Indian Journal of Pharmacology 2003; 35: 363-372

H. DUREJA et al.

EDUCATIONAL FORUM

DEVELOPMENTS IN NUTRACEUTICALS

H. DUREJA, D. KAUSHIK, V. KUMAR

Department of Pharmaceutical Sciences, M. D. University, Rohtak-124 001. Manuscript Received: 28.4.2003 ABSTRACT Revised: 19.7.2003 Accepted: 31.8.2003

In recent years there is a growing interest in nutraceuticals which provide health benefits and are alternative to modern medicine. Nutrients, herbals and dietary supplements are major constituents of nutraceuticals which make them instrumental in maintaining health, act against various disease conditions and thus promote the quality of life. The explosive growth, research developments, lack of standards, marketing zeal, quality assurance and regulation will play a vital role in its success or failure. Dietary supplements herbals nutrients

KEY WORDS

Introduction Consumers are deeply concerned about how their health care is managed, administered and priced. They are frustrated with the expensive, high-tech, disease-treatment approach predominant in modern medicine; the consumer is seeking complementary or alternative beneficial products and the red tape of managed care makes nutraceuticals particularly appealing. Nutraceuticals (often referred to as phytochemicals or functional foods) are natural bioactive, chemical compounds that have health promoting, disease preventing or medicinal properties. Nutraceuticals are found in a mosaic of products emerging from (a) the food industry, (b) the herbal and dietary supplement market, (c) pharmaceutical industry, and (d) the newly merged pharmaceutical/ agribusiness/ nutrition conglomerates. The present article reviews the general concept, categories, research developments, areas of concern and regulatory aspects of nutraceuticals. The term nutraceutical was coined in 1979 by Stephen DeFelice, founder and chairman of the Foundation for Innovation in Medicine located in Cranford, New Jersey. It was defined as a food or part of food, that provides medical or health benefits, including the prevention and treatment of disease1.
Correspondence: H. Dureja E-mail: harishdureja@rediffmail.com

Nutraceuticals may range from isolated nutrients, herbal products, dietary supplements and diets to genetically engineered ''designer'' foods and processed products such as cereals, soups and beverages. Doubtlessly, many of these products possess pertinent physiological functions and valuable biological activities 2. With the passage of the Dietary Supplement Health and Education Act of 1994, the definition of nutraceuticals has been expanded to include vitamins, minerals, herbs and other botanicals, amino acids and any dietary substance for use by humans to supplement the diet by increasing total dietary intake and subsequently increased the use of nutraceuticals dramatically3,4. However, functional food concept is different from nutraceuticals and can be defined as food products to be taken as part of the usual diet in order to have beneficial effects that go beyond what are known as traditional nutritional effects5. The goal of achieving an optimal or maximal state of nutrition and health is becoming an increasing challenge with the introduction of many nutraceuticals6. The ascribed health benefits of nutraceuticals are legion. Various products are claimed not only to reduce the risk of cancer and heart disease but also to prevent or treat hypertension, high cholesterol, excessive weight, osteoporosis, diabetes, arthritis, macular

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degeneration (leading to irreversible blindness), cataracts, menopausal symptoms, insomnia, diminished memory and concentration, digestive upsets and constipation and not to mention headaches 4. Nutraceuticals are marketed in concentrated forms as pills, capsules, powders and tinctures either as a single substance or as combination preparations 7 . Categories of nutraceuticals Nutraceuticals are non-specific biological therapies used to promote wellness, prevent malignant processes and control symptoms. These can be grouped into the following three broad categories 8: 1. substances with established nutritional functions, such as vitamins, minerals, amino acids and fatty acids - Nutrients herbs or botanical products as concentrates and extracts - Herbals reagents derived from other sources ( .g. e pyruvate, chondroitin sulphate, steroid hormone precursors) serving specific functions, such as sports nutrition, weight-loss supplements and meal replacements Dietary supplements.

