Int J Sports Med 2019; 40(02): 77-87
DOI: 10.1055/a-0802-9175
© Georg Thieme Verlag KG Stuttgart · New York

Peak Oxygen Uptake in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis: A Meta-Analysis

John Derek Franklin
1   School of Health and Social Care, Teesside University, Middlesbrough, United Kingdom of Great Britain and Northern Ireland
Greg Atkinson
1   School of Health and Social Care, Teesside University, Middlesbrough, United Kingdom of Great Britain and Northern Ireland
Janet M. Atkinson
2   Middlesbrough College, Middlesbrough, United Kingdom of Great Britain and Northern Ireland
Alan M. Batterham
1   School of Health and Social Care, Teesside University, Middlesbrough, United Kingdom of Great Britain and Northern Ireland
› Author Affiliations
Further Information

Publication History

accepted 08 November 2018

Publication Date:
17 December 2018 (online)


To evaluate the magnitude of the difference in VO2peak between patients with Chronic Fatigue Syndrome/ Myalgic Encephalomyelitis (CFS/ME) and apparently healthy controls, 7 databases (Cochrane, PubMed, PsycINFO, Web of Knowledge, Embase, Scopus, Medline) were searched for articles published up to March 2018. Search terms included “chronic fatigue syndrom*”AND (“peak” OR “maxim*” OR “max”) AND (“oxygen uptake” OR “oxygen consumption” OR “VO2peak” or “VO2max”. Eligibility criteria were adults>18 y with clinically diagnosed CFS/ME, with VO2peak measured in a maximal test and compared against an apparently healthy control group. The methodological quality of included studies was assessed using a modified Systematic Appraisal of Quality for Observational Research critical appraisal framework. A random effects meta-analysis was conducted on 32 cross-sectional studies (effects). Pooled mean VO2peak was 5.2 (95% CI: 3.8–6.6)−1min−1 lower in CFS/ME patients vs. healthy controls. Between-study variability (Tau) was 3.4 (1.5–4.5)−1min−1 indicating substantial heterogeneity. The 95% prediction interval was −1.9 to 12.2−1min−1. The probability that the effect in a future study would be>the minimum clinically important difference of 1.1−1min−1 (in favour of controls) was 0.88 – likely to be clinically relevant. Synthesis of the available evidence indicates that CFS/ME patients have a substantially reduced VO2peak compared to controls.

