IOSR Journal of Dental and Medical Sciences (IOSR-JDMS) e-ISSN: 2279-0853, p-ISSN: 2279-0861.Volume 13, Issue 5 Ver. V. (May. 2014), PP 30-33 www.iosrjournals.org www.iosrjournals.org 30 | Page Mitochondrial Dysfunction and Chronic Fatigue Syndromes: Issues in Clinical Care (modified version) Th. Bihari Singh 1 , Kh.Robindro Singh 2 1 (Associate Professor, Department of Psychiatry, Regional Institute of Medical Sciences, Imphal) 2 (Post-graduate Trainee, Department of Psychiatry, Regional Institute of Medical Sciences, Imphal) Abstract : Chronic fatigue syndrome (CFS) is an illness characterized by persistent and relapsing fatigue, often accompanied by numerous symptoms involving various body systems. The etiology of CFS remains unclear. Despite considerable worldwide efforts, no single etiology has been identified to explain the development of chronic fatigue syndrome (CFS). It is likely that multiple factors promote its development, sometimes with the same factors both causing and being caused by the syndrome. However, a number of recent studies have shown oxidative stress may be involved in its pathogenesis. Any dysfunction in the Mitochondria, the key organelle responsible for cellular energy production can result in the excess fatigue and other symptoms that are common complaints in almost every chronic disease. Several components of this system require routine replacement, and this need can be facilitated with natural supplements. A detailed review of the literature suggests a number of marginal nutritional deficiencies may have etiologic relevance. In this review article an attempt has been made to look into these factors in relation to chronic fatigue syndrome. Keywords: fatigue, mitochondria, ATP, energy, apoptosis, oxidative stress I. Introduction Chronic fatigue syndrome (CFS) is a relatively common disorder, particularly in women, affecting 522 women and 291 men per 100,000. 1 In addition to the characteristic persistent fatigue, CFS patients often complain of a number of symptoms including headache, joint pain, gastrointestinal (GI) disturbance, cognitive dysfunction, visual disturbance, and paresthesia. 2,3 Despite considerable worldwide efforts, no single etiology has been found to explain the syndrome. It is likely that multiple factors promote its development, sometimes with the same factors both causing and being caused by the syndrome. Many of these factors constitute specific pathophysiological entities that characterize certain subsets of chronic fatigue patients. Numerous factors appear to promote the development of the syndrome. 4 Mitochondria Structure And Function The largest number of mitochondria is found in the most metabolically active cells, such as skeletal and cardiac muscle and the liver and brain. Mitochondria are found in every human cell except mature erythrocytes (Cohen and Gold, 2001). Mitochondria produce more than 90% of our cellular energy by OXPHOS (Chance et al., 1979). Energy production is the result of two closely coordinated metabolic processes —the tricarboxylic acid (TCA) cycle, also known as the Kreb's or citric acid cycle, and the electron transport chain (ETC). The TCA cycle converts carbohydrates and fats into some ATP, but its major job is producing the coenzymes NADH and FADH so that they, too, are entered into the ETC. 5 Mitochondrial Dysfunction And Chronic Fatigue Syndrome Mitochondrial dysfunction is directly related to excess fatigue. Fatigue is considered a multidimensional sensation that is perceived to be a loss of overall energy and an inability to perform even simple tasks without exertion. Although mild fatigue can be caused by a number of conditions, including depression and other psychological conditions, moderate to severe fatigue involves cellular energy systems. At the cellular level, moderate to severe fatigue is related to loss of mitochondrial function and diminished production of ATP. 6 Suspected aetiologies for Chronic Fatigue Syndrome are viral infections and the post viral fatigue syndrome, fibromyalgia, neurally-mediated hypotension, psychogenic biological dysfunction, low natural killer cell syndrome. Factors suspected of promoting Chronic Fatigue Syndrome include hypoxemia endocrine dysfunction, immune dysfunction, stress-related dysfunction, somatoform disorder, marginal nutritional deficiencies, intestinal hyperpermeability, overgrowth of pathogenic intestinal flora (dysbiosis), food and chemical sensivities, chemical toxicity, heavy metal toxicity. 3,7,8,9,10