vaccines as a result of macrophage and T cell stimulation13 . Those genetically predisposed to pancreatic cancer have low serum levels of selenium; thus, it is assumed that supplementation with selenium may help to prevent this condition14,15. Those suffering from asthma and skin cancer have also been evaluated with selenium for its potential use, although results have been inconclusive 16. Zinc is an essential component of more than hundred enzymes involving digestion, metabolism and wound healing. L-arginine is a semi-essential amino acid that is a substrate for nitric oxide production. Ceremuzynski et al., demonstrated that supplementation of L-arginine improved exercise capacity in patients, who had angina17. A list of common nutrients with their health benefits is given in Table 1. Herbals: Herbals are as old as human civilization and they have provided a complete storehouse of remedies to cure acute and chronic diseases. The knowledge of herbals has accumulated over thousands of years so that today we possess many effective means of ensuring health care. Numerous nutraceuticals are present in medicinal herbs as key components. A list of commonly known herbal and phytochemical products with their therapeutic activity is shown in Table 2. Herbal extracts, including -sitosterols (found in Saw Palmetto berry), cernilton (pollen extract), and pygeum africum (African plum) have been clinically evaluated for use in the treatment of benign prostatic hyperplasia20. It has been found that common herbal treatment is in the use of Echinacea for the prevention and treatment of colds and flu. A series of five placebo controlled studies evaluating the use of Echinacea produced mixed results, which the authors attribute to either the use of healthy volunteers, rather than patients, or the use of extracts that were not standardized or chemically defined monopreparations 21. Ernst suggested that St Johns wort is efficacious for mild to moderate depression, but serious concern exists about its interactions with several conventional drugs 22 . Echinacea may be helpful in the treatment or prevention of upper respiratory tract infections, but trial data are not fully convincing. Saw Palmetto has been shown in short term trials to be efficacious in

2. 3.

Nutrients: The most commonly known nutrients are antioxidant, water and fat-soluble vitamins. Many potential benefits have been attributed to antioxidant use in the form of dietary intake or supplementation9-13. Antioxidants, in general, may be useful in the prevention of cancer and cerebrovascular disease9. High dietary intake of vitamin E may prevent Parkinsons disease10. Agus et al., determined that the oxidized form of vitamin C, dehydroascorbic acid, readily crosses the blood brain barrier11 . These findings have implications for increasing the uptake of antioxidants in the central nervous system; thus, some feel that this has the potential for improving the treatment of Alzheimers disease. Jialal and Fuller found that the combination of vitamin E, C and beta carotene has been useful in reducing low density lipoprotein oxidation and subsequent atherosclerosis12. Vitamin supplement is associated with increased antibody titre response to both hepatitis B and tetanus

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Table 1. Common nutrients and their associated health benefits 18. Nutrients Fat Soluble Vitamins Vitamin A Health benefits

Vitamin D Vitamin E Vitamin K Water Soluble Vitamins Vitamin C Vitamin B1 Vitamin B2 Vitamin B3 Vitamin B6 Vitamin B12 Folic acid Pantothenic acid Minerals Calcium Iron Magnesium Phosphorous Trace elements Chromium Cobalt Copper Iodine Selenium Zinc Vitamin like compounds Biotin L- Carnitine Choline Vitamin F Inositol Taurine

