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"

"

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

 

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Page table of contents (click to open)                                                                                                  click again to close 1)       Consistent Abnormalities found in CFS patients 2)       Reference book on CFS 'CHRONIC FATIGUE SYNDROME: A TREATMENT GUIDE, 2nd Edition' view or download 3)       Nomenclature  3b)   Nomenclature part 2 4)       RCCX Theory 5)       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 Links 6)       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 Charts 7)       Metabolism Irregularities  7a)   Metabolic Pathways associated with CFS  7b)   Impairment in Oxidative Phosphorylation oxidative phosphorylation  OXPHOS  7c)   Impaired Mitochondrial Pyruvate Oxidation, impaired pyruvate catabolism 8a)    National Library of Medicine search for chronic fatigue syndrome, Sample screenshot  8b)  National Library of Medicine search for chronic fatigue syndrome, Clickable capture 9)      Experiments with CFS                                                                                                                                                                      click here to closeback to top

1) Consistent
     Abnormalities
     Found in CFS
     Patients

The window below is taken from full report at https://bra.in/8pK4xB

 

 

2) Reference book

Reference book on CFS 'CHRONIC FATIGUE SYNDROME: A TREATMENT GUIDE, 2nd Edition' open in new window or download

 

 

3) Nomenclature

This section describes the difference between CFS, M.E., CFIDS etc, followed by a handy guide to those new to CFS.

3a) Nomenclature of CFS (link opens in new window)

 

3b) Nomenclature part 2

 

click here to download the page below

 

 

4) RCCX Theory

 

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"

Human Herpesvirus-6 Reactivation, Mitochondrial Fragmentation, and the Coordination of Antiviral and Metabolic Phenotypes in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

 

 

5b) CDR Descriptor

 

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, Mitochondrial Disfunction, 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

 

 

 

5c) CDR Articles 1
      and 2

                                                         5c) CDR  Article 1 ***

 

                                                           5c) CDR  Article 2 ***

 

 

 

 

 

5e) CDR Article 3

 

To download article as PDF click here

 

 

 

 

 

                                                         5e) Explaining ME/CFS? Prusty / Naviaux Study Ties Infections ***

 

 5f) Alterations in The HPA Axis as a result of and accompanied by CDR

 

To view the HPA axis page on full report, click https://bra.in/5j3eQE

 

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

 

   

>>
click pictures to the right for full size
             <>xclick here to close and return to report                click for full size, click 'x' button to close

 

 

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, Estivation 5g) 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

 

                   5i) Hypothalamus Chartsclick here for charts, link opens in new window, images too large for this pageChart 1 'Myalgic Encephalomyelitis/Chronic Fatigue Syndrome as Disturbed Homeostasis due to Focal Inflammation in the Hypothalamus'

 

 

 

 

                   5j) Focus on the Hipocampus 5j) Focus on the Hipocampus 2                                      at launch of site Version 2 will include article 2

 

 

                   5k) Links (click to open) 

 

 

 

6) Metabolism Irregularities

 

 

 

 

                  6a) Metabolism and Energy Production Dysfunction 2

 

                  6b) Irregularities in Metabolism Chartsclick here for charts, link opens in new window, images too large for this pageChart 1 Chart 2 Chart 3 Chart 4

 

 

6c) Mitochondrial      Topics Note: To view detailed Mitochondrial topics on full report click https://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).

 

Update will included a couple reports

 

 

6e) Abnormalities in    Mitochondrial and    Bioenergetic    Function

 

6e) Abnormalities in Bioenergetic Function

 

                                                              6e) Abnormalities in Bioenergetic Function***

 

6f) Abnormalities in Metabolism and Bioenergetic Function Charts click for full size

 

   

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click pictures to the right for full size
                            <>xclick here to close and return to report

 

click for full size

 

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

 

                            7a) Impairment in Oxidative Phosphorylation oxidative phosphorylation  OXPHOS***

 

                            7b) Impaired Mitochondrial Pyruvate Oxidation, impaired pyruvate catabolism

 

                            7c) Chronic Infection, Redox State and Mitochondria

 

 

8) National Library

 

8a) National Library of Medicine search for chronic fatigue syndrome

       https://www.ncbi.nlm.nih.gov/search/all/?term=chronic%20fatigue%20syndrome

      Sample screenshot

 

 

 

8b) visit site https://www.ncbi.nlm.nih.gov/search/all/?term=chronic%20fatigue%20syndrome

        below is a clickable capture

 

 

9) Experiments with CFS Version 2 of site will include articles

 

 

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