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'''Exercise''' is any movement or '''physical activity''' considered to contribute to general health and well-being. Exercise may be recommended as part of a wellness regimen in ''any'' chronic illness.<ref name="Pederson2006">{{Cite journal|last=Pederson|first=B.K.|last2=Saltin|first2=B.|date=2006|title=Evidence for prescribing exercise as therapy in chronic disease
'''Exercise''' is any movement or '''physical activity''' considered to contribute to general health and well-being. Exercise may be recommended as part of a wellness regimen in ''any'' chronic illness.<ref name="Pederson2006">{{Cite journal | last = Pederson | first = B.K. | last2 = Saltin | first2 = B. | date = 2006 | title=Evidence for prescribing exercise as therapy in chronic disease | url=https://www.essa.org.au/wp-content/uploads/2015/06/Chronic-disease_Review-2006.pdf | journal=Scand J Med Sci Sports|volume=16|issue =Suppl 1 | pages = 3-63|via=}}</ref><ref name="Hovanec2015">{{Cite journal | last = Hovanec | first = Nina | last2 = Bellemore | first2 = Derek | last3 = Kuhnow | first3 = Jason | last4 = Miller | first4 = Felicia | last5 = van Vloten | first5 = Alexi | last6 = Vandervoort | first6 = Anthony A. | date = March 3, 2015 | title = Exercise Prescription Considerations for Individuals with Multiple Chronic Diseases: Systematic Review | url =https://www.omicsonline.org/open-access/exercise-prescription-considerations-for-individuals-with-multiple-chronic-diseases-systematic-review-2167-7182-1000201.php?aid=41826|journal=J Gerontol Geriatr Res|volume = 4 | issue = 201 | pages =|via=}}</ref> However, [[Post-exertional malaise|exercise intolerance]] is a central feature of [[ME/CFS]],<ref name=":0">{{Cite web | url = https://www.cdc.gov/me-cfs/symptoms-diagnosis/symptoms.html | title = Symptoms of ME/CFS {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) | last = | first = | authorlink = | date = 2021-02-09 | website = cdc.gov|language=en-us|archive-url=|archive-date=|url-status=|access-date=2021-12-23}}</ref> 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.<ref name="PEM2017" /> Rather than increase health and well-being, evidence from ME/CFS patients shows that exercise or even increased activity significantly reduces their physical ''and'' [[Cognitive dysfunction|mental capacity]] over time, sometimes permanently.<ref name="nodecisions">{{Cite web | url = http://www.meassociation.org.uk/wp-content/uploads/2015-ME-Association-Illness-Management-Report-No-decisions-about-me-without-me-30.05.15.pdf | title=ME Association illness management report: no decisions about me without me | last = ME Association | first = | date = May 2015 | website = ME Association|archive-url=|archive-date=|url-status=|access-date=25 April 2018}}</ref>  
|url=https://www.essa.org.au/wp-content/uploads/2015/06/Chronic-disease_Review-2006.pdf|journal=Scand J Med Sci Sports|volume=16|issue =Suppl 1|pages=3-63|via=}}</ref><ref name="Hovanec2015">{{Cite journal|last=Hovanec|first=Nina|last2=Bellemore|first2=Derek|last3=Kuhnow|first3=Jason|last4=Miller|first4=Felicia|last5=van Vloten|first5=Alexi|last6=Vandervoort|first6=Anthony A.|date=March 3, 2015|title=Exercise Prescription Considerations for Individuals with Multiple Chronic Diseases: Systematic Review|url=https://www.omicsonline.org/open-access/exercise-prescription-considerations-for-individuals-with-multiple-chronic-diseases-systematic-review-2167-7182-1000201.php?aid=41826|journal=J Gerontol Geriatr Res|volume = 4 | issue = 201 | pages =|via=}}</ref> However, [[Post-exertional malaise|exercise intolerance]] is a central feature of [[ME/CFS]],<ref name=":0">{{Cite web|url=https://www.cdc.gov/me-cfs/symptoms-diagnosis/symptoms.html|title=Symptoms of ME/CFS {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)|last=|first=|authorlink=|date=2021-02-09|website=www.cdc.gov|language=en-us|archive-url=|archive-date=|url-status=|access-date=2021-12-23}}</ref> 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.<ref name="PEM2017" /> Rather than increase health and well-being, evidence from ME/CFS patients shows that exercise or even increased activity significantly reduces their physical ''and'' [[Cognitive dysfunction|mental capacity]] over time, sometimes permanently.<ref name="nodecisions">{{Cite web|url=http://www.meassociation.org.uk/wp-content/uploads/2015-ME-Association-Illness-Management-Report-No-decisions-about-me-without-me-30.05.15.pdf|title=ME Association illness management report: no decisions about me without me|last=ME Association|first=|date=May 2015|website=ME Association|archive-url=|archive-date=|url-status=|access-date=25 April 2018}}</ref>  


Worsening of symptoms due to exercise in ME/CFS patients cannot be explained by [[deconditioning]] (lack of fitness), or by [[Cognitive behavioral model|psychological theories]] like [[illness beliefs|"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.<ref name="Fulle2000">{{citation | last1   = Fulle           | first1 = S | authorlink1 = Stefania Fulle | last2 =Mecocci         | first2 = P | authorlink2 = Patrizia Mecocci | last3= Fanó             | first3 = G | authorlink3 = Giorgio Fanó | last4 =Vecchiet         | first4 = I | authorlink4 = Iacopo Vecchiet
Worsening of symptoms due to exercise in ME/CFS patients cannot be explained by [[deconditioning]] (lack of fitness), or by [[Cognitive behavioral model|psychological theories]] like [[illness beliefs|"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.<ref name="Fulle2000">{{citation | last1 = Fulle | first1 = S | author-link1 = Stefania Fulle | last2 =Mecocci | first2 = P | authorlink2 = Patrizia Mecocci | last3 = Fanó | first3 = G | authorlink3 = Giorgio Fanó | last4 =Vecchiet | first4 = I | authorlink4 = Iacopo Vecchiet | last5 = Vecchini | first5 = A | authorlink5 = Alba Vecchini | last6 = Racciotti | first6 = D | authorlink6 = Delia Racciotti | last7 = Cherubini | first7 = A | author-link8 = Antonio Cherubini | last8 = Pizzigallo | first8 = E | author-link8 = Eligio Pizzigallo | last9 = Vecchiet | first9 = L | author-link9 = Leonardo Vecchiet | last10 = Senin | first10 = U | author-link10 = Umberto Senin | last11 = Beal | first11 = MF | author-link11 = M Flint Beal | title = Specific oxidative alterations in vastus lateralis muscle of patients with the diagnosis of chronic fatigue syndrome | journal = Free Radical Biology & Medicine | issn = 0891-5849| volume = 29 | issue = 12| pages = 1252–1259 | date = 2000-12-15 | pmid = 11118815 | doi = 10.1016/S0891-5849(00)00419-6 | url = https://www.researchgate.net/profile/Stefania_Fulle/publication/223664992_Specific_oxidative_alterations_in_vastus_lateralis_muscle_of_patients_with_the_diagnosis_of_chronic_fatigue_syndrome/links/54db93eb0cf23fe133ad601d.pdf/download?version=vrp }}</ref>
| last5   = Vecchini         | first5 = A | authorlink5 = Alba Vecchini | last6 = Racciotti       | first6 = D | authorlink6 = Delia Racciotti | last7 =Cherubini       | first7 = A | authorlink7 = Antonio Cherubini | last8 = Pizzigallo       | first8 = E | authorlink8 = Eligio Pizzigallo | last9 =Vecchiet         | first9 = L | authorlink9 = Leonardo Vecchiet | last10 = Senin           | first10 = U | authorlink10= Umberto Senin | last11 = Beal             | first11 = MF               | authorlink11= M Flint Beal
| display-authors =
| title   = Specific oxidative alterations in vastus lateralis muscle of patients with the diagnosis of chronic fatigue syndrome
| journal = Free Radical Biology & Medicine | issn = 0891-5849| volume = 29| issue = 12| pages = 1252–1259
| date   = 2000-12-15
| pmid   = 11118815 | doi = 10.1016/S0891-5849(00)00419-6
| url     = https://www.researchgate.net/profile/Stefania_Fulle/publication/223664992_Specific_oxidative_alterations_in_vastus_lateralis_muscle_of_patients_with_the_diagnosis_of_chronic_fatigue_syndrome/links/54db93eb0cf23fe133ad601d.pdf/download?version=vrp
}}</ref>


==Physiological effects of exercise==
==Physiological effects of exercise==


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.<ref name="Burton2004">{{Cite journal|last=Burton|first=Deborah Anne|last2=Stokes|first2=Keith|last3=Hall|first3=George M|date=December 1, 2004|title=Physiological effects of exercise|url=https://academic.oup.com/bjaed/article/4/6/185/314696|journal=Continuing Education in Anaesthesia Critical Care & Pain|publisher=|volume=4|issue=6|pages=185-8|via=BJA Education}}</ref> The chemical reactions that break down nutrients -- [[glycolysis]], the [[citric acid cycle]], and the [[ion transportation|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.<ref name="Burton2004" />
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.<ref name="Burton2004">{{Cite journal | last = Burton | first = Deborah Anne | last2 = Stokes | first2 = Keith | last3 = Hall | first3 = George M | date = December 1, 2004 | title = Physiological effects of exercise | url =https://academic.oup.com/bjaed/article/4/6/185/314696|journal=Continuing Education in Anaesthesia Critical Care & Pain| publisher = |volume=4|issue=6 | pages = 185-8|via=BJA Education}}</ref> The chemical reactions that break down nutrients -- [[glycolysis]], the [[citric acid cycle]], and the [[ion transportation|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.<ref name="Burton2004" />


===Immune system===
===Immune system===


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.<ref name="GrayJB1994">{{citation | last1   = Gray | first1 = J B             | authorlink1 = J B Gray | last2 =Martinovic | first2 = A M               | authorlink2 = Andriya Martinovic
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.<ref name="GrayJB1994">{{citation | last1 = Gray | first1 = J B | author-link1 = J B Gray | last2 =Martinovic | first2 = A M | authorlink2 = Andriya Martinovic | title = Eicosanoids and essential fatty acid modulation in chronic disease and the chronic fatigue syndrome| journal = Medical Hypotheses | volume = 43 | issue = 1 | page = 31–42 | date = Jul 1994 | pmid = 7968718 | doi = 10.1016/0306-9877(94)90046-9 | url = http://www.sciencedirect.com/science/article/pii/0306987794900469 }}</ref>
| title   = Eicosanoids and essential fatty acid modulation in chronic disease and the chronic fatigue syndrome| journal = Medical Hypotheses | volume = 43 | issue = 1 | page = 31–42| date   = Jul 1994
| pmid   = 7968718 | doi = 10.1016/0306-9877(94)90046-9
| url     = http://www.sciencedirect.com/science/article/pii/0306987794900469 }}</ref>


