Understanding Muscle Dysfunction in Chronic Fatigue Syndrome

Abstract

Introduction. Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is a debilitating disorder of unknown aetiology, characterised by severe disabling fatigue in the absence of alternative diagnosis. Historically, there has been a tendency to draw psychological explanations for the origin of fatigue; however, this model is at odds with findings that fatigue and accompanying symptoms may be explained by central and peripheral pathophysiological mechanisms, including effects of the immune, oxidative, mitochondrial, and neuronal pathways. For example, patient descriptions of their fatigue regularly cite difficulty in maintaining muscle activity due to perceived lack of energy. This narrative review examined the literature for evidence of biochemical dysfunction in CFS/ME at the skeletal muscle level. Methods. Literature was examined following searches of PUB MED, MEDLINE, and Google Scholar, using key words such as CFS/ME, immune, autoimmune, mitochondria, muscle, and acidosis. Results. Studies show evidence for skeletal muscle biochemical abnormality in CFS/ME patients, particularly in relation to bioenergetic dysfunction. Discussion. Bioenergetic muscle dysfunction is evident in CFS/ME, with a tendency towards an overutilisation of the lactate dehydrogenase pathway following low-level exercise, in addition to slowed acid clearance after exercise. Potentially, these abnormalities may lead to the perception of severe fatigue in CFS/ME.

Altered muscle membrane potential and redox status differentiates two subgroups of patients with chronic fatigue syndrome

“…The present observations confirm the existence of redox disorders in many ME/CFS patients [3][4][5][6][7][8][9][10][11][14][15][16]. These data also show that abnormal redox status is generally present in ME/CFS patients with abnormal muscle membrane excitability, in contrast to patients with no muscle abnormalities.…”

“…Several body systems including the muscular and nervous systems are affected in ME/CFS [3][4][5]. Potential causes of muscle dysfunction in ME/CFS patients may include oxidative stress with reduced heat-shock protein production.…”

The regulation of skeletal muscle fatigability and mitochondrial function by chronically elevated interleukin‐6

“…The difficulty in determining whether this fatigue has central, peripheral or musculoskeletal origins has served as a significant barrier to understanding its aetiology. Skeletal muscle fatigability, or the ability to sustain force over time, relies on several physiological phenomena, most notably, adequate ATP production by mitochondrial respiration and glycolytic pathways and the accumulation of their metabolic byproducts (Fitts, ; Fitts & Holloszy, ; Holloszy & Booth, ; Munkvik, Lunde, & Sejersted, ; Rutherford, Manning, & Newton, ; Thompson, Balog, Riley, & Fitts, ).…”

“…Skeletal muscle fatigability, or the ability to sustain force over time, relies on several physiological phenomena, most notably, adequate ATP production by mitochondrial respiration and glycolytic pathways and the accumulation of their metabolic c 2018 The Authors. Experimental Physiology c 2018 The Physiological Society byproducts (Fitts, 1994;Fitts & Holloszy, 1977;Holloszy & Booth, 1976;Munkvik, Lunde, & Sejersted, 2009;Rutherford, Manning, & Newton, 2016;Thompson, Balog, Riley, & Fitts, 1992).…”

Evaluation of the Protective Effect of Ethanolic Extract of Leaves of Punica Granatum Linn. On Forced Swimming Induced Chronic Fatigue Syndrome in Mice

“…Studies suggest that chronic fatigue syndrome may be associated with altered carnitine homoeostasis in the light of carnitine's role in mitochondrial energy production. Disturbance in carnitine is reflexive of a reduction in carnitine palmitoyl transferase 1 (CPT-1) activity, possibly a result of the accumulation of omega 6 fatty acid [4]. Also elevated levels of inflammatory mediators NFκB which regulates inflammatory and oxidative stress mediators have also been reported in CFS/ME [3].…”