BJSM Peer Review: “There is a “biologically plausible explanation” for lower supramaximal oxygen uptake”

BJSM peer review of Noakes’ paper, “How did A.V. Hill understand the VO2max and the “plateau phenomenon”? Still no clarity?” by Mark Burnley, Department of Sport and Exercise Science, Aberystwyth University, Wales, UK.

“There is a “biologically plausible explanation” for lower supramaximal oxygen uptake”

I read with concern the recent review of Noakes[1] accepted for publication in the journal. Noakes suggests that there is no “biologically plausible explanation” for the observation of lower oxygen uptake (VO2) values in supramaximal exercise compared to incremental exercise.[2] Noakes further argues that those supramaximal data are therefore questionable and should be excluded, thus resulting in the conclusions of the original authors being disproved. Noakes’ first assertion (biological implausibility) is incorrect. His second assertion is at best biased, and at worst could be viewed as endorsing unethical practices.

The observation of lower VO2 values at exhaustion during supramaximal exercise could be attributed to normal biological variation (random error). However, the kinetics of VO2 dictates the rate at which VO2 rises to meet the energetic demand. In situations where exhaustion occurs before the kinetics drive VO2 to the maximum (so-called “extreme intensity exercise”[3]), VO2 will be lower than that measured in an incremental test performed to exhaustion. The boundary between “severe intensity exercise” (wherein VO2 reaches VO2max before exercise termination) and “extreme exercise” has been estimated to be ~110-135% VO2max,[3,4] providing the “biologically plausible explanation” Noakes wishes to deny.

To argue exclusion of the supramaximal data is ethically troubling.

Such exclusion, in this case solely for the purpose of interpretation, results in grossly biased conclusions. For any scientist, particularly one as influential as Noakes, to adopt such an approach does a disservice to students of exercise science. It would be tragic indeed
if these impressionable proto-scientists use Noakes’ precedence to endorse unethical data manipulation techniques to promote their own subjective opinions. Accordingly, I call upon Noakes to retract these statements to prevent further misleading interpretations from entering the literature.

References

1. Noakes TD. Peer review/fair review: How did A.V. Hill understand the VO2max and the “plateau phenomenon”? Still no clarity? Brit J Sports Med, in press. DOI: 10.1136/bjsm.2008.046771.

2. Hawkins MN, Raven PD, Snell PG, Stray-Gundersen J, Levine BD. Maximal oxygen uptake as a parametric parameter of cardiorespiratory capacity. Med Sci Sports Exerc. 2007;39:103-107.

3. Hill DW, Poole DC, Stevens JC. The relationship between power and the time to achieve VO2max. Med Sci Sports Exerc. 2002;34:709-714.

4. Wilkerson DP, Koppo K, Barstow TJ, Jones AM. Effect of work rate on the functional ‘gain’ of Phase II pulmonary O2 uptake response to exercise. Respir Physiol Neurobiol. 2004;142: 211-223.

Noakes response to Dr Burnley.

Dr Mark Burnley makes an important point. He is correct. No one has the right selectively to analyze data. Whilst I appreciate that this is how what I wrote can be interpreted, that was never my meaning (as should be apparent from the general gist of my argument).

The point I repeatedly make is that the “truth” in exercise science is so often model-dependant since few people actually bother to measure all the variables that comprise their particular model. Thus the basis for the Hill model (which I believe to be incorrect) is the use of oxygen consumption, measured at the mouth, as a surrogate measure of cardiac output and the state of muscle oxygenation during exercise. This model predicts that when the cardiac output reaches its maximum value, (“anaerobic”) conditions develop in the muscle which then cause the termination of exercise. If this is the case, then the cardiac output and hence the oxygen consumption and the state of muscle oxygenation must always be IDENTICAL at exhaustion. If this is not the case, then the model does not explain what is actually causing exhaustion.

