INTRODUCTION:
The principle, “Let food be thy medicine, and medicine be thy food”, advocated by Hippocrates (460–377 BC), the well recognized father of modern medicine, emphasize the association between nutrition and human health, and conceptualized the relationship between the use of appropriate foods for health and their therapeutic benefits (figure 1).
The role of dietary active compounds in human nutrition is one of the most important areas of investigation with the findings having wide-ranging implications for consumers, health care providers, regulators, food producers, processors and distributors.[[i], [ii]] Thus, the concept of ‘adequate nutrition’ is beginning to be replaced by ‘optimal nutrition’ with consumer belief increasing at an unprecedented pace.[3, 4] Scientists and food manufacturers have coined several terms to describe these physiologically active components and health benefits of these foods. None have clear and generally accepted definitions. [5, 6] This range of products cannot be truly classified as “food” or “pharmaceutical”, and a new hybrid term between nutrients and pharmaceuticals, ‘nutraceuticals’, has been coined to designate them.[7] The Nutraceutical industry is a dynamic, evolving industry that offers exciting opportunities to merge scientific discovery with growing consumer interest in health-enhancing foods.[11] Nutraceuticals will continue to have great appeal because they are convenient for today’s lifestyle. The greatest challenge still remains in the public policy and regulatory arenas, which will encourage research and development of products that provide health benefits and permit truthful, non-misleading communications of these products while protecting public health and maintaining public confidence. [8] The approach to regulating and marketing Nutraceuticals is notably heterogeneous on the global level. This is largely due to challenges in classifying these products, absence of a suitable regulatory category for these hybrid products, and varying views on what is considered sufficient scientific substantiation to conclude their functionality. [5]In the pharmaceutical development process, it is a requirement to have clinical test results from animal tests and studies, for verification of the effects. On the other hand, in the case of nutrition, there was no verification method for foods in preventing diseases in the past. In recent years however, as food composition has been scientifically proven to cause lifestyle-related diseases, and has become a social issue. [9]When nutrition required for health is used to treat sickness and injury then this nutrients comes under Nutraceutical this is the key concept of Nutraceutical. [10]
Figure: 1: Concept of nutraceuticals
CATEGORIES OF NUTRACEUTICALS
Nutraceuticals is a term used to demonstrate the product obtained from food sources that provides extra health benefits as well as basic nutritional value present in food. There are different types of products that comes under the class of Nutraceuticals e.g. Vitamins A, D, E, K, B, C. [11]
Nutrients: There are some established nutritional functions, such as vitamins, minerals, amino acids and fatty acids. Common nutrients and their associated health benefits are:
· Vitamin A supplies antioxidant which is essential for growth and development of eye and in the treatment of certain skin disorders.
· Vitamin E supplies antioxidant which helps to form blood cells, muscles, lung and nerve tissue, boosts the immune system.
· Vitamin K is essential for blood clotting.
· Vitamin C is used as antioxidant for healthy bones, gums, teeth and skin, wound healing and also prevent common cold and attenuate its symptoms.
· Vitamin B1 is supplied to convert food in to energy also essential in neurologic functions.
· Vitamin B2 helps in energy production and other chemical processes in the body, helps maintain healthy eyes, skin and nerve functions.
· Vitamin B3 maintains proper function of brain.
· Vitamin B6 helps to produce the genetic material of cells, formation of RBCs, and maintenance of central nervous system synthesize amino acids and metabolism of fats, protein and carbohydrates.
· Folic acid is widely prescribed during pregnancy for preventing birth defects, RBCs formation, protects against heart diseases.
· Calcium gives strength to bones and teeth, important in functioning of nerve, muscle and glands.
· Iron a major component in energy production, carry and transfer oxygen to tissues.
· Magnesium is useful to maintain a healthy nerve and muscle function and bone formation, may help to prevent premenstrual syndrome.[12]
Dietary supplements:
A dietary supplement is a product that contains nutrients derived from food products. The "dietary ingredients" present in these products are: metabolites, vitamins, minerals, vitamins, herbs, and amino acids.[13]
Functional foods:
Functional foods are designed foods which provide enriched foods close to their natural state to consumer, rather than manufactured dietary supplements in liquid or capsule form.[14]
Herbals:
Herbs or botanical products as concentrates and extracts. Some of the common herbal compounds used as Nutraceuticals are;
· Aloe Vera gel obtained from Aloe veraL. N.L. Burm. is used to dilates capillaries, anti-inflammatory, emollient and wound healing properties.
