Vitamin D for Painful Diabetic Neuropathy: A Systematic Review and Meta-Analysis of Randomised Controlled Trials.

Abstract

<h4>Background</h4>Painful diabetic neuropathy (PDN) is a common complication of type 1 and type 2 diabetes, causing substantial morbidity. Current treatments, including antidepressants and analgesics, are often only partially effective and may have significant side effects. Vitamin D deficiency affects around 60% of people with diabetes, making supplementation a low-toxicity, biologically plausible intervention. Observational studies suggest potential benefit, but robust evidence from randomised controlled trials (RCTs) is lacking.<h4>Objective</h4>To systematically review and synthesise RCT evidence on the effect of vitamin D supplementation on pain outcomes in PDN.<h4>Methods</h4>A systematic search was conducted in Medline, EMBASE, Web of Science, Cochrane Library, CINAHL, EBSCO and Google Scholar up to September 2025. Eligible studies were RCTs comparing vitamin D supplementation with placebo in adults with diabetes and PDN. The primary outcome was pain intensity measured with validated tools. A fixed-effects meta-analysis was performed, with results expressed as standardised mean differences (SMD). Risk of bias was assessed using the Cochrane RoB tool, and publication bias examined via Egger's funnel plot.<h4>Results</h4>Five studies met inclusion criteria; four (n = 320) were included in the meta-analysis. Pooled results showed a significant short-term reduction in pain with vitamin D versus placebo (SMD = -0.85; 95% CI: -1.07 to -0.62), with moderate heterogeneity (I² = 61.4%), equivalent to ~11 points on common pain scales. No studies reported medium- or long-term outcomes. Study quality varied, with concerns regarding allocation concealment and selective outcome reporting. Four trials were prospectively registered.<h4>Conclusion</h4>Vitamin D supplementation may reduce short-term pain in PDN, but evidence is limited by small sample sizes and methodological quality. Larger, rigorously designed RCTs with longer follow-up are needed before routine vitamin D testing or supplementation can be recommended for PDN in clinical practice.