The 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 showed mixed results. METHODS This systematic review and meta-analysis studied the association between PN/pain and B-vitamin biomarkers and investigated whether vitamins treatment can ameliorate the symptoms. PubMed and Web of Science were searched according to the study protocol. RESULTS 46 observational and 7 interventional studies were identified and included in data synthesis. The presence of PN was associated with lowered B12 levels [pooled estimate (95% confidence intervals) = 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 symptoms improvement 1.36 (0.66-2.79), n = 4, I2 = 28.9%. Treatment with B1 was associated with a significant improvement of symptoms 5.34 (1.87-15.19), n = 3, I2 = 64.6%, p = 0.059. Analysis of 7 trials combined showed a none-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 vitamin B12 and elevated methylmalonic acid and homocysteine. Overall, interventional studies suggested that B-vitamins could improve symptoms of PN. Available trails have limitations and they generally did not investigate vitamin status before the treatment. Well-designed studies, especially in non-diabetes PN are needed. This meta-analysis is registered at PROSPERO: CRD42020144917.