· Chamomile obtained from MatricariarecutitaL. is used in the treatment as anti-inflammatory, spasmolytic, antimicrobial and wound healing activity.
· Echinacea obtained from Echinacea purpureaL. act as an immune stimulant and treatment of cold and flu symptoms.
· Ephedra obtained from Ephedra sinicaStapf, Ephedra intermedia Schrank, EphedraequisetinaBunge. Have a therapeutic activity as bronchodilator, vasoconstrictor, reduces bronchial edema and appetite suppressant.
· Feverfew obtained from Tanacetum parthenium L. is used to treat headache, fever andmenstrual problems, prophylactic to reducefrequency, severity and duration of migraineheadaches.
· Galic obtained from Allium sativum L. and is used as antibacterial, antifungal, antithrombotic, hypotensive, fibrinolytic, antihyperlipidemic and for anti-inflammatory effect.
· Ginger obtained from ZingiberofficinaleRoseis used as carminative, antiemetic,cholagogue, positive inotropic and treatment ofdizziness.
· Ginkgo obtained from Ginkgo biloba L. and majorly used in the vasodilation, increased peripheral blood flow, treatment of postthrombotic syndrome, chronic cerebral vascular insufficiency, short term memory loss, cognitive disorders secondary to depression, dementia, tinnitus and vertigo.
· Goldenseal obtained from Hydrastis Canadensis L. and is used in the treatment as antimicrobial, astringent, antihemorrhagic, treatment of mucosal inflammation dyspepsia and gastritis.
Pro-biotic:
Foods containing bacteria that are believed to improve health e.g., YakultTM which contains lactobacillus caseishirota, bacteria which is thought to improve gut health, incidence of heart disease and certain cancers. A process of making enriched food is called Nutrification. Functional foods provide required amount of vitamins, fat, carbohydrate, amino acid etc to body. Established requirement that functional food should be in their naturally-occurring form, an essential part of our daily diet, they must regulate a biological process in hopes of preventing or controlling disease. [15]
Traditional and Non-Traditional nutraceuticals: Wide variety of Nutraceutical foods are available in the market which falls in the category of traditional foods and non traditional foods such as-
Traditional Nutraceuticals:
Under the category of Traditional Nutraceuticals that type of food comes, which are simply natural, whole foods with potential health qualities. There has been no change to the actual foods, other than the way the consumer perceives them. Many fruits, vegetables, grains, fish; dairy and meat products contain several natural components that deliver benefits beyond basic nutrition, such as lycopene in tomatoes, omega-3 fatty acids in salmon or saponins in soy. Even tea and chocolate have been noted in some studies to contain health-benefiting attributes. Tomatoes and salmon are two types of food that researchers have found to contain benefits beyond basic nutrition in this case, lycopene and omega-3 fatty acids, respectively.[13]
Non-Traditional Nutraceuticals:
They are the outcome from agricultural breeding or added nutrients and/or ingredients such as orange juice fortified with calcium, cereals with added vitamins or minerals and flour with added folic acid are Non-Traditional Nutraceuticals. Agricultural scientists successfully have come up with the techniques to boost the nutritional content of certain crops. Research currently is being conducted to improve the nutritional quality of many other crops. [8]
NUTRACEUTICALS AND DISEASES
Nutraceuticals are bio active substances and the constituents are either of known therapeutic activity or are chemically defined substance generally accepted to contribute substantially to the therapeutic activity of the drug. Nutraceuticals have received considerable interest because of their presumed safety and potential nutritional and therapeutic effects. The concept of Nutraceutical was stared from the survey in U.K., Germany and France which concluded that diet is rated more highly by consumers than exercise or hereditary factors for achieving good health. Nutraceutical is a term coined to describe substances which are not traditionally recognized nutrients but which have positive physiological effects on the human body. They do not easily fall into the legal category of food and drug and often inhabit a grey area between the two. Risk of toxicity or adverse effect of drugs led us to consider safer Nutraceutical and functional food based approaches for the health management.[16]
Major Nutraceuticals posses multiple therapeutic effect with lacking of unwanted effects hence attract more consumer interest. Increase in shift towards preventive therapies and increasing disposable income, favourable pricing environment growth in pharma retail chain and increase in healthcare spending is mainly responsible for increasing market for Nutraceuticals in India, but lack of standardization and awareness, high pricing, marketing and distribution are some challenges. Nutraceutical market is seeing tidal growth mainly in United States, India and European countries. Faster access to this market is possible through business partnership models, effective regulatory compliance and by evaluating key trends and consumer reference. [17]
