Vitamin D

Question 1

Vitamin D

Sources & Recommendations

Answer 1

• “Vit D” refers to all precursor forms of calcitriol
• Can synthesize Vit D from 7-dehydrocholesterol in skin with adequate sunlight
• Vit D found in lipid-rich foods
  
  • liver oils
  • fatty fish
  • egg yolk
  • fortified milk or orange juice → 1 cup = 25% RDA
• DRI increased as benefits elucidated
  
  • RDA ↑ from 400 IU to 600 IU/day
  • TUL ↑ from 2000 IU to 4000 IU
• Meeting recommended levels by diet alone difficult
• Absorption inhibited by:
  
  • fat malabsorption
  • cystic fibrosis
  • ingestion of non-absorbable lipids

Question 2

Vitamin D

Transport and Storage

Answer 2

1. Dietary Vit D → chylomicrons → liver or adipose tissue → storage & use
2. Synthesized Vit D → travels in blood bound to vitamin D binding protein (DBP) → liver

Question 3

Vitamin D

Precursors

Answer 3

Found in both yeast and animal tissues:

1. Yeast
   
   • ergosterol → Vit D₂ (ergocalciferol)
   • ergocalciferol most common additive to fortify milk
2. Animals (dermal tissues)
   
   • 7-dehydrocholesterol → Vit D₃ (cholecalciferol) by exposure to UV-B

Question 4

Vit D

Synthesis

Answer 4

1. In dermal tissues:
   7-dehydrocholesterol → Vit D₃ (cholecalciferol)
   by exposure to UV-B
   
   • depends on availability of precursor in skin
     
     • ↓ with age
   • excess converted to inactive compounds → no toxicity
   • cholecalciferol → DBP (blood) → liver
2. In liver:
   Vit D₃ (& Vit D₂:DBP) → 25-OH hydroxycholecaciferol (calcidiol)
3. In kidney:
   Calcidiol → active 1,25-dehydroxycholecalciferol (calcitriol)

Question 5

Vit D

Regulation

Answer 5

1. Activation via hydroxylation:
   Vit D₂ and D₃ → calcidiol → calcitriol
   
   • Only occurs when [PTH] elevated
     
     • PTH synthesized by parathyroid when [Ca²⁺]_plasma ↓
2. Inactivation via hydroxylation:
   Liver and kidney perform additional hydroxylation rxn → inactivate calcitriol
   
   • Ex. calcitriol hydroxylated @ C₂₄ → calcitrioic acid → excretion
   • hepatic/renal pathologies can cause Vit D/calcium disturbances

Question 6

Renal Osteodystrophy

Answer 6

CKD ⨂ calcidiol → calcitriol

↓ Ca²⁺ absorption → ↓ [Ca²⁺]_plasma → ↑ [PTH]_plasma

⟾ bone demineralization → release Ca²⁺ and phosphate

⟾ phosphate retention → CaPO₄ precipitates in soft tissue

Treat with Vit D supplements & phosphate reduction therapy (aluminum-containing antacid)

Question 7

Calcitriol

Functions

Answer 7

Functions as steroid-hormone to ∆ gene expression

1° to maintain plasma [Ca²⁺]

1. Intestines:
   
   • ⊕ calbindin expression
     
     • ↑ intestinal calcium absorption
   • ↑ phosphate absorption
2. Bone:
   
   • ⊕ conversion of monocytes → osteoclasts
     
     • ↑ bone demineralization
3. Influences growth of certain cells

Question 8

Vit D

Deficiency

Answer 8

Leads to low calcium stores and bone deformities.

1. Rickets
   
   • seen in children
   • bones do not harden and are malformed
     
     1. bow-leggedness
     2. thickened wrists
     3. epiphyseal plate enlargement
     4. accumulation of unmineralized bone matrix
2. Osteomalacia
   
   • seen in adults
   • Ca²⁺ or Vit D deficiency → demineralization/softening of mature bone
     
     1. bone density ∆ similar to osteoporosis
     2. bone pain & muscle weakness common

Question 9

Vit D

Supplementation

Answer 9

• Useful for people who never get sun:
  
  • house-bound
  • live at northern latitudes
  • work at night
  • complete clothing coverage
• Routine Vit D supplementation also recommended d/t difficulty getting enough PO.
• Mother’s milk w/ low Vit D but high calcium.
  
  • Recommend Vit D supplement for breast-fed or pre-term infants, esp. dark-skinned.
• Liver or kidney disease can disburb bone metabolism even with adequte sunlight exposure.

Question 10

Vit D

Toxicity

Answer 10

Only from Vit D supplements.

Pathologic sequelae due to exaggerated effects of calcitriol:

1. Hypercalcemia
2. Weakness, fatigue, N/V
3. Deposition of calcium phosphate crystals in soft tissues/joints → metastatic calcification
4. Impaired renal function
5. Stunted growth in children due to bone demineralization