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Low Vitamin D levels have been associated with multiple sclerosis (MS) disease risk and activity, but the issue remains unsettled due to variances in study methodologies. In this current study, researchers retrospectively evaluated vitamin D status within the BENEFIT trial, a prospective, phase IV clinical trial that compared early versus late treatment with a beta-interferon in preventing a second clinical event after presentation with a clinically isolated syndrome and abnormal magnetic resonance imaging (MRI) scan. Serum samples from baseline, 6, 12, and 24 months were available for measuring 25-hydroxyvitamin D (25[OH]D), with 465 patients having at least one measurement and 303 all four measurements. Patients were followed for up to 5 years, with long-term average 25(OH)D levels determined for up to 2 years.
Based on a 25(OH)D cut-off of 50 nmol/L, those with higher vitamin D levels had 52% reduced conversion rate to clinically definite MS, a 39% lower rate of new active lesion formation over 5 years, and a 34% reduction in brain volume loss after the first year — all significant findings. Nonsignificant trends were apparent for clinical outcomes, with a 27% reduction in relapses (P=0.19) and a 0.16 reduction in average EDSS score (P=0.11). MRI measures demonstrated a dose-response when 25(OH)D serum level was categorized based upon quintiles.
Ascherio A et al. Vitamin D as an early predictor of multiple sclerosis activity and progression. JAMA Neurol 2014 Jan 20; [e-pub ahead of print]. (http://dx.doi.org/10.1001/jamaneurol.2013.5993)
Comment
The association of serum vitamin D levels in this cohort with MRI activity in early multiple sclerosis is compelling. Study strengths include prospective data collection under strict clinical trial protocols, comprehensive statistical analysis, large patient numbers, having all patients start at first MS presentation, and consistency of the effect across imaging and clinical endpoints. The effect seemed to be greatest after the first year, suggesting that early vitamin D levels may have consequences for years to come. Whether intervention on 25(OH)D serum levels can result in improved disease outcomes remains to be determined. Such intervention trials are currently under way and should soon provide answers.