Vitamin D and Hypertension

Abstract

The prevalence of vitamin D insufficiency, defined by a 25-hydroxyvitamin D (25[OH]D) level <30 ng/mL, in the United States was 77% in 2004.1 Although the use of vitamin D supplementation may be increasing since 2004, it is likely that the majority of US citizens continue to have inadequate vitamin D status.2 Observational studies suggest that low 25(OH)D levels are associated with a higher risk of hypertension. However, findings from randomized trials of vitamin D supplementation to lower blood pressure are inconsistent, possibly stemming from variability in study population, sample size, vitamin D dose, and duration. If vitamin D supplementation lowers blood pressure, its widespread use could have major public health benefits. In this review, we summarize the existing literature dealing with the vitamin D-hypertension link, including mechanistic studies, observational data, and clinical trials; we place special emphasis on recent findings. Biological mechanisms relating vitamin D with hypertension have been proposed for >25 years. Vitamin D has been implicated in the proximal regulation of the renin-angiotensin system (RAS) and in interacting with the RAS to determine the intracellular calcium milieu in vascular smooth muscle. ### Vitamin D and the RAS Dietary sodium and increased activity of the RAS are known to contribute to hypertension; salt restriction and inhibition of RAS activity reduce blood pressure.3–5 Li et al6 provided convincing support for vitamin D as a proximal inhibitor of the RAS when they described a phenotype of excess plasma renin activity and hypertension in mice lacking the vitamin D receptor, which normalized after treatment with RAS antagonists. These vitamin D receptor–null mice also displayed an increased susceptibility to obstructive renal injury that could be prevented with RAS antagonism.7 Mice with deficient 1α-hydroxylase activity were also found to have increased plasma renin activity and hypertension, and this unfavorable phenotype could be reversed with 1,25-dihydroxyvitamin …