AbstractSo, to recap the little information the abstract gives: The CFS group exhibited significantly reduced anaerobic threshold, heart rate, VO2, VO2 peak and peak work compared to sedentary controls. Resting muscle pH was similar in controls and both CFS patient groups.
Loss of capacity to recover from acidosis on repeat exercise in chronic fatigue syndrome
Background: Chronic fatigue syndrome (CFS) patients frequently describe difficulties with repeat exercise. Here we explore muscle bioenergetic function in response to 3 bouts of exercise.
Methods: 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: CFS patients undertaking MVC fell into 2 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 intra-muscular acidosis compared to controls after similar work after each of the 3 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.
Conclusion: 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.
One half of the patients (remember, small study!) had low PCr depletion (Phosphocreatine?). (Are these the POTS patients?)
The other half of the patients showed normal PCr depletion (Phosphocreatine?) in response to exercise. However, this group showed increased intra-muscular acidosis compared to controls after similar work after each of the 3 exercise periods with no apparent reduction in acidosis with repeat exercise of the type reported in normal subjects. This group also exhibited 4-fold prolongation of the time taken for pH to recover to baseline.
I wonder how these groups map unto the two groups Alan Light found. Again, the "no apparent reduction with repeat exercise" is basically the same thing that other researcher see, that ME/CFS is something substantially different than deconditioning.
We observed that CFS patients as a group have reduced cardio-respiratory reserve with a lower anaerobic threshold than sedentary controls. This finding replicates previous studies . One implication of a lowered anaerobic threshold would be increased reliance on anaerobic as opposed to aerobic metabolism with a predicted consequence of increased short term acid generation within muscle due to over-utilization of the lactate dehydrogenase pathway. This prediction was confirmed by the use of MR spectroscopy methodologies which demonstrated increased post-exercise acidosis in the CFS group as a whole. The effect was not, however, uniform across the CFS patient group.
In the CFS subjects where normal PCr depletion was seen in the context of a normal MVC, exercise induced profound and sustained acidosis. This replicates our previous findings  in a second cohort of patients with CFS. Importantly, minimum pH values attained by this group of CFS patents were actually lower than those previously shown by us in the fatigue-associated chronic disease primary biliary cirrhosis (PBC) . We would suggest that the increased reliance upon anaerobic metabolism during even relatively lowlevel muscle contraction, shown by a decreased intramuscular pH, is at least partly a consequence of the decreased aerobic capacity (reduced anaerobic threshold and VO2peak) seen in CFS, and in this regard the physiology of fatigue in CFS closely mirrors that in PBC."I think the Lights should take this finding on board when they find increased acid sensors - that it's most likely because there's increased acid!"
There are aspects of the abnormality in acid homeostasis 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 , 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 to 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 post-exercise 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. We believe that the local and systemic sequelae of this sustained acid exposure contribute significantly to the expression of fatigue in CFS.
The reasons for slowed recovery from muscle acidosis in CFS are at present unclear but there are a number of possibilities. Our finding of a slow recovery time appears to be at least in part a result of slow kinetics of proton excretion and may point to potential mechanisms by which the increased muscle acid exposure occurs. Acid is actively transported from the muscle by Na-H antiporters which are in turn under autonomic regulation. Indeed, conditions which increase sympathetic tone such, as hypertension , or following sympathetic denervation  change acid handling in muscle. It is possible that impaired function of acid transporters occurs in CFS and that this related to the autonomic dysfunction found frequently in those with CFS [2, 19-22]. It is also possible that reduced vascular run off (related to autonomic dysregulation) may also contribute. Furtherwork is needed to explore the underlying mechanisms fully. Importantly, many of the pathways for acid excretion from muscle cells can be upregulated by exercise therapy suggesting a possible mechanism for benefit with graded exercise therapy (although our caveats about stratification should be noted).