News MedicalLong-term Use of Melatonin Supplements Linked to Higher Risk of Heart Failure and Death

This large retrospective cohort study (130,828 adults) examined long-term melatonin supplementation (≥12 months) in chronic insomnia patients using the TriNetX Global Research Network. Researchers matched 65,414 melatonin users with non-users across 40 variables including demographics, comorbidities, and medications. The study found significant associations between chronic melatonin use and adverse cardiovascular outcomes over 5 years, though causality cannot be established from this observational design.

🔬 Key Clinical Considerations

• Long-term melatonin use associated with 90% increased incident heart failure risk (4.6% vs 2.7%) and 82% increased risk in sensitivity analysis requiring ≥2 prescriptions 90+ days apart, suggesting dose-response relationship.
• Hospitalization rates for heart failure nearly 3.5-fold higher in melatonin users (19.0% vs 6.6%), though hospitalization codes may capture broader HF-related admissions beyond new diagnoses, potentially overestimating acute events.
• All-cause mortality nearly doubled in melatonin group (7.8% vs 4.3%) over 5 years, raising safety concerns beyond cardiovascular endpoints and suggesting systemic effects or confounding by indication.
• Study limitations include uncontrolled OTC melatonin use in non-prescription countries (U.S.), misclassification bias from electronic health record documentation, and unmeasured confounders including insomnia severity and psychiatric comorbidities.
• Melatonin remains unregulated supplement in US with variable potency and purity, lacks FDA approval for insomnia treatment, and clinical guidelines do not support chronic use beyond short-term circadian rhythm disorders.

🏥 Clinical Practice Impact

• Patient Communication: Counsel patients currently using chronic melatonin about preliminary safety signals and consider discontinuation or transition to evidence-based insomnia treatments including CBT-I, particularly in patients with cardiovascular risk factors or established CVD.
• Practice Integration: Screen insomnia patients for unreported OTC melatonin use during medication reconciliation, document duration and dosing patterns, and reassess necessity of continuation beyond short-term use (typically <3 months).
• Risk Management: Heightened surveillance for heart failure symptoms in chronic melatonin users, especially those with hypertension, diabetes, or other cardiac risk factors. Consider baseline and periodic cardiovascular assessment including BNP/NT-proBNP in high-risk patients.
• Action Items: Review current patient population on melatonin supplements, prioritize cardiovascular risk stratification, implement shared decision-making discussions about alternative insomnia management, and await confirmatory prospective studies before practice guideline changes.

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