– An Overview of the Nutraceutical Revolution –


April 10, 1997

Dockets Management Branch (HFA-305)
U.S. Food and Drug Administration
Department of Health & Human Services
Room 1-23
12420 Parklawn Drive
Rockville, MD 20857

Re: Docket No. 96N-0364
Comments Re: “Regulation of Medical Foods”

To The Food and Drug Administration:

The Foundation for Innovation in Medicine (FIM) congratulates the FDA for its Advance Notice of Proposed Rulemaking (ANPR) dealing with the regulation of medical foods. FIM is particularly supportive of FDA’s comments regarding the importance of producing quality products and encouraging clinical research. Unfortunately, there is a single item in this proposal that, if implemented, will nullify the general good of the ANPR for it will have a major negative impact on the health of the American people. The proposal which deals with the dramatic constriction of the definition of a medical food will significantly discourage U.S. corporate investment in the clinical research that is essential to demonstrate reasonable efficacy and safety of individual medical food products. We must ask ourselves, “Do we want this?”

Hopefully, the following points will convince FDA of the importance of FIM’s aforementioned point of view:


I. The Nutraceutical Revolution

“Nutraceuticals” is a comprehensive term which includes foods, dietary supplement (as defined in DSHEA), medical foods, etc. that have a health-medical benefit including the prevention and/or treatment of disease. I coined and defined the term in order to give this new U.S. health sector a basis from which the

Federal government could enact rational laws which would encourage nutraceutical research, and particularly clinical trials.

The revolution began in 1983 when the NIH consensus group recommended calcium for the prevention of post-menopausal osteoporosis. Within a very short period of time, the vast majority of Americans knew about this recommendation.

Historically in the United States, the health food industry was a consumer business largely based on traditional home and other remedies. Then in the early 1980’s, the potential medical benefits of products such as calcium and fiber rose to prominence – with university-based clinical data to support claims for their benefits. Sparked by mass and medical media coverage, for the first time in modern U.S. medicine, physicians joined consumers in their broad belief that nutrients have medical value. This marked the entry of nutraceuticals into the mainstream of clinical practice and scientific medical research. It gave rise to an increasingly urgent need to rationalize the scientific and medical development and commercial availability of these products, and factual communications about them, to a new audience of physicians and consumers. Clinical data stole center stage and continue to drive the nutraceutical revolution as exemplified by such products as folic acid and vitamin E.


II. The Federal Government Response – NLEA and DSHEA

Because of increasing consumer belief and media interest in the enormous benefits of nutraceuticals coupled with a continuous flow of positive clinical data supporting these benefits, understandable pressures were brought to bear on the federal government which resulted in the enactment of two historic laws – NLEA and DSHEA. Though symbolically a major breakthrough in the psychology of permitting nutraceutical claims, the NLEA primarily discourages research because it grants the right to make a health-medical claim on a specific food or category of foods to all companies. For example, let’s assume that company A sponsors the research which demonstrates that its chicken soup reduces the morbidity (signs and symptoms) of the common cold. Let’s also assume that the clinical data are sufficiently adequate to convince the FDA to grant the company the right to make that claim. FDA, according to NLEA, must then grant the right to make such a claim to all companies and not only the one that sponsored the research. Why then should company A sponsor the research? To support its competitor? Of course not! Company A will instead spend money on promotion, not research. The NLEA, though a major step forward, is indeed a major deterrent to research oriented companies. History has convincingly supported this view. NLEA has spawned few research-oriented nutraceutical companies .

After NLEA, the Congress passed DSHEA which deals with dietary supplements. DSHEA, unlike NLEA, permits companies, without prior FDA approval, to make claims on dietary supplements regarding structure-function, mechanism of action, well-being and classic deficiencies. DSHEA, however, prohibits claims made regarding the diagnosis, treatment, mitigation, cure, and prevention of disease.

