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Int J Sports Med 2007; 28(1): 9-15
DOI: 10.1055/s-2006-924029
Physiology & Biochemistry

© Georg Thieme Verlag KG Stuttgart · New York

Effect of Physical Fitness and Endurance Exercise on Indirect Biomarkers of Recombinant Erythropoietin Misuse

R. Abellan1 , 2 , R. Ventura1 , 2 , S. Pichini3 , I. Palmi3 , M. Bellver4 , R. Olive4 , R. Pacifici3 , J. A. Pascual1 , 2 , P. Zuccaro3 , J. Segura1 , 2
  • 1Pharmacology Research Unit, Institut Municipal d'Investigació Mèdica, Barcelona, Spain
  • 2Department of Experimental and Health Research, Universitat Pompeu Fabra, Barcelona, Spain
  • 3Drug Research and Evaluation Department, Istituto Superiore di Sanitá, Rome, Italy
  • 4Centre d'Alt Rendiment, Barcelona, Spain
Further Information

Publication History

Accepted after revision: February 9, 2006

Publication Date:
26 June 2006 (online)

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Abstract

Erythropoietin (EPO) and soluble transferrin receptor (sTfR) in serum have been proposed as indirect biomarkers for the detection of recombinant human EPO (rhEPO) misuse in sport. The purpose of the present study was to investigate the influence of different levels of physical fitness, sport, different training workload during the sport season, and endurance exercise in the concentrations of these serum biomarkers for their application into mathematical models to indirectly detect rhEPO misuse. Serum EPO and sTfR concentrations were measured in 96 elite athletes of various sports along the sport season, in 21 recreational athletes at baseline (non exercising) conditions and in 129 other recreational athletes before and after long-distance races (10 and 21 km). In elite athletes, hemoglobin concentrations and percentage of reticulocytes were also measured, and indirect detection models applied. In recreational athletes, for EPO and sTfR, significant differences were only observed after the 21-km race. In baseline conditions, no differences were observed between recreational and elite athletes for EPO and sTfR. In elite athletes, individual EPO and sTfR concentrations slightly changed over the sport season, with coefficients of variation (CV) of 26.1 % and 9.0 %, respectively. Hemoglobin and reticulocytes were influenced by sport, but their individual variation over the sport season was not physiologically relevant (CV of 3.7 % and 21.3 %, respectively). When applying mathematical models for detection of rhEPO administration, only one elite athlete obtained an individual model score above the established thresholds. Physical fitness, sport and different training workload during the sport season had no substantial effect on serum EPO and sTfR concentrations, except in recreational athletes after a 21-km race. Variations observed in mathematical models to detect EPO administration were mainly due to fluctuation in hemoglobin concentrations, commonly observed in elite athletes.

