Use of Zn Kinetics in the Design of Zn Supplementation Studies

Kinetic studies in humans have been used to develop models for the absorption, distribution and excretion of zinc. Studies in normal, Zn supplemented and Zn deficient states have been used to identify the major sites of regulation that maintain Zn homeostasis. The aim of our study was to combine and convert the kinetic models into a dynamic model that would represent metabolism for any Zn intake. The purpose was to use the dynamic model as a tool to examine ways to restore Zn in Zn –depleted subjects. The conversion of the kinetic models to a dynamic model was accomplished by replacing rate constants at five sites of regulation (absorption, RBC exchange, urinary excretion, endogenous excretion and release from muscle) by functions that describe how each site changes over time in response to Zn intake. The dynamic model was used to inform a strategy for Zn administration to alleviate Zn deficiency. Zn deficiency was simulated by either inadequate intake, poor absorption, or increased Zn losses and Zn repletion was simulated by administering different amounts of Zn, at different frequencies (e.g., daily or weekly), and for varying lengths of time. Regimens that failed to restore pool sizes to normal, or which exceeded safe levels were discarded while regimens that effectively and efficiently repleted Zn‐deficient individuals were retained for future experimental evaluation We conclude that dosing regimens can be designed to restore Zn pools in Zn deficient humans by use of existing information in the form of models, and through simulation. Support or Funding Information Bill & Melinda Gates Foundation