FIM originally believed this major piece of legislation would have an immediate and highly positive impact on creating an academic-corporate research-oriented nutraceutical complex such as exists in the traditional pharmaceutical and biotech industries. Unfortunately, the expected research surge is not yet evident. Companies inform FIM that the vagueness of DSHEA regarding the rules for claimsmaking profoundly discourages research initiatives. For example, if a company invested in clinical research which demonstrated that capsules containing a cranberry extract prevented the recurrence of urinary tract infections in women, it would not be able to make this claim. Instead of claiming, “Our cranberry extract prevents urinary tract infections” – which is the truth – it, under DSHEA, might be able to say, “Our cranberry extract provides dietary support for a healthy urinary tract”, which is a half-truth and can be easily misleading. The conclusion is that the more research one does, the less one can say about it, resulting not only in a corporate hesitancy to invest in research but also a deprivation of the delivery of nature’s promise to all of us. (For the record, FIM does not fully agree with the corporate opinion regarding the degree of the negative impact of DSHEA on research. In time, FIM believes that companies will become comfortable with DSHEA and invest in research. But, this is only a FIM opinion.)


III. Medical Foods

After the passage of DSHEA, companies, both large and small, turned to their legal consultants to advise them regarding the confusing rules of DSHEA concerning product claims. A significant number of them recommended that companies develop products as medical foods and not as dietary supplements. FDA prior approval is not necessary for a health claim for a medical food, and claims can be made regarding the positive nutritional properties of a product related to a disease, provided that corporations stress that the products must be given to patients under a physician’s or medical supervision. Corporations feel much more comfortable with these clear rules for claiming. As a result, though not yet quantified, companies have initiated a substantial number of clinical studies in order to demonstrate the safety and efficacy of many medical food products.

It appears, therefore, that the medical food category has led to what we all want — an increase in preclinical and particularly clinical research. This phenomenon should not be tampered with but encouraged. It naturally follows that the degree of restriction of the definition of a medical food will be followed by a proportional decrease in clinical research. Once more, “Do we want this?”


IV. Epistemologic Chaos: The Need to Understand it

After the NIH consensus group on calcium and osteoporosis, FIM predicted that future positive clinical trials of nutraceutical products would result in new Federal laws that would diminish the restrictions on making health-medical claims. Because of the complexity of the situation, FIM also predicted that these initial new laws would be substantially imperfect and would periodically be improved upon as the societal nutraceutical learning curve increased. The greatest obstacle to bringing about rational changes in new laws and regulations is the attempt by the government to distinguish a health versus a medical claim. The distinction is epistemologically false. In a vast majority of cases there is no distinction between a health and medical claim. Both primarily deal with the prevention and treatment of disease. People consume fiber to both prevent and treat heart disease, feverfew to prevent migraine, and echinacea and chicken soup to treat the common cold – all medical indications related to disease. Logical and effective legislation which encourages research cannot be brought about until the distinction between health and medical claims is abolished. The lack of a surge of clinical research after the passage of DSHEA is a powerful testimony to support this argument for the health related claims permitted in DSHEA are really medical or disease claims, yet companies are prohibited from making such medical or disease claims.

The ANPR distinguishes foods for special dietary use from medical foods. This unnecessary distinction is another example of the epistemologic chaos that creates confusion for research oriented companies. Also, any attempt to define what constitutes a “distinctive nutritional requirement” is truly a difficult one. I would strongly recommend that a group of medical and scientific experts be assembled by the FDA to attempt to clearly define this term for its definition will heavily impact on the degree of nutraceutical research.

The principles that should determine the acceptability of claims for medical foods are similar to those qualitatively similar to those governing medical-health claims for drugs – sufficient evidence for efficacy and safety regardless of its formulation or mechanism of action. At the 1996 FIM conference entitled, “How to Develop, Make Claims On and Market Medical Foods”, FIM recommended the following guidelines for standardizing health-medical claims for all nutraceuticals (foods, dietary supplements, medical foods, etc.):

1. There must be sufficient clinical data to support the claim. (The studies need not be double-blind.)

2. Acceptable surrogate markers (instead of clinical endpoints) can be sufficient to support a claim.

3. Acceptable clinical data to support the product rationale are desirable but not always necessary.

4. All pertinent data must be published in respected medical scientific journals. (This is the first step of the peer review process.)

