HerbalEGram: Volume 15, Issue 11, November 2018

An article published on October 12, 2018, in the Journal of the American Medical Association (JAMA) Network Open summarized and discussed US Food and Drug Administration (FDA) data from 2007 through 2016 on active pharmaceutical ingredients (APIs) illegally masquerading as dietary supplements. During this 10-year period, a total of 776 adulterated dietary supplement products were reported to the FDA and included in its Tainted Supplements database. Most of the reported products were marketed for sexual enhancement (353 products, or 45.5%), weight loss (317 products; 40.9%), or muscle building (92 products; 11.9%).¹

Despite the sensationalist and often misleading media reporting, the recent journal article did not reveal much new information but provided a more in-depth summary of the ongoing problem with undeclared APIs hidden in consumer products that are inappropriately marketed as dietary supplements. Similar findings, in the United States and in other countries around the world, have been published previously.^6-10 Although many media reports have characterized these tainted products as “dietary supplements,” such products are, in fact, from a regulatory perspective, drugs that contain unapproved APIs and are clearly mislabeled.

The FDA’s current Good Manufacturing Practice (cGMP) regulations for dietary ingredients and dietary supplements include specific rules (21 CFR Parts 111 and 117) to detect these illegal substances and prevent them from being included in consumer products. However, there has not yet been a concerted effort among members of the supply chain to adopt contract language and standard operating procedures (SOPs) to formalize these best practices. To fill that gap, the ABC-AHP-NCNPR Botanical Adulterants Prevention Program (BAPP) recently published a draft “Best Practices SOP for the Disposal/Destruction of Irreparably Defective Articles” (along with proposed language for supply contracts) for industry comment, and it expects to release the final version in the coming months.

The primary concern regarding the sale of undeclared APIs is their potential to cause harm. In a 2016 article, Calahan et al.⁶ described a number of case reports of patients who experienced adverse reactions due to undeclared APIs that were sold in products labeled as dietary supplements, food supplements, or herbal medicines. Increased awareness of the problem can be beneficial for health care professionals and consumers, and, as such, the FDA’s database of Tainted Products Marketed as Dietary Supplements¹¹ can serve as a useful resource for those interested in dietary supplements, particularly in the erectile dysfunction, weight loss, and bodybuilding categories. Several dietary supplement trade organizations such as the American Herbal Products Association,¹² the Council for Responsible Nutrition,¹³ and the Natural Products Association¹⁴ also have created websites to help consumers avoid purchasing such products.

Additionally, BAPP — a partnership among the American Botanical Council, the American Herbal Pharmacopoeia, and the National Center for Natural Products Research at the University of Mississippi — has previously raised concerns about APIs masquerading as specific ingredients, such as so-called “grapefruit (Citrus paradisi, Rutaceae) seed extracts”¹⁵ and maca (Lepidium meyenii, Brassicaceae) extracts, among numerous others.¹⁶

In an invited comment published in the same issue of JAMA Network Open, Pieter A. Cohen, MD, an assistant professor of medicine at Harvard Medical School, accused the FDA of dereliction of duty.¹⁷ He pointed out that the FDA issued voluntary recall requests to companies for only 360 of 748 distinct adulterated products, and only seven warning letters. Cohen suggested a mandatory product registration, which would allow for “immediately revoking a product’s registration if a supplement is found to be adulterated with pharmaceutical drugs,” as a practical solution to this problem.

While the usefulness of an FDA registry for dietary supplements can and should be debated, it is highly unlikely that it would have a big impact on removing such illegal products from the market. As indicated in the JAMA Network Open paper, 38.6% of the illegal products were identified through sampling of products purchased online, and 34.3% were identified through the examination of international mail shipments from 2014 to 2016. Manufacturers of these unlawful products are most often international and may use fictional addresses. The products often enter the United States in large numbers of small packages and are frequently sold online via social media or in community sales (e.g., farmers markets) (B. Pace [FDA] oral communication, February 16, 2018). Providing more resources to enforcement agencies and establishing a more global approach to tackling the illegal and fake supplement problem seems to be a more promising approach to dealing with this issue.

The sale of APIs as dietary supplements is a well-known issue that deserves more attention. These products are illegal, and — despite possibly containing dietary ingredients in addition to undeclared conventional drugs — are clearly not dietary supplements. Preventing these products from being brought into the market, and immediately removing them from store shelves and websites when discovered, along with vigorous regulatory enforcement across the supply chain, is in the best interest of consumers, health care professionals, regulators, and the dietary supplement industry.

