Do MEs cause CFS?

[Leopardtail]

@Jonathan Edwards I really appreciate your skepticism.

In my opinion, patients are desperate and will experiement a lot and will also subscibe to theories or anedoctal reports of improvements. We are all different and what one reports as helpful could be due to so many different things, or could be just temporary or represent the placebo effect.

We need to realize that if the majority of us is still on the furums, we haven't been cured of what ails us.

Regarding methylation protocol and generitc data. Have you ever looked at MTHFR gene mutation apparently is supposed to be the cause of a wide array of diseases? It's too good to be true. The other aspect that makes me skeptical is that apparently if it's not working, it's because you haven't done it right. give me a break.

i will see it when there is good research showing proofs of that. Personally I tested homozygous for one gene, have been on methyl B-12 and folate for 6 months, and there is absolutely no change in my condition. i am not going to discuss this further in case someone is wanting to tell me to try another brand or asking whether I did not 'methyl trap.' Avd I will not pay the 30$ a months it take for methylfolate, I bet it all goes in the sewage in the end.

We need sound research out there, and of course funding for our researchers.
Thank you @Jonathan Edwards

I feel the most important thing people need to take on board is that the original research by RVK was done on patients who had received treatment for fundamental ATP production, then hormonal deficiencies before Methylation was treated - hence it was part of a treatment package not an isolated treatment.

Describing patients as 'desperate' however is far from my experience. Large numbers of patients on Phoenix are very methodical, inspect the available science and closely monitor how well things are working.

Your point that far more research funding needs to be made available however I think we would all agree with. In particular there needs to be more small scale funding available to repeat studies. At the moment we have charities prepared to fund small studies only if they are 'novel' and state bodies wanting to fund large studies with very limited remits from experienced researchers. Studies like the Methylation issue need to be repeated small scale first, then scaled up if the results warrant it.

The big issue however is that access to funding is granted by doctors whose understanding of things like Methylation is bar and large very poor. We are hence told there is not enough evidence by the very group of people whose ignorance prevents access to funding. Vitamin digestion, absorption by cells and pre-processing into 'active' forms is highly complex and needs specialist knowledge that is currently separated out into 'functional medicine' that is regarded with suspicion by 'conventional' medicine due to ignorance rather than sound argument.

Medical Science is failing in mutli-system diseases such as ME, Fibromyalgia because its stuck in a very silly 'system model' and far too ignorant of biochemistry common to all cells.

 

[MeSci]

Describing patients as 'desperate' however is far from my experience. Large numbers of patients on Phoenix are very methodical, inspect the available science and closely monitor how well things are working.

One can be both desperate and methodical. One definition of 'desperate' is 'having a great need or desire for something'. This is our kind of desperation - a quiet desperation that motivates us to search for our own solutions.

The big issue however is that access to funding is granted by doctors whose understanding of things like Methylation is bar and large very poor.

I can't think of a context where doctors grant funding. Can you give an example?

 

[Leopardtail]

One can be both desperate and methodical. One definition of 'desperate' is 'having a great need or desire for something'. This is our kind of desperation - a quiet desperation that motivates us to search for our own solutions.

That is not the definition that meets the general tone of this statement.

"In my opinion, patients are desperate and will experiment a lot and will also subscribe to theories or anecdotal reports of improvements."

I can't think of a context where doctors grant funding. Can you give an example?

The MRC is entirely populated by Doctors, not a single biochemist on the panel. The panels of our national charities that assess funding applications all have medical rather than biochemical backgrounds. The panel also lacks an endocrine/diabetic specialist the one area of medicine that might best understand this stuff - in addition to the obvious lack of endocrine specialism.

 

[MeSci]

That is not the definition that meets the general tone of this statement.

"In my opinion, patients are desperate and will experiment a lot and will also subscribe to theories or anecdotal reports of improvements."


The MRC is entirely populated by Doctors, not a single biochemist on the panel. The panels of our national charities that assess funding applications all have medical rather than biochemical backgrounds. The panel also lacks an endocrine/diabetic specialist the one area of medicine that might best understand this stuff - in addition to the obvious lack of endocrine specialism.

I wasn't familiar with the structure of the MRC, but have just had a quick look at their website. As far as I can figure out, funding is decided/awarded by the various research boards, which are listed here.

Looking at them quickly, they seem to be dominated by professors attached to academic institutions.

I'm sure @Jonathan Edwards can give us a clearer picture!

 

[lansbergen]

One can be both desperate and methodical. One definition of 'desperate' is 'having a great need or desire for something'. This is our kind of desperation - a quiet desperation that motivates us to search for our own solutions.

Yes but not everybody has enough knowlegde to avoid the pitfalls and the chaotic ME brain is an obstacle.

