While nutritional supplements look like any other pill, they are classified as food and not medicine by the FDA, which means they’re not subject to the same scrutiny as even over-the-counter drugs. When the FDA does find something amiss with a supplement, it can take several actions, including writing a warning letter to the product manufacturer. But a study published July 26 in the JAMA shows that a warning letter is often not enough to get a dangerous ingredient off shelves. The study found that of 31 supplements found to have illegal stimulants by the FDA, almost none were recalled by manufacturers. More than a quarter are still available for sale online and in stores years later — with the dangerous ingredients still present. The study’s lead author, Pieter Cohen, MD, an associate professor at Harvard Medical School in Boston and an internist at Cambridge Health Alliance, says the supplements studied were mostly marketed for weight loss and sports performance, and contained the following banned substances:
β-methylphenylethylamine or BMPEA, which according to past research in Drug Testing and Analysis has never been tested for safety in humans, and which was shown in at least one study to raise blood pressure in rats.Methylsynephrine, or oxilofrine, a stimulant that is banned in the United States and has been shown to increase heart rate and blood pressure. A study published in the Journal of Sports Science and Medicine in June 2021 reported that oxilofrine is sometimes not declared on supplement labels, leading to unintentional doping violations for professional athletes as well as health risks including cardiac arrest.DMHA, or octodrine, which research published in 2018 in Brain Sciences linked to hypertension, dangerous body overheating, and difficulty breathing.
“These designer stimulants — BMPEA, methylsynephrine, and DMHA — are drugs that are used as ephedra replacements,” Dr. Cohen says, referring to a natural stimulant the FDA banned in 2004. Ephedra had been used in many weight loss and sports supplements before it was linked to cases of heart attacks and sudden death. The ban on ephedra as an ingredient eliminated deaths and drastically reduced poisoning from its use in the United States, a New England Journal of Medicine article found. “We have previously studied these drugs in depth and are concerned that they might, like ephedra, increase the risk of serious heart disease or increase the risk of sudden death in susceptible consumers,” Cohen says. Of the study’s 31 products, only one had been recalled by its manufacturer. Researchers found that you could still purchase nine of the products online an average of six years after the FDA sent its warning letters. Four of the nine available products listed the presence of at least one prohibited ingredient on the label: One product label included the same prohibited ingredient that prompted the FDA warning letter and three others declared different FDA-prohibited ingredients on their labels. When researchers chemically analyzed the products, they found that more than half contained at least one FDA-prohibited ingredient — meaning some contained banned ingredients that weren’t even listed. The study’s authors have called on the FDA to do more to make sure dangerous products are off the market. The FDA could test products sold after warning letters have been issued, and it could require recalls whenever products still have banned ingredients. There’s precedent for this, Cohen notes. “FDA has the authority to issue a mandatory recall and seize products if they continue to be sold,” he says. “They’ve done that before with another stimulant, called DMAA. If the manufacturer continues to sell the products after all that, [FDA] would need to refer the case to the Department of Justice.” A warning letter is not the first encounter FDA and a manufacturer might have. Any dietary supplement entering the market after implementation of the Dietary Supplement Health and Education Act of 1994 is legally required to submit a New Dietary Ingredient Notification (NDIN) to the FDA before promoting or selling a product. An NDIN describes a supplement’s composition, manufacturing method, dose limit, intended use, and safety profile. The FDA doesn’t approve NDINs, but it may issue “an acknowledgment letter with no objection,” which indicates a product can proceed to market, says Karen Hecht, PhD, the scientific affairs manager at AstaReal, a supplement manufacturer, and an industry expert on supplement production and safety in Burlington, New Jersey. But that doesn’t preclude any future objections from FDA based on new evidence of unsafe or unapproved ingredients. “Most NDINs submitted since 1994 have received letters of acknowledgment,” Dr. Hecht says. “The number of acknowledgment letters is trending upwards because FDA and the supplement industry are working together to improve compliance. Although there are bad actors about, the industry at large is a responsible one that’s driven by a desire to make products that support people’s health and wellness. And the regulatory framework for supplements is a living and breathing one that evolves as the industry grows.” FDA’s Dietary Supplement Ingredient Advisory List is an online tool consumers can use to check the ingredients of their supplements. If an ingredient listed on a supplement is on the advisory list, it is not considered legal in the United States. Hecht also points to trade organizations such as the Council for Responsible Nutrition, Natural Products Association, and American Herbal Products Association working with the FDA and Federal Trade Commission “to make things better” for consumers. The tougher problem for consumers is if ingredients are unnamed on labels — or if they assume that a listed ingredient is safe to use. “Right now, given that we have a major problem with manufacturers being compliant with the law and an equally disturbing problem that the FDA is not enforcing the law, it’s not possible for consumers to know if their weight loss or sports supplements contain prohibited stimulants,” Cohen says. Talk with your healthcare provider before you start any new supplement. They can walk you through which ingredients to look out for — to improve your health and protect your safety.
