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

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 D-3 supplementation on antibody levels against EBV nuclear antigen 1 (EBNA1) in RRMS. Methods: Serum 25-hydroxyvitamin D-3 (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 D-3 supplementation (20,000IU/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 61.8nmol/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 D-3 supplementation did not affect antibodies against VCA, CMV or VZV. Conclusion: The results indicate that high-dose oral vitamin D-3 supplementation can affect humoral immune responses against the latent EBV antigen EBNA1 in RRMS.