 

[chipmunk1]

"In my opinion, patients are desperate and will experiment a lot and will also subscribe to theories or anecdotal reports of improvements."

so do doctors. most psychosomatic disorders have no evidence other than a few selected anecdotal reports.

 

[Leopardtail]

I wasn't familiar with the structure of the MRC, but have just had a quick look at their website. As far as I can figure out, funding is decided/awarded by the various research boards, which are listed here.

Looking at them quickly, they seem to be dominated by professors attached to academic institutions.

I'm sure @Jonathan Edwards can give us a clearer picture!

You will need to look at the "Kew National Archive" the MRC appeared to have obfuscated the membership of the CFS/ME panel about a year ago. What makes you think professors of medical disciplines are not doctors? The fact remains that areas better understood by institutes of 'functional medicine' and biochemists are not represented on that panel, and that it lacks endocrine special expertise.

 

[MeSci]

You will need to look at the "Kew National Archive" the MRC appeared to have obfuscated the membership of the CFS/ME panel about a year ago. What makes you think professors of medical disciplines are not doctors? The fact remains that areas better understood by institutes of 'functional medicine' and biochemists are not represented on that panel, and that it lacks endocrine special expertise.

It is possible that some of the academic professors are also doctors. I did not say that they weren't.

Do you have a link to the info you are talking about?

 

[Leopardtail]

It is possible that some of the academic professors are also doctors. I did not say that they weren't.

Do you have a link to the info you are talking about?

They almost always are practicing doctors in medicine - doctors learn by doing.

I originally checked it at the MRC site in 2012 before they obfuscated it - so no cannot provide a link. The Kew National Archive keeps historic versions of documents.

 

[Jonathan Edwards]

You will need to look at the "Kew National Archive" the MRC appeared to have obfuscated the membership of the CFS/ME panel about a year ago. What makes you think professors of medical disciplines are not doctors? The fact remains that areas better understood by institutes of 'functional medicine' and biochemists are not represented on that panel, and that it lacks endocrine special expertise.

Excuse me, Leopardtail, but what makes you think that a biochemist who may happen to be have got medically qualified some years ago is not a biochemist. The MRC is up to the armpits in biochemists - and a lot of them are not medically qualified. Grants are sent out to review by experts way beyond those on the panels themselves. I think that one was a bit of hot air!

 

[Jonathan Edwards]

Regarding methylation protocol and generitc data. Have you ever looked at MTHFR gene mutation apparently is supposed to be the cause of a wide array of diseases? It's too good to be true.

Yes, there seems to be an awful lot of talk about methylation on the forum but I cannot see how it would be relevant to ME. I may be wrong but the interest seems to have been largely driven by people who are not biochemists - not even medically qualified biochemists. But I am prepared to listen and listen. Methylation is pervasive in cellular metabolism. A defect in methylation seems likely to me to be either fatal or to cause some severe congenital or developmental syndrome. So far it does not begin to make sense to me for ME.

 

[Leopardtail]

Excuse me, Leopardtail, but what makes you think that a biochemist who may happen to be have got medically qualified some years ago is not a biochemist. The MRC is up to the armpits in biochemists - and a lot of them are not medically qualified. Grants are sent out to review by experts way beyond those on the panels themselves. I think that one was a bit of hot air!

They are not on CFS/ME panel however which is where one needs to be. I spoke with several members of that panel all of whom were largely ignorant of the state of intracellular research.

I also checked the qualifications of each member of the panel and their research history looking for hidden expertise.

I do not assume you lack thoroughness even when I disagree. Show me the same courteous please.

 

[Jonathan Edwards]

You sounded as if you were talking about the MRC in general, Leopardtail. And the CFS/ME panel is surely only an extra ad hoc panel set up to try to foster CFS research anyway. Projects on methylation could go to a biochemistry panel. And also, looking at current the ME/CFS panel, it includes Professor Frank Kelly, whose main interest is free radical/antioxidant biochemistry - so presumably he is a biochemist?

The MRC may not have a brilliant track record for funding innovative research but it does look to me as if there is a biochemist on the ME panel!

 

[Leopardtail]

You sounded as if you were talking about the MRC in general, Leopardtail. And the CFS/ME panel is surely only an extra ad hoc panel set up to try to foster CFS research anyway. Projects on methylation could go to a biochemistry panel. And also, looking at current the ME/CFS panel, it includes Professor Frank Kelly, whose main interest is free radical/antioxidant biochemistry - so presumably he is a biochemist?

The MRC may not have a brilliant track record for funding innovative research but it does look to me as if there is a biochemist on the ME panel!

