Indian Journal of Pharmacology 2003; 35: 363-372H. 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 disease’1. Correspondence: H. Dureja E-mail:
[email protected] 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 Saw Palmetto has been shown in short term trials to be efficacious in 2.. Many potential benefits have been attributed to antioxidant use in the form of dietary intake or supplementation9-13. Ernst suggested that St John’s wort is efficacious for mild to moderate depression. Echinacea may be helpful in the treatment or prevention of upper respiratory tract infections. including β-sitosterols (found in Saw Palmetto berry). rather than patients. Nutraceuticals are marketed in concentrated forms as pills. Numerous nutraceuticals are present in medicinal herbs as key components. although results have been inconclusive 16. These findings have implications for increasing the uptake of antioxidants in the central nervous system. The knowledge of herbals has accumulated over thousands of years so that today we possess many effective means of ensuring health care. Zinc is an essential component of more than hundred enzymes involving digestion. cernilton (pollen extract). A list of commonly known herbal and phytochemical products with their therapeutic activity is shown in Table 2.. Antioxidants. Jialal and Fuller found that the combination of vitamin E. thus. substances with established nutritional functions. diminished memory and concentration. but serious concern exists about its interactions with several conventional drugs 22 . water and fat-soluble vitamins.Nutrients herbs or botanical products as concentrates and extracts . minerals. It has been found that common herbal treatment is in the use of Echinacea for the prevention and treatment of colds and flu. e pyruvate. in general. Herbals: Herbals are as old as human civilization and they have provided a complete storehouse of remedies to cure acute and chronic diseases. menopausal symptoms. determined that the oxidized form of vitamin C. who had angina17. Those genetically predisposed to pancreatic cancer have low serum levels of selenium. weight-loss supplements and meal replacements – Dietary supplements. metabolism and wound healing. such as sports nutrition. some feel that this has the potential for improving the treatment of Alzheimer’s disease. Agus et al. digestive upsets and constipation and not to mention headaches 4. A series of five placebo controlled studies evaluating the use of Echinacea produced mixed results. Herbal extracts. which the authors attribute to either the use of healthy volunteers. demonstrated that supplementation of L-arginine improved exercise capacity in patients. C and beta carotene has been useful in reducing low density lipoprotein oxidation and subsequent atherosclerosis12. chondroitin sulphate. Those suffering from asthma and skin cancer have also been evaluated with selenium for its potential use. Ceremuzynski et al. or the use of extracts that were not standardized or chemically defined monopreparations 21. and pygeum africum (African plum) have been clinically evaluated for use in the treatment of benign prostatic hyperplasia20. Categories of nutraceuticals Nutraceuticals are non-specific biological therapies used to promote wellness. readily crosses the blood brain barrier11 . it is assumed that supplementation with selenium may help to prevent this condition14.DEVELOPMENTS IN NUTRACEUTICALS 364 degeneration (leading to irreversible blindness). High dietary intake of vitamin E may prevent Parkinson’s disease10. cataracts.Herbals reagents derived from other sources ( . These can be grouped into the following three broad categories 8: 1. may be useful in the prevention of cancer and cerebrovascular disease9. Nutrients: The most commonly known nutrients are antioxidant.g. such as vitamins. but trial data are not fully convincing. steroid hormone precursors) serving specific functions. powders and tinctures either as a single substance or as combination preparations 7 . A list of common nutrients with their health benefits is given in Table 1. thus. amino acids and fatty acids .15. L-arginine is a semi-essential amino acid that is a substrate for nitric oxide production. insomnia. capsules. 3. vaccines as a result of macrophage and T cell stimulation13 . Vitamin supplement is associated with increased antibody titre response to both hepatitis B and tetanus . prevent malignant processes and control symptoms. dehydroascorbic acid. helps in formation of genetic material.Carnitine Choline Vitamin F Inositol Taurine Antioxidant. muscle and glanddular functions Helps in energy production. 