What Healthcare Professionals Should Know About Digital Technologies and Eating Disorders

Journal of the American College of Nutrition ISSN: 0731-5724 (Print) 1541-1087 (Online) Journal homepage: http://www.tandfonline.com/loi/uacn20 What Health Care Professionals Should Know about the Regulation and Safety of Dietary Supplements Sidney J. Stohs & Harry G. Preuss To cite this article: Sidney J. Stohs & Harry G. Preuss (2017) What Health Care Professionals Should Know about the Regulation and Safety of Dietary Supplements, Journal of the American College of Nutrition, 36:4, 306-309, DOI: 10.1080/07315724.2016.1275065 To link to this article: http://dx.doi.org/10.1080/07315724.2016.1275065 Published online: 30 May 2017. Submit your article to this journal View related articles View Crossmark data Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=uacn20 Download by: [The UC San Diego Library] Date: 31 May 2017, At: 08:39 JOURNAL OF THE AMERICAN COLLEGE OF NUTRITION 2017, VOL. 36, NO. 4, 306–309 https://doi.org/10.1080/07315724.2016.1275065 COMMENTARY What Health Care Professionals Should Know about the Regulation and Safety of Dietary Supplements Sidney J. Stohs, PhD, FACN, CNSa and Harry G. Preuss, MD, MACN, CNSb a School of Pharmacy and Health Professions, Creighton University School of Pharmacy and Health Professions, Omaha, Nebraska, Georgetown University Medical Center, Washington, DC, USA; bDepartments of Biochemistry, Medicine and Pathology, Georgetown University Medical Center, Washington, DC, USA ARTICLE HISTORY Received 8 December 2016; Accepted 16 December 2016 KEYWORDS dietary supplements; regulation; DSHEA; FDA; safety; nutrient–drug interactions Introduction The purpose of this commentary is to provide a clear understanding of the governmental regulation of dietary supplements and a brief overview of their relative safety. Statements are widely found in professional health care publications and multimedia that dietary supplements are poorly regulated or not even regulated by the U.S. Food and Drug Administration (FDA) [1–8]. The latter assertion that the FDA does not regulate them is at odds with the facts. Accordingly, it is imperative that health care professionals understand the regulatory authority granted to the FDA with respect to dietary supplements and be able to disseminate this information with some authority to their patients and clients. The Dietary Supplement Health and Education Act (DSHEA), which was passed by the U.S. Congress in 1994 [9], defined dietary supplements for the first time. By definition, a dietary supplement means a product (other than tobacco) intended to supplement the diet that bears or contains one or more of the following dietary ingredients: (A) a vitamin; (B) a mineral; (C) an herb or botanical; (D) an amino acid; (E) a dietary substance used by man to supplement the diet by increasing the total dietary intake; or (F) a concentrate, metabolite, constituent, extract, or combination of any ingredient described in clause (A), (B), (C), (D), or (E). [9] In addition, “A dietary supplement is a product that is labeled as a dietary supplement and is not represented for use as a conventional food or as a sole item of a meal or the diet” [9]. The definition also describes the variety of forms in which these products can be ingested and includes capsule, powder, softgel, gelcap, tablet, liquid, or other form. Dietary supplements are specifically excluded from the classification of food additives. Nutrients and other ingredients intended to supplement the daily diet have been regulated by the FDA for over a century, initially through the Federal Pure Food and Drug Act of 1906 [10,11] and then through the Federal Food, Drug and Cosmetic Act of 1938 [11,12], which defined a drug as a “substance that is intended for use in the diagnosis, cure, mitigation, treatment, CONTACT Sidney J. Stohs, PhD, FACN, CNS California Plaza, Omaha, NE 68178. © 2017 American College of Nutrition. sid.stohs9@gmail.com or prevention of disease in man or animals.” Various pieces of legislation regulating dietary supplements are described below. DSHEA, 1994 DSHEA [9] granted the FDA broad statutory authority to regulate dietary supplements with respect to safety, labeling, and health-related claims. It gave the FDA authority to regulate those that manufacture, distribute, and sell supplements and take enforcement actions against unsafe and mislabeled products. The FDA has the authority to remove from the market any products that are deemed unsafe, and it was given the authority to impose good manufacturing practices, which are described below. Dietary supplements are not classified as drugs based on DSHEA and are therefore not regulated by the FDA as drugs or over-the-counter drugs (OTCs). Rather, dietary supplements are regulated by the FDA as a special category of foods [9,11] which constitutes the primary cause for misunderstanding. Suffice it to say, dietary supplements are highly regulated but not as drugs or OTCs. Unfortunately, various publications do not understand the difference between OTCs and dietary supplements and erroneously refer to OTC supplements in their titles [1,7]. As a consequence, misunderstandings frequently arise, and incorrect and misleading statements are perpetuated regarding dietary supplements when individuals fail to understand the legal distinction between drugs, OTCs, and dietary supplements. This may at least in part account for the persistent misconception and myth that dietary supplements are unregulated [1–3]. A lack of adequate resources to fully enforce the law with respect to dietary supplements is a hurdle faced by the FDA and is a major factor behind much of the confusion. A survey of health care professionals found that almost 60% did not know what DSHEA is, what it means, how it affects them as practitioners, or how it affects the consumer of