My biochemical understanding from ME / CFS

[DrUniverse]

Hey,

Just wanted to share my understanding from ME/CFS ( only my opinion & pardon me no citations/sources )

Start: -> Persistent Antigen Stimulation through Virus/Bacteria/Leaky Gut
-> T Cell Exhaustion -> Virus persistence or reactivation
-> Mitchondrial fragmentation & fission through (EVB dUPTase, HHV6)
-> Decreased mitochondrial turnover efficiency
-> Autoantibody production which further fragments and & fissions mitchondria.
-> Autoantibody against various Receptors, Autoantibody against PDH.

And a lot more metabolic / biochemical abnormalties which cant be listed all because that would take a lot of effort.

It donts need to be a genious to conclude that the body is biochemical heavily impaired and in most cases cant overcome this devastating biochemical state.

 

[ruben]

There seem to be accounts here and there of people who have recovered from ME/CFS from taking antivirals. Why can't there be thorough studies done on this.?

 

[Norwegianlad]

There seem to be accounts here and there of people who have recovered from ME/CFS from taking antivirals. Why can't there be thorough studies done on this.?

My guess would be that there is not enough money being raised and awareness for the illness. Its a silent illness. If we would all die after 10 years of having ME/CFS the world would know all about it. But many with ME/CFS that can still go outside look healthy to the world when they see them. They don't the other 23 hours of the day we might spend in bed. Or even worse, the people who can't go outside at all aren't even seen.

Without Long Covid i would have had little hope but at least now we got some attention.

We still need to fight for it though. Let the world know we need more research and attention for the disease. Compared to tons of other diseases, we get maybe 5% of the funding for research..

 

[Wishful]

It donts need to be a genious to conclude that the body is biochemical heavily impaired

I disagree. Even at my worst, my body still feels like it can do strenuous activity if I need to. There are horrible feelings--pain, lethargy, brainfog--that requires overcoming, but my muscles, heart, etc, seem to be working normally. My view of ME is that neural pathways are involved and inhibited. Those pathways seem strongly affected by immune activation in the body. Stopping those immune signals can result in complete temporary remission for some people, but other people are left with some baseline of ME symptoms. Maybe some have other chronic immune activation, or maybe the pathway that triggers on those signals continues to trigger even in the absence of those signals.

I still see the ME state as a feedback loop with positive feedback, locking us into this state.

 

[Wishful]

There seem to be accounts here and there of people who have recovered from ME/CFS from taking antivirals.

I had the impression that most of those cases are only temporary remissions, and full ME returns when the antivirals stop. I had similar temporary remissions from prednisone, but only for the first two trials. I had much shorter remissions from two other treatments (cuminaldehyde and T2). I think that shows that there are multiple ways to break that feedback loop, but it probably varies with individuals. Unfortunately, all three of those treatments have so many effects on the body, many probably still unknown, so they're not much use as a trailblazer.

If those antivirals have their effect by reducing some immune signal, is it easier to test that hypothesis by applying antivirals and measuring changes in body fluids, or by applying drugs that block individual immune signals?

 

[Dude]

In my opinion, viral persistence is an old hat. Thousands of people on this forum alone have tried every conceivable antiviral remedy, and all we have are a few non-reproducible anecdotal reports. Recently, Carmen Scheibenbogen even stated in a study that she tends to exclude viral persistence in long COVID. I know that the majority of people on this forum believe in this theory, but it's all bias because every minor viral finding is glorified as if it has cured ME/CFS. Additionally, a significant portion of the frequent posters favor this theory, creating an incredible bias within the community. Viral persistence is the weakest theory of all. Firstly, people get ME/CFS from all sorts of things: vaccinations, fluoroquinolone antibiotics, traumas, viruses, dehydration, etc. How likely is it that twenty different viruses cause the same disease? It just doesn't make sense.

T-cells require large amounts of ATP, especially for their activation and maintenance of function. Mitochondrial dysfunction could lead to T-cells not having enough energy, causing them to enter an exhausted state. Why do severe patients have gastroparesis? Exactly, too little ATP. What do we consume when we watch TV, read, or think? ATP. Why do we lack energy? Too little ATP. Everything comes down to ATP, and where is it produced? Of course, in the mitochondria. What damages the mitochondria? No one knows for sure. But if I had to bet on a hypothesis, it would definitely be Scheibenbogen/Wirth's.

