Efficacy and safety of oral alpha-lipoic acid supplementation for type 2 diabetes management: a systematic review and dose-response meta-analysis of randomized trials.

Objective: To examine the dose-dependent influence of oral alpha-lipoic acid (ALA) supplementation on cardiometabolic risk factors in patients with type 2 diabetes (T2D). Design: We followed the instructions outlined in the Cochrane Handbook for Systematic Reviews of Interventions and the Grading of Recommendations, Assessment, Development, and Evaluation Handbook to conduct our systematic review. The protocol of the study was registered in PROSPERO (CRD42021260587). Method: We searched PubMed, Scopus, and Web of Science to May 2021 for trials of oral ALA supplementation in adults with T2D. The primary outcomes were HbA1c, weight loss, and LDL cholesterol (LDL-C). Secondary outcomes included fasting plasma glucose (FPG), triglyceride (TG), C-reactive protein (CRP), and blood pressure. We conducted a random-effects dose-response meta-analysis to calculate the mean difference (MD) and 95% CI for each 500 mg/day oral ALA supplementation. We performed a nonlinear dose-response meta-analysis using a restricted cubic spline. Results: We included 16 trials with 1035 patients. Each 500 mg/day increase in oral ALA supplementation significantly reduced HbA1c, body weight, CRP, FPG, and TG. Dose-response meta-analyses indicated a linear decrement in body weight at ALA supplementation of more than 600 mg/day (MD600 mg/day: -0.30 kg, 95% CI: -0.04, -0.57). A relatively J-shaped effect was seen for HbA1c (MD: -0.32%, 95% CI: -0.45, -0.18). Levels of FPG and LDL-C decreased up to 600 mg/day ALA intake. The point estimates were below minimal clinically important difference thresholds for all outcomes. Conclusion: Despite significant improvements, the effects of oral ALA supplementation on cardiometabolic risk factors in patients with T2D were not clinically important.