Weight loss and sports supplements were found to contain cocktails of banned and unapproved stimulants, including one dangerous stimulant FDA ordered manufacturers to stop using years ago.
That’s according to a study published Tuesday in Clinical Toxicology, with its lead author saying the FDA’s oversight of the supplement industry continues to lag.
Pieter Cohen, MD, of Harvard Medical School and Cambridge Health Alliance in Massachusetts, and co-authors examined the makeup of 17 brands of over-the-counter supplements in the U.S., purchased online, that were labeled to include deterenol, a beta-agonist that has never been approved for use in the U.S., and which FDA banned from supplements in 2004.
Across those brands, the researchers found nine stimulant compounds that are not allowed in supplements, and eight different combinations of stimulants. Fewer than half contained only deterenol (47%). Four brands included two stimulants, two brands combined three stimulants, and two other brands combined four stimulants.
These stimulants included phenpromethamine (Vonedrine), BMPEA, oxilofrine, octodrine, higenamine, 1,3-DMAA, 1,3-DMBA, and 1,4-DMAA.
Deterenol has been found in several supplements sold in the U.S. in previous studies, with its presence confirmed by FDA chemists — even though the agency has prohibited it. Yet, the researchers noted, the agency “has not advised manufacturers to remove deterenol from products nor warned consumers to avoid supplements labeled as containing deterenol.”
Cohen told MedPage Today that is why the new study was needed: “It’s really unfortunate it would require any new information like publishing our study to get the FDA to act,” Cohen said, “and they haven’t.”
He said he was especially surprised to find that phenpromethamine was the second most commonly detected stimulant. It was used briefly as a nasal inhaler in the 1940s, but has never been approved for oral administration.
FDA also noticed phenpromethamine’s presence in supplements while Cohen’s team was working on this study, he said, yet, as with deterenol, the agency has declined to ask manufacturers to remove it or to alert the public.
“The FDA is not removing the lowest-hanging fruit, not even warning consumers about their finding,” Cohen said.
FDA declined to answer specific questions from MedPage Today, instead emailing a statement: “The FDA is reviewing the findings of this paper,” a spokesperson wrote. “We appreciate studies like this for raising awareness and bringing needed attention to these matters. 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.”
Cohen’s group pointed out that theirs is not the first study to report such findings, some going back at least 7 years.
“It seems like the FDA is not active within this space so companies can do what they wish,” Cohen said. “Even when the FDA tries to do something … they clearly don’t follow up in a way that ensures that stimulants are removed.”
Banning ephedra in 2004 has led to the “explosion” of other questionable stimulants in supplements, Cohen said. Manufacturers have slipped lesser-known, untested stimulants into supplements, often listing them on the bottle. Sometimes “it’s a matter of FDA reading the label and doing its job,” Cohen said.
Cohen called for Congress to reform supplement laws and for FDA to enact “robust” enforcement.
Steve Tave, JD, who directed FDA’s Office of Dietary Supplement Programs for 5 years until this month, favored mandating that manufacturers be listed in a national database, he said at a conference in September. (A copy of his prepared remarks was shared with MedPage Today by Cohen.)
“The question of ‘are dietary supplements regulated’ is a red herring. Of course they are, and it’s silly to suggest otherwise,” Tave said. “I think we can comfortably say, at a minimum, that the dietary supplement market isn’t perfectly regulated…. While we might know about more than 10,000 registered facilities around the world, we do not know what they are producing, and we don’t have a systematic way to know when new products are introduced to the market or what ingredients they contain.”
FDA inspected less than 5% of registered supplement facilities annually pre-pandemic, he said, adding: “The rate of non-compliance when we do inspect is very high — probably the highest it is for any FDA-regulated commodity, with frequent deficiencies in fundamental requirements.”
“Why is there so much non-compliance?” he asked rhetorically. He went on to assert a “regulatory gap” that prevents the FDA from taking enforcement action in many cases, because of the need to establish proof, resource availability, and what he called “quirks in the law” that stay the agency’s hand.
And he denied that the agency turns a blind eye to illegal supplements, pointing out the agency had issued “at least 57 warning letters” and filed one injunction and two seizures in fiscal 2019.
In the study by Cohen’s group, 35 samples of 17 supplements were analyzed at NSF International and the Netherlands’ National Institute for Public Health and the Environment, yielding matching results. Most were marketed for either weight loss (eight) or sports/energy enhancement (six).
Study limitations included a small sample size, and the focus on products with deterenol clearly listed as an ingredient.
Last Updated March 23, 2021
Cohen reported relationships with Consumers Union and Pew Charitable Trusts, and having been a defendant in a lawsuit brought by a supplements company. One co-author is an employee of NSF International, which has supplement manufacturers among its clients.
Source Reference: Cohen P, 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” Clin Toxicol 2021; DOI: 10.1080/15563650.2021.1894333.