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- Angular cheilitis
- Birth defects
- Coarse bone growths
- Excessive skin dryness/peeling (desquamation)
- Hair loss
- Intracranial hypertension (see Idiopathic intracranial hypertension)
- Liver problems
- Premature epiphyseal closure
- Reduced bone mineral density that may result in osteoporosis
- Skin discoloration
Hypervitaminosis A occurs when the maximum limit for liver stores of retinoids is exceeded. The excess vitamin A enters the circulation causing systemic toxicity. Betacarotene, a precursor form of vitamin A typical of vegetable sources such as carrots, is selectively converted into retinoids, so it does not cause toxicity; however, overconsumption can cause carotenosis, a benign condition in which the skin turns orange.
Although hypervitaminosis A can occur when large amounts of liver (including cod liver oil and other fish oils) are regularly consumed, most cases of vitamin A toxicity result from an excess intake of vitamin A in the form of vitamin supplements. Toxic symptoms can also arise after consuming very large amounts of preformed vitamin A over a short period of time. (See Polar-bear liver below.) The U.S. Institute of Medicine says that the Lowest Observed Adverse Effect Level (LOAEL) for vitamin A, when taken over an extended period of time is 21,600 IU. Most multivitamins contain vitamin A doses below 10,000 IU, therefore multi-vitamins are unlikely to cause vitamin A toxicity when taken at their recommended dosages. But in high doses, its central nervous system toxicity can be enhanced by its lipid solubility because it is readily transported across the blood brain barrier and concentrated in the brain.
Vitamin A causes cells to swell with fluid; too much vitamin A causes them to rupture in hyposmotic environments, hence the toxicity.
Retinoids can be conjugated by taurine and other substances. Significant amounts of retinotaurine are excreted in the bile, and it is believed this retinol conjugate is an excretory form as it has little biological activity. In rats, the toxic effects of vitamin A were significantly reduced when diets were supplemented with taurine, and also Cholestin.
Recommended supplement limits
The U.S. Institute of Medicine has established Daily Tolerable Upper Levels (UL) of intake for vitamin A from supplements that apply to healthy populations, in order to help prevent the risk of vitamin A toxicity. These levels for preformed vitamin A in micrograms (µg) and International Units (IU) are
- 0–3 years: 600 µg or 2000 IU
- 4–8 years: 900 µg or 3000 IU
- 9–13 years: 1700 µg or 5665 IU
- 14–18 years: 2800 µg or 9335 IU
- 19+ years: 3000 µg or 10,000 IU
The dose over and above the RDA is among the narrowest of the vitamins and minerals. Possible pregnancy, liver disease, high alcohol consumption, and smoking are indications for close monitoring and limitation of vitamin A administration. However, vitamin A has also been repeatedly tested and used therapeutically over several decades in larger amounts. For example, a total dosage of 100,000 - 400,000 IU has been given for treatment of severe pediatric measles, in areas where vitamin A deficiency may be present, in order to reduce childhood mortality.
Toxicity from eating liver
This danger has long been known to the Inuit and has been used by Europeans since at least 1597 when Gerrit de Veer wrote in his diary that, while taking refuge in the winter in Nova Zemlya, he and his men became severely ill after eating polar bear liver. In 1913, Antarctic explorers Douglas Mawson and Xavier Mertz were both poisoned (and Mertz died) from eating the livers of their sled dogs during the Far Eastern Party. Another study suggest however that exhaustion and diet change are more likely to have caused the tragedy.
Pathological changes consistent with hypervitaminosis A have been seen in bones of Homo erectus, and have also been attributed to consumption of carnivore liver. More recently, the bone pathology of the Homo erectus KNM-ER 1808 has actually been attributed to treponematosis, a bacterial infection.
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