Past, Present, and Likely Future of Nutraceuticals in India: Evolving Role of Pharmaceutical Physicians
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10353663/
Nutraceuticals are gaining importance owing to the current pandemic situation and increasing focus on overall health. Nutraceuticals include products, which help in maintaining immunity and prevent diseases. It also includes products that support the optimal functioning of the human body. Poor nutrition plays an important role in lifestyle-related disorders as well. Various nutraceuticals have exhibited therapeutic potential, hence gaining popularity. Nutraceuticals are mainly categorized into dietary supplements and functional foods. With multiple factors contributing to the growth of nutraceutical industry in India, we are marching toward global leadership in nutraceuticals. Food Safety and Standards Authority of India (FSSAI) is solely responsible for regulating the approvals, promotions, and labeling standards for health supplements and nutraceuticals. As the understanding of these nutraceuticals is improving, the regulations are becoming stricter and there is a pressing need to monitor the usage of such products regularly and stringently. Nutrivigilance and phytovigilance are relatively new concepts in our country; however, regulatory authorities need to proactively observe the adverse effects and issues related to substandard and counterfeit nutraceutical products. Healthcare professionals including pharmaceutical physicians can play an important role in safeguarding the population by advocating the rational use of nutraceuticals, food supplements, and consumer health products.
INTRODUCTION
“Let food be thy medicine and medicine be thy food” was quoted by Hippocrates in 400 BC, which holds true in today’s world as well. The importance of food and nutrition in disease pathophysiology and prevention was never in doubt. Significance of right nutrition is ever increasing especially with the increasing trend of lifestyle-related diseases and novel infectious diseases these days. Focus of public health is moving from “curative” intent to “preventive” one. Although patients are pondering over the importance of food in both causing and relieving their problems, clinicians’ knowledge of nutrition is still limited. Most feel much more comfortable with drugs than foods, and the “food as medicine” philosophy of Hippocrates has been largely neglected. However, that attitude is changing over the last decade and the focus on “nutraceuticals” is ever-rising.
The word nutraceuticals contains “nutrition” and “pharmaceuticals.” The term “nutraceutical” was initially devised by Dr. Stephen DeFelice, originator of the Foundation of Innovation Medicine, Crawford, New Jersey, in 1989.[1] Now, the old proverb “an apple day keeps a doctor away” has become “a nutraceutical a day keeps the doctor away.” The idea of nutraceuticals has evolved in the last three decades.[2] Considering the growing importance of nutraceuticals, we present this narrative review of its usage, rationale, growth potential, regulatory scenario, and future challenges with the ever-increasing use of nutraceuticals in India. We also explored the expanding responsibility of pharmaceutical physicians to regulate the rational use of nutraceuticals, its promotion, and vigilance for adverse events due to such products.
Nutraceuticals and rationale for its use
Dietary components assume critical importance in health and disease pathophysiology. Most of the lifestyle-related disorders are related to diet, for example, obesity, hypertension, and diabetes. Poor nutritional status leads to poor immunity making the individual susceptible to various infections. Nutritional deficiencies are also common in developing countries such as India, which has led to the development of national healthcare programs for diseases such as anemia, goiter, and blindness. Fortification of table salt with iodine and wheat flour with folic acid has been utilized to counter iodine deficiency and iron deficiency for a long time in our country. The results of these healthcare programs highlighted the importance of fortified foods, nutraceuticals, and their role in well-being. With advances in science and innovative technologies, new ways of enriching food have evolved. Now, our understanding of nutraceuticals and their role as preventive and therapeutic treatments has much improved.[3,4]
The government of India has focused on improving the nutritional status of its citizen. The coronavirus disease 2019 (COVID-19) pandemic situation has highlighted the interdependence of nutritional status and economic status of our country.[5] The lessons from the pandemic are likely to enhance the attention and importance of nutrition in public health programs, healthcare strategies, and schemes than ever before to prevent disease. This pandemic has also led to a shift in consumer behavior with the focus on health and well-being. The focus on enhancing one’s immunity has increased significantly. It augurs well coupled with rich heritage of herbal and Ayurveda medicine that our country has. With agriculture being one of the biggest industries in India, there is abundant availability of raw materials and ingredients for nutraceuticals and food supplements.[5] Furthermore, there are other innovative sources such as marine environment being explored for nutraceuticals and health supplements.[6] There is enough skilled manpower, manufacturing expertise, and excellence, which can fast-track the growth of nutraceutical industry in India.
