Disability and Rehabilitation, 2011; 33(1718): 14931500

REVIEW

Tired of being inactive: a systematic literature review of physical

activity, physiological exercise capacity and muscle strength in patients
with chronic fatigue syndrome
JO NIJS1,2,3, SENNE AELBRECHT1,4, MIRA MEEUS1,2, JESSICA VAN OOSTERWIJCK1,2,3,
EVERT ZINZEN5 & PETER CLARYS4
1

Department of Human Physiology, Faculty of Physical Education & Physiotherapy, Vrije Universiteit Brussel, Belgium,
Division of Musculoskeletal Physiotherapy, Department of Health Care Sciences, Artesis University College Antwerp, Belgium,
3
Department of Physical Medicine and Physiotherapy, University Hospital Brussels, Belgium, 4Department of Human
Biometry and Biomechanics, Faculty of Physical Education & Physiotherapy, Vrije Universiteit Brussel, Belgium, and
5
Department of Sportstraining and Movement Education, Faculty of Physical Education & Physiotherapy, Vrije Universiteit
Brussel, Belgium
2

Accepted November 2010

Abstract
A systematic review was undertaken to examine whether patients with chronic fatigue syndrome (CFS) differ from healthy
sedentary controls in physiological exercise capacity, physical activity level and muscle strength. From the available literature,
it can be concluded that patients with CFS perform less physical activity during daily life, and have less peak isometric
muscle strength compared to healthy sedentary control subjects. Conflicting data in relation to physiological exercise
capacity of patients with CFS have been reported, but the weighted available evidence points towards a reduced physiological
exercise capacity in CFS. Future studies should use a wash-out period for medication use, blinded assessments, a priori
power calculation and a sedentary control group comparable for age, gender, body weight, body length and current physical
activity level.

Keywords: Chronic fatigue, exercise performance, physical activity, exercise capacity, exercise testing

Introduction
Chronic fatigue syndrome (CFS) describes a disorder that consists of chronic debilitating fatigue that
cannot be explained by any known chronic medical
or psychological condition [1]. The core feature of a
CFS diagnosis is the exclusion of any active medical
condition which may explain the presence of the
symptoms (e.g. primary sleep disorders, severe
obesity, cancer hypothyroidism, Hepatitis B or C,
major depressive disorders with psychotic or melancholic features, bipolar affective disorders, schizophrenia, dementia, alcohol abuse, etc.) [1]. In
addition, the presence of a new onset (not lifelong)
unexplained, persistent fatigue is required. The
fatigue should be unrelated to exertion, is not

substantially relieved by rest, and should be severely

disabling (i.e. causing substantial reductions in
activity levels). Finally, four or more of the following
symptoms should be present for 6 months or longer:
impaired memory or concentration; extreme, prolonged exhaustion and sickness as a result of physical
or mental exertion (post-exertional malaise); unrefreshing sleep; muscle pain; pain in multiple joints;
headaches of a new kind or greater severity; sore
throat and tender lymph nodes (cervical or axillary).
Continuing to be active despite increasing fatigue
is likely to be a crucial step in the development of
CFS [2]. Once CFS is established, post-exertional
malaise is a major characteristic of the illness.
Symptoms are typically made worse after modest
amounts of exercise [3], after increased daily physical

Correspondence: Jo Nijs, Department of Human Physiology, Faculty of Physical Education & Physiotherapy, Vrije Universiteit Brussel, Building L, Pleinlaan 2,
1050 Brussels, Belgium. Tel: 32-2-6292222. E-mail: jo.nijs@vub.ac.be
ISSN 0963-8288 print/ISSN 1464-5165 online 2011 Informa UK, Ltd.
DOI: 10.3109/09638288.2010.541543

