Increased Oxidative and Nitrosative stress

• Oxidative stress levels are raised in chronic fatigue syndrome and are associated with clinical symptoms. Gwen Kennedy, Vance Spence, Jill Belch et al.  Free Radical Biology and Medicine 2005:39:584-589

• Smirnova IV, Pall ML. 2003 Elevated levels of protein carbonyls in sera of chronic fatigue syndrome patients. Mol Cell Biochem 248:93-95.

• Pall ML. 2007 Explaining “Unexplained Illnesses”: Disease Paradigm for Chronic Fatigue Syndrome, Multiple Chemical Sensitivity, Fibromyalgia, Post-Traumatic Stress Disorder, Gulf War Syndrome and Others, Haworth Medical Press, in press.

• Increased plasma peroxides as a marker of oxidative stress in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Maes M, Kubera M, Uytterhoeven M, Vrydags N, Bosmans E.. Med Sci Monit. 2011 Apr;17(4):SC11-5

• Jammes Y, Steinberg JG, Mambrini O, et al. 2005 Chronic fatigue syndrome: assessment of increased oxidative stress and altered muscle excitability in response to incremental exercise. J Intern Med 257:299-310.

• G. Kennedy, V. A. Spence, M. McLaren, A. Hill, C. Underwood and J. Belch, "Oxidative Stress Levels are Raised in Chronic Fatigue Syndrome and are Associated with Clinical Symptoms," Free Radical Biology & Medicine, Vol. 39, No. 5, 2005, pp. 584-589. doi:10.1016/j.freeradbiomed.2005.04.020

• Jammes Y, Steinberg JG, Delliaux S, Brégeon F (2009) Chronic fatigue syndrome combines increased exercise-induced oxidative stress and reduced cytokine and Hsp responses. J Intern Med 266(2):196–206. doi:10.1111/j.1365-2796.2009.02079.x

• Chronic Lyme disease stimulates the same oxidative and nitrosative stress pathways as ME, and the same magnitude or intensity.
  
  
• M. Robinson, S. R. Gray, M.S.Watson, G. Kennedy, A. Hill, J.J. Belch, et al., "Plasma IL-6, its Soluble Receptors and F-Isoprostanes at Rest and During Exercise in Chronic Fatigue Syndrome," Scandinavian Journal of Medicine & Science in Sports, Vol. 13, No. 3,2009, pp. 1-9. doi: 10.1111/j.1600-0838.2009.00895.x

• Pall ML. 2000 Elevated, sustained peroxynitrite levels as the cause of chronic fatigue syndrome. Med Hypoth 54:115-125.

• Pall ML. 2000 Elevated peroxynitrite as the cause of chronic fatigue syndrome: Other inducers and mechanisms of symptom generation. J Chronic Fatigue Syndr 2000;7(4):45-58.

• Pall ML. 2002 Levels of Nitric Oxide Synthase Product Citrulline Are Elevated in Sera of Chronic Fatigue Syndrome Patients. J Chronic Fatigue Syndr 2002 Vol. 10, No. 3-4 , Pages 37-41
  
• Pall ML. 2002 Levels of nitric oxide synthase product citrulline are elevated in sera of chronic fatigue syndrome patients. J Chronic Fatigue Syndr 10(3/4):37-41.

• Morris G, Maes M (2014) Mitochondrial dysfunctions in myalgic encephalomyelitis/chronic fatigue syndrome explained by activated immuno-inflammatory, oxidative and nitrosative stress pathways. Metab Brain Dis 29(1):19–36. doi:10.1007/s11011- 013-9435-x

• Central pathways causing fatigue in neuro-inflammatory and autoimmune illnesses. Morris et al. 2015.

• The Neuro-Immune Pathophysiology of Central and Peripheral Fatigue in Systemic Immune-Inflammatory and Neuro-Immune Diseases Morris et al. 2015.

