Myalgic Encephalomyelitis is clear to see in the blood

[Oliver3]

I agree a spinal tap is not sufficient.
The vast majority have a myriad of problems not just limited to thr brain.
I.e vascular issues, , muscle issues, immune deficiencies, hormonal issues not directly related to the brain ir in feedback loops, collagen issues, leaky gut issues. You really can't say this disease is exclusive to the brain

 

[Wishful]

You really can't say this disease is exclusive to the brain

No, but many (most? all?) of the symptoms could be due to brain cells not doing their job properly. Heart failure doesn't kill you; it's the failure of the brain due to lack of blood flow that ends your life. Lack of blood flow, or low oxygen, would be a biomarker for that, but that's far easier to detect than the failure of possibly just a few brain cells whose dysfunction causes serious symptoms elsewhere in the body.

I was going to say "effects" rather than "symptoms", but so far they haven't found any clear markers of physical effects in the body. Some PWME can't get out of bed, but there's no apparent physical cause (muscle metabolism or whatever), but that doesn't rule out a malfunction in the control circuitry in the brain. We don't have the technology to readily identify that sort of malfunction, and it probably wouldn't show up in spinal fluid. One transistor failing in a CPU can crash your computer, but measuring the supply voltage or current isn't going to reveal that (one transistor out of billions, switching at GHz frequency). The marker is there, it's just buried in too much noise to be practical to dig out.

So yes, there might be some physical measurements of collagen, muscles, capillaries, etc, that are due to ME, but it's buried in too much noise and too far removed from the core dysfunction to be useful.

That's why I favour the black box approach: vary some inputs and hopefully find something that causes a reliable response in ME symptoms. If someone had studied my body when I had a reliable way (cuminaldehyde) to switch my PEM off, that might have revealed something. Dynamic abnormalities are much easier to identify than static ones, especially when they are weak abnormalities in a lot of noise, and what's "normal" varies a lot between individuals.

 

[Oliver3]

No, but many (most? all?) of the symptoms could be due to brain cells not doing their job properly. Heart failure doesn't kill you; it's the failure of the brain due to lack of blood flow that ends your life. Lack of blood flow, or low oxygen, would be a biomarker for that, but that's far easier to detect than the failure of possibly just a few brain cells whose dysfunction causes serious symptoms elsewhere in the body.

I was going to say "effects" rather than "symptoms", but so far they haven't found any clear markers of physical effects in the body. Some PWME can't get out of bed, but there's no apparent physical cause (muscle metabolism or whatever), but that doesn't rule out a malfunction in the control circuitry in the brain. We don't have the technology to readily identify that sort of malfunction, and it probably wouldn't show up in spinal fluid. One transistor failing in a CPU can crash your computer, but measuring the supply voltage or current isn't going to reveal that (one transistor out of billions, switching at GHz frequency). The marker is there, it's just buried in too much noise to be practical to dig out.

So yes, there might be some physical measurements of collagen, muscles, capillaries, etc, that are due to ME, but it's buried in too much noise and too far removed from the core dysfunction to be useful.

That's why I favour the black box approach: vary some inputs and hopefully find something that causes a reliable response in ME symptoms. If someone had studied my body when I had a reliable way (cuminaldehyde) to switch my PEM off, that might have revealed something. Dynamic abnormalities are much easier to identify than static ones, especially when they are weak abnormalities in a lot of noise, and what's "normal" varies a lot between individuals.

They're literally looking at muscle metabolism at the moment.
We are built different.
Referring to our bodies as simple machines doesn't cut it as we're massively complex. Is there just one computer in the human body. I doubt that very much. It's a system that's talks to itself all around the body.
Fir example, we don't understand the gut microbiology, the immune system,
Dynamic abnormalities? I don't think it's that simple in m.e.
The core dysfunction is eds anyway but that's going to show up differently in everyone

 

[cfs since 1998]

No, but many (most? all?) of the symptoms could be due to brain cells not doing their job properly. Heart failure doesn't kill you; it's the failure of the brain due to lack of blood flow that ends your life. Lack of blood flow, or low oxygen, would be a biomarker for that, but that's far easier to detect than the failure of possibly just a few brain cells whose dysfunction causes serious symptoms elsewhere in the body.

