Too many ME/CFS hypotheses! Where do you lean? (POLL)

[sometexan84]

Overwhelmed by all of the hypotheses out there? Well so am I.

IDO Metabolic Trap (Robert Phair)
Inhibition of IDO1 creates the possibility of metabolic bistability in cells expressing the kynurenine pathway

Vagus Nerve Hypothesis (Michael VanElzakker)
In some individuals, the symptoms of chronic fatigue syndrome (CFS) are caused by an infection in or around the vagus nerve

Viral Cardiomyopathy (Martin Lerner)
CFS is a persistent nonpermissive herpes virus infection of the heart

Cell Danger Response (Robert Naviaux)
A hypometabolic survival state that is triggered by encounters with chemical, physical, or biological threats that exceed the cellular capacity for homeostasis

Enteroviral infection hypothesis (John Chia, Byron Hyde, Melvin Ramsay)
A significant subset of patients had their illness triggered by an enterovirus, one that might continue to persist and contribute to symptoms

Ken Lassesen's "gut" model (Ken Lassesen)
CFS is caused by a stable dysfunction of the gut microbiome

Methylation cycle (Rich Van Konynenburg)
A core component of the pathophysiology of chronic fatigue syndrome involves a partial block in the methylation cycle

Nitric oxide hypothesis (NO/ONOO cycle) (Martin Pall)
Viral or bacterial infection induces one or more cytokines that lead to increased nitric oxide levels, which react with superoxide radicals to generate the potent oxidant peroxynitrite

Nitrogen metabolism (Christopher Armstrong)
Nitrogen-containing by-products of energy production accumulate more readily in the cells of people with ME / CFS, damaging the cells and their process of producing energy

Omega 3 fatty acid (Basant Puri)
ME/CFS symptoms due to abnormal production of eicosanoids, signaling molecules involved in inflammation that are produced from fatty acids found in cell membranes

RCCX Theory (Sharon Meglathery)
Co-inheritance of the highly mutable genes of the RCCX module may confer vulnerability to familial clusters of overlapping syndromes of chronic illness (hyper-mobility, autoimmune disease, CFS/ME, MCAS, POTS, and 80% of Psychiatric and neurodevelopmental disorders)

Mackay-Tate hypothalamus hypothesis (Mackay A, Tate WP)
Neuroinflammation causing dysfunction of the limbic system and its hypothalamus together with a consequently disrupted autonomic nervous system

B2 adrenergic receptor dysfunction (Klaus Wirth, Carmen Scheibenbogen)
An autoimmune process attacking the B2 adrenergic receptor

Hypercoagulation theory (David Berg, Joseph Brewer)
An infection causing excessive coagulation (due to a genetic or an acquired coagulation defect), where the immune system is unable to effectively fight.

Cortene's hypothesis (Lucinda Bateman, Cortene inc)
Upregulation of CRF2 in the limbic system deregulates serotonin, norepinephrine (and other neurotransmitters) and cortisol, leading to wide-ranging dysfunction.

 

[Davsey27]

I think it may possible that there are truths in alot of these.Also more than 1 cause is plausible like more than 1 thing that goes wrong and leads to a plane crash
So much yet to be discovered.Perhaps different causes in different subclasses .Though I think whatever the cause is the effect on the mitochondria may play a large role

 

[sometexan84]

I agree in both cases. I think many of these could be correct. And I believe that cellular mitochondrial metabolism plays a massive role.

 

[nyanko_the_sane]

The results are looking spread out across the board. Which will rank supreme? Only time will tell.

Here's a video to promote team Trap.

 

[sometexan84]

@nyanko_the_sane good call!

Vagus Nerve Hypothesis (Michael VanElzakker)
In some individuals, the symptoms of chronic fatigue syndrome (CFS) are caused by an infection in or around the vagus nerve

Cell Danger Response (Robert Naviaux)
A hypometabolic survival state that is triggered by encounters with chemical, physical, or biological threats that exceed the cellular capacity for homeostasis

Enteroviral infection hypothesis (John Chia, Byron Hyde, Melvin Ramsay)
A significant subset of patients had their illness triggered by an enterovirus, one that might continue to persist and contribute to symptoms

Methylation cycle (Rich Van Konynenburg)
A core component of the pathophysiology of chronic fatigue syndrome involves a partial block in the methylation cycle

Nitric oxide hypothesis (NO/ONOO cycle) (Martin Pall)
Viral or bacterial infection induces one or more cytokines that lead to increased nitric oxide levels, which react with superoxide radicals to generate the potent oxidant peroxynitrite

 

[sometexan84]

Nitrogen metabolism (Christopher Armstrong)
Nitrogen-containing by-products of energy production accumulate more readily in the cells of people with ME / CFS, damaging the cells and their process of producing energy

 

[Judee]

I really do still believe it is an infection or multiple infections--viral and/or bacteria or even parasitic could be in there somewhere too that caused this for most of us. Maybe at the time of infection we were more vulnerable because of chemical exposure, amalgams, or something else so that others who caught whatever got better when we did not.

