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

[Learner1]

If you look at this, Raman spectroscopy potential blood based diagnostic test, then it appears to indicate that people with ME/CFS have impaired cellular energy production [https://pubs.rsc.org/en/content/articlelanding/2018/an/c8an01437j#!divAbstract]. I.e. all of those tested had the same result - elevated intracellular phenylalanine.

The paper says that they only used 5 ME/CFS patients. It's not actionable either as there's no clinical test to look for intracellular phenylalanine, is there?

Same goes for Ron Davis's data from the Seahorse (impaired cellular energy production) and the nano needle [impedence test].

This seems to correlate well with the Acumen and MitiSeab tests some of us have had done looking at mitochondrial function.

Ron Tompkins pointed out that some diseases have different starting points but converge on a common outcome [OMF Symposium 2018 - my summary].

Yes, I was there and heard Ron Tompkins say that, and they seems to be some truth to it.

But, take a disease like a solid tumor cancer. It may look and behave similarly from patient to patient, but there are different metabolic triggers, environmental influences, and each tumor can contain differently mutated genes. And worse, the same treatment can either help or hurt patients due to their unique idiosyncracies.

I've met over 50 other women who all had the exact same "national standard of care" total hysterectomy and carboplatin/paclitaxel chemotherapy. I beat the odds and am cancer free, though others have had up to 3 occurrences, some have died, but I was the only one to end up with ME/CFS.

Same disease, different triggers, and different out comes from the same treatment. This is the fallacy of evidence based medicine. We aren't widgets, and though some factors are the same, our genetics, amount of accumulated DNA damage, level of toxicity, our diets and many other factors will confound standardized treatment.

What we need is data. E.g. does everyone with ME/CFS have elevated intracellular tryptophan (Phair OMF Symposium 2018]?

Or peroxynitrites, or thyroid dysfunction, or B12, glutathione, or phospholipid deficiency? Or?? It would be nice to have Metabolon tests for everyone...and intracellular nutrient and mitochondrial function and other tests.

What we need is a healing treatment plan with a set of tools that can be used to individualize treatment, as is done to optimize patients function and outcomes in cancer, Parkinson's, and autoimmune diseases.

 

[FMMM1]

The paper says that they only used 5 ME/CFS patients. It's not actionable either as there's no clinical test to look for intracellular phenylalanine, is there?


This seems to correlate well with the Acumen and MitiSeab tests some of us have had done looking at mitochondrial function.

Yes, I was there and heard Ron Tompkins say that, and they seems to be done truth to it.

But, take a disease like a solid tumor cancer. It may look and behave similarly from patient to patient, but there are different metabolic triggers, environmental influences, and each tumor can contain differently mutated genes. And worse, the same treatment can either help or hurt patients due to their unique idiosyncracies.

I've met over 50 other women who all had the exact same "national standard of care" total hysterectomy and carboplatin/paclitaxel chemotherapy. I beat the odds and am cancer free, though others have had up to 3 occurrences, some have died, but I was the only one to end up with ME/CFS.

Same disease, different triggers, and different out comes from the same treatment. This is the fallacy of evidence based medicine. We aren't widgets, and though some factors are the same, our genetics, amount of accumulated DNA damage, level of toxicity, our diets and many other factors will confound standardized treatment.

Or peroxynitrites, or thyroid dysfunction, or B12, glutathione, or phospholipid deficiency? Or?? It would be nice to have Metabolon tests for everyone...and intracellular nutrient and mitochondrial function and other tests.

What we need is a healing treatment plan with a set of tools that can be used to individualize treatment, as is done to optimize patients function and outcomes in cancer, Parkinson's, and autoimmune diseases.

Regarding the small number of people with ME/CFS tested, for intracellular phenylalanine, using the Raman spectroscopy. The authors of the study address this point; also, they are currently working on a larger study:
"Our results serve as a pilot study to explore the potential of SCRM as a tool to identify biomarkers in CFS. A larger-scale study is currently under preparation to consolidate the results from the current work." [from https://sci-hub.se/10.1039/C8AN01437J]
Ron Davis, in his talk at the symposium, highlighted that they were trying to understand the disease at a molecular level. There are no molecular based diagnostic tests for ME/CFS which are approved by the Government (where ever you are).

