Defect in the MTHFR Gene is Present in CFS and most all other Autoimmune Diseases

[JES]

Correlation doesn't prove causation, which sounds like a mantra, but this point cannot be stressed highly enough. Even if we grant that MTHFR defect is present more commonly in autoimmune diseases, that doesn't tell us whether MTHFR is the causative factor behind them. It could be, but to oversimplify a bit, I could claim that having two X chromosomes causes autoimmune diseases, because almost every autoimmune disease is more common in women than men, including ME/CFS. But obviously I think we all agree that being a woman cannot be considered a direct disease causative factor.

Now one possible mechanism, as you mention, for MTHFR actually causing ME/CFS would be from the resulting decrease in methylation. Here it is worth mentioning that heterozygous and homozygous MTHFR mutations have a different degree of effect, so not everyone with one or more MTHFR polymorphims has necessarily a much reduced methylation as a consequence. But to the extent that for example a homozygous MTHFR mutation would cause decreased methylation, the next question would be does this have any much impact in ME/CFS? I would say there is little evidence to show that methylation and methylation treatments are of particular importance in ME/CFS. You linked to a CFS/ME study with B12 supplementation, but that study did not have a placebo group and participants rated themselves improved or not improved, very much like in the PACE trial.

I would look at the methylation section of this forum rather than rely on one small scale study. Thousands of PhoenixRising users have tried various methylation protocols over the years and the effect has been overall disappointing. The late Rich van Konynenburg provided much insight into these treatments, but it seems B12 and methylfolate does not help us any more than other popular supplements like Omega-3's, magnesium, LDN, etc. For me, attempting to treat methylation was the single most disappointing experiment, but I don't deny its value completely. With a homozygous MTHFR mutation, folate supplementation does make sense either way to be safe.

 

[Rufous McKinney]

having two X chromosomes causes autoimmune diseases, because almost every autoimmune disease is more common in women than men,

This could be hormonal, and involving estrogen and testosterone; rather than being sex-linked (on the X chromosome).

As a red head, I"m homozygous for numerous red head genes. MTHFR seems to be a close friend.

And a totally random comment- my husband is rarely sick, and I"m frequently sick. My husband exhibits little or no stress and has never worked in a "stressful" environment. I worked for

 

[Rufous McKinney]

And a totally random comment- my husband is rarely sick, and I"m frequently sick. My husband exhibits little or no stress and has never worked in a "stressful" environment. I worked for

opps the comment was not completed: I worked for 40 years in an intensely stressful environment.

 

[pogoman]

I'm one of the members that has the bad MTHFR mutation and wasn't helped by B vitamins and folate.
I learned unless you have a high homocysteine level then MTHFR is not going to be an issue, pregnant women excepted.
I also learned genetic specialists will roll their eyes if you mention MTHFR lol

 

[Annikki]

thank you very much for this major information and all the work you've done summarizing this.

I didn't get tested: i just know I have this. (sorry if that sounds lame)

I've been slow to uptake all the latest but my foggy sense of the matter is: for whatever reason, that mutation happened and has been carried for a long time. I think it just pre-disposes those bodies to: having bit harder time of it, but not THAT hard.

You are welcome. I'd agree with you and say yes, toxins contribute to CFS. I also think because CFS occurs in epidemics and seems transmissible, that a virus is involved. I did this research on MTHFR and while doing this learned that virus activity can cause a MTHFR mutation. I will share, part of an article I mentioned in my first post on this thread:

"Any significant pathogen or toxin can impair the body's neurological and immune systems, mitochondrial energy, and subsequently, methylation function and gene expressions. Dozens of viruses are capable of posing this threat...
Acclaimed researchers Dr. Judy Mikovits and Dr. Frank Ruscetti brought great advances in the field of viral immunity and retroviral science. In particular, their work with Chronic Fatigue Syndrome (CFS) and its associations with the Herpes viruses and certain cancers was ground-breaking. While many doctors and practitioners have climbed onto the methylation bandwagon, unfortunately, CFS and its associated immune disorders are largely still considered to be psychosomatic problems with little understanding of the impacts the syndrome has upon methylation. Dr. Robert Naviaux stated very cleasrly in this Science Daily publication in March, 2013: "When cells are exposed to classical forms of danger, such as a virus or infection or toxic-environmental substances, a defense mechanism is activated. This causes changes to metabolism and gene expression, and reduces the communication between neighboring cells."
Dr's Mikovits and Ruscetti made scientific correlations between CFS and the XMRV retrovirus. In 67% of CFS patients, XMRV-like retroviruses and its telltale compromises of NKCs (natural killer cells) and T-cell rearrangements were identified. (1) A retrovirus is an RNA virus containing the enzyme reverse transcriptase. When the virus enters the cell, it utilizes reverse transcriptase to direct the cell to create viral DNA. This viral DNA becomes integrated into the host cell DNA. Once the DNA becomes impacted by this change in DNA transcription, the infected person is susceptible to numerous genetic mutations, including MTHFR and many other genes which control methylation. (Of note here also is the fact that once retroviruses become integrated into parents' DNA, they may become integrated into children's DNA in conception as well.)"

