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Exercise is any movement or activity considered to contribute to general health and well-being.  Exercise may be recommended as part of a wellness regimen in chronic illness.<ref>{{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(Suppl 1)|pages=3-63|via=}}</ref> <ref>{{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=4:201|pages=|via=}}&lt;nowiki&gt;</ref>  However, [[Post-exertional malaise|exercise intolerance]] is a central feature of ME/CFS, and patients show multiple documented abnormal responses to exercise.  Rather than increase health and well-being, ME/CFS patients report that increased activity has reduced their physical and cognitive capacity over time, sometimes permanently.<ref>{{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=|dead-url=|access-date=25 April 2018}}</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=":0">{{Cite journal|last=Burton|first=Deborah Anne|last2=Stokes|first2=Keith|last3=Hall|first3=George M|date=01 December 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|Krebs 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.<ref name=":0" />
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=":0">{{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|Krebs 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.<ref name=":0" />


===Immune system===
===Immune system===
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===Post Exertional Malaise===
===Post Exertional Malaise===
[[File:2010 VanNess Post exertional worsening of symptoms chart.png|right|frame|Post-exertional worsening of symptoms, VanNess et al 2010.png]]
 
[[File:2015 IOM report PEM chart.png|right|frame|PEM chart from the 2015 Institute of Medicine report]]
[[File:2010 VanNess Post exertional worsening of symptoms chart.png|right|frame|Post-exertional worsening of symptoms, VanNess et al 2010.png|377x377px]]
[[File:2015 IOM report PEM chart.png|right|frame|PEM chart from the 2015 Institute of Medicine report|378x378px]]


[[ME]] patients who exercise are likely to experience [[Post-exertional malaise]] which is a worsening of symptoms following physical, cognitive, or sensory exertion.
[[ME]] patients who exercise are likely to experience [[Post-exertional malaise]] which is a worsening of symptoms following physical, cognitive, or sensory exertion.
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===Pain threshold===
===Pain threshold===
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.<ref name="Whiteside, 2004" />
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.<ref name="Whiteside, 2004" />
===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>{{Cite journal|last=Romero|first=S.A.|last2=Hocker|first2=A.D.|last3=Magnum|first3=J.E.|last4=Luttrell|first4=M.J.|last5=Turnbull|first5=D.W. ...|last6=Halliwill|first6=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.<ref>{{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===
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=== Musculature ===
=== Musculature ===


Exercise has also been found to induce both early and excessive lactic acid formation in the [[muscle fatigability|muscles]]<ref name="Plioplys1995" /> with reduced intracellular concentrations of [[ATP]] and acceleration of [[glycolysis]].<ref name="McCully1996" /> Several studies have found abnormal increases in plasma lactate following short period of moderate exercise that cannot be explained by [[deconditioning]].<ref name="LaneRJ1998" />  There is evidence of abnormalities in pH handling by peripheral muscle,<ref name="JonesDE2010" /> and possible evidence of an increased acidosis and lactate accumulation.<ref name="LengertN2015" />
Exercise has also been found to induce both early and excessive lactic acid formation in the [[muscle fatigability|muscles]]<ref name="Plioplys1995" /> with reduced intracellular concentrations of [[ATP]] and acceleration of [[glycolysis]].<ref name="McCully1996" /> Several studies have found abnormal increases in plasma lactate following short period of moderate exercise that cannot be explained by [[deconditioning]].<ref name="LaneRJ1998" />  There is evidence of abnormalities in pH handling by peripheral muscle, and possible evidence of an increased acidosis and lactate accumulation.<ref name="JonesDE2010" /><ref name="LengertN2015" />


There is also evidence of loss of capacity to recover from acidosis on repeat exercise.<ref name="JonesDE2012" />  
There is also evidence of loss of capacity to recover from acidosis on repeat exercise.<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" /><ref name="Wellness20150420" />
Finally, there is evidence of abnormalities of [[AMPK]] activation and glucose uptake in cultured skeletal muscle cells in ME/CFS patients.<ref name="BrownAE2015" /><ref name="Wellness20150420" />
 
[[File:Light2011-geneexpression-figure3.jpg|right|frame|Gene expression changes following moderate exercise (Light et al, 2011)|516x516px]]
 