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. essential in neurologic functions Helps in energy production and other chemical processes in the body. Essential for formation of bones and teeth. helps with formation of red blood cells. protects against heart disease Aids in synthesis of cholesterol. may aid in the prevention and treatment of certain cancers and in the treatment of certain skin disorders. may help prevent premenstrual syndrome (PMS) Essential for building strong bones and teeth. energy production. boosts the immune system Essential for blood clotting Antioxidant. maintains healthy vision. for growth and development. maintenance of central nervous system and synthesize amino acids and is involved in metabolism of fats. teeth and skin. absorption of iron from digestive tract Essential for proper functioning of the thyroid Antioxidant. important in nerve. steroids and fatty acids. bile acid conjugation. crucial for intraneuronal synthesis of acetylcholine Essential for building bones and teeth and maintaining bone strength. production of sperm and testosterone Required for various metabolic functions Oxidation of fatty acids. normal growth and development in children. leukotrienes and various hydroxy fatty acids Lipotropic agent necessary for amino acid transport and movement of potassium and sodium Aids in retinal photoreceptor activity. CNS neuromodulation. lung and nerve tissue. protein and carbohydrates Necessary to produce the genetic materials of cells. but ingested cobalt is metabolized in vivo to form the B12 coenzymes Essential for hemoglobin and collagen production. skin and mucous membranes. Table 1. energy production and storage With insulin helps to convert carbohydrates and fats into energy Essential component of vitamin B12. 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. 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.365 H. Common nutrients and their associated health benefits 18. essential in first three months of pregnancy for preventing birth defects. cardiac contractility. essential. white blood cell antioxidant activity. helps in red blood cell formation. muscles. may prevent common cold and attenuate its symptoms Helps to convert food in to energy. gums. helps the body absorb and use calcium Antioxidant. helps in wound healing. helps form blood cells. helps to carry and transfer oxygen to tissues Essential for healthy nerve and muscle function and bone formation. DUREJA et al. sperm motility. wound healing. platelet aggregation. growth and insulin activity . helps maintain healthy eyes. essential for healthy functioning of the heart muscle Essential for cell reproduction. healthy functioning of the heart. necessary for healthy bones. Ephedra equisetina Bunge. Plantago ovata) Slippery elm (Ulmus rubra Muhl. vasoconstrictor. vertigo Antimicrobial..) Valerian (Valeriana officinalis L. treatment of cold and flu symptoms Adaptogen 366 Bronchodilator.) Topical antibacterial and antiviral Cathartic Mucilaginous demulcent. astringent.) Feverfew (Tanacetum parthenium L. tinnitus.) Eleuthera (Eleutherococcus senticosus Rupr. fibrinolytic.) Ginseng (Panax ginseng . appetite suppressant Dietary supplement of linoleic acid. antithrombotic. antipyretic. antifungal. cholagogue. cognitive disorders secondary to depression. analgesic.. dyspepsia.) Ginkgo (Ginkgo biloba L.) Echinacea (Echinacea purpurea L. antiemetic. headache and gout . severity and duration of migraine headaches Antibacterial.) Melissa (Melissa officinalis L. Maxim) Ephedra (Ephedra sinica Stapf. Ephedra intermedia Schrank. pentandra L.. short term memory loss. ulcerations of the digestive tract Anxiolytic. prophylactic to reduce frequency.) Plantago seed (Plantago arenaria Waldst.) St. positive inotropic. treatment of rheumatic and arthritic conditions. antihyperlipidemic. dementia. antidepressant. antiinflammatory Carminative. N.) Therapeutic activity Dilates capillaries.L. Burm. spasmolytic. chronic cerebral vascular insufficiency.) Horehound (Marrubium vulgare L.DEVELOPMENTS IN NUTRACEUTICALS Table 2.) Garlic (Allium sativum L. Plantago arenaria Kit. antiinflammatory. gastritis Expectorant.. G. anti-inflammatory. antimicrobial.) Licorice (Glycyrrhiza glabra L. treatment of post-thrombotic syndrome. Compound Aloe vera gel (Aloe vera L. astringent. fever and menstrual problems. emollient and nutrient.) Willow bark (Salix alba L. Panax quinquefolius L. mild sedative.) Ginger (Zingiber officinale Rosc. wound healing Immunostimulant. reduces bronchial edema.. antitussive. wound healing properties Antiinflammatory.) Chamomile (Matricaria recutita L. S. used to sooth irritated mucous membranes. choleretic Expectorant. & Maxim. uralensis Fisch.. S. treatment of peptic ulcer Goldenseal (Hydrastis canadensis L. daphnoides Villars. hypotensive. treatment of atopic eczema Treatment of headache. emollient. Common herbal and phytochemical products 