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It's all in the Gut. Why we get ME/CFS

*GG*

senior member
Messages
6,389
Location
Concord, NH
Not sure if i mentioned it in this thread before, but I think Low Dose Naltrexone (LDN) has helped my gut/digestion. Fewer loose stools, better digestion, therefore better health? I am feeling better than I ever have. Although I had a major flare 2 years ago, and changed a lot of things in my life!

GG
 

redo

Senior Member
Messages
874
richvank. With all your knowledge of the methylation process, I'd appreciate it if you could share your thoughts of what's causing ME patients to have problems with methylation to begin with. If you're leaning towards viral mechanisms (like I am at the moment, as in the simplified sketch), microbes, autoimmunity or other things. I think genes play a role no matter what, but aren't alone enough to cause ME.
 

richvank

Senior Member
Messages
2,732
@richvank. With all your knowledge of the methylation process, I'd appreciate it if you could share your thoughts of what's causing ME patients to have problems with methylation to begin with. If you're leaning towards viral mechanisms (like I am at the moment, as in the simplified sketch), microbes, autoimmunity or other things. I think genes play a role no matter what, but aren't alone enough to cause ME.

Hi, redo.

Here's the most recent relatively concise statement of my hypothesis:


Statement of The Glutathione DepletionMethylation Cycle Block (GD-MCB) Model for ME/CFS

1. There is a genetic predisposition toward developing ME/CFS, only part of which has been characterized.

2. Some combination of a variety of stressors (physical, chemical, biological and/or psychological/emotional), the combination differing from one case to another, together with the genetic predisposition, lead to depletion of glutathione.

3. The depletion of glutathione causes a functional deficiency of vitamin B12, so that both methylcobalamin and adenosylcobalamin become depleted.

4. The depletion of methylcobalamin inhibits the activity of the enzyme methionine synthase in the methylation cycle.

5. The partial block of the methylation cycle that results causes methylfolate to drain from the cells via the so-called methyl trap mechanism, eventually depleting the intracellular folates in general.

6. The partial block of the methylation cycle also deranges the sulfur metabolism in general and stabilizes the depletion of glutathione by a vicious circle mechanism, making ME/CFS a chronic condition.

7. The many abnormalities and symptoms of ME/CFS stem directly from this vicious circle mechanism.


As you can see, step 2 includes quite a variety of things. It's based on the published risk studies and the questionnaire responses I have received from PWMEs over the past 15 years. I ask what preceded the onset, and specifically ask about a variety of possibilities. What I get is a wide range of responses, but they fall into the general category of "stressors," and I have been able to connect all of them to glutathione depletion, which ultimately leads to a partial methylation cycle block. The viruses, microbes and autoimmunity fit under my category of biological stressors.

Best regards,

Rich
 

redo

Senior Member
Messages
874
Thank you for your perspective richvank. Appreciated.

About methylation and syndromes, do you see FMS and CFS as two separate entities or overlapping syndromes which most likely are variations of the same things? Questions is really; do you think the same mechanisms are relevant for CFS related syndromes (FMS being one of many). I am not trying to be inquisitive, just wondering what your thoughts are.

And, do you think once those stressors trigger methylation problems, that the patients will have those problems the remaining of their life?

I have to add, I appreciate differences of opinion. I think conformity is a road block for moving forward...
 

richvank

Senior Member
Messages
2,732
Thank you for your perspective richvank. Appreciated.

About methylation and syndromes, do you see FMS and CFS as two separate entities or overlapping syndromes which most likely are variations of the same things? Questions is really; do you think the same mechanisms are relevant for CFS related syndromes (FMS being one of many). I am not trying to be inquisitive, just wondering what your thoughts are.

And, do you think once those stressors trigger methylation problems, that the patients will have those problems the remaining of their life?

I have to add, I appreciate differences of opinion. I think conformity is a road block for moving forward...

Hi, redo.

I don't understand "pure" FM. I wish I did. It doesn't seem to have the same mechanism. For example, there doesn't seem to be oxidative stress, and the mitochondria don't seem to be dysfunctional, as evidenced by the exercise tolerance and even benefit in FM as opposed to ME/CFS.

