INTRODUCTION:

A nutraceutical is a combination of the words "nutrient" and "pharmaceutical" which was coined by Dr. Stephen DeFelice, Chairman of the foundation for innovation in medicine in 1989. Since it is now widely acknowledged that "nutraceuticals" play a significant role in improving health, there has been an increase in interest on a global scale^1.According to Association of American Feed Control Officials, 'Nutrient' refers to a feed component that will provide benefit to human or animal's life while 'pharmaceutical' refers to any dietary ingredient with non-toxic health advantages, such as the ability to prevent or treat disease, that has been scientifically demonstrated^2. Therefore, a "nutraceutical" is any substance that might be categorized as food or a component of food that has medical or health advantages, including the prevention and treatment of diseases. Such product can include everything from isolated nutrients, dietary supplements, and diets to genetically modified foods, herbal products, and processed foods including cereals, soups, and drinks. There are already approximately 470 nutraceutical and functional food items available with a demonstrated health benefit^3. The idea of nutraceuticals emerged from a survey conducted in the United Kingdom, Germany, and France, which found that consumers evaluated nutrition as more important for obtaining good health than exercise or inherited traits. Nutraceuticals were often utilized in the US, but there was no regulatory definition. Its meaning was modified by health ministry of Canada which defines nutraceutical as a product isolated or purified from the food, generally sold in medicinal form not associated with food and demonstrated to have a physiological benefit⁴. Nutraceuticals also referred as functional foods but there is difference between them. "Functional food" is defined as food that has been cooked or prepared using "scientific intelligence" with or without knowledge of how or why it is being used. As a result, functional food gives the body the precise amounts of vitamins, lipids, proteins, carbohydrates, etc. that it needs for a healthy existence. When functional food used in the prevention or treatment of diseases or disorders other than anemia, it is called as nutraceutical ^[5]. In the US, the nutraceutical market is estimated to be worth $86 billion. In Europe, this number is significantly greater, and in Japan, it accounts for around a fifth of the $6 billion in yearly food sales. Approximately 47 percent of Japanese people consume nutraceutical.

Classification of NUTRACEUTICAL:

1. Dietary fiber:

Dietary fiber is made up of lignins and non-digestible carbohydrates that are intrinsic and intact in plants. Functional fiber is made up of separate, indigestible carbohydrates that have advantageous physiological effects on people. Dietary and functional fiber are combined to form total fiber. Resistance starches, oligosaccharides, and other non-digestible carbohydrates can now be categorized as functional fibers according to these definitions. According to the Dietary Reference Intake (DRI), adult men should consume 38 grams of fiber per day, while adult women should consume 25 grams per day.

2. Probiotics:

Probiotics are beneficial live bacteria and yeasts for our digestive system. Generally, we associate bacteria with the development of illnesses. But our body is full of bacteria both good and bad. Because they assist in maintaining gut health, probiotics are frequently referred to as "good bacteria". In our body, probiotics occur naturally. People have only been interested in learning more about probiotics and their health advantages since roughly the middle of the 1990s. When patients have digestive issues, doctors frequently recommend them and due to their recent rise to fame, you can find them in anything from chocolate to yoghurt.

e. g. -

· Lactobacillus: This could be the most prevalent probiotic. You can get it in yoghurt and other fermented foods. Different strains can aid in the treatment of diarrhea and may be beneficial for those unable to digest the milk sugar lactose.

· Bifidobacterium: It is also present in several dairy products. Some conditions they treat are Irritable bowel syndrome, Inflammatory bowel disease, Infectious diarrhea, Antibiotic-related diarrhea, Skin conditions like eczema, Urinary and vaginal health, preventing allergies and colds etc.

3. Prebiotics:

Prebiotics are substances that stimulate the activity or growth of microorganisms that improve the health of their host. Prebiotics have the ability to change the makeup of the organisms in the gut microbiome, giving the digestive tract as its most prevalent example. For instance, it has been claimed that certain hand moisturizers function like prebiotics to enhance the activity or make up of skin bacteria^6. Prebiotics are typically non-digestible fiber components found in food that pass through the upper section of the digestive tract undigested and increase the activity of good bacteria that inhabit the large intestine by serving as a substrate for them^7. Prebiotics are conceptually transitional between foods and medications as a functional dietary component, similar to probiotics.

Classification of a food ingredient as a prebiotic requires scientific demonstration that the ingredient⁸:

1. Resists gastric acidity, hydrolysis by mammalian enzymes and absorption in the upper gastrointestinal tract,

2. Fermented by the intestinal microflora,

3. Selectively stimulates the growth or activity of intestinal bacteria potentially associated with health and well-being.

