Kinetics and teratogenicity of vitamin A. A literature study

This report describes a literature study of the kinetics of vitamin A in different animal species. The goal of this study was to collect data to develop a model for risk assessment of the teratogenic effects of vitamin A. In the diet vitamin A is present as esters of retinol and as carotenoids. In the gastro-intestinal tract the retinylesters are hydrolysed and the retinol formed are absorbed by the enterocytes in the lumen of the intestine. In the enterocytes esterification of retinol takes place and these esters are incorporated in chylomicrons which are transported by the lymph to the liver. Carotenoids are absorbed as such by the enterocytes and partially hydrolysed to retinol. In the liver retinol bound to binding proteins, is stored in fat-storing cells and parachym cells. Retinol and its metabolite retinoic acid, again bound to binding proteins, are excreted by the liver depending on the demands of the organism. After intake of large amounts of vitamin A it is presumed that the processes involved in the kinetics are saturable, and free retinol and retinoic acid can circulate in the body. The sensitivity of the different species to the teratogenic effect of vitamin A is very variable. This difference in sensitivity can be caused by the different routes of administration used, the kinetics of vitamin A as well as the specific sensitivity of the target organ, the embryo. From the literature can be concluded that the teratogenic effects are caused by retinol and retinoic acid. To develop a model for the kinetics and risk assessment of vitamin A in pregnant women some questions still remain after this literature study. What is the bioavailability of retinol after administration of retinol esters and carotenoids and is the absorption linear? Under which circumstances (vitamin A status) is the storage in the liver saturable? To what compound is the embryo exposed after intake of vitamin A and what are the differences in the kinetics of vitamin A after a high single dose intake and after chronically intake? These questions should be answered by investigations in our laboratory. The results of these studies shall contribute to the development of the model.HIG