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Davis speech from Millions Missing. Some new info on metabolic trap hypothesis

FMMM1

Senior Member
Messages
513
Is this because you think that modern toxins, nutrient depletion, and other poisons and stressors push the genetic adaptations we have beyond their limits?

I think Ron Davis has a tentative view that ME and CFS are so complex that one single definition might not really match the reality. One biomarker might not either. How medicine defines an illness is often not as clear cut as most doctors make it out. As a result one single cure delivered one way will probably not be enough for everyone.

I'm going to go for my own b--l s--t. If a disease is a breakdown at a particular point, and you have a fix (drug/protocol/whatever), and a diagnostic test i.e. to tell you when to deploy the fix; then you know enough to help people to get back to a normal life. Whether it's a family of breakdowns e.g. in metabolic processes which give a similar symptomatic outcome, or a viral trigger which results in a disturbed immune system, once you can identify the disease and the treatment options then you've improved the outcome for people with the disease and their families.
 

Dakota15

Senior Member
Messages
300
Location
Midwest, USA
Regarding the single cure - I wanted to share. I was communicating with one of the top CFS researchers in the country tonight (who is commonly referenced on here, but for sake of privacy I would like to remain nameless since he so kindly allows me to reach out to him) and I know in his medical opinion he shared with me that he, and he also said "most researchers", believe that they're looking at the very minimum 3 different diseases.

This is not earth-shattering in the slightest, but I think it is important to remember when we mention any one cure theory.
 

mariovitali

Senior Member
Messages
1,214
Regarding the single cure - I wanted to share. I was communicating with one of the top CFS researchers in the country tonight (who is commonly referenced on here, but for sake of privacy I would like to remain nameless since he so kindly allows me to reach out to him) and I know in his medical opinion he shared with me that he, and he also said "most researchers", believe that they're looking at the very minimum 3 different diseases.

This is not earth-shattering in the slightest, but I think it is important to remember when we mention any one cure theory.

Do we have a name for each disease or characteristics?
 

Gingergrrl

Senior Member
Messages
16,171
Do we have a name for each disease or characteristics?

I don't think we have a name for anything (as far as I know!) but IMO, one group has to be immune deficient and the other autoimmune. I don't mean the disease name, I mean the mechanism or characteristics.

I would assume one group constantly gets sick, fevers, flus, chills, swollen lymph nodes and is immune deficient on tests vs. the other group literally never gets sick, is autoimmune on tests, and is skewed toward allergic reactions. But I am just guessing. And I have no idea what the third group might be!
 

mariovitali

Senior Member
Messages
1,214
Right, i was just talking to a Woman at a FB Group with ME/CFS "for as long she can remember". Turns out after looking at the List of "Liver Stressors" that she has high Copper levels (which may suggest Wilson's Disease).

Perhaps the third disease is Liver Disease @Gingergrrl but no one is listening.
 
Messages
67
@Gingergrrl I will PM you so that we do not derail this Thread

I would like to hear it too.

Younger thinks there's a post-viral, an autoimmune and a purely metabolic subgroup each. Ron isn't denying that, but he's suggesting there's one underlying mechanism which unites them. This may be the mechanism for a hypometabolic state that's generalised over three subgroups.
 

FMMM1

Senior Member
Messages
513
Regarding the single cure - I wanted to share. I was communicating with one of the top CFS researchers in the country tonight (who is commonly referenced on here, but for sake of privacy I would like to remain nameless since he so kindly allows me to reach out to him) and I know in his medical opinion he shared with me that he, and he also said "most researchers", believe that they're looking at the very minimum 3 different diseases.

This is not earth-shattering in the slightest, but I think it is important to remember when we mention any one cure theory.

Thanks. This links with what Alex has been saying i.e.you need to separate out the disease into individual diseases otherwise your experiments don't make sense. Take rituximab as an example. Removing autoantibody producing B-cell (rituximab) may work for some people since they have B-cell autoimmunity resulting in the symptoms of ME/CFS. However, in a mixed study population where a small portion have B-cell autoimmunity you wouldn't be expected rituximab to work. The secret, in the case of autoimmune antibodies resulting in disease, would be to identify the autoantibodies (diagnostic test) and look at strategies (including rituximab) to deal with these. Other forms of the disease would be similar e.g.activation of certain genes following viral infection might be dealt with by other drugs (I.assume they've been developed for other diseases).