Indian nutraceutical market — A breakthrough success story
The nutraceutical market in India is evolving and is estimated to reach USD 18 billion by the end of 2025 as compared to USD 4 billion by end of 2020. So it is more than four times growth in a span of five years.[7,8] The interest of foreign investors in the nutraceutical market has gone up significantly due to the opening of 100% Foreign Direct Investment (FDI) in the nutraceutical and food supplement manufacturing sector, and such companies can also sell their products through wholesale, retail, or e-commerce platform. Thus, the FDI has increased from USD 131.4 million in 2012 to USD 584.7 million in 2019.[7,8] With such phenomenal growth, India is poised to be a global leader in nutraceuticals.
Regulation of nutraceuticals in India
Currently, the Food Safety and Standards Authority of India (FSSAI) regulates the standards for health supplements and nutraceuticals. The FSSAI defined regulatory guidelines for the approval of nutraceuticals in India. These guidelines cover eight categories of functional foods, as given in Figure 1. To avoid confusion between categories of nutraceuticals, FSSAI issued a guidance note on August 28, 2020. It clarifies that health supplements are intended to supplement the normal diet of a person with one or more nutrients with known benefits. Foods for special dietary use (FSDU) are specially processed or formulated to satisfy dietary requirements for specific ailments. Foods for special medical purposes (FSMP) are intended for exclusive or partial feed to people with digestive issues.[9] Nutraceuticals are naturally occurring ingredients that are extracted, isolated, and purified from food or nonfood sources, which when consumed provide physiological benefits and maintain the good health of the recipients. Health supplements and nutraceuticals are targeted for the healthy population with age above five years and above two years, respectively. However, the FSDU and FSMP are for people with specific requirements with age above two years.[9]
Classification of food products
The Food Safety and Standards Act (FSSA) of 2006 consists of 21 chapters, and in that, the fourth article of the act regulates nutraceuticals, dietary supplements and various functional foods, and their production, manufacturing, marketing, sale, distribution, and import. For a considerable length of time, Food and Drug Administration (FDA) controlled dietary supplements as sustenance to guarantee that they were protected and that their marking was honest and not deluding. In 2006, the Indian government passed FSSA to incorporate and streamline the numerous controls covering nutraceuticals, fortified food, and dietary supplements.[10]
FSSAI act was passed by the parliament in 2006, but FSSAI was implemented in 2008. On September 5, 2008, the government of India advised the foundation of the FSSAI as a top administrative expert, comprising a chairperson and 22 individuals.[11]
In 2011, FSSAI released the food safety and standard (FSS) rules. These rules included the regulations for licensing and registration of food products, food business, packaging and labeling methods, standards for food products, and additives used in the food product. The FSS rules were put into practice in August 2011. FSS regulations in 2015 provided guidelines regarding nutraceuticals along with food/health supplements, foods with special dietary purposes, medicinal purposes, and novel and functional foods. As per these regulations, nutraceuticals shall contain any of the ingredients specified in the “Food Act Schedule” as given in Table 1.[12] As per these rules, the following information should be included in any claimed novel foods: chemical composition of the engineered food, surface modification/surface chemistry, primary particle size, solubility, digestibility, amount of nanomaterial if any in the food product, and specific claim, if applicable.[12]
Table 1
Schedule wise ingredients as per FSSA 2016
| Schedule | Ingredients |
|---|---|
| I | Vitamins and minerals |
| II | Essential amino acids, Non-essential amino acids and Nucleotides |
| III | Values for vitamins, minerals and trace elements allowed to be used in food for special dietary use and food for special medical purpose |
| IV | Plants and botanical ingredients |
| V | Food additives |
| VI | Nutraceuticals |
| VII | Probiotics |
| VIII | Prebiotics |
In 1990, Nutrition Labeling and Education Act (NLEA) defined how food is labeled, including nutrition labeling, in accordance with definitions established by FDA, that was updated with “Food Safety and Standards (Packaging and Labeling) Regulation, 2011.” These regulations allowed greater legal security and more predictable environment. It supports innovation and prevents unfair competition from manufacturers using false or misleading claims. If positive claims cannot be made, the regulation does not oblige anyone to make negative claims about the product.[12,13] In 2018, Food Safety and Standards (Advertising and Claims) Regulations came into place. It was mainly to regulate the claims and advertisements by food business operators in respect of their food products. General principles for advertising and claims of nutraceuticals from these regulations are summarized in Table 2.[14] All important regulations and amendments can be accessed from the FSSAI website (https://www.fssai.gov.in/cms/food-safety-and-standards-regulations.php).
