Long-term melatonin use linked to higher risk of heart failure, preliminary study finds

Saudi regulator issues safety signal as researchers call for more study

By LineZotpaper

Published22 October 2026

Read Time3 min

A preliminary analysis of more than 130,000 adults with insomnia has found that those prescribed melatonin for more than a year had an 89 percent higher risk of heart failure and were about twice as likely to die from any cause over a five-year period compared to non-users. The findings, presented at the American Heart Association's Scientific Sessions in November 2025, have not yet been peer-reviewed, but they have already prompted a formal safety signal from Saudi Arabia's drug regulator.

The study, led by medical scientist Ekenedilichukwu Nnadi of SUNY Downstate/Kings County Primary Care in New York, used electronic health records from adults in the US and multiple other countries, including the UK where melatonin is available only by prescription. A secondary analysis found that those who took the supplement for over a year were almost 3.5 times as likely to be hospitalized for heart failure, with the risk of dying from any cause rising from 4.3 percent to 7.8 percent.

"Melatonin supplements are widely thought of as a safe and 'natural' option to support better sleep," Nnadi said. "So it was striking to see such consistent and significant increases in serious health outcomes, even after balancing for many other risk factors."

The research has a major limitation: melatonin use was estimated from prescription records, so the control group may have included people in the US who bought the supplement over the counter without a prescription. Carlos Egea, President of the Spanish Federation of Sleep Medicine Societies, who was not involved in the study, noted this caveat but said the associations should be taken seriously. "These findings challenge the perception of melatonin as a benign chronic therapy and highlight the need for a prospective trial with a control group to clarify its safety profile," he argued.

In April 2026, Saudi Arabia's drug regulator issued a formal safety signal on melatonin and heart failure after reviewing global case reports alongside the study, concluding the evidence is "suggestive for causal association." It is not a ban or a new warning, but a sign that regulators are beginning to take the possibility seriously.

Melatonin supplements are considered safe for short-term use of around one to two months, but comprehensive research on longer use is lacking. Nnadi and colleagues say this should be remedied, especially as the supplement grows in popularity. "If our study is confirmed, this could affect how doctors counsel patients about sleep aids," Nnadi said.

Analysis

Why This Matters

This is one of the largest studies to examine long-term melatonin use and heart health, challenging the common assumption that the supplement is harmless.
A regulatory safety signal from Saudi Arabia indicates that risk is being taken seriously, potentially leading to warnings or changes in availability elsewhere.
With melatonin use widespread and often unsupervised, any confirmed risk would affect millions of people.

Background

Melatonin is a hormone naturally produced by the brain. Supplements are widely used for sleep, especially in the US where they are available over the counter. Despite widespread use, long-term effects have not been well studied. The recent analysis is among the largest to examine links with heart health.

Key Perspectives

[Researchers]: The preliminary evidence suggests a concerning association, but caution is needed due to study limitations. They call for more research. [Carlos Egea, Spanish Federation of Sleep Medicine Societies]: The findings should be taken seriously and a prospective trial is needed to clarify safety. [Saudi Drug Regulator]: Issued a safety signal indicating the evidence is suggestive of a causal association, a step toward closer scrutiny but not yet a regulatory action.

What to Watch

Publication of the study in a peer-reviewed journal.
Actions by other regulators such as the FDA or EMA.
Future prospective trials designed to test causation.
Possible changes in medical guidance for sleep aids.

Sources

A Common Supplement Displays a Concerning Link to Heart Failure · ScienceAlert

Checked

11 claims in this story checked against 1 source: 8 supported.

Show each claim

SupportedA preliminary study linked long-term melatonin use to higher heart-failure risk.ScienceAlert: “A 2025 analysis of adults with insomnia has linked being prescribed melatonin for more than a year to a greater risk of heart issues.”
SupportedSaudi Arabia’s drug regulator issued a safety signal as researchers called for more study.ScienceAlert: “In April 2026, Saudi Arabia's drug regulator issued a formal safety signal on melatonin and heart failure”
SupportedThe analysis involved more than 130,000 adults with insomnia.ScienceAlert: “Among more than 130,000 adults across multiple countries”
SupportedPeople prescribed melatonin for more than a year had an 89 percent higher risk of heart failure over five years.ScienceAlert: “It found that people prescribed melatonin for more than a year had an 89 percent higher risk of heart failure over five years”
SupportedThose prescribed melatonin long-term were about twice as likely to die from any cause over five years.ScienceAlert: “those who were prescribed melatonin long-term were more at risk of heart failure and death in the following five years than those who were not prescribed it. It found that people prescribed melatonin for more than a year had an 89 percent higher risk of heart failure over five years, and were about twice as likely to die from any cause.”
SupportedThe findings were presented at the American Heart Association’s Scientific Sessions in November 2025 and have not yet been peer-reviewed.ScienceAlert: “The research, which has not yet been peer-reviewed, was presented in November 2025 at the American Heart Association's Scientific Sessions.”
Not in the sourcesNnadi led the study.ScienceAlert: “In the recent analysis, Nnadi and colleagues examined electronic health records”
SupportedNnadi said the results were striking despite balancing for many other risk factors.ScienceAlert: ““Melatonin supplements are widely thought of as a safe and 'natural' option to support better sleep,” said Nnadi. “So it was striking to see such consistent and significant increases in serious health outcomes, even after balancing for many other risk factors.””
Partly supportedEgea said the findings challenge the perception of melatonin as benign chronic therapy and highlight the need for a prospective trial.ScienceAlert: ““These findings challenge the perception of melatonin as a benign chronic therapy and only highlight the need for a prospective trial with a control group to clarify its safety profile,” argued Egea.”
Partly supportedMelatonin supplements are considered safe for short-term use of around one to two months.ScienceAlert: “However, melatonin is typically considered safe and well-tolerated for short-term use among those who are not pregnant or breastfeeding. That means around 1 to 2 months.”
SupportedSaudi Arabia’s regulator issued the safety signal after reviewing global case reports alongside the study, and said the evidence was “suggestive for causal association.”ScienceAlert: “In April 2026, Saudi Arabia's drug regulator issued a formal safety signal on melatonin and heart failure, after reviewing global case reports alongside the study's findings, concluding the evidence so far is “suggestive for causal association”.”