HormonesMelatonin

High-dose melatonin (30 mg/day) is safe and feasible but does not accelerate early biochemical or radiographic bone healing after tibial fracture fixation within 49 days

In a prospective controlled study, 25 adults with closed tibial shaft fractures received either 30 mg/day melatonin for 49 days post-surgery or standard care. Both groups showed significant increases in ALP and RUST scores over time, but no significant between-group differences were found for ALP (p=0.324) or RUST (p=0.261). The intervention was well tolerated with high adherence (91.7%) and no serious adverse events.

Last updated: Aug 26, 2026•0 RCTs•📖 Read as article →

Evidence Score

Evidence Score38/100
Human RCT☆☆☆☆☆
Meta-analysis☆☆☆☆☆
Mechanism★★★★★
Safety★★★★☆
Confidencelow

Study Evidence

Study 1. High-dose melatonin for early tibial fracture healing: A prospective study of safety, feasibility, and preliminary biological effects.

observational

Ninomiya AF, Bertolucci V, Nonose N, Messias LO, Beck WR, Pejon TMM, de Almeida Guerreiro F, Domingues VM, de Godoy Baruel GJ, da Silva LFM, Scariot PPM, Messias LHD · Injury (2026)

Participants: N/A
Duration: 49 days
Intervention: 30 mg oral melatonin nightly for 49 consecutive days after reamed intramedullary nailing
Outcome: Serum alkaline phosphatase (ALP) levels and Radiographic Union Score for Tibial fractures (RUST) at 21 and 49 days; adverse events, adherence, sleep quality
Effect Size: N/A (no significant between-group differences reported)
Population: Adults aged 18-60 years with closed tibial shaft fractures (AO/OTA 42-A/B/C)

Result:

PubMed: 42617392DOI: 10.1016/j.injury.2026.113548

Mechanism Graph

Melatonin has antioxidant and osteogenic properties in preclinical models
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Administered nightly at pharmacological dose to enhance bone healing
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Measured ALP and RUST as markers of bone formation and radiographic union
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No significant acceleration of healing observed within 49 days

Limitations

  • ⚠Small sample size (n=25) and non-randomized sequential allocation
  • ⚠Short follow-up (49 days) may not capture full healing trajectory
  • ⚠Lack of blinding and placebo control
  • ⚠Single-center design limits generalizability

Frequently Asked Questions

What dose of melatonin was used in this study?▼

30 mg per day, administered orally at night for 49 days.

Did melatonin improve bone healing in tibial fractures?▼

No, the study found no significant difference in ALP or RUST scores between melatonin and control groups at 49 days.

Was high-dose melatonin safe in this patient population?▼

Yes, it was well tolerated with high adherence (91.7%) and only one report of mild daytime sleepiness; no serious adverse events occurred.

What were the main limitations of this study?▼

Small sample size, non-randomized design, short follow-up, and lack of blinding/placebo control.

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References

  1. 1.Ninomiya AF, Bertolucci V, Nonose N, Messias LO, Beck WR, Pejon TMM, de Almeida Guerreiro F, Domingues VM, de Godoy Baruel GJ, da Silva LFM, Scariot PPM, Messias LHD. "High-dose melatonin for early tibial fracture healing: A prospective study of safety, feasibility, and preliminary biological effects.." Injury, 2026. PMID: 42617392 DOI: 10.1016/j.injury.2026.113548
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.