Melatonin and heart risk: Long-term use of melatonin supplements was associated with higher rates of heart failure diagnosis, heart-failure–related hospitalisation, and all-cause mortality among adults with chronic insomnia, according to a preliminary analysis to be presented at the American Heart Association’s Scientific Sessions 2025.
Melatonin, an over-the-counter hormone used widely for sleep problems, lacks rigorous, long-term cardiovascular safety data. Using the TriNetX Global Research Network, investigators analysed five years of electronic health records from 130,828 adults with chronic insomnia (average age 55.7; 61.4% women). People with prior heart failure or prescriptions for other sleep medicines were excluded. Long-term melatonin users (documented ≥12 months) were matched to non-users across 40 demographic and clinical factors.
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Compared with matched non-users, long-term melatonin users had about a 90% higher incidence of new heart failure over five years (4.6% vs. 2.7%). In secondary outcomes, melatonin users were ~3.5 times more likely to be hospitalised for heart failure (19.0% vs. 6.6%) and nearly twice as likely to die from any cause (7.8% vs. 4.3%). A sensitivity analysis that required at least 2 melatonin prescriptions, filled ≥90 days apart (relevant in countries where melatonin is prescription-only), showed a similar ~82% higher heart failure risk.
Lead author Dr Ekenedilichukwu Nnadi (SUNY Downstate/Kings County) said the findings challenge assumptions that melatonin is a benign, “natural” sleep aid. Outside experts urged caution: in the US, melatonin is not indicated for chronic insomnia, and unregulated supplement content may vary in dose and purity. Marie-Pierre St-Onge, PhD, FAHA (Columbia University), who was not involved in the study, noted that chronic use without a clear indication is concerning.
The analysis is observational and cannot prove cause and effect. Because over-the-counter use in countries like the US may not appear in medical records, some melatonin users could have been misclassified as non-users. Hospitalisation coding may not always denote incident heart failure, and data lacked insomnia severity and some psychiatric comorbidities that could confound results.
