Melatonin in Congestive Heart Failure
Melatonin supplementation at 10 mg nightly appears to be a beneficial adjunctive therapy in stable heart failure patients, particularly those with reduced ejection fraction, as it improves NT-Pro BNP levels, quality of life, and NYHA functional class without significant adverse effects.
Evidence for Melatonin Use in Heart Failure
The most recent and highest quality evidence comes from the MeHR trial (2022), a double-blind randomized controlled trial that demonstrated clear benefits of melatonin supplementation in heart failure with reduced ejection fraction (HFrEF) 1. This study provides the strongest foundation for recommending melatonin use in this population.
Primary Benefits Demonstrated
NT-Pro BNP Reduction: Melatonin 10 mg nightly for 24 weeks significantly decreased NT-Pro BNP levels compared to placebo (estimated marginal mean difference: 111.0 pg/mL, p = 0.044) 1
Quality of Life Improvement: Patients receiving melatonin showed significantly better quality of life scores (difference: 5.8 points, p = 0.037) 1
NYHA Functional Class: Melatonin improved NYHA class with an odds ratio of 12.9 (p = 0.015) 1
Composite Clinical Outcomes: The melatonin group demonstrated significantly better overall clinical outcomes (difference: 0.93, p = 0.017) 1
A 2025 meta-analysis confirmed these findings, showing melatonin significantly improved quality of life (mean difference: -5.95, p = 0.001) and NYHA class (odds ratio: 4.84, p = 0.05), while also reducing fatigue and NT-Pro BNP levels 2.
Recommended Dosing Protocol
Standard Regimen: 10 mg oral melatonin taken nightly for at least 24 weeks 1. This is the evidence-based dose that demonstrated clinical benefit in the MeHR trial.
Patient Selection Criteria
Appropriate Candidates
- Patients with stable HFrEF on guideline-directed medical therapy (GDMT) 1
- NYHA class II-III heart failure patients 3, 1
- Patients already receiving standard therapy including ACE inhibitors/ARBs, beta-blockers, and diuretics 1
Exercise Caution or Avoid
While no specific contraindications to melatonin were identified in the heart failure trials, standard heart failure precautions apply. Patients with severe (NYHA class IV) heart failure, recent heart failure exacerbation or hospitalization within 4 weeks, or significant bradycardia (heart rate <60/min) should be managed with specialist consultation 4.
Mechanism of Benefit
Melatonin provides multiple cardioprotective effects relevant to heart failure pathophysiology 5:
- Neurohumoral Modulation: Counteracts renin-angiotensin-aldosterone system and sympathetic overactivity 6, 5
- Antioxidant Effects: Reduces oxidative stress, a key pathological process in heart failure 5
- Anti-inflammatory Properties: Decreases inflammatory markers 6
- Anti-apoptotic Actions: Protects against cardiac cell death 5
- Cardiac Remodeling Prevention: May attenuate adverse structural changes 5
Monitoring and Follow-Up
When initiating melatonin in heart failure patients:
- Baseline Assessment: Measure NT-Pro BNP, assess NYHA class, and evaluate quality of life 1
- Follow-up Timing: Reassess clinical parameters at 24 weeks, as this was the duration demonstrating benefit in clinical trials 1
- Clinical Monitoring: Track symptoms, functional capacity, and signs of heart failure progression 1
- Laboratory Monitoring: Consider repeat NT-Pro BNP measurement to assess biochemical response 1
Integration with Guideline-Directed Medical Therapy
Melatonin should be used as adjunctive therapy, not as a replacement for established heart failure treatments 1. Patients must continue their GDMT, which includes:
- ACE Inhibitors or ARBs: First-line therapy for all NYHA class I-IV patients unless contraindicated 4
- Beta-blockers: Proven mortality benefit (bisoprolol, carvedilol, or metoprolol CR/XL) 4
- SGLT2 Inhibitors: Recommended for HFrEF to reduce morbidity and mortality 4
- Mineralocorticoid Receptor Antagonists: For appropriate candidates 4
- Diuretics: As needed for congestion management 4
Important Clinical Considerations
Pathophysiological Observations
Research demonstrates that nocturnal melatonin secretion is negatively correlated with NT-Pro BNP in advanced heart failure (NYHA III), suggesting endogenous melatonin deficiency may contribute to disease progression 3. This provides biological plausibility for supplementation.
Safety Profile
The MeHR trial found melatonin to be well-tolerated with no significant adverse effects reported 1. This favorable safety profile makes it an attractive adjunctive option for heart failure management.
Current Guideline Status
While major heart failure guidelines (ESC 2016, ACC/AHA 2022, ACC 2023) do not yet include melatonin recommendations 4, the emerging evidence from randomized controlled trials supports its consideration as adjunctive therapy in stable HFrEF patients.
Practical Implementation
Start melatonin 10 mg orally at bedtime in stable HFrEF patients already on optimized GDMT who seek additional symptomatic improvement and quality of life enhancement 1. Continue standard heart failure monitoring and medication titration protocols as outlined in established guidelines 4. Reassess clinical response after 24 weeks of therapy 1.