4. Fatty acids:

The polyunsaturated fatty acids (PUFA) are divided into 2 groups, omega-3 and omega-6 polyunsaturated fatty acids, which are differing in position of carbon-carbon double bond. These two are called essential fatty acids. Omega-3 fatty acids derived from linolenic acid, whereas omega-6 fatty acids derived from linoleic acid (LA). There are three most prevalent types of omega-3 fatty acids alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA). Oils like flaxseed, canola, and hemp seed oils, as well as other foods like cold-water fish like salmon and trout, nuts and seeds, are the main sources of omega-3 and omega-6 fatty acids^9. These three fatty acids are part of a metabolic pathway, with alpha-linolenic acid acting as the precursor and eicosapentaenoic acid and docosahexaenoic acid as the byproducts of ALA metabolism. Gas chromatography was used by Wang et al. in 2017 to establish a method for measuring the content and makeup of fatty acids in skin. Within two weeks of starting a diet enriched with fish oil, the study found a statistically significant rise in the levels of EPA and DHA in the skin of mice. After beginning the supplemented diet four weeks prior, this increase reached a plateau^10. Omega-3 polyunsaturated fatty acids have a significant anti-inflammatory function, while LA has the largest concentration of fatty acids in the epidermis and acts as an important structural component. The synthesis of proinflammatory cytokines such prostaglandins, leukotrienes, and TNF-alpha, interferon-gamma , and interleukins-6 and 12 is inhibited by ALA, EPA, and DHA. The Food and Nutrition Board of the Institute of Medicine does not have a recommended daily allowance (RDA) for any of the fatty acids listed above, but it have an adequate intake (AI), which is based on the greatest median intake where insufficiency is exceedingly rare. The adequate intake for alpha-linolenic acid is 1.6 g per day for men and 1.1 g per day for women ages 19 and older^11-14.

5. Polyphenols:

Polyphenols are secondary metabolites of plants and are mainly found in fruits, vegetables, whole grains, cereal, legumes, tea, wine and cocoa. Whole plant foods have been found to include over 8000 polyphenolic chemicals, such as phenolic acids, flavonoids, tilbenes, lignans, and polymeric lignans^15and16. These substances protect the plant against UV radiation, oxidants, and infections^17. Depending on how many phenol rings a polyphenol has and what structural components hold those rings together, it can be divided into a number of subcategories^18.However, we’ll only talk about two here - curcumin and Epigallocatechin gallate (EGCG).

Curcumin - A polyphenol obtained from the turmeric is called curcumin. It contain a yellow pigment, which is responsible for the characteristic yellow color of curry. Like EGCG, curcumin performs a variety of biologically active functions, including anticarcinogenic, anti-inflammatory, and antioxidant functions. Due to its capacity to suppress the growth of cancer cells and promote apoptosis, curcumin has been proposed as a potential cancer treatment similar to EGCG. The anti-inflammatory characteristics of curcumin are demonstrated by its capacity to inhibit pro-inflammatory cytokines like interleukins, tumor necrosis factor-alpha, chemokines, cyclooxygenase-2, and prostaglandin E2. Curcumin also acts as an antioxidant by reducing the generation of ROS, scavenging free radicals, and preventing lipid peroxidation. RDA for curcumin has not yet been determined by the Food and Nutrition Board of the Institute of Medicine, but it has been given the all-clear by the US Food and Drug Administration (FDA) for human consumption and pharmacologic use. The safe oral supplementation of curcumin between 2 and 8 g per kg per day was the subject of two investigations reported by Pal et al. in 2016. The best daily allowance while accounting for the health concerns of supplements must be determined through additional research. The anti-inflammatory activities of curcumin in albino rats were investigated by Shailaja et al. in 2017 as a potential anti-aging nutraceutical. In the study, three oral daily curcumin supplementation dosages were compared to 2 different standard rat feed and water diets. In comparison to the two control groups, the curcumin-supplemented group showed a statistically significant drop in C-reactive protein levels.

