The effects of vitamin D supplementation on endothelial activation among patients with metabolic syndrome and related disorders: a systematic review and meta-analysis of randomized controlled trials.

Background and objective: The current systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted to summarize the effect of vitamin D supplementation on endothelial activation among patients with metabolic syndrome and related disorders.

Methods: Cochrane library, Embase, PubMed, and Web of Science database were searched to identify related RCTs published before 30th April 2018. The heterogeneity among the included studies was assessed using Cochran's Q test and I-square (I2 ) statistic. Data were pooled by using the random-effect model and standardized mean difference (SMD) was considered as summary effect size.

Results: Fourteen clinical trials that contained a total of 1253 participants were included in the current meta-analysis. Vitamin D supplementation significantly decreased von willebrand factor (vWF) (SMD -0.27; 95% CI, - 0.46, - 0.08; P  = 0.006; I2 :40.5%). However, we found no significant impact of vitamin D supplementation on intercellular adhesion molecule 1(ICAM-1) (SMD -1.96; 95% CI, - 4.02, 0.09; P  = 0.06; I2 :97.4%), vascular celladhesion molecule 1 (VCAM-1) (SMD -0.50; 95% CI, - 1.19, 0.19; P  = 0.15; I2 :91.2%), on E-selectin (SMD -0.04; 95% CI, - 0.36, 0.28; P  = 0.81; I2 :78.8%) and endothelin (SMD -0.49; 95% CI, - 1.18, 0.19; P = 0.15; I2 :90.5%). The pooled data from trials of vitamin D supplementation with dosage of ≤4000 IU/day (- 0.37, 95% CI: -0.65, - 0.10, I2 : 73.5%) significantly reduced vWF concentrations, while there was no effect of vitamin D supplementation on vWF concentrations among trials with the dosage of intervention > 4000 IU/day (- 0.17, 95% CI: -0.43, 0.10, I2 : 0.0%). VWF concentrations significantly reduced in pooled data from trials with duration study ≤8 weeks (- 0.37, 95% CI: -0.67, - 0.07, I2 : 60.6%), but there was no effect of vitamin D supplementation on vWF concentrations among trials with > 8 weeks (- 0.20, 95% CI: -0.45, 0.05, I2 : 0.0%). While there was no effect of vitamin D supplementation on vWF concentrations among trials with total sample size of ≤60 patients (- 0.03, 95% CI: -0.42, 0.36, I2 : 0.0%), vWF concentrations in trials with more than 60 patients decreased significantly (- 0.34, 95% CI: -0.56, - 0.12, I2 : 60.9%).

Conclusions: Overall, the current meta-analysis demonstrated that vitamin D supplementation to patients with metabolic syndrome and related disorders resulted in an improvement in vWF, but did not affect ICAM-1, VCAM-1, E-selectin and endothelin levels.