Vitamin A Toxicity
Vitamin A is required for the formation of rhodopsin, a photoreceptor pigment in the retina (see table Sources, Functions, and Effects of Vitamins). Vitamin A helps maintain epithelial tissues and is important for lysosome stability and glycoprotein synthesis.
Dietary sources of preformed vitamin A include fish liver oils, liver, egg yolks, butter, and vitamin A–fortified dairy products. Normally, the liver stores 80 to 90% of the body’s vitamin A. To use vitamin A, the body releases it into the circulation bound to prealbumin (transthyretin) and retinol-binding protein. Beta-carotene and other provitamin carotenoids, contained in green leafy and yellow vegetables, carrots, and deep- or bright-colored fruits, are converted to vitamin A. Carotenoids are absorbed better from vegetables when they are cooked or homogenized and served with some fat (eg, oils).
Retinol activity equivalents (RAE) were developed because provitamin A carotenoids have less vitamin A activity than preformed vitamin A; 1 mcg retinol = 3.33 units.
Synthetic vitamin analogs (retinoids) are being used increasingly in dermatology. The possible protective role of beta-carotene, retinol, and retinoids against some epithelial cancers is under study. However, risk of certain cancers may be increased after beta-carotene supplementation.
(See also Overview of Vitamins.)
Acute vitamin A toxicity in children may result from taking large doses (> 300,000 units [> 100,000 RAE]), usually accidentally. In adults, acute toxicity has occurred when arctic explorers ingested polar bear or seal livers, which contain several million units of vitamin A.
Chronic vitamin A toxicity in older children and adults usually develops after doses of > 100,000 units (> 30,000 RAE)/day have been taken for months. Megavitamin therapy is a possible cause, as are massive daily doses (150,000 to 350,000 units [50,000 to 120,000 RAE]) of vitamin A or its metabolites, which are sometimes given for nodular acne or other skin disorders. Such megadoses can cause liver toxicity. Adults who consume > 4500 units (> 1500 RAE)/day of vitamin A may develop osteoporosis. Infants who are given excessive doses (18,000 to 60,000 units [6,000 to 20,000 RAE]/day) of water-miscible vitamin A may develop toxicity within a few weeks. Birth defects occur in children of women receiving isotretinoin (which is related to vitamin A) for acne treatment during pregnancy. Megadoses of vitamin A can cause liver toxicity.
Although carotene is converted to vitamin A in the body, excessive ingestion of carotene causes carotenemia, not vitamin A toxicity. Carotenemia is usually asymptomatic but may lead to carotenosis, in which the skin becomes yellow.
When taken as a supplement, beta-carotene has been associated with increased cancer risk; risk does not seem to increase when carotenoids are consumed in fruits and vegetables.
Although symptoms of vitamin A toxicity may vary, headache and rash usually develop during acute or chronic toxicity.
Acute toxicity causes increased intracranial pressure. Drowsiness, irritability, abdominal pain, nausea, and vomiting are common. Sometimes the skin subsequently peels.
Early symptoms of chronic toxicity are sparsely distributed, coarse hair; alopecia of the eyebrows; dry, rough skin; dry eyes; and cracked lips. Later, severe headache, pseudotumor cerebri, and generalized weakness develop. Cortical hyperostosis of bone and arthralgia may occur, especially in children. Fractures may occur easily, especially in the elderly. In children, toxicity can cause pruritus, anorexia, and failure to thrive. Hepatomegaly and splenomegaly may occur.
In carotenosis, the skin (but not the sclera) becomes deep yellow, especially on the palms and soles.
Diagnosis of vitamin A toxicity is clinical. Blood vitamin levels correlate poorly with toxicity. However, if clinical diagnosis is equivocal, laboratory testing may help. In vitamin A toxicity, fasting serum retinol levels may increase from normal (28 to 86 mcg/dL [1 to 3 mcmol/L]) to > 100 mcg/dL (> 3.49 mcmol/L), sometimes to > 2000 mcg/dL (> 69.8 mcmol/L). Hypercalcemia is common.
Differentiating vitamin A toxicity from other disorders may be difficult. Carotenosis may also occur in severe hypothyroidism and anorexia nervosa, possibly because carotene is converted to vitamin A more slowly.
Vitamin A toxicity can be caused by ingesting high doses of vitamin A—acutely (usually accidentally by children) or chronically (eg, as megavitamin therapy or treatment for skin disorders).
Acute toxicity causes rash, abdominal pain, increased intracranial pressure, and vomiting.
Chronic toxicity causes rash, increased intracranial pressure, sparse and coarse hair, dry and rough skin, and arthralgia; risk of fractures is increased, especially in the elderly.
Diagnose based on clinical findings.
When vitamin A is stopped, symptoms (except birth defects) usually resolve within 1 to 4 weeks.
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