American Journal of Sports Science and Medicine
ISSN (Print): 2333-4592 ISSN (Online): 2333-4606 Website: Editor-in-chief: Ratko Pavlović
Open Access
Journal Browser
American Journal of Sports Science and Medicine. 2013, 1(2), 17-27
DOI: 10.12691/ajssm-1-2-2
Open AccessArticle

Overestimated Effect of Epo Administration on Aerobic Exercise Capacity: A Meta-Analysis

Hein F.M. Lodewijkx1, , Bram Brouwer1, Harm Kuipers2 and René van Hezewijk1

1Department of Psychology, Open University, Heerlen, The Netherlands

2Department of Movement Sciences, University of Maastricht, Maastricht, The Netherlands

Pub. Date: April 28, 2013

Cite this paper:
Hein F.M. Lodewijkx, Bram Brouwer, Harm Kuipers and René van Hezewijk. Overestimated Effect of Epo Administration on Aerobic Exercise Capacity: A Meta-Analysis. American Journal of Sports Science and Medicine. 2013; 1(2):17-27. doi: 10.12691/ajssm-1-2-2


Recent studies examining the relationship between epo doping and aerobic performance (the EDAP–relationship) yield conflicting results. To resolve this inconclusiveness in an empirical way, we conducted a meta–analysis on 17 laboratory studies and assessed effect sizes (unbiased d, r and r2) of the epo–induced improvements in aerobic exercise capacity measured by maximal oxygen uptake (VO2max) and maximal aerobic power output (Wmap). The fixed, pooled EDAP effect size estimates were moderate, d = 0.41–0.49, r = .19–.44, and r2 = .04–.19, revealing a shift of approximately half SD in performances of the epo–treated compared to the non–treated participants. As to VO2max, we observed the strongest post test performance (M = 64.39ml kg-1 min-1) in double blind, placebo controlled studies on performances assessed at sea level with an increase from pre to post tests of M = 4.02ml kg-1 min-1. Regarding Wmap, the increase was M = 26W with the strongest post test performance of M = 398W observed in similar studies as VO2max. Percents improvement from pre to post tests varied between M = 6–7% (VO2max), and M = 7–8% (Wmap). The largest improvement in VO2max we found equals an increase in velocity of about 1km/h. Consistent with recent studies criticizing the EDAP-relationship our findings indicate that its strength is overestimated. In turn, this entails that the relationship between epo doping and cyclists’ performances at real contests is overrated too.

aerobic performance epo doping meta-analysis professional road racing

Creative CommonsThis work is licensed under a Creative Commons Attribution 4.0 International License. To view a copy of this license, visit


