What are all the theories of what causes ME CFS?

[Martin aka paused||M.E.]

Hey Martin, hope you doing well!

If I remember well you shared a picture somewhere of some substances to manage glial cell activation right? It was from some webinar, do you recall which webinar was this?

Yes it was by Jarred Younger on the ISCFS/ME. I PM you (copyrights)

 

[lenora]

Good Morning.......Yes, the brain and gut cell "theory" came out a few years ago....and it makes perfect sense.

Just think of how we can feel if we're in an argument with anyone, even a family member. The stomach immediately tightens up, you can feel it and I think it's that feeling that leaves us upset for the next couple of hours. I know that in my case, I can expect an immediate flare-up of stomach and blood pressure issues.

Personally, I really think one of the very best helpers we have is with our breathing. That helps and helps rather fast. There are a lot of youtube videos on breathing so if you're interested, please go there. Yours, Lenora.

 

[dyllanmurphy]

This may have been covered already, but I'll just point out the obvious that there may be multiple subtypes each more closely corresponding to other diseases but with the same endpoint.

For example, EDS, pesticide-caused multisystem illness, tickborne disease illness, and others all can be associated with CFS-like symptoms.

 

[gregh286]

Gut leak causing overactive immune response and stress cellular shutdown supported by of an abnormal cascade of hormonal imbalance.
Maybe short bowel syndrome exists in some.
Lactic acid pumped out by lower gut and colon in breakdown.
We have high serum lactate had it measured a few times....don't think anyone nailed is it caused by gut bacteria or awful cellular respiration.

Lactoferrin and enzymes I use best.
Ala mops up lactate pretty well. Infrared suana in home...used daily to extract lactic.

This certainly is my case as I can make my gut better and worse With diet and symptoms tend to be correlated alongside.

When my gut at worse every food will crash me after 15 mins.

 

[gregh286]

In the meantime also I found out my high trigger foods like grains even can crash me in extract form
Barley extract
Yeast extract
Gluten free beer
Whiskey

Now these things are in PPM gluten....parts pet million but body still goes bananas
That the level of sensitivity we deal with

I found out if it started life as a grain...its out the window...no matter what they did to it

But I also learned about much less talked about gliadin which could be the culprit after all and much less is known about it.

 

[ljimbo423]

Gut leak causing overactive immune response and stress cellular shutdown

After 14 years and over 20,000 hours of research, I've reached the same conclusion. If I go from my low carb diet of about 80 gms a day, to 150 gms a day, within 2 weeks my level of functioning drops from about a 6 to a 2.

Carbs feed inflammatory bacteria in the gut, and cause me profound fatigue, nausea and malaise. The increase in carbs cause me to become mostly bedridden within 2 weeks after I increase them.

 

[gregh286]

After 14 years and over 20,000 hours of research, I've reached the same conclusion. If I go from my low carb diet of about 80 gms a day, to 150 gms a day, within 2 weeks my level of functioning drops from about a 6 to a 2.

Carbs feed inflammatory bacteria in the gut, and cause me profound fatigue, nausea and malaise. The increase in carbs cause me to become mostly bedridden within 2 weeks after I increase them.

Yep on same page.
Grain products kills for days.....Air hunger....palpitations.....anxiety attacks.....quite the mad carry on.
We know not everyone in same boat but this highlights the body wide effect of what the body see as hostile.
Noticed that with carbs....the lactate starts to build then the issue get worse....fog....lead legs....heaviness

My stable diet revolves around tuna....eggs....tomatoes
.Olives and mushrooms for light lunch
Evening are meat and veg. Low carb

Try lactoferrin it's good juice.
Forget that probios crap....they never get there and its like trying to balance a snooker ball on a tripwire.