Key words

EPO - sTfR - indirect markers - doping detection - exercise

References

  • 1 Abellan R, Ventura R, Pichini S, Remacha A F, Pascual J A, Pacifici R, Di Giovannandrea R, Zuccaro P, Segura J. Evaluation of immunoassays for the measurement of erythropoietin (EPO) as an indirect biomarker of recombinant human EPO misuse in sport.  J Pharm Biomed Anal. 2004;  35 1169-1177
    CrossrefPubMedGoogle Scholar
  • 2 Abellan R, Ventura R, Pichini S, Sarda M P, Remacha A F, Pascual J A, Palmi I, Bacosi A, Pacifici R, Zuccaro P, Segura J. Evaluation of immunoassays for the measurement of soluble transferrin receptor (sTfR) as an indirect biomarker of recombinant human erythropoietin misuse in sport.  J Immunol Meth. 2004;  295 89-99
    CrossrefPubMedGoogle Scholar
  • 3 Allen J, Backstrom K R, Cooper J A, Cooper M C, Detwiler T C, Essex D W, Fritz R P, Means R T, Meier P B, Pearlman S R, Roitman-Johnson B, Seligman P A. Measurement of soluble transferrin receptor in serum of healthy adults.  Clin Chem. 1998;  44 35-39
    PubMedGoogle Scholar
  • 4 Ashenden M J, Gore C J, Parisotto R, Sharpe K, Hopkins W G, Hanh A G. Effect of altitude on second-generation blood tests to detect erythropoietin abuse by athletes.  Haematologica. 2003;  88 1053-1062
    PubMedGoogle Scholar
  • 5 Berglund B, Birgegard G, Hemmingsson P. Serum erythropoietin in cross-country skiers.  Med Sci Sports Exerc. 1988;  20 208-209
    PubMedGoogle Scholar
  • 6 Cooper M J, Zlotkin S H. Day-to-day variation of transferrin receptor in healthy men and women.  Am J Clin Nutr. 1996;  64 738-742
    PubMedGoogle Scholar
  • 7 Deruisseau K C, Roberts L M, Kushnick M R, Evans A M, Austin K, Haymes E M. Iron status of young males and females performing weight-training exercise.  Med Sci Sports Exerc. 2004;  36 241-248
    CrossrefPubMedGoogle Scholar
  • 8 Gore C J, Parisotto R, Ashenden M J, Stray-Gundersen J, Sharpe K, Hopkins W, Emslie K R, Howe C, Trout G J, Kazlauskas R, Hahn A G. Second-generation blood test to detect erythropoietin abuse by athletes.  Haematologica. 2003;  88 333-344
    PubMedGoogle Scholar
  • 9 Kargotich S, Goodman C, Keast D, Morton A R. The influence of exercise-induced plasma volume changes on the interpretation of biochemical parameters used for monitoring exercise, training and sport.  Sports Med. 1998;  26 101-117
    CrossrefPubMedGoogle Scholar
  • 10 Klausen T, Breum L, Fogh-Andersen N, Bennett P, Hippe E. The effect of short and long duration exercise on serum erythropoietin concentrations.  Eur J Appl Physiol. 1993;  67 213-217
    CrossrefPubMedGoogle Scholar
  • 11 Maes M, Bosmans E, Scharpe S, Hendriks D, Cooremans W, Neels H, De Meyer F, D'Hondt P, Peeters D. Components of biological variation in serum soluble transferrin receptor: relationships to serum iron, transferrin and ferritin concentrations, and immune and haematological variables.  Scand J Clin Lab Invest. 1997;  57 31-41
    PubMedGoogle Scholar
  • 12 Malczewska J, Blach W, Stupnicki R. The effects of physical exercise on the concentrations of ferritin and transferrin receptor in plasma of female judoists.  Int J Sports Med. 2000;  21 175-179
    PubMedGoogle Scholar
  • 13 Malczewska J, Stupnicki R, Blach W, Turek-Lepa E. The effects of physical exercise on the concentrations of ferritin and transferrin receptor in plasma of male judoist.  Int J Sports Med. 2004;  25 516-521
    Article in Thieme ConnectPubMedGoogle Scholar
  • 14 Parisotto R, Gore C J, Emslie K, Ashenden M J, Brugnara C, Howe C, Martin D T, Trout G J, Hahn A G. A novel method utilizing markers of altered erythropoiesis for the detection of recombinant human erythropoietin abuse in athletes.  Haematologica. 2000;  85 564-572
    PubMedGoogle Scholar
  • 15 Parisotto R, Ashenden M J, Gore C J, Sharpe K, Hopkins W, Hahn A G. The effect of common hematologic abnormalities on the ability of blood models to detect erythropoietin abuse by athletes.  Haematologica. 2003;  88 931-940
    PubMedGoogle Scholar
  • 16 Raya G, Henny J, Steinmetz J, Herbeth B, Siest G. Soluble transferrin receptor (sTfR): biological variations and reference limits.  Clin Chem Lab Med. 2001;  39 1162-1168
    CrossrefPubMedGoogle Scholar
  • 17 Remacha A F, Ordoñez J, Barceló M J, García-Die F, Arza B, Estruch A. Evaluation of erythropoietin in endurance runners.  Haematologica. 1994;  79 350-352
    PubMedGoogle Scholar
  • 18 Roberts D, Smith D J. Erythropoietin does not demonstrate circadian rhythm in healthy men.  J Appl Physiol. 1996;  80 847-851
    PubMedGoogle Scholar
  • 19 Robinson N, Saugy M, Mangin P. Effects of exercise on the secondary blood markers commonly used to suspect erythropoietin doping.  Clin Lab. 2003;  49 57-62
    PubMedGoogle Scholar
  • 20 Schmidt W, Eckardt K U, Hilgendorf A, Strauch S, Bauer C. Effects of maximal and submaximal exercise under normoxic and hypoxic conditions on serum erythropoietin level.  Int J Sports Med. 1991;  12 457-461
    Article in Thieme ConnectPubMedGoogle Scholar
  • 21 Schumacher Y O, Grathwohl D, Barturen J M, Wollenweber M, Heinrich L, Schmid A, Huber G, Keul J. Haemoglobin, haematocrit, and red blood cell indices in elite cyclists. Are the control values for blood testing valid?.  Int J Sports Med. 2000;  21 380-385
    Article in Thieme ConnectPubMedGoogle Scholar
  • 22 Schumacher Y O, Schmid A, Grathwohl D, Bültermann D, Berg A. Hematological indices and iron status in athletes of various sports and performances.  Med Sci Sports Exerc. 2002;  34 869-875
    CrossrefPubMedGoogle Scholar
  • 23 Schumacher Y O, Schmid A, König D, Berg A. Effects of exercise on soluble transferrin receptor and other variables of the iron status.  Br J Sports Med. 2002;  36 195-200
    CrossrefPubMedGoogle Scholar
  • 24 Schumacher Y O, Jankovits R, Bültermann D, Schmid A, Berg A. Hematological indices in elite cyclists.  Scand J Med Sci Sports. 2002;  12 301-308
    CrossrefPubMedGoogle Scholar
  • 25 Schumacher Y O, Temme J, Bueltermann D, Schmid A, Berg A. The influence of exercise on serum markers of altered erythropoiesis and the indirect detection models of recombinant human erythropoietin abuse athletes.  Haematologica. 2003;  88 712-714
    PubMedGoogle Scholar
  • 26 Sharpe K, Hopkins W, Emslie K R, Howe C, Trout G J, Kazlauskas R, Ashenden M J, Gore C J, Parisotto R, Hahn A G. Development of reference ranges in elite athletes for markers of altered erythropoiesis.  Haematologica. 2002;  87 1248-1257
    PubMedGoogle Scholar
  • 27 Shaskey D J, Green G A. Sports haematology.  Sports Med. 2000;  29 27-38
    CrossrefPubMedGoogle Scholar
  • 28 Virtanen M A, Viinikka L U, Virtanen M K, Svahn J C, Anttila R M, Krusius T, Cook J D, Axelsson I E, Raiha N C, Siimes M A. Higher concentrations of serum transferrin in children than adults.  Am J Clin Nutr. 1999;  69 256-260
    PubMedGoogle Scholar
  • 29 Weight L M, Alexander D, Elliot T, Jacobs P. Erythropoietic adaptations to endurance training.  Eur J Appl Physiol. 1992;  64 444-448
    CrossrefPubMedGoogle Scholar

PhD Jordi Segura

Pharmacology Research Unit
Institut Municipal d'Investigació Mèdica (IMIM)

Doctor Aiguader 80

08003 Barcelona

Spain

Phone: + 34932211009

Fax: + 34 9 32 21 32 37

Email: jsegura@imim.es

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