Epigallocatechin Gallate - Tea polyphenols decrease DNA damage caused by UV radiation, prevent lipid peroxidation, and lessen the production of ROS and free radicals in the skin. Epigallocatechin Gallate also has anti-inflammatory activity. Additionally, studies have demonstrated that Epigallocatechin Gallate promotes cell cycle arrest and death, which can reduce the proliferation of melanoma cells in humans. In a phase I clinical investigation, Pal et al. indicate that daily doses of 200–1200 mg were well tolerated^19-22.There is no Epigallocatechin Gallate RDA recommended by the Food and Nutrition Board of the Institute of Medicine. In order to assess the level of toxicity of Epigallocatechin Gallate in daily human ingestion, Yates et al. conducted a thorough literature review in 2017. Future research is necessary because the findings were inconclusive, although publications from France and Italy mention a suggested daily maximum limit of about 300 mg of Epigallocatechin Gallate ^[23].

6. Antioxidants:

Antioxidants are essential for maintenance of health and wellness since they act as our body's first line of defense against free radical damage. Due to its high level of reactivity, oxygen can become part of the potentially harmful molecules known as 'free radicals' which are thought to be harmful. The body's healthy cells are vulnerable to damage by free radicals. It consists of a number of elements, both endogenous and exogenous in origin, that interact with one another and work in concert to neutralize free radicals^24.

Amino acids ( N-Acetylcysteine) - The prodrug version of L-cysteine is N-acetylcysteine, which has both topical and oral bioavailability. The most prevalent endogenous intracellular antioxidant and a key player in the body's antioxidant defense is glutathione, which is produced from N-acetylcysteine. DNA damage and ageing are both exacerbated by elevated oxidative stress. As people get older, their bodies produce less glutathione, which causes a glutathione shortage that makes them more vulnerable to oxidative stress. The production and concentrations of intracellular glutathione were shown to be considerably lower in aged people than in younger subjects in a study by Sekhar et al. The amounts of glycine, cysteine, and glutathione in red blood cells of elderly adults significantly increased and decreased in oxidative stress after 2 weeks of cysteine and glycine supplementation. There is no RDA for N-Acetylcysteine^25-27.

Carotenoids - Over 600 fat-soluble plant pigments belong to the carotenoids family; just 20 of these pigments are found in human tissues and blood. Carotenoids must be consumed through diet or supplements because both humans and animals cannot produce them. The skin is shielded from oxidative stress by carotenoids, which are powerful reactive oxygen species scavengers^28. Here, we concentrate on lycopene, beta-carotene, lutein, and zeaxanthin; the four principal dietary carotenoids.

1. Lycopene: Lycopene is the finest singlet oxygen quencher in the carotenoid family but does not have vitamin-A activity. Studies conducted in vitro on lycopene have demonstrated its capacity to prevent the growth of a number of cancer cell by arresting the cell cycle and inducing apoptosis. Higher lycopene concentrations in the skin are significantly correlated with a reduction in skin roughness^29. According to studies, eating tomato paste, which is rich in lycopene, greatly reduces UV-induced erythema and lowers MMP-1 activity, which is an enzyme responsible for breaking down collagen^30. There is no RDA for lycopene.

2. Beta-carotene: Beta-carotene is precursor to vitamin-A so we can determined RDA by consumption of vitamin-A. The recommended daily allowance (RDA) for vitamin A according to the Food and Nutrition Board of the Institute of Medicine is 700 microgram RAE per day for females over the age of 19 and 900 microgram RAE per day for males. The Institute of Medicine's Interconversion of Vitamin A and Carotenoid Units Table states that 1 RAE is equal to 2 microgram of supplemental all-trans-beta-carotene and 12 microgram of dietary all-trans-beta-carotene. Therefore, RDA for supplementary all-trans-beta-carotene is 1800 microgram for men and 1400 microgram for women per day, while the RDA for dietary all-trans-beta-carotene is 10,800 microgram for men and 8400 microgram for women per day^31. Further research is required to establish the ideal daily amount while taking into account the potential health effects of b-carotene supplementation because long-term consumption has been linked to an increased risk of lung cancer^32.

3. Lutein and zeaxanthin: Although lutein and zeaxanthin are the retina's two main xanthophyll carotenoids and are widely regarded to support eye health, large amounts of both are also present in human skin. These carotenoids function as an antioxidant to stop free radical damage in the skin and eyes. RDA of lutein and zeaxanthin has not been established but previous studies have suggested taking 6–10 mg of lutein and 2 mg of zeaxanthin daily. Juturu et al.,examined a daily oral supplement comprising 2 mg of isomers of zeaxanthin and 10 mg of lutein. They came to the conclusion that the supplement boosted the mean MED within 12 weeks and considerably enhanced skin tone, brightness, and color. According to other research, lutein and zeaxanthin prevent the photoaging caused by UV radiation in keratinocytes, limit the breakdown of the extracellular matrix (ECM) by blocking MMPs, and lessen lipid peroxidation in the skin^33-36.

