Regular Melatonin Supplementation May Hide Hidden Heart Complications

Researchers find that prolonged use of melatonin for sleep disturbances or insomnia was associated with a 90% increased risk of heart failure diagnosis, heart failure hospitalization and mortality over 5 years.

The findings, to be presented at the American Heart Association’s Scientific Sessions 2025, found no evidence that melatonin supplements themselves cause heart problems. Rather, the need for melatonin as a sleep aid may hide underlying symptoms of cardiac risk.

Melatonin Supplementation

Melatonin is a naturally occurring hormone produced by the pineal gland that helps regulate the body’s sleep-wake cycle. Individuals experiencing sleep disturbances or insomnia often turn to over-the-counter melatonin as a sleep aid; however, melatonin supplementation may obscure symptoms that point to underlying heart complications.¹

Medical research confirms that sleep disorders, such as insomnia, are associated with poor cardiac outcomes. Sleep disturbances can increase blood pressure, stress hormones, and inflammation—all known risk factors for cardiovascular disease and other heart conditions.²

“Melatonin supplements are widely thought of as a safe and ‘natural’ option to support better sleep, so it was striking to see such consistent and significant increases in serious health outcomes, even after balancing for many other risk factors,” said Ekenedilichukwu Nnadi, MD, lead author of the study and chief resident in internal medicine at SUNY Downstate/Kings County Primary Care in Brooklyn, New York.¹

Although melatonin supplements are often recommended to patients by physicians, they are not FDA approved for the treatment of insomnia or sleep disorders.¹

“I’m surprised that physicians would prescribe melatonin for insomnia and have patients use it for more than 365 days, since melatonin, at least in the US, is not indicated for the treatment of insomnia,” said Marie-Pierre St-Onge, Ph.D., C.C.S.H., FAHA, chair of the writing group for the American Heart Association’s 2025 scientific statement, Multidimensional Sleep Health: Definitions and Implications for Cardiometabolic Health. “In the US, melatonin can be taken as an over-the-counter supplement and people should be aware that it should not be taken chronically without a proper indication.”¹

The Study

Researchers gathered electronic health records from 130,828 adults (average age of 55.7 years; 61.4% women) diagnosed with insomnia from the TriNetX database, a growing global network of real-world, de-identified patient data. They compared patients who were prescribed melatonin at least once (n = 65,414) with a control group who were never prescribed melatonin.¹

The groups were matched for age, sex, race/ethnicity, heart and nervous system diseases, medications for heart and nervous system diseases, blood pressure and body mass index.¹

Exclusionary criteria included prior diagnosis of heart failure or history of treatment with other types of sleeping aids, such as benzodiazepines. The researchers required participants in the melatonin group to have filled at least 2 melatonin prescriptions that were at least 90 days apart.¹

The Findings

The main analysis showed that adults with long-term melatonin use (12 months or more) had an estimated 90% increased risk of incident heart failure over 5 years compared with matched non-users (4.6% vs. 2.7%, respectively). Similar results (82%) were observed in patients when researchers analyzed people who had at least 2 melatonin prescriptions filled at least 90 days apart.¹

In a secondary analysis, individuals who took melatonin had a nearly 3.5-fold higher risk of hospitalization for heart failure compared with those who did not (19.0% vs 6.6%). Over the 5-year follow-up, all-cause mortality was also higher among melatonin users, who were almost twice as likely to die from any cause as non-users (7.8% vs 4.3%).¹

“Worse insomnia, depression/anxiety or the use of other sleep-enhancing medicines might be linked to both melatonin use and heart risk,” Nnadi said. “Also, while the association we found raises safety concerns about the widely used supplement, our study cannot prove a direct cause-and-effect relationship. This means more research is needed to test melatonin’s safety for the heart.”¹

Practice Implications

For pharmacists, these findings underscore the importance of assessing patients’ sleep concerns within a broader clinical context rather than viewing melatonin as a harmless supplement. Pharmacists can play a key role in identifying patients who use melatonin chronically and counseling them on potential underlying cardiovascular risks.

When discussing sleep aids, pharmacists should emphasize nonpharmacologic sleep hygiene strategies and encourage patients with persistent insomnia to seek medical evaluation for possible cardiac or metabolic contributors. Ongoing monitoring and collaboration with prescribers are essential to ensure safe, evidence-based use of melatonin.

REFERENCES

1. Long-term use of melatonin supplements to support sleep may have negative health effects. Presented at: American Heart Association Scientific Sessions 2025. November 7-10, 2025. New Orleans, Louisiana. Abstract MP2306

2. Sleep disorders and heart health. American Heart Association. June 26, 2023. Accessed November 4, 2025. https://www.heart.org/en/health-topics/sleep-disorders/sleep-and-heart-health