European Journal of Applied Physiology

, Volume 106, Issue 1, pp 51–59 | Cite as

Cumulative effects of consecutive running sessions on hemolysis, inflammation and hepcidin activity

  • Peter PeelingEmail author
  • Brian Dawson
  • Carmel Goodman
  • Grant Landers
  • Erwin T. Wiegerinck
  • Dorine W. Swinkels
  • Debbie Trinder
Original Article


The effect of two running sessions completed within a 12-h period on hemolysis, inflammation, and hepcidin activity in endurance athletes was investigated. Ten males completed two experimental trials in a randomized, counterbalanced order. The two trials included (a) a one-running-session trial (T1) including 10 × 1 km interval repeats (90% peak \( \dot{V}{\text{O}}_{2} \) velocity), and (b) a two-running-session trial (T2), comprising a continuous 10-km run (70% peak \( \dot{V}{\text{O}}_{2} \) velocity), and a 10 × 1 km interval run (90% peak \( \dot{V}{\text{O}}_{2} \) velocity) completed 12 h later. Interleukin-6 (IL-6), free hemoglobin (Hb), haptoglobin (Hp), iron, ferritin, and hepcidin were assessed post-exercise. After the T1 and T2 interval runs, free Hb was significantly increased and Hp significantly decreased (p ≤ 0.05), with a cumulative effect shown in T2 after the second run (p ≤ 0.05). The IL-6, serum iron, ferritin, and hepcidin activity were increased after each running session (p ≤ 0.05), with no cumulative effect in T2. In conclusion, a cumulative effect of two running sessions on hemolysis was shown, but no similar effect with inflammation and hepcidin activity was evident.


Iron deficient Cytokines Training Athlete 



The authors wish to acknowledge the grant funding received from the Fremantle Hospital Medical Research Foundation. The authors would also like to acknowledge the grant funding received from the University of Western Australia’s Research Grant Scheme. Grant funding for this project was received from the Fremantle Hospital Medical Research Foundation, and the University of Western Australia’s Research Grant Scheme.