Multiple groups have described endothelial dysfunction, neurovascular dysregulation, impaired peripheral oxygen extraction, etc. These things happen in the body not the brain. The only way your conclusion can be supported is by cherry-picking and ignoring the evidence that exists.

 

[Wishful]

The only way your conclusion can be supported is by cherry-picking and ignoring the evidence that exists.

No, as Oliver3 pointed out, we're a mass of interconnected systems. One malfunction in one subsystem can affect others, which affect others, for who knows how many levels.

As for multiple groups describing those various abnormalities, I haven't seen any really definitive evidence, at least nothing along the lines of "90% of PWME have capillaries that are 30% narrower than expected for their bodies". Studies with small cohorts and results that just barely exceed a probability threshold aren't convincing me. There's a lot of pressure to publish positive findings. I think it's a matter of perspective: if you are desperately wanting some sign of progress, you consider scant evidence that supports your beliefs as strong, while a skeptic considers it weak. Even if you gathered a panel of world experts to judge the evidence, they'd probably argue for a long time about it and maybe reach a we're not sure" conclusion.

I'm fairly sure than none of those studies provides strong evidence of those small abnormalities being the cause of a symptom rather than an effect of some malfunction elsewhere in the body (or brain), possibly far removed from the root cause.

Claiming that the weak evidence that supports something you want to believe (that ME is related to muscle or endothelial or mitochondrial dysfunction) is valid is cherry-picking too.

 

[Oliver3]

The vascular system is an integral part of m.e. tho.
The open medicine foundation are finding muscle abnormalities.
I watched Ron's lecture from last year and Chris Armstrongs recent chat. Their ideas seem to be converging on the energy switch in m.e. metabolic dysfunction. Combined with muscle dysfunction abd a shut down in nitric oxide production.
The findings are coming up frequently.
There is more than how the brain is acting for sure.
Mitochondrial dysfunction is an important part of many diseases, but this constellation of symptoms that keep cropping up suggest a phenotypical reaction to stressor of any kind.
Of course this will present slightly differently on ameveey patient.
If memory serves me correctly, they're going to elucidate on the reasons that shut down occurs.
He mentioned anti purigenic therapies, also mentioned by tmron Davies, to restore healing cycles in the organism. There are cardiologists researching anti purigenic therapies for high blood pressure and cerebral vasoconstriction.
Hypotfusion in the brain is another biomarker that keeps occurring.
When you start adding all these things up. The constellation as I said is a number of phenotypical responses to stressors of infection, mental stress, ecogenic stress in general.
I don't think you can say these are weak connections. They keep appearing

 

[Oliver3]

No, as Oliver3 pointed out, we're a mass of interconnected systems. One malfunction in one subsystem can affect others, which affect others, for who knows how many levels.

As for multiple groups describing those various abnormalities, I haven't seen any really definitive evidence, at least nothing along the lines of "90% of PWME have capillaries that are 30% narrower than expected for their bodies". Studies with small cohorts and results that just barely exceed a probability threshold aren't convincing me. There's a lot of pressure to publish positive findings. I think it's a matter of perspective: if you are desperately wanting some sign of progress, you consider scant evidence that supports your beliefs as strong, while a skeptic considers it weak. Even if you gathered a panel of world experts to judge the evidence, they'd probably argue for a long time about it and maybe reach a we're not sure" conclusion.

I'm fairly sure than none of those studies provides strong evidence of those small abnormalities being the cause of a symptom rather than an effect of some malfunction elsewhere in the body (or brain), possibly far removed from the root cause.

Claiming that the weak evidence that supports something you want to believe (that ME is related to muscle or endothelial or mitochondrial dysfunction) is valid is cherry-picking too.