Sugary foods make my heart race ...that's a given....I think the high GI of the chocolate etc hitting GI tract and moving too fast.....that's been a constant in this saga of mine

 

[gregh286]

I know lots of papers floating about but the standard one resonated well with me.

https://www.healthrising.org/blog/2021/09/23/fermented-foods-fiber-stanford-gut-study/

 

[gregh286]

One of the worst experience I had on hols a few years back....cruising nicely 3.or 4 days in. Low carbs....low sugar alcohol like gin or rum.
Complacency set in.
Had a rake of baileys liquor one afternoon unwittingly knowing how much sugar was in.
I worked out about 180g of sugar in just over an hour.

HR went from 60 to 160.
Couldn't get it down. Cold baths....elevated feet....it was the worst couple hours of my life. Body just could not deal with the sugar levels.
Suffice to say I was pure lactic for a day.or 2.
It spooked me mentally big time.
Almost being like a diabetic without an insulin issue?
Fckin mental.
Turn green now if I see a baileys

 

[sometexan84]

I know lots of papers floating about but the standard one resonated well with me.

https://www.healthrising.org/blog/2021/09/23/fermented-foods-fiber-stanford-gut-study/

This healthrising blog... I'd like to comment about something here...

The article says....

Indeed, Hanson’s 2018 study did not find significant evidence of dysbiosis in ME/CFS but Lipkin’s 100-person 2017 study, Hanson’s 2016 study, and a 2013 DeMeirleir study did.

Just want to point out that this study that did NOT find dysbiosis in ME/CFS was based on Eukaryotes in stool... which do NOT include either bacteria or archaea. It's these 2 that you should be checking. So come on, get real. Cort, pls do a better job offering some more context here, so people know...

Oh Hey! this guy knows what's up, lol...
Vijay, I like the cut of your jib.

Folks! I understand patients, and non-scientists like to just read Abstracts. Totally understandable. But WHY do I get the feeling that actual research scientists consistently fail to read more than the TL;DR...

It's like.. it wasn't until September of 2021, until an article came out that called out all the previous BS Enterovirus studies in ME/CFS because they decided to read more than the Abstract. They looked at the measurements, the methods, etc. And then we all finally see why researchers just decided to STOP looking into enterovirus in ME/CFS

Research Scientist, skimming article from 2012: "Hm, they didn't find Enterovirus in ME/CFS. Shit, I thought we were on to something there. Alright, well let's check out their kidney microbiomes..."

 

[gregh286]

Whatever the papers say I'm treating my own symptoms.
Whether it's gut bacteria or another energy mechanism we are not burning carbs or sugar efficiently. We rely on a certain level of ketones to maintain energy balance.

 

[ljimbo423]

Just want to point out that this study that did NOT find dysbiosis in ME/CFS was based on Eukaryotes in stool... which do NOT include either bacteria or archaea.

This seems to me to be like looking for a forest, but not counting the trees! Nice catch @sometexan84.

 

[Shanti1]

I think the vagus nerve explains a lot of it. The work of Dr. Michael VanElzakker was an eye-opener to me for how consistent the perceived symptoms are with the CNS dysregulation by vagus nerve stimulation and by immunological triggers such as microglia activation.

His work was eye-opening for me too and I have adopted this as my central theory, but one that is not exclusive to many of the other theories. I'm not sure if you have looked at them, but some of the animal studies on vagotomy, sickness behavior, cytokines, are interesting. To me they confirm vagally mediated CNS inflammation/sickness behavior, but as peripheral cytokines get higher, they no longer need vagal mediation and directly stimulate the CNS by entering through areas in the brain known to be more "leaky".

Fatigue, Sleep, and Autoimmune and Related Disorders
https://www.frontiersin.org/articles/10.3389/fimmu.2019.01827/full
Two mechanisms whereby peripheral inflammation can enhance CNS inflammation are through leaky areas in the blood-brain-barrier and the vagus nerve (312)....
The vagal nerve afferents project to the dorsal vagal complex, which consists of the NTS, the dorsal motor nucleus (DMN) of the vagus, and the area postrema, located in the medulla area of the brainstem. However, the NTS is the primary area of vagal afferent stimulation...

