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Commentary on Noakes’ Viewpoint
Blood lactate at high altitude: central command but also mass effect and adrenergic drive
Reduced skeletal muscle recruitment does not explain the lactate paradox – Part I
Reduced skeletal muscle recruitment does not explain the lactate paradox – Part II
Origin of the Lactate Paradox: muscles or brain?
Commentary on Viewpoint
Reduced skeletal muscle recruitment does not explain the lactate paradox
Origin of the Lactate Paradox: muscles or brain? Part II
Cerebral control of skeletal muscle recruitment during exercise at altitude
Commentary on Viewpoint: Evidence that reduced skeletal muscle recruitment explains the lactate para
To the Editor: It takes a Brain
To the Editor:
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Samuele M Marcora, Senior Lecturer in Exercise Physiology School of Sport, Health and Exercise Sciences, Bangor University, Wales, UK
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s.m.marcora{at}bangor.ac.uk Samuele M Marcora
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Noakes (5) and other authors have proposed that central motor command (CMC) and, consequently, exercise performance in hypoxia is determined either a) by simple negative feedback (1, 2) or complex feedback/feedforward (4) subconscious homeostatic control systems that, based on afferent information from central and peripheral chemoreceptors, limit skeletal muscle recruitment in order to avoid dangerous brain deoxygenation (4), respiratory failure (2) or excessive locomotor muscle fatigue and pain (1), or b) by the direct negative effects of severe brain hypoxia on maximal voluntary CMC and/or motivation to exercise (1, 6). However, these authors have overlooked a third possibility which, in our opinion, is simpler and biologically more plausible. Indeed, it is well established that the sensation of respiratory effort increases when ventilation is reflexly stimulated by hypoxia. According to our psychobiological model of exercise performance based on Brehm’s motivational intensity theory (3), this perceptual effect of hypoxia can increase overall perceived exertion and cause subjects to disengage from a task (which, in physiological terms, means a sudden reduction in CMC and exhaustion) earlier than in normoxic conditions even assuming no effect of hypoxia on motivation to exercise. During time trials, subjects are able to compensate for the increased sensation of respiratory effort by voluntarily reduce power output. This behavioural strategy maintains overall perception exertion within normal limits in order to ensure successful completion of the time trial despite hypoxia. Future studies need to control for rival hypotheses and establish experimentally which of the above three models is the most valid explanation for reduced CMC and exercise performance in hypoxia. References 1. Amann M, Romer LM, Subudhi AW, Pegelow DF, and Dempsey JA. Severity of arterial hypoxaemia affects the relative contributions of peripheral muscle fatigue to exercise performance in healthy humans. J Physiol 581: 389-403, 2007. 2. Kayser B, Narici M, Binzoni T, Grassi B, and Cerretelli P. Fatigue and exhaustion in chronic hypobaric hypoxia: influence of exercising muscle mass. J Appl Physiol 76: 634-640, 1994. 3. Marcora SM, Bosio A, and de Morree HM. Locomotor muscle fatigue increases cardiorespiratory responses and reduces performance during intense cycling exercise independently from metabolic stress. Am J Physiol Regul Integr Comp Physiol 294: R874-883, 2008. 4. Noakes TD and Marino FE. Arterial oxygenation, central motor output and exercise performance in humans. J Physiol 585: 919-921, 2007. 5. Noakes TD. Viewpoint: Evidence that reduced skeletal muscle recruitment explains the lactate paradox during exercise at high altitude. J Appl Physiol, in press, 2008. 6. Subudhi AW, Lorenz MC, Fulco CS, and Roach RC. Cerebrovascular responses to incremental exercise during hypobaric hypoxia: effect of oxygenation on maximal performance. Am J Physiol Heart Circ Physiol 294: H164-171, 2008. |
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Bengt Kayser, Professor, director Institute of movement sciences and sports medicine, University of Geneva, Switzerland
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bengt.kayser{at}medecine.unige.ch Bengt Kayser
