Vitamin D metabolism and extraskeletal outcomes: an update

Abstract

Vitamin D deficiency is a general health problem affecting individuals at all stages of life and on different continents. The musculoskeletal effects of vitamin D are well known. Its deficiency causes rickets, osteomalacia, and secondary hyperparathyroidism and increases the risk of fractures. Clinical and experimental evidence suggests that vitamin D performs multiple extraskeletal functions. Several tissues unrelated to calcium and phosphate metabolism express vitamin D receptor (VDR) and are directly or indirectly influenced by 1,25(OH) 2 D (calcitriol). Some also express the enzyme 1 alphahydroxylase (CYP27B1) and produce 1,25(OH) 2 D, inducing autocrine or paracrine effects. Among the pleiotropic effects of vitamin D are the regulation of cell proliferation and differentiation, hormone secretion, and immune function. In this review, we outline vitamin D physiology and the outcomes of recent large RCTs on its potential extraskeletal effects. Those studies exhibit a need for continued clinical analysis to elucidate whether vitamin D status can influence extraskeletal health. Longer longitudinal follow-up and standardized assays are crucial to better assess potential outcomes. Arch

Vitamin D Determinants, Status, and Antioxidant/Anti-inflammatory-Related Effects in Cardiovascular Risk and Disease: Not the Last Word in the Controversy

“…UVB sun rays are the main source of vitamin D, whereas less than 10% derives from dietary intake (e.g., salmon, mackerel and herring, mushrooms, eggs, and fish liver oil), but may be also added to other foods or available as a dietary supplement. Skin exposure to solar UV irradiation induces photolysis of a derivative of cholesterol (7-dehydrocholesterol) into pre-vitamin D3, then isomerized to vitamin D3 (cholecalciferol) [ 1 ]. As a liposoluble/hydrophobic molecule, vitamin D3 requires the binding with a transporter protein (vitamin D-binding protein, VDBP) to circulate in the blood.…”

“…As a liposoluble/hydrophobic molecule, vitamin D3 requires the binding with a transporter protein (vitamin D-binding protein, VDBP) to circulate in the blood. Then, it is hydroxylated in the liver to form 25(OH)D, the major circulating metabolite [ 1 ]. In the kidney, hydroxylation catalyzed by the 1alfa-hydroxylase enzyme produces the active hormone, 1,25-dihydroxy vitamin D (1,25(OH) 2 D), while 24-hydroxylase (CYP24) promotes the production of inactive forms [ 1 ].…”

“…Then, it is hydroxylated in the liver to form 25(OH)D, the major circulating metabolite [ 1 ]. In the kidney, hydroxylation catalyzed by the 1alfa-hydroxylase enzyme produces the active hormone, 1,25-dihydroxy vitamin D (1,25(OH) 2 D), while 24-hydroxylase (CYP24) promotes the production of inactive forms [ 1 ]. When released by its binding with DBP to the tissues, 1,25(OH) 2 D mediates a number of actions through its intracellular vitamin D receptor (VDR).…”

“…It is well known that the role of vitamin D extends well beyond the traditional effect on muscle and bone health, now including a number of extra-bone conditions, such as cancer, diabetes, and cardiovascular disease (CVD), many of them related to the antioxidant and anti-inflammatory in which this molecule is involved [ 1 ]. Thus, an increase in requests for serum total 25(OH)D, widely recognized as the most reliable marker of vitamin D status, has exponentially grown in the last few years as a consequence of its clinical value, in parallel to the improvement of methodological and standardization-related aspects.…”

Editorial: The role of vitamin D in metabolic and cardiovascular health

“…In the last few decades, interest in vitamin D (VitD) has grown significantly since numerous studies have suggested that besides its well-established roles in bone metabolism ( 1 ), it could have other important roles in organism, including roles in immunity, endocrine, cardiovascular, and reproductive system ( 2 – 7 ). Many studies indicated that VitD status is inversely associated with the incidence of several metabolic diseases and conditions, including obesity ( 8 , 9 ), insulin resistance ( 10 – 14 ), metabolic syndrome ( 15 – 17 ), dyslipidemia ( 13 , 18 , 19 ), diabetes ( 10 , 11 , 20 – 22 ), non-alcoholic fatty liver disease (NAFLD) ( 23 – 25 ), and cardiovascular diseases ( 7 , 26 – 28 ).…”