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Exercise is any movement or activity considered to contribute to general health and well-being. Exercise may be recommended as part of a wellness regimen in any chronic illness.[1][2] However, exercise intolerance is a central feature of ME/CFS, and patients show multiple documented abnormal responses to exercise, including significant worsening of all symptoms; this is the opposite response to how healthy people respond to exercise.[3] Rather than increase health and well-being, evidence from ME/CFS patients shows that exercise or even increased activity significantly reduces their physical and mental capacity over time, sometimes permanently.[4]

Worsening of symptoms in ME/CFS patients cannot be explained by deconditioning (lack of fitness), or by psychological theories like "symptom focusing" or catastrophizing; the effects of exercise or over-exertion in patients include increased immune system symptoms, an increase in inflammatory markers in the blood, increased lactate in blood plasma, an increase in lactic acid in the muscles, and oxidative damage to DNA.[5]

Physiological effects of exercise[edit | edit source]

Exercise causes a variety of temporary physiological changes in healthy people. This includes an increase in respiratory rate, heart rate, and blood pressure in order to keep up with higher energy demands.[6] The chemical reactions that break down nutrients -- glycolysis, the citric acid cycle, and the electron transport chain -- move more rapidly to liberate energy, and blood flow to muscles should increase. In healthy individuals, the amount of oxygen and carbon dioxide present in the blood should not alter significantly.[6]

Immune system[edit | edit source]

In healthy people, exercise induces a variety of temporary changes to immune markers. Immediately after exercise, natural killer cell activity is decreased and Leukotriene B4 (LTB4) increase, along with the LTB4/PGE2 ratio. Exercise elevates levels of prostaglandin E2 (PGE2) for up to five days.[7]

Infection[edit | edit source]

Several studies of a mouse model of Coxsackie B3 myocarditis have found that exercise increases the virulence of the infection and results in poorer outcomes.[8][9][10][11][12] 

Neurotransmitters[edit | edit source]

Acetylcholine, an important neurotransmitter that regulates immune response and muscle strength, decreases during exercise.

Effects of exercise in Chronic Fatigue Syndrome[edit | edit source]

Post Exertional Malaise[edit | edit source]

Post-exertional worsening of symptoms, VanNess et al. (2010)
PEM chart from the 2015 Institute of Medicine report

ME patients who exercise are likely to experience Post-exertional malaise, a worsening of symptoms following physical, cognitive, or sensory exertion.

Read the main page: Post-exertional malaise.

Pain threshold[edit | edit source]

Pain thresholds, or the point at which a stimulus becomes painful, drop in people with CFS (as per the Fukuda criteria) after graded exercise. In healthy controls, pain thresholds rise. This phenomenon has been attributed to a dysfunction of the central anti-nociceptive mechanism in CFS patients.[13]

Immune System[edit | edit source]

Histamine, a chemical that is released in response to cellular damage and inflammation, is released during exercise in healthy individuals. The histamine dilates blood vessels in order to deliver nutrients to working muscles.[14] However, patients with ME may experience increased histamine release due to increased mast cell populations at baseline.[15]

Microbiome[edit | edit source]

A small study of ten CFS patients found significant changes in the composition of the microbiome and increased bacterial translocation (movement from the intestine into the bloodstream) following exercise. The study found increased Clostridium in the blood fifteen minutes after exercise and increased Bacilli 48 hours later.[16]

Musculature[edit | edit source]

Exercise has also been found to induce both early and excessive lactic acid formation in the muscles[17] with reduced intracellular concentrations of ATP and acceleration of glycolysis.[18] Several studies have found abnormal increases in plasma lactate following short period of moderate exercise that cannot be explained by deconditioning.[19] There is evidence of abnormalities in pH handling by peripheral muscle, and possible evidence of an increased acidosis and lactate accumulation.[20][21]

There is also evidence of loss of capacity to recover from acidosis on repeat exercise.[22]

