Journal of IiME Volume 2 Issue 2 www.investinme.org The Physiology of Exercise Intolerance in Patients with Myalgic Eencephalomyelitis (ME) and the Utility of Graded Exercise Therapy By S. Pierce* & P.W. Pierce † * Department of Structural and Functional Biology, University of Insubria, Via J.H. Dunant 3, I-21100 Varese, Italy. simon.pierce@uninsubria.it † George Eliot Building, Clifton Campus, Nottingham Trent University, Nottingham, NG11 8NS, United Kingdom. ABSTRACT This review discusses the suitability of graded exercise therapy for the treatment of myalgic encephalomyelitis (ME), based on current knowledge of the underlying physiology of the condition and the physiological effects of exertion on ME patients. A large body of peerreviewed scientific literature supports the hypothesis that with ME an initial over-exertion (a period of metabolic stress) in conjunction with viral infection depletes concentrations of the metabolic regulator glutathione, initiating a cascade of physiological dysfunction. The immune system and muscle metabolism (including the muscles of the cardiovascular system) continually compete for glutathione, inducing a state of constant stress that renders the condition chronic. The impairment of a range of functions means that subtly different suites of symptoms are apparent for different patients. Graded exercise therapy has proven useful for a minority of these, and the exacerbation of symptoms for the majority is not subjective but has a physiological basis. Blanket recommendation of graded exercise therapy is not prudent for such a heterogeneous group of patients, most of which are likely to respond negatively to physical activity. Following exercise, patients with myalgic encephalomyelitis (ME) uniquely exhibit exacerbated symptoms and a suite of measurable physiological changes indicative of stress (sub-optimal metabolic performance; e.g. reduced respiration and heart rate, increased glycolysis and lactic acid production, and concomitant limitation of activity1-5). Although these symptoms may not be universal6, a significant subgroup of ME patients are affected in this manner7. The issue of exercise is critical for the treatment of the condition as one school of thought recommends “graded exercise therapy” as a general remedy for ME whilst another recognises that exercise intolerance may have an underlying physiological cause that may actually be aggravated by physical exertion. This difference of opinion influences policy: graded exercise therapy is one of the principal recommendations of the current Invest in ME (Charity Nr. 1114035) NICE draft guidelines for the treatment of patients “mildly to moderately affected” by ME (p. 21, lines 20 to 23) 8. Although recent general reviews of ME exist911, our aim is to specifically review evidence for the mechanisms by which physical activity affects ME patients, and to investigate how graded exercise therapy may help or hinder recovery. Although no single randomised controlled study has yet attempted to investigate every aspect of ME, the combined weight of empirical evidence to date indicates that the condition is characterised by a complex series of events involving reserves of metabolic regulators such as glutathione, muscle metabolism and the cardiovascular system. A significant body of literature suggests that these imbalances are associated with a (continued on page 56) Page 55/74

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