title: Low 25-hydroxyvitamin D, but not the bioavailable fraction of 25-hydroxyvitamin D, is a risk factor for multiple sclerosis.
abstract: OBJECTIVE
  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.
authors.affiliation: NeuroCure Clinical Research Center, Charité-Universitätsmedizin Berlin, Berlin, Germany.|Clinical and Experimental Multiple Sclerosis Research Center, Department of Neurology, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Janina R
authors.initials: JR
authors.lastname: Behrens
authors.affiliation: NeuroCure Clinical Research Center, Charité-Universitätsmedizin Berlin, Berlin, Germany.|Department of Neurology, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Ludwig
authors.initials: L
authors.lastname: Rasche
authors.affiliation: NeuroCure Clinical Research Center, Charité-Universitätsmedizin Berlin, Berlin, Germany.|Department of Neurology, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Rene M
authors.initials: RM
authors.lastname: Gieß
authors.affiliation: NeuroCure Clinical Research Center, Charité-Universitätsmedizin Berlin, Berlin, Germany.|Department of Neurology, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Catherina
authors.initials: C
authors.lastname: Pfuhl
authors.affiliation: NeuroCure Clinical Research Center, Charité-Universitätsmedizin Berlin, Berlin, Germany.|Department of Neurology, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Wakonig
authors.affiliation: NeuroCure Clinical Research Center, Charité-Universitätsmedizin Berlin, Berlin, Germany.|Department of Neurology, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Erik
authors.initials: E
authors.lastname: Freitag
authors.affiliation: Clinical and Experimental Multiple Sclerosis Research Center, Department of Neurology, Charité-Universitätsmedizin Berlin, Berlin, Germany.|Department of Psychiatry, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Katrin
authors.initials: K
authors.lastname: Deuschle
authors.affiliation: NeuroCure Clinical Research Center, Charité-Universitätsmedizin Berlin, Berlin, Germany.|Clinical and Experimental Multiple Sclerosis Research Center, Department of Neurology, Charité-Universitätsmedizin Berlin, Berlin, Germany.|Experimental and Clinical Research Center, Max Delbrück Center for Molecular Medicine and Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Judith
authors.initials: J
authors.lastname: Bellmann-Strobl
authors.affiliation: NeuroCure Clinical Research Center, Charité-Universitätsmedizin Berlin, Berlin, Germany.|Clinical and Experimental Multiple Sclerosis Research Center, Department of Neurology, Charité-Universitätsmedizin Berlin, Berlin, Germany.|Department of Neurology, Charité-Universitätsmedizin Berlin, Berlin, Germany.|Experimental and Clinical Research Center, Max Delbrück Center for Molecular Medicine and Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Friedemann
authors.initials: F
authors.lastname: Paul
authors.affiliation: Clinical and Experimental Multiple Sclerosis Research Center, Department of Neurology, Charité-Universitätsmedizin Berlin, Berlin, Germany.|Department of Neurology, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Klemens
authors.initials: K
authors.lastname: Ruprecht
authors.affiliation: NeuroCure Clinical Research Center, Charité-Universitätsmedizin Berlin, Berlin, Germany.|Clinical and Experimental Multiple Sclerosis Research Center, Department of Neurology, Charité-Universitätsmedizin Berlin, Berlin, Germany.|Experimental and Clinical Research Center, Max Delbrück Center for Molecular Medicine and Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Dörr
mesh_terms: D000328:Adult; D001682:Biological Availability; D002112:Calcifediol / Q000097:blood*; D004872:Ergocalciferols / Q000097:blood*; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000097:blood*; D012307:Risk Factors; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000097:blood; D055815:Young Adult
chemical_list: D004872:Ergocalciferols; D014807:Vitamin D; C104450:25-hydroxyvitamin D; D002112:Calcifediol
keywords: 25-hydroxyvitamin D; bioavailable vitamin D; clinically isolated syndrome; multiple sclerosis; risk factor; vitamin D binding protein