Figure of 4


[1]  Brouwer, B., Lodewijkx, H. F. M. and Kuipers, H., “Doping confessions of cyclists revisited.” [In Dutch: “Doping-bekentenissen van wielrenners langs de wetenschappelijke meetlat”]. Sportpsychologie Bulletin, 20: 24-37, 2009.
[2]  Lodewijkx, H.F.M., Give some and take some: Cycling as double play. [In Dutch: Tussen geven en nemen: Wielrennen als dubbelspel]. 2010 Uitgevers, Rotterdam, 2011.
[3]  Lodewijkx, H. F. M. and Brouwer, B. “Some empirical notes on the 'epo epidemic' in professional cycling.” Research Quarterly for Exercise and Sport, 82(4): 593-608, 2011.
[4]  Lodewijkx, H. F. M. and Brouwer B., “Tour, Giro Vuelta: Rapid progress in cycling performance starts in the 1980s.” International Journal of Sports Science, 2(3): 24-31, 2012.
[5]  Lodewijkx, H.F.M. and Verboon, P., “Lance Armstrong’s era of performance – Part 1: Are his time trial performances much different from other winners?” Journal of Athletic Enhancement, 2: 1, 2013.
[6]  Lundby, C. and Olsen, N. V., “Effects of recombinant human erythropoietin in normal humans.” Journal of Physiology, 589(6):1265-1271, 2011.
[7]  Ninot, G., Connes, P., and Caillaud, C., “Effects of recombinant human erythropoietin injections on physical self in endurance athletes.” Journal of Sports Sciences, 24: 383-391, 2006. (meta–analysis).
[8]  Catlin, D. H., Hatton, C. K., and Lasne, F., “Abuse of recombinant erythropoietins by athletes.” In G. Molineux, M. A. Foote, and S. G. Elliott (Eds.), Erythropoietins and erythropoiesis. Birkhäuser Verlag, Basel, 2006, 205-228.
[9]  Lasne, F., “Erythropoietin doping: Detection in urine.” In J. L.Fourcroy (Ed.), Pharmacology, doping and sport: Routledge, London, 2009, 107-124.
[10]  Varlet-Marie, E., Gaudard, A., Audran, M., and Bressolle, F., “Pharmacokinetics / pharmacodynamics of recombinant human erythropoietins in doping control.” Sports Medicine, 33(4): 301-315, 2003.
[11]  Bassett, D. R. and Howley, E. T., “Limiting factors for maximum oxygen uptake and determinants of endurance performance.” Medicine and Science in Sports and Exercise, 32: 70-84, 2000.
[12]  Coyle, E. F., Coggan, A. R., Hopper, M. K., and Walters, T. J., “Determinants of endurance in well-trained cyclists.” Journal of Applied Physiology, 64: 2622-2630, 1988.
[13]  Kuipers, H., “Putative effects of doping in cycling.” [In Dutch: “Vermeende effecten van doping in de wielersport”]. Nederlands Tijdschrift voor Geneeskunde, 150(48): 2643-2645, 2006.
[14]  Lucia, A., Hoyos, J., Pérez, M., Santalla, A., and Chicharro, J. L., “Inverse relationship between VO2max and economy/efficiency in world-class cyclists.” Medicine and Science in Sports and Exercise, 34: 2079-2084, 2002.
[15]  Lucia, A., Hoyos, J., Pérez, M., Santalla, A., Earnest, C. P., and Chicharro, J. L., “Which laboratory variable is related with time trial performance time in the Tour de France?” British Journal of Sports Medicine, 38: 636-640, 2004.
[16]  Heuberger, J. A. A. C., Cohen-Tervaert, J. M., Schepers, F. M. L., Vliegenthart. A. D. B., Rotmans, J. I., Daniels, J. M. A., Burggraaf, J. and Cohen, A. F., “Erythropoietin doping in cycling: Lack of evidence for efficacy and a negative risk–benefit.” British Journal of Clinical Pharmacology, 2012.
[17]  Hedges, L. V. and Olkin, I., Statistical methods for meta-analysis. Academic Press, New York, 1985.
[18]  Rosenthal, R., Rosnow, R. L., and Rubin, D. B., Contrast and effect sizes in behavioral research: A correlational approach. Cambridge University Press, Cambridge, UK, 2000.
[19]  Ashenden, M. J., Hahn, A. G., Martin, D. T., Logan, P., Parisotto, R., and Gore, C. J., “A comparison of the physiological response to simulated altitude exposure and r-HuEpo administration.” Journal of Sports Sciences, 19: 831-837, 2001. (meta–analysis).
[20]  Audran, M., Gareau, R., Matecki, S., Duran, F., Chenard, C., Sicart, M.T. et al., “Effects of erythropoietin administration in training athletes and possible indirect detection in doping control.” Medicine and Science in Sports and Exercise, 31: 639-645, 1999. (meta–analysis).
[21]  Balsom, P. D., Ekblom, B., and Sjodin, B., “Enhanced oxygen availability during high intensity intermittent exercise decreases anaerobic metabolite concentrations in blood.” Acta Physiologica Scandinavica, 150: 455-456, 1994. (meta–analysis).
[22]  Birkeland, K. I., Stray-Gundersen, J., Hemmersbach, P., Hallen, J., Haug, E., and Bahr, R., “Effect of rhEPO administration on serum levels of sTfR and cycling performance.” Medicine and Science in Sports and Exercise, 32: 1238-1243, 2000. (meta–analysis).
[23]  Connes, P., Caillaud, C., Mercier, J., Bouix, D., and Casties, J. F., “Injections of recombinant human erythropoietin increases lactate influx into erythrocytes.” Journal of Applied Physiology, 97(1): 326-332, 2004. (meta–analysis).
