Vitamin D, endothelial function and cardio-metabolic health

Abstract

The classical actions of vitamin D are to maintain bone health but vitamin D receptors are also expressed in several other tissues including the vascular system. The epidemiological evidence supports the associations between vitamin D status and vascular health but it is still uncertain whether the inadequate vitamin D status represents a risk factor for cardiovascular diseases (CVD). Nitric oxide (NO) is a soluble gas synthesized from the amino acid Larginine and plays an important role in maintaining vascular homeostasis. A reduced NO availability is an important hallmark of endothelial dysfunction, which is closely linked to the development of atherosclerosis and is an independent risk factor for cardiovascular events. Vitamin D may be involved in the maintenance of endothelial function (EF) through regulation of endothelium nitric oxide synthase (eNOS) activity which enhanced NO synthesis. This PhD project investigated the association between vitamin D intake and status, endothelial function and biomarkers of NO availability. In the first phase of the PhD, a systematic review and meta-analysis of randomized clinical trials was conducted to investigating the effects of vitamin D supplementation on EF. Overall, this showed no improvement of EF after vitamin D supplementation but there was evidence of positive effects in obese individuals and in diabetic patients. Next, a cross sectional study in postmenopausal overweight and obese women was conducted to evaluate the associations between vitamin D status and physiological and circulating biomarkers of EF. The study revealed increased pulse wave velocity (PWV), a marker of arterial stiffness, and higher concentrations of asymmetric dimethylarginine (ADMA, a marker of NO availability) in those women with vitamin D concentrations < 30 nmol/L. Detailed laboratory experiments were also conducted as part of this project to improve the measurement of concentrations of NO3 - and NO2 - in plasma and urine using ozone-based chemiluminescence. The final phase of the project investigated the association between whole-body NO availability (measured by a non-invasive stable-isotopic method), PWV, ADMA and vitamin D status and whether these associations were modified by age. The study did not find a significant association of NO production with vitamin D. However, NO production was significantly lower in older individuals and was significantly associated with systolic blood pressure and PWV.