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Updated: 3/2/2023

Fat Soluble Vitamins

Review Topic
  • 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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(M1.BC.15.4343) A 37-year-old female presents to her primary care physician with constipation and abdominal pain. She notes that the pain has been present for several days and is not related to food. She also reports increased urinary frequency without incontinence, as well as increased thirst. She takes no medications, but notes taking vitamin supplements daily. Her vital signs are: BP 130/72 mmHg, HR 82 bpm, T 97.0 degrees F, and RR 12 bpm. Lab studies reveal: Na 139, K 4.1, Cl 104, HCO3 25, Cr 0.9, and Ca 12.4. Further studies show an increased ionized calcium, decreased PTH, and increased phosphate. What is the most likely cause of this patient's symptoms?

QID: 107035

Vitamin deficiency



Vitamin overdose



Primary endocrine dysfunction



Plasma cell neoplasm



Inherited disorder



M 4 D

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(M1.BC.15.74) A 19-year-old African female refugee has been granted asylum in Stockholm, Sweden and has been living there for the past month. She arrived in Sweden with her 2-month-old infant, whom she exclusively breast feeds. Which of the following deficiencies is the infant most likely to develop?

QID: 106608

Vitamin A



Vitamin B1



Vitamin D



Vitamin E



Vitamin C



M 1 E

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(M1.BC.14.6) You are counseling a pregnant woman who plans to breast-feed exclusively regarding her newborn's nutritional requirements. The child was born at home and the mother only plans for her newborn to receive vaccinations but no other routine medical care. Which vitamins should be given to the newborn?

QID: 100071

Folic acid



Vitamin B6



Vitamin K



Vitamin D



Vitamin K and Vitamin D



M 1 E

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(M1.BC.14.1) A 73-year-old male presents to the the clinic with lumbar pain and symmetrical bone pain in his legs and arms. He has trouble going up to his bedroom on the second floor and getting up from a chair. Past medical history reveals that he has had acid reflux for the past 5 years that is refractory to medications (PPIs & H2 antagonists); thus, he had decided to stay away from foods which have previously given him heartburn - red meats, whole milk, salmon - and has eaten a mainly vegetarian diet. Which of the following processes is most likely decreased in this male?

QID: 106287

Bone mineralization



Iron absorption



Collagen synthesis



Degradation of branched chain amino acids



Degradation of hexosaminidase A



M 1 D

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(M1.BC.13.22) A 6-month-old boy presents with decreased growth, pigmented retinopathy, hemolytic anemia, and peripheral neuropathy. You suspect that these signs are the result of a vitamin deficiency leading to increased fatty acid oxidation. Which of the following is most likely responsible for this patient's symptoms?

QID: 101686

Pernicious anemia






Goat milk ingestion



Hartnup disease



Excessive boiling of formula



M 2 E

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Evidence (8)
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