The only proven benefit of calcitriol which is the active form of vitamin D is its role in absorbing calcium and helping to build bones and keep bones strong and healthy.
Vitamin D may also play a role in muscle function and the immune system. It helps protect it against infections and other illnesses
There have been studies to suggest that it might help prevent colon, prostate, and breast cancers. There is also some research that it might help prevent and treat diabetes, heart disease, high blood pressure, and multiple sclerosis.
Calcitriol is the active form of Vitamin D and acts as a hormone in human body. It exerts is effects mainly by activating the nuclear Vitamin D receptor (VDR).Its main role is in calcium homeostasis and the clasic target tissue are intestine,bone,kidney and parathyroid gland.The presence of VDR in all nucleated cells eg. skin, colon, brain, pancreas, breast, activated T and B lymphocytes, monocytes and macrophages etc points towards a greater role of calcitriol in addition to calcium homeostasis.Due to this fact almost every health disorder is associated to Vitamin D status.
Vitamin D (Calcitriol)
Bioactive vitamin D or calcitriol is a steroid hormone that has long been known for its important role in regulating body levels of calcium and phosphorus, and in mineralization of bone. More recently, it has become clear that receptors for vitamin D are present in a wide variety of cells, and that this hormone has biologic effects which extend far beyond control of mineral metabolism.
http://www.vivo.colostate.edu/hbooks/pathphys/endocrine/otherendo/vitamind.html
Vitamin D
Vitamin D is a hormone produced by the kidneys that helps to control the concentration of calcium in the blood and is vital for the development of strong bones.
A fall in the concentration of calcium in the bloodstream is detected by the parathyroid glands, which then produce parathyroid hormone. Parathyroid hormone increases the activity of the enzyme 1α-hydroxylase, which produces active vitamin D. This increase in the concentration of calcium together with vitamin D feeds back to the parathyroid glands to stop further parathyroid hormone release. The production of vitamin D is also directly regulated by calcium, phosphate and calcitriol.
http://www.yourhormones.info/hormones/vitamin-d/
Endocrine Functions of the Kidneys
Calcitriol stimulates the small intestine for protein synthesis allowing absorption of Ca2+and phosphates. This ensures the availability of Ca2+ and phosphate for bone growth. Calcitriol simultaneously activates osteoblasts to synthesize collagen.
Calcitriol
Calcitriol is the biologically active form of vitamin D and therefore has a more immediate onset of action (maximal effect in
Calcitriol
Calcitriol is available as a pill or an intravenous (IV) formulation. Oral calcitriol effectively decreases PTH levels, decreases bone resorption, improves endosteal fibrosis and mineralization, and to some extent helps in the bone pains associated with renal osteodystrophy. Calcitriol has a direct inhibiting effect on PTH synthesis. In predialysis patients (CKD stages 3 and 4), the usual starting dose is 0.25 μg every day or every other day. In dialysis patients, the dose can be titrated upward. The unfavorable effects associated with calcitriol are hypercalcemia and hyperphosphatemia, mainly due to increased intestinal absorption of calcium and phosphorus. Intravenous calcitriol is given to hemodialysis patients and is associated with less hypercalcemia and a more profound decrease in PTH levels. The usual starting dose of intravenous calcitriol is 0.5 to 1.0 μg per dialysis session, and it can be increased to 4 μg or more if hypercalcemia does not occur. Hypercalcemia with oral or intravenous calcitriol requires a decrease in the dose by 25% to 50% and rechecking calcium and PTH levels.
HORMONAL REGULATION OF PLASMA CALCIUM AND CALCIUM METABOLISM
Joy Hinson BSc PhD DSc FHEA, ... Shern Chew BSc MD FRCP, in The Endocrine System (Second Edition), 2010
Effects on plasma calcium and bone
Calcitriol acts on cells in the gastrointestinal tract to increase the production of calcium transport proteins, termed calbindin-D proteins, which results in increased uptake of calcium from the gut into the body. This is the only mechanism by which the body can increase its calcium stores.
The actions of calcitriol on bone are not well understood but it is essential for normal osteoblast differentiation and function. It has a minor effect on the kidney, decreasing urinary loss of calcium by stimulating reabsorption. Calcitriol acts directly on the parathyroid gland, regulating calcium receptor levels and directly inhibiting transcription of the gene encoding PTH. Calcitriol also has important secondary effects on PTH secretion. By increasing calcium uptake in the gastrointestinal system, calcitriol increases plasma calcium, maintaining PTH secretion at low levels and thus favouring osteoblast action and protecting bone structure.
