significant
source of carboydrates, as they contain 66.8% carbohydrates.The seeds are
sufficiently nutritious, although they do lack some essential nutrients, notably
lysine and threonine. The seeds have significant levels of protein (25% of dry
matter) and carbohydrates (60%). In these regards, seeds outperform local
staple cereals such as sorghum and millet. Additionally, seeds are rich in zinc,
iron, methionine, tryptophan, B-vitamins and linoleic acid (essential fatty acid).
Seeds contain 3.6 times the World Health Organization (WHO) ideal level of
tryptophan.Leaves have high antioxidant capacity (nearly 1.5 times that of
spinach) and are high in calcium, potassium, manganese and iron. The
bioavailability of these compounds, however, is not very well known.

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5.5. Balsam Apple

Momordica balsamina is a tendril-bearing annual vine native to the tropical

regions of Africa, introduced and invasive in Asia, Australia, and Central
America. It has pale yellow, deeply veined flowers and round, somewhat warty,
bright orange fruits, or "apples". When ripe, the fruits burst apart, revealing
numerous seeds covered with a brilliant scarlet, extremely sticky coating. The
balsam apple was introduced into Europe by 1568 and was used medicinally to
treat wounds. Over 100 studies using modern techniques have authenticated its
use in diabetes and its complications (nephropathy, cataract, insulin resistance),
as antibacterial as well as antiviral agent (including HIV infection), as
anthelmintic and abortifacient. Traditionally it has also been used in treating
peptic ulcers, interestingly in a recent experimental studies have exhibited its
potential against Helicobacter pylori. Most importantly, studies have shown its
efficacy in various cancers (lymphoid leukemia, lymphoma, choriocarcinoma,
melanoma, breast cancer, skin tumor, prostatic cancer, squamous carcinoma of
tongue and larynx, human bladder carcinomas and Hodgkin’s disease). There
are few reports available on clinical use of Momordica balsamina in diabetes
and cancer patients that have shown promising result.

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5.6. Desert Date

Balanites aegyptiaca is a species of tree, classified either as a member of the

Zygophyllaceae or the Balanitaceae.This tree is native to much of Africa and
parts of the Middle East.There are many common names for this plant.In
English the fruit has been called desert date, soap berry tree or bush, Thron tree,
Egyptian myrobalan, Egyptian balsam or Zachum oil tree; in Arabic it is known
as lalob, hidjihi, and heglig (hijlij). In Hausa it is called aduwa, in Swahili
mduguyu, and in Amharic bedena.Balanites aegyptiaca has been cultivated in
Egypt for more than 4000 years, and stones placed in the tombs as votive
offerings have been found as far back as the Twelfth Dynasty. The tree was
figured and described in 1592 by Prosper Alpinus under the name 'agihalid'.
Linnaeus regarded it as a species of Ximenia, but Adanson proposed the new
genus of Agialid. The genus Balanites was founded in 1813 by Delile. The
yellow, single-seeded fruit is edible, but bitter. Many parts of the plant are used
as famine foods in Africa; the leaves are eaten raw or cooked, the oily seed is
boiled to make it less bitter and eaten mixed with sorghum, and the flowers can
be eaten. The tree is considered valuable in arid regions because it produces
fruit even in dry times. The fruit can be fermented for alcoholic beverages.The
seed cake remaining after the oil is extracted is commonly used as animal
fodder in Africa. The seeds of the Balanites aegyptiaca have molluscicide effect
on Biomphalaria pfeifferi. Where the species coexist, African elephants
consume the desert date. Desert date fruit is mixed into porridge and eaten by
nursing mothers, and the oil is consumed for headache and to improve lactation.
Oil from the fruit is used to dressBark extracts and the fruit repel or destroy
freshwater snails and copepods, organisms that act as intermediary hosts host
the parasites Schistosoma, including Bilharzia, and guinea worm, respectively.
Existing worm infections are likewise treated with desert date, as are liver and

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spleen disorders. A decoction of the bark are also used as an Abortifacient and
an antidote for arrow-poison in West African traditional medicine. The seed
contains 30-48% fixed (non-volatile) oil, like the leaves, fruit pulp, bark and
roots, and contains the sapogenins diosgenin and yamogenin. Saponins likewise
occur in the roots, bark wood and fruit. Diosgenin can be used to produce
hormones such as those in combined oral contraceptive pills and corticoids.

Children like the sugary balanites fruits, and throughout the species’ range these
are widely consumed by the young. This makes it a key to malnutrition
reduction in the vast, parched, and perilous arid zone where few other useful
plant species exist. The pulp contains carbohydrate (notably sugars), protein, a
smidgen of fat, and undoubtedly notable levels of vitamins and minerals. In
addition, the seed kernel is rich in both an oil of the desirable unsaturated type
and a protein whose amino-acid quality almost matches that in peanut. The pulp
and seeds, separately or together, are thus excellent dietary means for assisting
the malnourished, both young and not so young.

5.7. Baobab

The baobab fruit has three times as much vitamin C as an orange, 50 per cent
more calcium than spinach and is a plentiful source of anti-oxidants, those
disease-fighting molecules credited with helping reduce the risk of everything
from cancer to heart disease. Nutritionally speaking, the strange chalky powder
from a baobab fruit can be considered nature’s gift to natural food fortification.
The dry, soluble flour provides a simple way to add protein, carbohydrate,
energy, fiber, provitamin A, vitamin C, several B vitamins, calcium,
phosphorus, and iron to other foods even in remote areas where delivering those
by other means is difficult. Moreover the protein has an excellent amino-acid
profile, including good quantities of such essential vegetative rarities as lysine,
methionine, cystine, and tryptophan. At least in principle, this seems like a
readily available homegrown means for reducing malnutrition on a long-term
and large-scale throughout much of Africa.

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5.8. Butterfruit (Safou, Bush Mango)

The colorful prunelike morsels of the butterfruit (Dacryodes edulis) are well
known in Central and West Africa. They are roasted or boiled with maize as a
main course, they are enjoyed (fresh or cooked) as snacks, and they feature in
traditional ceremonies and special functions. These are commercial fruits that
pour into cities and rural markets in considerable quantities. They are especially
important in the hot and humid zone stretching from Eastern Nigeria to Angola.
There, women peddling the fruits at locations along the highways are a common
sight.

Packing a combination of protein and energy, butterfruit pulp is promising for

reducing Africa’s worst humanitarian problem, protein-calorie malnutrition in
children. Although presently unreported in nutrition programs, it might prove a
lifesaver for children, nursing mothers, and thedesperately malnourished. Its
protein contains levels of essential amino acids similar to those found in eggs,
milk, and meat. Moreover, the oil making up roughly half the pulp is composed
mainly of desirable unsaturated fatty acids. And beyond protein and edible oil,
this fruit provides an array of minerals such as potassium, calcium, and
magnesium. Clearly, this fruit possesses the nutrient power to counteract what is
currently the most common form of malnutrition.

5.9. Carissa

Although generally eaten for pleasure rather than health, Carissa nevertheless
packs some nutritional wallop. Indeed, it contains somewhat more vitamin C

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than the average orange and enough calcium, phosphorus, and magnesium to
designate it a fine source of minerals. The red pulp looks and tastes so good it is
often added to sick-people’s foods to entice them into downing pasty-colored
porridges. The fruits are also dropped into water bottles and gourds to liven up
the liquid contents. For these and other features carissa could be a good delivery
system for the very nutrients everyone needs and not everyone gets.

5.10. Horned Melon

The horned melon (Cucumis metuliferus), also called African horned cucumber
or melon, kiwano, jelly melon, hedged gourd, or melano, is an annual vine in
the cucumber and melon family. It is considered to be the ancestor of the other
cultivated melons. Often known by its nickname in the southeastern United
States, blowfish fruit, it is grown for its fruit, which look like oval melons with
horn-like spines. The fruit of this plant is edible, but it is used as often for
decoration as for food. When ripe, it has a yellow-orange skin and a lime green,
jelly-like flesh with a tart taste, and texture similar to a cucumber. The horned
melon is native to Africa, and it is now grown in California, Chile, Australia
and New Zealand, as well.

In Zimbabwe, this cucumber is called gaka or gakachika, and it is primarily

used as a fruit-snack, salad, and, rarely, for decoration. It is eaten young, mature
green, or when ripe - bright yellow/orange (i.e., at any stage of its
development). It grows naturally in the fields and also in the bush. However,
some people leave some to rot in the fields for the next summer's seeds/plants.
Its taste has been compared to a combination of cucumber and zucchini. or a
combination of banana, cucumber and lemon. Some eat the peel, as well. The
fibrous structure and protein composition of the peel provides for a taste and
texture similar to the plantain family. One variety does not have horns, but
looks and tastes similar. The seeds are covered in a gel-like substance. The skin
is very rich in vitamin C and fiber. A small amount of salt or sugar can increase
the flavor. The fruit can be used in cooking, but when eaten raw, most suck out

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the pulp and spit out the seeds, although eating the skin and/or the seeds is also
known.The nutritional value of the horned melon’s flesh is low, and the seeds
are poorly known. The fruit seems unlikely in its present form to make a major
dietary contribution against malnutrition.

5.11. Kei Apple

The kei apple, Dovyalis caffra Warb. is also known as umkokolo in Africa and
this is abbreviated to umkolo in the Philippines. The generic name has been
rendered Doryalis by many writers but botanists now agree that this form was
not the original spelling. Kei apples are highly acidic for the simple reason they
have more vitamin C than oranges. Beyond that, little of their food value is
known. This fruit’s value in nutrition programs is certain to be good but not
necessarily good enough to warrant special effort on those grounds alone.

Most people consider the fruit too acid for eating out-of-hand even when fully
ripe. It is best cut in half, peeled, seeded, sprinkled with sugar and allowed to
stand for a few hours before serving as dessert or in fruit salads. The halves can
stand only a few minutes of cooking before they turn into sauce. Simmered
briefly in sirup, they make excellent shortcake. Kei apples are customarily made
into jam and jelly, and, when underripe, pickles.Fresh ripe fruits contain 83 mg
ascorbic acid per 100 g and 3.7% pectin. Scientists in Egypt have reported 15
amino acids: alanine, 0.41%; arginine, 0.36%; aspartic acid, 0.96%; glutamic
acid, 2.00%; glycine, 0.39%; histidine, 0.10%; isoleucine, 0.25%; leucine,
0.75%; lysine, 0.36%; methionine + valine, 0.28%; phenylalanine, 0.40%;
proline, trace; serine, 0.48%; threonine, 0.34%.

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5.12. Marula

Sclerocarya birrea, the marula, (Greek σκληρός, sklērós, "hard", and κάρυον,
káryon, "nut", in reference to the stone inside the fleshy fruit) is a medium-sized
dioecious tree, indigenous to the miombo woodlands of Southern Africa, the
Sudano-Sahelian range of West Africa, and Madagascar. The tree is a single
stemmed tree with a wide spreading crown. It is characterised by a grey mottled
bark. The tree grows up to 18 m tall mostly in low altitudes and open
woodlands. The fruits are used in the liqueur Amarula. The distribution of this
species throughout Africa and Madagascar has followed the Bantu in their
migrations, as it has been an important item in their diet since time
immemorial.Although an important source of several nutrients, marula fruit
stands out for its vitamin C. In this regard, the flesh commonly surpasses
orange, grapefruit, and lemon. Add to that macadamia-like nuts, possessing
protein, an edible oil ranked with the elites, and minerals such as calcium,
magnesium, and phosphorus, and you have a nutritional powerhouse borne by a
widespread plant seemingly created for today’s needs.

The bark is used both as treatment and a prophylaxis for malaria. An infusion of
the inner bark of the marula tree may be applied to scorpion stings and snake
bites to alleviate pain. The leaves are chewed on to help indigestion and to treat
heartburn. Marula oil, made from the seed kernel, can be used as a type of skin
care oil.

The seed kernels are high in protein and fat with a subtle nutty flavour and
constitute an important emergency food. Fruits are commonly eaten fresh or
used to prepare juice, jelly and alcoholic drink. Marula oil, made from the seed
kernel, is a delicious additive to meals in Africa. It contains antioxidants and
oleic acid.

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5.13. Melon

Melons originated in Africa and southwest Asia, but they gradually began to
appear in Europe toward the end of the Roman Empire. Melons were among the
earliest plants to be domesticated in both the Old and New Worlds. Early
American settlers are recorded as growing honeydew and casaba melons as
early as the 1600s. A number of Native American tribes in New Mexico,
including Acoma, Cochiti, Isleta, Navajo, Santo Domingo and San Felipe,
maintain a tradition of growing their own characteristic melon cultivars, derived
from melons originally introduced by the Spanish. Dietarily speaking, most
people consider melon a sugary nothing. But it provides potassium, vitamin C,
and almost as much provitamin A as mango.

5.14. Tamarind

Tamarind pulp is a good source of the B vitamins thiamin, niacin, and riboflavin
as well as phosphorus, potassium, and calcium (whose content is reportedly the
highest found in any fruit). There are claims that tamarinds are also high in iron,
which could make them useful anemia preventatives. The fact that kids love
sucking on these not-so-pretty fruits means this longlived and highly adaptable
tree could be a significant nutrition-delivery tool. Plant tamarinds beside the
tracks to school and you’ll likely feed generations of children and, in addition,

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leave a legacy of shade for the society and soothing scenery for the ages.
Tamarind fruit contains certain health benefiting essential volatile chemical
compounds, minerals, vitamins and dietary fibre. Its sticky pulp is rich source of
non-starch polysaccharides (NSP) or dietary-fibre such as gums,
hemicelluloses, mucilage, pectin and tannins. 100 g of fruit pulp provides 5.1 or
over 13% of dietary fibre. NSP or dietary fiber in the food increases its bulk and
augments bowel movements thereby help prevent constipation. The fibre also
binds to toxins in the food thereby help protect the colon mucus membrane from
cancer-causing chemicals. In addition, dietary fibres in the pulp bind to bile
salts (produced from cholesterol) and decrease their re-absorption in the colon;
thereby help excretion of “bad” or LDL cholesterol levels from the body. While
lemon composes of citric acid, tamarind is rich in tartaric acid. Tartaric acid
gives a sour taste to food but is also a very powerful antioxidant. (Anti-oxidant
E-number is E334). It helps the body protect from harmful free radicals.
Tamarind fruit contains many volatile phytochemicals such as limonene,
geraniol, safrole, cinnamic acid, methyl salicylate, pyrazine and alkyl­thiazoles.
Together these compounds account for the medicinal properties of
tamarind.This prized spice is a good source of minerals like copper, potassium,
calcium, iron, selenium, zinc and magnesium. Potassium is an important
component of cell and body fluids that helps control heart rate and blood
pressure. Iron is essential for red blood cell production and as a co-factor for
cytochrome oxidases enzymes.In addition, it is also rich in many vital vitamins,
including thiamin (36% of daily required levels), vitamin A, folic acid,
riboflavin, niacin, and vitamin-C. Much of these vitamins plays antioxidant, and
co-factor functions for enzyme metabolism inside the body.

5.15. Watermelon

Although no one eats watermelon for medicinal purposes, the contents of

carotenoids—especially beta-carotene and lycopene—are substantial.
Watermelon also is a significant source of vitamin C and fibre. As for minerals,
the fruit supplies potassium and is at the same time very low in sodium. It also
provides a safe liquid refreshment for washing down a meal.

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 Chapter 6
Profiling Popular Foods and Herbs - Nutraceutical Perspectives

6.1. Aloe Vera

Aloe vera, a member of the Liliaceae family, is a tropical plant originating in

the warm, dry climates of Africa. Of more than 360 Aloe species recognized,
Aloe barba-densis Miller is the main commercial one used for its medicinal
properties. Corsi and coworkers (1998) reported that Aloe vera had therapeutic
potential by reducing the growth in pleural tumor-bearing rats. Shamaan et al.
(1998) also found that vitamin C and Aloe vera both reduced the severity of
chemical hepatocarcinogenesis in rats. An Aloe vera gel was found to contain
small-molecular-weight immunomodulators, G1C2F1, capable of restoring
ultraviolet B (UVB)-suppressed accessory-cell function of epidermal
Langerhans cells (LC) in vivo. Lee and coworkers (1999) showed that topical
application of G1C2F1 to the abdominal skin of mice reduced the suppression
of contact sensitization exposed to UVB radiation. Aloe vera enhanced wound
healing by increasing the levels of type III collagen in dermal wounds in rats
(Chithra et al., 1998). Extracts of Aloe vera were found to exert anti-
inflammatory activity by inhibiting cyclooxygenase (Vasquez et al., 1996).
Avila and coworkers (1997), however, pointed out that Aloe vera gels contain
cytotoxic, low-molecular-weight compounds, which must be removed or
reduced in commercially prepared products. Pugh et al. (2001) identified a
highmolecular- weight immunostimulatory polysaccharide from commercial
Aloe vera juice, aloeride, containing glucose (37.2 percent), galactose (23.9
percent), mannose (19.5 percent), and arabinose (10.3 percent). While aloeride
only accounted for 0.015 percent of the crude juice, it exhibited very potent

111
immunostimulatory activity compared to the main carbohydrate component,
acemannan. Aloeride as an immunostimulant could be beneficial for wound
healing and immunotherapy. A supercritical carbon dioxide extract from Aloe
vera skin was shown by Hu et al. (2004) to be a superior antioxidant to BHT or
α-tocopherol. A quality and safety (HACCP) management system was recently
developed by He et al. (2005) for processing Aloe vera gel juice for the food
industry.

6.1.1. References

Avila, H., Rivero, J., Herrera, F., and Fraile, G., Cytotoxicity of a low
molecular weight fraction from Aloe vera (Aloa barbadensis Miller) gel,
Toxicon., 35: 1423–1430, 1997.

Chithra, P., Sajithial, G.B., and Chandrakasan, G., Influence of Aloe vera
on collagen characteristics in healing dermal wounds made in rats, Moll. Cell.
Biochem., 181:71–76, 1998.

Corsi, M.M., Bertelli, A.A., Gaja, G., Fulgenzi, A., and Ferrero, M.E., The
therapeutic potential of Aloe vera in tumor-bearing rats, Int. J. Tissue React.,
20: 115–118, 1998.

He, W., Changhong, L., Kojo, E., and Tian, Z., Quality and safety assurance
in the processing of aloe vera gel juice, Food Cont., 16:95–104, 2005.

Hu, Q., Hu, Y., and Xu, J., 2004. Free-radical scavenging activity of Aloe vera
(Aloe barbadensis Miller) extracts by supercritical carbon dioxide extraction,
Food Chem., 2004 (in press).

Lee, C.K., Han, S.S., Kim, R.S., Chung, M.H., Park, Y.I., Lee, S.K., and
Kim, Y.S., Prevention of ultraviolet radiation-induced suppression of sensory
cell function of langerhans cells of Aloe vera gel components,
Immunopharmacology, 37:153–162, 1997.

Pugh, N., Ross, S.A., ElSohly, M.A., and Pasco, D.S., Characterization of
aloeride, a new highmolecular polysaccharide from Aloe vera with potent
immunostimulatory activity, J. Agric. Food Chem., 49:1030–1034, 2001.

Shamaan, A., Kader, K.A., Rahmat, A., and Ngah, W.Z.W., Vitamin C and
aloe vera supplementation protects from chemical hepatocarcinogenesis in the
rat, Nutrition, 14:846–852, 1998.

Vazquez, B., Avila, G., Segura, D., and Escalante, B., Anti-inflammatory
activity of extracts from Aloe vera gel, J. Ethnopharmacol., 55:69–75, 1996.

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6.2. Apple Juice

Pearson and coworkers (1999) examined the ability of six commercial apple
juices to inhibit copper-catalyzed LDL-oxidation. Their results further support
the inclusion of apple and apple products in a healthy diet. In addition, some
apple phenolics also inhibited glucose transport via the Na-dependent glucose
transporter (SGLT1). One such phenolic, phloridzin (phloretin 2′-O-β-D-
glucoside), a flavonoid dihydrochalcone, is used in studies on glucose transport.
Phloridzin and related dihydrochalcones are found in apple products, such as
cider (Tomas-Barberan et al., 1993). Johnston and coworkers (2002) showed
that apple-juice consumption modulated glucose uptake by delaying the
intestinal absorption of glucose. Cloudy apple juice, containing higher levels of
phloridzin and other phenols, suppressed glucose absorption in the proximal GI
tract to a greater degree than clear apple juice. These researchers suggested that
such plant phenols could play a role in determining the glycemic index of plant
foods for the treatment of noninsulin-dependent diabetes mellitus (NIDDM). In
a recent paper by Andlauer et al. (2004), phloridzin amplified the absorption of
the isoflavone genistin in isolated rat small intestine. Because of the cancer-
protective effects associated with genistin, a functional food combining soy and
apple may provide distinct health benefits

Illustration : Phloridzin. (From Lu and Foo, Food Chem., 61:29–33, 1998.

With permission.)

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6.2.1. References

Andlauer, W., Kolb, J., and Furst, P., Phloridzin improves absorption of
genistin in isolated rat small intestine, Clin. Nutr., 23:989–995, 2004.

Pearson, D.A., Tan, C.H., German, J.B., Davis, P.A., and Gershwin, M.E.,
Apple juice inhibits low density lipoprotein oxidation, Life Sci., 64:1913–1920,
1999.

Johnston, K.L., Clifford, M.N., and Morgan, L.M., Possible role for apple
juice phenolic compounds in the acute modification of glucose tolerance and
gastrointestinal hormone secretions in humans, J. Sci. Food. Agric., 82:1800–
1805, 2002.

Lu, Y. and Foo, L.Y., Constitution of some chemical components of apple

seed, Food Chem., 61:29–33, 1998.

6.3. Beans

Beans are an important part of our diet and represent a good source of protein
and nutrients. The consumption of beans, particularly in Mexico, has a long
history and was estimated at 19.5 kg/annum per capita (Gonzalez de Mejia,
1990). The importance of phenolic compounds in plant foods, including beans,
is related to their effect on nutritional and esthetic properties. In addition to their
antioxidant and chelating properties, they are able to scavenge reactive-oxygen
species and electrophiles, as well as modulate cellular-enzyme activities (Huang
and Ferraro, 1992). The antimutagenic properties of the phenolic compounds
from common beans (Phaseolus vulgaris) were reported by Gonzalez de Maija
et al. (1999). The majority of poly phenols were located in the seed coat with
negligible amounts in the cotyledons. The key antimutagenic compounds in
beans, easily extracted with methanol, were phenols, while low-
molecularweight hydrolyzable phenols were present in the aqueous extract. The
phenolic compounds specifically identified were catechin, tannic acid, and
ellagic acid. These compounds were effective against the mutagenic activities of
1-nitropyrene (1-NP) and benzo[α]pyrene using the Salmonella typhimurium

114
tester strain YG1024 in the plateincorporation test. Dose-dependent inhibition
was observed for all the samples tested. Doses of 500 μg equivalent
catechin/plate resulted in 63%, 81%, and 83% inhibition for water,
water/methanol, and methanol extracts, respectively. The greatest inhibition was
evident for the methanol extract at lower doses of 50 μg equivalent
catechin/plate. These results were consistent with earlier findings by Mandal
and coworkers (1987) regarding the antimutagenic effects of ellagic acid.

6.3.1. References

Gonzalez de Mejia, E., Caracterizacion fiscoquimica e implicaciones nutricias

de las lectinas de frijol tepari y sus hibridos, Ph.D dissertation, CIN-VESTAV-
Unidad Irapuato, Irapuato, Gto, Mexico, 1990.

Gonzalez de Mejia, E., Castano-Tostado, E., and Loarca-Pina, G.,

Antimutagenic effects of natural phenolic compounds in beans, Met. Res. Gen.
Toxicol. Environ. Mutageneis., 441:1–9, 1999.

Huang, M. and Ferraro, T., Phenolic compounds in food and cancer

prevention, in Phenolic Compounds in Food and their Effects on Health. II.
Analysis, Occurrence and Chemistry, C.Ho,

C., Lee, C.Y., and Huang, M., Eds., American Chemical Society, Washington,
D.C., 1992, pp. 8–35.

Mandal, S., Ahuja, A., Shivapurkar, N.M., Sheng, S.J., Groopman, J.D.,
and Stoner, G.D., Inhibition of aflatoxin B in Salmonella typhimurium and
DNA damage in cultured rat and human tracheobronchial tissues by ellagic
acid, Carcinogenesis, 8:1651–1656, 1987.ihydrochalcones from apple juices
and jams, Food Chem., 46: 33–36, 1993.

6.4. Black Tea

115
Black tea is the fermented tea, which contains a group of yellow- to darkbrown-
colored polyphenolic compounds formed during fermentation (Xiao et al.,
1998). Theaflavins (TF) and thearubigins (TR) are the two major classes of
polyphenols responsible for its color and taste. During fermentation, these
pigments form a mixture of catechin dimers, trimers, or multipolymers, referred
to as tea pigments (Nursten, 1997). Animal and clinical studies have
demonstrated the ability of tea pigments to treat hypertension, decrease blood
sugar, and prevent atherosclerosis and cancer (Morse et al., 1997: Ye, 1997).
Tea pigments were also shown to increase superoxide dismutase (SOD) activity
and decrease lipid-peroxidation levels in experimental animals (Li et al., 1998;
Ren et al., 1998). Cadneri et al. (2000) showed that polyphenolic extracts from
black tea was similar to wine extracts in their ability to protect rats against
AOM-induced colon carcinogenesis Black-tea extracts were far more effective
than green-tea extracts in increasing apoptosis of the tumors. The
anticarcinogenic properties of black-tea extracts were demonstrated by Shukla
and Taneja (2002), who reported significant decreases in the number of
diethylnitrosamine (DEN)-induced pulmonary tumors in Swiss albino mice fed
2 percent and 4 percent blacktea extracts. Yaping and coworkers (2003) recently
showed that tea pigments had similar free-radical-scavenging abilities to tea
polyphenols, which further supports their role in disease prevention. A melanin-
like pigment was isolated by Sava et al. (2001) from black tea leaves by alkaline
extraction, acid hydrolysis, and precipitation. The isolated pigment ha
immunostimulating activity, suggesting possible health benefits. Significant
antimutagenic effects were also reported by Gupta et al. (2002) for black tea
and its polyphenols using the Ames Salmonella assays. Recent work by Besra et
al. (2003) also demonstrated the antidiarrheal properties of a hot-water extract
of black tea.

6.4.1. References

Besra, S.E., Gomes, A., Ganguly, D.K., and Vedasiromoni, J.R.,

Antidiarrhoeal activity of hot water extract of black tea (Camellia sinensis),
Phytother. Res., 17:380–384, 2003.

Caderni, G., De Filippo, C., Luceri, C., Salvadori, M., Giannini, A., Biggeri,
A., Remy, S., Cheynier, V., and Dolara, P., Effects of black tea, green tea and
wine extracts on intestinal carcinogenesis induced by azoxymethane in F344
rats, Carcinogenesis, 21: 1965–1969, 2000.

Gupta, S., Chaudhuri, T., Seth, P., Ganguly, D.K., and Giri, A.K.,
Antimutagenic effects of black tea (World Blend) and its two active
polyphenols theafla-vins and thearubigins in Salmonella assays, Phytother.
Res., 16:655–661, 2002.

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Li, N., Han, H., and Wang, Z., Protective effect of tea pigments on oxidative
damage by free radical in guinea pig, Zhong Guo Zhong Yi Yao Technology,
29:23–24, 1998 (in Chinese).

Morse, M.A., Kresty, L.A., Steele, V.E., Kelloff, G.J., Boone, C.W.,
Balentine, D.A., Harbowy, M.E., and Stoner, G.D, Effects of theaflavins on
N-nitrosomethylbenzylamine-induced esophageal tumorigenesis, Nutr. Cancer
Int. J., 29:7–12, 1997.

Nursten, H.E., 1997. Chemistry of tea infusions, in Chemical and Biological

Properties of Tea Infusions, Schubert, R. and Spiro, M., Eds., German Medical
Information Services, Frankfurt, 1997, pp. 10–83.

Ren, M., Zheng, Y., and Xu, S., 1998. The inhibitory effect of tea pigments on
lipid peroxidation in mice, Jiang Xi Med. Acta, 38:49–51, 1998 (in Chinese).

Sava, V.M., Galkin, B.N., Hong, M.Y., Yang, P.C., and Huang, G.S., A
novel melanin-like pigment derived from black tea leaves with immuno-
stimulating activity, Food Res. Inter., 34:337–343, 2001.

Shukla, Y. and Taneja, P., Anticarcinogenic effect of black tea on pulmonary

tumors in Swiss albino mice, Cancer Lett., 176:137–141, 2002.

Yaping, Z., Wenli, Y., Dapu, W., Xiaofeng, L., and Tianxi, H.,
Chemiluminescence determination of free radical scavenging abilities of “tea
pigments” and comparison with “tea polyphenols,” Food Chem., 80:115–118,
2003.

Ye, W., The study and application of tea pigment, China Food Add., 4:23–24,
1997 (in Chinese).

Xiao, W., Zhong, J., Xiao, H, and Li, D., The mechanism of formation of tea
pigments during the industrial processing of tea known as “fermentation,”
Fujian Tea, 3:8–12, 1998.

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6.5. Cabbage

The antioxidant and antiproliferative activities of 10 common vegetables

(broccoli, spinach, yellow onion, red pepper, carrot, cabbage, potato, lettuce,
and celery) were recently studied by Chu and coworkers (2002). The phenolic
content and antioxidant activity of cabbage fell in the middle, while
antiproliferative activity, using HepG(2) human liver cells, was highest in
spinach, followed by cabbage. Thus, cabbage had the second-highest bioactivity
index (BI) suggested as an alternative biomarker for future dietary cancer-
prevention studies. Bresnick and coworkers (1990) reported that a diet
containing cabbage significantly decreased the incidence of mammary cancer in
female Sprague-Dawley rats injected with a carcinogen, N-methyl-N-
nitrosourea (MNU). Later work by Mehta et al. (1995) reported that a synthetic
brassinin [3-(S-methyldithiocar-bamoyl)aminomethylindole], a phytoalexin first
identified in cabbage, inhibited 7,12-dimethyl-benz [a] anthracene (DMBA)
induction of mouse skin tumors.

6.5.1. References

Bresnick, E., Birt, D.F., Wolterman, K., Wheeler, M., and Markin, R.S.,
Reduction in mammary tumorigenesis in the rat by cabbage and cabbage
residue, Carcinogenesis, 11:1159–1163, 1990.

Chu, Y.F., Sun, J., Wu, X., and Liu, R.H., Antioxidant and antiproliferative
activities of common vegetables, J. Agric. Food Chem., 50:6910–6916, 2002.

Mehta, R.G., Liu, J., Constantinou, A., Thomas, C.F., Hawthorne, M., You,
M., Gerhauser, C., Pezzuto, J.M., Moon, R.C., and Moriarty, R.M., Cancer
chemopreventive activity of brassinin, a phytoalexin from cabbage,
Carcinogenesis, 16:399–404, 1995

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6.6. Cacao

The fruit of Caesalpinia ferrea or Juca, a leguminous tree in northern and

northeastern regions of Brazil, was reported to have analgesic and anti-
inflammatory properties (Carvalho et al., 1996). In addition, it was also used to
treat diabetes (Balbach, 1972) and coughs and injuries (Hashimoto, 1996). The
popular use of aqueous extracts of these fruit to treat cancer led to an
investigation of its antitumor properties by Nakamura and coworkers (2002)
using the in vitro Epstein-Barr virus early-antigen (EBV-EA) screening test.
They identified the active constituents in Caesalpinia ferrea fruits responsible
for antitumor effects as gallic acid and methylgallate. A total of 49 related
compounds were also identified, of which three acetophenone derivatives, 2,6-
dihydroxyacetophenone, 2,3,4-trihydroxyace-tophenone, and 2,4,6-
trihydroxyacetophenone, proved to be the most potent activity.

Figure: Acetophenone structure. (From Nakamura et al., Cancer Lett.,

177:119–124, 2002.)

6.6.1. References

Balbach, A., in As Plantas que Curam, Tree Press, Sao Paulo, 1972, pp. 302–
303.

Carvalho, J.C.T., Teixeira, J.R.M., Souza, P.J.C., Bastos, J.K., Santos

Filho, D., and Sarti, S.J., Preliminary studies of analgesic and anti-

119
inflammatory properties of Caesalpinia ferrea crude extract, J. Ethnopharm.,
53:175–178, 1996.

Hashimoto, G., in Illustrated Cyclopedia of Brazilian Medicinal Plants. Japan,

pp. 552–558, 1996.

Nakamura, E.S., Kurosaki, F., Arisawa, M., Mukainaka, T., Okuda, M.,
Tokuda, H., Nishino, H., and Pastore, F., Jr., Cancer chemoprotective effects
of constituents of Caesalpinia ferrea and related com pounds, Cancer Lett.,
177:119–124, 2002

6.7. Caffeine

Caffeine, 1,3,7-trimethylxanthine, consumed in such drinks as coffee and tea, is

wellknown for its biochemical and physiological activities. In recent years,
evidence has accrued that caffeine can inhibit carcinogenesis in mice and rat
lungs exposed to a nicotinederived carcinogen (Chung, 1999; Chung et al.,
1998), in mice skin exposed to ultraviolet light (Lu et al., 2001), and in rat
stomachs exposed to a carcinogen and sodium chloride (Nishikawa et al., 1995).
In contrast, however, no inhibition was observed when mammary glands were
exposed to specific carcinogens in the presence of caffeine (VanderPloeg et al.,
1991). Hagiwara and coworkers (1999) reported caffeine exerted a
chemoprotective action against the carcinogen 2-amino-1-methyl-6-phenyl-
imidazo pyridine (PhIP) in female F344 rats for 54 weeks by significantly
reducing mammary-gland tumor formation. Takeshita et al. (2003) were unable
to explain how caffeine differentially modifies PhIP-induced colon and
mammary carcinogenesis. The only parameter they found contributing to the
elevation of colon carcinogenesis was elevation in PhIP-DNA adduct formation.
Caffeine at a concentration of 2 mM enhanced the radiosensitivity of two rat
yolk-sac cell lines with a mutant-type p53 by inducing apoptosis through a p5 3-
independent pathway (Higuchi et al., 2000). Ito et al. (2003) also showed
caffeine-induced G2/M phase cellcycle arrest in NB4 promyelocytic leukemia
cells and apoptosis via activation of p53 by a novel pathway. Kitamoto et al.

120
(2003) reported that caffeine, combined with paclitaxel, a naturally occurring
chemotherapeutic agent from the bark of the Western yew, suppressed cell
proliferation in a dose-dependent manner. Examination of the dose responses of
paclitaxel alone and in combination with caffeine on the survival of a human
lung adenocarcinoma cell line, A549, is shown in Figure C.17. The cell-killing
effect of paclitaxel increased in a dose-response manner up to a maximum of 50
nM, with no further improvement at 100 nM. Combining with 5 mM caffeine,
however, reduced the cytotoxicity of paclitaxel, which was further dramatically
suppressed in the presence of 20 mM caffeine. These researchers showed that in
the cell-cycle analysis, caffeine caused early G1 accumulation, while paclitaxel
caused an early increase in G2-M and a decrease in G1. These effects suggested
that while cell-modifying agents, like caffeine, can diminish the cytotoxic
effects of paclitaxel, caution should be exercised in combining these substances.

Figure: Structure of caffeine. (From Nafisi et al., J. Mol. Struct., 705:35–39,

2004. With permission.)

6.7.1. References

Chung, F.L., The prevention of lung cancer induced by a tobacco-specific

carcinogen in rodents by green and black tea, Proc. Soc. Exp. Biol. Med.,
220:244–248, 1999.

Chung, F.L., Wang, M., Rivenson, A., Iatropoulos, M.J., Reinhardt, J.C.,
Pittman, B., Ho, C.T., and Amin, S.G., Inhibition of lung carcinogenesis by
black tea in Fischer rats treated with a tobaccospecific carcinogen: Caffeine as
an important constituent, Cancer Res., 58:4096–4101, 1998.

Hagiwara, A., Boonyaphiphat, H., Tanaka, H., Kawabe, M., Tamano, S.,
Kaneko, H., Matsui, M., Hirose, N., Ito, N., and Shirai, T., Organ-dependent
modifying effects of caffeine, and two naturally occurring antioxidants -
tocopherol and n-tritriacontane-16,18-dione, on 2-amino-1- methyl-6-
phenylimidazo[4,5-b]pyridine(PhIP)-induced mammary and colonic
carcinogenesis in female F344 rats, Jpn. J. Cancer Res., 90:399–405, 1999.

Higuchi, K., Mitsuhashi, N., Saitoh, J., Maebayashi, K., Sakurai, H.,
Akimoto, T., and Niibe, H., Caffeine enhanced radiosensitivity of rat tumor
cells with a mutant-type p53 by inducing apoptosis in a p5 3-independent
manner, Cancer Lett., 152:157–162, 2000.

Ito, K., Nakazato, T., Miyakawa, Y., Yamato, K., Ikeda, Y., and Masahiro,
K., Caffeine induces G2.M arrest and apoptosis via a novel p5 3-dependent
path-way in NB4 promyelocytic leukemia cells, J. Cell. Physiol., 2003 (in
press).

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Kitamoto, Y., Sakurai, H., Mitsuhashi, N., Akimoto, T., and Nakano, T.,
Caffeine diminishes cytotoxic effects of paclitaxel on a human lung
adenocarcinoma cell line, Cancer Lett., 191:101–107, 2003.

Lu, Y.P., Lu, Y.R., Lin, Y., Shih, W.J., Huang, M.T., Yang, C.S., and
Conney, A.H., Inhibitory effects of orally administered green tea, black tea and
caffeine on skin carcinogenesis in mice previously treated with ultraviolet B
light (high-risk mice): Relation-ship to decreased tissue fat, Cancer Res.,
61:5002–5009, 2001.

Nafisi, S., Manajemi, M., and Ebrahimi, S., The effects of mono- and
divalent metal cations on the solution structure of caffeine and theophylline, J.
Mol. Struct., 705:35–39, 2004.

Nishikawa, A., Furukawa, F., Imizaka, T., Ikezaki, S., Hasegawa, T., and
Takahasi, M., Effects of caffeine on glandular stomach carcinogenesis induced
in rats by N-methyl-N-nitro-Nnitrosoguanidine and sodium chloride, Food
Chem. Toxicol., 33:21–26, 1995.

Takeshita, F., Ogawa, K., Asomoto, M., and Shirai, T., Mechanistic
approach of contrasting modifying effects of caffeine on carcinogenesis in the
rat colon and mammary gland induced with 2-amino-1-methyl-6-phenylimidazo
[4,5-b]pyridine, Cancer Lett., 194:25–35, 2003.

VanderPloeg, L.C., Wolfrom, D.M., and Welsch, C.W., Influence of caffeine

on development of benign and carcinomatous mammary gland tumors in female
rats treated with the carcinogens, 7,12-dimethylbenz(a)anthracene and N-
methyl-N-nitrosourea, Cancer Res., 51:3399–3404,1991

6.8. Chocolate

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Chocolate contains fats, sugars, and protein, together with small quantities of
magnesium, potassium, calcium, iron, and riboflavin, as well as the stimulant
caffeine. The main ingredient in all chocolates is cocoa, derived from beans
cultivated in West Africa and Southeast Asia. Among the hundreds of
compounds in cocoa are a group of polyphenolic compounds or flavonoids. One
group of flavonoids, the procyanidins, account for 35 percent of all polyphenols
in cocoa. Procyanidins consist of flavan-3-ol(−) epicatechin (epicatechin) and
its polymers (Adamson et al., 1999). Evidence from epidemiological Studies
suggest that diets high in polyphenols reduce the risk of cardiovascular disease
and related chronic diseases. Chocolate flavonoids are potent antioxidants
capable of protecting LDL from oxidation. Richelle and coworkers (1999)
demonstrated a physiologically significant increase in plasma levels of
epicatechin (0.7 μmol/L) in eight healthy male volunteers after consuming 80 g
of black chocolates. Wang and coworkers (2000) demonstrated a marked
increase in plasma levels of epicatechin in healthy adults 2 hours following the
consumption of procyanidin-rich chocolates. Rein et al., (2000) showed that a
polyphenolic-rich cocoa beverage exerted an aspirin-like effect in 30 healthy
subjects by suppressing platelet activation and function, key factors in the
development of coronary artery disease. A recent study by Mursu et al. (2004)
showed that nonsmoking, healthy young volunteers consuming 75 g daily of
dark chocolate and dark chocolate enriched with cocoa polyphenols increased
their HDL-cholesterol levels by 11.4 percent and 13.7 percent, respectively. In
comparison, the control group consuming white chocolate had a small but
significant decrease in HDL cholesterol levels of -2.9 percent. No effect of
cocoa polyphenols on lipid peroxidation was observed in the young subjects
maintained on the study. Cocoa procyanidins were found by Mao et al. (1999)
to exhibit immunomodulatory effects by inhibiting proliferation and
suppressing the production of interleukin-2 and human T-lymphocytes.
Carnesecchi and coworkers (2002) further examined the antiproliferative effects
of cocoa polyphenols using human colon-cancer cells. The cocoa flavonols and
procyanidins caused nonapoptotic cell death and blocked the G2/M phase of the
cell cycle. They suggested polyamine biosynthesis as one of the targets affected.

