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

Eur J Neurol. 2016 Jan;23(1):62-7. doi: 10.1111/ene.12788. Epub 2015 Jul 28.


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)D3 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)D3 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)D3 levels <25 nmol/l (P = 0.03). In contrast, levels of 25(OH)D2, vitamin D binding protein and calculated levels of free and bioavailable vitamin D did not differ between the two groups.

Conclusions: Lower 25(OH)D3 levels already in the earliest phase of disease and in clinically hardly affected patients suggest that low 25(OH)D3 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)D3 and MS does not appear to be related to reduced bioavailability of vitamin D.

Keywords: 25-hydroxyvitamin D; bioavailable vitamin D; clinically isolated syndrome; multiple sclerosis; risk factor; vitamin D binding protein.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Biological Availability
  • Calcifediol / blood*
  • Ergocalciferols / blood*
  • Female
  • Humans
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Multiple Sclerosis / blood*
  • Risk Factors
  • Vitamin D / analogs & derivatives*
  • Vitamin D / blood
  • Young Adult


  • Ergocalciferols
  • Vitamin D
  • 25-hydroxyvitamin D
  • Calcifediol