=== Infection ===
=== Infection ===
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.<ref name="Cabinian1990">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.</ref><ref name="Kiel1989">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.</ref><ref name="Itback">{{Cite journal|last=Ilbäck|first=NG|date=June 1989|title=Exercise in coxsackie B3 myocarditis: Effects on heart lymphocyte subpopulations and the inflammatory reaction|url=https://www.ncbi.nlm.nih.gov/pubmed/2543197|journal=American Heart Journal|volume=117|pages=1298-302|via=}}</ref><ref name="Gatmaitan1970">{{Cite journal|last=Gatmaitan|first=Bienvenido|date=June 1, 1970|title=Augmentation of the Virulence of Murine Coxsackie Virus B-3 Myocardiopathy by Exercise|url=http://jem.rupress.org/content/131/6/1121|journal=Journal of Experimental Medicine|volume=131|pages=1121|via=}}</ref><ref name="Reyes2976">{{Cite journal|last=Reyes|first=MP|date=February 1976|title=Interferon and neutralizing antibody in sera of exercised mice with coxsackievirus B-3 myocarditis|url=https://www.ncbi.nlm.nih.gov/pubmed/1250870|journal=Proceedings of the Society for Experimental Biology and Medicine|volume=151|pages=333-8|via=}}</ref> 
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.<ref name="Cabinian1990">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.</ref><ref name="Kiel1989">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.</ref><ref name="Itback">{{Cite journal | last = Ilbäck | first = NG | date = June 1989 | title = Exercise in coxsackie B3 myocarditis: Effects on heart lymphocyte subpopulations and the inflammatory reaction | url =https://www.ncbi.nlm.nih.gov/pubmed/2543197|journal=American Heart Journal|volume=117 | pages = 1298-302|via=}}</ref><ref name="Gatmaitan1970">{{Cite journal | last = Gatmaitan | first = Bienvenido | date = June 1, 1970 | title = Augmentation of the Virulence of Murine Coxsackie Virus B-3 Myocardiopathy by Exercise | url =http://jem.rupress.org/content/131/6/1121|journal=Journal of Experimental Medicine|volume=131 | pages = 1121|via=}}</ref><ref name="Reyes2976">{{Cite journal | last = Reyes | first = MP | date = February 1976 | title = Interferon and neutralizing antibody in sera of exercised mice with coxsackievirus B-3 myocarditis |url =https://www.ncbi.nlm.nih.gov/pubmed/1250870|journal=Proceedings of the Society for Experimental Biology and Medicine|volume=151 | pages = 333-8|via=}}</ref> 


===Neurotransmitters===
===Neurotransmitters===
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[[File:2010 VanNess Post exertional worsening of symptoms chart.png|right|frame|Post-exertional worsening of symptoms, VanNess et al. (2010)|377x377px]]
[[File:2010 VanNess Post exertional worsening of symptoms chart.png|right|frame|Post-exertional worsening of symptoms, VanNess et al. (2010)|377x377px]]
{{Main article|page_name=Post-exertional malaise}}[[File:2015 IOM report PEM chart.png|right|frame|PEM chart from the 2015 Institute of Medicine report|378x378px]]
{{Main article| page_name=Post-exertional malaise}}[[File:2015 IOM report PEM chart.png|right|frame|PEM chart from the 2015 Institute of Medicine report|378x378px]]


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


===Pain threshold===
===Pain threshold===
Pain thresholds, or the point at which a stimulus becomes painful, drop in people with [[chronic fatigue syndrome|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 [[chronic fatigue syndrome|CFS]] patients.<ref name="Whiteside, 2004">{{Citation | last1   = Whiteside   | first1 = Alan       | authorlink1 = | last2 =Hansen       | first2 = Stig       | authorlink2 = | last3= Chaudhuri   | first3 = Abhijit   | authorlink3 = Abhijit Chaudhuri| title   = Exercise lowers pain threshold in chronic fatigue syndrome| journal = Pain   | volume = 109   | issue = 3   | page = 497-9| date   = 2004| pmid   = 15157711| doi     = 10.1016/j.pain.2004.02.029}}</ref>
Pain thresholds, or the point at which a stimulus becomes painful, drop in people with [[chronic fatigue syndrome|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 [[chronic fatigue syndrome|CFS]] patients.<ref name="Whiteside, 2004">{{Citation | last1 = Whiteside | first1 = Alan | author-link1 = | last2 =Hansen | first2 = Stig | authorlink2 = | last3 = Chaudhuri | first3 = Abhijit | authorlink3 = Abhijit Chaudhuri | title = Exercise lowers pain threshold in chronic fatigue syndrome| journal = Pain | volume = 109 | issue = 3 | page = 497-9| date = 2004 | pmid = 15157711| doi = 10.1016/j.pain.2004.02.029}}</ref>


===Immune System===
===Immune System===
[[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.<ref name="Romero2016">{{Cite journal|last=Romero|first=S.A.|last2=Hocker|first2=A.D.|last3=Mangum|first3=J.E.|last4=Luttrell|first4=M.J.|last5=Turnbull|first5=D.W.|last6=Halliwill|first6=J.R.|last7= Struck|first7= A.J.|last8= Ely|first8=M.R.|last9=Sieck|first9= D.C.|last10 =Dreyer|first10= H.C.|last11=Halliwill|first11=J.R|date=2016|title=Evidence of a broad histamine footprint on the human exercise transcriptome|url=http://doi.org/10.1113/JP272177|journal=The Journal of Physiology|volume=594|issue=17|pages=5009-5023|via=}}</ref>  However, patients with ME may experience increased histamine release due to increased mast cell populations at baseline.<ref name="Ronnberg2017">{{Cite journal|last=Rönnberg|first=E|last2=Calounova|first2=G|last3=Pejler|first3=G|date=June 2017|title=Novel characterisation of mast cell phenotypes from peripheral blood mononuclear cells in chronic fatigue syndrome/myalgic encephalomyelitis patients|url=https://www.ncbi.nlm.nih.gov/pubmed/27362406|journal=Asian Pac J Allergy Immunol|volume=35|issue=2|pages=75-81|via=}}</ref>
[[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.<ref name="Romero2016">{{Cite journal | last = Romero | first = S.A. | last2 = Hocker | first2 = A.D. | last3 = Mangum | first3 = J.E. | last4 = Luttrell | first4 = M.J. | last5 = Turnbull | first5 =D.W. | last6 = Halliwill | first6 = J.R. | last7 = Struck | first7 = A.J. | last8 = Ely | first8 = M.R. | last9 = Sieck | first9 = D.C. | last10 =Dreyer | first10 = H.C. | last11 = Halliwill | first11 = J.R | date = 2016 | title=Evidence of a broad histamine footprint on the human exercise transcriptome | url =http://doi.org/10.1113/JP272177|journal=The Journal of Physiology|volume=594|issue=17 | pages = 5009-5023|via=}}</ref>  However, patients with ME may experience increased histamine release due to increased mast cell populations at baseline.<ref name="Ronnberg2017">{{Cite journal | last = Rönnberg | first = E | last2 = Calounova | first2 = G | last3 = Pejler | first3 = G | date = June 2017 | title = Novel characterisation of mast cell phenotypes from peripheral blood mononuclear cells in chronic fatigue syndrome/myalgic encephalomyelitis patients |url =https://www.ncbi.nlm.nih.gov/pubmed/27362406|journal=Asian Pac J Allergy Immunol|volume=35|issue=2 | pages = 75-81|via=}}</ref>


===Microbiome===
===Microbiome===


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 [[blood|bloodstream]]) following exercise. The study found increased Clostridium in the blood fifteen minutes after exercise and increased Bacilli 48 hours later.<ref name="ShuklaS2015">{{citation | last1   = Shukla           | first1 = Sanjay K           | authorlink1 = Sanjay Shukla | last2 =Cook             | first2 = Dane               | authorlink2 = Dane Cook | last3= Meyer           | first3 = Jacob             | authorlink3 = Jacob Meyer | last4 =Vernon           | first4 = Suzanne D         | authorlink4 = Suzanne Vernon
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 [[blood|bloodstream]]) following exercise. The study found increased Clostridium in the blood fifteen minutes after exercise and increased Bacilli 48 hours later.<ref name="ShuklaS2015">{{citation | last1 = Shukla | first1 = Sanjay K | author-link1 = Sanjay Shukla | last2 =Cook | first2 = Dane | authorlink2 = Dane Cook | last3 = Meyer | first3 = Jacob | authorlink3 = Jacob Meyer | last4 =Vernon | first4 = Suzanne D | authorlink4 = Suzanne Vernon | last5 = Le | first5 = Thao | authorlink5 = Thao Le | last6 = Clevidence | first6 = Derek | authorlink6 = Derek Clevidence | last7 =Robertson | first7 = Charles E | author-link8 = Charles Robertson | last8 = Schrodi | first8 = Steven J | author-link8 = Steven Schrodi | last9 =Yale | first9 = Steven | author-link9 = Steven Yale | last10 = Frank | first10 = Daniel N | author-link10 = Daniel Frank | title = Changes in Gut and Plasma Microbiome following Exercise Challenge in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)| journal = PLoS ONE | date = Dec 18, 2015 | pmid = 26683192 | doi = 10.1371/journal.pone.0145453 | url = http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0145453 }}</ref>
| last5   = Le               | first5 = Thao               | authorlink5 = Thao Le | last6 = Clevidence       | first6 = Derek             | authorlink6 = Derek Clevidence | last7 =Robertson       | first7 = Charles E         | authorlink7 = Charles Robertson | last8 = Schrodi         | first8 = Steven J           | authorlink8 = Steven Schrodi | last9 =Yale             | first9 = Steven             | authorlink9 = Steven Yale | last10 = Frank           | first10= Daniel N           | authorlink10= Daniel Frank
| title   = Changes in Gut and Plasma Microbiome following Exercise Challenge in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)| journal = PLoS ONE | date = Dec 18, 2015| pmid   = 26683192 | doi = 10.1371/journal.pone.0145453
| url     = http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0145453 }}</ref>


