Effectiveness of vitamin E in the treatment of diabetic neuropathy: systematic review and meta-analysis

To evaluate whether tocotrienol-rich vitamin E improves nerve-conduction parameters and symptoms in diabetic peripheral neuropathy (DPN).

Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses PRISMA 2020 (PROSPERO CRD420250653145), we searched the PubMed, Web of Science, Scopus, and Embase databases up until 20 March 2025, for parallel-group randomized controlled trials (RCTs) of oral vitamin E in adults (≥ 18 years) with electrophysiologically confirmed DPN. Two independent reviewers performed screening, extraction, and the revised Cochrane Risk of Bias tool version 2.0 (RoB 2.0). Random-effects meta-analyses were conducted using the mean differences (MD) with 95% confidence intervals (CI).

Five RCTs (n = 660) met the criteria. Tocotrienol-rich vitamin E increased sural sensory nerve-conduction velocity (NCV) by 1.77 m s⁻¹ (0.80-2.74) and median sensory NCV by 1.53 m s⁻¹ (0.44-2.63); tibial motor NCV rose 1.47 m s⁻¹ (0.36-2.58) versus placebo. Nerve-action-potential amplitudes and glycated hemoglobin A1c (HbA₁c) were unchanged (MD - 0.06%, - 0.18-0.06). Adverse-event rates were similar between groups. Two trials had a low risk of bias; one presented some concerns.

Vitamin E yielded selective NCV gains without amplitude change, suggesting preservation or remyelination of sensory fibers rather than axonal regeneration. The absence of glycemic effects indicates neuroprotection independent of glucose control, positioning vitamin E as a potential adjunct-not substitute-to antidiabetic therapy. Heterogeneity in isoform, dose, and treatment duration (≤ 12 months) and modest sample sizes limit certainty. Larger, longer trials incorporating functional outcomes (pain, gait, and quality of life) are required.