The effect of vitamin D on renin-angiotensin system activation and blood pressure: a randomized control trial

Objective: Disruption of vitamin D signaling in rodents causes activation of the rennin-angiotensin system (RAS) and development of hypertension. Observational studies in humans found lower circulating 25-hydroxyvitamin D [25(OH) D] is associated with increased RAS activity and blood pressure (BP). We performed the first randomized control trial to investigate the effects of vitamin D supplementation on the RAS in humans. Methods: Vitamin D deficient, [25(OH) D <= 20 ng/ml), overweight individuals without hypertension were randomized into a double-blind, placebo-controlled trial of 8-weeks treatment with ergocalciferol or placebo. Kidneyspecific RAS activity, measured using renal plasma flow response to captopril in high sodium balance, was assessed at baseline and 8 weeks, as was systemic RAS activity and 24-h ambulatory BP. Results: In total, 84 participants completed the study. Mean 25[OH] D levels increased from 14.7 to 30.3 ng/ml in the ergocalciferol group, P value< 0.0001, and from 14.3 to 17.4 ng/ml in the placebo group, P value = 0.3. The renal plasma flow response to captopril was 33.9 +/- 56.1 ml/min per 1.73m(2) at baseline and 35.7 +/- 47.7 ml/min per 1.73m(2) at 8 weeks in the ergocalciferol group (P value = 0.83); and was 37.3 +/- 46.9 ml/min per 1.73m(2) at baseline and 35.9 +/- 26.2 ml/min per 1.73m(2) at 8 weeks in the placebo group (P value -0.78). Ergocalciferol had no effect on PRA, AngII, or 24-h BP measurements. Conclusions: This trial found no benefit from correcting vitamin D deficiency on RAS activity or BP after 8 weeks. These findings are not consistent with the hypothesis that vitamin D is a modifiable target for lowering BP in vitamin D deficient individuals.