Effects of coenzyme Q10 supplementation on glycemic control: A GRADE-assessed systematic review and dose-response meta-analysis of randomized controlled trials

Background Previous reviews reported that the effects of CoQ10 on glycemic control were inconsistent. There is no review exploring the optimal intake of CoQ10 for glycemic control. We aimed to investigate the efficacy of CoQ10 on glycemic control and evaluate the dose-response relationship via integrating the existing evidence from randomized control trials (RCTs).Methods Databases (PubMed, Embase, and Cochrane Library) were searched to identify RCTs for investigating the efficacy of CoQ10 on fasting glucose, fasting insulin, HbA1c, and HOMA-IR up to March 12, 2022. We performed a meta-analysis on 40 RCTs of CoQ10. Weighted mean difference (WMD) and 95% confidence intervals (CIs) were cal-culated for net changes. Evidence certainty was assessed using GRADE. Dose-response relationships were evaluated using 1-stage restricted cubic spline regression model. The protocol was registered in PROSPERO (CRD42021252933). Findings Forty studies (n = 2,424 participants) were included in this meta-analysis. CoQ10 significantly reduced fasting glucose (WMD:-5.22 [95% CI:-8.33,-2.11] mg/dl; P <0.001; I2=95.10%), fasting insulin (-1.32 [-2.06,-0.58] mIU/ml; P < 0.001; I2=78.86%), HbA1c (-0.12% [-0.23,-0.01]; P =0.04; I2=49.10%), and HOMA-IR (-0.69 [-1.00,-0.38]; P <0.001; I2=88.80%). The effect of CoQ10 on outcomes was greater in diabetes with lower heterogeneity. A "U" shape dose-response relationship curve revealed that 100-200 mg/day of CoQ10 largely decreased fasting glu-cose (chi 2 =12.08, Pnonlinearity =0.002), fasting insulin (chi 2 = 9.73, Pnonlinearity =0.008), HbA1c (chi 2 = 6.00, Pnonlinearity =0.049), HOMA-IR (chi 2 = 25.89, Pnonlinearity <0.001).Interpretation CoQ10 supplementation has beneficial effects on glycemic control, especially in diabetes, and 100-200 mg/day of CoQ10 could achieve the greatest benefit, which could provide a basis for the dietary guidelines of CoQ10 in patients with glycemic disorders.