=== Gene expression ===
=== Gene expression ===


[[File:Light2011-geneexpression-figure3.jpg|right|frame|Gene expression changes following moderate exercise (Light et al, 2011)]]
There is evidence of increased expression of certain genes following muscular exertion.<ref name="LightAR2009" /><ref name="LightAR2011" /><ref name="WhiteAT2012" />  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.<ref name="LightAR2011" /> (see graph at right)
 
There is evidence of increased [[gene expression]] in some genes following muscular exertion.<ref name="LightAR2009" /><ref name="LightAR2011" /><ref name="WhiteAT2012" />  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.<ref name="LightAR2011" /> (see graph at right)


=== Second day exercise test ===
=== Second day exercise test ===
[[File:Oxidative impairment.png|right|frame|Oxidative impairment on the second day of a two-day CPET, VanNess et al 2007]]
The seminal study on the response by CFS patients to a 2-day cardiopulmonary exercise test was published by [[Mark VanNess]], [[Christopher Snell]] and [[Staci Stevens]] in 2007: "Diminished Cardiopulmonary Capacity During Post-Exertional Malaise"<ref name="VanNess2007" /> A repeat study in 2013 confirmed these results.<ref name="SnellCR2013" />
The seminal study on the response by CFS patients to a 2-day cardiopulmonary exercise test was published by [[Mark VanNess]], [[Christopher Snell]] and [[Staci Stevens]] in 2007: "Diminished Cardiopulmonary Capacity During Post-Exertional Malaise"<ref name="VanNess2007" /> A repeat study in 2013 confirmed these results.<ref name="SnellCR2013" />


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== Graded exercise ==
== Graded exercise ==
{{main|Graded exercise therapy}}
{{main|Graded exercise therapy}}
 
Graded exercise therapy, or the incremental increase in physical activity over time, is a controversial treatment for ME/CFS, due to exercise intolerance being a central feature of the disease. See the main page for more.
Graded exercise therapy is a controversial treatment for ME.
 
== Examples of clinical recommendations ==
 
While there has been no research on physical therapy alternatives to graded exercise, and many patients find it harmful, many clinicians recommend some exercise or strength training for patients who are able, tending to apply this to non-severely affected patients.
 
===Dr [[Sarah Myhill]]===
Dr Myhill recommends patients who are well enough engage in strength training, specifically [[Body by Science]] created by Dr Doug McGuff and John Little. "If muscle strength is correctly developed, this automatically translates into cardiovascular fitness and increased numbers of mitochondria". Dr Myhill has a page on her web site [http://www.drmyhill.co.uk/wiki/Exercise_-_the_right_sort detailing her recommendations]<ref name="MyhillExercise" />.
 
===Dr. [[Lucinda Bateman]]===
Dr Bateman encourages her patients to find a way to exercise: "we try to focus on maintaining or improving muscle strength, flexibility and also bit of cardiovascular exercise". She discusses exercise and gene expression in [https://www.youtube.com/watch?v=F1PP21TmUPs an interview]<ref name="Bateman20151103interview" />.
 
===Dr. [[Nancy Klimas]]===
Dr Klimas recommends patients engage in exercise or movement without exceeding a certain heart rate, a proxy for an individual's [[anaerobic threshold]], as established by a [[Cardiopulmonary exercise test|VO2 max test]].<ref name="Klimas20110724phoenix" /> She also recommends alternating periods of exercise and rest.<ref name="Klimas2010" /> She says that exercise tends to be better tolerated when performed in a horizontal position, like recumbent bicycling or swimming.
 
===Dr. [[Ritchie Shoemaker]]===
See [https://youtu.be/jjEDcBbpS_0 YouTube video regarding resuming exercise gradually] for [[mold]] illness aka CIRS patients.
 
