The Effect of Short Term Vitamin D Supplementation on the Inflammatory and Oxidative Mediators of Arterial Stiffness

Abstract

Background Vitamin D deficiency has been implicated as a potential risk factor for cardiovascular disease. The high rate of vitamin D deficiency (<30 ng/ml) exhibited by African Americans may account for some of the excess prevalence of cardiovascular morbidity and mortality in this vulnerable US population. Vitamin D supplementation may reduce the risk of cardiovascular disease by ameliorating the onset and progression of arterial stiffness, a strong predictor of cardiovascular mortality, usually assessed by pulse wave velocity and augmentation index. Very few prospective studies have evaluated the effect of vitamin D supplementation on the inflammatory and oxidative stress mediators of arterial stiffness. Method In a double blind randomized placebo controlled study we evaluated the effect of a monthly dose of 100,000IU of vitamin D3 for three months on the level of serum 25(OH)D, intact parathyroid hormone (PTH), urinary isoprostane, adipocyte cytokine expression and arterial stiffness among 130 overweight and obese (BMI > 25) African Americans with elevated blood pressure (130 - 150/85 - 100 mmHg) and low serum vitamin D level (10 - 25 ng/ml). Results There was a significant increase in the serum 25(OH)D levels to a mean level of 34.5 ng/ml (SD = 7.1) with the intervention (p < 0.001). The increase in 25(OH)D levels was associated with a significant decrease in the serum level of intact PTH (p = 0.02), mean urinary isoprostane (p = 0.02) and adipocyte cytokine expression. Although the increase in the 25(OH)D levels was not associated with any significant change in the Pulse Wave Velocity (PWV) in the overall study sample, it was associated with a significant decrease in the augmentation index among the participants with the highest tertile of urinary isoprostane (p = 0.007). Conclusion We concluded that vitamin D supplementation increased serum 25(OH)D levels, decreased intact PTH level and the levels of select inflammatory and oxidative stress mediators of arterial stiffness. Longer term prospective studies are warranted to evaluate the effect of high dose vitamin D supplementation on arterial stiffness.

Effectiveness of Vitamin D Supplementation for Cardiovascular Health Outcomes

“…The results from RCTs on AIx are more contradicting; no improvement was reported in the majority of studies [61,62,64,71,72,77,83]. Alternatively, decreases in AIx were observed among patients with T2DM [66], overweight people with elevated BP [75], people with VitD deficiency [84] and those with pre-hypertension and VitD deficiency [85]. Conversely, 1 study reported significant increases in AIx in patients with T2DM and hypovitaminosis [63].…”

“…In terms of effects on BP, some RCTs have reported significant improvements in brachial BP after short-term supplementation of VitD among participants encompassing a variety of clinical characteristics, including patients with hypercalcaemia [53] or impaired glucose tolerance [54], patients with primary hyperparathyroidism [55], patients with T2DM [56,57,58], patients with elevated BP and VitD deficiency [59] and women with VitD deficiency [60]. However, the majority of RCTs have been ineffective in improving brachial BP in a range of populations as shown in Table 1[61,62,63,64,65,66,67,68,69,70,71,72,73,74,75,76,77,78,79]. Indeed, a recent individual-level meta-analysis of RCTs concluded that VitD was ineffective in lowering BP [80].…”

1,25-vitamin D3 promotes cardiac differentiation through modulation of the WNT signaling pathway

“…Moreover, our group shown previously that 1,25-D 3 is a potent anti-fibrotic factor promoting the decrease expression of TGF-β, PAI-1 and several collagen isoforms in mesenchymal multipotent cells There is an in vivo study showing that vitamin D deficiency results in maladaptive cardiac remodeling attributable to progressive myocyte hypertrophy and interstitial fibrosis (Meems et al, 2012). A recent study by our group did show repletion of hypovitaminosis D in humans led to down-regulation of protein expression in abdomen fat biopsies for tumor necrosis factor alpha, IFN gamma, interleukin 6 and soluble intercellular adhesion molecule-1 (sICAM-1), a biomarker of inflammatory process associated with endothelial damage and platelet activation, supporting an in vivo role for vitamin D in related signaling pathways (Martins et al 2014).…”

Vitamin D in Oxidative Stress and Diseases

“…For example, in a recent study performed on Framingham Offspring Heart Study participants [57], vitamin D 3 deficiency was associated with increased cardiovascular risk, above and beyond established cardiovascular risk factors. In another study, performed on elderly subjects, an association between low serum vitamin D 3 levels and high arterial blood pressure was found [58]. In addition, vitamin D 3 insufficiency/deficiency is associated with myocardial infarction, congestive heart failure, and calcific aortic stenosis, which can lead to the massive vascular calcification seen in chronic kidney disease.…”