So my argument is that if the oxygen consumption is not always exactly the same at exhaustion during maximum exercise testing, then the model has to be rather more complex than is this simple explanation we have inherited from Hill. Better stated, my point was that “submaximal” VO2max values must, according to the Hill model, indicate that exercise terminated before the maximal cardiac output and maximum levels of muscle de-oxygenation were achieved. But since this cannot happen according to the Hill model (since it is these two variables which cause exhaustion), the data are not compatible with his model and thus disprove it. In this sense it is my argument that those data cannot LOGICALLY be included in the analysis if their inclusion modifies the data suffficiently to “prove” a theory with which those specific data are actually incompatible. It was in this sense that I argued that the data should be LOGICALLY excluded from analysis since their inclusion led to the incorrect conclusion. Of course anyone wedded to the Hill model will find it difficult to follow this logic.

Dr Burnley may be one such person for he believes that exhaustion at submaximal VO2 values occurs before the “kinetics drive the VO2 to its maximum’. But how does the Hill model explain such exhaustion? Stating that it occurs because limiting “anaerobic” conditions develop in muscle even before the cardiac output reaches its maximum value is convenient but is ultimately unsatisfactory since it is again a model-dependant explanation. Would it not be better if defenders of this interpretation actually measured cardiac output and skeletal muscle oxygenation and not just their model-dependant surrogate – oxygen consumption at the mouth? The simulaneous measurement of muscle activation would be essential in my view if one wishes to test the alternate (central governor) theory that maximal exercise always terminates before there is 100% activation of all the available motor units in the exercising limbs.

However I am relieved that Dr Burnley does not find fault with the remainder of this quite long review. Does this mean that he accepts the logic of my argument that the regulation of maximal exercise performance must reside in the central nervous system?

Or what does he mean by the loaded phrase “further misleading interpretations from entering the literature”? To which other “misleading interpretations” does he refer?

Mark Burnley’s RESPONSE to Dr Noakes:

I now better appreciate Prof. Noakes’ reasons for using the words he used following his response to my eletter posted on the BJSM Blog, and consider the issue of “data exclusion” settled. However, I would like to make the following points to clarify my position and respond to Noakes’ interpretation of the physiology:

1. I do not consider myself “wedded to the Hill model” because the “Hill model” as presented by Noakes bears no relationship to my understanding of the physiological response to exercise. It is my contention that the “Hill model” is an erroneous caricature of the physiology of exercise that Noakes uses as a straw man in contrast to his central governor model. Few scientists are likely to defend the view that cardiac output and VO2 must always be identical at exhaustion, for the evidence against this proposition is overwhelming! In short, the “Hill model” is not a contemporary model of exercise physiology, it is a vehicle invented by Noakes.

2. “Oxygen consumption” or, more correctly, pulmonary oxygen uptake, is not a “surrogate measure of cardiac output and the state of muscle oxygenation”. To claim this indicates a misunderstanding or misrepresentation of basic physiological measurements. Pulmonary VO2 is useful because in both the non-steady state and the steady state it closely reflects muscle VO2, which itself reflects energetic events occurring in the cell. If one accepts that the rate of energy transfer is an important consideration during exercise, then measuring the most quantitatively significant energy transfer process is worthwhile. Furthermore, the phrase “state of muscle oxygenation” is hopelessly vague. Does Noakes mean “muscle O2 extraction”, “arterio-venous oxygen difference” or “intracellular [or mitochondrial] PO2”? The first two measures are difficult to make, whilst the latter is currently impossible to make during whole-body exercise.

3. I do not “believe” that exhaustion occurs before VO2max is attained during “extreme” exercise, it is an experimental fact: exercise is terminated whilst VO2 is still rising in a futile attempt to meet the energetic demand.[1] Exercise under these conditions is terminated because the subject is no longer able to sustain the power requirements of the task (in my experience not because the subject is unwilling), but this says little of the mechanism. Classic works on the aetiology of muscle fatigue acknowledge that fatigue processes occur at a number of sites within the neuromuscular system,[2,3] and I certainly embrace this. Exhaustion at these “extreme” work rates is attended by falling [PCr] and pH and rising [Pi] and [ADP], amongst other derangements known to cause a fall in tension produced by the myocyte.[4] However, measurements of these processes in whole-body exercise are presently too spatially or temporally crude to be definitive – but that is certainly not a reason to reject the periphery as a plausible or even pivotal contributor to task failure (exhaustion). Note also that the identification of metabolites involved in substrate-level phosphorylation does not imply that the conditions within the cell are “anaerobic”: the concentrations of these metabolites will change progressively during exercise above the so-called “critical power”[5] irrespective of cellular PO2.[6]