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Figure: Epicatechin. (Adapted from Babich et al., Toxicology, in vitro.,
19:231–242, 2005)

6.8.1. References

Adamson, G.E., Lazarus, S.A., Mitchell, A.E., Prior, R.L., Cao, G., Jacobs,
P.H., Kramer, B.G., Hammerstone, J.F., Rucker, R.B., Ritter, K.A., and
Schmidt, H.H., HPLC method for quantification of procyanidins in cocoa
chocolate and correlation to total antioxidant activity, J. Agric. Food Chem.,
47:4168–4186, 1999.

Babich, H., Kruska, M.E., Nissim, H.A. and Zuckerbraun, H.L. Differential
in vitro cytoxicity of (−)-epicatechin gallate (ECG) to cancer and normal cells
from human oral cavity. Toxicol. In vitro. 19:231–241, 2005.

6.9. Cocoa (Theobroma cacao)

Cocoa is a very rich source of procyanidins, oligomeric flavonoids containing

flavan-3-ol units. These compounds are extremely beneficial for their protection
against cardiovascular disease by scavenging oxygen and nitrogen species
(Rice-Evans et al., 1996). In addition, their ability to inhibit oxidant enzymes
has also been reported (Middleton et al., 2000). A recent paper by Mursu et al.
(2004) showed healthy, young volunteers consuming 73 g per day of dark
chocolate or dark chocolate enriched with cocoa polyphenols had their HDL
cholesterol increased by 11.4 percent and 13.7 percent. Schewe and coworkers
(2001) reported that epicatechin and cocoa procyanidins inhibited mammalian
15-lipoxygenase, a key enzyme in lipid peroxidation of biomembranes and
plasma lipoproteins. Recent research by Schewe et al. (2002) concluded that
(−)-epicatechin and its low-molecular-weight procyanidins inhibited both

124
dioxygenase and 5,6-leukotriene A4 (LTA4) synthase activities of human 5-
lipoxygenase, which could account for the antiinflammatory effects of cocoa
products. Inhibition of growth and polyamine biosynthesis by human colonic
cancer cells by cocoa powder and extracts was reported by Carnesecchi and
coworkers (2002). The procyanidin-enriched extracts significantly decreased
ornithine decarboxylase and S-adenosyl-methionine decarboxylase, two key
enzymes of polyamine biosynthesis. These results suggested polyamine
metabolism may be an important target in the antiproliferative effects of cocoa
polyphenols. Yamagishi et al. (2002) reported cocoa liquor proanthocyanidins
protected the lungs from 2-amino-1 -methyl-6-phenylimidazo[4,5-b] pyridine
(PhIP)-induced tumorigenesis, and rat pancreatic carcinogenesis in the initiation
stage but not mammary carcinogenesis.

6.9.1. References

Carnesecchi, S., Schneider, Y., Lazarus, S.A., Coehlo, D., Gosse, F., and
Raul, F., Flavonols and procyanidins of cocoa and chocolate inhibit growth and
polyamine biosynthesis of human colonic cancer cells, Cancer Lett., 175:147–
155, 2002.

Middleton, E., Jr., Kandaswami, C., and Theoharides, T.C., The effects of
plant flavonoids on mammalian cells: Implications for inflammation, heart
disease and cancer, Pharmacol. Rev., 52:673–751, 2000.

Mursu, J., Voutilainen, S., Nurmi, T., Rissanen, T.H., Virtanen, J.K.,
Kaikkonen, J., Nyyssonen, K., and Salonen, J.T., Dark chocolate
consumption increases HDL cholesterol concentration and chocolate fatty acids
may inhibit lipid peroxidation in healthy humans, Free Rad. Biol. Med.,
37:1351–1359, 2004.

Rice-Evans, C.A., Miller, N.J., and Pangana, G., Structure-antioxidant

activity relationship of flavonoids and phenolic acids, Free Rad. Biol. Med.,
20:933–956, 1996.

Schewe, T., Sadik, C., Klotz, L.O., Yoshimoto, T., Kuhn, H., and Sies, H.,
Polyphenols in cocoa: Inhibition of mammalian 15-lipoxygenase, Biol. Chem.,
383:1687–1696, 2001.

Schewe, T., Kuhn, H., and Sies, H., Flavonoids of cocoa inhibit recombinant
human 15- lipoxygenase, J. Nutr., 132:1825–1829, 2002.

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6.10. Coconut (Cocos nucifera)

Coconut is the seed of the coconut palm tree native to the Pacific region of the
tropics. It is composed of a thick outer fibrous husk surrounding a hard, stony
shell. The lining of the shell, or kernel, contains a white, fleshy, oily area called
the meat. Coconut oil is high in saturated fatty acids. Lauric acid, a 12-carbon
saturated acid, accounts for almost 50 percent of the total fatty acids present.
Feeding healthy Polynesians coconut oil, butter, and safflower diets, however,
still showed cholesterol synthesis was lower on the coconut/safflower-oil diets
compared to diets rich in butter (Cox et al., 1998). Padmakumaran Nair and
coworkers (1999) reported that human volunteers fed a diet of coconut oil and
coconut-kernel protein had lower serum-totaland LDL-cholesterol levels
compared to feeding coconut oil alone. The beneficial effects of the kernel
protein was attributed to its very low lysine/arginine ratio.

6.10.1. References

Cox, C., Sutherland, W., Mann, J., de Jong, S., Chisholm, A., and Skeaff,
M., Effects of dietary coconut oil, butter, and safflower oil on plasma lipids,
Eur. J. Clin. Nutr., 52:650–654, 1998.

Padmakumaran Nair, K.G., Rajamohan, T., and Kurup, P.A., Coconut

kernel protein modifies the effect of coconut oil on serum lipids, Plant Foods
Hum. Nutr., 53:133–144, 1999.

Pillai, M.G., Thampi, B.S.H., Menon, V.P., and Leelamma, S., Influence of
dietary fiber from coconut kernel (Cocos nucifera) on the 1,2-dimethylhy-
drazine-induced lipid peroxidation, J. Nutr. Biochem., 10:555–560, 1999.

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6.11. Coffee

Coffee is a popular beverage that is consumed worldwide. Epidemiological

studies on the relationship between coffee and cancer suggests that moderate
coffee consumption (2–5 cups/day) does not represent a risk to humans (Schiller
et al., 2001a). Many studies, in fact, showed an inverse relationship existed
between certain cancer risks and coffee consumption (Nishi et al., 1996;
Giovannucci, 1998; Inoue et al., 1998). Meta-analysis of five cohort and 12
case-control studies all pointed to a significant inverse relationship between
coffee consumption and colorectal cancer (Giovannucci et al., 1998). The
chemoprotective effect of coffee has been demonstrated in experimental
animals by its inhibitory effects on carcinogens, nitrosamines, and 1,2-
dimethyl-hydrazine (Gershbein, 1994; Nishikawa et al., 1986).
Anticarcinogenic effects were also demonstrated for green, as well as roasted,
coffees in animal models treated with 7,12-dimethyl-benz[α]anthacene (Miller
et al., 1988, 1993). Caffeine and polyphenols, such as chlorogenic acid and their
degradation products, were considered to be among the compounds responsible
for the chemoprotective properties of coffee (Stadler, 2001; Schilter et al.,
2001b). A specific lipid fraction in coffee was associated with its ability to
inhibit DMBA-induced cancer in rats, mice, and hamsters (Lam et al., 1982;
Wattenberg et al., 1986; Miller et al., 1991). This fraction contained diterpenes,
cafestol, and kahweol C+K

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Figure: Structures of coffee diterpenes cafestol (C) and kahweol (K). (From
Cavin et al., Food Chem. Toxicol., 40:1155–1163, 2002. With permission.)

The difficulty in isolating these components separately, combined with the

instability of kahweol, led to studies using a mixture of these two compounds.
Cavin et al. (2002) showed the diterpene mixture prevented DNA binding with
aflatoxin B1 and the environmental carcinogen, benzo[a]-pyrene(B[α])P in rat
hepatocyte cultures in a dosedependent response C.27). These diterpenes also
reduced the genotoxicity of several other carcinogens, including 7,12-
dimethylbenz[a]-anthracene (DMBA), aflatoxin B1, and 2-amino-1- methyl-6-
phenylimidazo[4,5-b]pyridine (PhIP), using animal models and cell cultures.
Chemoprotective effects were attributed to induction of conjugating enzymes
(e.g., gluthione S-tranferases and glucuronyl S-transferases), increased protein
expression involved in antioxidant defense (e.g., γ-glutamyl cysteine synthetase
and heme oxygenase-1), and inhibition of expression or activation of
cytochromes P450, the latter normally involved in activation of the carcinogen.
The molecular mechanism appeared similar to many cancer-chemopreventive
blocking agents and involves the Nrf2 transcription factor through regulation of
cis-acting, antioxidant-responsive-element (ARE)-driven gene expression.
Further work by Cavin and coworkers (2003) showed C+K inhibited B[a]P-

128
DNA adduct formation in primary rat hepatocytes and human bronchial Beas-
2B cells. Huber et al. (2003) showed that K/C and Turkish coffee (cafestol
alone) both increased hepatic DNA repair protein O6-methylguanine-DNA
methyl-transferase (MGMT) in a dose-dependent manner. The increase in
MGMT expression provides new insight regarding the
antimutagenic/anticarcinogenic potential of these coffee components. Van Dam
and Feskens (2002) reported coffee consumption may reduce the risk of type 2
diabetes mellitus. Of 17,111 Dutch men and women between the ages of 30–60,
those drinking a minimum of seven cups of coffee a day were 0.50 (95 percent
CI 0.35=0.72, p= 0.0002) times as likely to develop diabetes mellitus compared
to those drinking two or fewer cups. Components in coffee that could contribute
to this effect are caffeine, chlorogenic acid, and magnesium. Tavani and
coworkers (2003) observed an inverse relationship between coffee intake and
risk of oral, pharyngeal, and esophageal cancers. A total of 749 and 395 cases
were studied suffering from oral/pharyngeal and esophageal cancers,
respectively. The multivariate odds ratio (OR) for those drinking more than
three cups of coffee/day compared to one cup of coffee/day were 0.6 (95
percent CI 0.5–0.9) for oral/pharyngeal and 0.6 (95 percent CI 0.4–0.9) for
esophageal cancer, irrespective of age, sex, education, and alcohol
consumption. These results suggested coffee consumption may decrease the risk
of oral/pharyngeal and esophageal cancers.

6.11.1. References

Cavin, C., Bezencon, C., Guignard, G., and Schilter, B., Coffee diterpenes
prevent benzo[a]pyrene genotoxicity in rat and human culture systems,
Biochem. Biophys. Res. Commun., 306:488–495, 2003.

Cavin, C., Holzhaeuser, D., Scharf, G., Constable, A., Huber, W.W., and
Schilter, B., Cafestol and Kahweol, two coffee specific diterpenes with
anticarcinogenic activity, Food Chem. Toxicol., 40:1155–1163, 2002.

Gershbein, L.L., Action of dietary trypsin, pressed coffee oil, silmarin and iron
salt on 1,2- dimethylhy-drazine tumorigenesis by gavage, Anticancer Res.,
14:1113–1116, 1994.

Giovannucci, E., 1998. Meta-analysis of coffee consumption and risk of

colorectal cancer, Am. J. Epidemiol., 147:1043–1057, 1998.

Huber, W.W., Scharf, G., Nagel, G., Prustomersky, S., Schulte-Hermann,

R., and Kaina, B., Coffee and its chemopreventive components kahweol and
cafestol increase the activity of 60- methylguanine-DNA methyltransferase in
rat liver-comparison with phase II xenobiotic metabolism, Mutat. Res., 522:57–
68, 2003.

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Inoue, M., Tajima, K., and Hirose, K., Tea and coffee consumption and the
risk of digestive tract cancers: Data from a comparative case-referent study in
Japan, Cancer Causes Control, 9:209– 216, 1998.

Lam, L.K.T., Sparnins, V.L., and Wattenberg, L.W., Isolation and

identification of kahweol and cafestol palmitate as active constituents of green
coffee beans that enhance glutathione Stransferase activity in the mouse, Cancer
Res., 42:1193–1198, 1982.

Miller, E.G., Formby, W.A., Rivera-Hidalgo, F., and Wright, J.M.,

Inhibition of hamster buccal pouch carcinogenesis by green coffee, Oral Surg.,
65:745–749, 1988.

Miller, E.G., Gonzales-Sanders, A.P., Couvillon, A.M., Binnie, W.H.,

Sunahara, G.I., and Bertholet, R., Inhibition of oral carcinogenesis by roasted
beans and roasted coffee bean fractions, in Association Scientific International
du Café, 15th ASIC International Colloquium on Coffee, Paris, 1993, pp. 420–
425.

Miller, E.G., McWhorter, K., Rivera-Hidalgo, F., Wright, J.M.,

Hirsbrunner, P., and Sunahara, G.I., Kahweol and Cafestol: Inhibitors of
hamster buccal pouch carcinogenesis, Nutr. Cancer, 14:41– 46, 1991.

Nishi, M., Ohba, S., Hirata, K., and Miyake, H., Dose-response relationship
between coffee and the risk of pancreas cancer, Jpn. J. Oncol., 26:42–48, 1996.

Nishikawa, A., Tanaka, T., and Mori, H., An inhibi-tory effect of coffee on
nitrosaminehepatocarcinogenesis with aminopyrine and sodium nitrite in rats, J.
Nutr. Growth Cancer, 3:161–166, 1986.

Schilter, B., Cavin, C., Tritscher, A., and Constable, A., Coffee: Health and
safety considerations, in Coffee Recent Developments, Clarke, R.J., and
Vitzhthum, O.G., Eds., Blackwell Science, London, 2001a, pp. 165–183.

Schilter, B., Holzhaeuser, D., and Cavin, C., Health benefits of coffee,
Proceedings of the 19th International Scientific Colloqium on Coffee, Trieste,
May 14–18, 2001b.

Stadler, R.H., The use of chemical markers and model studies to assess the in
vitro pro- and antioxidative properties of methyl xanthine-rich beverages, Food
Rev. Int., 17:385–418, 2001.

Tavani, A., Bertuzzi, M., Talamini, R., Gallus, S., Parpinel, M., Franceschi,
S., Levi, F., and La Vecchia, C.L., Coffee and tea intake and risk of oral,
pharyngeal and esophageal cancer, Oral Oncol., 39:695–700, 2003.

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Van Dam, R.M. and Feskens, E.J.M., Coffee consumption and risk of type 2
diabetes mellitus, Lancet, 360:1477–1478, 2002.

Wattenberg, L.W., Hanley, A.B., Barany, G., Sparnins, V.L., and Fenwick,
G.R., Inhibition of carcinogenesis by some minor constituents, in Diet,
Nutrition and Cancer, Hayashi, Y., Ed., Japan Science Society Press, Tokyo,
1986, pp. 193–203.

6.12. Garlic

In addition to being a flavoring agent, garlic (Allium sativum L.) is also

pharmacologically active against microbial infection, thrombosis, hypertension,
hyperglycemia, hyperlipidemia, and cancer. The pharmacological properties of
garlic, such as lipid-lowering effects, appear to be related to sulphur-rich
compounds, particularly allicin. Shukla and Taneja (2002) clearly showed the
antimutagenic effects of garlic extract (GE) in Swiss albino mice using an “in
vivo chromosomal aberration assay.” Pretreatment with 2.5 percent and 5
percent GE significantly suppressed chromosomal aberrations in
cyclophosphamide (CP)-treated (a well-known mutagen) mice. The anticytoxic
effects of GE were demonstrated by a significant increase in mitotoxic idex, as
well as reduction in CP-induced clastogenicity. Sengupta et al. (2002) also
showed that garlic constituents protected Swiss mice from DMBA-induced
clastogenicity by significantly reducing chromosomal aberrations in the bone
marrow, Iimuro and coworkers (2002) found that a garlic extract suppressed
Helicobacter pyloriinduced gastritis in Mongolian gerbils. Infection by this
organism has been associated with the development of stomach cancer so that
garlic extract appeared to be useful for reducing the risk of gastric cancer.
Patients with benign prostate hyperplasia and prostate cancer showed significant
improvements after consuming an aqueous garlic extract (1 mL/kg weight) for a
month (Durak et al., 2003). In addition to reducing the mass of prostate, the
urinary frequency was decreased, while maximum and average rates of urine
flow increased. Cancer patients had significantly lower PSA values after
consumption of the garlic extract. Epidemiological data showed an inverse

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relationship between garlic consumption and reduced risk of cardiovascular
disease (Kendler, 1987; Keys, 1980). In their review of garlic and
cardiovascular disease, Banerjee and Maulik (2002) pointed to the need to
identify specific components responsible for its cardioprotective effects. Ozturk
et al. (1994) observed the beneficial effects of garlic extract on vascular
responsiveness in normal rats. A recent study by Baluchnejadmojarad et al.
(2003) showed an aqueous garlic extract significantly improved impaired
endothelium-dependent relaxations, as well as decreased the enhanced
contractile response to phenyl epinephrine in diabetic rats. Fresh garlic was
reported to lower blood pressure in spontaneously hypertensive rats (Foushee et
al., 1982). Further researchers confirmed the ability of garlic to control mild
hypertension. Al-Quattan et al. (1999) examined the effectiveness of garlic in
treating more severe hypertension, such as in unilateral renovascular
hypertension (URVH). Using a 2K1C hypertensive rat, they showed that a
single dose had a maximum antihypertensive effect 2–6 h after administration,
continuing for up to 24 h (Table G.33). Multiple doses of garlic also controlled
the rise in blood pressure in these hypertensive rats. Sharif et al. (2003) showed
a negative correlation between garlic, blood pressure, and angiotensin-
converting enzyme (ACE) using the same 2K1C hypertensive model. An
enteric-coated garlic-powder supplement suggested that the ability of garlic to
lower blood pressure was attributed, in part, to a reduction in ACE activity.

6.12.1. References

Al-Quattan, K.K., Alnaqeeb, M.A., and Ali, M., The antihypertensive effect
of garlic (Allium sativum) in the rat two-kidney-one-clip Goldblatt model, J.
Ethnopharmacol., 66:217–222, 1999.

Baluchnejadmojarad, T., Roghani, M., Homayounfar, H., and Hosseini,

M., Beneficial effect of aqueous garlic extract on the vascular reactivity of
streptozoticin-diabetic rats, J. Ethnopharmacol., 85:139–144, 2003.

Banerjee, S.K. and Maulik, S.K., Effect of garlic on cardiovascular disorders:

A review, Nutr. J., 1:4, 2002.

Durak, I., Yllmaz, E., Devrim, E., Perk, H., and Kacmaz, M., Consumption
of aqueous garlic extract leads to significant improvement in patients with
benign prostate hyperplasia and prostate cancer, Nutr. Res., 23:199–204, 2003.

Foushee, D.B., Ruffn, J., and Banerjee, U., Garlic as a natural agent for the
treatment of hypertension: A preliminary report, Cytobios, 34:142–152, 1982.

Iimuro, M., Shibata, H., Kawamori, T., Matsumoto, T., Arakawa, T.,
Sugimura, T., and Wakabayashi, K., Suppressive effects of garlic extract on

132
Helicobacter pylori-induced gastritis in Mongolian gerbils, Cancer Lett.,
187:61–68, 2002.

Kendler, B.S., Garlic (Allium sativum) and onion (Alliuim cepa): A review of
their relationship to cardiovascular disease, Prev. Med., 16:670–685, 1987.

Keys, A., Wine, garlic and CHD in seven countries. Lancet, 1:145–146, 1980.

Ozturk, Y., Aydin, S., Kosar, M., and Baser, K.H.C., Endothelium-
dependent and independent effects of garlic and rat aorta, J. Ethnopharmacol.,
44:109–116, 1994.

Sengupta, A., Ghosh, S., and Das, S., Administration of garlic and tomato can
protect from carcinogen induced clastogenicity, Nutr. Res., 22:859–866, 2002.

Sharifi, A.M., Darabi, R., and Akbarloo, N., Investigation of antihypertensive

mechanism of garlic in 2K1C hypertensive rat, J. Ethnopharmacol., 86:219–
224, 2003.

Shukla, Y. and Taneja, P., Antimutagenic effects of garlic extract on

chromosomal aberrations, Cancer Lett., 176:31–36, 2002.

Zhang, X.-H., Lowe, D., Giles, P., Fell, S., Connock, M.J., and Maslin, D.J.,
Gender may affect the action of garlic oil on plasma cholesterol and glucose
levels of normal subjects, J. Nutr., 131:1471–1478, 2001.

6.13. Ginseng

Ginseng, the root of Panax ginseng, has been used in Oriental medicine for
many centuries to treat a wide range of ailments. In Europe, it is sold over the
counter to enhance physical and mental performance. Ginseng products are
either white or red. White ginseng is the dried root with the skin peeled off,
whereas red ginseng is the steamed root, which is caramel-colored. White
ginseng (includes lateral roots and root hairs) is commonly used in the

133
European market, while red ginseng is the preferred form in Asia. The unique
constituents identified in ginseng include several classes of compounds:
triterpene saponins; essential oil-containing poly acetylenes and sesquiterpenes;
polysaccharides; peptidoglycans; and nitrogen-containing compounds (Tang
and Eisenbrand 1992). Triterpene saponins are referred to as ginsenosides, as
their property appears to be a function of the number of monosaccharide
residues in the sugar chain (Hostettmann and Marston, 1995). Thirty-one
ginsenosides have been isolated from the roots of white and red ginseng that can
be categorized into three groups, based on their aglycones, as protopanaxadiol-
type, protopanaxatriol-type, and oleanolic acid-type saponins (Sticher, 1998).
Ginseng is specified in the Swiss and German pharmacopeias on the total
ginsensoside content, calculated as ginsenoside Rg1, as not less than 2.0 percent
and 1.5 percent, respectively. The European pharmacopeia requires that the
ginsenoside Rga and Rb1 content in ginseng must not be less than 0.3 percent.
Research on ginseng suggests ginsenosides have antiaging properties by
enhancing the immune system by increasing serum-specific antibodies and IgG
content and protective B-lymphocytes (Nah et al, 1995; Liu et al., 1995;
Yamada et al., 1995). In addition to ginsenosides other isolated components,
such as polyacetylenes, panaxytriol, panaxynol, and panaxydol have cytotoxic,
antiplatelet, and antiinflammatory properties, respectively (Deng and Zhang,
1991; Matsunaga et al., 1995; Kobayashi et al., 1995). The hypoglycemic effect
of ginseng is attributed to its polysaccharides, the panaxans, which are
themselves peptidoglycans. Immunological activity is also associated with some
of its polysaccharides, the ginsenans. While the precise structures of these
polysaccharides are not fully known, their backbone chain is mainly β-1,3-
linked D-galactoside (Tomoda et al., 1993).

6.13.1. References

Deng, H. and Zhang, J., Anti-lipid peroxidative effect of ginsenoside Rb1 and
Rg1, Chin. Med. J., 104:395–398, 1991.

Hostettmann, K. and Marston, A., Saponins. Cambridge University Press,

Cambridge, U.K., 1995, p. 50.

Kobayashi, M., Mahmud, T., Umezome, T., and Kitgawa, I., The absolute
stereostructure of panaxytriol, a biologically active diacetylenic acetogenin,
from Ginseng Radix Rubra, Chem. Pharm. Bull., 43:1595–1597, 1995.

Liu, J., Wang, S., Liu, H., Yang, L., and Nan, G., Stimulatory effect of
saponin from Panax ginseng on immune function of lymphocytes in the elderly,
Mech. Ageing Dev., 83:43–53, 1995.

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Matsunaga, H., Saita, T., Nagumo, F., Mori, M., and Katano, M., A possible
mechanism for the cytoxicity of a polyacetylenic alcohol, panaxtriol, inhibition
of mitochondrial respiration, Cancer Chemother. Pharmacol., 35:291–296,
1995.

Nah, S., Park, H., and McCleskey, E.W., A trace component of ginseng that
inhibits Ca2+ channels through a pertussis toxin-sensitive G-protein, Proc. Natl.
Acad. Sci., 92:8739–8743, 1995.

Sticher, O., Getting to the root of ginseng, Chemtech, (April):26–32, 1998.

Tang, W. and Eisenbrand, G., Chinese Drugs of Plant Origin, Springer Verlag,
Berlin, 1992, pp. 711–737.

Yamada, H., Otsuka, H., and Kiyohra, H., Fractionation and characterization
of anticomplimentary and mitogenic substances from Panax ginseng extract G-
115, Phytother. Res., 9:264–269, 1995.

6.14. Green Tea

Green tea, a popular beverage in Japan made from the leaves of Camellia
sinensis, is recognized for its health benefits. It is a nonfermented product
obtained by leaf dessication that contains potent, polyphenolic antioxidants,
with a flavan-3-olic structure, referred to as green-tea catechins. They include
seven types, (−)-gallocatechin (GC), (−)- epigallocat-echin (EGC), (+)-catechin
(C), (−)-epigallocat-echin-3-gallate (EGCG), (−)- epigallocatechin (EC), (−)-
gallocatechingallate (GCG), and (−) epicatechingallate (ECG) (Bonoli et al.,
2003). Many studies have shown that drinking EGCG and green tea prevents
carcinogenesis in rodent organs (Wang et al., 1992; Fujiki, 2002). Kavanagh et
al. (2001) showed green tea had a significant chemoprotective effect against 7,
12-dimethyl(a)anthracene (DMBA)-induced mammary tumorigenesis in
Sprague-Dawley rats. Inhibition of human breast cancer Hs578T cell
proliferation by green tea appeared to be mediated, in part, by induction of
p27Kip cyclindependent kinase inhibitor (CKI) expression. Gupta et al. (2002)
summarized the antimutagenic and anticlastogenic properties of green and black
teas. Green tea inhibited mutagenesis at concentration levels equivalent to

135
human daily consumption. Using human umbilicalvein endothelial cells,
Kojima-Yuasa et al. (2003) demonstrated, for the first time, that green-tea
extracts reduced expression of vascular endothelial growth factor (VEGF)
receptors fms-like tyrosine kinase (Flt-1) and fetal liver kinase-1/Kinase insert
domain containing receptor (Flk-1/KDR). The antiangiogenic property of green-
tea extracts has therapeutic potential in preventing the development of new
microvascular networks (angiogenesis) needed for tumor growth. Maiti and
coworkers (2003) also found green-tea polyphenols inhibited angiogenesis by
reducing vascularization of chicken chorioallantoic membrane (CAM) by an
angiogenin-like protein isolated from goat serum. Kemberling et al. (2003)
showed greentea EGCG effectively inhibited bladder-tumor implantation
growth in a Fischer 344 rat model, pointing to its potential as an intravesical
chemotherapeutic agent. Reducing the risk of coronary artery disease is
associated with a number of factors, including inhibition of platelet function.
EGCG was reported to inhibit platelet aggregation, possibly by involving
inhibition of cytoplasmic calcium increase (Kang et al., 1999). Lill and
coworkers (2003) found that only those green catechins with a galloyl group in
the 3′ position inhibited platelet aggregation, while those without a galloyl
group (catechin and epicatechin) or withthe galloyl group in the 2′ position
(epigallo-catechin) did not. EGCG proved to be the most effective in reducing
thrombrin-induced aggregation of washed human platelets .The ability of green-
tea catechins to inhibit adenovirus infection and adenain, the human adenovirus
2 endopeptidase, was reported by Weber and coworkers (2003). EGCG proved
the most potent inhibitor of four green-tea catechins tested with a IC50 of 200
μM (Table G.36). Since the viral protease, adenain, appeared to be the target of
EGCG, it is possible that all adenoviruses are sensitive to its action.

6.14.1. References

Bono, M., Colabufalo, P., Pelillo, M., Toschi, T.G. and Lerker, G., First
determination of catechins and xanthines in tea beverage by micellar
electrokinetic chromatograph, J. Agric. Food Chem., 51:1141–1147, 2003.

Fujiki, H., Two stages of cancer prevention with green tea, J. Cancer Res. Clin.
Oncol., 125:589– 597, 1999.

Fujiki, H., Suganuma, M., Imai, K., and Nakachi, K., Green tea: Cancer
preventive beverage and/or drug, Cancer Lett., 188:1–2, 9–13, 2002.

Gupta, S., Saha, B. and Giri, A.K., Comparative antimutagenic and

anticlastogenic effects of green tea and black tea. Mutat. Res., 412:37–65, 2002.

136
Kang, W.S., Lim, I.H., Yuk, D.Y., Chung, K.H., Park, J.B., Yoo, H.S. and
Yu, Y.P., Antithrombotic activities of green tea catechins and C-1-
epigallocatechin gallate, Thromb. Res., 96:229–237, 1999.

Kavanagh, K.T., Hafer, L.J., Kim, D.W., Mann, K.K., Sherr, D.H., Rogers,
A.E. and Sonenshein, G.E., Green tea extracts decrease carcinogen-induced
mammary tumor burden in rats and rate of breast cancer cell proliferation in
culture, J. Cell Biochem., 82:387–398, 2001.

Kemberling, J.K., Hampton, J.A., Keck, R.W., Gomez, M.A. and Selman,
S.H., Inhibition of bladder tumor growth by the green tea derivative
epigallocatechin-3-gallate, J. Urol., 170:773– 776, 2003.

Lill, G., Voit, S., Schror, K., and Weber, A.-A., Complex effects of different
green tea catechins on human platelets, FEBS Lett., 546:265–270, 2003.

Maiti, T.K., Chatterjee, J. and Dasgupta, S., Effect of green tea polyphenols
on angiogenesis induced by an angiogenin-like protein, Biochem. Biophys. Res.
Commun., 308:64–67, 2003.

Toschi, T.G., Bordoni, A., Hrelia, S., Bendini, A., Lercker, G., and Biagi,
P.L., The protective role of different green tea extracts after oxidative damage
is related to their catechin composition, J. Agric. Food Chem., 48:3973–3978,
2000.

Wang, Z.Y., Hong, J.-Y., Huang, M.T., Ruehl, K.R., Conney, A.H., and
Yang, C.S., Inhibition of N-nitrosodiethylamine and 4-(methylnitrosamino)-1-
(3-pyridyl)-1-butanone induced tumorigenesis in A/J mice by green tea and
black tea, Cancer Res., 52: 1943–1947, 1992.

Weber, J.M., Ruzindana-Umunyana, A., Imbeault, L., and Sircar, S.,

Inhibition of adenovirus infection and adenain by green tea catechins, Antiviral
Res., 58:167–173, 2003

6.15. Honey

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Honey, a complex mixture of carbohydrates, has been studied extensively
(Horvath and Molnarl-Perl, 1998; Gomez Barez et al., 2000). In addition, some
cyclitols or poly alcohols, such as myo-inositol and mannitol, have also been
reported in edible honeys (Horvath and Molnarl-Perl, 1998). Sanz and
coworkers (2004) identified quercitol, pinitol, 1-O-methylmuco-inositol, and
muco-inositol for the first time in edible honey. Of 28 honeys examined, most
had myo-inositol and pinitol, while only in some samples were the other
cyclitols detected. The anti-inflammatory nature of (+)-pinitol, isolated from
Abies pindrow leaves, was demonstrated by Singh and coworkers (2001) using
the carrageenan-induced paw edema in rats. A significant reduction in edema
volume was evident in the presence of pinitol with a dose of 10 mg/kg
comparable to that of phenylbutazone . Certain honeys derived from such floral
sources as Leptospermum scoparium (Manuka) and L. polygalifolium
(Meadhoney) provide additional antioxidants, antibacterial agents, and other
unidentified compounds and are referred to as therapeutic honeys (Lusby et al.,
2002). The ability of these honeys to prevent microbial growth in the moist-
wound environment accounts, in part, for their beneficial effects in wound
healing. Tonks et al. (2003) examined the wound-healing ability of three honeys
(manuka, pasture, and jelly bush) on the activation state of immunoincompetent
cells, using the human monocytic cell-line model MonoMac-6. All of the
honeys significantly increased the release of important inflammatory cytokines
TNF-α, IL-1β, and IL-6 . These cytokines are both proinflammatory and anti-
inflammatory. While all three honeys showed significant increases in cytokines
compared to the sugar-solution control, the Australian jelly-bush honey had the
greatest effect. The ability of these honeys to regulate the production of
cytokines is probably due to the presence of components other than sugar.
These components have yet to be identified but could involve cyclitols.

Figure: Myo-inositol and D-pinitol. (From Hart et al., Carbohydr. Res.,

339:1857–1871, 2004. With permission.)

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6.15.1. References

Gomez Barez, J.A., Garcia Villanova, R.J., Elvira Garcia, S., Rivas Pala,
T., Gonzalez Paramas, A.M., and Sanchez Sanchez, J., Geographical
distribution of honeys through the employment of sugar patterns and common
chemical quality parameters, Eur. Food Res. Technol., 210:437– 444, 2000.

Hart, J.B., Kroger, L., Falshaw, A., Falshaw, R., Farkas, E., Thiem, J., and
Win, A.L., Enzymecatalysed synthesis of galactosylated 1D- and 1L-chiro-
inositol, 1D-pinitol, myo-inositol and selected derivatives using the β-
galactosidase from the thermophile Thermoanaerobacter sp. strain TP6-B1,
Carbohydr. Res., 339:1857–1871, 2004.

Horvath, K. and Molnarl-Perl, I., Simultaneous GC-MS quantitation of o-

phosphoric, aliphatic and aromatic carboxylic acids, proline,
hydroxymethylfurfural and sugars as their TMS derivatives: In honeys,
Chromatographia, 48:120–126, 1998.

Lusby, P.E., Coombes, A., and Wilkinson, J.M., Honey: A potent agent for
wound healing? JWOCN, 29:295–300, 2002.

Sanz, M.L., Sanz, S.J., and Martinez-Castro, I., Presence of some cyclitols in
honey, Food Chem., 84: 133–135, 2004.

Singh, R.K., Pandey, B.L., Tripathi, M., and Pandey, V.B., Anti-
inflammatory effect of (+)-pinitol, Fitoterapia, 72:168–170, 2001.

Tonks, A.J., Cooper, R.A., Jones, K.P., Blair, S., Parton, J., and Tonks, A.,
Honey stimulates inflammatory cytokine production from monocytes, Cytokine,
21:242–247, 2003.

6.16. Lemon

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 Lemon juice is a rich source of ascorbic acid and flavonoids. The antioxidant
properties of these compounds have been suggested to inhibit heart disease and
certain types of cancers (Salah et al., 1995). Marin and coworkers (2002) found
these nutraceuticals were higher in Fino lemon juice compared to the Vern
variety. In addition, they found that different industrial-extraction systems
affected the levels of these components. Miyake et al. (1997) identified the
flavonoid, eriocitrin, in lemon fruit, which had considerable antioxidant activity.
Ogata and coworkers (2000) showed this flavonoid induced apoptosis in HL-60
cells and may have therapeutic applications. A recent study of Citrus limon
flavonoids by Del Rio et al. (2004) found that immature fruit from Lisbon and
Fino-9 cultivars were excellent sources of the flavonone hesperidin, while
mature fruits from Fino-9 and leaves of Eureka were good sources of the
flavone diosmin and the flavonone eriocitrin. Each of these flavonoids have
been shown to have pharmaceutical properties.

6.16.1. References

Del Rio, J.A., Fuster, M.D., Gonez, P., Porras, I., Garcia-Lidon, A., and
Ortuno, A., Citrius limon: A source of flavonoids of pharmaceutical interest,
Food Chem., 84:457–461, 2004.

Marin, F.R., Martinez, M., Uribesalgo, T., Casillo, S., and Frutos, M.J.,
Changes in nutraceutical composition of lemon juices according to different
industrial extraction systems, Food Chem., 78:319–324, 2002.

Miyake, Y., Yamamoto, K., and Osawa, T., Isolation of eriocytrin

(eryodictiol-7-rutinoside) from lemon fruit (Citrus limon BURM.f.) and its
antioxidative activity, Food Sci. Tecnol. Int. Tokio., 3:84–89, 1997.

Ogata, S., Miyaje, Y., Yamomoto, K., Okumura, K., and Taguchi, H.,
Apoptosis induced by the flavonoid from lemon fruit (Citrus limon BURM. f.)
and its metabolites in HL-60 cells, Biosci. Biotechnol. Biochem., 64:1975–
1978, 2000.

Salah, N., Miller, N.J., Paganga, G., Tijburg, L., Bolwell, G.P., and Rice-
Evans, C., Polyphenolic flavonols as scavenger of aqueous phase radicals and
as chain-breaking antioxidants, Arch. Biochem. Biophys., 322:339–346, 1995.

140
6.17. Onions (Allium cepa Liliacae)

Onions are one of the major sources of flavonoids in the Western diet (Knekt et
al., 1996). They are particularly rich in quercetin, and its glycosides have been
used in traditional medicine for their antiasthmatic, antithrombotic,
antihypertensive, antihyperglycemic, antihyperlipidemic, and antitumor
properties (Bordia et al., 1975, 1977; Belman, 1983; Dorsch et al., 1985;
Kleijnen et al., 1990; Wagner et al., 1990). These health benefits are attributed
to the presence of flavonoids and alk(en)yl cysteine sulphoxides in onions
(Griffiths et al., 2002). In vitro studies by Glasser et al. (2002) showed
quercetin, a flavonoid in onion, inhibited hepatic cholesterol biosynthesis.
Kumari and Augusti (2002) found (+)-Smethyl- L-cysteine sulfoxide in onion
exhibited antidiabetic and antioxidant activities comparable to standard drugs.
However, Ali and coworkers (2000) found onion extracts ineffective in
lowering serum cholesterol in rabbits kept on a cholesterol-supplemented diet
compared to garlic. The presence of quercetin, alkyl sulfides, and diallyl
disulfide in onions suggested it had strong anticancer properties. Seki et al.
(2000) found that both onions and garlic equally suppressed the growth of
leukemia HL-60 cells. Hu and coworkers (1999) reported an inverse
relationship between onions in the diet and the risk of brain cancer. Shon and
coworkers (2004) found the antioxidant and antimutagenic activities of
ethylacetate extracts from red, yellow, and white onion extracts could be
attributed to the presence of phenols and flavonoids.

6.17.1. References

Ali, M., Thomson, M., and Afzal, M., Garlic and onions: Their effect on
eicosanoid mretabolism and its clinical relevance, Prost. Leuk. Essent. Fatty
Acids, 62:55–73, 2000.

Belman, S., Onion and garlic oils inhibit tumour promotion, Carcinogenesis,
4:1063–1065, 1983.

141
Bordia, A., Bansal, H.C., Arora, S.K., and Singh, S.V., Effect of essential
oils of garlic and onion on alimentary hyperlipemia, Atherosclerosis, 21:15–19,
1975.