I thought your response seemed odd! It followed the earlier thread of conversation relating to ME research.

Vis-a-vis (for example Methylation) and given how contentious it is do you think a biochem panel would be likely to even consider funding an ME/CFS specific project than referring back to the ME panel?

My understanding was the Kelly is a pulmonary specialist with an interest in free radical effects caused by pollution hence the biochemistry being a limited 'side interest' to his primary expertise rather than a fully expert biochemist. Have you found other information?

I understand that many medics have some interest in biochemistry localized around their special interest (e.g. Immunology in your case). Compared with a biochemist such as Alex though, that would warrant the term 'working knowlege' rather than 'expert'. Given that this is a multi-system illness the idea that it might well be primarily intra-cellular (e.g. Methylation, ATP synthase or similar) needs to be kept in mind and detailed appropriate knowledge available.

The desired focus for collaborative multi-system projects really should be treating the intra-cellular as a 'system' in this context. Among other reasons, energy generation occurs entirely within the cells if one ignores 'fuel supply'. Add to that the very high number of indirect interactions (based upon substrate use) in biochemistry between separate aspects of metabolism and it's every bit as complex as the lymphatic system, very likely with even more interactions. Initially I thought a 'good working knowledge of' was sufficient, however Alex has made me think otherwise.

Is the precise nature of my objection to the current panel clearer now?

Bear in mind I also highlighted the lack of expertise in Endocrinology (despite widespread reporting of dysfunctions in that field) or diabetes (the clearest form of energy management disease). A specialist in type II diabetes is involved principally in the intracellular hence (my guess) would be the medic with the strongest common of cellular biochemistry and likely to have a solid command of endocrinology.

 

[Kati]

i think it is fair to say that there are distincts gene expression for patients with ME. The recent work of Jonathan Kerr and allan and Kathleen Light have shown that in publication.

What is exactly means, we don't know. We need more research, large cohorts and funding.

i think the methylation protocols, Rich vanK and yasko for instance are theories. Glutathione and methylation are not mainstream medicine for anything at all.

For the patients who don't know better and buy a whole box of supplements each month, it doesn't make people much better and depletes the bank account. Moreover, there has been recommendations to eat more bananas for a patient with a critically low level of potassium with cardiac symptoms. We need sound research. Less self-medicine. Recommendations from patients to other patients needs to be balanced very carefully.

 

[Leopardtail]

i think it is fair to say that there are distincts gene expression for patients with ME. The recent work of Jonathan Kerr and allan and Kathleen Light have shown that in publication.

What is exactly means, we don't know. We need more research, large cohorts and funding.

i think the methylation protocols, Rich vanK and yasko for instance are theories. Glutathione and methylation are not mainstream medicine for anything at all.

For the patients who don't know better and buy a whole box of supplements each month, it doesn't make people much better and depletes the bank account. Moreover, there has been recommendations to eat more bananas for a patient with a critically low level of potassium with cardiac symptoms. We need sound research. Less self-medicine. Recommendations from patients to other patients needs to be balanced very carefully.

I can't speak for Yasko, I am not aware of any research she has conducted in ME/CFS. Rich van K is another issue entirely - it's now a theory tested in practice not a hypothesis. That research was however on a limited set of patients who had not fully responded to other therapy, hence it's use as a therapy was not independent any may well only have applied to that subset of ME patients. Other research has also shown that Glutathione and its raw material Cysteine are depleted. This is the general picture of ME research and something that for now we have to live with we have to operate on 'best available evidence' rather than ideal evidence until the research community and their funding bodies operate more effectively.

I agree entirely that more research, repeats and high cohort sizes are needed for many pieces of seemingly successful research give us solid reliable data. The problem with that may however be that as Jonathon stated at the start of this thread, we may not be dealing with a single illness, in which case its highly unlikely there will be a single reliable treatment.

The place I differ for you is that I am not prepared to remain ill for two more decades until they catch up - had I done that I would no longer be living. There are things that can be cautiously experimented with within reason (e.g. Vitamin C and certain B12s) much depends upon whether the risk of doing nothing outweighs the risks of action. Even with medical research however those risks remain - I have seen awful side effects from treatments formerly recommended by NICE using evidence based medicine.

My current primary concern is that medical researchers have no effective or consistent tool for identifying which patients response well or badly to treatments, or have expected / unexpected blood work. The symptoms of many people with severe ME amount to many pages of A4 and most do not even think about many of their symptoms unless asked because they are so used to feeling awful. This contrasts with diabetes where there is a marker separating type I from type II. People with ME have a much wider divergence of symptoms than do the various forms of diabetes, hence its well within the realm of possibility that we are much more different than the two forms of diabetes, each of which is poles apart in cause.