  • References

  • 1 Aerenhouts D, Ickmans K, Clarys P, Zinzen E, Meersdom G, Lambrecht L, Nijs J. Sleep characteristics, exercise capacity and physical activity in patients with chronic fatigue syndrome. Disabil Rehabil 2015; 37: 2044-2050
  • 2 Aspenese ST, Nilsen TIL, Skaug E-A, Berthwussen GF, Ellingsen Ø, Vatten L, Wisloff U. Peak oxygen uptake and cardiovascular risk factors in 4631 healthy women and men. Med Sci Sports Exerc 2011; 1465-1473
  • 3 Bazelmans E, Bleijenberg G, Van Der Meer JWM, Folgering H. 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: 107-114
  • 4 Carruthers BM, Jain AK, De Meirleir KL, Peterson DL, Klimas NG, Lerner AM, Bested AC, Flor-Henry P, Joshi P, Powles A, Sherkey JA, Van De Sande MI. Myalgic Eencephalomyelitis/ chronic fatigue syndrome: Clinical working case definition, diagnostic and treatment protocols. J Chronic Fatigue Syndr 2003; 11: 7-115
  • 5 Carruthers BM, Van de Sande MI, De Meirleir KL, Klimas NG, Broderick G, Mitchell T, Staines D, Powles ACP, Speight N, Vallings R, Bateman L, Baumgarten-Austrheim B, Bell DS, Carlo-Stella N, Chia J, Darragh A, Jo D, Lewis D, Light AR, Marshall-Gradisbik S, Mena I, Mikovits JA, Miwa K, Murovska M, Pall ML, Stevens S. Myalgic encephalomyelitis: International consensus criteria. J Intern Med 2011; 270: 327-338
  • 6 Claypoole K, Mahurin R, Fischer ME, Goldberg J, Schmaling KB, Schoene RB, Ashton S, Buchwald D. Cognitive compromise following exercise in monozygotic twins discordant for chronic fatigue syndrome: Fact or artifact?. Appl Neuropsychol 2001; 8: 31-40
  • 7 Collin SM, Nikolaus S, Heron J, Knoop H, White PD, Crawley E. Chronic fatigue syndrome (CFS) symptom-based phenotypes in two clinical cohorts of adult patients in the UK and The Netherlands. J Psychosom Res 2016; 81: 14-23
  • 8 Cook DB, Nagelkirk PR, Peckerman A, Poluri A, Lamanca JJ, Natelson BH. Perceived exertion in fatiguing illness: Civilians with chronic fatigue syndrome. Med Sci Sports Exerc 2003; 563-568
  • 9 Cook DB, Nagelkirk PR, Peckerman A, Poluri A, Lamanca JJ, Natelson BH. Perceived exertion in fatiguing illness: Gulf War veterans with chronic fatigue syndrome. Med Sci Sports Exerc 2003; 569-574
  • 10 Cook DB, Nagelkirk PR, Poluri A, Mores J, Natelson BH. The influence of aerobic fitness and fibromyalgia on cardiorespiratory and perceptual responses to exercise in patients with chronic fatigue syndrome. Arthritis Rheum 2006; 54: 3351-3362
  • 11 De Becker P, Roeykens J, Reynders M, Mcgregor N, De Meirleir K. Exercise capacity in chronic fatigue syndrome. Arch Intern Med 2000; 160: 3270-3277
  • 12 Digitizelt. Digitizer software.Available from Accessed 20th November 2017;
  • 13 Evering RMH, Van Weering MGH, Groothuis-Oudshoorn KCGM, Vollenbroek-Hutten MMR. Daily physical activity of patients with the chronic fatigue syndrome: A systematic review. Clin Rehabil 2011; 25: 112-133
  • 14 Farquhar WB, Hunt BE, Taylor JA, Darling SE, Freeman R, Andrew Tay-Lor J, Blood RF, Bldg P, Israel B. Blood volume and its relation to peak O2 consumption and physical activity in patients with chronic fatigue. Am J Physiol Hear Circ Physiol 2002; 282: H66-H71
  • 15 Fischler B, Dendale P, Michiels V, Cluydts R, Kaufman L, De Meirleir K. Physical fatigability and exercise capacity in chronic fatigue syndrome: Association with disability, somatization and psychopathology. J Psychosom Res 1997; 42: 369-378
  • 16 Fukuda K, Straus SE, Hickie I, Sharpe MC, Psych M, Dobbins JG, Komaroff A. The chronic fatigue syndrome: A comprehensive approach to its definition and study. Ann Intern Med 1994; 121: 953-959
  • 17 Fulcher KY, White PD. Strength and physiological response to exercise in patients with chronic fatigue syndrome. J Neurol Neurosurg Psychiatry 2000; 69: 302-307
  • 18 Garland T, Carter P. Evolutionary physiology. Annu Rev Physiol 1994; 56: 579-621
  • 19 Georgiades E, Behan WM, Kildduff LP, Hadjicharalambous M, Mackie EE, Wilson J, Ward SA, Pitsiladis YP. Chronic fatigue syndrome: New evidence for a central fatigue disorder. Clin Sci 2003; 105: 213-218
  • 20 Harriss DJ, Macsween A, Atkinson G. Standards for ethics in sport and exercise science research: 2018 update. Int J Sports Med 2017; 38: 1126-1131