===[[Workwell Foundation]]===
[[Workwell Foundation]], which specialises in [[two-day cardiopulmonary exercise testing]] ([[CPET]]), recommends short periods (eg: 30 seconds) of analeptic exercise, with periods of rest which are 3-6 times longer than the period of exercise. The amount of exercise that the individual undertakes should be guided by VO2 max testing (or a safe heart rate threshold (generally 60% of maximum heart rate)), and the use of a heart rate monitor (both during exercise and to help with [[pacing]]) is recommended to ensure that the individual doesn't exceed their capacity. The Foundation also advises against aerobic exercise for people with [[ME/CFS]].<ref name="Workwell201404rae" /><ref name="Workwell201404wwodwo" /><ref name="Workwell201512foar" />
 
This approach to exercise differs from [[Graded Exercise Therapy]] ([[GET]]) in several important ways:
 
*There is no claim that the exercise program will cure the condition. The aim is to increase functional strength and flexibility, and to improve quality of life, whilst not exacerbating the condition<ref name="Workwell201404wwodwo" />
*This program is based on a deep understanding of [[Post-exertional malaise]] ([[PEM]]), and the importance of staying within the [[energy envelope]] in order to not trigger [[PEM]]<ref name="Workwell201404rae" />
*There is a recognition that any approach to exercise with people with [[ME/CFS]] must be carefully tailored to the individual. There is no one-size fits all<ref name="Workwell201404wwodwo" />
*This approach utilises objective measures such as VO2 max testing and heart rate monitoring to guide the level of activity suitable for the individual<ref name="Workwell201512foar" />
 
===United States Centers for Disease Control===
The [[Centers for Disease Control]] in the [[United States]] recommends patients perform strength and conditioning exercise.<ref>[http://www.cdc.gov/cfs/management/managing-activities.html Chronic Fatigue Syndrome (CFS)]</ref>
 
===UK NICE Guidelines===
British blogger, Sally Burch, has written about the The UK [[National Institute for Health and Care Excellence]] (NICE) guidelines on maintaining a lower heart rate.<ref name="BurchS20151114slideshow" />


==Talks & Interviews==
==Talks & Interviews==
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| url    = http://www.prohealth.com/library/showarticle.cfm?libid=25096  
| url    = http://www.prohealth.com/library/showarticle.cfm?libid=25096  
}}</ref>
}}</ref>
<ref name="Riley,1990">{{Citation
| last1  = Riley                | first1 = MS                  | authorlink1 =
| last2  = O’Brien              | first2 = CJ                  | authorlink2 =
| last3  = McCluskey            | first3 = DR                  | authorlink3 =
| last4  = Bell                | first4 = NP                  | authorlink4 =
| last5  = Nicholls            | first5 = DP                  | authorlink5 =
| title  = Aerobic work capacity in patients with chronic fatigue syndrome
| journal = British Medical Journal    | volume = 301  | issue = 6758  | page = 953-956
| date    = 1990
| pmid    = 1664147
| url    = http://www.bmj.com/content/301/6758/953
}}
</ref>
<ref name="RutherfordG2016">{{citation
<ref name="RutherfordG2016">{{citation
| last1  = Rutherford      | first1 = Gina              | authorlink1 = Gina Rutherford
| last1  = Rutherford      | first1 = Gina              | authorlink1 = Gina Rutherford

Revision as of 06:21, April 26, 2018

Exercise is any movement or activity considered to contribute to general health and well-being. Exercise may be recommended as part of a wellness regimen in chronic illness.[1] [2] However, exercise intolerance is a central feature of ME/CFS, and patients show multiple documented abnormal responses to exercise. Rather than increase health and well-being, ME/CFS patients report that increased activity has reduced their physical and cognitive capacity over time, sometimes permanently.[3]

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.[4] The chemical reactions that break down nutrients -- glycolysis, the Krebs 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.[4]

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.[5]

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.png
PEM chart from the 2015 Institute of Medicine report

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

Read the main page: Post-exertional malaise.

Pain threshold[edit | edit source]

Pain thresholds, or the point at which a stimulus becomes painful, drop in people with CFS (as per the Fukuda criteria) after graded exercise. In healthy controls, pain thresholds rise. This phenomenon has been attributed to a dysfunction of the central anti-nociceptive mechanism in CFS patients.[6]

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.[7] However, patients with ME may experience increased histamine release due to increased mast cell populations.[8]

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.[9]

Musculature[edit | edit source]

Exercise has also been found to induce both early and excessive lactic acid formation in the muscles[10] with reduced intracellular concentrations of ATP and acceleration of glycolysis.[11] Several studies have found abnormal increases in plasma lactate following short period of moderate exercise that cannot be explained by deconditioning.[12] There is evidence of abnormalities in pH handling by peripheral muscle, and possible evidence of an increased acidosis and lactate accumulation.[13][14]

