Long-term melatonin use linked to 90% higher heart failure risk, study finds
New research presented at the American Heart Association's 2025 Scientific Sessions found that people with chronic insomnia who used melatonin for over a year had significantly higher rates of heart failure, hospitalization and death compared with non-users. Researchers stress the findings show an association, not proven causation.
Preliminary research presented at the American Heart Association's Scientific Sessions 2025 suggests that long-term use of melatonin, a widely used sleep supplement, may be linked to a higher risk of heart failure among people with chronic insomnia.
Using de-identified electronic health records from the international TriNetX database, researchers analyzed more than 130,000 adults diagnosed with insomnia. About 65,000 of them had used melatonin for at least a year; this group was compared with people who had no documented melatonin use. The groups were matched across 40 factors, including age, sex, existing health conditions and medications, and anyone already diagnosed with heart failure was excluded.
Over a five-year follow-up, heart failure developed in 4.6% of melatonin users compared with 2.7% of the comparison group — roughly a 90% higher risk. When researchers narrowed the analysis to people who had filled at least two melatonin prescriptions at least 90 days apart, the elevated risk persisted at 82%.
The study also found larger gaps in other outcomes: melatonin users were nearly 3.5 times more likely to be hospitalized for heart failure (19% versus 6.6%), and all-cause mortality over five years was 7.8% among melatonin users compared with 4.3% in the comparison group.
Lead author Dr. Ekenedilichukwu Nnadi said the consistency of the findings was striking even after adjusting for many other risk factors. Sleep researcher Marie-Pierre St-Onge, who was not involved in the study, said she was surprised physicians would prescribe melatonin for insomnia for over a year, since it is not approved for that use in the U.S.
The study has notable limitations. Melatonin regulation varies by country — it requires a prescription in the UK but is sold over the counter in the U.S. — and because the data were de-identified, researchers could not determine participants' locations, meaning some over-the-counter users may have been misclassified as non-users. The study also lacked data on insomnia severity or other psychiatric conditions that could independently affect both melatonin use and cardiovascular risk. Researchers emphasized the study was observational and cannot prove melatonin directly caused the outcomes, calling for further research.
