Brief History of Regulation Leading to the DSHEA
In the United States, dietary supplements are regulated by a comprehensive set of laws and regulations set forth in the Federal Food, Drug, and Cosmetic Act (FDCA) of 1938, and later amended by the DSHEA of 1994 (See Table 1.3 for a chronology of the legislative acts associated with dietary supplements). This set of legislations gives the FDA jurisdiction over product safety, manufacturing, and labeling. Advertising of dietary supplements is overseen by the Federal Trade Commission (FTC), also established in 1938 by the Wheeler–Lea Act.
Together, the FDA and FTC provide broad federal oversight of the dietary supplement industry as a whole.
Today, the statutes and regulations governing the dietary supplement industry are quite comprehensive, regulating everything from manufacturing to the wording used to market dietary supplements. This was not always the case, however, and we must look back well over a century to see where the first federal regulatory efforts began and why.
The Federal Food and Drugs Act of 1906, better known as the Wiley Act, was the first federal act passed to regulate food and drug production and transport. It prohibited the manufacture of any food or drug that was adulterated or misbranded. It also prohibited the transport of adulterated, misbranded, or otherwise unlawful foods or drugs across state lines or their importation from another country.
At the time, dietary supplements were yet to be conceived of as such, but there were folk remedies and “patent medicines,” which were the ancestors of both modern day drugs and dietary supplements. These concoctions and patent medicines, or nostrums as they were called, were sold as remedies for virtually any ailment. Much of the folk medicine was based on the idea that nature or God has provided remedies for common ailments of humanity in the fauna and flora of the geographical area where those ailments are most likely to occur (Young 1972). The patent medicines were called so because they were remedies that had received patents in Europe before being exported to the colonies of the United States. The many herbs, herbal extracts, glandular extracts, and drugs found in these remedies and patent medicines are too numerous to elaborate on here, but to give you an idea of the scene, it was not uncommon to find any number of opiates, cocaine, and even neurological poisons in these products. The product labels were not required to list the ingredients or warnings of any kind. Moreover, this had been going on for over a century before formal legislation was proposed.
In 1905, an American writer named Samuel Hopkins Adams wrote a series of 11 articles for Collier’s Weekly entitled “The Great American Fraud” (Adams 1911; Fee 2010). Adams exposed many of the false claims made by the purveyors of patent medicines, bringing to the public’s attention the many adverse and, in some cases, fatal events resulting from the use of such products. The articles were very influential and contributed in part to the passage of the 1906 Pure Food and Drug Act (PFDA).
In 1911, the Supreme Court ruled that the prohibition of falsifications referred only to the ingredients of the medicine and not its claims of efficacy. This meant that companies were again free to make false claims about their products. This inspired Adams to write another series of articles in Collier’s Weekly exposing the false and misleading advertising that companies were using to sell their products. Both series of articles were reprinted as a book in 1911 (Adams 1911).
We now jump to 1938 and the passage of the FDCA. The FDCA essentially replaced the Federal Food and Drugs Act of 1906. In the intervening years between 1906 and 1938, the science of human nutrition and the role of “essential” nutrients progressed, and by the 1920s and 1930s, the public at large had become aware of the concept and importance of vitamins.
Cod liver oil was marketed in 1920 to supply extra Vitamin D and Vitamin A (Hutt 2005). This is perhaps the first food supplement marketed as a dietary supplement. Later in 1934, a true vitamin and mineral supplement was produced and marketed by the Nutrilite Company (Wallace and MacKay 2013). It was crude by today’s standards, made simply by drying and compressing vegetable and fruit juice concentrates into a tablet, but it was by definition a true dietary supplement product.
