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Updated: Mar 2 2023

Fat Soluble Vitamins

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https://upload.medbullets.com/topic/102003/images/vitamin.jpg
  • Overview 
    • Examples 
      • A
      • D
      • E
      • K
    • Characteristics
      • precursors for coenzymes
      • pancreatic enzymes required for absorption in the ileum
        • malabsorption syndromes can cause fat-soluble vitamin deficiencies
          • e.g. steatorrhea, cystic fibrosis, and sprue
      • stored in fat making toxicity possible (unlike water soluble vitamins)
  • Vitamin A (Retinol)
    • Function
      • antioxidant
        • neutralize free radicals
      • constituent of visual pigments (retinal)
        • β-carotene from diet enzymatically converted to cis-retinal, which undergoes photoisomerization to trans-retinal when light is absorbed
        • co-factor for protein rhodopsin
      • essential for normal differentiation of epithelial cells into specialized tissue
        • pancreatic and mucus-secreting cells
        • binds intracellular receptors that regulate transcription at the retinoic acid response elements
      • immune system stimulation
        • stimulates T-cell differentiation and proliferation
        • vitamin A supplementation recommended for measles treatment
      • retinitis pigmentosa
        • vitamin A supplementation used as a treatment in retinitis pigmentosa (usually autosomal dominant)
    • Source
      • found in liver and green/yellow vegetables
      • β-carotene also a source
        • dimer of retinal that must be cleaved and converted to trans-retinol for intestinal absorption
      • isotretinoin
        • form of retinoic acid used in treatment of acne
    • Deficiency
      • causes
        • deficiency in dietary intake
          • due to storage in fat must occur over several months
        • malabsorption
        • fat-free diets
        • night blindness
        • xerophthalmia
        • squamous metaplasia of corneal epithelium
          • spots are known as Bitot spots
        • follicular hyperkeratosis
          • dry skin due to loss of sebaceous gland function
        • frequent infections
    • Excess
      • causes
        • over supplementation
          • regular intake > 15 x RDA
        • consumption of wild game liver
        • isotretinoin treatment
      • symptoms
        • arthralgias
          • periosteal proliferation
        • alopecia
        • papilledema and seizures
          • result of intracranial swelling
        • skin changes
          • yellow pigment with excess β-carotene but sclera remain white
            • contrasted with jaundice which sclera and skin turn yellow
      • teratogenic
        • cleft palate and cardiac abnormalities
        • a pregnancy test must be done before isotretinoin is prescribed for severe acne
  • Vitamin D
    • Function
      • raise low blood calcium concentrations
        • ↑ duodenal absorption of calcium and phosphate
        • ↑ reabsorption of calcium from distal renal tubules
        • ↑ bone resorption via activation of osteoclasts
          • bisphosphonates inhibit activation of osteoclasts and ↓ bone resorption
            • e.g., ibandronate, risedronate, and alendronate
      • remodeling of bone
        • osteoblasts have receptors for vitamin D
        • binding stimulates release of alkaline phosphatase (alk-phos)
        • alk-phos dephosphorylates pyrophosphate
          • pyrophosphate normally inhibits bone mineralization
      • matures macrophage stem cells into osteoclasts
    • Source
      • pre-formed ingestion in diet
        • D2 = ergocalciferol
          • ingested from plants
          • used as pharmacologic agent
        • D3 = cholecalciferol
          • consumed in milk and fish
      • formed in sun-exposed skin
        • 7-dehydrocholesterol → cholecalciferol (D3) in skin catalyzed by UV light
          • step insufficient in climates where low temperatures do not allow for sun exposure
        • cholecalciferol (D3) → 25-hydroxycholecalciferol (25-OH D3) in liver catalyzed by 25-hydroxylase
          • decrease in hepatic function may result in vitamin D deficiency
            • must supplement with 25-OH D3
          • occurs in the P450 system
        • 25-OH D3→ 1,25-dihydroxycholecalciferol (1,25-(OH)2 D3) in kidney catalyzed by 1α-hydroxylase
          • 1α-hydroxylase upregulated by PTH in response to hypocalcemia
          • decrease in renal function may result in vitamin D deficiency
            • pseudo-vitamin D deficiency rickets
              • hereditary deficiency in 1α-hydroxylase
            • must supplement with 1,25-(OH)2 D3 equivalent
      • 25-OH D3 = storage form
      • 1,25-(OH)2 D3 (calcitriol) = active form
    • Deficiency
      • causes
        • low sunlight exposures
        • hepatic or renal function decrease
        • fat malabsorption
        • induction of P450 which degrades active vitamin D precursors
        • exclusive breastfeeding
      • symptoms
        • rickets in children (bending bones)
        • osteomalacia in adults (soft bones)
        • hypocalcemic tetany
    • Excess
      • causes
        • supplementation > 10x RDA
        • seen in sarcoidosis
          • ↑ activation of vitamin D by epithelioid macrophages
      • symptoms
        • polyuria, polydipsia, and nocturia
        • hypercalcemia and hypercalciuria
          • high blood calcium concentration promotes metastatic calcification
        • loss of appetite and stupor
        • high levels of vitamin D promote bone resorption
  • Vitamin E (α-tocopherol)
    • Function
      • antioxidant
      • prevents peroxidation of fatty acids allowing membranes to maintain normal fluidity
      • prevents oxidation of LDL
      • protects against arteriosclerosis
    • Deficiency
      • rare
      • causes
        • fat malabsorption
          • abetaliproteinemia
      • symptoms
        • ↑ fragility of erythrocytes (hemolytic anemia)
        • muscle weakness
        • neurodysfunction
          • poor joint sensation and ataxia
    • Excess
      • synergistic ↓ in vitamin K dependent clotting factors with warfarin
        • potential hemorrhage in warfarin patients
  • Vitamin K
    • Function
      • catalyzes γ-carboxylation of glutamic acid residues on blood clotting proteins
        • cofactor for γ-glutamyl carboxylase
        • allows Ca2+ binding site
        • co-translational modification in RER
        • necessary for the synthesis of clotting factors II (prothrombin), VII, IX, X, and protein C and S
      • must be activated by epoxide reductase enzymes
        • inhibited by warfarin, which is a vitamin K antagonist
        • an anticoagulant in vivo (not in vitro)
        • 2-3 days required to achieve anticoagulation
          • heparin given for immediate results
    • Source
      • normal gut bacterial flora
      • green vegetables
      • breast milk does NOT contain vitamin K
    • Deficiency
      • causes
        • fat malabsorption
        • neonates have sterile intestines and are unable to synthesize vitamin K
          • aggravated by mothers who took anticonvulsants during pregnancy
          • neonates are given vitamin K injection at birth to prevent hemorrhage
        • can also occur after prolonged use of broad-spectrum antibiotics
          • destruction of normal gut flora
        • ↓ in hepatic function can ↓ vitamin K activation
      • symptoms
        • ↑ PT and normal aPTT, but normal bleeding time (can also see increased aPTT, but as factor VII has the shortest half-life, PT increases before aPTT)
          • easy bruising and bleeding
          • hemorrhagic disease of the newborn
    • Excess
      • rare
      • symptoms
        • hemolytic anemia and liver damage
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