5. Independent consensus or expert group opinion should be obtained. (This is the second step of the peer review process.)

6. Post-marketing surveillance. This effort should concentrate particularly, though not exclusively, on aspects of safety.

If our society is to enjoy the enormous benefits that ongoing medical food research would bring about, then it is imperative that the definition of the medical food remain unchanged. There is little evidence that DSHEA and the category of “foods for special dietary use” has sparked a surge of corporate preclinical and clinical research. On the other hand, it is common knowledge among industry observers that the medical food regulations have indeed sparked an abundance of research. Considering all the aforementioned points, the wise position would be for all of us to wait a few years to determine, in a quantifiable way, the impact of DSHEA and medical foods on the availability of products with demonstrated health-medical benefits that will positively impact the prevention and treatment of disease.

FDA is particularly concerned about the increasing number of insufficiently substantiated healthmedical claims being made by companies, many of which can be characterized as charlatanic. An effective way to increase such charlatanic behavior would be to constrict the definition of a medical food which, as repeatedly mentioned before, would decrease clinical research which is necessary to support truthful claims. The generation and promotion of sound clinical data supporting effective and safe products is the best way to drive out poorly documented or bad ones. I hope you agree.

Sincerely yours,
Stephen L. DeFelice, M.D.



As you can see, FIM is seriously concerned that DSHEA in its present form, coupled with the ANPR proposal (if implemented) to severely restrict the definition of a medical food, would lead to a very limited R&D nutraceutical industry instead of an expansive and productive one. This would be a catastrophic. Few presently doubt that nutraceuticals can have a major impact on the prevention, treatment and amelioration of many diseases within the very near future if sufficient research funding is available. For this reason, in the ANPR FIM has proposed that the government should not implement any significant changes with medical foods and dietary supplements for the time being. In this fashion, we can better judge if and how the present system will lead to new and robust nutraceutical discovery. More importantly, the dynamics of the system can be more objectively assessed. Having assessed the dynamics, then one can rationally design legal and regulatory modifications to further increase productive research and provide a more effective system to transmit truthful information which is generated by such research.



If, however, because of societal mandates modifications of DSHEA must be made within the near future, FIM proposes the following:

1. Companies be permitted to transmit the results of preclinical and clinical data regarding disease and other human conditions to physicians and other licensed health care professionals who can then transmit such messages both to their constituents and members of the communities either directly or via the media. This will surely encourage companies to conduct clinical research. This would also significantly decrease the negative impact of the potential future limitation of the definition of a medical food. It would further result in a system that would at least, in part, provide a professional and ethical mechanism to deliver truthful information to consumers.

2. The food industry has a vast resource of funds that has not yet been sufficiently mobilized to conduct clinical research. The NLEA certainly has not done so. A mechanism, therefore, to mobilize such funds that will ultimately enhance the health of the American people is sorely needed. FIM proposes, therefore, that conventional foods should have the same opportunities and standards for making claims as dietary supplements under DSHEA.

It is understandable that because of the sudden arrival of the nutraceutical revolution and the complexities of the nutraceutical marketplace, attempts at legislation and regulation would be imperfect; and so they are. FIM urges that further governmental attempts to modify existing laws and regulations should constantly keep in mind the critical need to encourage the growth of a productive nutraceutical research-intensive industry, and to establish a system where truthful information can be effectively delivered both to the healthy and the sick. Research and truthful information are, like the existing laws previously mentioned, inextricably intertwined. We cannot have one without the other.

Stephen L. DeFelice, M.D.