Inhibiting vagal afferents by a vagotomy and applying inflammatory substances to the periphery indicate that at lower dosages the vagal afferent nerves can be a major mechanism of translating peripheral inflammation to central inflammation and subsequently can affect behavior such as sleep (68, 69). Application of IL-1β, TNF-α, or LPS, which stimulates IL-1β and TNF-α production, into the peritoneum enhances sleep in mice and/or rats and is attenuated in animals that have their vagal nerves severed (69, 319, 320).

Using vagotomy animal models, it has been shown that peripheral inflammation achieves this, in part, through stimulating the vagal afferents that enhance IL-1β and TNF-α in the NTS—a brain area that projects to brain areas involved in regulating sleep and are associated with modulating fatigue (69).

Nevertheless, the types of cytokines stimulating the vagal afferents from the periphery likely stimulate CNS cytokines over different time courses and affect different brain areas and cytokines. Thus, differences in peripheral inflammation associated with the type of autoimmune disease and progression of the disease could interact with circadian, sleep/wake states, activity-dependent, and pharmaceutical-related alterations in inflammatory processes to affect the severity or development of specific types of fatigue.

I found the above interesting, in part accounting for the wide varriation of symptoms in ME/CFS

Vagotomy does not inhibit central inflammation induced by peripheral inflammation by large concentrations of inflammatory stimuli (69), suggesting that leaky areas of the blood-brain barrier also contribute to CNS inflammation. Leaky areas of the blood-brain-barrier exist in the circumventricular organs including the area postrema, and the subfornical organs, as well as the vascular organ of lamina terminalis (VOLT) (322).

I also found this study interesting where vagotomy inhibited sickness behavior but not fever when rats were injected systemically with IL-1: https://pubmed.ncbi.nlm.nih.gov/11189019/

 

[Shanti1]

I wonder if it's possible for the vagus CNS/NTS pathogenesis to develop just by having a prolonged exposure to a vagus nerve stimulus such as a long mononucleosis or prolonged physical trauma.

During exposure, there would be an increased glutamate threshold in the NTS, this might consequently change the homeostasis of the microglia. These would then contribute to the problem by releasing cytokines which then stimulate the NTS again, which then triggers the microglia again. Trauma or viral infection could also be part of the feedback because they are also enhanced by the downstream effects of this neurological dysregulation. Monocytes might migrate into the CNS just because of the cytokine signaling but not because there are pathogens necessarily.

We certainly see this happen in sensitization of both peripheral and central pain pathways, and it can happen in a spectrum, meaning pain pathways can be sensitized in varying degrees, from painful stimuli causing exaggerated pain response, normal stimuli causing pain response, and NO stimuli, yet continued pain perception. From my understanding, the central and peripheral pain pathway sensitization phenomena involve several mechanisms including dysfunctional mito/lack of 02 ---> lower ATP ---> less ATP to pump ions and maintain membrane potential in nerves ---> lowered action potential ---> increased pain perception and also sensitization from inflammation, oxidative stress ----> vagal perception of inflammation/oxidative stress ---> activated microglial (and I'm sure so much more).

So is it possible for CNS/NTS pathology to persist once the initial stimuli has been removed? It is a great question and perhaps, if it happens, like pain sensitization, it happens on a spectrum from over-reaction to stimuli to continued reaction to no stimuli. It seems though, that in pwME there is often something directly messing with mitochondrial function. If the pathology could persist with the initiator removed, the peripheral mitochondrial dysfunction would need to be mediated by the CNS.

 

[seamyb]

I've a brass neck posting an opinion when I have been wrong about my own illness so many times, but this time I think I'm right, like all the other times.

