Long-Term Melatonin Supplementation: A Reassessment of Cardiac Risks

In research being presented at the 2025 American Heart Association Scientific Sessions, investigators have reported that prolonged melatonin use was associated with higher rates of heart failure and death among adults with insomnia. Long-term users had roughly a 90% higher five-year incidence of heart failure and nearly double the all-cause mortality—findings that prompt reevaluation of indefinite over‑the‑counter melatonin use in routine care.

A large observational cohort of 130,828 adults with insomnia was followed for five years. The researchers examined incident heart failure, heart-failure hospitalization, and all-cause mortality. Compared with matched controls, long-duration melatonin users had about a 90% higher risk of new heart-failure diagnosis (4.6% vs. 2.7%), nearly 3.5-fold higher heart-failure hospitalization (19.0% vs. 6.6%), and roughly double the mortality (7.8% vs. 4.3%).

Associations were strongest in adults with chronic insomnia, older patients, and those with preexisting cardiovascular disease or multiple cardiometabolic risk factors. In subgroup descriptions, long-term melatonin use correlated with higher rates of heart-failure diagnosis and hospitalization and showed signals for arrhythmia and higher blood pressure in selected cohorts.

The report also noted metabolic and endocrine perturbations consistent with altered glucose regulation and potential disruption of insulin sensitivity. The pattern is biologically plausible given melatonin receptor biology and circadian-phase effects on glucose handling, but mechanistic confirmation is pending.