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In the Viewpoint by Timothy Noakes (5) on the lactate paradox at altitude, a decrease in muscle recruitment levels is proposed as an explanation for the reduction in blood lactate levels at exhaustion from large muscle group exercise. Even though I agree with this contention (3) as well as with the comments by Marcora (4) on possible explanations for the reduction in central motor command in hypoxia, it is important to remember that lactate levels, in general (and at altitude) are also under influence of other mechanisms (1). There are good reasons to postulate that changes of blood lactate levels during exercise at altitude are related to mass effect and sympathetic drive. During large muscle group endurance exercise, hypoxia decreases central motor command and thus the intensity/duration of muscle contraction. This decreases muscle energy expenditure and therefore reduces glycogenolysis and the rate of pyruvate entry into the Krebs cycle. One would therefore expect that the [lactate]-power relationship would remain the same while limited in amplitude. But in acute hypoxia the relationship is shifted to the left (2). This can be explained by the hypoxia induced increase in sympathetic drive. Since glycogenolysis is under adrenergic influence, for a given rate of Krebs cycling, excess pyruvate will lead to more lactate formation and vice versa (3). With acclimatization this adrenergic effect subsides and the relationship shifts back to the right (2). In conclusion, as defined by Noakes the lactate paradox can indeed by explained by a reduction in central motor command. But lactate concentrations in blood are influenced by many factors. Exposure and acclimatization to hypoxia influence several of these and therefore the changes in blood lactate concentrations in hypoxia are multifactorial. 1. Gladden B. A "Lactatic" Perspective on Metabolism. Med Sci Sports Exerc, 40(3):475-476, 2008. 2. Grassi B, Marzorati M, Kayser B, Bordini M, Colombini A, Conti M, Marconi C, Cerretelli P. Peak blood lactate and blood lactate vs. workload during acclimatization to 5,050 m and in deacclimatization. J Appl Physiol. 1996 Feb;80(2):685-92. 3. Kayser B. Lactate during exercise at high altitude. Eur J Appl Physiol Occup Physiol 74:195-205, 1996. 4. Marcora SM. Commentary on Noakes’ Viewpoint. J Appl Physiol, 2008 May 5. Noakes TD. Viewpoint: Evidence that reduced skeletal muscle recruitment explains the lactate paradox during exercise at high altitude. J Appl Physiol. 2008 May |
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Markus Amann, Senior Scientist University of Zürich, Institute of Physiology, and ETH Zürich, Exercise Physiology
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markus.amann{at}physiol.biol.ethz.ch Markus Amann
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Although Dr. Noakes (4) affirms that the results of previous –not his own– studies (1, 2) support his visions, his argumentation appears to be dissociated from those data. He obviously ignores clear findings and claims, entirely unfounded, that “the studies of Amann et al. (1, 2) provide the final evidence necessary to solve the lactate paradox”. However, we argue that the data from these authors actually refute his claim. First, although 5-km cycling time-trial exercise (workload voluntarily adjustable) in acute moderate hypoxia was characterized by a lower level of skeletal muscle recruitment (and power-output) compared to that measured in normoxia, end-exercise capillary blood lactate ([La-]B) values were almost identical in both conditions (1). Second, at exhaustion following high-intensity constant workload cycling exercise in acute moderate hypoxia vs normoxia, the levels of end-exercise skeletal muscle recruitment and [La-]B were identical, despite the shorter exercise time in simulated altitude (2). Third, the debilitating effects of acute severe hypoxia on the CNS led to the voluntarily termination of constant-workload exercise within only 2 min (2). This short duration exercise was accompanied by a substantial level of end-exercise peripheral fatigue. Although skeletal muscle recruitment was lower at exhaustion in acute severe hypoxia vs normoxia, the comparison of end-exercise [La-]B values is irrelevant since exhaustion in acute severe hypoxia was reached after only 2 minutes – a duration too short to reach a lactate equilibrium in capillary blood (5). Finally, the idea that the three “paradoxes” maybe explained with one theory seems at odds with findings of normal lactate concentrations but reduced heart rates (3). Combined, these data clearly contradict Noakes’ claims. References: 1. Amann M, Eldridge MW, Lovering AT, Stickland MK, Pegelow DF, and Dempsey JA. Arterial oxygenation influences central motor output and exercise performance via effects on peripheral locomotor muscle fatigue. J Physiol (Lond) 575.3: 937-952, 2006. 