Vitamin D Flashcards
What are the characteristics of fat soluble vitamins?
- Digestion, absorption, transport associated with that of lipids
- Vitamins D, E, and carotenoids present mostly in free unesterified forms in foods
- Absorption assisted by bile acids
- Transported into bloodstream in chylomicrons (lymphatic system), taken up during hydrolysis
- Stored in body lipids, although amount stored varies widely among fat-soluble vitamins
- CM remants return to liver with remaining vitD
Give a brief over view of the fat soluble vitamins:
1. Function
2. Deficiency/symptoms
3. Good sourves
4. RDA/AI
What is the biological function of vitamin D?
- Calcium balance
- Immunomodulator - Deficiency associated with increased risk of auto-immune disease
- Regulates cell growth - anti-proliferative effects
- Reduces hypertension - renin production is downregulated Vitamin D
How does Vitamin D impact calcium?
- Active vitamin D helps maintain normal plasma calcium concentrations
- Intestine: Increased efficiency of intestinal calcium absorption (from basal of 10-15%… also increases phosphorous absorption)
- Bones and kidneys: along with PTH, actve itD induces the formation and activation of osteoclasts (mobilizes Ca from bone) and increases renal distal tubule reabsorption of calcium
- Most of these effects are mediated through alterations in gene expression
What are the different structures of vitamin D and which is the active form
- Active has 2 hydroxyl groups. Addition of first hydroxyl happens in kidney. Second happens in liver.
- Forms: DHC, VitD3, Previtamin D (25(OH)D) and active vit D 1,25(OH)2D (calcitriol)
What factors can affect vitamin D synthesis from sunlight?
- Skin colour: increased skin pigmentation, decreased production of previtamin D (melanin blocks UVB)
- Ageing: decreased [7DHC] in the epidermis and the capacity for the skin to produce Vit D
- Sunscreens: diminished the production of Vit D from the skin because sunscreens absorb UV radiation
- Clothing
- Obesity: vitamin D is lipid soluble and with increased adipose tissue over time Vit D is stored and less is accessible.. may also have reduced sun exposure
Explain the concept of photobiology and how it impacts Vit D
How much sun do we need?
- by being exposed to the sun, and therefore UVB radiation, 7-DHC can be converted to previtamin D
- Time and body temp then converts this to Vitamin D3 which goes into circulation
- Adequate previtamin D may be obtainable by 5-15 minutes sun exposure, 10AM to 3PM, during summer
- Higher latitudes and during winter months, UVB photon path length too long for significant Vit D synthesis
Are foods good sources of Vitamin D?
- It is rare to find naturally occurring active Vit D in foods
- VitD2 - found in plants
- VitD3 - found in animals
What foods provide natural sources of vitamin D?
- fatty fish (tuna, salmon, sardines, mackerel)
- Egg yolks
- Beef liver
- Some mushrooms
What fortified food products are good sources of vitamin D?
- cow’s milk, yogurt, soy beverages
- OJ
- Ready to eat cereal
- Margarine
- Infant formula
What groups are at risk for vitamin D inadequacy?
- Breastfed infants - related to maternal intake
- Older adults
- People with limited sun exposure
- People with dark skin
- People with fat malabsorption
- People who are obese or have undergone bypass surgery - serum levels may rise temporarily with weight loss
Can you have toxicity of Vitamin D?
- Toxicity of vitamin D in the skin is impossible
- Vit D is photosensitive and degraded by increased exposure to sunlight
- Excess intake of Vit D can lead to a state of vit D “intoxication” or “hypervitaminosis D”
→ Leads to hypercalcemia and eventually soft tissue calcification = renal and cardiovascular damage if left unchecked (large amounts on a long term basis)
How does Vitamin D in children present? What are the symptoms?
- RICKETS
- If epiphyseal plates have not closed Vit D deficiency results in disorganization and hypertrophy of chondrocytes (bone is not organized/symmetrical)
- Symptoms: softening of the bones, short stature, bone deformities
What is the process of turning 7-DHC into active vitamin D?
- 7DHC in skin converted to previtamin D3 by UVB rays.
- Thermal isomerization to Vitamin D3.
- Vit D3 can translocate from skin to cells to blood via VDBP
- Once in liver 25-OH-ase hydroxylated to form 25-hydroxyvitamin D3
- 25Hydroxyvitamin D3 can be catabolized into 24,25 Dihydroxyvit D3 OR activated by Kidney 1alpha-OHase (CYP27B1) into 1,25Dihydroxyvit D3
- 1,25 DihidroxyvitD3 can be transported to tissues and a ligand for VDR or catabolized furthur into trihydroxyvit 3
What is the negative feedback loop for Vit D3 synthesis?
- As plasma concentration of 1,25(OH)2D increases, there is a decrease in CYT27B1 and increase in CYP23A1gene expression
- CYP27B also suppressed by FGF-23
What is the best measure of vitamin D status?
- 25(OH)D
What effect does PTH have?
Can increase CYP27B1 gene expression for more activation of VitD3
What are the proteins important in vitamin D metabolism?
- Vitamin D binding protein is responsible for binding Vit D3 from the skin or diet
- Then takes it to the liver where 25-OHase converts it to 25(OH)D3. Rebound to DBP
- Sent to kidney and periphery where 1alpha-OHase activates it! Leads to paracrine and autocrine effects or classical effects
Why does disorders affecting the parathyroid, liver, or kidney impair synthesis of active vitamin D?
- What three things are impacted by active Vit D?
- What effect does calcitonin, calcium, and phosphate have on the kidney?
- Thyroid releases PTH which stimulates kidney to convert previtamin D to active vitamin D
- Active Vitamin D acts on kidney, intestine, and bone to increase calcium and phosphate levels. Then inhibit PTH
- Low calcium and phosphate levels stimulate thyroid and kidney for more Vit D activation
- Calcitonin activates kidney
- Kidney can inhibit PTH release directly
In patients with renal disease, oral supplements or intravenous injections of calcitriol are often prescribed
Summarize the synthesis and metabolism of Vit D
Extremely important slide
What is the different between Vit D3 and Vit D2?
- Vit D3 in animal products is much more biologically active than Vit D2
- The biological activity of Vit D2 is 20-40% that of Vit D3
- Less biological activity due to the extra double bond on Vit D2
What are the AI values (1997) for vitamin D based on?
- Infants, children, adults
- Based on AIs because EARs were difficult to determine
- Infants: Based on the average intake from breast fed and formula fed infants
- Children: Based on children’s needs regardless of exposure to sunlight
- Adults: Based on serum concentration of 25(OH)D
- Currently available data on bone health outcomes-when considered as an integrated body of evidence - can be used to derive EARs and RDAs for calcium and vit D for all life stages except infants
What are the new DRI (RDAs) for Vit D?
What is the best indicator of vitamin D status and why?
- Serum [25(OH)D] best indicator
- Biomarker of exposure
- Reflects Vit D from cutaneous, food sources, supplements
- Long circulating half life (~15 days). Not degraded as quickly as other molecules
- Does not indicate amount stored though!!