Vitamins -

1. Vitamin C: Vitamin-C is water soluble substance. Since ascorbic acid cannot be produced by humans naturally, bodily concentrations must be maintained through vitamin C consumption. Vitamin C is converted to dehydroxy ascorbic acid by oxidation, which is subsequently transported into our cells by glucose transporters and converted back to ascorbic acid for cellular usage. Vitamin C has been found to protect human keratinocytes from UVA-induced lipid peroxidation and prevent UVB-induced oxidative damage and skin neoplasms in mice. Malondialdehyde, a sign of oxidative stress, is reduced by vitamin C in the skin^37-39. Our DNA, cell membranes, and tissues are all shielded from oxidative damage by vitamin C. During collagen hydroxylation, it also functions as a crucial cofactor and electron donor, promoting the maturation of both intracellular and extracellular collagen^[40].RDA for men and women aged 19 and older for vitamin C is 90 mg and 75 mg respectively, according to the Food and Nutrition Board of the Institute of Medicine^41.

2. Vitamin E: A class of fat-soluble substances is known as vitamin E. The predominant form of vitamin E used in human metabolism is alpha-tocopherol, which is both the most plentiful and biologically active form. Alpha-tocopherol shields the skin against UVB deterioration by preventing the production of ROS, scavenging free radicals, stabilizing cell surfaces and membranes, lowering the amount of apoptotic cells, and reducing nuclear factor kappa B activation. RDA of vitamin E is 15 mg a day for men and women ages 19 years^42-45.

Role of nutraceuticals in various diseases

1. Nutraceutical in cardiovascular disease:

According to the WHO, the main cardiovascular disease(CVD) that account for 17.5 million deaths each year are coronary heart disease, angina pectoris, CHF, hypertension, and myocardial infarction^46.According to a survey, a poor consumption of fruits and vegetables is linked to a high death rate for cardiovascular disease^47and48. For the prevention and treatment of CVD, it is also advised to combine physical activity with nutraceuticals such as antioxidants, dietary fiber, omega-3 PUFA, vitamins, and minerals. It has been established that compounds like polyphenols found in grapes and wine change cellular communication and metabolism, which is linked with a decrease in artery disease^49. In addition to other lifestyle changes, optimal diet, nutraceuticals, vitamins, antioxidants, minerals, weight loss, exercise, quitting smoking, limiting alcohol and caffeine are all effective ways to manage hypertension. Among the nutraceuticals that have the ability to block calcium channels are α-Lipoic acid, magnesium, Vitamin B6, Vitamin C, N-acetyl cysteine, Hawthorne, Celery, ω-3 fatty acids etc^50.

Plant sterols and stanols - Plant sterols are nutraceutical which naturally present in seeds, legumes, nuts, oils etc. These plant sterols having similar chemical structure to cholesterol differ in their side chains^[51].The level of LDL cholesterol can be reduced by stanols and plant sterols.

Green tea extract - Green tea extract is also well known nutraceutical. The presence of a significant amount of antioxidants like Flavon-3-ols and catechin makes green tea extract a cardiac preventative extract. Therefore, it is advised to consume green tea extracts for the treatment of CVD^52.

Dietary fiber - Defatted rice bran is a source of dietary fiber that also contains laxative and cholesterol-lowering properties, which can help to treat cardiovascular disease, cancer, and diabetes^53.

Garlic - Garlic is a nutraceutical with numerous health benefits. The component of garlic called allicin plays a key role in the mechanism that lowers the level of lipids in the body^54.Allicin is inhibitor of enzymes like HMG-CoA reductase, acetyl-CoA synthetase, squalene which are responsible for production of cholesterol.

2. Nutraceutical in cancer:

Cancer is a condition when cells in our bodies divide abnormally. Tumors develop as a result of the accumulation of these aberrant cells in any area of the body^55. Malignant tumors were the cause of 12% of the almost 56 million deaths globally in 2000 due to all causes. In 2020, there will be 15 million new instances of cancer, increase by 50%, according to the World Cancer Report's estimates^56.Due to low side effects of nutraceutical; these are used for cure of cancer. These nutraceuticals work through a variety of mechanisms, some of which include inducing cell cycle arrest, stimulating the host immune system, and increasing the sensitivity of proliferating cells to cytotoxic agents^57.

