IJCEM Copyright © 2008-All rights reserved. Published by e-Century Publishing Corporation, Madison, WI 53711
Int J Clin Exp Med 2012;5(3):208-220

Original Article
Mitochondrial dysfunction and the pathophysiology of Myalgic
Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)

Norman E Booth, Sarah Myhill, John McLaren-Howard

Department of Physics and Mansfield College, University of Oxford, Oxford UK; Sarah Myhill Ltd, Llangunllo, Powys UK; Acumen,
Tiverton, Devon UK

Received April 26, 2012; accepted May 21, 2012; Epub June 15, 2012; Published June 30, 2012

Abstract: The objectives of this study are to test the hypothesis that the fatigue and accompanying symptoms of Chronic Fatigue
Syndrome/Myalgic Encephalomyelitis 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 139 patients (ages
18-65) diagnosed with CFS/ME 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. This test yields 6 numerical factors that describe the availability of ATP
and the efficiency of oxidative phosphorylation in mitochondria. 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 CFS/ME. (IJCEM1204005)

Keywords: Chronic fatigue syndrome, myalgic encephalomyelitis, mitochondria, adenosine triphosphate (ATP), oxidative
phosphorylation, cellular energetic, glycolysis, cell-free DNA, exercise

Address all correspondence to:
Dr. Norman E Booth, PhD FInstP, Emeritus Professorial Fellow in Physics, Mansfield College, University of Oxford, UK.
E-mail: n.booth1@physics.ox.ac.uk