Antioxidant, essential, for growth and development, maintains healthy vision, skin and mucous membranes, may aid in the prevention and treatment of certain cancers and in the treatment of certain skin disorders. Essential for formation of bones and teeth, helps the body absorb and use calcium Antioxidant, helps form blood cells, muscles, lung and nerve tissue, boosts the immune system Essential for blood clotting Antioxidant, necessary for healthy bones, gums, teeth and skin, helps in wound healing, may prevent common cold and attenuate its symptoms Helps to convert food in to energy, essential in neurologic functions Helps in energy production and other chemical processes in the body, helps maintain healthy eyes, skin and nerve function Helps to convert food in to energy and maintain proper brain function Helps to produce essential proteins and convert protein in to energy Helps to produce the genetic material of cells, helps with formation of red blood cells, maintenance of central nervous system and synthesize amino acids and is involved in metabolism of fats, protein and carbohydrates Necessary to produce the genetic materials of cells, essential in first three months of pregnancy for preventing birth defects, helps in red blood cell formation, protects against heart disease Aids in synthesis of cholesterol, steroids and fatty acids, crucial for intraneuronal synthesis of acetylcholine Essential for building bones and teeth and maintaining bone strength, important in nerve, muscle and glanddular functions Helps in energy production, helps to carry and transfer oxygen to tissues Essential for healthy nerve and muscle function and bone formation, may help prevent premenstrual syndrome (PMS) Essential for building strong bones and teeth, helps in formation of genetic material, energy production and storage With insulin helps to convert carbohydrates and fats into energy Essential component of vitamin B12, but ingested cobalt is metabolized in vivo to form the B12 coenzymes Essential for hemoglobin and collagen production, healthy functioning of the heart, energy production, absorption of iron from digestive tract Essential for proper functioning of the thyroid Antioxidant, essential for healthy functioning of the heart muscle Essential for cell reproduction, normal growth and development in children, wound healing, production of sperm and testosterone Required for various metabolic functions Oxidation of fatty acids, promotion of certain organic acid excretion and enhancement of the rate of oxidative phosphorylation Lipotropic agent used to treat fatty liver and disturbed fat metabolism Involved in proper development of various membranes and synthesis of prostaglandins, leukotrienes and various hydroxy fatty acids Lipotropic agent necessary for amino acid transport and movement of potassium and sodium Aids in retinal photoreceptor activity, bile acid conjugation, white blood cell antioxidant activity, CNS neuromodulation, platelet aggregation, cardiac contractility, sperm motility, growth and insulin activity

DEVELOPMENTS IN NUTRACEUTICALS Table 2. Common herbal and phytochemical products 19. Compound Aloe vera gel (Aloe vera L. N.L. Burm.) Chamomile (Matricaria recutita L.) Echinacea (Echinacea purpurea L.) Eleuthera (Eleutherococcus senticosus Rupr. & Maxim., Maxim) Ephedra (Ephedra sinica Stapf., Ephedra intermedia Schrank., Ephedra equisetina Bunge.) Evening primrose oil (Oenothera biennis L.) Feverfew (Tanacetum parthenium L.) Garlic (Allium sativum L.) Ginger (Zingiber officinale Rosc.) Ginseng (Panax ginseng , Panax quinquefolius L.) Ginkgo (Ginkgo biloba L.) Therapeutic activity Dilates capillaries, anti-inflammatory, emollient, wound healing properties Antiinflammatory, spasmolytic, antimicrobial, wound healing Immunostimulant, treatment of cold and flu symptoms Adaptogen

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Bronchodilator, vasoconstrictor, reduces bronchial edema, appetite suppressant

Dietary supplement of linoleic acid, treatment of atopic eczema Treatment of headache, fever and menstrual problems, prophylactic to reduce frequency, severity and duration of migraine headaches Antibacterial, antifungal, antithrombotic, hypotensive, fibrinolytic, antihyperlipidemic, antiinflammatory Carminative, antiemetic, cholagogue, positive inotropic, treatment of dizziness Adaptogen

Vasodilation, increased peripheral blood flow, treatment of post-thrombotic syndrome, chronic cerebral vascular insufficiency, short term memory loss, cognitive disorders secondary to depression, dementia, tinnitus, vertigo Antimicrobial, astringent, antihemorrhagic, treatment of mucosal inflammation, dyspepsia, gastritis Expectorant, antitussive, choleretic Expectorant, secretolytic, treatment of peptic ulcer

Goldenseal (Hydrastis canadensis L.) Horehound (Marrubium vulgare L.) Licorice (Glycyrrhiza glabra L., G. uralensis Fisch.) Melissa (Melissa officinalis L.) Plantago seed (Plantago arenaria Waldst., Plantago arenaria Kit. Plantago ovata) Slippery elm (Ulmus rubra Muhl.) St. Johns wort (Hypericum perforatum L.) Valerian (Valeriana officinalis L.) Willow bark (Salix alba L., S. daphnoides Villars, S. pentandra L.)