The initial infection, whatever it is, made us vulnerable to later infections or stress events. I think I've read two ME/CFS or infectious disease doctors that said the 2nd event is likely the whammy that triggers the ME. I think one doctor was Dr Chaney and the other, I believe, was Dr Garth Nicholson PhD.

I do think these infections go on to damage organs--heart, brain, whatever. For me, I think it (they) damaged my heart. That seems to be where my fatigue is centered. The brain fog is likely because of brain damage and inflammation in the brain and brain stem.

Those doctors in UK that are post-covid said that the aftermath affected the organs in 60% of the cases in their group and it sounds like they did have MRIs of their hearts. (sorry can't find that article but it looked like this one: https://blogs.bmj.com/bmj/2020/06/2...d-cameras-unknown-limits-and-harsh-penalties/)

Dr Davis was looking at Suramin and that is for a parasitic infection, trypanasomes. He also said this disease is nearly identical to that genetically.

These infections are stealthy and covert. EBV can hide in B-cells. Lyme bacteria can morph into dormant forms. Not to mention we still do not have great testing for so many of them and by my understanding these pathogens don't usually stay in the blood, so blood tests have limited ability to detect them at every stage.

 

[nyanko_the_sane]

These infections are stealthy and covert. EBV can hide in B-cells. Lyme bacteria can morph into dormant forms. Not to mention we still do not have great testing for so many of them and by my understanding these pathogens don't usually stay in the blood, so blood tests have limited ability to detect them at every stage.

I can attest to the damage EBV does to the body. It is the gift that keeps on giving that nobody wants.

 

[Hip]

That's a great list of ME/CFS theories and hypotheses!

You can find a few more here.

I guess it can be overwhelming to see a large list of ME/CFS hypotheses all at once. For patients who have had ME/CFS for 10 or 20 years or longer, these hypotheses would have appeared one by one, when they were first published. At the time they are first proposed, you get lot of discussion about them on Phoenix Rising, and they become the interesting topic of the moment, so you learn about them via the discussion.

People are always hoping that the latest hypothesis will deliver the answers, and provide a cure or good treatment for ME/CFS that they can employ for their own ME/CFS. So that's why there's the interest.


In terms of which hypotheses might hold some truth, it's quite possible that several are actually going at the same time in ME/CFS. If we assume that ME/CFS has one primary cause (at present not known), with that cause throwing a spanner into the workings of the body, then you might expect many downstream effects, with multiple bodily systems going out of whack. This happens with other diseases.

So some of these hypotheses could be true, but they might not be the primary cause of ME/CFS, but rather secondary downstream effects, which of course may still contribute to ME/CFS symptoms.

For example, if for the sake of argument we assume that ME/CFS is caused by a chronic intracellular viral infection (primary cause), then we know that the immune system secretes nitric oxide (NO) in order to fight pathogens, and a chronic secretion of NO might well throw the whole nitric oxide system out of balance (leading to the Pall NO/ONOO hypothesis).

Or conceivably a chronic intracellular infection might trigger the cell danger response (even though Naviaux does not think viral infections cause ME/CFS).

Or the viral infection may trigger some autoimmunity, resulting in autoantibodies which target the adrenergic receptors, and the muscarinic cholinergic receptors, leading to POTS.



So for me, I think all these hypothesis are interesting, and may have relevance for ME/CFS.

 

[Rebeccare]

@sometexan84 thank you for compiling all of this information into one place! I also appreciate the brief summaries of each hypotheses you have written up.

 

[Wishful]

My thanks too for the compilation and links. I followed up the link to the MacKay-Tate hypothesis, and that's the closest fit to my own vague hypothesis for ME. I hadn't read that one before.

 

[sue1234]

I am going through with the path of Berg's hypercoagulation theory at the moment. Hint was I felt better when in the hospital and given anti-coagulants. After years of noticing this effect, I finally saw a doctor who understands it and did the initial testing and found I have hypercoagulation going on. So the journey begins, and will see if that is/was the root cause and everything falls into place during and after treatment.

 

[Davsey27]

That's a great list of ME/CFS theories and hypotheses!

You can find a few more here.

I guess it can be overwhelming to see a large list of ME/CFS hypotheses all at once. For patients who have had ME/CFS for 10 or 20 years or longer, these hypotheses would have appeared one by one, when they were first published. At the time they are first proposed, you get lot of discussion about them on Phoenix Rising, and they become the interesting topic of the moment, so you learn about them via the discussion.

