Circulating Folate Concentrations and Risk of Peripheral Neuropathy and Mortality: A Retrospective Cohort Study in the U.K

Abstract

BACKGROUND: Folate deficiency may increase the risk of peripheral neuropathy but there is a paucity of data from large prospective studies examining this association. METHODS: Longitudinal analysis of electronic health records in The Health Improvement Network (THIN), a U.K. primary care database including 594,338 patients aged 18-70 years with a folate measurement and without a history of peripheral neuropathy. RESULTS: After a mean follow-up of 3.71 (standard deviation (SD) = 3.14) years, 1949 patients were diagnosed with peripheral neuropathy and 20,679 patients died. In those <40 years, compared to patients with folate ≥13.6 nmol/L, those with folate <6.8 (deficient) and 6.8-13.5 nmol/L (insufficient) had a hazard ratio (HR) for peripheral neuropathy of 1.83 (95% confidence intervals (CI) = 1.16-2.91) and 1.48 (95% CI = 1.04-2.08), respectively. There was no significant association between folate and peripheral neuropathy among those aged 41-70 years. Compared to patients with folate ≥ 13.6 nmol/L, folate <6.8 nmol/L was associated with a greater risk of death among all ages. CONCLUSION: Folate deficiency and insufficiency was associated with a greater risk of peripheral neuropathy among younger patients. This investigation should be replicated in other large datasets and it may be important to monitor peripheral neuropathy incidence after the introduction of mandatory folic acid fortification of flour in the U.K.