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Effect of acute zinc depletion on zinc homeostasis and plasma zinc kinetics in men^1,2,3

¹ From the US Department of Agriculture, Agricultural Research Service, Western Human Nutrition Research Center, University of California, Davis; the US Department of Agriculture Children's Nutrition Research Center, Baylor College of Medicine, Houston; and the Department of Medicine, University of Liverpool, Liverpool, United Kingdom.

Background: Zinc homeostasis and normal plasma zinc concentrations are maintained over a wide range of intakes.

Objective: The objective was to identify the homeostatic response to severe zinc depletion by using compartmental analysis.

Design: Stable zinc isotope tracers were administered intravenously to 5 men at baseline (12.2 mg dietary Zn/d) and after 5 wk of acute zinc depletion (0.23 mg/d). Compartmental modeling of zinc metabolism was performed by using tracer and mass data in plasma, urine, and feces collected over 6–14 d.

Results: The plasma zinc concentration fell 65% on average after 5 wk of zinc depletion. The model predicted that fractional zinc absorption increased from 26% to essentially 100%. The rate constants for zinc excretion in the urine and gastrointestinal tract decreased 96% and 74%, respectively. The rate constants describing the distribution kinetics of plasma zinc did not change significantly. When zinc depletion was simulated by using an average mass model of zinc metabolism at baseline, the only change that accounted for the observed fall in plasma zinc concentration was a 60% reduction in the rate constant for zinc release from the most slowly turning over zinc pool. The large changes in zinc intake, excretion, and absorption—even when considered together—only explained modest reductions in plasma zinc mass.

Conclusion: The kinetic analysis with a compartmental model suggests that the profound decrease in plasma zinc concentrations after 5 wk of severe zinc depletion was mainly due to a decrease in the rate of zinc release from the most slowly turning over body zinc pool.

Key Words: Zinc depletion • compartmental model • kinetic analysis • rate constants • plasma zinc • zinc homeostasis • men

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