  1. Babić Z, Papa B, Sikirika-Bosnjaković M et al (2001) Occult gastrointestinal bleeding in rugby players. J Sports Med Phys Fitness 41:399–402PubMedGoogle Scholar
  2. Beard J, Tobin B (2000) Iron status and exercise. Am J Clin Nutr 72:594S–597SPubMedGoogle Scholar
  3. Bruunsgaard H, Galbo H, Halkjaer-Kristensen J et al (1997) Exercise-induced increase in serum interleukin-6 in humans is related to muscle damage. J Physiol 499:833–841PubMedGoogle Scholar
  4. Buchman AL, Keen C, Commisso J et al (1998) The effect of a marathon run on plasma and urine mineral and metal concentrations. J Am Coll Nutr 17:124–127PubMedGoogle Scholar
  5. DeRuisseau KC, Cheuvront SN, Haymes EM et al (2002) Sweat iron and zinc losses during prolonged exercise. Int J Sport Nutr Exerc Metab 12:428–437PubMedGoogle Scholar
  6. Giblett ER (1968) The haptoglobin system. Ser Haematol 1:3–20Google Scholar
  7. Jones AM, Doust JH (1996) A 1% treadmill grade most accurately reflects the energetic cost of outdoor running. J Sports Sci 14:321–327. doi: 10.1080/02640419608727717 PubMedCrossRefGoogle Scholar
  8. Kemna E, Pickkers P, Nemeth E et al (2005a) Time-course analysis of hepcidin, serum iron, and plasma cytokine levels in humans injected with LPS. Blood 106:1864–1866. doi: 10.1182/blood-2005-03-1159 PubMedCrossRefGoogle Scholar
  9. Kemna E, Tjalsma H, Laarakkers C et al (2005b) Novel urine hepcidin assay by mass spectrometry. Blood 106:3268–3270. doi: 10.1182/blood-2005-05-1873 PubMedCrossRefGoogle Scholar
  10. Kemna EH, Tjalsma H, Podust VN (2007) Mass spectrometry-based hepcidin measurements in serum and urine: analytical aspects and clinical implications. Clin Chem 53:620–628. doi: 10.1373/clinchem.2006.079186 PubMedCrossRefGoogle Scholar
  11. Kristiansen M, Graversen JH, Jacobsen C (2001) Identification of the haemoglobin scavenger receptor. Nature 409:198–201. doi: 10.1038/35051594 PubMedCrossRefGoogle Scholar
  12. Margeli A, Skenderi K, Tsironi M et al (2005) Dramatic elevations of interleukin-6 and acute-phase reactants in athletes participating in the ultradistance foot race spartathlon: severe systemic inflammation and lipid and lipoprotein changes in protracted exercise. J Clin Endocrinol Metab 90:3914–3918. doi: 10.1210/jc.2004-2346 PubMedCrossRefGoogle Scholar
  13. McInnis MD, Newhouse IJ, von Duvillard SP et al (1998) The effect of exercise intensity on hematuria in healthy male runners. Eur J Appl Physiol Occup Physiol 79:99–105. doi: 10.1007/s004210050480 PubMedCrossRefGoogle Scholar
  14. Miller B, Pate RR, Burgess W (1988) Foot impact force and intravascular hemolysis during distance running. Int J Sports Med 9:56–60. doi: 10.1055/s-2007-1024979 PubMedCrossRefGoogle Scholar
  15. Nemeth E, Rivera S, Gabayan V et al (2004a) IL-6 mediates hypoferremia of inflammation by inducing the synthesis of the iron regulatory hormone hepcidin. J Clin Invest 113:1271–1276PubMedGoogle Scholar
  16. Nemeth E, Tuttle MS, Powelson J et al (2004b) Hepcidin regulates cellular iron efflux by binding to ferroportin and inducing its internalisation. Science 306:2090–2093. doi: 10.1126/science.1104742 PubMedCrossRefGoogle Scholar
  17. Ostrowski K, Hermann C, Bangash A et al (1998) A trauma-like elevation of plasma cytokines in humans in response to treadmill running. J Physiol 513:889–894. doi: 10.1111/j.1469-7793.1998.889ba.x PubMedCrossRefGoogle Scholar
  18. Ostrowski K, Schjerling P, Pedersen BK (2000) Physical activity and plasma interleukin-6 in humans—effect of intensity of exercise. Eur J Appl Physiol 83:512–515. doi: 10.1007/s004210000312 PubMedCrossRefGoogle Scholar
  19. Park CH, Valore EV, Waring AJ et al (2001) Hepcidin, a urinary antimicrobial peptide synthesized in the liver. J Biol Chem 276:7806–7810. doi: 10.1074/jbc.M008922200 PubMedCrossRefGoogle Scholar
  20. Pattini A, Schena F, Guidi GC (1990) Serum ferritin and serum iron changes after cross-country and roller ski endurance races. Eur J Appl Physiol Occup Physiol 61:55–60. doi: 10.1007/BF00236694 PubMedCrossRefGoogle Scholar
  21. Pedersen BK, Steensberg A, Schjerling P (2001) Exercise and interleukin-6. Curr Opin Hematol 8:137–141. doi: 10.1097/00062752-200105000-00002 PubMedCrossRefGoogle Scholar
  22. Peeling P, Dawson B, Goodman C et al (2008a) Athletic induced iron deficiency: new insights into the role of inflammation, cytokines and hormones. Eur J Appl Physiol 103:381–391. doi: 10.1007/s00421-008-0726-6 PubMedCrossRefGoogle Scholar
  23. Peeling P, Dawson B, Goodman C et al (2008b) Training surface and intensity: inflammation, hemolysis and hepcidin expression. Med Sci Sports Exerc (in press)Google Scholar
  24. Poortmans JR, Haralambie G (1979) Biochemical changes in a 100 km run: proteins in serum and urine. Eur J Appl Physiol Occup Physiol 40:245–254. doi: 10.1007/BF00421516 PubMedCrossRefGoogle Scholar
  25. Roecker L, Meier-Buttermilch R, Brechtel L et al (2005) Iron-regulatory protein hepcidin is increased in female athletes after a marathon. Eur J Appl Physiol 95:569–571. doi: 10.1007/s00421-005-0055-y PubMedCrossRefGoogle Scholar
  26. Ronsen O, Lea T, Bahr R et al (2002) Enhanced plasma IL-6 and IL-1ra responses to repeated vs. single bouts of prolonged cycling in elite athletes. J Appl Physiol 92:2547–2553PubMedGoogle Scholar
  27. Schobersberger W, Tschann M, Hasibeder W et al (1990) Consequences of 6 weeks of strength training on red cell O2 transport and iron status. Eur J Appl Physiol Occup Physiol 60:163–168. doi: 10.1007/BF00839152 PubMedCrossRefGoogle Scholar
  28. Selby GB, Eichner ER (1986) Endurance swimming, intravascular hemolysis, anemia, and iron depletion, new perspective on athlete’s anemia. Am J Med 81:792–794. doi: 10.1016/0002-9343(86)90347-5 CrossRefGoogle Scholar
  29. Swinkels DW, Girelli D, Laarakkers C et al (2008) Advances in quantitative hepcidin measurements by time of flight mass spectrometry. PLoS ONE 3:e2706. doi: 10.1371/journal.pone.0002706 PubMedCrossRefGoogle Scholar
  30. Telford R, Sly GJ, Hahn AG et al (2003) Footstrike is the major cause of hemolysis during running. J Appl Physiol 94:38–42PubMedGoogle Scholar
  31. Van Dijk BA, Kemna EH, Tjalsma H et al (2007) Effect of the new HJV-L165X mutation on penetrance of HFE. Blood 109:5525–5526. doi: 10.1182/blood-2006-11-058560 PubMedCrossRefGoogle Scholar
  32. Van Vlierberghe H, Langloisb M, Delanghec J (2004) Haptoglobin polymorphisms and iron homeostasis in health and in disease. Clin Chim Acta 345:35–42. doi: 10.1016/j.cccn.2004.03.016 PubMedCrossRefGoogle Scholar
  33. Zoller H, Vogel W (2004) Iron supplementation in athletes—first do no harm. Nutrition 20:615–619. doi: 10.1016/j.nut.2004.04.006 PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Peter Peeling
    • 1
    Email author
  • Brian Dawson
    • 1
  • Carmel Goodman
    • 2
  • Grant Landers
    • 1
  • Erwin T. Wiegerinck
    • 3
  • Dorine W. Swinkels
    • 3
  • Debbie Trinder
    • 4
  1. 1.School of Sport Science, Exercise and HealthThe University of Western AustraliaCrawleyAustralia
  2. 2.Western Australian Institute of SportMt ClaremontAustralia
  3. 3.Department of Clinical ChemistryRadboud UniversityNijmegenThe Netherlands
  4. 4.School of Medicine and PharmacologyThe University of Western AustraliaFremantleAustralia

Personalised recommendations