=== Musculature ===
=== Musculature ===
Exercise has also been found to induce both early and excessive lactic acid formation in the [[muscle fatigability|muscles]]<ref name="Plioplys1995">{{citation | last1   = Plioplys       | first1 = AV           | authorlink1 = | last2 =Plioplys       | first2 = S           | authorlink2 =  
Exercise has also been found to induce both early and excessive lactic acid formation in the [[muscle fatigability|muscles]]<ref name="Plioplys1995">{{citation | last1 = Plioplys | first1 = AV | author-link1 = | last2 =Plioplys | first2 = S | authorlink2 = | title = Serum levels of carnitine in chronic fatigue syndrome: clinical correlates| journal = Neuropsychobiology | date = 1995 | volume = 32 | issue = 3 | page = 132-138 | pmid = 8544970| url = http://www.ncbi.nlm.nih.gov/pubmed/8544970 }}</ref> with reduced intracellular concentrations of [[ATP]] and acceleration of [[glycolysis]].<ref name="McCully1996">{{citation | last1 = McCully | first1 = KK | author-link1 = | last2 =Natelson | first2 = BH | authorlink2 = Benjamin Natelson | last3 = Iotti | first3 = S | authorlink3 = | last4 = Sisto | first4 = S | authorlink4 = | last5 = Leigh | first5 = JS Jr. | authorlink5 = | title = Reduced oxidative muscle metabolism in chronic fatigue syndrome | journal = Muscle Nerve | volume = 19 | issue = 5 | page = 621-625 | date = May 1996 | pmid = 8618560 | doi =| url = http://www.ncbi.nlm.nih.gov/pubmed/8618560 }}</ref> Several studies have found abnormal increases in plasma [[lactate]] following short period of moderate exercise that cannot be explained by [[deconditioning]].<ref name="LaneRJ1998">{{citation | last1 = Lane | first1 = R J | author-link1 = Russell Lane | last2 =Barrett | first2 = M C | authorlink2 = Michael Barrett | last3 = Taylor | first3 = D J | authorlink3 = Doris Taylor | last4 = Kemp | first4 = G J | authorlink4 = Graham Kemp | last5 = Lodi | first5 = R | authorlink5 = Raffaele Lodi | title = Heterogeneity in chronic fatigue syndrome: evidence from magnetic resonance spectroscopy of muscle| journal = Neuromuscul Disord | volume = 8 | issue = 3-4 | page = 204-9 | date = May 1998 | pmid = 9631403 | url = http://www.ncbi.nlm.nih.gov/pubmed/9631403 }}</ref>  There are abnormalities in pH handling by peripheral muscle, and possible evidence of an increased acidosis and lactate accumulation.<ref name="JonesDE2010">{{citation | last1 = Jones | first1 = David EJ | author-link1 = David Jones | last2 =Hollingsworth | first2 = Kieren G | authorlink2 = Kieren Hollingsworth | last3 = Taylor | first3 = Renee R | authorlink3 = Renee Taylor | last4 = Blamire | first4 = Andrew M | authorlink4 = Andrew Blamire | last5 = Newton | first5 = Julia L | authorlink5 = Julia Newton | title = Abnormalities in pH handling by peripheral muscle and potential regulation by the autonomic nervous system in chronic fatigue syndrome| journal = J Intern Med | volume = 267 | issue = 4 | page = 394-401 | date = Apr 2010 | pmid = 20433583 | doi = 10.1111/j.1365-2796.2009.02160.x | url = http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2796.2009.02160.x/abstract }}</ref>
| title   = Serum levels of carnitine in chronic fatigue syndrome: clinical correlates| journal = Neuropsychobiology | date = 1995 | volume = 32 | issue = 3 | page = 132-138| pmid   = 8544970| url     = http://www.ncbi.nlm.nih.gov/pubmed/8544970 }}</ref> with reduced intracellular concentrations of [[ATP]] and acceleration of [[glycolysis]].<ref name="McCully1996">{{citation | last1   = McCully         | first1 = KK | authorlink1 = | last2 =Natelson         | first2 = BH | authorlink2 = Benjamin Natelson | last3= Iotti           | first3 = S   | authorlink3 = | last4 =Sisto           | first4 = S   | authorlink4 =  
<ref name="JonesDE2012">{{citation | last1 = Jones | first1 = David EJ | author-link1 = David Jones | last2 =Hollingsworth | first2 = Kieren G | authorlink2 = Kieren Hollingsworth | last3 = Jakovljevic | first3 = Djordje G | authorlink3 = Djordje Jakovljevic | last4 =Fattakhova | first4 = Gulnar | authorlink4 = Gulnar Fattakhova | last5 = Pairman | first5 = Jessie | authorlink5 = Jessie Pairman | last6 = Blamire | first6 = Andrew M | authorlink6 = Andrew Blamire | last7 =Trenell | first7 = Michael I | author-link8 = Michael Trenell | last8 = Newton | first8 = Julia L | author-link8 = Julia Newton| display-authors = | title = Loss of capacity to recover from acidosis on repeat exercise in chronic fatigue syndrome | journal = Eur J Clin Invest | volume = 42 | issue = 2 | page = 186-94 | date = Jul 12, 2011 | pmid = 21749371 | doi = 10.1111/j.1365-2362.2011.02567.x | url = http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2362.2011.02567.x/abstract }}</ref><ref name="LengertN2015">{{citation | last1 = Lengert | first1 = Nicor | author-link1 = Nicor Lengert | last2 =Drossel | first2 = Barbara| authorlink2 = Barbara Drossel | title = In silico analysis of exercise intolerance in myalgic encephalomyelitis/chronic fatigue syndrome| journal = Biophysical Chemistry | volume = 202 | page = 21–31 | date = Jul 2015 | pmid = 25899994 | doi = 10.1016/j.bpc.2015.03.009| url = http://www.sciencedirect.com/science/article/pii/S0301462215000630 }}</ref>
| last5   = Leigh           | first5 = JS Jr. | authorlink5 =  
| title   = Reduced oxidative muscle metabolism in chronic fatigue syndrome
| journal = Muscle Nerve | volume = 19 | issue = 5 | page = 621-625
| date   = May 1996| pmid   = 8618560 | doi =| url     = http://www.ncbi.nlm.nih.gov/pubmed/8618560 }}</ref> Several studies have found abnormal increases in plasma [[lactate]] following short period of moderate exercise that cannot be explained by [[deconditioning]].<ref name="LaneRJ1998">{{citation | last1   = Lane             | first1 = R J               | authorlink1 = Russell Lane | last2 =Barrett         | first2 = M C               | authorlink2 = Michael Barrett | last3= Taylor           | first3 = D J               | authorlink3 = Doris Taylor | last4 =Kemp             | first4 = G J               | authorlink4 = Graham Kemp
| last5   = Lodi             | first5 = R | authorlink5 = Raffaele Lodi
| title   = Heterogeneity in chronic fatigue syndrome: evidence from magnetic resonance spectroscopy of muscle| journal = Neuromuscul Disord | volume = 8| issue = 3-4 | page = 204-9
| date   = May 1998| pmid   = 9631403 | url     = http://www.ncbi.nlm.nih.gov/pubmed/9631403 }}</ref>  There are abnormalities in pH handling by peripheral muscle, and possible evidence of an increased acidosis and lactate accumulation.<ref name="JonesDE2010">{{citation | last1   = Jones   | first1 = David EJ       | authorlink1 = David Jones | last2 =Hollingsworth   | first2 = Kieren G | authorlink2 = Kieren Hollingsworth| last3   = Taylor | first3 = Renee R | authorlink3 = Renee Taylor| last4   = Blamire | first4 = Andrew M | authorlink4 = Andrew Blamire| last5   = Newton | first5 = Julia L | authorlink5 = Julia Newton
| title   = Abnormalities in pH handling by peripheral muscle and potential regulation by the autonomic nervous system in chronic fatigue syndrome| journal = J Intern Med | volume = 267 | issue = 4 | page = 394-401| date   = Apr 2010
| pmid   = 20433583 | doi = 10.1111/j.1365-2796.2009.02160.x
| url     = http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2796.2009.02160.x/abstract }}</ref>
<ref name="JonesDE2012">{{citation | last1   = Jones           | first1 = David EJ       | authorlink1 = David Jones | last2 =Hollingsworth   | first2 = Kieren G       | authorlink2 = Kieren Hollingsworth | last3= Jakovljevic     | first3 = Djordje G       | authorlink3 = Djordje Jakovljevic | last4 =Fattakhova       | first4 = Gulnar         | authorlink4 = Gulnar Fattakhova
| last5   = Pairman         | first5 = Jessie         | authorlink5 = Jessie Pairman | last6 = Blamire         | first6 = Andrew M       | authorlink6 = Andrew Blamire | last7 =Trenell         | first7 = Michael I       | authorlink7 = Michael Trenell | last8 = Newton           | first8 = Julia L         | authorlink8 = Julia Newton| display-authors =  
| title   = Loss of capacity to recover from acidosis on repeat exercise in chronic fatigue syndrome
| journal = Eur J Clin Invest | volume = 42 | issue = 2 | page = 186-94
| date   = Jul 12, 2011
| pmid   = 21749371 | doi = 10.1111/j.1365-2362.2011.02567.x  
| url     = http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2362.2011.02567.x/abstract
}}</ref><ref name="LengertN2015">{{citation| last1   = Lengert | first1 = Nicor | authorlink1 = Nicor Lengert | last2 =Drossel | first2 = Barbara           | authorlink2 = Barbara Drossel
| title   = In silico analysis of exercise intolerance in myalgic encephalomyelitis/chronic fatigue syndrome| journal = Biophysical Chemistry | volume = 202 | page = 21–31| date   = Jul 2015| pmid   = 25899994 | doi = 10.1016/j.bpc.2015.03.009| url     = http://www.sciencedirect.com/science/article/pii/S0301462215000630 }}</ref>


There is also evidence of loss of capacity to recover from acidosis on repeat exercise, as demonstrated by the [[two-day cardiopulmonary exercise test|Two-Day Cardiopulmonary Exercise Test]].<ref name="JonesDE2012" />  
There is also evidence of loss of capacity to recover from acidosis on repeat exercise, as demonstrated by the [[two-day cardiopulmonary exercise test|Two-Day Cardiopulmonary Exercise Test]].<ref name="JonesDE2012" />  


Finally, there is evidence of abnormalities of [[AMPK]] activation and glucose uptake in cultured skeletal muscle cells in ME/CFS patients.<ref name="BrownAE2015">{{Citation | last1   = Brown           | first1 = Audrey E           | authorlink1 = Audrey Brown | last2 =Jones           | first2 = David E           | authorlink2 = David Jones | last3= Walker           | first3 = Mark               | authorlink3 = Mark Walker | last4 =Newton           | first4 = Julia L           | authorlink4 = Julia Newton
Finally, there is evidence of abnormalities of [[AMPK]] activation and glucose uptake in cultured skeletal muscle cells in ME/CFS patients.<ref name="BrownAE2015">{{Citation | last1 = Brown | first1 = Audrey E | author-link1 = Audrey Brown | last2 =Jones | first2 = David E | authorlink2 = David Jones | last3 = Walker | first3 = Mark | authorlink3 = Mark Walker | last4 = Newton | first4 = Julia L | authorlink4 = Julia Newton | title = Abnormalities of AMPK activation and glucose uptake in cultured skeletal muscle cells | journal = PLoS One | volume = 10 | issue = 4 | date = Apr 2, 2015 | pmid = 25836975 | doi = 10.1371/journal.pone.0122982 | url = http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0122982 }}</ref>
| title   = Abnormalities of AMPK activation and glucose uptake in cultured skeletal muscle cells
| journal = PLoS One | volume = 10 | issue = 4| date   = Apr 2, 2015
| pmid   = 25836975 | doi = 10.1371/journal.pone.0122982
| url     = http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0122982
}}</ref>
[[File:Light2011-geneexpression-figure3.jpg|right|frame|Gene expression changes following moderate exercise (Light et al, 2011)|516x516px]]
[[File:Light2011-geneexpression-figure3.jpg|right|frame|Gene expression changes following moderate exercise (Light et al, 2011)|516x516px]]