I do however agree that some patients appear to be 'under cautious' and under aware of possible side effects and interactions. As you rightly point out though, research should be answering those questions rather than leaving patients to work it out for themselves.

 

[Leopardtail]

Yes, there seems to be an awful lot of talk about methylation on the forum but I cannot see how it would be relevant to ME. I may be wrong but the interest seems to have been largely driven by people who are not biochemists - not even medically qualified biochemists. But I am prepared to listen and listen. Methylation is pervasive in cellular metabolism. A defect in methylation seems likely to me to be either fatal or to cause some severe congenital or developmental syndrome. So far it does not begin to make sense to me for ME.

Are you understanding Methylation defects to be total failure, or under activity? My understanding was that even with a homozygous defect that the issue was under production and feeling severely unwell rather than a complete lack of production. As you indicate that is purported to produce severe (and fatal) congenital issues such as Neural tube defects (I have not inspected the evidence of those congenital issues).

Bear in mind some forms to type II diabetes relate to under production of ATP and can leave people living but unwell for many years (pre-diabetes or mild type II with the body producing compensatory insulin). Complete lack of production would be deadly very quickly.

I am not however convinced that its the Etiology of ME if that is what you are arguing, the level of improvement with Methylation supplements is not high enough, nor is there research evidence from otherwise untreated patients.

 

[OverTheHills]

@Jonathan Edwards
I'd like to know whether autoimmune diseases are affected by exposure to allergens.

My particular reason for asking is I have an unusual (even for ME) and strong seasonal pattern to my disease: best in spring worst in summer. Its hard to tell whether autumn and winter are almost the same as summer and its just the contrast to spring that makes summer feel so bad.This applies to both northern and southern hemisphere: so in the UK mid April to Mid June are great. I get a sort of remission, my energy levels go way up, I can do loads more without PEM, think more clearly and then suddenly comes the summer and its back to very limited again.

Any thoughts?
Thankyou

OTH

 

[Persimmon]

@ Jonathan Edwards

Might some ME cases be caused by persistent enteroviral infection?

While this idea has been around for decades, Dr John Chia is currently carrying this baton. He thinks there are a number different MEs, and that some (only) of these are caused by persistent enterovirus ("EV") infection. His candidates are some of the Coxsackie viruses and some of the echoviruses.

He has tested ME patients' blood for the following:
- High concentrations to neutralising antibody to specific EVs;
- Evidence of the presence of EV RNA in plasma via PCR;
- Evidence of the presence of EV RNA in peripheral blood mononuclear cells via PCR;
(In a pilot study, he had selected samples PCR tested concurrently by two independent labs that used different primers and amplification conditions, as a precaution.(2))

He has tested ME patients' tissue for the following:
- Evidence of VP1 protein via immunoperoxidase staining of stomach (antrum) tissue using EV-specific monoclonal antibody;
- Evidence of the presence of EV RNA in antrum tissue via PCR (RT-PCR ELISA).

Of course, any of these tests could produce false positives, or positives attributable to a passing infection.

However, Chia has also performed these tests longitudinally in a large RCT. Some patients recorded strong positive findings in multiple tests; and reproduced these results longitudinally (over a period of years). (1)

He rarely obtains positives from PCR performed on plasma, but finds a significant rate of positives from PCR testing of ME patients' PBMC. (2)
For this reason, he anticipated that Lipkin's ME plasma study was highly unlikely to identify evidence of EV involvement (and apparently told many people of this expectation long before Lipkin reported his results).

Chia is baffled why nobody has attempted to replicate his results.

So, Professor Edwards:
(i.) Does Chia's research look credible?
(ii.) If an ME patient records strong positive results in multiple of these tests, would you consider that convincing evidence of enteroviral infection?
(iii.) If "yes" to qu-(ii), and if those results were reproduced over an extended period of time, then would it be reasonable to postulate that persistent EV infection might be the cause of that patient's ME?


(1) J Clin Pathol. 2008 Jan;61(1):43-8.
(2) J Clin Pathol. Nov 2005; 58(11): 1126–1132.

 

[MeSci]

A specialist in type II diabetes is involved principally in the intracellular hence (my guess) would be the medic with the strongest common of cellular biochemistry and likely to have a solid command of endocrinology.

This is not necessarily the case. Some of us have found endos specialising in diabetes to be astonishingly ignorant about other aspects of endocrinology.

For example, I saw a highly-regarded endo who has appeared in the media a number of times, about my polyuria. He specialises in diabetes, but presumably his expertise is limited to the mellitus variety.

He insisted that diabetes insipidus (which a number of us here appear to have) was something that was absolute (no grey areas) and that you had to be born with it, both of which are incorrect.