19. treatment of mucosal inflammation. John’s wort (Hypericum perforatum L. secretolytic. monoamine oxidase inhibitor Spasmolytic. increased peripheral blood flow. treatment of dizziness Adaptogen Vasodilation. antihemorrhagic. sleep aid Antiinflammatory.) Evening primrose oil (Oenothera biennis L. interacts with prescription drugs leading to potentially serious consequences 23 . A case describes a kidney transplant patient whose cyclosporin level dropped dramatically and dangerously after self-medicating St. However. Although ajoene is a powerful inhibitor of platelet aggregation. cabbage. whole grains. It was suggested that gingko is of questionable use for memory loss and tinnitus but has some effect on dementia and intermittent claudication22. Kava is an efficacious short term treatment for anxiety. sulfur compounds. 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. herbs. have antimutagenic activities and lycopene is the most active oxygen quencher with potential chemo preventive activities. A positive effect of Ginkgo biloba on cognitive function is not proven by data from rigorous clinical trials. 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. and other natural antioxidants that have been associated with protection from and/or treatment of conditions such as cardiovascular disease and cancer. breast and prostate cancer. have known antiinflammatory. reducing the symptoms of benign prostate hyperplasia. Green tea enhances humoral and cell mediated immunity while decreasing the risk of certain cancers and the risk of cardiovascular disease. 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. The foods and herbs with the highest anticancer activity include garlic. soybean. licorice root and the umbelliferous vegetables. None of these herbal medicines is free of adverse effects22 . 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 . The possible mechanisms by which phytosterols offer this protection include the effect on membrane structure and function of tumor and host tissue. St. folic acid. Ginseng enhances . there is still insufficient evidence to recommend it as a routine clinical therapy for the treatment of hypertensive subjects30. such as kaempferol and chlorogenic acid. John’s wort.26. Garlic is superior to placebo in reducing total cholesterol levels. fruits. ginger. the size of the effect is modest and the robustness of the effect is debatable. Similarly. Citrus. The possible protective effect of aqueous garlic extract against oxidative organ damage distant from the original burn wound was determined. 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. diallyl disulfides and quercetin which are active components of garlic. antimutagenic activities. 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.367 H. Compounds like diallyl sulfides. potassium. Ajoene is a synthetic derivative of garlic that inhibits aggregation of human platelets induced by all known agents. immune function of the host and cholesterol metabolism by the host29. Vegetables. terpenoids. nuts and seeds contain an abundance of phenolic compounds. The use of garlic for hypercholesterolemia is therefore of questionable value31. and soluble fibre. Honey has proven antimicrobial activity. such as colon. in addition to providing an ample supply of vitamin C. active components in tomato. John’s wort extract at only one-third of the recommended dose24. DUREJA et al. Silagy and Neil suggested that garlic powder preparation might be of some clinical use in subjects with mild hypertension. However. Epidemiological and experimental studies suggest that dietary phytosterols may offer protection from the most common cancers in Western societies. pigments. It is a mild monoaminoxidase inhibitor and cannot be used with high tyramine foods and antidepressants. for instance. signal transduction pathways that regulate tumor growth and apoptosis. Clinical trials have not yet been able to demonstrate the claimed protective effects from taking supplements28 . Since garlic extract reversed these oxidant responses it seems likely that garlic extract protects tissues against oxidative damage32. contains a host of active phytochemicals. This action may prevent against both hot flushes and breast cancer. Ketogenic diets. natural substances that mimic the structure of hormone oestrogen. Lentinus (shiitake). in epidemiological studies. several species of edible mushrooms in order of decreasing cultivated tonnage. prepackaged. For instance. antitumor and other beneficial or therapeutic health effects without any significant toxicity42. Immune milk products are promising examples of health promoting nutraceuticals48. a number of food items as well as herbal medicines have been reported to produce toxic effects by inducing programmed cell death35. New Zealand spinach leaves and turmeric rhizomes. to reduce the incidence of cancer may do so by inducing programmed cell death. garlic. B and T cells. ginger and green tea which have been suggested. Zbar and NiteBite are two products in the form of bars that contain sucrose. 