2. Amann M, Romer LM, Subudhi AW, Pegelow DF, and Dempsey JA. Severity of arterial hypoxaemia affects the relative contributions of peripheral muscle fatigue to exercise performance in healthy humans. J Physiol 581: 389-403, 2007. 3. Lundby C, Sander M, van Hall G, Saltin B, and Calbet JAL. Maximal exercise and muscle oxygen extraction in acclimatizing lowlanders and high altitude natives. J Physiol (Lond) 573: 535-547, 2006. 4. Noakes TD. Viewpoint: Evidence that reduced skeletal muscle recruitment explains the lactate paradox during exercise at high altitude. 90410.92008, 2008. 5. Rusko H, Luhtanen P, Rahkila P, Viitasalo J, Rehunen S, and Harkonen M. Muscle metabolism, blood lactate and oxygen uptake in steady state exercise at aerobic and anaerobic thresholds. Eur J Appl Physiol Occup Physiol 55: 181-186, 1986. |
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Carsten Lundby, PhD The Copenhagen Muscle Research Centre
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lundby{at}idraet.au.dk Carsten Lundby, PhD
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The “lactate paradox” is defined as “reduced blood lactate concentrations during submaximal and maximal exercise following acclimatization to high altitude”. Dr Noakes claims that the data of Amann (1; 2) “solve the lactate paradox”(5). This postulate however, is unsubstantiated since it ignores the real data (see Part I by M. Amann) and wrongly refers to data only from maximal exercise. Instead, the “paradox” seems to be due to changes in relative exercise intensity since the “paradox” is absent when comparing same relative workloads at sea level vs acute hypoxia (4). Also, since increases in CaO2 do not (3), but increases in CaO2 and PaO2 do (1; 2) lead to further muscle recruitment and increased exercise performance in severe hypoxia, PaO2 can be viewed as the dominant determinant of central fatigue at extreme altitudes (1; 2). With chronic exposure to altitude, CaO2 and PaO2 increase (3) and this adaptation might lead to additional muscle recruitment in the face of even lower end-exercise lactate values compared to acute severe hypoxia. In conclusion, reduced maximal blood lactate concentrations at extreme altitudes might not reflect the reduced potential for glycolytic energy production, but rather – assuming Noakes is in part right – that the maximal attainable lactate concentration is reduced because exercise is terminated due to different fatigue patterns at these extreme altitudes (1; 2). If, at the same time assuming that our research group is right by claiming that lactate is reduced during submaximal exercise because of changes in exercise intensity (i.e. no “lactate paradox”) – then the issue seems solved. References: 1. Amann M, Eldridge MW, Lovering AT, Stickland MK, Pegelow DF and Dempsey JA. Arterial oxygenation influences central motor output and exercise performance via effects on peripheral locomotor muscle fatigue in humans. J Physiol (Lond) 575: 937-952, 2006. 2. Amann M, Romer LM, Subudhi AW, Pegelow DF and Dempsey JA. Severity of arterial hypoxaemia affects the relative contributions of peripheral muscle fatigue to exercise performance in healthy humans. J Physiol (Lond) 581: 389-403, 2007. 3. Lundby C, Calbet JA, van Hall G, Saltin B and Sander M. Pulmonary gas exchange at maximal exercise in Danish lowlanders during 8 wk of acclimatization to 4,100 m and in high-altitude Aymara natives. Am J Physiol Regul Integr Comp Physiol 287: R1202-R1208, 2004. 4. Lundby C and van Hall G. Substrate utilization in sea level residents during exercise in acute hypoxia and after 4 weeks of acclimatization to 4100 m. Acta Physiol Scand 176: 195-201, 2002. 5. Noakes TD. Viewpoint: Evidence that reduced skeletal muscle recruitment explains the lactate paradox during exercise at high altitude. J Appl Physiol 90410, 2008. |
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Peter D. Wagner, Professor of Medicine University of California, San Diego
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pdwagner{at}ucsd.edu Peter D. Wagner
