Loss of capacity to recover from acidosis on repeat exercise in chronic fatigue syndrome: a case–control study, 2012, Jones et al.

SNT Gatchaman

SNT Gatchaman

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Loss of capacity to recover from acidosis on repeat exercise in chronic fatigue syndrome: a case–control study
David E. J. Jones; Kieren G. Hollingsworth; Djordje G. Jakovljevic; Gulnar Fattakhova; Jessie Pairman; Andrew M. Blamire; Michael I. Trenell; Julia L. Newton

BACKGROUND
Chronic fatigue syndrome (CFS) patients frequently describe difficulties with repeat exercise. Here, we explore muscle bioenergetic function in response to three bouts of exercise.

METHODS
A total of 18 CFS (CDC 1994) patients and 12 sedentary controls underwent assessment of maximal voluntary contraction (MVC), repeat exercise with magnetic resonance spectroscopy and cardio-respiratory fitness test to determine anaerobic threshold.

RESULTS
Chronic fatigue syndrome patients undertaking MVC fell into two distinct groups: 8 (45%) showed normal PCr depletion in response to exercise at 35% of MVC (PCr depletion >33%; lower 95% CI for controls); 10 CFS patients had low PCr depletion (generating abnormally low MVC values). The CFS whole group exhibited significantly reduced anaerobic threshold, heart rate, VO2 , VO2 peak and peak work compared to controls. Resting muscle pH was similar in controls and both CFS patient groups.

However, the CFS group achieving normal PCr depletion values showed increased intramuscular acidosis compared to controls after similar work after each of the three exercise periods with no apparent reduction in acidosis with repeat exercise of the type reported in normal subjects. This CFS group also exhibited significant prolongation (almost 4-fold) of the time taken for pH to recover to baseline.

CONCLUSIONS
When exercising to comparable levels to normal controls, CFS patients exhibit profound abnormality in bioenergetic function and response to it. Although exercise intervention is the logical treatment for patients showing acidosis, any trial must exclude subjects who do not initiate exercise as they will not benefit. This potentially explains previous mixed results in CFS exercise trials.

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This paper shows elevated muscle lactate that is much slower to clear, following exertion sufficient to deplete phosphocreatine stores.

Previous mentions here, here, here, here and here.

Evergreen said:
We might be able to start with something less intense than CPET. Jones et al. 2011 found higher levels of acidosis in patients (who exerted adequately) compared to controls with repeat plantar flexion. Patients also took nearly four times as long as controls to clear that acid.
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It would likely be of benefit to repeat this study with rigorous inclusion criteria, rather than Fukuda (and correlate with capillary basement membrane thickening).
 
SNT Gatchaman said:
This paper shows elevated muscle lactate that is much slower to clear, following exertion sufficient to deplete phosphocreatine stores.

Previous mentions here, here, here, here and here.



It would likely be of benefit to repeat this study with rigorous inclusion criteria, rather than Fukuda (and correlate with capillary basement membrane thickening).
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I challenge the assumption the muscle acidosis is lactate. Many ME/CFS patients exhibit low pyruvate and low to normal lactate. My metabolite tests revealed undetectable pyruvate and low/normal lactate. My peripheral blood gases tests however show acute respiratory acidosis. Perhaps the acidosis is poor gas exchange and clearance, accumulating inorganic phosphate, and poor ATP regeneration.
 
They also refer to this study of theirs, from the previous year (Jones et al. 2010):
Abnormalities in pH handling by peripheral muscle and potential regulation by the autonomic nervous system in chronic fatigue syndrome

Worth another thread perhaps? This is from the discussion (formatted for easier reading):
In this study, we have demonstrated that patients with CFS/ME have substantial abnormalities in the recovery of intramuscular pH following a standardised level of exercise.

Proton efflux from muscle (critical for acidosis resolution) is substantially lower immediately postexercise: in normal controls, it is well established that this is the point of maximal proton efflux. In CFS/ME patients, this immediate fast removal of protons from the muscle does not occur.

The time for proton efflux to reach a maximum is significantly prolonged compared to control subjects: the peak rate of proton efflux is also substantially impaired in CFS/ME patients.

There is a close relationship between the degree of acidosis and proton efflux suggesting a closely regulated process: this has been observed in controls in other studies [31], and the pH changes observed in the control group are also in agreement with similar studies [27, 32]. In CFS/ME patients this relationship is lost.
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Utsikt said:
They reference this previous study of theirs, how does it compare to these results?
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They summarize some relevant points about this in the discussion (formatted for ease of reading):
There are aspects of the abnormality in acid homoeostasis in CFS which differ to those seen in PBC and which may significantly contribute to the severity of fatigue in CFS. We have previously reported that when PBC patients undergo repeat exercise the degree of acidosis seen within muscle reduces with each exercise episode, suggesting the retention of some compensatory capacity for excess muscle acidosis in PBC (28). One mechanism for this is increase in proton flux, and the speed of onset of maximum proton excretion, with repeat exercise. This phenomenon, which is also a feature of mitochondrial disease where increased proton efflux after exercise helps compensate for reduced aerobic capacity [35], was absent from the CFS patients.


These findings suggest that CFS patients are unable to compensate for the increased reliance upon anaerobic energy sources during muscle contraction in comparison with other conditions with reduced aerobic capacity.


The net effect of these combined effects can be seen in terms of cumulative acid exposure determined from the area under the curve for pH. Using this approach, total postexercise acid exposure is of the order of 50-fold higher in CFS patients exercising to the same degree as normal controls, with no reduction in this pattern of sustained high level acidosis with repeat exercise.
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I think we should have threads on S4ME for all these studies. Cloudflare has an outage at the moment so I can't get to Wiley. I'll try again in the morning.
 
SNT Gatchaman said:
I think we should have threads on S4ME for all these studies. Cloudflare has an outage at the moment so I can't get to Wiley. I'll try again in the morning.
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Night night. I asked the moderators to copy a couple of my posts over to this thread too.
 
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