title: Vitamin D supplementation for patients with multiple sclerosis treated with interferon-beta: a randomized controlled trial assessing the effect on flu-like symptoms and immunomodulatory properties.
abstract: BACKGROUND
  Flu-like symptoms (FLS) are common side effects of interferon beta (IFN-β) treatment in patients with Multiple Sclerosis (PwMS) and are associated with post-injection cytokine surge. We hypothesized that vitamin D3 supplementation would ameliorate FLS by decreasing related serum cytokines' levels.
  
  
  METHODS
  In a randomized, double blind study of 45 IFNβ-treated PwMS, 21 patients were assigned to 800 IU of vitamin D3 per day (low dose), while 24 patients received 4,370 IU per day (high dose) for one year. FLS were assessed monthly by telephonic interviews. Serum levels of 25-hydroxy-D (25-OH-D), calcium, PTH, IL-17, IL-10 and IFN-γ were measured periodically. EDSS, relapses, adverse events and quality of life (QoL) were documented.
  
  
  RESULTS
  25-OH-D levels increased to a significantly higher levels and PTH levels decreased in the high dose group. There was no significant change in FLS. IL-17 levels were significantly increased in the low dose group, while patients receiving high dose vitamin D had a heterogeneous IL-17 response. No significant differences in relapse rate, EDSS, QoL, serum IL-10 and IFNγ were found. Hypercalcemia or other potential major adverse events were not observed.
  
  
  CONCLUSIONS
  Vitamin D supplementation to IFN-β treated PwMS, at the doses used, seems safe and associated with dose-dependent changes in IL-17 serum levels, while not affecting IFN-β related FLS.
  
  
  BACKGROUND
  ClinicalTrials.gov ID: NCT01005095.
authors.forename: Daniel
authors.initials: D
authors.lastname: Golan
authors.forename: Basheer
authors.initials: B
authors.lastname: Halhal
authors.forename: Lea
authors.initials: L
authors.lastname: Glass-Marmor
authors.forename: Elsebeth
authors.initials: E
authors.lastname: Staun-Ram
authors.forename: Orit
authors.initials: O
authors.lastname: Rozenberg
authors.forename: Idit
authors.initials: I
authors.lastname: Lavi
authors.forename: Sara
authors.initials: S
authors.lastname: Dishon
authors.forename: Mira
authors.initials: M
authors.lastname: Barak
authors.forename: Sophia
authors.initials: S
authors.lastname: Ish-Shalom
authors.forename: Ariel
authors.initials: A
authors.lastname: Miller
mesh_terms: D000328:Adult; D000368:Aged; D002762:Cholecalciferol / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D016207:Cytokines / Q000097:blood*; D004311:Double-Blind Method; D064420:Drug-Related Side Effects and Adverse Reactions / Q000517:prevention & control*; D005260:Female; D006801:Humans; D016899:Interferon-beta / Q000009:adverse effects*; D020381:Interleukin-17 / Q000097:blood; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000097:blood / Q000188:drug therapy / Q000503:physiopathology; D016896:Treatment Outcome
chemical_list: D016207:Cytokines; C508717:IL17A protein, human; D020381:Interleukin-17; D002762:Cholecalciferol; D016899:Interferon-beta