I understand your desire to want to focus on the brain because ut fits your symptoms. Fair enough. But the evidence for certainty are even more scant regarding issues of the brain.
I keep saying it. This is a connective tissue disease with everything else being downstream of that weakness.
There are numerous studies coming out in recent years saying thirty to fifty percent of m.e. and long covid sufferers are hypermobile.
Or meet citeria for the beighton scale.
the problem with that is the Beighton score us such a numb measurement. They haven't found the genes for heds and score to see how bendy you are justcisnt accurate enough a way to diagnose or realise the extent of eds in somones body.
I hope I'm wrong but it's just too common a finding

 

[Wishful]

I don't think you can say these are weak connections. They keep appearing

Actually, I can. Themes that are popular, for whatever reason, will spur a lot of "me too" studies based on looking for anything that even slightly supports the belief. It's not that hard to rig a study to show desired results. I haven't seen anything that convinces me that ME's core dysfunction is whole-body mitochondrial dysfunction or connective tissue problems. I don't have any apparent connective tissue problems, so it'll be hard to convince me that's the cause of my ME. Connective tissue problems don't fit the rapid switching of ME states either.

I can accept that ME could cause connective tissue problems downstream, or that comorbid connective tissue problems could worsen ME. I think ti's unlikely to be part of the core dysfunction, or even a critical part of the feedback loop that seems to be involved. It's just too slow to fit the rapid switching.

 

[Oliver3]

Sorry but that's just not the experience of so many m.e. sufferers. Your also making creative leaps to call the evidence weak

Like I said, what research are you referring to to say tgis is a brain disorder in origin.
As I've pointed out, akaheimers is now thought to originate from the kidneys first.

Ron Davies originally thought this was a diseqse of the kidneys coincidentally.
You're very unusual ( and I'm not saying this to other you, uts just an odd but relevant expression of the disease, in that you only get pem through mental / emotional exertion( for most if us, it's any kind of exertion .
It's so obviously phenotypical that ignoring that fact seems obtuse.
I can post the many studies saying all-round 50 percent of m.e. and long civid suffers are classically hypermobile? Or just Google glthem.
How many others have atypical connective tissue problems like Jen brea..I don't see how it's possible to call ut weak evidence

 

[Rufous McKinney]

I definitely think that connective tissue issues can arise, and my theory is this is induced by viruses over some longer term period of time. And then your head and neck start sliding around. Brain stem drops. Other things happen, too.

Connective tissue is "structure" and with structure weakened, the Flow is impaired. Anything which must flow, needs a functional structural component to contain the flow.

 

[Oliver3]

I'd say the rapid switching that you think of ( which is a vague description to be honest) is the result of naviauxs cell danger response. If you're going to and from the threshold where the resoonse gets triggered, you slip between being in better or worse states.
Naviaux has also proved ( with the use of suramin( that these healing cycles can be up or down regulated with anti purigenic therapies.
Autistic kids ( also having collagen issues) . Mitochindria can be less stressed , less leaky more effective. More ' electrical ' with these therapies.
I mean he proved that.
What you're describing good old fashioned ' shut down' which can be ameliorated by rest etc.
The other possibility us waxing and waning autoimmunity which is also more common in collagen based diseases. Leaky guy, cell integrity is a direct consequence if poor collagen.

I'm not saying the brain isn't involved. But this is a whole system disease

 

[Oliver3]

I definitely think that connective tissue issues can arise, and my theory is this is induced by viruses over some longer term period of time. And then your head and neck start sliding around. Brain stem drops. Other things happen, too.

Connective tissue is "structure" and with structure weakened, the Flow is impaired. Anything which must flow, needs a functional structural component to contain the flow.

Dr afrins work on mast cell virus induced degradation backs that idea massively. As does Jen breas experience.
Wishful would be insisting it's a problem in the brain...I mean it became a problem in the brain, but because of lax tissue in the neck.

