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What are the hazards of vitamin A overdose?

Update:24-09-2021

The side effects of vitamin A mainly depend on the intake of retinol and retinoyl esters, and are related to the body's physiological and nutritional status. The liver vitamin A concentration exceeding 300mg/g is considered to be excessive and will cause corresponding clinical toxicity. The clinical manifestations of acute vitamin A overdose include severe skin rashes, headaches, and pseudo-neoplastic coma leading to rapid death. Chronic overdose is relatively more common, and clinical manifestations include central nervous system disorders, liver fibrosis, ascites, and skin damage. Recently, there have been reports of bone marrow suppression caused by excessive vitamin A in infants, and hypercalcemia caused by chronic excessive vitamin A in adults. Studies have 
Studies have confirmed that 13-cis-retinoic acid has teratogenic effects, so there is concern that high-dose vitamin A supplementation in humans may have teratogenic effects. A large number of animal experiments have confirmed that excessive vitamin A can cause embryo malformations. Epidemiological data show that excessive intake of pre-formed vitamin A can cause birth defects. The most sensitive period is embryogenesis (early pregnancy). Birth defects caused by vitamin A overdose mainly occur in organs evolved from cranial nerves, such as craniofacial malformations, central nervous system malformations (excluding neural tube malformations), thyroid and Heart deformities, etc. It is estimated that long-term daily intake of pre-formed vitamin A exceeding 10,000 IU can cause teratogenicity. These birth defects may occur when oral retinol analogs are used to treat skin diseases. Topical use of vitamin A analogs in early pregnancy has little or no risk of causing growth abnormalities. 


Bone mineral loss and osteoporosis risk
Animal experiments have found that long-term vitamin A overdose can cause bone mineral loss, and it is speculated that it may have a similar effect in humans. The results of a cross-sectional survey and case-control study among Swedish women reported in 1998 showed that when the daily intake does not exceed 1.5 mg, the bone mineral density increases with the increase of vitamin A intake; but When the daily intake is greater than 1.5 mg, increasing the intake of vitamin A can increase the risk of osteoporosis and bone fractures.
As epidemiological studies are limited by various factors, the conclusions obtained have both support and evidence against the effects of vitamin A overdose on bone health. At present, great attention has been paid to this, but no clear conclusion has been reached. In particular, it is still far from confirming the pre-formed vitamin A intake as a risk factor for bone health, and it is not yet possible to establish a defined threshold for retinol intake that has a significant impact on bone health, but it is definitely an excess of vitamins. A intake should not be good for bone health. 

Liver damage
Animal experiments and human experimental data have confirmed that there is a very clear causal relationship between vitamin A overdose and abnormal liver function. This is because the liver is the main storage organ of vitamin A and the main target organ of vitamin A toxicity. Liver abnormalities caused by vitamin A overdose include reversible increase in liver enzyme activity, liver fibrosis, liver cirrhosis, and death. 

Increase the risk of cardiovascular disease
Observational studies on cardiovascular disease have found that excessive vitamin A may increase the risk of cardiovascular disease. In a cohort study of American adults, high serum retinol levels were associated with high cardiovascular disease risk, but only in men. Current research data show that carotenoids such as β-carotene have very low toxicity. Unlike vitamin A, there are no reports of carotenoid deficiency or toxicity. Excessive intake of β-carotene can cause caroteneemia and temporary yellowing of the skin. It has been reported that caroteneemia can occur when subjects consume a large amount of foods such as carrots or supplement 30 mg or more of β-carotene daily. These symptoms can be reversed a few days or weeks after reducing the intake of such carotenoids.