Look at the OMF site (Science Wednesday) the nano needle gave 100% positive results for 10 ME/CFS patients. If it's more than one disease is there a common outcome in all cases i.e. fatigue?
 

mariovitali

Senior Member
Messages
1,214
@FMMM1 @adambeyoncelowe @Gingergrrl


OK so here is my version and hypothesis in a nutshell. The place where all ends meet is the Liver. I have :

-Several Fibroscan tests suggesting LIver Fibrosis
-Several Tests with elevated Total Bile Acids (TBAs) a simple blood test which by the way has not been performed to any ME/CFS patient from anyone (...!)
-Several ME/CFS Patients having removed their Gallbladder, getting Hepatitis at some point, seen white stools (Cholestasis), Having Gallbladder stones, having "Rocky Mountain Fever", Toxic levels of Copper (=Wilson's Disease), Elevated Bilirubin (=Gilbert's Syndrome), EBV, Lyme Disease. What do all of these have in common?

Yes, they all stress the Liver (aka "Liver Stressors")

Complete list here :
https://docs.google.com/spreadsheets/d/1CLtqxW0-L8f25ZXD2H6FFDVbggc73GGC8KtYNkjdUBo/edit?usp=sharing

Now let's move on to the "autoimmune" side. In the 32-page document i sent to many ME/CFS Researchers i explain how the LXR Receptor along with Bile Acid and Phospholipid Dysregulation (Think of Naviaux and Hanson findings here) and Vitamin K Metabolism may set the stage for Inflammation and Autoimmunity. Here is the snapshot (Note that Gas6, ProS, Mer are Vitamin K related):

Screen Shot 2018-04-29 at 13.57.04.png


Also, did you know that we have "Drug Induced" Lupus ? (https://en.wikipedia.org/wiki/Drug-induced_lupus_erythematosus)


Could this be just another way (drugs may put stress on the Liver) that disrupt these Pathways and result to autoimmune disease? Can disruption or impaired functioning of these pathways be responsible for all autoimmune disease?

I do apologise for losing my patience. This hypothesis is quite easy to look at, just ask all ME/CFS Patients for any of these Conditions seen in the Google Sheet plus any medications they took before ME/CFS.

The reason for not circulating the document is because i do not want people to start experimenting with themselves. I asked from all researchers i contacted to test under medical supervision the usefulness of this Regimen. No reply so far.

And my last question : If an ME/CFS patient has undiagnosed Wilson's Disease will "Metabolic Trap" work? The following dialog just in today :

Screen Shot 2018-05-18 at 10.29.44.png
 
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alex3619

Senior Member
Messages
13,810
Location
Logan, Queensland, Australia
The way the data splits in many studies is one third to two thirds. This might or might not indicate two separate diseases. There are so many potential confounds that all I am prepared to say is both strictly defined CFS and ME could be mostly one disease (ignoring the massive misdiagnosis rate for CFS right now), all the way to CFS is a massive hodgepodge and ME is a bunch of different disorders. However most of the opinions we have come from a host of different symptoms, which the diversity of the biochemistry might easily explain, to some variations in biochemical markers, to some variations in treatment outcomes.

The reason to insist on quality ME definitions is that is how to advance the science faster. Very weak CFS definitions like Oxford are so bad they are anti-science. Most are just inadequate with lots of potential confounds in any study that uses them.

It is probably too late to use specific outbreak cohorts, as the numbers are too few, and each outbreak should ideally be treated as a separate cohort.

My best guess is that CFS is many conditions, and that ME is at least two. This is however a guess, and as the data becomes available from many of these new studies I predict there will be plenty of surprises for all of us, including our scientists.

If the metabolomic data proves stable across many subgroups over time, and it looks like it might, then it will strongly suggest that ME is one disorder with a great many variations.
 
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TreePerson

Senior Member
Messages
292
Location
U.K.
I don't think we have a name for anything (as far as I know!) but IMO, one group has to be immune deficient and the other autoimmune. I don't mean the disease name, I mean the mechanism or characteristics.

I would assume one group constantly gets sick, fevers, flus, chills, swollen lymph nodes and is immune deficient on tests vs. the other group literally never gets sick, is autoimmune on tests, and is skewed toward allergic reactions. But I am just guessing. And I have no idea what the third group might be!

I have both those things. Regular swollen glands flu like feelings chills etc but I almost never get a full blown cold or infection. To me that would suggest an immune system permanently switched to high. But then really quite low CD3 and CD4 in recent tests.
 

Dakota15

Senior Member
Messages
300
Location
Midwest, USA
Not to derail the thread, but I lastly wanted to also share, for what it's worth, that it sounds like the researching field's hypothesis of looking at least 3 different diseases all-in is pretty closely aligned at least with the CFS/ME clinician I saw in California last week at the Center for Complex Diseases.

