Understanding the Role of Vitamin D in Heart Failure

Abstract

Vitamin D is now believed to have a significant role in cardiac signal transduction and regulation of gene expression, and thus influences normal cardiomyocyte function. It has been reported to provide cardioprotection through its anti-inflammatory, anti-apoptotic and anti-fibrotic actions; and to prevent cardiac remodeling, ${\mathrm{Ca}}^{2+}$ -handling defects, and abnormal electrophysiological patterns. A vitamin D deficient state has been associated in the pathogenesis of heart failure; however, while many clinical studies report a benefit of vitamin D to heart function, other clinical studies are inconsistent with these findings. These uncertainties have led to a discord in the recommendation of vitamin D supplementation for the treatment of heart failure or as a preventive agent in patients deemed to be at risk for cardiac dysfunction. Accordingly, this article is intended to describe some of the mechanisms/sites of action of vitamin D in different animal models of heart failure, as well as to review the clinical observations and challenges in the interpretation and understanding of the clinical relevance of vitamin D in relation to heart function.

Keywords: heart failure; nutritional interventions; preventive nutrition; vitamin D.

Fig. 1.

The synthetic machinery and metabolic pathway of vitamin D. The precursors of vitamin D synthesis (vitamin D2 ergocalciferol and vitamin D3-cholecalciferol) undergo 1st hydroxylation step in the liver, followed a 2nd hydroxylation of the formed calcidiol to produce the biologically active form of vitamin D- 1,25-OH2 vitamin D (calcitriol) for distribution to tissues via vitamin D binding protein. 25-OH D, 25-hydroxy vitamin D3.

Fig. 2.

Underlying mechanisms of action of vitamin D. Experimental and some clinical studies have revealed several mechanisms of action for the potential benefits of vitamin D and include anti-inflammatory and anti-apoptotic effects as well as the ability to regulate gene expression and alter signal transduction processes.