Vitamin A

Question 1

Vitamin A sources

Answer 1

• Liver
• Dairy products: milk, cheese, butter
• Oily fish: tuna, sardines, herring
• Eggs
• Margarine - often fortified with vitamin A

Question 2

Vitamin A stability

Answer 2

• Lipid soluble

* Degraded by exposure to oxygen, light, and heat

Question 3

Vitamin A bio-availability

Answer 3

• 70-90% dietary vitamin A is absorbed as long as the meal contains about 10g of fat

Question 4

Vitamin A digestion

Answer 4

• 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)

Question 5

Vitamin A absorption

Answer 5

• 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

Question 6

Vitamin A transport

Answer 6

• 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

Question 7

Vitamin A storage

Answer 7

• 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

Question 8

Vitamin A functions

Answer 8

Visual functions
Normal cell differentiation
Reproduction
Immune defenses

Question 9

Vitamin A and visual functions

Answer 9

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

Question 10

Vitamin A and normal cell differentiation

Answer 10

• 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

Question 11

Vitamin A and reproduction

Answer 11

o Retinol only, not retinoic acid

o Spermatogenesis

Question 12

Vitamin A and immune defenses

Answer 12

o Vitamin A is involved in both humoral and cell mediated

Question 13

Vitamin A deficiency symptoms

Answer 13

• 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

Question 14

Vitamin A increased risk of deficiency

Answer 14

o	Hypothyroidism 
o	Fat malabsortive conditions
o	Liver or gallbladder disease
o	Chronic nephritis
o	Acute protein deficiency
o	Intestinal parasites
o	Acute infections

Question 15

Vitamin A clinical indications

Answer 15

• Opthalmological (blepharitis, chalazion, conjuctivitis, retinitis pigmentosa)
• Dermatological (acne vulgaris, actinic keratosis, burns, eczema, sunburn, warts)
• Infectious diseases (colds, measles)

Question 16

Vitamin A preparations

Answer 16

• 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

Question 17

Vitamin A toxicity

Answer 17

• 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

Question 18

Vitamin A duplicating study dose and supplementing high doses

Answer 18

• 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

Question 19

Vitamin A contraindication/cautions

Answer 19

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

Question 20

Acute hypervitaminosis A signs & symptoms

Answer 20

Increased intracranial pressure
Nausea/vomiting
Altered mental status
Headache 
Dizziness
Double vision
Weakness
Joint, muscle, and bone pain

Question 21

Chronic hypervitaminosis A signs & symptoms

Answer 21

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

Question 22

Vitamin A nutrient interactions

Answer 22

• 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

Question 23

Vitamin A assessment of status

Answer 23

• 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