Nutraceuticals as therapeutic agents: A Review

Abstract

Nutraceuticals have received considerable interest because of their presumed safety and potential nutritional and therapeutic effects". Pharmaceutical and nutritional companies are aware of the monetary success taking advantage of the more health-seeking consumers and the changing trends resulting in a proliferation of these value-added products aimed at heart health to cancer. Some popular nutraceuticals include glucosamine, ginseng, echinacea, folic acid, cod liver oil, omega-3 eggs, calcium-enriched orange juice, green tea etc. Majority of the nutraceuticals are claimed to possess multiple therapeutic benefits though substantial evidence is lacking for the benefits as well as unwanted effects. The present review has been devoted towards better understanding of the nutraceuticals based on their disease specific indications.

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Research J. Pharm. and Tech. 1(4): Oct.-Dec. 2008,
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ISSN 0974-3618 www.rjptonline.org
REVIEW ARTICLE
Nutraceuticals as therapeutic agents: A Review
A Rajasekaran*1, G Sivagnanam2 and R Xavier3
1KMCH College of Pharmacy, Coimbatore, Tamilnadu India
2Perunthalaivar Kamaraj Medical College and Research Center, Pondicherry, Tamilnadu India
3AIMST University, Kedah, Malaysia.
*Corresponding Author E-mail: rsekaran2001in@yahoo.co.in
ABSTRACT
Nutraceuticals have received considerable interest because of their presumed safety and potential nutritional and
therapeutic effects”. Pharmaceutical and nutritional companies are aware of the monetary success taking advantage of the
more health-seeking consumers and the changing trends resulting in a proliferation of these value-added products aimed
at heart health to cancer. Some popular nutraceuticals include glucosamine, ginseng, echinacea, folic acid, cod liver oil,
omega-3 eggs, calcium-enriched orange juice, green tea etc. Majority of the nutraceuticals are claimed to possess multiple
therapeutic benefits though substantial evidence is lacking for the benefits as well as unwanted effects. The present
review has been devoted towards better understanding of the nutraceuticals based on their disease specific indications.
KEY WORDS Nutraceuticals; therapy
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 DeFelice, Chairman of the Foundation for
Innovation in Medicine1 “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 definition2. 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 benefits3.
Received on 06.12.2008 Modified on 10.12.2008
Accepted on 20.12.2008 © RJPT All right reserved
Research J. Pharm. and Tech. 1(4): Oct.-Dec. 2008;Page 328-340
“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 billion4.
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

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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 deficiency conditions like anemia it is called
a “nutraceutical”5. 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 success6,7. 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 AND DISEASES
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 disease8,9.
Many research studies have identified a protective role for a
diet rich in fruits and vegetables against CVD10.
This apart, nutraceuticals in the form of antioxidants, dietary
fibers, 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
signaling, which is consistent with reducing arterial
disease11.
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

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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, N-
acetyl cysteine, Hawthorne, Celery, ω-3 fatty acids etc12.
Flavonoids are widely distributed in onion, endives,
cruciferous vegetables, black grapes, red wine,
grapefruits, apples, cherries and berries13. 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; rutin-
buckwheat; ginkgo flavonglycosides - ginkgo),14 play
a major role in curing the cardiovascular diseases 15,16.
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 style17.
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
activity18.
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 men19.
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]-paradol20.
Animal studies provide provides sound mechanistic basis
for the use of ginger in hypertension and palpitations. 21.
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 periods22.
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 23. 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 pressure24.
Dietary fiber preparation 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 fiber source (27%)
that can be added to various food products25.
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 diseases26. Nutritional
value of egg is increased because of added gamma linolenic
acid (GLA) which has many benefits, including prevention
and management of CVD like hypertension27.
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 arrhythmias28,29.
Octacosanol is a 28-carbon chain alcohol. This nutraceutical
is present in fruit, leaves and skin of many plants and whole
grains30. It has gastroprotective and lipid lowering effects.
Since it has no side effects further studies may be
undertaken to prove the claims31.

