Vitamin D₃ repletion versus placebo as adjunctive treatment of heart failure patient quality of life and hormonal indices: A randomized, double-blind, placebo-controlled trial

Background: Vitamin D status may influence heart failure (HF) patient outcomes by affecting b-type natriuretic peptide (BNP), parathyroid hormone (PTH), and enhancing cardiac contractility. Vitamin D deficiency is associated with morbidity and mortality in HF patients. The objective of this study was to determine if vitamin D3 at a comparatively high dose would replete 25-hydroxyvitamin D (25(OH)D) stores, improve BNP, PTH, cardiopulmonary function, reduce inflammatory markers, and improve quality of life (QOL) in HF patients. Methods: This was a 6 month, parallel group, double-blind, placebo-controlled, single clinic center, randomized trial of supplemental vitamin D3 using a dose of 10,000 IU daily or placebo in 40 vitamin D deficient or insufficient (25(OH)D level ≤ 32 ng/ml) patients with stable New York Heart Association Class II-III HF in a specialty cardiology clinic. All variables were measured at baseline and 6 months. Values between the two treatment groups were assessed using Student's t-test or Mann-Whitney Test. Univariate analysis of covariance was conducted to adjust for variance in baseline 25(OH)D. Results: All results were adjusted for baseline 25(OH)D. The change in BNP from baseline was Δ +30 ± 950 pg/ml for treatment vs. placebo Δ +400 ± 1900 pg/ml, p = 0.003. 25(OH)D serum levels rose by 49 ± 32 ng/ml in the treatment group vs 4 ± 10 ng/ml in the placebo group, p < 0.001. PTH and exercise chronotropic response index improved in the treatment group vs placebo group, respectively, but both were attenuated by adjustment ((Δ-20 ± 20 pg/ml vs Δ + 7 ± 53 pg/ml respectively (p = 0.01, adjusted p = 0.07)) and (Δ + 0.13 ± 0.26 vs. Δ-0.03 ± 02.9 respectively, p < 0.01, adjusted p = 0.17)). Other measured cardiopulmonary parameters remained unchanged. High sensitivity C-reactive protein (hsCRP) remained unchanged for women, but improved for men (Δ-2 ± 4 treatment versus Δ2 ± 5 mg/L placebo, p = 0.05). QOL scores, including composite overall and clinical summary scores significantly improved in treatment compared to placebo (Δ + 10 ± 15 versus -6 ± 15, p < 0.01 and Δ + 8 ± 14 versus -8 ± 18, p = 0.01, respectively). Conclusions: Repletion of 25(OH)D may improve QOL in HF patients and may help to normalize BNP, PTH, and hsCRP. Trial registration: Clinicaltrials.gov, Trial Registration Number: NCT01636570 , First registered 3 July 2012.