Abstract
Background and Objective: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by widespread inflammation and multisystem involvement, leading to substantial morbidity. Given the immunomodulatory role of vitamin D and its association with disease activity in SLE, supplementation has emerged as a potential therapeutic strategy. However, findings across individual studies remain inconsistent, underscoring the need for a systematic review and meta-analysis to synthesize the current evidence on vitamin D supplementation for this disease. Thus, this study aimed to conduct a systematic review and meta-analysis on the effects of vitamin D supplementation on disease activity among patients with SLE. Methods: Systematic searches were carried out in four electronic databases (PubMed, Scopus, Web of Science, and Science Direct) with only studies published after 2013 as a restriction for the search strategy. An assessment of the included studies was conducted according to the recommendations of the Cochrane Handbook for Systematic Reviews of Interventions, using the risk of bias assessment tool in Review Manager (Revman) version 5.3. Included studies were randomized trials with vitamin D supplementation in patients with SLE and with pre-post intervention measures of disease activity. Meta-analyses were performed using random-effects models to estimate mean differences with 95% confidence intervals (CIs). Heterogeneity was evaluated using the I(2) test, and sensitivity analysis and publication bias assessment were also performed. Results: A total of 186 articles were retrieved, of which 21 studies met the inclusion criteria. These studies had a combined sample size of 3177 adult participants and were conducted across 16 different countries. Regarding the impact of vitamin D supplementation on SLE patients, twelve (n = 12) studies reported positive associations, including reduced disease activity and improvements in clinical and laboratory parameters such as inflammatory markers, fatigue, and bone mineral density. In contrast, nine (n = 9) studies found no significant effects. In terms of meta-analytical data, our results indicate that, at the end of the supplementation, participants with vitamin D supplementation had significantly higher serum vitamin D levels compared to participants that receive a placebo (MD: 13.11 ng/mL; 95% CI: 8 to 19; p < 0.00001) despite comparable values before the onset of the supplementation. In addition, participants with vitamin D supplementation had lower scores in the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) compared to participants who received a placebo (MD: -1; 95% CI: -2 to -0.43; p = 0.002) despite comparable values before the onset of the supplementation. Conclusions: Our systematic review and meta-analysis suggest that vitamin D supplementation leads to a statistically significant reduction in SLEDAI scores, reflecting a meaningful decrease in disease activity. Given its immunomodulatory effects and favorable safety profile, vitamin D supplementation represents a simple and accessible adjunctive strategy that could support SLE management and improve patient outcomes in clinical practice.