Finally, there is evidence of abnormalities of AMPK activation and glucose uptake in cultured skeletal muscle cells in ME/CFS patients.[23][24]

Gene expression changes following moderate exercise (Light et al, 2011)

Gene expression[edit | edit source]

There is evidence of increased expression of certain genes following muscular exertion.[25][26][27] A 2011 study found that moderate exercise in CFS increased the expression of 13 genes (sensory, adrenergic and 1 cytokine) for 48 hours, and the increases correlated with fatigue and pain levels (see graph at right).[26]

Second day exercise test[edit | edit source]

The seminal study on the response by CFS patients to a 2-day cardiopulmonary exercise test was published by Mark VanNess, Christopher Snell and Staci Stevens in 2007: "Diminished Cardiopulmonary Capacity During Post-Exertional Malaise".[28] While people with CFS responded similarly to healthy controls on a first test, on a follow-up 24 hours later, they were unable to replicate their original normal results. Instead, they had significantly lower values for VO2 peak and AT; these differences could be used to identify the CFS patient over 90% of the time. A repeat study in 2013 confirmed these results.[29]

In a confirmation study, Doctor Betsy Keller also found that patients could not repeat their performance on a second cardiopulmonary exercise test performed a day after the first.[30]

A review by Nijs et al. found that multiple studies showed reduced peak heart rate, reduced endurance, reduced peak work rate, reduced peak oxygen uptake, lower blood lactate values, and an increased respiratory exchange ratio in people with ME, ME/CFS, or CFS; see 'Oxidative impairment' below.[31]

It is important to note that CPET testing oxygen uptake (VO2), carbon dioxide output (VCO2), tidal volume (VT), blood pressure, and oxygen saturation are objective measures, and cannot be invalidated with inadequate effort.

Oxidative impairment[edit | edit source]

DeBecker et al (2000) and VanNess et al (2003) found low VO2 during exercise testing;[32][33] Fulle et al. (2000) demonstrated oxidative damage to DNA[5]; and Wong et al. (1992) showed defects in oxidative metabolism and poor recovery of ATP after exercise.[34]

Graded exercise[edit | edit source]

Graded exercise therapy, or the incremental increase in physical activity over time, is a controversial treatment for ME/CFS, due to exercise intolerance being a central feature of the disease. See the main page for more.

Excessive exercise[edit | edit source]

Excessive exercise in healthy people, particularly athletes, is known to cause overtraining syndrome, which is often recognized by decreased exercise capacity. Overtraining syndrome has different signs and symptoms, effects of overtraining should not be confused with ME/CFS, which is a multi-systemic neurological illness with a different symptom profile and no known cure.[citation needed]

Talks and interviews[edit | edit source]

Notable studies[edit | edit source]

Learn more[edit | edit source]

See also[edit | edit source]

References[edit | edit source]

