The Relationship of Cobalamin and/or Folate to the Patient-Centred Outcomes in Multiple Sclerosis: A Systematic Review and Meta-analysis

Background: To examine the relationship of vitamin B12 and folate concentrations to cognitive function, fatigue measures, physical function, quality of life (patient-centred outcomes) and homocysteine plasma concentrations (intermediate marker of cobalamin and folate deficiency) for patients with Multiple Sclerosis (MS). Methods: Systematic searches for eligible articles of MEDLINE, CINAHL, EMBASE, Scopus, Web of Science and OpenGray databases were conducted from 1983 in March 2021. Heterogeneity, Weighted Mean Difference (WMD) and Confidence Intervals (CI) calculated using Random Effects Model. Results: Sixteen studies were included involving; 616 MS patients and 655 healthy controls. 14 of these had acceptable or better quality but there was high heterogeneity. No difference was found between MS, healthy controls for folate and cobalamin concentrations; WMD 0.00ug/L (95% CI: -0.01, 0.01) and WMD 7.01pmol/L (95% CI: -25.54, 39.55) respectively. MS group showed mild-to-moderate disability WMD was 2.78 (95% CI: 2.00, 3.56). MS may be associated with elevated plasma homocysteine concentrations on average 2.47 mu mol/L more than healthy controls. Discussion: Physical ability of MS group was worse than healthy controls, but there was no difference in folate and cobalamin concentrations. This suggests folate and cobalamin are not influential factors in worsening physical function. There may be an association between worse cognitive function, and increased homocysteine concentrations. Results were inconclusive due to high heterogeneity and limited number of studies. A core outcome set would enable easier synthesis of future results.