Effects of oral zinc loading on zinc metabolism in humans II: in vivo kinetics

Abstract

The effects of oral zinc loading on zinc metabolism were studied in 10 patients with taste and smell dysfunction following oral administration of Zn-65 (physical t1/2 = 245 d) and subsequent administration of oral stable zinc. Patients took an ad libitum dietary zinc intake of 8-13 mg daily for 290-440 days (mean, 336) following Zn-65 administration, followed by an intake of an additional 100 mg/day of zinc ion (as ZnSO4) over the next 112-440 days (mean, 307). A previously developed compartmental model, based on five day studies of patients with taste and smell dysfunction, was extended in such a way that it was consistent with both short term and long term kinetics. In this extended model, the turnover of 90% of total body zinc, previously unaccounted for by the kinetics in the short term studies could be explained by a single compartment, as postulated in the short term studies. Using the model, it was found that changes in the rate constants for gastrointestinal absorption and renal excretion of zinc were both necessary and sufficient to explain the changes seen in the kinetic curves following oral zinc loading. Michaelis-Menten type saturation mechanisms were adequate to explain the observed parameter changes. These changes also accounted for the observed mean plasma zinc mass increase of only 37% above pre-load levels in face of an 11-fold increase in zinc intake.