4. Noakes argues that the “simulaneous [sic] measurement of muscle activation” is required to test the alternate (central governor) theory “that maximal exercise always terminates before there is 100% activation of all the available motor units in the exercising limbs”. However, this is impossible to verify with current technology. Even if electromyographic recordings are taken from the surface of a large number of muscles and normalised to some measure of maximal voluntary muscle function (such as an MVC), this will not provide an estimate of the fractional number of motor units that are active. The EMG signal is determined, in part, by the number of active muscle fibres in the region of interrogation, their firing frequency, and the conductivity of the tissues between the fibres and the electrodes, not simply by the number of active motor units. A method of determining the total number of active motor units during whole-body exercise would be very useful but does not currently exist.

The processes leading to additional motor unit recruitment during rhythmic whole-body exercise are far from understood. However, it is logical that in conditions where the rate of O2 delivery is maximal (i.e., when cardiac output is maximal) the recruitment of additional motor units will lead to worsening metabolic conditions within the exercising muscles, as those newly recruited fibres will also extract O2 from the microvasculature. The consequent fall in microvascular PO2 will make the appropriate matching of O2 demand and supply (essential for the continuance of exercise) increasingly difficult. Additional motor unit recruitment is thus likely to yield diminishing returns in terms of sustaining the required power output. In this scenario, task failure will occur before all motor units are activated even in the absence of a “governor”.

In summary, Prof. Noakes’ representation of the physiology of exercise could be charitably described as inaccurate. The “Hill model” is not one that any physiologist is “wedded” to because it does not exist. Therein lay the “misleading interpretations” to which I referred in my first letter. One final point needs to be made:

If the “absence of any such catastrophe [myocardial ischaemia or rigor during exercise] suggests the presence of an anticipatory, complex, regulatory control system”[7], then surely the presence of myocardial ischaemia during exercise[8] suggests the absence of an anticipatory, complex regulatory control system? How long can the central governor theory survive with this elephant in the room?

“It does not make any difference how beautiful your guess is. It does not make any difference how smart you are, who made the guess, or what his name is – if it disagrees with experiment it’s wrong. That’s all there is to it.” Richard P. Feynman.

References

1. Hill DW, Poole DC, Stevens JC. The relationship between power and the time to achieve VO2max. Med Sci Sports Exerc. 2002;34:709-714

2. Bigland-Ritchie B, Woods JJ. Changes in muscle contractile properties and neural control during human muscular fatigue. Muscle Nerve. 1984;7:691-699.

3. Gandevia SC. Spinal and supraspinal factors in human muscle fatigue. Physiol Rev. 2001;81:1725-1789.

4. Fitts RH. The cross-bridge cycle and skeletal muscle fatigue. J Appl Physiol. 2008;104:551-558.

5. Jones AM, Wilkerson DP, DiMenna F, Fulford J, Poole DC. Muscle metabolic responses to exercise above and below the “critical power” assessed using 31-PMRS. Am J Physiol Regul Integr Comp Physiol. 2008;294:R585-R593.

6. Richardson RS, Newcomer SC, Noyszewski EA. Skeletal muscle intracellular PO2 assessed by myoglobin desaturation: response to graded exercise. J Appl Physiol. 2001;91:2679-2685.

7. Noakes TD. Peer review/fair review: How did A.V. Hill understand the VO2max and the “plateau phenomenon”? Still no clarity? Brit J Sports Med, in press. DOI: 10.1136/bjsm.2008.046771.

8. Bogaty P, Poirier P, Boyer L, Jobin J, Dagenais GR. What induces the warm-up ischemia/angina phenomenon: exercise or myocardial ischemia? Circulation. 2003;107:1858-1863.

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  • Angina has been one of the most horrific thing to happen to my health. I hope it goes away!