Flavonoids - Recent research demonstrates that eating a diet high in flavonoids reduces the risk of developing many cancers, including breast, colon, and prostate cancer. The several varieties of flavonoids, such as flavanols, flavones, and anthocyanins, are classified according to their structural characteristics. It causes apoptosis and inhibit proliferation in cancerous cell^58.

Saponins - Saponins are present in soybeans, spinach, tomatoes, potatoes, and alfalfa. Yucca schidigera and Quillaja saponaria are the primary sources of commercial saponin extraction. Because they stop cancer cells from proliferating, saponins are thought to have antitumor properties that reduce the chance of developing cancer^59.

Resveratrol - Recent studies have shown that resveratrol, a polyphenol, has many positive effects for the treatment of cancer. For example, it inhibits many stages of carcinogenesis and treats a variety of cancers, including those connected to the pancreas, breast, skin, colon, and prostate. Blueberries, peanuts, raspberries, and other fruits naturally contain resveratrol^60.

Pectin - Apples contain pectin. Modified citrus pectin , a new variety of citrus pectin, has been demonstrated to stop prostate cancer spread by preventing the cancer cells adhesion to healthy cells. Derivatives of phenolic acid that exist naturally are thought to have anticancer potential^61-63.

Other nutraceuticals like curcumin, garlic, tea polyphenol, beta-carotene, tannins, ellagic acid etc. also have anticancer properties.

3. Nutraceutical in diabetes:

Blood glucose levels that are unusually high are a sign of diabetes mellitus because inadequate insulin is produced. According to projections, there will be 366 million individuals living with diabetes worldwide by 2003, up from 171 million in 2000^64. Type 1 and Type 2 diabetes mellitus are the two categories of diabetes mellitus. People with poor health and young ages are more likely to develop type 1 diabetes. It is an autoimmune condition brought on by oxidative stress that harms the beta cells in the pancreas and result in decrease production of insulin. Type 2 diabetes is a hereditary condition that is passed down through families from one generation to the next and is linked to a relative insulin deficit. Persons over the age of 40 are more likely to have type 2 diabetes. In both types there is increase in blood glucose level^65.

Docosahexaenoic acid - It is essential for neurovisual development and affects insulin resistance. This is crucial for pregnant women who have gestational diabetes mellitus because it supports the requirement for essential fatty acids ^66.

Omega-3 fatty acid - The glucose tolerance of patients who are prone to diabetes may be reduced by omega-3 fatty acids. Patients with diabetes may benefit from n-3 fatty acid ethyl esters^67.

Dietary fiber - Psyllium derived dietary fibers have been widely employed as food additives, pharmaceutical supplements, and food products to help people lose weight, control their blood sugar levels, and treat hyperlipidemia and diabetes^68.

4. Nutraceutical in obesity:

The accumulation of an abnormal quantity of body fat is considered obesity, which is a global public health issue. It is a known risk factor for numerous diseases including osteoarthritis, cancer, angina pectoris, congestive heart failure (CHF), hypertension, hyperlipidemia, respiratory problems, renal vein thrombosis etc^69. The growing accessibility of high-fat, calorie-dense meals is one of the main reasons why obesity rates are rising so quickly^70. Buckwheat seed proteins help with obesity and constipation by acting like natural fibers found in meals^71. Weight loss may be aided by 5-hydroxytryptophan and green tea extract; the former reduces hunger, the latter raises metabolic rate. Additionally, some nutraceuticals that are derived from plants, such as caffeine, chitosan, ephedrine, and green tea, are used to reduce body weight^72. Vitamin C, chitosan, and glucomannan are a few more nutraceuticals that can be found in dietary supplements. Obesity is treated with the help of nutritional supplements including capsaicin, conjugated linoleic acid (CLA), and Momordica charantia (MC)^73.

Nutraceutical is also beneficial in inflammatory disorder, allergy, osteoarthritis, Alzheimer's disease, Parkinson's disease etc.

Conclusion:

Nutraceuticals have demonstrated their capacity to promote health and prevent disease, and they should be consumed in accordance with their acceptable recommended consumption. It is crucial that the well documented health advantages are caused by the nutrients included in a variety of foods, fruits, and vegetables. Nutraceuticals like lycopene protect the skin, lutein and zeaxanthin promotes eye health, vitamin C and vitamin E prevent the damaging of skin by UVA and UVB radiation. However, maintaining their effectiveness, safety, and purity is essential to their continued success.

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Received on 25.03.2023 Accepted on 14.04.2023

Int. J. Tech. 2022; 12(2):35-42.

DOI: 10.52711/2231-3915.2022.00007