Study Finds Long-term Melatonin Use May Increase Heart Failure Risk

While these results do not confirm a direct causative relationship, they raise important concerns about the safety of melatonin, which is often perceived as a harmless sleep aid.

Melatonin is a hormone produced by the pineal gland that regulates the sleep-wake cycle. Synthetic melatonin supplements, which are chemically identical to the natural hormone, are commonly used to treat insomnia and jet lag. In the United States, these supplements are available over the counter but are not regulated, leading to variations in strength and purity across different brands.

In the study, researchers analyzed medical records from a significant database, focusing on adults with chronic insomnia. Participants were categorized into a "melatonin group" for those with documented melatonin use of at least one year, and a "non-melatonin group" for those without such documentation.

Lead author Ekenedilichukwu Nnadi, M.D., noted that the findings challenge the perception of melatonin as a safe supplement and may change how physicians advise patients regarding sleep aids.

The study aimed to explore the long-term cardiovascular effects of melatonin. Heart failure, which occurs when the heart cannot pump sufficient blood, affects approximately 6.7 million adults in the U.S.

By examining five years of medical records from the TriNetX Global Research Network, researchers found that participants in the melatonin group had a 90% greater chance of developing heart failure compared to the non-users. Specifically, 4.6% of those in the melatonin group experienced heart failure, compared to 2.7% in the control group.

Further analysis revealed that participants who filled at least two melatonin prescriptions, at least 90 days apart, had an 82% higher risk of heart failure.

The study also indicated that individuals in the melatonin group were nearly 3.5 times more likely to be hospitalized for heart failure, with hospitalization rates of 19.0% compared to 6.6% for non-users. Furthermore, 7.8% of the melatonin group died during the observation period, almost double the 4.3% mortality rate seen in the non-melatonin group.

These findings prompted concern from sleep researcher Marie-Pierre St-Onge, Ph.D., who emphasized the importance of sensible use and proper indications for melatonin, especially given that it is not officially indicated for insomnia treatment in the U.S.

However, significant limitations of the study should be noted. Since melatonin is handled differently across countries, researchers could not access participants' locations, which could potentially affect results. Additionally, melatonin use was only recorded if documented in electronic medical records, meaning many users could have been misclassified.

The study did not assess the severity of insomnia or the presence of other psychiatric disorders, which could contribute to both melatonin use and cardiovascular risk.

Overall, while the study indicates a concerning association between long-term melatonin use and heart-related health outcomes, Nnadi emphasized that it does not establish a direct cause-and-effect relationship and called for further research to clarify these risks.