The FDCA of 1938 recognized that foods could be and were being marketed using claims about their nutritional value, even making what would be considered structure function claims to describe the benefits of consuming it. At the same time, the FDA used the drug provisions of the law to gain greater control and reclassify dietary supplements as drugs based on their label claims. With this act, the FDA was also granted authority to inspect the manufacturing facilities of food, drug, and cosmetic companies. This same year, an amendment was made to the FTC Act to grant FTC oversight of the advertising for FDA-regulated products (except prescription drugs). Today the FTC is the primary enforcer of laws protecting the public against false and misleading claims made by dietary supplement marketers.
In 1941, the FDA added language to specifically address food products marketed with a “special dietary use” label (Porter and Earl 1990). Food products with a special dietary use were defined as used for supplying particular dietary needs that exist by reason of a physical, physiological, pathological, or other conditions, including but not limited to the conditions of disease, convalescence, pregnancy, lactation, allergic hypersensitivity to food, underweight, and overweight. All products falling into this category, which obviously included dietary supplements, were required to have labeling declaring the name, quantity, and percent Minimum Daily Requirement of each added nutrient (6 Fed. Reg. 5921 [Nov. 22, 1941]). This part of the code of regulations remains unchanged to this day.
The next significant legislative act affecting dietary supplements happened in 1976 with the passage of the Proxmire Amendments (Public Law 94-278). Going back for a moment to events leading up to the Proxmire Amendments in the 1960s and early 1970s, the FDA attempted to limit the allowable formulations and potency of vitamin and mineral supplements. In 1962, the agency published a proposed notice that “only those nutrients recognized by ‘competent authorities’ as essential and of significant human value could be offered for sale” (27 Fed. Reg. 5815, 5817 [June 20, 1962]) (Scarbrough 2004 Third Year Paper). The FDA proposed to limit the potency of vitamins and minerals to 150 percent of the reference values. If a dietary supplement exceeded 150 percent of the reference value with one or more vitamins or minerals, the product would be classified as a drug. In addition to the potency of vitamins and minerals, the agency attempted to limit the number and types of combinations of vitamins and minerals that could be sold by issuing a regulation in 1973 that established a Standard of Identity for vitamin and mineral supplements (38 FR 20,730, 20732 [August 2, 1973]) (Wallace and MacKay 2013). Arriving full circle, in 1976 in response to pressure from the public and dietary supplement industry, Congress passed the Proxmire Amendments (1976 Proxmire Amendment, 21 USC §350 [April 22, 1976]). These amendments prevented FDA from limiting the formulations and potency of vitamins and minerals in nutritional supplements and nullified the agency’s authority to classify a vitamin or mineral product as a drug based solely on its potency. The Proxmire Amendments reinstated the original language of FDCA classifying drugs as, “intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease in man or other animals.” (52 Stat 1040 , 21 USC §301 et seq.). This would not be the last time the FDA attempted to limit the formulation of dietary supplements and reclassify them as drugs.
Some 20 years after the proposals put forth in 1973, the FDA issued an advanced notice of proposed rulemaking (ANPR). In this ANPR, the agency again attempted to restrict the potency of vitamins and minerals. It also declared that amino acids are food additives and were not legal in dietary supplements, and that herbal products are inherently therapeutic and should not be sold as dietary supplements. (58 FR 33690 [June 18, 1993]). Then in 1994, seeing that without some action on the part of Congress, the dietary supplement industry was in danger of excessive regulation, Senators Orrin Hatch and Tom Harkin drafted the DSHEA.
The Dietary Supplement Health and Education Act
According to U.S. Government Accountability Office, there were about 4,000 dietary supplement products on the market in 1994 when DSHEA was enacted (U.S. Government Accountability Office, 2009 GAO report—FDA should take further actions to improve oversight and consumer understanding, GAO-09- 250). That number has grown significantly since then, likely closer to 40,000 today. With so many products available to consumers, it became evident that a more proactive regulatory framework was needed. DSHEA was enacted for this purpose and was intended to: (1) establish a new framework for assuring safety, (2) outline guidelines for literature displayed where supplements are sold, (3) provide for use claims and nutritional support statements, (4) require ingredient and nutrition labeling, (5) grant FDA the authority to establish good manufacturing practice (GMP) regulations, and (6) form an executive level Commission on Dietary Supplement Labels and an Office of Dietary Supplements (ODS) within the National Institutes of Health (NIH).