I think it's mold. Or else some other chronic infection. I think if an immune system can get into this state without a foreign biological presence, it would be able to get out. I'm reading Neil Nathan's "toxic" at the minute. He says he sees 80% of patients with complex diseases like our's as having mold issues. 20% chronic Lyme disease. And that's with a range of these "syndromes". Fibro, CFS, MCS, etc. The variation in CFS, I believe, doesn't necessarily mean a range of different etiologies.

And mold isn't something I gave any credit to when I first started hearing about it. I actually had the reverse of the thought processes I should have had. I thought "Naa, I used to live in houses that had mold and I was fine then". Yea well it grows inside you, pal.

 

[Wishful]

I think if an immune system can get into this state without a foreign biological presence, it would be able to get out.

Not necessarily. I agree that it should be able to, but that 'return' mechanism could be dysfunctional. Also, we have so many different feedback loops that it seems reasonable that one of them could end up as positive feedback, locking us into the abnormal state.

To me, neither fungal nor other microbial infections fit the very rapid (minutes) switching of state between full ME and full remission, which I experienced quite a few times. Chemical switching of state (affecting the balance or reaction rates in cells) fits much better.

 

[lenora]

Agreed @seamyb......A lot of us lived didn't live in glass houses but those with mold somewhere in them. I think it's a pile on of viruses & other organisms that lead us to where we are now. Some worse than others.

Perhaps that's why some people are worse than others....they've been exposed to either a long-standing infection or a series of them before they could recover. Anyway, there is a reason why we've all ended up ill....and I think it's many.

The vagus nerve connection is a good one, and I'm living proof of the glial connection. Perhaps this should be our motto:

Yours, Lenora.

 

[nerd]

So is it possible for CNS/NTS pathology to persist once the initial stimuli has been removed? It is a great question and perhaps, if it happens, like pain sensitization, it happens on a spectrum from over-reaction to stimuli to continued reaction to no stimuli. It seems though, that in pwME there is often something directly messing with mitochondrial function. If the pathology could persist with the initiator removed, the peripheral mitochondrial dysfunction would need to be mediated by the CNS.

Certainly, it is possible to persist without a sustained etiology. I already described one possibility, I think. That is, the chronic or acute over-sensitization of the vagus nerve leads to a glutamate-mediated destabilization of microglia. These microglia then release cytokines and glutamate which leads to a cascade of localized neuronal overactivity. Just looking at the microglia, there are many other options on how they can be destabilized, e.g. viral infection of the stem brain, macrophage/monocyte migration into the stem brain, cytokine transport into the stem brain. The glutamate metabolism itself also plays a role, e.g. too much glutamate provision from glutamine or from a dysregulated citric acid cycle, or a dysfunctional glutamate decarboxylase due to B6 deficiency.

Moreover, there are secondary inflammatory feedback loops that can stimulate the vagus nerve after NTS pathology onset. For example, NTS pathology can alter the gut microbiome, dermal microbiome, and this then causes inflammation or opportunistic pathogens to take over, which again stimulates the vagus nerve. Viral reactivation is another factor. NTS pathology can trigger viral reactivation while the viral pathology then enhances the NTS pathology via the vagus nerve and possibly by macrophages and cytokines as well.

All of these feedback loops would have to be identified and solved in parallel. Otherwise, you're just trying to keep a ship from sinking by plugging one hole of many.

 

[lenora]

HI @nerd....so should everything with glutamate (supplements mainly) be cut out of the diet, in your opinion?

Personally, I think we're all subject to individualized problems....what's good for me may not do anything for you. Having said that, I'm willing to try. Gosh, the money I've spent on things over the years. No wonder this industry takes in so much money....there is always a new theory, always. Yours, Lenora.

 

[Pyrrhus]

I wonder if it's possible for the vagus CNS/NTS pathogenesis to develop just by having a prolonged exposure to a vagus nerve stimulus such as a long mononucleosis or prolonged physical trauma.

Brain fog cognitive dysfunction moment!

Remind me again - what does the "NTS" stand for?