Wüst has shown via MRI that sodium accumulates in front of the sodium-calcium pump during physical exertion in ME/CFS patients. This is a clear indication that this pump has a problem and is very likely the cause of PEM. Furthermore, this accumulation causes the cell to import calcium, thereby damaging the mitochondria. Of course, this is just a hypothesis, but it makes a thousand times more sense to me than viruses.

 

[Norwegianlad]

I disagree. Even at my worst, my body still feels like it can do strenuous activity if I need to.

This is very interesting. There seems to be 2 types of people with ME. The people who lost their strength and the people that can still force strength pretty easily.

For the past 10 years I pretty much always had all my strength still. Even in a bad crash I could walk and push through it. I could lift heavy things but ofc pay the price later.

4-5 months ago I started getting MCAS symptoms which got more intense and intense. I went from being over vasoconstricted to being way overvasodilated. I went from being always cold to being always way too hot. And.. I lost my strength. If I push one time now like I used to do i get so much worse so much faster. Crash hits me immediately instead of 3 days later.

Are you more of a vasoconstrictor would you say? I'm going to try medication soon to see if I can get my mast cells to relax again. Would love to get my strength and a huge part of my energy back (that I also lost since MCAS symptoms started).

 

[Estel]

I disagree. Even at my worst, my body still feels like it can do strenuous activity if I need to. There are horrible feelings--pain, lethargy, brainfog--that requires overcoming, but my muscles, heart, etc, seem to be working normally. My view of ME is that neural pathways are involved and inhibited. Those pathways seem strongly affected by immune activation in the body.

I have always felt that this was closer to the truth in my case. My body is also still capable of doing strenuous activity. I continue to be able to exercise (cardio, weight training, yoga) without PEM even though I'm symptomatic in other ways. I also always seem to have energy when I really need it. I once snapped out of some pretty bad brain fog and lethargy for about 20mins after a pipe burst under my kitchen sink requiring some creative "plumbing" (read plastic wrap and plumber's tape).

My symptoms also did not start with a virus and worsened after a major immune event. Getting someone to investigate possible immune causes, however, has so far been impossible.

 

[Wishful]

Are you more of a vasoconstrictor would you say?

I'm not sure how to judge that. I prefer a room temperature of 15C, and feel overly warm when it goes much above that. My hands do get cold in winter, but I think that's normal when it's -40. Once I acclimatize, I can go bare-handed for a reasonable length of time. I wash my hands in snow fairly often.

Interesting that you were in one category (full strength with ME), then switched to the other. I view that as more evidence that root cause of ME is not mitochondrial. The lack of strength or stamina is a result of ME, but doesn't affect all PWME, and thus isn't essential to ME.

 

[Wishful]

I once snapped out of some pretty bad brain fog and lethargy for about 20mins after a pipe burst under my kitchen sink requiring some creative "plumbing" (read plastic wrap and plumber's tape).

I've had similar experiences. That gives me an idea for a new poll: Does panic override your ME?

Getting someone to investigate possible immune causes, however, has so far been impossible.

Even people who are convinced they "know" the cause of their ME, don't really know for sure. There just aren't any tests to verify the hypothesis, or any understanding of ME's mechanisms that could help verify it. Furthermore, there might be no benefit from knowing for sure what the cause was. Knowing that Bob pulled the trigger of the gun that put a big hole in your thigh bone doesn't make the injury go away. I think ME is similar in that the trigger doesn't matter; once the feedback loop is triggered, it stays locked in that state.

 

[Norwegianlad]

I've had similar experiences. That gives me an idea for a new poll: Does panic override your ME?


Even people who are convinced they "know" the cause of their ME, don't really know for sure. There just aren't any tests to verify the hypothesis, or any understanding of ME's mechanisms that could help verify it. Furthermore, there might be no benefit from knowing for sure what the cause was. Knowing that Bob pulled the trigger of the gun that put a big hole in your thigh bone doesn't make the injury go away. I think ME is similar in that the trigger doesn't matter; once the feedback loop is triggered, it stays locked in that state.

I think it matters a LOT. I suffered a great deal not knowing whether I was ill or not. Got told I was healthy by all doctors while I felt weird in my body and mind

Early stage diagnosis and therefor knowing how to diagnose is extremely important. And only then you can look for a potential cure.

 

[Wishful]

I think it matters a LOT. I suffered a great deal not knowing whether I was ill or not.

That's different from knowing the trigger. An official diagnosis of ME would have answered the question of whether it was an actual medical problem. Knowing that the trigger was EBV (Bob) rather than salmonella (Alice) might make no difference for treatment/cure. Knowing the cause might make a difference someday if it was possible to switch out of the ME state, but still be vulnerable to the initial trigger. If I knew that a tetanus booster was likely to put me back into the ME state, I'd avoid any further booster (actually my booster should last longer than my remaining lifespan).

