Augmenting erythropoiesis using recombinant human erythropoietin at sea level blunts the high altitude induced increase in erythropoiesis

Erythropoiesis increases with high altitude (HA) acclimatization. Recombinant human erythropoietin (rEPO) induces erythropoiesis. However, it is unknown whether pharmacologically augmenting erythropoiesis with rEPO at sea level alters the erythropoietic response during subsequent HA acclimatization. We aimed to determine whether augmenting erythropoiesis with rEPO blunts the erythropoietic response during HA acclimatization. Twenty healthy participants completed sea level testing, a 4-week intervention at sea level with rEPO (n = 9; 2 females) or placebo (PL; n = 11; 3 females), 15-day HA exposure (4300 m), and testing the day after returning from high altitude (PostHA). Blood samples were collected throughout the study and haemoglobin mass (Hb_mass) was assessed before and after the sea level intervention and PostHA. As expected, at sea level, rEPO augmented Hb_mass (rEPO-PL mean diff: 88 g, 95% CI: 45.6 g, 130.6 g). At HA, the rEPO group had higher [Hb], which augmented arterial oxygen content (mean diff. = 1.93 mL O₂ dL^-1, 95% CI: 0.59 mL O₂ dL^-1, 3.27 mL O₂ dL^-1). Despite similar oxygen saturation, the rEPO group had lower EPO (∼7 mlU mL^-1) and reticulocyte count (∼1 percentage units) compared to PL group at HA. Hb_mass at PostHA was not different between rEPO (n = 5) and PL group (mean diff.: 35 g, 95% CI: -10.99 g, 81.02 g), which confirmed blunted erythropoiesis at HA. The present study demonstrates that pharmacologically augmenting erythropoiesis with rEPO at sea level blunts the HA induced increase in erythropoiesis. KEY POINTS: Erythropoiesis increases with high altitude (HA) acclimatization. Recombinant human erythropoietin (rEPO) stimulates erythropoiesis at sea level, but it is unknown whether pharmacologically augmenting erythropoiesis with rEPO alters erythropoietic response during subsequent HA acclimatization. We assessed erythropoiesis before and after a 4-week intervention of rEPO or placebo and after 15 days at 4300 m. Compared to placebo, rEPO augmented erythropoiesis at sea level but markedly attenuated the erythropoietic response to HA acclimatization. Our data indicate that pharmacologically augmenting erythropoiesis with rEPO at sea level blunts the HA induced increase in erythropoiesis.