Table 2
General principles for advertising and claims of Nutraceuticals
| Principle |
|---|
| • Claims must be truthful, unambiguous, meaningful, not misleading and help consumers to comprehend the information provided. |
| • Claims shall not encourage or condone excess consumption of a particular food. |
| • Claims shall not state, suggest or imply that a balanced and varied diet cannot provide appropriate quantities of nutrients as required by the body. |
| • Where the claimed benefit is related to or dependent on the method of preparation of the food the same shall be provided on the label. |
| • Claims shall specify the number of servings of the food per day for the claimed benefit. |
| • The claim that a food has certain nutritional or health attributes shall be scientifically substantiated by validated methods of characterizing or quantifying the ingredient or substance that is the basis for the claim. |
| • Where the meaning of a trade mark, brand name or fancy name containing adjectives such as “natural”, “fresh”, “pure”, “original”, “traditional”, “authentic”, “genuine”, “real”, etc., appearing in the labeling, presentation or advertising of a food is such that it is likely to mislead consumer as to the nature of the food, in such cases a disclaimer in not less than 3 mm size shall be given at appropriate place on the label stating that –“This is only a brand name or trade mark and does not represent its true nature”. |
| • All disclaimers related to a claim shall be conspicuous and legible. |
| • Notwithstanding the mandatory declaration of Food Safety and Standards Authority of India logo and license number as per Food Safety and Standards (Packaging and Labeling) Regulations, 2011, no claim or promotion of sale, supply, use and consumption of articles of foods shall be made using Food Safety and Standards Authority of India logo and license number. |
| • Advertisements shall also not undermine the importance of healthy lifestyles. |
| • Advertisements for food or beverages shall not be promoted or portrayed as a meal replacement unless otherwise specifically permitted as a meal replacement under any other Regulations made under Food Safety and Standards Act, 2006 |
| • Claims in advertisements shall be consistent with information on the label of the food or beverage. |
| • No advertisement shall be made for food products which is deceptive to the consumers. |
| • Every declaration which is required to be made on advertisements under these regulations shall be conspicuous and legible. |
Current stepwise process to register nutraceuticals in India is summarized in Figure 2[15]
Steps to register nutritional products in India
Important nutraceutical products in India and their uses
Nutraceuticals have been used for centuries. Their role is highlighted in various chronic diseases such as type 2 diabetes, inflammatory bowel disease, various enteropathies, and malabsorption syndromes leading to nutritional deficiencies.[16-25] Fish oil, vitamin B6, vitamin B12, and flaxseed oil reduce the risk of preterm labor, influence steroidal output, and regulate the menstrual cycle.[20] Dietary habits play a significant role in hypertension, coronary heart disease, heart failure, peripheral vascular disease, and cerebrovascular disease. Vitamin D, coenzyme Q 10, folic acid, omega-3, and polyphenols may reduce arterial disease by altering cellular metabolism. Flavonoids are present in vegetables such as onions and fruits such as grapes, apples, and cherries. Ginger has antioxidant and anti-inflammatory properties and is used to treat hypertension and palpitations. Green and yellow vegetables, rich in phytosterol, reduce the risk of cardiovascular diseases by blocking the uptake of cholesterol.[20] Nutraceuticals such as curcumin, lutein, lycopene, turmeric, and beta-carotene may exert positive effects on specific diseases such as neurodegenerative diseases—Alzheimer’s disease and Parkinson’s disease by combating oxidative stress. Jujube is shown to be effective in regaining memory in Alzheimer’s disease patients.[26,27] Various herbal products containing Amla, Guduchi, and Tulsi have also shown beneficial effects in improving learning and memory.[27-31] Important nutraceuticals with uses are summarized in Table 3, while important herbs and their properties are listed in Table 4.[16-31]
Table 3
Important nutritional products with their uses
| Nutrient | Uses |
|---|---|
| Calcium | Reduces risk of osteoporosis, |
| Iron | Helps in Hemoglobin formation and used for management of anemia |
| Magnesium | Diet high in magnesium, potassium, and calcium, and low in sodium and fat can decrease blood pressure, May reduce the risk of postmenopausal osteoporosis |
