Melatonin and cardiovascular risk: an NHANES reality check after recent heart failure concerns

A large electronic health record study presented at the American Heart Association Scientific Sessions 2025 reported a heart failure safety signal associated with long-term melatonin use among adults with insomnia. In parallel, melatonin use has increased in the US general population, making counselling questions increasingly common in cardiovascular practice.

Observational associations between melatonin and cardiovascular outcomes are unusually vulnerable to confounding-by-indication, reverse causality, and exposure misclassification because melatonin uptake often reflects insomnia severity, depression or anxiety symptoms and healthcare utilisation.

In a nationally representative NHANES (National Health and Nutrition Examination Survey) adult cohort (1999-2018), melatonin users differed markedly from non-users at baseline, particularly for sleep disturbance and depression. In updated survey-weighted, multiple-imputation models, recent melatonin use was not significantly associated with prevalent composite cardiovascular disease or heart failure. These findings provide a hypothesis-generating contextual counterpoint to recent alarm signals rather than causal evidence of benefit or harm.

Available observational data do not support strong claims of cardiovascular benefit, and they do not establish definitive cardiovascular harm or safety. Clinicians should document over-the-counter use, counsel pragmatically and prioritise evaluation and treatment of underlying sleep disorders while better evidence is developed.