Adulterant to watch: Higenamine hazards in the sports supplements market

May 23, 2019

Higenamine is a beta-2 agonist added to the list of banned substances by the World Anti-Doping Agency (WADA) in 2017.

In February, former FDA Commissioner Scott Gottlieb announced the agency’s planned efforts to modernize regulation of dietary supplements. Gottlieb’s statement kicked off with an acknowledgment affirming what most of the dietary supplement industry already knows: “The use of dietary supplements, such as vitamins, minerals or herbs, has become a routine part of the American lifestyle.”1 Supplement usage is widespread, especially in many sports-from running and cycling to baseball and bodybuilding. And it’s not limited to elite athletes and professionals. Students, recreational athletes, and “weekend warriors” are a significant segment of the fast-growing sports nutrition market. But dietary and sports supplements sometimes contain banned substances and mislabeled ingredients-just ask the many elite athletes who’ve been suspended from their sports due to inadvertent doping. While suspension from competition is a serious concern for elite athletes, it’s the greater public health risk for athletes and consumers which should remain the industry’s central focus.

In the last 10 years, I’ve worked closely with researchers from Harvard Medical School, the National Center for Natural Products Research (NCNPR) at the University of Mississippi, and the National Institute for Public Health and the Environment (RIVM) in the Netherlands. In our published research, we’ve found that some supplements in the global market contain potentially harmful ingredients and contaminants, including drugs and untested compounds that are not always listed on the label. We’ve identified ingredients in supplements that may cause adverse health events, including liver damage, cardiac arrest, and even death. These ingredients are often deceptively labeled as botanical extracts such as geranium oil, dendrobium extract, aconite root, or Nelumbo nucifera, making it difficult for consumers and athletes to choose a supplement based on the ingredient listings alone.

While most manufacturers are committed to ensuring quality and safety, there are a few irresponsible and unscrupulous supplement makers out there. As our research demonstrates, their actions can put consumers’ health at risk.

 

Unlabeled, Inaccurate, and Potentially Harmful

In 2018, we published findings on a substance called higenamine (sometimes labeled as its synonyms “norcoclaurine” or “demethylcoclaurine”) in unpredictable and potentially harmful quantities in some supplement products, ranging from trace levels to 62 mg per serving. Of the 24 products we tested, only five listed a specific quantity of higenamine on the label, and none of those five quantities were accurate. The findings were published in the peer-reviewed journal Clinical Toxicology2.

Higenamine is a beta-2 agonist added to the list of banned substances by the World Anti-Doping Agency (WADA) in 2017. Less than two years after higenamine was included on the WADA list of substances prohibited in sport, our international team of public health researchers published our peer-reviewed study2 documenting inaccurately labeled and potentially harmful levels of the substance in weight-loss and sports/energy supplements available for purchase via the internet in the United States. The potential public health threat from higenamine dosages found in supplements remains uncertain. A small number of clinical trials were performed in China, but none used an oral dosage form of higenamine. Consumers are urged to use caution when consuming supplements labeled as containing higenamine.

 

What Is a Beta-2 Agonist?

Beta-2 agonists act as smooth muscle relaxers and may be used to treat asthma and other pulmonary disorders. Beta-2 agonists are so-called because they activate the beta-2 adrenergic receptors, inducing relaxation of the trachea-bronchial muscle and bronchodilation to open the airways. An example of a common drug in this class is albuterol, which can be found in fast-acting inhalers. Potential risks of beta-2 agonists include tachycardia, or an accelerated heart rate, as well as tremors, excessive sweating, anxiety, insomnia, and agitation. While higenamine is a beta-2 agonist, there has not been sufficient clinical research to understand if it poses the same benefits and/or risks as the beta-2 agonists currently used in the treatment of asthma.

 

Independent Testing and Certification

The impact of mislabeled and inaccurate ingredient listing is well-known in the dietary supplement industry, but the public health risk it imposes justifies a consistent reminder to manufacturers to maintain the highest possible standards of quality and accountability. The actions of a few bad manufacturers can generate a potential public health risk and reflect negatively on the entire supplement industry. Fortunately, reputable companies can seize this opportunity to showcase their products’ safety, verify label claims, and differentiate themselves in the marketplace. Independent third-party certification of dietary and sports supplements and ingredients helps protect the public health by providing an avenue for consumers to choose independently verified products and brands to demonstrate their commitment to quality.

 

 

John Travis has more than 20 years of experience as an analytical chemist specializing in the analysis of dietary supplements. As senior research scientist, dietary supplements, at global public health organization NSF International (Ann Arbor, MI), Travis analyzes hundreds of dietary supplement products each year for various contaminants, emerging drugs, and harmful compounds. He is a subject matter expert on athletic banned substances and was instrumental in the development of the screening methods used for the NSF International Certified for Sport® program, which now screens products for more than 270 banned substances on the World Anti-Doping Agency, National Football League, Major League Baseball, and National Collegiate Athletic Association lists. Travis is currently involved in the analysis of pharmaceutical agents and illicit drugs, stimulants, and other prohibited substances as both adulterants and contaminants in dietary supplements and functional foods, co-authoring scientific papers on ingredients of concern found in dietary supplements, including stimulant drugs DMAA, DEPEA, and DMBA.

References:

  1. https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm631065.htm
  2. Cohen PA et al. “The stimulant higenamine in weight loss and sports supplements.” Journal of Clinical Toxicology. Published online September 6, 2018.