Low 25-hydroxyvitamin D (25(OH)D) concentration is a recognised risk factor for multiple sclerosis (MS). Associations with vitamin D metabolites and vitamin D binding globulin (VDBG) have not been widely studied. We assessed the association between vitamin D metabolites (25(OH)D, 25(OH)D, c3-epimer 25(OH)D, 1,25-dihydroxyvitamin D (1,25(OH)D), and 24,25-dihydroxyvitamin D (24,25(OH)D)) measured by liquid chromatography-tandem mass spectrometry assays, VDBG measured using a polyclonal immunoassay, and calculated free and bioavailable 25(OH)D, free 1,25(OH)D, and the 24,25(OH)D: total 25(OH)D and total 1,25(OH)D: total 25(OH)D ratios with risk of a first clinical diagnosis of CNS demyelination (FCD) in an Australian case-control study (n = 196 cases, n = 241 controls, matched on age, sex and study region). Higher 25(OH)D (adjusted odds ratio (AOR) = 0.94 (95 % confidence interval (CI) 0.85-1.03) per 10 nmol/L increment) and 24,25(OH)D (AOR = 0.81 (95 %CI 0.65-1.00) per 1 nmol/L increment) concentrations were associated with reduced FCD risk. Our results were compatible with no association for the other vitamin D metabolites, ratios, or VDBG with FCD risk. Thus, using standardised assays, and a comprehensive range of vitamin D metabolites, we confirmed the association of higher 25(OH)D and reduced FCD risk, and describe a similar effect for 24,25(OH)D; free or bioavailable 25(OH)D were not associated with FCD risk.
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