Bordia, A., Verma, S.K., Vyas, A.K., Khabya, B.L., Rathore, A.S., Bhu, N.,
and Bedi, H.K., Effect of essential oil of onion and garlic on experimental
atherosclerosis in rabbits, Atherosclerosis, 26:379–386, 1977.

Dorsch, W.V., W., Adam, H.O., Weber, J., and Ziegeltrum, T.,
Antiasthmatic effects of onion extracts—detection of benzyl- and other
isothiocyanates (mustard oils) as antiasthmatic compounds of plant origin, Eur.
J. Pharmacol., 107:17–24, 1984.

Glasser, G., Graefe, E.U., Struck, F., Veit, M., and Gebhardt, R.,
Comparison of antioxidative capacities and inhibitory effects on cholesterol
biosynthesis of quercetin and potential metabolites, Phytomedicine, 9:33–40,
2002.

Griffiths, G., Trueman, L., Crowther, T., Thomas, B., and Smith, B.,
Onions—a global benefit to health, Phytother. Res., 16:603–615, 2002.

Hu, J., La Vecchia, C., Nigri, E., Chatenoid, L., Bosetti, C., Jia, X., Liu, R.,
Huang, G., Bi, D., and Wang, C., Diet and brain cancer in adults: a case
controlled study in Northeat China, Inst. J. Cancer, 81:2–23, 1999.

Kleijnen, J., Knipschild, P., and Terriet, G., Garlic, onions and
cardiovascular risk factors: A review of the evidence from human experiments
with emphasis on commercially available preparations, Br. J. Clin. Pharmacol.,
28:535–544, 1989.

Knekt, P., Jarvinen, R., Reunanen, A., and Maatela, J., Flavonoid intake and
coronary mortality in Finland: A cohort study, Br. Med. J., 312:478–481, 1996.

Kumari, K. and Augusti, K.T., Antidiabetic and antioxidant effects of S-

methyl cysteine sulfoxide from onions (Allium cepa Linn) as compared to
standard drugs in alloxan diabetic rats, Ind. J. Exp. Biol., 40: 1005–1009, 2002.

Seki, T., Tsuji, K., Hayato, Y., Moritomo, T., and Ariga, T., Garlic and
onion oils inhibit proliferation and induce proliferation and induce
differentiation of HL60 cells, Cancer Lett., 160:29–35, 2000.

Shon. M.-Y., Choi, S.-D., Kahng, G.-G., Nam, S.-H., and Sung, N.-J.,
Antimutagenic, antioxidant and free radical scavenging activity of ethyl acetate
extracts from white, yellow and red onions, Food Chem. Toxicol., 42:659–666,
2004.

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Thomson, M., Alnaqeeb, M.A., Bordia, T., Al-Hassan, J., Afzal, M., and
Ali, M., Effects of aqueous extract of onion on the liver and lung of rats, J.
Ethnopharmacol., 61:91–99, 1998.

Wagner, H., Dorsch, W., Bayer, Th., Breu, W., and Wilier, F.,
Antiasthmatic effects of onions: Inhibition of 5-lipoxygenase and
cyclooxygenase in vitro by thiosulfinates and cepaenes, Prostagland. Leuk.
Essent. Fatty Acids, 39:59–62, 1990

6.18. Red Wines

Polyphenols, mainly flavonoids, exert protective effects on the cardiovascular

system (Wollin and Jones, 2001), as well as exhibit anticancer (Bianchini and
Vainio, 2003), antiviral, and antiallergic properties (Bhat et al., 2001). In
coronary heart disease, the protective effects of flavonoids are antithrombic,
antioxidant, antiischemic, and vasorelaxant properties (de Lorimier, 2000). It
has been hypothesized that the phenomenon of a low incidence of coronary
heart disease in French people may be partially related to the pharmacological
properties of polyphenolic compounds included in red wine (Zenebe and
Pechanova, 2002). The mechanisms underlying CHD protective benefits of red
wine have not been elucidated. Recently, the polyphenol resveratrol (3,5,4′-
trihydroxy-trans-stilbene), known to be abundantly present in red wine
compared to white wine, beer, or spirits, has been demonstrated to elicit a broad
spectrum of biological responses in in vitro and in animal studies, including
effects that are compatible with the cardioprotective roles proposed for red
wine. Other studies relate exposure to wine/resveratrol with reduction in
myocardial damage during ischemiareperfusion, modulation of vascular cell
functions (Wu et al., 2001), inhibition of LDL oxidation, and suppression of
platelet aggregation (Halpern et al., 1998; Wu et al., 2001; Wollin and Jones,
2001). Grapes contain a variety of antioxidants, including resveratrol, catechin,
epicatechin, and proanthocyanidins. Of these, resveratrol is present mainly in
grape skin, while proanthocyanidin is present in the seeds. Das and coworkers
(1999) demonstrated that red-wine extract, as well as resveratrol and

143
proanthocyanidins, are equally effective in reducing myocardial ischemic
reperfusion injury, which suggests that these redwine polyphenolic antioxidants
play a crucial role in cardioprotection. Schafer and Bauersachs (2002) reported
that red wine may beneficially affect the development of high-altitude
pulmonary edema, which is the predominant cause of death due to highaltitude
illness. Two cellular mechanisms have been described for the altituderelated
reduction in barometric pressure: enhanced endothelin 1 production and the
increased generation of reactive-oxygen species. Both were suppressed by red
wine.

6.18.1. References

Bhat, K.P.L., Kosmeder, II, J.W., and Pezzuto, J.M., Biological effects of
resveratrol, Antioxid. Redox Signal, 3:1041–1064, 2001.

Bianchini, F. and Vainio, H., Wine and resveratrol: Mechanisms of cancer

prevention? Eur. J. Cancer Prev., 12:417–425, 2003.

Das, D.K., Sato, M., Ray, P.S., Maulik, G., Engelman, R.M., Bertelli, A.A.,
and Bertelli, A., Cardioprotection of red wine: Role of polyphenolic
antioxidants, Drugs Exp. Clin. Res., 25:115–120, 1999.

de Lorimier, A.E., Alcohol, wine, and health, Am. J. Surg., 180:357–361,

2000.

Halpern, M.J., Dahlgren, A.L., Laakso, I., SeppanenLaakso, T., Dahlgren,

J., and McAnulty, P.A., Redwine polyphenols and inhibition of platelet
aggregation: Possible mechanisms, and potential use in health promotion and
disease prevention, J. Int. Med. Res., 26:171–180, 1998.

Schafer, A. and Bauersachs, J., High-altitude pulmonary edema: Potential

protection by red wine, Nutr. Metab. Cardiovasc. Dis., 12:306–310, 2002.

Wollin, S.D. and Jones, P.J., Alcohol, red wine and cardiovascular disease, J.
Nutr., 131:1401– 1404, 2001.

Wu, J.M., Wang, Z.R., Hsieh, T.C., Bruder, J.L., Zou, J.G., and Huang,
Y.Z., Mechanism of cardioprotection by resveratrol, a phenolic antioxidant
present in red wine (review), Int. J. Mol. Med., 8:3–17, 2001.

Zenebe, W. and Pechanova, O., Effects of red wine polyphenolic compounds

on the cardiovascular system, Bratisl. Lek. Listy., 103:159–165, 2002.

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6.19. Rooibos Tea

Rooibos tea is an herbal tea produced from the leaves and fine stems of the
South African leguminous shrub Aspalathus linearis, also known as Rooibos.
The herbal tea is considered a health drink due to the presence of beneficial
phenolic antioxidants. The antioxidant properties of Rooibos tea were found to
be similar to green, oolong, and black tea (von Gadow et al., 1997a). Rooibos
tea, however, contains a unique compound, aspalathin, that mimics superoxide
dismutase (SOD) (Yoshikawa et al., 1990; Ito et al., 1991). Compared to BHA,
BHT, and α-tocopherol, aspalathin exhibited the highest radical-scavenging
activity (von Gadow et al., 1997b). In vitro and in vivo studies found rooibos
tea exhibited anti-mutagenic properties against aflatoxin B1 and 2-acetylamino
fluorine-induced mutagenesis (Marnewick et al., 2000; Marnewick et al.,
2004a). In addition, aqueous extracts of rooibos tea enhanced phase II
detoxifying enzymes, glutathione-S transferase, and UDP-glucuronyl
transferase in rat liver, stabilizing glutathione (GSH) (Marnewick et al., 2003).
Ethanol/ acetone (E/A)-soluble fractions prepared from methanolic extracts of
processed and unprocessed South African herbal teas, rooibos, and honeybush
compared to green tea were recently shown by Marnewick and coworkers
(2004b) to inhibit tumor promotion in mouse skin. Using the two-stage mouse-
skin carcinogenesis assay with the tumor promoter 12-O-tetra decanoylphorbol-
13-acetate (TPA) on ICR mouse skin initiated with 7,12-dimethyl
benz[a]anthracene (DMBA), they found herbaltea fractions significantly
(p<0.001) decreased tumor volume, as well as delayed their development
(Figure R.87). Compared to the control, tumors did not appear in the
DMBA/TPA-treated mice at 4 and 12 weeks when maintained on processed and

145
unprocessed rooibos, respectively. Green tea exhibited 100 percent inhibition
compared to 90 percent and 84.2 percent inhibition for unprocessed and
processed honeybush. While processed and unprocessed rooibos proved to be
the least effective, they nevertheless accounted for an impressive 75 percent and
60 percent inhibition of tumor promotion, respectively. The variability in tumor
inhibition exhibited by these herbal teas was attributed to differences in their
flavonol/proanthocyanidin and flavonol/flavone composition and
nonpolyphenolic components.

6.19.1. References

Ito, A., Shinohara, K., and Kator, K., Protective action of Rooibos tea
(Aspalathis linearis) extract against inactivation of L5178Y cells by H2O2, in
Proceedings of the International Symposium on Tea Science, Shizuoka, Japan,
1991, pp. 381–384.

Jaganyi, D. and Wheeler, P.J., Rooibos tea: equilibrium and extraction

kinetics of aspalathin, Food Chem., 83:121–126, 2003.

Figure: Aspalathin. (From Jaganyi and Wheeler, Food Chem., 83:121–126,

2003. With permission.)

Marnewick, J.L., Batenburg, W., Wart, P., Joubert, E., Swanevelder, S.,
and Gelderblom, W.C.A., Ex vivo modulation of chemical-induced
mutagenesis by sub cellular liver fraction of rats treated with rooibos
(Aspalathus linearis) tea, honeybush (Cyclopia intermedia) tea, as well as green
and black (Camellia sinensis) teas, Mutat. Res., 558:145–154, 2004a.

Marnewick, J.L., Gelderblom, W.C.A., and Joubert, E., An investigation of

the antimutagenic properties of South African herbal teas, Mutat. Res.,
471:157–166, 2000. Marnewick, J., Joubert, E., Joseph, S., Swanevelder, S.,
Swart, P., and Gelderblom, W., Inhibition of tumor promotion in mouse skin by
extracts of rooibos (Aspalathis linearis) and honeybush (Cyclopedia
intermedia), unique South African herbal teas, Cancer Lett., 224:193–202,
2005.

146
Marnewick, J.L., Joubert, E., Swart, P., Joubert, E., van der Westhuizen,
F., and Gelderblom, W.C.A., Modulation of hepatic drug metabolizing
enzymes and oxidative status of rooibos (Aspalathus linearis) and honeybush
(Cyclopia intermedia) green and black (Camellia sinensis) teas in rats, J. Agric.
Food Chem., 51:8113–8119, 2003.

von Gadow, A., Joubert, E., and Hansmann, C.F., Comparison of the
antioxidant activity of rooibos tea (Aspalathus linearis) with green, Oolong and
black tea, Food Chem., 60:73–77, 1997a.

von Gadow, A., Joubert, E., and Hansmann, C.F., Comparison of the
antioxidant activity of aspalathin with that of other plant phenols of Rooibos tea
(Aspalathus linearis), alphatocopherol, BHT, and BHA, J. Agric. Food Chem.,
45:632–638, 1997b.

Yoshikawa, T., Naito, Y., Oyamada, H., Ueda, S., Tanigawa, S., Takemura,
T., Sugino, S., and Kondo, M., Scavenging effect of Aspalathus linearis
(Rooibos tea) on active oxygen species, in Antioxidants in Therapy and
Preventative Medicine, Emerit, I., Packer, L., and Auclair, C., Eds., Plenum
Press, New York. 1990, pp. 171–174.

6.20. Sorghum (Sorghum Vulgare)

Sorghum is the major food crop in the semiarid regions of Africa and Asia. It
provides a component to the diets of many people in the form of unleavened
breads, boiled porridge or gruel, malted beverages, and specialty foods, such as
popped grain and beer (Anglani, 1998). A syrup is produced from sweet
sorghum. The crop is also used for building material, fencing, fodder for
animals, and for brooms. In the United States, sorghum grain is used primarily
for livestock feed, and the stems and foliage for green chop, hay, silage, and
pasture. A comparison of the nutritional and chemical parameters of 10 varieties
of sorghum showed components to range from lipids (2.70–3.75 percent), raw
fiber (60.0–64.7 percent), protein (9.01–11.43 percent), no nitrogen extract

147
(77.65–83.07 percent), starch (60.5–64.20 percent), tannin (2.50–10.16 mg/g),
and total calories (380–4000 kcal). Ash content, with values of 1.17–1.91
percent, protein digestibility (23.8–38.8 percent), and in situ starch (54.4–66.6
percent) were not statistically different (Torres Cepeda et al., 1996) Sorghum is
a rich source of various phytochemicals, including tannins, phenolic acids,
anthocyanins, phytosterols, and policosanols (Awika and Rooney, 2004). These
phytochemicals are known to impact human health. Sorghum fractions possess
high antioxidant activity in vitro, relative to other cereals or fruits.
Epidemiological studies suggest that, in comparison to other cereals, sorghum
consumption reduces the risk of certain types of cancer in humans. Kamath et
al. (2004), using the DPPH model system for assessing antiradical properties,
recently identified various extracts from sorghum flour that exhibited
significant, greater antioxidant activity than BHT .

Figure : Effect of subfractions of methanol extracts on quenching DPPH

radicals-time related effect. 50 μL (0.2 mg) of either extract of sorghum
was employed for quenching. An equal volume of respective solvents was
used in control. 50 μL (10 mM) BHT was used. Each value represents mean
± standard error (n— 6). (From Kamath et al., J. Cereal Sci., 40:283–288,
2004. With permission.)

Even though they were unable to correlate anti-oxidant activity and phenolic
content, diets rich in sorghum could still be helpful in combating chronic
diseases involving free radicals. This explains why sorghum phytochemicals
promote cardiovascular health and are involved in cancer prevention (Awika
and Rooney, 2004).

6.20.1. References

148
Anglani, C., Sorghum for human food—a review, Plant Foods Hum. Nutr.,
52:85–95, 1998.

Awika, J.M. and Rooney, L.W., Sorghum phytochemicals and their potential
impact on human health, Phytochemistry, 65:1199–1221, 2004.

Kamath, V.G., Chandrashekar, A., and Ranjini, P.S., Antiradical properties

of sorghum (Sorghum bicolor L. Moench) flour extracts, J. Cereal Sci., 40:283–
288, 2004.

Torres Cepeda, T.E., Alanis Guzman, M.G., and Maiti, R., Relationship
between nutritional composition and anatomical parameters in sorghum
(Sorghum bicolor L. Moench), Arch. Latinoam. Nutr., 46: 253–259, 1996.

6.21. Soya Beans

A large number of components contribute to the diverse biological activities of

soybeans: hormonal, immunological, bacteriological, and digestive effects.
These components include isoflavones (genistein, daidzein, biochanin),
saponins, Kunitz inhibitor, Bowman-Birk inhibitor, soyacystatin,
phytoestrogens, Maillard products, soybean hydrophobic protein, soy allergens,
lecithins, allergens, raffinose, stachyose, and 2-pentyl pyridine (Csaky and
Fekete, 2004). Soy isoflavones (genistein, daidzein, biochanin) are known to
protect against different cancers (Sarkar and Li, 2003), cardiovascular disease
(Hasler, 2002), and bone loss (Harkness, 2004). Many studies have
demonstrated the effect of soy isoflavones on specific target molecules and
signaling pathways, cell proliferation and differentiation, cell-cycle regulation,
apoptosis, angiogenesis, cell adhesion and migration, metastasis, and activity of
different enzymes. Isoflavones are also classified as phytoestrogens with weak
estrogenic properties (Valachovicova et al., 2004). Interleukin-6 is a pleiotropic
cytokine that plays a crucial role in immune physiology and is tightly controlled
by hormonal-feedback mechanisms. Isoflavones modulate IL-6 gene-expression
levels and may have therapeutical benefit in preventing cancer progression,
aging discomforts, and restoring immune homeostasis (Dijsselbloem et al.,
2004). A systematic review of randomized clinical trials performed to evaluate

149
the benefit of soy for the treatment of perimenopausal symptoms provides some
evidence for the efficacy of soy preparations for perimenopausal symptoms, but
the heterogeneity of the studies performed makes it difficult to achieve a
definitive statement (Huntley and Ernst, 2004). The ability of soybean extracts
to inhibit mouse mammary adenocarcinoma tumor growth was not only due to
the presence of genistein but to other constituents present (Hewitt and
Singletary, 2003). Recent studies demonstrated a direct effect of soy saponins
on cancer cells, which further leads to elucidating the nature of soy constituents
involved in cancer protection (Kerwin, 2004). The Bowman-Birk inhibitor, a
serine protease inhibitor derived from soybeans, is presently being evaluated in
clinical trials for its ability to serve as a cancer preventive or anti-inflammatory
agent (Kennedy et al., 2002). Kunitz inhibitor was also found to inhibit cell
invasiveness through suppression of urokinasetype plasminogen activator
signalling cascade (Kobayashi et al., 2004). Soy infant formulas are widely
used, but only a few studies have evaluated their longterm safety or specific
forms of toxicity, such as the effects of genistein and daidzein in soy infant
formula, on the endocrine or immune systems. In addition, there is
inconsistency in the existing data, which point to the need for more clinical and
epidemiological studies (Chen and Rogan, 2004). Soybean oil is the world’s
most widely used, edible oil. In the United States, soybean oil accounts for
nearly 80 percent of edible-oil consumption. It contains 61 percent
polyunsaturated fat and 24 percent monounsaturated fat. It is one of the few
vegetable oils to contain linolenic acid, an omega-3 fatty acid (7.2 percent
C18:3n-3) known to prevent cardiovascular diseases. Soybean oil also contains
54 percent C18:2n-6

6.21.1. References

Csaky, I. and Fekete, S., Soybean: feed quality and safety. Part 1. Biologically
active components, a review, Acta Vet. Hung., 52:299–313, 2004.

Chen, A. and Rogan, W.J., Isoflavones in soy infant formula: a review of

evidence for endocrine and other activity in infants, Annu. Rev. Nutr., 24:33–
54, 2004.

Dijsselbloem, N., Vanden Berghe, W., De Naeyer, A., and Haegeman, G.,
Soy isoflavone phytopharmaceuticals in interleukin-6 affections, Multi-purpose
nutraceuticals at the crossroad of hormone replacement, anti-cancer and anti-
inflammatory therapy, Biochem. Pharmacol., 68:1171–1185, 2004.

Harkness, L., Soy and bone, where do we stand? Orthop. Nurs., 23:12–17,
2004.

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Hasler, C.M., The cardiovascular effects of soy products, J. Cardiovasc. Nurs.,
16:50–63, 2002.

Hewitt, A.L. and Singletary, K.W., Soy extract inhibits mammary

adenocarcinoma growth in a syngeneic mouse model, Cancer Lett., 192:133–
143, 2003.

Huntley, A.L. and Ernst, E., Soy for the treatment of perimenopausal
symptoms—a systematic review, Maturitas, 47:1–9, 2004.

Kennedy, A.R., Billings, P.C., Wan, X.S., and Newberne, P.M., Effects of
Bowman-Birk inhibitor on rat colon carcinogenesis, Nutr. Cancer, 43:174–186,
2002.

Kerwin, S.M., Soy saponins and the anticancer effects of soybeans and soy-
based foods, Curr. Med. Chem. Anti-Canc. Agents, 4:263–272, 2004.

Kobayashi, H., Suzuki, M., Kanayama, N., and Terao, T., A soybean Kunitz
trypsin inhibitor suppresses ovarian cancer cell invasion by blocking urokinase
upregulation, Clin. Exp. Metastasis, 21: 159–166, 2004.

Meydani, S.N., Lichtenstein, A.H., White, P.J., Goodnight, S.H., Elson,

C.E., Woods, M., Gorbach, S.L., and Schaefer, E.J., Food use and health
effects of soybean and sunflower oils, J. Am. Coll. Nutr., 10: 406–428, 1991.

Sarkar, F.H. and Li, Y., Soy isoflavones and cancer prevention, Cancer
Invest., 21:744–757, 2003.

Valachovicova, T., Slivova, V., and Sliva, D., Cellular and physiological
effects of soy flavonoids, Mini Rev. Med. Chem., 4:881–887, 2004.

6.22. Sweet Potatoes

Sweet potatoes, a crop native to South America, are easy to grow and have
become a staple food in many African countries. The orange-fleshed sweet-

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potato variety is rich in β-carotene, which offers hope to the population who are
currently beyond the reach of a vitamin A supplement. The effect of 60 days of
daily supplementation with 750 mg retinol equivalents (RE) of pureed sweet
potatoes were tested by Haskell et al. (2004). The overall geometric mean of
initial vitamin A stores was 0.108 +/− 0.067 mmol. Relative to the low vitamin
A control group, the estimated mean changes in vitamin A stores were 0.029
mmol. Vitamin A equivalency factors (β-carotene :retinol, wt:wt) were
estimated as approximately 13:1 for sweet potato. Thus, daily consumption of
pureed sweet potatoes has a positive effect on vitamin A stores in populations at
risk of vitamin A deficiency (Haskell et al., 2004). The major phenolic
components contained in the 70 percent methanol extract of sweet potatoes with
strong antioxidative activity were identified as chlorogenic acid and
isochlorogenic acid-1, -2, and -3. The other minor free phenolics were identified
as caffeic acid and 4-O-caffeoylquinic acid. Chlorogenic acid and
isochlorogenic acids, however, had only a slight antioxidative activity. Thus,
the effective a of the sweet-potato extract was proposed to be mainly based on
the synergistic effect of phenolic compounds with amino acids (Hayase and
Kato, 1984). The dietary fiber content of sweet potatoes was found to range
from 9–12 percent for cured roots. Soluble and insoluble dietary fiber averaged
5–30 percent and 543 percent, respectively (Mullin et al., 1994). Anthocyanins
are the chemical components that give the intense color to sweet potatoes, as in
many other fruits and vegetables. Epidemiological investigations have indicated
that moderate consumption of anthocyanin products is associated with a lower
risk of cardiovascular disease and improvement of visual functions (Hou, 2003).
Recently, the leaves of sweet potatoes were found to be rich in nutritive and
functional components. They were found to contain a large amount of protein,
showing high aminoacid score, soluble dietary fibers and minerals, particularly
iron, and vitamins, such as carotene, vitamin B2, vitamin C, and vitamin E.
Further-more, polyphenol content in the leaves was comparatively high. These
results suggest that the whole parts of sweet potatoes should be utilized as
valuable foodstuffs (Ishida et al., 2000).

6.22.1. References

Haskell, M.J., Jamil, K.M., Hassan, F., Peerson, J.M., Hossain, M.I., Fuchs,
G.J., and Brown, K.H., Daily consumption of Indian spinach (Basella alba) or
sweet potatoes has a positive effect on total-body vitamin A stores in
Bangladeshi men, Am. J. Clin. Nutr., 80:705–714, 2004.

Hayase, F. and Kato, H., Antioxidative components of sweet potatoes, J. Nutr.

Sci. Vitaminol., 30:37–46, 1984.

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Hou, D.X., Potential mechanisms of cancer. Dietary fibre in sweet potatoes,
Food Res. Int., 27:563–565, 1994.

Ishida, H., Suzuno, H., Sugiyama, N., Innami, S., Tadokoro, T. and
Maekawa, A., Nutritive evaluation of chemical components of leaves, stalks
and stems of sweet potatoes (Ipomoea batatas poir), Food Chem., 68:359–367,
2000.

Mullin, J., Rosa, N. and Reynolds, L.B., Dietary fibre in sweet potatoes, Food
Res. Int., 27:563– 565, 1994.

6.23. Taurine

Taurine is a conditionally essential amino acid that has been shown to be

involved in certain aspects of mammalian development (Sturman, 1993). The
molecule contains a sulfonic-acid group, rather than the carboxylic

acid moiety, that is not incorporated into proteins and is one of the most
abundant free amino acids in many tissues, including skeletal and cardiac
muscle and the brain (Huxtable, 1992). In vitro and animal studies demonstrated
that low levels of taurine are associated with various pathological lesions,
including cardiovascular disorders (Satoh and Sperelakis, 1998; Oudit et al.,
2004), retinal degeneration (Sheik et al., 1981), and growth retardation (Geggel
et al., 1985). Taurine is also involved in such metabolic activities as bile-acid
conjugation (Smith et al., 1991; Carrasco et al., 1990), detoxification
(Waterfield et al., 1993; Timbrell and Waterfield, 1996) membrane stabilization
(Qi et al., 1995), osmoregulation (Olivero and Stutzin, 2004), and modulation of
cellular calcium levels (Satoh and Sperelakis, 1998). Clinically, taurine has
been used in the treatment of cardiovascular diseases (Azuma et al., 1992; Modi
and Suleiman, 2004), ischemia-reperfusion injury (Kingston et al., 2004),

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hypercholesterolemia (Matsushima et al., 2003), epilepsy and other seizure
disorders (Airaksinen et al., 1980), macular degeneration (Sturman, 1986),
Alzheimer's disease (Csernansky et al., 1996), hepatic disorders (Matsuyama et
al., 1983), alcoholism, and cystic fibrosis (Smith et al., 1991; Carrasco et al.,
1990). Taurine was recently shown by Takatani and coworkers (2004) to inhibit
ischemicinduced apoptosis in cultured neonatal rat cardiomyocytes by
increasing the activities of Akt kinase and inactivating caspase-9. Figure T.95A
shows simulated ischemia induced a 4.5-fold and 11-fold increase in caspase-9
and caspase-3 compared to the control. In the presence of taurine caspase-9 and
caspase-3, activities were significantly reduced. Thus, taurine treatment could
be beneficial for treating heart failure.

Figure: Taurine prevents ischemia-induced caspase-9 and caspase-3

processing in cultured cardiomycetes. Cardiomyocytes were exposed to
ischemia for 30 h in the absence (−) or in the presence (+) of 20 mM
taurine. (From Takatani et al., Biochem. Biophys. Res. Commun., 316:484–
489, 2004. With permission.)

Recent in vivo and in vitro evidence found that taurine, through its ability to
control sarcolemmal excitability and muscle contractibility, could have
beneficial effects in many muscle dysfunctions (Conte Camerino et al., 2004).

6.23.1. References

Airaksinen, E.M., Oja, S.S., Marnela, K.M. et al., Effects of taurine

treatment on epileptic patients, Prog. Clin. Biol. Res., 39:157–166, 1980.

Azuma, J., Sawamura, A., and Awata, K., Usefulness of taurine in chronic
congestive heart failure and its prospective application, Jpn. Circ. J., 56:95–99,
1992.

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Carrasco, S., Codoceo, R., Prieto, G. et al., Effect of taurine supplements on
growth, fat absorption and bile acid on cystic fibrosis, Acta Univ. Carol., 36:
152–156, 1990.

Conte Camerino, D., Tricarico, D., Pierno, S., Desaphy, J.F., Liantonio, A.,
Pusch, M., Burdi, R., Camerino, C., Fraysse, B., and De Luca, A., Taurine
and skeletal muscle disorders, Neurochem. Res., 29:135–142; 2004

Csernansky, J.G., Bardgett, M.E., Sheline, Y.I. et al., CSF excitatory amino
acids and severity of illness in Alzheimer’s disease, Neurology, 46:1715–1720,
1996.

Geggel, H.S., Ament, M.E., and Heckenlively, J.R., Nutritional requirement

for taurine in patients receiving long-term parenteral nutrition, N. Engl. J. Med.,
312:142–146, 1985.

Huxtable, R.J., Physiological actions of taurine, Physiol. Rev., 72:101–163,

1992.

Kingston, R., Kelly, C.J., and Murray, P., The therapeutic role of taurine in
ischaemia-reperfusion injury, Curr. Pharm. Des., 10:2401–2410, 2004.

Matsushima, Y., Sekine, T., Kondo, Y., Sakurai, T., Kameo, K., Tachibana,
M., and Murakami, S., Effects of taurine on serum cholesterol levels and
development of atherosclerosis in spontaneously hyperlipidaemic mice, Clin.
Exp. Pharmacol. Physiol., 30:295–299, 2003.

Matsuyama, Y., Morita, T., Higuchi, M., and Tsujii, T., The effect of taurine
administration on patients with acute hepatitis, Prog. Clin. Biol. Res., 125:461–
468, 1983.

Modi, P. and Suleiman, M-S., Myocardial taurine, development and

vulnerability to ischemia, Amino Acids, 26:65–70, 2004.

Olivero, P. and Stutzin, A., Calcium modulates osmosensitive taurine efflux in

HeLa cells, Neurochem. Res., 29:169–176, 2004.

Oudit, G.Y., Trivieri, M.G., Khaper, N., Husain, T., Wilson, G.J., Liu, P.,
Sole, M.J., and Backx, P.H., Taurine supplementation reduces oxidative stress
and improves cardiovascular function in an iron-overload murine model,
Circulation, 109:1877–1885, 2004.

Qi, B., Yamagami, T., Naruse, Y., Sokejima, S. and Kogamimori, S., Effects
of taurine on depletion of erythrocyte membrane Na-K ATPase activity due to
ozone exposure or cholesterol enrichment, J. Nutr. Sci. Vitaminol., 41:627–634,
1995.

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Satoh, H. and Sperelakis, N., Review of some actions of taurine on ion
channels of cardiac muscle cells and others, Gen. Pharmacol., 30:451–463,
1998.

Sheik, K., Toskes, P., and Dawson, W., Taurine deficiency and retinal defects
associated with small intestinal bacterial overgrowth, Gastroenterology,
80:1363, 1981.

Smith, U., Lacaille, F., and Lepage, G., Taurine decreases fecal fatty acid and
sterol excretion in cystic fibrosis, a randomized double-blind study, Am. J. Dis.
Child, 145:1401–1404, 1991.

Sturman, J.A., Taurine in development, Physiol. Rev., 73:119–147, 1993.

Sturman, J.A., Nutritional taurine and central nervous system development,

Ann. N.Y. Acad. Sci., 477: 196–213, 1986.

Takatani, T., Takahasi, K., Uozumi, Y., Matsuda, T., Ito, T., Schaffer,
S.W., Fujio, Y., and Azuma, J., Taurine prevents the ischemia-induced
apoptosis in cultured neonatal rat cardiomycetes through Akt/caspase-9
pathway, Biochem. Biophys. Res. Commun., 316:484–489, 2004.

Timbrell, J.A. and Waterfield, C.J., Changes in taurine as an indicator of

hepatic dysfunction and biochemical perturbations, studies in vivo and in vitro,
Adv. Exp. Med. Biol., 403:125–134, 1996.

Waterfield, C.J., Turton, J.A., Scales, M.D., and Timbrell, J.A., Reduction
of liver taurine in rats by betaalanine treatment increases carbon tetrachloride
toxicity, Toxicology, 77:7–20, 1993.

6.24. Tomato

Epidemiology studies suggested that a higher intake of tomatoes and tomato

products may protect against cardiovascular disease (Arab and Steck, 2000) and
reduce the risk of several types of cancer, particularly prostate, lung, and
digestive tract (Giovannucci et al., 1999). One of the mechanisms proposed is

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that tomato extracts inhibit platelet aggregation (Lazarus and Garg, 2004). The
most abundant carotenoid in tomatoes is lycopene (Agarwal and Rao, 2000). It
appears to be responsible, in large part, for the potential health benefits of
tomato products (Clinton, 1998). Tomatoes showed high antioxidant activities.
For example, at the level of 1 g fresh sample, low-density lipoprotein
peroxidation was inhibited by at least 90 percent by tomato meat. The total
phenolic content was significantly correlated with antioxidant activities
measured (Huang et al., 2004).

Figure: Lycopene. (From Duvoix et al., Cancer Lett., 223:181–190, 2005.)

The consumption of tomato products is associated with reduced risk of prostate

cancer. Lycopene, the primary red carotenoid in tomatoes, may be the principal
phytochemical responsible for this reduction in risk. Lycopene can act as
antioxidant, enhance cell-tocell communication via increasing gap junctions
between cells, and modulate cell-cycle progression. Tomatoes also contain
folate, vitamin C, significant quantities of potassium, vitamin A, vitamin E, and
various other carotenoids and phytochemicals, such as polyphenols, which may
also be associated with lower cancer risk (Campbell et al., 2004). It was
recently demonstrated that tomato juice is a suitable raw material for the
production of probiotic juice by four lactic-acid bacteria (Latobacillus
acidophilus LA39, Lactobacillus plantarum C3, Lactobacillus casei A4, and
Lactobacillus delbrueckii D7). This juice could serve as a health beverage for
vegetarians or consumers who are allergic to dairy products (Yoon et al., 2004).

6.24.1. References

Agarwal, S. and Rao, A.V., Tomato lycopene and its role in human health and
chronic diseases, Can. Med. Assoc. J., 163:739–744, 2000.

Arab, L. and Steck, S., Lycopene and cardiovascular disease, Am. J. Clin.
Nutr., 71:1691S-1695S, discussion 1696S–1697S, 2000.

Campbell, J.K., Canene-Adams, K., Lindshield, B.L., Boileau, T.W.M.,

Clinton, S.K., and Erdman, J.W., Jr., Tomato phytochemicals and prostate
cancer risk, J. Nutr., 134:3486S–3492S, 2004.

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Clinton, S.K., Lycopene: chemistry, biology, and implications for human
health and disease, Nutr. Rev., 56:35–51, 1998.

Duvoix, A., Blasius, R., Delhalle, S., Schneckenburger, M., Morceau, F.,
Henry, E., Dicato, M., and Diederich, M., Chemopreventive and therapeutic
effects of curcumin, Cancer Lett., 223:181–190, 2005.

Giovannucci, E., Tomatoes, tomato-based products, lycopene, and cancer:

review of the epidemiologic literature, J. Natl. Cancer Inst., 91:317–331, 1999.

Huang, H.Y., Chang, C.K., Tso, T.K., Huang, J.J., Chang, W.W., and Tsai,
Y.C., Antioxidant activities of various fruits and vegetables produced in
Taiwan, Int. J. Food Sci. Nutr., 55(5):423–429, 2004.

Lazarus, S.A. and Garg, M.L., Tomato extract inhibits human platelet
aggregation in vitro without increasing basal cAMP levels, Int. J. Food Sci.
Nutr., 55(3):249–256, 2004.

Yoon, K.Y., Woodams, E.E., and Hang, Y.D., Probiotication of tomato juice
by lactic acid bacteria, J. Microbiol., 42(4):315–318, 2004.

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 Chapter 7
Research and Technology Trends of Nutraceuticals – A
Japanese Perspective

7.1. Introduction

7.1.1. Needs of Prophylactic Medicine

In recently years, the increase of so-called lifestyle related diseases, such as
diabetes mellitus and obesity. have been referred as social issues which leads to
the loss of QOL (Quality of Life) and increases in medical care expenses. On
the other hand, to positively guarantee elongation of a healthy life expectancy in
an aging society is a significant social issue in Japan. As a solution to the issue,
there has been an attempt to create a society for healthy aging, by shifting the
way of thinking away from lifestyle related diseases and “treatment by drugs”
to “positive prevention of disease by food”, based on the concept of “Ishoku
Dogen, Healthy Eating to Prevent Disease”.

7.1.2. Concept of Nutraceuticals

In the pharmaceutical development process, it is a requirement to have clinical
test results from animal tests and studies, for verification of the effects. On the
other hand, in the case of nutrition, there was no verification method for foods
in preventing diseases in the past. In recent years however, as food composition
has been scientifically proven to cause life style-related diseases, and has
become a social issue. The concept of Nutraceuticals has started to be
acknowledged as one of the measures for preventing such diseases.

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Figure 1 : Concept of nutraceuticals Source: Kalra E. K. (2003)

Figure 2: Nutorigenomics Technology Concept and Functional Food

Concept Source: : Kalra E. K. (2003)

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7.1.3. Procedure for Nutrigenomics
Nutraceuticals, the new concept of food with a new function to prevent
diseases, was started by the combination of genome science and technology,
which has been accomplishing remarkable development for the verification.
Thus, the genome technique called Nutrigenomics (nourishment genome
science) was created. Nutrigenomics is newly developed methodology
combined with multiple genomic techniques and molecular biology
technologies, as shown in Figure 2. It has been then used as a basic technology
that became a driving force for the creation of Nutraceuticals. In the field of the
pharmaceutical development, biomarkers such as proteins levels and gene
expression show the reaction to medicines, and is measured to verify the
medicinal effects of drugs. Nutrigenomics technology role is to verify the
medical effects of food and food composition, by linking with the biomarkers at
an early stage at a level of protein and gene expression. It is now possible to
determine the biomarker for each physiological function related to disease
which should be prevented in order to study the mechanism for preventing the
diseases, and to determine the amount of food necessary for a person to have a
preventive effect towards diseases. As of now, this is only for the assessment of
individual Nutraceuticals. Meanwhile, if it is possible to designate target
biomarkers in order to prevent the same disease, or to standardize the
assessments to have a uniform criterion, the assessment results will be further
objective. It is now essential to create such a mechanism to realize this.
Furthermore, various disorders can bepredicted indivisually, including the
difference of susceptibility or the difference of disease risk, and the
effectiveness of drugs by analyzing the SNPs (Single Nucleotide
Polymorphisms,: single nucleotide mutation), which represents personal
variation of genomes. Therefore, it is thought in the future that more
personalized information on food functions can be provided for disease
prevention, in correspondence with individual differences of genome.
Accordingly, development of the Nutrigenomics technology is expected to
highly contribute to the realization of disease prevention by foods, along with
Nutraceuticals, as individuals are able to obtain detailed food information
effective for their health.

7.2. Current Status of Nutraceuticals in Japan

7.2.1. Food with Function Claims

In 1984, the Education Ministry (currently Ministry of Education, Culture,

Sports, Science and Technology) launched the project “Systematic Analysis of
Food Functions” as a special project by a Research Grant Study Group. This

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project is the world’s first proposal of the effects of food on human bodies as a
“Function”, especially through the research on prevention of life-style related
diseases. With advancement of “functional food” research, “Functional Foods
(Tokutei Hoken-yo Shokuhin; “TOKUHO” in short Japanese” or Food for
Specified Health Uses; FOSHU” was put into effect in 1991. In 1993, when
Shiseido marketed rice with less allergens, as the first product of TOKUHO,
“Nature”, world famous English academic journal, introduced in the article
“Physiologically functional food” as a brand-new food concept from Japan. It
had a big impact and “Functional Food” was acknowledged internationally as a
future food category for human health. In 2002, “standardized Food with
Nutrient Function Claims; FNFC” was set up in addition to the existing FOSHU
(TOKUHO) foods. FOSHU and FNFC have become the main elements in the
current policy of “Food with Function Claims”. FOSHU must undergo
application for every individual product, and must be evaluated as effective and
safe by a committee of experts, to be permitted to be displayed as “TOKUHO”.
The conditions for permission are the confirmed effectiveness and safety
through tests of the human body and quantitative data of the functional
ingredient. Furthermore, TOKUHO was followed by “Standardized FOSHU”,
“Disease Risk Reduction FOSHU” and “Limited Conditional FOSHU” at the
time of revision in February, 2005. The concept of “Disease Risk Reduction
FOSHU” is to specifically designate the foods which are medically and
nutritionally proven to reduce the risk of diseases. This is one of the measures
for stepping forward with disease prevention, however, there are only two kinds
of elements designated in this category at the moment; calcium and folic
acid.“Standardized FOSHU”is the food on which has received permission, after
evaluating whether the ingredients comply with the standards set by the
authority. The standards are based on the preset standards concerning
ingredients that have been proven to function by sufficient scientific reasons.
There is no individual assessment of the target required. Several kinds of
ingredients including dietary fiber and oligosaccharide fall into this category. In
the contrast,“Limited Conditional FOSHU” is for foods permitted with the
condition that it should have a label to represent the limited scientific evidence
of ingredient effectiveness, even though it is insufficiently backed-up by
scientific data. As for FOSHU (TOKUHO), 752 items are now authorized and
listed as of December 2007. This shows that TOKUHO has been penetrating the
Japanese market. Meanwhile, “FNFC” lists only five kinds of minerals and 12
kinds of nutrients. These foods are sold in the market with a label for each
functional nutrient. FOSHU(TOKUHO) and FNFC a r e now internationally
acknowledged as global standards for nutritious functional foods. From the
disease prevention point of view, “Disease Risk Reduction FOSHU” is thought
to be the best suited for the purpose of Nutraceuticals. However, the foods
which are authorized in this category are only calcium and folic acid at the

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moment, and so that it is still insufficient to obtain effective evidence from the
human trials in Japan.

