Vitamin D

Vitamin D: Mechanisms of action in bone, and in cell differentiation/proliferation/growth?

+ Bone: - involved in mobilizing Ca and PO4 from bone (w/ PTH), used to maintain normal serum Ca concentration (bone resorption) - stimulate osteoclast activity - plays role in bone remodeling, calcitriol involved in synthesis of osteocalcin, which is used by osteoblasts to form new bone + Cell differentiation, proliferation, and growth: - calcitriol stimulates differentiation of hematopoietic cells, mucosal cells, osteoblasts, osteoclasts

Vitamin D: 3 general Mechanisms of action?

+ Calcitriol is active form + Mechanism of action: - steroid hormone - binds to vit D receptor on cell membranes and activates signaling pathways - binds to vit D receptor in nucleus and influences gene expression + Gene transcription: - vit D receptors (VDR) in nucleus are involved in gene transcription (e.g. intestine, bone)

Vitamin D: Structure? Sources? How much synthesized in skin in U.S?

+ D3 synthesized in skin from 7-dehydrocholesterol -> cholecalciferol, then bound to DBP in blood + also animal foods: meats, eggs, dairy, fatty salt-water fish - milk, some orange juice, and cereal is fortified + winter: 1.5 IU vit D/cm2/hour - summer: 6 IU vit D/cm2/hour - 10 minutes of summer sun on face and hands = 10 microG (400 IU)

Vitamin D deficiency in children?

+ Rickets in infants and children: - bone matrix grows, but minerals not laid down - bones become rubbery -sot and pliable - permanent bone deformations: bowlegs, knock knees - delayed closing of fontanelle - fortification of mild with vitamin D has greatly reduced incidence of rickets

Vitamin D: What do the liver and kidney do to vitamin D3? Main form in blood? Active form? Excretion?

+ Vit D3 is transported to liver by chylo remnants or DBP, then -25-hydroxylase->25-OH D3 (calcidiol) is released into blood bound to DBP. - calcidiol (25-OH D3) is main form in the blood + 25-OH D3 taken up by kidney then 1-hydroxylase -> 1,25-(OH)2 D3 (calcitriol, active form) which is released to blood bound to DBP + almost all calcitriol metabolites excreted in bile

Vitamin D: Deficiency causes? specifically in adults can cause?

+ can cause insufficient absorption of Ca and PO4 -> decreased bone mineralization - less calcium available for bone, and more bone breakdown to replenish blood calcium + osteomalacia in adults: - stable bone matrix with loss of bone minerals - soft, brittle bones, and bone pain

Vitamin D: Absorption and transport of dietary and synthesized? carrier protein? How is it transported in the blood?

+ half of dietary vitamin D3 is absorbed in micelles -> chylomicrons + chylomicrons transfer some to extrahepatic tissues or *DBP* but most delivered to liver by chylomicron remnants + DBP carries vitamin D synthesized in skin, some delivered to muscle and adipose tissue, most delivered to liver. + In blood, 40% in chylomicrons, and 60% bound to DBP

Vitamin D: mechanisms of action as hormone, in kidney, and intestine?

+ hormone: calcitriol and PTH regulate serum Ca2+ concentration + Kidney: calcitriol involved in PTH stimulation of Ca2+ and PO4 reabsorption + Intestine: - stimulates transcription of genes for proteins involved in Ca absorption/transport (calbindin) - may change topology of brush border to increase Ca absorption - also may increase activity of alkaline phosphatase at brush border to increase phosphorus absorption

Vitamin D: Risk factors for deficiency?

+ reduced synthesis: dark skin, insufficient sun exposure (indoors, clothes, sunscreen), elderly + reduced absorption: intestinal disorders + increased storage: obesity + breastfed infants: especially those with dark skin and/or minimal sun exposure; supplements recommended

Vitamin D: UL? Toxicity in infants and adults?

+ toxicity not possible from sun exposure + UL (2010): 4000 IU/day (>6x RDA) taken chronically can cause toxic effects; UL is lower for children <9 years. + hypercalcemia in infants: anorexia, nausea, vomiting, hypertension, renal failure, failure to thrive + hypercalcemia in adults: calcification of soft tissues (kidney, heart, lungs, blood vessels), hyperphosphatemia, hypertension, anorexia, nausea, weakness, polyuria, renal failure, death

Vitamin D: Recommended intake? RDA? Assessment?

IU = activity in 0.025 microG cholecalciferol + RDA (2010): - 600 IU for children and adults (1-70 years old) - 800 IU for adults >70 years old + Assessment: - Plasma 25-OH D3