Better Predictions of Vitamin A Total Body Stores by the Retinol Isotope Dilution Method Are Possible with Deeper Understanding of the Mathematics and by Applying Compartmental Modeling

Retinol isotope dilution (RID) is a well-accepted technique for assessing vitamin A status [i.e., total body stores (TBS)]. Here, in an effort to increase understanding of the method, we briefly review RID equations and discuss their included variables and their coefficients (i.e., assumptions that account for the efficiency of absorption of an orally administered tracer dose of vitamin A, mixing of the dose with endogenous vitamin A, and loss due to utilization). Then, we focus on contributions of another technique, model-based compartmental analysis and especially the “super-person” approach, that advance the RID method. Specifically, we explain how adding this modeling component, which involves taking 1 additional blood sample from each subject, provides population-specific estimates for the RID coefficients that can be used in the equation instead of values derived from the literature; using model-derived RID coefficients results in improved confidence in predictions of TBS for both a group and its individuals. We note that work is still needed to identify the optimal time for applying RID in different groups and to quantify vitamin A absorption efficiency. Finally, we mention other contributions of modeling, including the use of theoretical data to verify the accuracy of RID predictions and the additional knowledge that model-based compartmental analysis provides about whole-body vitamin A kinetics.