One has to ask why some are more susceptible than other s. The fact that so many long covid sufferers are hypermobile is more than just selection bias

 

[cfs since 1998]

No, as Oliver3 pointed out, we're a mass of interconnected systems. One malfunction in one subsystem can affect others, which affect others, for who knows how many levels.

You have written a lot, without really saying anything. The above does not mean anything. It's not evidence for anything. It's not a theory. It's not a medical hypothesis. It's just rhetoric.

Claiming that the weak evidence that supports something you want to believe (that ME is related to muscle or endothelial or mitochondrial dysfunction) is valid is cherry-picking too.

This is intellectually lazy and dishonest. Most of the research you attempt to debunk, you haven't even read. You tried to debunk the paper about vildagliptin/saxagliptin, but it was clear you didn't read or understand it.

I haven't cherry picked anything. In order to accuse me of something, present some evidence. In order to assert that research is weak, present some evidence. In every critique you ever post, your only evidence is your own personal anecdotes. Should we just believe the evidence is weak just because you say so? That's not good enough. You never back up any of your claims. You can't criticize science in such a fantastically unscientific way.

Attributing my posts to bias because I "want" to believe ME works a particular way, is the epitome of hypocrisy. I've read the research. I spend hundreds of hours reading research every month. You criticize research without reading it, based on your feelings. You literally ignore ALL evidence that refutes your narrow-minded, niche, unusual, and unsupported view of how ME/CFS works. You are deliberately ignorant of the research that has been published.

 

[Gala]

Definitivamente, dio con algo importante. Siento que mis intestinos tienen muchos problemas, en parte debido a problemas con el tejido conectivo y los componentes estructurales asociados.

Recientemente empecé a tomar una pequeña dosis de Lyrica por la noche, lo que inesperadamente parece haberme ayudado a calmar un poco el estómago. De lo contrario, suele interrumpir mi sueño.

It appears that between 35–92% of ME/CFS patients also have Irritable Bowel Syndrome (IBS), and another very interesting finding is that when combining microbiota data and immune markers, researchers were able to identify ME/CFS patients from healthy controls with 83% accuracy (multivariate classification model).

These findings are reported in an excellent and very recent study (2025):

“The data collection involved a detailed search of peer-reviewed English literature from January 1995 to January 2025, focusing on studies related to the microbiome and ME/CFS.”
— [Hsu et al., 2025]. https://doi.org/10.1186/s12967-025-06527-x

If you ask for my opinion on how to improve your gut health, I’d say it would be necessary to do two things:

Diagnostic testing:​

• Gut microbiota test by NGS
• Zonulin, secretory IgA, and EPX in stool
• Urinary organic acids test (to assess dysbiosis, SCFAs, neurotransmitters)
• Food intolerance testing (non-IgE mediated)

Then, treatment should be based on the altered results.
If you're unable to do the tests (due to economic or logistical reasons), there are a number of recommendations for us based on the issues observed in several studies to date. You could try introducing some of these changes gradually and assess whether they're beneficial:

• Specific probiotics (e.g., Lactobacillus plantarum, Bifidobacterium longum, Akkermansia)
• Sodium butyrate or tributyrin to restore SCFA production
• Glutamine, zinc carnosine, quercetin, vitamin D to repair mucosal barriers
• Antimicrobial herbal therapy (when specific pathogens are detected)
• Personalized elimination diets (low-FODMAP, gluten-free, histamine-free…)
• Antifungal treatments (if Candida spp. overgrowth is present)

I talk about this topic in more detail in this article:
https://fatigacronica.es/alteraciones-digestivas-sfc-em/

 

[Gala]

Regarding the recent debate on vascular problems, the brain, dysautonomia, muscles, and of course the well-known issue with mitochondrial energy function, I’d like to share my modest opinion.

I believe that infections have always been—and will continue to be—behind this disease once known as "Post-Viral Syndrome." The assumption was that patients suffered lingering effects after overcoming an infection, and I think this is the core issue. There are dozens of studies showing the recurrent infections we experience. These are not past infections; they are chronic and synergistic infections.

