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12 Jun 2012

Erythropoietic & non-erythropoietic aspects of athlete performance after hypoxic exposure

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The prevailing paradigm is that sea level performance benefits subsequent to training at moderate altitude (~2000-3000m) are directly linked to an accelerated production of red blood cells, which lead to an increase in maximal oxygen consumption

Autor(es): Christopher J Gore, Sally A Clark, Philo U Saunders.
Entidades(es): University of South Australia
Congreso: International symposium of altitude training
Granada 2008
Palabras claves:

Erythropoietic & non-erythropoietic aspects of athlete performance after hypoxic exposure

Erythropoietic changes

The prevailing paradigm is that sea level performance benefits subsequent to training at moderate altitude (~2000-3000m) are directly linked to an accelerated production of red blood cells, which lead to an increase in maximal oxygen consumption (VO2max), and in turn results in improved endurance performance 16-18. Exposure to sufficient altitude for an adequate duration will accelerate the production of red blood cells 4,25,26, but we failed to detect changes in haemoglobin mass (Hbmass) greater than 1-2% in a carefully conducted experiment with world-class cyclists (mean VO2max = 81.4 ml.kg-1.min-1) after one month living and training at ~2700m 10, an approach referred to as living high, training high (LHTH). This result contrasted with the findings of other LHTH studies where 2050m for 3 wk increased red cell volume (RCV) by 12-13% 12, 2200m for 3 wk elevated Hbmass by 6% 9 and 2500m for 4 wk lifted RCV by 10% 16. In 2007, we repeated our LHTH study on top level Australian cyclists who spent 3 wk at 2850m and observed a ~3% increase in Hbmass, using a double baseline to verify the initial value and approximate weekly measures during the training block. Unlike our earlier study the cyclists remained healthy in 2007 and were not training >3500 km per month. Nevertheless, the relatively modest increase in Hbmass, is in accord with our prior suggestion that highly trained athletes may have limited scope to increase Hbmass 10 compared with untrained people or non-elite athletes who sojourn to altitude. Living high, training low (LHTL) is an alternate method of using terrestrial altitude 16 or simulated altitude 15 to increase RCV or Hbmass. Analysis of 15 LHTL studies 1,2,5,7,15,16,20- 22,27-30,33,34 indicates that moderate altitude exposure of >12 h.day-1 increases Hbmass by ~1% per 100 hours of exposure.

