Vitamin B Supplementation for Diabetic Peripheral Neuropathy: A Review and Meta-Analysis

Background/Objectives: Diabetic peripheral neuropathy (DPN) is a common and disabling complication of diabetes. B vitamins play essential roles in neuronal metabolism, but evidence on their therapeutic efficacy remains inconsistent. The review and meta-analysis aimed to evaluate the effects of vitamin B supplementation on clinical and neurophysiological outcomes in DPN. Methods: We searched PubMed, Cochrane Database, and ClinicalTrials.gov, supplemented by reference screening of relevant systematic reviews. Randomized controlled trials (RCTs) comparing vitamin B (any form, dose, route) versus placebo or standard care in adults with DPN were included. Primary outcomes were pain intensity, neuropathy scores, and nerve conduction parameters. Risk of bias was assessed using RoB 2. Random-effects meta-analyses were performed where appropriate. Results: Thirteen RCTs (834 participants) were included. Vitamin B supplementation significantly improved Michigan Neuropathy Screening Instrument Questionnaire (MNSIQ: MD −1.44, 95% CI −2.48 to −0.39) and Examination (MNSIE: MD −0.39, 95% CI −0.66 to −0.12). However, the improvement in MNSIE did not reach the established minimal clinically important difference (MCID) of 0.5 points. Pain intensity on numeric/visual analogue scales showed no significant effect (MD −0.44, 95% CI −1.77 to 0.89; high heterogeneity, I2 = 84.5%), but disease-specific pain scales favoured vitamin B (MD −3.06, 95% CI −5.61 to −0.51). Sural nerve conduction velocity (MD 2.10 m/s, 95% CI 0.35 to 3.86) and amplitude (MD 0.88 µV, 95% CI 0.08 to 1.67) improved significantly. Peroneal and tibial nerve parameters showed no consistent benefit; tibial velocity favoured control (MD −1.23 m/s, 95% CI −2.37 to −0.09). Combination B-vitamin regimens appeared more effective than monotherapy. Formal subgroup analysis did not demonstrate a statistically significant difference between monotherapy and combination therapy for MNSIE, MNSIQ, or sural nerve NCV (interaction p > 0.05) but demonstrated one for peroneal nerve NCV (interaction p = 0.039), although a numerical trend towards greater benefit with combination regimens was observed. Risk of bias was low in six studies, some concerns in five, and high in two. Conclusions: Vitamin B supplementation may improve certain clinical neuropathy scores and sural nerve function in DPN, but effects on pain and motor nerve parameters are inconsistent. Combination therapy (multiple B vitamins) seems more promising than single agents. However, substantial heterogeneity and risk of bias preclude firm recommendations for routine use. Well-designed RCTs stratified by baseline vitamin status are needed.