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Noakes proposes, without giving evidence, that the so-called lactate paradox (LP) seen in chronic hypoxia is due to reduced muscle recruitment imposed by a central nervous system governor that, sensing its imminent demise, shuts down O2 transport and muscle contraction to protect itself from dangerous hypoxia (3). He focuses on lactate at maximal exercise, but the LP is manifest just as clearly over the entire exercise range from rest to exhaustion by the initially elevated lactate-VO2 relationship in acute hypoxia (nearly) falling back to its normoxic sea level trajectory after acclimatization--despite persistent hypoxemia (4). He does not address this. Note that because in acute hypoxia, maximal lactate is as high as at sea level (2, 4), the LP depends completely on this return of the lactate-VO2 relationship to its sea level configuration after acclimatization. We do agree that, upon acclimatization, maximal lactate falls progressively with increasing altitude because maximal power output falls progressively with increasing altitude. However, we disagree on the physiological mechanism of the reduced maximal power output. There is much evidence from studies in intact humans (5), as well as in isolated perfused contracting muscles where the brain has no influence (1), that reduced maximal power output reflects limits to muscle O2 availability caused by finite O2 transport system conductance. Additionally, Noakes’ viewpoint implies that cerebral O2 availability is a function of exercise intensity—that some level of exercise is reached at which the brain ceases to receive enough O2, directing the legs to quit. Is there evidence for that? References 1. Hogan, M.C., J. Roca, P.D. Wagner and J.B. West. Limitation of maximal O2 uptake and performance by acute hypoxia in dog muscle in situ. J. Appl. Physiol. 65(2):815-821, 1988. 2. Lundby, C., M. Sander, G. van Hall, B. Saltin and J.A.L. Calbet. Maximal exercise and muscle oxygen extraction in acclimatizing lowlanders and high altitude natives. J. Physiol. 573.2: 535-547, 2006 3. Noakes, T.D. Viewpoint: Evidence that reduced skeletal muscle recruitment explains the lactate paradox during exercise at high altitude. J. Appl. Physiol., in press. 4. Pronk, M., I. Tiemessen, M.D.W. Hupperets, B.P. Kennedy, F.L. Powell, S.R. Hopkins, P.D. Wagner. Persistence of the lactate paradox over 8 weeks at 3800 m. High Alt. Med. Biol. 4(4): 431-443, 2003 5. Roca, J., M.C. Hogan, D. Story, D.E. Bebout, P. Haab, R. Gonzalez, O. Ueno and P.D. Wagner. Evidence for tissue diffusion limitation of V. O2MAX in normal humans. J. Appl. Physiol. 67(1):291-299, 1989. |
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Lars Nybo, Department of Human Physiology Institute of Exercise and Sport Sciences, University of Copenhagen, Denmark
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lnnielsen{at}aki.ku.dk Lars Nybo
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It appears that the cerebral metabolism and motor function of the human brain becomes deteriorated if the average cerebral mitochondrial oxygen tension is reduced by more than ~ 7 mmHg (5). This may occur during acute exposure to strenuous exercise at high altitude and central fatigue seems be a main factor influencing performance and muscle recruitment during such exercise conditions (1; 5). However, this does not provide the complete explanation for the lactate paradox. Thus, peak lactate levels following maximal exercise with an incremental protocol seems to be unaffected during acute exposure to severe hypoxia (3), whereas maximal constant load cycling resulting in exhaustion after 5-6 min is reported to be associated with lower blood lactate levels at the point of exhaustion (2). Therefore, blood lactate levels following maximal exercise may depend on the applied exercise protocol and it should be considered that blood lactate only provides indirect information about the metabolic state of the skeletal muscles and it is not a particular good indicator of the functional state of the skeletal muscle. It is correct that hypoxia may impair muscle recruitment and that the physiological determinants of exercise performance may switch from a predominantly peripheral origin to a hypoxia-sensitive central component of fatigue. However, the physiological explanation for the lactate paradox may be a little more complex than the one provided by Noakes (4). References 1. Amann M and Calbet JA. Convective oxygen transport and fatigue. J Appl Physiol 104: 861-870, 2008. 2. Amann M, Romer LM, Subudhi AW, Pegelow DF and Dempsey JA. Severity of arterial hypoxaemia affects the relative contributions of peripheral muscle fatigue to exercise performance in healthy humans. J Physiol 581: 389-403, 2007. 3. Lundby C, Saltin B and van HG. The 'lactate paradox', evidence for a transient change in the course of acclimatization to severe hypoxia in lowlanders. Acta physiol Scand 170: 265-269, 2000. 4. Noakes TD. Viewpoint: Evidence that reduced skeletal muscle recruitment explains the lactate paradox during exercise at high altitude. J Appl Physiol 2008. 5. Nybo L and Rasmussen P. Inadequate Cerebral Oxygen Delivery and Central Fatigue during Strenuous Exercise. Exerc Sport Sci Rev 35: 110- 118, 2007. |
