Effectiveness of alpha lipoic acid supplementation on biochemical, clinical, and inflammatory parameters in patients with diabetic polyneuropathy: A systematic review and meta-analysis

Introduction: In this article, we perform a systematic review and meta-analysis evaluating the effects of alpha-lipoic acid (ALA) supplementation on biochemical, clinical, inflammatory, and functional parameters in patients with diabetic polyneuropathy or diabetic peripheral neuropathy (DPN). A total of 15 articles were included, of which 12 were analyzed for outcomes. DPN is a chronic complication of Diabetes Mellitus (DM) characterized by symptoms, such as pain, sensory disturbances, and reduced quality of life. Currently, there is no definitive cure. Management focuses on controlling blood glucose and alleviating symptoms through pharmacological and non-pharmacological therapies. The aim of this study is to analyze the evidence regarding the efficacy of alpha-lipoic acid (ALA) supplementation in the management of DPN. Results: A systematic search across multiple databases was conducted using keywords, such as “diabetes mellitus,” “diabetes mellitus type I,” “diabetes mellitus type II,” “alpha-lipoic acid,” and “ALA supplementation.” A total of 15 studies met the inclusion criteria. Of the 23 outcomes analyzed, 19 showed significant differences in favor of alpha-lipoic acid (ALA) supplementation at different doses versus a placebo or other treatments. Notable improvements were observed in Total Symptom Score (TSS) paresthesia (SMD = −1.04; 95 % CI = −1.24 to −0.84; p < 0.00001), TSS numbness (SMD = −0.23; 95 % CI = −0.44 to −0.01; p = 0.04), and the Hamburg Pain Adjective List (HPAL) (SMD = −1.00; 95 % CI = −1.15 to −0.85; p < 0.00001), among others. These improvements were particularly evident for symptoms, such as paresthesia, numbness, and burning sensations, especially at a dose of 600 mg/day. In contrast, four of the outcomes HbA1c, nitric oxide levels, sural sensory nerve action potential, and peroneal motor nerve conduction velocity showed no significant changes. Conclusion: The evidence suggests that ALA, especially at 600 mg/day, is a safe and potentially effective adjunct therapy for symptom management in DPN, although its impact on nerve conduction and long-term glycemic control remains inconclusive.