Dr. Chheda shared with me that she firmly believes "we're not all looking at the same thing". Obviously again, time will tell with research if there truly is one underlying mechanism but with Dr. Chheda and Dr. Kaufman's background (at the CCD) with OMF I think their thinking is largely based off the research they have been involved with.
 

JES

Senior Member
Messages
1,320
OK so here is my version and hypothesis in a nutshell. The place where all ends meet is the Liver. I have :

-Several Fibroscan tests suggesting LIver Fibrosis
-Several Tests with elevated Total Bile Acids (TBAs) a simple blood test which by the way has not been performed to any ME/CFS patient from anyone (...!)
-Several ME/CFS Patients having removed their Gallbladder, getting Hepatitis at some point, seen white stools (Cholestasis), Having Gallbladder stones, having "Rocky Mountain Fever", Toxic levels of Copper (=Wilson's Disease), Elevated Bilirubin (=Gilbert's Syndrome), EBV, Lyme Disease. What do all of these have in common?

Yes, they all stress the Liver (aka "Liver Stressors")

While interesting, this hypothesis could at best explain a subgroup. I'm not aware of any big group of CFS/ME patients that have had their gallbladder removed or show abnormal copper or bilirubin. These type of liver disease symptoms that you listed are pretty well understood by medicine, so I have a hard time grasping how doctors who have treated CFS/ME patients for centuries could have missed them. At least in the bigger medical studies conducted on CFS/ME patients something like Wilson's disease which has obvious signs like Kayser-Fleischer rings should have been identified.
 

mariovitali

Senior Member
Messages
1,214
@JES

Thank you for this comment, makes perfect sense. Please allow me to elaborate a bit more.

First ,i am not suggesting that all patients fall into such category hence the phrase 'several patients having removed" as opposed to all.

Second, in speaking with many people by now i can definitely tell you that it is very easy to miss important information. Perhaps the most strking example was with a woman in her 30s who has severe ME/CFS. I started asking her about all of these conditions listed to the Google sheet. She replied with a resounding 'no' to everything. Interestingly the next day she sent me a message saying that she asked her mother about any incidences and her mother replied that when she was 7 years old there was an incidence of white stools (=Cholestasis?) and she was rushed at the Hospital For me this was a clear sign of impaired Liver function that i've been waiting for.

Here is a snapshot from the document i circulated to ME/CFS Researchers with the first version being sent out in October 2017:

Screen Shot 2018-05-18 at 18.55.46.png
Screen Shot 2018-05-18 at 18.55.59.png


Ideally i would like from ME/CFS Researchers to specifically ask for these conditions and then identify whether there is a statistically significant association / comorbidity between ME/CFS and any of the conditions discussed in the Spreadsheet. There are conditions as "benign" as Fatty Liver. But Fatty Liver in combination with other issues may be bringing the Perfect storm we are looking for.

I do not know if this investigative work has been performed on a large scale. To be honest i am really worried because of the fact that not even one paper suggests that a simple test such Total Bile Acids (TBAs) has been performed. Also, note that the only way to rule out a silent Liver Disease is Liver Biopsy from multiple sites. Obviously such testing is not possible. The liver may have very serious problems and despite this, Liver enzymes may be entirely normal (...)

In other words, many things may have been missed.
 

Gingergrrl

Senior Member
Messages
16,171
@Gingergrrl I will PM you so that we do not derail this Thread

Thank you so much and I got your PM but it will probably take me a few days to reply.

Take rituximab as an example. Removing autoantibody producing B-cell (rituximab) may work for some people since they have B-cell autoimmunity resulting in the symptoms of ME/CFS. However, in a mixed study population where a small portion have B-cell autoimmunity you wouldn't be expected rituximab to work. The secret, in the case of autoimmune antibodies resulting in disease, would be to identify the autoantibodies (diagnostic test) and look at strategies (including rituximab) to deal with these.

I agree with this completely and have tried to articulate it in many prior posts but feel like I never did a very good job! I am convinced there is a group of people out there (myself included) who are responders to Rituximab. We are either a sub-group of ME/CFS or we are a group who were misdiagnosed with ME/CFS but never truly had it. But we were very ill and told there was no help out there when this is incorrect.

I have inmune deficiency ( low Nk and T cells). And I have presume autoimmunity ( colitis and POTs).Would be interesting to see then where do I fall.

I agree that nothing is clear cut and there would be many individuals who fit into both groups. I have very low NK cell functioning on blood tests and yet I completely fit the autoimmune profile and went into remission from autoimmune treatments. But I was also very blessed to have the opportunity to try them over a long course of time (in July/Aug it will be two years of IVIG and one year of Rituximab). I want my experience to help someone else, I just don't know how to do this yet.