In the first article on my blog, I discussed the striking findings of a 2020 study that analyzed the damage caused by HHV-6. I’m sure these symptoms sound familiar (pay special attention to point 3):

Key Findings from the Study:​

• MITOCHONDRIAL DYSFUNCTION: Reactivation of HHV-6 in human cells triggered mitochondrial fragmentation—the very structures responsible for producing energy in the cells. This suggests a possible explanation for the extreme fatigue seen in ME/CFS patients.
• ANTIVIRAL RESPONSE: Cells with reactivated HHV-6 exhibited an antiviral response that protected them from other viruses like influenza and herpes simplex. However, this defense seems to come at a cost: altered cellular metabolism and energy production.
• PATIENT SERUM EFFECT: When serum from ME/CFS patients was introduced into healthy cells, similar mitochondrial fragmentation and antiviral responses were observed, indicating that factors in the patients’ blood may be causing these effects.

Komaroff, A.L., Lipkin, W.I., & Levine, S.M. (2020). HHV-6 Reactivation and Its Possible Role in Mitochondrial Dysfunction and Chronic Fatigue. ImmunoHorizons, 4(4), 201–210.
https://academic.oup.com/immunohorizons/article/4/4/201/7820503

And in anothers studies:

“Primary lymphocyte cultures showed active HHV-6 replication in 70% of patients compared to 20% of controls (P < 10⁻⁸)” — [Buchwald et al., 1992]. https://pubmed.ncbi.nlm.nih.gov/1309285/

“The number of patients in studies that found an association between CFS and active HHV-6 infection (N = 717) is much greater than the number in studies that failed to find an association (N = 48).”
“First, active HHV-6 infection occurs in a considerable proportion of CFS patients. Second, HHV-6 is tropic for cells of the nervous and immune systems, and CFS is characterized by neurological and immunological abnormalities.”
— [Yao et al., 2010]. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4758195/

I don’t believe this illness is caused solely by this herpesvirus, although it may well be the most implicated one. I think we are simply facing a cascade of viral reactivations that gradually deplete our immune system. The key question then becomes: why are we more vulnerable than others to these reinfections?

Most likely, it all stems from weakness in our natural barriers (intestinal, blood-brain, and endothelial). If these are porous, countless associated disorders arise, which in turn reinforce an anaerobic (low-oxygen) environment, as described by Dr. Berg back in the 1990s.

What I believe hasn’t been addressed until now is how to restore these barriers quickly and safely while also fighting off other pathogens: herpesviruses, of course, and many others that colonize the body as we progress into immunosenescence (immune exhaustion) due to chronic activation and inflammation.

I believe this illness is much simpler to understand than it seems: it’s about analyzing our genetic weaknesses in connective and endothelial tissues and beginning to combat pathogens while simultaneously restoring homeostasis in these tissues. I believe this second objective—restoring tissue balance—has often been neglected in research.

I’m continuing to search for affordable biomarkers and genetic markers of vulnerability. But it's clear that if we show signs of intestinal fragility, cartilage weakness, hyperlaxity (which could suggest Ehlers-Danlos syndrome, possibly even the vascular type), and dysautonomia (such as cerebral hypoperfusion), then we need to start a comprehensive approach, mainly using supplements—unless infections are clearly very active.

But I insist: priority should go to the gut and blood vessels, because otherwise it will be extremely difficult to eliminate pathogens in a system that is so inflamed and permeable.


Don't give up—this illness has turned us into human beings with levels of resilience and patience that are rarely seen in other conditions. (I just hope other patients aren’t sent to the psychologist as often as we are, haha!)

 

[Oliver3]

Very good post. Especially the idea of restoring tissue integrity. Regenerative medicine is the way out of this.
Just to add , as wishful was saying that connective tissue is not an issue here, adhd, low dopamine states are comorbid with connective tissue disorders. Again it's something that is clearly seen in many studies.
The vulnerability to infection is smthg that weaker tissue also predisposed us to.

