The term Nutraceutical, coined by Dr. Stephen De Felice in 1989 from the words nutrition and pharmaceutical, refers to food extracts claimed to have a medicinal effect on human health. The other definition of a nutraceutical is “a food extract that has physiological benefits or that provides protection against chronic disease.” Unlike pharmaceuticals, nutraceuticals are widely available and minimally monitored. Until now, marketing firms have had no regulatory obligation to provide evidence-based claims about the function and effectiveness of their product, but many firms have still attempted to provide some scientific backing of their products in order to increase their credibility. The fact remains that a marketing firm has a moral responsibility to state what is proven or not proven to the consumers. This article delves into these issues.

The US FDA has recently released a guideline, as, Section 403(r) (6), of the Federal Food, Drug, and Cosmetic Act (the Act) (21 U.S.C. 343(r)(6)) which states that a manufacturer of a dietary supplement making a nutritional deficiency, structure/function, or general well-being claim should have substantiation that the claim is truthful and not misleading. Now, terms such as “substantiation,” “truthfulness,” and “not misleading” are open to individual interpretation, and in the absence of any specific and precise definitions, one can argue that these are the best possible terminologies. Thus, it is essential for all stakeholders to consistently work to bring in precision and to eliminate ambiguities in a labeled claim.

Pharmaceuticals vs  nutraceuticals
According to the World Health Organization, “A drug is any substance or product that is used or intended to be used to modify or explore physiological systems or pathological states for the benefit of the recipient.” Such being the case, one can argue that a nutraceutical need not have a different regulation if it is going to “modify or explore physiological systems or pathological states for the benefit of the recipient.” Also, the term “dietary supplement” could refer to (1) supplements that either aid/help/complement a specific drug or (2) supplements that simply give a small incremental value in the treatment of certain diseases, for which no specific treatment exists. When all is said and done, factually, one cannot obtain the same information (e.g., complete toxicology data, pharmacokinetics, and adverse drug reactions profile) from nutraceuticals and dietary supplements as one can from drugs. Trying to obtain the same information from nutraceuticals would mean having to ignore the basic experience-based medicinal practice outright and would make the development of the nutraceutical industry yet another high cost activity.  At the same time, the nutraceutical industry cannot make evasive maneuvers by giving anecdotes and yet make a label claim. While regulatory guidelines are being framed, erring on the right side remains a challenge for all stakeholders.

Labeled claims of nutraceuticals
Labeled claims on nutraceutical components give information about the health potential of the dietary supplement and how it may be supportive in reducing the risk of certain diseases. Some examples of dietary supplements include folic acid in breakfast cereals, calcium in dairy products, and vitamins in health drinks

Many scientific, academic, and regulatory organizations are facing the challenge of establishing a scientific basis to support the claims made for the key components of a nutraceutical. The US FDA has classified claims into four categories, as shown in the table below.

Role of regulatory boards
The Food Safety and Standards (FSAS) Act 2006 (India) clarifies in the clause titled “Duties and functions of Food Authority” 16 3 (b) that the Food Authority of India will (a) provide scientific advice and technical support to the Central Government and the State Governments in matters of framing the policy and rules in areas which have a direct or indirect bearing on food safety and nutrition and
 (b) search, collect, collate, analyze, and summarize relevant scientific and technical data particularly relating to
(i)    food consumption and the exposure of individuals to risks related to the consumption of food
(ii)    incidence and prevalence of biological risk
(iii)    contaminants in food
(iv)    residues of various contaminants
(v)    identification of emerging risks and
(vi) introduction of rapid alert system

Although the FSAS Act in India had issued guidelines in the year 2006, a firm regulation for the labeling of nutraceutical components is yet to be established. In the meantime, FDA regulations can be looked upon as a tenet for labeled claims.

Evidence-based claims
Evidence-based claims pertain to having proper and valid evidence for a nutraceutical product. Such claims may be of two types:

Claims based on anecdotes
Claims based on studies that are published and peer reviewed
Needless to say, the latter is preferred more in the nutraceutical industry since there are  scientific rationales behind it. The former gives consumers a vague idea about the product, leaving it up to them to decide whether to consume the product or not. For instance, a popular health drink brand promotes its product for an entire family. However, if the company opines, on the basis of some epidemiological data, that their product also prevents cardiovascular events, then the company should necessarily prove all of their claims.

The most ideal methodology would be to first work on the evidence—both direct and indirect—and then to market the product. At present, not many nutraceutical products fall into this category, and it is now time that manufacturers work on proving their claims through proper clinical trials. For instance, if a manufacturer is promoting a certain nutraceutical biscuit containing fiber meant to minimize the effects of hyperglycemia in diabetics, the company should undertake a study; the outcome of the study should clearly show that patients consuming X number of biscuits had greater percentage reduction of glucose over the baseline in comparison to the control group.

