Jones DE, Hollingsworth KG, Jakovljevic DG, Fattakhova G, Pairman J, Blamire AM, Trenell MI, Newton JL
Institute of Cellular Medicine, Newcastle University, Newcastle, UK
Chronic fatigue syndrome (CFS) patients frequently describe difficulties with repeat exercise. Here, we explore muscle bioenergetic function in response to three bouts of exercise.
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.
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.
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.
Comment by ME Research UK
Bioenergetics concerns the flow of energy through living things, and its research involves the exploration of cellular processes, including cell respiration and the plethora of other metabolic events that result in the production and use of energy. In the past two years, researchers at the School of Clinical Medical Sciences, University of Newcastle have identified a distinctive muscle bioenergetic abnormality in people with ME/CFS. This abnormality is associated with the autonomic dysfunction found in the majority of ME/CFS patients and with a characteristic cardiac bioenergetic impairment.
The research interests of the group – which receives funding from ME Research UK, the John Richardson Research Foundation and the Irish ME Trust – also include the chronic disease primary biliary cirrhosis which shares some symptoms with ME/CFS, notably a difficulty sustaining repeat exercise. Since the researchers recently found evidence of abnormalities in the regulation of muscle acid in PBC patients during a programme of repeat exercise, they wondered whether similar bioenergetic abnormalities might also occur in ME/CFS.
To explore the issue, 18 consecutive new patients recruited from the local CFS/ME Clinical Service, and 12 matched healthy control participants attended the exercise laboratory for a range of assessments of cardiopulmonary fitness, maximum voluntary contraction (MVC), and muscle bioenergetic function using magnetic resonance spectroscopy (MRS) during repeat exercise.
To assess maximal exercise capacity, the patients undertook five 5-second maximal isometric contractions of the foot (plantar flexion) while lying down. Force generation was assessed using a calibrated strain gauge and the peak force was regarded as the MVC. For MRS measurements, subjects performed controlled plantar flexion using a purpose-built exercise apparatus within the MRI scanner. Subjects performed three 180-second bouts of plantar flexion contractions at 35% of MVC (to standardise “work done” between patients and controls). Immediately after the MRI exercise protocol subjects were asked to assess their degree of effort, and were asked to grade any discomfort that they were feeling, and they were telephoned 24 hours later and then again five days later with the same questions.
The major observation was that the peripheral muscles of ME/CFS patients took four times longer to recover (reduce acid levels and restore baseline pH) than those in matched control subjects, and that furthermore there was a significant slowing of the proton excretion response needed to normalise acid levels. The net effect was a sustained and significant accumulation of acid (acidosis) in muscle during and following exercise, which could affect muscle function and contribute to the experience of muscle fatigue.
The authors point out that total post-exercise acid exposure was approximately 50-fold higher in ME/CFS patients when exercising to the same degree as normal controls, with none of the apparent reduction in acidosis with repeat exercise observed in healthy subjects. Why this should be remains unknown, but – since acid is actively transported from the muscle by Na-H antiporters which are in turn regulated by the autonomic nervous system – it is possible that the acid transporters are impaired (a phenomenon that might be related to the autonomic dysfunction found frequently in ME/CFS patients), although a reduction in vascular run-off may also be a possibility.
This essay is an extract from our article (pdf 1.1 MB) in the Autumn 2011 issue of Breakthrough.