International study

Melatonin under observation: prolonged use is linked to heart risk

Conducted on more than 130,000 adults with insomnia, the survey points to an association between prolonged intake of the hormone and an increased likelihood of heart failure and hospitalisation. Researchers: 'Further verification of cardiovascular safety needed'

by Francesca Cerati

3 November 2025

3' min read

Translated by AI

Versione italiana

Key points

What the study found
Melatonin, between nature and chemistry
Doubts and caution from the scientific world
Heart failure in numbers

3' min read

Translated by AI

Versione italiana

What millions of people consider a natural and safe aid to sleep may not be so harmless. Prolonged use of supplements containing melatonin, the hormone that regulates the sleep-wake cycle, may be associated with a higher risk of heart failure, hospitalisation and general mortality.

These are the findings of a large international analysis that will be presented at the Scientific Sessions 2025 of the American heart association (AHA), scheduled for 7-10 November in New Orleans. The study, which involved 130,828 adults diagnosed with insomnia, was conducted using data from the TriNetX Global Research Network, a platform that collects millions of anonymised electronic medical records.

What the study found

The researchers compared the medical records of patients with chronic insomnia who had been taking melatonin for at least a year with those of subjects with the same condition but never treated with the supplement. The aim: to see whether long-term use could alter the risk of heart disease.

The results were stark. 4.6% of those taking melatonin developed heart failure over the next five years, compared to 2.7% in the control group: almost double the risk. Even more marked was the difference in hospital admissions: 19% among melatonin users versus 6.6% among non-users, a 3.5-fold increase in likelihood. And the overall mortality rate was also almost double (7.8% versus 4.3%).

A sensitivity analysis, based on patients with at least two melatonin prescriptions 90 days apart, confirmed an 82% increased risk of heart failure compared to non-users.

Melatonin, between nature and chemistry

Melatonin is a hormone produced by the pineal gland, which helps synchronise the circadian rhythm; its levels increase during darkness and decrease during the day. Synthetic versions, chemically identical to the natural molecule, are widely available without prescription, even in Italy and the US, where they are not subject to strict regulation. Each brand may differ in concentration and purity.

It was precisely this perception of a "natural and safe supplement" that prompted the researchers to investigate. "Melatonin supplements are considered harmless, but we found consistent and significant increases in serious cardiovascular events, even after correcting for other risk factors," commented Ekenedilichukwu Nnadi, lead author of the study and chief of internal medicine at Suny Downstate/Kings County Primary Care in Brooklyn, New York.

Doubts and caution from the scientific world

Along the same lines is Marie-Pierre St-Onge, director of the Center of Excellence for Sleep & Circadian Research at Columbia University Irving Medical Center and president of the Aha group that developed the scientific statement 'Multidimensional Sleep Health': 'I am surprised,' she explained, 'that melatonin is prescribed for more than a year. In the United States, it is not indicated for chronic insomnia, and people should know that it should not be taken for a long time without a specific medical indication.

The study, although relevant in terms of size, had some methodological limitations. It was not possible to know the geographical location of the patients (in countries such as the UK, melatonin is by prescription only, elsewhere it is over-the-counter), nor to distinguish those who were taking it independently without it being recorded in their medical records. Furthermore, there was a lack of data on the severity of insomnia, the presence of psychiatric disorders or the concomitant use of other sleeping medications.

'It is possible that worsening insomnia or conditions such as anxiety and depression are linked to both melatonin use and cardiac risk,' Nnadi pointed out. 'Our work shows an association, but does not demonstrate a direct cause-and-effect link. New controlled studies are needed to clarify the cardiovascular safety of this supplement,' he said.

Heart Failure in Numbers

According to American Heart Association 2025 statistics, heart failure affects 6.7 million adults in the U.S. alone. It is a chronic condition in which the heart cannot pump enough blood to meet the body's needs. The authors point out that, if confirmed, the findings could influence medical recommendations on the use of melatonin-based sleeping pills, now often considered a harmless solution.

Pending further research, the experts' message is one of caution. Melatonin remains useful for sleep-wake rhythm disorders such as jet lag or occasional insomnia, but chronic intake without medical supervision may not be without risk.

As is often the case in medicine, what is 'natural' is not automatically safe. And the heart, even when seeking just a little extra sleep, always deserves caution.