Page Synopsis: This page highlights various forms of CFS as well as a focus on two prevailing theories. For complete CFS report which details all theories, visit cfshelp.info/cf2
This page focuses largely on metabolism which is central to the topic (see Metabolic switch may bring on chronic fatigue syndrome | New Scientist https://www.newscientist.com/article/2121162-metabolic-switch-may-bring-on-chronic-fatigue-syndrome/)
Skill Level 4
Relevance:4 Technical Level:4
the condition could in many cases be due to people losing their ability to burn carbohydrate sugars in the normal way to generate cellular energy.
Instead, the cells of people with CFS stop making as much energy from sugar as usual, and start relying more on lower-yielding fuels, such as amino acids and fats. This kind of metabolic switch produces lactate, which can cause pain when it accumulates in muscles.
Together, this would explain both the shortness of energy, and why even mild exercise can be exhausting"
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There are 30 or so theories on CFS all of which can be viewed at the full site https://bra.in/8vGWBa . Here I explore an interesting theory (RCCX) as well as the most likely (most important) scenario theory CDR
The site is still in 'beta' and this is the page that will most be filled in
Page table of contents (click to open) click again to close1) Consistent Abnormalities found in CFS patients2) Reference book on CFS 'CHRONIC FATIGUE SYNDROME: A TREATMENT GUIDE, 2nd Edition' view or download3) Nomenclature 3b) Nomenclature part 24) RCCX Theory5) Cell Danger Response Theory (CDR) 5a) CDR Introduction 5b) CDR Descriptor 5c) CDR Article 1 5d) CDR Article 2 5e) CDR Article 3 5f) Alterations in The HPA Axis during CDR 5g) Echo of Hibernation the vestigial analogues of the Dauer State, Torpor, Dormancy, and Estivation as CDR as it relates to CFS 5h) Focus on brain regions associated with CDR as Vestigial Echo and Analogue of Hibernation etc 5h) Focus on the Hypothalamus 5i) Hypothalamus Charts 5j) Focus on the Hipocampus 5k) CDR Links6) Metabolism Irregularities 6a) Metabolism and Energy Production Dysfunction 6b) Irregularities in Metabolism Charts 6c) Abnormalities in Mitochondrial and Bioenergetic Function 6c) Mitochondria and CFS 6d) Mitochondrial Topics 6e) Abnormalities in Bioenergetic Function 6f) Abnormalities in Metabolism and Bioenergetic Function Charts7) Metabolism Irregularities 7a) Metabolic Pathways associated with CFS 7b) Impairment in Oxidative Phosphorylation oxidative phosphorylation OXPHOS 7c) Impaired Mitochondrial Pyruvate Oxidation, impaired pyruvate catabolism8a) National Library of Medicine search for chronic fatigue syndrome, Sample screenshot 8b) National Library of Medicine search for chronic fatigue syndrome, Clickable capture9) Experiments with CFS click here to closeback to top
1) Consistent Abnormalities Found in CFS Patients
RCCX mutations likely result in a brain wired for danger with sensory sensitivities, enhanced orienting/hyperfocus, enhanced processing/pattern recognition, special abilities and other autistic features due to hormonal shifts in utero/infancy along with exaggerated stress response in setting of low basal cortisol, resulting in associated dysautonomia and high catecholamines. All of this results in a higher likelihood for turning on inflammatory cascades via CRH (increased due to 21 hydroxylase deficiency) with prolonged stress and going into Naviaux’s cell danger response. RCCX mutations are co-inherited: TNXB (hypermobility), C4 (autoimmune and immunodeficiency disorders), CYP21A2 (aberrations in the acute stress response and sex hormones under stress, carriers are known to have low basal cortisol and exaggerated acute stress response
5) CDR Theory
This section describes the Cell Danger Response Theory. Preliminary tests are promising and targeted drugs trialled, however there is still much to be learned and understood. To learn of actionable medicines, true CFS help, please continue onto the next page
5a) CDR Introduction
Cell Danger Response Theory
