The Physician and Sportsmedicine
Menubar About Us Advertiser Services CME Resource Center Personal Health Journal Home

Chronic Fatigue Syndrome

Matching Exercise to Symptom Fluctuations

James S. Skinner, PhD


In Brief: Physical activity decreases insulin resistance and can aid in both preventing type 2 diabetes mellitus and managing the disease. Before patients with type 2 diabetes begin an exercise program, they should undergo a preparticipatory clinical assessment and screening for micro- and macrovascular disease. Patients older than 35 and those with additional cardiovascular risk factors, peripheral vascular disease, long-standing disease, or peripheral neuropathy should have an exercise stress test. Adequate glycemic control and selection of appropriate physical activity, such as brisk walking or swimming, are essential to avoid associated complications. Patients on diabetes medications should monitor blood glucose levels and adjust their diet to minimize fluctuations in blood glucose during exercise.

The cause of chronic fatigue syndrome (CFS) remains unknown. CFS is diagnosed when patients have an unexplained onset of fatigue for more than 6 months that is severe enough to limit daily activity and not resolved by rest. In addition, patients must have at least four of the following eight symptoms to meet the established criteria1: muscle pain, joint pain, sore throat, tender lymph nodes, cognitive difficulty (memory and concentration), headaches of a new pattern or severity, postexercise discomfort lasting 24 hours or more, and sleep disturbance (table 1). They may, however, have other symptoms as well (table 2).2 Just under 1% of the population experiences CFS. A disproportionate number of this group are women,3 but the reasons for the disparity are not clear.

TABLE 1. The Centers for Disease Control and Prevention Criteria for Chronic Fatigue Syndrome

Chronic fatigue syndrome is defined by the presence of:

1. Clinically evaluated, unexplained, persistent or relapsing fatigue that is of new or definite onset; is not from ongoing exertion; is not alleviated by rest; and results in substantial reduction of previous levels of occupational, educational, social or personal activities;


2. Four or more of the following symptoms that persist or recur during 6 or more consecutive months of illness and that do not predate the fatigue:
  • Self-reported impairment in short-term memory or concentration
  • Sore throat
  • Tender cervical or axillary lymph nodes
  • Muscle pain
  • Multijoint pain without redness or swelling
  • Headaches of a new pattern or severity
  • Unrefreshing sleep
  • Postexertional malaise lasting ≥ 24 hr

Adapted from Straus SE: Chronic fatigue syndrome, in Braunwald E, Fauci AS, Kasper DL, et al (eds): Harrison's Principles of Internal Medicine, ed 15. New York City, McGraw-Hill, 2001, pp 2541-2542.

TABLE 2. Symptoms Observed in Chronic Fatigue Syndrome

Common Symptoms (≥40%, in decreasing order)
Difficulty in concentrating
Sore throat
Tender lymph nodes
Muscle aches
Joint aches
Difficulty in sleeping
Psychiatric problems
Abdominal cramps

Less Common Symptoms (≤20%, in decreasing order)
Weight loss
Rapid pulse
Weight gain
Chest pain
Night sweats

Adapted from Straus SE: Chronic fatigue syndrome, in Braunwald E, Fauci AS, Kasper DL, et al (eds): Harrison's Principles of Internal Medicine, ed 15. New York City, McGraw-Hill, 2001, pp 2541-2542.

Chronic Fatigue Syndrome and Physical Activity

CFS is difficult to study, because the population of patients is heterogeneous and the symptoms have a tendency to fluctuate.4 Many patients reduce their physical activity to avoid symptoms and rest longer after exercise than do healthy controls.5 Silver et al6 also found that exercise can provoke anxiety and a feeling of increased vulnerability to pain and fatigue. Vercoulen et al7 reported that patients with CFS were less active than healthy subjects and were more likely to avoid activities that they perceived to be fatiguing. As a result, part of their increased fatigue may be associated with or exaggerated by deconditioning. Sleep deprivation or psychological distress or both may also contribute to the higher levels of fatigue.

The hallmark of CFS is an increase in symptoms following exercise. This phenomenon is usually the result of high-intensity or prolonged exercise. For many CFS patients, very minimal exertion (ie, less than what others might consider exercise) can exacerbate symptoms from 6 hours to as long as 5 days afterward. In contrast, Clapp et al8 found no changes immediately after 30 minutes of light, intermittent exercise (three 10-minute bouts) or 1 week later.

Those with CFS tend to be weaker and have delayed recovery after strenuous strength training. Paul et al9 had participants perform 18 maximal voluntary contractions of the quadriceps. The contractions of the control group were consistently higher than those of the patients with CFS, but both groups had a similar reduction in force over the 18 contractions. While normal participants showed no change over the next day, patients with CFS had reduced strength 3 hours and 24 hours later.