Category Definition of category Ingredients

FOSHU The food with labels to
displays the function
for those who intends
to take it for specific
purposes in diet
FOSHU Specific Function Food Calcium (which should be
(disease risk authorized to display a specified as an additive in
reduction) label of disease risk Food Additive Definition
controlled when the etc., and
risk control ingredient has fully been proved to
of the food is verified have the function Folic
from the viewpoints of Acid (PteGlu acid)
medicine and nutrition
FOSHU Specific Function Food Dietary fibre:
(Standardized) authorized upon indigestibility dextrin,
evaluation of the polydextrose, guar gum
compatibility to the catabolite Oligosaccharide:
standard by Secretariat, galacto-oligosaccharide,
without individual fructo oligosaccharide, lac
evaluation of the ankle
Council. This is based oligosaccharide, galacto-
on the standard of oligo glucose, xyleorigo
ingredients which the glucose,
scientific data has isomaltooligosaccharide
sufficiently
accumulated
as it is proven to be
appropriate as Specific
Function Food
Limited Conditional Food, not meeting the
FOSHU scientific proof level of
effectiveness
requirements of
Specific
Function Food but
certain effectiveness
has been verified. It is
authorized with
conditions as long as it
has a label to show
the limited function

Table: Food for specified health uses (FOSHU)

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 About a system Nutrient
Food with Nutrient FNFC Zinc, calcium, iron,
Function Claims is a food product with copper, niacin,
labels to show its pantothenic acid, biotin,
nutrition. To be a vitamin A, β - carotene,
nutrient function food for vitamin
sale, it is necessary for B1, vitamin B2, vitamin
the food to contain a B6, vitamin B12,
certain amount of vitamin C, vitamin E,
nutrition in the intake per folic acid
day within the
lower/upper limit, as
well as to have a notice
of its risk.

Table: Food with nutrient function claims (FNFC)

7.2.2.Nutraceuticals research in Japan

7.2.2.1. Research on analysis and systematization of non-trophic functions

of food

As the basic study of food ingredient functions and its roles in Japan, “Research
concerning Analysis and Systematization of Non-trophic Functions of Food”
(2000-2004) is one of the most advanced examples of Nutraceuticals research in
Japan, and it is funded by the Ministry of Education, Culture, Sports, Science
and Technology Technical Promoting Adjustment Expense. Professor Soichi
Arai of Faculty of Agriculture of Tokyo University and his group made of a
scientific evaluation of various non-nutritious ingredients of food, such as
flavonoids, carotenoids and peptides, and then created useful databases. This
assessment started in 2000.

At first, the expected effects of taking functional ingredients, such as anti

oxidation, bone formation / absorption, glucose incorporation, influence to
immune system, influence to carcinogenic rate of a patient with cirrhosis, liver
enzyme induction, learning and biophylaxis factor, were chosen for assessment
and verification. However, a big problem which was found out was that
sufficient verification was not possible for prevention of diseases such as anti-
inflammation action, diabetic control, anti-cancer action and the improvement
of the study, because the number of biomarkers, for example, the blood proteins
which were proven to have direct effects to prevention of diseases, was too little
to judge the overall effects.

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During the intermediate stage of the research, it was realized that the attempt to
analyze the function of non-nourishment materials in food should not be done
by investigating individual biomarkers, but by using a more comprehensive
analysis, such as utilizing serum proteome metaborome, which in the future will
be able to handle proteins in bulks. This resulted in the conclusion that
Nutrigenomics technology needed to be further developed.

Moreover, the effectiveness and safety data obtained through the process
above, should be standardized through the examination and evaluation by
specialists. It will also need highly reliable evidence, and should be open to
public. In order to discover the new functionality of foods and the importance of
scientific proof of effectiveness of functional food ingredients, it is necessary to
promptly apply the technique of Nutrigenomics. This database will be the key
for the development of Nuraceuticals in the future.

7.2.2.2. Cooperative research with industries

Nutraceuticals are food products addressed to public and consumed by ordinal

people, therefore, collaboration and technology transfer to various foods and
food related companies is essential. It is also thought that the participation of
pharmaceutical manufacturers and its affiliated companies, is also essential for
advanced evaluations of the effect and safety to the human body. Accordingly, a
contribution course by the International Life Sciences Institute, ILSI
“Functional food genomics” (Functional Food Science and Nutrigenomics) was
founded by The University of Tokyo graduate school Agricultural Life Science
Research Course, for the aspects of industrialization and practical use of
Nutraceuticals for the period of December, 2002 to November, 2008. Thirty-
two food companies are participating in this program, as well as industry-
academia projects led by Professor Keiko Abe. Specifically, each company is
trying to examine the variation and clarify the function of the gene expression
level by the intake of food elements, such as proteins and amino acids, which
they are interested in developing They have also started to create a shared
database linked with the gene expressions obtained from food functions and
DNA chips. The industry-academia projects have gained a lot of attentions
globally, as it is aimed at thoroughly evaluating the overall function and safety
of food and food ingredients, and assuring the foundation for quality design and
quality control.

Item
Research on the functions of
non-trophic material included
in food
Description
1) Extraction/measurement/function
assessment of non-trophic material
New methodology of functionality
and safety, especially introduction of
Genomics (Phase 2: to be an

165
 independence item from the second
stage)
2) Research concerning the amount of
flavonoid, and polyphenol, and its
function
3) Research concerning the amount and
function of terpenoid and carotenoid
4) Research concerning the amount and
function of sulphur containing
compound, volatile ingredient and
spice
5) Research concerning the amount and
function of peptides
Research on database of non- 1) Research concerning non-trophic
trophic material materials for mutual reaction→
included in food Effectiveness
2) Non-trophic materials integrated
database creation/disclosure→ Safety

Table: Research on analysis and systematization of the non-trophic functions of

food

7.2.2.3. Scientific evaluation in humans

It is essential to obtain data of disease prevention, by showing the effectiveness

in human for developing Nutraceuticals. In order to achieve this, it is necessary
to prepare teams similar to pharmaceutical development, such as selection of
biomarkers and end point, creation of the standard protocols for the
examination, recruitment of appropriate examinees, and objective evaluation by
medical doctors. Unfortunately, it is notable that Japan is lags behind other
countries in terms of Nutraceuticals development. Professor Toshikazu
Yoshikawa of the Department of Medicine at Kyoto Prefectural University
Professor Soichi Arai of Tokyo University of Agriculture and others are taking
the lead to establish the “Society for the Function of Food and Exercise”, which
was established in 2006. The purposes of this association are to study the
relationship between food and medical functions by advanced technologies, to
develop new functional foods which contribute to health maintenance for
people and to develop physical programs suitable for various age and health
conditions. A cluster system for industrial development will be created based on
the above activities. Specifically, this is to create a database by using
Nutrigenomics, for example, by collecting information about the scientific
effectiveness using biomarkers related to food. The “Society of Functionality
Research of Food and Movement” started to acquire scientific data of functional
foods on human body by collecting various functional foods from the industry

166
in 2007. This is an activity to analyze the potential of foods by medical doctors
and academic researchers. They received 15 entries and 5 items (5 companies)
were selected for further assessment. Currently, it is scheduled to form 5
assessment teams, in collaboration with Japan Physicians Association, to create
specific assessment programs and tests for scientific evidence using volunteers
in 2008. In addition, the “Healthy Food Material Evaluation Committee” has
been formed, based on the achievement of the projects, for the research and
development, evaluation, and creation of the information systems.

7.3. Nutraceuticals research in Europe

In Europe, many countries such as the Netherlands, France, Germany, Belgium

and Spain place emphasis on agriculture. Above all, in the Netherlands, dairy
products and beer have a long history of food processing / fermentation
technology, which makes this country one of the prominent food industry
countries in Europe. For example, the amount of exported farm products such as
meat, dairy products, grain, seed, food and beverage products, and tobacco and
its processed products, is in second place in the world. Above all, dairy products
and beer are tops in the world. The Netherlands is competitive in regards to
advanced technologies, as they have a wide range of knowledge, know-how,
experiences, and supports, from basic research to industrialization for
processing and fermentation technologies for foods, dairy products, and beer. In
the Netherlands, “Food Valley” is the largest scale food products cluster in
Wageningen. The Nutrigenomics Institute of the nourishment genome research
center in Europe also works in this city. This is a place for research for the
European food industry. This document introduces examples of the
Nutraceuticals research and development in Europe, referring to the case studies
of the Netherlands.

7.3.1. Food valley in the Netherlands

The Agriculture Ministry of the Netherlands integrated the Wageningen

Agricultural University and Institute of Technology of Agricultural Ministry, to
establish Wageningen University (Wageningen UR: Wageningen University
and Research Center) in 1988, for focusing on the research and development of
food. On the other hand, Wageningen Center for Food Science was established
in 199 7 by Ministry of Economic Affairs in Wageningen as a center of
activation for the food industry. Both organizations are strongly supported by
the government of the Netherlands. When Wageningen University and
Wageningen Nutrition Center were established, a strong research infrastructure
for the application was formed concerning food in this country. In addition to
this, the organizations supporting industrialization and technological transfers

167
such as TNO Nutrition & Food Research and NIZO Food Research made a
partnership, therefore, the technological transfer and industrialization of
advanced technologies have been conducted continuously. Afterwards, many
food companies have come to the city to create Food Valley, thus, enterprises,
administration and technical institutes could work in cooperation to make the
largest food research and development cluster in Europe. Thus, this city became
a place of innovation for new food companies.

Purpose New industries are to be created through collection and database

of various information of scientific evidences
concerning the physiological function and the health care
related to food (especially, functional food materials)
by making best use of advanced technologies (genomics,
proteomics, and metabolomics)
Contents of 1) Research of functionality and safety of side goods involved
research in human health
2) Clarification of fundamental molecular mechanism
concerning health care and disease prevention of food
and ingredients
3) Research concerning the relationship between nutrition
intake and health associated with genes
4) Development and application of the biomarkers to clarify
functionality and risk
5) Scientific elucidation of health care by exercise and
establishment of individual exercise menu
6) Evaluation and development of health care and exercise
supporting tool

Table: Purpose and research items of society of functionality research of

food and movement

University, laboratory, and Role and function

research institutes
in Food Valley
Wageningen University &
Research Centre: Basic and fundamental research
- Wageningen Institute for
Food Safety A part of European Nutorigenomics
- Agrotechnology and Food Organization (NuGO)
Science Group Basic research of science of food
- Plant Research
International Wageningen Plant improvement using the genomics
- Animal Sciences Group technology.
- Wageningen Institute for Animal test research
Food Law
TNO Food & Nutrition Technological transfer of basic research

168

NIZO Food Research（NIZO)
Centre for BioSystems Genomics
Nutrigenomics Consortium
Top Institute Food and Nutrition
Table: Various organizations in food valley and their function
results to enterprises, commitment of
researches for enterprises
Technological transfer of basic research
results to enterprises, commitment of
researches for enterprises
Consortium composed of several ten
enterprises, including Wageningen UR
to play a key role. For improvement of
quality and nature of grains by using
Nutorigenomics technology.
Research of biomarkers using
Nutorigenomics technology, focusing
on diabetic, hyperlipemia, and high
blood pressure resulted from the
Metabolic syndrome.
Technical assistance necessary to
provide new food products that
contribute to health

7.3.2. TNO nutrition & food research

TNO of the Netherlands is the largest general contracting institution in Europe,

and was established in 1932 for application studies in the science and
technology fields. The total number of staff is more than 5,000. The five
research areas cover: (1) Quality of Life, (2) Defense and Public Safety, (3)
Natural and Built Environment, (4) Advanced Products, (5) Process Systems
and (6) ICT and Services. Amongst these, the Quality of Life department is
working on nourishing food products, mainly for technology transfers upon
contract with industrial companies. In particular, applicability and toxicity tests
are conducted for nourishing food products. They provide assessment services
for new food product safety, the applicability for functional foods. In addition,
they submit the necessary paperworks for registration and application to the
European Food Safety Authority: EFSA and American Food and Drug
Administration: FDA. Above all, it is notable that they have expertise in the
tests for functional foods and new food products on human volunteers. They
have many achievements in human volunteer tests of functional foods, as they
have the evaluation and analytical technologies for various in-body markers,
and human metabolism test facilities. Along with this, the nourishment database
is further fulfilled with their vast database. Several thousands of volunteer
databases are available for the testing of various new food products, which will
provide a smooth launching and operation for new tests.

169
7.3.3.NIZO food research BV

The NIZO Food Research Facility, for contracting with enterprises on research
activities, is located in Ede city near Wageningen. NIZO has food related
laboratories and the pilot plants for the testing of food production. Clients
inquire to them to conduct various tests for production before the full
investment of a production facilities. Thus the companies can have business
supports from NIZO just before the production.

7.3.4. NuGO; European nutrigenomics organization

When Nutrigenomics was established as new nourishment genomic

technologies for development of Nutraceuticals, the European Nutrigenomics
Organization was founded with the members of 22 organizations from 10
countries in Wageningen in January 2004. This location became the center of
the food science in Europe for (1) education of post genomic science, that is,
Nutrigenomics technology’ (2) promotion and integration ofNutrigenomics
technologies for contribution to nourishment science in Europe, (3) application
and industrialization of Nutrigenomics technology from the global aspects and
(4) establishment of the advanced virtual center of the Nutrigenomics
technology. Currently, 23 organizations (university and enterprise) participate
in the projects as partner organizations, for not only for the research but also for
the promotion of the industrialization. The technologies in which NuGO is
specialized, is the creation of the database for bioinformatics (Nutrientgene
database), concerning the ingredients of foods and its function and
physiological activities. This is done by making good use of a genomic
technologies and microarray technologies. This database is designed, from the
beginning, to be shared for practical use. The data format is common for NuGO
participants. Moreover, the research protocols for data acquisition are also
standardized in a common format, which is effective for the faultless and
prompt process from academy to industry. The databases are currently
available to be shared by the participants. The standards and formats that NuGO
are promoting may be used not only in Europe, but also as the global standard
in the future. Nutraceuticals research in the United States In Europe, a focus is
placed on a faultless approach, from research to industrialization, of
Nutraceuticals, mainly promoted in Food Valley. On the contrary, the United
States is focusing on the approaches for prevention of diseases and life-style
related diseases based on the study of Nutraceuticals. Some venture companies
are now working a service to provide Nutraceuticals for those who easily
contract diseases, through individual genetic information analysis.

170
Committed test and registration Consulting investigation concerning
services regulations
1) Confirmation of applicable
regulations
2) Confirmation of required data
3) Pre-assessment of customer data
4) Proposal of cost
Committed test and registration 1) Evaluation of data
services 2) Safety testing
3) Preparation of application forms
Other services ･Examination of human volunteer - Test
design
・Enterobacteria/immunization test -
Allergic examination
･Various analyses of nourishment,
chemical substances, and
microorganisms
･Nourishment evaluation and
nourishment genomics
･The biomarker's identification -
Epidemiology examination
All processes from the regulation ･Research on laws and regulations –
investigation to the application Implementation of toxic test
・Preparation of application forms

Table: TNO commitments and services for testing and research

7.3.5. UC Davis : disease prevention

It has been acknowledged that Nutrigenomics technology is effective for

identifying the relationship of food ingredients and physiology. The Centre of
Excellence for Nutritional Genomics was established by UC Davis (University
of California, Davis) in 2004 in the United States, backed by the funds of NIH,
coinciding with the establishment of the NuGO (mentioned above) in Europe.
Dr. Rodriguez of UC Davis has been engaged in the administration of the
research. His philosophy is that now is the time to shift the mindset concerning
medicine, from remedy of sickness to pursuing health and wellness. In other
words, it should be shifted from medication to prevention. This is because of the
increase of life-style related diseases resulting from bad eating habits and lack
of exercise becoming a social issue. Foods should play a key role for prevention
of diseases, so that Nutrigenomics technologies are effective for development of
functional foods of Nutraceuticals. For instance, research is conducted mainly
for bioactive substances contained in plants, such as food herbs, to identify

171
relationships of foods and gene expression, or medical treatment and
preventative medicine. The nonlinearity algorithm called an Isomap is used to
process a large number of genetic information about a biomarker, by using
microchip technologies. The examination has been progressed.

7.4. Reference

Yoshihiko Sumi; Science & Technology Trends; Quarterly Review No 28;2008

172
 Chapter 8
Analysis of Nutraceuticals – An Advanced and Comprehensive
Perspective

8.0. Introduction

For a long time, natural products obtained mainly from plants have been used as
a prominent source of prophylactic agents for the prevention and treatment of
diseases in humans and animals . Hippocrates (460–370 BC) stated “Let food be
your medicine and medicine be your food”. Nowadays, the relationship between
food and drugs is getting closer. Thus, the term nutraceutical was firstly
mentioned 20 years ago to describe a union between nutrition and
pharmaceutics, both key contributors to human wellness . In the last 20 years,
many research publications were devoted to so-called “functional foods” and
“nutraceuticals”. Research into functional ingredients was showing promising
prospects for the use of such ingredients in food products, thereby creating
added value for manufacturers and benefits for consumer health . It is also
interesting to mention that more than 150 revision works related to
nutraceuticals and functional foods have been published in the same period of
time. Some of them are focussed onto the beneficial properties of a particular
natural matrix as sesame , tea or spices , other manuscripts paid their attention
onto specific natural compounds like phytochemicals , proteins and peptides or
lipids , meanwhile other works showed the benefits of nutraceuticals against
several diseases like atherosclerosis and degenerative joint diseases . It must be
pointed out that, to our knowledge, there is not a revision work in which the
advanced analytical techniques used to analyze nutraceuticals are summarized
and discussed. Nutraceuticals as defined by Zeisel are dietary supplements that
deliver a concentrated form of a presumed bioactive agent from a food,
presented in a non-food matrix, and used with the purpose of enhancing health
in dosages that exceed those that could be obtained from normal foods. No
specific regulation exists in Europe to control nutraceuticals, although they are
considered under the same laws that regulate medicine and drug. In the USA,
the Food and Drug Administration regulates dietary supplements under a
different set of guidelines than those covering conventional foods and drug
products.

173
Otherwise, functional foods are those that when consumed regularly produce a
specific beneficial health effect beyond their nutritional properties. The
boundary between nutraceuticals and functional foods is not always clear being
the main difference the format in which they are consumed: nutraceuticals are
consumed as capsules, pills, tablets, etc. while functional foods are always
consumed as ordinary foods. Thus, when a phytochemical is included in a food
formulation is considered a functional food. If the same phytochemical is
included in a capsule it will constitute a nutraceutical. The capacity of some
plant-derived foods to reduce the risk of chronic diseases has been associated, at
least in part, to the occurrence of secondary metabolites (phytochemicals) that
have been shown to exert a wide range of biological activities. In general, these
metabolites have low potency as bioactive compounds when compared to
pharmaceutical drugs, but since they are ingested regularly and in significant
amounts as part of the diet, they may have a noticeable long-term physiological
effect. There are numerous biological mechanisms by which nutraceuticals
might be expected to exert favourable influences on pathophysiological
processes. These products are safe and well tolerated, but interpretation of the
collective results is hampered by heterogeneity of the studies, inconsistent
results, and/or not well designed investigations. On the other hand,
nutraceuticals are expected to be substantially safer and with less secondary
effects than many drugs routinely prescribed in the treatment of certain
symptoms; however, they are often expensive, lack pharmaceutical-level
manufacturing standard controls, and may not work . An additional problem
related to the production and consume of nutraceuticals is that the composition
and contents of active constituents in natural plants (like in any other natural
source) vary depending on season, climate, temperature, humidity, soil and
several other factors. So the collection, identification and maintenance of
uniform quality, quantification and standardization are critical factors to
consider. The development of advanced analytical techniques is, therefore,
indispensable in nutraceuticals research. It includes the identification of new
nutraceuticals, characterization of their chemical structure and bioactivity,
quantification in the natural source, product development, quality control in
their dosage forms, etc. Due to the complexity of these natural matrices, the use
of advanced analytical techniques (such as Mass Spectrometry (MS), Nuclear
Magnetic Resonance (NMR), High performance Liquid Chromatography
(HPLC), Capillary Electrophoresis (CE), HPLC-NMR, HPLC-MS, GC-MS and
CE-MS) is mandatory in order to carry out the mentioned studies. Some of
these techniques are already applied for quality control of the natural product
confirming their composition from lot to lot and assuring the safety of the final
product. Also, these techniques are typically used in a combined way for
product development at the initial stages of their discovery, mainly for facing
the challenge to analyse multiple components or multiple classes of

174
components. Moreover, the choice of the analytical technique depends also on
the target compounds and the matrix in which they can be found. For example,
their physico-chemical properties (polarity, size, volatility,...) will have a strong
influence onto the sample preparation procedure, separation mechanism and
technique (GC, HPLC, CE) and the type of detector to be employed (Ultraviolet
Detector (UV), Fluorescence Detector (FLD), Flame Ionization Detector (FID),
MS, etc.). Moreover, advanced analytical techniques are also needed to obtain a
better understanding of the health promoting effects of the nutraceuticals, and
for knowing the body exposure and bioavailability after the intake of these
compounds. Important aspects during product development should include
nutraceuticals bioactivity and bioavailability studies, so, in vitro, in vivo and
clinical trials should ideally be employed. However, the current legislation on
these compounds is in many countries not as demanding as for standard drugs,
what usually results in minimum studies to confirm their activity.

8.1. Lipids
Lipids are a large group of natural compounds which includes fats, waxes,
sterols, fat-soluble vitamins (such as vitamins A, D, E and K), monoglycerides,
diglycerides, phospholipids, carotenoids and others. Molecules such as fatty
acids and their derivatives (including tri-, di-, and monoglycerides and
phospholipids), sterol containing metabolites, such as cholesterol, are also
grouped as lipids. The main biological functions of lipids include energy
storage, structural components of cell membranes, and important signalling
molecules. Although humans and other mammals use various biosynthetic
pathways to both break down and synthesize lipids, some essential lipids cannot
be made this way and must be obtained from diet. Interestingly, many papers
have discussed the health benefits that can be derived from some of these lipids.
Lipids with potential benefits for human health have been identified in several
natural sources (cereals, fruits, animals, oils, plants, mushrooms. . .) using for
their chemical identification Gas Chromatography (GC) coupled to several
detectors (FID, Electronic Capture Detector, MS. . .), High Performance Liquid
Chromatography (HPLC) with different detection modes - UV, Photodiode
Array Detector, MS, Tandem Mass Spectrometry, Nuclear Magnetic
Resonance (NMR) and Mass Spectrometry (MS) as stand-alone techniques.

Matrix Analytical Reference

techniques
Vegetable oils (plant and GC-FID  F. Anwar, R. Przybylski, M.
seed of bittermelon, Rudzinska, E. Gruczynska, J.
Kalahari melon, kenaf, Bain, Fatty acid, tocopheroland
pumpkin and roselle, sterol compositions of
Ethiopian mustard, Canadian prairie fruit seed
pumpkin, apiaceae, lipids, J. Am. Oil Chem. Soc.
kachnar, black currant, 85 (2008) 953–959.

175
fruits, nut, soybean).  R. Zadernowski, M. Naczk, S.
Czaplicki, Chemical
composition of Pinus sibirica
nut oils, Eur. J. Lipid Sci.
Technol. 111 (2009) 698–704.
Rice oil GC and HT-GC  R. Denev, I. Kuzmanova, S.
(FID, MS) TLC Panayotova, S. Momchilova,
V. Kancheva, B.R. Lokesh,
Lipid composition of Indian
rice bran oil, C. R. Acad. Bulg.
Sci. 62 (2009) 709–716.
 R. Przybylski, D. Klensporf-
Pawlik, F. Anwar, M.
Rudzinska, Lipid components
of North American wild rice
(Zizania palustris), J. Am. Oil
Chem. Soc. 86 (2009) 553–559.
Aquatic animals (salmon, GC (FID, MS)  T. Sun, Z. Xu, W.
catfish, crustacean) Prinyawiwatkul, FA
composition of the oil extracted
from farmed atlantic salmon
(Salmo salar L.) viscera, J. Am.
Oil Chem. Soc. 83 (2006) 615–
619.
 Di.L. Badiu, A.M. Balu, L.
Barbes, R. Luque, R. Nita, M.
Radu, E. Tanase, N. Rosoiu,
Physico-chemical
characterisation of lipids from
Mytilus galloprovincialis (L.)
and Rapana venosa and their
healing properties on skin
burns, Lipids 43 (2008) 829–
841.
Grass-fed and grain-fed GC (FID, MS) C.A. Daley, A. Abbott, P.S. Doyle,
beef G.A. Nader, S. Larson, A review of
fatty acid
profiles and antioxidant content in grass-
fed and grain-fed beef, Nutr. J. 9 (2010)
1–12.
Leuconostoc GC-MS R.P. Shobha, R. Agrawal, Volatile
paramesenteroides, compounds of therapeutic importance
isolated from cheddar produced by Leuconostoc
cheese paramesenteroides, a native laboratory
isolate, Turk. J. Biol. 31 (2007) 35–40.
Plants (Typhonium GC (FID, MS)  C.-S. Lai, R.H.M.H. Mas,
flagelliforme, Cistus N.K. Nair, S.M. Mansor, V.
ladanifer, Cupressus Navaratnam, Chemical
lusitanica and Eucalyptus constituents and in vitro
gunnii) anticancer activity of
Typhonium flagelliforme
(Araceae), J. Ethnopharmacol.
127 (2010) 486–494.
 R. Guimarães, R. Guimarães,
L. Barros, A.M. Carvalho,
M.J. Sousa, J.S. Morais,
I.C.F.R. Ferreira, Aromatic

176
 plants as a source of important
phytochemicals: vitamins,
sugars and fatty acids in Cistus
ladanifer, Cupressus lusitanica
and Eucalyptus gunnii leaves,
Ind. Crop. Prod. 30 (2009)
427–430.
Wild and commercial GC-FID  L. Barros, T. Cruz, P.
mushrooms Baptista, L.M. Estevinho,
C.F.R. Isabel, Ferreira, Wild
and commercial mushrooms as
source of nutrients and
nutraceuticals, Food Chem.
Toxicol. 46 (2008) 2742–2747.
 L. Barros, B.A. Venturini, P.
Baptista, L.M. Estevinho,
I.C.F.R. Ferreira, Chemical
composition and biological
properties of Portuguese wild
mushrooms: a comprehensive
study, J. Agric. Food Chem. 56
(2008) 3856–3862.
Alga (Porphyridium GC (FID, MS)  Rodríguez-Meizoso, L. Jaime,
cruentum, Himanthalia HPLC-QTOF-MS S. Santoyo, A. Cifuentes, G.
elongata and García-Blairsy Reina, F.J.
Synechocystis s, Se˜noráns, E. Ibá˜nez,
Chaetoceros muelleri, Pressurized fluid extraction of
Chlorella vulgari, Spirulina bioactive compounds from
platensis) Phormidium species, J. Agric.
Food Chem. 56 (2008) 3517–
3523.
 M.G. Sajilata, S. Rekha,
Singhal, Y. Madhusudan,
Kamat, Supercritical CO2
extraction of g-linolenic acid
(GLA) from Spirulina platensis
ARM 740 using response
surface methodology, J. Food
Eng. 84 (2008) 321–326.
Fruits (Italian walnut, GC-FID, ESR, spin-  V. Verardo, A. Bendini, L.
Black mulberry, orange, label oximetry Cerretani, D. Malaguti, E.
blackthorn and rose fruits) methods. Cozzolino, M.F. Caboni,
Capillary gas chromatography
analysis of lipid composition
and evaluation of phenolic
compounds by micellar
electrokinetic chromatography
in Italian walnut (Juglans Regia
L.): irrigation and fertilization
influence, J. Food Quality 32
(2009) 262–281
 J.-J Yin, J.K.G. Kramer,
M.P. Yurawecz, A.R. Eynard,
M.M. Mossoba, L. Yu, Effects
of conjugated linoleic acid
(CLA) isomers on oxygen
diffusion-concentration

177
 products in liposomes and
phospholipid solutions, J.
Agric. Food Chem. 54 (2006)
7287–7293

Table 8.1. : Natural matrices containing fatty acids and analytical

techniques employed for their analysis.

Notation: HT-GC, High Temperature Gas Chromatography; TLC, Thin Layer

Chromatography; ESR, Electron Spin Resonance; QTOF, Quadrupole-Time of
Flight mass analyzer.

8.2. Fatty Acids

Nutraceutical Matrix Possible Analytica Reference

health effect l
technique
s
Plant sterols Vegetable Phytosterols GC (FID,  F. Anwar, R.
(Phytosterols) oils (olive, decrease MS) Przybylski, M.
sunflower, cholesterol Rudzinska, E.
rice bran, associated with Gruczynska, J. Bain,
seeds,. . .) LDL, have Fatty acid, (2008)
anti-cancer  A.M. Bakowska-
activity and Barczak, A. Schieber,
modulate the P. Kolodziejczyk,
immune (2009)
function and  K.L. Nyam, C.P.
inflammation. Tan, O.M. Lai, K.
Long, Y.B. Che Man,
(2009)
 M.F. Ramadan, G.
Sharanabasappa,
Y.N. Seetharam,M.
Seshagiri, J.-T.
Moersel, (2006) 3
 R. Denev, I.
Kuzmanova, S.
Panayotova, S.
Momchilova, V.
Kancheva, B.R.
Lokesh,(2009)
 G. Sivakumar, C.B.
Bati, E. Perri, N.
Uccella, (2006)
 L. Vázquez, C.F.
Torres, T. Fornari, N.
Grigelmo, F.J.
Se˜noráns, G.
Reglero,(2006)
Glycerolipids Seed oils Skin care and GC-FID  C. Ngo-Duy, F.
source of fatty Destaillats, M.
acids Keskitalo, J. Arul,

178
 P. Angers,
Triacylglycerols of
Apiaceae seed oils:
composition and
regiodistribution of
fatty acids, Eur.
J.Lipid Sci. Technol.
111 (2009) 164–169.
 M.F. Ramadan, G.
Sharanabasappa,
Y.N. Seetharam,M.
Seshagiri, J.-T.
Moersel,Characterisa
tion of fatty acids and
bioactive compounds
of kachnar (Bauhinia
purpurea L.) seed oil,
Food Chem. 98
(2006) 359–365.
Phytosterols, γ- Rice Antioxidant, HPLC-  R. Przybylski, D.
oryzanol and decrease GC-FID, Klensporf-Pawlik,
steryl ferulates cholesterol GC (FID, F. Anwar, M.
octacosanol, absorption, MS) Rudzinska, Lipid
and squalene. protect against HPLC- components of North
atherosclerosis, PDA American wild rice
nerve (Zizania palustris), J.
imbalance and Am. Oil Chem. Soc.
disorders of 86 (2009) 553–559
menopause  A. Miller, K.-H.
Engel, Content of γ-
oryzanol and
composition of steryl
ferulates in Brown
Rice (Oryza sativa
L.) of European
origin, J. Agric. Food
Chem. 54 (2006)
8127–8133.
 T.-Y. Ha, S.-N. Ko,
S.-M. Lee, H.-R.
Kim, S.-H. Chung,
S.-R. Kim, H.-H.
Yoon, I.-H. Kim,
Changes in
nutraceutical lipid
components of rice at
different degrees of
milling, Eur. J. Lipid
Sci. Technol. 108
(2006) 175–181.
Sterols Mediterranea Skin-care GC-MS Di.L. Badiu, A.M. Balu, L.
n mussel and Barbes, R. Luque, R. Nita,
Rapana M. Radu, E. Tanase, N.
venosa Rosoiu, Physico-chemical
(hard- characterisation of lipids from
shellclam) Mytilus galloprovincialis (L.)
and Rapana venosa and their

179
 healing properties on skin
burns, Lipids 43 (2008)
829–841.
Glycerolipids Microalga Antimicrobial HPLC-  J.A. Mendiola, C.F.
and anti- ELSD, Torres, P.J. Martín-
inflammatory HPLC- Álvarez, S. Santoyo,
activities QTOF- B.O. Arredondo,
MS F.J. Se˜norans, A.
Cifuentes, E.
Ibá˜nez, Use of
supercritical CO2 to
obtain extracts with
antimicrobial activity
from Chaetoceros
muelleri microalga.
A correlation with
their lipidic content,
Eur. Food Res.
Technol. 224 (2007)
505–510.
 M. Herrero, M.J.
Vicente, A.
Cifuentes, E.
Ibá˜nez,
Characterization by
highperformance
liquid
chromatography/elect
rospray ionization
quadrupole time-of-
flight mass
spectrometry of the
lipid fraction of
Spirulina platensis
pressurized ethanol
extract, Rapid
Commun. Mass
Spectrom. 21 (2007)
1729–1738.
Sterols Italian Decrease GC-FID V. Verardo, A. Bendini, L.
walnut cholesterol and Cerretani, D. Malaguti, E.
reduce the Cozzolino, M.F. Caboni,
risk of Capillary gas chromatography
coronary heart analysis of lipid composition
disease and evaluation of phenolic
compounds by micellar
electrokinetic chromatography
in Italian walnut (Juglans
Regia L.): irrigation and
fertilization influence, J. Food
Quality 32 (2009) 262–281.
Phytosterols Milk and Decrease GC-MS R. Santos, E. Limas, M.
and yoghurt cholesterol Sousa, M. da, C. Castilho, F.
phytostanols levels Ramos, M.I. Noronha da
Silveira, Optimization of
analytical procedures for GC-
MS determination of

180
 phytosterols and phytostanols
in enriched milk and yoghurt,
Food Chem. 102 (2007) 113–
117.
Phytosterols Tetraploid Decrease GC (FID, G. Iafelice, V. Verardo, E.
and cholesterol MS) Marconi, M.F. Caboni,
hexaploid levels Characterization of total, free
wheats and esterified phytosterols in
tetraploid and hexaploid
wheats, J. Agric. Food Chem.
57 (2009) 2267–2273.
Squalene Vegetable Decrease HPLC- L. Vázquez, C.F. Torres, T.
oil cholesterol and ELSD, Fornari, F.J. Se˜noráns, G.
anti-cancer GC-FID Reglero, Recovery of
activity squalene from vegetable oil
sources using countercurrent
supercritical carbon dioxide
extraction, J. Supercrit. Fluids
40 (2007) 59–66.
Terpenes and Essential oils Antiseptic, GC-MS,  M.-T. Golmakani,
terpenoids carminative, HPLC K. Rezaei,
antimicrobial, (DAD, Comparison of
and MS) microwave-assisted
antioxidative hydrodistillation with
effects. the traditional
hydrodistillation
method in the
extraction of essential
oils from Thymus
vulgaris L., Food
Chem. 109 (2008)
925–930.
 L. Pérez-Fons, F.J.
Aranda, J. Guillén,
J. Villalaín, V.
Micol, Rosemary
(Rosmarinus
officinalis) diterpenes
affect lipid
polymorphism and
fluidity in
phospholipid
membranes, Arch.
Biochem. Biophys.
453 (2006) 224–236.
Terpenoids Quinoa flour Antibacterial HPLC K. Brady, C.-T. Ho, R.T.
(pseudo- and (UV, MS) Rosen, S. Sang, M.V. Karwe,
cereal) antineoplastic NMR Effects of processing on the
properties. nutraceutical profile of
quinoa, Food Chem. 100
(2007) 1209–1216.
Milk lipids Milk Immuno- HPLC- B. Casado, M. Affolter, M.
(triglycerides, suppressive, MS/MS, Kussmann, OMICS-rooted
diacylglyceride anti- GC/LC. studies of milk proteins,
s, saturated inflammatory, oligosaccharides and lipids, J.
fatty acids and andantimicrobi Proteomics 73 (2009) 196–
PUFAs). al 208.

181
 properties.
Gangliosides Dairy Protect against MALDI-  R. Lacomba, J.
products enteric TOF-MS, Salcedo, A. Alegría,
(milk) pathogens, and HPTLC, M.J. Lagarda, R.
prebiotic HPLC- Barberá, E.
functions. MS Matencio,
Determination of
sialic acid and
gangliosides in
biological samples
and dairy products: a
review, J.
Pharmaceut. Biomed.
51 (2010) 346–357.
 I. Mocchetti,
Exogenous
gangliosides,
neuronal plasticity
and repair, and the
neurotrophins, Cell.
Mol. Life Sci. 62
(2005) 2283–2294.

Table 8.2. : Lipids with potential nutraceutical activity found in different

natural matrices, potential health effect and analytical techniques
employed for their analysis.

Notation: ELSD, Evaporative Light Scattering Detector; MALDI, Matrix-

assisted laser desorption/ionization; HPTLC, High Performance TLC.

