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.

Background: Low circulating concentrations of B vitamins are linked to various chronic and neurodegenerative diseases. Notably, pyridoxal 5´-phosphate (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 (B9) and vitamin B12, leaving other B vitamins understudied.

Objective: 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: 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 three-weeks of intervention. Prior to analysis, participants were dichotomized to one of two 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 (B6) concentrations (rs=-0.32, 95%CI [-0.49, -0.12], p=.011), with the EDSS≥4.5 group also showing lower baseline pyridoxal 5'-phosphate (B6) concentrations (β=-0.18, 95%CI [-0.30, -0.07], p=.007) compared to the EDSS<4 group. Significant time x EDSS group interactions were evident for pyridoxal 5'-phosphate (B6) (β=0.05, 95%CI [0.02, 0.08], p=.011), pyridoxal (B6) (β=0.05, 95% CI [0.02, 0.09], p=.005) and riboflavin (B2) (β=0.06, 95%CI [0.02, 0.09], p=.008), showing increases in these vitamers in the EDSS≥4.5 group post-exercise. N1-methylnicotinamide (B3) (β=-0.11, 95%CI [-0.15, -0.06], p<.001) decreased in both groups over time.

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