Retinol vitamin hypervitaminosis

Retinoic acid (vitamin A acid), in which the alcohol group has been oxidized, shares some but not all of the actions of retinol. Retinoic acid is ineffective in restoring visual or reproductive function in certain species in which retinol is effective. Flowever, retinoic acid is very potent in promoting growth and controlling differentiation and maintenance of epithelial tissue in vitamin A-deficient animals. Indeed, all-trans-retinoic acid (tretinoin) appears to be the active form of vitamin A in all tissues except the retina, and is 10- to 100-fold more potent than retinol in various systems in vitro. Isomerization of this compound in the body yields 13-n.v-rctinoic acid (isotretinoin), which is nearly as potent as tretinoin in many of its actions on epithelial tissues but may be as much as fivefold less potent in producing the toxic symptoms of hypervitaminosis A. 

Vitamin A toxicity appears to occur only when the amount of vitamin A exceeds the binding capability of the retinol binding protein. Hypervitaminosis A can canse severe anemia and thrombocytopenia, resulting from retinol-dependent bone marrow cell growth inhibition (39). 

For the diagnosis of hypervitaminosis A, plasma concentrations and retinol-binding protein may be misleading. Cases have been reported of hepatic fibrosis, secondary to chronic ingestion of massive doses of vitamin A, where plasma concentrations of vitamin A and retinol-binding protein at the time of diagnosis were within the reference range (43). 

A. Specific levels. Serum vitamin A (retinol) or carotenoid assays may assist in the diagnosis of hypervitaminosis A. Levels of 25-hydroxy vitamin D are useful in assessing excessive intake. Other serum vitamin concentration measurements are not useful. 

Excessive intakes of vitamin A intake leads to hypervitaminosis A that has been associated with birth defects, including malformations of the eye, skull, lungs, and heart [21]. High intakes are possible in the diet for MPKU if a medical food containing vitamin A is taken along with a prenatal supplement or fish oil. The upper safe limit for vitamin A intake during pregnancy is 2,800-3,000 pg/day, or approximately equal to 10,000 lU (1 pg retinol... 

Vitamin A (retinol), a simple fat-soluble molecule discovered in 1913 by McCollum and Davis (/), is essential for proper development, growth, and maintenance of a normal adult vertebrate organism (2-4). Dietary deficiency of vitamin A results in structural and functional abnormalities of a multitude of organs and organ systems (5-7). Likewise, excess of vitamin A is deleterious to life, particularly in its early development where hypervitaminosis A leads to profound embryonic malformations (6,8,9). 

Data consistent with this interpretation have been obtained in studies on vitamin A transport in human vitamin A toxicity (Smith and Goodman, 1976). In three patients with chronic hypervitaminosis A, the toxic state in each was associated with increased plasma levels of total vitamin A and particularly of retinyl esters. In contrast, plasma RBP levels were normal, and there was a molar excess of total vitamin A in relation to RBP. The data suggest that vitamin A toxicity appears to occur in vivo only when the level of vitamin A in the body is such that retinol begins to circulate in plasma and is presented to membranes in a... 

Babb and Kieraldo (1978) reported a case of cirrhosis and portal hypertension attributable to hypervitaminosis A in a 72-year-old male who had been taking 12 mg/day of retinol for 6-7 years. Meunter et al. (1971) reviewed 17 cases of chronic vitamin A toxicity in patients receiving 12.3-180 mg retinol equiv-alents/day for several months up to 9 years. Two patients showed marked liver function impairment at 2i and 12 years, respectively, after discontinuing retinol. Marked elevations of plasma lipid levels were also noted. Deuel (1957) reported that hypervitaminosis A is accompanied by hyperlipidemia involving most of the plasma lipid fractions. 

If the rate of uptake of retinol from the intestine consistently exceeds the capacity of the liver to dispose of it, significant amounts of retinol, mainly in the form of retinyl palmitate, appear in the general circulation and may give rise to toxic effects. The effects of hypervitaminosis A are many and varied. They include increased intracranial pressure, severe headache, hyperirritability, vomiting, diarrhoea, bone decalcification and skin lesions. The condition can be fatal. It has in the past been caused by over-zealous administration of concentrated sources of the vitamin such as halibut liver oil. This may contain several hundred times as much vitamin A and 40 times as much vitamin D as cod liver oil. It has also occurred in people who have eaten polar bear or husky dog liver which contain massive amounts of vitamin A. 

In 3 patients with chronic hypervitaminosis A increased plasma concentrations of total vitamin A and particularly of retinyl esters were seen. The concentration of plasma retinol-binding protein and pre-albumin... 

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