| Zinc | Increases circulating T cells and increased killing capacity of lymphocytes, Reduction in the incidence of common cold |
| Selenium | Neurological deficits due to iodine deficiency may improve with selenium, Antioxidant effects delayed progression of HIV |
| Chromium | With the help of insulin converts carbohydrates and fats into energy, Deficiency is associated with weight loss, neuropathy and glucose intolerance |
| Polyphenols, flavonoids | Present in fruits, vegetables, nuts. Flavonoids include proanthocyanidins, quercetin, and epicatechin, found mainly in chocolate, tea, and wine and possess antioxidant properties. It Inhibits LDL oxidation and platelet aggregation and enhances production of NO, thus leading to cardio-protection |
| Fish oils | Contains N-3 polyunsaturated fatty acids, Biological effects: inhibition of hepatic synthesis and secretion of triacylglycerol and VLDL and reduced postprandial lipemia, increased circulating HDL, inhibition of platelet aggregation and prevention of cardiac arrhythmias. Diets which include cold water fish are associated with reduced incidence of heart ailments |
| Probiotics | Live microorganisms when administered in adequate amounts give out to health benefit on the host e.g. yogurts. Physiological effects: reduction of gut pH, production of some digestive enzymes and vitamins, production of antibacterial substances, e.g., organic acids, bacteriocins, reconstruction of microbiomes in diarrhea, antibiotic therapy, reduction of cholesterol level in the blood, suppression of bacterial infections, removal of carcinogens |
| Prebiotics | Non-digestible or low-digestible food ingredients that benefit the host organism by selectively stimulating the growth or activity of one or a limited number of probiotic bacteria in the colon. Lactulose, galacto-oligosaccharides, fructo-oligosaccharides, inulin and its hydrolysates, malto-oligosaccharides, and resistant starch. Food sources: onion, garlic, asparagus, artichoke, leek, bananas, tomatoes, chicory. Advantage: Can be stable for longer period of time |
| Antioxidants | Onions, Broccoli, Soybean, Tomato, Carrot, Brussels sprouts, Kale, Cabbage, Green tea, Cauliflower, Red beets, Garlic, Cocoa, Blackberry, Cranberries Blueberry, Red grapes, Prunes, Citrus fruits are rich in antioxidants. |
Table 4
Important herbs/herbal products with their properties
| Herb | Properties |
|---|---|
| Emblica officinalis / Phyllanthus Emblica (Amla) | A potent Rasayana with antimicrobial, antipyretic, antioxidant, cardio- and hepatoprotective, anticancer, anti-diabetic, analgesic, immunomodulatory effects |
| Withania somnifera (Ashwagandha) | Used for maintaining vitality and longevity. A popular Rasayana with historic uses in cases of lack of libido, chronic illnesses including mental illness and fatigue. Possesses anti-microbial, antioxidant, immunomodulatory, cardiovascular and hepatic protection and anti-aging effects |
| Bacopa monnieri (Bramhi) | Medhya Rasayana; Nervous system and a memory enhancer known to have anamnestic, nootropic, neuroprotective, immune-stimulatory and antifertility effects. |
| Tinospora cordifolia (Guduchi) | Rich in Vitamin C and trace elements with antibacterial and immune-boosting effects. Known to generate immune resistance, boosting memory, digestive health, longevity |
| Ocimum Sanctum (Tulsi) | Leaves are rich in essential oil while seeds contain fixed oil and mucilage. Eugenol is the major component of Tulsi’s essential oil and has wide importance as a nutraceutical. Secondary metabolites of Tulsi have antioxidant, anti-cancer, anti-inflammatory, anti-microbial, anti-stress, immunomodulatory and radiation protective activities. Bhavana with Ocimum Sanctum augment the actions of other herbal products. |
| Brahma rasayana | Boosts vitality, youth, longevity, memory, physical strength and concentration. Also known to be an antioxidant and immunity stimulator. |
| Chyawanaprasha | “Foremost of all Rasayana” and “elixir of life”. Known to boost intellect, memory, concentration, longevity, physical and mental strength, immunity against diseases, digestion and complexion. It is antitussive and anti-asthmatic. |
Examples of marketed nutraceutical products, include Revital, Complan, Horlicks, Ensure, Peptamen, NutriMix, and capsules containing fish liver oils—Nutrova, Curcumin Boost, Chyawanprash, etc. Example for nutraceutical are as follows: use of nutraceuticals in clinical practice, a randomized, double-blinded, placebo-controlled, clinical study of the effects of a nutraceutical combination (LEVELIP DUO®) on LDL cholesterol levels and lipid pattern in subjects with suboptimal blood cholesterol levels (NATCOL Study). Nutraceutical-related ongoing clinical studies in India are also available at https://clinicaltrials.gov/.
