Long-term use of melatonin supplements to help you sleep may have negative effects on heart health

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 due to chronic insomnia, according to a preliminary study published by the American Heart Association. Science Session 2025Held in New Orleans, November 7-10.

Melatonin is a hormone produced naturally in the pineal gland that helps regulate the body’s sleep-wake cycle. Melatonin levels increase in darkness and decrease during the day. Chemically identical synthetic versions of the hormone are often used to treat insomnia (difficulty falling and/or staying asleep) and jet lag.

Supplements are widely sold over the counter in many countries, including the United States. Because over-the-counter supplements are not regulated in the United States, strength, purity, etc. may vary between supplement brands.

In this study, researchers classified people who had been long-term users of melatonin (defined as long-term use recorded in electronic health records for more than a year) as part of the “melatonin group.”

On the other hand, people who had no melatonin recorded anywhere in their medical records were classified as the ‘non-melatonin group’.

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

Melatonin supplements are promoted and sold as safe sleep aids. However, a lack of data demonstrating long-term cardiovascular safety led researchers to examine whether melatonin use changes the risk of heart failure, especially in patients with chronic insomnia.

Heart failure, which occurs when the heart cannot supply enough oxygen-rich blood to the body’s organs to function properly, is a common condition that affects 6.7 million American adults, according to the American Heart Association’s 2025 Heart Disease and Stroke Statistics.

Using a large international database (TriNetX Global Research Network), the researchers reviewed five years of electronic health records of adults with chronic insomnia who had melatonin recorded in their health records and had used it for at least one year. They were matched with peers in the database who had insomnia but never had melatonin recorded in their health records.

People who had previously been diagnosed with heart failure or were prescribed other sleeping pills were excluded from the analysis.

Key analysis findings include:

• Among adults with insomnia, those whose electronic health records indicated long-term melatonin use (>12 months) were approximately 90% more likely to develop heart failure over 5 years than those who did not (4.6% vs. 2.7%, respectively).
• Similar results (82% higher) were found when researchers analyzed people who had received at least two melatonin prescriptions at least 90 days apart. (Melatonin is only available by prescription in the UK.)

Secondary analysis results:

• Participants taking melatonin were nearly 3.5 times more likely to be hospitalized for heart failure than those not taking melatonin (19.0% vs. 6.6%, respectively).
• Over five years, participants in the melatonin group were nearly twice as likely to die from any cause than those in the non-melatonin group (7.8% vs. 4.3%, respectively).

“Melatonin supplements are widely known as a safe and ‘natural’ option to support better sleep, so it was surprising to see consistent and significant increases in serious health outcomes even after taking into account many other risk factors,” said Nnadi.

“I am surprised that, at least in the United States, doctors are prescribing melatonin for insomnia and having patients use it for more than 365 days because melatonin is not appropriate for the treatment of insomnia. In the United States, melatonin is available over-the-counter, and people should know that melatonin should not be taken chronically without appropriate indications,” said Marie-Pierre St-Onge, MD, CCSH, FAHA. He is chair of the writing group for the American Heart Association’s 2025 scientific report, “Multidimensional Sleep Health: Definition and Implications for Cardiometabolic Health.”

Dr. St-Onge, who was not involved in the study, is a professor of nutritional medicine in the Department of General Medicine and director of the Center of Excellence in Sleep and Circadian Research at the Columbia University Irving Medical Center School of Medicine in New York.

This study has several limitations. First, the database included countries that required melatonin prescriptions (e.g., the United Kingdom) and countries that did not (e.g., the United States), and patient location was not part of the de-identified data available to researchers.

Because melatonin use in the study was based only on what was identified in the medication section of electronic health records, anyone taking melatonin as a regular supplement in the United States or other countries where it does not require a prescription would have been in the non-melatonin group. Therefore, our analysis may not accurately reflect this.

Hospitalization figures were also higher for initial heart failure diagnoses because a variety of related diagnosis codes may be entered for hospitalization and new diagnosis codes for heart failure may not always be included. Researchers also lacked information about the severity of insomnia and the presence of other psychiatric disorders.

“Severe insomnia, depression/anxiety, or use of other sleep-enhancing medications may be associated with melatonin use and cardiac risk,” Nnadi said.

“The association we found also raises safety concerns for this widely used supplement, but our study cannot demonstrate a direct causal relationship, which means more research is needed to test the cardiac safety of melatonin.”

Study details, background and design

• The study included 130,828 adults (mean age 55.7 years, 61.4% women) diagnosed with insomnia.
• Study data comes from TriNetX, founded in 2013. TriNetX is a growing global network of real-world, de-identified patient data that can be used for research.
• 65,414 participants reported being prescribed melatonin at least once and taking it for at least 1 year.
• A second group of people were studied for comparison (control group). They had never been prescribed melatonin and were matched to the group taking melatonin on 40 factors, including demographic information, health conditions and medications.
• Participants who had already been diagnosed with heart failure or were prescribed other types of sleeping pills, such as benzodiazepines, were excluded.
• The melatonin and control groups were matched for age, sex, race/ethnicity, cardiac and neurological disease, medications for heart and neurological disease, blood pressure, and body mass index. The researchers looked at electronic medical records for five years from the date of matching.
• For key findings, we searched records for codes associated with an initial diagnosis of heart failure. Secondary outcomes included hospitalization codes related to heart failure or death.
• Following the initial analysis, the researchers performed a sensitivity analysis to verify the reliability of the study results. The criteria here have changed slightly. Participants in the melatonin group were required to fill at least two melatonin prescriptions at least 90 days apart. This adjustment aimed to determine whether the extended duration of confirmed melatonin prescription affected the results.