What Are Melatonin Side Effects? Doctors Warn Long-Term Use Could Lead to Health Problems - Even Death

A preliminary study to be presented at the American Heart Association's Scientific Sessions 2025 found that long-term use of Melatonin supplements may lead to health problems such as heart failure and even death.

Melatonin is a hormone produced naturally in the body by the pineal gland in the brain. This hormone helps to regulate the body's sleep-wake cycle. The brain produces melatonin on its own, and its levels increase during darkness, typically one to three hours before bedtime, and decrease during daylight.

Chemically identical synthetic versions (made in labs) of the hormone, like melatonin supplements, give the body extra melatonin that can help some people fall asleep and are also often used to treat insomnia and jet lag.

What are Over-The-Counter Melatonin Supplements?

These supplements are widely available over-the-counter in many countries, including the US. Unlike in the UK, where melatonin is only available by prescription, which indicates regulation, over-the-counter supplements in the US are not regulated, so each brand of supplement can vary in strength, purity, etc.

Melatonin supplements are often advertised as a safe way to help people sleep, but there isn't enough evidence about their long-term effects on the heart. Because of this, researchers studied whether taking melatonin could affect the risk of heart failure in people with chronic insomnia.

'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, MD, lead author of the study and chief resident in internal medicine at SUNY Downstate/Kings County Primary Care in Brooklyn, New York.

Melatonin Supplement's Side Effects — Study Findings

The study has examined people who have been taking melatonin supplements for long-term—a year or more, as documented on their electronic health records based on a large international database from TriNetX Global Research Network. And they are identified as part of the 'melatonin group'.

On the other hand, people who have not taken any melatonin supplements recorded in their medical records are classified as the 'non-melatonin group'.

The main analysis of the study found that among adults suffering from insomnia who had been taking melatonin supplements for a long period, there was about a 90% higher likelihood of developing heart failure over five years compared with the matched 'non-melatonin group' (4.6% vs 2.7%, respectively).

A similar result was observed among people who had at least two melatonin prescriptions filled at least 90 days apart, showing an 82% higher risk. These participants were individuals prescribed melatonin in the United Kingdom.

Meanwhile, the secondary analysis found that people taking melatonin supplements were nearly 3.5 times more likely to be hospitalised for heart failure compared with those not taking them. It was 19.0% over 6.6% respectively.

But the worst is yet to come, as researchers found something even more concerning; they discovered that melatonin users were almost twice as likely to die from any cause over five years compared with non-users. The data show that it's 7.8% vs 4.3%, respectively.

Findings Shock Doctors

'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,' Dr Nnadi said.

These findings came as a surprise to Marie-Pierre St-Onge, Ph.D., C.C.S.H., FAHA, chair of the writing group for the American Heart Association's 2025 scientific statement Multidimensional Sleep Health: Definitions and Implications for Cardiometabolic Health.

'I'm surprised that physicians 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 supplement, and people should be aware that it should not be used chronically without a proper indication,' said Dr St-Onge, a professor at Columbia University Irving Medical Center and director of the Centre for Sleep and Circadian Research in New York City, who was not involved in the study.

Further Research Needed

According to the American Heart Association's 2025 Heart Disease and Stroke Statistics, heart failure occurs when the heart is unable to pump enough oxygen-rich blood to the body's organs, preventing them from functioning properly. The condition currently affects around 6.7 million adults in the United States.

Dr Nnadi added that 'worse insomnia, depression or anxiety, or the use of other sleep-inducing medicines may be linked to both melatonin use and an increased risk of heart problems.'

However, he clarified that 'although our findings raise safety concerns about this widely used supplement, the study does not prove a direct cause-and-effect link — further research is needed to determine melatonin's impact on heart health.'