Dietary supplements and nutraceuticals (Proceedings)

Passage of the Dietary Supplement Health and Education Act of 1994 (DSHEA) dramatically changed the market for both human and pet supplement products. This is because while the Act doesn't legally apply to products intended for animals, the massive influx of new and different products in the human supplement market as a result of DSHEA has not unexpectedly crossed over to products for pets. However, that places many dietary supplement and so-called "nutraceutical" products for pets in a precarious regulatory position.

Effects of DSHEA

Basically, DSHEA added a new term, "dietary supplement," to the regulatory lexicon to describe a product that, while under the umbrella of "foods," was granted leeway in terms of both ingredients and claims not allowed for foods prior to passage of the Act. As passed by Congress, those products containing vitamins, minerals and other essential nutrients, as well as herb and botanicals, "metabolites," and other substances were no longer subject to the requirements for all food ingredients to be GRAS (generally recognized as safe), approved food additives, or otherwise sanctioned for their intended use in food. Historically, the US Food & Drug Administration (FDA) could take action against a product containing an ingredient that did not meet the above requirements as an "adulterated food" by virtue of the presence of an "unapproved food additive." However, DSHEA says that as long as the product meets the statutory definition of a "dietary supplement," and otherwise complies with the Act (e.g., in pill, powder, liquid, bar or other non-conventional food form, represented as a "supplement" and not represented as a meal or diet replacement), that regulatory remedy did not apply. Essentially, it shifted the burden from a manufacturer having to prove an ingredient was safe (e.g., via a Food Additive Petition) before the product could be on the market to FDA having to prove an ingredient was unsafe before it could be removed from the market. To date, only one dietary supplement ingredient has been codified in the regulations as unsafe by FDA, namely ephedra, AKA the Chinese herb ma huang.

The nature and extent of acceptable claims on dietary supplements has also been affected by DSHEA. Historically, any claim that explicitly or implicitly indicated use for the treatment or prevention of disease, or to affect the structure or function of the body beyond traditional nutritional precepts was considered a "drug claim." Further, since the product had not undergone testing and submission of data as required for approval as a drug, it could be subject to enforcement action as an "adulterated drug." This still holds true for dietary supplements that make disease treatment/prevention claims. However, DSHEA allows for statements of "support," wherein claims for an effect not related to traditional nutritive value of the ingredient can be made. For example, an herbal supplement containing saw palmetto may make a claim akin to "helps support healthy prostate function," even though its purported effect does not appear to be through provision of a vitamin, mineral, or other recognized essential nutrient. However, "cures benign prostatic hypertrophy" or "helps urinary flow problems" would not be acceptable. Also, "support" claims must be accompanied by the disclaimer "This statement has not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.''

These provisions under DSHEA do not apply to human foods in conventional form. Thus, while an herbal product in capsule form containing echinacea may be sold to "help support a healthy immune system" (for the implicit but undeclared effect on the treatment or prevention of colds), a similar statement on a chicken soup product would not be tolerated. In fact, unless the herb was determined to be GRAS or approved as a food additive, its inclusion in the chicken soup product could cause the soup to be subject to enforcement action.

Regulatory status of pet supplements

In a Federal Register Notice in 1996, FDA informed the public that it did not interpret DSHEA as applying to products intended for animals. For one, it was clear (to FDA) in the statutory language that Congress did not consider animal supplements as part of the law or intend the Act to apply. Further, FDA concerns about the lack of sufficient historical safety data in intended species, and the possibility for unsafe residues in meat milk or eggs or for misleading "production" claims when given to food-producing animals were all good reasons for it not to apply. To date, FDA's interpretation does not appear to have been challenged through legal proceedings.

As a result of this interpretation, the law that prevailed prior to DSHEA still applies to products intended for animals. Thus, products that contain ingredients that are not GRAS substances, approved food additives or otherwise sanctioned (e.g., defined by AAFCO) could be subject to enforcement action as an "adulterated food." Similarly, claims that state or imply function beyond provision of normal nutrition (including treatment, but not prevention of recognized nutritional deficiencies) could be considered "adulterated drugs." These interpretations apply regardless of product type (i.e., whether in pill or powder form or conventional petfood or treat form).

Pet supplement products that contain and are intended to provide essential nutrients such as vitamins and minerals have existed for many years, and have continued to do so unfettered after passage of DSHEA. These products must be labeled in accordance with FDA and AAFCO animal feed labeling regulations. Considering the prevalence of "complete and balanced" petfoods that are available to meet the needs of the vast majority of healthy animals, the true utility of these products may be argued. At minimum, though, they often provide "insurance" where the nutritional adequacy of the mainstay diet is questionable. This may be particularly true for homemade diets, where there is less likelihood of full knowledge of the nutrient content of all the component ingredients. Judicious use of nutritional supplements by veterinarians might also be indicated to address the risk of a recognized nutritional deficiency.

