The worldwide distribution of MS strongly indicates a role for environmental factors in the development of MS. Epstein Barr Virus (EBV) is one possible causative agent which may explain the similarities between the epidemiology of MS and infectious mononucleosis (IM). It has been proposed that vitamin D modulates the immune response against EBV and that these factors might interact in the development of MS.

This multinational case-control study included 1660 people with MS and 3050 controls from Norway and Italy (countries of different latitude), to see if vitamin D status modulates the primary immune response to EBV and risk of MS. If so, one would expect a seasonal accumulation of IM among patients. The researchers found that IM was reported more frequently in Norway. However, IM was associated with MS to a similar degree in Norway and Italy. There was a higher frequency of IM during spring compared to fall in all people included in the study. Overall, this shows that IM is associated with MS independent of season. The results do not support the view that seasonal factors like low vitamin D levels during the spring, are biologically interacting with IM in the development of MS