Community symposium on molecular basis of ME/CFS at Stanford Discussion Thread

[Peter Pain]

Do you think the thing about tryptophan is the key of ME? I'm really curious what Ron finds out about it, but I think it will not be ME's solution. rather a small puzzle piece.

 

[Badpack]

Why ? You will never know what the source of the problem really is. I mean, i dont believe it either but in the end it can be something very trivial. Diabetes is one missing hormone and it kills you. Hypothyroidism is one missing hormone and it will kill you. Why shouldnt it be a missing enzyme in the cell that nearly kills you ? In medicine the easiest answer is often the right one. And if you see, what all follows a missing tryptophan metabolism, its def. possible.

 

[sb4]

If someone followed a low/zero tryptophan diet, wouldn't the body just start catabolising muscle to reach it's requirement?

 

[Badpack]

Good Question, i looked up the composition of the muscle. It is around 2% tryptophan. Dont know if that would be enough to satisfy the needs or keep the trap active for to long. Maybe a good enough inhibition of tryptophan into the cell could block that.

 

[Peter Pain]

Why ? You will never know what the source of the problem really is. I mean, i dont believe it either but in the end it can be something very trivial. Diabetes is one missing hormone and it kills you. Hypothyroidism is one missing hormone and it will kill you. Why shouldnt it be a missing enzyme in the cell that nearly kills you ? In medicine the easiest answer is often the right one. And if you see, what all follows a missing tryptophan metabolism, its def. possible.

I do not see how tryptophan could produce PENE?
It might explain some symptoms. but many other proofs can do that too. as an example: a lack of blood volume and lack of oxygen in the cells can explain PENE better.

 

[Badpack]

i think 100% that the lack of blood volume and oxygen is the main problem for PEM, But what now ? Where does this come from ? Or is it just there for you ?

I think its a chain. PEM <- bad blood flow / low oxygen intake <- AAbs against ß2/m2 that tighten up your arteries and close transmembran receptors <- activated because of the missing kynurenine <- no tryptophan metabolism. Metabolic trap for you right there.

Its like saying its not the missing insulin that kills you and your nervous system but the to high glucose levels. You are making the same mistake you just accused us of making

And i will quote you here now "It seems to me that you lose yourself in little things and do not see the big picture anymore"

 

[Peter Pain]

i think 100% that the lack of blood volume and oxygen is the main problem for PEM, But what now ? Where does this come from ? Or is it just there for you ?

I think its a chain. PEM <- bad blood flow / low oxygen intake <- AAbs against ß2/m2 that tighten up your arteries and close transmembran receptors <- activated because of the missing kynurenine <- no tryptophan metabolism. Metabolic trap for you right there.

Its like saying its not the missing insulin that kills you and your nervous system but the to high glucose levels. You are making the same mistake you just accused us of making

And i will quote you here now "It seems to me that you lose yourself in little things and do not see the big picture anymore"

Only 30 (?)% of ME patients have these AABs against ß2/m2.

 

[Badpack]

Im not saying i know the answer for ME, i was just trying to explain to you that it is possible that just a disturbance in the tryptophan metabolism could be an answer. And btw. its 30% in ELISA and over 70% in bioessays. And for now every month new AAbs are added to that list found in ME. So i was just trying to make a point here that, no matter how insignificant something might look for you, it could be the main problem.

 

[Learner1]

i think 100% that the lack of blood volume and oxygen is the main problem for PEM,

I get PEM and I don't have low blood volume. I also HBOT 2-3 times a week, so I don't think I'm hypoxic.

However, I do have a lot of oxidative stress, as identified by low glutathione, ALA, and C, and high peroxynitrites and lipid peroxides. Oxidative stress has been identified in other ME/CFS patients, too.

I have found that I can avoid PEM much of the time or reverse it by taking liposomal glutathione snd BCAAs prior to exertion and then r-glutathione and BCAAs afterward.

 

[Badpack]

its not about being hypoxic in the blood, its about the cells not taking the oxygen from the red blood cells. Why would you use a HBOT then if you dont think you are hypoxic ?

 

[Research 1st]

Only 30 (?)% of ME patients have these AABs against ß2/m2.

With respect.

This is 30% of people with CFS have these antibodies in small scale studies. Undoubtedly due to ststistics, some will have ME. Until we have a new test, and using an ME criteria separate from the SEID/CDC CFS clinical based fatigue syndrome that does not permit CFS or ME patients with established inflammation to be in research studies (inflammation would lead to explained central fatigue) we cannot legitimately call any autoimmune subsets of CFS or indeed anyone else (including Ron's patients at the OMF) genuine ME patients.

