The study was published in the journal Clinical Toxicology. It was conducted by prominent dietary supplement industry critic Pieter Cohen, MD, of Harvard; John Travis, PhD, of NSF International; and others, including researchers associated with the Dutch National Institute for Health and the Environment. The report analyzed the contents of 24 supplements that were labeled to contain higenamine or one of its synonyms, such as norcoclaurine or demethylcoclaurine.
Higenamine, according to the authors, is a stimulant ingredient that can be isolated from several botanical sources, including Aconitum carmichaelii and Nandina domestica. The authors said it “has beta-agonist activity with chronotropic and inotropic properties.”
Risky ingredient within risky category
The paper places the potential risks of higenamine against the backdrop of a concern about the safety of dietary supplements in general, which is in concord with Dr Cohen’s long-held view that this is an unsafe category of products. The paper cites a 2015 study in the New England Journal of Medicine that links dietary supplement use with a troubling number of emergency room visits. The methodology and conclusions of that study have been refuted by experts within the dietary supplement industry.
Higenamine is a fairly new entrant on the list of dietary supplement ingredients. It seems to be part of the constant churn of new ingredients in the sports and weight loss categories, Travis said. As stimulant ingredients are discredited or banned outright, product developers move on to others.
“I heard whispers about it right after the DMBA paper came out,” Travis told NutraIngredients-USA. “A raw material supplier came to us asking about it, though they were using one of the synonyms. I think it’s fair to say that this is the ‘next new thing’ after DMBA.”
Travis did say that unlike DMBA or DMAA, there is no debate about the botanical origins of higenamine. Whether the higenamine used in products on the shelf came from plants or was synthesized is another question, one that was not covered in the present study.
Amounts of higenamine varied widely
The researchers identified 32 products that met their search criteria, but narrowed the field down to those that actually listed higenamine or one of the other names on the label. Of the 24 products tested, about half were marketed for weight loss and half for sports/energy applications. Two products had no discernible product positioning.
The products were analyzed both at NSF’s own laboratory in Michigan as well as a facility in the Netherlands. The results showed that the amount of higenamine in the products ranged from trace amounts to a high of about 62 mg of the ingredient per serving.
Of the five products that both listed the stimulant as an ingredient and claimed a dosage for it on the label, none came close to meeting label claim. Some had as much as twice as much listed, while others had virtually none.
Risks remain mostly unknown
The risks of higenamine remain poorly characterized, the authors said. The ingredient has been studied as a drug in China. In the US, the authors noted that several studies have been cited by marketers of the ingredient in support of its safety, but these papers are of dubious value because of methodological flaws.
Travis said there is a legitimate safety concern with the ingredient. While there is some information about the effects of injectable doses of higenamine ranging from 2.5 mg to 5 mg via the Chinese studies, there is no information that equates those effects to oral dosages of the ingredient.
The most easily identified risk associated with the use of higenamine is a quasi legal one. In 2017 the World Anti Doping Agency added the substance to its banned list of ingredients, meaning athletes risk suspension or worse if they test positive for having used the stimulant.
“My concern is primarily with athletes, but that being said, the safety studies have not been done, especially for oral dosage forms,” Travis said.
Clarity on NDI issue called for
The paper’s authors advocated that FDA could bring some clarity to the situation by finalizing the NDI draft guidance.
“[S]timulants such as higenamine that are natural constituents of botanical remedies will likely remain in unpredictable dosages in US dietary supplements. The FDA may be able to reduce consumers’ exposure to higenamine by finalizing their draft guidance on new dietary ingredients,” the authors wrote.
While mainstream press reports (and the authors’ own press release) said that the authors had ‘warned’ consumers and health care professionals against higenamine-containing products, the paper’s actual conclusion was somewhat more muted.
“Physicians, in the meantime, should be aware that supplements listing higenamine as an ingredient may contain a stimulant with important cardiovascular properties,” the authors said.
Source: Clinical Toxicology
2018 Sep 6:1-6. doi: 10.1080/15563650.2018.1497171. [Epub ahead of print]
“The stimulant higenamine in weight loss and sports supplements”
Authors: Cohen PA, Travis JC, Keizers PHJ, Boyer FE, Venhuis BJ