Patients who have CFS perform poorly compared with healthy controls on tests of focused and sustained attention and have a greater impairment in cognitive processing immediately after exhaustive treadmill exercise and 24 hours later.10 Using a battery of cognitive measures, Fuentes et al11 found that patients with CFS were slower but not less accurate than healthy persons. However, those with CFS had greater intraindividual variability over 10 weekly sessions compared with healthy persons.

Fitness Status in CFS

Depending on the study examined, researchers find that patients with CFS are either no different from or less fit than control patients. Most clinical studies report a maximal oxygen uptake (VO2max) of 20 to 40 mL/kg/min for patients 25 to 55 years old.12-15

This wide range in results can be caused by a number of factors. For example, it is not certain that the patients studied are representative of the population of patients with CFS, because those who have the greatest symptoms tend to avoid activity and may not volunteer to be tested. There may also be a large variation in the ages of the subjects tested. Average fitness levels of persons at age 55 are quite different from those at age 25. Sargent et al16 make another point: Data from men and women have been pooled in some studies, even though women tend to have lower fitness levels. Finally, the severity and duration of symptoms among patients with CFS may vary widely; in the studies reviewed, symptoms were present from 6 months to 7 years.

Patients with CFS are not as likely to push themselves to their true maximum, because they do not want to worsen symptoms. Some studies have used "typical" or "normal" patients without CFS as controls, while others have used very sedentary individuals as control patients. Results from two recent, well-conducted studies15,16 showed no difference in fitness between patients and controls. Sargent et al16 also found that VO2max, maximal heart rate, and VO2 at the lactate threshold in patients of both sexes were not different from values expected in healthy, sedentary, unfit subjects of a similar age.

There is another possible reason for the large variation in fitness status that has been reported. Although clinicians know that the symptoms of CFS fluctuate, most studies tested subjects only once. In an unpublished study, Shona Halson, MS, and David G. Rowbottom, PhD (personal written communication, September 2000) had eight participants with CFS perform progressive exercise tests to exhaustion once a week for 4 weeks to examine intraindividual variability. The investigators found that the mean coefficient of variation in VO2max was 11.8%, with one subject varying as much as 25% over the four tests. In the literature, typical coefficients of variation for VO2max range from 4% to 6%.17 Halson and Rowbottom reported no systematic upward or downward trend in peak values that would suggest either a training effect or progressive fatigue with repeated testing. Therefore, results from only one exercise test should be viewed with caution, because individuals' results could vary from day to day.

Adjustments for Exercise Testing

Although patients with CFS might have a greater prevalence of chronic diseases associated with a sedentary lifestyle, they do not generally appear to present a greater risk in exercise testing.18,19 Thus, any precautions normally taken with older patients should be appropriate.

During a progressive exercise test, patients with CFS have the same VO2 per watt on a cycle ergometer as healthy persons,17 as well as a similar rise in VO2 per unit increase in watts.20 Both of these results should be interpreted to mean that the metabolism in affected patients is not different from that of normal persons. Studies suggest that the heart rate (HR) at absolute submaximal power outputs is the same,13 lower,21 or higher14 than that seen in normal persons. A higher HR suggests that they are less fit, a similar HR suggests no difference in fitness, and a lower HR suggests a higher level of fitness or, more probably, an elevated vagal tone.

Inbar et al13 found no difference in HR and ventilation at the same VO2 but inferred that patients with CFS have a slow increase in HR. The investigators state that this hypodynamic cardiac response may lead to a lower cardiac output and an earlier onset of fatigue. In general, the rating of perceived exertion (RPE) of patients with CFS is higher at the same VO218,22; this may be due to a lower fitness level, greater fatigue, or a higher level of anxiety during exercise.

As previously noted, patients with CFS have difficulty attaining a maximal level of exertion, and their peak HR is often about 75% to 85% of the maximal value predicted for their age in some studies11 but not in others.16 Thus, it appears that the basic metabolism of patients who have CFS is similar to that of healthy persons but that deconditioning from avoidance of activity may cause higher HR and RPE responses to given power outputs.

Interventions and Their Effect on CFS

Whiting et al23 systematically reviewed many studies of various interventions employed to treat and manage CFS. Of the 350 studies initially identified by literature search, 44 studies that evaluated interventions in 2,801 patients with CFS were included in the analysis. Although the review found results mixed in terms of effectiveness, cognitive behavioral therapy (CBT) and graded exercise therapy showed promising results.

Aerobic exercise appears to be more effective than flexibility exercise and relaxation for patients with CFS. An exercise training study22 in CFS patients that lasted 4 to 6 months revealed that the ability to perform aerobic exercise increased 13%. As a result of training, the patients had less fatigue, a lower HR, a lower RPE, increased functional capacity, and fewer symptoms.