Non-erythropoietic changes

An alternate but complementy paradigm has been proposed 11 based on the known molecular response to hypoxia, which is mediated a transcription factor called hypoxia inducible factor-1 (HIF-1). HIF-1 is present in every tissue in the body and is the global regulator of oxygen homeostasis; its target genes include not only those associated with erythropoiesis and iron metabolism [such as erythropoietin (EPO) and transferrin receptor), but also those associated with vascular angiogenesis and tone (such as vascular endothelial growth factor and endothelin-1), glucose uptake and glycolysis (such as glucose transporter- 1 and lactate dehydrogenase) and pH regulation (such as carbonic anhydrase (CA)]. The ubiquitous effects of HIF-1 indicate that an increase in serum EPO of responders to hypoxia may be co-incident with, but not solely causative of, any performance benefits. One potentially beneficial response to hypoxia is improved economy of exercise as has been demonstrated by seven independent research groups 11, since performance in endurance events has been ascribed to the product of VO2max, the fractional utilization of VO2max and economy 8. The concept that hypoxia may improve the coupling of ATP demand and supply in mitochondria was first raised by Hochachka in 1988 13. Some recent support for this concept is evident in the effects of hypoxia training on improved mitochondrial function 23. Improvements in pH regulation and muscle buffer capacity are other responses to hypoxia that may be beneficial to sea level performance of elite athletes 11. We have observed a substantial reduction in plasma lactate concentration during exercise at 85% of VO2max after a 20-d period of LHTL, but when seeking a mechanism could not detect an increase in monocarboxylate transporter-1 (MCT-1) or MCT-4 6. Others have reported that hypoxic training increases muscle mRNA concentration of CA-3 (74%) and MCT-1 (44%) and that time to exhaustion after training in hypoxia was correlated to both the increase in CA-3 and MCT-1 35, but these results require replication particularly after both LHTH and LHTL. Several studies with and without control groups have reported 5-18% improvements in muscle buffer capacity (?m) after both LHTH and LHTL 19, but this is not a universal finding 32 and our own attempts to replicate the 18% increase in ?m after 21 nights at 3000m LHTL also failed 6. These conflicting results suggest that the changes in ?m may be relatively small compared with the precision of the titration technique. Consequently, further studies are warranted but obtaining muscle samples from elite athletes is problematic. Performance The reliability of race performance of elite athletes is ~1-2% 24,31 and half of this (~0.5-1%) is worthwhile in terms of improving their chances of medalling 14. Against these criteria we can evaluate the magnitude of benefit of altitude training for subsequent sea-level performance. A forthcoming meta-analysis of performance after altitude training provides some perspective about the magnitude of improvement that may come from LHTH or LHTL and other hypoxic modalities 3. For elite athletes the performance benefit after LHTH was 1.9± 2.4% (mean ± 90% confidence limits) for all studies evaluated and 1.6 ± 2.7% when controlled studies only were analysed. The corresponding values for LHTL were 1.6± 1.8% for all studies and 4.0 ± 3.7% for the controlled studies, although in the controlled studies the performance of the control groups deteriorated. Summary and conclusions Sufficient exposure to moderate altitude (>12h/day for >300h) likely increases Hbmass or RCV by ~3% in elite athletes, but the HIF-1 response to hypoxia suggest that other effects including improved mitochondrial efficiency, muscle pH and ?m may also be possible. The performance benefit of hypoxic training/living is ~1-2%, which is more than adequate to improve an elite athlete’s chances of medalling, although there is substantial variability between, and likely within, athletes in terms of their responsiveness.


Ashenden MJ, Gore CJ, Dobson GP, Hahn AG. “Live high, train low” does not change the total haemoglobin mass of male endurance athletes sleeping at a simulated altitude of 3000 m for 23 nights. Eur J Appl Physiol. 1999;80:479-484. Ashenden MJ, et al. Effects of a 12-day “live high, train low” camp on reticulocyte production and haemoglobin mass in elite female road cyclists. Eur J Appl Physiol. 1999;80:472-478.

Bonetti DL, Hopkins WG. Sea-Level Exercise Performance Following Adaptation to Hypoxia: a Meta-Analysis. Sports Med. 2008; In review.

Böning D, Maassen N, Jochum F et al. After-effects of a high altitude expedition on blood. Int J Sports Med. 1997;18:179-185.

Brugniaux JV, et al. Eighteen days of “living high, training low” stimulate erythropoiesis and enhance aerobic performance in elite middle-distance runners. J Appl Physiol. 2006;100:203-211.

Clark SA, Aughey RJ, Gore CJ et al. Effects of live high, train low hypoxic exposure on lactate metabolism in trained humans. J Appl Physiol. 2004;96:517-525.

Dehnert C, Hutler M, Liu Y et al. Erythropoiesis and performance after two weeks of living high and training low in well trained triathletes. Int J Sports Med. 2002;23:561-566.

di Prampero PE. The energy cost of human locomotion on land and in water. Int J Sports Med. 1986;7:55-72.

Friedmann B, et al. Individual variation in the erythropoietic response to altitude training in elite junior swimmers. Br J Sports Med. 2005;39:148-153.

Gore C, Craig N, Hahn A et al. Altitude training at 2690m does not increase total haemoglobin mass or sea level VO2max in world champion track cyclists. J Sci Med Sport. 1998;1:156-170.

Gore CJ, Clark SA, Saunders PU. Non-hematological mechanisms of improved sea level performance after hypoxic exposure. Med Sci Sports Exerc. 2007;39:1600-1609.

Heinicke K, et al. A three-week traditional altitude training increases hemoglobin mass and red cell volume in elite biathlon athletes. Int J Sports Med. 2004;26:350-355.

Hochachka PW. Patterns of O2-dependence of metabolism. Adv Exp Med Biol. 1998;222:143-51.

