Application of compartmental modeling to determination of trace element requirements in humans

The potential of compartmental modeling for determining dietary requirements of the trace elements is explored. Transport kinetics of tracee and tracer within a physiologically meaningful arrangement of compartments were simulated by using whole body copper (Cu) metabolism in adult humans as an example. The simulation was based on known, quantitative Cu metabolism, and required a non-steady-state model rather than a more conventional steady-state model. The simulation indicated that a reduction in dietary Cu intake could result in (1) loss of Cu from storage compartments, (2) maintenance of homeostasis by adaptive changes in dietary Cu absorption and endogenous excretion, or (3) a response intermediate between the two. By performing tracer experiments, it should be possible to determine the relative significance of mechanisms 1 and 2 in response to progressively smaller dietary intakes of Cu. Whether the body conserves Cu by adapting metabolically to low Cu intake or, alternatively, undergoes significant Cu loss because of an inability to adapt, may be an important factor in recommending a dietary requirement. The basic structure of the whole-body model of Cu metabolism used in this study has features consistent with the metabolism of other trace elements. Thus, the present example may also provide an approach to the study of dietary requirements of other elements.