Alpha lipoic acid: advancing insights in diabetic neuropathy through updated systematic review and meta-analysis

Background: This study aims to assess oral alpha lipoic acid’s (ALA’s) safety and effectiveness in managing diabetic neuropathy. Methods: A thorough search of the literature was conducted using PubMed, Google Scholar, and Embase databases, and the study was performed as per Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Results: Based on inclusion and exclusion criteria, nine randomized controlled trials (RCTs) comprising 1,345 subjects were selected. The results showed that ALA has shown significant reduction in glycated hemoglobin (HbA1C) [inverse variance (IV): –0.66, (–0.81 → –0.51) at 95% CI, p < 0.00001, I2 = 92%], neuropathy impairment score (NIS) [IV: –1.19, (–2.28 → –0.09) at 95% CI, p = 0.03, I2 = 58%], along with improving the neuropathy symptoms and change (NSC) number [IV: –0.18, (–0.35 → –0.01) at 95% CI, p = 0.04, I2 = 0%], NSC severity score [IV: –0.65, (–0.83 → –0.48) at 95% CI, p < 0.00001, I2 = 89%], total severity score (TSS) [IV: –0.43, (–0.59 → –0.27) at 95% CI, p < 0.00001, I2 = 98%], neurological disability score (NDS) [IV: –0.72, (–1.03 → –0.40) at 95% CI, p < 0.00001, I2 = 98%], vibration perception threshold (VPT) [IV: –0.35, (–0.50 → –0.19) at 95% CI, p < 0.0001, I2 = 96%] and global satisfaction [Mantel-Haenszel (M-H) odds ratio (OR): 3.51, (1.06 → 11.61) at 95% CI, p = 0.04, I2 = 72%] when compared to the control or placebo group. However, ALA has not shown significant changes in motor nerve conduction velocity (MNCV) score [IV: 0.26, (–0.44 → 0.96) at 95% CI, p = 0.47, I2 = 49%] and NIS-low limb (NIS-LL) [IV: –0.58, (–1.35 → 0.19) at 95% CI, p = 0.14, I2 = 0%] when compared to the placebo group. Discussion: Based on the available moderate to high-quality evidence, we can conclude that oral administration of ALA at doses of 600–1,800 mg may be beneficial in improving/alleviating the symptoms resulting from diabetic neuropathy.