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

Abstract

Background: Weight loss and sports supplements containing deterenol have been associated with serious adverse events including cardiac arrest. Objective: To determine the presence and quantity of experimental stimulants in dietary supplements labeled as containing deterenol sold in the United States. Methods: Dietary supplements available for sale in the US and labeled as containing deterenol or one of its synonyms (e.g., isopropylnorsynephrine and isopropyloctopamine) were purchased online. For each brand, one container or subsample was analyzed by NSF International (Ann Arbor, MI) and one container or subsample by the Netherland's National Institute for Public Health and the Environment (RIVM, Bilthoven, The Netherlands). When differences existed between the two containers or subsamples of the same brand, both products were reanalyzed by Sciensano (Brussels, Belgium). NSF International carried out qualitative and quantitative analyses using ultra-high-performance liquid chromatography (UHPLC) quadrupole-Orbitrap mass spectrometry. RIVM performed qualitative and quantitative analysis using UHPLC quadrupole time-of-flight mass spectrometry. Sciensano carried out qualitative analysis using UHPLC quadrupole-Orbitrap mass spectrometry. Results: Seventeen brands of supplements were analyzed. Many brands included more than one prohibited stimulant in the same product: 4 brands (24%, 4/17) included 2 stimulants, 2 (12%, 2/17) combined 3 stimulants, and 2 (12%, 2/17) combined 4 stimulants. The range of quantities per recommended serving size of the 9 stimulants detected were 2.7 mg to 17 mg of deterenol; 1.3 mg to 20 mg of phenpromethamine (Vonedrine); 5.7 mg to 92 mg of beta-methylphenylethylamine (BMPEA); 18 mg to 73 mg of octodrine; 18 mg to 55 mg of oxilofrine; 48 mg of higenamine; 17 mg of 1,3-dimethylamylamine (1,3-DMAA); 1.8 mg to 6.6 mg of 1,3-dimethylbutylamine (1,3-DMBA); and 5.3 mg of 1,4dimethylamylamine (1,4-DMAA). Conclusion: Weight loss and sports supplements listing deterenol as an ingredient contained 9 prohibited stimulants and 8 different mixtures of stimulants, with as many as 4 experimental stimulants per product. These cocktails of stimulants have never been tested in humans and their safety is unknown.

Lack of supplement regulation: A potential for ethical and physiological repercussions

“…Notwithstanding efforts to increase supplement safety via the FDA introduction of the Dietary Supplement Health and Education Act of 1994 (DSHEA)—most supplements are sold without a prescription, meaning that consumers may make purchases without adequate counselling (Nutrition C for FS and A, 2020). Additionally, in opposition to FDA recommendations, a more recent study revealed a concerning fact that 17 US-branded sports and weight loss supplements contained 9 FDA-prohibited stimulants (Cohen et al, 2021). These include deterenol, beta adrenergic agonist, which induce serious side effects such as respiratory distress and hypotension.…”

“…As a result of these incidents, coupled with a lack of safety data, the FDA issued a warning to manufacturers and distributors in 2012 in order to halt DMAA sales; now, DMAA is no longer an option for patients who could otherwise benefit from its lipolytic effects (Bloomer et al, 2018). However, despite deaths and subsequent prohibition, a recent study showed that 17 fitness or weight loss supplements currently on the market contain DMAA in their formulation (Cohen et al, 2021).…”

Development and Validation of UPLC-Qtof-MS Method for Blood Analysis of Amphetamine-Related Drug Isomers

“…The positional isomer of amphetamine, BMPEA, is currently uncontrolled, whereas amphetamine is a controlled substance. BMPEA can also be found in nutritional supplements for athletes and dieters [5][6][7]. Because of their positional isomers, their similar mass spectra can lead to incorrect identification [8].…”

Pre‐workout supplements marketed in Brazil: Caffeine quantification and caffeine daily intake assessment

“…Considerable labeling inconsistencies are reported in the literature with respect to the analysis of dietary supplements 19–21 . Regarding PWS, there are three major issues: the contamination with undeclared substances; the presence of stimulants that are declared on label but are not approved by the regulatory agencies; and inaccurate caffeine values 22–24 . In fact, the inaccurately labeling problem is not specific to caffeine but rather reflects a broader problem regarding the quantity of stimulants found in PWS, including other substances, such as small components of botanicals (e.g., yohimbine and higenamine) 25,26 …”

“…[19][20][21] Regarding PWS, there are three major issues: the contamination with undeclared substances; the presence of stimulants that are declared on label but are not approved by the regulatory agencies; and inaccurate caffeine values. [22][23][24] In fact, the inaccurately labeling problem is not specific to caffeine but rather reflects a broader problem regarding the quantity of stimulants found in PWS, including other substances, such as small components of botanicals (e.g., yohimbine and higenamine). 25,26 Studies that quantified caffeine in supplements reported numerous irregularities, including products without statement of the caffeine content, intra-and inter-lot variations of caffeine content, or even the absence of this compound.…”