Over-the-counter (OTC) cognitive enhancement supplements may contain multiple unapproved pharmaceutical drugs, and the health effects of consuming untested combinations of unapproved drugs at unpredictable dosages in supplements without clinician oversight are unknown, according to Pieter A. Cohen, MD.

“Americans spend more than $600 million per year on OTC cognitive enhancement supplements, but very little is known about the safety of these products,” Dr. Cohen says. “Neurologists should counsel their patients to avoid supplements that are sold to improve memory, not just because they are unlikely to be effective, but also because the OTC products might include unapproved pharmacological drugs.”

Drugs Analyzed by a Team of Chemists

In a study published in Neurology Clinical Practice, Dr. Cohen and colleagues aimed to identify the presence of unapproved drugs in OTC dietary supplements marketed to improve memory and cognitive function. Supplements were identified by searching two supplement databases for products labeled as containing omberacetam, aniracetam, phenylpiracetam, or oxiracetam, four drugs not approved for human use in the United States. Products were analyzed using nontargeted liquid chromatography-quadruple time-of-flight mass spectrometry methods. “We used the National Institute of Health’s supplement database, along with another very reputable database, to select supplement brands,” Dr. Cohen explains. “The chemists on our team analyzed each product to determine the type and quantity of drugs in each of the OTC products.”

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Patients Could Be Putting Themselves at Risk

In the 10 products tested, omberacetam and aniracetam were detected along with three additional unapproved drugs: phenibut, vinpocetine, and picamilon. In some cases, consumers could be exposed to up to four-fold greater than pharmaceutical dosages and as many as four unapproved drugs when using individual products, Dr. Cohen notes.

Dr. Cohen and his team also found five drugs that are only approved for use outside of the US (Table). “These drugs were from four classes of medications and are used to treat a wide variety of conditions, including ischemic stroke, traumatic brain injury, and dementia,” he says.  “Some drugs were openly listed on the label, while others were not. Sometimes, the label listed specific dosages of the drug, but these dosages were often inaccurate. In some products, we found quantities of drugs that are similar to prescription dosages used in other countries. In other instances, the quantity we found was much greater than what a patient would consume if they were prescribed the medication under the supervision of a physician. At prescription doses, these unapproved drugs might cause insomnia, changes in blood pressure, and agitation. Of particular concern, however, is that we don’t know the effect of supratherapeutic dosages, as they have never been studied in humans.”

Given that these OTC products might directly affect patients’ health, Dr. Cohen recommends that physicians actively ask patients with memory difficulties if they have tried OTC supplements to improve their memory or cognitive functioning. “Opening up a dialogue will provide an important opportunity to educate patients about the lack of efficacy of these products and discuss the dangers of taking hidden, unapproved drugs in OTC supplements. In addition, we need to create a functioning system to monitor the safety of all supplements on the market so that the most dangerous products can be removed expeditiously by the FDA.”