[Skip to Content]
[Skip to Content Landing]
Table.  Quantities of 4 Experimental Stimulants Subject to FDA Public Notices in Supplements Purchased in 2014 and 2017
Quantities of 4 Experimental Stimulants Subject to FDA Public Notices in Supplements Purchased in 2014 and 2017
1.
Cohen  PA, Bloszies  C, Yee  C, Gerona  R.  An amphetamine isomer whose efficacy and safety in humans has never been studied, β-methylphenylethylamine (BMPEA), is found in multiple dietary supplements.  Drug Test Anal. 2016;8(3-4):328-333. doi:10.1002/dta.1793PubMedGoogle ScholarCrossref
2.
US Food and Drug Administration. Methylsynephrine in dietary supplements. April 2016. https://www.fda.gov/Food/DietarySupplements/ProductsIngredients/ucm493282.htm. Accessed May 15, 2018.
3.
US Food and Drug Administration. Stimulant potentially dangerous to health, FDA warns. April 11, 2013. https://www.fda.gov/ForConsumers/ConsumerUpdates/ucm347270.htm. Accessed May 15, 2018.
4.
US Food and Drug Administration. DMBA in dietary supplements. April 2015. https://www.fda.gov/Food/DietarySupplements/ProductsIngredients/ucm444719.htm. Accessed May 15, 2018.
5.
Harel  Z, Harel  S, Wald  R, Mamdani  M, Bell  CM.  The frequency and characteristics of dietary supplement recalls in the United States.  JAMA Intern Med. 2013;173(10):929-930. doi:10.1001/jamainternmed.2013.379PubMedGoogle ScholarCrossref
6.
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. doi:10.1001/jama.2014.10308PubMedGoogle ScholarCrossref
Limit 200 characters
Limit 25 characters
Conflicts of Interest Disclosure

Identify all potential conflicts of interest that might be relevant to your comment.

Conflicts of interest comprise financial interests, activities, and relationships within the past 3 years including but not limited to employment, affiliation, grants or funding, consultancies, honoraria or payment, speaker's bureaus, stock ownership or options, expert testimony, royalties, donation of medical equipment, or patents planned, pending, or issued.

Err on the side of full disclosure.

If you have no conflicts of interest, check "No potential conflicts of interest" in the box below. The information will be posted with your response.

Not all submitted comments are published. Please see our commenting policy for details.

Limit 140 characters
Limit 3600 characters or approximately 600 words
    Research Letter
    December 2018

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

    Author Affiliations
    • 1Department of Medicine, Cambridge Health Alliance, Somerville, Massachusetts
    • 2Department of Medicine, Harvard Medical School, Boston, Massachusetts
    • 3Department of Nutrition, University of California, Davis
    • 4Clinical Toxicology and Environmental Biomonitoring Laboratory, University of California, San Francisco
    JAMA Intern Med. 2018;178(12):1721-1723. doi:10.1001/jamainternmed.2018.4846

    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.

    Methods

    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.

    Results

    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.

    Discussion

    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.

    Back to top
    Article Information

    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.

    References
    1.
    Cohen  PA, Bloszies  C, Yee  C, Gerona  R.  An amphetamine isomer whose efficacy and safety in humans has never been studied, β-methylphenylethylamine (BMPEA), is found in multiple dietary supplements.  Drug Test Anal. 2016;8(3-4):328-333. doi:10.1002/dta.1793PubMedGoogle ScholarCrossref
    2.
    US Food and Drug Administration. Methylsynephrine in dietary supplements. April 2016. https://www.fda.gov/Food/DietarySupplements/ProductsIngredients/ucm493282.htm. Accessed May 15, 2018.
    3.
    US Food and Drug Administration. Stimulant potentially dangerous to health, FDA warns. April 11, 2013. https://www.fda.gov/ForConsumers/ConsumerUpdates/ucm347270.htm. Accessed May 15, 2018.
    4.
    US Food and Drug Administration. DMBA in dietary supplements. April 2015. https://www.fda.gov/Food/DietarySupplements/ProductsIngredients/ucm444719.htm. Accessed May 15, 2018.
    5.
    Harel  Z, Harel  S, Wald  R, Mamdani  M, Bell  CM.  The frequency and characteristics of dietary supplement recalls in the United States.  JAMA Intern Med. 2013;173(10):929-930. doi:10.1001/jamainternmed.2013.379PubMedGoogle ScholarCrossref
    6.
    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. doi:10.1001/jama.2014.10308PubMedGoogle ScholarCrossref
    ×