Background Vitamin D insufficiency is common among multiple sclerosis patients, and hypovitaminosis D has been associated with multiple sclerosis (MS) risk and disease activity. 

Objective To investigate how recommendations on vitamin D3 supplements affect 25-hydroxyvitamin D (25(OH)D) levels in patients with relapsing-remitting MS (RRMS) and to examine the clinical effects associated with changes in 25(OH)D levels. 

Methods In this prospective cohort study, baseline blood samples were collected from 170 natalizumab-treated RRMS patients during winter 2009–2010 and were repeated the following winter. Vitamin D supplements were recommended according to standard clinical practice in our clinic to patients with serum 25(OH)D<50 nmol/l at baseline. Information was obtained on annualized relapse-rate (ARR) the year prior to baseline and the following year. 

Results We found that recommending vitamin D supplements in patients with vitamin D insufficiency was associated with a significant increase in serum 25(OH)D concentrations (p=5.1×10⁻¹⁰), which was significantly related with decreases in ARR; for each nmol/l increase in Δ25(OH)D a −0.014 (95% CI −0.026 to −0.003) decrease in ΔARR was observed, p=0.02. 

Conclusion Correction of hypovitaminosis D in clinical practice by recommending oral D3 supplements resulted in increases in 25(OH)D levels in serum, which were associated with decreases in ARR in RRMS.