vitamin D

DRI for vitamin D

AIs recently changed to RDAs assume inadequate exposure to sunlight adults >19: 15 ug (600 IU) adults >51 : 15 ug (600 IU) elderly >70: 20 ug (800 IU) conversion: 1 ug = 40 IU - most elderly require a supplement - a few minutes of sunlight generates significant amounts of the vitamin...US summer, 10 mins on face and hands produces 400 IU UL doubled from 2000 IUs to 4000 IU/day

calcium absorption levles

30% if necessary, calcitriol can increase that to 80%

how do vit D2 and 3 become activated?

hydroxylated

how does vitamin D2 get synthesized?

in plants, ergosterol (previtamin D2) exposed to irradiation and converts to ergocalciferol (vitamin d2)

what mechanism does the body have when it has made enough D3 from the sun?

previtamin D3 converts to Lumisterol and Tachysterol which are lost as skin cells are sloughed

assessment of vit D status

*The plasma conc of 25-OH D3 (calcidiol) is often used as an index of vit D status.* - Concentrations <37 nmol/L are associated with subclinical deficiency - Concentrations <28 nmol/L suggest Vit D deficiency - Optimal may be 80-120 nmol/L - Toxicity is considered when 25-OH D3 conc typically exceed ~375 nmol/L - Serum Ca or P are NOT good indicators of Vitamin D status

calcitriol and the kidney

- Calcitriol appears to be involved in the PTH-stimulated reabsorption of calcium and especially phosphorus in the kidney - in the kidneys, calbindin decreases calcium excretion - Calbindin D 28K is thought to play a role in renal calcium reabsorption - Synthesis of this protein appears to be calcitriol-responsive - Synthesis may be increased by nVDR mechanism - It is a larger version of the calbindin protein of the small intestine

what are the main functions of calcitriol?

- maintain serum calcium and phosphorus at high concentrations for bone mineralization - maintain calcium homeostasis to support cellular metabolic processes and neuromuscular functions

vit D deficiency in children

- Infants and Children develop Rickets - failure of bone to mineralize. - Epiphyseal (growth plate) cartilage continues to grow and enlarge without replacement by bone matrix and minerals. - Results in bone deformities, bowed legs and rachitic rosary of the rib cage. - Can be caused by dietary deficiency or lack of sunlight or combination - Craniotabes (softening of bones of skull) - Sitting, crawling, and walking are delayed and if individual is active at this time, weight bearing results in bowing of arms, knock-knees or outward bowing

what happens to 25-OH-D after the liver?

- taken up by the kidney (tightly regulated, ParaThyroid Hormone) - converts to 1,25-(OH)2 (calcitriol bc 3 OH groups)

vit D deficiency in adults

- Osteomalacia (soft bones) - D deficiency in adults and is a defect in mineralization - The defect results from abnormal phosphorus and calcium absorption and excretion - For example, with Vit D deficiency, less calcium is absorbed - Declining blood calcium triggers secretion of PTH - If conditions persist, PTH remains elevated in the blood for prolonged periods and this can lead to bone resorption, and increased urinary phosphorus excretion, among other changes - In Vit D-deficient adults, as bone turnover occurs the bone matrix becomes progressively demineralized which can lead to bone pain and osteomalacia

calcitriol in the bone

- PTH alone or with calcitriol leads to mobilization of Ca and phosphorus from bone to maintain blood levels - This may be mediated by calcitriol's effects on bone cell differentiation: Calcitriol can induce bone marrow (stem) cells to become osteoclasts Osteoblasts, the cells partly responsible for forming bone, also respond to calcitriol by producing: Collagen, osteocalcin and other proteins involved in bone mineralization

toxicity of vit D

- Toxicity Due to Sunlight = not a problem - Toxicity Due to Dietary Ingestion *the most likely of all vitamins to cause overt toxic reactions* Chylo remnants deliver Vit D to the liver and the liver hydroxylates the vitamin to form 25-OH The 25-OH molecule (aka calcidiol) can stimulate some of the same effects as calcitriol - Signs and symptoms: anorexia, vomiting, overall weakness - typical toxic effects: calcification of soft tissue such as the kidneys, lungs, and blood vessels

what happens to vitamin D3 after it is synthesized in the blood?

- Vitamin D Binding Protein (DBP) moves Vit D3 from skin to blood, portal vein, liver

what are the forms of vitamin D??

