Vitamin D Flashcards
Cholecalciferol (Vitamin D3) sources
o Synthesis in skin – from sunlight o Animal sources: • Saltwater fish: herring, salmon, tuna, and sardines - especially fish liver • Meat: liver and beef • Egg yolks • Dairy: milk, cheese and butter
Ergocalciferol (Vitamin D2) sources
o Plant sources: mushrooms
o Fortified foods: milk and margarine
• Canada:
• Milk & margarine are required to be fortified by law
o Milk: 88 IU/250 ml – cow, evaporated, powdered, goat & plant
o Margarine: ≥530 IU/100 g
• Some yogurt & cheese if made with fortified milk
• United States:
• No foods require fortification by law
• Allowable foods include: milk, fruit juice, breads, ready to eat cereals, Olestra
Ultraviolet synthesis of Vitamin D in plants
o Ergosterol absorbs photons producing previtamin D2
o Previtamin D2 has unstable bonds that rearrange with heat forming ergocalciferol
Ultraviolet synthesis of Vitamin D in humans/animals
o 7-dehydrocholesterol (aka provitamin D3)
• Synthesized in the sebaceous glands of skin from cholesterol
• Secreted onto surface of skin and reabsorbed into epidermis and dermis
• Absorbs photons producing precalciferol
o Precalciferol (aka previtamin D3)
• Unstable bonds rearrange in 2-3 days resulting in cholecalciferol
o cholecalciferol (aka Vitamin D3, aka calciol)
• Diffuses from the skin into the blood
• Transported in the blood by an alpha-2 globulin vitamin D binding protein (DBP) aka transcalciferin
Vitamin D digestion
Dietary vitamin D in association with dietary fats is packaged into micelles with the aid of bile salts
Vitamin D absorption
- By passive diffusion
* Primarily in the distal small intestine
Vitamin D transport from skin
o Diffuses into blood
o Picked up by DBP for transport
o Travels primarily to the liver but can be picked up by other tissues, especially muscle and adipose tissues
Dietary vitamin D transport
o Incorporated into chylomicrons within the enterocytes for transport
o Chylomicron remnants then deliver vitamin D to the liver
o Some vitamin D from chylomicrons can be transferred from chylomicrons to DBP for delivery to extrahepatic tissues
Vitamin D metabolism (25-hydroxy vitamin D3)
o Aka calcidiol
o Synthesized from vitamin D in the liver
• Enzyme required for conversion is: 25-hydroxylase
• Requires magnesium as a cofactor
o Most is released into the blood bound to DBP
o Main circulating form of vitamin D
• Accurately reflects vitamin D status from food and sunlight
o T1/2 = 10 days – 3 weeks
Vitamin D metabolism (1,25-dihydroxy vitamin D3)
o Aka calcitriol
o Synthesized from 25-hydroxy vitamin D3 in kidney tubules
• Enzyme required for conversion is: 1-hydroxylase
o Active form of vitamin D
o Functions as a steroid hormone
o Transported in blood via DBP
o Binds to vitamin D receptors (VDR) on target tissues
o T1/2 = 4-6 hrs
Regulation of vitamin D metabolism
• 1-hydroxylase activity o Increased by: • Parathyroid hormone • Low plasma calcium concentrations • Low 1,25(OH)2 D3 concentrations o Decreased by: • High 1,25(OH)2 D3 concentrations • High phosphorus intake • When 1,25-(OH)2 D3 levels are high: o 1,25(OH)2 D3 is converted into 1,24,25(OH)3 D3 o 25(OH) D3 is converted into 24,25(OH)2 D3
Vitamin D storag
- Cholecalciferol is stored in the skin and adipose tissue
* 25-OH D3 is stored in the blood and muscle
Vitamin D functions
Calcium homeostasis Cell differentiation, proliferation and growth Also roles in -blood pressure -immune system modulation -pancreatic B cell function
Vitamin D and calcium homeostasis
o Hypoclacemia stimulates secretion of PTH
o PTH stimulates 1-hydrolase activity in the kidney which converts 25-OH D3 to calcitriol
o Calcitriol binds to:
• Intestine cells → enhances intestinal Ca and P absorption
• Kidney cells → along with PTH stimulates Ca reabsorption in distal renal tubules
• Bone cells
• In hypocalcemic conditions PTH and calcitriol:
o Stimulate the production and maturation of osteoclasts, mobilizing Ca and P from bone
• In hypercalcemic conditions calctonin and calcitriol:
o Promote mineralization of Ca and P in the bone
o This is controlled by a negative Feedback loop
• Increasing serum calcium and calcitriol levels inhibit PTH secretion
Vitamind D and cell differentiation, proliferation and growth
o Clacitriol is required for the differentiation of:
• Premyeloid WBCs and stem cells into macrophages and monocytes
• Stem cell monocytes in bone marrow into mature osteoclasts
