Effect of Vitamin D on the Treatment and Prevention of Essential Hypertension

Abstract

The vast majority of epidemiological studies have consistently shown that vitamin D levels are inversely related to blood pressure (BP) and the incidence of hypertension (HTN). Animal studies from diet-induced or genetic models of vitamin D deficiency suggest that vitamin D deficiency directly causes HTN. Based on basic and clinical studies, modestly increased renin expression in genetic mouse models of vitamin D deficiency is associated with, but not causally linked to vitamin D deficiency-induced HTN. Our mechanistic studies indicate that overexpression of a novel target gene seems to play a critical role in vitamin D-deficient HTN, and that vitamin D signaling defect in vascular smooth muscle cells and CD4+ T lymphocytes seems predominantly be responsible for vitamin D deficiencymediated HTN. The data from many clinical trials have consistently demonstrated a minimal or no effect of shortterm vitamin D supplementation on BP in normotensive healthy individuals, but long-term vitamin D supplementation should prevent the development of essential HTN (EH) at high-risk susceptible people. More than 13 randomized controlled trials have shown that vitamin D repletion significantly reduces BP in vitamin D-deficient EH patients, which appears to be more effective in those with type 2 diabetes or impaired glucose tolerance. Short-term administration of active vitamin D or its analogue has a better antihypertensive role than natural vitamin D in the treatment of vitamin D-deficient EH. While these promising data from relatively small trials have displayed potential beneficial vitamin D effect on EH, it is urgently needed to comprehensively elucidate molecular mechanisms of vitamin D deficiency-induced HTN, which will provide a solid theoretical basis to well design large randomized controlled trials to further address the antihypertensive role of vitamin D in vitamin D-deficient EH patients. Currently, EH is lacking an etiology-specific therapy. Identification of vitamin D deficiency as an environmental stressor that triggers the development of EH at vulnerable individuals will make a great advance in the field of EH research.Keywords: Vitamin D; Deficiency; Blood pressure; Essential hypertension; Molecular mechanisms; Clinical trials Etiology-Specific Treatment for EH is a Knowledge GapMore than 95% hypertensive patients suffer from EH, a chronic disease that displays an elevated BP phenotype with unknown etiology. EH can lead to stroke, coronary artery disease, peripheral artery disease, heart failure, renal failure and increased mortality if it is not well controlled [1]. Although there are several classes of antihypertensive medications available, in America, 50% of hypertensive patients do not have their BP well-controlled and about 5 million patients are resistant to antihypertensive treatment with a combination of at least three antihypertensive medications [2]. One of critical problems is lacking an etiology-specific effective therapy for EH. Currently, treatment of EH is largely empiric, and the lesseff...

Is Vitamin D Supplementation an Effective Treatment for Hypertension?

“…Over the past 20 years, large-scale cross-sectional and cohort analyses, as well as Mendelian randomization and prospective studies, have demonstrated that serum 25[OH]D levels are inversely related to elevated BP, HTN, and adverse cardiovascular events [8]. These findings are supported by the results of studies using genetic and nutrient-depleted VD-deficient animal models that display hypertensive phenotypes [9]. Collectively, the results of these studies suggest that VDD may also contribute to human HTN and that VD supplementation may be effective means for its prevention and treatment.…”

“…This direction was largely based on the theory that VD could suppress basal expression of the endogenous hormone, renin [ 14 ]. Since that time, many lines of evidence have emerged that suggest that a modest increase in renin levels has little to no impact on VDD-associated HTN [ 8 , 9 ].…”

“…Low serum VD levels have been associated with an increased risk of developing HTN [ 8 , 9 ]. Thus, VD supplementation should reduce the incidence of HTN in susceptible subjects with VDD and normotension at baseline.…”