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Bruno Grassi, Associate Professor of Physiology Dip. Scienze Tecnologie Biomediche, University of Udine, Italy
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bgrassi{at}mail.dstb.uniud.it Bruno Grassi
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In his paper (1) Dr. Noakes forwards the interesting hypothesis that the “lactate paradox” observed during altitude acclimatization may be due to a reduced maximal “muscle recruitment”, possibly aimed at “protecting” cerebral oxygenation. Two pieces of evidence, gathered by our group during the Pyramid (5,050 m asl) expeditions in the 1990s, would be against such hypothesis. In those experiments (2) we observed a clear lactate paradox: with incremental exhausting cycloergometric exercises, peak blood lactate concentration ([La]b peak) fell from 11.5 ± 2.2 (mM, x ± SD) before the expedition to 8.0 ± 3.3 and 6.3 ± 0.9, respectively, after 1 and 5 weeks at altitude. The lower [La]b peak was associated with lower peak workload and peak heart rate (35% and 25 b/min lower, respectively, vs. pre- expedition), apparently in agreement with Dr. Noakes’s hypothesis. Interestingly enough, however, when the experiments were repeated at altitude in a condition of acute hypobaric normoxia (FIO2 0.4), peak workload increased, vs. hypoxia, by about 25-30%, whereas [La]b peak did not significantly change. Moreover, in the same study (2) experiments were repeated weekly during the first month after return to sea level. In the presence of peak workload values only about 7% lower than pre-expedition, [La]b peak was significantly lower than pre-expedition for 2 weeks (8.0 ± 1.9 and 9.4 ± 1.7 mM, respectively). Thus, the lactate paradox developed during 5 weeks of acclimatization to 5,050 m, persisted for a few weeks after the subjects returned to sea level, and was not directly related to the reduced peak workload. References 1. Noakes TD. Viewpoint: Evidence that reduced skeletal muscle recruitment explains the lactate paradox during exercise at high altitude. J Appl Physiol, May 2008; doi:10.1152/japplphysiol.90410.2008. 2. Grassi B, M Marzorati, B Kayser, M Bordini, A Colombini, M Conti, C Marconi, P Cerretelli. Peak blood lactate and blood lactate vs. work load during acclimatization to 5,050 m and in the deacclimatization. J Appl Physiol 80: 685-692, 1996. |
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stephane perrey, Assistant Professor University of Montpelier I, Motor Efficiency and Deficiency Lab
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stephane.perrey{at}univ-montp1.fr stephane perrey
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The viewpoint by Timothy Noakes (2) on the lactate paradox at altitude is mainly based on the central governor model that postulates that the extent of muscle recruitment by the central nervous system is determined by the need of the brain to protect itself and the body by ensuring the maintenance of integrity, during and after exercise. In the context of the neuromuscular system in vivo there are so far any known evidence that reduced skeletal muscle recruitment explains the lactate paradox during exercise in hypoxia. It looks like an oversimplification to consider such a link. While our research group is in favor of a progressive central contribution to muscle fatigue prior to the moment of task failure at sea level (3, 4), the full explanation for the so-called lactate paradox at altitude is likely more complex. Decreased cerebral oxygenation might reflect reduced central motor command at volitional fatigue in response to global (3, 5) and local (4) exercise with reduced skeletal muscle recruitment in hypoxia in cycling (1) but not during a local fatiguing exercise (4). Importantly we need to consider and better emphasize mechanisms underlying the lactate paradox. Working muscle beds can simultaneously produce and consume lactate, diverse tissues can produce lactate for consumption by working muscle, and the sympathetic nervous system greatly influences carbohydrate metabolism at altitude. No longer can we regard lactate as a simple by-product of glycolytic energy production measured in the blood compartment. 