Abstract
This analysis of dietary supplements purchased in 2014 and purchased again in 2017 examines whether stimulants that were initially present were still present after issuance of public notices by the US Food and Drug Administration to remove potentially hazardous ingredients.
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).1,2,3,4 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.
Table. Quantities of 4 Experimental Stimulants Subject to FDA Public Notices in Supplements Purchased in 2014 and 2017.
| Producta | Claim on Label or Website | BMPEA,b Mean (SD), mg per Pill or Capsule | 1,3-DMAA,c Mean (SD), mg per Pill or Capsule | DMBA,d Mean (SD), mg per Pill or Capsule | Oxilofrine,e Mean (SD), mg per Pill or Capsule |
|---|---|---|---|---|---|
| Supplements Purchased in 2014 | |||||
| A | Cognitive function | ND | ND | ND | 0.07 (0.04) |
| B | Weight loss | ND | ND | ND | 54.31 (0.82) |
| C | Weight loss | 18.71 (2.16) | 36.70 (11.91)f | ND | 34.07 (10.06) |
| D | Weight loss | 5.74 (1.15) | ND | ND | 26.48 (2.56) |
| E | Weight loss | 27.35 (5.87) | 34.68 (0.89)f | ND | 34.31 (2.06) |
| F | Weight loss | ND | ND | ND | 0.31 (0.04) |
| G | Sports supplement | 3.22 (0.67) | ND | ND | 7.78 (0.49) |
| H | Sports supplement | 31.23 (5.72) | ND | ND | 31.07 (1.94) |
| I | Weight loss | 9.89 (1.26) | 12.17 (1.23)f | ND | 25.62 (1.53) |
| J | Weight loss | 3.35 (0.74) | 12.03 (1.31)f | ND | 37.45 (1.21) |
| K | Weight loss | 0.97 (0.31) | 11.39 (1.74)f | ND | 40.75 (5.31) |
| L | Weight loss | 23.05 (2.79) | 26.89 (6.05)f | ND | 37.44 (7.43) |
| Supplements Purchased in 2017 | |||||
| A | Cognitive function | ND | ND | ND | 0.05 (0.01)f |
| B | Weight loss | ND | ND | ND | 40.84 (6.48)f |
| C | Weight loss | ND | ND | 30.43 (3.26)f | 7.09 (0.91)f |
| D | Weight loss | ND | ND | ND | 28.38 (0.82)f |
| Eg | Weight loss | 17.23 (1.47)f | 36.12 (5.45)f | ND | 27.43 (1.06)f |
| F | Weight loss | ND | ND | ND | ND |
| G | Sports supplement | ND | ND | ND | ND |
| H | Sports supplement | ND | ND | ND | ND |
| I | Weight loss | ND | ND | 10.98 (3.09)f | 5.59 (0.85)f |
| J | Weight loss | ND | 27.99 (1.37)f | ND | 8.77 (0.47)f |
| K | Weight loss | ND | ND | 17.05 (1.63)f | 8.44 (0.51)f |
| L | Weight loss | ND | ND | 39.53 (4.39)f | 8.85 (0.81)f |
Abbreviations: BMPEA, indicates β-methylphenylethylamine; DMBA, 1,3-dimethylbutylamine; 1,3-DMAA, 1,3-dimethylamylamine; FDA, US Food and Drug Administration; ND, not detectable.
Coded indicator of the product.
β-Methylphenylethylamine is not approved for use in humans. Quantities of BMPEA in products purchased in 2014 were previously reported.1
1,3-Dimethylamylamine is a 1940s to 1960s nasal decongestant (Eli Lilly & Co) that was withdrawn from the market in the 1970s. It was never approved for oral use.
1,3-Dimethylbutylamine is not approved for use in humans.
Oxilofrine was previously available in several European countries. It increased blood pressure and cardiac output and was available in 16- to 40-mg capsules. It was never approved for use in the United States.
Quantities represent stimulants in supplements after the FDA issued a public notice about the stimulant. The date of the FDA warning for 1,3-DMAA was July 2013; DMBA, April 2015; BMPEA, April 2015; and oxilofrine (referred to as methylsynephrine), April 2016.
Manufacturer of product E also received an FDA warning letter in 2015 that BMPEA was a prohibited ingredient listed on the label of product E.
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.
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.1793 [DOI] [PubMed] [Google Scholar]
- 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.2013.379 [DOI] [PubMed] [Google Scholar]
- 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.2014.10308 [DOI] [PubMed] [Google Scholar]