Roger D. Hoestenbach, Jr.
Feed and Fertilizer Control Service, Texas Agricultural Experiment Station, Texas A&M University System, College Station, TX, USA
Abstract
The marketing of nutraceuticals is exceeding the science needed to ensure safe marketing. While many may have beneficial uses, the processes to ensure safety and standards should not be circumvented. There is no compelling reason to hold these products to a lesser standard than that of other feed ingredients.
In the 1980s, we began seeing the term “nutraceutical,” along with similar terms2 like “functional foods,” “designer foods,” “chemopreventive agents,” and “pharmafoods,” and although they have no official standing, they do have recognition with consumers and health care professionals alike. There exist several variations within the definitions that have been suggested for these products, such as provided by the North American Veterinary Nutraceutical Council,”4 a substance which is produced in a purified or extracted form and administered orally to patients to provide agents required for normal body structure and function and administered with the intent of improving the health and well-being of animals” or as described by Boothe,5 “a product that has characteristics of both nutrients and pharmaceuticals.” Boothe5 further suggests that the products are neither drugs nor food. Thus, no federal agency regulates nutraceuticals, and the products are not subject to premarket approval. The Food and Drug Administration (FDA) may not require premarket approval for dietary supplements; however, that does not mean the products do not fall under regulation.
The Dietary Supplements, Health and Education Act (DSHEA) of 1994 is generally considered the definitive legislation for dietary supplements and was an amendment of the Federal Food, Drug, and Cosmetic Act and, therefore, under the regulation authority of the FDA. The passage of DSHEA created considerable confusion over what and how the dietary supplements market is regulated. For example, it appears some have interpreted DSHEA as implied consent for animals since “if it is alright for humans, it has to be okay for animals.” But DSHEA does not apply to animals (Federal Register, 4/22/96).
To best understand current interpretations regarding the regulations as they apply to animals, consider the following definitions:
1. Federal Food, Drug, and Cosmetic Act §201 (f) The term “food” means (1) articles used for food or drink for man or other animals, (2) chewing gum, and (3) articles used for components of any other such article. This definition does not differentiate between food and feed (for animals), and it does not offer separate regulation for food producing animals from those non-food producing animals, as has been suggested by some.
2. Federal Food, Drug, and Cosmetic Act §201 (g)(1) The term “drug” means (A) articles recognized in the official United States Pharmacopeia, official Homeopathic Pharmacopeia of the United States, or official National Formulary, or any supplement to any of them; and (B) articles intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease in man or other animals; and (C) articles (other than food) intended to affect the structure or any function of the body of man or other animals; and (D) articles intended for use as a component of any articles specified in clause (A), (B), or (C); but does not include devices or their components, parts, or accessories. A product that affects the structure or function of the body by providing nutrients is acceptable, but questions have arisen if the product is not usually recognized as a nutrient.
3. Federal Food, Drug, and Cosmetic Act §201 (s) The term “food additive” means any substance the intended use of which results or may reasonably be expected to result, directly or indirectly, in its becoming a component or otherwise affecting the characteristics of any food,… While “food additives are generally considered non-nutritive, they may also include products that are not traditional sources of recognized essential nutrients.
4. 21 C.F.R. §570.30 (a) Generally Recognized As Safe or GRAS may be established by either (1) scientific procedures or (2) use in food prior to January 1, 1958. GRAS is usually approved or affirmed for a specific use. The preponderance of evidence is the responsibility of the applicant and the requirement is the same as for a food additive petition, except a certain amount of the support is expected to come from the public domain.
The term “Commercial Feed,” as defined in the Model Bill1 promoted by the Association of American Feed Control Officials (AAFCO) means all materials or combination of materials which are distributed or intended for distribution for use as feed or for mixing in feed, unless such materials are specifically exempted. Unmixed whole seeds and physically altered entire unmixed seeds, when such whole or physically altered seeds are not chemically changed or are not adulterated within the meaning of section 7(a) of this act, are exempt. The (blank) by rule may exempt from this definition, or from specific provisions of this Act, commodities such as hay, straw, stover, silage, cobs, husks, hulls, and individual chemical compounds or substances when such commodities, compounds or substances are not inter-mixed with other materials, and are not adulterated within the meaning of section 7(a) of this Act. (Note: the only exempted product suggested by the AAFCO Model Regulations is loose salt.) This loosely interprets commercial feed to include essentially everything ingested orally, other than water, except what is exempted by rule.