=== Gene expression ===
=== Gene expression ===
There is evidence of increased expression of certain [[gene]]s following muscular exertion.<ref name="LightAR2009">{{citation | last1   = Light           | first1 = Alan R             | authorlink1 = Alan Light | last2 =White           | first2 = Andrea T           | authorlink2 = Andrea White | last3= Hughen           | first3 = Ronald W           | authorlink3 = Ronald Hughen | last4 =Light           | first4 = Kathleen C         | authorlink4 = Kathleen Light
There is evidence of increased expression of certain [[gene]]s following muscular exertion.<ref name="LightAR2009">{{citation | last1 = Light | first1 = Alan R | author-link1 = Alan Light | last2 =White | first2 = Andrea T | authorlink2 = Andrea White | last3 = Hughen | first3 = Ronald W | authorlink3 = Ronald Hughen | last4 =Light | first4 = Kathleen C | authorlink4 = Kathleen Light | title = Moderate exercise increases expression for sensory, adrenergic, and immune genes in chronic fatigue syndrome patients but not in normal subjects| journal = J Pain | volume = 10 | issue = 10 | page = 1099-112 | date = Jul 31, 2009 | pmid = 19647494 | doi = 10.1016/j.jpain.2009.06.003 | url = http://www.jpain.org/article/S1526-5900(09)00574-4/abstract}}</ref>
| title   = Moderate exercise increases expression for sensory, adrenergic, and immune genes in chronic fatigue syndrome patients but not in normal subjects| journal = J Pain | volume = 10 | issue = 10 | page = 1099-112| date   = Jul 31, 2009| pmid   = 19647494 | doi = 10.1016/j.jpain.2009.06.003
<ref name="LightAR2011">{{citation | last1 = Light | first1 = Alan R | author-link1 = Alan Light | last2 =Bateman | first2 = Lucinda | authorlink2 = Lucinda Bateman | last3 = Jo | first3 = Daehyun | authorlink3 = Daehyun Jo | last4 =Hughen | first4 = Ronald W | authorlink4 = Ronald Hughen | last5 = Vanhaitsma | first5 = TA | authorlink5 = Timothy VanHaitsma | last6 = White | first6 = Andrea T | authorlink6 = Andrea White | last7 =Light | first7 = Kathleen C | author-link8 = Kathleen Light | title = Gene expression alterations at baseline and following moderate exercise in patients with Chronic Fatigue Syndrome and Fibromyalgia Syndrome | journal = J Intern Med | volume = 271 | issue = 1 | page = 64-81 | date = Jul 13, 2011 | pmid = 21615807 | doi = 10.1111/j.1365-2796.2011.02405.x | url = http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2796.2011.02405.x/abstract }}</ref><ref name="WhiteAT2012">{{citation | last1 = White | first1 = Andrea T | author-link1 = Andrea White | last2 =Light | first2 = Alan R | authorlink2 = Alan Light | last3 = Hughen | first3 = Ronald W | authorlink3 = Ronald Hughen | last4 = VanHaitsma | first4 =Timothy A | authorlink4 = Timothy VanHaitsma | last5 = Light | first5 = Kathleen C | authorlink5 = Kathleen Light | title = 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 | journal = Psychosom Med | volume = 74 | issue = 1 | page = 46-54 | date = Dec 30, 2011 | pmid = 22210239 | doi = 10.1097/PSY.0b013e31824152ed | url = http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3256093/}}</ref>  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).<ref name="LightAR2011" />  
| url     = http://www.jpain.org/article/S1526-5900(09)00574-4/abstract}}</ref>
<ref name="LightAR2011">{{citation | last1   = Light | first1 = Alan R             | authorlink1 = Alan Light | last2 =Bateman | first2 = Lucinda | authorlink2 = Lucinda Bateman | last3= Jo | first3 = Daehyun | authorlink3 = Daehyun Jo | last4 =Hughen | first4 = Ronald W | authorlink4 = Ronald Hughen
| last5   = Vanhaitsma | first5 = TA | authorlink5 = Timothy VanHaitsma | last6 = White | first6 = Andrea T           | authorlink6 = Andrea White | last7 =Light| first7 = Kathleen C | authorlink7 = Kathleen Light
| display-authors =
| title   = Gene expression alterations at baseline and following moderate exercise in patients with Chronic Fatigue Syndrome and Fibromyalgia Syndrome
| journal = J Intern Med | volume = 271 | issue = 1 | page = 64-81
| date   = Jul 13, 2011
| pmid   = 21615807 | doi = 10.1111/j.1365-2796.2011.02405.x
| url     = http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2796.2011.02405.x/abstract
}}</ref><ref name="WhiteAT2012">{{citation| last1   = White | first1 = Andrea T | authorlink1 = Andrea White | last2 =Light | first2 = Alan R             | authorlink2 = Alan Light | last3= Hughen | first3 = Ronald W           | authorlink3 = Ronald Hughen
| last4 = VanHaitsma | first4 =Timothy A | authorlink4 = Timothy VanHaitsma
| last5   = Light | first5 = Kathleen C | authorlink5 = Kathleen Light
| title   = 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
| journal = Psychosom Med | volume = 74 | issue = 1 | page = 46-54
| date   = Dec 30, 2011| pmid   = 22210239 | doi = 10.1097/PSY.0b013e31824152ed
| url     = http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3256093/}}</ref>  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).<ref name="LightAR2011" />  


=== Second day exercise test ===
=== Second day exercise test ===
{{Main article|page_name=Two-day cardiopulmonary exercise test}}
{{Main article| page_name=Two-day cardiopulmonary exercise test}}


The seminal study on the response of chronic fatigue syndrome patients to a two-day cardiopulmonary exercise test was published by [[Mark VanNess]], [[Christopher Snell]] and [[Staci Stevens]] in 2007: "Diminished Cardiopulmonary Capacity During Post-Exertional Malaise".<ref name="VanNess2007">{{citation | last1   = VanNess         | first1 = J Mark             | authorlink1 = Mark VanNess | last2 =Snell           | first2 = Christopher R     | authorlink2 = Christopher Snell | last3= Stevens         | first3 = Staci R           | authorlink3 = Staci Stevens| title   = Diminished Cardiopulmonary Capacity During Post-Exertional Malaise| journal = Journal of Chronic Fatigue Syndrome | volume = 14 | issue = 2 | page = 77-85
The seminal study on the response of chronic fatigue syndrome patients to a two-day cardiopulmonary exercise test was published by [[Mark VanNess]], [[Christopher Snell]] and [[Staci Stevens]] in 2007: "Diminished Cardiopulmonary Capacity During Post-Exertional Malaise".<ref name="VanNess2007">{{citation | last1 = VanNess | first1 = J Mark| author-link1 = Mark VanNess | last2 =Snell | first2 = Christopher R | authorlink2 = Christopher Snell | last3 = Stevens | first3 = Staci R | authorlink3 = Staci Stevens| title = Diminished Cardiopulmonary Capacity During Post-Exertional Malaise| journal = Journal of Chronic Fatigue Syndrome | volume = 14 | issue = 2 | page = 77-85 | date = 2007| doi = 10.1300/J092v14n02_07 | url = http://www.tandfonline.com/doi/abs/10.1300/J092v14n02_07 }}</ref> 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.<ref name="SnellCR2013">{{citation | last1 = Snell | first1 = Christopher R | author-link1 = Christopher Snell | last2 =Stevens | first2 = Staci R | authorlink2 = Staci Stevens | last3 = Davenport | first3 = Todd E | authorlink3 = Todd Davenport | last4 =VanNess | first4 = J Mark | author-link4 = Mark VanNess| title = Discriminative Validity of Metabolic and Workload Measurements for Identifying People With Chronic Fatigue Syndrome | journal = Physical Therapy (APTA) | volume = 93 | issue = 11 | page = 1484-1492 | date = Oct 31, 2013 | pmid = 23813081 | doi = 10.2522/ptj.20110368 | url = https://academic.oup.com/ptj/article-lookup/doi/10.2522/ptj.20110368}}</ref>
| date   = 2007| doi     = 10.1300/J092v14n02_07
| url     = http://www.tandfonline.com/doi/abs/10.1300/J092v14n02_07
}}</ref> 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.<ref name="SnellCR2013">{{citation | last1   = Snell           | first1 = Christopher R     | authorlink1 = Christopher Snell | last2 =Stevens         | first2 = Staci R           | authorlink2 = Staci Stevens | last3= Davenport       | first3 = Todd E             | authorlink3 = Todd Davenport | last4 =VanNess         | first4 = J Mark             | authorlink4 = Mark VanNess| title   = Discriminative Validity of Metabolic and Workload Measurements for Identifying People With Chronic Fatigue Syndrome
| journal = Physical Therapy (APTA) | volume = 93 | issue = 11 | page = 1484-1492| date   = Oct 31, 2013
| pmid   = 23813081 | doi = 10.2522/ptj.20110368
| url     = https://academic.oup.com/ptj/article-lookup/doi/10.2522/ptj.20110368}}</ref>


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.<ref name="KellerBA2014">{{citation | last1   = Keller           | first1 = Betsy A           | authorlink1 = Betsy Keller | last2 =Pryor           | first2 = John Luke         | authorlink2 = John Pryor | last3= Giloteaux       | first3 = Ludovic           | authorlink3 = Ludovic Giloteaux
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.<ref name="KellerBA2014">{{citation | last1 = Keller | first1 = Betsy A | author-link1 = Betsy Keller | last2 =Pryor | first2 = John Luke | authorlink2 = John Pryor | last3 = Giloteaux | first3 = Ludovic| authorlink3 = Ludovic Giloteaux | title = Inability of myalgic encephalomyelitis/chronic fatigue syndrome patients to reproduce VO₂peak indicates functional impairment | journal = J Transl Med | volume = | issue = 12 | page = 104 | date = Apr 23, 2014 | pmid = 24755065 | doi = 10.1186/1479-5876-12-104 | url = http://translational-medicine.biomedcentral.com/articles/10.1186/1479-5876-12-104 }}</ref>
| title   = Inability of myalgic encephalomyelitis/chronic fatigue syndrome patients to reproduce VO₂peak indicates functional impairment
| journal = J Transl Med | volume = | issue = 12 | page = 104| date   = Apr 23, 2014| pmid   = 24755065 | doi = 10.1186/1479-5876-12-104
| url     = http://translational-medicine.biomedcentral.com/articles/10.1186/1479-5876-12-104 }}</ref>


A review by [[Jo Nijs|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_impairement|Oxidative impairment]].<ref name="Nijs2014">{{Citation | last1   = Nijs | first1 = J   | authorlink1 = Jo Nijs | last2 =Nees | first2 = A   | authorlink2 = | last3= Paul | first3 = L   | authorlink3 = | last4 =De Kooning           | first4 = M   | authorlink4 =  
A review by [[Jo Nijs|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_impairement|Oxidative impairment]].<ref name="Nijs2014">{{Citation | last1 = Nijs | first1 = J | author-link1 = Jo Nijs | last2 =Nees | first2 = A | authorlink2 = | last3 = Paul | first3 = L | authorlink3 = | last4 = De Kooning | first4 = M | authorlink4 = | last5 = Ickmans | first5 = K | authorlink5 = | last6 = Meeus | first6 = M | authorlink6 = Mira Meeus | last7 =Van Oosterwijck | first7 = J | author-link8 = Jessica Van Oosterwijck | title = Altered immune response to exercise in patients with chronic fatigue syndrome/myalgic encephalomyelitis: a systematic literature review | url = https://repository.uantwerpen.be/docman/irua/338b0c/9322.pdf | journal =  Exercise Immunology Review | volume = | issue =  20  | page = 94-116 | date = 2014 | pmid = 24974723}}</ref>
| last5   = Ickmans               | first5 = K   | authorlink5 = | last6 = Meeus | first6 = M | authorlink6 = Mira Meeus | last7 =Van Oosterwijck | first7 = J | authorlink7 = Jessica Van Oosterwijck | title = Altered immune response to exercise in patients with chronic fatigue syndrome/myalgic encephalomyelitis: a systematic literature review
| url = https://repository.uantwerpen.be/docman/irua/338b0c/9322.pdf
| journal =  Exercise Immunology Review | volume =   | issue =  20  | page = 94-116| date   = 2014
| pmid   = 24974723}}</ref>


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.
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.
Line 132: Line 64:
===Oxidative impairment===
===Oxidative impairment===


