Long-term use of melatonin supplements, commonly taken to improve sleep and reduce insomnia, may be associated with a significantly higher risk of heart failure and death, according to new research presented at the American Heart Association’s Scientific Sessions 2025.
Melatonin is a hormone that helps regulate the sleep-wake cycle and is produced naturally by the brain. Synthetic melatonin supplements are widely available, especially in the U.S., where they are sold over the counter. However, these supplements are not regulated, meaning their strength and purity can vary greatly.
Researchers analyzed electronic health records from the TriNetX Global Research Network, focusing on over 130,000 adults with chronic insomnia.
Participants were split into two groups: those who had melatonin listed in their records for at least a year (the “melatonin group”) and those with no record of melatonin use (the “non-melatonin group”). The groups were matched by 40 factors, including age, sex, BMI, health conditions, and medication use.
Key findings included adults using melatonin long-term had a 90% higher risk of developing heart failure over five years (4.6% vs. 2.7%). In a secondary analysis, those with at least two melatonin prescriptions 90 days apart had an 82% higher risk.
Melatonin users were nearly 3.5 times more likely to be hospitalized for heart failure and nearly twice as likely to die from any cause during the study period.
“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,” said lead author Dr. Ekenedilichukwu Nnadi of SUNY Downstate/Kings County.
Experts caution that while melatonin can help in some short-term cases—like jet lag—it is not FDA-approved for treating chronic insomnia in the U.S. “It’s surprising that melatonin is being used for such long periods when it’s not indicated for chronic insomnia,” said Dr. Marie-Pierre St-Onge, a professor at Columbia University and an American Heart Association volunteer expert.
The study has several limitations. Melatonin use was only recorded through prescriptions, which could underrepresent over-the-counter use in countries like the U.S.
Researchers did not have access to information about participants’ severity of insomnia or co-existing psychiatric conditions, which could influence both sleep aid use and heart risk. The results show an association, not a proven cause-and-effect relationship.
The study included 130,828 adults (average age 55.7 years; 61.4% women). Of those, 65,414 had taken melatonin for at least one year. Researchers followed their health outcomes for five years.
Melatonin users had no prior diagnosis of heart failure or history of using other sleep medications such as benzodiazepines. The research team validated their findings by doing a sensitivity analysis, which strengthened the results by ensuring that the increased risk still applied to those with confirmed long-term melatonin use.
While more research is needed to confirm these findings and explore the mechanisms, this study raises important safety questions about chronic melatonin use—especially in people with ongoing insomnia. Doctors and patients may need to rethink the long-term use of melatonin and consider alternative strategies for managing sleep health.
If you care about heart health, please read studies about top foods to love for a stronger heart, and why oranges may help fight obesity, diabetes, and heart disease.
For more health information, please see recent studies about simple guide to a 7-day diabetes meal plan, and why you should add black beans to your plate.
Copyright © 2025 Knowridge Science Report. All rights reserved.
