A low vitamin D status predicts a higher risk of exacerbations and magnetic resonance imaging activity in people with early relapsing–remitting multiple sclerosis (RRMS).

Clinical trials on vitamin D supplementation in RRMS are negative on primary clinical endpoints.

The effect of vitamin D on multiple sclerosis activity is less pronounced than suggested by observational studies.

This discrepancy may reflect reverse causality or confounding in the observational studies, or differences in trial designs in terms of inclusion criteria, power for primary and secondary outcomes, disease-modifying therapy use, and duration and dose of vitamin D supplementation in the clinical trials.