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