Cardiovascular diseases:
Many research studies have identified a protective role for a diet rich in fruits and vegetables against CVD .This apart, Nutraceuticals in the form of antioxidants, dietary fibres, omega-3 polyunsaturated fatty acids (n-3 PUFAs), vitamins, and minerals are recommended together with physical exercise for prevention and treatment of CVD. It has been demonstrated that the molecules like polyphenols present in grapes and in wine alter cellular metabolism and signalling, which is consistent with reducing arterial disease.[11] Flavonoids are widely distributed in onion, endives, cruciferous vegetables, black grapes, red wine, grapefruits, apples, cherries and berries. Flavanoids in plants available as flavones (containing the flavonoid a pigenin found in chamomile); flavanones (hesperidins - citrus fruits; silybin- milk thistle flavonols (tea: quercetin, kaempferol and rutin grapefruit; rutin buckwheat; ginkgo flavonglycosides -ginkgo)play a major role in curing the cardiovascular diseases. Flavonoids block the angiotensin-converting enzyme (ACE) that raises blood pressure; by blocking the “suicide" enzyme cyclooxygenase that breaks down prostaglandins, they prevent platelet stickiness and hence platelet aggregation. Flavonoids also protect the vascular system and strengthen the tiny capillaries that carry oxygen and essential nutrients to all cells. Flavonoids block the enzymes that produce estrogens, thus reducing the risk of estrogen induced cancers. [18, 19, 20]
Diabetes:
Diabetes mellitus is metabolic disorder characterized by hyperglycaemia, glycosuria, hyperlipidemia, negative nitrogen balance and sometimes ketonaemia. The most common forms of diabetes are type 1diabetes (5%), an autoimmune disorder, and type 2 diabetes (95%), which is associated with obesity. Gestational diabetes occurs in pregnancy. Globally the total number of people with diabetes is projected to raise from 171 million in 2000 to 366 million in 2003. Docosahexaenoic acid modulates insulin resistance and is also vital for neurovascular development.Lipoic acid an universal antioxidant is used for treatment of diabetic neuropathy. Dietary fibres from psyllium have been used for glucose control in diabetic patient and to reduce lipid level in hyperlipidemia.[ 21, 22, 23]
Obesity:
Herbal stimulants, such as ephedrine, caffeine, ma huang-guarana, chitosen and green tea help in body weight loss. 5-hydroxytryptophan and green tea extract may promote weight loss, while the former decreases appetite, the later increases the energy expenditure.A blend of glucomannan, chitosan, fenugreek, G sylvestre, and vitamin C in the dietary supplement significantly reduced body weight. Conjugated linoleic acid (CLA), capsaicin, Momordica Charantia (MC) possesses potential anti obese properties. [24, 25]
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 andother joint disorders may reduce physical activity in individuals experiencing this condition, resulting in energy imbalance and weight gain. Increased weight can exacerbate existing problems, through additional stress on joints. Glucosamine (GLN) and chondroitin sulphate (CS) are widely used to alleviate symptoms of OA. These nutraceuticals have both nutrient and pharmaceutical properties and seem to regulate gene expression and synthesis of NO and PGE2, providing a plausible explanation for their anti-inflammatory activities. [26, 27, 28]
Osteoarthritis (OA) is a degenerative disease characterized by cartilage and synovium inflammation that can cause joint stiffness, swelling, pain, and loss of mobility. OA is a very complex and multifactorial disease. Due to the high percentage of people suffering from this disease, with a greater percentage in women after menopause (18%) than in men (9.6%), and the increase in life expectancy, OA is considered one of the most significant causes of disability in which occur in chondrocytes and synovial fluid of the joints. Nutraceuticals are dietary compounds that, from data in literature, seem to play a role in these processes within articular cartilage. Although there are many papers in the scientific literature concerning the use of a great variety of nutraceuticals as an alternative treatment of OA, the aim of our descriptive review is to highlight the importance of non-invasive strategies in the treatment of OA and easily available nutraceuticals, such as olive oil, fish oil, and botanical extracts. The integration with nutraceutical compounds in diet increases the treatment options for patients with established OA beyond the traditional rehabilitation, medications, and surgical strategies such as non-pharmacologic treatment. [29, 30]
