Abnormalities in pH handling by peripheral muscle on 31P magnetic resonance spectroscopy and potential regulation by sympathetic autonomic function in chronic fatigue syndrome


Jones DEJ, Hollingsworth KG, Taylor R, Blamire AM, Newton JL


Institute of Cellular Medicine, Newcastle University, Newcastle-upon-Tyne, UK


To examine muscle acid handling following exercise in chronic fatigue syndrome (CFS/ME) and the relationship with autonomic dysfunction.


Observational study.


Regional fatigue service.

Subjects and Interventions

Chronic fatigue syndrome (n=16) and age and sex matched normal controls (n=8) underwent phosphorus magnetic resonance spectroscopy (MRS) to evaluate pH handling during exercise. Subjects performed plantar flexion at fixed 35% load maximum voluntary contraction. Heart rate variability was performed during 10 min supine rest using digital photophlethysmography as a measure of autonomic function.


Compared to normal controls, the CFS/ME group had significant suppression of proton efflux both immediately postexercise (CFS: 1.1±0.5 mmol/L per min vs. normal: 3.6±1.5 mmol/L per min, P<0.001) and maximally (CFS: 2.7±3.4 mmol/L per min vs. control: 3.8±1.6 mmol/L per min, P<0.05). Furthermore, the time taken to reach maximum proton efflux was significantly prolonged in patients (CFS: 25.6±36.1 s vs. normal: 3.8±5.2 s, P<0.05). In controls the rate of maximum proton efflux showed a strong inverse correlation with nadir muscle pH following exercise (r²=0.6; P<0.01). In CFS patients, in contrast, this significant normal relationship was lost (r²=0.003; P=ns). In normal individuals, the maximum proton efflux following exercise were closely correlated with total heart rate variability (r²=0.7; P=0.007) this relationship was lost in CFS/ME patients (r²<0.001; P=ns).


Patients with CFS/ME have abnormalities in recovery of intramuscular pH following standardised exercise degree of which is related to autonomic dysfunction. This study identifies a novel biological abnormality in patients with CFS/ME which is potentially open to modification.


Journal of Internal Medicine, 2010 Apr; 267(4): 394–401

Comment by ME Research UK

The autonomic nervous system has a range of important functions, so the consequences can be severe when it goes wrong. Since ME/CFS patients experience symptoms such as dizziness, altered vision, nausea and fatigue when they are standing, particularly when they are standing still, the possibility exists that the autonomic nervous system could be at fault.

Since 2006, with the financial help of ME Research UK, Professors Julia Newton and David Jones of the School of Clinical Medical Sciences, University of Newcastle, have examined a large group of patients using a battery of tests of autonomic function, including heart rate and blood pressure. In a series of fascinating scientific papers, they have reported finding autonomic dysfunction in three-quarters of ME/CFS patients, a most unexpected result; they have shown that the heart rate response to standing is abnormal in a significant proportion of patients; and they have confirmed that blood pressure is lower, and blood pressure regulation abnormal, in this clinical group compared with healthy people.

The autonomic nervous system also plays a part in regulating events in exercising muscle, however, and the researchers hypothesised that it might be involved in the exercise-induced symptoms so characteristic of ME/CFS. To examine this, they enlisted the help of phosphorus magnetic resonance spectroscopy (MRS), a marvelous tool which allows assessment of acid (pH) handling inside the muscle where the problems might lie.

Sixteen ME/CFS patients and healthy controls matched for age and sex underwent MRS to examine acid handling in their soleus and gastrocnemius muscles during exercise, which involved raising and lowering the foot under very controlled conditions. Measures of autonomic function were also assessed.

Compared with normal controls, the patients’ proton efflux (a measure of acid handling) was reduced immediately after exercise, while their time taken to reach maximum proton efflux was significantly prolonged, and the magnitude of maximum proton efflux was reduced compared with the controls. Taken together, these findings point to a significant impairment of proton excretion in the recovery phase following exercise – in simple terms, ME/CFS patients recovered substantially more slowly than controls.

Could simple deconditioning be the cause? Probably not, since both maximum voluntary contraction measurements and muscle volume were similar in patients and in the inactive controls. Rather, the researchers think it more likely that impaired acid handing could be one of the mechanisms through which autonomic abnormalities act to produce post-exercise symptoms and fatigue, given the role played by the autonomic nervous system in the regulation of acid transporter pathways and vascular flow in muscle.

Despite the key role of post-exercise symptoms in the illness, there has actually been very little scientific investigation into muscle physiology during exercise in ME/CFS – a fact that makes these novel findings so important.

This essay is an extract from our article (pdf 941 KB) in the Autumn 2010 issue of Breakthrough.

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