Patients with chronic fatigue syndrome performed worse than controls in a controlled repeated exercise study despite a normal oxidative phosphorylation  capacity.

Abstract

BACKGROUND: The aim of this study was to investigate the possibility that a decreased mitochondrial ATP synthesis causes muscular and mental fatigue and  plays a role in the pathophysiology of the chronic fatigue syndrome (CFS/ME).  METHODS: Female patients (n = 15) and controls (n = 15) performed a  cardiopulmonary exercise test (CPET) by cycling at a continuously increased work  rate till maximal exertion. The CPET was repeated 24 h later. Before the tests,  blood was taken for the isolation of peripheral blood mononuclear cells (PBMC),  which were processed in a special way to preserve their oxidative  phosphorylation, which was tested later in the presence of ADP and phosphate in  permeabilized cells with glutamate, malate and malonate plus or minus the complex  I inhibitor rotenone, and succinate with rotenone plus or minus the complex II  inhibitor malonate in order to measure the ATP production via Complex I and II,  respectively. Plasma CK was determined as a surrogate measure of a decreased  oxidative phosphorylation in muscle, since the previous finding that in a group  of patients with external ophthalmoplegia the oxygen consumption by isolated  muscle mitochondria correlated negatively with plasma creatine kinase, 24 h after  exercise. RESULTS: At both exercise tests the patients reached the anaerobic  threshold and the maximal exercise at a much lower oxygen consumption than the  controls and this worsened in the second test. This implies an increase of  lactate, the product of anaerobic glycolysis, and a decrease of the mitochondrial  ATP production in the patients. In the past this was also found in patients with  defects in the mitochondrial oxidative phosphorylation. However the oxidative  phosphorylation in PBMC was similar in CFS/ME patients and controls. The plasma  creatine kinase levels before and 24 h after exercise were low in patients and  controls, suggesting normality of the muscular mitochondrial oxidative  phosphorylation. CONCLUSION: The decrease in mitochondrial ATP synthesis in the  CFS/ME patients is not caused by a defect in the enzyme complexes catalyzing  oxidative phosphorylation, but in another factor. CLINICAL TRIALS REGISTRATION  NUMBER: NL16031.040.07.