  1. Pederson, B.K.; Saltin, B. (2006). "Evidence for prescribing exercise as therapy in chronic disease" (PDF). Scand J Med Sci Sports. 16(Suppl 1): 3–63. 
  2. Hovanec, Nina; Bellemore, Derek; Kuhnow, Jason; Miller, Felicia; van Vloten, Alexi; Vandervoort, Anthony A. (Mar 3, 2015). "Exercise Prescription Considerations for Individuals with Multiple Chronic Diseases: Systematic Review". J Gerontol Geriatr Res. 4:201. <nowiki>
  3. 3.03.1 Cook, Dane B.; Light, Alan R.; Light, Kathleen C.; Broderick, Gordon; Shields, Morgan R.; Dougherty, Ryan J.; Meyer, Jacob D.; VanRiper, Stephanie; Stegner, Aaron J. (May 1, 2017). "Neural consequences of post-exertion malaise in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome". Brain, Behavior, and Immunity. 62: 87–99. doi:10.1016/j.bbi.2017.02.009. ISSN 0889-1591. 
  4. ME Association (May 2015). "ME Association illness management report: no decisions about me without me" (PDF). ME Association. Retrieved Apr 25, 2018. 
  5. 5.05.1 Fulle, S; Mecocci, P; Fanó, G; et al. (Dec 15, 2000), "Specific oxidative alterations in vastus lateralis muscle of patients with the diagnosis of chronic fatigue syndrome", Free Radical Biology & Medicine, 29 (12): 1252–1259, doi:10.1016/S0891-5849(00)00419-6, ISSN 0891-5849, PMID 11118815 
  6. 6.06.1 Burton, Deborah Anne; Stokes, Keith; Hall, George M (Dec 1, 2004). "Physiological effects of exercise". Continuing Education in Anaesthesia Critical Care & Pain. 4 (6): 185–8 – via BJA Education. 
  7. Gray, J B; Martinovic, A M (Jul 1994), "Eicosanoids and essential fatty acid modulation in chronic disease and the chronic fatigue syndrome", Medical Hypotheses, 43 (1): 31–42, doi:10.1016/0306-9877(94)90046-9, PMID 7968718 
  8. Cabinian AE, Kiel RJ, Smith F, Ho KL, Khatib R, Reyes MR. Modification of exercise-aggravated coxsackie virus B3 murine myocarditis by T-lymphocyte suppression in an inbred model. J. Lab. Clin. Med. 1990; 115: 454– 62.
  9. Kiel RJ, Smith FE, Chason J, Khatib R, Reyes MD. Coxsackie B3 myocarditis in C3H/HeJ mice: Description of an inbred model and the effect of exercise on the virulence. Eur. J. Epidemiol. 1989; 5: 248– 67.
  10. Ilbäck, NG (June 1989). "Exercise in coxsackie B3 myocarditis: Effects on heart lymphocyte subpopulations and the inflammatory reaction". American Heart Journal. 117: 1298–302. 
  11. Gatmaitan, Bienvenido (Jun 1, 1970). "Augmentation of the Virulence of Murine Coxsackie Virus B-3 Myocardiopathy by Exercise". Journal of Experimental Medicine. 131: 1121. 
  12. Reyes, MP (February 1976). "Interferon and neutralizing antibody in sera of exercised mice with coxsackievirus B-3 myocarditis". Proceedings of the Society for Experimental Biology and Medicine. 151: 333–8. 
  13. Whiteside, Alan; Hansen, Stig; Chaudhuri, Abhijit (2004), "Exercise lowers pain threshold in chronic fatigue syndrome", Pain, 109 (3): 497-9, doi:10.1016/j.pain.2004.02.029, PMID 15157711 
  14. Romero, S.A.; Hocker, A.D.; Magnum, J.E.; Luttrell, M.J.; Turnbull, D.W. ...; Halliwill, J.R. (2016). "Evidence of a broad histamine footprint on the human exercise transcriptome". The Journal of Physiology. 594 (17): 5009–5023. 
  15. Rönnberg, E; Calounova, G; Pejler, G (June 2017). "Novel characterisation of mast cell phenotypes from peripheral blood mononuclear cells in chronic fatigue syndrome/myalgic encephalomyelitis patients". Asian Pac J Allergy Immunol. 35 (2): 75–81. 
