Treating Chronic Fatigue states as a disease of the regulation of energy metabolism

Bains, William

doi:10.1016/j.mehy.2008.02.022

Cited by 16 publications

(6 citation statements)

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“…Such intolerance, if real, may involve a switch to anaerobic glycolysis, i.e., a reduction in oxidative metabolism and an increase in lactate production (Murrough et al, 2010;Shungu et al, 2012), which constitute the most common metabolic alterations observed in patients with ME/CFS. These characteristics have mainly been attributed to deconditioning, a state characterized by loss of muscle tone and power from prolonged lack of use (Bains, 2008). However, even though increased lactate production was originally noted, possibly related to the reduction of postexercise oxygen delivery (McCully et al, 2004), the same effect could not be substantiated, suggesting a possible decrease in oxygen delivery perhaps due to reduced blood flow (McCully and Natelson, 1999).…”

Section: Metabolic Irregularitiesmentioning

confidence: 99%

“…There are currently no Food and Drug Administration approved drugs for the treatment of ME/CFS and the available psychological, physical, and pharmacological interventions do not appear to be effective (Bains, 2008;Pae et al, 2009;Collatz et al, 2016;Loades et al, 2016;Brigden et al, 2017;Castro-Marrero et al, 2017). Mitochondria appear as one appealing drug target for the treatment of ME/CFS, but other papers reported no apparent alteration in ATP production (Shungu et al, 2012).…”

Section: Does Any Treatment Modality Work?mentioning

confidence: 99%

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Myalgic Encephalomyelitis/Chronic Fatigue Syndrome—Metabolic Disease or Disturbed Homeostasis due to Focal Inflammation in the Hypothalamus?

Hatziagelaki

Adamaki

Tsilioni

et al. 2018

The Journal of Pharmacology and Experimental Therapeutics

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Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex disease characterized by debilitating fatigue, lasting for at least 6 months, with associated malaise, headaches, sleep disturbance, and cognitive impairment, which severely impacts quality of life. A significant percentage of ME/CFS patients remain undiagnosed, mainly due to the complexity of the disease and the lack of reliable objective biomarkers. ME/CFS patients display decreased metabolism and the severity of symptoms appears to be directly correlated to the degree of metabolic reduction that may be unique to each individual patient. However, the precise pathogenesis is still unknown, preventing the development of effective treatments. The ME/CFS phenotype has been associated with abnormalities in energy metabolism, which are apparently due to mitochondrial dysfunction in the absence of mitochondrial diseases, resulting in reduced oxidative metabolism. Such mitochondria may be further contributing to the ME/CFS symptomatology by extracellular secretion of mitochondrial DNA, which could act as an innate pathogen and create an autoinflammatory state in the hypothalamus. We propose that stimulation of hypothalamic mast cells by environmental, neuroimmune, pathogenic and stress triggers activates microglia, leading to focal inflammation in the brain and disturbed homeostasis. This process could be targeted for the development of novel effective treatments.

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Section: Metabolic Irregularitiesmentioning

confidence: 99%

Section: Does Any Treatment Modality Work?mentioning

confidence: 99%

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome—Metabolic Disease or Disturbed Homeostasis due to Focal Inflammation in the Hypothalamus?

Hatziagelaki

Adamaki

Tsilioni

et al. 2018

The Journal of Pharmacology and Experimental Therapeutics

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“…with CFS have a reduced ability for mitochondrial energy production during times of exertion. 38) Fewer mitochondria indicate that maximum energy output cannot be achieved. Accordingly, treatment that restores mitochondrial function or number is considered an effective remedy for fatigue development.…”

Section: Effect Of Cos Administration On the Immobility Period In A Fmentioning

confidence: 99%

Effects of Chitooligosaccharide Lactate Salt on Sleep Deprivation-Induced Fatigue in Mice