Topical antibacterial and antiviral Cathartic

Mucilaginous demulcent, emollient and nutrient, used to sooth irritated mucous membranes, ulcerations of the digestive tract Anxiolytic, antiinflammatory, antidepressant, monoamine oxidase inhibitor Spasmolytic, mild sedative, sleep aid Antiinflammatory, analgesic, antipyretic, astringent, treatment of rheumatic and arthritic conditions, headache and gout

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reducing the symptoms of benign prostate hyperplasia. Kava is an efficacious short term treatment for anxiety. None of these herbal medicines is free of adverse effects22 . St. Johns wort, for instance, interacts with prescription drugs leading to potentially serious consequences 23 . It is a mild monoaminoxidase inhibitor and cannot be used with high tyramine foods and antidepressants. A case describes a kidney transplant patient whose cyclosporin level dropped dramatically and dangerously after self-medicating St. Johns wort extract at only one-third of the recommended dose24. It was suggested that gingko is of questionable use for memory loss and tinnitus but has some effect on dementia and intermittent claudication22. The increase in microcirculation observed with ginkgo may be a mechanism of the improvement of cognitive function seen in healthy individuals and those with dementia25,26. A positive effect of Ginkgo biloba on cognitive function is not proven by data from rigorous clinical trials. The use of Ginkgo biloba as a "smart" drug cannot be recommended on the basis of the evidence available to date and there is a particular need for further long term trials with healthy subjects27. Vegetables, fruits, whole grains, herbs, nuts and seeds contain an abundance of phenolic compounds, terpenoids, sulfur compounds, pigments, and other natural antioxidants that have been associated with protection from and/or treatment of conditions such as cardiovascular disease and cancer. The foods and herbs with the highest anticancer activity include garlic, soybean, cabbage, ginger, licorice root and the umbelliferous vegetables. Citrus, in addition to providing an ample supply of vitamin C, folic acid, potassium, and soluble fibre, contains a host of active phytochemicals. Clinical trials have not yet been able to demonstrate the claimed protective effects from taking supplements28 . Epidemiological and experimental studies suggest that dietary phytosterols may offer protection from the most common cancers in Western societies, such as colon, breast and prostate cancer. The possible mechanisms by which phytosterols offer this protection include the effect on membrane structure and function of tumor and host tissue, signal transduction pathways that regulate tumor growth and apoptosis, immune function of the host and cholesterol metabolism by the host29.