The position regarding the potential diagnostic tests which Ron Davis is working on (see his symposium presentation - Seahorse, Nano needle etc.) is similarly i.e. small numbers of samples have been tested and the results look promising.

We don't know enough about ME/CFS e.g. we don't know if many different treatments will be required or one.

I don't think we are on different sides here i.e. we are both looking for effective diagnostic tests and treatments.


Consider writing to your elected representative i.e. to request funding for ME/CFS research including the development of a diagnostic test.
I've written to the European Union Committee on the Environment, Public Health and Food Safety (ENVI) requesting that they lobby for funding for research into ME/CFS including the development of a diagnostic test [https://forums.phoenixrising.me/ind...ch-theyre-working-for-you.61516/#post-1003111].
Currently the ENVI Committee is lobbying for increased funding for research into Lyme disease and the development of a diagnostic test.
In 2016 the European Commission [European Union civil service] said [regarding Lyme disease] that "Both basic research and the development of new diagnostics, treatments and vaccines for Lyme borreliosis are funded by EU research and innovation framework programmes. The total EU contribution to such projects since 2007 amounts to EUR 33.9 million [US dollars]" [http://www.europarl.europa.eu/doceo/document/E-8-2016-008631-ASW_EN.html].

ME/CFS received no funding from the European Union [http://www.europarl.europa.eu/doceo/document/E-8-2017-006901-ASW_EN.html].

 

[Ben H]

Hi all,

Just to let you know that the individual talks are now on OMF's YouTube channel-posted thread here:

https://forums.phoenixrising.me/ind...s-now-available-on-omf-youtube-channel.62161/

Enjoy,


B

 

[Dr Who]

Can you not just use currently approved drugs i.e. provided they are known to be effective and you can get a doctor to prescribe them?

In short, no.

In the UK drugs are approved in terms of safety/danger versus effectiveness for a given condition. For example, some of the older chemotherapy agents are fantastic at getting rid of psoriasis, but if a doctor prescribed them for the treatment of psoriasis the doctor would be struck off the GMC register for prescribing the drug 'off licence' and quite rightly so. The risks of such chemotherapy agents, such as causing cancer, wiping out the immune system and causing fatal infections, liver failure, renal failure, heart failure, hair loss, infertility and so many more side effects might be acceptable if it cures you of your cancer or even if it prolongs your life for a year or two but would be unacceptable if it was to stop your scalp or back from being itchy and flakey. Drugs are licenced for specific conditions. If it is found that ME/CFS patients might benefit from an existing drug used for something else, a study would need to be licenced to use the drug on these specific patients in the study and no-one else. The incidence of the already known side-effects of that drug in this group of ME/CFS patients would need to be monitored, as they may be more frequent or more severe than in the patients for which the drug is commonly used and the risk/benefit ratio may be different. Equally, their may be new side effects from the drug because the patients have ME/CFS. It is only once enough of these 'off-licence' studies have been done, with enough ME/CFS patients, revealing no unacceptable risk or side-effects and that have shown a benefit to the ME/CFS sufferer that any drug would then be licenced for prescribing to ME/CFS sufferers by general physicians to the general public.

The good news is that, if an already existing drug is suspected of being helpful to ME/CFS sufferers, then the drug will have already been through the "can you kill mice with it?" stage, the "does it kill humans?" stage, the "(if it does kill or harm humans) how much can a human take without it being likely to cause any harm?" and its manufacture on a mass scale will have already been developed and may still be up and running. If it is a recent enough drug that it is still under patent, the drug may still be expensive, but has the benefit that the drug manufacturing company may be interested in funding the research as the drugs widened usage will mean greater profit for the company. If it is an old drug, off-patent, it will be that much cheaper, which is good in the long term perhaps, but means that the scientific and pharmaceutical world will have little interest in studying it because no-one will fund the research because their is no financial profit in it. This is why funding the current research at Stanford is is so important. If we do not support it, no-one else will. Once enough progress is made, attempts to jump on board will be made by those only really interested in making money and we may have to welcome them. Until then, support Dr Davis and everyone else working to find the cause and the cure and be patient.