Fatty acids are carboxylic acids with a variable unbranched aliphatic tail
(chain), which is either saturated or unsaturated. They are important as
nutritional substances in living organisms. Longchain polyunsaturated fatty
acids (PUFA), especially those of the ω-3 series, such as α-linolenic (18:3 n−3),
are essential for human metabolism and have many beneficial effects including
the prevention of a number of diseases, such as coronary heart diseases,
inflammation, autoimmune disorders, hypertension, hypotriglyceridemic effect,
etc. [83,84]. Regarding to the analytical techniques more used for determining
fatty acids, 95% of the works summarized in the Table above employed gas
chromatography or high temperature gas chromatography (HT-GC) with FID or
MS detectors. It must be taken into account that most of the times, before GC
analysis, it is necessary to prepare non-reactive derivatives of fatty acids
(methyl esters, FAMEs, steryl esters FASEs, or other derivatives) which are
also more volatile than the free acid components. There are only few works in
which other analytical techniques have been used. As an example, Herrero et al.
characterized several free fatty acids in Spirulina platensis by using LC-QTOF-
MS, while Yin et al. used electron spin resonance (ESR) and spin-label
oximetry methods to determine conjugated linoleic acids (CLAs) in soybean

182
and other matrices . Approximately in 40% of the articles devoted to the
analysis of fatty acids the matrix was oil (vegetable or animal) , and all of them
employed gas chromatography with FID or MS detectors. The analysis by GC-
FID of fatty acids in rice oil have been carried out in several works , discussing
the importance of, this matrix as source of fatty acids. Fatty acids have also
been determined by GC-FID and GC-MS in salmon, catfish or crustaceans ,
beef , cheese and plants . Fatty acids could also be found in several fruits by
using GC-FID and in daily dietary intakes . The nutritional and biological
properties of mushrooms have also been studied , identifying several fatty acids
that were analysed by GC-FID previous methylation of these compounds.
According to the published literature in the reviewed period (2005–2010), an
important source of fatty acids are algae. Fatty acids, mainly as methyl or ethyl
esters, were determined by GC-MS and GC-FID in several varieties of alga
(e.g., C. muelleri, Chlorella vulgaris, S. platensis, etc.) . Liquid chromatography
coupled to aMS detector has also been employed in the analysis of fatty acid in
algae [51]. The separation provided by HPLC combined with the high mass
accuracy and MS/MS capability of the QTOF mass analyzer made possible the
direct identification of four free fatty acids and nine polar lipids (Glycerolipids)
in this complex matrix without any further sample pre-treatment or
derivatization.
Nutraceutical Matrix Possible health Analytical Reference
effect techniques
β-carotene β- Mandarin, Antioxidant, LCxLC-  P. Dugo, M. Herrero,
cryptoxanthin, Orange juices inmunomodulation DAD- T. Kumm, D.
mutatoxanthin, and cancer MS(APCI- Giuffrida, G. Dugo, L.
antheraxanthin, prevention IT-TOF-MS) Mondello,
luteoxanthin, Comprehensive normal-
epoxycarotenoids phase×reversed-phase
esters. . . liquid chromatography
coupled to photodiode
array and mass
spectrometry detection
for the analysis of free
carotenoids and
carotenoid esters from
mandarin, J.
Chromatogr. A 1189
(2008) 196–206.
 P. Dugo, D. Giuffrida,
M. Herrero, P. Donato,
L. Mondello,
Epoxycarotenoids
esters analysis in intact orange
juices using two-dimensional
comprehensive
liquid chromatography, J. Sep. Sci.
32 (2009) 973–980
β-carotene, Thai fruits Antioxidant, anti- HPLC- R. Charoensiri, R.
lycopene cancer, UV/Vis Kongkachuichai, S. Suknicom, P.
prevent degenerative Sungpuag, β-carotene, lycopene,
diseases and α tocopherol contents of
selected Thai fruits, Food Chem.
113 (2009) 202–207
β-carotene, lutein, Chesnut Antioxidant, HPLC-PDA d.C.B.M. de Vasconcelos, R.N.
lycopene inmunomodulation Bennett, S. Quideau, R. Jacquet,
and cancer E.A.S. Rosa, J.V. Ferreira-

183
 prevention Cardoso, Evaluating the potential
of chestnut (Castanea sativa Mill.)
fruit pericarp and integument as a
source of tocopherols, pigments and
polyphenols, Ind. Crops Prod. 31
(2010) 301–311.
β-carotene Tea seed oils Antioxidant effects HPLC-DAD M. Fazel, M.A. Sahari, M.
Barzegar, Determination of main
tea seed oil antioxidants and their
effects on common kilka oil, Int.
Food. Res. J. 15 (2008)
209–217
Astaxanthin, β- Alga Antioxidant, HPLC  L. Barros, B.A.
carotene, lutein, inmunomodulation (UV/Vis, Venturini, P. Baptista,
cantaxanthin, and cancer DAD) L.M. Estevinho,
violaxanthin, prevention. I.C.F.R. Ferreira,
neoxanthin Chemical composition
and biological properties
of Portuguese wild
mushrooms: a
comprehensive study, J.
Agric. Food Chem. 56
(2008) 3856–3862
 B.P. Nobre, F.
Marcelo, R. Passos, L.
Beiráo, A. Palabra, L.
Gouveia, R. Mendes,
Supercritical carbon
dioxide extraction of
astaxanthin and other
carotenoids from the
microalga
Haematococcus
pluvialis, Eur. Food
Technol. 223 (2006)
787–790.
 M. Herrero, L. Jaime,
P.J. Martin-Alvarez, A.
Cifuentes, E. Ibanez,
Optimization of the
extraction of
antioxidants from
Dunaliella salina
microalga by pressurized
liquids, J. Agric. Food
Chem. 54 (2006) 5597–
5603.
Lycopene Tomato Antioxidant, anti- HPLC (UV,  D. Naviglio, T. Caruso,
products, cancer DAD) NMR, P. Iannece, A. Aragón,
nutritional ESI-MS/MS, A. Santini,
supplements HPTLC Characterization of high
purity lycopene from
tomato wastes using a
new pressurized
extraction approach, J.
Agric. Food Chem. 56
(2008) 6227–6231.
 P. Benatti, G. Peluso,
R. Nicolai, M. Calvani,
Polyunsaturated fatty
acids: biochemical,
nutritional and
epigenetic properties, J.
Am. Coll. Nutr. 23
(2004) 281–302.

Table 8.3. : Carotenoid nutraceuticals found in different matrices, potential

health effect and analytical techniques employed for their analysis

184
Notation: ESI, Electrospray ionization; APCI, Atmospheric Pressure Chemical
Ionization; IT, Ionic Trap.

Figure 8.0. : Chromatograms obtained from the HPLC-UV-QTOF-MS

analysis of a selected ethanolic PLE extract obtained from Spirulina
platensis, using theUVdetector at 280nm(a), and the ESI-QTOF-MS
detector in negative (b) and positive (c) ion modes. Reprinted from M.
Herrero, M.J. Vicente, A. Cifuentes, E. Ibá˜nez, (2007) ; Copyright (2007)
John Wiley & Sons, Inc.

8.3. Sterols

Sterols are an important group of organic molecules that can be found in plants,
animals, and fungi, being cholesterol the most popular animal sterol. Sterols
from plants, which are known as phytosterols, have been shown in clinical trials
to block cholesterol absorption sites in the human intestine, and decrease the
level of plasma cholesterol associated with low density lipoproteins (LDL), thus
helping to reduce cholesterol in humans. According to some studies they have
anti-cancer anti-inflammatory and antithrombotic activities. For these reasons,
its use has been approved by US-FDA as food additive. After checking the
published literature , it could be stated that sterols compounds have been usually

185
identified using GC coupled to FID or MS. Analysis of sterols has been carried
out in several classes of vegetable oils, like: olive , sunflower , Indian rice bran
and other plants . Sterols could be also found in enriched milk and yoghurt by
using an optimized GC-MS method ,meanwhile total, free and esterified
phytosterols in tetraploid and hexaploid wheats where determined by GC-FID
and GC-MS . GC was also employed in the analysis of the lipid composition of
Italian walnut and for the chemical characterization of lipids from crustacean
which can be employed for the skin-care, with potential benefits on burns,
inflammations, etc. . Sterols have been also analyzed in different varieties of
rice together with γ-oryzanol and other compounds like steryl ferrulates or
squalene, showing antioxidant activity and decreasing cholesterol .
Chromatographic techniques as GC or HPLC have been used to determine the
sterol composition in the different rice samples. Also, on-line coupling between
LC and GC (on-line LC-GC-FID) can be used to determine sterols . This
coupling is an efficient approach for the analysis of minor constituents in
complex matrices, because it avoids laborious off-line purification steps. In that
work γ-oryzanol is pre-separated by normal phase HPLC from other rice lipids
and transferred on-line to GC analysis to separate its major constituents . Total
γ-oryzanol content was quantified by HPLC-UV and the ratios of each
individual steryl ferulate calculated by GC-FID.

8.4. Terpenes

Terpenes, which could be also named as isoprenoids, constitute the largest and
most diverse class of natural products. Amajority of these compounds are found
only in plants, but some of the larger and more complex terpenes occur in
animals. Squalene, which is a natural complex terpene produced by all plants
and animals, has been proposed to be an important ingredient of the
Mediterranean diet as it may be a chemopreventive substance that protects
against cancer. Squalene has been analyzed in rice by GC coupled to FID and
MS detectors . This compound has also been identified in vegetable oils using
HPLC with evaporative light scattering detection (ELSD) . Terpenes and
terpenoids are the primary constituents of the essential oils of many types of
plants and flowers or cereals and they have shown antibacterial and
antioxidant activity among other beneficial effects for human health. They have
been usually analyzed by GC-MS or HPLC-UV-MS although sometimes to
elucidate the real structure of these compounds NMR is preferred .

186
8.5. Glycerolipids

Glycerolipids are mainly composed of mono-, di- and trisubstituted glycerols,

the most well-known being the fatty acid esters of glycerol (triacylglycerols),
also known as triglycerides. These compounds posses several functional
activities like antimi- crobial, antiinflammatory and are beneficial for the skin
care . There is not a unique analytical tool to analyze glycerolipids. For
example, GC-FID has been used to determine these compounds in seed oils ,
while silver ion thin layer chromatography (TLC) and HPLC were employed for
the analysis of triacylglycerols in rice bran oil . GC-MS and HPLC-MS have
been also employed to identify the milk lipids that possess antimicrobial or anti-
inflammatory properties , and LC-MS was used to characterize triacylglycerols
in black currant seed oil . HPLC-ELSD has been used to identify those
compounds in C. muelleri microalgae , and LC-QTOF-MS has been used to
determine substituted glycerols in S. platensis microalgae .

187
Figure 8.1. : On-line LC-GC analysis of γ-oryzanol in a crude lipid extract
from brown rice. (a) LC chromatogram; UVdetection of γ-oryzanol at 325
nm. The fraction transferred to GC is shown by the indicated time window.
(b) GC chromatogram of the γ- oryzanol-containing fraction; separation of
γ-oryzanol into campesteryl ferulate (1), campestanyl ferulate (2), β -
sitosteryl ferulate (3), cycloartenyl ferulate (4), and 24-
methylenecycloartanyl ferulate (5). (I) and (II) were identified as the co-
transferred free sterols cycloartenol and 24-methylenecycloartanol.
Reprinted from A. Miller, K.-H. Engel, (2006) Copyright (2006) American
Chemical Society.

8.6. Sphingolipids

Gangliosides are molecules composed of a glycosphingolipid with one or more

sialic acids linked on the sugar chain. A glycosphingolipid is composed of an
oligosaccharide plus a ceramide, the latter composed of sphingosine and a fatty
acid. Gangliosides have protective action against enteric pathogens, prebiotic
functions and are considered to present some therapeutic effect against
neurodegenerative disorders . These compounds have been determined in
biological samples, including milk using several techniques. Thus, high
performance thin layer chromatography (HPTLC), GCMS, LC-MS and matrix
assisted laser desorption ionization time of flight MS (MALDI-TOF-MS) have
been used to analyse gangliosides .
Nutraceutical Matrix Possible health effect Analytical Reference
techniques
Tocopherols Vegetable and Antioxidant, HPLC (PDA,  F. Anwar, R.
(Vitamin E) vegetable oils antitumor, FLD, MS), Przybylski, M.
hypocholesterolemic GC-FID Rudzinska, E.
potential Gruczynska, J. Bain, F
and for the treatment (2008)
of  A.M. Bakowska-
cardiovascular disease Barczak, A. Schieber,
and P. Kolodziejczyk,
angiogenic disorders (2009)
 M.F. Ramadan, G.
Sharanabasappa, Y.N.
Seetharam,M.
Seshagiri, J.-T.
Moersel,(2006)
 C. Balachandran, P.N.
Mayamol, Shiny
Thomas, A. Divya
Sukumar, C.
Sundaresan,
Arumughan, (2008)

188
  M.B. Reena, B.R.
Lokesh, (2007)
 V. Verardo, A.
Bendini, L. Cerretani,
D. Malaguti, E.
Cozzolino, M.F.
Caboni, (2009) .
Tocopherols Microalga Antioxidant and HPLC (DAD,  Y. Durmaz, M.
(Vitamin E) prevents FLD) Monteiro, N.
degenerative disorders Bandarra, S.
Gokpinar, O. Isik,
The effect of
lowtemperature on
fatty acid composition
and tocopherols of the
red
microalgaPorphyridiu
m cruentum, J. Appl.
Phycol. 19 (2007)
223–227.
 L. Gouveia, B.P.
Nobre, F.M.Marcelo,
S. Mrejen, M.T.
Cardoso, A.F.
Palavra,
R.L.Mendes,
Functional food oil
coloured by pigments
extracted from
microalgaewith
supercritical CO2,
Food Chem. 101
(2007) 717–723.
 J.A. Mendiola, D.
García-Martínez,
F.J. Rupérez, P.J.
Martín-Álvarez, G.
Reglero,A. Cifuentes,
C. Barbas, E.
Ibá˜nez, F.J.
Se˜noráns,
Enrichment of vitamin
E fromSpirulina
platensis microalga by
SFE, J. Supercrit.
Fluid. 43 (2008) 484–
489.
Vitamin B1 and Mushrooms Antioxidant HPLC (DAD, R.P. Zanes Furlani, H. Teixeira
B2 FLD) Godoy, Vitamins B1, B2
contents in cultivated
mushrooms, Food Chem. 106
(2008) 816–819.
Water-soluble Maize flour, Antioxidant and co- HPLC- A. Gentili, F. Caretti, G.
vitamins (B1, green and enzymes MS/MS D’Ascenzo, S. Marchese, D.
B2, two B3 golden Perret, D. Di Corcia,
vitamins, B5, five kiwi and tomato L. Mainero Rocca, Simultaneous
B6 vitamins, B8, pulp. determination of water-soluble
B9, B12 and vitamins in selected food
C). matrices by liquid
chromatography/electrospray
ionization tandem mass
spectrometry, Rapid Commun.
Mass Spectrom. 22 (2008)
2029–2043.
Vitamins B2, B3 Energy drinks Antioxidant and co- HPTLC, ESI M. Aranda, G. Morlock,
and B6 enzymes MS/MS Simultaneous determination of
riboflavin, pyridoxine,
nicotinamide, caffeine and
taurine in energy drinks by planar
chromatography-multiple
detection with confirmation by
electrospray ionization mass

189
 spectrometry, J. Chromatogr. A
1131 (2006) 253–260
Vitamin C (L- Fruits Antioxidant HPLC  G. Oms-Oliu, I.
ascorbic acid) (UV/Vis) Odriozola-Serrano,
R. Soliva-Fortuny,
O. Martín-
Belloso,Antioxidant
content of fresh-cut
pears stored in high-
O2 active packages
compared with
conventional low-O2
active and passive
modified atmosphere
packaging, J. Agric.
Food Chem. 56 (2008)
932–940.
 H. Borochov-Neori,
S. Judeinstein, A.
Greenberg, B.
Fuhrman, J. Attias,
T. Nina Volkova, M.
Hayek, Aviram,
Phenolic antioxidants
and antiatherogenic
effects of marula
(Sclerocarrya birrea
Subsp. caffra) fruit
juice in healthy
humans, J. Agric.
Food Chem. 56 (2008)
9884–9891.
 R. González-
Montelongo, M.G.
Lobo, M. González,
Antioxidant activity in
banana peel extracts:
testing extraction
conditions and related
bioactive compounds,
Food Chem. 119
(2010) 1030–1039.
L-ascorbic Buckwheats Antioxidant HPLC- S.J. Kim, C. Kawaharada, T.
acid UV/Vis Suzuki, K. Saito, N. Hashimoto,
dehydroascorbic S. Takigawa, T. Noda,
acid) C. Matsuura-Endo, H.
Yamauchi, Effect of natural light
periods on rutin, free amino acid
and vitamin C contents in the
sprouts of common (Fagopyrum
esculentum Moench) and tartary
(F. tataricum Gaertn.)
buckwheats, Food Sci.
Technol. Res. 12 (2006) 199–
205.
S-methyl-L- Centella asiatica Wound healing HPLC-UV W.-J. Kim, J. Kim, B.
methionine Veriansyah, J.-D. Kim, Y.-W.
(vitamin U) Lee, S.-G. Oh, R.R.
Tjandrawinata,
Extraction of bioactive
components from Centella
asiatica using subcritical water, J.
Supercrit. Fluid. 48 (2009) 211–
216.
Fat and water Beer and Antioxidant and co- HPLC-DAD J.A. Mendiola, F.R. Marin, F.J.
soluble vitamins bioactive drinks enzymes Se˜norans, G. Reglero, P.J.
Martín-Álvarez, A.
Cifuentes, E. Ibá˜nez, Profiling
of different bioactive compounds
in functional drinks by high-
performance liquid
chromatography, J. Chromatogr.

190
 A 1188 (2008) 234–241.

Table 8.4. : Vitamins found in different matrices, potential health effect

and analytical techniques employed for their analysis.

Carotenoids

Carotenoids are a class of more than 600 naturally occurring pigments

synthesized by plants, algae, yeast, fungi and photosynthetic bacteria. They are
prominent for their distribution, structural diversity and various functions. Fruits
and vegetables provide most of the carotenoids in the human diet. Carotenoids
can be broadly classified into two classes, carotenes (α-carotene, β-carotene or
lycopene) and xanthophylls (β-cryptoxanthin, lutein or zeaxanthin). These
compounds show antioxidant and immunomodulation activities, and they can
prevent degenerative diseases, such as cardiovascular diseases, diabetes, and
several types of cancer especially prostate and digestive-tract tumors. HPLC
with DAD or UV detectors is the analytical technique of choice for determining
carotenoids. Nevertheless, comprehensive liquid chromatography coupled to
photodiode array and mass spectrometry detection (LCxLC-DAD-MS) have
been also shown to provide impressive results in carotenoid analysis . Free
carotenoids and carotenoid esters from mandarin and orange juice have been
identified with this methodology . Some carotenoids, like β-carotene, and
lycopene, which presents antioxidant, inmunomodulation and anti-cancer
properties have been determined by HPLC-UV/Vis or DAD in Thai fruits ,
chesnut and tea seed oils . Algae and microalgae are also an important sources
of carotenoids as astaxanthin, β-carotene, lutein, cantaxanthin, violaxanthin,
lutein and neoxanthin, being HPLC the analytical tool most frequently
employed to identify thesecompounds. In some cases, a strongly hydrophobic
column (C30) has been used to separate and quantify certain carotenoids
isomers from microalgae . Lycopene, a bright red carotene and carotenoid
pigment, and β- carotene have been also identified in different tomato products
and wastes by using HPLC,NMRorMS but other more easy techniques like
HPTLC could be used for the lycopene determination in nutritional
supplements.

8.7. Vitamins

Vitamins are a diverse group of organic compounds essential in trace amounts

for the normal growth and maintenance of life. To ensure the adequate intake of
vitamins the human diet can be completed with a high range of multivitamin
tablets and food products enriched with vitamins, in other words, these
compunds are usually administered as nutraceutical or functional ingredient.

191
They are classified as either water-soluble or fat soluble. In humans there are 13
vitamins: 4 fat-soluble (A, D, E and K) and 9 water-soluble (8 B vitamins and
vitamin C). These compounds have diverse biochemical roles. Some have
hormone-like functions as regulators of mineral metabolism (e.g., vitamin D),
or regulators of cell and tissue growth and differentiation (e.g., some forms of
vitamin A). Others work as antioxidants (e.g., vitamin E and sometimes
vitamins B and C). The largest numbers of vitamins (e.g., Bcomplex vitamins)
work as precursors of enzyme cofactors. Recently, it has been published one
work where vitamins have been usually determined by HPLC with several
detectors as UV/Vis, VWD, PDA, FLD, MS. ; although GC-FID and HPTLC
have been also employed. Some compounds related to vitamin B group have
been identified in mushrooms by HPLC-DAD-FLD , in more complex food
matrices by using HPLC-MS/MS [92] and in energy drinks employing HPTLC .
VitaminC(L-ascorbic acid or L-ascorbate) is an essential nutrient for humans
and other animal species. Deficiency in this vitamin causes the disease known
as scurvy in humans. This compound is also widely used as a food additive
because of its antioxidant activity. Compared to the other vitamins, the number
of works about Vitamin E is by far the highest one. Vitamin E is a generic term
for tocopherols and tocotrienols, and it is a fat-soluble antioxidant that block the
production of reactive oxygen species formed when lipids undergoes oxidation.
The most frequently employed analytical tool for determining vitamin E has
also been HPLC coupled to all possible types of detectors as FLD, UV, PDA,
MS. However, in two works , based on the relative volatility and thermal
stability of vitamin E, GC-FID was employed to detect vitamin E in vegetable
and fruit matrix.Some algae can also be good natural sources of this vitamin as
reported in several works in which HPLC with FLD or DAD was used to
identify vitamin E. However, it has to be noted that the main natural source of
vitamin E arevegetable and vegetable oils, being HPLC the analytical tool more
usually employed . A new HPLC-DAD method was recently developed for the
simultaneous detection and quantification of water- and fat-soluble vitamins in
different beverages from different natural sources (orange, strawberry, apple,
peach pineapple, plum and blackcurrant juices, soybean milk and beers) , with
the additional advantage that it was not required any previous sample
preparation prior to their analysis. This fact was attributed to the use of an
endcapped column, which posses an ultralow silanol activity.
Nutraceutical Matrix Possible health Analytical Reference
effect techniques
Milk proteins, peptides Milk and Antihypertensive, HPLC-MS/MS,  R. Lacomba, J.
Lactoferrin and derived antimicrobial, 2D-PAGE, Salcedo, A.
immunoglobulin G. products anti-inflammatory MALDI- Alegría, M.J.
and TOFMS, Lagarda, R.
inmunostimulating Inmunosensors, Barberá, E.
activities. CE (UV, MS), Matencio,
Important source of Determination of
amino acids sialic acid and
gangliosides in

192
 biological samples
and dairy
products: a review,
J. Pharmaceut.
Biomed. 51 (2010)
346–357.
 G. Oms-Oliu, I.
Odriozola-
Serrano, R.
Soliva-Fortuny,
Olga Martín-
Belloso,
Antioxidant
content of fresh-
cut pears stored
inhigh-O2 active
packages
compared with
conventional low-
O2 active and
passive modified
atmosphere
packaging, J.
Agric. Food
Chem. 56 (2008)
932–940.
 C. De Simone, G.
Picariello, G.
Mamone, P.
Stiuso, A.
Dicitore, D.
Vanacore, L.
Chianese, F.
Addeo, P.
Ferranti,
Characterisation
and
cytomodulatory
properties of
peptides from
Mozzarella di
Bufala Campana
cheese whey, J.
Pept. Sci. 15
(2009) 251–258.
Amino acids Sprouts, Effect on the HPLC (UV/Vis,  S.J. Kim, C.
alga and nervous system, MS) MEKC- Kawaharada, T.
sport drinks antioxidant, anti- LIF, Suzuki, K. Saito,
and tablets cancer and source Microchip N. Hashimoto, S.
of muscle energy electrophoresis Takigawa, T.
(MCE) Noda, C.
Matsuura-Endo,
H. Yamauchi,
Effect of natural
light periods on
rutin, free amino
acid and vitamin C
contents in the
sprouts of
common
(Fagopyrum
esculentum
Moench) and
tartary (F.
tataricum Gaertn.)
buckwheats, Food
Sci. Technol. Res.
12 (2006) 199–
205.
 M. Herrero, E.
Ibá˜nez, S.
Fanali, A.

193
 Cifuentes,
Quantitation of
chiral amino acids
from microalgae
by MEKC and LIF
detection,
Electrophoresis 28
(2007) 2701–2709.
 H. Ueno, J.
Wang, N. Kaji,
M. Tokeshi, Y.
Baba, Quantitative
determination of
amino acids in
functional foods
by microchip
electrophoresis, J.
Sep. Sci. 31 (2008)
898–903.
Peptide Fishes Antihypertensive, HPLC-MS/MS,  L. Beaulieu, J.
antioxidant and QTOFMS, Thibodeau, P.
anticoagulant GPC, Bryl, M.-E.
activities HPLC-FLD Carbonneau,
Proteolytic
processing of
herring (Clupea
harengus):
biochemical and
nutritional
characterisation of
hydrolysates, Int.
J. Food Sci.
Technol. 44 (2009)
2113– 2119.
 S.-H. Lee, Z.-J.
Qian, S.-K. Kim,
A novel
angiotensin I
converting enzyme
inhibitory peptide
from tuna frame
protein
hydrolysate and its
antihypertensive
effect in
spontaneously
hypertensive rats,
Food Chem. 118
(2010) 96–102.
Type II collagen Chick Can suppress SDS-PAGE, H. Cao, S.-Y. Xu,
Rheumatoid HPLC-UV/Vis, Purification and
arthritis FTIR characterization of type II
(RA) and promote collagen from chick sternal
healthy joints cartilage, Food Chem. 108
(2008) 439–445.
∼35 kDa antioxidant Curry Antioxidant SDS-PAGE, M.B. Ningappa, L. Srinivas,
protein leaves properties MALDI-TOF- Purification and
MS characterization of ∼35 kDa
antioxidant protein from curry
leaves (Murraya koenigii L.),
Toxicol. in Vitro 22 (2008)
699–709.
Immunomodulatoryproteins Garlic Immunomodulation SDS-PAGE F. Clement, S.N. Pramod,
(Allium activity Y.P. Venkatesh, Identity of
sativum) the immunomodulatory
proteins from garlic (Allium
sativum) with themajor garlic
lectins or agglutinins,
Int. Immunopharmacol. 10
(2010) 316–324.
Total proteins Ganoderma Prevention and 2D-PAGE R. Saltarelli, P. Ceccaroli,
lucidum treatment of M. Iotti, A. Zambonelli, M.

194
 (fungi) hypertension, Buffalini, L. Casadei, L.
diabetes, hepatitis, Vallorani, V. Stocchi,
cancers and AIDS Biochemical characterisation
and antioxidant activity of
mycelium of Ganoderma
lucidum from Central Italy,
Food Chem. 116 (2009)
143–151.
Lysozyme-derivedpeptides Hen’s egg Antimicrobial HPLC-MS/MS S.-J. You, C.C. Udenigwe,
activity R.E. Aluko, J. Wu,
Multifunctional peptides from
egg
white lysozyme, Food Res.
Int. 43 (2010) 848–855.
Cyclopeptides Cow cockle Estrogen like HPLC-MS Ö. Güclü-Üstünda˘g, G.
seed activity in vivo Mazza, Extraction of
saponins and cyclopeptides
from
cow cockle seed with
pressurized low polarity
water, Food Sci. Technol. 41
(2008) 1600–1606.
Phaseolamin Kidney May reduce calorie HPAEC-PAD M. Mosca, C. Boniglia, B.
bean absorbance, Carratù, S. Giammarioli, V.
(Phaseolus thereby promoting Nera, E. Manzini,
vulg.) weight loss Determination of α-amylase
inhibitor activity of
phaseolamin from kidney
bean
(Phaseolus vulgaris) in dietary
supplements by HPAEC-
PAD, Anal. Chim. Acta 617
(2008) 192–195.
Selenopeptides Nuts Antioxidant, anti- nanoLC- M. Dernovics, P. Giusti, R.
cancer, anti-heart Q/TOFMS/MS. Lobinski, ICP-MS-assisted
disease ICP-MS nanoHPLC-electrospray
Q/time-of-flight MS/MS
selenopeptide mapping in
Brazil nuts, J. Anal. At.
Spectrom. 22 (2007) 41–50.

Table 8.5. : Proteins, peptides and aminoacids with potential nutraceutical

activity found in different matrices, bioactivity and analytical techniques
employed for their analysis.

8.8. Proteins, Peptides and Amino Acids

According to the information showed in the table above, there are several
benefits for the human health that can de derived from the consume of some
proteins, peptides and/or aminoacids. They can have antibacterial, antioxidant,
immunostimulating, antithrombotic and anti-inflammatory activities; they could
be used for prevention and treatment of hypertension, diabetes and hepatitis
among other positive effects in the organism. All these health promoting effects
make these compounds of great relevance as nutraceuticals. Proteins, peptides
and/or aminoacids are found in a great variety of matrices including animals,
fungi, vegetables, cereals, etc., Their identification requires the use of advanced
analytical techniques due to the complexity of these compounds. As a result,
HPLC, GC, CE, NMR, Fourier Transform Infrared Spectroscopy (FTIR),

195
Inductively Coupled Plasma Mass Spectrometry (ICP-MS), inmunosensors, etc,
have been used to analyze these compounds. Thus, amino acids have been
identified and quantified in different natural matrices using Micellar
Electrokinetic Chromatography coupled to Laser Induced Fluorescence
(MEKC-LIF), micro chip electrophoresis or HPLC . Marine animals like
sardinelle , tuna , and echiuroid worms are important sources of peptides with
antioxidant, anticoagulant and antihypertensive properties. For their
identification HPLC coupled to mass spectrometry (Triple Quadrupole Mass
Analyzer (QQQ), QTOFMS) have been usually employed. Amino acids and
protein hydrolisates have been analyzed in fishes, as herring [106], using gel
permeation chromatography (GPC) and HPLC-FLD. Another important source
of proteins, peptides and amino acids is milk and dairy products. An omics-
rooted study of milk proteins has been carried out using advanced analytical
techniques (HPLC-MS/MS, Bidimensional Polyacrylamide Gel Electrophoresis
(2D-PAGE), MALDI-TOFMS) showing the great potential of this modern
approach . Analysis of these compounds in milk usually is carried out
employing liquid chromatography coupled to mass spectrometry, although other
analytical techniques like capillary electrophoresis have also been used for this
purpose. Also, immunosensors have been applied for the determination of
lactoferrin and immunoglobulin G in milk . PAGE, sodium dodecyl sulfate
PAGE (SDS-PAGE) and 2D-PAGE have been employed to analyze proteins in
several matrices like milk, chick, curry leaves, garlic or fungi . These more
classical techniques do not provide an identification of these biomolecules as
accurate as CE or HPLC coupled to mass spectrometry. Thus, mass
spectrometry alone or coupled to HPLC has been used to characterize, identify
and analyze proteins, peptides and amino acids in several matrices, for example
lisozyme derived peptides with antimicrobial activity were detected in hen eggs
, while several cyclopeptides with estrogen activity in vivo were found in cow
cockle seeds. High-performance anion exchange chromatography coupled with
pulsed amperometric detection (HPAEC-PAD) has been used to measure the α-
amylase inhibitor activity of phaseolamin from kidney bean . Using several
advanced analytical techniques, as ICP-MS, MALDI-TOF-MS, nano-HPLC-
MS/MS it was possible to obtain the whole selenopeptide map of Brazilian nuts
.

8.9. Carbohydrates, Glycosides and Related Compounds

Carbohydrates perform numerous essential roles in living beings. Thus,

monosaccharides are the major source of energy for metabolism, while
polysaccharides serve for the storage of energy and can act as structural
components. Moreover, other beneficial health effects have been linked to these
compounds, including their prebiotic effect or other less common as antioxidant

196
or anti-inflammatory activity. The identification and quantification of these
compounds have brought about the development of multiple analytical trategies
mainly based on analytical techniques such as HPLC, GC, CE and/or NMR .
Chondritin sulphate is a mucopolysaccharide, or sulfated glycosaminoglycan,
that acts as an important structural component of cartilage providing much of its
resistance to compression. Along with glucosamine, chondroitin sulfate has
become a widely used dietary supplement for treatment of osteoarthritis. It has
been determined in raw materials and formulations by CEUV . It has also been
analyzed in dietary supplements by using a specific and sensitive agarose-gel
electrophoresis and strong-anion exchange–high performance liquid
chromatography (SAX-LC) method , and this latter technique was followed by
a high-performance size-exclusion chromatography (HPSEC) to determine the
chondritin sulphate molecular mass. Other saccharides have been analyzed in
different matrices (plant, fungus, etc.) with different analytical techniques like
NMR, HPLC or CE . Two different CE approaches have been developed to
determine glucosamine, an important and abundant monosacharide, in
nutraceutical preparations . This compound is shown to be effective in treating
osteoarthritis pain, rehabilitating cartilage, renewing synovial fluid and
repairing joints that have been damaged by osteoarthritis. Glycosides are
compounds containing a carbohydrate molecule (sugar) bound to a non-
carbohydrate moiety. These compounds are mainly found in plants, and they
can be converted, by hydrolytic cleavage, into a sugar and a non-sugar
component (aglycone). They are named specifically by the type of sugar that
they contain, as glucosides (glucose), pentosides (pentose), fructosides
(fructose), etc. Many plant glycosides have shown activity for cancer
prevention, as well as antidiabetic, anti-obese, antibacterial or antineoplastic
effect . Among the multiple glycosides, several complex glucosides have been
determined in plants and cereals using HPLC, MS, NMR or GC. Saponins,
which are amphipathic glycosides, have been also studied in seeds, plants and
cereals. Saponins can stimulate muscle growth and raise testosterone levels and
they can also show antibacterial, immunological and antidiabetic properties .
The analytical methods used to determine saponins have been GC-MS as well
as HPLC, NMR, and MS.

197
Figure 8.2. : (a) Size-exclusion–ICP MS chromatogram of the extracted
Brazil nut proteins. Regular line: 78Se; thin line: 34S.The rectangular area
indicates the fraction collected for further analyses; (b) MALDI-TOF mass
spectrum of the fraction indicated in subpart a. The insets show the zooms
of the 6 and 12 kDa peaks (doubly and singly charged ions, respectively);
(c) size-exclusion–ICP MS chromatogram of the tryptic digest (5 kDa

198
cutoff filtered) of the fraction indicated in subpart a. The arrowsmark the
elution volumes of the calibration standards. The rectangular fractions
labelled with numbers were collected for nanoHPLC analyses. Reprinted
from M. Dernovics, P. Giusti, R. Lobinski, (2007) . Copyright (2007) The
Royal Society of Chemistry.

Nutraceutical Matrix Possible Analytic Reference

health effect al
techniqu
es
Saponins Vegetables Stimulate GC–MS,  K. Brady, C.-T.
muscle HPLC Ho, R.T. Rosen,
growth and (UV/Vis, S. Sang, M.V.
raise MS) Karwe, Effects
testosterone ESI- of processing on
levels. MS/MS, the nutraceutical
Antidiabetic NMR profile of quinoa,
or Food Chem. 100
anti-obese (2007) 1209–
effects, 1216.
antibacterial  Ö. Güclü-
and Üstünda˘g, G.
antineoplastic Mazza,
properties Extraction of
saponins and
cyclopeptides
from cow cockle
seed with
pressurized low
polarity water,
Food Sci.
Technol. 41
(2008) 1600–
1606.
 T. Li, Z. Zhang,
L. Zhang, X.
Huang, J. Lin,
G. Chen, An
improved facile
method for
extraction and
determination of
steroidal saponins
in Tribulus
terrestris by
focused
microwaveassiste
d extraction
coupled with GC-
MS, J. Sep. Sci.
32 (2009) 4167–
4175.
 H. Kimura, S.
Ogawa, M.
Jisaka, Y.
Kimura, T.

199
 Katsube, K.
Yokota,
Identification of
novel saponins
from edible seeds
of Japanese horse
chestnut
(Aesculus
turbinata Blume)
after treatment
with wooden
ashes and their
nutraceutical
activity, J.
Pharmaceut.
Biomed. 41
(2006) 1657–
1665.
Chondroitin sulphate Raw Treatment of CE-UV,  C.J. Malavaki,
materials, osteoarthritis SAX-LC, A.P.
formulation and some HPSEC Asimakopoulou,
s ophthalmolog F.N. Lamari,
and dietary ic diseases. A.D. Theocharis,
supplement G.N.
s Tzanakakis,
N.K.
Karamanos,
Capillary
electrophoresis
for the quality
control of
chondroitin
sulfates in raw
materials and
formulations,
Anal. Biochem.
374 (2008) 213–
220.
 N. Volpi, F.
Maccari,
Quantitative and
qualitative
evaluation of
chondroitin
sulfate in dietary
supplements,
Food Anal.
Methods 1 (2008)
195–204.
Polysaccharide Poria cocos Anti- 1D and M.-K. Lu, J.-J. Cheng,
(1,3-α-galactan) (fungus inflammatory 2D NMR C.-Y. Lin, C.-C. Chang,
effects Purification, structural
elucidation, and anti-
inflammatory effect of a
water-soluble 1,6-
branched 1,3-α-D galactan
from cultured mycelia of

200
 Poria cocos, Food Chem.
118 (2010)
349–356.

Saccharides Black Antioxidant HPLC- MSójk, B. Król,

currant properties UV Composition of industrial
pomace seedless black currant
pomace, Eur. Food Res.
Technol. 228 (2009) 597–
605.
Galactooligosacchari Dairy- Increased GC-FID F. Monta˜nés, A. Olano,
des based absorption of G. Reglero, E. Ibá˜nez,
prebiotic calcium and T. Fornari, Supercritical
ingredient. magnesium, technology as an
and improved alternative to fractionate
elimination prebiotic
of toxic galactooligosaccharides,
compounds Sep.
Purif. Technol. 66 (2009)
383–389.
Glucosamine Nutraceutic Treatment of CE  N. Volpi,
al osteoarthritis (PDA.UV Capillary
preparation ) electrophoresis
s and determination of
tablets glucosamine in
nutraceuticalform
ulations after
labeling with
anthranilic acid
and UV
detection,
J.Pharmaceut.
Biomed. Anal. 49
(2009) 868–871.
 J.-J. Chen, Y.C.
Lee, T.-J.
Cheng, H.-Y.
Hsiao, R.L.C.
Chen,
Determination of
glucosamine
content in
nutraceuticals by
capillary
electrophoresis
using incapillary
OPA labeling
techniques, J.
Food Drug Anal.
14 (2006) 203–
206.
Glycosides Plants Choleretic, HPLC-  Erkucuk, I.H.
(glucosinolates, anti UV/Vis, Akgun, O. Yesil-
glycyrrhetic acid, inflammatory HR-MS, Celiktas,

201
glycyrrzhin, , 1D and Supercritical CO2
liquiritin, anti-cancer, 2D extraction of
steroidal glycosides. . antioxidant, NMR. glycosides from
.) anorexant Stevia rebaudiana
and diuretic leaves:
properties identification and
optimization, J.
Supercrit. Fluid.
51 (2009) 29–35.
 S. Dall’Acqua,
G. Innocenti,
Steroidal
glycosides from
Hoodia gordonii,
Steroids 72
(2007) 559–568.

Table 8.6. : Glycosides with potential nutraceutical activity found in

different matrices, bioactivity and analytical techniques employed for their
analysis.

8.10. Phenolic Compounds

Under the denomination “phenolic compounds” there are more than 4000
compounds divided in 12 subclasses. Vegetables, fruits, fungi and some bacteria
produce, as part of their secondary metabolism, a wide variety of phenolic
compounds. Some of them are highly important for their physiological
functions, some others are used to defend themselves from stress situations or to
attract or repeal other organisms. In the early 1960s, phenolic compounds were
widely viewed as metabolic waste products that were stored in the plant
vacuole. Whilst there was interest at that time in their function as flower
colorants, and in their distribution between plant taxa, the earliest investigations
of their biosynthesis had just begun . In foods this kind of compounds acts as
pigments, antioxidants, flavour precursors, etc. and, nowadays, as part of our
diet they have been associated with several health promoting activities such as:
decreasing blood sugar levels, reducing body weight , anticarcinogenic ,
antiinflamatory, antiaging and antithrombotic activity . However, the major
claimed activity of phenolic compounds has been as antioxidans. The main
difference between bioactive phenolic compounds that can act as nutraceuticals
and other phenolic compounds without noticeable bioactivity is their metabolic
origin. The first ones are derived from two biosynthetic routes: shikimic acid
and/or polyacetates routes. Usually phenolic compounds bind sugars or other
phenolic compounds. A fast classification of phenolic compounds could be
done as follows :

 Benzenediols: are simplest structures, based on the hidroxy phenol.

202
  Phenolic acids: derived from benzoic acid (C6-C1) or cinnamic acid (C6-
C3), when phenolic acids are associated as long polymers form tannins
and lignans.
 Coumarins: with a basic structure of 2H-1-benzopiran-2-one.
 Flavonoids: with a basic structure of diarylpropane (C6-C3- C6), this
group is the widest and is formed by subfamilies like catechins,
flavones, flavonols, flavanones, isoflavonoids and anthocyanes .

