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Meta-Analysis
. 2025 Dec 31;18(1):134.
doi: 10.3390/nu18010134.

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

Shooka Mohammadi  1 , Damoon Ashtary-Larky  2 , Mahsa Erfanian-Salim  3 , Navid Alaghemand  2 , Mojtaba Yousefi  4 , Pouyan Sanjari Pirayvatlou  5 , Mohammadreza Mirkarimi  6 , Sara Ayazian Mavi  7 , Ilnaz Alavi  8 , Yeganeh Ettehad  5 , Milad Mehrbod  9 , Omid Asbaghi  10 , Katsuhiko Suzuki  11 , Russel J Reiter  12
Affiliations
Meta-Analysis

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

Shooka Mohammadi et al. Nutrients. .

Abstract

Background/Objectives: There is no definitive consensus regarding the effects of melatonin on cardiometabolic risk factors (CMRFs). This systematic review and dose-response meta-analysis of randomized controlled trials (RCTs) evaluated the impacts of melatonin supplementation on CMRFs, including anthropometric, lipid, glycemic, inflammatory, oxidative, and liver function parameters. Methods: A systematic search across multiple databases retrieved 63 eligible RCTs published up to October 2025. Results: This random-effects meta-analysis indicated that melatonin supplementation significantly reduced hip circumference (weighted mean difference (WMD): -1.18 cm, 95% confidence interval (CI): -2.28, -0.08), systolic blood pressure (WMD: -2.34 mmHg, 95% CI: -4.13, -0.55), fasting blood glucose (WMD: -11.63 mg/dL, 95% CI: -19.16, -4.10), low-density lipoprotein 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), C-reactive protein (WMD: -0.59 mg/L, 95% CI: -0.94, -0.23), malondialdehyde (WMD: -1.54 μmol/L, 95% CI: -2.07, -1.01), tumor necrosis factor-alpha (WMD: -1.61 pg/mL, 95% CI: -2.31, -0.90), interleukin-6 (WMD: -6.43 pg/mL, 95% CI: -10.72, -2.15), and alanine aminotransferase (WMD: -2.61 IU/L, 95% CI: -4.87, -0.34). Supplementation with melatonin substantially increased serum total antioxidant capacity (WMD: 0.15 mmol/L, 95% CI: 0.08, 0.22) and high-density lipoprotein cholesterol (WMD: 2.04 mg/dL, 95% CI: 0.50, 3.57). No significant effects of melatonin were observed on body weight, waist circumference, body fat percentage, body mass index, fasting insulin, homeostasis model assessment of insulin resistance, hemoglobin A1c, triglycerides, diastolic blood pressure, aspartate aminotransferase, or gamma-glutamyl transferase. Conclusions: Melatonin supplementation significantly ameliorated multiple CMRFs.

