Recent observational research has raised fresh questions about the cardiovascular safety of long-term melatonin supplementation. A large multinational cohort study presented at the American Heart Association’s 2025 Scientific Sessions reported that adults who used melatonin for a year or more had higher rates of incident heart failure, more heart-failure hospitalisations and a higher all-cause mortality over a five-year follow-up compared with matched controls. However, the investigators and independent experts explicitly caution that the results are associative — the study was an observational analysis and an abstract presented at a conference rather than a peer-reviewed paper.

Understanding this finding requires context. For decades, basic and animal research has shown melatonin has multiple effects on the cardiovascular system — some potentially protective (antioxidant, anti-remodelling, reduction of ischemia-reperfusion injury) and others that could alter cardiac function (changes in heart rate, blood pressure, and autonomic tone). Systematic reviews and experimental studies have therefore produced mixed signals: many preclinical and small clinical reports suggest cardioprotective actions, while larger real-world data now hint at possible harms when melatonin is used chronically.

Mechanistically, theorised pathways by which melatonin could influence heart failure risk include modulation of autonomic tone (eg, causing bradycardia), influences on blood pressure regulation, interactions with other medications, and effects mediated by the sleep disorder itself. Importantly, people who use melatonin long-term often have chronic insomnia or comorbid conditions (obesity, older age, pre-existing cardiovascular disease) that independently raise heart-failure risk — a key confounder that observational studies may not fully adjust for. Expert commentaries therefore emphasise that the observed association may reflect underlying illness or prescribing patterns rather than a direct causal effect of melatonin. 

What should readers take away? Short-term, low-dose melatonin remains commonly recommended for circadian problems and occasional insomnia, and many clinical trials and reviews have reported benign or even beneficial cardiovascular effects in controlled settings. But until peer-reviewed longitudinal analyses and randomised trials clarify long-term safety, clinicians and patients should exercise caution: avoid routinely taking high doses nightly for years without medical review, discuss long-term sleep problems with a healthcare professional, consider non-drug options (CBT-I), and review drug interactions and cardiovascular risk factors. Regulatory guidance and ongoing research will be needed to determine whether practice should change. 

Key sources (selected)

AHA 2025 abstract / conference coverage (association between long-term melatonin use and higher HF risk).

American College of Cardiology / AHA news summaries discussing the findings and need for further research. 

HealthLine / Medical News Today reporting summarising the study and expert caution that association ≠ causation.

Reviews and preclinical literature showing both cardioprotective effects and biological plausibility for cardiovascular impact. 

Expert reaction summaries (Science Media Centre) emphasising limitations of conference abstracts and confounding.