Neglecting tissue regeneration research is such a missed opportunity like you say.

I posted on here about using telemorase to increase muscle density and reverse some of the markers of ageing such as fatty liver and diabetes, all of which are showing in that crude but important test showing smthg in the blood.

Stem cell therapies should be at the forefront on m.e. research and ultimately crispr to restore endothelial dysfunction.

Everything else is downstream in my opinion.

I apologise if I come across as strident but I'm so sure this is the core problem. There's too much evidence pointing in that direction.

Any bridging treatment s that help tide us over are obviously gladly welcome.

I agree, we are tested beyond belief.
My posts are out if desperation really.
I appreciate the tone of your post. Thank you

 

[Wishful]

Like I said, what research are you referring to to say tgis is a brain disorder in origin.

My perception of the disease is mainly on personal experience: factors that affect brain function, while a lack of ones that seem to involve problems elsewhere in the body. There's much less published evidence for brain involvement in ME because it's so much more difficult to do. Taking blood samples is cheap and easy; measuring brain cells in living humans is difficult and expensive.

I can post the many studies saying all-round 50 percent of m.e. and long civid suffers are classically hypermobile?

That doesn't prove that it's a cause, rather than an effect. I see that evidence as 50% of PWME don't have obvious connective tissue problems, so it's an effect for some people, but not a cause.

'd say the rapid switching that you think of ( which is a vague description to be honest)

I think "My ME switches completely off over the space of minutes, and switches completely back on over the space of minutes (some hours later)" is quite precise. Other people have reported similar experiences.

What you're describing good old fashioned ' shut down' which can be ameliorated by rest etc.

No, there wasn't any rest involved. I had my level of symptoms, took something (iodine, T2, cumin, or prednisone), and shortly after for the first 3 and 5 days for the prednisone, my ME abruptly switched off and stayed off for the rest of the day. I doubt that sleep was responsible for switching it back on, but I can't rule that out based on the scant evidence.

I'm not saying the brain isn't involved. But this is a whole system disease

I'm not saying it's solely a brain problem. The feedback loop sustaining the ME state could involve many subsystems, and it could involve different subsystems in different people. Collagen could be involved in sustaining or worsening the ME state in some people, while having no effect on others. If a significant percentage of PWME don't show a factor (collagen, mitochondrial, endothelial, viral, etc problems), then that's likely a downstream factor not essential to ME. Proving that the brain isn't an essential part of ME's mechanism would be a lot harder, since the brain is still so little understood, and so difficult to study.

 

[Wishful]

low dopamine states are comorbid with connective tissue disorders

There was a recent study about how "what everyone knows about dopamine" was wrong. The discovery was that dopamine acted in a highly localized and rapid manner, so theories based on global measurements of dopamine (blood, CSF) might not be valid. At this point we don't know which theories involving dopamine are valid or invalid.

 

[Oliver3]

Man. I don't know what to tell you. Your ignoring all the research, most patient experience. Most patient intuition.
That's your opinion.
I believe it to be wrong and you provide zero evidence.
Most peopke do better using dopamine enhancement therapies.
You could make, and I do, the argument that connective tissue is poorly understood too.
vascular endothelium, dopamine, mitochondria are important aspects of the brains make up aren't they. It's proven beyond doubt that vascular integrity is compromised. Leaky vessels, leaky blood brain barrier etc.
Ignoring thus in some quixotic search for' sometging' that you don't even elaborate on more than a few cells going wrong idea seems obscure to me

 

[Oliver3]

There was a recent study about how "what everyone knows about dopamine" was wrong. The discovery was that dopamine acted in a highly localized and rapid manner, so theories based on global measurements of dopamine (blood, CSF) might not be valid. At this point we don't know which theories involving dopamine are valid or invalid.

Regardless of that finding. Low dopamine illnesses are comorbid with connective tissue disorders.
That. Is a fact.