Vitamin D Hormone & anticancer properties
M. Kyle Hadden1, in Vitamins & Hormones, 2016
4.1.2
Calcitriol
Calcitriol has also been evaluated for its anti-Hh and anticancer properties in multiple Hh-dependent cellular model systems. Calcitriol significantly reduces Gli1 expression in Hh-dependent MEFs at low nanomolar concentrations (100 nM) (Banerjee et al., 2012). Studies exploring the ability of calcitriol to inhibit Hh signaling in ASZ cells have proven contradictory (Tang et al., 2011; Uhmann et al., 2012a). In one report, neither cellular proliferation nor Gli1 expression was significantly reduced in ASZ cells following administration of calcitriol (100 nM) (Tang et al., 2011). A second report demonstrated significant reductions in both Gli1 expression and BrdU incorporation in ASZ cells treated with calcitriol (10 nM), suggesting it does maintain anti-Hh effects in this cellular model (Uhmann et al., 2012a). Gli1 expression and Ki67 staining were reduced in BCC-bearing skin punches from Hh-dependent murine BCC following administration of calcitriol (10 nM) (Uhmann et al., 2012a). Similar results for Gli1 downregulation and BrdU incorporation were seen in a primary cell culture model of embryonal rhabdomyosarcoma (ERMS; Uhmann et al., 2012b). In each of these cellular models, calcitriol significantly upregulated Cyp24A1 expression, further highlighting its nonselective effects on both the Hh and VDR signaling pathways.
Similar to the results seen in ASZ cells, the in vivo effects of calcitriol in murine models of Hh-dependent BCC have also proven contradictory (Tang et al., 2011; Uhmann et al., 2012a). Direct topical administration of calcipotriene cream (Dovonex, 0.0005% calcitriol, 4 days) to murine BCC tumors did not decrease Gli1 mRNA expression; however, it did reduce Ki67 staining, indicating inhibition of tumor cell proliferation (Tang et al., 2011). By contrast, daily IP administration of calcitriol(100 ng/kg, 90 days) resulted in decreased expression of Gli1 and Gli2 mRNA and a reduction in Ki67 positive cells in BCC tissue (Uhmann et al., 2012a). Most likely, these in vivodiscrepancies are primarily a result of experimental differences, and prolonged topical administration with higher doses of calcitriol would result in effects similar to those seen with the IP studies. A significant increase in expression of the keratinocyte differentiation markers Tgm1 and K10 was also detected following IP dosing (Uhmann et al., 2012a). While IP dosing increased serum calcium levels, associated hypercalcemic side effects (weight loss, kidney damage) were not observed, suggesting a dose range that could deliver positive anticancer effects without the requisite side effects primarily associated with prolonged calcitriol treatment. IP administration of calcitriol (50 ng/kg/d for 8 weeks) in an Hh-dependent murine model of ERMS also reduced Gli1 expression, BrdU incorporation, and tumor volume (Uhmann et al., 2012b). Finally, both topical and IP administration of calcitriol in each of these in vivo models significantly upregulated CYP24A1 expression.
Growth and Puberty in Chronic Kidney Disease
Dieter Haffner, Richard Nissel, in Comprehensive Pediatric Nephrology, 2008
Calcitriol
Calcitriol deficiency is a major cause of secondary hyperparathyroidism and renal osteodystrophy. Although calcitriol supplementation reverses the biochemical, radiographic, and histological signs of high turnover bone disease, the improvement of longitudinal height was not consistently observed in clinical trials. Alternatively, there is limited experimental and clinical evidence that a low turnover bone state, which is the typical complication of calcitrioltherapy, may compromise longitudinal growth. Therefore, plasma PTH levels should be kept at two to three times the upper-normal range in patients with CKD stages IV and V and within the upper limit of the normal range in patients with CKD stages I through III.84 Although these recommendations have not been formally proven in prospective clinical trials, these target levels are thought to allow for the sufficient control of secondary hyperparathyroidism (and thus avoid adynamic bone disease) and therefore optimal growth in children with CKD.84,92,199
Mineral Bone Disease in Chronic Kidney Disease
In Pocket Companion to Brenner and Rector's The Kidney (Eighth Edition), 2011
Calcitriol or Alfacalcidol
Calcitriol is an effective agent both orally and intravenously for the treatment of SHPT. Early reports suggested that the therapeutic use of calcitriol worsened renal function in patients with established CKD. This, however, appeared to be associated with treatment-related hypercalcemia and hypercalciuria. The development of hypercalcemia and hypercalciuria is uncommon, however, when the daily oral dose of calcitriol does not exceed 0.5 μg or when the daily dose of alfacalcidol, or 1α-hydroxyvitamin D3 (which undergoes 25-hydroxylation in the liver), does not exceed 0.9 μg. These amounts are often effective in lowering plasma PTH levels, and the use of small daily oral doses of calcitriol has been reported to prevent the progressive rise of plasma PTH levels in CKD stages 3 and 4. Nevertheless, the therapeutic index for such patients is rather narrow, and serum calcium, phosphorus, and PTH levels must be monitored regularly.
