Low 25‐hydroxyvitamin D, but not the bioavailable fraction of 25‐hydroxyvitamin D, is a risk factor for multiple sclerosis

Background and purpose Low 25‐hydroxyvitamin D [25( OH ) D ] levels correlate with higher disease activity in patients with multiple sclerosis ( MS ). However, it is not clear whether low 25( OH ) D levels directly contribute to increased disease activity or merely represent a consequence of reduced endogenous vitamin D synthesis in more disabled MS patients. Furthermore, recent data suggest that bioavailable vitamin D , which also integrates the levels of vitamin D binding proteins and albumin, could be a biologically more relevant parameter than 25( OH ) D . Methods Measured de‐seasonalized 25( OH ) D 3 and vitamin D binding protein and calculated bioavailable and free vitamin D were compared in the baseline serum samples of 76 patients with clinically isolated syndrome enrolled in a longitudinal observational study and in 76 age‐ and sex‐matched healthy controls ( HC ). Results 25( OH ) D 3 levels were lower in patients with clinically isolated syndrome ( P  = 0.002) than in HC , and more patients (8/76, 10.5%) than HC (1/76, 1.3%) had 25( OH ) D 3 levels <25 nmol/l ( P  =   0.03). In contrast, levels of 25( OH ) D 2, vitamin D binding protein and calculated levels of free and bioavailable vitamin D did not differ between the two groups. Conclusions Lower 25( OH ) D 3 levels already in the earliest phase of disease and in clinically hardly affected patients suggest that low 25( OH ) D 3 levels are rather a risk factor for than a consequence of MS . Nevertheless, because bioavailable vitamin D levels did not differ between the two groups, the mechanism underlying the association of 25( OH ) D 3 and MS does not appear to be related to reduced bioavailability of vitamin D .