The NO/ONOO-Vicious Cycle Mechanism as the Cause of Chronic Fatigue Syndrome/Myalgic Encephalomyelitis pp. 27-56
Authors: Martin L. Pall, Washington State University and Research Director, The Tenth Paradigm Research Group
Abstract: Cases of chronic fatigue syndrome/mylagic encephalomyelitis (CFS) are reported to be initiated by nine different short-term stressors, each of which increases levels of nitric oxide in the body. Elevated nitric oxide, acting through its oxidant product, peroxynitrite, initiates a local biochemical vicious cycle, the NO/ONOO- cycle, which is proposed to be the cause of CFS and related diseases. Evidence supporting this cycle mechanism in CFS comes from each of the following types of evidence: Case initiation by such stressors, the extensive evidence supporting the existence of individual cycle mechanisms, evidence showing that various cycle elements are elevated in CFS cases, evidence for a basically local mechanism in CFS and related diseases, evidence from CFS animal models, genetic evidence from genetic polymorphism studies and evidence from clinical trials of agents predicted to down-regulate the NO/ONOO-cycle. Each of the five principles underlying the NO/ONOO- cycle mechanism is supported by one or more of the above described types of evidence. The cycle involves oxidative stress, excessive nitric oxide synthase (NOS) activity, mitochondrial dysfunction, inflammatory biochemistry, excitotoxicity including excessive NMDA activity and tetrahydrobiopterin depletion. There is evidence, ranging from extensive to modest, supporting roles for each of these in CFS.
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