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SYNOPSIS: Investigators analyzed data collected from 2007 to 2016 regarding FDA warnings. Unapproved ingredients in dietary supplements continue to be found.
SOURCE: Tucker J, Fischer T, Upjohn L, et al. Unapproved pharmaceutical ingredients included in dietary supplements associated with US Food and Drug Administration warnings. JAMA Netw Open 2018;1:e183337.
Adulterate: to corrupt, debase, or make impure by the addition of a foreign or inferior substance or element.1
The name Clark Stanley (a.k.a., the rattlesnake king) may not ring bells immediately, but his notoriety as the original snake-oil salesman has survived the test of time. Today, the snake-oil salesman label implies fakery or fraud. This term arose in the early 1900s, after investigators working under the Pure Food and Drug Act of 1905 inspected a shipment of Stanley’s anti-inflammatory “snake oil” and found mineral oil to be the main ingredient.2
The medical world has moved forward since the early 1900s, but concern about mislabeled and/or adulterated products remains. The Pure Food and Drug Act gave birth to the U.S. Food and Drug Administration (FDA) in 1906. In 1994, the Dietary Supplement Health and Education Act (DSHEA) defined the FDA’s role in regulation of dietary supplements, including vitamins, minerals, herbs, amino acids, and enzymes.3
DSHEA classifies supplements as a distinct category of “food.” Because of this classification, the FDA regulates supplements in a separate category than pharmaceuticals, which by definition are meant to treat or control a disease state. Thus, the FDA monitors supplements only after distribution; the FDA plays no role in inspecting or approving supplements before distribution as is required for conventional pharmaceuticals. Products come to the attention of the FDA in several ways, but usually a consumer complaint or FDA screening triggers the process. Evidence of mislabeling or adulteration can lead to a warning to the public and/or the company. If there are dangerous potential health implications, the FDA may issue a recall.3,4
FDA screening currently appears to be concentrated at international mail facilities. In March 2018, the FDA announced updated mobile screening technology at these points of entry into the U.S. market.5 Concerns about this oversight role are numerous. Proponents of the supplement industry mostly believe DSHEA serves the industry well,6 but others advocate for a more stringent process in the name of consumer safety.7 Tucker et al approached this study in a neutral fashion to look at the outcomes or trends after a product or company receives an FDA warning. Notably, if a supplement contains active pharmaceuticals approved by the FDA for specific purposes, but at unknown concentrations and/or without a label or identification, the pharmaceutical is characterized as unapproved.
The FDA often works in conjunction with the Federal Trade Commission to issue such warnings, as the two agencies have overlapping but separate mandates.8 Tucker et al focused only on products with FDA warnings.
The FDA maintains a public website: Tainted Products Marketed as Dietary Supplements.9 Tucker et al reviewed each entry on this website. To avoid double-counting, multiple warnings for the same product were counted if they were issued more than six months apart.
The FDA received reports on 776 dietary supplements involving more than 140 companies between 2007 and 2016. The most serious warnings for each product were: voluntary recall (46.4%; 360), public notification (44.1%; 342), news release (7.5%; 58), consumer update (1%; 8), warning letter to company (0.9%; 7), and U.S. Department of Justice press release (0.1%; 1).
Increase in public notification and decrease in recall over the study period: Tucker et al noted public notification was used more frequently than voluntary recall in the later years of the study period. Between 2007 and 2012, the number of products undergoing voluntary recall exceeded or was close to the number of public warnings issued. However, from 2012 to 2016, 72.5% of adulterated products were issued a public warning only (no recall). In 2015 and 2016, this trend appeared stronger, with more than 80% of adulterated products receiving public warnings. In all, a voluntary recall was issued for slightly less than half of the identified products. No mandatory recall was instituted.
Single products with multiple warnings: Of the 776 products, 96.2% tested positive only once for adulteration while 3.8% tested positive for unapproved ingredients two or three times. Of these products, 67.9% contained new unapproved ingredients after the first warning.
Multiple pharmaceuticals per product: Although the majority of identified products contained only one active, unapproved pharmaceutical, 20% contained more than one such ingredient. Thirty-three products contained three of more adulterants. Of these 33 products, the majority were marketed for either weight loss or improved sexual function.
Specifics of active, unapproved pharmaceuticals: Most of the identified adulterated products were marketed for either sexual enhancement, weight loss, or muscle building. Table 1 provides a breakdown of the number of products involved and adulterated ingredient(s) found.
