Brain-boost supplements contain unapproved drug that could harm users

The FDA has sent warning letters to companies including Pure Nootropics for selling piracetam as a dietary supplement.

Promising to lift brain fog or improve memory, brain-boosting supplements have joined sexual-enhancement and weight-loss remedies in the lightly regulated world of dietary supplements. These products may be sold legally with broad-brush come-ons like these, as long as they don’t make specific claims about treating a disease — or contain actual drugs.

New research led by Dr. Pieter Cohen of Harvard Medical School documents five supplement brands for sale in the U.S. that contain various amounts of piracetam, a drug prescribed in European countries for cognitive impairment in dementia but not approved in the U.S.

The Food and Drug Administration doesn’t allow piracetam to be sold as a dietary supplement and has issued warning letters in the past to other companies marketing supplements that contain it. Though the drug is approved in Europe, evidence for using piracetam to improve cognition was “inadequate,” a Cochrane Review analyzing 24 studies that enrolled more than 11,000 patients concluded in 2012.

Cohen and his colleagues reported in JAMA Internal Medicine on Monday that piracetam is listed as an ingredient on the labels of five supplements for sale online. Relentless Improvement, Nootropics, and Specialty Pharmacy sold their products as piracetam. BPS named its supplement Compel, and Cognitive Nutrition called its NeuroPill but included piracetam on the label.

“It seems kind of bold to put a non-approved substance on the label,” said Dr. David Seres, associate professor of medicine at the Institute of Human Nutrition at Columbia University Medical Center, who was not involved in the study. “It’s horrifying but not terribly surprising.”

Side effects of piracetam include agitation, anxiety, and depression, but that’s when prescribed at a standard dose of the drug, whose mechanism of action was described in one research paper as “an enigma.” In Europe, older patients tend to be prescribed lower doses, Cohen said, to account for reduced kidney function that comes with age. That could be a concern for an older person seeking help with memory problems.

Cohen, who also practices internal medicine at Cambridge Health Alliance, worries that consumers could be taking a drug under no medical supervision at a dangerous dosage. In the study, Cohen’s team found wide variation in how much piracetam a person could be ingesting. “You just do not know from day to day if you’re getting zero of a drug or if you’re getting an amount that is more than a prescription.”

“It seems like this is a case where the FDA knows that something’s not permitted,” Cohen said. “They know it’s still on sale and they haven’t used their full enforcement power, nor have they informed the public that this is out there and should be avoided.”

Companies can start selling dietary supplements without notifying the FDA. But under the Dietary Supplement Health and Education Act, the FDA can take action if products are unsafe or misbranded. Marketing messages can’t claim the supplements treat Alzheimer’s disease, for example, nor can they contain unsafe ingredients. If they purport to treat, diagnose, prevent, or cure disease, the FDA can send warning letters or remove the products from the market.

These actions can seem like a game of whack-a-mole in the $46 billion arena of supplements, which has ballooned from 4,000 products in 1994 to as many as 80,000 products in the 25 years since Congress passed the dietary supplement law. In general, the FDA does not comment on individual studies like Cohen’s, spokeswoman Lindsay Haake told STAT, but it does step in for certain cases.

“The FDA prioritizes its actions based on available resources and the level of safety concern identified,” she said in a statement. “The agency faces the challenge of having limited resources to monitor the marketplace for potentially harmful, or otherwise unlawful, dietary supplements.”

The Council for Responsible Nutrition, an industry group that represents makers of dietary supplements, took a dim view of the small sample size in Cohen’s paper — “out of the entire internet, he was only able to find five products” — but agreed with him on the need for more enforcement of current law.

“We think there is more the FDA can be doing,” said Steve Mister, president of the trade group. “There are tools the agency has that it is simply not using as aggressively as it should.”

Change may be coming. In its 2020 budget, the FDA has proposed requiring supplement makers and distributors to list with the FDA all products marketed as dietary supplements. The FDA would then know when new products are introduced and take action against dangerous or otherwise illegal ones, Haake said.

Until then, Seres of Columbia has some advice.

“Eat a well-balanced diet,” he said. “And unless a health care professional suggests to you that you are deficient in any substance, perhaps consider that these may not be of benefit to you.”

Some brain-boosting supplements contain an unapproved drug that could harm users, study warns