 

[Moof]

In the UK drugs are approved in terms of safety/danger versus effectiveness for a given condition. For example, some of the older chemotherapy agents are fantastic at getting rid of psoriasis, but if a doctor prescribed them for the treatment of psoriasis the doctor would be struck off the GMC register for prescribing the drug 'off licence' and quite rightly so. The risks of such chemotherapy agents, such as causing cancer, wiping out the immune system and causing fatal infections, liver failure, renal failure, heart failure, hair loss, infertility and so many more side effects might be acceptable if it cures you of your cancer or even if it prolongs your life for a year or two but would be unacceptable if it was to stop your scalp or back from being itchy and flakey. Drugs are licenced for specific conditions. If it is found that ME/CFS patients might benefit from an existing drug used for something else, a study would need to be licenced to use the drug on these specific patients in the study and no-one else. The incidence of the already known side-effects of that drug in this group of ME/CFS patients would need to be monitored, as they may be more frequent or more severe than in the patients for which the drug is commonly used and the risk/benefit ratio may be different. Equally, their may be new side effects from the drug because the patients have ME/CFS. It is only once enough of these 'off-licence' studies have been done, with enough ME/CFS patients, revealing no unacceptable risk or side-effects and that have shown a benefit to the ME/CFS sufferer that any drug would then be licenced for prescribing to ME/CFS sufferers by general physicians to the general public.

The good news is that, if an already existing drug is suspected of being helpful to ME/CFS sufferers, then the drug will have already been through the "can you kill mice with it?" stage, the "does it kill humans?" stage, the "(if it does kill or harm humans) how much can a human take without it being likely to cause any harm?" and its manufacture on a mass scale will have already been developed and may still be up and running. If it is a recent enough drug that it is still under patent, the drug may still be expensive, but has the benefit that the drug manufacturing company may be interested in funding the research as the drugs widened usage will mean greater profit for the company. If it is an old drug, off-patent, it will be that much cheaper, which is good in the long term perhaps, but means that the scientific and pharmaceutical world will have little interest in studying it because no-one will fund the research because their is no financial profit in it. This is why funding the current research at Stanford is is so important. If we do not support it, no-one else will. Once enough progress is made, attempts to jump on board will be made by those only really interested in making money and we may have to welcome them. Until then, support Dr Davis and everyone else working to find the cause and the cure and be patient.

I agree with this, both in terms of practice and ethics, but there can be a bit of 'creep' in some cases. It depends very much in the individual drug and its capacity for harm, as you say.

For instance, I was suffering from a common menopausal symptom about 10 years ago – hot flushes – but to the point where I was drenched with sweat every four or five minutes, which soaked my clothes and hair, and made it hard to work.

I couldn't take HRT because of a family history of oestrogen-receptor positive breast cancer, so my GP was struggling to help me manage it. She mentioned it to a colleague, who's heard anecdotal reports that gabapentin helped some people with severe hot flushes......long story short, she prescribed it off-label, and it reduced the symptom by around 90% (as well as saving my sanity and my employment).

Obviously, this example hardly compares to prescribing cancer drugs for psoriasis. It's also true that gabapentin has a history of being used off-label, so there are well-established precedents. But if a drug of a similar 'weight' to gabapentin (i.e., with a reasonable risk/benefit/cost profile) showed significant promise, might we possibly see a situation where GPs feel able to prescribe off-label?

 

[FMMM1]

---- This is why funding the current research at Stanford is is so important. If we do not support it, no-one else will. Once enough progress is made, attempts to jump on board will be made by those only really interested in making money and we may have to welcome them. Until then, support Dr Davis and everyone else working to find the cause and the cure and be patient.

Fully agree.


Consider writing to your elected representative i.e. to request funding for ME/CFS research including the development of a diagnostic test.
I've written to the European Union Committee on the Environment, Public Health and Food Safety (ENVI) requesting that they lobby for funding for research into ME/CFS including the development of a diagnostic test [https://forums.phoenixrising.me/ind...ch-theyre-working-for-you.61516/#post-1003111].
Currently the ENVI Committee is lobbying for increased funding for research into Lyme disease and the development of a diagnostic test.
In 2016 the European Commission [European Union civil service] said [regarding Lyme disease] that "Both basic research and the development of new diagnostics, treatments and vaccines for Lyme borreliosis are funded by EU research and innovation framework programmes. The total EU contribution to such projects since 2007 amounts to EUR 33.9 million [US dollars]" [http://www.europarl.europa.eu/doceo/document/E-8-2016-008631-ASW_EN.html].