1494

J. Nijs et al.

activity [4] and after a maximal exercise stress test

[5,6]. A delayed recovery from exercise typically
occurs in patients with CFS [7]. Hence, resting and
activity avoidance could be a way to cope with the
illness and its post-exertional malaise [8]. These
observations would indirectly imply that patients
with CFS perform less physical activity. Yet it
remains unclear whether this notion is directly
supported by findings from scientific studies. Is there
scientific evidence showing that patients with CFS
perform less physical activity compared to healthy
controls? Are patients with CFS too tired to be
active?
Prolonged physical inactivity has many sideeffects, including muscle wasting, decreased cardiovascular function and decreased lung function
[9,10]. Furthermore, prolonged physical inactivity
results in decreased physical fitness and decreased
physiological exercise capacity. Physiological exercise capacity testing is widely used for the assessment
of patients with CFS, and it appears to be both
reproducible and valid [11]. Physiological exercise
capacity is related to activity limitations and participation restrictions in patients with CFS, supporting
its clinical relevance [12]. However, conflicting data
addressing physiological exercise capacity in CFS
have been reported [e.g. 13,14]. At current, it
remains unclear whether patients with CFS have
decreased physiological exercise capacity compared
to healthy sedentary controls.
Prolonged physical inactivity and decreased physiological exercise capacity were originally viewed as
important reasons for applying cognitive behaviour
therapy and graded exercise therapy as treatment
strategies for CFS. Graded activity is generally
included in cognitive behavioural programmes for
patients with CFS; it encourages the patient to
gradually increase activity levels [15]. Likewise,
graded exercise therapy focuses on improving physiological exercise capacity and exercise tolerance by
gradually increasing exercise intensity and duration
[16,17]. There is strong evidence to support the use
of cognitive behaviour therapy and graded exercise
therapy for the treatment of CFS [1619]. However,
it remains unclear whether patients with CFS are
physically inactive and have a decreased physiological exercise capacity.
For the reasons outlined above, an indepth review of the literature on physical activity,
physical performance and physiological exercise
capacity in patients with CFS is conducted. The
aim of this systematic literature review is therefore
threefold:
1.

examining whether patients with CFS differ

from healthy sedentary controls in physiological exercise capacity,

2.

3.

examining whether patients with CFS are

more physically inactive than healthy sedentary controls,
examining whether patients with CFS differ
from healthy sedentary controls in muscle
strength.

Methods
To identify relevant articles, PubMed (http://
www.ncbi.nlm.nih.gov/entrez) and Web of Science
(http://isiwebofknowledge.com) were searched in
October 2009. The search strategy was based on
the following key words: chronic fatigue syndrome,
myalgic encephalomyelitis or chronic fatigue immune dysfunction syndrome in combination with
pedometer, ergometry, cycle ergometer, exercise
capacity, exercise performance, energy expenditure,
handgrip strength, isometric handgrip, accelerometer, activity monitoring and actigraphy.
To be included in the review, an article had to
meet the following criteria: (1) subjects of the study
had to be human adults diagnosed with CFS; (2) the
title of the article had to include either chronic
fatigue syndrome, myalgic encephalomyelitis, or
chronic fatigue immune dysfunction syndrome; (3)
the papers were written in English, Dutch, or
French; (4) the study design had to be either a
casecontrol study, prospective study (longitudinal)
or randomised controlled clinical trial; (5) the
abstract had to include information of relevance to
either three aims of the literature review and (6)
articles were full text reports, and not abstracts,
letters or editorials. If any of the inclusion criteria
were not fulfilled, then the article was excluded from
the literature review.
In case of disagreement across studies addressing
any of the three major aims of the literature review,
the methodological quality of the selected studies
was assessed and compared. As this was the case only
for the first aim (examining whether patients with
CFS differ from healthy sedentary controls in
physiological exercise capacity), appropriate quality
criteria were identified in line with the nature of such
studies. The amount of daily physical activity,
gender, body weight, body length and age are
potential sources of bias in physiological exercise
capacity studies. These criteria were included for the
quality assessment of the studies. In addition, the
diagnostic criteria and exercise testing protocol were
listed, and the use of a medication wash-out period
prior to testing, a priori power calculation and
blinded assessment were included as general quality
criteria for casecontrol studies. All quality criteria
were combined in a quality score expressed in
percentages. Higher percentages indicate superior

Exercise performance and physical activity in CFS

methodological quality. The quality score is obtained
by counting all quality criteria, except for three which
vary substantially across studies (diagnostic criteria,
type of exercise test and exercise protocol). One
point was provided for each met criterion. A quality
score of at least 50% was required for inclusion of the
study in the literature review.

Results
The study selection is presented in Figure 1. After
screening the abstract and title of the 315 selected
records, 42 full-text articles were assessed for
eligibility. Of those, 27 were excluded. The main
reason for exclusion was an inappropriate study
design (uncontrolled study, letter or review article;
n 17) to answer any of the three research questions
of the literature review. The content of 10 additional
papers was unrelated to any of the three research
questions. Fifteen full text articles were included in
the review [13,14,2032]. Those articles were
screened and reviewed. The findings from the
articles are organised and discussed below following
the three aims of the systematic literature review.

Physiological exercise capacity

The quality score of the selected papers varied
between 38 and 75% (mean score + standard
deviation 58 + 14%). Two studies [23,24] were
excluded because they did not reach the required

Figure 1. Flow chart study selection (adapted from [47]).