Parkinson's disease:
Parkinson’s disease is an extrapyramidal motor disorder characterized by rigidity, tremor and hypokinesia with secondary manifestation like defective posture, mask like face and sial-orrhorrhoea, dementia may accompany.Canadian researchers indicated that vitamin E in food may be protective against Parkinson's disease. Creatine appeared to modify Parkinson’s disease features as measured by a decline in the clinical signs. Researchers have also studied glutathione to determine its effect on nerve and its power as an antioxidant. The appropriate long-term dosing, side-effects and the most effective method of administration are not yet clear. Nutritional supplements have shown some promising results in preliminary studies, it is important to remember that there is not sufficient scientific data to recommend them for Parkinson's disease at present. The patients should be cautioned that over-the counter medications do have side effects and interactions with other drugs and are also expensive. [31]
Alzheimer's disease:
Alzheimer's disease (AD), Characterized by progressive dementia, is a neurodegenerative disorder, primarily affecting cholinergic neurones in the brain. Various measures to augment cholinergic transmission in the brain have been tried.β-carotene, curcumin, lutein, lycopene, turmerinetc may exert positive effects on this diseases by neutralizing the negative effects oxidative stress mitochondrial dysfunction, and various forms of neural degeneration.Other important nutraceuticals are antioxidants. There are plentiful antioxidants in food; we get a surplus of them from flavonoids, vitamin E and vitamin C. Alpha-lipoic acid (ALA) also plays are sponsibility in brain function. Oxidative stress and energy diminutions are biochemical characteristics and brand of AD. Alpha lipoic acid is potent antioxidant, which also progress glucose metabolism and consumption in the brain. Hager et al gave 600 mg ALA day by day to nine patients with AD and related dementia, who were already getting standard acetyl cholinesterase inhibitors, in an open study lasting about 337 days. Results showed that those receiving the ALA had stabilization Phosphatidylserine is a very interesting complex. Phosphatidlyserine is the key phospholipids in the brain and it makes up the basic configuration of the cell membrane. Membrane phosphatidlyserine and phospholipids play a vital role in cell-to-cell announcement and transfer of biochemical letters to the cell. Phosphatidylserine boost dementia, early AD, and age-related cognitive decline of cognitive function demonstrated by stables cores on the MMSE scale and AD assessment scales [32, 33]
Anti-inflammatory activities:
Curcumin (diferuloylmethane) which is a polyphenol of turmeric possesses anticarcinogenic, antioxidative and anti-inflammatory properties.Gamma linolenic acid (found in green leafy vegetables, nuts, vegetable oils i.e.-evening primrose oil, blackcurrant seed oil, and hemp seed oil, and from spirulina, cyanobacteria) is used for treating problems with inflammation and auto-immune diseases.Cat’s claw has 17 alkaloids, along with glycosides, tannins, flavonoids, sterol fractions, and other compounds and work as potent anti-inflammatory agent. [34, 35]
Anticancer activity:
Flavonoids which block the enzymes that produce estrogens reduce chances of estrogen-induced cancers.To prevent prostate/breast cancer a broad range of phyto-pharmaceuticals with a claimed hormonal activity, called “phyto-estrogens” is recommended.Soy foods source of isoflavones, curcumin from curry and soya isoflavones possess cancer chemo preventive properties.Lycopene concentrates in the skin, testes, adrenal and prostate where it protects against cancer.Saponins (found in peas, soybeans, some herbs, spinach, tomatoes, potatoes, alfalfa and clover) contain antitumor and antimutagenic activities. Cucumber fruit Nutritional modulation may be beneficial in the treatment of cancer patients. There is evidence that foods, relatively low in simple carbohydrates with moderate amounts of high-quality protein, fiber, and fat (especially fats of the omega-3 fatty acid series) are beneficial for cancer patients. [36]
In addition, nutraceuticals may also be helpful in reducing toxicity, associated with chemotherapy and radiation therapy, and may lead to better life conditions by reducing cancer cachexia. The phytochemicals have shown different mechanism of actions at different cellular levels. Most of them have emerged as a versatile source of antioxidants affecting the signaling pathway related to redox mediated transcription factors. Besides, they directly modulate the endocrine system, immunological cascade and enzymes related to inflammation. Some of them have shown direct effect on DNA repair and cleavage process spinach leaves, and turmeric rhizomes, were reported to possess anti tumor activity. [37]
Anti-allergic activities:
