Effect of vitamin D supplementation on endothelial function - An updated systematic review with meta-analysis and meta-regression

Background and aims: Atherogenesis and endothelial dysfunction contribute to cardiovascular risk and vitamin D has been implemented in endothelial repair. This systematic review, meta-analysis and meta-regression aims to establish the effect of vitamin D supplementation on endothelial function. Methods and Results: To conduct the systematic review we searched the Cochrane Library of Controlled Trials, PubMed, ProQuest and EMBASE for randomized controlled trials that investigated the effects of vitamin D supplementation on flow-mediated dilation (FMD%), pulse wave velocity (PWV), and central augmentation index (AIx). Meta-analysis was based on a random effects model and inverse-variance methods to calculate either mean difference (MD) or standardized mean difference (SMD) as effects sizes. This was followed by meta-regression investigating the effect of baseline vitamin D concentrations, vitamin D dosing and study duration. Risk of bias was assessed using the JADAD scale and funnel plots. We identified 1056 studies of which 26 studies met inclusion criteria for quantitative analysis. Forty-two percent of the 2808 participants had either deficient or insufficient levels of vitamin D. FMD% (MD 1.17% (95% CI −0.20, 2.54), p = 0.095), PWV (SMD −0.09 m/s (95% CI −0.24, 0.07), p = 0.275) and AIx (SMD 0.05% (95% CI −0.1, 0.19), p = 0.52) showed no improvement with vitamin D supplementation. Sub-analysis and meta-regression revealed a tendency for AIx and FMD% to increase as weekly vitamin doses increased; no other significant relationships were identified. Conclusions: Vitamin D supplementation showed no improvement in endothelial function. More evidence is required before recommendations for management of endothelial dysfunction can be made.