Vitamin D in inflammatory rheumatic diseases: still a challenge

To critically evaluate the current evidence on the role of vitamin D in inflammatory rheumatic diseases, including its association with disease activity, potential immunomodulatory effects, and the clinical impact of supplementation.

A narrative review was conducted based on a comprehensive search of MEDLINE, Cochrane Library, and Epistemonikos databases up to October 2025. Eligible studies included randomized controlled trials, observational studies, systematic reviews, and meta-analyses evaluating vitamin D status and/or supplementation in adult patients with inflammatory rheumatic diseases. Evidence was synthesized qualitatively, prioritizing study design and level of evidence.

Vitamin D deficiency is highly prevalent across inflammatory rheumatic diseases and is associated with higher disease activity, fatigue, and poorer musculoskeletal outcomes. Experimental data support immunomodulatory effects; however, clinical evidence remains heterogeneous. Randomized controlled trials demonstrate that supplementation effectively corrects deficiency and is safe, with modest improvements in disease activity and fatigue mainly in patients with low baseline 25(OH)D levels. In contrast, large trials and Mendelian randomization studies do not support a causal role of vitamin D in disease onset or sustained remission. Meta-analyses show small and inconsistent benefits, limited by heterogeneity in study design, dosing regimens, and populations.

Vitamin D deficiency is a common and clinically relevant finding in inflammatory rheumatic diseases. While supplementation reliably restores adequate levels and may provide modest clinical benefits in deficient patients, current evidence does not support a causal or disease-modifying role. Maintaining serum 25(OH)D ≥30 ng/mL remains advisable for skeletal health, whereas its immunological benefits require further investigation through well-designed randomized trials.