Overconsumption of beta-carotene can only cause carotenosis, a harmless and reversible cosmetic condition in which the skin turns orange. Preformed vitamin A absorption and storage in the liver occur very efficiently until a pathologic condition develops. When ingested, 70–90% of preformed vitamin A is absorbed and used. Sources of toxicity
Diet – Liver is high in vitamin A. The liver of certain animals, including the polar bear, bearded seal, fish, walrus, and moose, are particularly toxic (see Liver (food) § Poisoning). It has been estimated that consumption of 500 grams of polar bear liver would result in a toxic dose for a human. Supplements – Dietary supplements can be toxic when taken above recommended dosages. Types of toxicity
Acute toxicity occurs over a period of hours or a few days, and is less of a problem than chronic toxicity. Chronic toxicity results from daily intakes greater than 25,000 IU for 6 years or longer and more than 100,000 IU for 6 months or longer. Mechanism
Absorption and storage in the liver of retinol occur very efficiently until a pathologic condition develops. Delivery to tissues
Absorption
When ingested, 70–90% of preformed vitamin A is absorbed and used.According to a 2003 review, water-miscible, emulsified, and solid forms of vitamin A supplements are more toxic than oil-based supplement and liver sources. Storage
80–90% 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).
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.