Silagy and Neil suggested that garlic powder preparation might be of some clinical use in subjects with mild hypertension. However, there is still insufficient evidence to recommend it as a routine clinical therapy for the treatment of hypertensive subjects30. Garlic is superior to placebo in reducing total cholesterol levels. However, the size of the effect is modest and the robustness of the effect is debatable. The use of garlic for hypercholesterolemia is therefore of questionable value31. The possible protective effect of aqueous garlic extract against oxidative organ damage distant from the original burn wound was determined. Burn injury caused a significant decrease in glutathione level and significant increases in malondialdehyde and protein oxidation levels and myeloperoxidase activity at postburn 2 and 24 h. Since garlic extract reversed these oxidant responses it seems likely that garlic extract protects tissues against oxidative damage32. The infusion of pig growth factor-mobilized peripheral blood leukocytes (containing 1 to 2% progenitor cells) (pPBPC) into baboons is associated with a thrombotic microangiopathy which results from a direct effect of these pig cells on platelet aggregation. Ajoene is a synthetic derivative of garlic that inhibits aggregation of human platelets induced by all known agents. Although ajoene is a powerful inhibitor of platelet aggregation, the need for repeated administration and its partial effect on pPBPC-induced platelet aggregation would suggest that it may be of only limited value in preventing the thrombotic microangiopathy that develops when pPBPC are infused into baboons 33 . Compounds like diallyl sulfides, diallyl disulfides and quercetin which are active components of garlic, have known antiinflammatory, antimutagenic activities. Similarly, active components in tomato, such as kaempferol and chlorogenic acid, have antimutagenic activities and lycopene is the most active oxygen quencher with potential chemo preventive activities. These results suggest that tomato and garlic suspensions have a protective effect on colon carcinogenesis which is mediated by modulation of different biological pathways during carcinogenesis34. Honey has proven antimicrobial activity. Green tea enhances humoral and cell mediated immunity while decreasing the risk of certain cancers and the risk of cardiovascular disease. Ginseng enhances

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production of macrophages, B and T cells, natural killer cells and colony-forming activity of bone marrow 13 . Panax ginseng prevents irradiationinduced programmed cell death in hair follicles, suggesting important therapeutic implications. Nutraceuticals (dietary plants) like soya bean, garlic, ginger and green tea which have been suggested, in epidemiological studies, to reduce the incidence of cancer may do so by inducing programmed cell death. Soybean extract has been shown to prevent development of disease like polycystic kidneys, while Artemisia asiatica attenuates cerulein-induced pancreatitis in rats. Interestingly enough, a number of food items as well as herbal medicines have been reported to produce toxic effects by inducing programmed cell death35. Four nutraceuticals, sugar beet roots, cucumber fruits, New Zealand spinach leaves and turmeric rhizomes, were evaluated for their comparative effectiveness against dimethylbenz (a)anthraceneinitiated and croton oil-promoted skin tumours and found that turmeric is the most potent nutraceutical against such tumours 36. Scientific evaluation of herbal products has been limited, yet herbal products are the most commonly consumed health care products. Because of known pharmacological effects and potential interaction of many of these compounds with therapeutic drugs, a history of herbal intake should be considered as part of routine medical history and should be evaluated before any change in prescription drugs and before medical procedures 37. Dietary supplements: Dietary supplements have also been developed to manage a variety of diseases. For instance, prepackaged, nutritionally balanced meals that meet the recommendations of national health organizations influenzed multiple risk factors for patients with cardiovascular disease and increased patient compliance with dietary restrictions 38. Ketogenic diets, comprised of foods high in fat and low in protein and carbohydrate content, have been reported to improve seizure control. However, these diets are widely acknowledged to be unpalatable, making sustained compliance with dietary restrictions difficult39. Cereals and grains is an area of nutraceuticals in which calcium fortification is very strong. Kelloggs is a leader with calcium fortified All-Bran plus and Nutrigrain bars. Researchers have found that

