Vitamin A Toxicity
Vitamin A is an important fat-soluble vitamin. Its basic molecule is a retinol, or vitamin A alcohol. After absorption, retinol is transported via chylomicrons to the liver, where it is either stored as retinol ester or re-exported into the plasma in combination with retinol-binding protein for delivery to tissue sites.
Dietary vitamin A is obtained from preformed vitamin A (or retinyl esters) from animal food (liver, milk, kidney, and fish oil), fortified foods, and drug supplements, as well as from provitamin A carotenoids from plant sources, principally carrots. Dietary vitamin A is available mainly as preformed vitamin A in western countries and as provitamin A carotenoids in developing countries.
The bioavailability of retinol is generally more than 80%, whereas the bioavailability and bioconversion of carotenes are lower. These may be affected by species, molecular linkage, amount of carotene, nutrition status, genetic factors, and other interactions. While in general the body absorbs retinoids and vitamin A very efficiently, it lacks the mechanisms to destroy excessive loads. Thus, the possibility of toxicity exists unless intake is carefully regulated. Revision of earlier estimates of daily human requirements of vitamin A has been suggested; the suggestion is that estimates ought to be revised downwards. Concerns exist about the teratogenicity of vitamin A.
The recommended daily allowance for vitamin A is 5000 international units (IU) for adults and 8000 IU for pregnant or lactating women. Being fat-soluble, vitamin A is stored to a variable degree in the body, making it more likely to cause toxicity when taken in excess amounts. In contrast, water-soluble vitamins are generally excreted in the urine and stored only to a limited extent; hence, adverse effects only occur when extremely large amounts are taken.
Nutritional surveys indicate that about 35-50% of adults regularly consume vitamin and mineral supplements. Data are not available for consumption of vitamins in children.
Mortality is rare from vitamin A toxicity.
Morbidity is evident by the wide range of complications observed in this condition.
The use of supplements is generally higher in whites as well as individuals with higher levels of education and income.
The use of vitamin supplements is more common among females.
Single vitamins are consumed more often by adults, while multivitamins are administered more frequently to children.
Carotenemia, the ingestion of excessive amounts of vitamin A precursors in food, mainly carrots, is manifested by a yellow-orange coloring of the skin, primarily the palms of the hands and the soles of the feet. It differs from jaundice in that the sclerae remain white.
In acute vitamin A toxicity, a history of some or all of the following may be obtained:
Altered mental status
Muscle pain with weakness
In chronic vitamin A toxicity, a history of some or all of the following may be obtained:
Dryness of mucus membranes
Fissures of the lips
Bone and joint pains
Manifestations of acute toxicity
Muscle and bone tenderness, especially over the long bones of the upper and lower extremities
Neurologic manifestations with signs of increased intracranial pressure (eg, children may have bulging fontanelles)
Manifestations of chronic toxicity
Premature epiphysial closure in children
Benign intracranial hypertension
Causes of carotenemia
Carotenemia is the result of excessive intake of vitamin A precursors in foods, mainly carrots.
Other than the cosmetic effect, carotenemia has no adverse consequences because the conversion of carotenes to retinol is not sufficient to cause toxicity.
Causes of vitamin A toxicity are generally categorized into acute and chronic.
Acute toxicity occurs within a few hours or days after a very large intake as a result of accidental over-ingestion or inappropriate therapy. The estimated toxic dose is about 25,000 IU/kg.
Chronic toxicity appears after ingestion of 25,000 IU or more daily for prolonged periods.