Vitamin B6 status is related to disease severity and modulated by endurance exercise in individuals with multiple sclerosis: a secondary analysis of a randomized controlled trial

Abstract

Background: Low circulating concentrations of B vitamins are linked to various chronic and neurodegenerative diseases. Notably, pyridoxal 5'-phosphate (vitamin B₆) deficiency is linked to altered inflammatory responses and cellular immune function, both critical in multiple sclerosis (MS). Nevertheless, most MS research has focused on folate (vitamin B₉) and vitamin B₁₂, leaving other B vitamins understudied.

Objectives: This secondary analysis investigated B-vitamin serum concentrations and related metabolites across MS phenotypes (primary progressive MS, relapsing-remitting MS, and secondary progressive MS) and disease severity levels. Additionally, the impact of endurance exercise on B-vitamin concentrations was investigated.

Methods: In total, 106 individuals with MS participated in a randomized controlled trial, including different endurance exercise conditions. Serum B-vitamin concentrations were analyzed in 99 participants before and after 3 wk of intervention. Before analysis, participants were dichotomized to 1 of the 2 disability groups based on their expanded disability status scale (EDSS) score: EDSS_≥4.5 (n = 47, EDSS: 5.86 ± 0.56) and EDSS_<4 (n = 52, EDSS: 3.59 ± 0.83).

Results: Higher EDSS scores were associated with lower pyridoxal 5'-phosphate (vitamin B-6) concentrations (r_s: -0.32; 95% CI: -0.49, -0.12; P = 0.011), with the EDSS_≥4.5 group also showing lower baseline pyridoxal 5'-phosphate (vitamin B₆) concentrations (β: -0.18; 95% CI: -0.30, -0.07; P = 0.007) than the EDSS_<4 group. Significant time × EDSS group interactions were evident for pyridoxal 5'-phosphate (vitamin B₆; β: 0.05; 95% CI: 0.02, 0.08; P = 0.011), pyridoxal (vitamin B₆; β: 0.05; 95% CI: 0.02, 0.09; P = 0.005), and riboflavin (vitamin B₂; β: 0.06; 95% CI: 0.02, 0.09; P = 0.008), showing increases in these vitamers in the EDSS_≥4.5 group postexercise. N1-Methylnicotinamide (vitamin B₃; β: -0.11; 95% CI: -0.15, -0.06; P < 0.001) decreased in both groups over time.

Conclusions: Disease severity is associated with distinct B-vitamin profiles in individuals with MS, although endurance exercise appears to modify specific B-vitamin concentrations. This trial was registered at clinicaltrials.gov as NCT04356248.

Keywords: B vitamins; endurance training; expanded disability status scale; multiple sclerosis; pyridoxal 5'-phosphate; vitamin B(6).