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Abstract

As discussed in Part I of this review, the geographic distribution of multiple sclerosis (MS) and the change in risk among migrants provide compelling evidence for the existence of strong environmental determinants of MS, where “environmental” is broadly defined to include differences in diet and other behaviors. As we did for infections, we focus here primarily on those factors that may contribute to explain the geographic variations in MS prevalence and the change in risk among migrants. Among these, sunlight exposure emerges as being the most likely candidate. Because the effects of sun exposure may be mediated by vitamin D, we also examine the evidence linking vitamin D intake or status to MS risk. Furthermore, we review the evidence on cigarette smoking, which cannot explain the geographic variations in MS risk, but may contribute to the recently reported increases in the female/male ratio in MS incidence. Other proposed risk factors for MS are mentioned only briefly; although we recognize that some of these might be genuine, evidence is usually sparse and unpersuasive. Ann Neurol 2007