A compromise may be to call ourselves, (as individuals told we have CFS, ME, ME/CFS) prototype Myalgic Encephalomyelitis patients.

Without extensive and expensive organic CFS research based tests that MIGHT mean someone told they have ME truly has it, a patient being diagnosed with ME is not reliable. It's infuriating, but this is reality.

Due to this we cannot say only 30% of ME patients have a certain biological finding because remembers these patients only need to meet subjective self reported symptom based CFS criteria, all which require no evidence of being organically ill, to enter a study on ME/CFS, thus wrecking the research relevance and accuracy!

So yes, it could be only 30% of ME patients have an autoimmune finding, such as adrenergic antibodies. Or it could be 100% of ME patients do, and 70% were misdiagnosed. Or it could be 0% of ME or CFS do, and 30% were maybe even undiagnosed POTS patients.

The exception to this is if cohorts of ME/CFS with PROVEN neuroinflammation then had the adrenergic antibodies found in CFS and POTS research, and all other research that has been completed of good quality and apparent consistent abnormal findings.

For this to happen it is critical that the FDG-PET scans of the Japanese using optimised radioligands, and Younger's MRI thermal scans link up to interesting CFS neuroimaging studies of apparent brain tract damage, (DTI scan), increased ventricular lactate, increased choline and then maybe all this can link back to potentials to say, yup, organic CFS is definitely ME.

Then honest scientists can agree, ME is 100% not Fukuda criteria CDC CFS and yes most of our ME patients have autoimmune brain markers, and so some develop POTS and or autoimmune psych illnesses - for which the poor patients were too ashamed to confess to, so suffered in silence fearing further discrimination.

To be honest, at best, this is 10-20 years away with the current lack of robust government funding because even if the OMF and friends proved CFS is a novel metabolic illness, these are not neuroinflammation studies. Ron's group would not be proving ME exists, all they would do is prove CFS subsets are organic. Yet we knew this anyway, we just had little proof.

The sad reality is CDC and Beth Unger, Fauci at NIH and others do NOT want ME to emerge from the muddle of CBT/GET era CFS, which is why if you see the proposed new CFS criteria, they still fail to detect ME and would still block many with ME appearing in what researchers call ME/CFS research. This is how we ended up as ME being subsets of CFS in the first place and psychological theories running rampant, and tragically, they still do this and get funding for it.

The situation is very difficult politically to get out of. Funding won't be given for honest biomedical research on a large scale as proving ME is organic subsets of CDC CFS/SEID, means social care bills would rise for insurers to potentially, millions of dollars over a lifetime, each person who is bedridden. It would also cost socialised medical systems in the UK and other countries, hence CDC cosy up to the extremist British psychiatrists who claim CFS patients pose more danger than the Taliban, in the educated British press. They are then awarded.

As a community we are ignored and still hated by some - like LGBT actually. Like gays with HIV we CFS are all left to die but in severe ME this death is slow motion unlike AIDS. Once the CDC agreed to this in 1988 this was the most cost effective decision for them.

The people in charge of sacrificing us don't give two hoots about biological research to prove ME exists- hence to this day, they ignore us, because to attain their $400,000 pension plan the legitimacy of ME has to be annihilated, and the annihilation will never end for as long as ME is hidden within fatigue based criteria that remove ME patients with explained reasons for fatigue (ME) from ME/CFS.

This is why you get a small autoimmune subset here and there you pointed out. Logically, these are likely the PWME, the 30%, or in terms of charity representation in the UK for example - the 25% group. But without the tens of millions per year we need, we can't prove it.

Catch 22 and it's not just us caught in a sticky political web it's the scientists who try and save our lives.

 

[Neunistiva]

Cort Johnson just published a post about metabolic trap The Metabolic Trap Shines During the Symposium on the Molecular Basis of ME/CFS at Stanford. It's a very exciting prospect, I love how all the pieces fit together and if you can

please donate to OMF for metabolic trap.

Once again the warning not to self-experiment has been given

You can actually induce autoimmunity – an autoimmunity you cannot recover from – by taking tryptophan. Note that if the trap is correct, the brains of people with ME/CFS have probably become adapted to very high serotonin levels. What happens when a brain that’s been wired to high serotonin levels suddenly gets deprived of it? Nobody knows, but everyone can guess what might happen if the process is not done correctly. The results could be awful – and possibly permanent.

If increased tryptophan levels are the culprit in ME/CFS, the treatment has to be worked out using computer and animal models first. Davis requested that the ME/CFS community give them some time to figure out what’s going on.
​

Also, according to mathematical models it seems tryptophan input doesn't matter once you're in the trap

If that situation dragged on for just 8 weeks, the system would essentially never recover – even if all tryptophan inputs were halted. This is a system which demonstrates remarkable “stuckness.”​

 

[JES]

To be honest, at best, this is 10-20 years away with the current lack of robust government funding because even if the OMF and friends proved CFS is a novel metabolic illness, these are not neuroinflammation studies. Ron's group would not be proving ME exists, all they would do is prove CFS subsets are organic. Yet we knew this anyway, we just had little proof.

