Vitamin A Flashcards
Vitamin A sources
- Liver
- Dairy products: milk, cheese, butter
- Oily fish: tuna, sardines, herring
- Eggs
- Margarine - often fortified with vitamin A
Vitamin A stability
- Lipid soluble
* Degraded by exposure to oxygen, light, and heat
Vitamin A bio-availability
• 70-90% dietary vitamin A is absorbed as long as the meal contains about 10g of fat
Vitamin A digestion
- Retinol is typically bound to retinyl esters
- These retinyl esters (and carotenoid esters) are often complexed with proteins in the diet
- These proteins need to be removed by pepsin in the stomach & proteolytic enzymes in duodenum
- Because of their fat solubility the retinol esters form fat globules
- Bile acids & phospholipids emulsify the fat globules and form micelles
- Pancreatic and brush boarder enzymes are required to break off fatty acid chains to form free retinol (and/or carotenoids)
Vitamin A absorption
- Vitamin A & carotenoids are absorbed in the duodenum and jejunum by a specific protein carrier in low doses and by passive diffusion in high doses
- Vitamin A is also absorbed through the skin after topical application
Vitamin A transport
• Retinol
o Requires esterification for transport
o Esterification is regulated by cellular retinol binding protien (CRBP) II
o Lecithin retinol acyltransferase (LRAT) or acyl-retinol acyltransferase (ARAT) converts retinol bound to CRBPII to retinyl esters
o Retinyl esters in enterocytes are then incorporated into chylomicrons for transport
o Chylomicrons carry retinyl esters to various peripheral cells and tissues in the body
o The remaining retinyl esters are then brought to the liver in the chylomicron remnants
• Retinyl esters are transported out of the liver in blood via 2 proteins
o Retinol binding protein (RBP)
• Carries retinol from liver to the tissues
• Dependent on protein, retinol, and zinc status
• RBP binds to transthyretin (TTR) preventing filtration by the kidney
o Transthyretin (TTR)
• Circulates bound to T4
• Retinoic acid
o Unlike retinol can enter circulation through the portal vein
o Is bound to albumin in the blood
Vitamin A storage
• Retinol that is esterified may be stored in the liver
o In stellate cells (primarily) & parenchymal cells
o Bound to cellular retinol-binding protein I (CRBPI)
• Liver contains 90% of the body’s vitamin A stores
o 100 to 1000 IU per gram of tissue
o A healthy person has about 500,000 IU, enough to last for several years
o Hypervitaminosis A develops when stellate cells cannot take up anymore vitamin A
Vitamin A functions
Visual functions
Normal cell differentiation
Reproduction
Immune defenses
Vitamin A and visual functions
o Vitamin A (retinol only, no retinoic acid) is involved in dark adaptation (dim light rod functioning)
o LRAT converts retinol into all-trans retinyl esters (and some 11-cis retinyl esters), which can be stored until needed in the pigment epithelium of the eye
o The retinyl esters are then converted into 11-cis retinol and then into 11-cis retinal, still in the pigment epithelium
o Cis-retinal is transported into the retina where it combines with opsin to form rhodopsins
o Light causes a conversion to trans-retinal
o Opsin and retinal separate as a nerve impulse is sent to the brain
o Trans-retinal is released from rod cell into the pigment epithelium of the retina and is converted back to cis-retinal
o The eye only contains 0.1% of the vitamin A in the body
o Retinoic acid cannot be used for vision
Vitamin A and normal cell differentiation
- Skin, conjunctiva, sinuses, gastrointestinal, respiratory, and genitourinary tracts
- In vitamin A deficiency squamous and keratinized cells increase while mucin-secreting columnar and cuboidal cells decrease
Vitamin A and reproduction
o Retinol only, not retinoic acid
o Spermatogenesis
Vitamin A and immune defenses
o Vitamin A is involved in both humoral and cell mediated
Vitamin A deficiency symptoms
• Uncommon in North America but it is fairly common in children under 5 in the developing world
• Deficiency symptoms:
o Follicular hyperkeratosis (phrynoderma)
o Retarded growth
o Impaired spermatogenesis
o Increased infections