https://www.truenaturehealthconsult...ylation-and-functional-approaches-for-healing

Simply put, you are right, hazardous chemicals and products are contributing to CFS. There also many other problems at work in CFS. From pollutants and environmental toxins, to viruses, to genetics, the various contributing factors work together and exacerbate each other

I think because it is a combination of many things that send the body over the edge into CFS, it is difficult to treat. It is also worth noting that if you remove heavy metals and pollutants you get some improvement in symptoms. This doesn't cure it, really nothing does, but it helps. I think full recovery entails fixing all the various systems sent into chaos from CFS. As for a cure, we are likely going to have to wait, so fixing what we can is all we can do to get improvement. Is addressing folate metabolism important to recovery? It isn't a cure, but it might help.

It helps to look at CFS like a totaled vehicle after a collision. There are a lot of broken or ruined parts. When I point out MTHFR, it is like me saying, "it looks like the fuel line is snapped, too." It's just one more damaged part, in a vast many.

About your thoughts on environmental stressors- I agree. I look at the science and how Simon Wessely lambasts Multiple Chemical Sensitivity patients as kooks, also. He also "debunked" people who got sick from what I think was a nickel cadmium spill. Wessely has a history of gunning for people damaged by bad industrial practices. Wessely could get some extra part time work doing climate change denial "studies" and do very well at it.

I think he and the lot of those people know more about what causes CFS and that what causes it will make some industries and people look very bad. Why deny an illness? It's a lot of work put into keeping people miserable. If you say there are no sick people, and in effect, hide the illness, would anyone work to find the cause of it? No! We all have suffered immensely from this. This much I am sure of.

 

[Annikki]

It keeps getting stranger, there seem to be more and more crossover and similarity among all the autoimmune diseases. Again, it's worthy of paying attention to, since there's not a sufficient amount of research or research money put into CFS. However, some of the studies done about comorbid diseases have much to teach about what is driving CFS and generating its symptoms. Now EBV has been found to in the bladders of interstitial cystitis patients, and is said by study to place a causative role in the disease:
Interstitial Cystitis/Bladder Pain Syndrome Linked to EBV
https://www.renalandurologynews.com...cystitis-bladder-pain-syndrome-linked-to-ebv/
Viruses are indeed playing a role in these diseases and EBV is a big one. It's been seen to cause problems in Chronic Fatigue Syndrome, Chronic Lyme Disease, Fibromyalgia, rheumatoid arthritis, systemic lupus erythematosus, Sjögren’s syndrome, autoimmune thyroiditis and Multiple Sclerosis, according to the following article:
About Chronic Lyme, fibromyalgia and EBV:
"Epstein-Barr Virus: A Key Player in Chronic Illness"
https://rawlsmd.com/health-articles/epstein-barr-virus-a-key-player-in-chronic-illness
This is a great article, it explains the behavior of EBV very clearly and how it relates to these illnesses that are associated with CFS. EBV is part of the puzzle. My goal is to get as many of the pieces of the puzzle and see how they fit together.

Viruses and pathogens which don't cause problems in normal people appear in CFS, and related diseases. EBV was excluded as the cause of CFS. EBV is still present in many CFS patients. A good assumption to make is that something is affecting immunity in CFS. I have never believed autoimmune disease to be the body attacking itself for no reason. It's more likely the immune system is faced with an infection it can't clear. Find the pathogen provoking the immune response, and the inflammation and swelling should be reduced. It would alleviate inflammation in the brain to allow it to heal and recuperate.

