Effects Of Intravenous Iron Or Erythropoietin On Hemoglobin Mass, Performance, And AMS During Altitude Acclimatization

Rapid ascent to high altitude often leads to symptoms of acute mountain sickness (AMS) and decrements in exercise performance due to the decreased partial pressure of oxygen and subsequent decrease in arterial oxygen content (CaO2). One mechanism for increasing CaO2 is through increasing hemoglobin mass (Hbmass). It is possible that treatment with pharmacological interventions such as intravenous iron or erythropoietin (EPO) prior to ascent may accelerate the increases in Hbmass, improving both AMS and performance during altitude exposure. PURPOSE: To evaluate the influence of iron and EPO treatment on Hbmass, exercise performance, and AMS during a 14 d exposure to 3094 m. METHODS: Thirty-nine participants (12 F) completed the study which was conducted in Eugene, OR (sea level (SL), 130 m) and Leadville, CO (3094 m). Participants were dosed with either a placebo (PL; saline; n = 13), iron (Fe(III)- hydroxide sucrose 200 mg 2x over 3 wk; n = 14), or EPO (epoetin alpha 50 IU/kg 3x per wk/3 wk; n = 12) treatment at SL. Hbmass, 5 k run time, and AMS symptoms were measured at SL prior to treatment and on d 1, 7, and 13 at altitude. A timed uphill ruck march was performed on d 2 and 14. RESULTS: Absolute Hbmass (g) increased similarly between all groups from SL and d1 to d13. Relative Hbmass (g/kg body weight) in the EPO group increased from SL to d1 (P < 0.05) but did not increase further by d13. Relative Hbmass increased in the iron group from SL and d1 to d13 (P < 0.05). There was no change in relative Hbmass in the PL group at any timepoint. 5 k run time increased from SL to d1 (P < 0.05) and did not improve with acclimatization by d13, regardless of treatment. Ruck march times improved with acclimatization from d2 to d14 (P < 0.05) in all groups, independent of treatment. The incidence and severity of AMS remained low across all subjects and time points, regardless of treatment. CONCLUSION: While exogenous EPO treatment led to more rapid increases in relative Hbmass vs iron and PL, this did not translate into differences in AMS or performance. Future studies examining the influence of EPO and iron on AMS and performance at altitude should consider either higher doses or longer dosing regimens. Funded by SOCOM and PCC; author views not representative of the U.S. Army or DoD.

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Journal
Medicine & Science in Sports & Exercise
Published
2025-09-16
DOI
https://doi.org/10.1249/01.mss.0001159008.81522.8d
Primary Topic
High Altitude and Hypoxia
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article
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article

Effects Of Intravenous Iron Or Erythropoietin On Hemoglobin Mass, Performance, And AMS During Altitude Acclimatization

Colin D. Hubbard, Marissa N. Baranauskas, Michael Miller, Aaron W. Betts et al.
Medicine & Science in Sports & Exercise
High Altitude and Hypoxia
article

Effects Of Intravenous Iron Or Erythropoietin On Hemoglobin Mass, Performance, And AMS During Altitude Acclimatization

Colin D. Hubbard, Marissa N. Baranauskas, Michael Miller, Aaron W. Betts, Kyle A. Davis, Andrew W. Subudhi, Elizabeth A. Gideon, Tyler Kelly, Robert C. Roach, Michael Stephens, Kaitlyn G. DiMarco, Joseph W. Duke, Karleigh E. Bradbury, Morgan B. Pendleton, Wade E. Quilter, Jamie A. Rhodine, David J. Lore
article en

Abstract

Rapid ascent to high altitude often leads to symptoms of acute mountain sickness (AMS) and decrements in exercise performance due to the decreased partial pressure of oxygen and subsequent decrease in arterial oxygen content (CaO2). One mechanism for increasing CaO2 is through increasing hemoglobin mass (Hbmass). It is possible that treatment with pharmacological interventions such as intravenous iron or erythropoietin (EPO) prior to ascent may accelerate the increases in Hbmass, improving both AMS and performance during altitude exposure. PURPOSE: To evaluate the influence of iron and EPO treatment on Hbmass, exercise performance, and AMS during a 14 d exposure to 3094 m. METHODS: Thirty-nine participants (12 F) completed the study which was conducted in Eugene, OR (sea level (SL), 130 m) and Leadville, CO (3094 m). Participants were dosed with either a placebo (PL; saline; n = 13), iron (Fe(III)- hydroxide sucrose 200 mg 2x over 3 wk; n = 14), or EPO (epoetin alpha 50 IU/kg 3x per wk/3 wk; n = 12) treatment at SL. Hbmass, 5 k run time, and AMS symptoms were measured at SL prior to treatment and on d 1, 7, and 13 at altitude. A timed uphill ruck march was performed on d 2 and 14. RESULTS: Absolute Hbmass (g) increased similarly between all groups from SL and d1 to d13. Relative Hbmass (g/kg body weight) in the EPO group increased from SL to d1 (P < 0.05) but did not increase further by d13. Relative Hbmass increased in the iron group from SL and d1 to d13 (P < 0.05). There was no change in relative Hbmass in the PL group at any timepoint. 5 k run time increased from SL to d1 (P < 0.05) and did not improve with acclimatization by d13, regardless of treatment. Ruck march times improved with acclimatization from d2 to d14 (P < 0.05) in all groups, independent of treatment. The incidence and severity of AMS remained low across all subjects and time points, regardless of treatment. CONCLUSION: While exogenous EPO treatment led to more rapid increases in relative Hbmass vs iron and PL, this did not translate into differences in AMS or performance. Future studies examining the influence of EPO and iron on AMS and performance at altitude should consider either higher doses or longer dosing regimens. Funded by SOCOM and PCC; author views not representative of the U.S. Army or DoD.

Medicine & Science in Sports & ExerciseVol. 57(10S)
Rocky Vista University (US), West Virginia University (US), U.S. Army Research Institute of Environmental Medicine (US), University of Oregon (US), Northern Arizona University (US), University of Utah (US), United States Army (US), University of Colorado Colorado Springs (US), University of Colorado Denver (US)
Openalex Percentile: Top 73%
High Altitude and Hypoxia
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