Except for the finding of reduced symptoms, however, the other changes observed are typical of those seen in healthy persons after aerobic training. Given that healthy persons do not generally have symptoms, it is unlikely that they would have "reduced" symptoms, as was found among those with CFS. In addition to improved fitness and strength,24 other reasons why aerobic training might reduce CFS symptoms include the fact that the activity produces an analgesic effect, improves the sense of well-being and locus of control, and has an antidepressant effect.

Gulf War veterans' illnesses (GWVI) include CFS, fibromyalgia, and neurocognitive dysfunction. In a recent large-scale study,25 1,092 veterans with GWVI were randomly assigned to one of four treatment arms: CBT plus aerobic exercise; aerobic exercise alone; CBT alone; or usual and customary care. All veterans were treated for 3 months using standard protocols and had follow-up visits in the clinic at 3, 6, and 12 months. Investigators found that neither aerobic exercise nor CBT had a significant impact on physical function for veterans with GWVI, but both treatments, especially exercise, resulted in less fatigue, fewer cognitive symptoms, less distress, and improved mental health functioning.

Tailoring the Exercise Prescription

Because an exercise program appears to help patients, it is important for patients with CFS to make exercise a regular part of their lifestyle. Initially, these patients will worry about exacerbating symptoms of fatigue, and fatigue may be greater for the first few days. However, fatigue should diminish within a few days to a few weeks. Thus, it is important that physicians emphasize the need to stay with any exercise program, even if it means exercising at a reduced level. For this reason, the exercise prescription should be flexible and easily modified so that the participants can find different ways to be active.

Exercise type. It appears that a rapid introduction of overly strenuous exercise is likely to exacerbate symptoms and reduce subsequent adherence to a therapeutic exercise program. If the frequency, duration, and, especially, intensity of exercise are greater than that to which patients with CFS have adapted, they are likely to drop out of an exercise program. Therefore, exercise in this population must be introduced and increased gradually.

Based on only a few studies, it appears that intermittent exercise is better than continuous exercise and that light-to-moderate intensity is better than high-intensity exercise. Clapp et al8 found that patients with CFS could walk for three 10-minute sessions without any abnormal responses. While this small study did not determine the effects of 30 minutes of continuous walking, all 10 patients believed they could not walk for 30 minutes without exacerbating their symptoms.

Exercise intensity. The typical way to prescribe exercise intensity using a percentage of VO2max may not be appropriate for patients who have CFS, because their VO2max can vary widely from day to day. Prescribing exercise based on HR may also not be appropriate, because patients with CFS may not be able to reach a given target HR on days they feel fatigued. Consequently, some patients might decide not to exercise at all, knowing that they cannot reach the target HR.

One approach that I have used is to prescribe exercise using submaximal aerobic exercise based on Borg's RPE scale.25 This approach allows participants to select activities based on how they are feeling on a given day. For example, by exercising at an RPE between 12 to 14 ("somewhat hard" on the Borg scale), patients can control intensity and minimize chances of exercising at levels that are too hard or too easy based on their level of fatigue on that particular day. One advantage of this approach is that patients with CFS are encouraged to do something, regardless of how much fatigue they are experiencing.

Cautions. Lloyd and Frankenberg19 note that the intensity, frequency, duration, or mode of exercise that exacerbates CFS symptoms is not known. They suggest that it would be useful to find the threshold of activity that produces symptoms in each individual so that exercise below that level can be prescribed. However, because symptoms may vary from one day to another, the threshold may also change. While there is no consensus about the type of exercise to recommend, it is likely that low-impact activities (eg, walking, cycling, swimming) are appropriate.

Exercise as Medicine

Exercise appears to be a useful and effective form of therapy for patients with CFS. As with any therapy, the prescription should be individualized to (1) minimize the risks of exacerbating fatigue and other symptoms, (2) gradually increase the amount of exercise done, (3) improve the physiologic and psychological functioning of patients, and (4) promote lifelong physical activity.


