Main Findings of the Study

Long-term use of melatonin for sleep correction has been linked to an increased risk of heart failure, related hospitalizations, and overall mortality among adults with chronic insomnia. These findings were presented at the American Heart Association scientific sessions in 2025.

The study did not establish that melatonin itself was the direct cause of the increased risks. However, the results highlight the need to assess the long-term safety of this supplement, which is often considered harmless or a “natural” alternative for improving sleep.

About Melatonin

Melatonin is a hormone naturally produced by the pineal gland that regulates circadian rhythms, including the sleep-wake cycle. Its levels rise during the night and decrease in daylight. Synthetic melatonin is identical to the natural hormone and is widely used to treat insomnia and jet lag. In several countries, including the United States, melatonin is available over the counter, and its composition may vary depending on the manufacturer.

Study Design

The study utilized data from the international TriNetX Global Research Network database of anonymized electronic medical records. Researchers analyzed five years of medical records from adults with chronic insomnia who had taken melatonin for at least one year. These patients were compared to a group of people with insomnia who did not use melatonin. Individuals with a prior diagnosis of heart failure or those taking other sleep medications were excluded from the analysis.

The main analysis included 130,828 adults (average age 55.7 years, 61.4% women) diagnosed with insomnia. Of these, 65,414 had received melatonin prescriptions for at least one year. The control group consisted of individuals who had never been prescribed melatonin and was matched on 40 factors, including demographic characteristics, comorbidities, and concurrent medications.

Results

Among adults with insomnia, the likelihood of developing heart failure over five years was about 90% higher in those who had taken melatonin long-term (12 months or more) compared to those who had not used the supplement (4.6% vs. 2.7%). An additional analysis, which considered patients who had received at least two melatonin prescriptions at intervals of at least 90 days, showed an 82% increased risk.

Secondary analysis revealed that participants taking melatonin were nearly 3.5 times more likely to be hospitalized for heart failure (19.0% vs. 6.6%), and all-cause mortality over five years was almost twice as high (7.8% vs. 4.3%).

Study Limitations

The study has several limitations. Melatonin regulations differ by country: in some, such as the UK, it is available only by prescription, while in others, including the US, it can be purchased over the counter. Researchers did not have information about participants’ locations, as the data were anonymized. Melatonin use was recorded only if documented in medical records, so some individuals who purchased the supplement independently may have been mistakenly classified as non-users.

The severity of insomnia and the presence of other mental health disorders were not accounted for, which could influence both melatonin use and cardiovascular risk independently of supplement intake. Additionally, the number of hospitalizations for heart failure exceeded the number of new diagnoses, which may be related to coding practices in medical institutions.

Conclusion

The study identified an association between long-term melatonin use and an increased risk of serious adverse outcomes in people with chronic insomnia, though a causal relationship has not been established. Further research is needed to confirm the cardiovascular safety of melatonin.