A policy of FDA requires these types of nutritional supplements to provide nutritionally "meaningful" amounts of the nutrients it purports to contain. The agency has been using the recommendations of the National Research Council Nutrient Requirements of Dogs and Cats (2006), and not the AAFCO Dog and Cat Food Nutrient Profiles, as the basis for determining meaningful amounts. Under the policy, a product must provide at least 10% of the animal's daily needs for a given body weight and life stage when fed as directed on the label. To determine whether the product meets the burden, FDA looks at the "minimal requirement," or when not available, the "adequate intake" value for a given nutrient in terms of units per metabolic body weight. Then, based on the amount per capsule, teaspoon, etc., as guaranteed on the label it calculates the amount of nutrient per unit. Multiplying that value by the number of units given to a given weight animal, the daily intake can be compared to the NRC recommendation.

In the case of supplements intending to provide nutrients other than those recognized as essential, their regulatory status depends on the regulatory status of the individual ingredients and associated claims. Ascorbic acid and beta-carotene, for example, are not recognized as essential in the dog or cat, but are still codified as GRAS for use in animal feed under FDA regulations. As such, they are frequently components of pet supplement products. Claims for functionality are generally restricted, though, and the label guarantees for either substance must include the disclaimer that they are "Not recognized as an essential nutrient by the AAFCO Dog (or Cat) Food Nutrient Profiles." A similar disclaimer must appear on dog, but not cat product labels that include supplemental taurine.

Glucosamine and chondroitin sulfate, substances frequently found in both pet supplements and complete petfoods, are not GRAS or approved for use in animal feeds. In fact, most regulatory officials, including FDA, consider them unapproved food additives when added to pet products. However, most states tolerate their inclusion as long as they are disclaimed as "not essential nutrients" and the claims are not egregious (e.g., "helps maintain healthy joints," but not "prevents hip dysplasia" or "treats arthritis"). The Office of the Texas State Chemist has additional restrictions, including limits on the intended species (dogs only), intended life stage (adult maintenance only) and maximums inclusion rates when fed as directed (no more than 15 mg/kg BW per day for glucosamine hydrochloride and no more than 12 mg/kg BW per day for chondroitin sulfate).

A pending guidance document from FDA may conclude that glucosamine and chondroitin are "drugs" by definition, hence challenging their inclusion in any animal feed or petfood product. However, it is anticipated that the agency will deem them "unapproved drugs of low regulatory priority." Like many other products on the market with this status (e.g., petrolatum-containing hairball remedies), this would allow the products to be marketed without formal approval as a drug as long as certain provisions are met. Such conditions may include labeling the product as a "drug" vs. as a "food" (including absence of any nutritional claims), meeting "drug listing" requirements, and following the Good Manufacturing Practices required for pharmaceutical products. While many pet supplements may be able to meet these requirements, most petfood products in conventional form cannot. Thus, the long-term status of use of these substances in complete and balanced petfoods is unclear.

Although the aforementioned FDA guidance on glucosamine and chondroitin has not been publicly released, some products have already been revised to accommodate its "unapproved drug" status. In fact, some manufacturers are labeling other supplements containing unapproved food additives such as herbs and botanicals as "drugs." In part, this helps avoid the scrutiny by AAFCO and many state feed control officials, since drugs do not fall within their regulatory purview. However, whether foods or drugs, they still fall under FDA authority. It is not known how many of them are actually following all the FDA provisions set forth for "unapproved drugs of low regulatory priority," though.

The veterinarian's role

A frequent comment in the press, on web sites, etc., regarding pet supplements is that they "aren't regulated." This is not accurate, in that in fact, they are subject to very strict regulatory requirements. However, the problem often boils down to regulators detecting non-compliant products in the market and taking effective enforcement action. In many states, all animal feeds, including pet foods and supplements, must be registered in that state prior to distribution. This typically includes products distributed via catalog or internet sales. However, if a company fails to register as required, it may take years until the product is brought to the attention of the authority, e.g., through chance discovery during a retail outlet inspection, notification by a concerned citizen, or more often, by a competitor.

Effective enforcement action is often dependent on available resources. Thus, the egregiousness of the claims (e.g., "cures cancer" vs. "supports well-being") and the presence of any known or potential safety concerns may affect the priority given to enforcement. Bottom line, just because a product is on the market does not mean it has passed regulatory muster.

Therefore, it is prudent for the veterinarian to be duly cautious when using or recommending use of dietary supplements for pets. It behooves the veterinarian to practice due diligence in assessing the clinical need for a given supplement in an individual animal, evaluating the strength, quality and source of data to support its use, and judging the integrity and competence of a given commercial source of the supplement prior to using or recommending any supplement product. Veterinarians must also objectively assess outcomes of supplement administration and be open to revising use or recommendations as necessary. Observation of adverse effects should be reported to the manufacturer as well as the appropriate regulatory officials. Under membership requirements, companies that are members of the National Animal Supplement Council (NASC) must convey reports of adverse events to be included in the association's database. However, while the database is reportedly available for review by state and federal regulatory officials, it is not accessible to the public at large.

Selected sources of information

www.fda.gov/cvm

www.aafco.org

www.nas.edu

www.nasc.cc

otscweb.tamu.edu/Laws/PDF/Feed/FdInd-3-17.pdf