DeBecker et al (2000) and VanNess et al (2003) found low VO2 during exercise testing;<ref name="DeBecker2000">{{Citation | last1   = De Becker       | first1 = P | authorlink1 = Pascale De Becker | last2 =Roeykens         | first2 = J | authorlink2 = Johan Roeykens | last3= Reynders         | first3 = M | authorlink3 = Masha Reynders | last4 =McGregor         | first4 = N | authorlink4 = Neil McGregor
DeBecker et al (2000) and VanNess et al (2003) found low VO2 during exercise testing;<ref name="DeBecker2000">{{Citation | last1 = De Becker | first1 = P | author-link1 = Pascale De Becker | last2 =Roeykens | first2 = J | authorlink2 = Johan Roeykens | last3 = Reynders | first3 = M | authorlink3 = Masha Reynders | last4 =McGregor | first4 = N | authorlink4 = Neil McGregor | last5 = De Meirleir | first5 = K | authorlink5 = Kenny de Meirleir| display-authors = | title = Exercise capacity in chronic fatigue syndrome | journal = Archives of Internal Medicine | issn = 0003-9926| volume = 160 | issue = 21| pages = 3270–3277 | date = 2000-11-27 | pmid = 11088089 | doi = 10.1001/archinte.160.21.3270 | url = http://archinte.jamanetwork.com/article.aspx?articleid=485564 }}</ref><ref name="Vanness2003">{{citation | last1 = VanNess | first1 = JM | author-link1 = Mark VanNess | last2 =Snell | first2 = CR | authorlink2 = Christopher Snell | last3 = Strayer | first3 = DR | authorlink3 = David Strayer | last4 = Dempsey | first4 = L | authorlink4 = Line Dempsey | last5 = Stevens | first5 = SR | authorlink5 = Staci Stevens | title = Subclassifying chronic fatigue syndrome through exercise testing | journal = Medicine and Science in Sports and Exercise | issn = 0195-9131| volume = 35 | issue = 6| pages = 908–913 | date = June 2003 | pmid = 12783037 | doi = 10.1249/01.MSS.0000069510.58763.E8 | url = https://www.researchgate.net/profile/Mark_Van_Ness/publication/10728803_Subclassifying_chronic_fatigue_syndrome_through_exercise_testing/links/0c96051793fc9a83e4000000.pdf }}</ref> Fulle et al. (2000) demonstrated oxidative damage to DNA<ref name="Fulle2000" />; and Wong et al. (1992) showed defects in oxidative metabolism and poor recovery of ATP after exercise.<ref name="Wong1992">{{citation | last1 = Wong | first1 = R | author-link1 = Roger Wong | last2 = Lopaschuk | first2 = G | authorlink2 = Gary Lopaschuk | last3 = Zhu | first3 = G | authorlink3 = Gang Zhu | last4 =Walker | first4 = D | authorlink4 = Dorothy Walker | last5 = Catellier | first5 = D | authorlink5 = Dianne Catellier | last6 = Burton | first6 = D | authorlink6 = David Burton | last7 =Teo | first7 = K | author-link8 = Koon Teo | last8 = Collins-Nakai | first8 = R | author-link8 = Ruth Collins-Nakai | last9 =Montague | first9 = T | author-link9 = Terrence Montague | title = Skeletal muscle metabolism in the chronic fatigue syndrome. In vivo assessment by 31P nuclear magnetic resonance spectroscopy| journal = Chest | issn = 0012-3692| volume = 102 | issue = 6| pages = 1716–1722 | date = Dec 1992 | pmid = 1446478 | doi = 10.1378/chest.102.6.1716 | url = http://www.sciencedirect.com/science/article/pii/S0012369216408469}}</ref>
| last5   = De Meirleir     | first5 = K | authorlink5 = Kenny de Meirleir| display-authors =  
| title   = Exercise capacity in chronic fatigue syndrome
| journal = Archives of Internal Medicine | issn = 0003-9926| volume = 160| issue = 21| pages = 3270–3277
| date   = 2000-11-27
| pmid   = 11088089 | doi = 10.1001/archinte.160.21.3270
| url     = http://archinte.jamanetwork.com/article.aspx?articleid=485564
}}</ref><ref name="Vanness2003">{{citation | last1   = VanNess         | first1 = JM | authorlink1 = Mark VanNess | last2 =Snell           | first2 = CR | authorlink2 = Christopher Snell | last3= Strayer         | first3 = DR | authorlink3 = David Strayer | last4 =Dempsey         | first4 = L | authorlink4 = Line Dempsey
| last5   = Stevens         | first5 = SR | authorlink5 = Staci Stevens
| title   = Subclassifying chronic fatigue syndrome through exercise testing
| journal = Medicine and Science in Sports and Exercise | issn = 0195-9131| volume = 35| issue = 6| pages = 908–913
| date   = June 2003
| pmid   = 12783037 | doi = 10.1249/01.MSS.0000069510.58763.E8
| url     = https://www.researchgate.net/profile/Mark_Van_Ness/publication/10728803_Subclassifying_chronic_fatigue_syndrome_through_exercise_testing/links/0c96051793fc9a83e4000000.pdf
}}</ref> Fulle et al. (2000) demonstrated oxidative damage to DNA<ref name="Fulle2000" />; and Wong et al. (1992) showed defects in oxidative metabolism and poor recovery of ATP after exercise.<ref name="Wong1992">{{citation| last1   = Wong | first1 = R | authorlink1 = Roger Wong| last2   = Lopaschuk | first2 = G | authorlink2 = Gary Lopaschuk | last3= Zhu | first3 = G | authorlink3 = Gang Zhu | last4 =Walker | first4 = D | authorlink4 = Dorothy Walker
| last5   = Catellier | first5 = D     | authorlink5 = Dianne Catellier | last6 = Burton | first6 = D | authorlink6 = David Burton | last7 =Teo | first7 = K | authorlink7 = Koon Teo | last8 = Collins-Nakai | first8 = R     | authorlink8 = Ruth Collins-Nakai | last9 =Montague | first9 = T     | authorlink9 = Terrence Montague
| display-authors = | title = Skeletal muscle metabolism in the chronic fatigue syndrome. In vivo assessment by 31P nuclear magnetic resonance spectroscopy| journal = Chest | issn = 0012-3692| volume = 102| issue = 6| pages = 1716–1722| date   = Dec 1992| pmid   = 1446478 | doi = 10.1378/chest.102.6.1716
| url     = http://www.sciencedirect.com/science/article/pii/S0012369216408469}}</ref>


== Graded exercise therapy==
== Graded exercise therapy==
{{main article|page_name=Graded exercise therapy|title1=Graded exercise therapy (GET)}}
{{main article| page_name=Graded exercise therapy|title1=Graded exercise therapy (GET)}}
Graded exercise therapy involves incremental increases in physical activity or exercise over time, is a controversial treatment for ME/CFS, due to [[exercise intolerance]] being a central feature of the disease.
Graded exercise therapy involves incremental increases in physical activity or exercise over time, is a controversial treatment for ME/CFS, due to [[exercise intolerance]] being a central feature of the disease.


== Excessive exercise ==
== Excessive exercise ==
Excessive exercise in healthy people, particularly athletes, is known to cause [[overtraining syndrome]], which is typically recognized by unexplained decreased exercise capacity in combination with other symptoms.<ref name="jointstatement2012">{{Cite journal|last=Meeusen|first=Romain|last2=Duclos|first2=Martine|last3=Foster|first3=Carl|last4=Fry|first4=Andrew|last5=Gleeson|first5=Michael|last6=Nieman|first6=David|last7=Raglin|first7=John|last8=Rietjens|first8=Gerard|last9=Steinacker|first9=Jürgen|date=2013-01-01|title=Prevention, diagnosis and treatment of the overtraining syndrome: Joint consensus statement of the European College of Sport Science (ECSS) and the American College of Sports Medicine (ACSM)|url=https://doi.org/10.1080/17461391.2012.730061|journal=European Journal of Sport Science|volume=13|issue=1|pages=1–24|doi=10.1080/17461391.2012.730061|issn=1746-1391}}</ref><ref name="Kreher2019">{{Cite journal|url=https://doi.org/10.1177%2F1941738111434406|title=Overtraining Syndrome: A practical guide|website=SAGE Journals|language=en|doi=10.1177/1941738111434406|pmc=3435910|pmid=23016079|access-date=2019-02-28|date=2012|last=Kreher|first=Jeffrey|authorlink=|last2=Schwartz|first2=Jennifer B.|authorlink2=|archive-url=|archive-date=|url-status=|volume=4|issue=2|pages=128-138}}</ref> Overtraining syndrome, while commonly fatiguing, has different signs and symptoms than CFS,<ref name=":0" /><ref name="jointstatement2012" /><ref name="Derman2000" /> and effects of overtraining should not be confused with ME/CFS,<ref name="Mommersteeg2006">{{Cite journal|title=Clinical burnout is not reflected in the cortisol awakening response, the day-curve or the response to a low-dose dexamethasone suppression test|date=2006-02-01|url=https://www.sciencedirect.com/science/article/pii/S0306453005001757|journal=Psychoneuroendocrinology|volume=31|issue=2|pages=216–225|last=Mommersteeg|first=Paula M. C.|last2=Heijnen|first2=Cobi J.|last3=Verbraak|first3=Marc J. P. M.|last4=van Doornen|first4=Lorenz J. P.|language=en|doi=10.1016/j.psyneuen.2005.07.003|issn=0306-4530}}</ref> which is a multi-systemic neurological disease with a different symptom profile, involves multiple processes including [[mitochondria dysfunction]], [[neuroinflammation]], and [[#immune_system|abnormal immune system responses to exercise]], and has no known cure or established treatment.<ref name="ICC2011primer">{{citation | last1 = Carruthers | first1 = BM | authorlink1 = Bruce Carruthers| last2 = van de Sande | first2 = MI | authorlink2 = Marjorie van de Sande| last3 = De Meirleir | first3 = KL | authorlink3 = Kenny de Meirleir| last4 = Klimas | first4 = NG | authorlink4 = Nancy Klimas| last5 = Broderick | first5 = G | authorlink5 = Gordon Broderick| last6 = Mitchell | first6 = T | authorlink6 = Terry Mitchell| last7 = Staines | first7 = D | authorlink7 = Donald Staines| last8 = Powles | first8 = ACP | authorlink8 = A C Peter Powles | last9 = Speight | first9 = N | authorlink9 = Nigel Speight | last10 = Vallings | first10= R | authorlink10= Rosamund Vallings | last11 = Bateman | first11= L | authorlink11= Lucinda Bateman | last12 = Bell | first12= DS | authorlink12= David Bell | last13 = Carlo-Stella | first13= N | authorlink13= Nicoletta Carlo-Stella | last14 = Chia | first14= J | authorlink14= John Chia | last15 = Darragh | first15= A | authorlink15= Austin Darragh | last16 = Gerken | first16= A | authorlink16= Anne Gerken | last17 = Jo | first17= D | authorlink17= Daehyun Jo | last18 = Lewis | first18= DP | authorlink18= Donald Lewis | last19 = Light | first19= AR | authorlink19= Alan Light | last20 = Light | first20= KC | authorlink20= Kathleen Light | last21 = Marshall-Gradisnik | first21= S | authorlink21= Sonya Marshall-Gradisnik | last22 = McLaren-Howard | first22= J | authorlink22= John McLaren-Howard | last23 = Mena | first23= I | authorlink23= Ismael Mena| last24 = Miwa | first24= K | authorlink24= Kunihisa Miwa| last25 = Murovska | first25= M | authorlink25= Modra Murovska| last26 = Stevens | first26= SR | authorlink26= Staci Stevens| title = Myalgic encephalomyelitis: Adult & Paediatric: International Consensus Primer for Medical Practitioners | date = 2012| isbn = 978-0-9739335-3-6 | url = http://www.investinme.org/Documents/Guidelines/Myalgic%20Encephalomyelitis%20International%20Consensus%20Primer%20-2012-11-26.pdf}}</ref><ref name=":0" /> ME/CFS cannot be diagnosed when symptoms may be the result of excessive exertion, for example prolonged or intense exercise, or when there is inadequate nutrition, and the [[Definitions of myalgic encephalomyelitis and chronic fatigue syndrome|most widely used diagnostic criteria]] also requires 6 months of symptoms before diagnosis.<ref name=":0" /><ref name="spence">{{Cite web |last=Spence|first=Vance|author-link=Vance Spence|website=Irish M.E. Association|title =Snippets {{!}} A presentation by MERGE Chairman Dr Vance Spence on 12 November 2005 at the Oak Tree Court Conference Centre, Coventry, at the invitation of the Warwickshire Network for ME  
Excessive exercise in healthy people, particularly athletes, is known to cause [[overtraining syndrome]], which is typically recognized by unexplained decreased exercise capacity in combination with other symptoms.<ref name="jointstatement2012">{{Cite journal | last = Meeusen | first = Romain | last2 = Duclos | first2 = Martine | last3 = Foster | first3 = Carl | last4 = Fry | first4 = Andrew | last5 = Gleeson | first5 = Michael | last6 = Nieman | first6 = David | last7 = Raglin | first7 = John | last8 = Rietjens | first8 = Gerard | last9 = Steinacker | first9 = Jürgen | date = 2013-01-01 | title = Prevention, diagnosis and treatment of the overtraining syndrome: Joint consensus statement of the European College of Sport Science (ECSS) and the American College of Sports Medicine (ACSM)| url = https://doi.org/10.1080/17461391.2012.730061|journal=European Journal of Sport Science|volume=13|issue=1 | pages = 1–24|doi=10.1080/17461391.2012.730061|issn=1746-1391}}</ref><ref name="Kreher2019">{{Cite journal| url = https://doi.org/10.1177%2F1941738111434406 | title = Overtraining Syndrome: A practical guide|website=SAGE Journals|language=en|doi=10.1177/1941738111434406|pmc=3435910|pmid=23016079|access-date=2019-02-28 | date = 2012 | last = Kreher | first = Jeffrey | authorlink = | last2 = Schwartz | first2 = Jennifer B. | authorlink2 = |archive-url=|archive-date=|url-status=|volume=4|issue=2 | pages = 128-138}}</ref> Overtraining syndrome, while commonly fatiguing, has different signs and symptoms than CFS,<ref name=":0" /><ref name="jointstatement2012" /><ref name="Derman2000" /> and effects of overtraining should not be confused with ME/CFS,<ref name="Mommersteeg2006">{{Cite journal | title = Clinical burnout is not reflected in the cortisol awakening response, the day-curve or the response to a low-dose dexamethasone suppression test | date = 2006-02-01| url = https://www.sciencedirect.com/science/article/pii/S0306453005001757|journal=Psychoneuroendocrinology|volume=31|issue=2 | pages = 216–225 | last = Mommersteeg | first = Paula M.C. | last2 = Heijnen | first2 = Cobi J. | last3 = Verbraak | first3 = Marc J.P.M. | last4 = van Doornen | first4 = Lorenz J.P. |language=en|doi=10.1016/j.psyneuen.2005.07.003|issn=0306-4530}}</ref> which is a multi-systemic neurological disease with a different symptom profile, involves multiple processes including [[mitochondria dysfunction]], [[neuroinflammation]], and [[#immune_system|abnormal immune system responses to exercise]], and has no known cure or established treatment.<ref name="ICC2011primer">{{citation | last1 = Carruthers | first1 = BM | author-link1 = Bruce Carruthers | last2 = van de Sande | first2 = MI | authorlink2 = Marjorie van de Sande | last3 = De Meirleir | first3 = KL | authorlink3 = Kenny de Meirleir | last4 = Klimas | first4 = NG | authorlink4 = Nancy Klimas | last5 = Broderick | first5 = G | authorlink5 = Gordon Broderick | last6 = Mitchell | first6 = T | authorlink6 = Terry Mitchell | last7 = Staines | first7 = D | author-link8 = Donald Staines | last8 = Powles | first8 = ACP | author-link8 = A C Peter Powles | last9 = Speight | first9 = N | author-link9 = Nigel Speight | last10 = Vallings | first10 = R | author-link10 = Rosamund Vallings | last11 = Bateman | first11 = L | author-link11 = Lucinda Bateman | last12 = Bell | first12 = DS | author-link12 = David Bell | last13 = Carlo-Stella | first13 = N | author-link13 = Nicoletta Carlo-Stella | last14 = Chia | first14 = J | author-link14 = John Chia | last15 = Darragh | first15 = A | author-link15 = Austin Darragh | last16 = Gerken | first16 = A | author-link16 = Anne Gerken | last17 = Jo | first17 = D | author-link17 = Daehyun Jo | last18 = Lewis | first18 = DP | author-link18 = Donald Lewis | last19 = Light | first19 = AR | author-link19 = Alan Light | last20 = Light | first20 = KC | authorlink20 = Kathleen Light | last21 = Marshall-Gradisnik | first21 = S | authorlink21 = Sonya Marshall-Gradisnik | last22 = McLaren-Howard | first22 = J | authorlink22 = John McLaren-Howard | last23 = Mena | first23 = I | authorlink23 = Ismael Mena | last24 = Miwa | first24 = K | authorlink24 = Kunihisa Miwa | last25 = Murovska | first25 = M | authorlink25= Modra Murovska | last26 = Stevens | first26 = SR | authorlink26 = Staci Stevens| title = Myalgic encephalomyelitis: Adult & Paediatric: International Consensus Primer for Medical Practitioners | date = 2012| isbn = 978-0-9739335-3-6 | url = http://www.investinme.org/Documents/Guidelines/Myalgic%20Encephalomyelitis%20International%20Consensus%20Primer%20-2012-11-26.pdf}}</ref><ref name=":0" /> ME/CFS cannot be diagnosed when symptoms may be the result of excessive exertion, for example prolonged or intense exercise, or when there is inadequate nutrition, and the [[Definitions of myalgic encephalomyelitis and chronic fatigue syndrome|most widely used diagnostic criteria]] also requires 6 months of symptoms before diagnosis.<ref name=":0" /><ref name="spence">{{Cite web | last = Spence | first = Vance | authorlink = Vance Spence|website=Irish M.E. Association| title = Snippets {{!}} A presentation by MERGE Chairman Dr Vance Spence on 12 November 2005 at the Oak Tree Court Conference Centre, Coventry, at the invitation of the Warwickshire Network for ME | url = https://www.imet.ie/imet_website/snippets/7th_december_2005_snippets.html}}</ref><ref name="Derman2000" />
|url =https://www.imet.ie/imet_website/snippets/7th_december_2005_snippets.html}}</ref><ref name="Derman2000" />
{{Main article|Overtraining syndrome}}
{{Main article|Overtraining syndrome}}


