Effect of vitamin D on renin concentration in chronic heart failure patients: a randomized placebo-controlled trial

Background: Hypovitaminosis D and hyperreninemia are associated with poor prognosis in patients with chronic heart failure (CHF). We aimed to evaluate the effect of vitamin D (VitD) supplementation on the renin-angiotensin-aldosterone system (RAAS) in CHF patients with reduced left ventricular ejection fraction (HFrEF). Methods: A double-blind placebo-controlled randomized clinical trial was conducted in HFrEF patients. Patients were randomized to receive two doses of 200,000 IU VitD3 (VitD group) or saline solution (placebo group) at a two-week interval. Plasma 25-hydroxyvitamin D and renin concentrations were assessed at baseline and one month after the first dose. The primary outcome was plasma renin change. The study was registered at the Pan African Clinical Trials Registry as PACTR201908774181973. Results: Forty patients in each group completed the trial. At baseline, hypovitaminosis D and hyperreninemia were found in 85% and 77.5% of patients, respectively, with no differences between VitD and placebo groups. VitD supplementation resulted in an increase in 25-hydroxyvitamin D in the VitD group, only. In parallel, plasma renin decreased in the VitD group [renin change: median (25th percentile; 75th percentile), -34.9 (-110; -7.1)], but did not change in the placebo group [1.35 (-1.2; 8.8)]. No significant changes were found for clinical, echocardiographic, and other biochemical parameters in both groups. Conclusions: A mega-dose of vitamin D resulted in middle-term RAAS suppression but didn't affect cardiac function and clinical features in HFrEF patients. Further research with longer follow-ups is needed to evaluate whether persistent adequate VitD status results in long-term RAAS suppression and cardiac function improvement.