Prohibited Stimulants in Dietary Supplements After Enforcement Action by the US Food and Drug Administration

The US Food and Drug Administration (FDA) is responsible for eliminating adulterated and potentially hazardous dietary supplements from the marketplace. The FDA uses a variety of enforcement actions, including public notices, to remove potentially hazardous ingredients. However, it is not known whether public notices are effective. We explored the effectiveness of the FDA’s public notices issued between 2013 and 2016 targeting prohibited sympathomimetic stimulants in supplements. We analyzed supplements purchased in 2014 and the same brands purchased again in 2017 to determine the presence of prohibited stimulants before and after the FDA issued public notices.

From January 1, 2013, to December 31, 2016, the FDA issued notices regarding 4 prohibited sympathomimetic stimulants: 1,3-dimethylamylamine (1,3-DMAA), 1,3-dimethylbutylamine (DMBA), β-methylphenylethylamine (BMPEA), and methylsynephrine (oxilofrine).^1-4 The FDA notices regarding ingredients in supplements not categorized as sympathomimetic stimulants, such as picamilon, were excluded from the current analysis. We previously analyzed all supplements on sale in 2014 listing Acacia rigidula as an ingredient for the presence of 1 stimulant, BMPEA.¹ For the current study, we purchased the same brands of supplements in 2017. Supplements purchased in 2014 were reanalyzed for 1,3-DMAA, DMBA, and oxilofrine, and supplements purchased in 2017 were analyzed for all 4 prohibited stimulants subject to FDA enforcement action. As previously described,¹ liquid chromatography–quadrupole time-of-flight mass spectrometry was used to analyze the supplements, and the presence of each stimulant was confirmed by accurate mass, retention time, isotope pattern, and at least 1 fragment ion in the mass spectra.

Of the 21 brands of supplements analyzed in 2014, a total of 12 brands (57%) were still available for purchase in 2017. The 12 brands that were available in both 2014 and 2017 were included in the current analysis (Table). In 2013, the FDA issued a public notice about the use of 1,3-DMAA. Of the 12 supplements purchased in 2014, 1,3-DMAA was present in 6 (50%). The FDA issued notices about the use of DMBA and BMPEA in 2015 and oxilofrine in 2016. Of the 12 supplements purchased in 2017, a total of 9 (75%) contained at least 1 of the 4 stimulants subject to FDA notices, and 6 (50%) contained 2 or more. One stimulant, DMBA, was not detected in any supplement purchased in 2014. After the FDA issued a public notice about DMBA in 2015, DMBA was detected in 4 of the 12 supplements (33%) purchased in 2017.

To eliminate potentially hazardous supplements from the marketplace, the FDA recalls individual products and issues public notices regarding individual ingredients. The effectiveness of FDA recalls of individual products has been previously studied.^5,6 One analysis⁶ found that 67% of brands subject to FDA recalls still on sale contained adulterants. Our current study explores the use of public notices targeting individual ingredients in supplements rather than individual products. Two findings are notable. First, the number of products that contained 1,3-DMAA, BMPEA, and oxilofrine decreased, but most supplements tested contained 1 or more prohibited stimulant, some up to 4 years after FDA action. Second, 1 stimulant was introduced only after FDA enforcement action. Future studies will be necessary to determine whether the FDA’s public notices may, on occasion, inadvertently lead to the introduction of prohibited stimulants in supplements.

Our study has several limitations. It was small; we analyzed 12 brands of supplements at 2 time points during a 3-year period. Larger studies will be necessary to confirm our findings. Furthermore, we analyzed only 1 sample of each supplement, and stimulants might vary from batch to batch.

Despite these limitations, our study provides further evidence that a regulatory system that relies on postmarket enforcement activities is insufficient to ensure the safety of dietary supplements. Practitioners should advise patients that dietary supplements may contain prohibited stimulants.

Accepted for Publication: July 26, 2018.

Corresponding Author: Pieter A. Cohen, MD, Department of Medicine, Cambridge Health Alliance, 236 Highland Ave, Somerville, MA 02143 (pcohen@challiance.org).

Published Online: October 22, 2018. doi:10.1001/jamainternmed.2018.4846

Author Contributions: Drs Gerona and Cohen had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: All authors.

Acquisition, analysis, or interpretation of data: Wen, Gerona.

Drafting of the manuscript: Cohen.

Critical revision of the manuscript for important intellectual content: Wen, Gerona.

Statistical analysis: Wen, Gerona.

Administrative, technical, or material support: Wen, Gerona.

Supervision: Cohen, Gerona.

Conflict of Interest Disclosures: Dr Gerona and Dr Cohen were subjects of a civil suit brought by Hi-Tech Pharmaceuticals, a supplement company, regarding β-methylphenylethylamine; Dr Gerona’s case was dismissed and the jury found in Dr Cohen’s favor. Dr Cohen has collaborated in research with NSF International and received research support from Consumers Union. No other disclosures were reported.

Additional Information: While the study was being conducted, Ms Wen was affiliated with the Clinical Toxicology and Environmental Biomonitoring Laboratory, University of California, San Francisco.