minimally refined grains may reduce the incidence of diabetes 40 and may be beneficial in the prevention of gastrointestinal cancers 41. Burgeon is bread containing soya flour and linseeds, which provide phytoestrogens, natural substances that mimic the structure of hormone oestrogen. Phytoestrogens have been documented to enhance oestrogens levels when hormonal levels are low or to weaken the effects of oestrogen when levels are high. This action may prevent against both hot flushes and breast cancer. Other common foods that may have potential therapeutic value include edible mushrooms. For example, several species of edible mushrooms in order of decreasing cultivated tonnage, Lentinus (shiitake), Pleurotus (oyster), Auricularia (mu-er), Flammulina (enokitake), Tremella (yin-er), Hericium, and Grifola (maitake) have varying degrees of immunomodulatory, lipid lowering, antitumor and other beneficial or therapeutic health effects without any significant toxicity42. Zbar and NiteBite are two products in the form of bars that contain sucrose, protein and uncooked starch in order to provide continuous glucose release to diabetics during the night. The sucrose is released immediately while the protein is converted to glucose approximately 2-5 hours after ingestion and the uncooked starch is converted to glucose 6-8 h post ingestion43,44. Stadelman found a novel and exciting application of egg technology by using the egg antibodies to prevent or treat diseases 45. The two nutraceuticals namely glucosamine sulfate and chondroitin sulfate are effective and safer to alleviate symptoms of osteoarthritis46 whereas Deal and Moskowitz emphasized that glucosamine sulfate and chondroitin sulfate are not FDA-evaluated or recommended for treatment of osteoarthritis 47 . Immune milk products are promising examples of health promoting nutraceuticals48. Numerous casein and whey protein derived angiotensin-I-converting enzyme inhibitory peptides/hydrolysates have been identified. These peptides/hydrolysates may be classified as nutraceuticals due to their ability to provide health benefits49. Buckwheat has been used and will be better used as an important raw material for functional food production. Buckwheat proteins have unique amino acid composition with special biological activities of cholesterol-lowering effects, antihypertension effects and improving constipation

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and obesity by acting similar to dietary fiber and interrupting the in vivo metabolism. The trypsin inhibitor isolated from buckwheat seeds are heat stable and can cause poor digestion if they are not suitably cooked before consumption. The buckwheat seeds may also contain some allergenic proteins, which induces allergy. Buckwheat flour can improve diabetes, obesity, hypertension, hypercholesterolemia and constipation50. An emerging area of nutraceuticals is that of dairy foods containing friendly or probiotic bacteria claimed to promote gut health. Bio yoghurts containing Lactobacillus acidophilus and Bifidobacteria lead the sector; whilst specialist fermented products such as yakut (providing L casei Shirota), nestles LC1 (providing Lactobacillus johnsonii) and the culturelle (providing Lactobacillus GG) are also strong players 51. Drinks are a fast developing area of functional foods. A new range of herb and vitamin enhanced drinks called Phuse claims to help overcome problems ranging from postmenstrual syndrome to lack of energy 52. Recently, Mei et al. prepared calcium caseinate and whey protein isolate films and found that these films may be used for wrapping or coating to enhance the nutritional value of foods 53. Because of these findings, nutraceuticals are becoming more widely accepted as an adjunct to conventional therapies for enhancing general well being. As a result of extensive research on these nutraceuticals various products are available in National and International market and some of these are shown in Table 3. Areas of concern The lack of quality control is a major area of concern for nutraceuticals56. The quality of plant material and manufacturing processes used for nutraceuticals are regulated by food laws, which lack the specificity required for botanical drugs. This can have serious consequences. Contamination, for instance, with toxins after fungal infection of raw plant material or with other ingredients has been repeatedly reported and can have potential fatal consequences 57 . Adulterations and numerous other types of impurity of nutraceuticals conceivably remain undetected simply because there is an almost total absence of specific quality control. Absence of quality control not only increases the risk to the consumer, it also results in a total lack of impetus to conduct adequate