o Night blindness (impaired dark adaptation)
o Xerophthalmia
• Disappearance of goblet cells of the conjunctiva resulting in dryness (keratomalacia) from inadequate mucin production
• This leads to enlargement and keratinization of epithelial cells and the appearance of Bitot’s spots over the keratinized epithelia
• This will eventually cause scarring and ulceration of the cornea which can ultimately result in permanent blindness
Vitamin A increased risk of deficiency
o Hypothyroidism o Fat malabsortive conditions o Liver or gallbladder disease o Chronic nephritis o Acute protein deficiency o Intestinal parasites o Acute infections
Vitamin A clinical indications
- Opthalmological (blepharitis, chalazion, conjuctivitis, retinitis pigmentosa)
- Dermatological (acne vulgaris, actinic keratosis, burns, eczema, sunburn, warts)
- Infectious diseases (colds, measles)
Vitamin A preparations
- Most commonly available as all-trans retinyl palmitate or all-trans retinyl acetate
- Oil-based forms have the least risk of toxicity
- For people with fat malabsorptive disorders use a water-miscible form (e.g. Aquasol A), emulsified form, or a solid (dry) form
Vitamin A toxicity
• Tolerable Upper Intake Level (UL) = 3,000 µg RAE (10,000 IU) per day of preformed vitamin A
• Varies with type of preparation used
o Water-miscible, emulsified, and solid (dry) preparations have toxic effects seen at doses 10% as high as oil preparations (i.e. 50,000 IU/d versus 500,000 IU/d)
• Teratogenicity
o >4,500 µg RAE (1500 IU) per day of preformed vitamin A in pregnant women has been associated with birth defects
o However, women should not be of vitamin A while pregnant as deficiency has also been associated with defects
Vitamin A duplicating study dose and supplementing high doses
• When duplicating dosages of vitamin A in published reports that do not specify the type of preparation administer oil based vitamin A to decrease risk of toxicity
• When supplementing at high doses:
o Watch for early warning signs of toxicity:
• Dry skin
• Fatigue
• Headaches
• Pain in joints, muscles and bones
o Periodically monitor serum calcium and liver function tests in patients taking high dose vitamin A
Vitamin A contraindication/cautions
o Elevated serum vitamin A levels are common in patients with end stage renal disease and therefore these patients should not be given supplemental vitamin A
o People with liver disease, malnutrition, and alcoholism have developed vitamin A toxicity while taking <50,000 IU/d
Acute hypervitaminosis A signs & symptoms
Increased intracranial pressure Nausea/vomiting Altered mental status Headache Dizziness Double vision Weakness Joint, muscle, and bone pain
Chronic hypervitaminosis A signs & symptoms
Increased intracranial pressure Ataxia Anorexia Headache Dry, itchy & general desquamation of the skin Alopecia & brittle nails Joint, muscle, and bone pain Increased bone fractures Conjunctivitis & ocular pain Liver damage
Vitamin A nutrient interactions
• Vitamin K – excess vitamin A intake inhibits vitamin K2 synthesis by intestinal bacteria
• Vitamin E – may enhance absorption and tissue uptake of vitamin A
• Iodine – doses of vitamin A >50,000 IU/d may decrease iodine uptake by thyroid
• Iron – Vitamin A deficiency is associated with decreased iron incorporation into RBCs and diminished mobilization of iron from stores
• Protein & zinc
o Cleavage of beta-carotene to vitamin A is depressed with inadequate protein intake
o Transport & use of vitamin A depends on several binding proteins and zinc is required for the synthesis of these proteins
o Conversion of retinol to retinal also requires zinc
Vitamin A assessment of status
• In the absence of frank deficiency or excess, serum retinol levels are not a reliable indicator of vitamin A status
• Physical exam – look for follicular hyperkaretosis, not specific
• Conjunctival impression cytology (CIC)
o Absence of goblet cells and the presence of enlarged epithelial cells in the conjunctiva indicate vitamin A deficiency
• Relative dose response (RDR) test
o Measures plasma retinol levels before and 5 hours after oral administration
o The difference in concentration is calculated