 

[andyguitar]

Firstly, people get ME/CFS from all sorts of things: vaccinations, fluoroquinolone antibiotics, traumas, viruses, dehydration, etc. How likely is it that twenty different viruses cause the same disease? It just doesn't make sense.

It would make sense if all those triggers could be shown to result in what could be described as a Metabolic Disorder that gives rise to the symptoms of me/cfs.

Wüst has shown via MRI that sodium accumulates in front of the sodium-calcium pump during physical exertion in ME/CFS patients. This is a clear indication that this pump has a problem and is very likely the cause of PEM. Furthermore, this accumulation causes the cell to import calcium, thereby damaging the mitochondria. Of course, this is just a hypothesis, but it makes a thousand times more sense to me than viruses.

Yes it does sound like a hypothesis that could be near the truth. But the problem I have with it is how come the patients having experienced a range of infections, stressful events and other things over the years that seem to trigger me/cfs and not got it earlier in life?

 

[Estel]

Even people who are convinced they "know" the cause of their ME, don't really know for sure.

"Cause" was perhaps the wrong word. Mechanism might be better. I'm trying some things for immune support in any case, but doing so a little less blindly would certainly be helpful. I do have some pretty objective signs of immune dysfunction, so there is some there there. Though, of course, there are likely other things going on as well.

One of my newer doctors has the habit of saying, "Okay, so you have chronic fatigue. But why do you have chronic fatigue?" Of course, he also says "I can't guarantee we'll find anything," but at least he's willing to look.

Where the cause/trigger conversation can become problematic (as was mentioned up-thread by @Dude ) is when there's too much focus on a single idea like viruses. I've read quite a lot here about viral onset and have always come out of it thinking, "No, that's not me." That's not to say it isn't the case for someone else, but I think we need to be cautious when positing all-encompassing theories of ME. Because of the wide spectrum of symptoms and subsets it can wind out leaving quite a few people on the wrong side of the line. But I don't want to turn this into a debate about the nature of categories and definitions.

I've frequently pondered conducting some kind of ME census on PR, but it would be quite a lot of work and that kind of research is not my area of expertise.

 

[Wishful]

"Okay, so you have chronic fatigue.

Is it really chronic fatigue, or is it a chronic fatigue-like symptom? Assuming that it's standard fatigue might lead to tests or treatments that are a waste of time. When I do an activity that causes normal fatigue, that does feel different from my ME's fatigue-like symptom. There are lots of studies based on fatigue in ME, but I think that's because the researchers' careers are based on standard fatigue, so that's what they can get funding for, even if it has nothing to do with ME's fatigue-like symptom.

 

[ruben]

It's been said before, but it's worth repeating. For me personally, primarily I see myself as ill, of which tiredness is one of my symptoms.

 

[Estel]

Is it really chronic fatigue, or is it a chronic fatigue-like symptom? Assuming that it's standard fatigue might lead to tests or treatments that are a waste of time. When I do an activity that causes normal fatigue, that does feel different from my ME's fatigue-like symptom.

That's a fair distinction and certainly one I make as well. Though I'm curious how you make it. Do you say fatigue-like because the mechanism is different? Like regular fatigue = depleting the bodies resources which can be fixed by eating, resting, etc., but ME fatigue is something else entirely?

Again, not questioning the distinction itself. Just curious based on your experience/knowledge.

 

[Wishful]

Like regular fatigue = depleting the bodies resources which can be fixed by eating, resting, etc., but ME fatigue is something else entirely?

Yes. Even when my ME makes me feel horribly "fatigued", I could, if I needed to, do strenuous activities at the same level as if I didn't have ME. My standard fatigue is reduced by resting and food, while my ME's fatigue-like symptom isn't affected. I could spend days resting, but if I eat foods that trigger the fatigue-like symptom, I'll feel fatigue-liked. My feeling is that ME's fatigue-like symptom is neurological. Some PWME might have additional physical limitations through some other mechanism, but that's separate.

 

[ruben]

This ISN'T my experience of my ME/CFS at all.

 

[Wishful]

This ISN'T my experience of my ME/CFS at all.

Would you care to elaborate? Does, for example. food fix your ME fatigue, while resting doesn't fix your normal fatigue?

I'll add to my description that I could have standard fatigue and ME's fatigue-like symptom simultaneously or separately, and the recovery of either were separate. So, two radically different mechanisms.