Quercetine (found in Onions, red wine and green tea) reduce the inflammation that results from hay fever, bursitis, gout, arthritis, and asthma. [38]
Vision improving agents:
Lutein (found in mangoes, corn, sweet potatoes, carrots, squash, tomatoes and dark, leafy geens such as kale, collards and bok choy) also known as helenien is used for the treatment of visual disorders.Zeaxanthin (found in 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) used in traditional Chinese Medicine mainly for the treatment of Visual Disorders. [39]
Nutraceuticals to Prevent Brain Disorder
In recent years, interest in the use of nutraceuticals has risen substantially, largely because of their safety, adequate efficacy, and potency. Nutraceuticals is a broad term that describes products, which other than nutrition are also used as medicine. The ‘Nutritional Psychiatry’ is a new field of research focused on the role of diet and nutrition in mental health. Good nutrition and healthy lifestyles are important not only to prevent mental disorders but equally during treatment of brain disorder to improve patient’s response to treatment. Most brain disorders can be prevented by adopting healthy dietary habits and lifestyle modification (i.e. physical activity, exercise, meditation, diet, and restriction of caffeine, alcohol, and nicotine. Amongst the ‘nutraceuticals and functional foods’ recommended for the prevention of mental illnesses include, but are not limited to, nutrient-dense foods (vegetables, fruits, and fish), Mediterranean diet, Olea europaea, and Nigella sativa.[40, 41]
A traditional Mediterranean diet, for instance, appears to have prophylactic benefits against anxiety, depression, and dementia. Mediterranean diet includes higher intakes of fruits and vegetables, cereals with limited processing, fibre, fish, seafood, and only modest amounts of dairy and lean meats. Specific items within traditional dietary patterns (soy foods, honey, turmeric, blueberries, and pomegranate) have been individually associated with protection against depression and, experimentally, these components have also demonstrated antidepressant properties. The isolated polyphenols and different phytochemicals within these foods have likewise been reported to provide anti depressive properties in experimental models. In addition, specific nutrients, for example, magnesium, zinc, vitamin C, folic acid, and vitamin B12, have additionally been associated with resiliency against depression or improvement in depressive symptoms. [42, 43]
AREA COVERED BY NUTRACEUTICAL PRODUCTS
All therapeutic areas such as anti-arthritic, pain killers, cold and cough, sleeping disorders, digestion and prevention of certain cancers, osteoporosis, blood pressure, cholesterol, depression and diabetes have been covered by Nutraceuticals (figure 2).
Figure 2. Percentage area covered by nutraceuticals
CONCLUSION
Nutraceuticals have received considerable interest because of their presumed safety and potential nutritional and therapeutic effects”. Nutraceuticals are available in the form of isolated nutrients, dietary supplements and specific diets to genetically engineered foods, herbal products and processed foods such as cereals, soups and beverages. 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 defences, 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 diseases.
Nutraceuticals have great future as people of whole world are more aware about their fitness and health from past. In future it will be the goal to provide minimally processed food with extra nutritional benefits and organoleptic value to the consumer.
The developing countries will more focus on development of new nutraceuticals from their neighbouring environment which much be cheap and easily extracted. Fermentation technology using microbes have exciting frontier in nutraceuticals. Enzymes are another field of hot research in future.
Although nutraceuticals have significant promise in the promotion of human health and disease prevention, health professional, nutritionists and regulatory toxicologist should strategically work together to plan appropriate regulation to provide the ultimate health and therapeutic benefit to mankind. Long-term clinical studies are required to scientifically validate the nutraceuticals in various medical conditions. The interaction of nutraceuticals with food and drugs is another area, which should be taken into consideration. The effect of different processing methods on the biological unavailability and effectiveness of nutraceuticals remains to be determined. As like drugs, there should be strict regulatory controls for nutraceuticals.
ACKNOWLEDGEMENT
The authors duly acknowledge the Bhavdiya Institute of Pharmaceutical Sciences and Research Faizabd to facilitate the research work and Dr. Rahul Shukla for his kind support.
CONFLICTS OF INTEREST
The authors declare no conflict of interest.
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