ME/CFS received no funding from the European Union [http://www.europarl.europa.eu/doceo/document/E-8-2017-006901-ASW_EN.html].

 

[Dr Who]

I agree with this, both in terms of practice and ethics, but there can be a bit of 'creep' in some cases. It depends very much in the individual drug and its capacity for harm, as you say.

For instance, I was suffering from a common menopausal symptom about 10 years ago – hot flushes – but to the point where I was drenched with sweat every four or five minutes, which soaked my clothes and hair, and made it hard to work.

I couldn't take HRT because of a family history of oestrogen-receptor positive breast cancer, so my GP was struggling to help me manage it. She mentioned it to a colleague, who's heard anecdotal reports that gabapentin helped some people with severe hot flushes......long story short, she prescribed it off-label, and it reduced the symptom by around 90% (as well as saving my sanity and my employment).

Obviously, this example hardly compares to prescribing cancer drugs for psoriasis. It's also true that gabapentin has a history of being used off-label, so there are well-established precedents. But if a drug of a similar 'weight' to gabapentin (i.e., with a reasonable risk/benefit/cost profile) showed significant promise, might we possibly see a situation where GPs feel able to prescribe off-label?

One would hope so, but I could never confess to doing such a thing. I have prescribed chlophenamine (Piriton) for itchy sleeplessness, itchy anxiety, itchy agitation and even itchy psychosis (when the antipsychotics can't be increased) all with the remarkable side-effect of helping the non-itch symptoms. I have always prescribed the chlorphenamine for the "itch" however and explained to the patient exactly what I was doing and why if they were capable of understanding. Indeed, the explanation might start with me saying "it is a pity that you are not itchy because I could prescribe something for the itch that might have the side effect of......". I remember only one patient taking a very long time for the "penny to drop" before starting to scratch themselves and say, "Now you come to mention it!......!"

 

[Martin aka paused||M.E.]

@Ben H Did you get a update on Copaxone?
Best
Martin

 

[PinkPanda]

EXPERIMENTAL SUPPORT

The rubber really hits the road when he tests patients. (n=6, so very preliminary.) Experiments in me/cfs patients cells comapared to healthy controls show tryptophan is high, kynurenine is low, and the ratio of the two is high, just like the metabolic trap hypothesis would predict.

(This is not the whole story, much has been omitted for simplicity, but it is, I think, the key parts.)

Was tryptophan elevated after giving the patients a tryptophan supplement or just a standard measurement?

 

[Learner1]

I believe it was intracellular tryptophan.

 

[Tally]

Was tryptophan elevated after giving the patients a tryptophan supplement or just a standard measurement?

They didn't give patients tryptophan

 

[FMMM1]

Was tryptophan elevated after giving the patients a tryptophan supplement or just a standard measurement?

Short answer in no supplement - just a standard measurement.
This is the result they got when they analysed intracellular tryptophan in peripheral blood monocytes (PBMs) in a small group of (severely ill) people with ME/CFS. So the assumption is that this would apply generally in people with ME/CFS. You use IDO1 to clear lower levels of intracellular tryptophan (conversion to kynurenine) but IDO1 stops working at higher tryptophan levels (substrate inhibited). IDO2 is not functioning i.e. clearing the higher levels of intracellular tryptophan (conversion to kynurenine) owing to a genetic mutation on the IDO2 gene. Theory is people with ME/CFS are trapped i.e. they have high intracellular levels of tryptophan which they cannot clear and which causes ME/CFS.

There's no need to add anything i.e. it's presumed that you already have high intracellular tryptophan.

 

[Kenshin]

Theory is people with ME/CFS are trapped i.e. they have high intracellular levels of tryptophan which they cannot clear and which causes ME/CFS.

There's no need to add anything i.e. it's presumed that you already have high intracellular tryptophan.

My immediate response to that is how do we lower tryptophan, stop eating turkey?

