Written by Joyce Smith, BS. Weight loss and sports supplements containing deterenol have been associated with serious adverse events including cardiac arrest.
In the US, weight loss and sports supplements are responsible for thousands of annual emergency department visits and serious adverse events such as hemorrhagic stroke and sudden death 1. A sports supplement company, iForce Nutrition is, has been known to combine in their products experimental stimulants that have been linked to nausea, vomiting, sweating, agitation, palpitations, chest pain and even cardiac arrest 2. The implicated product, Dexaprine, contains deterenol, a beta- agonist that has not been approved for use in dietary supplements. Yet, in 2018, the CDC, who acknowledged its presence in dietary supplements 3, allowed manufacturers to continue their use of deterenol and to do so without placing warning labels on the products 4.
The following study 5, by Cohen et al 2021, was designed to detect the presence and quantity of experimental stimulants in dietary supplements that are labeled as containing deterenol and which are sold in the United States. Using the Google search engine allowed researchers to identify all dietary supplements listing deterenol or its synonyms on the label. Each brand was analyzed twice, once by an independent not for profit organization (NSF international in Ann Arbor, Michigan) that develops public health standards and certification programs, the other by the Netherlands National Institute for Public Health and the Environment (RIVM).
The most commonly found stimulant was deterenol, which, ranging from 2.7mg to 17 mg per serving, provided up to 69 mg of deterenol per day based on the recommended daily servings. Deterenol was the only stimulant present in 47% (8 out of 17) of the tested brands, and was not detected in four brands (24%). Phenpromethamine, the next most commonly detected stimulant, was present in 24% (4 out of 17) of tested brands and contained 1.3 mg to 20 mg per serving. Of the 17 brands, four brands included two stimulants, two brands contained a combination of three stimulants, and two other brands a combination of four stimulants.
Researchers found a total of nine prohibited stimulants that were formulated into eight different combinations, none of which have been studied in humans. Both the oral supplement ingredient deterenol, a beta-agonist with potentially serious side effects, and phenpromethamine, a stimulant found in the Vonedrine nasal inhaler that was marketed in the 1940s and 1950s, have not been approved for use anywhere in the world; yet, the FDA failed to require the companies to provide warning labels on the products. The following additional experimental stimulants were identified as well: oxilofrine, octodrine, beta-methylphenylethylamine (BMPEA), 1,3- DMAA, 1,4-DMAA, 1,3-DMBA and higenamine. While they have previously been subject to FDA regulatory actions including product seizures, warning letters and public notices, we are still unaware of the risks of consuming these combinations of stimulants.
The researchers caution against the use of experimental stimulants in weight loss and sports supplements and believe that the FDA should not only warn an unsuspecting public of their presence, but take immediate measures to effectively remove these potentially harmful and even life-threatening stimulants from the market. In the US, the FDA, which is responsible for removing adulterated supplements from the marketplace, has failed to recall more than half of 746 brands of supplements found to be adulterated with drugs 6,7. In addition, the FDA failed to warn consumers after the agency’s scientists discovered β-methylphenylethylamine (BMPEA), an amphetamine isomer whose efficacy and safety in humans has never been studied, in multiple dietary supplements 8. As an additional caution, the community of medical clinicians should “remain alert to the possibility that patients may be inadvertently exposed to experimental and prohibited stimulants when consuming weight loss and sports supplements”.
Study limitations include the small number of supplements tested. Only samples containing deterenol were analyzed and analysis was done at only one time point which fails to account for any future changes in product stimulants.
Source: Cohen, Pieter A., et al. “Nine prohibited stimulants found in sports and weight loss supplements: deterenol, phenpromethamine (Vonedrine), oxilofrine, octodrine, beta-methylphenylethylamine (BMPEA), 1, 3-dimethylamylamine (1, 3-DMAA), 1, 4-dimethylamylamine (1, 4-DMAA), 1, 3-dimethylbutylamine (1, 3-DMBA) and higenamine.” Clinical Toxicology (2021): 1-7.
© 2021 Informa UK Limited, trading as Taylor & Francis Group
Posted April 12, 2021.
Joyce Smith, BS, is a degreed laboratory technologist. She received her bachelor of arts with a major in Chemistry and a minor in Biology from the University of Saskatchewan and her internship through the University of Saskatchewan College of Medicine and the Royal University Hospital in Saskatoon, Saskatchewan. She currently resides in Bloomingdale, IL.
References:
- Geller AI, Shehab N, Weidle NJ, et al. Emergency Department Visits for Adverse Events Related to Dietary Supplements. The New England journal of medicine. 2015;373(16):1531-1540.
- Venhuis B, Keizers P, van Riel A, de Kaste D. A cocktail of synthetic stimulants found in a dietary supplement associated with serious adverse events. Drug testing and analysis. 2014;6(6):578-581.
- Zhao J, Wang M, Avula B, Khan IA. Detection and quantification of phenethylamines in sports dietary supplements by NMR approach. Journal of pharmaceutical and biomedical analysis. 2018;151:347-355.
- Pawar RS, Sagi S, Leontyev D. Analysis of bitter orange dietary supplements for natural and synthetic phenethylamines by LC-MS/MS. Drug testing and analysis. 2020;12(9):1241-1251.
- Cohen PA, Travis JC, Vanhee C, Ohana D, Venhuis BJ. Nine prohibited stimulants found in sports and weight loss supplements: deterenol, phenpromethamine (Vonedrine), oxilofrine, octodrine, beta-methylphenylethylamine (BMPEA), 1,3-dimethylamylamine (1,3-DMAA), 1,4-dimethylamylamine (1,4-DMAA), 1,3-dimethylbutylamine (1,3-DMBA) and higenamine. Clinical toxicology (Philadelphia, Pa). 2021:1-7.
- Cohen PA. The FDA and Adulterated Supplements-Dereliction of Duty. JAMA Netw Open. 2018;1(6):e183329.
- 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 Netw Open. 2018;1(6):e183337.
- 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 testing and analysis. 2016;8(3-4):328-333.
