Dietary Supplements Often Contain Banned Stimulants That May Be Harmful

By Megan Brooks

March 25, 2021

NEW YORK (Reuters Health) - Sports and weight-loss supplements on the market in the United States often contain prohibited stimulants and cocktails of stimulants that may be harmful, new research indicates.

Researchers analyzed 17 dietary supplements on the market and found nine prohibited stimulants formulated into eight different combinations - none of which have been studied in humans.

"We began our investigation to look for (a Food and Drug Administration)-prohibited stimulant in supplements called deterenol that has been linked to serious adverse events including sudden death in Europe," Dr. Pieter Cohen of Cambridge Health Alliance and Harvard Medical School, in Boston, told Reuters Health by phone.

"We not only found this banned stimulant, but we also discovered eight other prohibited stimulants including one last marketed as a World War II-era nasal inhaler, vonedrine," said Dr. Cohen.

The study appears in the journal Clinical Toxicology, the official journal of the American Association of Poison Control Centers.

Deterenol is a beta-adrenoceptor agonist that has never been approved for use in humans in the U.S. and is not permitted as an ingredient in dietary supplements. Since 2018, however, the drug has been detected in several brands of dietary supplements sold in the U.S.

Dr. Cohen, with colleagues at NSF International of Ann Arbor, Michigan, Sciensano, Belgium, and National Institute for Public Health and the Environment, the Netherlands, evaluated 17 brands of dietary supplements.

All of them were labeled as containing deterenol or one of its synonyms (isopropylnorsynephrine and isopropyloctopamine). Most of the supplements were marketed as either weight loss (47%) or sports/energy supplements (35%); three brands did not list an indication.

The prohibited stimulants were present in a range of quantities.

For example, the amount of deterenol ranged from 2.7 mg to 17 mg per serving. Consumers could be exposed to up to 69 mg of deterenol per day when following recommended serving sizes provided on the label.

Deterenol was the only stimulant present in eight of the brands (47%); deterenol was not detected in four brands (24%) despite being listed on the label.

Phenpromethamine (vonedrine) was the next-most commonly detected stimulant and ranged in quantity from 1.3 mg to 20 mg per serving. Only one of the four products found to contain phenpromethamine listed a synonym of the drug (n-methyl-beta-methylphenylethylamine) on the label.

Eight brands contained more than one prohibited stimulant: one brand, for example, contained 92 mg of beta-methylphenylethylamine (BMPEA), 55 mg of oxilofrine, 11 mg of deterenol and 11 mg of phenpromethamine per serving.

Seven stimulants - 1,3-dimethylamylamine (1,3-DMAA), 1,4-DMAA, 1,3-dimethylbutylamine (1,3-DMBA), BMPEA, higenamine, oxilofrine and octodrine - have previously been subject to Food and Drug Administration (FDA) regulatory actions including product seizures, warning letters and public notices. However, the FDA has not issued warnings to manufacturers or consumers on deterenol or phenpromethamine, according to the researchers.

"Doctors should recognize that when their patients are taking dietary supplements. It might not be the relatively benign amino acids, protein powders and caffeine that they're probably suspecting are in the products. Instead, they may contain very potent drugs that never been tested in human trials," Dr. Cohen told Reuters Health.

A spokesperson with the FDA Center for Food Safety and Applied Nutrition (CFSAN) told Reuters Health that the agency is "reviewing the findings of this paper."

"The FDA is dedicated to advancing our strategic priorities for dietary supplements: safety, product integrity, and informed decision-making. We appreciate studies like this for raising awareness and bringing needed attention to these matters," the spokesperson said by email.

"However, in general, the FDA does not comment on specific studies, but evaluates them as part of the body of evidence to further our understanding about a particular issue and assist in our mission to protect public health."

The study had no commercial funding. Dr. Cohen has received research support from Consumers Union and PEW Charitable Trusts. He was the subject of a civil suit brought by Hi-Tech Pharmaceuticals, a supplement company, in which the jury found in his favor.

SOURCE: Clinical Toxicology, online March 23, 2021.