==Exercise in other chronic illnesses ==
==Exercise in other chronic illnesses ==
Exercise and increased physical activity is increasingly being promoted and encouraged for patients with chronic diseases<ref name="MiraleCure2015">{{Citation|title=Exercise: The miracle cure and the role of the doctor in promoting it|date=2015|url=https://www.aomrc.org.uk/wp-content/uploads/2016/05/Exercise_the_Miracle_Cure_0215.pdf|last=McNally|first=S.|author-link=|work=Academy of Medical Royal Colleges|location=London}}</ref> due to the positive effects found in a considerable number of different chronic illnesses and diseases, including:
Exercise and increased physical activity is increasingly being promoted and encouraged for patients with chronic diseases<ref name="MiraleCure2015">{{Citation | title = Exercise: The miracle cure and the role of the doctor in promoting it | date = 2015 | url=https://www.aomrc.org.uk/wp-content/uploads/2016/05/Exercise_the_Miracle_Cure_0215.pdf | last = McNally | first = S. | author-link = |work=Academy of Medical Royal Colleges|location=London}}</ref> due to the positive effects found in a considerable number of different chronic illnesses and diseases, including:
*psychiatric diseases:
*psychiatric diseases:
** [[depression]]
** [[depression]]
Line 191: Line 105:
** [[osteoarthritis]] - under certain conditions  
** [[osteoarthritis]] - under certain conditions  
** [[osteoporosis]] - exercise should not involve risk of a fall  
** [[osteoporosis]] - exercise should not involve risk of a fall  
** [[rheumatoid arthritis]]<ref name="Pederson2015">{{Cite journal|title=Exercise as medicine - evidence for prescribing exercise as therapy in 26 different chronic diseases|date=Dec 2015|url=https://onlinelibrary.wiley.com/doi/10.1111/sms.12581|journal=Scandinavian Journal of Medicine & Science in Sports|volume=25|issue=|pages=1–72|last=Pedersen|first=B. K.|author-link=|last2=Saltin|first2=B.|author-link2=|language=en|doi=10.1111/sms.12581|pmc=|pmid=|access-date=|quote=|via=}}</ref> - under certain conditions and with supervision
** [[rheumatoid arthritis]]<ref name="Pederson2015">{{Cite journal | title = Exercise as medicine - evidence for prescribing exercise as therapy in 26 different chronic diseases | date = Dec 2015 | url = https://onlinelibrary.wiley.com/doi/10.1111/sms.12581|journal=Scandinavian Journal of Medicine & Science in Sports|volume=25|issue= | pages = 1–72 | last = Pedersen | first = B.K. | author-link = | last2 = Saltin | first2 = B. | authorlink2 = |language=en|doi=10.1111/sms.12581|pmc=|pmid=|access-date=|quote=|via=}}</ref> - under certain conditions and with supervision


Regular exercise has general benefits in chronically ill people '''without ME/CFS''' depend on doing the correct type and intensity of physical activity for the illness in order to avoid aggravating symptoms; if done correctly these include
Regular exercise has general benefits in chronically ill people '''without ME/CFS''' depend on doing the correct type and intensity of physical activity for the illness in order to avoid aggravating symptoms; if done correctly these include
Line 197: Line 111:
* reduced risk of additional chronic diseases
* reduced risk of additional chronic diseases
* reduced [[depression]], especially for people medically ill with mild or moderate depression
* reduced [[depression]], especially for people medically ill with mild or moderate depression
*reduced [[Chronic pain|pain]] in certain conditions, particularly musculoskeletal or pain conditions, if the most appropriate type and intensity of  physical activity is used.<ref name="Gloth2001">{{Cite journal|title=Physical therapy and exercise in pain management|date=2001-09-01|url=https://www.sciencedirect.com/science/article/pii/S0749069005700847|journal=Clinics in Geriatric Medicine|volume=17|issue=3|pages=525–535|last=Gloth|first=Mark J.|last2=Matesi|first2=Ann M.|language=en|doi=10.1016/S0749-0690(05)70084-7|issn=0749-0690}}</ref><ref name="Kujala2006">{{Cite journal|title=Benefits of exercise therapy for chronic diseases|date=2006-01-01|url=https://bjsm.bmj.com/content/40/1/3|journal=British Journal of Sports Medicine|volume=40|issue=1|pages=3–4|last=Kujala|first=U. M.|language=en|doi=10.1136/bjsm.2005.021717|pmc=PMC2491939|pmid=16371482|issn=0306-3674}}</ref>
*reduced [[Chronic pain|pain]] in certain conditions, particularly musculoskeletal or pain conditions, if the most appropriate type and intensity of  physical activity is used.<ref name="Gloth2001">{{Cite journal | title = Physical therapy and exercise in pain management | date = 2001-09-01| url = https://www.sciencedirect.com/science/article/pii/S0749069005700847|journal=Clinics in Geriatric Medicine|volume=17|issue=3 | pages = 525–535 | last = Gloth | first = Mark J. | last2 = Matesi | first2 = Ann M.|language=en|doi=10.1016/S0749-0690(05)70084-7|issn=0749-0690}}</ref><ref name="Kujala2006">{{Cite journal | title = Benefits of exercise therapy for chronic diseases | date = 2006-01-01| url = https://bjsm.bmj.com/content/40/1/3|journal=British Journal of Sports Medicine|volume=40|issue=1 | pages = 3–4 | last = Kujala | first = U.M. | language=en|doi=10.1136/bjsm.2005.021717|pmc=PMC2491939|pmid=16371482|issn=0306-3674}}</ref>


==Talks and interviews==
==Talks and interviews==
Line 207: Line 121:
*2013, [https://www.youtube.com/watch?v=zZ8aPYihkpQ CFS gene expression after exercise (part 1)] - [[Lucinda Bateman]]
*2013, [https://www.youtube.com/watch?v=zZ8aPYihkpQ CFS gene expression after exercise (part 1)] - [[Lucinda Bateman]]
*2014, [https://www.youtube.com/watch?v=q_cnva7zyKM Exercise and ME/CFS, Part 1] - [[Mark VanNess]] at Bristol Watershed
*2014, [https://www.youtube.com/watch?v=q_cnva7zyKM Exercise and ME/CFS, Part 1] - [[Mark VanNess]] at Bristol Watershed
*2015, [https://www.youtube.com/watch?v=F1PP21TmUPs 72. Gene-expression and exercise / Gen-expressie en inspanning]<ref name="Bateman20151103interview">{{Citation| last1   = Bateman         | first1 = Lucinda           | authorlink1 = Lucinda Bateman| title   = Video interview: Gene-expression and exercise
*2015, [https://www.youtube.com/watch?v=F1PP21TmUPs 72. Gene-expression and exercise / Gen-expressie en inspanning]<ref name="Bateman20151103interview">{{Citation | last1 = Bateman | first1 = Lucinda| author-link1 = Lucinda Bateman| title = Video interview: Gene-expression and exercise | journal = Wetenschap voor Patienten - ME/cvs Vereniging | date = Nov 3, 2015 | url = https://www.youtube.com/watch?v=F1PP21TmUPs}}</ref> – Dr. [[Lucinda Bateman]], [[Science for Patients]])
| journal = Wetenschap voor Patienten - ME/cvs Vereniging
| date   = Nov 3, 2015
| url     = https://www.youtube.com/watch?v=F1PP21TmUPs}}</ref> – Dr. [[Lucinda Bateman]], [[Science for Patients]])
*2016, [https://www.youtube.com/watch?v=FXN6f53ba6k Expanding Physical Capability in ME/CFS. Part 1 of 2.] Dr. [[Mark VanNess]]
*2016, [https://www.youtube.com/watch?v=FXN6f53ba6k Expanding Physical Capability in ME/CFS. Part 1 of 2.] Dr. [[Mark VanNess]]
*2016, [https://www.youtube.com/watch?v=7BceGgEdMpA Expanding Physical Capability in ME/CFS. Part 2 of 2.] - [[Mark VanNess]]
*2016, [https://www.youtube.com/watch?v=7BceGgEdMpA Expanding Physical Capability in ME/CFS. Part 2 of 2.] - [[Mark VanNess]]


