Safety and efficacy of oral Alpha lipoic acid in the management of Diabetic Neuropathy: A Systematic Review and Meta-analysis

Abstract Objective:To evaluate the efficacy and safety of oral alpha lipoic acid for the management of diabetic neuropathy. Methods: A detailed literature search was performed using databases like Pubmed, Embase, and Google Scholar. The search was mainly focused on randomised controlled trials (RCTs) for evaluating the safety and efficacy of alpha-lipoic acid in managing diabetic neuropathy. Based on inclusion and exclusion criteria Eight studies were selected. Data were extracted to examine the quality and characteristics of the studies. Primary outcomes were HbA1c, neuropathy impairment score (NIS), neuropathy impairment score-low limb (NIS-LL), motor nerve conduction velocity (MNCV), neuropathy symptoms and change (NSC), total severity score (TSS), neurological disability score (NDS), and vibration perception thresholds (VPT). The secondary outcome was safety parameters. Results: Eight randomized controlled trials met the inclusion criteria were selected and the efficacy and safety of Alpha lipoic acid in treating diabetic neuropathy were critically analyzed in comparison to the placebo group. The results of this systematic review and meta-analysis showed: Alpha lipoic acid has reduced HbA1c levels (Inverse variance (IV): -1.01 (-1.14 to -0.88) at 95% CI, p < 0.00001, I2 = 96%). ALA administration significantly decreased the Neuropathy Impairment Score (Inverse variance (IV): -1.18 (-1.35 to -1.02) at 95% CI, p<0.00001, I2=16%), ALA administration significantly decreased NIS-LL (Inverse variance (IV): -0.83 (-0.94 to -0.71) at 95% CI, p < 0.00001, I2 = 0%), ALA didn’t show significant improvement in MNCV Score (Inverse variance (IV): 0.07 (-0.67 to 0.81) at 95% CI, P = 0.85, I2 = 0%), ALA found to be beneficial in improving both NSC Number and NSC Severity score (Inverse variance (IV): -0.18 (-0.36 to -0.01) at 95% CI, P = 0.04, I2 = 0%) and (Inverse variance (IV): -0.64 (-0.82 to -0.47) at 95%CI, P < 0.00001, I2 = 89% ) respectively, ALA found to improve TSS (Inverse variance (IV): -0.45 (-0.61 to -0.28) at 95% CI, P < 0.00001, I2 = 98%), ALA shows significant improvement in NDS (Inverse variance (IV): -0.72 (-1.03 to -0.40) at 95% CI, p < 0.00001, I2 = 98%), ALA shows significant improvement in VPT (Inverse variance (IV): -0.36 (-0.52 to -0.20) at 95% CI, P < 0.0001, I2 = 96%) when compared with Placebo/control group. Conclusion: The findings indicate that oral treatment with 600–1800 mg of alpha-lipoic acid may improve a few symptoms resulting from diabetic neuropathy and is a safe option when given at a low dose. At higher doses, it has shown adverse effects.