In 2009, the FDA initiated a recall of 66 muscle enhancement products. Of the 92 adulterated products identified for muscle-building in this study, the majority (96.7%) were found in the year of the recall (2009; 80.4%) and the following year (2010; 16.3%.)
Disclaimer from the FDA Tainted Products website:7
This list only includes a small fraction of the potentially hazardous products with hidden ingredients marketed to consumers on the internet and in retail establishments. FDA is unable to test and identify all products marketed as dietary supplements on the market that have potentially harmful hidden ingredients. Even if a product is not included in this list, consumers should exercise caution before using certain products. To learn more about how to reduce your risk of encountering a product marketed as a dietary supplement with a hidden ingredient, please visit FDA’s Medication Health Fraud webpage.
In medicine, it is usually wise to tread cautiously and perform confirmatory investigations and studies before adopting new methods, procedures, or interventions. This study by Tucker et al looking at supplements with adulterated substances identified by the FDA is consistent with other similar investigations. Although it is true that longer periods of study or a more in-depth look at aspects of supplement adulteration and usage could clarify and pinpoint patterns, there seems to be little to gain and true potential harm by waiting for further confirmatory studies.
In 2013, Harel et al published research describing an investigation into class 1 recalls. They noted that of the 332 adulterated products listed on the FDA tainted supplement website between 2007 and 2012, only 222 were subject to a recall. The characteristics of the adulterated products mirrored those described by Tucker et al, with marketing of the most common adulterated products pointed toward sexual enhancement, weight loss, and bodybuilding.
In a 2015 study, Geller et al found that 23,000 emergency department visits and 2,000 hospitalizations each year can be attributed to the use of dietary supplements.11 Once again, the main culprits were products marketed for sexual enhancement, weight loss, or bodybuilding.
It is no wonder that in a related opinion piece, Dr. Pieter Cohen pointed to “a dereliction of duty” by the FDA. He noted that Congress could reform DSHEA and mandate that supplement manufacturers register with the FDA prior to any distribution or marketing. In keeping with the theme of his editorial, he concluded by assigning blame to the FDA, noting “the agency’s failure to aggressively use all available tools to remove pharmaceutically adulterated supplements … leaves consumers’ health at risk.”12
Although not mentioned in these studies, the rapidly growing popularity and widespread availability of hemp products and cannabidiol (CBD) lends urgency to strengthening the ability of the FDA to enforce regulations for unconventional products. As of this writing, the FDA does not consider CBD a supplement, but the status of this product remains murky and subject to question. For the most part, it appears that the FDA is leaning toward the classification of CBD as a drug, which would make CBD-containing products subject to premarketing approval. Despite the FDA position, CBD products can be purchased online and are found in many retail stores as a dietary supplement.13,14
In February 2019 (prior to his March 2019 resignation announcement), FDA Commissioner Scott Gottlieb, MD, announced new steps the FDA intends to take to strengthen the regulatory arm of the agency as it pertains to dietary supplements. His announcement included the intention to develop new enforcement policies and to modernize DSHEA.15 It certainly appears that action on multiple levels is warranted to address a clear problem of active pharmaceuticals in dietary supplements.
Given a position on the “front lines” of medicine, primary care and integrative providers are a natural fit for educating Congress and other lawmakers regarding the implications of lax regulation of widely distributed products such as supplements. Aside from governmental work, an essential role of the provider is communicating the information about these supplements to our patients, asking patients about use, advising caution, and investigating medical complaints with an awareness of these products and the potential health effect of inadvertent ingestion of the hidden, active pharmaceuticals. Two resources, in particular, may be useful to patients and providers interested in verifying safety of supplements. Consumer Lab conducts and publishes results of independent testing of products.16 The Botanical Adulterants Prevention Program, backed by three nonprofit groups, publishes a free, up-to-date newsletter and website with information pertaining to adulterated products.17 Using these and other resources, patients and providers can design an individualized treatment plan with a goal of minimizing risk and maximizing health benefits of supplements and related products.
Financial Disclosure: Integrative Medicine Alert’s Executive Editor David Kiefer, MD; Peer Reviewer Suhani Bora, MD; Relias Media Executive Editor Leslie Coplin; Editor Jonathan Springston; Editorial Group Manager Terrey L. Hatcher; and Accreditations Manager Amy M. Johnson, MSN, RN, CPN, report no financial relationships relevant to this field of study.