Dietary Supplements

Comprehensive Effects of Melatonin Supplementation on Cardiometabolic Risk Factors: A Systematic Review and Dose-Response Meta-Analysis.

TL;DR

Melatonin supplementation significantly ameliorated multiple cardiometabolic risk factors including hip circumference, systolic blood pressure, fasting blood glucose, LDL cholesterol, total cholesterol, C-reactive protein, malondialdehyde, TNF-alpha, IL-6, and ALT, while increasing HDL cholesterol and total antioxidant capacity.

Key Findings

Melatonin supplementation significantly reduced hip circumference compared to control.

  • WMD: -1.18 cm, 95% CI: -2.28, -0.08
  • Based on a random-effects meta-analysis of 63 eligible RCTs published up to October 2025
  • No significant effect was observed on body weight, waist circumference, body fat percentage, or BMI

Melatonin supplementation significantly reduced systolic blood pressure.

  • WMD: -2.34 mmHg, 95% CI: -4.13, -0.55
  • No significant effect was observed on diastolic blood pressure
  • Analysis derived from a systematic search across multiple databases yielding 63 eligible RCTs

Melatonin supplementation significantly reduced fasting blood glucose.

  • WMD: -11.63 mg/dL, 95% CI: -19.16, -4.10
  • No significant effects were observed on fasting insulin, HOMA-IR, or hemoglobin A1c
  • Glycemic parameters were among the cardiometabolic risk factors evaluated across 63 RCTs

Melatonin supplementation significantly reduced LDL cholesterol and total cholesterol while increasing HDL cholesterol.

  • LDL cholesterol WMD: -6.28 mg/dL, 95% CI: -10.53, -2.03
  • Total cholesterol WMD: -6.97 mg/dL, 95% CI: -12.20, -1.74
  • HDL cholesterol WMD: +2.04 mg/dL, 95% CI: 0.50, 3.57
  • No significant effect was observed on triglycerides

Melatonin supplementation significantly reduced the inflammatory markers C-reactive protein, tumor necrosis factor-alpha, and interleukin-6.

  • CRP WMD: -0.59 mg/L, 95% CI: -0.94, -0.23
  • TNF-alpha WMD: -1.61 pg/mL, 95% CI: -2.31, -0.90
  • IL-6 WMD: -6.43 pg/mL, 95% CI: -10.72, -2.15

Melatonin supplementation significantly reduced malondialdehyde and increased total antioxidant capacity, indicating beneficial oxidative stress effects.

  • Malondialdehyde WMD: -1.54 µmol/L, 95% CI: -2.07, -1.01
  • Total antioxidant capacity WMD: +0.15 mmol/L, 95% CI: 0.08, 0.22
  • These findings reflect melatonin's known antioxidant properties evaluated across the included RCTs

Melatonin supplementation significantly reduced alanine aminotransferase but had no significant effect on other liver function markers.

  • ALT WMD: -2.61 IU/L, 95% CI: -4.87, -0.34
  • No significant effects were observed on aspartate aminotransferase or gamma-glutamyl transferase
  • Liver function parameters were included as part of the comprehensive cardiometabolic risk factor assessment

The systematic review identified 63 eligible randomized controlled trials published up to October 2025 evaluating melatonin supplementation on cardiometabolic risk factors.

  • A systematic search across multiple databases was conducted
  • Studies assessed anthropometric, lipid, glycemic, inflammatory, oxidative, and liver function parameters
  • A random-effects meta-analysis model was used for pooling results
  • A dose-response meta-analysis was also performed as part of the analytical approach

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Citation

Mohammadi S, Ashtary-Larky D, Erfanian-Salim M, Alaghemand N, Yousefi M, Sanjari Pirayvatlou P, et al.. (2026). Comprehensive Effects of Melatonin Supplementation on Cardiometabolic Risk Factors: A Systematic Review and Dose-Response Meta-Analysis.. Nutrients. https://doi.org/10.3390/nu18010134