Beware of melatonin: study warns it’s not as safe as it seems

Taking melatonin supplements on a prolonged basis to combat insomnia may not be harmless; according to one study, people who take this compound for at least a year are more likely to suffer heart failure, to be hospitalized for it and to die from other causes.

The study, based on a five-year follow-up of 130,000 adults with insomnia who took melatonin, failed to demonstrate a cause-effect relationship between melatonin intake and health problems, but raises questions about its safety.

The study has not yet been peer-reviewed or published in a scientific journal, so its results are preliminary.

However, the authors will present their findings at the annual scientific meeting of the American Heart Association to be held November 7-10 in New Orleans (United States) because, in their opinion, these results demonstrate that research is needed on the use of melatonin to evaluate its cardiovascular safety and possible adverse effects.

Melatonin without prescription

Prolonged use of melatonin may increase risk of heart failure and death.
Getting better sleep may come at a hidden price. A new study from the American Heart Association warns that prolonged consumption of melatonin, the popular supplement for… pic.twitter.com/tbocY6gAtZ

– Enrique Coperías (@CienciaDelCope) November 3, 2025

Melatonin is a hormone secreted by the pineal gland that helps regulate the body’s sleep-wake cycle.

Melatonin levels increase at night and decrease during daylight.

Synthetic compounds identical to this hormone are often used to treat sleep difficulties or to combat jet lag.

In addition, they can be purchased without a prescription in many countries, such as Spain or the United States, where their sale is not regulated and each brand can vary the composition of these supplements in terms of potency, purity, etc.

These supplements are marketed as safe sleeping pills but there are no data demonstrating their safety, so the researchers examined whether melatonin use alters the risk of heart failure, specifically in patients with chronic insomnia.

Using a large international database (the TriNetX Global Research Network), the study included 130,000 adults with chronic insomnia and 55 years of age on average (61% women).

The researchers compared a group that had taken melatonin for more than a year with another group that had never taken melatonin.

In addition, people who had previously been diagnosed with heart failure or who had been prescribed other sleep medications were excluded from the analysis.

Among adults with insomnia who had taken melatonin for 12 months or more were approximately 90% more likely to suffer heart failure over a five-year period compared to those who had not.

Participants taking melatonin were almost 3.5 times more likely to be hospitalized for heart failure compared with those not taking melatonin (19% vs. 6.6%, respectively) and were almost twice as likely to die from any cause as those not taking melatonin (7.8% vs. 4.3%, respectively) over 5 years.

“Melatonin supplements are generally considered a safe and ‘natural’ option for improving sleep, so it was surprising to observe such a consistent and significant increase in serious health problems, even after balancing many other risk factors,” says Ekenedilichukwu Nnadi, lead author of the study and chief resident in internal medicine at SUNY Downstate/Kings County Primary Care in Brooklyn, New York.

The authors of the study acknowledge that the work has several limitations, such as the fact that the database includes countries that require a prescription for melatonin (such as the United Kingdom) and countries that do not (such as the United States), that the hospitalization figures may be inaccurate, or that they lacked information on the severity of insomnia or the presence of psychiatric disorders.

However, although “we cannot prove a direct cause-effect relationship,” the data “raise questions about the safety of this widely used supplement,” Nnadi notes.

“This means that more research is needed to prove the safety of melatonin for the heart,” he concludes.

Expert opinions

“I am surprised that doctors prescribe melatonin for insomnia and that patients use it for more than 365 days, since melatonin, at least in the United States, is not indicated for the treatment of insomnia,” opined Marie-Pierre St-Onge, chair of the American Heart Association’s 2025 scientific statement writing group, who was not involved in the study.

“In this country, it can be taken as a supplement without a prescription, but people should be aware that it should not be taken chronically without a proper indication,” he warns.

In addition, in statements to the scientific dissemination platform SMC Spain, Óscar Larrosa, clinical neurophysiologist and expert in Sleep Medicine, believes that the study is well designed, although it would be important to know what dose of melatonin the study participants took.

“The alleged harmlessness of melatonin in the long term and/or at high doses is still not entirely confirmed at present. This work can change a lot of things,” he says.

Also for Carlos Egea Santaolalla, president of the Spanish Federation of Sleep Medicine Societies, although the study has clear limitations, its findings underscore the need for a trial to clarify the safety of the supplement.

And for Javier Garjón, head of the Medicines Advisory and Information Service at the Subdirectorate of Pharmacy and Benefits of the Navarra Health Service, it is an important study on the risks of a product “that should be evaluated by the regulatory agencies”.

With information from EFE