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

Abstract

Objective: To examine the dose-dependent influence of oral ALA supplementation on cardiometabolic risk factors in type 2 diabetes (T2D) patients. Design: We followed 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 low-density lipoprotein cholesterol (LDL-C). Secondary outcomes included fasting plasma glucose (FPG), triglyceride, C-reactive protein, 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/d oral ALA supplementation. Non-linear dose-response meta-analyses were also conducted. Results: We included 16 trials with 1035 patients. Each 500 mg/d 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/d (mean difference 600 mg/d: -0.30 kg, 95%CI: -0.04, -0.57). A relatively J-shaped effect was seen for HbA1c (mean difference: -0.32%, 95%CI: -0.45, -0.18). Levels of FPG and LDL decreased up to 600 mg/d ALA intake. The point estimates of the certainty of evidence 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 T2D patients were not clinically important.

The effects of alpha-lipoic acid supplementation on post-stroke patients: a systematic review and meta-analysis of randomized controlled trials

“…In line with our study, Tabrizi et al demonstrated that ALA supplementation has no signi cant effect on total cholesterol and TG level in patients who had experienced stroke [33]. Furthermore, Jibril et al reported no signi cant impact of ALA on the lipid pro le like our study [44]. Our analysis diverges from that conducted by Akbari et al (2018), whose recent systematic review and meta-analysis indicated that ALA supplementation led to a reduction in fasting cholesterol (total and LDL) and TG [45].…”

“…In line with our study, a previous meta-analyses reported that ALA supplementation was effective for serum glucose reduction [33,44,46]. ALA exerts multifaceted mechanisms to in uence blood glucose levels.…”

Effect of Alpha Lipoic Acid Supplementation on Oxidative Stress and Lipid Parameters in Women Diagnosed with Low-Grade Squamous Intraepithelial Lesions (LSILs): A Double-Blind, Randomized, Placebo-Controlled Trial

“…A meta-analysis by Haghighatdoost and Hariri [ 6 ] showed that ALA may significantly decrease total CHO, LDL and TG levels but that the results obtained so far are contradictory and more research is needed to draw more specific conclusions. A more recent meta-analysis [ 43 ] found that the observed effects of ALA in diabetic patients were not clinically significant.…”

Alpha-Lipoic Acid and Its Enantiomers Prevent Methemoglobin Formation and DNA Damage Induced by Dapsone Hydroxylamine: Molecular Mechanism and Antioxidant Action

“…Furthermore, ALA contains a single central chiral carbon, C6, which is asymmetric and results in two optical enantiomers or stereoisomers: R-(+)-lipoic acid (R-ALA) and S-(-)-lipoic acid (S-ALA) [41,44]. Additionally, ALA is found in the form of supplements composed of the racemic mixture of its R-ALA and S-ALA isomers in doses of 200 to 1200 mg/day [45], or of the isolated R-ALA isomer, with doses of 200 at 300 mg [46]. The R-ALA isomer is unstable at temperatures above 49 • C, while the racemic mixture remains stable at temperatures of up to between 60 and 62 • C. In pharmacokinetic studies in healthy subjects, the R-ALA isomer presents a higher level of absorption, while the S-LA isomer helps in this percentage, preventing the polymerization of the R-ALA form [47] (SEIFAR et al 2017).…”