ABSTRACT
Vitamin A deficiency is characterized by changes in the tissue of the eye that ultimately result in irreversible blindness. Clinical symptoms are collectively referred to as xerophthalmia2 and include the following:
1. Night blindness-the inability to see in dim light 2. Conjunctival and corneal xerosis 3. Keratomalacia-ulceration and scarring of the cornea that leads to loss of vision
Other symptoms include skin lesions, loss of appetite, epithelial keratinization, lack of growth, and increased susceptibility to infections.2-4 Human status assessment methods include dietary assessment, assessment of content of liver, plasma, and breast milk, and functional assessment by dark adaptation and conjunctival impression cytology.4 Biochemical tests include the relative dose response test (RDR) and the modified relative dose response test (MRDR) that estimate liver stores of vitamin A. Such tests are useful to assess marginal vitamin A deficiency.5 Plasma retinol concentration is a commonly used measure of status.2,5 Measurement of the concentration of retinol binding protein in plasma is becoming an accepted status measure for clinical studies. However, the relationship of the retinol-binding protein concentration to the accepted retinol concentration of <0.70 µmol L−1 that reflects inadequacy is not completely defined.5 More recent clinical studies of deficiency use serum retinol concentration as the status indicator.6,7
Vitamin A toxicity (hypervitaminosis A) can occur because of high intake from either food high in vitamin A or high-potency supplements. Toxicity to retinoids has been
classified as acute, chronic, and teratogenic.2,8,9 Acute toxicity results from a single dose or a limited number of large doses over a short time period. A single dose greater than 200 mg (>200,000 retinol activity equivalent [RAE] >660,000 IU or 0.7 mmol) or all-trans-retinol can result in acute toxicity in adults. For children, 50% of the adult dose can cause acute toxicity.8 Symptoms include nausea, vomiting, headache, increased cerebrospinal fluid pressure, vertigo, blurred vision, muscle incoordination, and bulgind fonanel in infants.2 Chronic toxicity results from ingestion of large doses at or above 30 mg (30,000 RAE) per day for months or years.2 Symptoms of chronic toxicity include alopecia, ataxia, liver abnormalities, membrane dryness, bone and skin changes, visual impairment, and nervous system effects.2,8 Most symptoms are reversible when vitamin A intake is decreased.8 Teratogenic effects can result from simple, large doses (30-90 mg) or long-term intakes that result in chronic toxicity.8 Common teratogenic defects include physical malformations, heart, kidney, and thymic disorders, and central nervous system disorders.8 Penniston and Tanumihardjo9 show in a recent review that new studies suggest that subtoxicity without clinical signs of toxicity may be problematic in developed countries. Intake from preformed sources often exceeds recommended dietary allowances (RDAs). As an example of such concern, osteoporosis and hip fracture are associated with retinol intakes only twice the RDA.9
