Long-term use of melatonin supplements, often used to promote sleep and address insomnia, was associated with a higher risk of heart failure diagnosis, heart failure hospitalization and death from any cause in chronic insomnia, according to a preliminary study to be presented at the American Heart Association’s (AHA) Scientific Sessions 2025.

In the study, researchers classified people who had used melatonin long-term (with long-term use defined as a year or more documented in their electronic health records) as part of the “melatonin group.” In contrast, those who never had melatonin recorded anywhere in their medical records were classified as the “non-melatonin group.”

“Melatonin supplements may not be as harmless as commonly assumed. If our study is confirmed, this could affect how doctors counsel patients about sleep aids,” said Ekenedilichukwu Nnadi, MD, lead author of the study and chief resident in internal medicine at SUNY Downstate/Kings County Primary Care in Brooklyn, NY.

Using a large international database (the TriNetX Global Research Network), the researchers reviewed 5 years of electronic health records for adults with chronic insomnia who had melatonin recorded in their health records and used it for more than a year. They were matched with peers in the database who also had insomnia but never had melatonin recorded in their health records. People were excluded from the analysis if they had previously been diagnosed with heart failure or had been prescribed other sleep medications.

The main analysis found:

• Among adults with insomnia, those whose electronic health records indicated long-term melatonin use (12 months or more) had about a 90 percent higher chance of incident heart failure over five years compared with matched non-users (4.6 percent vs. 2.7 percent, respectively).
• There was a similar result (82 percent higher) when researchers analyzed people who had at least two melatonin prescriptions filled at least 90 days apart. (Melatonin is only available by prescription in the United Kingdom.)

A secondary analysis found:

• Participants taking melatonin were nearly 3.5 times as likely to be hospitalized for heart failure when compared to those not taking melatonin (19.0 percent vs. 6.6 percent, respectively).
• Participants in the melatonin group were nearly twice as likely to die from any cause than those in the non-melatonin group (7.8 percent vs. 4.3 percent, respectively) over the five-
• year period.

The Natural Products Association (NPA) said that it was disappointed in the AHA’s erroneous statement that over-the-counter supplements in the U.S. “are not regulated.” Dietary supplements — including products containing melatonin — are subject to cGMPs (current good manufacturing practices) to confirm their identity, purity, strength and composition and that they contain no harmful adulterants. FDA (U.S. Food and Drug Administration) inspects hundreds of supplement companies every year to review their manufacturing processes, and NPA has been committed to ensuring that its members follow the cGMPs applicable to dietary supplements since the final rule was promulgated in 2007.

“We recommend that consumers with chronic sleeplessness and other chronic diseases always consult with their physicians to properly diagnose and treat their medical conditions,” said Daniel Fabricant, PhD, president and CEO of NPA. “The preliminary study examined whether melatonin use alters the risk of heart failure in chronic insomnia patients, which is not the supplement industry’s target population. Furthermore, the established literature demonstrates that short-term use of melatonin is safe. NPA agrees that consumers should not take melatonin supplements for chronic insomnia without a proper indication and in close consultation with a medical professional.”

In a statement, the Council for Responsible Nutrition (CRN) said that it urges all stakeholders to interpret these preliminary findings with caution and context. As the AHA itself noted, this research represents early, non–peer-reviewed data that cannot establish cause and effect. Chronic insomnia—a condition shared by all study participants—may itself be a contributing factor to heart health outcomes, raising more questions than answers.

The study cited several limitations, including that the patient database did not include countries (including the U.S.) that don’t require a prescription for melatonin. Individuals who took over-the-counter melatonin supplements in the U.S. or other countries that don’t require a prescription would fall in the non-melatonin group, the AHA said. This limitation raises additional questions about whether there is an actual cause-and-effect relationship and emphasizes that the study did not focus on the occasional use of melatonin for sleeplessness or other conditions, or FDA-regulated supplements containing versions of the hormone.

For more information, visit www.heart.org, www.npanational.org or www.crnusa.org.