  • 21 Higgins JPT, Green S.(editors) Section and Section 7.7.a Formula for combining groups.In Higgins JPT, Green S. (editors) Cochrane Handbook for Systematic Reviews of Interventions: Version 5.1.0 [updated March 2011].. The Cochrane Collaboration 2011 Accessed 20th March 2017
  • 22 Hodges LD, Nielson T, Baken D. Physiological measures in participants with chronic fatigue syndrome, multiple sclerosis and healthy controls following repeated exercise: a pilot study. Clin Physiol Funct Imaging 2017; 37: 639-644
  • 23 Holmes GP, Kaplan JE, Gantz NM, Komaroff AL, Schonberger LB, Straus SE, Jones JF, Dubois RE, Cunningham-rundles C, Pahwa S, Tosato G, Zegans LS, Purtilo DT, Brown N, Schooley RT, Brus I, York N, Francisco S. Chronic fatigue syndrome: A working case definition. Ann Intern Med 1988; 108: 387-389
  • 24 Hopkins WG, Marshall SW, Batterham AM, Hanin J. Progressive statistics for studies in sports medicine and exercise science. Med Sci Sports Exerc 2009; 41: 3-12
  • 25 Ickmans K, Clarys P, Nijs J, Meeus M, Aerenhouts D, Zinzen E, Aelbrecht S, Meersdom G, Lambrecht L, Pattyn N. Association between cognitive performance, physical fitness, and physical activity level in women with chronic fatigue syndrome. J Rehabil Res Dev 2013; 50: 795-810
  • 26 Inbar O, Dlin R, Rotstein A, Whipp BJ. Physiological responses to incremental exercise in patients with chronic fatigue syndrome. Med Sci Sports Exerc 2001; 33: 1463-1470
  • 27 Inthout J, Ioannidis JPA, Rovers MM, Goeman JJ. Plea for routinely presenting prediction intervals in meta-analysis. BMJ Open 2016; 6: e010247
  • 28 Jammes Y, Steinberg JG, Mambrini O, Bré EONFG, Jammes AY. Chronic fatigue syndrome: assessment of increased oxidative stress and altered muscle excitability in response to incremental exercise. J Intern Med 2005; 257: 299-310
  • 29 Jammes Y, Steinberg JG, Delliaux S, Brégeon F. Chronic fatigue syndrome combines increased exercise-induced oxidative stress and reduced cytokine and Hsp responses. J Intern Med 2009; 266: 196-206
  • 30 Jammes Y, Steinberg JG, Delliaux S. Chronic fatigue syndrome: Acute infection and history of physical activity affect resting levels and response to exercise of plasma oxidant/antioxidant status and heat shock proteins. J Intern Med 2012; 272: 74-84
  • 31 Jones DEJ, Hollingsworth KG, Jakovljevic DG, Fattakhova G, Pairman J, Blamire AM, Trenell MINJ. Loss of capacity to recover from acidosis on repeat exercise in chronic fatigue syndrome: a case–control study. Eur J Clin Invest 2012; 42: 186-194
  • 32 Keteyian SJ, Brawner CA, Savage PD, Ehrman JK, Schairer J, Divine G, Aldred H, Ophaug K, Ades PA. Peak aerobic capacity predicts prognosis in patients with coronary heart disease. Am Heart J 2008; 156: 292-300
  • 33 Khan H, Kunutsor S, Rauramaa R, Savonen K, Kalogeropoulos AP, Georgiopoulou VV, Butler J, Laukkanen JA. Cardiorespiratory fitness and risk of heart failure: A population-based follow-up study. Eur J Heart Fail 2014; 16: 180-188
  • 34 Komaroff AL, Fagioli LR, Geiger AM, Doolittle TH, Lee J, Kornish J, Gleit MA, Guerriero RT. An examination of the working case definition of chronic fatigue syndrome. Am J Med 1996; 100: 56-64
  • 35 LaManca JJ, Sisto SA, Zhou X-D, Ottenweller JE, Cook S, Peckerman A, Zhang Q, Denny TN, Gause WC, Natelson BH. Immunological response in chronic fatigue syndrome following a graded exercise test to exhaustion. J Clin Immunol 1999; 19: 135-142
  • 36 LaManca JJ, Peckerman A, Ann Sisto S, DeLuca J, Cook S, Natelson BH. Cardiovascular responses of women with chronic fatigue syndrome to stressful cognitive testing before and after strenuous exercise. Psychosom Med 2001; 63: 756-764
  • 37 Larun L, Malterud K. Finding the right balance of physical activity. A focus group study about experiences among patients with chronic fatigue syndrome. Patient Educ Couns 2011; 83: 222-226
  • 38 Laukkanen JA, kurl S, Salonen R, Rauramaa R, Salonen JT. The predictive value of cardiorespiratory fitness. Eur Heart J 2004; 25: 1428-1437
  • 39 Laukkanen JA, Zaccardi F, Khan H, Kurl S, Jae SY, Rauramaa R. Long-term change in cardiorespiratory fitness and all-cause mortality: A population-based follow-up study. Mayo Clin Proc 2016; 91: 1183-1188
  • 40 Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gøtzsche PC, Ioannidis JPA, Clarke M, Devereaux PJ, Kleijnen J, Moher D. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: Explanation and elaboration. PLoS Med 2009; 6: 7