The classical method to analyze total phenolic compounds is the Folin-

Ciocalteau method where the measured colour change is associated with the
reduction of a molibdo-tungstate reagent induced by the phenols in the sample.
Curently, HPLC has become the analytical method of choice for phenolic
compounds. HPLC was first used for the determination of flavonoids in 1976 by
Fisher and Wheaton. Since then, many methods have been developed for the
detection and quantification of phenolic compounds, being liquid
chromatography the most used technique. Besides HPLC, other separation
techniques have been used, namely, GC , TLC or CE , and also spectrometric
techniques . In HPLC, reversed-phase columns (RP) are the most commonly
used, mainly C18, ranging from 150 to 250mm in length with ID ranging from
4.6mm, and particle sizes of 5m. In general terms, endcapped columns provide
better separations. Elution mobile phases are usually binary, with an aqueous
acidified solvent (solvent A) such as aqueous acetic acid, perchloric acid, or
formic acid and an organic solvent such as methanol or acetonitrile, generally
acidified (solvent B). Trifluoroacetic acid in both solvents enhances the
resolution and eliminates peak tailing of catechins. In terms of detection
systems, UV–visible with diode array detection is the standard method used for
detection of phenolic compounds . Simple phenolic compounds present a single
absorption band in the range 240–290 nm, while, more complex phenolic
compound (flavonoids family) present a second absorption band with a
maximum in the 300–550-nm range, induced by the B ring . When MS is used
the most employed ion source is ESI due to both the polarity and molecular
weight of these analytes match well the requirements of this interface. For
example Abad-García et al. developed an interesting method based in
HPLCDAD- ESI-MS/MS (triple quadrupole mass spectrometer) for the
characterization of unknown phenolic compounds in fruit juices. Their HPLC
method consisted of using a C18 column with a gradient and acetic acid–water
(0.5:99.5, v/v) and methanol as eluents.

203
Nutraceutical Matrix Possible health Analytica Reference
effect l
technique
s
Phenolic acids Seed-oil Antioxidant HPLC- K.L. Nyam, C.P. Tan,
UV O.M. Lai, K. Long,
Y.B. Che Man,
Physicochemical
properties
and bioactive
compounds of selected
seed oils, LWT-Food
Sci. Technol.
42 (2009) 1396–1403.
Phenolics Fruits, Antioxidant HPLC-  L. Barros,
Mushrooms,legu DAD B.A.
mes Venturini, P.
Baptista,
L.M.
Estevinho,
I.C.F.R.
Ferreira,
Chemical
composition
and biological
properties of
Portuguese
wild
mushrooms: a
comprehensiv
e study, J.
Agric. Food
Chem. 56
(2008) 3856–
3862.
 L. Barros,
A.M.
Carvalho,
J.S. Morais,
I.C.F.R.
Ferreira,
Strawberry-
tree,
blackthorn
and rose
fruits:
detailed
characterisati
on in
nutrients and
phytochemica
ls with
antioxidant
properties,
Food Chem.
120 (2010
247–254

204
  d.C.B.M. de
Vasconcelos,
R.N.
Bennett, S.
Quideau, R.
Jacquet,
E.A.S. Rosa,
J.V.
Ferreira-
Cardoso,
Evaluating
the potential
of chestnut
(Castanea
sativa Mill.)
fruit pericarp
and
integument as
a source of
tocopherols,
pigments and
polyphenols,
Ind. Crops
Prod. 31
(2010) 301–
311.
 M. Fazel,
M.A. Sahari,
M. Barzegar,
Determinatio
n of main tea
seed oil
antioxidants
and their
effects on
common
kilka oil, Int.
Food. Res. J.
15 (2008)
209–217.
 G. Oms-
Oliu, I.
Odriozola-
Serrano, R.
Soliva-
Fortuny, O.
Martín-
Belloso,
Antioxidant
content of
fresh-cut
pears stored
in high-O2
active
packages
compared
with

205
 conventional
low-O2 active
and passive
modified
atmosphere
packaging, J.
Agric. Food
Chem. 56
(2008) 932–
940.
Phenolics Fruits, Antioxidant HPLC-  B. Abad-
Mushrooms, MS, García, L.A.
legumes HPLC- Berrueta, S.
MS/MS Garmón-
Lobato, B.
Gallo, F.
Vicente, A
generalanalyti
cal strategy
for the
characterizati
on of
phenolic
compounds
infruit juices
by high-
performance
liquid
chromatograp
hy with diode
arraydetection
coupled to
electrospray
ionization and
triple
quadrupole
mass
spectrometry,
J.
Chromatogr.
A 1216
(2009) 5398–
5415.
 W. Zhang, F.
Han, J. He,
C. Duan,
HPLC-DAD-
ESI-MS/MS
analysis and
antioxidantact
ivities of
nonanthocyan
in phenolics
in mulberry
(Morus alba
L.), J.Food
Sci. 73 (2008)

206
 C512–C518.
Anthocyanins Fruits, Antioxidant HPLC-  H.
Nutraceutical DAD Alighourchi,
Capsules M. Barzegar,
S. Abbasi,
Anthocyanins
characterizati
on of 15
Iranian
pomegranate
(Punica
granatum L.)
varieties and
their variation
aftercold
storage and
pasteurization
, Eur. Food
Res. Technol.
227 (2008)
881–887.
 Y. Yan, Z.
Li, M.A.G.
Koffas, High-
yield
anthocyanin
biosynthesis
in
engineeredEs
cherichia coli,
Biotechnol.
Bioeng. 100
(2008) 126–
140.
Anthocyanins Fruits, tubers Antioxidant HPLC-  R. Chirinos,
MS, D. Campos,
HPLC- I. Betalleluz,
MS/MS M.M. Giusti,
S.J.
Schwartz, Q.
Tian, R.
Pedreschi, Y.
Larondelle,
High-
performance
liquid
chromatograp
hy with
photodiode
array
detection
(HPLC-
DAD)/HPLC-
mass
spectrometry
(MS)
profilingof

207
 anthocyanins
from andean
mashua
tubers
(Tropaeolum
tuberosum
Ruíz and
Pavón) and
their
contribution
to the overall
antioxidant
activity, J.
Agric. Food
Chem. 54
(2006) 7089–
7097.
 C. Vasco, K.
Riihinen, J.
Ruales, A.
Kamal-
Eldin,
Phenolic
compounds in
rosaceae
fruits from
Ecuador, J.
Agric. Food
Chem. 57
(2009) 1204–
1212.
Phenolics Marula Antioxidants HPLC- H. Borochov-Neori,
(Sclerocarrya and DAD S. Judeinstein, A.
birrea) Antiatherogeni Greenberg, B.
c Fuhrman, J. Attias,
T. Nina
Volkova, M. Hayek,
Aviram, Phenolic
antioxidants and
antiatherogenic effects
of marula
(Sclerocarrya birrea
Subsp. caffra) fruit
juice in healthy
humans, J.
Agric. Food Chem. 56
(2008) 9884–9891.
Catecholamines Banana peel Antioxidant HPLC- R. González-
DAD Montelongo, M.G.
Lobo, M. González,
Antioxidant activity in
banana peel extracts:
testing extraction
conditions and related
bioactive compounds,
Food Chem. 119
(2010) 1030–1039.

208
Rutin Buckwheats Antioxidant HPLC- S.J. Kim, C.
DAD Kawaharada, T.
Suzuki, K. Saito, N.
Hashimoto, S.
Takigawa, T. Noda,
C. Matsuura-Endo,
H. Yamauchi, Effect
of natural light periods
on rutin, free
amino acid and
vitamin C contents in
the sprouts of common
(Fagopyrum
esculentum Moench)
and tartary (F.
tataricum Gaertn.)
buckwheats, Food Sci.
Technol. Res. 12
(2006) 199–205.
Flavone isomers lemon juice Antioxidant HPLC- B. Abad-García, S.
DAD- Garmón-Lobato,
ESI- L.A. Berrueta, B.
MS/MS Gallo, F. Vicente,
New features
on the fragmentation
and differentiation of
C-glycosidic flavone
isomers by positive
electrospray ionization
and triple quadrupole
mass spectrometry,
Rapid Commun. Mass
Spectrom. 22 (2008)
1834–1842.
Phenolics Potatoe Antioxidant HPLC- A.A. Barba, A.
DAD, Calabretti, M.
NMR d’Amore, A.L.
Piccinelli, L.
Rastrelli, Phenolic
constituents
levels in cv. Agria
potato under
microwave processing,
LWT–Food Sci.
Technol. 41 (2008)
1919–1926.
Phenolic acids Cooked meat Antioxidant HPLC- A. Brettonnet, A.
DAD Hewavitarana, S.
DeJong, M.C.
Lanari, Phenolic acids
composition
and antioxidant
activity of canola
extracts in cooked
beef, chicken and
pork, Food Chem. 121
(2010) 927–933

209
Flavonol Bean Antioxidant HPLC- G Dinelli, A. Bonetti,
DAD, M. Minelli, I.
prepHPL Marotti, P. Catizone,
C, NMR [ A. Mazzanti, Content
of flavonols in Italian
bean (Phaseolus
vulgaris L.) ecotypes,
Food Chem. 99 (2006)
105–114.
Phenolics Moscatel sweet Antioxidant HPLC- R.P. Feliciano, M.N.
wines DAD, Bravo, M.M. Pires,
HPLC- A.T. Serra, C.M.
FD Duarte, L.V. Boas,
M.R.
Bronze, Phenolic
content and
antioxidant activity of
moscatel dessert wines
from the setÃ◦bal
region in portugal,
Food Anal. Meth. 2
(2009) 149–161.
Phenolics Carex distachya Antioxidant HPLC- A. Fiorentino, A.
roots DAD-MS, Ricci, B. D’Abrosca,
NMR S. Pacifico, A. Golino,
M. Letizia, S.
Piccolella, P.
Monaco, Potential
food additives from
Carex distachya roots:
identification and in
vitro antioxidant
properties, J. Agric.
Food Chem. 56
(2008) 8218–8225.
Curcuminoids Curcuma longa Antioxidant HPLC C.E. Green, S.L.
HPTLC Hibbert, Y.A. Bailey-
Shaw, L.A.D.
Williams, S. Mitchell,
E.
Garraway, Extraction,
processing and storage
effects on
curcuminoids and
oleoresin yields from
Curcuma longa L.
grown in Jamaica, J.
Agric. Food Chem.
56 (2008) 3664–3670.
Lignans Flaxseed Antioxidant PLE C.H.L. Ho, J.E.
HPLC- Cacace, G. Mazza,
UV Mass transfer during
pressurized low
polarity
water extraction of
lignans from flaxseed
meal, J. Food Eng. 89

210
 (2008) 64–71.
Phenolic acids, Triticale Antioxidant HPLC- F.S. Hosseinian, G.
proanthocyanidin DAD Mazza, Triticale bran
s, and and straw: potential
lignans new sources
of phenolic acids,
proanthocyanidins,
and lignans, J. Funct.
Foods 1 (2009)
57–64.
Flavonoids Ulmus davidiana Antioxidant HPLC- M.J. Jung, S.-I. Heo,
DAD M.-H. Wang, HPLC
analysis and
antioxidant activity of
Ulmus davidiana and
some flavonoids, Food
Chem. 120 (2010)
313–318.
Resveratrol Grape canes Antioxidant HPLC- E. Karacabey, G.
DAD Mazza, Optimization
of solid-liquid
extraction of
resveratrol
and other phenolic
compounds from
milled grape canes
(Vitis vinifera), J.
Agric. Food Chem. 56
(2008) 6318–6325
Phenolic acids Glycin tomentella Antioxidant HPLC- J.-T. Lin, S.-C. Liu,
and flavonoids Hayata DAD G.J. Tsay, D.-J.
(Leguminosae Yang, Composition of
family) flavonoids and
phenolic
acids in Glycin
tomentella Hayata
cultivated in various
soils, Food Chem. 121
(2010) 659–665.
Phenolic acids Mulberry Antioxidant HPLC- A.A. Memon, N.
DAD Memon, D.L.
Luthria, M.I.
Bhanger, A.A. Pitafi,
Phenolic acids
profiling and
antioxidant potential
of mulberry (Morus
laevigata W., Morus
nigra L., Morus alba
L.) Leaves and fruits
grown in Pakistan, Pol.
J. Food Nutr.
Sci. 60 (2010) 25–32.
Chicoric acid seagrass Antioxidant HPLC- G. Nuissier, B.
Syringodium DAD-MS Rezzonico, M.
filiforme Grignon-Dubois,
Chicoric acid from

211
 Syringodium
filiforme, Food Chem.
120 (2010) 783–788.
Resveratrol Nutritional Antioxidant HPLC- J. Prokop, P.
suplements UV Abrman, A.L.
Seligson, M. Sovak,
Resveratrol and its
glycon piceid
are stable polyphenols,
J. Med. Food 9 (2006)
11–14.
Flavonoids Wild rice Antioxidant HPLC- Y. Qiu, Q. Lin, T.
DAD- Beta, Antioxidant
MS/MS activity of commercial
wild rice and
identification
of flavonoid
compounds in active
fractions, J. Agric.
Food Chem. 57
(2009) 7543–7551.
Phenolic acids Rice Antioxidant HPLC- Y. Qiu, Q. Liu, T.
DAD- Beta, Antioxidant
MS/MS properties of
commercial wild rice
and analysis of soluble
and insoluble phenolic
acids, Food Chem. 121
(2010) 140–147
Silymarin Milk thistle Antioxidant HPLC- T. Radjabian, S.
UV Rezazadeh, H.F.
Huseini, Analysis of
silymarin components
in
the seed extracts of
somemilk thistle
ecotypes from Iran by
HPLC, Iran. J. Sci.
Technol. A 32 (2008)
141–146.
Flavonoid black currant Antioxidant HPLC- G. Rak, P. Fodor, L.
aglycones MS/MS Abrankó, Three-step
HPLC-ESI-MS/MS
procedure for
screening and
identifying non-target
flavonoid derivatives,
Int. J. Mass Spectrom.
290 (2010) 32–38.
Flavonoids Cranberry Antioxidant HPLC- A.P. Singh, T.
DAD-MS, Wilson, A.J. Kalk, J.
NMR Cheong, N. Vorsa,
Isolation of specific
cranberry
flavonoids for
biological activity
assessment, Food

212
 Chem. 116 (2009)
963–968.
Demethyloleurop Olive fruit Antioxidant HPLC- G. Sivakumar, C.B.
ein DAD-MS Bati, N. Uccella,
Demethyloleuropein
and b-glucosidase
activity in olive fruits,
Biotechnol. J. 2 (2007)
381–385
Alkil phenols Anacardum Antioxidant HPLC- M.T.S. Trevisan, B.
MS, GC- Pfundstein, R.
MS, Haubner, G.
NMR Würtele, B.
Spiegelhalder, H.
Bartsch, R.W. Owen,
Characterization of
alkyl phenols in
cashew (Anacardium
occidentale) products
and assay of their
antioxidant capacity,
Food Chem.
Toxicol. 44 (2006)
188–197
Flavonoids Hypericum Antioxidant HSCCC, Y. Wei, Q. Xie, W.
perforatum prep- Dong, Y. Ito,
HPLC, Separation of
NMR epigallocatechin and
flavonoids from
Hypericum perforatum
L. by high-speed
counter-current
chromatography and
preparative high-
performance liquid
chromatography, J.
Chromatogr. A 1216
(2009) 4313–4318.
Phenolic acids, Black Soybeans Antioxidant HPLC- B. Xu, S.K.C. Chang,
isoflavones DAD Total phenolics,
phenolic acids,
isoflavones, and
anthocyanins and
antioxidant properties
of yellow and black
soybeans as affected
by thermal processing,
J. Agric. Food Chem.
56 (2008) 7165–7175
Phenolics Pepper Antioxidant GC, TLC, S. Chatterjee, Z.
Voltamet Niaz, S. Gautam, S.
ry Adhikari, P.S.
Variyar, A. Sharma,
Antioxidant
activity of some
phenolic constituents
from green pepper

213
 (Piper nigrum L.) and
fresh nutmeg mace
(Myristica fragrans),
Food Chem. 101
(2007) 515–523.
Phenolic acids Malt Antioxidant GC-MS J. Pejin, O. Grujic, J.
Canadanovic-Brunet,
D. Vujic, V. Tumbas,
Investigation of
phenolic acids content
and antioxidant
activity in malt
production, J. Am.
Soc.
Brew. Chem. 67
(2009) 81–88
Catechins and Green Tea Antioxidant GC-MS F. Shadkami, S.
condensed Estevez, R. Helleur,
tannins Analysis of catechins
and condensed tannins
by thermally assisted
hydrolysis/methylation
-GC/MS and by a
novel two step
methylation, J. Anal.
Appl. Pyrolysis 85
(2009) 54–65.
Phenolic acids Mangosteen Antioxidant GC-FID R. Zadernowski, S.
GC-MS Czaplicki, M. Naczk,
Phenolic acid profiles
of mangosteen
fruits (Garcinia
mangostana), Food
Chem. 112 (2009)
685–689.
Phenolics Bergenia ciliata Antioxidant HPTLC K. Dhalwal, V.M.
Shinde, Y.S. Biradar,
K.R. Mahadik,
Simultaneous
quantification
of bergenin, catechin,
and gallic acid from
Bergenia ciliata and
Bergenia ligulata by
using thin-layer
chromatography, J.
Food Comp. Anal. 21
(2008)
496–500
Phenolics Vanilla planifolia Antioxidant HPTLC U.K. Sharma, N.
PLE Sharma, A.P. Gupta,
MAE V. Kumar, A.K.
Sinha, RP-HPTLC
densitometric
determination and
validation of vanillin
and related phenolic

214
 compounds in
accelerated solvent
extract of Vanilla
planifolia, J. Sep. Sci.
30 (2007) 3174–3180.
Phenolics Grape Antioxidant CE-UV F. Berli, J. D’Angelo,
B. Cavagnaro, R.
Bottini, R. Wuilloud,
M.F. Silva, Phenolic
composition in grape
(Vitis vinifera L. cv.
Malbec) ripened with
different solar
UV-B radiation levels
by capillary zone
electrophoresis, J.
Agric. Food Chem.
56 (2008) 2892–2898.
Flavonoids and Chinese herbal Antioxidant CZE-AD L. Chi, Z. Li, S.
phenolic acids tea Dong, P. He, Q.
Wang, Y. Fang,
Simultaneous
determination
of flavonoids and
phenolic acids in
Chinese herbal tea by
beta-cyclodextrin
based capillary zone
electrophoresis,
Microchimica Acta
167 (2009)
179–185.
Resveratrol Nutraceutical Prevention of CE S. Orlandini, I.
capsules atherosclerosis Giannini, S. Pinzauti,
S. Furlanetto,
Multivariate
optimisation
and validation of a
capillary
electrophoresis method
for the analysis of
resveratrol
in a nutraceutical,
Talanta 74 (2008)
570–577.
Phenolics Grape skin Antioxidant CE-FLD F. Priego Capote,
CE-DAD J.M. Luque
Rodríguez, M.D.
Luque de Castro,
Determination
of phenolic
compounds in grape
skin by capillary
electrophoresis with
simultaneous
dual fluorescence and
diode array absorption

215
 detection after
dynamic
superheated liquid
leaching, J.
Chromatogr. A 1139
(2007) 301–307.
Lignans Myristica Anticariogenic NMR, J.Y. Chung, J.H.
fragrans MS, GPC Choo, M.H. Lee, J.K.
(nutmeg) Hwang,
Anticariogenic activity
of macelignan
isolated from
Myristica fragrans
(nutmeg) against
Streptococcus mutans,
Phytomedicine 13
(2006) 261–266.
Prunate Prunus Anticarcinogen MS, J.T. Jeong, J.-H.
ic NMR Moon, K.-H. Park,
C.S. Shin, Isolation
and characterization of
a new compound from
Prunus mume fruit that
inhibits cancer cells, J.
Agric.
Food Chem. 54 (2006)
2123–2128.
Polymethoxilated Orange Oil Antioxidant FTIR J.A. Manthey, Fourier
Flavones transform infrared
spectroscopic analysis
of the
polymethoxylated
flavone content of
orange oil residues, J.
Agric. Food Chem. 54
(2006) 3215–3218.
Carnosic Rosemary Antioxidant NMR I. Rodríguez-
FTIR Meizoso, A.
Cifuentes, J. San
Román, E. Ibá˜nez,
C. Elvira, A
systematic study on
the interactions
between carnosic acid
and ethylpyrrolidine
methacrylate-methyl
methacrylate
copolymer in
supercritical media,
J. Supercrit. Fluids 41
(2007) 452–460.
Licochalcone A Glycyrrhiza Lipase NMR MS S.-R. Won, S.-K.
uralensis inhibition Kim, Y.-M. Kim, P.-
H. Lee, J.-H. Ryu, J.-
W. Kim, H.-I. Rhee,
Licochalcone A: a
lipase inhibitor from

216
 the roots of
Glycyrrhiza uralensis,
Food
Res. Int. 40 (2007)
1046–1050.
Phlorotannins Alga (Ishige Cholinesterase NMR N.Y. Yoon, S.-H. Lee,
okamurae) inhibition L. Yong, S.-K. Kim,
Phlorotannins from
Ishige okamurae
and their acetyl- and
butyrylcholinesterase
inhibitory effects, J.
Funct. Foods
1 (2009) 331–335.
Phytoestrogens Dietary Estrogenic HPLC- C. Boniglia, B.
supplements activity UV Carratù, R. Gargiulo,
S. Giammarioli, M.
Mosca, E. Sanzini,
Content
of phytoestrogens in
soy-based dietary
supplements, Food
Chem. 115
(2009) 1389–1392.
Flavonol Ginkgo biloba Memory HPLC- D.E. Gray, R. Upton,
glycosides enhancing UV A. Chandra, A.
Porter, R.K. Harris,
Quantitative analysis
of
flavonol glycosides in
Ginkgo biloba: a
comparison of two
analytical methods,
Phytochem. Anal. 17
(2006) 56–62.
Isoflavones Soy milk Estrogenic HPLC- S. Jung, P.A.
activity DAD Murphy, I. Sala,
Isoflavone profiles of
soymilk as affected by
high-pressure
treatments of soymilk
and soybeans, Food
Chem. 111 (2008)
592–598.
Isoflavones Soy supplements Antimenopausi HPLC- L. Krenn, V. Patsch,
al sympthoms DAD An efficient HPLC
method for the
quantification of
isoflavones in soy
extracts and soy
dietary supplements in
routine quality
control, Pharmazie 61
(2006) 582–585.
Phenolics Tamarix gallica Antioxidant HPLC- R. Ksouri, H. Falleh,
and DAD W. Megdiche, N.
antimicrobial Trabelsi, B. Mhamdi,

217
 K. Chaieb, A.
Bakrouf,
C. Magné, C.
Abdelly, Antioxidant,
antimicrobial activities
of the edible medicinal
halophyte Tamarix
gallica L. and related
polyphenolic
constituents, Food
Chem. Toxicol. 47
(2009) 2083–2091.
Flavonoids Citrus peel Antiinflammato HPLC- S. Li, C.-Y. Lo, C.-T.
ry, ESI-MS Ho, Hydroxylated
anticarcinogeni NMR polymethoxyflavones
c and and methylated
antiatherogenic flavonoids in sweet
orange (Citrus
sinensis) peel, J.
Agric. Food Chem. 54
(2006)
4176–4185.
Resveratrol Carex folliculata Antioxidant, HPLC- L. Li, G.E. Henry,
Oligomers and Seeds cytotoxicity DAD, N.P. Seeram,
Flavonoids and NMR Identification and
antibacterial bioactivities of
resveratrol
oligomers and
flavonoids from carex
folliculata Seeds, J.
Agric. Food Chem. 57
(2009) 7282–7287
Phenolic acids Infant cereals Antioxidant & HPLC- W. Li, J. Friel, T.
aroma DAD- Beta, An evaluation of
MS/MS the antioxidant
properties and aroma
quality of infant
cereals, Food Chem.
121 (2010) 1095–1102
O-glucoside Olive by- Antioxidant, HPLC- R. Japón Luján, F.
phenolic products maturity DAD- Priego Capote, M.D.
compounds indicators MS/MS Luque de Castro,
Temporal
metabolomic
analysis of O-
glucoside phenolic
compounds and their
aglycone forms in
olive
tree and derived
materials, Phytochem.
Anal. 20 (2009) 221–
230.
Isoflavones Soybean seeds Antimenopausi HPLC- M. Oliveira, N.
al sympthoms UV Piovesan, I. José, E.
Barros, M. Moreira,
L. Oliveira, Protein,

218
 oil and isoflavone
contents in
lipoxygenase- and
kunitz trypsin
inhibitordeficient
soybean seeds,
Chromatographia 66
(2007) 521–527.
Isoflavones Red clover Antifungal HPLC- N.M.M. Saviranta,
activity DAD M.J. Anttonen, A.
Von Wright, R.O.
Karjalainen, Red
clover
(Trifolium pratense L.)
isoflavones:
determination of
concentrations by
plant
stage, flower colour,
plant part and cultivar,
J. Sci. Food Agric. 88
(2008) 125–132.
Isoflavones Nutritional Estrogenic HPLC- M. Stürtz, V. Lander,
supplements activity DAD W. Schmid, P.
Winterhalter,
Quantitative
determination
of isoflavones in soy
based nutritional
supplements by high-
performance
liquid
chromatography, J.
Verbr. Lebensm. 3
(2008) 127–136.

Table 8.7. : Phenolic compounds with potential nutraceutical activity found

in different matrices, bioactivity and analytical techniques employed for
their analysis.

219
Figure 8.3. : MS/MS product ion spectra of [M+H]+ ion of apigenin-8-C-
glucoside-4I-O-rhamnoside (cone voltage 30 V, collision energy 20 and 40
eV). Reprinted from B. Abad-García, L.A. Berrueta, S. Garmón-Lobato, B.
Gallo, F. Vicente, (2009) ; Copyright (2009) Elsevier B.V.

Figure: FTIR spectum of polymethoxylated flavones (PMFs) in orange peel

oil isolated by 95% ethanol extraction and LH20 column chromatography
(A) and spectum of the non-PMF residue recovered after 95% ethanol
extraction (B). The spectra are a summation of eight scans taken with the
residue thinly applied to a PTFE IR card. Reprinted from F. Monta˜nés, A.
Olano, G. Reglero, E. Ibá˜nez, T. Fornari, (2009)

Their strategy was based in four steps: (i) taking into account its UV–visible
spectrum and elution order, assign the unknown polyphenol to a polyphenol
class, (ii) identify the quasi-molecular ion using positive and negative MS
spectra, being supported by adducts generated with solvent or sodium and
molecular complexes, (iii) determinate the pattern of glycosylation in positive
mode using ESI(+)-CID MS/MS product ion scan experiments (CID: Collision
Induced Dissociation), selecting the quasi-molecular ion as precursor ion, and
finally, (iv) study the identity of the aglycone through ESI(+)-CID MS/MS
product ion spectra from the protonated aglycone, [Y0]+. In this work, a triple
quadrupole mass spectrometer was used, which is more indicated for the
quantification of known analytes. To overcome this limitation, Abad-García et
al. studied the elution time, UV spectra and fragmentation patterns of each
polyphenol before analyzing real samples.

The previously depicted strategy is highly useful when dealing with known
compounds, but for the study of previously undescribed compounds, other kind
of mass spectrometers must be used. For example, Fu et al. used LC-DAD
coupled to a timeof- flight mass spectrometer (ESI-TOF-MS) and an ion-trap
multiple mass spectrometer (ESI-IT-MSn) to characterize novel phenolic
compounds in extra virgin olive oils. Despite LC is the most used separation

220
technique to analyse phenolic compounds, some authors have used CE for this
purpose . For example, Orlandini et al. developed by chemometric optimization
a rapid and simple method based on capillary electrophoresis for the quality
control of nutraceuticals (effervescent tablets) containing resveratrol. This
compound is thought to be one of the compounds responsible for the
cardioprotective action of red wine and is promoted as an antioxidant for the
prevention of atherosclerosis. Resveratrol also has mixed agonist/antagonist
activity at oestrogen receptors and some anti-inflammatory and antiproliferative
activity . In order to set up the method for the quality control of the mentioned
nutraceuticals (effervescent tablets), amultivariate strategy based in response
surfaces was followed. In this study, the factors considered were buffer
concentration, percentage of acetonitrile and voltage. The factors were studied
in the following experimental range: X1, buffer concentration; X2, percentage
of acetonitrile; X3, voltage. The resulting method, found by Derringer
desirability function, made it possible to achieve good resolution and low
analysis time (7min) also in the presence of a complex sample matrix. The
optimization involved the separation of 11 effervescent tablet components
industry. Polymethoxylated flavones exhibit anticancer and ant inflammation
actions, as well as triglyceride and low-density lipoprotein cholesterol-lowering
properties. Although this analysis (FTIR) does not provide information on the
levels of individual PMFs, it provides a rapid, solvent-free measurement of the
total PMF content in orange oil residues. The ethanol extraction of the PMFs
from the bulk of the oil residue provides a rapid and easy enrichment and
recovery of the PMF from the oil residues. LH20 size exclusion
chromatography provides a means of isolating high percentage PMF material,
consisting of relative proportions of the individual PMFs similar to those in the
original oil residues. The near absence of other non-PMF constituents is evident
by the low intensity of the (C O) vibration at 1724cm−1. The intensities of the
FTIR vibrations of the phenyl ring (C C) stretch at 1515cm−1 of the PMFs can
be used, relative to the intensity of the carbonyl stretch at 1733cm−1 of the non-
PMF orange oil residue components, to measure PMF content. Excellent
correlations for the ratios of the intensities of these vibrations and the total PMF
content were observed irrespective of the source, viscosity, and presence of
particulate material.

References:

F.S. Hosseinian, W. Li, T. Beta, Measurement of anthocyanins and other

phytochemicals in purple wheat, Food Chem. 109 (2008) 916–924.

L. Jakobek, M. Seruga, M. Medvidovic-Kosanovic, I. Novak, Anthocyanin

content and antioxidant activity of various red fruit juices, Dtsch. Lebens.
Runds. 103 (2007) 58–64.

221
J. Lee, C. Rennaker, R.E. Wrolstad, Correlation of two anthocyanin
quantification methods: HPLC and spectrophotometric methods, Food Chem.
110 (2008) 782–786.

S. Tural, I. Koca, Physico-chemical and antioxidant properties of cornelian

cherry fruits (Cornus mas L.) grown in Turkey, Sci. Hort. 116 (2008) 362–366.

Y. Yan, Z. Li, M.A.G. Koffas, High-yield anthocyanin biosynthesis in

engineered Escherichia coli, Biotechnol. Bioeng. 100 (2008) 126–140.

R. Chirinos, D. Campos, I. Betalleluz, M.M. Giusti, S.J. Schwartz, Q. Tian,

R. Pedreschi, Y. Larondelle, High-performance liquid chromatography with
photodiode array detection (HPLC-DAD)/HPLC-mass spectrometry (MS)
profiling of anthocyanins from andean mashua tubers (Tropaeolum tuberosum
Ruíz and Pavón) and their contribution to the overall antioxidant activity, J.
Agric. Food Chem. 54 (2006) 7089–7097.

G.A. Garzón, K.M. Riedl, S.J. Schwartz, Determination of anthocyanins, total

phenolic content, and antioxidant activity in andes berry (Rubus glaucus Benth),
J. Food Sci. 74 (2009) C227–C232.

M. Netzel, G. Netzel, Q. Tian, S. Schwartz, I. Konczak, Sources of

antioxidant activity in Australian native fruits. Identification and quantification
of anthocyanins, J. Agric. Food Chem. 54 (2006) 9820–9826.

C. Vasco, K. Riihinen, J. Ruales, A. Kamal-Eldin, Phenolic compounds in

rosaceae fruits from Ecuador, J. Agric. Food Chem. 57 (2009) 1204–1212.

B. Abad-García, S. Garmón-Lobato, L.A. Berrueta, B. Gallo, F. Vicente,

New features on the fragmentation and differentiation of C-glycosidic flavone
isomers by positive electrospray ionization and triple quadrupole mass
spectrometry, Rapid Commun. Mass Spectrom. 22 (2008) 1834–1842.

A.A. Barba, A. Calabretti, M. d’Amore, A.L. Piccinelli, L. Rastrelli,

Phenolic constituents levels in cv. Agria potato under microwave processing,
LWT–Food Sci. Technol. 41 (2008) 1919–1926.

A. Brettonnet, A. Hewavitarana, S. DeJong, M.C. Lanari, Phenolic acids

composition and antioxidant activity of canola extracts in cooked beef, chicken
and pork, Food Chem. 121 (2010) 927–933.

G Dinelli, A. Bonetti, M. Minelli, I. Marotti, P. Catizone, A. Mazzanti,

Content of flavonols in Italian bean (Phaseolus vulgaris L.) ecotypes, Food
Chem. 99 (2006) 105–114.

222
R.P. Feliciano, M.N. Bravo, M.M. Pires, A.T. Serra, C.M. Duarte, L.V.
Boas, M.R. Bronze, Phenolic content and antioxidant activity of moscatel
dessert wines from the setÃ◦bal region in portugal, Food Anal. Meth. 2 (2009)
149–161.

A. Fiorentino, A. Ricci, B. D’Abrosca, S. Pacifico, A. Golino, M. Letizia, S.

Piccolella, P. Monaco, Potential food additives from Carex distachya roots:
identification and in vitro antioxidant properties, J. Agric. Food Chem. 56
(2008) 8218–8225.

C.E. Green, S.L. Hibbert, Y.A. Bailey-Shaw, L.A.D. Williams, S. Mitchell,

E. Garraway, Extraction, processing and storage effects on curcuminoids and
oleoresin yields from Curcuma longa L. grown in Jamaica, J. Agric. Food
Chem. 56 (2008) 3664–3670.

C.H.L. Ho, J.E. Cacace, G. Mazza, Mass transfer during pressurized low
polarity water extraction of lignans from flaxseed meal, J. Food Eng. 89 (2008)
64–71.

F.S. Hosseinian, G. Mazza, Triticale bran and straw: potential new sources of
phenolic acids, proanthocyanidins, and lignans, J. Funct. Foods 1 (2009) 57–64.

M.J. Jung, S.-I. Heo, M.-H. Wang, HPLC analysis and antioxidant activity of
Ulmus davidiana and some flavonoids, Food Chem. 120 (2010) 313–318.

E. Karacabey, G. Mazza, Optimization of solid-liquid extraction of resveratrol

and other phenolic compounds from milled grape canes (Vitis vinifera), J.
Agric. Food Chem. 56 (2008) 6318–6325.

J.-T. Lin, S.-C. Liu, G.J. Tsay, D.-J. Yang, Composition of flavonoids and
phenolic acids in Glycin tomentella Hayata cultivated in various soils, Food
Chem. 121 (2010) 659–665.

A.A. Memon, N. Memon, D.L. Luthria, M.I. Bhanger, A.A. Pitafi, Phenolic
acids profiling and antioxidant potential of mulberry (Morus laevigata W.,
Morus nigra L., Morus alba L.) Leaves and fruits grown in Pakistan, Pol. J.
Food Nutr. Sci. 60 (2010) 25–32.

G. Nuissier, B. Rezzonico, M. Grignon-Dubois, Chicoric acid from

Syringodium filiforme, Food Chem. 120 (2010) 783–788.

J. Prokop, P. Abrman, A.L. Seligson, M. Sovak, Resveratrol and its glycon

piceid are stable polyphenols, J. Med. Food 9 (2006) 11–14.

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Y. Qiu, Q. Lin, T. Beta, Antioxidant activity of commercial wild rice and
identification of flavonoid compounds in active fractions, J. Agric. Food Chem.
57 (2009) 7543–7551.

Y. Qiu, Q. Liu, T. Beta, Antioxidant properties of commercial wild rice and

analysis of soluble and insoluble phenolic acids, Food Chem. 121 (2010) 140–
147.

T. Radjabian, S. Rezazadeh, H.F. Huseini, Analysis of silymarin components

in the seed extracts of somemilk thistle ecotypes from Iran by HPLC, Iran. J.
Sci. Technol. A 32 (2008) 141–146.

G. Rak, P. Fodor, L. Abrankó, Three-step HPLC-ESI-MS/MS procedure for

screening and identifying non-target flavonoid derivatives, Int. J. Mass
Spectrom. 290 (2010) 32–38.

A.P. Singh, T. Wilson, A.J. Kalk, J. Cheong, N. Vorsa, Isolation of specific

cranberry flavonoids for biological activity assessment, Food Chem. 116 (2009)
963–968.

G. Sivakumar, C.B. Bati, N. Uccella, Demethyloleuropein and b-glucosidase

activity in olive fruits, Biotechnol. J. 2 (2007) 381–385.

M.T.S. Trevisan, B. Pfundstein, R. Haubner, G. Würtele, B. Spiegelhalder,

H. Bartsch, R.W. Owen, Characterization of alkyl phenols in cashew
(Anacardium occidentale) products and assay of their antioxidant capacity,
Food Chem. Toxicol. 44 (2006) 188–197.

Y. Wei, Q. Xie, W. Dong, Y. Ito, Separation of epigallocatechin and

flavonoids from Hypericum perforatum L. by high-speed counter-current
chromatography and preparative high-performance liquid chromatography, J.
Chromatogr. A 1216 (2009) 4313–4318.

B. Xu, S.K.C. Chang, Total phenolics, phenolic acids, isoflavones, and

anthocyanins and antioxidant properties of yellow and black soybeans as
affected by thermal processing, J. Agric. Food Chem. 56 (2008) 7165–7175.

S. Chatterjee, Z. Niaz, S. Gautam, S. Adhikari, P.S. Variyar, A. Sharma,

Antioxidant activity of some phenolic constituents from green pepper (Piper
nigrum L.) and fresh nutmeg mace (Myristica fragrans), Food Chem. 101
(2007) 515–523.

J. Pejin, O. Grujic, J. Canadanovic-Brunet, D. Vujic, V. Tumbas,

Investigation of phenolic acids content and antioxidant activity in malt
production, J. Am. Soc. Brew. Chem. 67 (2009) 81–88.

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F. Shadkami, S. Estevez, R. Helleur, Analysis of catechins and condensed
tannins by thermally assisted hydrolysis/methylation-GC/MS and by a novel
two step methylation, J. Anal. Appl. Pyrolysis 85 (2009) 54–65.

R. Zadernowski, S. Czaplicki, M. Naczk, Phenolic acid profiles of

mangosteen fruits (Garcinia mangostana), Food Chem. 112 (2009) 685–689.

K. Dhalwal, V.M. Shinde, Y.S. Biradar, K.R. Mahadik, Simultaneous

quantification of bergenin, catechin, and gallic acid from Bergenia ciliata and
Bergenia ligulata by using thin-layer chromatography, J. Food Comp. Anal. 21
(2008) 496–500.

U.K. Sharma, N. Sharma, A.P. Gupta, V. Kumar, A.K. Sinha, RP-HPTLC

densitometric determination and validation of vanillin and related phenolic
compounds in accelerated solvent extract of Vanilla planifolia, J. Sep. Sci. 30
(2007) 3174–3180.

F. Berli, J. D’Angelo, B. Cavagnaro, R. Bottini, R. Wuilloud, M.F. Silva,

Phenolic composition in grape (Vitis vinifera L. cv. Malbec) ripened with
different solar UV-B radiation levels by capillary zone electrophoresis, J. Agric.
Food Chem. 56 (2008) 2892–2898.

L. Chi, Z. Li, S. Dong, P. He, Q. Wang, Y. Fang, Simultaneous

determination of flavonoids and phenolic acids in Chinese herbal tea by beta-
cyclodextrin based capillary zone electrophoresis, Microchimica Acta 167
(2009) 179–185.

S. Orlandini, I. Giannini, S. Pinzauti, S. Furlanetto, Multivariate

optimisation and validation of a capillary electrophoresis method for the
analysis of resveratrol in a nutraceutical, Talanta 74 (2008) 570–577.

F. Priego Capote, J.M. Luque Rodríguez, M.D. Luque de Castro,

Determination of phenolic compounds in grape skin by capillary electrophoresis
with simultaneous dual fluorescence and diode array absorption detection after
dynamic superheated liquid leaching, J. Chromatogr. A 1139 (2007) 301–307.

J.Y. Chung, J.H. Choo, M.H. Lee, J.K. Hwang, Anticariogenic activity of
macelignan isolated from Myristica fragrans (nutmeg) against Streptococcus
mutans, Phytomedicine 13 (2006) 261–266.

J.T. Jeong, J.-H. Moon, K.-H. Park, C.S. Shin, Isolation and characterization
of a new compound from Prunus mume fruit that inhibits cancer cells, J. Agric.
Food Chem. 54 (2006) 2123–2128.