In our clinical study, most of the women satisfied the diagnostic criteria for both ME/CFS and FM, and two-thirds of them reported significant benefit from methylation treatment. So when the two are combined, it may be that the FM results from some aspect of the ME/CFS. But when it is "pure" FM, I don't know what the pathogenesis mechanism is. I hope to learn more about this, because it may affect more people than ME/CFS does, and as you know, there is no cure for it at present, either.

Because there is a genetic predisposition to ME/CFS, I believe that a person will have the predisposition for their whole life. I believe that they can recover from a case of ME/CFS, and we have seen a small number of examples of people who appear to be fully recovered (able to work full-time, able to exercise, able to cope with significant stress, etc.), but I think that if their nutritional status for the important nutrients drops low enough and their stressors level gets high enough, they could develop another case of ME/CFS. I won't call it a relapse, because I truly believe that they recovered from it the first time.

I appreciate differences of opinion, too. I have learned a great deal from them, and hope to learn a lot more. I've appreciated your focus on the gut. I think that some cases of ME/CFS do indeed start there, for example with poor diet or antibiotic treatment that kills off the beneficial bacteria and starts a chain of events that leads eventually to glutathione depletion and so on. And I also believe that once the gut is heavily involved, which occurs in most people with ME/CFS, however this disorder starts in them, it is necessary to treat the gut problems along with restoring the methylation cycle. Either one will drag the other down, so both need to be supported. The interactions between these two are manifold.

Best regards,

Rich
 

markmc20001

Guest
Messages
877
If one has a bacterial infection, what is the bet approach? What about antibiotic IV's to kill the infection, but protect gut health?
 

richvank

Senior Member
Messages
2,732
If one has a bacterial infection, what is the bet approach? What about antibiotic IV's to kill the infection, but protect gut health?

Hi, markmc.

What kind of bacterial infection? Do you mean bacterial dysbiosis in the gut, or intracellular bacterial infections such as chlamydia, mycoplasma or rickettsias, or something like Lyme disease and its coinfections, or a coagulase negative multiple antibiotic resistant staph infection in the sinuses, or what? All of these are found in various cases of ME/CFS.

Rich
 

markmc20001

Guest
Messages
877
Hi Rich.

I have chlamydia pneumonia and probably lyme disease. However, my gut has been messed up lately due to something. Maybe Hpylori, along with some high liver enzymes.

It's really the gut issue I need to straighten out. I have high liver enzymes now too.

Somehow the other day(when I asked that question) it seemed like maybe an IV would treat the Chlamydia and Lyme while leaving the Gut in better shape?

Now I have this gut dysfunction, I've been having a tougher time cognitively. probably more than one thing going on right now with me.
 

JPV

ɹǝqɯǝɯ ɹoıuǝs
Messages
858
Gaia health - Gut Biota Never Recover from Antibiotic Use: Loss Extends to Future Generations by Heidi Stevenson

Evidence shows the mass antibiotics experiment is devastating our children's health. It may be the reason so many struggle for breath and can't assimilate food properly.

by Heidi Stevenson

29 August 2011


Emerging research shows that the harmful effects of antibiotics go much further than the development of drug resistant diseases. The beneficial bacteria lost to antibiotics, along with disease-inducing bacteria, do not recover fully. Worse, flora lost by a mother is also lost to her babies. The missing beneficial gut bacteria are likely a major factor behind much of the chronic disease experienced today. The continuous use of antibiotics is resulting in each generation experiencing worse health than their parents.

Martin Blaser, the author of a report in the prestigious journal Nature writes:

Antibiotics kill the bacteria we do want, as well as those we don't. These long-term changes to the beneficial bacteria within people's bodies may even increase our susceptibility to infections and disease.

Overuse of antibiotics could be fuelling the dramatic increase in conditions such as obesity, type 1 diabetes, inflammatory bowel disease, allergies and asthma, which have more than doubled in many populations.

Aside from the development of superbugs, we're now seeing clear documentation that the overall long term effects of antibiotics are devastatingly harmful to our health. Speaking to ABC News, Blaser said:

Antibiotics are miraculous. They've changed health and medicine over the last 70 years. But when doctors prescribe antibiotics, it is based on the belief that there are no long-term effects. We've seen evidence that suggests antibiotics may permanently change the beneficial bacteria that we're carrying. [Emphasis my own.]

Notice that term, permanent. Without considering the potential risks in the casual use of antibiotics, it now looks like conventional medicine is creating several pandemics of some of the worst chronic diseases known.