1. Amann M, Romer LM, Subudhi AW, Pegelow DF, and Dempsey JA. Severity of arterial hypoxaemia affects the relative contributions of peripheral muscle fatigue to exercise performance in healthy humans. J Physiol 581: 389-403, 2007. 2. Noakes TD. Viewpoint: Evidence that reduced skeletal muscle recruitment explains the lactate paradox during exercise at high altitude. 90410.92008, 2008. 3. Rupp T, Perrey S. Prefrontal cortex oxygenation and neuromuscular responses to exhaustive exercise. Eur J Appl Physiol 102: 153-163, 2008. Erratum p 251. 4. Rupp T, Perrey S. Effect of severe hypoxia on prefrontal cortex and muscle oxygenation responses at rest and during exhaustive exercise. Adv Exp Med Biol, in press, 2008. 5. Subudhi AW, Dimmen AC, Roach RC. Effects of acute hypoxia on cerebral and muscle oxygenation during incremental exercise. J Appl Physiol 103: 177-183, 2007. |
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Johannes J van Lieshout, Director Medium Care Unit Internal Medicine & Human Cardiovascular Physiology Unit Academic Medical Center, University of Amsterdam
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j.j.vanlieshout{at}amc.uva.nl Johannes J van Lieshout
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Regulation of blood flow to the activated brain is different from the regulation of flow to working skeletal muscles. When the brain is activated by exercise, the increment in cerebral blood flow enhances cerebral oxygenation whereas muscle oxygenation progressively decreases with work rate (3). A lower O2 availability does not influence cerebral uptake of lactate or glucose during exercise (5) whereas brain function deteriorates when its average oxygenation becomes reduced more than 10% (1, 3). A reduced skeletal muscle recruitment during high altitude exercise by less cerebral oxygenation is proposed as an explanation for the reduction in blood lactate levels during maximal exercise at altitude (2). We consider that acclimatization to high altitude exposure gradually returns the initially reduced peak blood lactate accumulation during exhaustive exercise to values equal to those seen at sea level and equally during acute hypoxia at sea level (4). Thus, allowing lowlanders to accustom to altitude uncovers the transient nature of the ‘lactate paradox’ (4). Where the brain decides when to slow down work rate, Noake’s choice for a reduced skeletal muscle recruitment by inadequate cerebral oxygenation seems attractive (2). However, considering that e.g. increased skeletal muscle capillary density and a gradual increase in arterial O2 delivery capacity by elevation of hemoglobin are as well among the numerous undefined players in the cardiovascular adaptation to high altitude, this hypothesis may set a preliminary limit to their identification. 1. Gonzalez-Alonso J, Dalsgaard MK, Osada T, Volianitis S, Dawson EA, Yoshiga CC, Secher NH. Brain and central hemodynamics and oxygenation during maximal exercise in humans. J Physiol 557: 331-342, 2004. 2. Noakes TD. Viewpoint: Evidence that reduced skeletal muscle recruitment explains the lactate paradox during exercise at high altitude. J Appl Physiol 2008. 3. Secher NH, Seifert T, Van Lieshout JJ. Cerebral blood flow and metabolism during exercise, implications for fatigue. J Appl Physiol 104: 306-314, 2008. 4. van Hall G, Calbet JA, Sondergaard H, Saltin B. The re- establishment of the normal blood lactate response to exercise in humans after prolonged acclimatization to altitude. J Physiol 536: 963-975, 2001. 5. Volianitis S, Fabricius-Bjerre A, Overgaard A, Stromstad M, Bjarrum M, Carlson C, Petersen NT, Rasmussen P, Secher NH, Nielsen HB. The cerebral metabolic ratio is not affected by oxygen availability during maximal exercise in humans. J Physiol 586: 107-112, 2008. |
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Frank E Marino Charles Sturt University, Bathurst NSW, Australia
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fmarino{at}csu.edu.au Frank E Marino