- Vitamins D2 (ergocalciferol) in plants, yeast, some fungi - Vitamin D3 (cholecalciferol) in animals, fortified dairy products, skin, supplements - its actually a hormone!

calcitriol and PTH maintenance of blood calcium levles

- as blood calcium starts to drop - parathyroid hormone is released from parathyroid gland - PTH goes into blood, stimulates kidney 1-hydroxylase (increases calcitriol levels) - the 25-OH-D (from liver) converts to 1,25(OH)2D which goes into blood, bound to DBP - enter intestinal cells and increase the absorption of calcium and phosphorus from the gut (as calcium blood levels drop, absorption goes up)

effects of PTH

- as calcium blood levels drop, calcium absorption efficiency goes up, helps restore levels to normal - increases calcium reabsorption in the kidneys (decreases calcium excretion) - PTH and calcitriol together increase osteoclast (cell type in bone that degrade bone) activity in the bone, which increases blood calcium, but decreases bone calcium

functions and mechanism of action of calcitriol

- calcitriol (D3) is the main active form of vit D and functions like a steroid hormone - D3 must bind to a receptor in order to elict a response - calcitriol binds to 2 different types of receptors (membrane and nuclear) - these receptors are denoted as vit D receptors (VDR) - vit D has nongenomic and genomic mechanisms - cell membrane receptors are present in intestine, kidney, bone, cardiac, muscle, pancreas (beta-cells), brain, skin, hemapoietic, and immine system tissues among others

nuclear VDRs

- calcitriol bound to DBP in the blood - goes through plasma membrane, into the nucleus - VDR goes back and forth in between the cytosol and the nuclues - in the nucleus it binds calcitriol, confomational change - binds RXR - VDR phosphorylated - complex binds VDRE - VDR can interact with other transcription factors after it binds VDRE, and that can affect transcription levels - VDR helps recruit transcription factors and RNA Polymerase - increases Calbindin (calcium binding protein)...helps move calcium from apical membrane to basal lateral membrane - increases osteocalcin (a bone protein involved in calcium mineralization in bone)

membrane VDRs

- calcitriol travels through blood, binds to VDRs on the plasma membrane and changes its shape - VDR interacts with signaling molecules - signaling molecules cause an appropriate response in the cell - responses may include Transcaltachia (rapid calcium transport) and opening of Ca channels

how does vitamin D3 get synthesized?

- cholesterol in the body converts to 7-dehydocholesterol (found in the skin's glands) - exposed to UV light - converts to previtamin D3 (precalciferol) - when exposed to body heat, converts to vitamin D3 (cholecalciferol)

dietary sources

- fortified milk, fatty fish, fortified cereals - Naturally occurring Vit D is rare in foods - Fortified products represent the major dietary source of Vitamin D - Fortified milk does not always contain adequate amounts of Vitamin D - Milk is supposed to be fortified at 10 ug/quart

hepatic 25-hydroxylase feature that helps assess vit D status

- hepatic 25-hydroxylase is not tightly regulated - if vit D goes to liver, it will be hydroxylated - circulating levels of 25-OH-D3 reflects both intake and exposure to UV light - commonly used to asses status

why might the elderly be at risk for deficiency?

- inadequate sun exposure - poor intake of Vit D - aging reduces synthesis of cholecalciferol on the skin and - Decreased renal 1-hydroxylase synthesis in response to PTH -Disorders affecting the parathyroid, liver, and/or kidney will impair synthesis of the active form of the vitamin

how does calcitriol perform its functions?

- increases Ca and P absorption in the SI - increases Ca and P mobilization from the bone - increases Ca and P reabsorption in the kidney

absorption and transport of vitamin D

- vit D from the diet is absorbed from micelles - in intestinal cells, most goes into chylomicrons - some D3 transferred to DBP goes to extrahepatic tissues or liver - remaining vit D stays in chylos and delivered to liver as chylo remnants

how is vitamin D metabolized in the liver?

- vit d is bound to either DBP or chylo remnants - hepatic vit D 25-hydroxylase adds an OH to C25 - becomes 25-OH-vitD2 or 3 (calcidiol bc 2 OH groups) - exported into the blood and binds DBP

calcitriol and phosphorus absorption

1. cacitriol is thought to increase the activity of brush border alkaline phosphatase (this phosphatase hydrolyzes phosphate ester bonds thereby allowing phosphorus to be absorbed) - increases enzyme that converts phosphate to phosphorus for absorption 2. calcitriol is thought to increase the number of transporters for Na-dependent phosphorus absorption at the BBM - increases transporters that phosphorus needs - helps phosphorus status for humans

absorption rate of vitamin d?

50%

25-OH Vitamin D 3 or 2

calcidiol

the most active and potent form of vit D

calcitriol 1,25 (OH)2 - vitamin D

recognize structure of D3, 25-OH-D3 (calcidiol), and 1,25-(OH)2-D (calcitriol)

where da OHs at?