Effects of Vitamin D Supplementation on Plasma Aldosterone and Renin—A Randomized Placebo‐Controlled Trial

Abstract

Increasing evidence describes a possible interplay between vitamin D insufficiency with increased aldosterone. The authors sought to evaluate the effect of vitamin D supple-mentation on plasma aldosterone concentration (PAC) in patients with hypertension and 25-hydroxyvitamin D[25(OH) D] insufficiency. The Styrian Vitamin D Hypertension Trial was a single-center, double-blind, placebo-controlled randomized clinical trial conducted from 2011 to 2014. Two hundred patients with arterial hypertension and 25(OH) D levels <30 ng/mL were enrolled. Study participants were randomized to receive either 2800 IU of vitamin D3 or placebo. The present investigation is a post hoc analysis using analysis of covariance adjusting for baseline differences. A total of 188 participants (meanAEstandard deviation age, 60.1AE11.3 years; 47% women; 25(OH)D, 21.2AE5.6 ng/ mL) completed the trial. Mean differences between baseline and follow-up PAC in the control and intervention arm were +3.3 ng/dL and +0.9 ng/dL, respectively (P=.04). The findings indicate that vitamin D3 supplementation significantly decreases PAC in patients with arterial hypertension and 25(OH)D insufficiency. J Clin Hypertens (Greenwich). 2016;18:608-613. ª 2016 Wiley Periodicals, Inc. Vitamin D insufficiency is an established risk factor for cardiovascular (CV) events and mortality. 1-5 However, it remains unclear whether low 25-hydroxyvitamin D (25[OH]D) concentrations are a causal risk factor or simply an epiphenomenon 6 related to adverse outcomes that reflect confounding factors. 1-5 The physiological effects of vitamin D receptor (VDR) activation in experimental studies include the suppression of neuro-humoral activation and improvements in endothelial and vascular function. 1-5 These factors have been linked to high blood pressure (BP), myocardial infarction, and CV mortality. 1,2,7-9 It has been suggested that an interplay between the renin-angiotensin-aldosterone system (RAAS) and VDR activation could mediate the link of 25(OH)D insufficiency with arterial hyperten-sion and CV disease. 10-13 In 1986, Resnick and colleagues 14 described a continuous relationship between calcitriol (1-alpha,25(OH)2 vitamin D3) levels and plasma renin activity. Zhang and colleagues 15 demonstrated a marked increase in angiotensin II and renin in VDR knockout mice. These results were in line with findings from a cohort study in patients with high CV risk, showing that lower 25(OH)D and calcitriol levels are related to an upregulated circulating RAAS. 16 So far, interventional data in humans on the effects of vitamin D supplementation on plasma aldosterone concentration (PAC) are missing. In our previous publication of a vitamin D randomized controlled trial (RCT), we adhered to a prespecified analysis plan and observed a moderate yet nonsignificant trend for a PAC-lowering effect of vitamin D supplementation. 17 In that work, we did not adjust for differences in the placebo vs the treatment group with regard to parameters with relevance for the RAAS, ie, the use of ACE inhibito...

Effects of Vitamin D Supplementation on IGF-1 and Calcitriol: A Randomized-Controlled Trial

“…Serum concentrations of IGF-1, 25(OH)D, and 1,25(OH) 2 D were measured by chemiluminescence immunoassays (Immunodiagnostic Systems Ltd., Boldon, UK) with intra-assay and inter-assay coefficients of variation (CVs) of 2.9–4.2% and 5.4–7.2% (IGF-1); 6.2% and 11.6% (25(OH)D); 6.4–12.1% and 6.6–9.6% (1,25(OH) 2 D), respectively. Details on several other specifics of laboratory measurements have been published [17,25,26,27]. …”

Vitamin D deficiency is an independent predictor of mortality in patients with chronic heart failure

“…The consequences of 25[OH]D deficiency [32] and elevated PTH levels [33][34][35][36] are calcium loading, with cardiomyocyte and skeletal muscle contractile dysfunction, cellular hypertrophy, oxidative stress, immune activation, endothelial dysfunction (including enhanced endothelin-1 release) [30,34,[37][38][39][40][41]. These influences are reflected clinically with an increased risk of hospitalisation [7,42], and worsening renal function [43], whilst vitamin D supplementation may be associated with a reduction of plasma renin and aldosterone levels [44,45]. Consistent with these observations, we found lower mean sodium levels and higher mean heart rates in 25[OH]D-deficient heart failure patients.…”

Effects of treatment with an angiotensin 2 receptor blocker and/or vitamin D3 on parathyroid hormone and aldosterone: A randomized, placebo‐controlled trial

“…In some previous randomized trials, reduced levels of renin, aldosterone, and blood pressure have been reported in response to vitamin D3 supplementation . However, our findings do not support such effects, although we included participants with low vitamin D levels who, assumable, are those most likely to benefit from vitamin D3 supplementation.…”