[24]  Connes, P., Perry, S., Varray, A., Préfaut, C., and Caillaud, C., “Faster oxygen uptake kinetics at the onset of submaximal cycling exercise following 4 weeks recombinant human erythropoietin (rHuEPO) treatment.” European Journal of Physiology, 447: 231-238, 2003. (meta–analysis).
[25]  Ekblom, B. and Berglund, B., “Effect of erythropoietin administration on maximal aerobic power.” Scandinavian Journal of Medicine and Science in Sports, 1(2): 88-93, 1991. (meta–analysis).
[26]  Lundby, C., Achman-Andersen, N. J., Thomsen, J. J., Norgaard, A. M., and Robach, P., “Testing for recombinant human erythropoietin in urine: Problems associated with current anti-doping testing.” Journal of Applied Physiology, 105: 417-419, 2008. (meta–analysis).
[27]  Lundby, C. and Damsgaard, R., “Exercise performance in hypoxia after novel erythropoiesis stimulating protein treatment.” Scandinavian Journal of Medicine and Science in Sports, 16: 35-40, 2006. (meta–analysis).
[28]  Lundby, C., Robach, P., Boushel, R., Thomsen, J. J., Rasmussen, P., Koskolou, M. et al., “Does recombinant human epo increase exercise capacity by means other than augmenting oxygen transport.” Journal of Applied Physiology, 105: 581-587, 2008. (meta–analysis).
[29]  Parisotto, R., Gore, C. J., Emslie, K. R., Ashenden, M. J., Brugnara, C., Howe, C. et al., “A novel method utilizing altered erythropoiesis for the detection of recombinant human erythropoietin abuse in athletes.” Haematologica, 85: 564-572, 2000. (meta–analysis).
[30]  Rassmussen, P., Foged, E. M., Krogh-Madsen, R., Nielsen, J., Nielsen, T. R., Olsen, N. V. et al., “Effects of erythropoietin administration on cerebral metabolism and exercise capacity in men.” Journal of Applied Physiology, 109 (2): 476-483, 2010. (meta–analysis).
[31]  Robach, P., Calbet, J. A. L., Thomsen, J. J., Boushel, R., Mollard, P., Rasmussen, P. et al., “The ergogenic effect of recombinant human erythropoietin on VO2max depends on the severity of arterial hypoxemia.” PLoS ONE, 3: 1-13, 2008. (meta–analysis).
[32]  Russell, G., Gore, C. J., Ashenden, M. J., Parisotto, R., and Hahn, A. G., “Effects of prolonged low doses of recombinant human erythropoietin during submaximal and maximal exercise.” European Journal of Applied Physiology, 86: 442-449, 2002. (meta–analysis).
[33]  Thomsen, J. J., Rentsch, R. L., Robach, P., Calbet, J. A. L., Boushel, R., Rasmussen, P. et al., “Prolonged administration of recombinant human erythropoietin increases submaximal performance more than maximal aerobic capacity.” European Journal of Applied Physiology, 101 (4): 481-486, 2007. (meta–analysis).
[34]  Wilkerson, D. P., Rittweger, J., Berger, N. J. A., Naish, F., and Jones, A. M., “Influence of recombinant human erythropoietin treatment on pulmonary O2 uptake kinetics during exercise in humans.” Journal of Physiology, 568: 639-652, 2005. (meta–analysis).
[35]  Rosenthal, R., “Parametric measures of effect size.” In H. Cooper and L. V. Hedges (Eds.), The handbook of research synthesis. Russell Sage Foundation, New York, 1994, 231-244.
[36]  Egger, M., Smith, G. D., Schneider, M., and Minder, C., “Bias in meta-analysis detected by a simple, graphical test.” British Medical Journal, 315: 629-634, 1997.
[37]  Cohen, J., Statistical power analysis for the behavioral sciences (2nd ed.). Lawrence Earlbaum Associates, Hillsdale, NJ, 1988.
[38]  Nevill, A. M., Jobson, S. A., Palmer, G. S., Olds, T. S., “Scaling maximal oxygen uptake to predict cycling time-trial performance in the field: a non-linear approach”. European Journal of Applied Physiology, 94: 705-710, 2005.
[39]  Jeukendrup, A. E., Craig, N. P., and Hawley, J. A., “The bioenergetics of World Class Cycling.” Journal of Science and Medicine in Sports, 3: 414-433, 2, 2000.
[40]  Johnson, A. T., Biomechanics and exercise physiology: Quantitative modeling. CRCPress / Taylor and Francis Group, New York, 2007.
[41]  Joyner, M. J., and Coyle, E. F., “Endurance exercise performance: The physiology of champions.” Journal of Physiology, 586: 35-44, 2008.
[42]  Wilmore, J. H., Costill, D. L., and Kenney, W. L., Physiology of sport and exercise. Human Kinetics, Champaign, Il., 2008.
[43]  Atkinson, G., Peacock, O., St Clair Gibson, A., and Tucker, R., “Distribution of power output during cycling: Impact and mechanisms.” Sports Medicine, 37: 647-667, 2007.
[44]  Myburg, K. H., “What makes an endurance athlete world-class?: Not simply a physiological conundrum. Comparative Biochemistry and Physiology - part A. Molecular and Integrative Physiology, 136: 171-190, 2003.
[45]  Hopkins, W. G., Hawley, J. A., and Burke, L. M., “Design and analysis of research on sport performance enhancement.” Medicine and Science in Sports and Exercise, 31: 472-485, 1999.
[46]  Lucia, A., Earnest, C., and Arribas, C., “The Tour de France: a physiological review.” Scandinavian Journal of Medicine and Science in Sports, 13: 275-283, 2003