Melatonin, one of the most widely used sleep supplements in the United States, may be associated with an increased risk of heart failure and death when used long term, according to new research. Although this hormone-based supplement is widely regarded as a gentle, natural sleep aid, scientists caution that its long-term safety remains poorly understood.
In a recent analysis involving more than 130,000 adults with insomnia from several countries, individuals prescribed melatonin for longer than one year had a significantly higher risk of heart failure and death during the subsequent five years than those who were not prescribed the supplement. Because the study has not yet undergone peer review, experts urge caution when interpreting the findings.
What the New Study Found
The research, presented at the American Heart Association’s Scientific Sessions, analyzed electronic health records from the United States, the United Kingdom, and several other countries. In some of these countries, including the United Kingdom, melatonin is available only by prescription, allowing researchers to more accurately assess medically documented use.
According to the analysis, individuals prescribed melatonin for more than 12 months had an 89 percent higher risk of developing heart failure over the following five years than those who had not been prescribed the supplement. Overall mortality also appeared to increase, with long-term users nearly twice as likely to die from any cause during the follow-up period.
A secondary analysis suggested even stronger associations. Patients prescribed melatonin for more than one year were almost 3.5 times more likely to be hospitalized for heart failure than individuals not taking the supplement. The proportion of participants who died from any cause increased from 4.3 percent in the comparison group to 7.8 percent among long-term melatonin users.
Why Experts Urge Caution
The authors, led by medical scientist Ekenedilichukwu Nnadi of SUNY Downstate/Kings County Primary Care in New York, emphasize that their findings demonstrate an association rather than proof of causation. Melatonin use may simply be a marker of more severe sleep disorders or underlying health conditions that independently increase cardiovascular risk.
Another important limitation concerns how melatonin exposure was measured. The researchers relied on prescription records to identify users, an approach that works well in countries where melatonin is tightly regulated. However, in the United States, many people purchase melatonin over the counter, meaning some users may have been misclassified as non-users, potentially weakening or distorting the observed associations.
Independent experts also note that the observational study design cannot eliminate the possibility of confounding. Individuals prescribed melatonin may have higher rates of obesity, diabetes, depression, or other medical conditions that independently increase the risk of heart failure. Although the researchers adjusted for several known risk factors, residual confounding is likely to remain.
Reassessing a ‘Natural’ Sleep Aid
Melatonin is a hormone produced by the pineal gland in the brain that helps regulate the body’s internal clock and sleep-wake cycle. Synthetic melatonin, widely available in tablet and gummy formulations, is designed to mimic this natural signal and can modestly reduce the time it takes some people to fall asleep.
In the United States, melatonin is regulated as a dietary supplement rather than a medication. As a result, it can be purchased without a prescription and is subject to less stringent regulatory oversight. Surveys indicate that melatonin use has increased substantially over the past decade, particularly among older adults and individuals with chronic insomnia.
Short-term melatonin use, generally for up to one or two months, is considered safe for most healthy adults who are neither pregnant nor breastfeeding. The most commonly reported adverse effects include daytime drowsiness, headache, and dizziness. However, robust evidence regarding safety beyond several months of use remains limited, particularly among individuals with cardiovascular disease.
Calls for Stronger Evidence
Carlos Egea, president of the Spanish Federation of Sleep Medicine Societies, who was not involved in the study, stated that the apparent increase in serious adverse outcomes should not be dismissed. He argued that the findings challenge the perception of melatonin as a harmless long-term therapy and support the need for rigorous randomized clinical trials.
Experts emphasize that a large prospective study with a carefully monitored control group is necessary to determine whether melatonin itself contributes to heart failure or whether the observed associations are explained by other factors. Until such evidence becomes available, clinicians are encouraged to carefully weigh the potential risks and benefits of long-term melatonin use, particularly in patients with existing cardiovascular disease.
The new findings emerge amid broader concerns about the widespread use of unregulated dietary supplements. Previous investigations have shown that the actual melatonin content of commercially available products can differ substantially from the amount listed on the label, in some cases by several hundred percent, raising additional concerns about dosing accuracy and safety.
Implications for Patients and Parents
Even when used short term, melatonin is not entirely without risk. Case reports and poison control data have documented increasing numbers of accidental ingestions and non-fatal overdoses among children, particularly involving flavored gummy formulations that are easily accessible in the home.
Health authorities generally recommend behavioral interventions as the first-line treatment for insomnia, including maintaining a consistent sleep schedule, limiting screen exposure before bedtime, and reducing caffeine and alcohol consumption. Medications and dietary supplements, including melatonin, are typically recommended only when these strategies prove insufficient.
Nnadi and colleagues caution that if their findings are confirmed, physicians may need to reconsider how they counsel patients regarding chronic melatonin use. Individuals who have been taking melatonin for many months or years are advised to discuss any concerns with a healthcare professional before discontinuing the supplement or changing the dosage.
As research continues, scientists agree on one important point: a substance derived from a naturally occurring hormone should not automatically be assumed to be harmless. With millions of people relying on melatonin to improve sleep, clarifying its long-term cardiovascular safety has become an important priority for both clinicians and public health authorities.