Types of proposed evidences for making claims
The key word in the present context is “evidence.” Proof, justification, or substantiation is the responsibility of the manufacturer and the regulator. The regulator and manufacturers should take utmost care while creating the proof or justification or substantiation so that the public or the community is not misled.

Hard end points
These end points should be a direct evidence for the claim.
To elucidate one point: Many traditional edible pastes (like herbal pastes) are claimed to elicit immune response and help cure asthma. Some herbals are also approved as diet supplements although they would fit better into a traditional system of medicine. However, the labels on these herbal products do not state the role of the ingredients of the product in the cure of the disease (asthma, in this case). Thus, it is important that the labels carry a definite substantiation of the claim. For instance, the product should not act on the hypothalamo-pituitary axis like corticosteroids do and should not be unsuitable or harmful to people with cardiovascular disease. The evidence must show improvement in lung function or a significant reduction in the frequency and severity of asthmatic attacks as compared to the control group.

Surrogate end points
These end points may or may not be direct evidence for the claim, but they should come under the scope of the product. For example, a calcium supplement is claimed to prevent fractures in post-menopausal women owing to its greater bioavailability. In such a case, the hard end point would be reduction in the number of fractures or frequency of fractures during the post-menopausal period in women consuming this calcium supplement in comparison with the placebo group or another reference calcium supplement. However, practically, this is a very difficult criterion to establish on the basis of clinical studies. Henceforth, a surrogate marker of the following types may be recommended:

1) Measurement of bone mineral density (BMD) over a period of one year. However, at times, even this may require a large capital and the process is time-consuming.
2) Alternatively studying the urinary excretion pattern of calcium and nocturnal parathyroid hormone (PTH) levels for a short period of time, which, if increased, indicates calcium absorption by the bones.

Existing regulations and their efficacies
Although some guidelines exist in many countries, the existing regulations are not uniform and, in many areas, still have some limitations. For instance, the demarcation of claims has not yet been established in India, and the US and Europe have a contrasting opinion on this. A Codex Alimentarius meeting was commissioned in 1963 by FAO and WHO to discuss this issue. The Codex Alimentarius Commission was created to develop food standards, guidelines, and related texts such as codes of practice under the Joint FAO/WHO Food Standards Programme. The main purposes of this Programme are to protect the health of the consumers and to ensure fair trade practices in the food trade, and to promote coordination of all food standards work undertaken by international governmental and non-governmental organizations.

While 74 countries had participated and a conclusion was reached, the regulations are inadequate.

Countries have been categorized into 4 groups on the basis of the types of regulations they have imposed on the labeling of health foods:

• Mandatory labeling enforced (e.g., U.S.A, Canada, Australia, Malaysia)
• Voluntary labeling unless a nutrition claim has been made (e.g., EU, South Africa)
• Voluntary, except for certain foods with special dietary uses (e.g., China, India)
• No regulations in place (e.g., Pakistan, Egypt, Nepal)

What can be done?
The four health claims mentioned above - nutrient content, health claim, qualified health claim, and structural/functional claim— need to be regulated by the government. The FSAS Act that was proposed in 2006 is yet to establish a standard protocol or guidelines. Therefore, the time is ripe to ponder over this issue to contribute ideas towards restrictions on labeled claims in the fast-growing nutraceuticals market. Listed below are suggestions for making and implementing such labeled claims:

Health claims should have the Recommended Dietary Allowance (RDA) on their label.
While this is currently being implemented (the India RDA norms were introduced in the year 1989), the government has to establish a process or protocol for periodical review. The Indian standards for various micronutrients also need a review.

The authorities should review all health claims and regulate the product approval processes at least in a condensed form as compared to drug regulatory norms.

The manufacturers should ideally provide package inserts containing the required evidence of the claims made. The labeled claims should be more informative and evidence based. While we recommend this, we also acknowledge the fact that India is a multilingual country and that an insert for products sold in India would run into a large number of pages, which could become a logistics issue. The regulator may preferably check one full text and the abbreviated multilingual texts to determine whether the smaller versions meet the needs.

The websites of the products could contain the results of the studies done or the evidenced amassed to support the claims.

Conclusion
Evidence creation does not mean “cooking up” a story. Evidence creation is a matter of commitment. Every claim that is made should be backed by evidence. Evidence created should stand up to the best of prevailing scientific knowledge. Concerns regarding the cost and time that would go into developing these evidences are very much real. We need to create a body of experts who would mentor the scientists and help them develop their discoveries into a commercial reality. We need to bring in a robust public-private partnership that could act as angel investors to help scientists or research organizations realize their full potential. We need to develop more centers of excellence in various parts of the country while we harmonize our regulatory guidelines to the best of global standards. Evidence creation is no more a necessity to live with; it is the core of product development.