• Skin epidermal cells
o Calcitriol inhibits the proliferation of:
• Fibroblasts, keratinocytes, and lymphocytes
• Abnormal intestinal, lymphatic, mammary, and skeletal cells
• Down regulates abnormal cell growth in some tissues and able to induce apoptosis if needed
• Low vitamin D levels are associated with increased risk of developing and dying of several cancers including: prostate, breast colon, ovarian, and non-Hodgkin’s lymphoma
Vitamin D and blood pressure
• Vitamin D down regulates the production of renin and angiotensin
Vitamin D and immune system modulation
- Autoimmune conditions
- Inadequate vitamin D levels are linked with rheumatoid arthritis, Crohn’s disease, multiple sclerosis, and type I diabetes
- Immune system function
- Cytokine production, lymphocyte and macrophage activity, monocyte maturation, and the production of certain antimicrobial peptides are mediated by vitamin D
Vitamin D and pancreatic B cell function
• Higher 25-OH D3 levels are associated with decreased insulin secretion and increased insulin sensitivity
Vitamin D mechanism of action
• Not fully understood
• 2 primary proposed mechanisms
o Functions as a steroid hormone
• Activation of signal transduction pathways linked to cell membrane VDRs
o Promotes genomic actions
• Interacts with nuclear VDRs influencing gene transcription
Vitamin excretion
• Metabolites are excreted in feces (>70%) and urine
Vitamin D skin production depends on
o Season o Latitude o Time of day o Degree of pigmentation o Age
Vitamin D deficiency in children
Children = rickets o Bone mineralization defects • Epiphyseal cartilage continues to grow without replacement by bone matrix and minerals • Wrists, ankles, and knees enlarge • Legs bow and knees knock as walking begins • Spine becomes curved • Pelvic and thoracic deformities occur o Dental abnormalities o Growth retardation o Muscle weakness o Seizures
Vitamin D deficiency in adults
Adults = osteomalacia o Bone mineralization defects • Secondary to changes in calcium and phosphate absorption and excretion • This stimulates PTH secretion • Which promotes bone resorption • Bone matrix is preserved but remineralization is impaired • Bone pain and softening of the bones results o Muscle weakness o Low back pain o Diffuse aches and pains o Hyperesthesia o Fatigue o Head sweating
Vitamin D deficiency increased risk
o Insufficient sun exposure o Living above 35 degrees latitude o The critically ill o Elderly, adolescents, and exclusively breastfed infants o Obesity o Fat malabsorption o Parathyroid disorders o Liver and kidney disease o Strict vegans
Vitamin D clinical indications
- Osteoporosis
- Psoriasis
- Cancer prevention
- Influenza prevention
Vitamin D preparations
• Ergocalciferol (D2)
o By prescription: 50,000 IU/pill, usually given once a week
• Cholecalciferol (D3)
o Preferred form for supplementation
• Natural form in humans
• More potent than D2
• More stable
• Less toxic
o Supplement: 400 - 1,000 IU/pill (Canada) - 50,000 IU/pill (US)
o Tablets, capsules, oil based liquids, emulsified liquids
Vitamin D toxicity
• Tolerable Upper Intake Level
o 1997: 50 µg (2,000 IU)
o 2010: 100 µg (4,000 IU)
• This may still be overly conservative
• 10,000 IU has been proposed based on risk assessment
• All documented cases of toxicity have been with >40,000 IU/d (1 case report with 25,000 IU/d)
• D2 may be more toxic than D3
• Excessive sun exposure is not associated with risk of vitamin D toxicity
Vitamin D toxicity symptoms
o Hypercalcemia and hypercalciuria o Hyperphosphatemia o Anorexia, constipation, nausea and vomiting o Muscle weakness o Hypertension and cardiac arrhythmias o Calcification of soft tissues o Renal dysfunction: polyuria, polydipsia, nephrolithiasis and renal failure o Mental confusion o Death
Vitamin D nutrient interactions
• Calcium and Phosphorus
o Vitamin D increases their intestinal absorption
o Vitamin D promotes their deposition into bone
• Magnesium is required for conversion to the active form
• Vitamin K
o Osteocalcin and matrix Gla protein synthesis are stimulated by 1,25(OH)2 D3
Vitamin D assessment of status
• Plasma concentration of 25-OH D3
o Deficient: 375 nmol/L
o Optimal: 125-200 nmol/L???
• Serum vitamin D levels
o Unreliable
o Very short t1/2 (~24 hrs)
o Only indicate recent intake or production
• Plasma concentration of 1,25(OH)2D3
o Unreliable d/t compensatory increase in PTH
o Levels often normal or elevated with vitamin D deficiency