Prior to DSHEA, nutritional supplements were regulated primarily as food products. DSHEA provides an unambiguous definition of a dietary supplement and dictates when a product is to be regulated as a food or as a dietary supplement. DSHEA defines a dietary supplement as:
Any product that:
- is intended to supplement the diet and that bears or contains one or more of the following dietary ingredients: a vitamin, a mineral, an herb (other than tobacco) or other botanical, an amino acid (a dietary substance for use by man to supplement the diet by increasing the total daily intake), or a concentrate, metabolite, constituent, extract, or combinations of these ingredients;
- is intended for ingestion in pill, capsule, tablet, or liquid form;
- is not represented for use as a conventional food or as the sole item of a meal or diet;
- is labeled as a “dietary supplement”; and
- includes products such as an approved new drug, certified antibiotic, or
- licensed biologic that was marketed as a dietary supplement or food before approval, certification, or license (unless the Secretary of Health and Human Services waives this provision).
If a product or ingredient was already marketed as a dietary supplement prior to 1994, it was “grandfathered” and did not require any notification of the FDA. A new ingredient introduced after the passage of DSHEA, however, must be registered with the FDA as a “new dietary ingredient” (NDI). If a manufacturer wishes to market an NDI, it must notify the FDA with the appropriate safety documentation at least 75 days before marketing it. Appropriate documentation includes information about the chemical identity of the ingredient and justification that the new ingredient “will reasonably be expected to be safe” (DSHEA, 108 Stat 4325 ).
The FDA will then respond acknowledging that the file was received and may pose additional questions about the ingredient. The FDA does not “approve” an NDI. By only acknowledging receipt of the premarket filing for an NDI, the FDA reserves the right to have the ingredient removed from the market at its discretion at a later date should it feel it is unsafe. All other nonactive ingredients and excipients used in the manufacture of dietary supplements must be FDA-approved food additives or generally recognized as safe (GRAS).
Good Manufacturing Practices. The manufacturing of dietary supplements is regulated by the FDA with the establishment of GMPs similar to those established for foods. GMPs put controls in place over how dietary supplements are manufactured to ensure they are produced in a consistent manner and meet quality standards for identity, purity, concentration, potency, and composition.
The GMPs apply to all domestic and foreign companies that manufacture, package, label, or hold dietary supplements, including those involved with the activities of testing, quality control, packaging and labeling, and distributing them in the United States (21 CFR Part 111). The requirements include provisions related to:
- the design and construction of physical plants that facilitate maintenance and compliance;
- hiring of qualified personnel;
- cleaning and maintenance of manufacturing equipment and facilities;
- proper manufacturing operations;
- quality control procedures and personnel;
- testing the final product and incoming and in-process raw materials;
- handling consumer complaints; and
- maintaining records.
Under DSHEA, the responsibility of ensuring the safety of a dietary supplement falls on the manufacturer. GMPs do not ensure whether a dietary supplement is good for you or not or whether the substance itself is even safe to consume. A dietary supplement is only considered unsafe or “adulterated” if it or one of its ingredients presents “a significant or unreasonable risk of illness or injury” when used as directed on the label or under normal conditions of use when there are no directions. As mentioned with the requirements of premarket notification of NDIs, the FDA does not formally approve dietary supplements before they can be marketed, but under DSHEA, the FDA has the authority to remove any product from the market should it be deemed unsafe. In addition, the manufacturer, bottler, or distributor whose name appears on the label of a dietary supplement marketed in the United States is required to submit to FDA all serious adverse event reports associated with the use of the dietary supplement in the United States (FDA n.d.).
