Retinol excessive intake

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... 

Excessive doses of vitamin A lead to accelerated resorption of trabecular and cortical bone because of increased osteoclastic activity. A raised alkaline phosphatase, increased urinary hydroxyproline concentrations, and hypercalciuria correlate with these findings (54). One study suggested that high dietary intake of retinol might be associated with osteoporosis (55). 

Ingestion of vitamin A in large excess of the RDA can cause toxicity. Daily intake of more than 7500 retinol equivalents (25,000 lU) is not recommended, and doses in excess of 3000 retinol equivalents (10,000 lU) should only be used with medical supervision. Acute toxicity after... 

Excessive retinol intake by animals and humans produces distinct toxic manifestations, as discussed in other chapters (Chapter 6, Vol. 1 Chapter 13, Vol. 2). Considerable information is available about the mechanism of the toxic effects of vitamin A on tissues..Studies both in vivo and in vitro have shown that excess retinol results in increased lability of biological membranes (Roels et al., 1969 Fell, 1970). This effect of retinol is believed to be due to its surface-active membranolytic properties (Bangham et al., 1964). In particular, excess retinol has been shown to lead to increased synthesis and release of lysosomal enzymes, and these hydrolases have been shown to be critically involved in the effects of vitamin A on cartilage and limb-bone rudiments (Fell, 1970 Fell and Dingle, 1963 Dingle e/a/., 1971). 

At normal levels of intake, most retinol is catabolized by oxidation to retinoic acid and excreted in the bile as retinoyl glucuronide. As the liver concentration or retinol rises above 70 LLmol/kg, there is microsomal cytochrome P -dependent oxidation, leading to a number of polar metabolites, which are excreted in the urine and bile. At high intakes this pathway becomes saturated, and excess retinol is toxic because there is no further capacity for its catabolism and excretion. 

Although there is an increase in the rate of metabolism and excretion of retinol as the concentration in the liver rises above 70 imol/kg, there is only a limited capacity to metabolize the vitamin. Excessively high intakes led to accumulation in the liver and other tissues, beyond the capacity of normal binding proteins, so that free, unbound, vitamin A is present, leading to tissue damage. 

Under conditions of either insufficient or excessive dietary retinoid intake an individual s circulating level of retinol is defended irrespective of the abundance of liver retinol stores, until liver stores reach some critical level beyond which the amount of circulating RBP-ROH is affected [35, 42, 52]. The regulatory factors responsible for establishing and maintaining this homeostatic set point within an individual are not well understood. In addition to any individual s normal serum retinol homeostatic set point, the critical level of hepatic stores also varies from one individual to another, and it has been suggested that it is influenced by non-retinoid factors such as the protein quality and quantity of the diet [34-36, 47, 53]. 

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