Effect of high-dose vitamin D3 supplementation on antibody responses against Epstein-Barr virus in relapsing-remitting multiple sclerosis

Mult Scler. 2017 Mar;23(3):395-402. doi: 10.1177/1352458516654310. Epub 2016 Jul 11.


Background: Elevated antibody levels against Epstein-Barr virus (EBV) and a poor vitamin D status are environmental factors that may interact in relapsing-remitting multiple sclerosis (RRMS) aetiology.

Objectives: To examine effects of high-dose oral vitamin D3 supplementation on antibody levels against EBV nuclear antigen 1 (EBNA1) in RRMS.

Methods: Serum 25-hydroxyvitamin D3 (25(OH)D) and immunoglobulin G antibody levels against EBNA1 (whole protein and amino acid 385-420 fragment), EBV viral capsid antigen (VCA), cytomegalovirus (CMV) and varicella zoster virus (VZV) were measured in 68 RRMS patients enrolled in a 96-week randomised double-blinded placebo-controlled clinical trial of oral vitamin D3 supplementation (20,000 IU/week) (NCT00785473).

Results: The mean 25(OH)D level more than doubled in the vitamin D group and was significantly higher than in the placebo group at study conclusion (123.2 versus 61.8 nmol/L, p < 0.001). Compared to the placebo group, both anti-EBNA1 protein and fragment antibody levels decreased in the vitamin D group from baseline to week 48 ( p = 0.038 and p = 0.004, respectively), but not from baseline to week 96. Vitamin D3 supplementation did not affect antibodies against VCA, CMV or VZV.

Conclusion: The results indicate that high-dose oral vitamin D3 supplementation can affect humoral immune responses against the latent EBV antigen EBNA1 in RRMS.

Keywords: EBV antibodies; Relapsing-remitting multiple sclerosis; vitamin D.

MeSH terms

  • Adolescent
  • Adult
  • Antibodies, Viral / blood
  • Cholecalciferol / therapeutic use*
  • Epstein-Barr Virus Infections / drug therapy*
  • Epstein-Barr Virus Infections / immunology
  • Epstein-Barr Virus Nuclear Antigens / blood
  • Female
  • Herpesvirus 4, Human / drug effects*
  • Herpesvirus 4, Human / pathogenicity
  • Humans
  • Immunoglobulin G / blood
  • Male
  • Middle Aged
  • Multiple Sclerosis, Relapsing-Remitting / drug therapy*
  • Young Adult


  • Antibodies, Viral
  • Epstein-Barr Virus Nuclear Antigens
  • Immunoglobulin G
  • Cholecalciferol
  • EBV-encoded nuclear antigen 1

Associated data

  • ClinicalTrials.gov/NCT00785473