FDA regulations require that a descriptive name of the product stating that it is a “dietary supplement” be present on the label. Further, dietary supplement labels must list the ingredient names and amounts in a standardized “supplement facts” panel. The amounts per serving must be listed as a percentage of the Daily Value for each ingredient. Active ingredients that do not have an established Daily Value should also be listed in the supplement facts panel. DSHEA allows the listing of a “proprietary blend” by ingredient without disclosing the amounts of each individual ingredient in the blend. This protects companies using proprietary formulations from having to disclose their formula.
Products are required to meet label claims, which is to say they must contain the levels of active ingredients listed in the supplement facts panel for the duration of the products’ shelf life (i.e., up to the date of expiration). Products may be labeled “high potency” if they contain at least 100 percent of the Reference Daily Intake (RDI) for that nutrient. Ingredients that are naturally occurring are allowed to be within 80 percent of the label claim without being considered misbranded. All dietary supplements marketed in the United States must also contain the address and contact information of the manufacturer, packer, or distributor.
Health Benefit Claims
Dietary supplements should not claim or imply that it may be used to treat, mitigate, or cure any disease or illness not directly caused by a nutrient deficiency; more on that later. Statements can be made, however, that describe the role of a nutrient or dietary ingredient intended to affect a structure or function in the body or that characterize the documented mechanism by which a nutrient or dietary ingredient acts to maintain such structure or function, provided that such statements are not disease claims. These are called structure function claims such as those used historically for food and drugs. An example of a structure claim would be, “calcium is important for strong bones and teeth.” An example of a function claim might be, “Dietary fiber helps maintain bowel regularity.”
FDA regulation stipulates that claims of any type must have adequate substantiation before they can be used to market a dietary supplement. The FDA has stated that it considers two randomized placebo controlled trials of sufficient power and size to be the standard for substantiating a claim. Even an unstated “implied claim” must not be untruthful or misleading and have adequate substantiation. A company must have this substantiation in place before making any health benefit claim to market a product. The FDA must also be notified that you intend to use the claim within 30 days of first marketing the product. All labels that contain health benefit claims must also carry a “disclaimer” that the FDA has not evaluated the claim. The disclaimer must also state that the dietary supplement product is not intended to “diagnose, treat, cure or prevent any disease.”
Disease claims cannot be made for any dietary supplement. A disease claim is defined as any claim, implied or otherwise, that the product is intended to diagnose, mitigate, treat, cure, or prevent any disease. In fact, within DSHEA a drug is not defined by its chemical composition but by the wording used to describe its function. For example, vitamin C can be either a drug or a dietary supplement depending on what you say it will do; thus the statement “Vitamin C may reduce the incidence or duration of a cold” would qualify the product as a new and unapproved drug. Any new or unapproved drug would be required to be removed from the market immediately pending FDA evaluation, again, regardless of what the substance actually is. On the other hand, the statement, “Vitamin C supports the immune system” qualifies the product as a dietary supplement. The one exception for disease claims are nutrient deficiency disease claims. These describe a benefit related to a nutrient deficiency disease (like vitamin D and rickets, or vitamin C and scurvy), but such claims are allowed only if they also inform the consumer of the prevalence of such a disease in the United States.
The Office of Dietary Supplements
The enactment of DSHEA brought with it the creation of the ODS as part of the NIH. The purpose of the ODS is twofold: to explore the potential role of dietary supplements as a significant part of the efforts of the United States to improve health care and to promote scientific study of the benefits of dietary supplements in maintaining health and preventing chronic diseases and other health-related conditions. Though not directly stated, the ODS serves to balance or temper the FDA’s long-standing position against dietary supplements by objectively furthering the science and understanding of the role of dietary supplements in public health.
This was only a brief survey of Federal regulation over dietary supplements. For a more in-depth treatment of the subject, the author suggests Wallace’s Dietary Supplement Regulation in the United States (Wallace and MacKay 2013). Free access to the DSHEA, and all amendments, is also available through the FDA’s website.