Vitamin D

Question 1

Vitamin D Background: First use, disease, etc.

Answer 1

• Ocean phytoplankton:
  
  • First sunscrren, photochemical signaling
• Anti-rachitic (cod liver oil/sunlight)
  
  • Bowed legs/rosary knobbed ribs
  • Smog with industrialization
  • C sections
  • Heat denatured cod liver oil cured rickets, not vitamin A
• UV radiate one arm cured whole body-hormone?
• D2 and D3 are pro-hormones→converted to hormone 1,25Dihydroxy D3
• Maintain serum ca/phosphate

Question 2

Two main forms of Vitamin D

Answer 2

• secosteroids
• B ring split by light
• D1: lumisterol and Vitamin D2
  
  • Tried to make D2 from ergosterol
• D3: Cholecalciferol
  
  • Skin to UVB
  • From 7-dehydrocholesterol
• D2: Ergocalciferol
  
  • Plants
  • From ergosterol

Question 3

Potency of D2 versus D3

Answer 3

• Use D3
• More effective at increasing 25,OH-D
  
  • What is measured in blood
• Metabolites bind stronger to VDR
• D2 half shorter shelf life

Question 4

Synthesis/Activation of D3

Answer 4

• Be able to draw
• 7-Dehydrocholesterol (Pro-VitD3)→Pre-VitD3 with UV light
• Pre-VitD3→VitD3 with heat
• VitD3→25-OHD3 (Calcidiol)
  
  • Bioactivation in liver; 25-Hydroxylase
  • CYP2R1 (rickets); CYP27A1
• Calcidiol→1,25(OH)₂D3 (Calcitrol-active)
  
  • kidney; CYP27B1; 1 alpha hydroxylase
  • Most important control point
• CYP24A1 inactivates to Calcitroic acid
• CYP3A4 and CYP24A1 to 1,24/23,25 (OH)₃D3
  
  • Drug induced osteomelacia with phenytoin
• UGT1A4 to glucoronide

Question 5

Photoactivation of 7-Dehydrocholesterol

Answer 5

• Be able to draw
• At 295 nm; need sun >45º above horizon; 35th parallel
• B ring absorb photon
• [1,7] hydrogen shift

Question 6

Vitamin D Receptor Activation

Answer 6

• 1,25 DHCC binds to VDR (hormone receptor)
• VDR heterodimerizes with RXR and goes to VDRE
• Promoter of calbindin and osteocalcin/ostepontin (bone forming)

Question 7

Vitamin D and Calcium Homeostasis Pathway

Answer 7

• VDR actiation of calbindin and ca transporters (TRPV5-kidney and TRPV6-gut)
• Calcium: teeth/bone, clotting, synapse, muscle
• Low calcium→PTH
• PTH→increase bone/kidney resorption, kidney calcidiol→calcitrol
• → increase fut absortion
• →Calcium sensor→GPCR→Negative feedback
• Kidney failure
  
  • Decrease ca resorption, decreased activation
  • Low Ca; Increased PTH
  • Bone resorption; metabolic bone disease

Question 8

VDR in Cell Proliferation/Differentiation

Answer 8

• High intake may reduce risk of certain cancer
• Calcitrol promotes apoptosis
• VDR polymorphisms and cancers
• Inconsistent data on protective effect of vitD
• Overall decreased death due to all causes

Question 9

Vitamin D sources

Answer 9

• Fish, sun, effs, liver, milk
• Cod liver oil=400IU/5ml

Question 10

Vitamin D: DV, UL, RDA

Answer 10

• DV: 400 IU
• UL:4,000 IU
• RDA: 600 IU (800 >70yo)
• 1 µg=40 IU

Question 11

Vitamin D toxicity

Answer 11

• Hypercalcification
• Over a period of time
• Under 12
  
  • 1-4 mo of 1,000 mg (40,000 IU)
• Adults: 2,500 mg (100,000 IU) in a few months

Question 12

VitD Deficency

Answer 12

• Assesed on 25-OH D3
• Natural if in sun=50-70 ng/ml
• Min to prevent ricket and osteomalacia: 15 ng/mL
• Deficency if <20 ng/ml (15 mmol)

Question 13

At risk for vitamin D deficiency

Answer 13

• Minmal sun (oldsters and youngster)
• Dark skin
• Religous skin cover
• Fat malabsorption
• Kidney failure
• Phenytoin (CYP3A4)

Question 14

Vitamin D Use

Answer 14

• 700-900 IU/day prevent fracture in postmenopausal
• Renal failure
  
  • hypocalcemia and secondary hyperparathyroidism
  • Rocaltrol (1, 25DHCC)
  • Paricalcitol, modification of calcitrol; 1 mg TIW

Question 15

Vitamin D Consumer Counseling and Advice (4)

Answer 15

• At least 400 IU/day-Multivit
• If minimal sun; 800 IU/day
• bone, reduce cancer risk
• Postmenopausal should take vitD supplement and calcium supplement