Eur J Appl Physiol (2007) 99:325–326 DOI 10.1007/s00421-006-0344-0
L E T TE R T O TH E E D IT O RS
Determining an erythropoietin threshold is not suYcient for accelerating erythrocyte production Julien Brugniaux · Aurélien Pichon
Accepted: 31 October 2006 / Published online: 13 December 2006 © Springer-Verlag 2006
The study published by McLean et al. (2006) dealt with a very relevant topic. Actually, behind the question of the mechanisms involved in the improvement in performance following a living high–training low (LHTL) session, emerge the query of the suYcient dose of hypoxia insofar as one hypothesizes that oxygen carrying transport capacities are implicated in this improvement. However, we have some concerns mainly with the conclusions of the study of McLean and coworkers. Methodological concerns The authors compare their results to those obtained from the LHTL model; however subjects did not train during the study and were maybe even sedentary. It is far from unreasonable to think that training could have modiWed erythropoiesis. Moreover, an acute exposure of eight consecutive hours to an altitude of 4,925 m without any preliminary acclimatization have certainly triggered symptoms of acute mountain sickness (Richalet and Rathat 1991), but this is not reported in the article. Recovery after training would certainly be impeded by using such a high altitude. It has been recently proposed by Levine and Stray-Gundersen (in press) that an altitude below 3,000 m gives the best results in LHTL sessions. Lastly, for such a short exposure, a nocturnal exposure would be more eYcient that a diurnal one since it is known that the serum EPO level is at its zenith during night (Cahan et al. 1992). Markers of erythropoiesis To our mind the markers of erythropoiesis used by the authors are not the most accurate. Actually, total hemoglobin mass (Hbmass) J. Brugniaux (&) · A. Pichon Université Paris 13, Laboratoire Réponses cellulaires et fonctionnelles à l’hypoxie, ARPE, Bobigny Cedex, France e-mail:
[email protected]
measured by the CO-rebreathing method seems to be more pertinent since the variations in Hbmass are independent of circulating blood volume. Otherwise, the time course of Hct, Hb and RBC presented on Figs. 4, 5, and 6, respectively are very similar, which is not surprising. However what is remarkable is the very similar time course observed between control and hypoxic groups for these three parameters. The existing basal diVerence between groups persists during the whole study suggesting a limited eVect of the intervention. The signiWcant diVerence more suggests measurement artefacts rather than a physiological variation despite the absence of signiWcance among the control group on day 7. Is the proposition of the 34 UL–1 threshold in EPO secretion pertinent? In the conclusion, the authors speculate for a threshold EPO before any evidence of accelerated erythroid production. For the authors, this threshold is related to a daily exposure longer than 10 h per day. All the studies that have evidenced a role of the modiWcations of O2 carrying capacities as a responsible factor for the improvement in aerobic performance did not report the level of EPO. In a work of our team (Brugniaux et al. 2006b) the maximal level of EPO never exceeded half of the level proposed by McLean et al., but we have shown a clear stimulation of erythropoiesis as mentioned by the authors in this article. Paradoxically we even evidenced a higher Hbmass after 13 days of LHTL despite any increased EPO at the moment of the measurement (Robach et al. 2006a). Nevertheless to our mind, the propositions of the authors of the present article are interesting and relevant but incomplete. It seems preferable to consider the entire hypoxic stimulation more than a level of EPO by itself. Actually, the recent debate is focused on the dose
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of hypoxia needed to increase Hbmass or RBC. It appears that subjects have to spend daily more time in hypoxia than in normoxia to avoid neocytolysis (Levine and Stray-Gundersen 2005). Moreover, besides the daily exposure time, it has been suggested that the total duration of such a sojourn should exceed 18 days. Our team has proposed a total exposure superior to 250 h taking into account the precedent recommendation (Brugniaux et al. 2006b). Finally the choice of the altitude has its importance. Levine and Stray-Gundersen (in press) have proposed an optimal altitude ranged between 2,000 and 2,500 m. Using an altitude higher than 3,000 m does not add anything; it even appears that when the intermittent exposure is coupled with training an altitude corresponding to 3,500 m is somewhat detrimental (Brugniaux et al. 2006a; Robach et al. 2006b). Hence the proWle of the altitude exposure proposed by the authors seems inaccurate to a “real” LHTL training session. References Brugniaux JV, Schmitt L, Robach P, Jeanvoine H, Zimmermann H, Nicolet G, Duvallet A, Fouillot JP, Richalet JP (2006a) Living high–training low: tolerance and acclimatization in elite endurance athletes. Eur J Appl Physiol 96:66–77
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Eur J Appl Physiol (2007) 99:325–326 Brugniaux JV, Schmitt L, Robach P, Nicolet G, Fouillot JP, Moutereau S, Lasne F, Pialoux V, Saas P, Chorvot MC, Cornolo J, Olsen NV, Richalet JP (2006b) Eighteen days of “Living High–Training Low” stimulate erythropoiesis and enhance aerobic performance in elite middle-distance runners. J Appl Physiol 100:203–211 Cahan C, Decker MJ, Arnold JL, Washington LH, Veldhuis JD, Goldwasser E, Strohl KP (1992) Diurnal variations in serum erythropoietin levels in healthy subjects and sleep apnea patients. J Appl Physiol 72:2112–2117 Levine BD, Stray-Gundersen J (2005) Point: positive eVects of intermittent hypoxia (live high:train low) on exercise performance are mediated primarily by augmented red cell volume. J Appl Physiol 99:2053–2055 Levine BD, Stray-Gundersen J Dose-response of altitude training: how much altitude is enough? Adv Exp Med (in press) McLean SR, Kolb JC, Norris SR, Smith DJ (2006) Diurnal normobaric moderate hypoxia raises serum erythropoietin concentration but does not stimulate accelerated erythrocyte production. Eur J Appl Physiol 96:651–658 Richalet JP, Rathat C (1991) Pathologie et altitude. Masson, Paris Robach P, Schmitt L, Brugniaux JV, Roels B, Millet G, Hellard P, Nicolet G, Duvallet A, Fouillot JP, Moutereau S, Lasne F, Pialoux V, Olsen NV, Richalet JP (2006a) Living high–training low: eVect on erythropoiesis and aerobic performance in highly-trained swimmers. Eur J Appl Physiol 96:423–433 Robach P, Schmitt L, Brugniaux JV, Nicolet G, Duvallet A, Fouillot JP, Moutereau S, Lasne F, Pialoux V, Olsen NV, Richalet JP (2006b) Living high–training low: eVect on erythropoiesis and maximal aerobic performance in elite Nordic skiers. Eur J Appl Physiol 97:695–705