—Stefan Gafner, PhD, Michael Levin, and Mark Blumenthal

References

1. Tucker J, Fischer T, Upjohn L, Mazzera D, Kumar M. Unapproved pharmaceutical ingredients included in dietary supplements associated with US food and drug administration warnings. JAMA Network Open. 2018;1(6):e183337.
2. Cohen R. No wonder it works so well: There may be Viagra in that herbal supplement. NPR. October 12, 2018. Available at: www.npr.org/sections/health-shots/2018/10/12/656875443/no-wonder-it-works-so-well-there-may-be-viagra-in-that-herbal-supplement. Accessed November 15, 2018.
3. Allday E. Those dietary supplements you’re taking may be contaminated, study shows. San Francisco Chronicle. October 12, 2018. Available at: www.sfchronicle.com/health/article/Those-dietary-supplements-you-re-taking-may-be-13303121.php. Accessed November 15, 2018.
4. Lee BY. What is in your dietary supplements? Study reveals unapproved ingredients. Forbes. October 12, 2018. Available at: www.forbes.com/sites/brucelee/2018/10/12/what-is-in-your-dietary-supplements-study-reveals-unapproved-ingredients/#22bce96f77e9. Accessed November 15, 2018.
5. Bernstein L. Diet, weight loss and sex supplements are tainted with unapproved drugs. The Washington Post. October 12, 2018. Available at: www.washingtonpost.com/national/health-science/diet-weight-loss-and-sex-supplements-are-tainted-with-unapproved-drugs/2018/10/12/b3e93bfc-cd7c-11e8-a360-85875bac0b1f_story.html. Accessed November 15, 2018.
6. Calahan J, Howard D, Almalki AJ, Gupta MP, Calderón AI. Chemical adulterants in herbal medicinal products: A review. Planta Med. 2016;82(06):505-515.
7. Sarma N, Giancaspro G, Venema J. Dietary supplements quality analysis tools from the United States Pharmacopeia. Drug Test Anal. 2016;8(3-4):418-423.
8. Skalicka-Woźniak K, Georgiev MI, Orhan IE. Adulteration of herbal sexual enhancers and slimmers: The wish for better sexual well-being and perfect body can be risky. Food Chem Toxicol. 2017;108:355-364.
9. Cohen PA, Maller G, DeSouza R, Neal-Kababick J. Presence of banned drugs in dietary supplements following FDA recalls. JAMA. 2014;312(16):1691-1693.
10. Petroczi A, Taylor G, Naughton DP. Mission impossible? Regulatory and enforcement issues to ensure safety of dietary supplements. Food Chem Toxicol. 2011;49(2):393-402.
11. Tainted products marketed as dietary supplements US Food and Drug Administration. October 16, 2018. Available at: www.accessdata.fda.gov/scripts/sda/sdNavigation.cfm?sd=tainted_supplements_cder. Accessed October 16, 2018.
12. KeepSupplementsClean.org. American Herbal Products Association. 2011. Available at: www.keepsupplementsclean.org/. Accessed October 16, 2018.
13. Three reminders for consumers when purchasing dietary supplements — A public service announcement from the Council for Responsible Nutrition [press release]. Washington DC: Council for Responsible Nutrition; October 12, 2018. Available at: https://crnusa.org/newsroom/three-reminders-consumers-when-purchasing-dietary-supplements-public-service-announcement. Accessed October 16, 2018.
14. NPA’s fight against tainted products. Available at: www.npanational.org/npas-fight-against-tainted-products/. Accessed November 15, 2018.
15. Cardellina II JH. Adulteration of grapefruit seed extract. Botanical Adulterants Prevention Bulletin. Austin, TX: ABC-AHP-NCNPR Botanical Adulterants Prevention Program; 2017:1-5.
16. Stewart J, Chioffi B. Adulteration of maca (Lepidium meyenii). Botanical Adulterants Prevention Bulletin. Austin, TX: ABC-AHP-NCNPR Botanical Adulterants Prevention Program; 2018:1-7.
17. Cohen PA. The FDA and adulterated supplements—dereliction of duty. JAMA Network Open. 2018;1(6):e183329.