Undeclared Drugs Common in OTC Supplements, FDA Data Show

More than 700 over-the-counter dietary supplements were found to contain unauthorized and undeclared pharmaceuticals between 2007 and 2016, according to data from the US Food and Drug Administration (FDA).

"These products have the potential to cause severe adverse health effects owing to accidental misuse, overuse, or interaction with other medications, underlying health conditions, or other drugs within the same dietary supplement," write the authors of a quality improvement study evaluating the FDA data that was published online October 11 in JAMA Network Open.

Madhur Kumar, PhD, from the California Department of Public Health, Sacramento, and colleagues analyzed data from the FDA's tainted supplements database entered between 2007 and 2016. Each FDA warning included the date, product name, company, name of the hidden ingredient identified, lot number, and indication for which the product was marketed.

Kumar and colleagues identified a total of 776 dietary supplements after accounting for duplicate warnings. The majority of the products included were marketed for sexual enhancement (45.5%), weight loss (40.9%), or muscle building (11.9%).

Whereas the majority of products (96.2%) tested positive only once for adulteration, the investigators found that 3.8% of products were found to be adulterated in two or three instances. Further 67.9% of those products with multiple warnings contained new ingredients at the time of their second or third warning.

Among products marketed for sexual enhancement, the researchers found that 81.3% contained sildenafil and/or at least one of its structural analogs, and 20.4% contained tadalafil. These drugs, phosphodiesterase-5 (PDE5) inhibitors used to treat erectile dysfunction, are the main ingredients in Viagra and Cialis, respectively. The authors also note that dapoxetine, a selective serotonin reuptake inhibitor (SSRI) antidepressant not approved by the FDA, was found in 4% (14/353) of sexual enhancement supplements.

Among the weight loss drugs, Kumar and colleagues found that sibutramine, a drug removed from the US market in 2010 because of cardiovascular risks, was identified in 84.9% of products. They also note that fluoxetine, a prescription antidepressant, was found in 5.4% of the drugs in this category. Overall, 25.2% of adulterated weight loss supplements contained more than one unauthorized drug ingredient.

Among products marketed for muscle building, 89.1% contained undeclared anabolic steroids or steroid-like substances.

When evaluating the FDA's response to finding unauthorized ingredients, the researchers found that, among the 776 adulterated supplements identified, the FDA requested voluntary recall of fewer than half the adulterated supplements identified (360/776; 46.4%), and just 342 (44.1%) were associated with a public notification.

"The FDA data show that anyone consuming sexual enhancement dietary supplements has the potential to be unknowingly consuming PDE5 inhibitors or SSRIs, risking interaction with other medications or pre-existing health conditions," Kumar and colleagues write. Further, products containing stimulants such as sibutramine can pose "a risk to patients with a history of heart disease or stroke."

The researchers note that postmarket surveillance of dietary supplements is challenging, "mainly owing to difficulties in asserting causality and under-reporting." The authors also acknowledge limitations of the study itself including the fact that the analysis was performed independent of FDA involvement and that findings are limited to drugs that the FDA tested.

Surveillance Is Good, but More Stringent Enforcement Required

In an invited commentary, Peter A. Cohen, MD, from the Cambridge Health Alliance, Somerville, and Harvard Medical School, Boston, Massachusetts, writes: "The database does not provide information as to why the FDA fulfilled its responsibilities less than half of the time, but it is possible that some firms might have refused to voluntarily recall their products."

In discussing other tools that the FDA has at its disposal when sanctioning companies found to be selling adulterated supplements, Cohen notes that "the FDA reported no mandatory recalls and only one Department of Justice investigation in response to the 746 brands of adulterated supplements."

Yet, the authors note that the problem is not going away. "Potentially harmful active pharmaceuticals continue to be identified in over-the-counter dietary supplements," write Kumar and colleagues.

"As the dietary supplement industry continues to grow in the United States, it is essential to further address this significant public health issue," they conclude.

No funding was provided for the study; however, the study was conducted as part of a fellowship with the California Epidemiologic Investigation Service. The study authors have declared no relevant financial relationships. Cohen was the subject of a civil suit brought by Hi-Tech Pharmaceuticals, a supplement company, regarding β-methylphenethylamine (BMPEA); the jury ruled in Cohen's favor. Cohen has collaborated in research with NSF International and received research support from Consumers Union.

JAMA Network Open. Published online October 12, 2018. Abstract, Editorial

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