I don't see why research specifically needs to focus on neuroinflammation. The term neuroinflammation is very much trending in the sense that it's now associated with a bunch of disease, including for example depression, Parkinson's and Alzheimer's. All these diseases have some form of neuroinflammation present, but researchers are still none the wiser as to what actually causes this inflammation in a widely studied disease like depression. And none of the anti-inflammatory drugs and supplements available seem to do anything for these diseases, especially not for ME/CFS.

I have a hunch that maybe the OMF studies about metabolic traps actually go deeper to the root cause than the studies about inflammation, which have produced no treatments for any of the mentioned diseases. Only time will tell, but if OMF can find a treatment that doesn't require development of a new drug as Davis has hinted, then that will be huge. As soon as there is an approved treatment, the condition will instantly be taken more seriously, as happened with AIDS, depression, etc.

 

[Murph]

Cort Johnson just published a post about metabolic trap The Metabolic Trap Shines During the Symposium on the Molecular Basis of ME/CFS at Stanford. It's a very exciting prospect,

Janet Dafoe is in the comments responding to a few questions there.

e.g. she says
>They have identified quite a large number of potential traps but more investigation is needed to determine if they fit all the requirements to be traps.

>The way to test if someone is in the trap is to check the tryptophan/kynurinine ratio in white blood cells, not plasma. Regular medical labs are not equipped to do this. Scientists at the genome center are working on a simpler and cheaper method for doing this. Right now it requires a $100,000 – $1,000,000 mass spectrometer.

Totally incidentally, Janet, citing Ron, also drops a rebuttal to the work done by the Aussie researchers on calcium. I had wondered whether anyone had tried to replicate their findings.

> Ron says: We do not find that those mutations that are reported from Griffiths come out as significant in our studies (see Wenzhong’s SIPs study slide on mutations from the symposium). Furthermore, those mutations appear to be common in the European population of healthy people.

 

[raghav]

What is the "Aha" moment of Neil Mcgregor ?. It was in a tweet.

 

[used_to_race]

And none of the anti-inflammatory drugs and supplements available seem to do anything for these diseases, especially not for ME/CFS.

Can you elaborate on this? I can't really say much about depression or any other disease, but I thought it's clear that in ME/CFS, most reported success these days pretty much comes through anti-inflammatory and immune modulating treatments. Sure there is some stuff here and there about antivirals and antibiotics, but people are responding in many cases to IVIG, Rituximab, Plaquenil, Sulfasalazine, and other drugs. Sure these aren't perfect treatments, but that's unrealistic to expect with how this disease has been marginalized. Things will improve as we are taken more seriously.

 

[Tally]

I thought it's clear that in ME/CFS, most reported success these days pretty much comes through anti-inflammatory and immune modulating treatments. Sure there is some stuff here and there about antivirals and antibiotics, but people are responding in many cases to IVIG, Rituximab, Plaquenil, Sulfasalazine, and other drugs.

To be fair all of those reports are anecdotal. In placebo-controlled research nothing they've tried so far has helped, not even to a subset of patients.

 

[used_to_race]

To be fair all of those reports are anecdotal. In placebo-controlled research nothing they've tried so far has helped, not even to a subset of patients.

And to be fair there has been embarrassingly little placebo-controlled research on any of these medications. The only one that's had a reasonably well-designed (albeit negative) trial has been Rituximab. IVIG studies are contradictory, plasma exchange has showed a bit of promise, and there is anecdotal evidence behind the use of other immune modulating or suppressing treatments as diverse as plaquenil, rapamune, cyclophosphamide, and LDN. Nobody has done any kind of trial on, say, sulfasalazine, a DMARD with moderate potency and minimal risk. The only trial ever done on TNF inhibitors was discontinued after literally 2 out of 4 people had an unspecified adverse reaction. Even people with RA and IBD have adverse reactions to these drugs somewhat commonly so it could be a great treatment and we just wouldn't know.

 

[keenly]

What is missing is how the environment effects our mitochondria.

As far as I know there are no studies looking at the locations of CFS patients?

I believe 100% that we are in a protective mode, a dauer state, but I think part of this is a poor environment.

 

[Sing]

I thank @Research 1st for what I thought was a brilliant, comprehensive post. The second half of it summarizes the political trap we are in—as I am seeing it now, a parallel or mirror for the metabolic trap.