Keywords: blood pressure; cardiometabolic risks; glycemic control; inflammation; lipid profile; melatonin; oxidative stress.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Flow diagram of study selection.
Figure 2
Figure 2
Summary of the effects of melatonin supplementation on cardiometabolic risk factors based on the meta-analysis of 63 RCTs. Arrows indicate the direction of effect (↑increase,↓ decrease).
Figure 3
Figure 3
Forest plots illustrate weighted mean differences (WMDs) and 95% confidence intervals (CIs) for the effects of melatonin supplementation on anthropometric parameters, including (A) BW (kg), (B) BMI (kg/m2), (C) WC (cm), (D) HC (cm), and (E) BFP (%) [75,76,77,79,80,85,86,87,89,91,92,94,99,101,108,109,111,113,115,116,117,119,121,124,125,126,128,131,134,135].
Figure 3
Figure 3
Forest plots illustrate weighted mean differences (WMDs) and 95% confidence intervals (CIs) for the effects of melatonin supplementation on anthropometric parameters, including (A) BW (kg), (B) BMI (kg/m2), (C) WC (cm), (D) HC (cm), and (E) BFP (%) [75,76,77,79,80,85,86,87,89,91,92,94,99,101,108,109,111,113,115,116,117,119,121,124,125,126,128,131,134,135].
Figure 3
Figure 3
Forest plots illustrate weighted mean differences (WMDs) and 95% confidence intervals (CIs) for the effects of melatonin supplementation on anthropometric parameters, including (A) BW (kg), (B) BMI (kg/m2), (C) WC (cm), (D) HC (cm), and (E) BFP (%) [75,76,77,79,80,85,86,87,89,91,92,94,99,101,108,109,111,113,115,116,117,119,121,124,125,126,128,131,134,135].
Figure 4
Figure 4
Forest plots illustrate weighted mean differences (WMDs) and 95% confidence intervals (CIs) for the effects of melatonin supplementation on glycemic parameters, including (A) FBG (mg/dL), (B) HbA1c (%), (C) FI (µIU/mL), and (D) HOMA-IR [75,76,80,85,86,89,94,95,96,100,101,103,108,109,111,112,115,124,125,134,135].
Figure 4
Figure 4
Forest plots illustrate weighted mean differences (WMDs) and 95% confidence intervals (CIs) for the effects of melatonin supplementation on glycemic parameters, including (A) FBG (mg/dL), (B) HbA1c (%), (C) FI (µIU/mL), and (D) HOMA-IR [75,76,80,85,86,89,94,95,96,100,101,103,108,109,111,112,115,124,125,134,135].
Figure 5
Figure 5
Forest plots illustrate weighted mean differences (WMDs) and 95% confidence intervals (CIs) for the effects of melatonin supplementation on lipid parameters, including (A) TG (mg/dL), (B) TC (mg/dL), (C) LDL-C (mg/dL), and (D) HDL-C (mg/dL) [75,76,78,80,85,86,90,95,100,101,109,111,112,115,124,125,126,130,134,135].
Figure 5
Figure 5
Forest plots illustrate weighted mean differences (WMDs) and 95% confidence intervals (CIs) for the effects of melatonin supplementation on lipid parameters, including (A) TG (mg/dL), (B) TC (mg/dL), (C) LDL-C (mg/dL), and (D) HDL-C (mg/dL) [75,76,78,80,85,86,90,95,100,101,109,111,112,115,124,125,126,130,134,135].
Figure 6
Figure 6
Forest plots illustrate weighted mean differences (WMDs) and 95% confidence intervals (CIs) for the effects of melatonin supplementation on blood pressure, including (A) SBP (mmHg) and (B) DBP (mmHg) [76,82,85,86,87,89,94,101,102,105,109,110,111,115,121,123,125,134,135,136,137].
Figure 7
Figure 7
Forest plots illustrate weighted mean differences (WMDs) and 95% confidence intervals (CIs) for the effects of melatonin supplementation on oxidative stress parameters, including (A) MDA (μmol/L) and (B) TAC (mmol/L) [78,79,83,84,95,99,105,106,108,114,117,118,120,122,128,133,137].
Figure 8
Figure 8
Forest plots illustrate weighted mean differences (WMDs) and 95% confidence intervals (CIs) for the effects of melatonin supplementation on inflammatory parameters, including (A) CRP (mg/L), (B) IL-6 (pg/mL), and (C) TNF-α (pg/mL) [79,81,83,84,85,88,90,93,96,97,98,104,107,109,114,117,118,121,122,125,127,128,129,132,137].
Figure 8
Figure 8
Forest plots illustrate weighted mean differences (WMDs) and 95% confidence intervals (CIs) for the effects of melatonin supplementation on inflammatory parameters, including (A) CRP (mg/L), (B) IL-6 (pg/mL), and (C) TNF-α (pg/mL) [79,81,83,84,85,88,90,93,96,97,98,104,107,109,114,117,118,121,122,125,127,128,129,132,137].
Figure 9
Figure 9
Forest plots illustrate weighted mean differences (WMDs) and 95% confidence intervals (CIs) for the effects of melatonin supplementation on liver function markers, including (A) AST (IU/L), (B) ALT (IU/L), and (C) GGT (IU/L) [87,90,98,100,109,112,114,121,130].
Figure 9
Figure 9
Forest plots illustrate weighted mean differences (WMDs) and 95% confidence intervals (CIs) for the effects of melatonin supplementation on liver function markers, including (A) AST (IU/L), (B) ALT (IU/L), and (C) GGT (IU/L) [87,90,98,100,109,112,114,121,130].
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