Extraskeletal actions of vitamin D

Abstract

The vitamin D receptor (VDR) is found in nearly all, if not all, cells in the body. The enzyme that produces the active metabolite of vitamin D and ligand for VDR, namely CYP27B1, likewise is widely expressed in many cells of the body. These observations indicate that the role of vitamin D is not limited to regulation of bone and mineral homeostasis, as important as that is. Rather, the study of its extraskeletal actions has become the major driving force behind the significant increase in research articles on vitamin D published over the past several decades. A great deal of information has accumulated from cell culture studies, in vivo animal studies, and clinical association studies that confirms that extraskeletal effects of vitamin D are truly widespread and substantial. However, randomized, placebo controlled clinical trials, when done, have by and large not produced the benefits anticipated by the in vitro cell culture and in vivo animal studies. In this review, I will examine the role of vitamin D signaling in a number of extraskeletal tissues, and assess the success of translating these findings into treatments of human diseases affecting those extracellular tissues.

The effect of high‐dose vitamin D supplementation on muscular function and quality of life in postmenopausal women—A randomized controlled trial

“…The effects of vitamin D on calcium homoeostasis and its importance for skeletal health are well‐known . In recent times, there has been an increased focus on nonskeletal effects of vitamin D, following the discovery of vitamin D receptors (VDRs) and the vitamin D activating enzyme 1‐alfa‐hydroxylase in extraskeletal tissues . Observational studies have reported associations between higher serum 25‐hydroxyvitamin D (25(OH)D) levels and lower risk of multiple pathological conditions .…”

“…In recent times, there has been an increased focus on nonskeletal effects of vitamin D, following the discovery of vitamin D receptors (VDRs) and the vitamin D activating enzyme 1‐alfa‐hydroxylase in extraskeletal tissues . Observational studies have reported associations between higher serum 25‐hydroxyvitamin D (25(OH)D) levels and lower risk of multiple pathological conditions . It is of note, however, the general lack of data from randomized controlled trials (RCTs) confirming the positive effects hypothesized from the descriptive studies …”

Active Vitamin D in Chronic Kidney Disease: Getting Right Back Where We Started from?

“…In these settings, calcitriol regulates multiple cellular processes, effecting normal and malignant cell growth and differentiation, innate immune function, and cardiovascular function. Unlike the renal enzyme, the extrarenal CYP27B1 expression is regulated by specific local factors, receiving feedback from locally expressed CYP27B1 and CYP24A1 and also available calcidiol [8]. …”

Untitled

“…6,33 Although there are many different causative pathologies, both kidney disease and eventual graft failure are associated with inflammation and fibrosis, the latter characterized by excess connective tissue deposition. 2,34,35 Chronic injury leads to scarring with excessive myofibroblast proliferation and consequent production of ECM proteins, particularly collagens.…”