Effects of altitude and recombinant human erythropoietin on iron metabolism: a randomized controlled trial
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Effects of altitude and recombinant human erythropoietin on iron metabolism: a randomized controlled trial. / Breenfeldt Andersen, Andreas; Bonne, Thomas Christian; Bejder, Jacob; Jung, Grace; Ganz, Tomas; Nemeth, Elizabeta; Olsen, Niels Vidiendal; Rodriguez Huertas, Jesus; Nordsborg, Nikolai Baastrup.
I: American Journal of Physiology: Regulatory, Integrative and Comparative Physiology, Bind 321, Nr. 2, 2021, s. R152-R161.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Effects of altitude and recombinant human erythropoietin on iron metabolism: a randomized controlled trial
AU - Breenfeldt Andersen, Andreas
AU - Bonne, Thomas Christian
AU - Bejder, Jacob
AU - Jung, Grace
AU - Ganz, Tomas
AU - Nemeth, Elizabeta
AU - Olsen, Niels Vidiendal
AU - Rodriguez Huertas, Jesus
AU - Nordsborg, Nikolai Baastrup
N1 - CURIS 2021 NEXS 247
PY - 2021
Y1 - 2021
N2 - Current markers of iron deficiency (ID) such as ferritin and hemoglobin have shortcomings, and hepcidin and erythroferrone (ERFE) could be of clinical relevance in relation to early assessment of ID. Here, we evaluate whether exposure to altitude-induced hypoxia (2,320 m) alone, or in combination with recombinant human erythropoietin (rHuEPO) treatment, affects hepcidin and ERFE levels before alterations in routine ID biomarkers and stress erythropoiesis manifest. Two interventions were completed, each comprising a 4-wk baseline, a 4-wk intervention at either sea level or altitude, and a 4-wk follow-up. Participants (n=39) were randomly assigned to 20 IU·kg body wt-1 rHuEPO or placebo injections every second day for 3 wk during the two intervention periods. Venous blood was collected weekly. Altitude increased ERFE (P ≤ 0.001) with no changes in hepcidin or routine iron biomarkers, making ERFE of clinical relevance as an early marker of moderate hypoxia. rHuEPO treatment at sea level induced a similar pattern of changes in ERFE (P < 0.05) and hepcidin levels (P < 0.05), demonstrating the impact of accelerated erythropoiesis and not of other hypoxia-induced mechanisms. Compared to altitude alone, concurrent rHuEPO treatment and altitude exposure induced additive changes in hepcidin (P < 0.05) and ERFE (P ≤ 0.001) parallel with increases in hematocrit (P < 0.001), demonstrating a relevant range of both hepcidin and ERFE. A poor but significant correlation between hepcidin and ERFE was found (R2 = 0.13, P < 0.001). The findings demonstrate that hepcidin and ERFE are more rapid biomarkers of changes in iron demands than routine iron markers. Finally, ERFE and hepcidin may be sensitive markers in an anti-doping context.Clinical trial registration: Clinical trials identifier, NCT04227665
AB - Current markers of iron deficiency (ID) such as ferritin and hemoglobin have shortcomings, and hepcidin and erythroferrone (ERFE) could be of clinical relevance in relation to early assessment of ID. Here, we evaluate whether exposure to altitude-induced hypoxia (2,320 m) alone, or in combination with recombinant human erythropoietin (rHuEPO) treatment, affects hepcidin and ERFE levels before alterations in routine ID biomarkers and stress erythropoiesis manifest. Two interventions were completed, each comprising a 4-wk baseline, a 4-wk intervention at either sea level or altitude, and a 4-wk follow-up. Participants (n=39) were randomly assigned to 20 IU·kg body wt-1 rHuEPO or placebo injections every second day for 3 wk during the two intervention periods. Venous blood was collected weekly. Altitude increased ERFE (P ≤ 0.001) with no changes in hepcidin or routine iron biomarkers, making ERFE of clinical relevance as an early marker of moderate hypoxia. rHuEPO treatment at sea level induced a similar pattern of changes in ERFE (P < 0.05) and hepcidin levels (P < 0.05), demonstrating the impact of accelerated erythropoiesis and not of other hypoxia-induced mechanisms. Compared to altitude alone, concurrent rHuEPO treatment and altitude exposure induced additive changes in hepcidin (P < 0.05) and ERFE (P ≤ 0.001) parallel with increases in hematocrit (P < 0.001), demonstrating a relevant range of both hepcidin and ERFE. A poor but significant correlation between hepcidin and ERFE was found (R2 = 0.13, P < 0.001). The findings demonstrate that hepcidin and ERFE are more rapid biomarkers of changes in iron demands than routine iron markers. Finally, ERFE and hepcidin may be sensitive markers in an anti-doping context.Clinical trial registration: Clinical trials identifier, NCT04227665
KW - Faculty of Science
KW - Hepcidin
KW - Erythroferrone
KW - Altitude
KW - Anti-doping
KW - Biomarker
U2 - 10.1152/ajpregu.00070.2021
DO - 10.1152/ajpregu.00070.2021
M3 - Journal article
C2 - 34160288
VL - 321
SP - R152-R161
JO - American Journal of Physiology
JF - American Journal of Physiology
SN - 0363-6119
IS - 2
ER -
ID: 272724257