Cho

Lee

Song

et al. 2010

Biological & Pharmaceutical Bulletin

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Fatigue is defined as difficulty in initiating or sustaining voluntary activity.1) Despite the prevalence of fatigue in developed countries, the pathophysiology and etiology of fatigue are unknown. Several underlying mechanisms of chronic fatigue syndrome (CFS) have been suggested: for example, allergic and psychological factors, 2) heavy exercise, viral infection, 3) muscle damage, 4,5) CNS disorders and immunological factors.6) Recent studies have demonstrated that energy metabolism is involved in the pathophysiology of fatigue. 7) At the biochemical level, fatigue is represented as the depletion of metabolic energy available to the cells that perform a myriad of functions vital to the survival of an organism.7) Metabolic energy is generated in the form of ATP through oxidative metabolism in the mitochondria. During energy generation, however, reactive oxygen species (ROS) are produced which have the potential to cause mitochondrial damage. The accumulation of mitochondrial dysfunction induced by ROS is proposed as "the mitochondrial theory of aging." 8) In addition, in CFS, impairment of mitochondrial function is frequently observed as represented by reduced oxidative metabolism, 9) increased anaerobic metabolism and subsequently increased lactate production.10,11) Mitochondrial abnormalities and degeneration are also frequently found in patients with CFS,12) reflecting the crucial role of mitochondria in the development of fatigue syndrome. In line with this, a wide variety of natural health products are used or are being developed to replenish the production of cellular energy in the mitochondria. 13)Chitooligosaccharides (COS) is an oligosaccharide made from chitin or chitosan by chemical or enzymatic decomposition.14,15) COS has attracted huge attention as a new biomedical material owing to its water-soluble character and versa- COS is also used as a health food for the treatment of fatigue. It has been suggested that the anti-fatigue effect of COS is related to its improvement of peripheral circulation, anti-oxidation, immunomodulation and nutritional effects. However, the exact mechanism underlying the anti-fatigue effect of COS remains to be elucidated. Sleep disturbance causes excessive energy consumption which leads to daytime fatigue and mental enervation. 26,27) Sleep deprivation increases the levels of the stress hormone cortisol, 28) and elevated cortisol levels induce the development of depression. 29) Researchers from the Karolinska Institute recently reported that decreased production of ATP in mitochondria may aggravate depressive disorders through the induction of high levels of somatization (physical symptoms). 30)In this study, we investigated the effect of COS in a sleep deprivation-induced fatigue model 31) in an effort to explore the utility of COS as a novel functional food with anti-fatigue effects, and examined its efficacy in terms of mitochondrial function and antioxidant activities. We discovered that COS lactate markedly decreased the severity of fatigue, as demonstrated by the d...

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“…CFS is defined as debilitating fatigue of at least six months duration accompanied by at least four of the following case defining symptoms: post exertional fatigue lasting longer than 24 hours, unrefreshing sleep, diffculty concentrating or remembering, headaches unusual in frequency or duration, muscle pain, joint pain, sore throat and tender lymph nodes [ 24 ]. CFS has been associated with similar debilitating conditions such as fibromyalgia, connective tissue disease and mitochondrial deficiency [ 25 , 26 ]. CFS has been shown to affect the endocrine, muscular and immune systems [ 27 - 29 ] and some cases may be triggered by viruses [ 30 ].…”

Section: Introductionmentioning

confidence: 99%

Integrated Weighted Gene Co-expression Network Analysis with an Application to Chronic Fatigue Syndrome

et al. 2008

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Treating Chronic Fatigue states as a disease of the regulation of energy metabolism

Cited by 16 publications

References 75 publications

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome—Metabolic Disease or Disturbed Homeostasis due to Focal Inflammation in the Hypothalamus?

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome—Metabolic Disease or Disturbed Homeostasis due to Focal Inflammation in the Hypothalamus?

Effects of Chitooligosaccharide Lactate Salt on Sleep Deprivation-Induced Fatigue in Mice

Integrated Weighted Gene Co-expression Network Analysis with an Application to Chronic Fatigue Syndrome

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