Vitamin D Supplementation, Serum 25(OH)D Concentrations and Cardiovascular Disease Risk Factors: A Systematic Review and Meta-Analysis

Abstract

Background: Cardiovascular disease (CVD) risk factors are associated with low serum 25 hydroxyvitamin D (25(OH)D) concentrations in observational studies; however, clinical trial findings are inconsistent.Objective: We assessed the effect of vitamin D supplementation and increased serum 25(OH)D concentrations on CVD risk factors in a systemic review and meta-analysis of randomized controlled trials (RCTs).Design: MEDLINE, CINAHL, EMBASE, and Google Scholar were searched for RCTs that evaluated vitamin D supplementation and cardiovascular outcomes [blood pressure, parathyroid hormone (PTH), serum high-sensitivity C-reactive protein (hs-CRP), total cholesterol, high and low density lipoprotein (HDL and LDL, respectively), triglycerides, peak wave velocity (PWV) and Augmentation Index (AI)] from 1992 through 2017. Meta-analysis was based on a random-effects model and inverse variance method to calculate standardized mean difference (SMD) as effect sizes, followed by a leave-one-out method for sensitivity analysis. Risk of publication bias was assessed using Cochrane checklist and Begg funnel plots. The systematic review is registered as CRD42015025346.Results: We identified 2341 studies from which 81 met inclusion criteria. The meta-analysis indicated a significant reduction in systolic blood pressure (SMD = −0.102 ± 0.04 mmHg, 95% confidence interval (CI), −0.20 to −0.03), diastolic blood pressure (SMD = −0.07 ± 0.03 mmHg, 95% CI, −0.14 to −0.006), serum PTH (SMD = −0.66 ± 0.08 ng/L, 95% CI, −0.82 to −0.49), hs-CRP (SMD = −0.20 ± 0.07 mg/L, 95% CI, −0.34 to −0.06), total cholesterol (SMD = −0.15 ± 0.06 mmol/L, 95% CI, −0.25 to −0.04), LDL (SMD = −0.10 ± 0.05 mmol/L, 95% CI, −0.20 to −0.003), triglycerides (SMD = −0.12 ± 0.06 mmol/L, 95% CI, −0.23 to −0.003) and a significant increase in HDL (SMD = 0.09 ± 0.04 mmol/L, 95% CI, 0.00 to 0.17) with vitamin D supplementation. These findings remained significant in sensitivity analyses for blood pressure, lipid profile, serum PTH, and serum hs-CRP. There was no significant effect of vitamin D supplementation on PWV (SMD = −0.20 ± 0.13 m/s, 95% CI, −0.46 to 0.06, p = 0.14) and AI (SMD = −0.09 ± 0.14%, 95% CI, −0.37 to 0.19, p = 0.52) for vitamin D supplemented groups.Conclusion: These findings suggest that vitamin D supplementation may act to protect against CVD through improving risk factors, including high blood pressure, elevated PTH, dyslipidemia, and inflammation.

Serum Vitamin D Concentration ≥75 nmol/L Is Related to Decreased Cardiometabolic and Inflammatory Biomarkers, Metabolic Syndrome, and Diabetes; and Increased Cardiorespiratory Fitness in US Adults

“…Vitamin D 3 (33000 IU) administration for every 2-weeks for six months reduced systolic blood pressure significantly [63]. A large meta-analysis of 81 studies by Mirhosseini et al [64] reported that vitamin D improved blood pressure, dyslipidemia, and hypertension. A recent meta-analysis on 17 RCTs reported that vitamin D supplementation reduced systolic and diastolic pressures in vitamin D deficient and in hypertensive individuals [65].…”

Diminished 25‐OH vitamin D3 levels and vitamin D receptor variants are associated with susceptibility to type 2 diabetes with coronary artery diseases

“…19 There is growing evidence suggesting an association of lower vitamin D levels with susceptibility to CAD and mortality. 20,21 A recent report highlighted connotation between deficient vitamin D levels and severity of CAD. 22 In addition to vitamin D levels, vitamin D receptors (VDR) polymorphisms are also associated with genetic susceptibility to T2D and CAD patients.…”

Vitamin D in insulin sensitivity and obesity

“…Interestingly, it has been shown that vitamin D 3 supplementation for 4 weeks results in an increased microbial diversity and a decrease in relative abundance of Gammaproteobacteria in the upper gastro-intestinal tract in healthy men and women (76). Furthermore, intraperitoneal injection of 1,25(OH) 2 D 3 (5 ng/g body weight) for one month attenuated metabolic endotoxemia (as evidenced by lower plasma lipopolysaccharides, LPS), and improved intestinal tight junction integrity, as well as Paneth cell defense in HFD+VDD fed mice (77). An elegant review by Zheng and colleagues showed that evidence is accumulating for a role of Vitamin D in improved beta cell function in Type 1 Diabetes (T1D), possibly via effects on the microbiome (78).…”

“…A study in twin male showed that genetic variation in vitamin D related metabolism genes may explain more than 50% of the variation in vitamin D metabolite concentrations particularly during winter (73). However, genome-wide association studies have shown that genetic variants in vitamin D-related genes explain a modest (~10%) of variations in circulating vitamin D concentrations (74)(75)(76)(77). Genetic variations of vitamin D receptor (VDR) is most often associated with vitamin D concentration and metabolic health outcomes (78).…”

“…However, it is possible that vitamin D supplementation may have a beneficial effect on other cardiometabolic risk factor like low-grade inflammation. Recent systematic reviews and meta-analyses (77,78) reported small, but significant, decreases in high-sensitivity C-reactive protein (hs-CRP) and Tumor Necrosis Factor alpha (TNF-α) concentrations following vitamin D supplementation. It has been shown recently from a Mendelian Randomization study, that hs-CRP is one of 4 inflammatory biomarkers in 3 independent clusters (ILs, adhesion molecules, acute-phase proteins) which was inversely associated with serum 25(OH)D 3 concentration (79).…”