  • 41 Midgley AW, McNaughton LR, Polman R, Marchant D. Criteria for determination of maximal oxygen uptake: A brief critique and recommendations for future research. Sport Med 2007; 1019-1028
  • 42 Moneghetti KJ, Skhiri M, Contrepois K, Kobayashi Y, Maecker H, Davis M, Snyder M, Haddad F, Montoya JG. Value of circulating cytokine profiling during submaximal exercise testing in myalgic encephalomyelitis/chronic fatigue syndrome. Sci Rep 2018; 8: 2779
  • 43 Myers J, Prakash M, Froelicher V, Partington S, Atwood E. Exercise capacity and mortality among men referred for exercise testing. N Engl J Med 2002; 346: 793-800
  • 44 National Institute for Health and Care Excellence (NICE). NICE clinical guideline [CG53]. Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (or Encephalopathy): Diagnosis and Management. London: National Institute for Health and Clinical Excellence; 2007
  • 45 Nijs J, Aelbrecht S, Meeus M, Van Oosterwijck J, Zinzen E, Clarys P. Tired of being inactive: A systematic literature review of physical activity, physiological exercise capacity and muscle strength in patients with chronic fatigue syndrome. Disabil Rehabil 2011; 33: 1493-1500
  • 46 Poole DC, Wilkerson DP, Jones AM. Validity of criteria for establishing maximal O2uptake during ramp exercise tests. Eur J Appl Physiol 2008; 102: 403-410
  • 47 Riley MS. O CJ McCluskey DR, Bell NP, Nicholls DP. Papers Aerobic work capacity in patients with chronic fatigue syndrome. BMJ 1990; 301: 953-956
  • 48 Robinson M, Gray SR, Watson MS, Kennedy G, Hill A, Belch JJF, Nimmo MA, Nimmo MA. Plasma IL-6, its soluble receptors and F 2-isoprostanes at rest and during exercise in chronic fatigue syndrome. Scand J Med Sci Sports 2010; 20: 282-290
  • 49 Ross LE, Grigoriadis S, Mamisashvili L, Koren G, Steiner M, Dennis CL, Cheung A, Mousmanis P. Quality assessment of observational studies in psychiatry: An examplefrom perinatal psychiatric research. Int J Methods Psychiatr Res 2011; 20: 224-234
  • 50 Rowbottom D, Keast D, Pervan Z, Morton A. The physiological response to exercise in chronic fatigue syndrome. J Chronic Fatigue Syndr 1998; 4: 33-50
  • 51 Sargent C, Scroop GC, Nemeth PM, Burnet RB, Buckley JD. Maximal oxygen uptake and lactate metabolism are normal in chronic fatigue syndrome. Med Sci Sports Exerc 2002; 51-56
  • 52 Schluederberg A, Straus SE, Peterson P, Blumenthal S, Komaroff AL, Spring SB, Landay A, Buchwald D. Chronic fatigue syndrome research definition and medical outcome assessment. Ann Intern Med 1992; 117: 325-331
  • 53 Sharpe M, Archard LC, Banatvala J, Clare A, David A, Edwards R, Hawton K, Lambert H, Lane R, McDonald E, Mowbray J, Pearson D, Peto T, Preedy V, Smith A, Smith D, Taylor D, Tyrell A, Wessely S, White PD. A report-chronic fatigue syndrome: guidelines for research. J R Soc Med 1991; 84: 118-121
  • 54 Sisto SA, Ma J, Lamanca DL. Metabolic and cardiovascular effects of a progressive exercise test in patients with chronic fatigue syndrome. Am J Med 1996; 100: 634-640
  • 55 Snell CR, Stevens SR, Davenport TE, Van Ness JM. Discriminative validity of metabolic and workload measurements for identifying people with chronic fatigue syndrome. Phys Ther 2013; 93: 1484-1492
  • 56 Suárez A, Guillamó E, Roig T, Blázquez A, Alegre J, Bermú Dez J, Ventura JL, María García-Quintana A, Comella A, Segura R, Javierre C. Nitric oxide metabolite production during exercise in chronic fatigue syndrome: A case-control study. J Womens Health (Larchmt) 2010; 19: 1073-1077
  • 57 Togo F, Natelson BH, Cherniack NS, Klapholz M, Rapoport DM, Cook DB. Sleep is not disrupted by exercise in patients with chronic fatigue syndromes. Med Sci Sports Exerc 2010; 42: 16-22
  • 58 VanNess JM, Snell CR, Stevens SR. Diminished Cardiopulmonary Capacity During Post-Exertional Malaise. J Chronic Fatigue Syndr 2007; 14: 77-85
  • 59 Vermeulen RCW, Kurk RM, Visser FC, Sluiter W, Scholte HR. Patients with chronic fatigue syndrome performed worse than controls in a controlled repeated exercise study despite a normal oxidative phosphorylation capacity. J Transl Med 2010; 8: 93
  • 60 Vermeulen RC, Vermeulen van Eck IW. Decreased oxygen extraction during cardiopulmonary exercise test in patients with chronic fatigue syndrome. J Transl Med 2014; 12: 20