Multiple Sclerosis in Women: Vitamin D and Estrogen Synergy for Autoimmune T-Cell Regulation and Demyelinating Disease Prevention

Multiple sclerosis (MS) incidence has tripled since 1950. The scope, magnitude, and rapidity of this trend imply that its origins are environmental. To discover these origins, we summarize genetic, environmental, and hormonal factors that fuel MS pathology, sex-based differences in MS, and estrogen's mechanisms in demyelinating disease. The fine details of the incidence trend reveal that the trend is female-biased, specific for relapsing-remitting disease, and most evident at high latitudes, although it has recently emerged with a vengeance among very young Islamic women. Lifestyle changes have fueled a global epidemic of vitamin D deficiency that may be driving MS incidence upward. A female-specific mechanism requiring estrogen and vitamin D synergy for immune tolerance may explain the sex bias. An international task force designed the Mothers and Children study to determine experimentally whether vitamin D supplementation would reduce MS incidence. Implementation of their recommendations is certainly warranted.