Vitamin D Sources, Metabolism, and Deficiency: Available Compounds and Guidelines for Its Treatment

Abstract

Studies on vitamin/hormone D deficiency have received a vast amount of attention in recent years, particularly concerning recommendations, guidelines, and treatments. Moreover, vitamin D's role as a hormone has been confirmed in various enzymatic, metabolic, physiological, and pathophysiological processes related to many organs and systems in the human body. This growing interest is mostly due to the evidence that modest-to-severe vitamin D deficiency is widely prevalent around the world. There is broad agreement that optimal vitamin D status is necessary for bones, muscles, and one's general health, as well as for the efficacy of antiresorptive and anabolic bone-forming treatments. Food supplementation with vitamin D, or the use of vitamin D supplements, are current strategies to improve vitamin D levels and treat deficiency. This article reviews consolidated and emerging concepts about vitamin D/hormone D metabolism, food sources, deficiency, as well as the different vitamin D supplements available, and current recommendations on the proper use of these compounds.

Keywords: bone; calcifediol; calcitriol; cholecalciferol; fracture; osteoporosis; vitamin D.

Figure 1

The synthesis of vitamin D3 (cholecalciferol, D3) occurs at the skin where pro-vitamin D3 (7-dehydrocholesterol) is converted to pre-vitamin D3 in response to sunlight exposure (ultraviolet B radiation). Vitamin D3, obtained from the isomerization of pre-vitamin D3 in the epidermal basal layers, or intestinal absorption of natural and fortified foods and supplements D2 (ergocalciferol) and D3, binds to vitamin D-binding protein (DBP) in the bloodstream, and is transported to the liver. D2 and D3 are hydroxylated by liver 25-hydroxylases. The resultant 25-hydroxycholecalciferol [25(OH)D] (calcifediol or calcidiol) is 1-hydroxylated in the kidney by 1α-hydroxylase. This yields the active secosteroid 1,25(OH)₂D (calcitriol), which has different effects on various target tissues. The synthesis of 1,25(OH)₂D from 25(OH)D is stimulated by the parathyroid hormone and suppressed by calcium, phosphate, and 1,25(OH)₂D itself.

Figure 2

Vitamin D receptor (VDR) action at target cells. Intracellular calcitriol [1,25(OH)₂D] binds to the VDR; thus, causing its dimerization with the retinoid X receptor (RXR). The ligand-bound VDR–RXR complex binds to structurally distinct vitamin D response elements (VDREs) in multiple, widely spaced vitamin D-responsive regions, and this causes a modification in the recruitment of co-activators or co-repressors, which leads to positive or negative transcriptional regulation of gene expression.