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TO THE EDITOR: Dr. Noakes (4) presents a view previously put but seemingly ignored “that heavy exercise at high altitude involving large muscle groups my be limited by a reduced central drive” (3). Although the existence of the lactate paradox is a common feature of many exercise physiology texts and has been recently debated (5), the evidence for the occurrence of this physiological phenomenon is indeed overwhelming. The issue, however, is not whether the lactate paradox occurs but rather what its likely cause might be. To answer this question, Dr. Noakes (4) attempts to pull together two other paradoxes which could provide the insights needed to explicate this physiological phenomenon. One, the overwhelming fatigue that develops at high altitude with low blood and muscle lactate concentrations and, two the observation that maximum cardiac output falls with increasing altitude. For the reduced maximum cardiac output when tissue oxygenation is lowest cannot occur to protect the muscle from desaturation as presumably this does not occur given the very low concentrations of blood and muscle lactate. This understanding is entirely consistent with findings which show that electromyographic activity is reduced as hypoxia increases (1) but more salient is that muscle twitch force is attenuated across the range of normoxia to severe hypoxia so that the major determinants of central motor output are most likely related to a hypoxia-sensitive central component of fatigue (1). If this is the case then the only logical explanation would be to reduce the amount of skeletal muscle recruitment to protect the brain from the consequences of hypoxia (2). 1. Amann M, Romer LM, Subudhi AW, Pegelow DF, and Dempsey JA. Severity of arterial hypoxaemia affects the relative contributions of peripheral muscle fatigue to exercise performance in healthy humans. J Physiol 581: 389-403, 2007. 2. Imray CHE, Myers SD, Pattinson KTS, Bradwell AR, Chan CW, Harris S, Collins P, Wright AD, and the Birmingham Medical Research Expeditionary S. Effect of exercise on cerebral perfusion in humans at high altitude. J Appl Physiol 99: 699-706, 2005. 3. Kayser B, Narici M, Binzoni T, Grassi B, and Cerretelli P. Fatigue and exhaustion in chronic hypobaric hypoxia: influence of exercising muscle mass. J Appl Physiol 76: 634-640, 1994. 4. Noakes TD. Viewpoint: Evidence that reduced skeletal muscle recruitment explains the lactate paradox during exercise at high altitude. J Appl Physiol 2008. 5. Van Hall G. Counterpoint: the lactate paradox does not occur during exercise at high altitude. J Appl Physiol 102: 2399-2401, 2007. |
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George A. Brooks, Professor, Integrative Biology University of California, Berkeley
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gbrooks{at}berkeley.edu George A. Brooks
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In his commentary once again Noakes (3) emphasizes that the study of neuromuscular recruitment requires a brain. Beyond recognizing the obvious, the main criticism is that Reeves et al. (5) should have been referenced along with Kayser et al. (4) as being supportive of his position that central limitations can affect muscle power output at high altitude. Proceeding from the specific to the general, two sequels unfold. The first is that if one holds to a Pasteur effect and believes that lactate accumulation is the result of oxygen-limited metabolism, then the reduction in circulating lactate seen during maximal exertion at high altitude seems paradoxical (1). Instead, if one recognizes that muscle power output is reduced at altitude, then the reduction muscle recruitment results in decreased glycolytic flux and lactate production (5). The original finding of a Lactate Paradox (1) is highly reproducible if studies are adequately controlled, (e.g., 4). However, it is to be recognized that in the absence of controls for dietary carbohydrate and energy, body mass, the extent of pre-study acclimatization, lack of statistical power analysis and the like, not all can reproduce the Lactate Paradox (e.g., 2). By his reference to a ‘Lactate Paradox’ Noakes calls our attention to the more encompassing concept of a Central Governor in regulating, and at times limiting various forms of athletic performances ranging from running at sea level to climbing the highest mountains. To some, exhortation to basic designs physiology may seem overly simplistic, but it is irrefutable that the motor cortex and higher centers control numerous organ systems. It is perhaps regrettable also that the brain’s role in exercise physiology has been overlooked. Admittedly, it is extremely difficult to assess central function during human exercise, but the presence of a Lactate Paradox during maximal exertion at altitude is one of the strongest demonstrations of a central limitation to exercise performance. References 1. Edwards, H.T. Lactic acid in rest and work at high altitude. Am J. Physiol. 116:367-375, 1936. 