Vitamin A toxicity can be acute (usually due to accidental ingestion by children) or chronic. Both types usually cause headache and increased intracranial pressure. Acute toxicity causes nausea and vomiting. Chronic toxicity causes changes in skin, hair, and nails; abnormal liver test results; and, in a fetus, birth defects. Diagnosis is usually clinical. Unless birth defects are present, adjusting the dose almost always leads to complete recovery.
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 and retinoids against some epithelial cancers is under study, but beta-carotene and retinoids are not recommended for prevention of cancer or cardiovascular disease (1).
When taken as a supplement, beta-carotene has been associated with increased cancer (eg, lung cancer) (2) and cardiovascular risk (3); risk does not seem to increase when carotenoids are consumed in fruits and vegetables.
(See also Overview of Vitamins.)
References
1. Moyer VA; U.S. Preventive Services Task Force. Vitamin, mineral, and multivitamin supplements for the primary prevention of cardiovascular disease and cancer: U.S. Preventive services Task Force recommendation statement. Ann Intern Med. 2014;160(8):558-564. doi:10.7326/M14-0198
2. O'Connor EA, Evans CV, Ivlev I, et al. Vitamin and Mineral Supplements for the Primary Prevention of Cardiovascular Disease and Cancer: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force. JAMA. 2022;327(23):2334-2347. doi:10.1001/jama.2021.15650
3. Yang J, Zhang Y, Na X, Zhao A. β-Carotene Supplementation and Risk of Cardiovascular Disease: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Nutrients. 2022;14(6):1284. Published 2022 Mar 18. doi:10.3390/nu14061284
Etiology of Vitamin A Toxicity
Acute vitamin A toxicity in children may result from taking large doses (> 300,000 international units [IU] [> 100,000 mcg RAE]), usually accidentally. In adults, acute toxicity has occurred when arctic explorers ingested polar bear or seal livers, which contain several million IU of vitamin A.
Chronic vitamin A toxicity in older children and adults usually develops after doses of >>vitamin Avitamin A) for acne treatment or who have taken megadoses of vitamin A 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.
Symptoms and Signs of Vitamin A Toxicity
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, idiopathic intracranial hypertension (pseudotumor cerebri), and generalized weakness develop.
Cortical hyperostosis of bone and arthralgia may occur, especially in children. Fractures may occur easily, especially in older adults. In children, toxicity can cause pruritus, anorexia, and failure to thrive. Hepatomegaly and splenomegaly may occur; children are affected most.
In carotenosis, the skin (but not the sclera) becomes deep yellow, especially on the palms and soles.
Diagnosis of Vitamin A Toxicity
Clinical evaluation
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.
Treatment of Vitamin A Toxicity
Vitamin A is stopped.
Prognosis for Vitamin A Toxicity
Complete recovery usually occurs if vitamin A ingestion stops. Symptoms and signs of chronic toxicity usually disappear within 1 to 4 weeks. However, birth defects in the fetus of a mother who has taken megadoses of vitamin A or isotretinoin are not reversible.
Key Points
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 older adults.
Diagnose based on clinical findings.
When vitamin A is stopped, symptoms (except birth defects) usually resolve within 1 to 4 weeks.
