Use of Model-Based Compartmental Analysis to Study Vitamin A Kinetics and Metabolism

We discuss the use of mathematical modeling, and specifically model-based compartmental analysis, to analyze vitamin A kinetic data obtained in rat and human studies over the past 25 years. Following an overview of whole-body vitamin A metabolism, a review of early kinetic studies, and an introduction to the approach and terminology of compartmental analysis, we summarize studies done in this laboratory to develop models of whole-body vitamin A metabolism in rats at varying levels of vitamin A status. Highlights of the results of these studies include the extensive recycling of vitamin A among plasma and tissues before irreversible utilization and the existence of significant extrahepatic pools of the vitamin. Our studies also document important differences in vitamin A kinetics as a function of vitamin A status and the importance of plasma retinol pool size in vitamin A utilization rate. Later we describe vitamin A kinetics and models developed for specific organs including the liver, eyes, kidneys, small intestine, lungs, testes, adrenals, and remaining carcass, and we discuss the effects of various exogenous factors (e.g., 4-HPR, dioxin, iron deficiency, dietary retinoic acid, and inflammation) on vitamin A dynamics. We also briefly review the retrospective application of model-based compartmental analysis to human vitamin A kinetic data. Overall, we conclude that the application of model-based compartmental analysis to vitamin A kinetic data provides unique insights into both quantitative and descriptive aspects of vitamin A metabolism and homeostasis in the intact animal.