Vitamin D: Newer Concepts of Its Metabolism and Function at the Basic and Clinical Level

Abstract

The interest in vitamin D continues unabated with thousands of publications contributing to a vast and growing literature each year. It is widely recognized that the vitamin D receptor (VDR) and the enzymes that metabolize vitamin D are found in many cells, not just those involved with calcium and phosphate homeostasis. In this mini review I have focused primarily on recent studies that provide new insights into vitamin D metabolism, mechanisms of action, and clinical applications. In particular, I examine how mutations in vitamin D metabolizing enzymes—and new information on their regulation—links vitamin D metabolism into areas such as metabolism and diseases outside that of the musculoskeletal system. New information regarding the mechanisms governing the function of the VDR elucidates how this molecule can be so multifunctional in a cell-specific fashion. Clinically, the difficulty in determining vitamin D sufficiency for all groups is addressed, including a discussion of whether the standard measure of vitamin D sufficiency, total 25OHD (25 hydroxyvitamin) levels, may not be the best measure—at least by itself. Finally, several recent large clinical trials exploring the role of vitamin D supplementation in nonskeletal diseases are briefly reviewed, with an eye toward what questions they answered and what new questions they raised.

Associations of Serum 25-Hydroxyvitamin D with Adiposity and At-Risk Lipid Profile Differ for Indigenous (Orang Asli) Male and Female Adults of Peninsular Malaysia

“…Vitamin D metabolism involves three steps, including 25-hydroxylation, 1α-hydroxylation, and 24-hydroxylation, that are performed by cytochrome P450 mixed-function oxidases (CYPs) [47]. Recent studies showed that the regulation of these vitamin D metabolizing enzymes may relate to vitamin D metabolism and further play a potential role in enhancing the regulation of metabolic processes [48]. The cholesterol side-chain cleavage enzyme (CYP11A1), which catalyzes the first step in steroidogenesis, has been found to involve in the sequential hydroxylation, predominantly at C-20 or C-22, in the vitamin D metabolism [49].…”

Nuclear Receptors, Ligands and the Mammalian B Cell

“…Vitamin D is ingested from plant (D2) or animal (D3) sources including dairy products (often vitamin fortified) and fish. Vitamin D is also synthesized when 7-dehydrocholesterol in the skin is converted to cholecalciferol upon exposure to sunlight (ultra violet B (UVB)) rays) [67]. In the liver, Debates continue as to the appropriate levels of vitamin D in blood, but most scientists agree that blood levels of >30 ng/mL vitamin D will support a healthy immune system.…”

“…Vitamin D is ingested from plant (D2) or animal (D3) sources including dairy products (often vitamin fortified) and fish. Vitamin D is also synthesized when 7-dehydrocholesterol in the skin is converted to cholecalciferol upon exposure to sunlight (ultra violet B (UVB)) rays) [ 67 ]. In the liver, 25-hydroxylase converts cholecalciferol to 25 hydroxy-vitamin D (25(OH)D, also termed calcidiol), a common metabolite in the blood.…”

Relationships between Total, Free and Bioavailable Vitamin D and Vitamin D Binding Protein in Early Pregnancy with Neonatal Outcomes: A Retrospective Cohort Study

“…Collectively, these findings suggest that total 25(OH)D, while relevant, may not be suitable as a single measure to adequately reflect functional vitamin D status in certain conditions, including in pregnancy [ 23 ]. To further clarify the relationship between maternal vitamin D status and neonatal outcomes, measurement of free and bioavailable metabolites should be considered, particularly given the elevated concentrations of VDBP in the pregnant state.…”