I think it's more than MTHFR, there is something happening to activate these pathogens in a way that leads to disease in some people. Judy Mikovits said that there's an underlying retroviral infection activating latent viruses and causing co-infections. A retrovirus can change MTHFR and alter its expression.

 

[Hip]

Now EBV has been found to in the bladders of interstitial cystitis patients

That's a good find, I have added that EBV connection to IC to my List of Chronic Human Diseases Linked to Infectious Pathogens website.

EBV was excluded as the cause of CFS.

I don't think it has been excluded as a possible cause, as there are several studies which show ME/CFS is triggered after around 4% of cases of mononucleosis. And some ME/CFS patients have high antibody titers to EBV.

Note that viruses can engage more types of infection than just active infection and latency. We normally think of a virus as either being active, or going into the dormant state of latency. But there are other shades of gray here, and other modes of infection than a virus can enter into.

For example, EBV is known to have three states of latency, called I, II and III. In latency I, the virus is pretty much dormant, but in latency II and III states, the virus is actively doing things (it's not a full infection, but it's not dormant either).

And viruses may create what are known as abortive infections. These occur when a virus infects the "wrong" type of cell.

Normally viral infections are of the permissive type, but if the virus enters the wrong type of cell, it can create an abortive infection instead. Abortive infections can be chronic, but they do not produce new viral particles, so you may not see much virus in the blood, which may make abortive infections hard to detect.

Dr Lerner's theory is that ME/CFS is caused by abortive infection of either EBV, cytomegalovirus or HHV-6.

I have never believed autoimmune disease to be the body attacking itself for no reason. It's more likely the immune system is faced with an infection it can't clear.

I also think that's very likely, or at least very likely that infection is an important factor on the road to triggering autoimmunity.

You might enjoy reading the works of Prof Paul Ewald. He proposes that most chronic diseases and cancers of currently unknown etiology will likely turn out to be caused by common pathogens in circulation.

He points out that in the 1970s, no cancers had ever been linked to pathogens. Decades of research later, as it stands at present, we've found that 20% of cancers are now known to be caused by pathogens. Ewald suspects that in the future, we will have found that around 80% of cancers are causes by pathogens.

 

[Rufous McKinney]

Why deny an illness? It's a lot of work put into keeping people miserable. If you say there are no sick people, and in effect, hide the illness, would anyone work to find the cause of it? No! We all have suffered immensely from this. This much I am sure of.

Definately see this sinister underbelly. Really dangerous if they acknowledge "us".

Look at the vaccination issue. I note: Vaccinations were presented as a trigger (there were several) in todays' NIH conference. And we are not allowed to debate vaccinations.

 

[Rufous McKinney]

"it looks like the fuel line is snapped, too."

what a great Analogy!

 

[Rufous McKinney]

It keeps getting stranger, there seem to be more and more crossover and similarity among all the autoimmune diseases.

During a momentary lapse in rational judgement and brief episode of lift, I tweeted. I was upset about the mandatory vaccinations and general hysteria happening at the moment.

My first tweet said: this huge increase in autoimmune disorders should be very very concerning and we are playing roulette with the vaccination schedule and failure to identify and protect sensitive individuals (that include my gene pool).

so I am self impresssed with self for this briliance. (hah)

 

[Rufous McKinney]

Now EBV has been found to in the bladders of interstitial cystitis patients

Come over here and meet: my bladder. Mine has improved but really gives me grief. So it flares during crashes also. Really painful at times. I would totally believe EBV is hanging out there. Now: take off ! Blow on out of there please.

 

[junkcrap50]

. That's why I'm intrigued by the MTHFR finding. MTHFR accounts for this. And I highly expect, MTHFR defects found in CFS patients gives rise to some CFS patients having EBV. We know EBV isn't found in all CFS patients. A deficient MTHFR gene probably is what allows EBV to remain active in CFS patients.

The study mentioned earlier found MTHFR mutations to be more common in ME/CFS, so that suggests these mutations may be playing some sort of causal role in this disease. But what that role might be is anybody's guess.

A handful of healthy people having the defect doesn't change that a vast multitude of studies confirm there is a link between MTHFR polymorphism and disease.

I wonder if they are finding the defect in so many disease types, because the defect is so common in EVERYONE though. You would need to take a huge sample from the healthy population to prove they DON'T have the defect to make the connection that the defect is responsible for disease. Not saying I know one way or the other but correlation does not always equal causation. Like I said before, my husband has the exact defect I do, and he has no health problems.