Hopkins, W. G. How to interpret changes in an athletic performance test. Sportscience2004;8:1-7. http://www.sportsci.org/jour/04/wghtests.htm

Laitinen, H., et al. Acclimatization to living in normobaric hypoxia and training in normoxia at sea level in runners. Med Sci Sports Exerc 1995;27: S109.

Levine BD, Stray-Gundersen J. “Living high-training low”: effect of moderate-altitude acclimatization with low altitude training on performance. J Appl Physiol. 1997;83:102-112.

Levine BD, Stray-Gundersen J. The effects of altitude training are mediated primarily by acclimatization, rather than by hypoxic exercise. Adv Exp Med Biol. 2001;502:75-88.

Levine BD, Stray-Gundersen J. Dose-response of altitude training: how much altitude is enough? Adv Exp Med Biol. 2006;588:233-247.

Mizuno M, Juel C, Bro-Rasmussen T et al. Limb skeletal muscle adaptation in athletes after training at altitude. J Appl Physiol. 1990;68:496-502.

Muir, I. H., Salazar, A. B., and Dahms, T. Effect of 40 days sleeping in normobaric hypoxia on total hemoglobin mass in competitive runners. Med Sci Sports Exerc 2003;35: S115.

Neya M, Enoki T, Kumai Y, Sugoh T, Kawahara T. The effects of nightly normobaric hypoxia and high intensity training under intermittent normobaric hypoxia on running economy and hemoglobin mass. J Appl Physiol. 2007;103:834. Piehl Aulin K. Normobaric hypoxia – physical performance. J Sports Sci. 1998;16:478-479.

Ponsot E et al. Exercise training in normobaric hypoxia in endurance runners. II. Improvement of mitochondrial properties in skeletal muscle. J Appl Physiol. 2006;100:1249-1257.

Pyne D, Trewin C, Hopkins W. Progression and variability of competitive performance of Olympic swimmers. J Sports Sci. 2004;22:613-620.

Reeves JT, Zamudio S, Dahms TE et al. Erythropoiesis in women during 11 days at 4,300 m is not affected by menstrual cycle phase. J Appl Physiol. 2001;91:2579-2586.

Robach P, Fulla Y, Westerterp KR, Richalet JP. Comparative response of EPO and soluble transferrin receptor at high altitude. Med Sci Sports Exerc. 2004;36:1493-1498.

Robach P, Schmitt L, Brugniaux JV et al. Living high-training low: effect on erythropoiesis and maximal aerobic performance in elite Nordic skiers. Eur J Appl Physiol. 2006;97:695-705.

Robach P, Schmitt L, Brugniaux JV et al. Living high-training low: effect on erythropoiesis and aerobic performance in highly-trained swimmers. Eur J Appl Physiol. 2005;1-11.

Rusko, HK, et al. Effect of living in hypoxia and training in normoxia on sea level VO2max and red cell mass. Med Sci Sports Exerc 1999;31: S86.

Saunders PU, et al. Improved running economy and increased hemoglobin mass in elite runners after extended moderate altitude exposure. J Sci Med Sport. 2007;Dec 7 [Epub ahead of print].

Stewart AM, Hopkins WG. Consistency of swimming performance within and between competitions. Med Sci Sports Exerc. 2000;32:997-1001.

Stray-Gundersen J, Levine BD, Bertocci LA. Effect of altitude training on runner’s skeletal muscle. Med Sci Sports Exerc. 1999;31:S182.

Wehrlin JP, Marti B. Live high-train low associated with increased haemoglobin mass as preparation for the 2003 World Championships in two native European world class runners. Br J Sports Med. 2006;40:e3. http://bjsm.bmj.com/cgi/content/full/40/2/e3

Wehrlin JP, Zuest P, Hallen J, Marti B. Live high – train low for 24 days increases hemoglobin mass and red cell volume in elite endurance athletes. J Appl Physiol. 2006;100:1938-1945.

Zoll J, Ponsot E, Dufour S et al. Exercise training in normobaric hypoxia in endurance runners. III. Muscular adjustments of selected gene transcripts. J Appl Physiol. 2006;100:1258-1266.

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