Dr. Pieter Cohen studies the borderline between drugs and ingredients billed as botanicals in dietary supplements. In one instance, his research led the Food and Drug Administration to crack down on weight-loss supplements illegally containing BMPEA, a compound chemically akin to amphetamine and linked to serious health risks. Its makers claimed it came from a Southwestern shrub but evidence pointed to its synthetic origin.
Higenamine is found in the plant Nelumbo nucifera lotus seed.
Cohen’s latest target is the stimulant higenamine, an ingredient listed on the labels of weight loss and sports supplements. Working with a public health team from the Netherlands and an international testing lab, the Harvard Medical School associate professor studied 24 products containing higenamine. The amount on the label was never the same as the amount found in the bottle, the team found in a study published Thursday, and the serving sizes also varied, from trace amounts to 110 milligrams per day.
“There are situations where you find something that is present in plants, but at a high-end dose, it becomes a drug,” said Cohen, who is also an internist at Cambridge Health Alliance.
Too much caffeine, for example, can be dangerous. With higenamine, little is known about its safety. It’s allowed by law to be sold in a supplement because it is found in plants, but the World Anti-Doping Agency banned it from sports in 2017 and sanctioned several athletes who said they didn’t know they were consuming it. While WADA’s prohibition doesn’t speak to safety, it suggests the agency suspected higenamine would improve an athlete’s performance.
As Cohen and his team reported in the journal Clinical Toxicology, the scientific literature about higenamine’s health effects is scant, limited to studies from China in which the stimulant was used to simulate cardiac stress tests for when a patient can’t run on a treadmill. Those studies said small amounts injected intravenously made the heart beat faster, pumping more blood in a way that replicated exercise. Patients felt shortness of breath, dizziness, headaches, and chest tightness.
How higenamine affects people who swallow it in supplement pills isn’t known, and that troubles Cohen.
“There are at least a hundred questions we would need to study, a hundred different types of investigations, just to figure out how these supplements would get into the bloodstream. Then we’d look at how much is in the urine, then we’d have a better sense of the effect on the heart,” he said. “Right now, it’s really a black box.”
These products fall under the 1994 Dietary Supplement Health and Education Act, which permits traditional botanical remedies to be sold. A draft guidance from the FDA, last updated in 2016, would not allow synthetic versions of botanical ingredients.
“The FDA is reviewing the findings of the paper,” FDA spokeswoman Megan McSeveney said in a statement responding to questions about the Cohen study and the draft guidance. “Since the FDA has no authority to approve dietary supplement products before they go to market and very limited opportunities for premarket review, it is particularly important for consumers, health professionals, and industry members to report health-related reactions or illnesses to the FDA, so we can take action to protect the public from unsafe products.”
An executive at the Council for Responsible Nutrition, a trade group representing the supplement industry, said while all the products examined in Cohen’s paper listed ingredients, regulations do allow companies not to list their proprietary blend of ingredients. “Coke and Pepsi do not give out their formulas,” said Duffy Mackay, senior vice president of scientific and regulatory affairs. “We … recommend to consumers, especially in sports nutrition and weight loss, buy from brands you know and trust. Talk to your doctor, do your due diligence.”
The trade group has a registry on which its members list their products, labels, individual ingredients, and amounts. It now contains 10,000 labels.
Dr. Joshua Sharfstein, a former deputy commissioner at the FDA and a professor of practice in health policy and management at Johns Hopkins Bloomberg School of Public Health, has previously called for registration of all dietary supplements to make enforcement against rogue products easier. Such a registry would require all supplement makers to say what a product contains before marketing it. In that way, the FDA would know what’s on the market and could ask for more data if there is a concern about safety.
“People shouldn’t have to wait for Dr. Cohen to publish a paper to figure out what’s in different dietary supplements,” Sharfstein said.
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