A compartmental model of zinc metabolism in healthy women using oral and intravenous stable isotope tracers

Abstract

A mathematical model of zinc metabolism in six healthy women (average age: 30 +/- 11 y) was developed by using stable isotopes of zinc. After equilibration on a constant diet containing 7.0 mg Zn/d, an oral tracer highly enriched in 67Zn and an intravenous tracer highly enriched in 70Zn were administered simultaneously. Multiple plasma and 24-h urine samples were collected for the next 7 d with complete fecal collections for 11 d. Tracer-trace ratios in plasma, urine, and feces were calculated from isotope ratios of 67Zn to 66Zn and 70Zn to 66Zn measured by using inductively coupled plasma-mass spectrometry. An a priori identifiable model composed of seven compartments was developed to describe the kinetics of both tracers as well as that of naturally occurring zinc. The parameters of the model were fitted to the data by using the SAAM-CONSAM modeling software and were estimated with good precision. Several important, not directly measurable zinc variables were estimated (mean +/- SEM) from the model including the fractional absorption from the gastrointestinal tract (0.279 +/- 0.043), the rates of endogenous secretion (2.79 +/- 0.49 mg/d) and excretion (2.01 +/- 0.35 mg/d), the fractional turnover rate of the plasma pool (131 +/- 20/d), and the sizes (7.2 +/- 1.2 and 77.1 +/- 6.4 mg) and fractional turnover rates (22.3 +/- 7.1 and 1.49 +/- 0.18/d) of the fast and slow tissue pools equilibrating with the plasma, respectively.

Reduced production of immunoregulatory cytokines in vitamin A- and zinc-deficient Indonesian infants

“…Many other indicators of zinc status have been studied, however, none have been able to supplant plasma zinc as the most practical indicator (Dijkhuizen et al, 2003). Isotope dilution techniques have been used to measure body pools of zinc, which give a more precise estimate of zinc status, but the cost prevents widespread use of this technique (Lowe et al, 2001). Also thymulin and metallothionein have been used as indirect indicators of zinc ion availability, but proved to have similar or more severe limitations as plasma zinc.…”

Double isotope tracer method for measuring fractional zinc absorption: theoretical analysis

“…By using the average parameters of Ref. 6, one can obtain the simulation of 70 z 1 (t) and 67 z 1 (t) in response to unitary intravenous and oral doses, respectively, displayed in Fig. 2, A and B.…”

“…2, A and B. It is worth noting that the order of the (linear) dynamic system originating 70 z 1 (t) is 5 [the state variables corresponding to compartments 4,6,8, and 9 do not play any role in 70 z 1 (t)], whereas that of the system that generates 67 z 1 (t) is 6 (the input occurs in compartment 4). Indeed, the (early) time course in plasma of 67 Zn-tr reflects the first-pass kinetics of movement through and absorption from the gastrointestinal tract.…”

“…1 (6). In a given individual, FZA can be obtained by making use of the rate constants of the kinetic model by…”

“…This was the procedure used in Ref. 6. It is also important to note that, because tracer concentration data are unavoidably affected by error, the FZA value obtainable by Eq.…”