• Maes M (2009) Inflammatory and oxidative and nitrosative stress pathways underpinning chronic fatigue, somatization and psychosomatic symptoms. Curr Opin Psychiatry 22(1):75–83

• Brown GC, Borutaite V (2004) Inhibition of mitochondrial respiratory complex I by nitric oxide, peroxynitrite and S-nitrosothiols. Biochim Biophys Acta 1658(1–2):44–9

• Pall ML. 2001 Cobalamin used in chronic fatigue syndrome therapy is a nitric oxide scavenger. J Chronic Fatigue Syndr 8(2):39-44.

• Smirnova IV, Pall ML. 2003 Elevated levels of protein carbonyls in sera of chronic fatigue syndrome patients. Mol Cell Biochem 248:93-95.

• Pall ML. 2005. Nitric oxide and the etiology of chronic fatigue syndrome: Giving credit where credit is due. Med Hypotheses. 2005 Jun 2;

• Pall ML. 2001 Common etiology of posttraumatic stress disorder, fibromyalgia, chronic fatigue syndrome and multiple chemical sensitivity via elevated nitric oxide/peroxynitrite. Med Hypoth 57:139-145.

• Pall ML. 2002 NMDA sensitization and stimulation by peroxynitrite, nitric oxide and organic solvents as the mechanism of chemical sensitivity in multiple chemical sensitivity. FASEB J 16:1407-1417.

• Kennedy G, Khan F, Hill A, Underwood C, Belch JF. Biochemical and vascular aspects of pediatric chronic fatigue syndrome. Arch Pediatr Adolesc Med ( 2010 ) 164 : 817 - 823. doi: 10.1001/archpediatrics.2010.157.

• "Oxidative stress corrupts muscle components via lipid peroxidation [367], oxidation of mitochondrial and nuclear DNA [368], protein carbonylation [369], tyrosine nitration [369], and thiol group oxidation [367]."
  The Neuro-Immune Pathophysiology of Central and Peripheral Fatigue in Systemic Immune-Inflammatory and Neuro-Immune Diseases Morris et al. 2015.

• Tomic S, Brkic S, Maric D, Mikic AN. Lipid and protein oxidation in female patients with chronic fatigue syndrome. Arch Med Sci ( 2012 ) 8 : 886 - 891. doi: 10.5114/aoms.2012.31620.

• Suárez A, Guillamo E, Roig T, Blázquez A, Alegre J, Bermúdez J, et al. Nitric oxide metabolite production during exercise in chronic fatigue syndrome: a case - control study. J Womens Health (Larchmt) ( 2010 ) 19 : 1073 - 1077.

• Zhang C, Baumer A, Mackay IR, Linnane AW, Nagley P. Unusual pattern of mitochondrial DNA deletions in skeletal muscle of an adult huma n with chronic fatigue syndrome. Hum Mol Genet ( 1995 ) 4 : 751 - 754. doi: 10.1093/hmg/4.4.751.

• Brown GC, Borutaite V (2004) Inhibition of mitochondrial respiratory complex I by nitric oxide, peroxynitrite and S-nitrosothiols. Biochim Biophys Acta 1658(1–2):44–9

• Oxidative and Nitrosative Stress and Immune-Inflammatory Pathways in Patients with Myalgic Encephalomyelitis (ME)/Chronic Fatigue Syndrome (CFS). Maes et al. Curr Neuropharmacol. 2014 Mar;12(2):168-85.

• Explaining 'Unexplained Illnesses': Disease Paradigm for Chronic Fatigue Syndrome, Multiple Chemical Sensitivity, Fibromyalgia, Post-Traumatic Stress Disorder, and Gulf War Syndrome by Dr. Martin Pall

• Jason LA, Sorenson M, Porter N, Belkairous N (2010), "An Etiological Model for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome", Neuroscience & Medicine, 2011, 2, 14-27, PMID: 21892413

• L. A. Jason, M. Sorenson, N. Porter, M. Brown, A. Lerch, J. Mikovits, L. J. Roberts, K. Sebally, D. Alkazemi and S. Kubow, "Increased HDAC is Associated with Hypocortisolism in Older Adults," Manuscript Submitted for Publication, 2011.