Nutrivigilance, phytovigilance, and its importance
Due to our limited knowledge of nutraceuticals and herbal products, we often end up misusing them. Irrational use of such products is common in our country. There is a rampant use of nutraceuticals, herbal products, and health supplements with no clear pathway to report the associated adverse events. It poses a major challenge of identifying such adverse events and taking the corrective actions for the same.[32-34]
FSSAI needs to adopt proactive role for nutrivigilance. Stricter regulations are needed for the approval of nutraceuticals and health supplements. There must be a plan to monitor the long-term effect of these products. The lack of robust clinical studies with such products is a major limitation in a current regulatory scenario. Healthcare professionals can play an important role in nutrivigilance by proactively identifying the use of such products and any adverse events. It is essential to impart education at the primary care level about the rational use of nutraceuticals and the possible limitations associated with the products. Special populations need to use such products carefully; for example, sport persons and athletes should be careful about the ingredients of health supplements or sport drinks they are taking to avoid inadvertent doping.[35,36] The use of digital tools to educate the general population about the possible impacts of irrational use of nutraceuticals should be initiated by FSSAI. The time has come to specify the indications for complex nutraceutical products as it is specified for pharmaceutical products. It is also essential to curb unsubstantiated and false claims and their advertisement at the mass level. Need to strictly regulate the promotional materials for nutraceuticals.
Evolving role of medical affairs/pharmaceutical physician for nutraceuticals and consumer health products
The medical affairs function is a connecting link between commercial teams such as sales and marketing with research and development and with external stakeholders such as healthcare professionals and public. Hence, it plays an integral role in disseminating important and scientifically valid information on nutraceutical products to commercial teams and healthcare professionals, that is, to internal and external stakeholders. Medical affairs need to interact with key opinion leaders or key medical experts (KME) to understand the unmet needs and to impart key scientific messages related to the products. As regulatory norms are getting stricter for the promotion and use of nutraceutical products, the role of medical affairs further becomes indispensable. There is increasing scrutiny of promotional materials and product claims for nutraceuticals, which needs to be thoroughly backed by scientific evidence. Medical affairs can support the claim substantiation with evidence generation from proof of concept and clinical studies for nutritional products as part of evidence-based practice. Real-world data on product usage at large population can be generated. The value proposition of the products with health economics and outcomes research (HEOR) data can be justified.[37-39] Understanding the unmet needs and guiding the future development of novel and innovative products are also key roles of medical affairs. The innovation cycle with such nutraceutical products is small, and there is a need to continue evaluating new formulations, innovative ingredients, and/or delivery mechanisms with strong scientific rationale. Disseminating the evidence-based data on nutraceutical products in ethical and scientific manner forms a core for the medical affairs function. There is an increasing responsibility for the medical affairs team to promote the rationale use of nutraceuticals and nutrivigilance. This adds to the ever-expanding role of pharmaceutical physicians.[37-39] as summarized in Figure 3.
Role of medical affairs in consumer health
To summarize, nutraceuticals are of importance and its significance in maintaining a healthy lifestyle is increasing. However, it is important to use them judiciously. The market is flooded with irrational combinations of nutraceutical products; hence, regulatory authorities need to take stringent actions for the same. Nutrivigilance and phytovigilance are the need of hour, and healthcare professionals will have to play the role of a torch bearer. Pharmaceutical physicians need to play their part with their multifaceted role in medical affairs in nutraceuticals and consumer health industry.
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