Diabetic neuropathy (DN) is one of the most prevalent and expensive microvascular consequences of diabetes mellitus (DM), which is noteworthy given that it is frequently both underdiagnosed and undertreated in daily clinical practice. The aim of the current article was to review the efficiency of vitamin B12 supplementation in isolation or in combination therapy for the treatment of diabetic peripheral neuropathy. This meta-analysis was designed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). A systematic electronic search was performed in PubMed and Cochrane Library to identify randomized controlled trials (RCTs) assessing the impact of vitamin B12 outcomes in patients with diabetic neuropathy without putting restrictions on the year of publication. A combination of the following keywords was used: "diabetic neuropathy," "vitamin B12," and "outcomes." The primary outcomes assessed in the current meta-analysis included neuropathic symptoms and vibration perception threshold (VPT). Secondary outcomes included a change in pain score from baseline, total cholesterol (mg/dL), high-density lipoprotein (HDL), and low-density lipoprotein (LDL). A total of six articles were selected to be included in the current meta-analysis. Patients receiving vitamin B12 showed a greater reduction of mean neuropathic symptoms (standardized mean difference (SMD): -0.39, 95% confidence interval (CI): -0.73, -0.05, p-value: 0.03) and pain score (SMD: -3.60, 95% CI: -4.68, -1.43, p-value<0.001) compared to the control group. No significant effect of vitamin B12 was found on VPT (mean difference (MD): -4.80, 95% CI: -11.03, 1.42, p-value: 0.13), change in HDL (MD: 0.14, 95% CI: -2.37, 2.65, p-value: 0.91), LDL (MD: 2.59, 95% CI: -5.94, 11.12, p-value: 0.55), and total cholesterol (MD: -2.72, 95% CI: -11.52, 6.08, p-value: 0.54). The current meta-analysis found that vitamin B12 can improve neuropathic symptoms and reduce pain in patients with diabetic neuropathy. However, the current study did not report any significant difference between patients who received vitamin B12 and placebo in terms of HDL, LDL, and total cholesterol.
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