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Pathologically, multiple sclerosis (MS) is characterized by inflammation and neurodegeneration; the latter is the substrate of loss of brain volume, detectable by serial MRI. Clinically, MS is often characterized by progressive cognitive and physical impairment, and these impairments are associated with changes in brain volume. The accessibility of brain volume measurement and ability to determine change over relatively short periods make it a potentially useful phenotype for studying prognostic factors that may influence the risk of developing impairments over longer periods. Given that existing disease-modifying therapies are only partially effective and have potentially serious toxicities, potentially modifiable prognostic factors such as health behaviors and vitamin D insufficiency are of particular interest. The effects of obesity on brain volume change in MS have received limited attention. One cross-sectional study suggested that obesity is associated with decreased gray matter volume among persons with relapsing-remitting MS,1 but a longitudinal study found that being overweight or obese was not associated with change in brain volume over time.2 To date, studies examining the association of 25-hydroxyvitamin D [25(OH)D] levels with brain volume also have produced conflicting findings.3,4
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