A “dietary or nutritional supplement” could be defined as any product that provides essential nutrients that supplement the diet to meet physiologic needs and prevent nutritional deficiencies. However, any explicit or implicit claims that a product treats, cures, prevents, or mitigates a disease, or affects the structure or function of the body in a manner other than providing essential nutrients as in food identifies the product as a drug. This requires premarket approval via a new animal drug.
A number of the products being marketed as nutraceuticals (dietary or nutritional supplements) are offered by either implied or specific claims for the prevention or treatment of disease. This identifies them as a drug. Why would they then be identified and offered as “dietary supplements?” Many are not patentable and, since they do not have the profit potential of a patentable substance, it has been perceived that by offering them as dietary supplements, they do not have to meet premarket approvals. This has been speculated as most likely reason that drug clearance is not attempted on many of these products.
While some of these supplements may play a beneficial role in health as part of a varied diet, research regarding the health benefits should be supported.2 And, despite the excitement over potential health benefits, experts should remain cautious. Safety should be of primary concern, and clients should be encouraged not to neglect traditional therapies in lieu of nutraceuticals unless clinical evidence of efficacy exists.6 Safety is the critical issue. Optimum levels must be determined because a number of animal studies show that some of the same phytochemicals (e.g., allyl isothiocyanate) investigated for cancer preventing properties can be carcinogenic at high concentrations.3 Thus, the 15th century doctrine of Paracelsus, that “nutriment is both food and poison, its dosage makes it either poison or remedy” receives additional support.
The veterinary profession should support the development of production standards. Many of these products, though represented by certificates of content, are not being tested or prepared by any established standards. Without proper testing methods and standards for production, neither concentrations nor quality can be assured either between products or even within product lines.
What about “natural products?” Natural does not mean safe—arsenic is natural. What about products used by ancient cultures? Surely hundreds of years of use indicate both safety and efficacy? Gossypol and ground rhinoceros horn are still being used. Established American companies may not always be trusted as they push for new or expanded markets. A prominent manufacturer was recently found to be promoting formulas not supported by research, but by anecdotal information and market trend analysis. Yank Coble, MD, AMA, said a lot when he stated, “In God we trust, all others need research.”
In conclusion, how can anyone argue that generally acceptable scientific principles* should be utilized to support the safety, utility, and efficacy of these products. There does not appear to be any valid reasons for holding these substances to a lesser standard than those used for other nutrients.
*Here are some good general guidelines7,8 for evaluating studies, particularly clinical trials, that have been adapted from User’s Guide to the Medical Literature:
Validity of the study?
Was the assignment of subjects randomized?
Were all the subjects entering into the study accounted for and attributed at its conclusion?
Were the study participants “blind” to the assigned treatments?
Were groups similar at the start of the study?
Aside from the intervention studied, were the groups treated equally?
Assessing study results?
How large was the treatment effect?
How precise was the estimate of treatment effect?
Claim supportable?
Can the results be applied to the target species?
Were all important outcomes considered?
Was the claim supported?
Literature Cited
1. AAFCO. 1999. Model Bill. Official Publication. Association of American Feed Control Officials. Pp. 69–80.
2. A.D.A. 1995. Position of The American Dietetic Association: Phytochemicals and functional foods. J Am Dietetic Assoc. 95(4):493–496.
3. Ames, B.N., R. Magaw, and L.W. Gold. 1990. Ranking possible carcinogenic hazards. Science. 236:271–280.
4. Anonymous. 1998. Nutraceuticals Products List. Available at: http://www.premium-ingredients.com/nutra.htm. Accessed July, 1998. (VIN editor: link could not be accessed on 3/8/21).
5. Boothe, D.M. 1997. Nutraceuticals in veterinary medicine. Part I. Definitions and regulations. The Compendium. Nov:1248–1255.
6. Boothe, D.M. 1998. Nutraceuticals in veterinary medicine. Part II. Safety and efficacy. The Compendium. Jan:15–21.
7. Guyatt, G.H., D.L. Sackett and D.J. Cook, 1993.User’s guide to the medical literature. II. How to use an article about therapy or prevention. A. Are the results of the study valid? JAMA. 270:2598–2601.
8. Guyatt, G.H., D.L. Sackett and D. J. Cook, 1994.User’s guide to the medical literature. II. How to use an article about therapy or prevention. B. What were the results and will they help me in caring for my patients? Evidence-Based Medicine Working Group. JAMA. 271:59–63.
9. Nutraceutical Regulatory Advisory Panel. 1999. NRAP Report. Available at: http://www.aafco.org/nrapr.htm. Accessed April, 1999. (VIN editor: link could not be accessed on 3/8/21).