Impact of intravenous iron or exogenous erythropoietin on hemoglobin mass, exercise performance, and acute mountain sickness during altitude acclimatization

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Abstract

Chronic exposure to high altitude leads to increases in hemoglobin mass (Hbmass), which may improve exercise performance and decrease acute mountain sickness (AMS) symptoms. We evaluated the influence of intravenous iron or erythropoietin (EPO) treatment on Hbmass, exercise performance, and AMS during a 14-day exposure to 3,094 m. Thirty-nine participants (12 F) completed the study conducted in Eugene, Oregon [sea level (SL), 130 m] and Leadville, Colorado (3,094 m). Participants were dosed with either a placebo (saline; n ¼ 13), iron [Fe(III)-hydroxide sucrose 200 mg, 2 times; n ¼ 14], or EPO (epoetin alfa 50 IU/kg, 3 times/wk; n ¼ 12) at SL for ̴3.5 wk. Hbmass, exercise performance, and AMS symptoms were measured at SL before treatment and on days 1, 2, 7, 13, and 14 at altitude. Absolute Hbmass (g) increased from SL and day 1 to day 13 (P < 0.0001) with no differences between treatment groups (P ¼ 0.3868). Five-kilometer run times were slower at altitude compared with SL (P < 0.0001) and did not improve over the 14-day period at altitude for any group (P > 0.05). Hike times improved with acclimatization from day 2 to day 14 (P ¼ 0.0018) in all groups, independent of treatment. The incidence and severity of AMS remained low across all participants and time points, regardless of treatment. In the current study and dosing, intravenous iron and EPO did not lead to improvements in Hbmass, exercise performance, or AMS with rapid ascent and residence at 3,100 m.

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Bradbury, K. E., Gideon, E. A., Baranauskas, M. N., Betts, A. W., Davis, K. A., DiMarco, K. G., … Subudhi, A. W. (2025). Impact of intravenous iron or exogenous erythropoietin on hemoglobin mass, exercise performance, and acute mountain sickness during altitude acclimatization. Journal of Applied Physiology, 139(4), 954–963. https://doi.org/10.1152/japplphysiol.00076.2025

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