Mass Use of Antibiotics

By the time a child reaches age 18 in the industrialized world, the chances are he or she has been given 10-20 courses of antibiotics. That misuse continues into adulthood, and they're casually prescribed to pregnant women.

That's where the situation grows ever worse. Part of a normal childbirth is a baby's passage through the birth canalwhere it's exposed to its first dose of beneficial bacteria. (This should give pause to anyone considering a caesarian birth that isn't absolutely necessary.)

When a mother's microbiota is deficient, her child is born to a deficiency. The evidence now appears to show that, once a probiotic deficiency exists, it is never recoveredand it's passed down the generations. Therefore, each generation is likely to suffer from poorer health than the parents enjoyed.

Costs of Antibiotic-Induced Chronic Conditions

Healthcare costs rise and rise in treating this chronic ill health. Consider the pandemic status of diabetes and asthma in children today. Those diseases were extremely rare 50 years ago, and now they're literally routine. Yet, the focus continues to be on treatmentwhich increasingly lines the pockets of Big Pharma and doctors.

The search for cause has practically been ignored, even in the face of rising rates of chronic illness. Instead, treatment is the touchstone. Ever more toxic methods of suppressing symptoms, while hiding adverse effects, are researched and pushed on conventional medicine's victims.

Two of the most critical functions in health are drastically compromised in enormous numbers of today's children. The ability to metabolize food and the ability to breathe are being stolen from this generation. Yet the treatment they're receiving for this poor health does nothing to make them well. It only masks the symptoms and makes their children even sicker!

On top of those losses, children suffer from allergies, their bodies' inability to distinguish between disease-inducing agents and harmless substances. They suffer from autoimmune disorders, their bodies' inability to distinguish between foreign substances and parts of their own bodies.

Has there ever been a generation of children whose inherent health has been so devastated by the very medical system that is supposedly responsible for their health?

Iatrogenic Disease


Iatrogenic disorders are health problems caused by medical errors. They are now officially the third-leading cause of death in the United States. But those numbers do not include early deaths from diabetes, asthma, allergies, chronic bowel disorders, or cancerall of which have been documented as results of antibiotic usenor are the miseries suffered by the people burdened with them reckoned in the iatrogenic toll.

If we were to add all those early deaths to the iatrogenesis numbers, as should be done, it would be obvious that conventional medicine is the greatest killer and thief of health the world has ever known. And apparently, one of the most significant causes of iatrogenic illness is antibiotics, that most common of treatments handed out like candy.
 

MonkeyMan

Senior Member
Messages
405
Now, I make these sketches just as much for myself as for others, but anyway here's how I think (with emphasis on think) the dots are connected.

I think that the difference between a gradual onset of CFS and a abrupt onset of CFS is if the virus builds up slowly in the body over years or if a significant trigger speeds up the process (vaccine, EBV, Herpes, flu, tick borne diseases etc). If the trigger not only triggers, but also stays there afterwards than it would add to the burden, making the CFS even worse.

The active virus is likely a retrovirus.

2ikf7kk.png

Hi Redo--

I've been thinking about this, and was wondering, do you think the a fecal transplant procedure would be helpful, based upon this?

Thanks,
Drew
 

mellster

Marco
Messages
805
Location
San Francisco
Drew - I believe it def would help reducing bacteria overgrowth and gut permeability which is huge. I also do believe that most PWC's initially have the high cortisol response to this situation and the cortisol only depletes over time (adrenal fatigue).
 

MonkeyMan

Senior Member
Messages
405
Drew - I believe it def would help reducing bacteria overgrowth and gut permeability which is huge. I also do believe that most PWC's initially have the high cortisol response to this situation and the cortisol only depletes over time (adrenal fatigue).

Thanks Mellster, this is encouraging. Now I just wish I could find a clinic that would do the procedure. I've called several and they will not.

Anyone know of anywhere in the United States that will do a fecal transplant?

Drew
 

redo

Senior Member
Messages
874
Like I wrote earlier, the scheme is made just as much to sort my thoughts as it is to use for others. But nevertheless I post it, as I appreceite comments (both pro and con).

