Melatonin and Heart Failure Risk in Long-Term Users
Based on the highest quality prospective evidence with up to 23 years of follow-up, melatonin supplement use is not associated with increased risk of cardiovascular disease, including heart failure, in middle-aged and older adults. 1
Key Evidence on Cardiovascular Safety
The most robust data comes from a 2024 pooled analysis of three large US prospective cohorts (Nurses' Health Study, Health Professionals Follow-up Study, and Nurses' Health Study II) involving 159,072 participants followed for up to 23 years. 1 This study documented 16,917 incident cardiovascular disease events during 2,609,068 person-years of follow-up and found:
- No increased cardiovascular disease risk: Multivariable-adjusted hazard ratio of 0.94 (95% CI 0.83-1.06, p=0.32) comparing melatonin users to non-users 1
- No increased type 2 diabetes risk: Hazard ratio of 0.98 (95% CI 0.86-1.12, p=0.80), which is relevant since diabetes is a major cardiovascular risk factor 1
Potential Cardioprotective Mechanisms
Rather than causing harm, research suggests melatonin may offer cardiovascular benefits through multiple mechanisms:
- Direct cardioprotection: Melatonin protects against ischemia-reperfusion myocardial damage, particularly when administered during reperfusion 2
- Antioxidant effects: Acts as a free radical scavenger, upregulates antioxidant enzymes, and downregulates pro-oxidant enzymes 2, 3
- Blood pressure reduction: Decreases blood pressure through effects on the hypothalamus, antioxidant mechanisms, catecholamine reduction, and smooth muscle relaxation 4
- Lipid profile improvement: Suppresses cholesterol formation by 38% and reduces LDL accumulation by 42% 4
Clinical Context for Your Patient
For a 40-year-old male who has used melatonin for 10 years:
- No documented heart failure risk: Major cardiovascular guidelines from the American Heart Association, American College of Cardiology, and Heart Failure Society of America do not list melatonin as contraindicated or harmful in cardiac patients 5
- Favorable safety profile: The American Academy of Sleep Medicine reports no serious adverse reactions documented across all age groups, with the most common side effects being headache (0.74%) and dizziness (0.74%) 6
- Paradoxical findings in cardiac disease: Patients with coronary heart disease and acute myocardial infarction actually have lower endogenous melatonin levels, suggesting deficiency rather than excess may be problematic 4, 2
Important Caveats and Monitoring
While cardiovascular risk appears minimal, consider these factors:
- Glucose metabolism: Melatonin has been associated with impaired glucose tolerance in some studies, though the large prospective cohort found no increased diabetes risk 5, 1
- Drug interactions: Use caution if taking warfarin due to potential interactions 6, 5
- Product quality: Melatonin is regulated as a dietary supplement in the US, raising concerns about purity and reliability of stated doses—choose United States Pharmacopeial Convention Verified formulations 6, 5
- Optimal dosing: The American Academy of Sleep Medicine recommends 3-5 mg daily, as higher doses (10 mg) may cause receptor desensitization and more frequent adverse effects 6, 5
Long-Term Use Considerations
- Limited data beyond several months: The American Academy of Sleep Medicine notes that long-term safety data beyond several months is limited for chronic insomnia, though available evidence suggests good tolerability 6
- Periodic reassessment: Consider evaluating continued need every 3-6 months and attempting dose reduction to determine the lowest effective dose 6
- Shift work benefit: In secondary analyses, melatonin appeared to attenuate cardiovascular disease risk associated with long-term shift work (>5 years), suggesting potential protective effects in specific populations 1