Toxicity

The condition caused by vitamin A toxicity is called hypervitaminosis A. It is caused by overconsumption of preformed vitamin A, not carotenoids. Preformed vitamin A is rapidly absorbed and slowly cleared from the body, so toxicity may result acutely from high-dose exposure over a short period of time, or chronically from much lower intake. Vitamin A toxicity is relatively rare. Symptoms include nausea, headache, fatigue, loss of appetite, dizziness, and dry skin. Signs of chronic toxicity include, dry itchy skin, loss of appetite, headache, and bone and joint pain. Severe cases of hypervitaminosis A may result in liver damage, and coma. Generally, signs of toxicity are associated with long-term consumption of vitamin A in excess of 10 times the RDA (8,000 to 10,000 mcg/day or 25,000 to 33,000 IU/day). However, there is evidence that some populations may be more susceptible to toxicity at lower doses, including the elderly, chronic alcohol users, and some people with a genetic predisposition to high cholesterol. In January 2001, the Food and Nutrition Board (FNB) of the Institute of Medicine set the tolerable upper level (UL) of vitamin A intake for adults at 3,000 mcg (10,000 IU)/day of preformed vitamin A.

Although normal fetal development requires sufficient vitamin A intake, consumption of excess preformed vitamin A (retinol) during pregnancy is known to cause birth defects. No increase in the risk of vitamin A-associated birth defects has been observed at doses of preformed vitamin A from supplements below 3,000 mcg/day (10,000 IU/day). Since a number of foods in the U.S. are fortified with preformed vitamin A, pregnant women should avoid multivitamin or prenatal supplements that contain more than 1,500 mcg (5,000 IU) of vitamin A. Vitamin A from beta-carotene is not known to increase the risk of birth defects. Etretinate and isotretinoin (Accutane), synthetic derivatives of retinol, are known to cause birth defects and should not be taken during pregnancy or if there is a possibility of becoming pregnant. Tretinoin (Retin-A), another retinol derivative, is prescribed as a topical preparation that is applied to the skin. Because of the potential for systemic absorption of topical tretinoin, its use during pregnancy is not recommended.

Do high intakes of vitamin A increase the risk of osteoporosis?

The results of several recent prospective studies suggest that long term intakes of preformed vitamin A in excess of 1,500 mcg/day (5,000 IU/day) are associated with increased risk of osteoporotic fracture and decreased bone mineral density (BMD) in older men and women. Although this level of intake is greater than the RDA of 700-900 mcg/day (2,300-3,000 IU/day), it is substantially lower than the UL of 3,000 mcg/day (10,000 IU/day). Only excess intakes of preformed vitamin A (retinol), not beta-carotene, were associated with adverse effects on bone health. Although these observational studies cannot provide the reason for the association between excess retinol intake and osteoporosis, limited experimental data suggest that excess retinol may stimulate bone resorption or interfere with the ability of vitamin D to maintain calcium balance. In the U.S., retinol intakes in excess of 5,000 IU/day can be easily attained by those who regularly consume multivitamin supplements and/or fortified foods, including some breakfast cereals. At the other end of the spectrum, a significant number of elderly people have insufficient vitamin A intakes, which have also been associated with decreased BMD. One study of elderly men and women found that BMD was optimal at vitamin A intakes close to the RDA. Until supplements and fortified foods are reformulated to reflect the current RDA for vitamin A, it makes sense to look for multivitamin supplements that contain 2,500 IU of vitamin A or multivitamin supplements that contain 5,000 IU of vitamin A, of which at least 50% comes from beta-carotene.

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