==Notable studies==
==Notable studies==
*2000, The Differential Diagnosis and Clinical Approach to the Athlete With Chronic Fatigue<ref name="Derman2000">{{Cite journal|last=Lambert|first=M. I.|last2=Derman|first2=W. E.|date=2000-01-01|title=The differential diagnosis and clinical approach to the athlete with chronic fatigue|url=https://www.researchgate.net/profile/Wayne_Derman/publication/304013746_The_Differential_Diagnosis_and_Clinical_Approach_to_the_Athlete_With_Chronic_Fatigue/links/5762fb7e08aecb4f6fee0463/The-Differential-Diagnosis-and-Clinical-Approach-to-the-Athlete-With-Chronic-Fatigue.pdf |journal=International SportMed Journal|language=en|volume=1|issue=3|issn=1528-3356}}</ref>
*2000, The Differential Diagnosis and Clinical Approach to the Athlete With Chronic Fatigue<ref name="Derman2000">{{Cite journal | last = Lambert | first = M.I. | last2 = Derman | first2 = W.E. | date = 2000-01-01 | title = The differential diagnosis and clinical approach to the athlete with chronic fatigue | url =https://www.researchgate.net/profile/Wayne_Derman/publication/304013746_The_Differential_Diagnosis_and_Clinical_Approach_to_the_Athlete_With_Chronic_Fatigue/links/5762fb7e08aecb4f6fee0463/The-Differential-Diagnosis-and-Clinical-Approach-to-the-Athlete-With-Chronic-Fatigue.pdf |journal=International SportMed Journal|language=en|volume=1|issue=3|issn=1528-3356}}</ref>
*2011, [[PACE trial]]
*2011, [[PACE trial]]
*2011, Tired of being inactive: a systematic literature review of physical activity, physiological exercise capacity and muscle strength in patients with chronic fatigue syndrome<ref name="Nijs2011">{{Cite journal|last=Nijs|first=Jo|author-link=Jo Nijs|last2=Aelbrecht|first2=Senne|author-link2=Senne Aelbrecht|last3=Meeus|first3=Mira|author-link3=Mira Meeus|last4=Van Oosterwijck|first4=Jessica|author-link4=Jessica Van Oosterwijck|last5=Zinzen|first5=Evert|author-link5=Evert Zinzen|last6=Clarys|first6=Peter|author-link6=Peter Clarys|date=2011|title=Tired of being inactive: a systematic literature review of physical activity, physiological exercise capacity and muscle strength in patients with chronic fatigue syndrome|url=http://emerge.org.au/wp-content/uploads/2014/11/Nijs-J.-et-al.-Tired-of-being-inactive.-Disabil-Rehabil-2011-3317-18.1493-1500.pdf|journal=Disability and Rehabilitation|volume=33|issue=17-18|pages=1493–1500|doi=10.3109/09638288.2010.541543|issn=1464-5165|pmid=21166613|quote=|via=}}</ref> [http://emerge.org.au/wp-content/uploads/2014/11/Nijs-J.-et-al.-Tired-of-being-inactive.-Disabil-Rehabil-2011-3317-18.1493-1500.pdf (Abstract)]
*2011, Tired of being inactive: a systematic literature review of physical activity, physiological exercise capacity and muscle strength in patients with chronic fatigue syndrome<ref name="Nijs2011">{{Cite journal | last = Nijs | first = Jo | author-link = Jo Nijs | last2 = Aelbrecht | first2 = Senne | authorlink2 = Senne Aelbrecht | last3 = Meeus | first3 = Mira | authorlink3 = Mira Meeus | last4 = Van Oosterwijck | first4 = Jessica | authorlink4 = Jessica Van Oosterwijck | last5 = Zinzen | first5 = Evert | authorlink5 = Evert Zinzen | last6 = Clarys | first6 = Peter | authorlink6 = Peter Clarys | date = 2011 | title = Tired of being inactive: a systematic literature review of physical activity, physiological exercise capacity and muscle strength in patients with chronic fatigue syndrome | url =http://emerge.org.au/wp-content/uploads/2014/11/Nijs-J.-et-al.-Tired-of-being-inactive.-Disabil-Rehabil-2011-3317-18.1493-1500.pdf | journal=Disability and Rehabilitation|volume=33|issue=17-18 | pages = 1493–1500|doi=10.3109/09638288.2010.541543|issn=1464-5165|pmid=21166613|quote=|via=}}</ref> [http://emerge.org.au/wp-content/uploads/2014/11/Nijs-J.-et-al.-Tired-of-being-inactive.-Disabil-Rehabil-2011-3317-18.1493-1500.pdf (Abstract)]
*2016, [https://www.ncbi.nlm.nih.gov/pubmed/27187093 Effect of Acute Exercise on Fatigue in People with ME/CFS/SEID: A Meta-analysis]
*2016, [https://www.ncbi.nlm.nih.gov/pubmed/27187093 Effect of Acute Exercise on Fatigue in People with ME/CFS/SEID: A Meta-analysis]
*2016, [[Cochrane|Cochrane meta-analysis]]
*2016, [[Cochrane|Cochrane meta-analysis]]
*2017, [https://www.sciencedirect.com/science/article/pii/S088915911730051X Neural consequences of post-exertion malaise in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome]<ref name="PEM2017">{{Cite journal|last=Cook|first=Dane B.|author-link=Dane Cook|last2=Light|first2=Alan R.|author-link2=Alan Light|last3=Light|first3=Kathleen C.|author-link3=Kathleen Broderick|last4=Broderick|first4=Gordon|author-link4=Gordon Broderick|last5=Shields|first5=Morgan R.|author-link5=Morgan Shields|last6=Dougherty|first6=Ryan J.|author-link6=Ryan Dougherty|last7=Meyer|first7=Jacob D.|author-link7=Jacob Meyer|last8=VanRiper|first8=Stephanie|author-link8=Stephanie Land|last9=Stegner|first9=Aaron J.|author-link9=Aaron Stegner|date=May 1, 2017|title=Neural consequences of post-exertion malaise in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome|url=http://www.sciencedirect.com/science/article/pii/S088915911730051X|journal=Brain, Behavior, and Immunity|volume=62|issue=|pages=87–99|doi=10.1016/j.bbi.2017.02.009|issn=0889-1591|quote=|via=}}</ref>
*2017, [https://www.sciencedirect.com/science/article/pii/S088915911730051X Neural consequences of post-exertion malaise in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome]<ref name="PEM2017">{{Cite journal | last = Cook | first = Dane B. | author-link = Dane Cook | last2 = Light | first2 = Alan R. | authorlink2 = Alan Light | last3 = Light | first3 = Kathleen C. | authorlink3 = Kathleen Broderick | last4 = Broderick | first4 = Gordon | authorlink4 = Gordon Broderick | last5 = Shields | first5 = Morgan R. | authorlink5 = Morgan Shields | last6 = Dougherty | first6 = Ryan J. | authorlink6 = Ryan Dougherty | last7 = Meyer | first7 = JacobD. | author-link8 = Jacob Meyer | last8 = VanRiper | first8 = Stephanie | author-link8 = Stephanie Land | last9 = Stegner | first9 = Aaron J. | author-link9 = Aaron Stegner | date = May 1, 2017 | title = Neural consequences of post-exertion malaise in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome | url =http://www.sciencedirect.com/science/article/pii/S088915911730051X|journal=Brain, Behavior, and Immunity|volume=62|issue= | pages = 87–99|doi=10.1016/j.bbi.2017.02.009|issn=0889-1591|quote=|via=}}</ref>
* 2020, Prediction of Discontinuation of Structured Exercise Programme in Chronic Fatigue Syndrome Patient<ref name="Kujawski2020">{{Cite journal|last=Kujawski|first=Sławomir|author-link=|last2=Cossington|first2=Jo|author-link2=|last3=Słomko|first3=Joanna|author-link3=|last4=Dawes|first4=Helen|author-link4=|last5=Strong|first5=James W.L.|author-link5=|last6=Estevez-Lopez|first6=Fernando|author-link6=|last7=Murovska|first7=Modra|author-link7=Modra Murovska|last8=Newton|first8=Julia L.|author-link8=Julia Newton|last9=Hodges|first9=Lynette|author-link9=Lynette Hodges|date=2020-10-26|title=Prediction of Discontinuation of Structured Exercise Programme in Chronic Fatigue Syndrome Patients|url=https://www.mdpi.com/2077-0383/9/11/3436|journal=Journal of Clinical Medicine|language=en|volume=9|issue=11|pages=3436|doi=10.3390/jcm9113436|issn=2077-0383|pmc =  7693605|pmid=33114704|access-date=|quote=|via=}}</ref> - [https://www.mdpi.com/2077-0383/9/11/3436/htm (Full text)]
* 2020, Prediction of Discontinuation of Structured Exercise Programme in Chronic Fatigue Syndrome Patient<ref name="Kujawski2020">{{Cite journal | last = Kujawski | first = Sławomir | author-link = | last2 = Cossington | first2 = Jo | authorlink2 = | last3 = Słomko | first3 = Joanna | authorlink3 = | last4 = Dawes | first4 = Helen | authorlink4 = | last5 = Strong | first5 = James W.L. | authorlink5 = | last6 = Estevez-Lopez | first6 = Fernando | authorlink6 = | last7 = Murovska | first7 = Modra | author-link8 = Modra Murovska | last8 = Newton | first8 = Julia L. | author-link8 = Julia Newton | last9 = Hodges | first9 = Lynette | author-link9 = Lynette Hodges | date = 2020-10-26 | title = Prediction of Discontinuation of Structured Exercise Programme in Chronic Fatigue Syndrome Patients |url =https://www.mdpi.com/2077-0383/9/11/3436|journal=Journal of Clinical Medicine|language=en|volume=9|issue=11 | pages = 3436|doi=10.3390/jcm9113436|issn=2077-0383|pmc =  7693605|pmid=33114704|access-date=|quote=|via=}}</ref> - [https://www.mdpi.com/2077-0383/9/11/3436/htm (Full text)]