  1. Fukuda K, Straus SE, Hickie I, et al: The chronic fatigue syndrome: a comprehensive approach to its definition and study. International Chronic Fatigue Syndrome Study Group. Ann Intern Med 1994;121(12):953-959
  2. Straus SE: Chronic fatigue syndrome, in Braunwald E, Fauci AS, Kasper DL, et al (eds): Harrison's Principles of Internal Medicine, ed 15. New York City, McGraw-Hill, 2001, pp 2541-2542
  3. Tuck I, Wallace D: Chronic fatigue syndrome: a woman's dilemma. Health Care Women Int 2000:21(5):457-466
  4. Buchwald D, Umali P, Umali J, et al: Chronic fatigue and the chronic fatigue syndrome: prevalence in a Pacific Northwest health care system. Ann Intern Med 1995;123(2):81-88
  5. van der Werf SP, Prins JB, Vercoulen JH, et al: Identifying physical activity patterns in chronic fatigue syndrome using actigraphic assessment. J Psychosom Res 2000;49(5):373-379
  6. Silver A, Haeney M, Vijayadurai P, et al: The role of fear of physical movement and activity in chronic fatigue syndrome. J Psychosom Res 2002;52(6):485-493
  7. Vercoulen JH, Bazelmans E, Swanink CM, et al: Physical activity in chronic fatigue syndrome: assessment and its role in fatigue. J Psychiatr Res 1997;31(6):661-673
  8. Clapp LL, Richardson MT, Smith JF, et al: Acute effects of thirty minutes of light-intensity, intermittent exercise on patients with chronic fatigue syndrome. Phys Ther 1999;79(8):749-756
  9. Paul L, Wood L, Behan WM, et al: Demonstration of delayed recovery from fatiguing exercise in chronic fatigue syndrome. Eur J Neurol 1999;6(1):63-69
  10. Blackwood SK, MacHale SM, Power MJ, et al: Effects of exercise on cognitive and motor function in chronic fatigue syndrome and depression. J Neurol Neurosurg Psychiatry 1998;65(4):541-546
  11. Fuentes K, Hunter MA, Strauss E, et al: Intraindividual variability in cognitive performance in persons with chronic fatigue syndrome. Clin Neuropsychol 2001;15(2):210-227
  12. De Becker P, Roeykens J, Reynders M, et al: Exercise capacity in chronic fatigue syndrome. Arch Intern Med 2000;160(21):3270-3277
  13. Inbar O, Dlin R, Rotstein A, et al: Physiological responses to incremental exercise in patients with chronic fatigue syndrome. Med Sci Sports Exerc 2001;33(9):1463-1470
  14. Riley MS, O'Brien CJ, McCluskey DR, et al: Aerobic work capacity in patients with chronic fatigue syndrome. BMJ 1990;301(6758):953-956
  15. Bazelmans E, Bleijenberg G, Van Der Meer JW, et al: Is physical deconditioning a perpetuating factor in chronic fatigue syndrome? a controlled study on maximal exercise performance and relations with fatigue, impairment and physical activity. Psychol Med 2001;31(1):107-114
  16. Sargent C, Scroop GC, Nemeth PM, et al: Maximal oxygen uptake and lactate metabolism are normal in chronic fatigue syndrome. Med Sci Sports Exerc 2002;34(1):51-56
  17. Skinner JS, Wilmore KM, Jaskólska A, et al: Reproducibility of maximal exercise test data in the HERITAGE family study. Med Sci Sports Exerc 1999;31(11):1623-1628
  18. Sisto SA, LaManca J, Cordero DL, et al: Metabolic and cardiovascular effects of a progressive exercise test in patients with chronic fatigue syndrome. Am J Med 1996;100(6):634-640
  19. Lloyd LK, Frankenberg AJ: The effects of exercise therapy on chronic fatigue syndrome (CFS) patients. Int Sport Med J 2000;1(3):1-6
  20. Mullis R, Campbell IT, Wearden AJ, et al: Prediction of peak oxygen uptake in chronic fatigue syndrome. Br J Sports Med 1999;33(5):352-356
  21. Montague TJ, Marrie TJ, Klassen GA, et al: Cardiac function at rest and with exercise in the chronic fatigue syndrome. Chest 1989;95(4):779-784
  22. Fulcher KY, White PD: Randomised controlled trial of graded exercise in patients with the chronic fatigue syndrome. BMJ 1997;314(7095):1647-1652
  23. Whiting P, Bagnall AM, Sowden AJ, et al: Interventions for the treatment and management of chronic fatigue syndrome: a systematic review. JAMA 2001;286(11):1360-1368
  24. Fulcher KY, White PD: Strength and physiological response to exercise in patients with chronic fatigue syndrome. J Neurol Neurosurg Psychiatry 2000;69(3):302-307
  25. Donta ST, Clauw DJ, Engel CC Jr, et al: Cognitive behavioral therapy and aerobic exercise for Gulf War veterans' illnesses: a randomized controlled trial. JAMA 2003;289(11):1396-1404

Dr Skinner is a professor in the department of kinesiology at Indiana University in Bloomington, and also works out of his home in Brevard, NC. Address correspondence to James S. Skinner, PhD, 11 Gasga Ct, Brevard, NC 28712; e-mail to [email protected].

Disclosure information: Dr Skinner discloses no significant relationship with any manufacturer of any commercial product mentioned in this article. No drug is mentioned in this article for an unlabeled use.