research that demonstrates the potential benefits of nutraceuticals or ensures their safety58. New clinical applications of nutraceuticals are increasingly being reported, but there are fundamental differences between formulation, production and the evidence supporting clinical use. Nutraceuticals generally fall within the novel foods and ingredients regulations but their purity, dosage requirements and clinical consequences exceed those of most healthfoods. Replacement of one nutrient or antioxidant is unlikely to correct the cascade of interconnected metabolic abnormalities associated with many diseases 59. Cost is another factor that receives scant attention. These products sell for substantial amounts more than mainstream products, in as much as botanicals are costly to produce. Regulatory aspects In USA, watershed legislation was passed in 1994 to regulate the manufacture and marketing of nutraceuticals. This law, known as the Dietary Supplement Health and Education Act, reversed 45 years of increasing FDA regulation of health related products60 . The FDA may establish good manufacturing practices for nutraceuticals as long as these regulations are molded after the less stringent regulations for foods as opposed to those for drugs. A draft law reminiscent of the Dietary Supplement Health and Education Act is in development in India to regulate manufacturing, importing and marketing of health foods/dietary supplements and other nutraceuticals. Also the country's central drug control department has put some structures in place for dietary supplements, but it is taking a long time for states to cooperate and some states have rejected the structures when their own rules and regulations conflict. Also a new independent association has been formed in India to address some of these issues. The Indian Health and Dietary Supplement Association was created to represent pharmaceutical, nutraceutical, herbal, direct selling and other service oriented industry companies and plans to affiliate with the International Alliance of Dietary Supplement Associations in the near future. The association is planning a scientific conference to bring the industry and government together to share information, experience and perspectives on the use and regulation of dietary supplements.

DEVELOPMENTS IN NUTRACEUTICALS Table 3. List of marketed nutraceutical products 54-55. Product Coral calcium Weight smartTM Omega woman Category Calcium supplement Nutritional supplement Immune supplement Contents Calcium and trace minerals Vitamins and trace elements Antioxidants, vitamins and phytochemicals (eg. Lycopene, and resveratrol) Caffeine, tyrosine and phenylalanine Activated calcium carbonate and vegetable carbon Taurine, caffeine and glucuronolactone Mushrooms, polysaccharides and Folic acid Vinpocetine Soy proteins Manufacturer Natures answer, Hauppauge, NY, USA Bayer corporation, Morristown, NL, USA Wassen, Surrey, U.K.

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Appetite InterceptTM ChaserTM Rox Mushroom optimizerTM BiovincaTM Proplus

Appetite suppressant Hangover supplement Energy drink Immune supplement Neurotonic Nutritional supplement

Natrol, Chatsworth, CA, USA Living essentials, Walled lake, MI, USA Rox America, Spartanburg, SA, USA Jarrow formulas, Los Angeles, CA, USA Cyvex nutrition, Irvine, CA, USA Campbell soup company, Camden, NJ, USA Snapple beverage group, White Plains, NY, USA Daesang America Inc., Hackensach, NJ, USA NeuroHelp, San Antonio, Texas, USA Cre Agri, Hayward, CA, USA Raptakos, Brett & Co. Ltd., Mumbai, India Zydus Cadila Ltd. Ahmedabad, India Pfizer Ltd., Mumbai, India Cadilla healthcare limited, Ahmedabad, India.

Snapple-a-day TM WelLife PNer plus TM OlivenolT M Threptin Diskettes GRD Proteinex Calcirol D-3

Meal replacement beverage Vitamins and minerals Amino acid supplement Neuropathic pain supplement Dietary supplement Protein supplements Nutritional supplement Protein supplement Calcium supplement Granulated-L-glutamine Vitamin and other natural supplement Natural antioxidant, hydroxytyrosol Proteins and vitamin B Proteins, vitamins, minerals and carbohydrates Predigested proteins, vitamins, minerals and carbohydrates Calcium and vitamins

Conclusion Nutraceuticals are destined to play an important role in future therapeutic developments but their success will be governed by control of purity, safety and efficacy without inhibiting innovation. Nutraceuticals will continue to appeal because they are convenient for todays lifestyle. Some are also genuinely

researched and offer novel ingredients that can bring about health benefits quicker than would normally be the case through eating conventionally healthy foods alone. The present accumulated knowledge about nutraceuticals represents undoubtedly a great challenge for nutritionists, physicians, food technologists and food chemists. Public health authorities consider prevention and treatment with

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nutraceuticals as a powerful instrument in maintaining health and to act against nutritionally induced acute and chronic diseases, thereby promoting optimal health, longevity and quality of life. A place for nutraceuticals in clinical practice is emerging, but important pharmaceutical and clinical issues need to be addressed by further research. REFERENCES
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