Hypervitaminosis A

Symptoms may include: • Changes in consciousness • Decreased appetite • Dizziness • Bone pain or swelling • Bulging fontanelle (in infants) • Gastric mucosal calcinosis • Heart valve calcification • Hypercalcemia • Increased intracranial pressure manifesting as cerebral edema, papilledema, and headache (may be referred to as idiopathic intracranial hypertension) • Liver damage • Premature epiphyseal closure • Spontaneous fracture == Causes ==

, a potentially toxic source of vitamin A. Hypervitaminosis A can result from ingestion of too much vitamin A from diet (rare), supplements, or prescription medications. Hypervitaminosis A results from excessive intake of preformed vitamin A. Genetic variations in tolerance to vitamin A intake may occur, so the toxic dose will not be the same for everyone. Children are particularly sensitive to vitamin A, with daily intakes of 1500 IU/kg body weight reportedly leading to toxicity. When ingested, 70–90% of preformed vitamin A is absorbed. fish and walrus, are particularly toxic (see ). It has been estimated that consumption of of polar bear liver would result in an acute toxic dose for humans. The tolerable upper intake level (UL) is 3000 μg/day for adults, 600 μg/day for children ages 1–3 years and 900 μg/day for children ages 4–8 years, so for all ages, but especially for young children, a tablespoon a day exceeds the UL. Types of toxicity • Acute toxicity occurs over hours or a few days. • Chronic toxicity results from adult daily intakes greater than 25,000 IU for 6 years or longer and more than 100,000 IU for 6 months or longer. == Mechanism ==

Retinol is absorbed and stored in the liver very efficiently until a pathologic condition develops. Storage Eighty to ninety percent of the total body reserves of preformed vitamin A are in the liver (with 80–90% of this amount being stored in hepatic stellate cells and the remaining 10–20% being stored in hepatocytes). Fat is another significant storage site, while the lungs and kidneys may also be capable of storage. The range of serum retinol concentrations under normal conditions is 1–3 μmol/L. Elevated amounts of retinyl ester (i.e., >10% of total circulating vitamin A) in the fasting state have been used as markers for chronic hypervitaminosis A in humans. Candidate mechanisms for this increase include decreased hepatic uptake of vitamin A and the leaking of esters into the bloodstream from saturated hepatic stellate cells. and bone lesions. Altered fat-soluble vitamin metabolism Preformed vitamin A is fat-soluble and high levels have been reported to affect the metabolism of the other fat-soluble vitamins D, == Diagnosis ==

Retinol concentrations are nonsensitive indicators Assessing vitamin A status in persons with sub-toxicity or toxicity is complicated because serum retinol concentrations are not sensitive indicators in this range of liver vitamin A reserves. The range of serum retinol concentrations under normal conditions is 1–3 μmol/L and, because of homeostatic regulation, that range varies little with widely disparate vitamin A intakes. Retinol esters have been used as markers Retinyl esters can be distinguished from retinol in serum and other tissues and quantified with the use of methods such as high-performance liquid chromatography. Elevated amounts of retinyl ester (i.e., >10% of total circulating vitamin A) in the fasting state have been used as markers for chronic hypervitaminosis A in humans and monkeys. This increased retinyl ester may be due to decreased hepatic uptake of vitamin A and the leaking of esters into the bloodstream from saturated hepatic stellate cells. ==Prevention==

Hypervitaminosis A can be prevented by not ingesting more than the US Institute of Medicine Daily Tolerable Upper Level of intake for Vitamin A. This level is for synthetic and natural retinol ester forms of vitamin A. Carotene forms from dietary sources are not toxic. Possible pregnancy, liver disease, high alcohol consumption, and smoking are indications for close monitoring and limitation of vitamin A administration. Daily tolerable upper level ==Treatment==

• Stopping high vitamin A intake is the standard treatment. Most people fully recover. • Phosphatidylcholine (in the form of PPC or DLPC), the substrate for lecithin retinol acyltransferase, which converts retinol into retinyl esters (the storage forms of vitamin A). • Vitamin E may alleviate hypervitaminosis A. • Liver transplantation may be a valid option if no improvement occurs. If liver damage has progressed into fibrosis, synthesizing capacity is compromised and supplementation can replenish PC. However, recovery is dependent on removing the causative agent: halting high vitamin A intake. == History ==

Vitamin A toxicity is known to be an ancient phenomenon; fossilized skeletal remains of early humans suggest bone abnormalities may have been caused by hypervitaminosis A, Vitamin A toxicity has long been known to the Inuit, as they will not eat the liver of polar bears or bearded seals due to them containing dangerous amounts of Vitamin A. It is claimed that, 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 suggests, however, that exhaustion and diet change are more likely to have caused the tragedy. == Other animals ==

Some Arctic animals demonstrate no signs of hypervitaminosis A despite having 10–20 times the level of vitamin A in their livers as non-Arctic animals. These animals are top predators and include the polar bear, Arctic fox, bearded seal, and glaucous gull. Plasma concentrations are maintained in a non-toxic range despite the high liver content. == See also ==