 

[FMMM1]

My immediate response to that is how do we lower tryptophan, stop eating turkey?

Yea that thought had crossed my mind i.e. how do we lower intracellular tryptophan levels? OMF are thinking the same.

We also need to know if high intracellular tryptophan is present in everyone with ME/CFS. OMF have been using a mass spectrometry method but they are looking for another method [from memory i.e. Janet Defoe on Health Rising]. @Janet Dafoe (Rose49)

 

[JES]

My immediate response to that is how do we lower tryptophan, stop eating turkey?

That was actually trialed by a member few pages back in this thread, however, the low tryptophan diet seems almost impossible for anyone sane to follow for a longer period of time. A much safer and easier approach is to increase BCAA uptake, which would lower tryptophan on the basis that BCAA competes with tryptophan for entry into the brain. Another thing that I thought could possibly help is a low-carb diet, as carbohydrates trigger an insulin response, which enhances the transport of tryptophan. This is why some people start feeling tired after a carb-heavy meal.

 

[Mary]

A much safer and easier approach is to increase BCAA uptake, which would lower tryptophan on the basis that BCAA competes with tryptophan for entry into the brain.

I've been taking BCAAs (4000 - 5000 mg a day) for 4 years. They've cut my PEM recovery time in half. But I still get PEM, and my activity/energy envelope has not increased unfortunately. I won't be without them though, cutting my recovery time is huge. There are many people on the board taking them with good results. @ljimbo423 is having very good results with 15000 mg a day; I tried that dose briefly but unfortunately it caused bad insomnia for me. But we are all different of course!

 

[ljimbo423]

I've been taking BCAAs (4000 - 5000 mg a day) for 4 years. They've cut my PEM recovery time in half. But I still get PEM, and my activity/energy envelope has not increased unfortunately. I won't be without them though, cutting my recovery time is huge. There are many people on the board taking them with good results. @ljimbo423 is having very good results with 15000 mg a day; I tried that dose briefly but unfortunately it caused bad insomnia for me. But we are all different of course!

I'm now taking 14 grams a day of BCAA's first thing in the morning, to help prevent insomnia, which I rarely get now. I will go up to 15-17 grams if I need the extra energy. Like you Mary, I won't be without them!! They help waaaay too much.

Ironically, they have reduced my need for 5htp (which is made from tryptophan) I have been taking for anxiety for years. I now get the same benefits from half as much 5htp as I did before I started taking the BCAA's.

 

[Mary]

I'm now taking 14 grams a day of BCAA's first thing in the morning, to help prevent insomnia, which I rarely get now

Okay, you've given me an idea When I took the 15000 mg I split it in two. Maybe I will try going up to 6000 or 7000 in one dose, first thing in the morning, and see how I do with that!

 

[dannybex]

I'm now taking 14 grams a day of BCAA's first thing in the morning, to help prevent insomnia, which I rarely get now. I will go up to 15-17 grams if I need the extra energy. Like you Mary, I won't be without them!! They help waaaay too much.

Ironically, they have reduced my need for 5htp (which is made from tryptophan) I have been taking for anxiety for years. I now get the same benefits from half as much 5htp as I did before I started taking the BCAA's.

Besides taking 5-htp -- which is critical here -- I think the other key though is that you were treating your SIBO for years. I've been trying the BCAAs as you know @ljimbo423, and finally had to stop yesterday, as they were making me more and more agitated and extremely tense, possibly contributing to higher cortisol, stress, and possibly muscle loss. Why, I'm not certain, but I think it may be because as @JES pointed out, they block/inhibit tryptophan synthesis.

Some may have higher tryptophan levels while others may have lower. Some may have high quinolinic acid as a result of not enough B3, etc. And then there's other neurotransmitters, other nutrients, on and on and on.

As @Learner1 said, there are probably many other factors that will be different in all of us...

FWIW, I found an interesting podcast on the gut-brain axis and how these neurotransmitters affect immune function. Very eye opening, at least for this mushy brain.

https://www.thesibodoctor.com/2017/...is-neurotransmitters-and-sibo/?v=7516fd43adaa

 

[dannybex]

I'd also add that if tryptophan is high in the cell, maybe it's high because the body needs it there. It may not be a bad thing...