• Maes M, Mihaylova I, Leunis JC: Chronic fatigue syndrome is accompanied by an IgM-related immune response directed against neopitopes formed by oxidative or nitrosative damage to lipids and proteins. Neuro Endocrinol Lett 2006, 27:615-621.

• Maes M, Mihaylova I, Kubera M, Uytterhoeven M, Vrydags N, Bosmans E: Increased 8-hydroxy-deoxyguanosine, a marker of oxidative damage to DNA, in major depression and myalgic encephalomyelitis/chronic fatigue syndrome. Neuro Endocrinol Lett 2009, 30:715-722.

• Maes M, Mihaylova I, Kubera M, Uytterhoeven M, Vrydags N, Bosmans E: Coenzyme Q10 deficiency in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is related to fatigue, autonomic and neurocognitive symptoms and is another risk factor explaining the early mortality in ME/CFS due to cardiovascular disorder. Neuro Endocrinol Lett 2009, 30:470-476.

• Maes M, Kubera M, Uytterhoeven M, Vrydags N, Bosmans E: Increased plasma peroxides as a marker of oxidative stress in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Med Sci Monit 2011, 17:SC11-SC15.

• Maes M: Inflammatory and oxidative and nitrosative stress pathways underpinning chronic fatigue, somatization and psychosomatic symptoms. Curr Opin Psychiatry 2009, 22:75-83.

• Manuel y Keenoy B, Moorkens G, Vertommen J, Noe M, Neve J, De Leeuw I: Magnesium status and parameters of the oxidant-antioxidant balance in patients with chronic fatigue: effects of supplementation with magnesium. J Am Coll Nutr 2000, 19:374-382.

• Manuel-y-Keenoy B, Moorkens G, Vertommen J, De Leeuw I: Antioxidant status and lipoprotein peroxidation in chronic fatigue syndrome. Life Sci 2001, 68:2037-2049.

• Maes M, Mihaylova I, Leunis JC: Chronic fatigue syndrome is accompanied by an IgM-related immune response directed against neopitopes formed by oxidative or nitrosative damage to lipids and proteins. Neuro Endocrinol Lett 2006, 27:615-621.

• Vecchiet J, Cipollone F, Falasca K, Mezzetti A, Pizzigallo E, Bucciarelli T, De Laurentis S, Affaitati G, De Cesare D, Giamberardino MA: Relationship between musculoskeletal symptoms and blood markers of oxidative stress in patients with chronic fatigue syndrome. Neurosci Letters 2003, 335:151-154.

• Miwa K, Fujita M: Fluctuation of serum vitamin E (alpha-tocopherol) concentrations during exacerbation and remission phases in patients with chronic fatigue syndrome. Heart Vessels 2010, 25:319-323.

• Maes M, Mihaylova I, Kubera M, Bosmans E: Not in the mind but in the cell: increased production of cyclo-oxygenase-2 and inducible NO synthase in chronic fatigue syndrome. Neuro Endocrinol Lett 2007, 28:463-469.

• Jammes Y, Steinberg JG, Delliaux S: Chronic fatigue syndrome: acute infection and history of physical activity affect resting levels and response to exercise of plasma oxidant/antioxidant status and heat shock proteins. J Intern Med 2011, 272:74-84.

• Increased ventricular lactate in chronic fatigue syndrome. III. Relationships to cortical glutathione and clinical symptoms implicate oxidative stress in disorder pathophysiology.Shungu DC, Weiduschat N, Murrough JW, Mao X, Pillemer S, Dyke JP, Medow MS, Natelson BH, Stewart JM, Mathew SJ. NMR Biomed. 2012 Sep;25(9):1073-87.

• Vitamin E Deficiency
  Miwa K, Fujita M: Fluctuation of serum vitamin E (alpha-tocopherol) concentrations during exacerbation and remission phases in patients with chronic fatigue syndrome. Heart Vessels 2010, 25:319-323.