I think MTHFR is fairly common. But most people live and die without ever knowing of its existence, because it doesn't bother most people enough that they would notice. Their bodies are capable of compensating. Some people's bodies are not, and it causes problems. I think it is a piece of a very large puzzle, but not necessarily the key to unlocking the door. Just my thoughts.

So we should be in agreement that a higher prevalence of MTHFR mutations in a given disease shows that these mutations may be playing a causal role, because that's what the studies you listed are saying.

Just how much of a causal role MTHFR mutations are playing depends on how high the prevalence is in a given disease, compared to the general population.

for whatever reason, that mutation happened and has been carried for a long time. I think it just pre-disposes those bodies to: having bit harder time of it, but not THAT hard. I was able to reproduce (in theory, two, in reality, only one made it). That one probably is a carrier but not homozygous. I will then bet money my husband who never gets any of this stuff: does not have the MTHFRE.

I think a lot of people are missing an important point on these methylation SNIP mutations (MTHFR, MTRR, CBS, DHPR, etc. ). (And of course, correct me if I'm wrong. But this is/was my understanding. Its been a while since I visited methylation. And the more that I think of it, I doubt myself more.) You're all forgetting the needed epigenetic changes on these genes. Just because you have a particular mutation, does not necessarily mean a decrease or loss in function, no? The gene still has to undergo a stress or change in someway to function inefficiently. Which could be caused by a variety of factors, including viral. It may explain the difference in symptoms & illness of various groups.

Also, multiple SNIPs (of the same gene or genes further down the chemical pathway) may compound on top of each other - resulting a widely variable effectiveness. Also, there may be more variants of a particular SNIP/gene (discovered and undiscovered) which may be able to carry some/most of the gene load of a a major SNIP C6771T that's nonfunctioning or underperforming. A person's constellation of SNIP variants or other different SNIPs on those other variants could have a big effect when looking at only variant (eg: MTHFR C6771T).

 

[SWAlexander]

Infections and autoimmunity: risk factors for [CFS] and subsequent B cell lymphoma and chronic lymphocytic leukemia development (planned study) Rosén

Funding announcement by the Swedish Cancer Society:

Infections and autoimmunity: risk factors for chronic fatigue syndrome and subsequent B cell lymphoma and chronic lymphocytic leukemia development

Anders Rosén
Linköping University, Sweden
2022

SEK 1 600 000
Diagnosis: lymphoma
Research area: preclinical research

https://www.cancerfonden.se/forskning/projekt/62bda998a7d6e40004146505

Auto-translate:

"Background

Chronic bacterial and viral infections, such as pneumonia and glandular fever, can lead to the conversion of certain white blood cells into leukaemia cells. We are studying how this may be the starting point for chronic lymphocytic leukemia, CLL, and myalgic encephalomyelitis/chronic fatigue syndrome, ME/CFS. CLL arises from white blood cells called B lymphocytes, which produce so-called natural antibodies directed against microbes as well as their own cells called autoantigens. Infection + autoantibody formation is also seen in ME/CFS. We now know that several genetic defects exist, but we do not know how infections interact with these to cause disease development.

Description

We are studying basic molecular mechanisms in the development of CLL and ME/CFS, which confer an increased risk of B lymphoma. In B cells, various signals are generated from receptors such as membrane IgM, as well as DNA sensors. These interact to prevent the entry of bacteria and viruses e.g. into damaged mucosa or skin. In the case of long-lasting infections, which do not heal completely, B cells can start to multiply. But unfortunately, the risk of chromosome damage increases at the same time, because the inflamed environment of an infection contains harmful reactive oxygen radicals. These modify proteins, lipids and DNA, which can lead to autoimmunity and the risk of B malignancy.

Target

CLL is the most common type of leukaemia in adults. Every year, about 500 people are diagnosed in Sweden. Some patients can live for decades without treatment, while others develop more aggressive disease and die within a few years despite intensive treatment. There is currently no cure.
We want to elucidate the cellular drivers of CLL and ME/CFS. In particular, the importance of blocking the signals that drive cell growth, with a focus on signals from microbe-induced modifications. One possible strategy is to block multiple signals simultaneously and thereby prevent the growth of leukemia. We are participating in multicentre studies where these therapeutic approaches are tested clinically."
https://www.s4me.info/threads/infec...opment-planned-study-rosén.28380/#post-426573​