Assessing Human Iron Kinetics Using Stable Iron Isotopic Techniques.

Nicole U Stoffel, Christophe Zeder, Michael B Zimmermann

Journal: Clinical pharmacokinetics 2024;63(10):1389-1405

PMID: 39414725

Abstract

Stable iron isotope techniques are critical for developing strategies to combat iron deficiency anemia, a leading cause of global disability. There are four primary stable iron isotope methods to assess ferrokinetics in humans. (i) The fecal recovery method applies the principles of a metabolic balance study but offers enhanced accuracy because the amount of iron isotope present in feces can be directly traced back to the labeled dose, distinguishing it from endogenous iron lost in stool from shed intestinal cells. (ii) In the plasma isotope appearance method, plasma samples are collected for several hours after oral dosing to evaluate the rate, quantity, and pattern of iron absorption. Key metrics include the time of peak isotope concentration and the area under the curve. (iii) The erythrocyte iron incorporation method measures iron bioavailability (absorption and erythrocyte iron utilization) from a whole blood sample collected 2 weeks after oral dosing. Simultaneous administration of oral and intravenous tracers allows for separate measurements of iron absorption and iron utilization. These three methods determine iron absorption by measuring tracer concentrations in feces, serum, or erythrocytes after administration of a tracer. In contrast, (iv) in iron isotope dilution, an innovative new approach, iron of natural composition acts as the tracer, diluting an ad hoc modified isotopic signature obtained via prior isotope administration and equilibration with body iron. This technique enables highly accurate long-term studies of iron absorption, loss, and gain. This review discusses the application of these kinetic methods and their potential to address important questions in hematology and iron biology.

© 2024. The Author(s).

Address: Department of Health Sciences and Technology, ETH Zurich, Zurich, Switzerland. [email protected].; Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Medicine, Botnar Research Centre, University of Oxford, Old Rd, Headington, Oxford, OX3 7LD, UK. [email protected].; Department of Health Sciences and Technology, ETH Zurich, Zurich, Switzerland.; Radcliffe Department of Medicine, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.

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