Article - The efficacy of resveratrol supplementation on inflammation and oxidative stress in type-2 diabetes mellitus patients: randomized double-blind placebo meta-analysis.

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Take home message

The use of resveratrol may be of benefit for patients with T2DM to help reduce oxidative stress and inflammation. However, based on the quality of evidence presented, and limited number of studies, findings should be interpreted with caution

Evidence category

A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)

Summary review

Introduction

The aim of this meta-analysis was to evaluate the effect of resveratrol on oxidative stress and inflammation in patients with type 2 diabetes mellitus (T2DM).

Methods

Meta-analysis of randomised, placebo-controlled trials of resveratrol in patients with T2DM.
Where heterogeneity was large (P ≤ 0.1 and I(2) > 50%), the random effects model was used for pooled analysis, otherwise fixed effects model was used.
Cochrane Risk of Bias 2 tool was used to assess quality of studies and Grading of Recommendations Assessment, Development and Evaluation (GRADE) tool was employed to assess the certainty of evidence.

Results

6 trials with 7 study arms were included, with a total of 563 participants. Doses used ranged from 40-1000mg resveratrol and duration ranged from 4-24 weeks.
The following biomarkers were significantly improved: C-reactive protein (CRP, SMD = -1.40, 95%CI(-2.60, -0.21), P = 0.02, n=7); lipid peroxide (SMD = -0.99, 95%CI(-1.36, -0.61), P < 0.00001, n=2); 8-isoprostanes (SMD = -0.79, 95%CI(-1.16, -0.42), P < 0.0001, n=2); glutathione peroxidase (SMD = 0.38, 95%CI(0.03, 0.74), P = 0.04, n=2); catalase (SMD = 0.33, 95%CI(0.03, 0.63), P = 0.03, n=3); oxidative stress scores (SMD = -1.62, 95%CI(-2.49, -0.75), P = 0.0003, n=2);
The following biomarkers were not significantly improved: interleukin-6 (IL-6, SMD = -1.35, 95%CI(-2.75, -0.05), P = 0.06, n=5); tumour necrosis factor alpha (SMD = -3.30, 95%CI(-7.47, 0.87), P = 0.12, n=3); superoxide dismutase (SMD = 0.39, 95%CI(-0.26, 1.04), P = 0.24, n=3); total antioxidant capacity (SMD = 0.39, 95%CI(-0.23, 1.00), P = 0.21, n=3); malondialdehyde (SMD = -3.36, 95%CI(-10.30, 3.09), P = 0.29, n=2).
Subgroup analysis of CRP and IL-6 based on dose (< 500mg vs ≥ 500mg) showed no difference of effect with dose. (P > 0.05).
None of the studies reported any adverse events.
Except for one study, the risk of bias of the included studies was assessed as low.
The certainty of the evidence was rated as low or very low.
A funnel plot suggested a publication bias for CRP.

Conclusion

The authors stated that resveratrol improves oxidative stress and inflammation in patients with T2DM to some extent, but that more large-scale studies are needed to confirm this finding.

Clinical practice applications

The use of resveratrol may be considered in patients with T2DM to support an antioxidant and anti-inflammatory protocol. However, based on the quality of evidence presented, and limited number of studies, findings should be interpreted with caution

Considerations for future research

Larger, high-quality randomised controlled trials to confirm these findings would be of benefit.
Clinical trials using resveratrol in combination with diet, lifestyle and/or other supplements for a more comprehensive approach and taking into consideration potential synergistic effects as well as background intakes could be considered.

Abstract

BACKGROUND

The effects of resveratrol supplementation on inflammation and oxidative stress in patients with type 2 diabetes mellitus (T2DM) were controversial. A meta-analysis was performed to assess the changes in levels of inflammation and oxidative stress in patients with T2DM.

METHODS

Relevant literatures before November 6, 2024 were screened through Web of Science,Embase,the Cochrane Library and other sources (ClinicalTrials, ProQuest Dissertations and Theses). The quality of the literature was evaluated according to the Cochrane Handbook of Systematic Reviews. The study quality was assessed using the risk-of-bias 2 tool and the Grading of Recommendations Assessment,Development and Evaluation (GRADE) system. Review Manager 5.3 conducted meta-analysis of the data included in the literature.

RESULTS

This meta-analysis was conducted in six randomized controlled trials involving 533 participants. Our results showed that supplementation with resveratrol significantly reduced C-reactive protein levels(SMD = -1.40, 95%CI(-2.60, -0.21), P = 0.02; Level of evidence: low), lipid peroxide levels (SMD = -0.99, 95%CI(-1.36, -0.61), P < 0.00001; Level of evidence: low), 8-isoprostanes(SMD = -0.79, 95%CI(-1.16, -0.42), P < 0.0001; Level of evidence: low) and oxidative stress score (SMD = -1.62, 95%CI(-2.49, -0.75), P = 0.0003; Level of evidence: very low). In addition, compared to placebo, Supplementation with resveratrol significantly increased glutathione peroxidase levels (SMD = 0.38, 95%CI(0.03, 0.74), P = 0.04; Level of evidence:low) and catalase levels (SMD = 0.33, 95%CI(0.03, 0.63), P = 0.03; Level of evidence: low). However, no significant difference was observed in improving interleukin-6 levels (SMD = -1.35, 95%CI(-2.75, -0.05), P = 0.06; Level of evidence: very low), tumor necrosis factor α levels (SMD = -3.30, 95%CI(-7.47, 0.87), P = 0.12; Level of evidence: very low), superoxide dismutase levels (SMD = 0.39, 95%CI(-0.26, 1.04), P = 0.24; Level of evidence: very low), total antioxidant capacity levels (SMD = 0.39, 95%CI(-0.23, 1.00), P = 0.21; Level of evidence: very low) and malondialdehyde levels (SMD = -3.36, 95%CI(-10.30, 3.09), P = 0.29; Level of evidence: very low).

CONCLUSION

Resveratrol improved inflammation and oxidative stress in T2DM patients to some extent. This provides a new idea and method for clinical treatment. However, due to the limitations of the study, more large-sample, multi-center clinical studies are needed to verify this conclusion.