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J.A. Manthey, Fourier transform infrared spectroscopic analysis of the
polymethoxylated flavone content of orange oil residues, J. Agric. Food Chem.
54 (2006) 3215–3218.

I. Rodríguez-Meizoso, A. Cifuentes, J. San Román, E. Ibá˜nez, C. Elvira, A

systematic study on the interactions between carnosic acid and ethylpyrrolidine
methacrylate-methyl methacrylate copolymer in supercritical media, J.
Supercrit. Fluids 41 (2007) 452–460.

S.-R. Won, S.-K. Kim, Y.-M. Kim, P.-H. Lee, J.-H. Ryu, J.-W. Kim, H.-I.
Rhee, Licochalcone A: a lipase inhibitor from the roots of Glycyrrhiza
uralensis, Food Res. Int. 40 (2007) 1046–1050.

N.Y. Yoon, S.-H. Lee, L. Yong, S.-K. Kim, Phlorotannins from Ishige
okamurae and their acetyl- and butyrylcholinesterase inhibitory effects, J.
Funct. Foods 1 (2009) 331–335.

C. Boniglia, B. Carratù, R. Gargiulo, S. Giammarioli, M. Mosca, E.

Sanzini, Content of phytoestrogens in soy-based dietary supplements, Food
Chem. 115 (2009) 1389–1392.

D.E. Gray, R. Upton, A. Chandra, A. Porter, R.K. Harris, Quantitative

analysis of flavonol glycosides in Ginkgo biloba: a comparison of two
analytical methods, Phytochem. Anal. 17 (2006) 56–62.

S. Jung, P.A. Murphy, I. Sala, Isoflavone profiles of soymilk as affected by

high-pressure treatments of soymilk and soybeans, Food Chem. 111 (2008)
592–598.

L. Krenn, V. Patsch, An efficient HPLC method for the quantification of

isoflavones in soy extracts and soy dietary supplements in routine quality
control, Pharmazie 61 (2006) 582–585.

R. Ksouri, H. Falleh, W. Megdiche, N. Trabelsi, B. Mhamdi, K. Chaieb, A.

Bakrouf, C. Magné, C. Abdelly, Antioxidant, antimicrobial activities of the
edible medicinal halophyte Tamarix gallica L. and related polyphenolic
constituents, Food Chem. Toxicol. 47 (2009) 2083–2091.

S. Li, C.-Y. Lo, C.-T. Ho, Hydroxylated polymethoxyflavones and methylated

flavonoids in sweet orange (Citrus sinensis) peel, J. Agric. Food Chem. 54
(2006) 4176–4185.

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 Chapter 9
Selected Nutraceutical and health Glossary of Terms and
Concepts

Ascorbic acid: a sugar acid with antioxidant properties. Its

appearance is white to light-yellow crystals or
powder, and it is water-soluble. One form of
ascorbic acid is commonly known as vitamin C.

Acidophilus: a general name for a group of probiotics often

added to milk or sold as a capsule, which contains
one or more of the following bacteria which aid in
digestion:

 Lactobacillus
 acidophilus (A)
 Lactobacillus casei (C)
 Lactobacillus bulgaricus (L)
 Bifidobacterium species (B)
 Streptococcus thermophilus
Only L. acidophilus is the true acidophilus
species, but many producers use it as a more
generic name for mixtures of bacteria, one of
which is L. acidophilus.

Aging: the accumulation of changes in an organism or

object over time. Aging in humans refers to a
multidimensional process of physical,
psychological, and social change. Some
dimensions of ageing grow and expand over time,
while others decline

Allergies: a disorder of the immune system often also

referred to as atopy. Allergic reactions occur to
normally harmless environmental substances
known as allergens; these reactions are acquired,
predictable, and rapid. Strictly, allergy is one of
four forms of hypersensitivity and is called type I

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 (or immediate) hypersensitivity. It is
characterized by excessive activation of certain
white blood cells called mast cells and basophils
by a type of antibody known as IgE, resulting in
an extreme inflammatory response.

Aloe vera: Also known as the medicinal aloe is a species of

succulent plant that probably originated in
Northern Africa. Aloe vera grows in arid climates
and is widely distributed in Africa and other arid
areas.

Amino acids: Are critical to life, and have a variety of roles in

metabolism. One particularly important function
is as the building blocks of proteins, which are
linear chains of amino acids. Amino acids are also
important in many other biological molecules,
such as forming parts of coenzymes, as in S-
adenosylmethionine, or as precursors for the
biosynthesis of molecules such as heme. Due to
this central role in biochemistry, amino acids are
very important in nutrition.

Antioxidants: An antioxidant is a molecule capable of slowing

or preventing the oxidation of other molecules.
Oxidation is a chemical reaction that transfers
electrons from a substance to an oxidizing agent.
Oxidation reactions can produce free radicals,
which start chain reactions that damage cells.
Antioxidants terminate these chain reactions by
removing free radical intermediates, and inhibit
other oxidation reactions by being oxidized
themselves. As a result, antioxidants are often
reducing agents such as thiols, ascorbic acid or
polyphenols. Although oxidation reactions are
crucial for life, they can also be damaging; hence,
plants and animals maintain complex systems of
multiple types of antioxidants, such as
glutathione, vitamin C, and vitamin E as well as
enzymes such as catalase, superoxide dismutase
and various peroxidases. Low levels of
antioxidants, or inhibition of the antioxidant

228
 enzymes, causes oxidative stress and may damage
or kill cells.

Arginine: Is an α-amino acid. The L-form is one of the 20

most common natural amino acids. Its codons are
CGU, CGC, CGA, CGG, AGA, and AGG. In
mammals, arginine is classified as a semi
essential or conditionally essential amino acid,
depending on the developmental stage and health
status of the individual. Infants are unable to meet
their requirements and thus arginine is
nutritionally essential for infants.

Arteriosclerosis: Refers to a stiffening of arteries. It is a general

term describing any hardening (and loss of
elasticity) of medium or large arteries (from the
Greek Arterio, meaning artery, and sclerosis,
meaning hardening).

Arthritis: (from Greek arthro-, joint + -itis, inflammation;

plural: arthritides) is a group of conditions
involving damage to the joints of the body. There
are over 100 different forms of arthritis. The most
common form, osteoarthritis (degenerative joint
disease) is a result of trauma to the joint, infection
of the joint, or age. Other arthritis forms are
rheumatoid arthritis and psoriatic arthritis,
autoimmune diseases in which the body attacks
itself. Septic arthritis is caused by joint infection.
Gouty arthritis is caused by deposition of uric
acid crystals in the joint, causing inflammation.
There is also an uncommon form of gout caused
by the formation of rhomboid crystals of calcium
pyrophosphate. This gout is known as
pseudogout.

Ayurveda: Is a system of traditional medicine native to India,

and practiced in other parts of the world as a form
of alternative medicine.

Beta 1,3,D Glucan: Are polysaccharides of D-glucose monomers

linked by glycosidic bonds. They occur most
commonly as cellulose in plants, the bran of
cereal grains, the cell wall of baker’s yeast certain

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 fungi, mushrooms and bacteria. Some forms of
beta glucans are useful in human nutrition as
texturing agents and as soluble fibre supplements.
One of the most common sources of beta(1,3)D
glucan for supplement use is derived from the cell
wall of baker’s yeast (Saccharomyces cerevisiae).
Beta-glucans are known as “biological response
modifiers” because of their ability to activate the
immune system.

Beta-amyloid: Is a peptide of 39–43 amino acids that appear to

be the main constituent of amyloid plaques in the
brains of Alzheimer’s disease patients.

Beta-carotene: Is an organic compound – a terpenoid, a red-

orange pigment abundant in plants and fruits.

Bilberry: Is a name given to several species of low-growing

shrubs in the genus Vaccinium (family
Ericaceae) that bears fruits. Laboratory studies
have provided preliminary evidence that bilberry
consumption may inhibit or reverse eye disorders.

Bioflavonoids: (Or flavonoids) are a class of plant secondary

metabolites. According to the IUPAC
nomenclature. Flavonoids are most commonly
known for their antioxidant activity. Flavonoids
are also commonly referred to as bioflavonoids in
the media – the terms are largely equivalent and
interchangeable, for most flavonoids are
biological in origin. Flavonoids are “the most
common group of polyphenolic compounds in the
human diet and are found ubiquitously in plants”.

Biotin: Also known as vitamin H or B7, is a water-

soluble B-complex vitamin. It is a cofactor in the
metabolism of fatty acids and leucine, and it
plays a role in gluconeogenesis. It is necessary for
cell growth, the production of fatty acids, and the
metabolism of fats and amino acids. It plays a
role in the citric acid cycle, which is the process
by which biochemical energy is generated during
aerobic respiration. Biotin not only assists in
various metabolic reactions, but also helps to

230
 transfer carbon dioxide. Biotin is also helpful in
maintaining a steady blood sugar level. Biotin is
often recommended for strengthening hair and
nails. Consequently, it is found in many cosmetic
and health products for the hair and skin.

Boron: Is an essential plant nutrient, required primarily

for maintaining the integrity of cell walls.

Boswellia: Is a genus of trees known for their fragrant resin

which has many pharmacological uses
particularly as anti-inflammatories. The Biblical
incense frankincense was probably an extract
from the resin of the tree, Boswellia sacra.

Bromelain: Has a number of medical uses. It was first

introduced in this area in 1957, and works by
blocking some pro-inflammatory metabolite that
accelerate and worsen the inflammatory process.
Studies have shown that bromelain can also be
useful in the reduction of platelet clumping and
blood clots in the bloodstream, especially in the
arteries.

Burdock: Some studies indicate that Burdock root oil

extract is rich in phytosterols and essential fatty
acids (including rare long-chain EFAs), the
nutrients required to maintain a healthy scalp and
promote natural hair growth. It combines an
immediate relieving effect with nutritional
support of normal functions of sebaceous glands
and hair follicles. Burdock has been used for
centuries as a blood purifier clearing the
bloodstream of some toxins, and as a diuretic
(helping rid the body of excess water by
increasing urine output), and as a topical remedy
for skin problems.

Candida albicans: C. albicans is commensal and is among the gut

flora, the many organisms which live in the
human mouth and gastrointestinal tract. Under
normal circumstances, C. albicans lives in 80% of
the human population with no harmful effects,
although overgrowth results in candidiasis.

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Carnitine: It is required for the transport of fatty acids from
the cytosol into the mitochondria during the
breakdown of lipids (or fats) for the generation of
metabolic energy.

Carotenes: Is an orange photosynthetic pigment important for

photosynthesis. Carotenes are responsible for the
orange colour of the carrot for which it is named,
and many other fruits and vegetables. Carotene
can be stored in the liver and body fat and
converted to retinal as needed, thus making it a
form of vitamin A for humans and some other
mammals.

Cascara: Sagrada-The dried, aged bark of this tree has been

used continually for at least 1,000 years by both
native and immigrant Americans as a laxative
natural medicine, commercially called “Cascara
Sagrada”.

Casein: An attractive property of the casein micelle is its

ability to form a gel or clot in the stomach. The
ability to form this clot makes it very efficient in
nutrient supply. The clot is able to provide a
sustained slow release of amino acids into the
blood stream, sometimes lasting for several hours.
This provides better nitrogen retention and
utilization by the body.

Cayenne: Is a hot, red chilli pepper used to flavour dishes

and for medicinal purposes. Cayenne (Capsicum
frutescens or Capsicum annuum) is a flavon and
as such is a vasodilator, causing blood vessels to
dilate. Cayenne pepper is used commonly as a
thermogenic and to improve blood circulation and
general circulatory health.

Circadian rhythm: Is a roughly-24-hour cycle in the biochemical,

physiological or behavioural processes of living
entities, including plants, animals, fungi and
cyanobacteria. Circadian rhythmicity is present in
the sleeping and feeding patterns of animals,
including human beings. There are also clear
patterns of core body temperature, brain wave

232
 activity, hormone production, cell regeneration
and other biological activities. In addition,
photoperiodism, the physiological reaction of
organisms to the length of day or night, is vital to
both plants and animals, and the circadian system
plays a role in the measurement and interpretation
of day length.

Coenzyme A: Is a coenzyme, notable for its role in the synthesis

and oxidation of fatty acids, and the oxidation of
pyruvate in the citric acid cycle. It assists in
transferring fatty acids from the cytoplasm to
mitochondria.

Coenzyme Q10: (also known as ubiquinone, ubidecarenone,

coenzyme Q, and abbreviated at times to
CoQ10).This oil-soluble vitamin-like substance is
present in most eukaryotic cells, primarily in the
mitochondria. It is a component of the electron
transport chain and participates in aerobic cellular
respiration, generating energy in the form of ATP.
Ninety-five percent of the human body’s energy is
generated this way. Therefore, those organs with
the highest energy requirements—such as the
heart and the liver—have the highest CoQ10
concentrations. Because of its ability to transfer
electrons and therefore act as an antioxidant,
Coenzyme Q10 is used as a dietary supplement.

Collagen: Is the main protein of connective tissue in animals

and the most abundant protein in mammals,
making up about 25% to 35% of the whole-body
protein content.

Colostrum: (also known as beestings or first milk or

“immune milk”) is a form of milk produced by
the mammary glands of mammals in late
pregnancy. Most species will generate colostrum
within one day of giving birth. Colostrum is
known to contain antibodies called
immunoglobulins such as IgA, IgG and IgM in
mammals. IgA is absorbed through the intestinal
epithelium, travels through the blood, and is

233
 secreted onto other Type 1 mucosal surfaces.
Colostrum also contains a variety of growth
factors (IGfs)

Copper: Is essential in all plants and animals. The human

body normally contains copper at a level of about
1.4 to 2.1 mg for each kg of body weight. Copper
is distributed widely in the body and occurs in
liver, muscle and bone. Copper is transported in
the bloodstream on a plasma protein called
ceruloplasmin. When copper is first absorbed in
the gut it is transported to the liver bound to
albumin. Copper metabolism and excretion is
controlled delivery of copper to the liver by
ceruloplasmin, where it is excreted in bile. Copper
is found in a variety of enzymes, including the
copper centres of cytochrome c oxidase and the
enzyme superoxide dismutase (containing copper
and zinc). In addition to its enzymatic roles,
copper is used for biological electron transport.

Cranberry: Are a group of evergreen dwarf shrubs or trailing

vines in the genus Vaccinium subgenus
Oxycoccos, or in some treatments, in the distinct
genus Oxycoccos. They are found in acidic bogs
throughout the cooler parts of the Northern
Hemisphere. Cranberries have moderate levels of
vitamin C, dietary fibre and the essential dietary
mineral, manganese, as well as a balanced profile
of other essential micronutrients. By measure of
the Oxygen Radical Absorbance Capacity with an
ORAC score of 9,584 units per 100 g, cranberry
ranks near the top of 277 commonly consumed
foods in the United States.

Cysteine: Cystine-Is a non-essential amino acid, which

means that humans can synthesize it. Its codons
are UGU and UGC. With a thiol side chain,
cysteine is classified as a hydrophobic amino
acid. Because of the high reactivity of this thiol,
cysteine is an important structural and functional
component of many proteins and enzymes.
Cysteine is named after cystine, its oxidized

234
 dimer. Due to the ability of thiols to undergo
redox reactions, cysteine has antioxidant
properties. Cysteine’s antioxidant properties are
typically expressed in the tripeptide glutathione,
which occurs in humans as well as other
organisms. The systemic availability of oral
glutathione (GSH) is negligible; so it must be
biosynthesized from its constituent amino acids,
cysteine, glycine, and glutamic acid.

Damiana: (Turnera diffusa, syn. Turnera aphrodisiaca) is a

shrub native to Central America, Mexico, South
America, and the Caribbean. It belongs to the
family Turneraceae. In herbal medicine, damiana
is used to treat conditions dealing with
reproductive organs in both males and females.

DHA-Docosahexaenoic acid (DHA): Is an omega-3 fatty acid. Fish oils

are rich in DHA. Most of the DHA
in fish and more complex
organisms originates in
photosynthetic and heterotrophic
microalgae, and becomes
increasingly concentrated in
organisms as it moves up the food
chain. DHA is also commercially
manufactured from microalgae.
DHA manufactured using
microalgae is vegetarian.

Essential amino acids: An essential amino acid or indispensable

amino acid is an amino acid that cannot be
synthesized de novo by the organism
(usually referring to humans), and
therefore must be supplied in the diet.
Eight amino acids are generally regarded
as essential for humans: phenylalanine,
valine, threonine, tryptophan, isoleucine,
methionine, leucine, and lysine.
Additionally, cysteine (or sulphur-
containing amino acids), tyrosine (or
aromatic amino acids), histidine and
arginine are required by infants and

235
 growing children. Essential amino acids
are so called not because they are more
important to life than the others, but
because the body does not synthesize
them, making it essential to include them
in one’s diet in order to obtain them. In
addition, the amino acids arginine,
cysteine, glycine, glutamine, histidine,
proline, serine and tyrosine are considered
conditionally essential, meaning they are
not normally required in the diet, but must
be supplied exogenously to specific
populations that do not synthesize it in
adequate amounts.

Essential fatty acids: Or EFA’s, are fatty acids that cannot be

constructed within an organism (generally
all references are to humans) from other
components by any known chemical
pathways, and therefore must be obtained
from the diet. The term refers to fatty
acids involved in biological processes, and
not those which may just play a role as
fuel. As many of the compounds created
from essential fatty acids can be taken
directly in the diet, it is possible that the
amounts required in the diet (if any) are
overestimated. It is also possible they can
be underestimated as organisms can still
survive in non-ideal, malnourished
conditions. There are two families of
EFA’s: ω-3 (or omega-3 or n−3) and ω-6
(omega-6, n−6). Fats from each of these
families are essential, as the body can
convert one omega-3 to another omega-3,
for example, but cannot create an omega-
3 from omega-6 or saturated fats. Essential
fatty acids play a part in many metabolic
processes, and there is evidence to suggest
that low levels of essential fatty acids, or
the wrong balance of types among the

236
 essential fatty acids, may be a factor in a
number of illnesses.

Ester C-Ester-C: Calcium Ascorbate is a unique and

patented form of vitamin C. It is made
using a proprietary, water-based
manufacturing process which results in a
pH neutral product that contains naturally
occurring vitamin C metabolites. These
metabolites activate the vitamin C
molecules making it easier for the body to
transport them from cell to cell.

Fibre: Is a class of materials that are continuous

filaments or are in discrete elongated
pieces, similar to lengths of thread. They
are very important in the biology of both
plants and animals, for holding tissues
together. Dietary fibre sometimes called
roughage, is the indigestible portion of
plant foods that pushes food through the
digestive system, absorbing water and
easing defecation. Chemically, dietary
fibre consists of non-starch
polysaccharides such as cellulose and
many other plant components such as
dextrins, inulin, lignin, waxes, chitins,
pectins, beta-glucans and
oligosaccharides. The term “fibre” is
somewhat of a misnomer, since many
types of so-called dietary fibre are not
fibres at all. Dietary fibre can be soluble
(able to dissolve in water) or insoluble
(not able to dissolve in water). Soluble
fibre, like all fibre, cannot be digested. But
it does change as it passes through the
digestive tract, being transformed
(fermented) by bacteria there. Soluble
fibre also absorbs water to become a
gelatinous substance that passes through
the body. Insoluble fibre, however, passes
through the body largely unchanged. Food
sources of dietary fibre are often divided

237
 according to whether they provide
(predominantly) soluble or insoluble fibre.
To be precise, both types of fibre are
present in all plant foods, with varying
degrees of each according to a plant’s
characteristics.

Fish oil: Is oil derived from the tissues of oily fish.

It is recommended for a healthy diet
because it contains the omega-3 fatty
acids, eicosapentaenoic acid (EPA), and
docosahexaenoic acid (DHA), precursors
to eicosanoids that reduce inflammation
throughout the body. Fish do not actually
produce omega-3 fatty acids, but instead
accumulate them from either consuming
microalgae that produce these fatty acids,
as is the case with fish like herring and
sardines, or, as is the case with fatty
predatory fish, by eating prey fish that
have accumulated omega-3 fatty
acidsfrom microalgae.

Flavonoids: (both flavonols and flavanols) are most

commonly known for their antioxidant
activity. Flavonoids (specifically
flavonoids such as the catechins) are “the
most common group of polyphenolic
compounds in the human diet and are
found ubiquitously in plants”. Flavonols,
the original bioflavonoids such as
quercetin, are also found ubiquitously, but
in lesser quantities. Both sets of
compounds have evidence of health-
modulating effects in animals which eat
them.

Folic acid: (also known as vitamin B9 or folacin) and

folate (the naturally occurring form), as
well as pteroyl-L-glutamic acid and
pteroyl-L-glutamate, are forms of the
water-soluble vitamin B9. It is especially
important during periods of rapid cell

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 division and growth. Both children and
adults require folic acid to produce healthy
red blood cells and prevent anemia.

Free radicals: (often referred to as free radicals) are

atoms, molecules, or ions with unpaired
electrons on an otherwise open shell
configuration. These unpaired electrons
are usually highly reactive, so radicals are
likely to take part in chemical reactions.
Radicals play an important role in
combustion, atmospheric chemistry,
polymerization, plasma chemistry,
biochemistry, and many other chemical
processes, including human physiology.
For example, superoxide and nitric oxide
regulate many biological processes, such
as controlling vascular tone. “Radical” and
“free radical” are frequently used
interchangeably. Free radicals play an
important role in a number of biological
processes, some of which are necessary
for life, such as the intracellular killing of
bacteria by neutrophil granulocytes. Free
radicals have also been implicated in
certain cell signalling processes. The two
most important oxygen-centered free
radicals are superoxide and hydroxyl
radical. They are derived from molecular
oxygen under reducing conditions.
However, because of their reactivity, these
same free radicals can participate in
unwanted side reactions resulting in cell
damage

Ginko biloba: May have three effects on the human

body: improvement in blood flow
(including microcirculation in small
capillaries) to most tissues and organs;
protection against oxidative cell damage
from free radicals; and blockage of many
of the effects of platelet-activating factor
(platelet aggregation, blood clotting) that

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 have been related to the development of a
number of cardiovascular, renal,
respiratory and central nervous system
disorders. Ginkgo can be used for
intermittent claudication.

Glutamine: Is the most abundant naturally occurring,

non-essential amino acid in the human
body and one of the few amino acids
which directly crosses the blood-brain
barrier. In the body it is found circulating
in the blood as well as stored in the
skeletal muscles. It becomes conditionally
essential (requiring intake from food or
supplements) in states of illness or injury.
Dietary sources of L-glutamine include
beef, chicken, fish, eggs, milk, dairy
products, wheat, cabbage, beets, beans,
spinach, and parsley. Small amounts of
free L-glutamine are also found in
vegetable juices and fermented foods,
such as miso.

Glutathione: Is an antioxidant and helps protect cells

from reactive oxygen species such as free
radicals and peroxides. Glutathione is
found almost exclusively in its reduced
form, since the enzyme that reverts it from
its oxidized form, glutathione reductase, is
constitutively active and inducible upon
oxidative stress. In fact, the ratio of
reduced glutathione to oxidized
glutathione within cells is often used
scientifically as a measure of cellular
toxicity.

Guar gum: Is a water-soluble fibre that acts as a bulk

forming laxative, and as such, it is claimed
to be effective in promoting regular bowel
movements and relieve constipation and
chronic related functional bowel ailments.
The increased mass in the intestines
stimulates the movement of waste and

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 toxins from the system, which is
particularly helpful for good colon health,
because it speeds the removal of waste and
bacteria from the bowel and colon. In
addition, because it is soluble, it is also
able to absorb toxic substances (bacteria)
that cause infective diarrhoea.

HDL’s (High density lipoproteins): Is one of the five major groups of

lipoproteins (chylomicrons, VLDL, IDL,
LDL, HDL) which enable lipids like
cholesterol and triglycerides to be
transported within the water based blood
stream. In healthy individuals, about thirty
percent of blood cholesterol is carried by
HDL. It is hypothesized that HDL can
remove cholesterol from atheroma within
arteries and transport it back to the liver
for excretion or re-utilization—which is
the main reason why HDL-bound
cholesterol is sometimes called “good
cholesterol”, or HDL-C.

Iron: Is essential to nearly all known

organisms. In cells, iron is generally
stored in the centre of metalloproteins,
because “free” iron (which binds non-
specifically to many cellular components)
can catalyse production of toxic free
radicals. Iron deficiency can lead to iron
deficiency anemia. Good sources of
dietary iron include red meat, fish poultry,
lentils, beans, leaf vegetables, tofu,
chickpeas, black-eyed peas, fortified
bread, and fortified breakfast cereals. Iron
in low amounts is found in molasses, teff
and farina. Iron in meat (haem iron) is
more easily absorbed than iron in
vegetables.

Kava: Is an ancient crop of the western Pacific.

The word kava is used to refer both to the
plant and the beverage produced from its

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 roots. Kava is sedating and is primarily
consumed to relax without disrupting
mental clarity

LDL’s (low-density lipoproteins): Is a type of lipoprotein that transports

cholesterol and triglycerides from the
liver to peripheral tissues. LDL is one of
the five major groups of lipoproteins;
these groups include chylomicrons, very
low-density lipoprotein (VLDL),
intermediate-density lipoprotein (IDL),
low-density lipoprotein, and high-density
lipoprotein (HDL). Like all lipoproteins,
LDL enables fats and cholesterol to move
within the water-based solution of the
blood stream. LDL also regulates
cholesterol synthesis at these sites. It is
used medically as part of a cholesterol
blood test, and since high levels of LDL
cholesterol can signal medical problems, it
is sometimes called “bad cholesterol,” (as
opposed to HDL, which is frequently
referred to as “good cholesterol” or
“healthy cholesterol”).

Leucine: Is an essential amino acid, which means

that humans cannot synthesise it. As a
dietary supplement, leucine has been
found to slow the degradation of muscle
tissue by increasing the synthesis of
muscle proteins. Leucine is utilized in the
liver, adipose tissue, and muscle tissue. In
adipose and muscle tissue, leucine is used
in the formation of sterols, and the
combined usage of leucine in these two
tissues is seven times greater than its use
in the liver.

Lutein: Is one of over 600 known naturally

occurring carotenoids. Found in green
leafy vegetables such as spinach and kale,
lutein is employed by organisms as an
antioxidant and for blue light absorption.

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 Lutein was found to be concentrated in the
macula, a small area of the retina
responsible for central vision. The
hypothesis for the natural concentration is
that lutein helps protect from oxidative
stress and high-energy light. Various
research studies have shown that a direct
relationship exists between lutein intake
and pigmentation in the eye.

Lysine: This amino acid is an essential amino

acid, which means that humans cannot
synthesize it. As an essential amino acid,
lysine is not synthesized in animals, hence
it must be ingested as lysine or lysine-
containing proteins. L-Lysine is necessary
building block for all protein in the body.
L-Lysine plays a major role in calcium
absorption; building muscle protein;
recovering from surgery or sports
injuries; and the body’s production of
hormones, enzymes, and antibodies.

Maca: is rich in essential minerals, especially

selenium, calcium, magnesium, and iron,
and includes fatty acids including linolenic
acid, palmitic acid, and oleic acids, and 19
amino acids, as well as polysaccharides.
Maca’s reported beneficial effects for
sexual function could be due to its high
concentration of proteins and vital
nutrients, though maca contains a
chemical called p-methoxybenzyl
isothiocyanate, which reputedly has
aphrodisiac properties.

Maitake-Grifola frondosa: is a polypore mushroom that grows in

clusters at the base of trees, particularly
oaks. The mushroom is commonly known
among English speakers as Sheep’s Head,
Ram’s Head and Hen of the Woods. In the
United States’ supplement market, as well
as in Asian grocery stores, the mushroom

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 is known by its Japanese name “Maitake,”
which means “dancing mushroom.” The
underground tubers from which hen of the
woods arises have been used in traditional
Chinese and Japanese medicine to
enhance the immune system. Researchers
have also indicated that whole maitake has
the ability to regulate blood pressure,
glucose, insulin, and both serum and liver
lipids, such as cholesterol, triglycerides,
and phospholipids, and may also be useful
for weight loss. Maitake is rich in minerals
(such as potassium, calcium, and
magnesium), various vitamins (B2, D2 and
Niacin), fibres and amino acids. The
active constituent in maitake for
enhancing the immune activity has been
identified in the late 1980s to be the
protein-bound polysaccharide compound,
beta-glucan, an ingredient found
especially in the family of polyporaceae.

Manganese: Is an essential trace nutrient in all forms of

life. The human body contains about 10
mg of manganese, which is stored mainly
in the liver and kidneys. In the human
brain the manganese is bound to
manganese metalloproteins most notable
glutamine synthetase in astrocytes.

Melatonin: Is a naturally occurring hormone found in

animals and in some other living
organisms, including algae. Circulating
levels vary in a daily cycle, and melatonin
is important in the regulation of the
circadian rhythms of several biological
functions. Many biological effects of
melatonin are produced through activation
of melatonin receptors, while others are
due to its role as a pervasive and powerful
antioxidant with a particular role in the
protection of nuclear and mitochondrial
DNA. Melatonin is produced by

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 pinealocytes in the pineal gland (located in
the brain, but outside of the blood-brain
barrier) and also by the retina, lens, GI
tract and other tissues. The largest organ
in humans to biosynthesize melatonin is
the skin. All machinery for melatonin
synthesis has been identified in skin cells
and both melatonin and its by-product,
AFMK, have been found. Both of these
molecules are naturally synthesized from
the amino acid tryptophan (via synthesis
of serotonin). Serotonin is converted to
melatonin by the enzymes N-
acetyltransferase and 5-hydroxyindole-O-
methyltransferase. Besides its function as
synchronizer of the biological clock,
melatonin also exerts a powerful
antioxidant activity.

Methylcobalamin: Is a cobalamin used in peripheral

neuropathy, diabetic neuropathy etc. It is
a form of vitamin B12. This vitamin is one
of two active coenzymes used by B12
dependent enzymes in the body.
Methylcobalamin is notable for being one
of the few examples in nature of a bona
fide organometallic bond. One study
suggests that once absorbed,
methylcobalamin may be retained in the
body better than cyanocobalamin.

Milkthistle: Seeds of milk thistle that herbalists have

used for 2000 years to treat chronic liver
disease and protect the liver against toxins.
S. marianum is by far the more widely
known species. Milk thistle is believed to
give some remedy for liver and the
extract, silymarin, is used in medicine.
Research suggests that milk thistle extracts
both prevent and repair damage to the
liver from toxic chemicals and
medications.

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Molybdenum:
MSM (Methylsulfonylmethane):
NAC (N-acetylcysteine):
Niacin:
Olive leaf extract:
Human body contains about 0.07 mg of
molybdenum per kilogram of weight. It
occurs in higher concentrations in the liver
and kidneys and in lower concentrations in
the vertebrae. Molybdenum is also present
within human tooth enamel and may help
preventing its decay. Pork, lamb and beef
liver each have approximately 1.5 parts
per million of molybdenum. Other
significant dietary sources include green
beans, eggs, sunflower seeds, wheat flour,
lentils and cereal grain.
Is an organosulphur compound. It is also
known by several other names: DMSO2,
MSM, methylsulfonylmethane and methyl
sulfone. Some researchers have suggested
that MSM has anti-inflammatory effects.
Is the N-acetyl derivative of the amino
acid L-cysteine, and is a precursor in the
formation of the antioxidant glutathione in
the body. The thiol (sulfhydryl) group
confers antioxidant effects and is able to
reduce free radicals.
Also known as vitamin B3 or nicotinic
acid, is a water-soluble vitamin. The terms
niacin, nicotinamide, and vitamin B3 are
often used interchangeably to refer to any
one of this family of molecules, since they
have a common biochemical activity.
Niacin is involved in both DNA repair,
and the production of steroid hormones in
the adrenal gland.
While olive oil is well known for its
flavour and health benefits, the leaf has
been used medicinally in various times
and places. Natural olive leaf and olive
leaf extracts (OLE), are now marketed as
anti-aging, immunostimulators, and even
antibiotics. The primary medical
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 constituents contained in unprocessed
olive leaf is believed to be the antioxidant
oleuropein and hydroxytyrosol, as well as
several other polyphenols and flavonoid
including Oleocanthal.

OPC (Oligomeric proanthocyanidins): Also known as procyanidin,

oligomeric proanthocyanidin (OPC),
leukocyanidin, leucoanthocyanin and
condensed tannins, is a class of flavanols.
Proanthocyanidins are essentially polymer
chains of flavonoid such as catechins.
One was discovered in 1936 by Professor
Jacques Masquelier and called Vitamin P,
although this name did not gain official
category status and has since fallen out of
usage. It was Masquelier who first
developed techniques for the extraction of
proanthocyanidins from certain plant
species. This information attracted the
attention of public news media, describing
that red wine consumption was associated
with favourable intake of health-
promoting flavonoids which correlate with
oxygen radical absorbance capacity
(ORAC). Proanthocyanidins suppress
production of a protein endothelin-1 that
constricts blood vessels. These studies
provide data supporting the French
Paradox which hypothesizes that intake of
proanthocyanidins and other flavonoids
from regular consumption of red wines
prevents occurrence of a higher disease
rate (cardiovascular diseases, diabetes) in
French citizens on high-fat diets.
Proanthocyanidins have antioxidant
activity and they play a role in the
stabilization of collagen and maintenance
of elastin — two critical proteins in
connective tissue that support organs,
joints, blood vessels, and muscle.
Common antioxidants currently used are

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 vitamin C and vitamin E; however,
studies show that proanthocyanidins
antioxidant capabilities are 20 times more
powerful than vitamin C and 50 times
more potent than vitamin E.
Proanthocyanidins found in pine bark and
grape seed extract work directly to help
strengthen all the blood vessels and
improve the delivery of oxygen to the
cells. Proanthocyanidins also have an
affinity for cell membranes, providing
nutritional support to reduce capillary
permeability and fragility. Although
flavonoids are widespread in nature, the
powerful proanthocyanidin compound is
most abundant and available from the bark
of the maritime pine and in grape seeds, or
pips.

Papain: Is proteolytic, which means that it digests

proteins. Papain hydrolyzes proteins to
form oligopeptides and amino acids.
Papain has milk-clotting (rennet) and
protein digesting properties and is active
over a wide pH range, papain is useful in
medicine, combatting dyspepsia and other
digestive orders.

Phytochemicals: Are chemical compounds that occur

naturally in plants. The term is generally
used to refer to those chemicals that may
affect health. Phytochemicals in freshly
harvested plant foods may be destroyed or
removed by modern processing
techniques, possibly including cooking.
For this reason, industrially processed
foods likely contain fewer phytochemicals
and may thus be less beneficial than
unprocessed foods. Absence or deficiency
of phytochemicals in processed foods may
contribute to increased risk of preventable
diseases.

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Phytosterols: Are a group of steroid alcohols,
phytochemicals naturally occurring in
plants. Plants contain a range of
phytosterols. They act as a structural
component in the cell membrane, a role
which in mammalian cells is played by
cholesterol. The FDA has approved the
following claim for phytosterols: “Foods
containing at least 0.4 gram per serving of
plant sterols, eaten twice a day with meals
for a daily total intake of at least 0.8 gram,
as part of a diet low in saturated fat and
cholesterol, may reduce the risk of heart
disease.” To date, more than 20 clinical
studies on the effects of phytosterols on
cholesterol have been conducted. One
study published in Food Technology
indicated that consuming two grams of
phytosterols daily could slash the risk of
heart disease by 25% (Hicks 2001).
Another study published in the American
Journal of Clinical Nutrition revealed that
phytosterols interfered with cholesterol
absorption by 33% to 42%

Proanthocyanidin-(PA or PAC): also known as procyanidin, oligomeric

proanthocyanidin (OPC), leukocyanidin,
leucoanthocyanin and condensed tannins,
is a class of flavanols. Proanthocyanidins
are essentially polymer chains of
flavonoids such as catechins. One was
discovered in 1936 by Professor Jacques
Masquelier and called Vitamin P, although
this name did not gain official category
status and has since fallen out of usage. It
was Masquelier who first developed
techniques for the extraction of
proanthocyanidins from certain plant
species. In the human body, they might act
as antioxidants (free radical
scavengers).OPCs may help protect
against the effects of internal and

249
 environmental stresses such as cigarette
smoking and pollution, as well as
supporting normal body metabolic
processes. The effects may include
depressing blood fat, emolliating blood
vessels, lowering blood pressure,
preventing blood vessel scleroses,
dropping blood viscidity and preventing
thrombus formation. OPCs are available
from fresh grapes, grape juice, and red
wine. Although in milligrams per ounce
red wine may contain more OPCs than red
grape juice, red grape juice contains more
OPCs per average serving size. An 8
ounce serving of grape juice averages 124
milligrams OPCs, while a 5 ounce serving
of red wine averages 91 milligrams. Many
other foods and beverages also contain
high amounts of OPCs, but very few come
close to the levels found in red grape seeds
and skins (which readily disperse into
grape juice when crushed

Probiotics: Are dietary supplements of live

microorganisms thought to be healthy for
the host organism. According to the
currently adopted definition by
FAO/WHO, probiotics are: “Live
microorganisms which when administered
in adequate amounts confer a health
benefit on the host”. Lactic acid bacteria
(LAB) and bifidobacteria are the most
common types of microbes used as
probiotics; but also certain yeasts and
bacilli are available.

Proline: Is an α-amino acid, one of the twenty

DNA-encoded amino acids. It is not an
essential amino acid, which means that
humans can synthesize it. It is unique
among the 20 protein-forming amino acids
because the α-amino group is secondary.

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Pygeum: Is a herbal remedy containing extracts
from the bark of Prunus africana. It is used
to alleviate some of the discomfort caused
by inflammation in patients suffering from
benign prostatic hyperplasia(enlarged
prostate).

Quercetin: Is a plant-derived flavonoid, specifically a

flavonol, used as a nutritional
supplement. Laboratory studies show it
may have anti-inflammatory and
antioxidant properties. From in vitro
studies, quercetin has demonstrated
significant anti-inflammatory activity by
inhibiting both manufacture and release of
histamine and other allergic/inflammatory
mediators. In addition, it exerts potent
antioxidant activity and vitamin C-sparing
action.

Red yeast rice: Used in traditional Chinese herbology and

traditional Chinese medicine. Its use has
been documented as far back as the Tang
Dynasty in China in 800 A.D. and taken
internally to invigorate the body, aid in
digestion, and remove “blood blockages”
(which could refer to what modern-day
science has documented as a cholesterol-
lowering effect).

SAMe-S-Adenosyl methionine (SAM, SAMe, SAM-e): is a common co-

substrate involved in
methyl group transfers. In
the United States, SAM is
sold as a nutritional
supplement under the
marketing name SAM-e
(also spelled SAME or
SAMe; pronounced “sam
ee”). Some research has
indicated that taking SAM
on a regular basis may help
fight depression, liver

251
 disease, and the pain of
osteoarthritis. Multiple
clinical trials indicate
benefits for depression,
some liver conditions and
osteoarthritis.

Saw palmetto: The fruits of the saw palmetto are highly

enriched with fatty acids and phytosterols,
and extracts of the fruits have been the
subject of intensive research for the
treatment of urinary tract infections. This
extract is also commonly used for other
medical conditions. Early studies of S.
repens in the treatment of benign
prostatic hyperplasia were encouraging,
suggesting good tolerability and “mild to
moderate improvement in urinary
symptoms and flow measures”.

Serotonin: Is found extensively in the gastrointestinal

tract of animals, and about 80 to 90
percent of the human body’s total
serotonin is located in the
enterochromaffin cells in the gut, where
it is used to regulate intestinal movements.
The remainder is synthesized in
serotonergic neurons in the central
nervous system (CNS) where it has
various functions, including the regulation
of mood, appetite, sleep, muscle
contraction, and some cognitive functions
including memory and learning.