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. Burgeon is bread containing soya flour and linseeds. Soybean extract has been shown to prevent development of disease like polycystic kidneys. Buckwheat has been used and will be better used as an important raw material for functional food production. Pleurotus (oyster).44. Scientific evaluation of herbal products has been limited. sugar beet roots. However. antihypertension effects and improving constipation . Buckwheat proteins have unique amino acid composition with special biological activities of cholesterol-lowering effects. For example. protein and uncooked starch in order to provide continuous glucose release to diabetics during the night. have been reported to improve seizure control. Hericium. These peptides/hydrolysates may be classified as nutraceuticals due to their ability to provide health benefits49. Auricularia (mu-er). making sustained compliance with dietary restrictions difficult39. Other common foods that may have potential therapeutic value include edible mushrooms. Kellogg’s is a leader with calcium fortified All-Bran plus and Nutrigrain bars. 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. Panax ginseng prevents irradiationinduced programmed cell death in hair follicles. Four nutraceuticals. which provide phytoestrogens. while Artemisia asiatica attenuates cerulein-induced pancreatitis in rats. and Grifola (maitake) have varying degrees of immunomodulatory. Phytoestrogens have been documented to enhance oestrogens levels when hormonal levels are low or to weaken the effects of oestrogen when levels are high. Stadelman found a novel and exciting application of egg technology by using the egg antibodies to prevent or treat diseases 45. lipid lowering. Interestingly enough. natural killer cells and colony-forming activity of bone marrow 13 . Dietary supplements: Dietary supplements have also been developed to manage a variety of diseases. cucumber fruits. Tremella (yin-er). 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 . Numerous casein and whey protein derived angiotensin-I-converting enzyme inhibitory peptides/hydrolysates have been identified. comprised of foods high in fat and low in protein and carbohydrate content. suggesting important therapeutic implications. 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. Because of known pharmacological effects and potential interaction of many of these compounds with therapeutic drugs.DEVELOPMENTS IN NUTRACEUTICALS 368 production of macrophages. 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. Flammulina (enokitake). Cereals and grains is an area of nutraceuticals in which calcium fortification is very strong. these diets are widely acknowledged to be unpalatable. yet herbal products are the most commonly consumed health care products. Nutraceuticals (dietary plants) like soya bean. 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. Cost is another factor that receives scant attention. herbal. in as much as botanicals are costly to produce. The trypsin inhibitor isolated from buckwheat seeds are heat stable and can cause poor digestion if they are not suitably cooked before consumption. Absence of quality control not only increases the risk to the consumer. watershed legislation was passed in 1994 to regulate the manufacture and marketing of nutraceuticals. Adulterations and numerous other types of impurity of nutraceuticals conceivably remain undetected simply because there is an almost total absence of specific quality control. known as the Dietary Supplement Health and Education Act. This can have serious consequences. which induces allergy. 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. dosage requirements and clinical consequences exceed those of most ‘healthfoods’. for instance. 