What is the pathophysiology and of vitamin A toxicity?

Updated: Jun 01, 2020
  • Author: Mark Rosenbloom, MD, MBA; Chief Editor: Michael A Miller, MD  more...
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Being fat-soluble, vitamin A is stored to a variable degree in the body, making it more likely to cause toxicity when taken in excess amounts. [15] In contrast, water-soluble vitamins are generally excreted in the urine and stored only to a limited extent; hence, adverse effects occur only when extremely large amounts are taken.

The bioavailability of retinol is generally more than 80%, whereas the bioavailability and bioconversion of carotenes (ie, provitamin A) are lower. These may be affected by species, molecular linkage, amount of carotene, nutritional status, genetic factors, and other interactions.

While in general the body absorbs retinoids and vitamin A very efficiently, it lacks the mechanisms to destroy excessive loads. Thus, the possibility of toxicity exists unless intake is carefully regulated. [16] It has been suggested that earlier estimates of daily human requirements of vitamin A be revised downward. [17]

Vitamin A is highly teratogenic in pregnancy, especially in the first 8 weeks with daily intake more than 10,000 IU; however, it is also a cofactor in night vision and bone growth.

Carotenemia is the result of excessive intake of vitamin A precursors in foods, mainly carrots. Other than the cosmetic effect, carotenemia has no adverse consequences, because the conversion of carotenes to retinol is not sufficient to cause toxicity.

Isotretinoin (Accutane), a drug used for the treatment of severe forms of acne, is closely related to the chemical structure of vitamin A, which means that the pharmacology and toxicology of these two compounds are similar. Birth defects (when taken during pregnancy), intracranial hypertension, depression, and suicidal ideation have been reported with isotretinoin. [18] A careful drug history to uncover this possibility of isotretinoin use is important in patients presenting with manifestations suggestive of vitamin A intoxication.

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