“No place” for deterenol in sports and weight loss supplements, FDA enforcement concerns raised

24 Mar 2021 --- An international study published in Clinical Toxicology found nine prohibited stimulants and eight different mixtures of stimulants in 17 analyzed weight management and sports supplement brands available for sale in the US. 

The most abundant stimulant was deterenol, a beta-agonist with “potentially serious adverse effects when consumed orally in humans,” including nausea, vomiting, sweating, agitation, palpitations, chest pain and cardiac arrest.

The next most prevalent substance was phenpromethamine, marketed as a pharmaceutical stimulant in the Vonedrine nasal inhaler in the 1940s and 1950s. 

“These ingredients have no place in dietary supplements,” says co-author Dr. Pieter Cohen, associate professor of medicine at Harvard Medical School and internist at Cambridge Health Alliance.

“We’re talking about active pharmaceutical stimulants that have not been approved by the US Food and Drug Administration (FDA) for oral use as either prescription medications or dietary supplements.” 

Weakening sports nutrition’s rep?
The report arrives as the sports nutrition sector continues to present a lucrative market. Innova Market Insights reports the global number of F&B launches, including supplements tracked with a sports and recovery claim grew 29 percent (2015 to 2019).

To the authors’ knowledge, the only study on orally administered deterenol was published in 1949, conducted with 16 human subjects (Credit: NSF International).Meanwhile, the use of “recovery” claims in Sports Nutrition launches featured 30 percent year-over-year growth when comparing 2019 and 2018 launches. Sports nutrition now also promotes weight management, skin, cognitive, digestive and immune support.

“The small collection of products identified in the [Clinical Toxicology-published] report certainly does not represent the mainstream sports nutrition and weight management categories,” the Council of Responsible Nutrition (CRN) issued in a statement responding to the study.

“The products identified in the analysis are illegal products that masquerade as supplements, hoping to evade detection. This report serves as a reminder for consumers that it matters where one purchases dietary supplements.”

Marketed for sports and weight management
All 17 analyzed products listed a synonym for deterenol on respective labels, including isopropylnorsynephrine, isopropylnorsynephrine HC1, N-isopropylnorsynephrine HC1 and isopropyloctopamine. 

The majority of supplements were marketed as either weight loss (47 percent) or sports/energy supplements (35 percent). Three brands did not list an indication.

For each supplement brand, one subsample was analyzed by the NSF International and one by the Dutch National Institute for Public Health and Environment. When differences existed between the two samples of the same brand, both products were reanalyzed by Belgium-based Sciensano.

“Especially concerning” findings
Many brands included more than one unlabeled stimulant in the same product. Of the 17 tested products, four included two stimulants, two included three stimulants and two included four stimulants.

Detected stimulants included higenamine, beta-methylphenylethylamine and oxilofrine, all of which the study authors identified as “experimental” stimulants with “unknown” consumption risks.

Chemical structures of the nine stimulants found in the 17 tested products.“You never want to find unlabeled ingredients in supplements, but it is especially concerning to find these strange brews of experimental stimulants in products that are readily available in the US,” adds co-author John Travis, senior researcher at NSF International. 

After deterenol, phenpromethamine was the second most common stimulant identified in the tested supplement brands. 

“Given the very limited data available in the scientific literature, the dose at which oral phenpromethamine poses risks to humans is not known,” the study authors write.

“To our knowledge, no published study of animals or humans has investigated the safety of consuming phenpromethamine combined with other experimental stimulants identified in the current study.”

Lacking FDA action
Furthermore, the authors underscore that neither deterenol nor phenpromethamine have been subject to any FDA enforcement actions or consumer warnings.

In 2004, the FDA determined deterenol is not permitted as an ingredient in dietary supplements. Nevertheless, since 2018, two studies detected deterenol in several brands of US-sold dietary supplements. 

The Clinical Toxicology study points out FDA chemists have also previously confirmed the presence of deternol in supplements.

“Our study provides further evidence that the FDA may fail to act even when the agency’s own scientists identify adulterated supplements, as appears to be the case for deterenol,” the researchers note. “We also detected many stimulants that the FDA has attempted to remove from supplements.”

CRN agrees with the report’s conclusion that stronger, more proactive enforcement action is needed to protect the public from adulterated products in the market. 

“When illicit products are brought to the agency’s attention, FDA must act more quickly and decisively, both to establish a deterrent and to protect consumers,” the council maintains.

“FDA lacks a system to efficiently track products that come to market, so CRN continues to advocate for a mandatory product listing as a solution. This would allow the FDA to identify new products and act more quickly to remove illegal products from the market.”

NutritionInsight previously covered FDA-issued warning letters to supplements illegally marketed for mental health and COVID-19 treatments. 

By Anni Schleicher