Mitochondrial dysfunction and the pathophysiology of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)
– Source: International Journal of Clinical and Experimental Medicine, June 30, 2012
By Norman E Booth, Sarah Myhill, John McLaren-Howard
[Note: The full text of this article is available free at http://www.ijcem.com/files/IJCEM1204005.pdf. To read the authors’ press release summarizing their crucial findings,
click here. The concluding paragraph of their clearly written paper reads:
“Implications for the treatment of ME/CFS. Here we have emphasized the use of biomedical tests to aid in the diagnosis and to vastly improve our knowledge of the pathophysiology involved in this illness. In addition, these biomedical tests can act as a valuable guide for medical and therapeutic interventions. These will be discussed in a paper which is in preparation.” They also note that “no mildly ill patients were tested” and the findings may not be specific just to ME/CFS because certain other illnesses/syndromes are associated with mitochondrial dysfunction.]
The objectives of this study are to:
• Test the hypothesis that the fatigue and accompanying symptoms of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome are in part due to defects in energy provision at the cellular level,
• And to understand the pathophysiology of the defects so that effective medical intervention can be implemented.
We performed an audit of 138 patients (ages 18-65) diagnosed with ME/CFS and attending a private practice.
The patients and 53 normal, healthy controls had the ATP Profile test carried out on neutrophils from a 3-ml venous blood sample. [Ed note: Neutrophils are the most common kind of white blood cell.]
This test yields 6 numerical factors that describe the availability of ATP and the efficiency of oxidative phosphorylation in mitochondria. [Oxidative phosphorylation is the metabolic pathway that uses energy released by oxidation of nutrients to produce energy-supplying ATP.]
Other biomedical measurements, including the concentration of cell-free DNA in plasma, were made.
The results of the audit are compared with the controls and a previous cohort of 61 patients.
We find that:
• All patients tested have measureable mitochondrial dysfunction which correlates with the severity of the illness.
• The patients divide into two main groups differentiated by how cellular metabolism attempts to compensate for the dysfunction.
• Comparisons with exercise studies suggest that the dysfunction in neutrophils also occurs in other cells. This is confirmed by the cell-free DNA measurements which indicate levels of tissue damage up to 3.5 times the normal reference range.
• The major immediate causes of the dysfunction are lack of essential substrates and partial blocking of the translocator protein sites in mitochondria.
• The ATP Profile is a valuable diagnostic tool for the clinical management of ME/CFS.
Source: International Journal of Clinical and Experimental Medicine, June 30, 2012;5(3):208-220. www.ijcem.com /ISSN:1940-5901/IJCEM1204005, by Booth NE, Myhill S, McLaren-Howard J. Department of Physics and Mansfield College, University of Oxford, Oxford UK; Sarah Myhill Ltd, Llangunllo, Powys UK; Acumen, Tiverton, Devon UK. Address all correspondence to: Dr. Norman E Booth, PhD FInstP, Emeritus Professorial Fellow in Physics, Mansfield College, University of Oxford, UK. [E-mail: firstname.lastname@example.org]