There is also evidence of loss of capacity to recover from acidosis on repeat exercise.[15]

Finally, there is evidence of abnormalities of AMPK activation and glucose uptake in cultured skeletal muscle cells in ME/CFS patients.[16][17]

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.[18][19][20] 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.[19] (see graph at right)

Second day exercise test[edit | edit source]

The seminal study on the response by CFS patients to a 2-day cardiopulmonary exercise test was published by Mark VanNess, Christopher Snell and Staci Stevens in 2007: "Diminished Cardiopulmonary Capacity During Post-Exertional Malaise"[21] A repeat study in 2013 confirmed these results.[22]

In a confirmation study, Doctor Betsy Keller found that patients could not repeat their performance on a second cardiopulmonary exercise test performed a day after the first.[23]

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;[24] see 'Oxidative impairment', below.

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

Read the main page: Two-day cardiopulmonary exercise testing.

Oxidative impairment[edit | edit source]

DeBecker et al (2000) and VanNess et al (2003) found low VO2 during exercise testing;[25][26] Fulle et al (2000) demonstrated oxidative damage to DNA.[27]; and Wong et al (1992) showed defects in oxidative metabolism and poor recovery of ATP after exercise.[28]

Graded exercise[edit | edit source]

Main article: Graded exercise therapy

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

Talks & Interviews[edit | edit source]

