Health Risks from Excessive Vitamin A
Because vitamin A is fat soluble, the body stores excess amounts, primarily in the liver, and these levels can accumulate. Although excess preformed vitamin A can have significant toxicity (known as hypervitaminosis A), large amounts of beta-carotene and other provitamin A carotenoids are not associated with major adverse effects . The manifestations of hypervitaminosis A depend on the size and rapidity of the excess intake. The symptoms of hypervitaminosis A following sudden, massive intakes of vitamin A, as with Arctic explorers who ate polar bear liver, are acute . Chronic intakes of excess vitamin A lead to increased intracranial pressure (pseudotumor cerebri), dizziness, nausea, headaches, skin irritation, pain in joints and bones, coma, and even death [2,4,5]. Although hypervitaminosis A can be due to excessive dietary intakes, the condition is usually a result of consuming too much preformed vitamin A from supplements or therapeutic retinoids [3,5]. When people consume too much vitamin A, their tissue levels take a long time to fall after they discontinue their intake, and the resulting liver damage is not always reversible.
Observational studies have suggested an association between high intakes of preformed vitamin A (more than 1,500 mcg daily—only slightly higher than the RDA), reduced bone mineral density, and increased fracture risk [1,4,40]. However, the results of studies on this risk have been mixed, so the safe retinol intake level for this association is unknown.
Total intakes of preformed vitamin A that exceed the UL and some synthetic retinoids used as topical therapies (such as isotretinoin and etretinate) can cause congenital birth defects [2-4]. These birth defects can include malformations of the eye, skull, lungs, and heart . Women who might be pregnant should not take high doses of vitamin A supplements .
Unlike preformed vitamin A, beta-carotene is not known to be teratogenic or lead to reproductive toxicity . And even large supplemental doses (20–30 mg/day) of beta-carotene or diets with high levels of carotenoid-rich food for long periods are not associated with toxicity. The most significant effect of long-term, excess beta-carotene is carotenodermia, a harmless condition in which the skin becomes yellow-orange [1,25]. This condition can be reversed by discontinuing beta-carotene ingestion.
Supplementation with beta-carotene, with or without retinyl palmitate, for 5–8 years has been associated with an increased risk of lung cancer and cardiovascular disease in current and former male and female smokers and in male current and former smokers occupationally exposed to asbestos [27,41]. In the ATBC study, beta-carotene supplements (20 mg daily) were also associated with increased mortality, mainly due to lung cancer and ischemic heart disease . The CARET study ended early, after the investigators found that daily beta-carotene (30 mg) and retinyl palmitate (7,500 mcg RAE [25,000 IU]) supplements increased the risk of lung cancer and cardiovascular disease mortality .
The FNB has established ULs for preformed vitamin A that apply to both food and supplement intakes . The FNB based these ULs on the amounts associated with an increased risk of liver abnormalities in men and women, teratogenic effects, and a range of toxic effects in infants and children. The FNB also considered levels of preformed vitamin A associated with decreased bone mineral density, but did not use these data as the basis for its ULs because the evidence was conflicting. The FNB has not established ULs for beta-carotene and other provitamin A carotenoids . The FNB advises against beta-carotene supplements for the general population, except as a provitamin A source to prevent vitamin A deficiency.
Table 3: Tolerable Upper Intake Levels (ULs) for Preformed Vitamin A *