European Journal of Applied Physiology

, Volume 116, Issue 3, pp 623–633 | Cite as

RhEPO improves time to exhaustion by non-hematopoietic factors in humans

  • Simon Annaheim
  • Matthias Jacob
  • Alexander Krafft
  • Christian Breymann
  • Markus Rehm
  • Urs BoutellierEmail author
Original Article



Erythropoietin (EPO) controls red cell volume (RCV) and plasma volume (PV). Therefore, injecting recombinant human EPO (rhEPO) increases RCV and most likely reduces PV. RhEPO-induced endurance improvements are explained by an increase in blood oxygen (O2) transport capacity, which increases maximum O2 uptake (\(\dot{V}\)O2max). However, it is debatable whether increased RCV or \(\dot{V}\)O2max are the main reasons for the prolongation of the time to exhaustion (t lim) at submaximal intensity. We hypothesized that high rhEPO doses in particular contracts PV such that the improvement in t lim is not as strong as at lower doses while \(\dot{V}\)O2max increases in a dose-dependent manner.


We investigated the effects of different doses of rhEPO given during 4 weeks [placebo (P), low (L), medium (M), and high (H) dosage] on RCV, PV, \(\dot{V}\)O2max and t lim in 40 subjects.


While RCV increased in a dose-dependent manner, PV decreased independent of the rhEPO dose. The improvements in t lim (P +21.4 ± 23.8 %; L +16.7 ± 29.8 %; M +44.8 ± 62.7 %; H +69.7 ± 73.4 %) depended on the applied doses (R 2 = 0.89) and clearly exceeded the dose-independent \(\dot{V}\)O2max increases (P −1.7 ± 3.2 %; L +2.6 ± 6.8 %; M +5.7 ± 5.1 %; H +5.6 ± 4.3 %) after 4 weeks of rhEPO administration. Furthermore, the absolute t lim was not related (R 2 ≈ 0) to RCV or to \(\dot{V}\)O2max.


We conclude that a contraction in PV does not negatively affect t lim and that rhEPO improves t lim by additional, non-hematopoietic factors.


rhEPO doping Oxygen transport capacity Red blood cell volume Plasma volume 



Analysis of variance


Anaerobic work capacity




Constant-load test


Carbon monoxide


Critical power


Coefficient of variation


End point (after 4 weeks)




Cellular factor (HctWB/Hct)


High dosage of rhEPO (10,000 IU)




Whole body haematocrit


Intra venous


Indocyanine green


Incremental cycling test


Low dosage of rhEPO (2,500 IU)


Medium dosage of rhEPO (5,000 IU)


Mid point (after 2 weeks)


Sodium chloride




Placebo (physiological NaCl solution)


Maximal power


Plasma volume


Red cell volume


Respiratory exchange rate


Recombinant human EPO


Revolution per min


Time after 360 s


Time of CLT


Carbon dioxide production


Minute ventilation


Oxygen consumption


Mean \(\dot{V}\)O2 during the last 30 s before t lim


Maximum oxygen consumption



The authors are grateful to the participants for their voluntarily contribution. We also thank Renate Huch, Christian Bauer, Marco Toigo and René Rossi for scientific assistance. The study was financially supported by the Eidgenössische Sportkommission, Magglingen (to UB).

Compliance with ethical standards

Conflict of interest

The authors have no conflicts of interest.


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Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • Simon Annaheim
    • 1
    • 2
    • 3
  • Matthias Jacob
    • 4
  • Alexander Krafft
    • 5
  • Christian Breymann
    • 5
  • Markus Rehm
    • 4
  • Urs Boutellier
    • 1
    • 3
    • 6
    Email author
  1. 1.Exercise Physiology, Institute of Human Movement SciencesETH ZurichZurichSwitzerland
  2. 2.Laboratory for Protection and PhysiologyEMPA, Swiss Federal Laboratories for Materials Science and TechnologySt. GallenSwitzerland
  3. 3.Exercise Physiology, Institute of PhysiologyUniversity of ZurichZurichSwitzerland
  4. 4.Department of AnaesthesiologyUniversity HospitalMunichGermany
  5. 5.Division of Obstetrics, Department of Obstetrics and GynaecologyUniversity HospitalZurichSwitzerland
  6. 6.Exercise PhysiologyETH ZurichWinterthurSwitzerland

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