vitamin d hilarie stubbins colleen linehan. chemical name calciferol two main forms are vitamin d 2...
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Vitamin D
Hilarie StubbinsColleen Linehan
Chemical Name
• Calciferol
• Two main forms are Vitamin D2 and D3
– Ergocalciferol (D2)
– Cholecalciferol (D3)
Source: 1
Structure
• Derived from a steroid• Considered a seco-steroid because one of its
four rings is broken• Contains three intact rings (A, B, and D) with a
break between carbons 9 and 10 in the B ring
• Vitamin D2 and D3 have differing side chain structures
Source: 1
Vitamin D2
Vitamin D3
Vitamin D2 is obtained from plant sources
Vitamin D3 is obtained from the sun
Source: 1
Chief Functions
• The primary function of Vitamin D is to work with and help the body absorb and use calcium in order to sustain and build strong bones.
• Regulate immune system.
• Protection of the pancreas and stimulation of insulin.• Improve blood glucose control in those with a high
risk for diabetes.
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Functions Cont.
• Diminishes the production of hormones associated with high blood pressure.
• Decreases LDL.• Increases HDL.
• Protective against autoimmune conditions:– Rheumatoid Arthritis– Type I Diabetes– Multiple Sclerosis
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Metabolic Pathways
• Vitamin D3 begins in the skin by exposure to UV rays from sunlight.
• 7-dehydrocholesterol absorbs the photons from the UV radiation to stimulate previtamin D3.
• Thermal isomerization occurs to form vitamin D3.• This synthesis increases 25-OH D levels.• When Vitamin D2 is taken in, it is considered an
active substance.
Source: 2, 3
Metabolic Pathways Cont.
• Transported via chylomicrons.• Metabolic activation begins with the
hydroxylation of carbon 25.• Process occurs in the liver.• Hydroxylation cannot be regulated.• Indication of Vitamin D status is seen through
the plasma 25-OH D levels.
Source: 2, 3
Metabolic Pathways Cont.
• After the hydroxylation of Vitamin D, bioactivation occurs.
• Formed into 1, 25-dihydroxyvitamin D.
• Occurs in the kidneys.
Source: 2, 3
Vitamin D Transportation
• Transported into circulation by plasma proteins.• Most commonly bound to Vitamin D Binding
Protein (DBP).• DBP levels can be approximately 20x higher
than the total amount of vitamin D metabolites in plasma.
• This leaves limited access to target cells.
Source: 2, 3
Cont.
• The limited access reduces its susceptibility to hepatic metabolism and biliary excretion.
• This increases its circulating half-life.
• Predominately excreted through bile in the feces.
• Less than 30% is excreted through the urine.
Source: 1, 2, 3
Recommendations• Recommendations assume minimal sun
exposure RDAsInfants: 400 IU/dayChildren and adults, (ages 1-70), male and Female : 600 IU/day Adults 70+ : 800 IU/day
Pregnancy/lactating: 600 IU/day
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Factors affecting synthesis in skin
• Skin color/tone• Age • Latitudes• Season• Time of day• Clothing interference• Glass in windows
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Skin Color
• Persons with darker skin (due to their higher melanin content) require longer exposure to the sun than persons with lighter skin.
• This is because melanin blocks some of the UVB rays.
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Age
• Older people with diminished organ function and 7-dehydrocholesterol content in the skin impair calcitrol production.
7-dehydrocholesterol: a cholesterol precursor
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Latitude
• At latitudes above 35degrees, the UVB photon path length is longer, and fewer UVB photons reach the Earth.– This results in less Vitamin D synthesis in the skin.
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Season/Time of Day
• During spring, summer, and fall, exposure to sunlight for 5-15 minutes from the times of 10am-3pm is thought to provide sufficient amounts of vitamin D.
• In U.S.:1.5 IU/cm2/hour in winter6.0 IU/cm2/hour in summer Can be synthesized by skin.
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Deficiency
• Widespread throughout the United States and the World.
• Linked to several health conditions but most directly linked to rickets and osteomalacia
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Rickets
• Most common in children • Characterized by seizure, growth retardation,
and failure of bone to mineralize. • In deficient infants, the epiphyseal cartilage
grows and enlarges however, without replacement by bone matrix and minerals.
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Rickets Effects
• Effects are typically visible at wrists, ankles, and knees, which all enlarge.
• Long bones of legs bow, and knees knock as child grows and begins weight bearing activity.
• The spine becomes curved, and pelvic and thoracic deformities occur.– Characterized by costochondral beading at the
juncture of the ribs and cartilages.
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Osteomalacia
• Occurs in adults and some children• Characterized by bone demineralization• Results from prolonged elevations in blood
parathyroid hormone (PTH).• PTH promotes bone resorption and increased
urinary phosphorus excretion. • As bone turnover occurs, the bone matrix is
preserved but mineralization cannot occur.
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Osteomalacia
• Indicators of bone resorption include increased urinary excretion of bone collagen by-products such as:- Hydroxyproline- N-telopeptide- Pyridinoline- Deoxypyridinoline
• With insufficient serum calcium and phosphorous concentrations, the mineralization of bones cannot occur.
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Osteomalacia
• Progressive demineralization results in bone pain (throbbing or aching) and soft bones.
• Muscle weakness and general pain occur as well.
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Toxicity
• Tolerable Upper Intake = 4,000 IU for children, adolescents and adults.
• Vitamin D is one of the most likely vitamins to cause toxicity.
• Occurs with an intake of 10,000 IU/day for several months.
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Toxicity
• Too much sunlight cannot cause toxicity – Only raises serum concentrations to ~100-
200nmol/L, whereas levels greater than 500nmol/l• Manifestions of toxicity include:– Hypercalccemia, calcinosis and the calcification of
the soft tissues including the heart, kidneys, lungs and blood vessels.
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Toxicity
• Additional effects include, hyperphosphatemia, hypertension, anorexia, nausea, weakness, headache, renal dysfunction, and sometime death.
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Significant Sources
• Provided by a small number of foods of animal origin.
• Liver (1 ug/3oz)• Eggs (1.1 ug/egg)• Fatty Fish- herring (2.4ug/3oz), salmon
11ug/3oz), tuna 1.7ug/3oz) and sardines (4.1ug/3oz)
• Small amounts in cheese and butter
Source: 1
Significant Sources
• Plant Origin-shitake mushrooms (0.5ug/1/2C)• Fortified sources:
– Milk– Yogurt– Cheese– Butter, margarine– Orange juice– Breads– Some cereals
• Supplements
Source: 1
References
1. Gropper SS, Smith JL. Advanced Nutrition and Human Metabolism, 6th ed. Belmont, CA: Wadsworth; 2013.
2. Battault S, Whiting SJ, Peltier SL, Sadrin S, Gerber G, Maixent JM (2012) 'Vitamin D metabolism, functions and needs: from science to health claims', Eur J Nutr, 52, pp. 429-441.
3. Dusso AS, Brown AJ, Slatopolsky E (2005) 'Vitamin D', Am J Physiol Renal Physiol, 289, pp. 8-22