Association between neuropathy and B-vitamins: A systematic review and meta-analysis.

BACKGROUND: Peripheral neuropathy (PN) is common in patients with diseases that are in turn associated with deficiency of the B-vitamins, and vitamin treatment has shown mixed results. METHODS: This systematic review and meta-analysis studied the association between PN/pain and B-vitamin biomarkers and investigated whether vitamin treatment can ameliorate the symptoms. PubMed and Web of Science were searched according to the study protocol. RESULTS: A total of 46 observational and seven interventional studies were identified and included in the data synthesis. The presence of PN was associated with lowered B12 levels (pooled estimate [95% CIs] = 1.51 [1.23-1.84], n = 34, Cochran Q Test I2  = 43.3%, p = 0.003) and elevated methylmalonic acid (2.53 [1.39-4.60], n = 9, I2  = 63.8%, p = 0.005) and homocysteine (3.48 [2.01-6.04], n = 15, I2  = 70.6%, p < 0.001). B12 treatment (vs. the comparators) showed a non-significant association with symptom improvement (1.36 (0.66-2.79), n = 4, I2  = 28.9%). Treatment with B1 was associated with a significant improvement in symptoms (5.34 [1.87-15.19], n = 3, I2  = 64.6%, p = 0.059). Analysis of seven trials combined showed a non-significant higher odds ratio for improvement under treatment with the B-vitamins (2.58 [0.98-6.79], I2  = 80.0%, p < 0.001). CONCLUSIONS: PN is associated with lowered plasma vitamin B12 and elevated methylmalonic acid and homocysteine. Overall, interventional studies have suggested that B-vitamins could improve symptoms of PN. Available trials have limitations and generally did not investigate vitamin status prior to treatment. Well-designed studies, especially in non-diabetes PN, are needed. This meta-analysis is registered at PROSPERO (ID: CRD42020144917).