supplements [13]. The fact that dietary supplements are widely ingested is without question. It is estimated that over 85% of athletes consume nutritional and dietary Dean Emeritus, Creighton University School of Pharmacy and Health Professions, 2500 JOURNAL OF THE AMERICAN COLLEGE OF NUTRITION supplements on a daily basis [14], and more than 166 million Americans take supplements [15]. Furthermore, almost 70% of physicians at least occasionally use dietary supplements [14]. Other dietary supplement regulation Dietary supplements are also regulated by various other pieces of federal legislation since the passage of DSHEA in 1994 [16,17]. Several primary examples of legislation follow. The Anabolic Steroid Control Act of 2004 [16-18] prohibited steroid precursors from being sold as supplements. The Dietary Supplement and Nonprescription Drug Consumer Protection Act of 2006 [16,17,19] mandated manufacturers and distributors to maintain records of all adverse events (AERs) and report all AERs associated with supplements and OTCs to the FDA. An understanding of the incidence of adverse events associated with the use of dietary supplements is important in assessing overall safety, and safety of dietary supplements is frequently brought into question. Data obtained to date regarding AERs associated with dietary supplements indicate that the incidence is a small fraction of the AERs reported for prescription drugs and OTCs [7], as should be the case. The FDA Amendments Act of 2007 prohibited addition of drugs or biologics to foods or dietary supplements, and authorized creation of a “reportable food registry” to collect information regarding articles of food that may pose serious health risks. The Food Safety Modernization Act of 2011 [16,17,20] enhanced the FDA’s authority to prevent, detect, and respond to safety problems associated with dietary supplements and foods and furthermore required the FDA to issue guidance on new dietary ingredients (NDIs) in dietary supplements (initially issued by the FDA in July 2011) [16-18]. The FDA also works closely with the Federal Trade Commission regarding product claims and truth in advertising. The Federal Trade Commission levies stiff fines and removes products from the market for violations. Other federal agencies that collaborate with the FDA include the Drug Enforcement Administration (DEA) and the U.S. Customs and Border Protection. The DEA assists the FDA in uncovering and investigating illegal manufacture and distribution of anabolic steroids that are illegally included or sold as dietary supplements. Customs and Border Protection, which is within the Department of Homeland Security, assists the FDA in preventing the importation into the United States of unsafe and improperly labeled dietary supplements [16,17]. Although authority varies by state, state health departments are responsible for inspecting and certifying dietary supplement manufacturing and distribution facilities. Current good manufacturing practices DSHEA granted the FDA authority to establish current good manufacturing practices (cGMPs) for dietary supplements, which went into effect in June 2007, with the final rule for cGMPs regarding manufacturing, packaging, labeling, or holding operations for dietary supplements being last updated August 8, 2015 [21]. These regulations are finally in place. These cGMPs address general provisions, personnel, physical 307 plant and grounds, and equipment and utensils. Furthermore, they establish requirements with respect to production and process control systems, quality control, master manufacturing records, batch production records, and laboratory operations, as well as requirements for components, packaging, labels, and product received for packaging or labeling of dietary supplements. Various parts of the cGMPs were phased in over about 3 years [21]. These cGMPs clearly establish the fact that dietary supplements are regulated by the FDA and in turn emphasize the regulatory authority of the FDA with respect to dietary supplements. However, worth reemphasizing is the FDA’s shortage of manpower and resources needed to perform all of the necessary inspections and oversight to effectively and fully enforce the regulations. New dietary ingredient notifications In August 2016, the FDA published “Dietary Supplements: New Dietary Ingredients Notifications and Related Issues: Guidance for Industry, Draft Guidance,” which will replace a draft guidance document issued in July 2011 [22]. This 102page document states that the manufacturer or distributor of a new dietary ingredient (NDI) that has not been present in the food supply as an article used for food, or a dietary supplement containing such an NDI, must submit a premarket safety notification to FDA at least 75 days before introducing the product into commerce. This guidance is intended to help manufacturers and distributors of dietary ingredients and dietary supplements decide whether to submit premarket safety notification to FDA for a product that is or contains an NDI. [17] The document [22] provides information and addresses numerous questions regarding what qualifies as an NDI, when an NDI notification is required, the procedures for submitting an NDI, what types of information and data the FDA recommends when evaluating safety of NDIs and dietary supplements, and what information should be included in an NDI notification. Although it has been 22 years since the passage of DSHEA, the FDA is slowly asserting the regulatory authority that it was granted. Conversely, many individuals in industry are concerned that the FDA is overstepping the authority granted to it by DSHEA and attempting to treat dietary supplements as if they were classified as drugs. Safety of dietary supplements Many scientific as well as lay publications question the safety of dietary supplements, and a number of examples are provided [3,5,8,23–27]. The questioning of the safety constitutes the basis for demanding greater regulation of dietary supplements [4,10,25,26,29]. One publication concluded that an estimated 23,000 emergency room visits per year were attributed to adverse events related to dietary supplements [24], which raised questions in the minds of many individuals. However, careful dissection of the information indicated that the number of visits actually due to dietary supplements was far smaller [28]. About one third of the visits were due to pill swallowing issues and not the contents, and 20% of the visits were due to unsupervised 308 S. J. STOHS AND H. G. PREUSS ingestion by children and in only a few cases would require intervention. Furthermore, a number of substances included in the analysis as dietary supplements should have been excluded, because they were legally drugs or other chemicals and not dietary supplements by definition [24,28]. As previously noted, an estimated 166 million people use dietary supplements in the United States [15,28]. If the actual number of emergency room visits due to adverse events associated with dietary supplements is closer to 10,000 per year, this number represents a very small numerator relative to a very large denominator, indicating a high degree of safety. Furthermore, if one looks at the number of deaths that can be directly attributable to dietary supplements over the past 15 years, the number is less than one per year—a number of these deaths have been due to the ingestion of massive amounts of caffeine [30,31]. To put this number into perspective, over 25,000 deaths occur annually from FDA-approved prescription drugs according to the National Institutes of Health [32]. Mandatory reporting of AERs for dietary supplements has been required by the FDA since 2006 and constitutes another indicator of relative safety. In 2012, 2013, and 2014, the FDA received 2844, 3289, and 2793 AERs, respectively, compared to over a million AERs per year for drugs [33]. These results again suggest a high degree of safety involving the use of dietary supplements, while also pointing out that some dietary supplements are not without the potential for adverse events. Although the overall incidence of adverse events associated with dietary supplements is very low, hepatotoxicity associated with consumption of dietary supplements may be of greatest concern as a result of using herbal ingredients with inherent toxicity, adulteration with unapproved chemicals and drugs, and/or contamination with unidentified botanical ingredients by unscrupulous manufacturers and distributors [11,34]. Some manufacturers and distributors of dietary supplements are conducting postproduction analysis to verify composition of products, but this is not currently the case for the majority of supplements in commerce. Obviously, prescription and over-the-counter drugs as well as dietary supplements and herbal products are widely used by the general population. As a consequence, herb–drug (nutrient– drug) interactions constitute a potential avenue for the production of drug-related adverse events. Another possible hazard is the inhibition of the therapeutic effects of drugs because botanical dietary supplements are frequently used in combination with conventional drugs [35–30]. A detailed discussion of this topic is beyond the scope of this commentary. Although a large number of interactions are possible due to the number of plant-based chemicals that can potentially interact with drug metabolizing and transporting systems, the number of interactions of pharmacological significance is small and involves relatively few botanicals [35–39]. Antiplatelet agents and anticoagulants are the most commonly interacting drugs [40]. Many factors determine the importance of herb–drug interactions, including the herb or combination of herbs (dietary supplement), drug or combination of drugs, doses, and patient. Finally, vitamins and trace elements are essential to normal and optimal body function and are common components of dietary supplements. For the sake of completeness, it should be noted that various commonly prescribed drugs can precipitate micronutrient deficiencies, and these effects are rarely considered or assessed in clinical practice [41]. The effects of drugs on nutrients and micronutrients may occur through multiple mechanisms involving drug-altered absorption, transport, and/ or metabolism. Conclusions Dietary supplements are extensively regulated as a special category of foods—not as drugs. That dietary supplements are not regulated as drugs does not imply that they are unregulated. The FDA has greater substantive authority over dietary supplements than conventional foods. Health care providers should be well informed regarding how dietary supplements are regulated and be able to appropriately transmit this information to their patients and clients. Because of very widespread consumption of dietary supplements and the continued increase in their use, health care professionals must be familiar with commonly consumed dietary supplements as well as those that may be problematic with respect to inherent potential toxicity or may realistically (not just theoretically) cause drug–nutrient interactions. Furthermore, health care professionals should become familiar with various manufacturers and distributors so that they can make recommendations involving quality products. Summary Many health care professionals believe that dietary supplements are unregulated and may pose serious health threats because they are unregulated. On the other hand, the most common misconception for consumers and patients is that they are regulated as drugs. The DSHEA granted the FDA broad statutory authority to regulate dietary supplements with respect to safety, labeling, and health-related claims. 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