The occurrence of hypercalcemia during calcitriol therapy may provide insight into the existing state of skeletal remodeling and underlying bone disease. When hypercalcemia develops after many months of treatment, with normalization of previously elevated plasma PTH and alkaline phosphatase, it is likely that the skeletal changes of hyperparathyroidism have resolved substantially or completely. In contrast, episodes of hypercalcemia that occur within the first few weeks of treatment suggest the presence of either low-turnover bone disease or severe SHPT. The hypercalcemic effects of calcitriol are aggravated by the concomitant use of large amounts of calcium-containing phosphate-binding agents, although recommendations for the limitation of daily consumption of elemental calcium now exist. The recommended calcium concentration of dialysate was also changed in an attempt to limit net calcium transfer from dialysate to plasma, with current K/DOQI guidelines advising a 2.5 mEq/L or 1.25 mmol/L calcium concentration.
The use of parenteral calcitriol is often limited by the occurrence of recurrent hypercalcemia and hyperphosphatemia, and given the associated cardiovascular concerns, therapy has now largely been replaced by parenteral use of the new vitamin D sterols (see later discussion).
Vitamin D Deficiency
Ian H. de Boer M.D., M.S., in Chronic Kidney Disease, Dialysis, and Transplantation (Third Edition), 2010
Calcitriol
Calcitriol is commonly prescribed and relatively well-studied in the setting of CKD. It does not require renal activation for potent binding to the vitamin D receptor. As a result, it is an established therapy for the treatment of secondary hyperparathyroidism in all stages of CKD and is known to effectively lower serum PTH concentration (see Chapter 8). In addition, calcitriol has been associated with improved survival in observational studies of CKD and ESRD (see Consequences). Calcitriol can be administered intravenously with hemodialysis or orally at any stage of CKD.
Because calcitriol potently activates the vitamin D receptor, one potential adverse effect is adynamic bone disease due to oversuppression of PTH (see Chapter 8). In addition, calcitriolcarries a risk of hypercalcemia and, less frequently, hyperphosphatemia. Regular monitoring is therefore required.
Vitamin D and the Immune System
Nobuto Yamamoto, in Encyclopedia of Immunology (Second Edition), 1998
Effect of calcitriol in vitro on lymphocytes
Calcitriol has also been shown to act on T and B lymphocytes, and antibody-producing function of lymphocytes (Table 1). Studies in vitro have suggested that the main effect of calcitriolis to inhibit the proliferation of activated T cells which, unlike resting T cells, express VDR. Lymphocytes require activation in order to express the calcitriol receptor. Following this initial activation induced by antigen, cytokine or mitogens, incubation with calcitriol inhibits T lymphocyte proliferation. IL-2 production by activated T lymphocytes is strongly inhibited by calcitriol and this seems to be one of the crucial events in the immunoregulatory activities of calcitriol, linking it to the immunosuppressive properties exerted by known immunosuppressants such as cyclosporine.
Calcitriol also inhibits interferon γ synthesis by T cells, and this may act as part of the control of calcitriol synthesis by macrophages which produce the hormone (calcitriol) when stimulated with interferon γ.
T cell development takes place in the thymus with VDR being expressed in medullary cells, but not in the less mature cortical cells. However, the precise role of calcitriol in T lymphocyte development is unclear as VDR expression is lost after the cells leave the thymus. VDR are also present in natural killer cells, indicating that calcitriol may have a role in modulating the immune response to viral infection and neoplastic development. The interaction of vitamin D with B cells is less clear than its effects on T cells, and although calcitriol inhibits immunoglobulin production by B cells this appears to be due to indirect suppression of the antibody-stimulating activity of T helper cells rather than a direct effect on B cells.
The metabolism and functions of vitamin D.
https://www.ncbi.nlm.nih.gov/pubmed/3012979
Overview of general physiologic features and functions of vitamin D.
Overview of Vitamin D
https://www.ncbi.nlm.nih.gov/books/NBK56061/
DIETARY REFERENCE INTAKES Calcium Vitamin D Committee to Review Dietary Reference Intakes for Vitamin D and Calcium Food and Nutrition Board A. Catharine Ross, Christine L. Taylor, Ann L. Yaktine, and Heather B. Del Valle, Editors
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