Silymarin: Also known as silybin, is the major active

constituent of silymarin, the mixture of
flavonolignans extracted from blessed
milk thistle (Silybum marianum).
Silymarin is popular in alternative
medicine in which it is purportedly useful
for the treatment of varicose veins,
menstrual problems, depression, low
breast milk production, liver disorders and

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 gall bladder problems. A recent study
suggested that silymarin may help patients
with type II diabetes by assisting in blood
sugar control.

SOD (Superoxide dismutase): Are a class of enzymes that catalyse the

dismutation of superoxide into oxygen
and hydrogen peroxide. As such, they are
an important antioxidant defence in
nearly all cells exposed to oxygen.
Superoxide is one of the main reactive
oxygen species in the cell and as such,
SOD serves a key antioxidant role.

Spirulina: Is the common name for human and

animal food supplements produced
primarily from two species of
cyanobacteria: Arthrospira platensis, and
Arthrospira maxima. Spirulina is
cultivated around the world, and is used
as a human dietary supplement as well as
a whole food and is available in tablet,
flake, and powder form. It is also used as a
feed supplement in the aquaculture,
aquarium, and poultry industries. Spirulina
contains an unusually high amount of
protein, between 55% and 77% by dry
weight, depending upon the source. It is a
complete protein, containing all essential
amino acids, though with reduced amounts
of methionine, cysteine, and lysine when
compared to the proteins of meat, eggs,
and milk. It is, however, superior to
typical plant protein, such as that from
legumes. Spirulina contains vitamin B1
(thiamine), B2 (riboflavin), B3
(nicotinamide), B6 (pyridoxine), B9 (folic
acid), vitamin C, vitamin D, and vitamin
E. Spirulina is a rich source of potassium,
and also contains calcium chromium,
copper, iron, magnesium, manganese,
phosphorus, selenium, sodium, and zinc.

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Taurine: Is an organic acid. It is also a major
constituent of bile and can be found in the
lower intestine and in small amounts in the
tissues.

Trans-fatty acids: Is the common name for unsaturated fat

with trans-isomer fatty acid(s). Trans fats
may be monounsaturated or
polyunsaturated but never saturated.
Unlike other dietary fats, trans fats are not
essential, and they do not promote good
health. The consumption of trans fats
increases one’s risk of coronary heart
disease by raising levels of “bad” LDL
cholesterol and lowering levels of “good”
HDL cholesterol. Health authorities
worldwide recommend that consumption
of trans fat be reduced to trace amounts.
Trans fats from partially hydrogenated oils
are more harmful than naturally occurring
oils.

Whey protein: is a mixture of globular proteins isolated

from whey, the liquid material created as
a by-product of cheese production. Some
preclinical studies in rodents have
suggested that whey protein may influence
glutathione production and possess anti-
inflammatory or properties.

Wild yam: Is a species of a twining tuberous vine that

is native to and found growing wild in
North America. Its fame is based on its
steroid-like saponins which can be
chemically converted to progesterone
contraceptives; and cortisone. Wild Yam
is believed to be helpful to the liver and
endocrine system. It regulates the female
system, particularly during menstrual
distress and menopause, as well as used in
treating infertility.

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 Chapter 10
Current Status of the Global Nutraceuticals and Vitamins
Industry – 2011 Review

10.0. Status – 2011

A combination of the words “nutrition” and “pharmaceutical,” the term

nutraceutical encompasses foods or food products that claim to prevent chronic
diseases, improve health, delay the aging process, and/or increase life
expectancy. Products in this category range from isolated nutrients, dietary
supplements and specific diets to genetically engineered foods, herbal products,
and processed foods such as cereals and beverages. This is an industry wrought
with controversy, beginning with the mere definition of the term nutraceutical
to the U.S. Food and Drug Administration’s minimal regulation over which
products display the nutraceutical designation on their labels. As a result, the
market is chock full of products with varying uses and effectiveness. Steady
growth during the upcoming years is expected to drive the global nutraceutical
market value to more than $180 billion in 2017. Factors that will contribute to
this growth include a globally aging population, increased prevalence of serious
diseases, and an enhanced concentration on preventative medicine. According
to World Health Organization (WHO) projections, by 2020 the number of
people 60 years old and older around the world will exceed 1 billion, with 700
million of them in developing countries. The industry will be widely influenced
in upcoming years by an aging population, particularly in developed countries;
access to healthy food in emerging countries; the evolving understanding of
food impact on health and the expectancy of more targeted foods and products
to address specific needs. Within the varied nutraceutical market, experts
predict strong performances from omega-3 fatty acids, probiotics, and soy. The
strict regulatory environment and consumer skepticism of alternative treatments
are challenges that the nutraceutical market must overcome. To maintain growth
in the nutraceutical segment, companies must concentrate on the scientific
evidence backing the efficacy claims of their products. Many experts believe
that in some instances, pharmaceuticals can be replaced by naturally derived
products to reduce side effects, eliminate unfavourable drug interactions, and
improve patient outcomes. Most chronic illnesses are linked to long-term
lifestyle and behavior choices. Experts are hopeful that the trend of personalized
health science nutrition will contribute to successfully preventing, improving
and treating acute and chronic medical conditions. Nathan S. Bryan, Ph.D.,
professor of molecular medicine at The University of Texas School of Medicine

255
in Houston and chief science officer of Neogenis Labs Inc., believes that the
industry is prepared to meet the needs of a rising demand for health foods and
products. As more companies enter the space, science will be the driver and
factor that distinguishes successful companies from the pretenders, he says.
Predicted to generate a compound annual growth rate of roughly 8% through
2015, the U.S. nutraceutical market is among the largest and fastest-growing
sectors in the world. Nutraceutical market growth in the United States has been
spurred mainly by consumers’ desire to improve their health. The high
prevalence of obesity and cardiovascular and chronic diseases in America has
created significant business opportunities for the leading companies. U.S.
healthcare expenditure in 2010 totalled $2.6 trillion and is expected to rise to
$3.4 trillion by 2015. Due to their preventive nature, nutraceuticals are being
targeted by public and private entities as a potential means to contain some of
these costs. According to Dr. Bryan, there is a significant difference between
developing and marketing pharmaceutical and nutraceutical products,
particularly when considering cost of development and time to market.
“Whereas pharmaceuticals take an average of 10 years and $800 million,
nutraceuticals are less expensive, have fewer regulatory hurdles to overcome
and can be just as efficacious,” he says. Consolidation activity is common in the
nutraceutical marketplace. The Swiss company Nestlé Health Science S.A.
acquired Prometheus Laboratories Inc. in May 2011. San Diego-based
Prometheus’ gastrointestinal diagnostic capabilities were one of the primary
reasons Nestle made the acquisition. Additional major acquisitions in the
nutraceutical market during the past year have included Pfizer Inc.’s acquisition
of Ferrosan Consumer Health from Altor 2003 Fund GP Ltd. in February 2011;
PepsiCo Inc.’s 66% acquisition of Wimm-Bill- Dann Foods OJSC during
February 2011; BASF SE’s acquisition of Cognis Holding Luxembourg S.à r.l.
in December 2010; and The Carlyle Group’s acquisition of NBTY Inc. during
October 2010. Another important trend in the nutraceutical market is major
licensing deals. Significant license transactions in 2010 included Danone and
Chiquita Brands International Inc. as well as Ajinomoto Co. and Kellogg Co.
There is often an overlap between the food and pharmaceutical industries. For
example, long-time pharma leader Abbott Laboratories developed a
nutraceutical and nutrition division as part of its business strategy. Similarly,
Nestlé SA’s Nestlé Health Science business unit started operations in January
2011 to pioneer personalized nutritional solutions to address chronic medical
conditions including gastrointestinal disorders, metabolic conditions, and
cognitive decline.
Vital Foods announced on July 14, 2011, that Nestlé Health Science has
become a strategic investor and taken a minority stake in the company. Nestlé
Health Science is interested in Vital Foods’ portfolio of dietary supplements for
digestive health, particularly constipation. The dietary supplements – Kiwi
Crush and Phloe – are widely used and recommended in New Zealand, and are
supported by clinical trials. Nestlé announced the creation of Nestlé Health
Science and the Nestlé Institute of Health Sciences on Sept. 27, 2010. These
two separate organizations enable Nestlé to develop the innovative area of
personalized health science nutrition to prevent and treat health conditions such

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as diabetes, obesity, cardiovascular disease and Alzheimer’s disease. These
health conditions place an unsustainable burden on the world’s healthcare
systems. Personalized medicine is an area of healthcare that is becoming more
widely used to focus on how an individual’s molecular makeup can affect one’s
ability to respond to medications. This allows physicians better precision in
selection or dosing of a drug, thereby improving drug safety and efficacy.
According to the Centers for Disease Control and Prevention (CDC), in the
United States chronic illness affects nearly half of all adults and contributes to
seven out of 10 deaths. Even more alarming, chronic illness costs Americans
more than $1.5 trillion annually in direct medical costs. Researchers and others
in the medical profession believe that re-focusing medical practice treatments
on the provision of lifestyle therapy will not only significantly improve the
health status of most Americans, but will reduce costs. Two-thirds of adults
with high cholesterol and half with high blood pressure are not being treated
effectively for these conditions, according to an announcement by the CDC.
These findings spotlight the crucial need for new solutions to reduce the risk
factors that are behind the current epidemic of chronic illness in the United
States. “Changing our lifestyles is the only way to overcome our nation’s
chronic disease epidemic,” says Jeff Bland, Ph.D., chief science officer of
Metagenics Inc. “Doctors must be provided with the tools and training to
practice lifestyle medicine, so that they can help their patients become healthier
and reduce the incidence of chronic illnesses such as heart disease and
diabetes.” According to Jeremy A. Holt, health services manager for Ajinomoto
USA Inc., “Very often, the use of nutraceuticals depends heavily on the nature
of the health care professional’s practice.
Medical practitioners are less likely to use nutraceuticals than those healthcare
providers that practice complementary and alternative medicine.” In the 10
years he has worked within the nutraceutical industry, Mr. Holt has developed a
specific focus on teaching physicians and other healthcare providers how to
implement nutraceuticals and other lifestyle therapies in clinical practice. Mr.
Holt believes that there has been a shift during the past decade that has led to an
increase in the use of nutraceuticals within the medical community, the majority
of which has been in conjunction with traditional drug therapy. “This has
allowed patients to get the best of both worlds while increasing the exposure of
nutraceuticals and other complementary therapies,” he says. Industry analysts
observe that physicians have become accustomed to prescribing drugs for
people with lifestylerelated conditions when the first-line recommended course
of treatment is lifestyle therapy. Currently, one-third of American adults suffer
(most, unknowingly) from metabolic syndrome, the presence of three or more
of five metabolic abnormalities: high cholesterol, hypertension, central obesity,
elevated blood sugar, or high triglycerides. People with metabolic syndrome
have more than double the risk for diabetes, heart attack, and stroke. Top health
authorities recommend initially treating metabolic syndrome with lifestyle
changes, such as diet and exercise. However, most physicians do not have the
know-how or resources to actually implement lifestyle medicine. An increasing
amount of physicians are using Metagenics’ unique lifestyle therapy program,
called FirstLine Therapy, to address patients’ needs for lifestyle change. A key

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component of FirstLine Therapy is the use of a lifestyle educator to coach
patients and help them adopt long-term, healthy habits. This allows the doctor
to practice lifestyle medicine while actually increasing his or her patient load. In
addition to continuing professional supervision, the program features a
scientifically validated combination of medical foods, diet, and exercise and
bioelectrical impedance technology to measure body composition and other
health-status indicators. Results of a recently completed multicentre clinical
trial conducted by the University of Connecticut, University of Florida, and the
University of California at Irvine indicate that FirstLine Therapy significantly
outperformed diet alone in reducing several risk factors for cardiovascular
disease. “We’ve known that certain food components are more healthful than
others, and that diet and exercise play a role in keeping us healthy,” Dr. Bland
notes. “Now, the science is there to tell us how to harness the therapeutic
properties of certain nutrients to actually turn back the progression of chronic
disease. We can measure these effects at the cellular level, showing how the
body’s chemistry is actually changing. “Not only do patient outcomes improve,
but as a preventive tactic, lifestyle medicine is far less expensive than treating
chronic diseases after they develop. And, physicians are inspired by being able
to see patients get well, instead of treating just their symptoms.”
According to Dr. Bryan, the nutraceutical segment consists of natural products
that confer some type of health benefit. Dr. Bryan believes that in the vitamins
sector, Vitamins D and C lead market; in the mineral category, calcium is the
clear leader; under the herbals group, ginseng paces the marketplace; whereas in
the functional foods category, there is no clear front-runner. Nutraceuticals are
typically safer than standard therapeutics provided they are manufactured under
“good manufacturing practice GMP” and tested for heavy metals and
microbiology, according to Dr. Bryan. “Nutraceuticals generally have fewer
side effects since they are naturally occurring compounds and not synthetic
compounds our bodies have never seen,” he says. Nutraceuticals are most
efficacious when they restore some type of nutrient deficiency, Dr. Bryan notes.
Chronic statin use, for example, can deplete Co-enzyme Q10 and cause a
deficiency in this mitochondrial component. Supplementing with CoQ10 can
alleviate many side effects of statin therapy Dr. Bryan believes that while many
companies have entered this arena, including big pharma, there is no stand out
leader. “Metagenics stands out because the company was one of the first to
enter and create this market, although their market share and sales have
dwindled during the last decade,” he shares. Metagenics is a nutrigenomics and
lifestyle medicine company dedicated to reducing chronic illness and improving
health. In 1983, the company began to focus on the premise that the right
nutrition could help people realize their best health possible by positively
influencing what makes them unique: their genes. The science of
nutrigenomics, as its now called, is the study of food as one of the most
important environmental modifiers of gene expression in determining health
and disease patterns. Through its substantial and continuing commitment to
nutrigenomic research, the company has been able to identify natural
compounds with powerful therapeutic applications. These are to be used in
Metagenics’ science-based TLC programs, medical foods, and nutraceuticals.

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Metagenics’ U.S. medical foods products include Bariatrix Essentials, Estrium,
UltraCare for Kids, UltraClear, UltraGlycemX, UltraInflamX, and Ultra- Meal.
The company has at least 43 patents and roughly 230 more pending. “Consistent
growth in the nutraceuticals sector is fueled by mistrust and adverse side effects
from standard pharmaceuticals and consumers looking for a natural approach to
health and wellness,”

Dr. Bryan states. “Education and the emergence of rigorous quality control of
nutraceuticals will ensure continued growth.” The aging baby-boomer
population will cause this sector to explode, Dr. Bryan observes. “This
particular demographic is the largest in the history of our nation and they
control a majority of the expendable income,” he says. “This is an educated and
empowered population who are actively seeking natural solutions to better
living and optimal health.” Although there is no universally recognized
definition of the term nutraceutical, the widely used definitions of nutraceutical
appear to have several things in common, says Cynthia M. Bouchez, Ph.D., of
Sterne, Kessler, Goldstein & Fox P.L.L.C.
Most industry experts define a nutraceutical as a natural product, or one that is
derived from a natural product and has a positive effect on health.
Nutraceuticals are mostly perceived to be effective in preventing disease or
supporting a healthy lifestyle, rather than treating disease. “The government
views nutraceuticals as a different class of compounds than pharmaceuticals,
and therefore, nutraceuticals and pharmaceuticals are subject to different
regulations,” Dr. Bouchez observes. Multivitamins remain the most popular
nutraceutical supplement, followed by calcium, omega-3, vitamin C and
vitamin D, according to Dr. Bouchez. The popularity of supplements such as
multivitamins relates to the perception that the daily diet does not contain
enough essential nutrients, and therefore supplements are necessary to make up
for this nutrient deficit. Calcium and vitamin D are often taken by older adults
because physicians advise taking these supplements to ward off diseases such as
osteoporosis. Likewise, omega- 3 fatty acids are known to be useful in aiding
cardiovascular health, but are lacking in the daily diet of most Americans. “The
deficit of omega-3 fatty acids in American diets, combined with the aging
population, contribute to the popularity of this supplement,” Dr. Bouchez
shares. In the functional food category, beverages topped the sales list in 2010,
followed by snacks, prepared or packaged foods, dairy and bread/grains.
“Antioxidants top the list of beverage ingredients, as the anti-aging benefits of
these compounds have become publicized,” Dr. Bouchez explains. Consumers
generally use nutraceuticals in the prevention of disease and the promotion of
health, rather than in the treatment of disease, according to Dr. Bouchez. “As
consumers age, maintaining health and reducing risk of disease is at the
forefront of their minds,” she says. Studies show that aging consumers often
consume functional foods for their preventative health benefits, looking to fruits
and vegetables, fish or oils containing omega-3 fatty acids, whole grains and
herbs and spices to maintain health. Aside from food, consumers of course use
supplements such as multivitamins to maintain balanced nutrition. FDA
regulations at least partially account for the fact that nutraceuticals are used
more for preventing, rather than treating, disease. FDA regulates dietary

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supplement products and dietary ingredients under a different set of regulations
than those covering pharmaceuticals, including prescription and over-the-
counter drugs. “Under FDA rules regulating the labelling of dietary
supplements, it is illegal to market a dietary supplement product as a treatment
or cure for a specific disease or condition,” Dr. Bouchez explains. “In fact, if a
label of a supplement makes a structure/function claim on a dietary supplement,
the label must also state that the product is not intended to ‘diagnose, treat, cure
or prevent any disease.’ Legally, only a pharmaceutical product can make a
claim of treating or curing a particular disease.” According to Mr. Holt,
nutraceuticals can best be defined as a segment of the overall dietary
supplement market where the products are intended for a specific therapeutic
outcome. According to Mr. Holt, the market leaders within the heath-care
provider niche are well-researched, evidence-based therapies where the
mechanisms of action are clearly understood and where there are demonstrable
benefits to the patient. In the nutraceutical space, examples include omega-3
supplements, Vitamin D and probiotics.

10.1. Sector Growth and Challenges

The nutraceutical sector is growing at a rapid pace and the industry is prepared
to meet the rising demand for health foods and products, says Michael Shahani,
director of operations for Nebraska Cultures Inc. He points out that continuing
scientific research is essential to the success of the industry. “Consumers must
look for products backed by quality scientific research,” Mr. Shahani says. “A
few case studies or testimonials are not enough; manufactures should be able to
show consumers the real, peer-reviewed scientific research that stands behind
their products.” The largest driver of growth is consumer interest and education,
according to Mr. Holt. “Consumers are ever becoming more informed and
aware of their options when it comes to their health,” he says. “According to
many of the doctors we work with, a growing percentage of patients are drug
adverse. When a doctor explains to a patient that he has hypertension, for
instance, the patient wants to be involved in the treatment decisions and have a
clear understanding of his options. No longer does a doctor simply hand a
patient a script without discussion. Because of their increased role in education,
patients are concerned about side effects, drug interactions and effectiveness,
Mr. Holt shares. “The old idea that drug therapy is the only therapy no longer
holds true,” he says. Patients are asking their doctors for alternatives to drug
therapy with greater regularity that creates a need for physicians to be
nutraceutical experts and to have access to high-quality, effective therapies,
according to Mr. Holt. Ajinomoto USA provides doctors with side-effect free,
well-researched alternatives. If a patient is “drug hesitant,” then the provider
can present him with additional treatment options. “Physicians are starting to
recognize that they need to have more tools in the tool bag, above and beyond
prescription drugs,” Mr. Holt observes. Patients generally have specific criteria
when evaluating nutraceuticals, Mr. Holt shares. “They look for published
human randomized controlled trials, colleague experience and most importantly
patient outcomes.” The enormous growth of the nutraceuticals sector

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throughout the last decade is due in large part to increased purchasing by
mainstream consumers, as opposed to traditional ‘health food’ consumers,
according to Dr. Bouchez. “Factors for the growth in this segment include
increased access to medical information on the Internet, the proliferation of
functional foods that taste good at lower prices, the rise in health-care costs and
an aging population,” she says. The increased level of information regarding the
preventative effects of supplements has driven consumers to purchase foods
with nutritional benefits, Dr. Bouchez says.

Medical information showing the benefits of supplements is easily available on

the Internet, so consumers do not have to rely solely on a middle party, such as
their physician, for nutrition advice. Dr. Bouchez points to the well-publicized
negative health effects of trans fats and saturated fats as an example of informed
consumers learning to avoid products with these compounds. By contrast, Dr.
Bouchez shares, information on the positive health benefits of “super foods” has
driven consumers to purchase more of these foods, and foods and supplements
containing the ingredients found in these “super foods.” “For continued growth
in this sector, efficacy claims must be backed up by scientific evidence,” Dr.
Bouchez explains. “The safety of nutraceuticals, is also a factor in continued
growth in this segment.” Recent safety concerns regarding food products from
China, for example, have made consumers more vigilant regarding the
ingredients in their foods. According to FDA findings in recent years, China is
one of the world’s largest producers and consumers of agricultural products.
The country hopes to further increase agricultural production through improved
plant stocks, fertilizers, and technology. China is a major U.S. supplier of
seafood, canned vegetables, fruit juices, honey, and numerous other varieties of
processed foods.
During the 1980s through the late 1990s, FDA encountered several serious
compliance problems with Chinese food exports, including lead and cadmium
in ceramic ware used to store and ship food products, and staphylococcal
contamination of canned mushrooms. Although improvements have been made
in some Chinese products with which the regulatory agency had concerns in the
past, there is unfortunately still a pattern of substandard products that continue
to be shipped to the United States. This pattern has continued, and the safety of
food and other FDA-regulated products from China have become a concern for
FDA, Congress, and U.S. consumers. One of the challenges with the Chinese
food industry is its sheer size and the number of people involved in the
production and distribution chains. The Chinese food industry consists of large
multi-national corporations, mid-size corporations and many small family-run
operations. Price is also an issue for mainstream consumers, especially with the
economic downturn. In order for growth to continue in this area, companies
must be mindful that the middle class has been hit hard by the recession, and
therefore is spending less money on household stables such as laundry detergent
and diapers, according to Dr. Bouchez. Companies, therefore, must market to
these consumers nutraceutical products, such as functional foods, that are safe
and effective at a good value. Mainstream consumers appear to appreciate that
preventing disease is less expensive than treating disease, especially with the
soaring costs of health care. “Because nutraceuticals are consumed in large part

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for their preventative effects, the segment is well positioned to address the
concerns associated with escalating health care,” Dr. Bouchez observes. Aging
Baby Boomers, for example, are generally well educated regarding healthy
living, which includes consuming foods having health benefits.” On May 19,
2011, researchers at the University of Florida and Metagenics announced that a
program consisting of a breakthrough medical food combined with a low-
glycemic, Mediterranean-style diet is almost twice as effective as one of the
best diets alone for lowering risk factors for cardiovascular disease, the leading
cause of death in the United States. In addition, the medical food Ultra- Meal
PLUS 360° is 40% more likely to resolve metabolic syndrome, a condition
affecting one-third of all American adults that increases the risk for heart
disease and diabetes. Researchers believe that patients who incorporate the
medical food into their diets as well as make necessary lifestyle changes can
improve their health faster than by using a Mediterranean diet alone. The results
of the multicenter clinical trial were published in the May/June issue of the
Journal of Clinical Lipidology, a publication of the National Lipid Association.
“Chronic illness is draining our healthcare resources and keeping millions of
people from enjoying healthy, vibrant lives,” says Robert H. Lerman, M.D.,
Ph.D., director of medicine and extramural clinical research for Metagenics.
“Many of these illnesses are the result of long-term lifestyle and behavior
choices.
This study is important because it shows how effective UltraMeal PLUS 360° is
in resolving metabolic syndrome and cardiovascular risk factors in affected
individuals, and identifies a powerful new approach to combating chronic
illness.” Metabolic syndrome is a cluster of conditions that increase an
individual’s risk for developing heart disease, diabetes, and other chronic
illnesses. As more countries adopt Western dietary habits and sedentary
lifestyles, the number of chronic illnesses such as type II diabetes, obesity, heart
disease, arthritis and autoimmune diseases has increased. “Preventing chronic
illness is far more effective from both a cost and treatment perspective than
treating the illness once it develops,” Dr. Lerman said. “Physicians have
evidence-based research that now enables them to actually use lifestyle therapy
in their patients to help them avoid chronic illness by treating the cause, not just
the symptoms of these conditions.” Inter-Continental Oils & Fats (ICOF)
introduced its new product line Vitrenol to the nutraceuticals market on Sept. 6,
2011. Vitrenol is a complete Vitamin E that delivers all the natural benefits of
Vitamin E Tocopherol plus the life-enhancing functions of palm Tocotrienols.
The company’s solvent-free manufacturing process gives the unique assurance
of no trace residues of solvent in the ingredient. Palm Vitamin E was
acknowledged as GRAS (Generally Recognized As Safe) by FDA in 2010.
ICOF uses sophisticated extraction technology to purify natural palm oil
without the use of chemicals such as solvents. This preserves every natural
property of palm oil Tocotrienols and ensures that there are no solvent residues
in the final products. Vitrenol is solvent-free, and there is absolutely no trace
residue as solvent is not used at all in ICOF’s extraction process. Fully natural,
safe and with the power to care for health and heart, a combination of Vitamin
E Tocotrienols and Tocopherols has the potential to enhance quality of life by

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promoting healthy cholesterol levels, supporting cardiovascular health and even
battling cancer cells. Improved immune responses and better skin and hair are
other benefits of consuming Tocotrienols. Vitrenol contains other beneficial
phytonutrients including phytosterols and squalene. Vitrenol is available as a
liquid and powder, and there are concentrations for specific needs and
applications.

ICOF is a Singapore-based, multinational company with subsidiaries in Asia,

European Union and the United States. ICOF is a member of the Global Traders
Program, a status granted by International Enterprise Singapore to international
companies with a sterling track record in worldwide commodities trading,
procurement, distribution and transportation. On Sept. 3, 2011, BioSorb
Nutraceuticals announced immediate availability of Bio D Supreme. This
product provides a quick and easy solution for people suffering the effects of
low Vitamin D levels. “In all my years of practice of medicine, I’ve never seen
one vitamin, even vitamin C, have such profound effects on human health,”
says Dr. Soram Khalsa, board-certified internist and medical director for the
East-West Medical Research Institute. Experts contend that obtaining adequate
levels of Vitamin D through traditional means has become increasingly
difficult. Some foods are a good source, but extreme amounts must be
consumed to reach the recommended 5,000 IU per day. Modern lifestyles have
led to more time spent indoors, and heavy use of sun screen is another factor
contributing to the Vitamin D Deficiency affecting more than 90% of America.
Bio D Supreme’s Patented Spray Technology provides up to 10 times more
absorption of Vitamin D when compared to a typical multivitamin pill. Using
Bio D Supreme is a safe way to increase energy (without stimulants), elevate
mood and self-confidence, boost alertness and mental energy, and experience
fewer aches and pains. Bio D Supreme is a non-prescription supplement
formulated to provide the nutrition necessary to improve and maintain immune,
heart, colon, prostate, bone, cardiovascular, breast, blood sugar, and joint
health. The synergistic use of pure Vitamins A, B6, B12, D3, K2, Folic Acid,
Zinc, and Boron, combined with maximum absorption technology, ensure the
body can fully realize the positive effects of Vitamin D. Biosorb Nutraceuticals
is a growing force in the nutritional industry that continues to partner with
leading scientists and researchers in the field. Biosorb specializes in developing
clinically tested formulas and services focused on meeting the needs of the
human brain. Biosorb is privately owned and has headquarters in Austin, Texas.
Sign ificant Acquisitions in Recent Years Aventis Pharma Ltd., an India-based
unit of the $44 billion French pharmaceutical giant Sanofi SA, announced its
plans in August 2011 to acquire Universal Medicare Pvt Ltd.’s marketing and
distribution business of branded nutraceutical formulations in India. Although
the pact size was not disclosed, Aventis Pharma is reportedly paying Rs 450-
500 crore for the business. The transaction is expected to close by fourth-quarter
2011. This was the second major inbound deal in the Indian nutraceutical
market during August 2011. French food products giant Danone announced
plans to acquire the nutrition business of the Wockhardt Group for $355 million
to enter the Indian baby nutrition and medical nutrition market. Of the global
nutraceutical market of $117 billion (Rs 514,800 crore), India has less than 1%

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share and is estimated to be around Rs 4,400 crore in size, according to a 2009
report by Ernst & Young. Mumbai-based Universal Medicare manufactures,
markets and distributes branded nutraceutical formulations. The business had a
turnover of Rs 110 crore for fiscal year 2011. Universal Medicare’s portfolio of
more than 40 brands includes nutraceutical products in categories such as
antioxidants, vitamins and mineral supplements, anti-arthritics, anti-
osteoporotics, liver tonics and other nutrients.
Around 750 employees of Universal Medicare will transition to Aventis Pharma
as a part of this accord. Universal Medicare, which primarily markets
formulations, will continue to manufacture the products acquired by Aventis.
With this deal, Aventis Pharma will advance its sustainable growth strategy in
India and facilitate the creation of a consumer healthcare and wellness platform,
according to a company statement. “This strategic acquisition will allow
Aventis Pharma and Sanofi Group to reach out to large sections of India’s
population through a broad offering comprising of pharmaceuticals, vaccines
and now nutraceuticals,” reports Dr. Shailesh Ayyangar, managing director of
Aventis Pharma and VP (South Asia) of Sanofi. In 2009, Sanofi picked up a
controlling stake in Hyderabad-based vaccine maker Shantha Biotechnics,
valuing the Indian company at Rs 3,770 crore. Universal Medicare has two lines
of business – marketing its own formulations and contract manufacturing for
other pharmaceutical companies. The group started operations by marketing the
United Kingdom-based Seven Seas’ cod liver oil in India and over time has
built its own product portfolio focused on the nutraceutical and lifestyle
segments. The company has two manufacturing facilities – one at Sarigam
(Gujarat) and the other located in Bengaluru (Karnataka). On Feb. 7, 2011,
Pfizer entered into a definitive agreement to buy Ferrosan’s consumer
healthcare business, which includes dietary supplements and lifestyle products,
from Altor 2003 Fund. Based in Copenhagen, Ferrosan is an innovative and
long-established consumer healthcare company in the Nordic region with a
portfolio of leading brands. Since 1920, Ferrosan has grown to serve a broader
market including Russia, the Ukraine, Poland, Turkey and many countries
throughout Central and Eastern Europe. “Ferrosan is an excellent strategic fit
that strengthens our presence in dietary supplements with a new set of
compelling brands and product pipeline,” says Paul Sturman, president of Pfizer
Consumer Healthcare. “The transaction will mark an important step towards
expanding Ferrosan’s brands through Pfizer’s global footprint. As an immediate
result of this acquisition, we will gain greater distribution and scale for Pfizer’s
well-known brands such as Centrum and Caltrate in Ferrosan’s regions.”
Ferrosan Consumer Health offers a concentrated product portfolio of
wellestablished brands. The portfolio includes Multi-tabs, which is a popular
multivitamin brand and the reference product in the multivitamin segment in the
Nordic region; Bifiform, which is a market-leading fast-growing probiotics
product range; Fri Flyt/Active Omega, a premium product range addressing the
omega-3 market for heart and joint health; and Imedeen, which is a worldwide
oral skin-care leader. These Ferrosan brands are among the top-selling products
in their respective categories. “We are very pleased that Ferrosan’s innovative
portfolio of leading brands will be joining Pfizer,” shares Ola Erici, president of

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Ferrosan. “We expect that, as part of the Pfizer portfolio, our products will build
on their industry-leading positions and become available in more countries
around the world. And, at the same time, Pfizer will be able to leverage its
footprint in key Ferrosan markets with new Pfizer products.”

The transaction, which is subject to customary closing conditions, including

regulatory approval in certain jurisdictions, is expected to close during second-
quarter 2011. Financial terms were not disclosed. Ferrosan was founded during
1920 and the company has a long-standing pharmaceutical heritage. With
headquarters in Copenhagen, Ferrosan Consumer Health employs about 640
people and is engaged in the sale of science-based consumer healthcare
products primarily in the Nordic region and the emerging markets of Russia as
well as Central and Eastern Europe.

On Feb. 3, 2011, PepsiCo completed the acquisition of about 66% of the

outstanding shares of Wimm-Bill-Dann Foods OJSC, Russia’s leading branded
food-andbeverage company, from certain selling shareholders of Wimm-Bill-
Dann for about $3.8 billion. The acquisition increased PepsiCo’s total
ownership of Wimm-Bill-Dann’s ordinary shares to about 77%. This
transaction makes PepsiCo the largest food-and-beverage business in Russia
and bolsters the company’s position in the fast-growing Eastern European and
Central Asian markets. The acquisition raises PepsiCo’s annual global revenue
from nutritious and functional foods from about $10 billion to nearly $13
billion. This moves the company closer to its strategic goal of building a $30
billion nutrition business by 2020. PepsiCo expected to make an offer in Russia
on or before March 11, 2011, to acquire all of the remaining Wimm- Bill-Dann
shares. The price per share was $132, which is the highest price PepsiCo paid to
the selling shareholders, converted to Russian rubles at the highest Central Bank
of Russia exchange rate established for Feb. 3, 2011, and all days subsequent to
the date on which the WBD shares purchased under the previously announced
purchase agreement were transferred to PepsiCo. PepsiCo offers the world’s
largest portfolio of billion-dollar food and beverage brands, including 19
different product lines that each generate more than $1 billion in annual retail
sales. The company’s main businesses – Frito-Lay, Quaker, Pepsi-Cola,
Tropicana and Gatorade – make hundreds of other nourishing, tasty foods and
drinks sold in 200-plus countries.

On May 17, 2011, PepsiCo announced the completion of its tender offer in the
United States for all outstanding American Depositary Shares (ADSs) of
Wimm- Bill-Dann Foods OJSC for 970.925 Russian rubles per ADS. A total of
about 23,758,556 ADSs, representing about 13.5% of Wimm- Bill-Dann’s
shares, were validly tendered at expiration. PepsiCo accepted for payment all
ADSs validly tendered pursuant to the U.S. offer.

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On June 23, 2010, BASF reached a pact with Cognis Holding Luxembourg –
controlled by Permira Funds, GS Capital Partners and SV Life Sciences – to
acquire the specialty chemicals company Cognis for an equity purchase price of
E700 million. Including net financial debt and pension obligations, the
enterprise value of the transaction is E3.1 billion. BASF completed the
acquisition of Cognis effective Dec. 9, 2010. “With the acquisition of Cognis,
we are strengthening our portfolio with cyclically robust and profitable
businesses and further expanding our position as the world’s leading chemical
company,” reports Dr. Jürgen Hambrecht, chairman of the board of executive
directors of BASF SE. Cognis is a worldwide supplier of innovative solutions
and products based on renewable raw materials for the health and nutrition
market as well as the cosmetics, detergents and cleaners industries. Another
main focus is on products for a number of other industries, such as mining,
lubricants, coatings as well as agriculture. The company employs about 5,500
people, and operates production sites and service centers in 30 countries. In
2009, Cognis had sales of about E2.6 billion and an EBITDA (earnings before
interest, taxes, depreciation and amortization) of E322 million. “With the
support of our owners Permira Funds and CS Capital Partners, we have become
a leading innovative supplier of specialty chemicals,” stated Dr. Antonio Trius,
CEO of Cognis. “In particular, our focus on wellness and sustainability and our
expertise in renewable raw-material based products have been our main success
factors. We are convinced that there are excellent opportunities through
combining the strengths of Cognis and BASF.”

Cognis customers have included worldwide consumer goods companies and

regional suppliers from the personal and home care industries, as well as from
the area of health and nutrition. The company also offers products for coatings
and paints, lubricants for the transport industries and additives for chemical-
technical applications for agriculture and mining. “With this acquisition, we
want to achieve a leading position in personal care ingredients, strengthen our
leading position in value added products for home care and establish a strong
position in health and nutrition products,” said Dr. John Feldmann, member of
the board of executive directors of BASF and responsible for the Performance
Products segment. “By purchasing Cognis, we will in particular expand our
portfolio with products based on renewable raw materials. A broader and more
attractive offering of products and services combined with our research and
development expertise will allow us to become an even more important partner
for joint development projects with our customers. This will contribute to
making them even more successful.” Cognis was integrated into BASF’s
Performance Products segment. That business generated sales of E12.29 billion
in 2010. Performance products help customers improve their products and
processes. They give special characteristics to products including diapers,

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paper, vitamins for food supplements, UV filters for sunscreen, plastic additives
and products for water treatment, mining applications and for the oil,
automotive and coatings industries. “The acquisition of Cognis is an important
step in our segment strategy of growth, value and sustainability,” Dr. Feldmann
explains.

In July 2010, NBTY – a leading global manufacturer and marketer of nutritional

supplements – was acquired by The Carlyle Group for $3.8 billion. Under the
terms of the merger pact, Carlyle acquired all outstanding common shares of
NBTY for $55.00 per share in cash. This represented a premium of about 57%
over NBTY’s average closing share price during the 30 trading days ended July
14, 2010. “NBTY is an outstanding business with well-established brands, a
proven vertically integrated multi-channel/multi-geography strategy and strong,
long-standing customer relationships,” says Sandra Horbach, managing director
and head of the consumer and retail sector team for Carlyle. NBTY is a leading
worldwide vertically integrated manufacturer, marketer and distributor of a
broad line of high-quality, value-priced nutritional supplements in the United
States and globally. Under a number of NBTY and third party brands, the
company offers 22,000-plus products including those marketed by its Nature’s
Bounty, Vitamin World, Puritan’s Pride, Holland & Barrett, Rexall, Sundown,
MET-Rx, Worldwide Sport Nutrition, American Health, GNC (UK), DeTuinen,
LeNaturiste, SISU, Solgar, Good ‘n’ Natural, Home Health, Julian Graves,
Ester-C and Natural Wealth brands. Carlyle completed its acquisition of NBTY
on Oct. 1, 2010. Pursuant to the terms of the merger agreement, NBTY’s
stockholders are entitled to receive $55 in cash, without interest, less any
applicable withholding taxes, for each share of NBTY common stock owned by
them.

Attune Foods, maker of the world’s first Probiotic Chocolate Bar, acquired the
Uncle Sam and Erewhon cereal brands from US Mills LLC on Dec. 14, 2009.
This transaction expands Attune Foods’ portfolio of great tasting food products
that deliver digestive health benefits. Uncle Sam cereal, introduced in 1908, is
an all-natural high-fibre cereal that contains a unique blend of toasted whole
grain wheat flakes and flaxseed. In addition to providing an excellent source of
naturally occurring dietary fibre, the product is low in sodium and sugar.
Erewhon is a leading all-natural gluten- free cereal brand that is available in
more than a dozen delicious varieties. Many varieties are wheat free, low in
sodium, low in fat and have long been a staple in gluten free diets. In addition to
the purchase of Uncle Sam and Erewhon, Attune Foods acquired Skinner’s
Raisin Bran and New Morning cereal and graham cracker brands. “We are
thrilled to add Uncle Sam and Erewhon cereals, two brands firmly rooted in the
digestive health space, to the Attune Foods line-up of innovative products,” says
Rob Hurlbut, CEO of Attune Foods. “With the addition of these great cereals

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 along with our existing probiotic chocolate and granola bars, Attune Foods has
cemented its status as a leading natural digestive health company. The
American Gastroenterological Association found that nearly half of Americans
(46 percent) say that digestive problems affect their day-to-day lives. Attune is
committed to delivering a full set of all natural digestive health products to help
consumers better address these needs.” According to Ilya Nykin, managing
director of Prolog Ventures and chairman of Attune Board, “Attune has
dramatically changed the way consumers access probiotics and is clearly
committed to offering natural digestive health products to help people feel their
best every day. With this acquisition, Attune is expanding its footprint to a
bigger and broader platform, providing a tremendous growth opportunity with
our customers and consumers when it comes to digestive health.” Attune
Chocolate and Granola Probiotic Bars contain probiotics clinically proven to
support a healthy digestive system and boost immunity. Each bar includes 6.1
billion CFUs (colony forming units) of the most clinically tested probiotic
strains, is an excellent source of calcium and consists of less sugar than most
yogurts.

References:

2011 PharmaLive’s Nutraceuticals and Vitamins Review and Special

Outlook Report [with Michael Shahani] pharmalive.com

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