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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
prospectively32. 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 unlikely33. Treatment with beta carotene,
vitamin A, and vitamin E may increase mortality. The
potential roles of vitamin C and selenium on mortality
need further study34.
There are possibilities to develop nutraceuticals to
prevent and manage thrombosis risk in women with
thrombophilic gene mutations35.
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
etc36. 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 foods37. 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 stimulants, such as ephedrine, caffeine, ma
huang-guarana, chitosan and green tea have proved
effective in facilitating body weight loss38-41. 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 fibers present
in food24. 5-hydroxytryptophan and green tea extract
may promote weight loss, while the former decreases
appetite, the later increases the energy expenditure42.
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
potential43. 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 fiber
possess potential antiobese properties44.
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 pregnancy45.
Globally the total number of people with diabetes is
projected to rise from 171 million in 2000 to 366 million in
200346.
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 totaled $85.7 (11.9% of total health care
expenditures) in 199247.
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 cancers48.
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 pregnancy50.
Lipoic acid is a universal antioxidant, now used in Germany
for the treatment of diabetic 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 complications51.

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Dietary fibers 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 hyperlipidemia52.
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 legally53.
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 cancer54,55. 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 cancer56.
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 immuno
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 sequence57.
Recently, attention has been on phytochemicals that
possess cancer-preventive properties. Besides
chemopreventive 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
cancer58.
Flavonoids found in citrus fruit appear to protect
against cancer by acting as antioxidants59. Soyfoods are
a unique dietary source of isoflavones, the
polyphenolic phytochemicals exemplified by
epigallocatechin gallate from tea60, curcumin from
curry and soya isoflavones possess cancer
chemopreventive properties61. The main soybean
isoflavones, genistein, daidzein, biochanin inhibits prostate
cancer cell growth.62,63. Carotenoids are a group of
phytochemicals that are responsible for different colors 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 quencher64. Lycopene
prevents cancer, cardiovascular disease, and gastrointestinal
tract. It concentrates in the skin, testes, adrenal and prostate
where it protects against cancer65. The linkage 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 papaya67.
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 lutein68 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 anti-
mutagenic 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 diseases69.
Tannins also called proanthocyanidins, detoxify carcinogens
and scavenge harmful free radicals 70. 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-carcinogen71 is used in
alternative medicine and to prevent cancer72. It is present in
strawberries, cranberries, walnuts, pecans, pomegranates
and the best source, red raspberry seeds.

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Pectin is a soluble fiber 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 properties74,75. Phenolics
such as ferulic, caffeic, gallic acids and curcumin are
reported to possess anticancer activity76.
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 enzymes77. 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 of all immune
cells. Bio-transformation products of glucosinolates
include isothiocyanates, dithiolthiones and
sulforaphane. They block the enzymes that promote
tumor growth, particularly in the breast, liver, colon,
lung, stomach and esophagus78.
The sulfur 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 sulfur compounds known as
glucosinolates. Sulforaphane rich in broccoli is a
potent phase 2 enzyme inducer. It produces D-
glucarolactone, a significant inhibitor of breast cancer.
Sulforaphane 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
effects79.
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 properties80-82. The
anticancer potential of curcumin stems from its ability to
suppress proliferation of a wide variety of tumor cells. Top
of Form Beet roots, cucumber fruits, spinach leaves, and
turmeric rhizomes, were reported to possess anti tumor
activity83.
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 cancer84.
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 use85.
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 done86
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
goals87.
Cancer was not prevented by beta-carotene, alpha-
tocopherol, retinol, retinyl palmitate, N-acetylcysteine, or
isotretinoin in smokers88. Ongoing 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 cancer.
Several studies have demonstrated the improvement in
quality of life and the value of complimentary 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.

