A large-scale study reviewing health records of more than 130,000 adults with chronic insomnia has found that people who took prescribed melatonin for over a year were more likely to develop heart failure within five years than those who didn’t use the supplement, according to findings announced Monday by the American Heart Association (AHA).
Researchers also reported that long-term melatonin users had higher hospitalization rates for heart failure and an increased risk of death from any cause compared to nonusers.
The study, which has not yet been peer-reviewed, has already sparked debate among cardiologists and sleep medicine experts, many of whom urge caution but not panic, emphasizing that more research is needed before any firm conclusions can be drawn.
The preliminary results—set to be presented at the AHA’s Scientific Sessions conference on cardiovascular science—appear to contradict smaller studies that previously suggested melatonin might protect heart health.
Using an international database of electronic health records, researchers tracked adults with insomnia over a five-year period. Approximately 65,000 people, or about half, had been prescribed melatonin for at least one year.
Over that time, nearly 3,000 melatonin users developed heart failure, compared to about 1,800 who were identified as nonusers. Patients already diagnosed with heart failure or prescribed other sleep medications were excluded from the study.
Muhammad Rishi, an associate professor of clinical medicine and spokesperson for the American Academy of Sleep Medicine, reviewed the findings and stated that they should be given attention.
“The findings are certainly provocative and warrant attention, especially given the widespread perception of melatonin as a benign, ‘natural’ sleep aid. However, the study is observational and based on electronic health record data, which limits its ability to establish causality.”
Lead author Ekenedilichukwu Nnadi, chief resident in internal medicine at SUNY Downstate/Kings County Primary Care in Brooklyn, told The Washington Post the results surprised even the research team.
“What stood out most was that we found any association at all. Melatonin is generally viewed as a very safe supplement, as something people, and even physicians, don’t usually worry much about, so we honestly didn’t expect to see a clear signal linking long-term use with higher rates of heart failure, hospitalizations and death.”
Melatonin is a hormone naturally produced by the pineal gland in the brain to signal the body that it’s time for sleep. In the U.S., the supplement is available over the counter, unlike in some countries where it requires a prescription and is more tightly regulated for purity and dosage.
Doctors often recommend small, short-term doses to help with jet lag or shift work. But for chronic insomnia, cognitive behavioral therapy remains the preferred treatment, as the evidence supporting long-term melatonin use is inconsistent.
Joyce Oen-Hsiao, an associate professor of cardiovascular medicine at Yale School of Medicine, said sleep quality plays a crucial role in cardiovascular health. People who don’t sleep well tend to have higher heart rates and blood pressure and experience more cardiovascular events, she said.
She noted that melatonin’s antioxidant properties could theoretically protect against coronary artery disease and help regulate blood pressure when taken at the right time and dose.
“The new study appears to be the only one that is saying that melatonin can cause heart failure,” said Oen-Hsiao, who was not involved in the research.
While previous studies on melatonin’s neutral or positive cardiac effects have often been small, short-term, or limited to controlled laboratory conditions, Nnadi emphasized that the strength of his research lies in its large, real-world data. Still, he cautioned that it shows correlation, not causation.
“This doesn’t prove that melatonin directly causes heart failure. It simply shows that people with chronic insomnia who took melatonin long-term were more likely to experience these outcomes. It’s an unexpected and important signal that needs to be studied further, ideally in randomized trials.”
Experts reviewing the data say it’s essential to interpret the results carefully. David Neubauer, a sleep specialist at Johns Hopkins University, pointed out the biggest issue: researchers couldn’t be sure whether the control group, classified as nonusers, actually avoided melatonin altogether.
“The most problematic part of the study is we don’t know whether or not those people in the control group were taking melatonin,” Neubauer said.
Because over-the-counter melatonin isn’t typically tracked in medical databases, some nonusers may have actually been taking it, said Rishi. That misclassification could have distorted the results, leading to an overestimation of risk. The health records also didn’t indicate how much melatonin was prescribed, or whether patients’ insomnia improved once they started using it.
Oen-Hsiao emphasized that distinction matters.
“If they had such bad insomnia that they needed prescription-dose melatonin, were they actually getting the benefit of the melatonin for sleep? And if the answer is no, then you cannot have a correlation that melatonin causes heart failure.”
She suggested that severe, untreated insomnia itself might be driving heart issues, not the supplement. The study also did not differentiate between types of heart failure, which could impact the understanding of potential effects.
The limitations are “why we need randomized, prospective trials to confirm whether melatonin itself is contributing to these risks,” Nnadi said.
“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.”
Even with those caveats, the research raises new questions about a supplement widely viewed as harmless. The associations observed in the latest study “raise questions as to whether long-term use of melatonin is harmful or not as benign as one would think,” said Marie-Pierre St-Onge, a professor of nutritional medicine at Columbia University. “These questions deserve investigation to determine causality.”
“Worse insomnia, depression/anxiety or the use of other sleep-enhancing medicines might be linked to both melatonin use and heart risk,” Nnadi said in a news release.
“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.”
For now, experts say there’s no reason for the average person to panic. “We don’t have enough information to blanketly say all people should stop using melatonin,” Oen-Hsiao said.
Kelly Gill, a sleep medicine specialist at Northwestern Medicine, noted that the study underscores the importance of more cautious prescribing practices. In countries where melatonin is available as an over-the-counter supplement, people often want to avoid more prescriptions, given a more accessible option.
“It’s difficult because many patients are searching for help with insomnia. Now, we have to be careful about how we recommend it and how patients utilize it, especially in the context of heart failure.”
Neubauer said timing and dosage are key. The supplement should be taken one to two hours before bedtime, and higher doses don’t enhance its effect. “Melatonin is not a sedating substance,” he said. “You don’t get more sedated by taking more.”
Low-dose melatonin, or less than 5 milligrams, taken over short periods, is still considered safe.
“The takeaway isn’t that melatonin is ‘bad’ or that everyone should stop taking it,” Nnadi said. “It’s that we shouldn’t assume something is risk-free just because it’s natural or sold over the counter.”
Moumita Basuroychowdhury is a Contributing Reporter at The National Digest. After earning an economics degree at Cornell University, she moved to NYC to pursue her MFA in creative writing. She enjoys reporting on science, business and culture news. You can reach her at moumita.b@thenationaldigest.com.
