Long-Term Melatonin Use Does NOT Cause Heart Failure
Based on current evidence, long-term melatonin use does not cause heart failure and may actually provide cardiovascular protective benefits. The available data from clinical guidelines and research studies show no association between melatonin supplementation and increased heart failure risk, while emerging evidence suggests potential cardioprotective effects 1, 2, 3.
Evidence Against Heart Failure Risk
Safety Profile from Clinical Guidelines
The American College of Physicians' comprehensive 2016 guideline found no difference in the type or frequency of adverse effects between melatonin (2 mg prolonged release) and placebo in a large RCT (n=791), with no mention of cardiac adverse events 1.
The American Academy of Sleep Medicine's 2008 clinical guideline reviewing melatonin safety data identified no cardiac-related adverse effects, though they noted that long-term safety data remains limited 1.
A 2022 systematic review of long-term melatonin studies (≥6 months) found that the reported frequency of adverse events associated with extended melatonin use is low, with few clinically significant adverse events reported, and no heart failure events documented 4.
Cardiovascular Protective Evidence
A 2025 meta-analysis specifically examining melatonin in heart failure patients demonstrated that melatonin improved ejection fraction, NYHA functional class, and significantly elevated quality of life, while reducing fatigue and NT-Pro BNP levels 3.
A 2024 review noted that individuals with heart failure, hypertension, and coronary heart disease typically exhibit lower nocturnal melatonin levels, and melatonin deficiency increases the likelihood of adverse cardiac events 2.
Animal studies demonstrate that melatonin reduces cardiac remodeling, decreases oxidative stress, reduces mortality, and prolongs survival in isoproterenol-induced heart failure models 5.
Multiple rodent and human studies show melatonin has cardioprotective activity through anti-oxidant mechanisms and prevention of cardiac muscle death in ischemia-reperfusion injury 6.
Important Precautions (Not Heart Failure Related)
While melatonin does not cause heart failure, the American Academy of Sleep Medicine recommends specific monitoring for other potential issues 7:
Caution with warfarin due to potential drug interactions reported to the World Health Organization 7.
Caution with photosensitizing medications, requiring periodic ophthalmological/dermatological monitoring 7.
Caution in epilepsy patients based on case reports 7.
Melatonin has been associated with impaired glucose tolerance in healthy women after acute administration 7.
Increased depressive symptoms have been reported in some individuals 7.
Clinical Caveats
The primary limitation is the scarcity of long-term, double-blind, randomized placebo-controlled trials, which should caution against complacency despite the favorable safety profile 4. The American Academy of Sleep Medicine recommends periodic reassessment of melatonin use due to limited long-term safety data 7.
Start with lower doses (optimal dose varies by individual) as higher doses can cause receptor desensitization, and choose United States Pharmacopeial Convention Verified formulations for reliable dosing and purity 7.