2. Lundby C, Boushel R, Robach P, Møller K, Saltin B, Calbet JA. During hypoxic exercise some vasoconstriction is needed to match O2 delivery with O2 demand at the microcirculatory level. 2008 Jan 1;586(1):123-30. 3. Noakes TD. “Evidence that reduced skeletal muscle recruitment explains the lactate paradox during exercise at high altitude.” J Appl Physiol, May 2008 4. B. Kayser, M. Narici, T. Binzoni, B. Grassi, and P. Cerretelli. Fatigue and exhaustion in chronic hypobaric hypoxia: influence of exercising muscle mass. J Appl Physiol, Feb 1994; 76: 634 - 640. 5. Reeves. J.T., E.E. Wolfel, H.J. Green, R.S. Mazzeo, A.J. Young, J.R. Sutton, and G.A. Brooks. Oxygen transport during exercise at high altitude and the lactate paradox: lessons from Operation Everest II and Pikes Peak. EXERCISE AND SPORT SCIENCES REVIEWS. Vol. 20, Williams and Wikins, 1992, pp. 275-296. |
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Jean-Paul Richalet, Professor UFR Medecine, Labo Physiologie, France
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richalet{at}smbh.univ-paris13.fr Jean-Paul Richalet
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T. Noakes’ viewpoint on “lactate paradox” at high altitude is not based on direct evidence of central limitation of exercise “performance” in hypoxia, but indirect measurements such as integrated EMG as indicators of muscle fatigue or recruitment (5). He argues that maximal exercise may be limited by a reduced central drive, the teleological argument of which being the protection of noble organs such as brain or heart. All experiments using O2 inhalation fail to give any decisive argument on the site of exercise limitation since they restore oxygen availability in all organs (brain, heart, muscles) (1). Brain as the location of a hypoxia sensor which would limit motor drive is doubtful since a decrease in maximal aerobic performance has been demonstrated at altitudes as low as 800m (especially in trained athletes), where brain hypoxia is improbable. Chronic hypoxia is associated with a decrease in O2 availability in the muscle capillary through hypoxia and exercise-induced decrease in arterial O2 saturation (SaO2). This occurs despite the increase in haemoglobin, offset by a decrease in maximal heart rate, fully explained by biochemical processes involving signal transduction in cardiac receptor pathways: downregulation of beta-adrenergic and up-regulation of muscarinic receptors, confirmed by extensive experimental evidence (2). This autoregulation process clearly aims at protecting the myocardium against a too high energy demand in conditions of reduced O2 availability. In endurance athletes, the importance of O2 diffusion limitation in altitude- induced reduction in performance is exacerbated. Physical laws of convection and diffusion are sufficient to account for this “double limitation”: exaggerated exercise-induced decrease in SaO2 limits O2 diffusion at the periphery, and extremely low O2 pressure in venous blood returning to the lungs limits O2 transfer at the pulmonary level, leading to a vicious circle dramatically limiting O2 availability (4). However, limited O2 diffusion from the capillary to the mitochondria should give rise to biochemical and/or EMG signs of muscle fatigue (3). Local biochemical feedback systems remain to be explored that could account for a hypoxia-induced inhibition of contractile machinery without production of anaerobic metabolites such as lactate (6). 1. Amann M, Romer LM, Subudhi AW, Pegelow DF, Dempsey JA. Severity of arterial hypoxaemia affects the relative contributions of peripheral muscle fatigue to exercise performance in healthy humans. J Physiol 581: 389-403, 2007. 2. Favret F, Richalet JP. Exercise and hypoxia: the role of the autonomic nervous system. Respir Physiol Neurobiol. 158: 280-286, 2007. 3. Kayser B, Narici M, Binzoni T, Grassi B, Cerretelli P. Fatigue and exhaustion in chronic hypobaric hypoxia: influence of exercising muscle mass. J Appl Physiol 76: 634-640, 1994. 4. Mollard P, Woorons X, Letournel M, Lamberto C, Favret F, Pichon A, Beaudry M, Richalet JP. Determinants of maximal oxygen uptake in moderate acute hypoxia in endurance athletes. Eur J Appl Physiol 100: 663-673, 2007. 5. Noakes TD. Evidence that reduced skeletal muscle recruitment explains the lactate paradox during exercise at high altitude. J Appl Physiol May 2008 6. Westerblad H, Allen DG, Lännergren J. Muscle fatigue: lactic acid or inorganic phosphate the major cause? News Physiol Sci 17: 17-21, 2002. |
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