Preliminary research presented at the American Heart Association’s Scientific Sessions 2025 found that long-term melatonin use (defined as at least one year) among adults with chronic insomnia was associated with a significantly higher risk of heart failure, hospitalization for heart failure, and all-cause mortality compared to non-users. Specifically, the study identified a 90% increased likelihood of developing heart failure in the melatonin group (4.6%) versus the non-melatonin group (2.7%) over a five-year period. A secondary analysis revealed that melatonin users were nearly 3.5 times more likely to be hospitalized for heart failure (19.0% vs. 6.6%) and had almost twice the risk of death from any cause (7.8% vs. 4.3%).
The researchers utilized de-identified electronic health records from the TriNetX Global Research Network, matching participants with chronic insomnia who had documented long-term melatonin use against those without such use, while excluding individuals with pre-existing heart failure or concurrent sleep medication use. Despite these controls, the study acknowledges several limitations, including potential misclassification of melatonin use due to over-the-counter availability in some countries, lack of data on insomnia severity or comorbid psychiatric conditions, and variability in how heart failure hospitalizations were recorded. Consequently, while the findings suggest a concerning association between prolonged melatonin use and adverse cardiovascular outcomes, they do not establish a causal relationship, and further investigation is warranted to assess the supplement’s long-term safety.