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. Check date values in: |date= (help)<nowiki>
  3. ↑ ME Association (May 2015). "ME Association illness management report: no decisions about me without me" (PDF). ME Association. Retrieved April 25, 2018. Cite has empty unknown parameter: |dead-url= (help)
  4. ↑ 4.0 4.1 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.
  5. ↑ 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
  6. ↑ 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
  7. ↑ Romero, S.A.; Hocker, A.D.; Magnum, J.E.; Luttrell, M.J.; Turnbull, D.W. ...; Halliwill, J.R. (2016). "Evidence of a broad histamine footprint on the human exercise transcriptome". The Journal of Physiology. 594 (17): 5009–5023.
  8. ↑ 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.
  9. ↑ Shukla, Sanjay K; Cook, Dane; Meyer, Jacob; et al. (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
  10. ↑ Plioplys, AV; Plioplys, S (1995), "Serum levels of carnitine in chronic fatigue syndrome: clinical correlates", Neuropsychobiology, 32 (3): 132-8, PMID 8544970
  11. ↑ McCully, KK; Natelson, BH; Iotti, S; Sisto, S; Leigh, JS Jr. (May 1996h), "Reduced oxidative muscle metabolism in chronic fatigue syndrome", Muscle Nerve, 19 (5): 621-5, PMID 8618560
  12. ↑ Lane, R J; Barrett, M C; Taylor, D J; Kemp, G J; Lodi, R (May 1998), "Heterogeneity in chronic fatigue syndrome: evidence from magnetic resonance spectroscopy of muscle", Neuromuscul Disord, 1998 May, 8 (3–4): 204-9, PMID 9631403
  13. ↑ Jones, David EJ; Hollingsworth, Kieren G; Taylor, Renee R; Blamire, Andrew M; Newton, Julia L (April 2010), "Abnormalities in pH handling by peripheral muscle and potential regulation by the autonomic nervous system in chronic fatigue syndrome", J Intern Med, 267 (4): 394-401, doi:10.1111/j.1365-2796.2009.02160.x, PMID 20433583
  14. ↑ Lengert, Nicor; Drossel, Barbara (July 2015), "In silico analysis of exercise intolerance in myalgic encephalomyelitis/chronic fatigue syndrome", Biophysical Chemistry, 202: 21–31, doi:10.1016/j.bpc.2015.03.009, PMID 25899994
  15. ↑ Jones, David EJ; Hollingsworth, Kieren G; Jakovljevic, Djordje G; et al. (July 12, 2011), "Loss of capacity to recover from acidosis on repeat exercise in chronic fatigue syndrome", Eur J Clin Invest, 2012 Feb, 42 (2): 186-94, doi:10.1111/j.1365-2362.2011.02567.x, PMID 21749371
  16. ↑ Brown, Audrey E; Jones, David E; Walker, Mark; Newton, Julia L (April 2, 2015), "Abnormalities of AMPK activation and glucose uptake in cultured skeletal muscle cells", PLoS One, 10 (4), doi:10.1371/journal.pone.0122982, PMID 25836975
  17. ↑ Dobberstein, Linda J. (April 20, 2015), "Master Enzyme Switch Deactivated In Chronic Fatigue Syndrome and Fibromyalgia", Wellness Resources
  18. ↑ Light, Alan R; White, Andrea T; Hughen, Ronald W; Light, Kathleen C (July 31, 2009), "Moderate exercise increases expression for sensory, adrenergic, and immune genes in chronic fatigue syndrome patients but not in normal subjects", J Pain, 2009 Oct, 10 (10): 1099-112, doi:10.1016/j.jpain.2009.06.003, PMID 19647494
  19. ↑ 19.0 19.1 Light, Alan R; Bateman, Lucinda; Jo, D; et al. (July 13, 2011), "Gene expression alterations at baseline and following moderate exercise in patients with Chronic Fatigue Syndrome and Fibromyalgia Syndrome", J Intern Med, 2012 271 (1): 64-81, doi:10.1111/j.1365-2796.2011.02405.x, PMID 21615807
  20. ↑ White, Andrea T; Light, Alan R; Hughen, Ronald W; VanHaitsma, Timothy A; Light, Kathleen C (December 30, 2011), "Differences in metabolite-detecting, adrenergic, and immune gene expression after moderate exercise in patients with chronic fatigue syndrome, patients with multiple sclerosis, and healthy controls", Psychosom Med, 2012 Jan, 74 (1): 46-54, doi:10.1097/PSY.0b013e31824152ed, PMID 22210239
  21. ↑ VanNess, J Mark; Snell, Christopher R; Stevens, Staci R (2007), "Diminished Cardiopulmonary Capacity During Post-Exertional Malaise", Journal of Chronic Fatigue Syndrome, 14 (2): 77-85, doi:10.1300/J092v14n02_07
  22. ↑ Snell, Christopher R; Stevens, Staci R; Davenport, Todd E; VanNess, J Mark (October 31, 2013), "Discriminative Validity of Metabolic and Workload Measurements for Identifying People With Chronic Fatigue Syndrome", Physical Therapy (APTA), 93 (11): 1484-1492, doi:10.2522/ptj.20110368, PMID 23813081
  23. ↑ Keller, Betsy A; Pryor, John Luke; Giloteaux, Ludovic (April 23, 2014), "Inability of myalgic encephalomyelitis/chronic fatigue syndrome patients to reproduce VO₂peak indicates functional impairment", J Transl Med, 2014 Apr 23 (12): 104, doi:10.1186/1479-5876-12-104, PMID 24755065
  24. ↑ Nijs, J; Nees, A; Paul, L; De Kooning, M; Ickmans, K; Meeus, M; Van Oosterwijck, J (2014), "Altered immune response to exercise in patients with chronic fatigue syndrome/myalgic encephalomyelitis: a systematic literature review", Exercise Immunology Review, 2014 (20): 94-116., PMID 24974723
  25. ↑ De Becker, P; Roeykens, J; Reynders, M; et al. (November 27, 2000), "Exercise capacity in chronic fatigue syndrome", Archives of Internal Medicine, 160 (21): 3270–3277, doi:10.1001/archinte.160.21.3270, ISSN 0003-9926, PMID 11088089
  26. ↑ VanNess, JM; Snell, CR; Strayer, DR; Dempsey, L; Stevens, SR (June 2003), "Subclassifying chronic fatigue syndrome through exercise testing" (PDF), Medicine and Science in Sports and Exercise, 35 (6): 908–913, doi:10.1249/01.MSS.0000069510.58763.E8, ISSN 0195-9131, PMID 12783037
  27. ↑ Fulle, S; Mecocci, P; Fanó, G; et al. (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
  28. ↑ Wong, R; Lopaschuk, G; Zhu, G; et al. (December 1992), "Skeletal muscle metabolism in the chronic fatigue syndrome. In vivo assessment by 31P nuclear magnetic resonance spectroscopy", Chest, 102 (6): 1716–1722, doi:10.1378/chest.102.6.1716, ISSN 0012-3692, PMID 1446478
  29. ↑ VanNess, J Mark (February 5, 2014), Video: A Realistic Approach to Exercise and Rehabilitation in ME/CFS, Bristol Watershed
  30. ↑ Blake, Nancy (February 10, 2016), "Lost in Translation - The ME-Polio Connection and the Dangers of Exercise", ProHealth website
  31. ↑ Rutherford, Gina; Manning, Philip; Newton, Julia L (January 13, 2016), "Review Article: Understanding Muscle Dysfunction in Chronic Fatigue Syndrome", Journal of Aging Research, 2016 (2016) (Article ID 2497348, 13 pages), doi:10.1155/2016/2497348, PMID 26998359
  32. ↑ Twisk, Frank NM; Geraghty, Keith J (July 11, 2015), "Deviant Cellular and Physiological Responses to Exercise in Myalgic Encephalomyelitis and Chronic Fatigue Syndrome" (PDF), Jacobs Journal of Physiology, 2015, 1(2): 007
  33. ↑ Burch, Sally; VanNess, J Mark (January 17, 2015), Dr VanNess on recent press reports
  34. ↑ Deseret News (May 16, 2014), Sufferers of chronic fatigue, fibromyalgia have hope in new diagnostic tool