People are always hoping that the latest hypothesis will deliver the answers, and provide a cure or good treatment for ME/CFS that they can employ for their own ME/CFS. So that's why there's the interest.


In terms of which hypotheses might hold some truth, it's quite possible that several are actually going at the same time in ME/CFS. If we assume that ME/CFS has one primary cause (at present not known), with that cause throwing a spanner into the workings of the body, then you might expect many downstream effects, with multiple bodily systems going out of whack. This happens with other diseases.

So some of these hypotheses could be true, but they might not be the primary cause of ME/CFS, but rather secondary downstream effects, which of course may still contribute to ME/CFS symptoms.

For example, if for the sake of argument we assume that ME/CFS is caused by a chronic intracellular viral infection (primary cause), then we know that the immune system secretes nitric oxide (NO) in order to fight pathogens, and a chronic secretion of NO might well throw the whole nitric oxide system out of balance (leading to the Pall NO/ONOO hypothesis).

Or conceivably a chronic intracellular infection might trigger the cell danger response (even though Naviaux does not think viral infections cause ME/CFS).

Or the viral infection may trigger some autoimmunity, resulting in autoantibodies which target the adrenergic receptors, and the muscarinic cholinergic receptors, leading to POTS.



So for me, I think all these hypothesis are interesting, and may have relevance for ME/CFS.

@Hip

Good points

I think it may be possible that chronic viral infection(s) may be triggering the cell danger response as well as an infection that is hit and run though it may be tricky to know if it actually left

Probably same can be applied to mold,lyme,emf,chemicals and other triggers or combo of triggers.

 

[Rufous McKinney]

I think I've read two ME/CFS or infectious disease doctors that said the 2nd event is likely the whammy that triggers the ME.

I'm a believer in these- Second Events. Either intensely stressful in the mental emotional category- or intensely stressful to the body in terms of chemical exposures, or subsequent infections....

(I've likely experienced several in my lifetime).

I did not get meaningful PEM- for about 40 years of having something I'd describe then as: chronic eppstein barr, or now we would say "mild" ME. Cycles of getting run down...but not real frequent...would take a while to pull out of. Always felt like a low grade fever, lymphatic, air hungar, exhausted. But then I"d pull out and I did not have- these strange neurological issues going on...until things got much much more severe and that happened over an almost exact Six Month Time frame. (fire consumes everything except our bodies, Dec 6; I'm starring in an episode of ER by July 5).

 

[xebex]

I believe that it’s is most likely a combination of several or possibly even all of these theories. Most likely triggered by any number of viruses most likely from the herpes family, then possibly a nasty case of a non herpes virus could kick it off though the process was probably already in action before that, and that is why it sometimes looks like stress or a chemical exposure is the “cause” in genetically (potentially RCCX or other gene) susceptible people.

 

[wastwater]

Genetics and The complement immune system is interesting to me and Thrombospondin-1 platelets and platelet activation
I wonder if I may have aHUS

 

[Wishful]

I believe that it’s is most likely a combination of several or possibly even all of these theories.

I think it's unlikely that the core of ME is a combination of multiple factors; the more factors required, the fewer cases there would be. I think it's more likely that several of these theories apply to specific downstream symptoms or even upstream sensitivities or predisposition to develop them.

 

[xebex]

I think it's unlikely that the core of ME is a combination of multiple factors; the more factors required, the fewer cases there would be. I think it's more likely that several of these theories apply to specific downstream symptoms or even upstream sensitivities or predisposition to develop them.

That’s what I mean, the virus triggers all or a number of these responses.

 

[sometexan84]

thank you for compiling all of this information into one place! I also appreciate the brief summaries of each hypotheses you have written up.

My thanks too for the compilation and links. I followed up the link to the MacKay-Tate hypothesis, and that's the closest fit to my own vague hypothesis for ME. I hadn't read that one before.

You are welcome! It was time-consuming, but fun.

I am going through with the path of Berg's hypercoagulation theory at the moment.

I had seen that one. I don't recall why I chose not to add it. But I went ahead and added it now. (wish it would let me re-order the poll so it would stay in alpha order!)

I really do still believe it is an infection or multiple infections

I guess I chose not to put "Viral onset hypothesis" or "Multiple infection hypothesis" because I was under the impression most of us thought this was the case already. And because I felt those seemed sort of vague, whereas the other hypotheses represented more specific potential outcomes of the infections (in many cases).

I've also added Cortene's hypothesis

 

[sometexan84]

@bertiedog @Art Vandelay @Judee @pattismith @Jackb23 @Imse @lint7 @BrightCandle
You guys voted "None". What hypothesis do you think I should add?

I would very much like your opinions. I think others would as well.

@Hip
Hip, you are so crazy. Why you never vote on these things? lol