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Immune boosters and anti-inflammatory agents
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 phyto-
pharmaceuticals 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 signaling
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 diarrhea 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 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 tissue91.
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 conditions92. Lactobacillus GG has
been shown to be effective in the treatment or prevention of
a number of problems including acute diarrhea in children93,
travelers’ diarrhea in adults94, Crohn’s disease95, and
reduction of the incidence of antibiotic-associated diarrhea
in infants96. 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 97,98.
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 cancer99..
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, S-
adenosylmethionine, 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 results100.
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
compounds101. 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

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335
not contain significant amounts of alkaloids were found
to possess strong antioxidant and anti-inflammatory
effects are independent of their alkaloid content102,103.
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 contain resveratrol, the level of
this chemoprotective compound in these fruits was
<10% that reported for grapes104. 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 effects105.
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
diseases106.
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
eicosanoids107. 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.
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 joints108.
Glucosamine (GLN) and chondroitin sulfate (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 antiinflammatory
activities109.
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 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 asthma110. 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 radicals111.
Degenerative diseases
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 AMD112.
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—

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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 activity113.
Antioxidant therapy is supposed to be effective in the
early stages of atherosclerosis by preventing LDL
oxidation and the oxidative lesion of endothelium114.
Astaxanthin is an important naturally occurring
molecule and the most abundant carotenoid in the
marine world. It can be found in many of our favorite
seafood such as salmon, trout, seabream 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 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
reported115.
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 zeaxanthin116.
Alzheimer's disease
Alzheimer's disease (AD) is characterized by progressive
dementia with memory loss as the major clinical
manifestation117. 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
degeneration120.
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 centered
on metal ions are expected to be aggravated by frequent
nutraceutical intake121.
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 walking122, usually occurring
in mid to late adult life. Canadian researchers indicated that
vitamin E in food may be protective against Parkinson's
disease123. Creatine appeared to modify Parkinson’s disease
features as measured by a decline in the clinical signs124.
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 .
Miscellaneous
In our modern society women can be over-fed, but under-
nourished 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 diet125. 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 fetus126.

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Angiogenesis is an enzymatic process involved in
almost all classes of enzymes. It is a process that is
generally down regulated in healthy individuals. Anti-
angiogenic 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 etc127.
Psyllium, a dietary fiber is valuable in the management
of irritable bowel syndrome, inflammatory bowel
disease-ulcerative colitis, colon cancer, constipation52.
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
circulatory stimulants, possess antitumor, antipyretic,
antiepileptic, antiinflammatory, 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 Asia128.
CONCLUSION:
Nutraceuticals are currently receiving recognition as
being beneficial in coronary heart disease, obesity,
diabetes, cancer, osteoporosis and other chronic and
degenerative diseases such as Parkinson's and
Alzheimer's diseases. Evidences indicate that the
mechanistic actions of natural compounds involve a
wide array of biological processes, including activation
of antioxidant defenses, signal transduction pathways,
cell survival-associated gene expression, cell
proliferation and differentiation and preservation of
mitochondrial integrity. It appears that these properties
play a crucial role in the protection against the
pathologies of numerous age-related or chronic
diseases60.
It is very imperative that the nutrients found in many foods,
fruits and vegetables are responsible for the well-
documented health benefits. For example, lutein and
zeaxanthin prevent cataracts and macular degeneration;
beta-carotene and lycopene protect the skin from ultraviolet
radiation damage; lutein and lycopene may benefit
cardiovascular health, and lycopene may help prevent
prostate cancer. Because of these and other marked health
benefits of these, it must be taken regularly and to reduce
the risk factors like high cholesterol, high blood pressure
and diabetes. Some of the most popular nutraceutical
products marketed today are botanicals such as St. John’s
wort, echinacea, ginkgo biloba, saw palmetto, and ginseng.
Many industries manufacture and market the nutraceuticals,
where the side effects (especially consumed in large
quantities) of these nutraceuticals not reported or often
unproven. In order to have scientific knowledge about the
nutraceuticals, publics should be educated, where
recommended daily doses of these nutraceuticals should be
known by each consumer.
With the rapidly increasing interest in the nutraceutical
revolution, we need to establish a vibrant nutraceutical
research community which is absolutely necessary to
convert the majority of potential nutraceuticals to
established ones thereby truly delivering their enormous
benefits to all of us.
The list of nutraceuticals being studied is changing
continually and reflects ongoing research, market
developments and consumer interest129.
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