Deficient vitamin D levels exacerbate diabetic peripheral neuropathy, and supplementation alleviates neuropathic pain

Objectives: Vitamin D deficiency has been proposed as a contributing factor to diabetic peripheral neuropathy (DPN), but evidence regarding its clinical relevance remains inconsistent. This systematic review, meta-analysis, and meta-regression evaluated the association between vitamin D deficiency and DPN and assessed the effects of vitamin D supplementation on neuropathic outcomesMethods: PubMed, Scopus, and Web of Science were searched from inception to June 2025. We included observational studies comparing vitamin D levels in diabetic patients with and without DPN and interventional studies evaluating vitamin D supplementation. Random-effects meta-analyses were performed using standardized mean differences (SMDs) with 95% confidence intervals (CIs). Meta-regression assessed the influence of age and body mass index (BMI).Results: Thirty-three studies involving 17,369 participants were included. In 12 observational studies (n = 2,937), patients with DPN had significantly lower serum vitamin D levels than those without neuropathy (SMD = -0.90, 95% CI -1.51 to -0.30; p = 0.003). Seven interventional studies (n = 437) showed that vitamin D supplementation significantly increased serum vitamin D concentrations (SMD = 2.54, 95% CI 1.05 to 4.03; p = 0.008) and reduced neuropathic pain severity (SMD = -1.30, 95% CI -1.73 to -0.86; p < 0.0001). No significant effect was observed on HbA1c levels (SMD = -0.35, 95% CI -0.87 to 0.17; p = 0.18). Meta-regression demonstrated no significant moderating effects of age or BMI.Discussion: Vitamin D deficiency is significantly associated with DPN, and vitamin D supplementation improves neuropathic pain while increasing serum vitamin D concentrations. These benefits appear independent of glycemic control. Although substantial heterogeneity exists among studies, the findings support vitamin D supplementation as a potentially safe and low-cost adjunctive therapy for diabetic neuropathy. Further large-scale randomized controlled trials are needed to establish optimal supplementation strategies and confirm long-term clinical benefits.