==Learn more==
==Learn more==
Line 229: Line 140:
*2014 - [http://www.deseretnews.com/article/865603384/Sufferers-of-chronic-fatigue-fibromyalgia-have-hope-in-new-diagnostic-tool.html Sufferers of chronic fatigue, fibromyalgia have hope in new diagnostic tool] by Wendy Leonard for ''Deseret News''
*2014 - [http://www.deseretnews.com/article/865603384/Sufferers-of-chronic-fatigue-fibromyalgia-have-hope-in-new-diagnostic-tool.html Sufferers of chronic fatigue, fibromyalgia have hope in new diagnostic tool] by Wendy Leonard for ''Deseret News''
*2015 - [http://sallyjustme.blogspot.co.uk/2015/01/dr-vanness-on-recent-press-reports.html Dr. VanNess on recent press reports] by Sally Burch in [[Just ME]] blog
*2015 - [http://sallyjustme.blogspot.co.uk/2015/01/dr-vanness-on-recent-press-reports.html Dr. VanNess on recent press reports] by Sally Burch in [[Just ME]] blog
*2015 - [http://www.jacobspublishers.com/images/Physiology/J_J_Physiology_1_2_007.pdf Deviant Cellular and Physiological Responses to Exercise in Myalgic Encephalomyelitis and Chronic Fatigue Syndrome] by [[Frank Twisk|Frank N.M. Twisk]], and [[Keith Geraghty|Keith J. Geraghty]]<ref name="TwiskF2015">{{citation | last1   = Twisk           | first1 = Frank NM           | authorlink1 = Frank Twisk | last2 =Geraghty         | first2 = Keith J           | authorlink2 = Keith Geraghty| title   = Deviant Cellular and Physiological Responses to Exercise in Myalgic Encephalomyelitis and Chronic Fatigue Syndrome| journal = Jacobs Journal of Physiology | volume = 1 | issue =2 | pages = 007| date   = Jul 11, 2015
*2015 - [http://www.jacobspublishers.com/images/Physiology/J_J_Physiology_1_2_007.pdf Deviant Cellular and Physiological Responses to Exercise in Myalgic Encephalomyelitis and Chronic Fatigue Syndrome] by [[Frank Twisk|Frank N.M. Twisk]], and [[Keith Geraghty|Keith J. Geraghty]]<ref name="TwiskF2015">{{citation | last1 = Twisk | first1 = Frank NM | author-link1 = Frank Twisk | last2 = Geraghty | first2 = Keith J | authorlink2 = Keith Geraghty| title = Deviant Cellular and Physiological Responses to Exercise in Myalgic Encephalomyelitis and Chronic Fatigue Syndrome| journal = Jacobs Journal of Physiology | volume = 1 | issue =2 | pages = 007 | date = Jul 11, 2015 | url = http://www.jacobspublishers.com/images/Physiology/J_J_Physiology_1_2_007.pdf}}</ref>  
| url     = http://www.jacobspublishers.com/images/Physiology/J_J_Physiology_1_2_007.pdf}}</ref>  
*2015 -  [https://www.omicsonline.org/open-access/objective-evidence-of-postexertional-malaise-in-myalgic-encephalomyelitis-and-chronic-fatigue-syndrome-2161-0673-1000159.pdf Objective Evidence of Post-exertional “Malaise” in Myalgic Encephalomyelitis and Chronic Fatigue Syndrome] by Frank N.M. Twisk
*2015 -  [https://www.omicsonline.org/open-access/objective-evidence-of-postexertional-malaise-in-myalgic-encephalomyelitis-and-chronic-fatigue-syndrome-2161-0673-1000159.pdf Objective Evidence of Post-exertional “Malaise” in Myalgic Encephalomyelitis and Chronic Fatigue Syndrome] by Frank N.M. Twisk
*2015 - [https://cfsremission.wordpress.com/2015/12/19/exercise-alteration-of-the-cfs-microbiome/ Exercise alteration of the CFS Microbiome] from [[CFS Remission]] blog  
*2015 - [https://cfsremission.wordpress.com/2015/12/19/exercise-alteration-of-the-cfs-microbiome/ Exercise alteration of the CFS Microbiome] from [[CFS Remission]] blog  
*Jan 2016 - [http://www.hindawi.com/journals/jar/2016/2497348/ Review Article: Understanding Muscle Dysfunction in Chronic Fatigue Syndrome] by Gina Rutherford, Philip Manning, and [[Julia Newton|Julia L. Newton]]<ref name="RutherfordG2016">{{citation | last1   = Rutherford       | first1 = Gina             | authorlink1 = Gina Rutherford | last2 =Manning         | first2 = Philip           | authorlink2 = Philip Manning | last3= Newton           | first3 = Julia L           | authorlink3 = Julia Newton
*Jan 2016 - [http://www.hindawi.com/journals/jar/2016/2497348/ Review Article: Understanding Muscle Dysfunction in Chronic Fatigue Syndrome] by Gina Rutherford, Philip Manning, and [[Julia Newton|Julia L. Newton]]<ref name="RutherfordG2016">{{citation | last1 = Rutherford | first1 = Gina | author-link1 = Gina Rutherford | last2 =Manning | first2 = Philip| authorlink2 = Philip Manning | last3 = Newton | first3 = Julia L | authorlink3 = Julia Newton | title = Review Article: Understanding Muscle Dysfunction in Chronic Fatigue Syndrome | journal = Journal of Aging Research | volume = 2016 | issue = 4| pages = 1-13 | date = Jan 13, 2016 | pmid = 26998359 | doi = 10.1155/2016/2497348 | url = http://www.hindawi.com/journals/jar/2016/2497348/}}</ref>
| title   = Review Article: Understanding Muscle Dysfunction in Chronic Fatigue Syndrome
| journal = Journal of Aging Research | volume = 2016 | issue = 4| pages = 1-13| date   = Jan 13, 2016
| pmid   = 26998359 | doi = 10.1155/2016/2497348
| url     = http://www.hindawi.com/journals/jar/2016/2497348/}}</ref>
*Feb 10, 2016 - [http://www.prohealth.com/library/showarticle.cfm?libid=25096 Lost in Translation - The ME-Polio Connection and the Dangers of Exercise] by [[Nancy Blake]] for [[ProHealth]]
*Feb 10, 2016 - [http://www.prohealth.com/library/showarticle.cfm?libid=25096 Lost in Translation - The ME-Polio Connection and the Dangers of Exercise] by [[Nancy Blake]] for [[ProHealth]]
*Jul 2016 - [https://meaustralia.net/2016/07/06/australian-metabolomics-study-of-young-women/ Australian metabolomics study of young women with ME/CFS (CCC)] by Sasha Nimmo for ''ME Australia''  
*Jul 2016 - [https://meaustralia.net/2016/07/06/australian-metabolomics-study-of-young-women/ Australian metabolomics study of young women with ME/CFS (CCC)] by Sasha Nimmo for ''ME Australia''  

Latest revision as of 14:08, April 2, 2023

Exercise is any movement or physical 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,[3] 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.[4] 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.[5]

Worsening of symptoms due to exercise 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.[6]

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.[7] 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.[7]

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.[8]

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.[9][10][11][12][13] 

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.

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.[14]

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.[15] However, patients with ME may experience increased histamine release due to increased mast cell populations at baseline.[16]

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.[17]

Musculature[edit | edit source]

Exercise has also been found to induce both early and excessive lactic acid formation in the muscles[18] with reduced intracellular concentrations of ATP and acceleration of glycolysis.[19] Several studies have found abnormal increases in plasma lactate following short period of moderate exercise that cannot be explained by deconditioning.[20] There are abnormalities in pH handling by peripheral muscle, and possible evidence of an increased acidosis and lactate accumulation.[21] [22][23]

There is also evidence of loss of capacity to recover from acidosis on repeat exercise, as demonstrated by the Two-Day Cardiopulmonary Exercise Test.[22]

Finally, there is evidence of abnormalities of AMPK activation and glucose uptake in cultured skeletal muscle cells in ME/CFS patients.[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).[26]

Second day exercise test[edit | edit source]

The seminal study on the response of chronic fatigue syndrome patients to a two-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.[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[6]; and Wong et al. (1992) showed defects in oxidative metabolism and poor recovery of ATP after exercise.[34]

Graded exercise therapy[edit | edit source]

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

Excessive exercise[edit | edit source]

Excessive exercise in healthy people, particularly athletes, is known to cause overtraining syndrome, which is typically recognized by unexplained decreased exercise capacity in combination with other symptoms.[35][36] Overtraining syndrome, while commonly fatiguing, has different signs and symptoms than CFS,[3][35][37] and effects of overtraining should not be confused with ME/CFS,[38] which is a multi-systemic neurological disease with a different symptom profile, involves multiple processes including mitochondria dysfunction, neuroinflammation, and abnormal immune system responses to exercise, and has no known cure or established treatment.[39][3] ME/CFS cannot be diagnosed when symptoms may be the result of excessive exertion, for example prolonged or intense exercise, or when there is inadequate nutrition, and the most widely used diagnostic criteria also requires 6 months of symptoms before diagnosis.[3][40][37]

Exercise in other chronic illnesses[edit | edit source]

Exercise and increased physical activity is increasingly being promoted and encouraged for patients with chronic diseases[41] due to the positive effects found in a considerable number of different chronic illnesses and diseases, including:

Regular exercise has general benefits in chronically ill people without ME/CFS depend on doing the correct type and intensity of physical activity for the illness in order to avoid aggravating symptoms; if done correctly these include

  • reduced risk of falls and fractures
  • reduced risk of additional chronic diseases
  • reduced depression, especially for people medically ill with mild or moderate depression
  • reduced pain in certain conditions, particularly musculoskeletal or pain conditions, if the most appropriate type and intensity of physical activity is used.[43][44]

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. (March 3, 2015). "Exercise Prescription Considerations for Individuals with Multiple Chronic Diseases: Systematic Review". J Gerontol Geriatr Res. 4 (201).
  3. 3.0 3.1 3.2 3.3 "Symptoms of ME/CFS | Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)". cdc.gov. February 9, 2021. Retrieved December 23, 2021.
  4. 4.0 4.1 Cook, Dane B.; Light, Alan R.; Light, Kathleen C.; Broderick, Gordon; Shields, Morgan R.; Dougherty, Ryan J.; Meyer, JacobD.; 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.
  5. ME Association (May 2015). "ME Association illness management report: no decisions about me without me" (PDF). ME Association. Retrieved April 25, 2018.
  6. 6.0 6.1 Fulle, S; Mecocci, P; Fanó, G; Vecchiet, I; Vecchini, A; Racciotti, D; Cherubini, A; Pizzigallo, E; Vecchiet, L; Senin, U; Beal, MF (December 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
  7. 7.0 7.1 Burton, Deborah Anne; Stokes, Keith; Hall, George M (December 1, 2004). "Physiological effects of exercise". Continuing Education in Anaesthesia Critical Care & Pain. 4 (6): 185–8 – via BJA Education.
  8. Gray, J B; Martinovic, A M (July 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
  9. 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.
  10. 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.
  11. Ilbäck, NG (June 1989). "Exercise in coxsackie B3 myocarditis: Effects on heart lymphocyte subpopulations and the inflammatory reaction". American Heart Journal. 117: 1298–302.
  12. Gatmaitan, Bienvenido (June 1, 1970). "Augmentation of the Virulence of Murine Coxsackie Virus B-3 Myocardiopathy by Exercise". Journal of Experimental Medicine. 131: 1121.
  13. 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.
  14. 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
  15. Romero, S.A.; Hocker, A.D.; Mangum, J.E.; Luttrell, M.J.; Turnbull, D.W.; Halliwill, J.R.; Struck, A.J.; Ely, M.R.; Sieck, D.C.; Dreyer, H.C.; Halliwill, J.R (2016). "Evidence of a broad histamine footprint on the human exercise transcriptome". The Journal of Physiology. 594 (17): 5009–5023.
  16. 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.
  17. Shukla, Sanjay K; Cook, Dane; Meyer, Jacob; Vernon, Suzanne D; Le, Thao; Clevidence, Derek; Robertson, Charles E; Schrodi, Steven J; Yale, Steven; Frank, Daniel N (December 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
  18. Plioplys, AV; Plioplys, S (1995), "Serum levels of carnitine in chronic fatigue syndrome: clinical correlates", Neuropsychobiology, 32 (3): 132-138, PMID 8544970
  19. McCully, KK; Natelson, BH; Iotti, S; Sisto, S; Leigh, JS Jr. (May 1996), "Reduced oxidative muscle metabolism in chronic fatigue syndrome", Muscle Nerve, 19 (5): 621-625, PMID 8618560
  20. 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, 8 (3–4): 204-9, PMID 9631403
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