1495

50% quality score. Table I summarises the findings

on physiological exercise capacity studies in CFS;
Table II provides an overview of the methodological
quality of the studies. Five casecontrol studies
found that patients with CFS have reduced physiological exercise capacity compared to healthy sedentary controls [13,2528]. According to these studies,
patients with CFS have reduced peak heart rate
[13,25,26,28], reduced endurance (i.e. test duration)
[13,2628], reduced peak work rate [13,25], reduced
peak oxygen uptake [13,25,28], lower blood lactate
values [2527] and an increased respiratory exchange ratio [13,28]. All together, 558 patients with
CFS and 300 healthy sedentary control subjects were
studied. Still, these studies were not in total
agreement with each others findings. The study by
Fulcher and White [26] did not find a difference in
peak oxygen uptake, Wallman et al. [25] found
reduced peak respiratory exchange ratio, and Riley
et al. [27] found lower mean respiratory exchange
ratio and a lower mean submaximal heart rate in
patients with CFS.
In contrast, four studies concluded that patients
with CFS differ from sedentary controls in physiological exercise capacity [14,2022]. These studies
found no difference in endurance [20,21], peak work
rate [20,22], peak oxygen uptake [14,20,22], oxygen
uptake at the lactate threshold [14], blood oxygen
pressure [20], peak heart rate [14,20,21], average
heart rate [22], blood pressure [22], respiratory
exchange ratio [21], functional aerobic impairment
[14], blood lactate values [14], blood lactate increase
relative to workload [14] or respiratory rate [21]. All
together, 89 patients with CFS and 99 healthy
sedentary control subjects were studied. However,
these studies were not unitary in favour of a normal
physiological exercise capacity in CFS. Cook et al.
[21] found that Gulf War Veterans with CFS had
decreased peak ventilation as compared to Gulf War
Veterans without CFS. Bazelmans et al. [20]
reported that the blood CO2 pressure declined more
in patients with CFS than for controls, and that CFS
patients reach a lower percentage of the predicted
peak workload.
Taken together, the number of study subjects is
much larger in the studies reporting decreased
physiological exercise capacity in CFS. Likewise,
the number of studies with sufficient methodological
quality reporting decreased physiological exercise
capacity in CFS is larger. Indeed, two studies
reporting similar physiological exercise capacity in
CFS and healthy controls did not reach the required
quality quorum (a quality score of at least 50%).
Hence, the available evidence points towards reduced physiological exercise capacity in CFS.
Still, some discrepancy addressing physiological
exercise capacity in CFS versus healthy controls

1496

J. Nijs et al.
Table I. Overview of physiological exercise variables studied in patients with CFS.

Exercise variable

Studies that found a difference with

healthy sedentary controls

Studies that found no

difference with healthy sedentary controls

Peak heart rate

Endurance
Peak work rate
Peak oxygen uptake
Oxygen uptake at lactate threshold
Blood oxygen pressure
Functional aerobic impairment
Respiratory exchange ratio
Respiratory rate
Peak ventilation
Blood lactate
Blood lactate increase relative to workload
Blood CO2 pressure

Reference
Reference
Reference
Reference
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None
None
Reference
None
Reference
Reference
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Reference

Reference
Reference
Reference
Reference
Reference
Reference
Reference
Reference
Reference
None
Reference
Reference
None

numbers
numbers
numbers
numbers

[13,23,25,26,28]
[13,2628]
[13,25]
[13,25,28]

numbers [13,25,27,28]
number [21]
numbers [2527]
number [20]

remains. The attempts to control for specific sources

of bias (i.e. to control for potential bias) were not
really fruitful. First, the amount of daily physical
activity is likely to influence physiological exercise
capacity data. Therefore, many studies used sedentary healthy control subjects [13,14,25,26]. One
study matched CFS patients with healthy controls
for current activity levels, age, body height, body
mass, and gender [25]. This brings us to the issue of
pooling of gender data, which has been identified as
an important source of bias in studies addressing
exercise physiology in patients with CFS [14].
Therefore, the majority of studies controlled for
gender bias by either studying women solely,
analysing the data obtained from women and men
separately, or studying a similar amount of women in
the
CFS
and
sedentary
control
group
[13,14,20,21,26,27]. Third, several studies addressed the issue of defining a maximal effort
[13,14,25]. Finally, a clear distinction between
physiological response during and at completion of
an exercise test has been made [25]. It was found
that the absolute physiological results recorded at the
end of each incremental work level of the exercise
test did not differ between CFS and controls, but the
peak exercise values were remarkably lower in the
CFS group [25].

