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Iron Status & Fatigue in the Endurance Athlete

Iron Status & Fatigue in the Endurance Athlete. Should I get a serum ferritin?. Example Case. RJ Dimeff. Clin J Sports Med 2000 Female college middle-distance runner CC: Fatigue, abdominal cramping History, exam, labs unremarkable... Low Ferritin with a “normal” Hb/Hct

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Iron Status & Fatigue in the Endurance Athlete

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  1. Iron Status & Fatiguein theEndurance Athlete • Should I get a serum ferritin?

  2. Example Case • RJ Dimeff. Clin J Sports Med 2000 • Female college middle-distance runner • CC: Fatigue, abdominal cramping • History, exam, labs unremarkable... • Low Ferritin with a “normal” Hb/Hct • Rx: Ferrous sulfate, iron-rich foods • Slowly gets better • Same song, second verse the following year

  3. Rowland, et al. (1989) • This study was very poorly done... • but was a catalyst for the concept of using Fe++ • supplements in endurance athletes • Convenience sample of girl H.S. runners • Pre-season & post-season • Traditional max tests (ramp protocol) • Time to volitional exhaustion • No control of training programs

  4. Fatigue Work-Up • History (>90% in athletes) • Exercise/Rest Provocative or Palliative? • Anxiety & Depression • Meds/Substance Abuse • Exam (<5%) • Infection/Inflammatory/Metabolic • Cardiopulmonary/Neuromuscular • Malignancy (PM/DM)

  5. JL Beard. J. Nutr. 131: 568S–580S, 2001.

  6. Fatigue Work-Up • Labs (5-10%) • CBC • UA • Complete Metabolic Profile • TSH • Consider ECG / CXR / OGTT • Rheum screen • ESR, CK, Rheumatoid Factor, ANA

  7. Overtraining...or maybe Iron? • Definition of fatigue vs endurance • Quantifying fatigue in the physiology lab • Studies of iron supplementation & fatigue • Iron metabolism • Fear & loathing (hemochromatosis) • A (not so) final analysis

  8. What is Fatigue? • Christensen, E.H. 1960. Muscular work and fatigue, in Muscle as a Tissue, eds. K.Rodahl, S.M.Horvath, New York, McGraw-Hill. • Physical fatigue: a state of disturbed homeostasis attributable to work and to work environment.

  9. What is Endurance? • Åstrand, P.-O., Rodahl, K., Dahl, H.A., Strømme, S.B. 2003. Textbook of Work Physiology, 4th edition. Champaign, IL. • No definition of endurance • Physical endurance - GEM definition: • A state of prolonged homeostasis despite elevated levels of external physical work; resistance to physical fatigue.

  10. What is Fatigue? • Characterization of exertional fatigue: • Muscle fatigue = 1/endurance • In situ / In vitro preparations • Multiple parameters needed to quantify • Highly sensitive to independent parameters • N.B.: SERCA the likely final common pathway

  11. What is Fatigue? • Loss of muscle contractility & lusitropy • Highly sensitive to independent parameters: • Tpass • Stimulation frequency (twitch vs tetanic) • O2 supply (ml O2 / min, not just Hb/Hct) • Other (e.g., sympathetic stimulation, pressors)

  12. JL Beard. J. Nutr. 131: 568S–580S, 2001.

  13. JL Beard. J. Nutr. 131: 568S–580S, 2001.

  14. Again, Fatigue is... • Loss of contractility and lusitropy • Highly sensitive to O2 supply • TCA cycle and Ox Phos pathways are notrate-limiting in the O2 transport chain and are in excess capacity, • It is unlikely that skeletal muscle iron-dependent compounds are related to fatigability during exercise therefore...

  15. OK...What About Humans? • Problem: no good objective measure of “muscle failure” • Volitional exhaustion • Relative intensity a critical factor • Max steady-state (i.e., Vt, [La]4 mM, etc.) • Poor control of non-oxidative energy contribution • Failure of contractility • Rhythmic isometric/isokinetic contractions • Low %MVC, low duty cycle • 1 contraction / 5 sec, electrical stimulation, etc.

  16. Fatigue in Humans? • Longitudinal studies are very problematic • Constant O2 supply? • Increase in Hb increases O2 delivery • Constant fitness? • Constant absolute vs relative intensity? • Constant non-oxidative contribution? • Existing studies do two interventions • Training • Iron supplementation

  17. Haas, et al. • Examine effect of Fe++ supplements on running economy • Examine effect of Fe++ supplements and training on virtual time-trial performance • Examine effect of Fe++ supplements on isokinetic contractility of knee extensors (not electrically stimulated) • Examine effect of Fe++ supplements on ventilatory threshold in trained subjects

  18. Haas group. Am J Clin Nutr. 1997. 66:334-341.

  19. Hinton et al., (Haas group). JAP. 2000. 88:1103-1111.

  20. Hinton et al., (Haas group). JAP. 2000. 88:1103-1111.

  21. Hinton et al., (Haas group). JAP. 2000. 88:1103-1111.

  22. Brutsaert et al. (Haas group). Am J Clin Nutr. 2003. 77:441-448.

  23. Brutsaert et al. (Haas group). Am J Clin Nutr. 2003. 77:441-448.

  24. Brutsaert et al. (Haas group). Am J Clin Nutr. 2003. 77:441-448.

  25. Hinton & Sinclair. Eur J Clin Nutr. 2007. 61:30-39.

  26. Iron / Fatigue Research • Difficult studies, but fatally-flawed designs • Hb increases with Fe++ supplements • Little/no control of relative intensity • Various inequalities between groups • Multiple interventions (exercise and Fe++) • Volitional fatigue • Vt effect? - possibly but Vt ≠ fatigue

  27. Iron Metabolism • Could sub-normal iron metabolism contribute to fatigue via non-O2 transport mechanisms? • What does ferritin do, anyway?!

  28. JL Beard. J Nutr 2001; 131: 568S–580S.

  29. JL Beard. J Nutr. 2001; 131: 568S–580S.

  30. Ponka, et al. Semin Hematol. 1998; 35:35-54.

  31. EC Thiel. J Nutr. 2003; 133:1549S-1553S. Ryter & Tyrrell. Free Rad Bio Med. 2000; 28:289-309.

  32. Ponka, et al. Semin Hematol. 1998; 35:35-54.

  33. Ryter & Tyrrell. Free Rad Bio Med. 2000; 28:289-309.

  34. Smith & Roberts. Clin Chem. 1994. 27:335-440.

  35. Forget About Ferritin? • Well,...no. It can be dangerous. • Hemochromatosis genotypes (HFE mutations) are highly prevalent in the population - one of the most common congenital mutations. • There continue to be no case-reports of a runner with phenotypic hemochromatosis. • Never is a long time.

  36. Athletes: 50 pro cyclists + 15 “Olympic class endurance runners” (vs only cyclists in Deugnier et al. MSSE. 2002; 34:876-880.) Chicharro, et al. Br J Sports Med. 2004; 38:418-421.

  37. Forget About Ferritin? • Ferritin gene knockout - lethal in utero • Population prevalence of HFE - 33% • Athlete prevalence of HFE - 50% • Could the hemochromatosis gene be protective against iron-deficiency in runners?

  38. Non-O2 Transport Fe++? • CNS structures that contain Fe++ • Cortex, striatum, cerebellum, thalamus • Fe++ a co-factor in myelination • Dopaminergic regions “affected” ≥15% low • Mesolimbic & striatonigral tracts • Motor control, perception, motivation • Serotonin/Norepinephrine - not affected

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