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 calculated 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; I(2)=95.10%), fasting insulin (-1.32 [-2.06, -0.58] μIU/ml; P < 0.001; I(2)=78.86%), HbA(1c) (-0.12% [-0.23, -0.01]; P =0.04; I(2)=49.10%), and HOMA-IR (-0.69 [-1.00, -0.38]; P <0.001; I(2)=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 glucose (χ(2) = 12.08, P(nonlinearity) =0.002), fasting insulin (χ(2) = 9.73, P(nonlinearity) =0.008), HbA(1c) (χ(2) = 6.00, P(nonlinearity) =0.049), HOMA-IR (χ(2) = 25.89, P(nonlinearity) <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. FUNDING: This work was supported by the National Natural Science Foundation of China (No. 82030098, 81872617 and 81730090), Shenzhen Science, Technology, and Innovation Commission (No. JCYJ20180307153228190), CNS Research Fund for DRI, and National innovation and entrepreneurship training program for undergraduate student (No. 202210558161).