People who regularly used melatonin supplements for at least a year were found to have a higher likelihood of being diagnosed with heart failure, being hospitalized for heart failure, or dying from any cause compared with those who did not use the supplement.

The finding comes from a preliminary study that will be presented at the American Heart Association’s Scientific Sessions 2025, held November 7–10 in New Orleans.

Melatonin is a hormone produced naturally by the pineal gland in the brain, where it helps control the body’s internal clock and the cycle of sleep and wakefulness. Levels rise at night and drop during the day. Synthetic melatonin, which is chemically identical to the natural hormone, is commonly taken to help with insomnia (difficulty falling and/or staying asleep) and jet lag. The supplement can be purchased without a prescription in many countries, including the United States. However, because over-the-counter products in the U.S. are not regulated, the amount and purity of melatonin can differ significantly between brands.

For this research, scientists reviewed electronic health records and grouped participants according to their melatonin use. Individuals who had documented use of melatonin for one year or longer were placed in the “melatonin group.” Those who had no record of melatonin use in their medical files were categorized as the “non-melatonin group.”

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

Why Researchers Investigated Melatonin’s Heart Effects

Melatonin supplements are widely advertised as a safe and natural way to improve sleep. However, there has been little research on how long-term use might affect heart health. This gap in knowledge led scientists to investigate whether taking melatonin regularly could influence the risk of developing heart failure, particularly among people with chronic insomnia.

According to the American Heart Association, heart failure occurs when the heart is unable to pump enough oxygen-rich blood to meet the body’s needs. The condition is common, affecting about 6.7 million adults in the United States.

To explore a possible connection, researchers analyzed data from the TriNetX Global Research Network, a large international database of electronic health records. They examined five years of records from adults with chronic insomnia who had documentation of melatonin use lasting more than one year. These participants were compared with others who also had insomnia but no record of taking melatonin. Individuals were excluded from the study if they already had a diagnosis of heart failure or had been prescribed other types of sleep medication.

The main analysis found:

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

A secondary analysis found:

• Participants taking melatonin were nearly 3.5 times as likely to be hospitalized for heart failure when compared to those not taking melatonin (19.0% vs. 6.6%, respectively).
• 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) over the 5-year 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, even after balancing for many other risk factors,” Nnadi said.