ORIGINAL CONTRIBUTION Serum 25-Hydroxyvitamin D Levels and Risk of Multiple Sclerosis

MULTIPLE SCLEROSIS (MS) ISamong the most commonneurological diseases inyoung adults, affecting 350 000 individuals in the United States and 2 million worldwide.1 Prevailing thought is thatMSisanautoimmunedis-order whereby an unknown agent or agents triggersaTcell–mediated inflam-matoryattack, causingdemyelinationof central nervous system tissue.2 A striking feature of the global dis-tribution of MS is a multifold increase in incidence with increasing latitude, both north and south of the equator.3 Genetic predisposition contributes to this variation,4 but the change in MS risk with migration among people of common ancestry5 strongly supports a role for environmental factors. One po-tential factor may be vitamin D,6-9 a po-tent immunomodulator that in its hor-monal form can prevent experimental autoimmune encephalomyelitis (EAE), an animal model of MS.10 Because food provides little vitamin D, the major source for most people is through skin exposure to sunlight.11 At latitudes of 42 ° or more (eg, Boston, Mass), in win-ter most UV-B radiation is absorbed by the atmosphere, and even prolonged sun exposure is insufficient to gener-ate vitamin D.12 As a result, seasonal vi-tamin D deficiency is common.11 AprotectiveeffectofvitaminDonMS is supported by the reduced MS risk as-sociated with sun exposure13,14 and use ofvitaminDsupplements,15 butevidence remainsinconclusive.Inthepresentstudy, we examined prospectively for the first time whether high blood levels of 25-hydroxyvitamin D, a good marker of vi-tamin D availability to tissues,11 predict a lower risk of MS. METHODS This study has been approved by the institutional review boards of th