• Coenzyme Q10 Deficiency
  Maes M, Mihaylova I, Kubera M, Uytterhoeven M, Vrydags N, Bosmans E: Coenzyme Q10 deficiency in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is related to fatigue, autonomic and neurocognitive symptoms and is another risk factor explaining the early mortality in ME/CFS due to cardiovascular disorder. Neuro Endocrinol Lett 2009, 30:470-476.

• Glutathione Deficiency
  Shungu DC, Weiduschat N, Murrough JW, Mao X, Pillemer S, Dyke JP, Medow MS, Natelson BH, Stewart JM, Mathew SJ: Increased ventricular lactate in chronic fatigue syndrome. III. Relationships to cortical glutathione and clinical symptoms implicate oxidative stress in disorder pathophysiology. NMR Biomed 2012, 25:1073-1087.

• Magnesium Deficiency
  Manuel y Keenoy B, Moorkens G, Vertommen J, Noe M, Neve J, De Leeuw I: Magnesium status and parameters of the oxidant-antioxidant balance in patients with chronic fatigue: effects of supplementation with magnesium. J Am Coll Nutr 2000, 19:374-382.

• Richards RS, Roberts TK, McGregor NR, Dunstan RH, Butt HL: Blood parameters indicative of oxidative stress are associated with symptom expression in chronic fatigue syndrome. Redox Rep 2000, 5:35-41.

• Animal Models
  • Gupta A, Vij G, Sharma S, Tirkey N, Rishi P, Chopra K: Curcumin, a polyphenolic antioxidant, attenuates chronic fatigue syndrome in murine water immersion stress model. Immunobiol 2009, 214:33-39.
  • Singh A, Naidu PS, Gupta S, Kulkarni SK: Effect of natural and synthetic antioxidants in a mouse model of chronic fatigue syndrome. J Med Food 2002, 5:211-220.
  • Rosa EF, Takahashi S, Aboulafia J, Nouailhetas VL, Oliveira MG: Oxidative stress induced by intensend exhaustive exercise impairs murine cognitive function. J Neurophysiol 2007, 98:1820-1826.

• Scandinavian Journal of Medicine and Science in Sports 2009: doi:10.1111/j.1600-0838.2009.00895.x

• Jammes, Y., Steinberg, J. G. and Delliaux, S. (2012), Chronic fatigue syndrome: acute infection and history of physical activity affect resting levels and response to exercise of plasma oxidant/antioxidant status and heat shock proteins. Journal of Internal Medicine, 272: 74–84. doi: 10.1111/j.1365-2796.2011.02488.x

• Miwa K, Fujita M. Fluctuation of serum vitamin E (alpha-tocopherol) concentrations during exacerbation and remission phases in patients with chronic fatigue syndrome. Heart Vessels. 2010;25:319–23.

• Fulle et al. 2000;

• Richards et al. 2000

• Logan et al. 2001

• Kim C, Kim JY, Kim JH (2008) Cytosolic phospholipase A(2), lipoxygenase metabolites, and reactive oxygen species. BMB Rep 41(8):555–9 366.

• Vasilaki A, van der Meulen JH, Larkin L, Harrison DC, Pearson T, Van Remmen H, Richardson A, Brooks SV, Jackson MJ, McArdle A (2010) The age-related failure of adaptive responses to contractile activity in skeletal muscle is mimicked in young mice by deletion of Cu, Zn superoxide dismutase. Aging Cell 9(6):979–90. doi:10.1111/ j.1474-9726.2010.00635.x

• Fulle S, Pietrangelo T, Mancinelli R, Saggini R, Fanò G. Specific correlations between muscle oxidative stress and chronic fatigue syndrome: a working hypothesis. J Muscle Res Cell Motil. 2007;28:355–62.
• An article in the journal Life Science described a study that showed that patients with CFS had lower serum transferrin levels and higher lipoprotein peroxidation. These results indicate that patients with CFS have increased susceptibility of LDL and VLDL to copper-induced peroxidation and that this is related both to their lower levels of serum transferrin and to other unidentified pro-oxidizing effects of CFS (Manuel y Keenoy et al. 2001).