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. A draft law reminiscent of the Dietary Supplement Health and Education Act is in development in India to regulate manufacturing. obesity. nutraceuticals are becoming more widely accepted as an adjunct to conventional therapies for enhancing general well being. Drinks are a fast developing area of functional foods. Also a new independent association has been formed in India to address some of these issues. which lack the specificity required for botanical drugs. direct selling and other service oriented industry companies and plans to affiliate with the International Alliance of Dietary Supplement Associations in the near future. Contamination. An emerging area of nutraceuticals is that of dairy foods containing friendly or probiotic bacteria claimed to promote gut health. The buckwheat seeds may also contain some allergenic proteins. with toxins after fungal infection of raw plant material or with other ingredients has been repeatedly reported and can have potential fatal consequences 57 . Buckwheat flour can improve diabetes. reversed 45 years of increasing FDA regulation of health related products60 . Also the country's central drug control department has put some structures in place for dietary supplements. The association is planning a scientific conference to bring the industry and government together to share information. Recently. Bio yoghurts containing Lactobacillus acidophilus and Bifidobacteria lead the sector. hypertension. it also results in a total lack of impetus to conduct adequate research that demonstrates the potential benefits of nutraceuticals or ensures their safety58. Replacement of one nutrient or antioxidant is unlikely to correct the cascade of interconnected metabolic abnormalities associated with many diseases 59. Because of these findings. production and the evidence supporting clinical use. Mei et al. These products sell for substantial amounts more than mainstream products. DUREJA et al. 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. nestles LC1 (providing Lactobacillus johnsonii) and the culturelle (providing Lactobacillus GG) are also strong players 51. New clinical applications of nutraceuticals are increasingly being reported. and obesity by acting similar to dietary fiber and interrupting the in vivo metabolism. . Nutraceuticals generally fall within the novel foods and ingredients regulations but their purity. The Indian Health and Dietary Supplement Association was created to represent pharmaceutical. 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. This law. whilst specialist fermented products such as yakut (providing L casei Shirota). 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. but there are fundamental differences between formulation.369 H. importing and marketing of health foods/dietary supplements and other nutraceuticals. experience and perspectives on the use and regulation of dietary supplements. nutraceutical. hypercholesterolemia and constipation50. The quality of plant material and manufacturing processes used for nutraceuticals are regulated by food laws. Regulatory aspects In USA. Areas of concern The lack of quality control is a major area of concern for nutraceuticals56. vitamins. 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. minerals and carbohydrates Predigested proteins. MI. India Cadilla healthcare limited. Nutraceuticals will continue to appeal because they are convenient for today’s lifestyle. USA Living essentials. polysaccharides and Folic acid Vinpocetine Soy proteins Manufacturer Nature’s answer. Camden. USA Cre Agri. Surrey. Ahmedabad. SA. Spartanburg. List of marketed nutraceutical products 54-55. CA. Lycopene. Hauppauge. Ltd. Irvine.. USA Raptakos. Mumbai. CA. hydroxytyrosol Proteins and vitamin B Proteins. Morristown. USA Cyvex nutrition. 370 Appetite InterceptTM ChaserTM Rox® Mushroom optimizerTM BiovincaTM Proplus ® Appetite suppressant Hangover supplement Energy drink Immune supplement Neurotonic Nutritional supplement Natrol. 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. Mumbai. Ahmedabad.. and resveratrol) Caffeine. USA Jarrow formulas. Hayward. food technologists and food chemists. U. Product Coral calcium Weight smartTM Omega woman Category Calcium supplement Nutritional supplement Immune supplement Contents Calcium and trace minerals Vitamins and trace elements Antioxidants. NJ. Brett & Co. The present accumulated knowledge about nutraceuticals represents undoubtedly a great challenge for nutritionists. NL. CA. Public health authorities consider prevention and treatment with . USA Campbell soup company. vitamins and phytochemicals (eg. NJ. Los Angeles. Chatsworth. NY. NY. vitamins.DEVELOPMENTS IN NUTRACEUTICALS Table 3. USA Daesang America Inc. USA Rox America. caffeine and glucuronolactone Mushrooms. tyrosine and phenylalanine Activated calcium carbonate and vegetable carbon Taurine.. USA NeuroHelp. 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.K. physicians. CA. White Plains. India Pfizer Ltd. Hackensach. Walled lake. Texas. USA Snapple beverage group. USA Bayer corporation. San Antonio. India Zydus Cadila Ltd. USA Wassen. safety and efficacy without inhibiting innovation. Furst P.17:301-8. Kendall SC. Krugert H. Turnbull BW.1:145-60. Vitamin C crosses the blood brain barrier in the oxidized form through the glucose transporters.100:2842-8. Mobarhan S. DUREJA et al. 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