  16. Shukla, Sanjay K; Cook, Dane; Meyer, Jacob; et al. (Dec 18, 2015), "Changes in Gut and Plasma Microbiome following Exercise Challenge in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)", PLoS ONE, doi:10.1371/journal.pone.0145453, PMID 26683192 
  17. Plioplys, AV; Plioplys, S (1995), "Serum levels of carnitine in chronic fatigue syndrome: clinical correlates", Neuropsychobiology, 32 (3): 132-8, PMID 8544970 
  18. McCully, KK; Natelson, BH; Iotti, S; Sisto, S; Leigh, JS Jr. (May 1996h), "Reduced oxidative muscle metabolism in chronic fatigue syndrome", Muscle Nerve, 19 (5): 621-5, PMID 8618560 
  19. Lane, R J; Barrett, M C; Taylor, D J; Kemp, G J; Lodi, R (May 1998), "Heterogeneity in chronic fatigue syndrome: evidence from magnetic resonance spectroscopy of muscle", Neuromuscul Disord, 1998 May;8 (3-4): 204-9, PMID 9631403 
  20. Jones, David EJ; Hollingsworth, Kieren G; Taylor, Renee R; Blamire, Andrew M; Newton, Julia L (Apr 2010), "Abnormalities in pH handling by peripheral muscle and potential regulation by the autonomic nervous system in chronic fatigue syndrome", J Intern Med, 267 (4): 394-401, doi:10.1111/j.1365-2796.2009.02160.x, PMID 20433583 
  21. Lengert, Nicor; Drossel, Barbara (Jul 2015), "In silico analysis of exercise intolerance in myalgic encephalomyelitis/chronic fatigue syndrome", Biophysical Chemistry, 202: 21–31, doi:10.1016/j.bpc.2015.03.009, PMID 25899994 
  22. Jones, David EJ; Hollingsworth, Kieren G; Jakovljevic, Djordje G; et al. (Jul 12, 2011), "Loss of capacity to recover from acidosis on repeat exercise in chronic fatigue syndrome", Eur J Clin Invest, 2012 Feb;42 (2): 186-94, doi:10.1111/j.1365-2362.2011.02567.x, PMID 21749371 
  23. Brown, Audrey E; Jones, David E; Walker, Mark; Newton, Julia L (Apr 2, 2015), "Abnormalities of AMPK activation and glucose uptake in cultured skeletal muscle cells", PLoS One, 10 (4), doi:10.1371/journal.pone.0122982, PMID 25836975 
  24. Dobberstein, Linda J. (Apr 20, 2015), "Master Enzyme Switch Deactivated In Chronic Fatigue Syndrome and Fibromyalgia", Wellness Resources 
  25. Light, Alan R; White, Andrea T; Hughen, Ronald W; Light, Kathleen C (Jul 31, 2009), "Moderate exercise increases expression for sensory, adrenergic, and immune genes in chronic fatigue syndrome patients but not in normal subjects", J Pain, 2009 Oct;10 (10): 1099-112, doi:10.1016/j.jpain.2009.06.003, PMID 19647494 
  26. 26.026.1 Light, Alan R; Bateman, Lucinda; Jo, D; et al. (Jul 13, 2011), "Gene expression alterations at baseline and following moderate exercise in patients with Chronic Fatigue Syndrome and Fibromyalgia Syndrome", J Intern Med, 2012 271 (1): 64-81, doi:10.1111/j.1365-2796.2011.02405.x, PMID 21615807 
  27. White, Andrea T; Light, Alan R; Hughen, Ronald W; VanHaitsma, Timothy A; Light, Kathleen C (Dec 30, 2011), "Differences in metabolite-detecting, adrenergic, and immune gene expression after moderate exercise in patients with chronic fatigue syndrome, patients with multiple sclerosis, and healthy controls", Psychosom Med, 2012 Jan;74 (1): 46-54, doi:10.1097/PSY.0b013e31824152ed, PMID 22210239 
  28. VanNess, J Mark; Snell, Christopher R; Stevens, Staci R (2007), "Diminished Cardiopulmonary Capacity During Post-Exertional Malaise", Journal of Chronic Fatigue Syndrome, 14 (2): 77-85, doi:10.1300/J092v14n02_07 