"In this collaboration with the Prusty Lab in Germany, we show that when HHV-6 leaves a copy of its DNA in a chromosome, it leaves behind a two-edged sword. While over 90% of people are exposed to HHV-6 by 3 years of age, the virus leaves its DNA behind in only a few cells and can remain dormant for life. However, when cells containing a latent copy of HHV-6 are exposed to new infections later in life, or exposed to environmental chemicals, or physical injury, they secrete powerful molecular signals that warn neighboring and distant cells and trigger the cell danger response (CDR). This is the two-edged sword. On the one hand, the secreted signals protect neighboring cells from infection by many RNA and DNA viruses like Influenza A and Herpes Simplex Virus 1. On the other hand, the signals cause mitochondria to change their shape, to fragment, and the cells receiving the signal to lose energy. This paper shows that the serum of more than 90% of patients with ME/CFS contains this mitochondrial fragmenting activity. The activity produced a strong anti-viral effect, but at the cost of profound cellular energy loss"
Cell Danger Response theory is exciting as it makes sense, is testable and explains all the symptoms of CFS. My understanding is as follows: The vast majority carries latent viral load, some respond to it some don't. With CFS infected cells signal neighbors to halt mitochondrial function so as to starve out viral replication. This leads the patient into a hibernation like state and none of the systems are given the required energy, a hypometabolic state: affecting the HPA axis to t1 dominant ('fight or flight') activated Stress Response leading to ANS dysfunction/Dysautonomia, affecting many systems including digestion (t2 dominant state, 'rest and digest')). Without mitochondrial production, adrenaline is used leading to buildup of lactic acid and PEM (Lactate kinetics and mitochondrial respiration in skeletal muscle of healthy humans under influence of adrenaline, Effects of adrenaline on lactate, glucose, lipid and protein metabolism in the placebo controlled bilaterally perfused human leg, MitochondrialDisfunction, Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes). Navieux et all are searching for the signal that tells the neighbors to shut down production, they put blood plasma from CFS patients into healthy controls and the mitochndria of their cells similarly went into the Dauer type state, so we know of the signaling but have not yet identified the mechanism. When they do, medicines can be developed to block the signal, reversing CFS and related autoimmunities. Until that somnogen is discovered, the team is trialling medicines to help alleviate CFS
5f) Chart of Alterations in The HPA Axis as a result of and accompanied by CDR (large picture not linked, for reference only. For linked page click https://bra.in/5j3eQE
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5g) Echo of Hibernation the vestigial analogues of the Dauer State, Torpor, Dormancy, and Estivation as CDR as it relates to CFS
5g) CDR as Vestigial analogue of Hibernation, Dauer State, Torpor, Dormancy, Estivation5g) CDR as Vestigial analogue of Hibernation, Dauer State, Torpor, Dormancy article 2
5h) Focus on brain regions associated with CDR as Vestigial Echo and Analogue of Hibernation etc
5h) Focus on the Hypothalamus 5h) Focus on the Hypothalamus 2 at launch of site, (Version 2) will include article 2
6c) Mitochondrial TopicsNote: To view detailed Mitochondrial topics on full report clickhttps://bra.in/9j3eQE
6d) Click this picture click here to close and return to reportxxto view Mitochondrial topic catagories (needless to say there are many topics and nuances).
6f) Abnormalities in Metabolism and Bioenergetic Function Charts click for full size
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7) Metabolic Pathways associated with CFS
There are 135 known human metabolic pathways 2,709 human enzymes to 896 bioreactions;
203 pathway holes (missing enzymes within the predicted pathways
The disease phenotypes themselves are normally the consequence of the cell's inability to breakdown or produce an essential substrate. However, an enzyme defect at one reaction may affect the fluxes of other subsequent reactions. These cascading effects couple the metabolic diseases associated with subsequent reactions resulting in comorbidity effects. Thus, metabolic disease networks can be used to determine if two disorders are connected due to their correlated reactions