Toxicity
Since vitamin A is fat-soluble, disposing of any excesses taken in through diet takes much longer than with water-soluble B vitamins and vitamin C. This allows for toxic levels of vitamin A to accumulate.
In general, acute toxicity occurs at doses of 25,000 IU/kg of body weight, with chronic toxicity occurring at 4,000 IU/kg of body weight daily for 6–15 months. However, liver toxicities can occur at levels as low as 15,000 IU per day to 1.4 million IU per day, with an average daily toxic dose of 120,000 IU per day, particularly with excessive consumption of alcohol. In people with renal failure, 4000 IU can cause substantial damage. In addition, excessive alcohol intake can increase toxicity. Children can reach toxic levels at 1,500 IU/kg of body weight.
Excessive vitamin A consumption can lead to nausea, irritability, anorexia (reduced appetite), vomiting, blurry vision, headaches, hair loss, muscle and abdominal pain and weakness, drowsiness, and altered mental status. In chronic cases, hair loss, dry skin, drying of the mucous membranes, fever, insomnia, fatigue, weight loss, bone fractures, anemia, and diarrhea can all be evident on top of the symptoms associated with less serious toxicity. Some of these symptoms are also common to acne treatment with Isotretinoin. Chronically high doses of vitamin A, and also pharmaceutical retinoids such as 13-cis retinoic acid, can produce the syndrome of pseudotumor cerebri. This syndrome includes headache, blurring of vision and confusion, associated with increased intracerebral pressure. Symptoms begin to resolve when intake of the offending substance is stopped.
Chronic intake of 1500 RAE of preformed vitamin A may be associated with osteoporosis and hip fractures because it suppresses bone building while simultaneously stimulating bone breakdown. This may be due to the fact that an excess of vitamin A can block the expression of certain proteins dependent on vitamin K to reduce the efficacy of vitamin D, but has not yet been proven. High vitamin A intake has been associated with spontaneous bone fractures in animals. Cell culture studies have linked increased bone resorption and decreased bone formation with high intakes. This interaction may occur because vitamins A and D may compete for the same receptor and then interact with parathyroid hormone, which regulates calcium. Indeed, a study by Forsmo et al. shows a correlation between low bone mineral density and too high intake of vitamin A.
Toxic effects of vitamin A have been shown to significantly affect developing fetuses. Therapeutic doses used for acne treatment have been shown to disrupt cephalic neural cell activity. The fetus is particularly sensitive to vitamin A toxicity during the period of organogenesis. These toxicities only occur with preformed (retinoid) vitamin A (such as from liver). The carotenoid forms (such as beta-carotene as found in carrots), give no such symptoms, except with supplements and chronoic alcoholism, but excessive dietary intake of beta-carotene can lead to carotenodermia, which causes orange-yellow discoloration of the skin.
Smokers and chronic alcohol consumers have been observed to have increased risk of mortality due to lung cancer, esophageal cancer, gastrointestinal cancer and colon cancer. Hepatic (liver) injury has been found in human and animal studies where consumption of alcohol is paired with high dose vitamin A and beta-carotene supplementation.
Researchers have succeeded in creating water-soluble forms of vitamin A, which they believed could reduce the potential for toxicity. However, a 2003 study found water-soluble vitamin A was approximately 10 times as toxic as fat-soluble vitamin. A 2006 study found children given water-soluble vitamin A and D, which are typically fat-soluble, suffer from asthma twice as much as a control group supplemented with the fat-soluble vitamins.
In some studies, the use of Vitamin A supplements has been linked to an increased rate mortality, but there is minimal evidence to show this.
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