Hepcidin and erythroferrone response to 3 weeks of exposure to normobaric hypoxia at rest in trained cyclists

Kamila Płoszczyca; Miłosz Czuba; Małgorzata Chalimoniuk; Konrad Witek; Marcin Baranowski

doi:10.3389/fphys.2023.1279827

Hepcidin and erythroferrone response to 3 weeks of exposure to normobaric hypoxia at rest in trained cyclists

Front Physiol. 2023 Nov 27:14:1279827. doi: 10.3389/fphys.2023.1279827. eCollection 2023.

Authors

Kamila Płoszczyca¹, Miłosz Czuba², Małgorzata Chalimoniuk³, Konrad Witek⁴, Marcin Baranowski⁵

Affiliations

¹ Department of Kinesiology, Institute of Sport-National Research Institute, Warsaw, Poland.
² Department of Applied and Clinical Physiology, Collegium Medicum University of Zielona Gora, Zielona Gora, Poland.
³ Department of Physical Education and Health in Biala Podlaska, Józef Piłsudski University of Physical Education in Warsaw, Warsaw, Poland.
⁴ Institute of Sport-National Research Institute, Warsaw, Poland.
⁵ Department of Physiology, Medical University of Bialystok, Bialystok, Poland.

Abstract

Purpose: The effectiveness of altitude training on haematological adaptations is largely dependent on iron metabolism. Hepcidin and erythroferrone (ERFE) are key iron-regulating hormones, yet their response to altitude training is poorly understood. The aim of this study was to analyze changes in hepcidin and ERFE under the influence of 3 weeks of the Live High-Train Low (LH-TL) method. Methods: Twenty male trained cyclists completed a 3-week training program under normoxic conditions (NORM) or with passive exposure to normobaric hypoxia (LH-TL; FiO₂ = 16.5%, ∼2000 m; 11-12 h/day). Hepcidin, ERFE, hypoxia inducible factor-2 (HIF-2), ferroportin (Fpn), erythropoietin (EPO), serum iron (Fe) and hematological variables were assessed at baseline (S1), then immediately after (S2) and 3 days after (S3) intervention. Results: In the LH-TL group, hepcidin decreased by 13.0% (p < 0.001) in S2 and remained at a reduced level in S3. ERFE decreased by 28.7% (p < 0.05) in S2 and returned to baseline in S3. HIF-2α decreased gradually, being lower by 25.3% (p < 0.05) in S3. Fpn decreased between S1 and S2 by 18.9% (p < 0.01) and remained lower during S3 (p < 0.01). In the NORM group, in turn, hepcidin levels increased gradually, being higher by 73.9% (p < 0.05) in S3 compared to S1. No statistically significant differences in EPO were observed in both groups. Conclusion: Three weeks of LH-TL suppresses resting hepcidin and ERFE levels in endurance athletes. We found no association between hepcidin and ERFE after LH-TL. Probably, ERFE is not the only factor that suppresses hepcidin expression in response to moderate hypoxia, especially in later stages of hepcidin downregulation. With the cessation of hypoxia, favorable conditions for increasing the availability of iron cease.

Keywords: altitude training; athletes; erythroferrone; ferroportin; hepcidin; hypoxia; iron; live high-train low.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This research was supported by the grant 2018/31/B/NZ7/02543 from the National Science Centre, Poland and statutory funds of the Institute of Sport–National Research Institute, Warsaw, Poland.