Physical activity
All included articles on physical activity (n 5)
reported reduced habitual physical activity among
patients with CFS compared to healthy controls
[20,2932]. In total, 99 patients with CFS and 101
healthy control subjects were studied. Each of the
studies used real-time continuous activity monitoring (accelerometers).

numbers [14,20,21,24]
numbers [20,21,23]
numbers [20,22,23]
numbers [14,2022,24,26]
number [14]
number [20]
number [14]
number [21]
number [21]
number [14]
number [14]

Muscle strength
Two studies examined peak muscle power in patients
with CFS [24,26]. One study compared the maximally voluntary contraction of the anterior tibialis
muscle between patients with CFS (n 7) and
healthy controls (n 7) [24]. The second study
examined the maximally voluntary contraction of
the quadriceps muscle in 66 patients with CFS and
30 healthy controls [26]. Both studies found reduced
peak isometric muscle strength in patients with CFS
compared to healthy controls.

Discussion
From the available literature, it can be concluded
that patients with CFS perform less physical activity
during daily life, and have less peak isometric muscle
strength compared to healthy sedentary control
subjects. Conflicting data in relation to physiological
exercise capacity of patients with CFS have been
reported, but from the available data it appears that
physiological exercise capacity in CFS is reduced.

Physiological exercise capacity

Besides gender, physical activity level or the criteria
defining a maximal effort, other factors are likely to
account for the discrepancy across studies. The lack
of uniformity in exercise testing protocols might be
such a factor. Both a linear [5,12,13,34] and a
stepwise [14,25] increase in bicycle workload have
been used to study physiological exercise capacity in
people with CFS. One study randomly allocated
patients with CFS to either a linear exercise stress
testing protocol or a stepwise exercise testing

1994 CDC [1]

1994 CDC [1]

1994 CDC [1]

Oxford [33]
1988 CDC
1994 CDC [1]

Oxford [33]

1988 CDC

1988 CDC

Bazelmans et al. 2001 [20]

Cook et al. 2003 [21]

Cook et al. 2005 [22]

Gibson et al. 1993 [23]

Kent-Braun et al. 1993 [24]
Wallman et al. 2004 [25]

Fulcher & White 2000 [26]

Riley et al. 1990 [27]

Sisto et al. 1996 [28]

bicycle test until exhaustion

bicycle test until exhaustion
submaximal bicycle
test until 75% of
age-predicted maximal
heart rate
treadmill walking test until
exhaustion
treadmill walking test until
exhaustion
treadmill walking test
until exhaustion

bicycle test until exhaustion

submaximal bicycle exercise

bicycle test until subject could not

maintain target power output
bicycle test until exhaustion

bicycle test until exhaustion

Type of exercise test

7
7
7

34 34
20 20
15 19
39 26
12 12
77
31 31

5 kph 2.5% min71

gradient increase
Bruce protocol with initial
stage at 5% gradient
6 4-min stages (1 mph, 2,
1.5, 2.5, 3 and 3.5
mph) followed by
2% min71
incline increase

increase of 10% of estimated

maximal workload/min
0 W 30 W min71
40% of peak oxygen
consumption for 20 min
60 W 30 W 3 min71
100kilopond-mtere. 2 min71
increase of 25 W min71

427 204

CFS: 10 W 10 W min71
Controls: 40 W 30 W min71
0 W 25 W 2 min71

7
7
7

66 30
13 13
21 22

nCFS nControls

Controls
comparable
for age?

Exercise protocol

A priori
power
calculation?

Controls
comparable
for gender?

7
7

7
7

7
7
7

Blind
assessment?

7
7

Sedentary
controls?
7

Controls
comparable
for current
physical
activity
level?

7
7
7

7
7

Medication
wash-out or
exclusion of
medication
use?

6 (75)

5 (63)

4 (50)

3 (38)
3 (38)
5 (63)

6 (75)
5 (63)

4 (50)

6 (75)

4 (50)

Quality
score*/
8 (%)

*The quality score indicates the methodological quality of the studies and is expressed in percentages. Higher percentages indicate superior methodological quality. It is obtained by counting all quality
criteria included in the table, except for the first 3 which vary substantially across studies (diagnostic criteria, type of exercise test and exercise protocol). One point is provided for each met criterion.

Sargent et al. 2002 [14]

1988 and/or
1994 CDC [1]
1994 CDC [1]

De Becker et al. 2000 [13]

Reference

Diagnostic criteria
for CFS

Controls
comparable
for body
height or
weight?

Table II. Critical analysis of the quality of the studies examining physiological exercise capacity in CFS.

