title: Safety and T cell modulating effects of high dose vitamin D3 supplementation in multiple sclerosis.
abstract: BACKGROUND
  A poor vitamin D status has been associated with a high disease activity of multiple sclerosis (MS). Recently, we described associations between vitamin D status and peripheral T cell characteristics in relapsing remitting MS (RRMS) patients. In the present study, we studied the effects of high dose vitamin D3 supplementation on safety and T cell related outcome measures.
  
  
  RESULTS
  Fifteen RRMS patients were supplemented with 20,000 IU/d vitamin D3 for 12 weeks. Vitamin D and calcium metabolism were carefully monitored, and T cell characteristics were studied by flowcytometry. All patients finished the protocol without side-effects, hypercalcaemia, or hypercalciuria. The median vitamin D status increased from 50 nmol/L (31-175) at week 0 to 380 nmol/L (151-535) at week 12 (P<0.001). During the study, 1 patient experienced an exacerbation of MS and was censored from the T cell analysis. The proportions of (naïve and memory) CD4+ Tregs remained unaffected. Although Treg suppressive function improved in several subjects, this effect was not significant in the total cohort (P=0.143). An increased proportion of IL-10+ CD4+ T cells was found after supplementation (P=0.021). Additionally, a decrease of the ratio between IFN-γ+ and IL-4+ CD4+ T cells was observed (P=0.035).
  
  
  CONCLUSIONS
  Twelve week supplementation of high dose vitamin D3 in RRMS patients was well tolerated and did not induce decompensation of calcium metabolism. The skewing towards an anti-inflammatory cytokine profile supports the evidence on vitamin D as an immune-modulator, and may be used as outcome measure for upcoming randomized placebo-controlled trials.
  
  
  BACKGROUND
  Clinicaltrials.gov NCT00940719.
authors.affiliation: School for Mental Health and Neuroscience, Maastricht University Medical Center, Maastricht, The Netherlands. j.smolders@mumc.nl
authors.forename: Joost
authors.initials: J
authors.lastname: Smolders
authors.forename: Evelyn
authors.initials: E
authors.lastname: Peelen
authors.forename: Mariëlle
authors.initials: M
authors.lastname: Thewissen
authors.forename: Jan Willem
authors.initials: JW
authors.lastname: Cohen Tervaert
authors.forename: Paul
authors.initials: P
authors.lastname: Menheere
authors.forename: Raymond
authors.initials: R
authors.lastname: Hupperts
authors.forename: Jan
authors.initials: J
authors.lastname: Damoiseaux
mesh_terms: D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology; D002762:Cholecalciferol / Q000378:metabolism* / Q000627:therapeutic use; D019587:Dietary Supplements; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D006801:Humans; D007371:Interferon-gamma / Q000097:blood; D016753:Interleukin-10 / Q000097:blood; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000378:metabolism*; D013601:T-Lymphocytes / Q000166:cytology*; D016896:Treatment Outcome; D014807:Vitamin D / Q000378:metabolism
chemical_list: D016753:Interleukin-10; D014807:Vitamin D; D002762:Cholecalciferol; D007371:Interferon-gamma