Effect of vitamin D on inflammatory and clinical outcomes in patients with rheumatoid arthritis: a systematic review and dose–response meta-analysis of randomized controlled trials

Abstract

Abstract Context Rheumatoid arthritis is a chronic inflammatory disease that causes synovitis. Vitamin D deficiency is common in rheumatoid arthritis. Objective This systematic review and meta-analysis investigated whether vitamin D supplementation affects the inflammatory and clinical outcomes in patients with rheumatoid arthritis on the basis of randomized clinical trials. Data Sources A literature search was performed in the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, MEDLINE, Embase, and Google Scholar for articles published until May 2022. Data Extraction The studies were selected according to PRISMA guidelines, and the risk of bias was assessed for randomized controlled trials. Data Analysis A random effects model was used to conduct a meta-analysis, and heterogeneity was assessed using the I2 statistic. Of 464 records, 11 studies were included from 3049 patients. Conclusion: Vitamin D supplementation did not significantly reduce C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), disease activity score in 28 joints (DAS28), or the health assessment questionnaire score; however, the response to supplementation was highly heterogeneous. The pooled analysis showed that vitamin D significantly reduced the pain–visual analogue scale (VAS) weighted mean difference (WMD = –1.30, 95% confidence interval [CI] [–2.34, −27], P = .01), DAS28–CRP (WMD = –.58, 95% CI [–.86, –.31], P < .0001), and DAS28–ESR (WMD = –.58, 95% CI [–.86, –.31], P = .0001). Subgroup analysis for vitamin D doses (>100 µg per day versus <100 µg per day) showed that the higher doses had a more significant effect on CRP than the lower doses (P < .05). Conclusions There was no significant difference between the effect of 2 vitamin D doses on ESR and DAS28. To minimize the high heterogeneity among studies in this meta-analysis, other confounding factors such as baseline vitamin D, age, dietary vitamin D, time of year, sun exposure, drug interaction, effect dosage, and power of study should be examined.