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

Dr Gwen Kennedy Authors
Kennedy G, Spence VA, McLaren M, Hill A, Underwood C, Belch JJF

Institution
Vascular Diseases Research Unit, The Institute of Cardiovascular
Research, Ninewells Hospital and Medical School, Dundee, UK

Support
The study was funded by ME Research UK, and further support was
received from the Sir John Fisher Foundation (Educational Grant).

Introduction
The aetiology of chronic fatigue syndrome (CFS) is unknown; however,
recent evidence suggests that excessive free radical (FR) generation
may be involved. This study investigated for the first time levels of
8-iso-prostaglandin-F2a-isoprostanes alongside other plasma markers of
oxidative stress in CFS patients and control subjects.

Methods
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 sex and age-matched healthy volunteers (13 males, 21 females,
46 [19–63] years) were enrolled in the study. The CFS patients were
divided into two groups: those with previously defined cardiovascular
risk factors of obesity and hypertension (group 1) and those who were
normotensive and non-obese (group 2). Blood samples were collected,
from which red blood cell GSH levels were measured on a
spectrophotometer, oxidised low-density lipoprotein levels were
measured by ELISA, plasma isoprostanes were measured by gas
chromatography–mass spectrometry, and high-density lipoprotein levels
were measured on a Cobas Bio centrifugal analyser.

Results
Patients with CFS had significantly increased levels of isoprostanes
(group 1, p=0.007; group 2, p=0.03) and oxidised low-density
lipoproteins (group 2, p=0.02), compared with controls, indicative of
a FR attack on lipids. Patients also had significantly lower high-
density lipoproteins (group 1, p=0.011; group 2, p=0.005), and lower
levels of the antioxidant GSH (p=0.05). CFS symptoms correlated with
isoprostane levels (total symptom score, p=0.005; joint pain, p=0.002;
post-exertional malaise, p=0.027), but only in group 2 CFS patients
with low cardiovascular risk.

Conclusion
This new data provides further evidence of dysfunction to oxidative
pathways in CFS. The finding of high levels of isoprostanes in people
with CFS is particularly important given this measure’s sensitivity,
reliability and correlation with other measures of lipid peroxidation
in vivo. Furthermore, isoprostanes may not only be markers of
oxidative injury, but may in fact mediate the effects of free radicals
and reactive oxygen species.

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