  29. Snell, Christopher R; Stevens, Staci R; Davenport, Todd E; VanNess, J Mark (Oct 31, 2013), "Discriminative Validity of Metabolic and Workload Measurements for Identifying People With Chronic Fatigue Syndrome", Physical Therapy (APTA), 93 (11): 1484-1492, doi:10.2522/ptj.20110368, PMID 23813081 
  30. Keller, Betsy A; Pryor, John Luke; Giloteaux, Ludovic (Apr 23, 2014), "Inability of myalgic encephalomyelitis/chronic fatigue syndrome patients to reproduce VO₂peak indicates functional impairment", J Transl Med, 2014 Apr 23 (12): 104, doi:10.1186/1479-5876-12-104, PMID 24755065 
  31. Nijs, J; Nees, A; Paul, L; De Kooning, M; Ickmans, K; Meeus, M; Van Oosterwijck, J (2014), "Altered immune response to exercise in patients with chronic fatigue syndrome/myalgic encephalomyelitis: a systematic literature review", Exercise Immunology Review, 2014 (20): 94-116., PMID 24974723 
  32. De Becker, P; Roeykens, J; Reynders, M; et al. (Nov 27, 2000), "Exercise capacity in chronic fatigue syndrome", Archives of Internal Medicine, 160 (21): 3270–3277, doi:10.1001/archinte.160.21.3270, ISSN 0003-9926, PMID 11088089 
  33. VanNess, JM; Snell, CR; Strayer, DR; Dempsey, L; Stevens, SR (June 2003), "Subclassifying chronic fatigue syndrome through exercise testing" (PDF), Medicine and Science in Sports and Exercise, 35 (6): 908–913, doi:10.1249/01.MSS.0000069510.58763.E8, ISSN 0195-9131, PMID 12783037 
  34. Wong, R; Lopaschuk, G; Zhu, G; et al. (Dec 1992), "Skeletal muscle metabolism in the chronic fatigue syndrome. In vivo assessment by 31P nuclear magnetic resonance spectroscopy", Chest, 102 (6): 1716–1722, doi:10.1378/chest.102.6.1716, ISSN 0012-3692, PMID 1446478 
  35. VanNess, J Mark (Feb 5, 2014), Video: A Realistic Approach to Exercise and Rehabilitation in ME/CFS, Bristol Watershed 
  36. Bateman, Lucinda (Nov 3, 2015), "Video interview: Gene-expression and exercise", Wetenschap voor Patienten - ME/cvs Vereniging 
  37. Nijs, Jo; Aelbrecht, Senne; Meeus, Mira; Van Oosterwijck, Jessica; Zinzen, Evert; Clarys, Peter (2011). "Tired of being inactive: a systematic literature review of physical activity, physiological exercise capacity and muscle strength in patients with chronic fatigue syndrome" (PDF). Disability and Rehabilitation. 33 (17-18): 1493–1500. doi:10.3109/09638288.2010.541543. ISSN 1464-5165. PMID 21166613. 
  38. Deseret News (May 16, 2014), Sufferers of chronic fatigue, fibromyalgia have hope in new diagnostic tool 
  39. Burch, Sally; VanNess, J Mark (Jan 17, 2015), Dr VanNess on recent press reports 
  40. Twisk, Frank NM; Geraghty, Keith J (Jul 11, 2015), "Deviant Cellular and Physiological Responses to Exercise in Myalgic Encephalomyelitis and Chronic Fatigue Syndrome" (PDF), Jacobs Journal of Physiology, 2015, 1(2): 007 
  41. Rutherford, Gina; Manning, Philip; Newton, Julia L (Jan 13, 2016), "Review Article: Understanding Muscle Dysfunction in Chronic Fatigue Syndrome", Journal of Aging Research, 2016 (2016) (Article ID 2497348, 13 pages), doi:10.1155/2016/2497348, PMID 26998359 
  42. Blake, Nancy (Feb 10, 2016), "Lost in Translation - The ME-Polio Connection and the Dangers of Exercise", ProHealth website 

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From MEpedia, a crowd-sourced encyclopedia of ME and CFS science and history.