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cognition Thought processes, including attention, reasoning, and memory.

physiological Concerning living organisms, such as cells or the human body.  Physio logical (as in physio) is not to be confused with psych ological (emotional stress).

physiological Concerning living organisms, such as cells or the human body.  Physio logical (as in physio) is not to be confused with psych ological (emotional stress).

heart rate (HR) - the number of times the heart beats within a certain time period, usually a minute

post-exertional malaise (PEM) - A notable exacerbation of symptoms brought on by small physical or cognitive exertions. PEM may be referred to as a "crash" or "collapse" and can last for days or weeks. Symptoms can include cognitive impairments, muscle pain, trouble remaining upright (orthostatic intolerance), sleep abnormalities, and gastro-intestinal impairments, and others.

post-exertional malaise (PEM) - A notable exacerbation of symptoms brought on by small physical or cognitive exertions. PEM may be referred to as a "crash" or "collapse" and can last for days or weeks. Symptoms can include cognitive impairments, muscle pain, trouble remaining upright (orthostatic intolerance), sleep abnormalities, and gastro-intestinal impairments, and others.

National Academy of Medicine (NAM) - An American non-profit, non-governmental organization which provides expert advice to governmental agencies on issues relating to biomedical science, medicine and health. Formerly known as the Institute of Medicine (IOM).

microbiome The full collection of microscopic organisms (especially bacteria and fungi) which are present in a particular environment, particularly inside the human body.

cytokine any class of immunoregulatory proteins secreted by cells, especially immune cells. Cytokines are small proteins important in cell signaling that modulate the immune system. (Learn more: me-pedia.org)

two-day cardiopulmonary exercise test (CPET) - A diagnostic test which involves testing an ME/CFS patient exercising on an exercise machine, while monitoring their respiration, especially oxygen consumption. This test is repeated the following day in order to confirm the patient's inability to replicate the first-day performance. This test is thought to be the most objective way to detect post-exertional malaise.

two-day cardiopulmonary exercise test (CPET) - A diagnostic test which involves testing an ME/CFS patient exercising on an exercise machine, while monitoring their respiration, especially oxygen consumption. This test is repeated the following day in order to confirm the patient's inability to replicate the first-day performance. This test is thought to be the most objective way to detect post-exertional malaise.

two-day cardiopulmonary exercise test (CPET) - A diagnostic test which involves testing an ME/CFS patient exercising on an exercise machine, while monitoring their respiration, especially oxygen consumption. This test is repeated the following day in order to confirm the patient's inability to replicate the first-day performance. This test is thought to be the most objective way to detect post-exertional malaise.

graded exercise therapy (GET) - A gradual increase in exercise or activity, according to a pre-defined plan. Focuses on overcoming the patient's alleged unhelpful illness beliefs that exertion can exacerbate symptoms, rather than on reversing physical deconditioning. Considered controversial, and possibly harmful, in the treatment or management of ME. One of the treatment arms of the controversial PACE trial.

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