Think melatonin is safe? New research reveals hidden heart risk

• A large review of health data from more than 130,000 adults with insomnia found that people who took melatonin for a year or longer were more likely to develop heart failure, be hospitalized for the condition, or die from any cause compared with those who did not take the supplement.
• Although the study cannot prove that melatonin directly causes these outcomes, the strong association raises important safety questions about the long-term use of this popular sleep aid. The researchers stress that more research is needed to fully understand melatonin’s impact on heart health and ensure its safe use.

Long-term use of melatonin is associated with a higher risk of heart failure

People who regularly take melatonin to improve sleep may face serious health risks. A preliminary study presented at the American Heart Association’s 2025 Scientific Sessions found that adults with chronic insomnia who used melatonin for a year or longer were more likely to develop heart failure, be hospitalized for heart failure, and die from any cause than those who did not take the supplement. The findings will be discussed at the AHA Annual Meeting Nov. 7-10 in New Orleans, the leading international event for cardiovascular science and clinical research updates.

Melatonin is a hormone produced by the pineal gland that regulates the body’s sleep-wake cycle. Its levels naturally rise in the dark and fall during the day. Synthetic melatonin, which is chemically identical to the natural hormone, is widely used in the treatment of insomnia (difficulty falling and/or sleeping) and jet lag. In many countries, including the US, melatonin supplements can be purchased over the counter. However, since they are not regulated in the US, the products can vary greatly in purity and dosage.

How the study was conducted

The researchers divided the participants into two groups based on their medical records. Those who took melatonin for at least one year were classified as the “melatonin group,” while individuals with no data on melatonin use were classified as the “non-melatonin group.”

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

Research into heart failure and the safety of sleep aids

Although melatonin is touted as a safe and natural sleep aid, there is little evidence of its long-term effects on the cardiovascular system. The research team wanted to know if long-term use could affect the risk of heart failure in people with chronic insomnia. According to the American Heart Association’s 2025 Heart Disease and Stroke Statistics, heart failure occurs when the heart cannot pump enough oxygen-rich blood to support the body’s organs. The condition affects about 6.7 million adults in the US.

To investigate this question, the researchers used data from the TriNetX Global Research Network, an international database of de-identified medical records. They reviewed five years of data on adults diagnosed with chronic insomnia who documented melatonin use for more than a year. Each was paired with another person who also had insomnia but had never used melatonin. Individuals with a previous diagnosis of heart failure or prescribed other sleep medications were excluded.

The main analysis found:

• Among adults with insomnia, those whose electronic health records indicated long-term melatonin use (12 months or more) were about 90% more likely to have incident heart failure over 5 years compared with matched nonusers (4.6% vs. 2.7%, respectively).
• There was a similar result (82% higher) when the researchers analyzed people who had at least 2 melatonin prescriptions at least 90 days apart. (Melatonin is only available on prescription in the UK.)

Secondary analysis determined:

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

“Melatonin supplements are generally considered a safe and ‘natural’ option for better sleep, so it was striking to see such consistent and significant increases in serious health outcomes, even after balancing many other risk factors,” Nnadi said.

Reactions of experts and caution of sleep researchers

“I am surprised that doctors 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. In the US, melatonin can be taken as an over-the-counter dietary supplement and people should be aware that it should not be taken chronically without an appropriate indication,” said Marie-Pierre St-Onge, MD. Sc., CCSH, FAHA, Chair of the American Heart Association’s 2025 Science Statement Writing Group, Multidimensional Sleep Health: Definitions and Implications for Cardiometabolic Health. St-Onge, who was not involved in this study, is a professor of nutritional medicine in the department of general medicine and director of the Center of Excellence for Sleep and Circadian Research in the department of medicine at Columbia University Irving Medical Center in New York.

The study has several limitations. First, the database includes countries that require a prescription for melatonin (like the United Kingdom) and countries that do not (like the United States), and patient locations were not part of the de-identified data available to the researchers. Because melatonin use in the study was based only on those identified from medication entries in the electronic health record, anyone taking it as an over-the-counter supplement in the US or other nonprescription countries would be in the no-melatonin group; therefore, analyzes may not accurately reflect this. Hospitalization numbers were also higher than those for an initial diagnosis of heart failure because a number of related diagnosis codes can be entered for a hospitalization, and these may not always include a code for a new diagnosis of heart failure. The researchers also lacked information on the severity of insomnia and the presence of other psychiatric disorders.

“Worsening insomnia, depression/anxiety, or use of other sleep-enhancing medications may be associated with melatonin use and heart risk,” Nnadi said. “Also, although the association we found raises concerns about the safety of a widely used supplement, our study cannot prove a direct cause-and-effect relationship. This means that more research is needed to examine melatonin’s safety for the heart.”

Study details, background and design:

• The study included 130,828 adults (average age 55.7 years; 61.4% women) who were diagnosed with insomnia.
• The study’s data comes from TriNetX, established in 2013, a growing global network of de-identified real-world patient data available for research.
• 65,414 participants received melatonin at least once and reported taking it for at least a year.
• Another group of people was examined for comparison (the control group) — those who had never been prescribed melatonin and were matched to the melatonin group based on 40 factors including demographics, health status and medications.
• Participants were excluded if they had already been diagnosed with heart failure or had been prescribed other types of sleeping pills such as benzodiazepines.
• Melatonin and control groups were matched for age, sex, race/ethnicity, heart and nervous system disease, heart and nervous system medications, blood pressure, and body mass index. Researchers reviewed electronic medical records five years after the matching date.
• For the main findings, records were searched for codes related to the initial diagnosis of heart failure. Secondary findings included codes for hospitalization related to heart failure or death.
• After the initial analyses, the researchers confirmed the credibility of their findings by conducting a sensitivity analysis. This involved a slight change in the criteria: they required participants in the melatonin group to have at least two melatonin prescriptions at least 90 days apart. This adjustment aimed to determine whether the increased duration of validated melatonin prescriptions affected the results.

Note: the study presented in this article is a research summary. Abstracts presented at American Heart Association scientific meetings are not peer-reviewed, and findings are considered preliminary until published as full manuscripts in a peer-reviewed scientific journal.