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

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.

Keywords: inflammation; meta-analysis; rheumatoid arthritis; systematic review; vitamin D.