Vitamin D metabolism is associated with disability and lower brain parenchymal fraction in patients with MS.
Vitamin D metabolites have protective associations with disability and brain atrophy in patients with multiple sclerosis (MS), according to a study in the February issue of the Journal of Neurology, Neurosurgery, and Psychiatry. In particular, the results indicate strong associations for the 24, 25(OH)2VD3 metabolite, which has not been extensively investigated in patients with MS, reported Bianca Weinstock-Guttman, MD, of the Department of Neurology, State University of New York, Buffalo, and colleagues.
Dr. Weinstock-Guttman and colleagues evaluated the significance of vitamin D and its active metabolites in brain tissue injury and clinical disability in 193 patients with MS (152 women; mean age, 46.1; disease duration, 13.8 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.
The investigators used the Expanded Disability Status Scale (EDSS) and the MS Severity Scale (MSSS) to assess disability. MRI measures included T2 lesion volume, T1 lesion volume, and brain parenchymal fraction. The associations between deseasonalized levels of vitamin D metabolites and clinical and MRI measurements were assessed using regression analyses.
Dr. Weinstock-Guttman’s group found that lower deseasonalized levels of total 25(OH)VD, 25(OH)VD3, and 24, 25(OH)2VD3 were associated with a higher MSSS score. Similarly, lower deseasonalized levels of 24, 25(OH)2VD3 were associated with a higher EDSS score. Higher values of the 25(OH)VD3 to 24, 25(OH)2VD3 ratio were associated with a higher MSSS score and lower brain parenchymal fraction.
“Our µLC/MS/MS assay was important for enabling the systems pharmacology approach, which to our knowledge has not been used to investigate vitamin D metabolism in MS disease progression,” stated the researchers. “The low serum concentration of 1, 25 (OH)2VD3, low ionization efficiency and fragmentation patterns of vitamin D metabolites precluded sensitive detection by selected reactions monitoring. To obtain higher sensitivity, samples were derivatized with 4-phenyl-1,2,4-triazoline-3,5-dione (PTAD), which is specific for vitamin D metabolites, and the solid phase extraction step enabled loading of analytes extracted from a relatively high volume of sample into the µLC separation step. The method achieved sensitive and selective quantification of vitamin D metabolites in 0.2 ml of serum.”