Original Contribution
Oxidative stress levels are raised in chronic fatigue syndrome and are associated with clinical symptoms

https://doi.org/10.1016/j.freeradbiomed.2005.04.020Get rights and content

Abstract

The aetiology of chronic fatigue syndrome (CFS) is unknown; however, recent evidence suggests excessive free radical (FR) generation may be involved. This study investigated for the first time levels of 8-iso-prostaglandin-F-isoprostanes alongside other plasma markers of oxidative stress in CFS patients and control subjects. Forty-seven patients (18 males, 29 females, mean age 48 [19–63] years) who fulfilled the Centres for Disease Control classification for CFS and 34 healthy volunteers (13 males, 21 females, 46 [19–63] years) were enrolled in the study. The CFS patients were divided into two groups; one group had previously defined cardiovascular (CV) risk factors of obesity and hypertension (group 1) and the second were normotensive and nonobese (group 2). Patients had significantly increased levels of isoprostanes (group 1, P = 0.007; group 2, P = 0.03, unpaired t test compared to controls) and oxidised low-density lipoproteins (group 2, P = 0.02) indicative of a FR attack on lipids. CFS patients also had significantly lower high-density lipoproteins (group 1, P = 0.011; group 2, P = 0.005). CFS symptoms correlated with isoprostane levels, but only in group 2 low CV risk CFS patients (isoprostanes correlated with; total symptom score P = 0.005; joint pain P = 0.002; postexertional malaise P = 0.027, Pearson). This is the first time that raised levels of the gold standard measure of in vivo oxidative stress (isoprostanes) and their association with CFS symptoms have been reported.

Introduction

Chronic fatigue syndrome (CFS) is a condition characterised by debilitating fatigue and other nonspecific symptoms resulting in significant disability, and its pathophysiology continues to remain elusive. A number of biological systems have been implicated and there is mounting evidence that oxidative stress [1], [2], [3], [4], [5] and, more specifically, lipid peroxidation contribute to the disease process [6] and to some of the symptoms in the illness [1]. Oxidative stress has been defined as a disturbance to the equilibrium status of prooxidant and antioxidant systems in favour of prooxidation. The term oxidative stress is used to describe a number of chemical reactions involved in the production of free radicals and other reactive molecules that are potentially able to induce cellular injury.

While free radicals may generate tissue oxidative injury it is also evident that other oxidative by-products, especially peroxidised lipids such 8-iso-prostaglandin F, may be even more pivotal in the pathological process. 8-Iso-prostaglandin F is a member of the F2-isoprostane family and can exert potent biological activity, such as platelet activation, and act as a powerful vasoconstrictor of the peripheral vasculature [7], [8]. Such biological effects may be instrumental in the development of some of the vascular features that characterise patients with CFS [9], [10].

A further indication of the in vivo consequences of increased lipid peroxidation would be higher levels of oxidised low-density lipoproteins (oxLDL) accompanied by low levels of high-density lipoproteins (HDL), which are associated with the development of atherosclerosis [11]. This study set out to investigate, for the first time, levels of 8-iso-prostaglandin F alongside other markers of oxidative stress and antioxidant status in well-defined CFS patients and comparable control subjects, and to relate these levels to reported clinical symptoms of CFS.

Section snippets

Subjects and methods

Fifty-four patients were recruited from a register of several hundred local CFS patients. After a medical examination 47 patients (19 males and 28 females, mean age 48 years [19–63 years], 6 current, 3 ex-, and 38 nonsmokers) were found to fulfil the Centres for Disease Control (CDC) classification for CFS [12]. Seven of the patients were excluded: one had diabetes, one had a possible neurological condition underlying the fatigue, one had angina, two patients were unable to undertake the tests,

Results

CFS patients in group 1 (CVD risk factor group) [n = 16; 5 males and 11 females, mean age 52.4 years (35–62 years)] were obese (BMI >30) and hypertensive, as defined by the European Society of Hypertension [systolic >140 mm Hg, or diastolic >90 mm Hg] [15]. CFS patients in group 2 [n = 31; 14 males and 17 females, mean age 46 years (19–64 years)] were normotensive and had a BMI of <30. Each patient group was compared with sex- and age-matched controls. Four of the controls had hypertension and

Discussion

The novel findings of this study are that patients with CFS have significantly elevated levels of F2-isoprostanes alongside other key markers of oxidative stress, and that these correlate with various CFS symptoms.

This is the first time that elevated levels of isoprostanes have been reported in patients with CFS and the finding is particularly important given their sensitivity, reliability, and association with other measures of lipid peroxidation in vivo [17], [18]. F2-isoprostanes are a

Acknowledgments

This study was supported by a grant from MERGE (Myalgic Encephalomyelitis Research Group for Education and Support, registered UK charity number 1080201), Perth PH1 5PP, Scotland, UK. J.J.F.B and M.McL receive funding from the Sir John Fisher Foundation.

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