HormonesMelatonin

Long-term melatonin therapy (≥1 year) is associated with increased risk of new onset heart failure, heart failure requiring hospitalization, and all-cause mortality in adult insomnia patients

A single unpublished conference abstract reported a statistically significant increased risk of new onset heart failure, heart failure requiring hospitalization, and all-cause mortality associated with long-term melatonin therapy (one year or longer) in adult patients with insomnia. This observation has not undergone peer review or independent validation and is considered hypothesis-generating.

Last updated: Jul 8, 20260 RCTs📖 Read as article →

Evidence Score

Evidence Score34/100
Human RCT☆☆☆☆☆
Meta-analysis☆☆☆☆☆
Mechanism★★★★★
Safety★★★★
Confidencelow

Study Evidence

Study 1. Melatonin supplementation, hyperprolactinemia, and incident heart failure: A proposed prolactin-mediated pathway for cardiovascular risk.

observational

Savvidis C, Thomopoulos C, Ilias I · World journal of experimental medicine (2026)

Participants: N/A
Duration: ≥1 year
Intervention: Long-term melatonin supplementation (≥1 year) for insomnia
Outcome: New onset heart failure, heart failure requiring hospitalization, all-cause mortality
Effect Size: N/A (not reported in abstract)
Population: Adult patients suffering from insomnia

Result:

Mechanism Graph

Melatonin modulates hypothalamic dopaminergic neurons
Increased prolactin (PRL) release
Sustained hyperprolactinemia (hypothetical)
Cleavage of PRL to cardiotoxic 16-kDa fragment in patients with oxidative stress and cardiovascular risk factors
Increased risk of heart failure analogous to peripartum cardiomyopathy

Limitations

  • The primary association is from a single unpublished conference abstract that has not undergone peer review or independent validation
  • The proposed mechanistic pathway is speculative and unconfirmed, with unresolved critical knowledge gaps regarding sustained hyperprolactinemia with long-term melatonin use

Frequently Asked Questions

Is melatonin definitely linked to heart failure?

No. The reported association is from a single unpublished conference abstract that has not been peer-reviewed or independently validated. The paper itself describes the observation as hypothesis-generating and calls for further investigation.

How might melatonin increase heart failure risk?

The paper speculates that melatonin may increase prolactin release, and in patients with oxidative stress and cardiovascular risk factors, prolactin could be cleaved into a cardiotoxic 16-kDa fragment, similar to the mechanism in peripartum cardiomyopathy. This pathway is unconfirmed.

Should I stop taking melatonin based on this study?

No. This is a speculative hypothesis based on preliminary evidence. Melatonin is widely used and has historically been researched for cardioprotective effects. Consult your healthcare provider before making any changes.

What population was studied in this paper?

The abstract refers to adult patients suffering from insomnia who used long-term melatonin therapy (one year or longer). The specific demographics and sample size are not detailed in the abstract.

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References

  1. 1.Savvidis C, Thomopoulos C, Ilias I. "Melatonin supplementation, hyperprolactinemia, and incident heart failure: A proposed prolactin-mediated pathway for cardiovascular risk.." World journal of experimental medicine, 2026. PMID: 42394777 DOI: 10.5493/wjem.v16.i2.120754
Disclaimer: This content is for educational purposes only and is not medical advice. Evidence scores reflect the quality and quantity of available research, not clinical recommendations. Always consult a healthcare professional before starting any supplement or intervention.