Monday, March 15, 2010

Exercise: Cause and Effect

  Dangerous exercise: lessons learned from dysregulated inflammatory responses
  to physical activity

  Dan Michael Cooper, Shlomit Radom-Aizik, Christina Schwindt, and Frank
  Zaldivar, Jr.

  J Appl Physiol 103: 700-709, 2007.
  First published May 10, 2007;

  Pediatric Exercise Research Center, Department of Pediatrics, University of
  California, Irvine, California

  Exercise elicits an immunological "danger" type of stress and inflammatory
  response that, on occasion, becomes dysregulated and detrimental to health.
  Examples include anaphylaxis, exercise-induced asthma, overuse syndromes,
  and exacerbation of intercurrent illnesses. In dangerous exercise, the
  normal balance between pro- and anti-inflammatory responses is upset. A
  possible pathophysiological mechanism is characterized by the concept of
  exercise modulation of previously activated leukocytes. In this model,
  circulating leukocytes are rendered more responsive than normal to the
  immune stimulus of exercise. For example, in the case of exercise
  anaphylaxis, food-sensitized immune cells may be relatively innocuous until
  they are redistributed during exercise from gut-associated circulatory
  depots, like the spleen, into the central circulation. In the case of
  asthma, the prior activation of leukocytes may be the result of genetic or
  environmental factors. In the case of overuse syndromes, the normally
  short-lived neutrophil may, because of acidosis and hypoxia, inhibit
  apoptosis and play a role in prolongation of inflammation rather than
  healing. Dangerous exercise demonstrates that the stress/inflammatory
  response caused by physical activity is robust and sufficiently powerful,
  perhaps, to alter subsequent responses. These longer term effects may occur
  through as yet unexplored mechanisms of immune "tolerance" and/or by a
  training-associated reduction in the innate immune response to brief
  exercise. A better understanding of sometimes failed homeostatic
  physiological systems can lead to new insights with significant implication
  for clinical translation.

  inflammation; innate immunity; leukocyte; asthma


  Free full text at:  

  [Tom: Somebody summarised this to me with the following "take-home" points:
  - exercise is a major stimulus of the immune system
  - very little research done on exercise in chronic inflammatory states (p.
  705) (which CFS likely has some components of)]

  I just had this e-letter posted. It's not very exciting. I'm hoping that
  others interested in the issue might get interested in ME/CFS.

  Editor said:
  We have sent your commentary to the authors and invited them to submit a

  Numerous exercise abnormalities been found in Chronic Fatigue Syndrome (CFS)

  One curious omission from this interesting review[1] is Chronic Fatigue
  Syndrome (CFS), which is also sometimes known as Myalgic Encephalomyelitis
  (ME). An abnormal response to physical activity is an essential part of
  widely used ME/CFS clinical criteria for adults[2] and children[3]. The most
  frequently used research criteria for CFS [4] require that patients, along
  with suffering from chronic debilitating fatigue lasting at least 6 months,
  have at least 4 out of a list of 8 symptoms, one of which is "postexertional
  malaise lasting more than 24 hours."

  There is a growing body of research on abnormal responses to exercise in
  CFS. A recent review[5] covers the issue in a fairly comprehensive manner -
  here's a summary: "Exertion induces post-exertional malaise with a decreased
  physical performance/aerobic capacity, increased muscoskeletal pain,
  neurocognitive impairment, "fatigue", and weakness, and a long lasting
  "recovery" time. This can be explained by findings that exertion may amplify
  pre-existing pathophysiological abnormalities underpinning ME/CFS, such as
  inflammation, immune dysfunction, oxidative and nitrosative stress,
  channelopathy, defective stress response mechanisms and a hypoactive
  hypothalamic-pituitary-adrenal axis."

  High rates of adverse reactions to graded exercise programs have been
  reported in patients with CFS - sometimes 50% or greater[6].

  CFS remains a fairly poorly understood condition. There is increasing
  evidence that CFS is heterogeneous and this heterogeneity could be of
  relevance to therapeutic programs involving exercise [7,8]. Those interested
  in researching abnormal responses to physical activity, including
  dysregulated inflammatory responses, could find much of interest if they
  chose to study CFS.


  1) Cooper DM, Radom-Aizik S, Schwindt C, Zaldivar F Jr. Dangerous exercise:
  lessons learned from dysregulated inflammatory responses to physical
  activity. J Appl Physiol. 2007 Aug;103(2):700-9. Epub 2007 May 10.

  2) Carruthers BM, Jain AK, De Meirleir KL, Petersn DL, Klimas MD, Lerner AM,
  Bested AC, Flor-Henry P, Joshi P, Powles ACP, Sherkey JA, van de Sande MI
  (2003). "Myalgic encephalomyelitis.chronic fatigue syndrome: Clinical
  working definition, diagnostic and treatment protocols". Journal of Chronic
  Fatigue Syndrome 11 (1): 7-36.

  3) Jason LA, Porter N, Shelleby E, Bell DS, Lapp CW, Rowe K, & De Meirleir
  K. (2008). A case definition for children with Myalgic Encephalomyelitis/
  chronic fatigue syndrome. Clinical Medicine: Pediatrics, 1, 53-57.

  4) Fukuda K, Straus SE, Hickie I, Sharpe MC, Dobbins JG, Komaroff A. The
  chronic fatigue syndrome: a comprehensive approach to its definition and
  study. International Chronic Fatigue Syndrome Study Group. Ann Intern Med.
  1994 Dec 15;121(12):953-9.

  5) Twisk FN, Maes M. A review on cognitive behavorial therapy (CBT) and
  graded exercise therapy (GET) in myalgic encephalomyelitis (ME) / chronic
  fatigue syndrome (CFS): CBT/GET is not only ineffective and not
  evidence-based, but also potentially harmful for many patients with ME/CFS.
  Neuro Endocrinol Lett. 2009;30(3):284-99.

  6) Kindlon T, Goudsmit EM. Graded exercise for chronic fatigue syndrome: too
  soon to dismiss reports of adverse reactions. J Rehabil Med. 2010
  Feb;42(2):184; author reply 184-6.

  7) Jason LA, Corradi K, Torres-Harding S, Taylor RR, & King C. Chronic
  fatigue syndrome: The need for subtypes. Neuropsychology Review 2005, 15,

  8) Kindlon T. Stratification using biological factors should be performed in
  more CFS studies. Psychol Med. 2010 Feb;40(2):352. Epub 2009 Oct 12.

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