Exercise performance and physical activity in CFS

1497

1498

J. Nijs et al.

protocol [35]. Based on the ratio peak workload/peak

oxygen uptake, mechanical efficiency was lower
among the subjects performing the stepwise protocol
(p 0.002) [35]. When analysing the mean linear
regression slope values between oxygen uptake and
workload from the minute-by-minute exercise data
points for each subject, mechanical efficiency was
lower among the subjects performing the stepwise
protocol (p 0.039). These findings stress the
importance of the nature of the exercise testing
protocol.
Apart from the lack of uniformity in exercise
testing protocols, the highly heterogeneous nature of
the CFS population and the lack of uniformity in the
utilised diagnostic criteria, may account for the
differences between investigators. Indeed, a previous
study showed that a method for the prediction of
peak oxygen uptake established in Oxford-defined
CFS patients was not applicable to CFS patients
defined according to the Centre for Disease Control
and Prevention criteria [36]. Compared to the 1994
case definition for CFS [1], the Oxford criteria for
CFS [33] do not include symptoms of depressive
illness and anxiety disorders as exclusion factors, and
use fewer symptom criteria. This brings us to the
issue of heterogeneity and subgrouping. While some
patients are only mildly affected, others have severe
symptoms and are bedridden. It seems reasonable to
state that more severely affected patients might have
poorer physiological exercise capacity compared to
mildly affected patients. In absence of a definite
conclusion in relation to physiological exercise
capacity in patients with CFS, it is concluded that
the available study findings point towards a reduced
physiological exercise capacity in CFS. Further study
in this area is needed and should account for
potential sources of bias like the type of exercise
testing protocol and the utilised diagnostic criteria
for CFS. In addition, future studies should use a
wash-out period for medication use, blinded assessments, a priori power calculation, and a sedentary
control group comparable for age, gender, body
weight, body length and current physical activity
level. A study complying with each of these quality
criteria is currently unavailable in the scientific
literature.

performance. It has been shown that specific

activities, which were expected to result in high
fatigue levels, were less frequently performed by CFS
patients, and high fatigue expectations were related
to low activity levels [30]. Kinesiophobia, a specific
kind of fear-avoidance behavior, is defined as an
excessive, irrational, and debilitating fear of physical
movement and activity resulting from a feeling of
vulnerability to painful injury or reinjury [37]. In
patients with CFS, kinesiophobia represents a
common feature that was found to be of clinical
importance (i.e. related to disability), but did not
appear to be a determinant of physiological exercise
capacity [3840]. This observation is in line with a
study showing stronger voluntary efforts (i.e. stronger brain signals recorded with electroencephalogram) during motor tasks in CFS patients compared
to healthy controls [41].
It has been shown that too vigorous exercise
[12,13,42] or even a 30% increase in activity [34]
frequently triggers a relapse, which may consequently explain at least part of the physical inactivity
seen in patients with CFS. This post-exertional
malaise has been linked to acute immune changes
following physical activity that exceeds a CFS
patients physical capabilities [4345]. It is concluded that fatigue and other CFS characteristics like
post-exertional malaise make it difficult, if not
impossible, to be physically active. Anyone who has
worked with CFS patients can confirm that they do
not choose to be physically inactive. On the contrary,
patients with CFS are tired of being inactive. Current
rehabilitation approaches for CFS emphasise the
importance of pacing daily activities and respect
physical and mental limitations inherent to CFS
[46]. This approach aims at preventing post-exertional malaise in patients with CFS [46].

Muscle strength
Given the limited number of studies on muscle
strength in CFS (n 2), more work in this area is
required. Less muscle strength in those with CFS
can be due to deconditioning [26] or central fatigue
[24]. Both central and peripheral fatigue can explain
impaired motorneuron recruitment.

Physical activity
Conclusion
All studies on physical activity in CFS used real time
accelerometry and found reduced habitual physical
activity among patients with CFS compared to
healthy controls [20,2932]. The question arises:
why are people with CFS physically inactive?
Avoidance behavior towards physical activity is likely
to influence physical activity level and exercise

Patients with CFS perform less physical activity

during daily life, and have less peak isometric muscle
strength as compared to healthy sedentary control
subjects. Addressing physiological exercise capacity,
the literature review points towards variability in the
CFS population. It is concluded that the available

Exercise performance and physical activity in CFS

evidence points towards a reduced physiological
exercise capacity in CFS. Future studies should use
a wash-out period for medication use, blinded
assessments, a priori power calculation, and a
sedentary control group comparable for age, gender,
body weight, body length and current physical
activity level.

Acknowledgements
Mira Meeus is a postdoctoral research fellow of the
Research Foundation Flanders (FWO). Jessica Van
Oosterwijck is a research fellow of the Vrije
Universiteit Brussel (OZR1596).

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