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Iron Status & Fatigue in the Endurance Athlete Should I get a serum ferritin?

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Presentation on theme: "Iron Status & Fatigue in the Endurance Athlete Should I get a serum ferritin?"— Presentation transcript:

1 Iron Status & Fatigue in the Endurance 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 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 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.



12 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






18 What is Fatigue? Loss of muscle contractility & lusitropy Highly sensitive to independent parameters: T pass Stimulation frequency (twitch vs tetanic) O 2 supply (ml O 2 / min, not just Hb/Hct) Other (e.g., sympathetic stimulation, pressors)




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



25 Again, Fatigue is... Loss of contractility and lusitropy Highly sensitive to O 2 supply TCA cycle and Ox Phos pathways are not rate-limiting in the O 2 transport chain and are in excess capacity, It is unlikely that skeletal muscle iron-dependent compounds are related to fatigability during exercise therefore...

26 OK...What About Humans? Problem: no good objective measure of muscle failure Volitional exhaustion Relative intensity a critical factor Max steady-state (i.e., V t, [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.

27 Fatigue in Humans? Longitudinal studies are very problematic Constant O 2 supply? Increase in Hb increases O 2 delivery Constant fitness? Constant absolute vs relative intensity? Constant non-oxidative contribution? Existing studies do two interventions Training Iron supplementation

28 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

29 Haas group. Am J Clin Nutr :

30 Hinton et al., (Haas group). JAP :



33 Brutsaert et al. (Haas group). Am J Clin Nutr :




37 Hinton & Sinclair. Eur J Clin Nutr :30-39.

38 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 V t effect? - possibly but V t fatigue

39 Iron Metabolism Could sub-normal iron metabolism contribute to fatigue via non-O 2 transport mechanisms ? What does ferritin do, anyway?!

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

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

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

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

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

45 Ryter & Tyrrell. Free Rad Bio Med. 2000; 28:

46 Smith & Roberts. Clin Chem :

47 Forget About Ferritin? Well, 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.

48 Chicharro, et al. Br J Sports Med. 2004; 38: Athletes: 50 pro cyclists + 15 Olympic class endurance runners (vs only cyclists in Deugnier et al. MSSE. 2002; 34: )

49 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?

50 Non-O 2 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

51 A (Not So) Final Analysis James Beard on iron deficiency: Thus, although it is convenient at times to categorize individuals as iron-deficient anemic vs iron-deficient non- anemic, this is not a biological reality.

52 A (Not So) Final Analysis Ian Shrier on iron deficiency: Low ferritin with hemoglobin in the mid- to upper normal range is at best a relative indication for iron supplementation: low ferritin with hemoglobin in the low normal range is a stronger, yet still relative, indication for iron supplementation in athletes.

53 A (Not So) Final Analysis Ferritin still could be related to fatigue through CNS- mediated pathways Motor control Motivation Thermoregulation Other?

54 Should Runners Take Iron? All things being equal, if your competitor has a higher arterial O2 content than you, your only hope is that they will have a bad day... Competitive distance runners should probably take an iron supplement and/or eat iron-containing foods, i.e., red meats, unless not winning doesnt bother them Menstruating Women - very low risk of hemochromatosis Men - also at low risk? Someday...check a ferritin. If its not high, forget about it (at least while theyre a competitive runner)

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