Diego Moretti1, Samuel Mettler1,2,3, Christophe Zeder1, Carsten Lundby4, Anneke Geurts-Moetspot5, Arnaud Monnard1, Dorine W Swinkels5, Gary M Brittenham1, Michael B Zimmermann1. 1. Laboratory of Human Nutrition, Institute of Food, Nutrition and Health, Swiss Federal Institute of Technology, ETH Zürich, Zurich, Switzerland. 2. Swiss Federal Institute of Sports, Magglingen, Switzerland. 3. Department of Business, Health, and Social Work, Bern University of Applied Sciences, Bern, Switzerland. 4. Zurich Center for Integrative Human Physiology, Institute of Physiology, University of Zurich, Zurich, Switzerland. 5. Hepcidinanalysis.com and Department of Laboratory Medicine, Translational Metabolic Laboratory, Radboud University Medical Center, Nijmegen, Netherlands.
Abstract
Background: Iron status is a determinant of physical performance, but training may induce both low-grade inflammation and erythropoiesis, exerting opposing influences on hepcidin and iron metabolism. To our knowledge, the combined effects on iron absorption and utilization during training have not been examined directly in humans. Objective: We hypothesized that 3 wk of exercise training in recreational male runners would decrease oral iron bioavailability by increasing inflammation and hepcidin concentrations. Design: In a prospective intervention, nonanemic, iron-sufficient men (n = 10) completed a 34-d study consisting of a 16-dcontrol phase and a 22-d exercise-training phase of 8 km running every second day. We measured oral iron absorption and erythroid iron utilization using oral 57Fe and intravenous 58Fe tracers administered before and during training. We measured hemoglobin mass (mHb) and total red blood cell volume (RCV) by carbon monoxide rebreathing. Iron status, interleukin-6 (IL-6), plasma hepcidin (PHep), erythropoietin (EPO), and erythroferrone were measured before, during, and after training. Results:Exercise training induced inflammation, as indicated by an increased mean ± SD IL-6 (0.87 ± 1.1 to 5.17 ± 2.2 pg/mL; P < 0.01), while also enhancing erythropoiesis, as indicated by an increase in mean EPO (0.66 ± 0.42 to 2.06 ± 1.6 IU/L), mHb (10.5 ± 1.6 to 10.8 ± 1.8 g/kg body weight), and mean RCV (30.7 ± 4.3 to 32.7 ± 4.6 mL/kg) (all P < 0.05). Training tended to increase geometric mean iron absorption by 24% (P = 0.083), consistent with a decreased mean ± SD PHep (7.25 ± 2.14 to 5.17 ± 2.24 nM; P < 0.05). The increase in mHb and erythroid iron utilization were associated with the decrease in PHep (P < 0.05). Compartmental modeling indicated that iron for the increase in mHb was obtained predominantly (>80%) from stores mobilization rather than from increased dietary absorption. Conclusions: In iron-sufficient men, mild intensification of exercise intensity increases both inflammation and erythropoiesis. The net effect is to decrease hepcidin concentrations and to tend to increase oral iron absorption. This trial was registered at clinicaltrials.gov as NCT01730521.
RCT Entities:
Background: Iron status is a determinant of physical performance, but training may induce both low-grade inflammation and erythropoiesis, exerting opposing influences on hepcidin and iron metabolism. To our knowledge, the combined effects on iron absorption and utilization during training have not been examined directly in humans. Objective: We hypothesized that 3 wk of exercise training in recreational male runners would decrease oral iron bioavailability by increasing inflammation and hepcidin concentrations. Design: In a prospective intervention, nonanemic, iron-sufficient men (n = 10) completed a 34-d study consisting of a 16-d control phase and a 22-d exercise-training phase of 8 km running every second day. We measured oral iron absorption and erythroid iron utilization using oral 57Fe and intravenous 58Fe tracers administered before and during training. We measured hemoglobin mass (mHb) and total red blood cell volume (RCV) by carbon monoxide rebreathing. Iron status, interleukin-6 (IL-6), plasma hepcidin (PHep), erythropoietin (EPO), and erythroferrone were measured before, during, and after training. Results: Exercise training induced inflammation, as indicated by an increased mean ± SD IL-6 (0.87 ± 1.1 to 5.17 ± 2.2 pg/mL; P < 0.01), while also enhancing erythropoiesis, as indicated by an increase in mean EPO (0.66 ± 0.42 to 2.06 ± 1.6 IU/L), mHb (10.5 ± 1.6 to 10.8 ± 1.8 g/kg body weight), and mean RCV (30.7 ± 4.3 to 32.7 ± 4.6 mL/kg) (all P < 0.05). Training tended to increase geometric mean iron absorption by 24% (P = 0.083), consistent with a decreased mean ± SD PHep (7.25 ± 2.14 to 5.17 ± 2.24 nM; P < 0.05). The increase in mHb and erythroid iron utilization were associated with the decrease in PHep (P < 0.05). Compartmental modeling indicated that iron for the increase in mHb was obtained predominantly (>80%) from stores mobilization rather than from increased dietary absorption. Conclusions: In iron-sufficient men, mild intensification of exercise intensity increases both inflammation and erythropoiesis. The net effect is to decrease hepcidin concentrations and to tend to increase oral iron absorption. This trial was registered at clinicaltrials.gov as NCT01730521.
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