NutriStack
Melatonin and Metoprolol, a synergy.
Metoprolol suppresses endogenous melatonin production by approximately 50% through blockade of beta-1 adrenergic receptors on the pineal gland. This is a primary mechanism for the insomnia and sleep disturbance commonly reported with beta-blockers. Melatonin supplementation (2.5 mg nightly) has been shown in a randomized controlled trial to significantly improve sleep quality in beta-blocker-treated patients without tolerance development or rebound effects.
One pair, every claim cited. The two substances, the type, the mechanism, the recommendation, and the primary literature.
Same shape as the other 1,729 pairs in the public database.
From the interaction database
What the row says.
Every entry follows the same shape: what is happening, the mechanism, the recommendation, and the primary literature.
At a glance
- Substances
- Melatonin and Metoprolol
- Pair type
- Synergy
- Evidence (highest tier)
- Strong
- Source citations
- 5 sources
- Stack Score effect
- +2 to your Stack Score (per scored synergy row).
- Scope
- Supplement × Prescription
- Last verified
- May 30, 2026
Synergy · Strong evidence
Synergy
What is happening. Metoprolol suppresses endogenous melatonin production by approximately 50% through blockade of beta-1 adrenergic receptors on the pineal gland. This is a primary mechanism for the insomnia and sleep disturbance commonly reported with beta-blockers. Melatonin supplementation (2.5 mg nightly) has been shown in a randomized controlled trial to significantly improve sleep quality in beta-blocker-treated patients without tolerance development or rebound effects.
Mechanism. Melatonin synthesis in the pineal gland is stimulated by norepinephrine via beta-1 adrenergic receptors. Metoprolol blocks these receptors, suppressing nocturnal melatonin secretion and disrupting circadian rhythm signaling. Exogenous melatonin replaces the suppressed endogenous production, restoring sleep architecture.
Recommendation. If experiencing sleep disturbance on metoprolol, consider melatonin supplementation (2-3 mg at bedtime). Clinical trials show this is safe and effective. No dose adjustment of metoprolol is needed. Take melatonin 30-60 minutes before desired sleep time.
Sources (5)
- Scheer FA et al. Repeated melatonin supplementation improves sleep in hypertensive patients treated with beta-blockers: a randomized controlled trial. Sleep. 2012;35(10):1395-1402. PMID 23024438
- Stoschitzky K et al. Melatonin secretion related to side-effects of beta-blockers from the central nervous system. J Neural Transm. 1986;67(3-4):303-309. PMID 3291558
- Fatemeh G, Sajjad M, Niloufar R et al.. Effect of melatonin supplementation on sleep quality: a systematic review and meta-analysis of randomized controlled trials.. Journal of Neurology. 2022. PMID 33417003
- Tang BHY, Manalo J, Chowdhury SR et al.. Melatonin Use in the ICU: A Systematic Review and Meta-Analysis.. Critical Care Medicine. 2025. PMID 40662882
- Chan V, Lo K. Efficacy of dietary supplements on improving sleep quality: a systematic review and meta-analysis.. Postgraduate Medical Journal. 2022. PMID 33441476
Stack Score
How this pair moves the number.
Effect on the composite score
If both Melatonin and Metoprolol are in the same stack, this pair applies +2 to your Stack Score (per scored synergy row).
The full algorithm, the clamping rules, and four worked stacks are documented at /methodology/stack-score.
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