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

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.

To systematically review and synthesise RCT evidence on the effect of vitamin D supplementation on pain outcomes in PDN.

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.

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.

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.