The effects of correction of vitamin D deficiency on arterial stiffness: A systematic review and updated meta-analysis of randomized controlled trials.

It is unclear whether nutritional vitamin D supplementation in vitamin d-deficient persons improves arterial stiffness. To conduct a meta-analysis of the effects of the nutritional vitamin D therapy on arterial stiffness in adults with vitamin D deficiency, the Scopus, PUBMED, EMBASE, and Cochrane databases were searched for systematic reviews conducted up to October 5, 2018. Randomized clinical trials that compared nutritional vitamin D therapy with placebo in adults with vitamin D deficiency were eligible. Two reviewers independently evaluated eligibility of all retrieved studies based on titles and abstracts. Meta-analysis was performed using random effect or fixed effects model and inverse variance method was used to calculate the effect using standardized mean difference (SMD) and weighted mean difference. A leave-one-out method was used for sensitivity analysis. The main outcome was arterial stiffness, indicated by the carotid-femoral pulse wave velocity (PWV). We identified 237 records, of which 9 satisfied the inclusion criteria of the study. Our meta-analysis included relatively high-quality placebo-controlled randomized trials. In a random-effects model, nutritional vitamin D was associated with significant reductions in the pooled difference of PWV [(SMD: -0.29; 95 % CI: -0.51 to -0.06), p = 0.01; Cochran's Q test: chi2 = 21.85; df = 9; p = 0.009; I2 = 59 %; n = 909 from 9 studies]. All sensitivity analyses yielded similar results. Nutritional vitamin D supplementation significantly improved arterial stiffness (PWV) in several subgroups by correcting vitamin D deficiency, for a study duration of ≥4 months and a daily dose of vitamin D3 ≥ 2000 IU. The study indicated that the correction of vitamin D deficiency by nutritional vitamin D supplementation may improve arterial stiffness in vitamin d-deficient persons, especially by the correction of vitamin D deficiency with a daily dose of vitamin D3 ≥ 2000 IU. However, further studies are required to confirm this.

Effect of Vitamin D Supplementation on Markers of Vascular Function: A Systematic Review and Individual Participant Meta-Analysis.

BACKGROUND: Low 25-hydroxyvitamin D levels are associated with an increased risk of cardiovascular events, but the effect of vitamin D supplementation on markers of vascular function associated with major adverse cardiovascular events is unclear. METHODS AND RESULTS: We conducted a systematic review and individual participant meta-analysis to examine the effect of vitamin D supplementation on flow-mediated dilatation of the brachial artery, pulse wave velocity, augmentation index, central blood pressure, microvascular function, and reactive hyperemia index. MEDLINE, CINAHL, EMBASE, Cochrane Central Register of Controlled Trials, and http://www.ClinicalTrials.gov were searched until the end of 2016 without language restrictions. Placebo-controlled randomized trials of at least 4 weeks duration were included. Individual participant data were sought from investigators on included trials. Trial-level meta-analysis was performed using random-effects models; individual participant meta-analyses used a 2-stage analytic strategy, examining effects in prespecified subgroups. 31 trials (2751 participants) were included; 29 trials (2641 participants) contributed data to trial-level meta-analysis, and 24 trials (2051 participants) contributed to individual-participant analyses. Vitamin D3 daily dose equivalents ranged from 900 to 5000 IU; duration was 4 weeks to 12 months. Trial-level meta-analysis showed no significant effect of supplementation on macrovascular measures (flow-mediated dilatation, 0.37% [95% confidence interval, -0.23 to 0.97]; carotid-femoral pulse wave velocity, 0.00 m/s [95% confidence interval, -0.36 to 0.37]); similar results were obtained from individual participant data. Microvascular function showed a modest improvement in trial-level data only. No consistent benefit was observed in subgroup analyses or between different vitamin D analogues. CONCLUSIONS: Vitamin D supplementation had no significant effect on most markers of vascular function in this analysis.