An updated systematic review and dose-response meta-analysis of the effects of α-lipoic acid supplementation on glycemic markers in adults

Nutrition. 2021 Feb:82:111041. doi: 10.1016/j.nut.2020.111041. Epub 2020 Oct 17.


This systematic review and dose-response meta-analysis was conducted to summarize data from available clinical trials on the effects of α-lipoic acid (ALA) supplementation on glycemic markers including glucose, hemoglobin A1c (HbA1c), insulin, homeostatic model assessment of insulin resistance (HOMA-IR), HOMA-β, and quantitative insulin check index in adults. A comprehensive literature search was conducted in the electronic databases of PubMed, Web of Science, ProQuest, Embase and SCOPUS from inception to February 2020. Among all of the eligible studies, 28 articles were selected. The weighted mean differences (WMD) and 95% confidence intervals (CI) were calculated to evaluate the pooled effect size. Between-study heterogeneity was evaluated using Cochran's Q test and I2. Subgroup analysis was done to evaluate the potential sources of heterogeneity. The dose-response relationship was evaluated using fractional polynomial modeling. Twenty eight eligible studies with a total sample size of 1,016 participants were included in the current meta-analysis. The findings of the meta-analysis showed that ALA supplementation significantly reduced insulin (WMD: -0.64; CI: -1.287 to 0.004, P = .04), HOMA-IR (WMD: -0.48; 95% CI: -0.79 to -0.16; P = .002). No change in glucose or HbA1C was reported. Moreover, the effect of ALA on insulin was duration-dependent (Pnon-linearity = 0.04). No evidence of departure from linearity was observed between dose and duration of the ALA supplementation on other markers. The subgrouping revealed that ALA dosage and duration of ALA supplementation, health status of participants, geographic locations and the studies' quality are possible sources of heterogeneity. In summary, ALA supplementation improves serum insulin and insulin resistance in a two-class and duration dependent non-linear analysis.

Keywords: Dose–response; Glucose; Glycemic markers; Insulin; Meta-analysis; Supplement; α-lipoic acid.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Adult
  • Biomarkers
  • Blood Glucose
  • Dietary Supplements
  • Glycated Hemoglobin
  • Humans
  • Insulin Resistance*
  • Thioctic Acid* / therapeutic use


  • Biomarkers
  • Blood Glucose
  • Glycated Hemoglobin A
  • Thioctic Acid