Having got more data, I have made some changes. Especially how the fatigue almost vanished in this study http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2711959/ has got me thinking that the methylation problems are most likely a result of autoimmunity (rather than something which comes direct from a pathogen). I am not sure where to place mitochondrial problems, whether it fits best as a result of methylation problems (if someone knows if that's possible, please weigh in) or as a consequence of the immune system acting out.

I also appreciated Richvank's video lecture on methylation, and I really think it's absolutely central to especially the fatigue symptom.

So here's the 2.0 version of the hypothesis as to why we've got the symptoms we've got.

28m1x04.jpg


Edting of the post, 14. October (adding the text below)

How does this fit with how patients respond to treatments and stressors
Rituximab. The treatment stops the immune system from having the detrimental effects on the patient. It's also possible that the reason the patients feel better is that it has a clearing effect on a virus, although I find that less likely at the time being.

Antibiotics. They might also work against pathogens which are active because the immune system is having a hard time due to the retrovirus. Antibiotics may have strong immunemodulating effects and can make symptoms better that way. They can also actually have beneficial effects on the gut (if there's a pathogenic overgrowth of harmful bacteria -- of course they may have the opposite effect as well).

Antiretrovirals. Some patients get worse. Some on this forum as well. For others it's rollercoaster ride (worse/better). As for why they get worse, it could be something similar which happens in the studies where they give ARVs to mice with MLVs (the virus gets "whipped up" and the autoimmunity exacerbates). We don't know which retrovirus we're dealing with, so it wouldn't surprise me if such mechanisms where present. Others may improve.

Antivirals. Montoya had a study where concluded that it might be immune modulating effects which made the patients better of Valcyte. Otherwise the immune problems which causes persistence of other infections (illustrated in the immune box above) could be a reason why various antivirals work. Such as Valtrex, Valcyte and more.

Imunovir. It might work because it has a slight effect on the virus behind the whole shebang. It might work because it has an effect on (other) viruses which are activated because of the compromised state the immune system is in, it might work because of immune modulating effects making the patient better (just because the autoimmunity gets less exacerbated).

Mentally demanding tasks. Psychological stress or mentally demanding tasks. Stress in the psychological sense is known to make the ME symptoms more severe, at least for a short period of time. The reason for this seems to me that the stress makes the immune system function a lot worse for a period of time. It also sends more sensory signals to the brain, and with problems handling it as it is, it makes it a lot worse when this happens. I think this also has a strong connection to the gut sketch above. If there are a pathogenic mix/load of bacteria there, it can change the person. Breakdown of dopamine and noradrenalin can take a whole lot longer time. The result? Dopamine and noradrenalin builds up to way to high levels in the body (much the same as what happens when we CFS patients concentrate on a demanding subject for a period of time). It can take days or more for the ME patient to clear out the large amounts of dopamine and noradrenaline which healthy people clears out in a glimpse.

Exercise. The vast majority of ME patients experience a symptom worsening after exercise. Not only do they get more problems with the fatigue symptom. Most symptoms get worse. This fits very well with the immune modulating effects exercise does have on ME patients, which it does not have on healthy controls. http://www.ncbi.nlm.nih.gov/pubmed/20230500 It may be the cytokines mentioned there, but it may very well be other (not yet discovered) immune abnormalities which gets exaggerated when PWME exercise.

Other treatments?? Other stressors. Please come with suggestions as to why something fits or doesn't fit into the sketch above. If something doesn't fit, it's valuable to know! :)
 

maddietod

Senior Member
Messages
2,859
So Redo, where can I buy the poster? My doctor needs this (he just doesn't know it yet).

Madie
 

mellster

Marco
Messages
805
Location
San Francisco
Agree I need to order this - this is IMO the best explanation for the pathway to mitochondrial dysfunction and methylation issues as well as Th1/Th2 shift. We need that as a poster ;)
 

redo

Senior Member
Messages
874
I am glad you liked that I posted it. As I wrote earlier, the reason I am making them is sorting my thoughts (and not presenting fact :). So I am more than willing to adjust accordingly if I change my mind, and I am not embarrassed to do so. Actually I appreciate input telling me I this or that is wrong or correct because of this and that. Here's my sketch as for the triggering.

It's enough that the trigger is there for a short period of time. After the trigger has triggered the pathogen, it can go away, and the patient is still sick...

