D is metabolically ChaetocinMedChemExpress Chaetocin inactive until it is converted to 1,25-dihydroxyvitamin D [1,25(OH)2D] by an enzymatic hydroxylation process (25-hydroxyvitamin D-1-hydroxylase) [2]. The active metabolite, 1,25(OH)2D, acting through vitamin D receptors (VDR) can produce a wide range of skeletal and purchase BX795 non-skeletal effects [6,19]. 1,25(OH)2D acts either synergistically with parathyroid hormone (PTH) or alone and modulates calcium homeostasis and bone metabolism. 1,25(OH)2D increases serum calcium concentrations by increasing skeletal mobilisation of calcium, renal calcium re-absorption [18] and intestinal calcium absorption [20]. Evidence in the laboratory also indicates that 1,25(OH)2D3 has a number of non-skeletal effects including, inhibition of autoimmune diseases [21] and cancer progression [22,23], modulation of immune system [24], and regulation of cardiovascular system [25] and adipocyte apoptosis [23,26]. The system of vitamin D metabolism acts according to the first-order reaction enzyme kinetics [27]. When vitamin D supplies are low, the enzymatic capacity of non-renal tissues to produce 1,25(OH)2D is diminished. Accordingly, flow of 25(OH)D through other potential pathways is compromised to maintain the circulating concentration of 1,25(OH)2D at the level determined by the priority requirements of calcium homeostasis and bone metabolism. In contrast, under conditions of adequate supply of vitamin D, higher 25(OH)D concentrations meet all physiological requirements for both skeletal and non-skeletal pathways on one hand, and up-regulate 24-hydroxylase and the catabolic pathways associated with it on the other hand. More than 50 different vitamin D metabolites have been identified, of which vitamin D, 1,25(OH)2D and 25(OH)D have been the focus of vitamin D assay methods [28]. Circulating 25(OH)D is currently considered the best determinant of vitamin D status compared to other vitamin D metabolites namely vitamin D and 1,25(OH)2D because: (1) its half-life is much longer, though the definite time is controversial (ranging from three weeks to three months) [29,30]; (2) its production in the liver is not significantly regulated and depends on the substrate availability [28] and (3) its concentration reflects body stores of both vitamin D synthesized in the skin and the vitamin D ingested from a diet or supplement. Vitamin D [28] and 1,25(OH)2D [29], in contrast, have a short half-life of 24 h and 4 to 6 h, respectively. Compared to 25(OH)D, serum concentration of 1,25(OH)2D is very low (about a thousand-fold less) [29] and its production is tightly regulated by a person’s calcium requirements [28]. Not only is circulating 25(OH)D an indicator of vitamin D status, but it is also a marker of good health. Serum 25(OH)D concentrations <25 nmol/L are associated with decreased intestinal calcium absorption [31], though a minimum level of 75 nmol/L has been proposed for optimal calcium absorption by Barger-Lux and Heaney (2002) [32]. It is generally recognised that prolonged and severe vitamin D deficiency (25(OH)D < 20 nmol/L) is associated with the symptoms and signs of rickets in children and osteomalacia in adults [33], albeit higher 25(OH)D levels are required to ensureNutrients 2015,multiple health outcomes. Evidence shows that circulating 25(OH)D levels >75 nmol/L are associated with decreased risk of cardiovascular diseases [34], decreased activity and progression of multiple sclerosis [35] and increased survival in patients with colorectal and.D is metabolically inactive until it is converted to 1,25-dihydroxyvitamin D [1,25(OH)2D] by an enzymatic hydroxylation process (25-hydroxyvitamin D-1-hydroxylase) [2]. The active metabolite, 1,25(OH)2D, acting through vitamin D receptors (VDR) can produce a wide range of skeletal and non-skeletal effects [6,19]. 1,25(OH)2D acts either synergistically with parathyroid hormone (PTH) or alone and modulates calcium homeostasis and bone metabolism. 1,25(OH)2D increases serum calcium concentrations by increasing skeletal mobilisation of calcium, renal calcium re-absorption [18] and intestinal calcium absorption [20]. Evidence in the laboratory also indicates that 1,25(OH)2D3 has a number of non-skeletal effects including, inhibition of autoimmune diseases [21] and cancer progression [22,23], modulation of immune system [24], and regulation of cardiovascular system [25] and adipocyte apoptosis [23,26]. The system of vitamin D metabolism acts according to the first-order reaction enzyme kinetics [27]. When vitamin D supplies are low, the enzymatic capacity of non-renal tissues to produce 1,25(OH)2D is diminished. Accordingly, flow of 25(OH)D through other potential pathways is compromised to maintain the circulating concentration of 1,25(OH)2D at the level determined by the priority requirements of calcium homeostasis and bone metabolism. In contrast, under conditions of adequate supply of vitamin D, higher 25(OH)D concentrations meet all physiological requirements for both skeletal and non-skeletal pathways on one hand, and up-regulate 24-hydroxylase and the catabolic pathways associated with it on the other hand. More than 50 different vitamin D metabolites have been identified, of which vitamin D, 1,25(OH)2D and 25(OH)D have been the focus of vitamin D assay methods [28]. Circulating 25(OH)D is currently considered the best determinant of vitamin D status compared to other vitamin D metabolites namely vitamin D and 1,25(OH)2D because: (1) its half-life is much longer, though the definite time is controversial (ranging from three weeks to three months) [29,30]; (2) its production in the liver is not significantly regulated and depends on the substrate availability [28] and (3) its concentration reflects body stores of both vitamin D synthesized in the skin and the vitamin D ingested from a diet or supplement. Vitamin D [28] and 1,25(OH)2D [29], in contrast, have a short half-life of 24 h and 4 to 6 h, respectively. Compared to 25(OH)D, serum concentration of 1,25(OH)2D is very low (about a thousand-fold less) [29] and its production is tightly regulated by a person’s calcium requirements [28]. Not only is circulating 25(OH)D an indicator of vitamin D status, but it is also a marker of good health. Serum 25(OH)D concentrations <25 nmol/L are associated with decreased intestinal calcium absorption [31], though a minimum level of 75 nmol/L has been proposed for optimal calcium absorption by Barger-Lux and Heaney (2002) [32]. It is generally recognised that prolonged and severe vitamin D deficiency (25(OH)D < 20 nmol/L) is associated with the symptoms and signs of rickets in children and osteomalacia in adults [33], albeit higher 25(OH)D levels are required to ensureNutrients 2015,multiple health outcomes. Evidence shows that circulating 25(OH)D levels >75 nmol/L are associated with decreased risk of cardiovascular diseases [34], decreased activity and progression of multiple sclerosis [35] and increased survival in patients with colorectal and.
