Does long-term use of melatonin have negative health effects?

A new study raises safety concerns about long-term use of melatonin supplements by those with insomnia, noting that it appears to be associated with increased risk of heart failure. But while urging caution and suggesting more study, the authors also point out they have not shown that melatonin causes the adverse effects. Instead, they say caution is needed.

The findings are being presented as an abstract this weekend at the American Heart Association’s Scientific Sessions 2025 in New Orleans, according to a news release from the association.

Melatonin is a hormone the body produces that helps regulate a person’s sleep-wake cycle. The levels of the hormone increase in darkness and decrease in daylight. Per the association, “Chemically identical synthetic versions of the hormone are often used to treat insomnia (difficulty falling and/or staying asleep) and jet lag. The supplements are widely available over the counter in many countries, including the U.S.”

The release notes that in the U.S. supplements are not regulated and can vary in strength and purity.

The researchers looked at five years of health records for 130,000 adults who had a diagnosis of insomnia and had used melatonin for at least a year. They found those individuals were more likely to be diagnosed with heart failure, need hospitalization for it or die from any cause.

The findings are preliminary and have not been peer reviewed, the association said.

But “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 Dr. Ekenedilichukwu Nnadi, lead author of the study and chief resident in internal medicine at SUNY Downstate/Kings County Primary Care in New York.

About the study

Researchers classified those who had used melatonin for at least a year as documented in medical records as long-term melatonin users. Those with no melatonin use recorded anywhere in records were classified as the “non-melatonin” group.

The heart association defines heart failure as a condition that occurs when the heart can’t pump enough oxygen-rich blood out to the body’s organs, which need them to function properly. An estimated 6.7 million adults in the U.S. have heart failure.

After identifying those with a diagnosis of insomnia and documented long-term melatonin use, they matched them against peers in the database who had insomnia but didn’t use melatonin supplements. Those with a previous diagnosis of heart failure or who were prescribed other sleep aids were not part of the study.

Researchers found:

• Those taking melatonin had a 90% higher chance of incident heart failure over the five years, compared with the control subjects (4.6% vs. 2.7%).
• Those taking melatonin were 3.5 times as likely to be hospitalized for heart failure compared to the control group (19% vs. 6.6%)
• Those in the melatonin group were almost twice as likely to die from any cause compared to the control group (7.8% vs. 4.3%) over the five years.

The study had limitations. The database included some countries that sell melatonin over the counter and others that prescribe it. And since use was based only on those who had it noted in medical records, an unknown number taking the supplement over-the-counter could be in the control group as non-users. The researchers also noted that different diagnostic codes when one is hospitalized might contribute to an incorrect count. And the researchers didn’t know how severely insomniac anyone was or if they had other psychiatric disorders. And for the most part, the percentages were small.

“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.”