Purpose The associations between vitamin D and MRI measures of brain tissue injury have not been previously investigated in multiple sclerosis (MS). This research evaluates the significance of vitamin D and its active metabolites in brain tissue injury and clinical disability in MS patients.

Methods The study population consisted of 193 MS patients (152 women and 41 men; mean age 46.1 (SD 8.4) years; disease duration 13.8 (SD 8.4) years). Serum levels of 25-hydroxyvitamin D₃ (25(OH)VD₃), 25-hydroxyvitamin D₂ (25(OH)VD₂), 1α, 25-dihydroxyvitamin D₃ (1, 25(OH)₂VD₃) and 24(R), 25-dihydroxyvitamin D₃ (24, 25(OH)₂VD₃) were measured using a novel capillary liquid–chromatography–mass spectrometry method. Disability was assessed with the Expanded Disability Status Scale (EDSS) and the MS Severity Scale (MSSS). MRI measures included T2 lesion volume (LV), T1-LV and brain parenchymal fraction. The associations between deseasonalised levels of vitamin D metabolites and clinical and MRI measurements were assessed using regression analyses.

Results Lower deseasonalised levels of total 25(OH)VD (p=0.029), 25(OH)VD₃ (p=0.032) and 24, 25(OH)₂VD₃ (p=0.005) were associated with higher MSSS. Similarly, lower deseasonalised levels of 24, 25(OH)₂VD₃ (p=0.012) were associated with higher EDSS. Higher values of the 25(OH)VD₃ to 24, 25(OH)₂VD₃ ratio were associated with higher MSSS (p=0.041) and lower brain parenchymal fraction (p=0.008).

Conclusions Vitamin D metabolites have protective associations with disability and brain atrophy in MS. In particular, the results indicate strong associations for the 24, 25(OH)₂VD₃ metabolite, which has not been extensively investigated in MS patients.