I could add hormonal changes to triggers. Some gets sick in adolescence without any specific even prior to it. In these cases I suspect the patients gets a gradual onset instead of a abrupt onset. Sometimes the patient could also get a gradual onset if the virus doesn't activate as quickly as it does with others.


2i06gbr.png



It's only working model I've got as to why such totally different things such as a vaccine, an EBV infection or a giardia infection can trigger the same bucket of symptoms (ME/CFS)... I am thinking that the only common nominator between those vastly different things is that they challenge and stress the immune system for a short period of time, and in that time frame, a previously (specific) latent infection (which CFS patients share) becomes active. Now I am leaning towards that previously latent infection being a retrovirus. But I am open to other views, it might be a bacteriological infection which lies latent instead, although I find that less likely at the time being.
 

redo

Senior Member
Messages
874
The way the disease often begins can have some resemblance to how HIV infections begin:

Different phases. At first patients often have a period with swollen lymph nodes, and general malaise, flu like feeling. And often the predominant symptoms later are the extreme brain fog, exhaustion, coordinating problems, plus flu like feeling et cetera. It's not a parallel to HIV, but there are some similarities. Some weeks, up to a half year or so, the first phase of the disease is there, and later on other symptoms become the main problems.

729px-Hiv-timecourse_copy.svg.png
 

redo

Senior Member
Messages
874
How does this fit with how patients respond to treatments and stressors
Rituximab. The treatment stops the immune system from having the detrimental effects on the patient. It's also possible that the reason the patients feel better is that it has a clearing effect on a virus, although I find that less likely at the time being.

Antibiotics. They might also work against pathogens which are active because the immune system is having a hard time due to the retrovirus. Antibiotics may have strong immunemodulating effects and can make symptoms better that way. They can also actually have beneficial effects on the gut (if there's a pathogenic overgrowth of harmful bacteria -- of course they may have the opposite effect as well).

Antiretrovirals. Some patients get worse. Some on this forum as well. For others it's rollercoaster ride (worse/better). As for why they get worse, it could be something similar which happens in the studies where they give ARVs to mice with MLVs (the virus gets "whipped up" and the autoimmunity exacerbates). We don't know which retrovirus we're dealing with, so it wouldn't surprise me if such mechanisms where present. Others may improve.

Antivirals. Montoya had a study where concluded that it might be immune modulating effects which made the patients better of Valcyte. Otherwise the immune problems which causes persistence of other infections (illustrated in the immune box above) could be a reason why various antivirals work. Such as Valtrex, Valcyte and more.

Imunovir. It might work because it has a slight effect on the virus behind the whole shebang. It might work because it has an effect on (other) viruses which are activated because of the compromised state the immune system is in, it might work because of immune modulating effects making the patient better (just because the autoimmunity gets less exacerbated).

Mentally demanding tasks. Psychological stress or mentally demanding tasks. Stress in the psychological sense is known to make the ME symptoms more severe, at least for a short period of time. The reason for this seems to me that the stress makes the immune system function a lot worse for a period of time. It also sends more sensory signals to the brain, and with problems handling it as it is, it makes it a lot worse when this happens. I think this also has a strong connection to the gut sketch above. If there are a pathogenic mix/load of bacteria there, it can change the person. Breakdown of dopamine and noradrenalin can take a whole lot longer time. The result? Dopamine and noradrenalin builds up to way to high levels in the body (much the same as what happens when we CFS patients concentrate on a demanding subject for a period of time). It can take days or more for the ME patient to clear out the large amounts of dopamine and noradrenaline which healthy people clears out in a glimpse.

Exercise. The vast majority of ME patients experience a symptom worsening after exercise. Not only do they get more problems with the fatigue symptom. Most symptoms get worse. This fits very well with the immune modulating effects exercise does have on ME patients, which it does not have on healthy controls. http://www.ncbi.nlm.nih.gov/pubmed/20230500 It may be the cytokines mentioned there, but it may very well be other (not yet discovered) immune abnormalities which gets exaggerated when PWME exercise.

Other treatments?? Other stressors. Please come with suggestions as to why something fits or doesn't fit into the sketch above. If something doesn't fit, it's valuable to know! :)

As for the symptom of intolerance of chemicals. I'll try and fit that in later. I'll see where I think it goes best, and change accordingly if it doesn't fit. I am updating the post above instead of making a new one. As for the gender discrepancies. I'll fit that in later. I wrote some about that in another thread.