Determining an erythropoietin threshold is not sufficient for accelerating erythrocyte production by Julien V. Brugniaux and Aurélien Pichon

Abstract

The physiological mechanisms responsible for performance enhancement following the "live high-train low" model has been a hot button topic as evidenced by the recent Point-Counterpoint (Levine and Stray- Gundersen 2005). As such, the altitude exposure research conducted by our laboratory has focused on exploring the complicated interaction between duration and intensity of hypoxia, irrespective of training state, on physiological parameters. Our recent work (McLean et al. 2006) investigated the hematological adaptations resulting from three consecutive days of normobaric hypoxia. Brugniaux and co-workers have presented some concerns with our methodology, our markers of erythropoiesis, and our speculation that there may be a threshold EPO that must be surpassed to stimulate erythroid production. We would like to address and clarify these concerns.Methodological areas that were questioned included the training status of our subjects, the presence or absence of symptoms of acute mountain sickness (AMS), and the use of a diurnal exposure. In keeping with our altitude research vision, we chose to avoid the confounding stimulus of prescribed exercise on erythropoiesis by not allowing our subjects to train during the study. This is in agreement with the second postulate put forth by Levine and Stray-Gundersen (2005) (p. 2053), whereby "the mechanism must be isolatable and demonstrated to have an unequivocal relationship to altitude exposure and improved performance".Granted, we did not measure performance but the purpose of our work was not to improve performance but rather to track hematological markers of erythropoiesis during and following an intermittent hypoxic protocol. Secondly, it is well accepted that acute exposure to high altitude may present with symptoms of AMS, however, with great individual variability (Ward et al. 2000). All of the subjects in our hypoxic group reported having mild to moderate headaches on day 1, which lessened on day 2 and were gone by day 3 of the exposures. Lastly, Brugniaux and coworkers criticize our use of diurnal hypoxic exposures instead of nocturnal hypoxic exposures because it appears EPO undergoes diurnal variation with its zenith being around 01:00 (Cahan et al. 1992). We chose an awake daytime hypoxic intervention to avoid the potential confounding occurrence of periodic breathing, or other sleep disturbances, which could exacerbate hypoxemia during a sleep night time protocol (Weil and White 2001). Despite exposing our subjects to hypoxia during daytime hours, which appear to correspond to the nadir of the EPO diurnal variation, we were still able to show a 237% increase from baseline levels to a peak serum EPO concentration of 31.9 § 8.3 U l ¡1 . In our recent work we speculate that there is possibly a threshold erythropoietin (EPO) concentration (we proposed 34 U l ¡1 ) that must be surpassed before accelerated erythroid production is evidenced.In the present study, s-[EPO] increased to 31.9 § 8.3 U l ¡1 after 2 days at a simulated altitude equivalent to 4,925 m with no o...