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A Metabolic Trap for ME/CFS?

mariovitali

mariovitali

Senior Member
Messages
1,214
@FMMM1

Right, so what Chris Armstrong describes in the link you provided is definitely towards the right direction according to the Liver Hypothesis (as suggested by Machine Learning). FYI i already sent to Chris Armstrong the 32-page document a month ago but there was no reply.

In the only discussion i had with Professor Davis i asked him if ME/CFS Patients had a test called "Total Bile Acids" apart from a Fibroscan test and unfortunately this test has not been performed. There are many cases of patients that had elevated levels (which is toxic to the Liver and possibly not good for the Gut as well). Dr Robert Phair is also aware of this as i have also sent to him some cases with elevated total bile acids.

Given the fact that many researchers find problems with Bile Acids and that Bile Acids affect the composition of gut microbiome and that Liver function affects the composition of Bile acids and the Gut Lining and findings about metabolites suggesting hepatotoxicity (according to Maureen Hanson) isn't it time to finally look at the Liver more closely ?

As a latest development, i may be presenting my work to ME/CFS Researchers of the EUROMENE Network in September. I had a positive response from Professor Modra Murovska expressing interest but i will have to confirm. I will keep you posted.
 
F

FMMM1

Senior Member
Messages
513
mariovitali said:
@FMMM1

Right, so what Chris Armstrong describes in the link you provided is definitely towards the right direction according to the Liver Hypothesis (as suggested by Machine Learning). FYI i already sent to Chris Armstrong the 32-page document a month ago but there was no reply.

In the only discussion i had with Professor Davis i asked him if ME/CFS Patients had a test called "Total Bile Acids" apart from a Fibroscan test and unfortunately this test has not been performed. There are many cases of patients that had elevated levels (which is toxic to the Liver and possibly not good for the Gut as well). Dr Robert Phair is also aware of this as i have also sent to him some cases with elevated total bile acids.

Given the fact that many researchers find problems with Bile Acids and that Bile Acids affect the composition of gut microbiome and that Liver function affects the composition of Bile acids and the Gut Lining and findings about metabolites suggesting hepatotoxicity (according to Maureen Hanson) isn't it time to finally look at the Liver more closely ?

As a latest development, i may be presenting my work to ME/CFS Researchers of the EUROMENE Network in September. I had a positive response from Professor Modra Murovska expressing interest but i will have to confirm. I will keep you posted.
Click to expand...

Good luck with the presentation. I would have thought the OMF group would have tested pretty much everything. The OMF group seem to have some of the leading scientists Chris Armstrong, Pair etc; it will be interesting to see what they come up with regarding the metabolic trap by the end of the summer.
 
mariovitali

mariovitali

Senior Member
Messages
1,214
@FMMM1

Thank you.

To the best of my knowledge, Total Bile Acids ( a simple blood test) and Fibroscan test for Liver Fibrosis have not been performed to any ME/CFS Patient by any Researcher to this day.

There is a second version of Bile Acid testing using HPLC which identifies the exact composition of the Bile Acids which may also be of great importance.
 
B

bthompsonjr1993

Senior Member
Messages
176
Tally said:
The theory is that it's all the same disease and that differences we are seeing in symptom presentation and severity are all due to genetic differences
Click to expand...

Man, what a miracle if this is true. That would be such a huge finding that it seems like they would have to rename CFS to "metabolic trap disease" or something like that
 
W

Wally

Senior Member
Messages
1,167
Is it correct to say that the “metabolic trap” is a hypothesis as to a place in the body where pathways or a central
pathway may be blocked that in turn cause different types and levels of dysfunction depending on the severity of that block(s)?
 
Jackb23

Jackb23

Senior Member
Messages
293
Location
Columbus, Ohio
Wally said:
Is it correct to say that the “metabolic trap” is a hypothesis as to a place in the body where pathways or a central
pathway may be blocked that in turn cause different types and levels of dysfunction depending on the severity of that block(s)?
Click to expand...

It may or may not be the severity of what is blocked, but also the cascade of events that occur and interact due to this “blockage.” Feedback loops and down stream effects may play a role in how this disease is expressed in each individual.
 
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W

Wally

Senior Member
Messages
1,167
@Jackb23 - Thank you for responding to my question. Can you provide an example(s) of a feedback loop or downstream event that might happen when there is a metabolic block and how/why it may differ between individuals?
 
JES

JES

Senior Member
Messages
1,322
Wally said:
@Jackb23 - Thank you for responding to my question. Can you provide an example(s) of a feedback loop or downstream event that might happen when there is a metabolic block and how/why it may differ between individuals?
Click to expand...

The body is full of feedback loops so it's hard to pinpoint one that would be altered by a metabolic block. One example of a feedback loop would be blood sugar control. When glucose levels increase, receptors in pancreas get triggered to produce more insulin. When opposite happens, glucagon is produced to increase glucose levels. So glucose is tightly controlled and it's actually through several feedback loops. When the body's ability to control glucose reduces, result would be diabetes.

If this hypothesized metabolic block affects cellular energy metabolism as the Norwegian researchers have speculated, it would have a downstream effect on a huge number of other processes. The Norwegian researchers found that pyruvate dehydrogenase enzyme function is impaired in ME/CFS patients and that inhibitory PDH kinases are up-regulated. So even this metabolic block itself is maintained by many feedback loops and it can only be speculated what all feedback loops are affected as a result of this block.
 
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FMMM1

Senior Member
Messages
513
Wally said:
@Jackb23 - Thank you for responding to my question. Can you provide an example(s) of a feedback loop or downstream event that might happen when there is a metabolic block and how/why it may differ between individuals?
Click to expand...

I seem to keep referring to the same data. Check out Chris Armstrong's December 2016 webinar and his responses to questions on this website [search for posted by Chris Armstrong].

Basically it starts off with impaired metabolism, burning amino acids [papers by Armstrong, Fluge and Mella, and Naviaux etc] for energy i.e. rather than glucose. This results in lower stomach acid production [Armstrong], lower stomach acid production results in changes to gut flora (microbiome) i.e. to more pathogenic species [Hanson, Armstrong]. Increased migration (translocation) of pathogenic species i.e. into bloodstream - leaky gut [Unutmaz, Hanson, Armstrong]. Increased translocation leads to sepsis (Wenzhong Xiao*) which maintains the altered metabolism - less acid - increased translocation - metabolic trap.

The fatigue may be due to the production of dUTPase by human cells/viruses; dUTPase activates the innate immune system (T-cells) [Komaroff's video (27 minutes ish)].

So a downstream effect of altered metabolism could be altered microbiome and fatigue. Lets say you could reduce the levels of dUTPase; the result (i.e. reduced fatigue) would only be temporary since the cause (altered metabolism) has not been addressed. This is what's key about downstream effects i.e. they are not causal just consequence.

If ME/CFS is chronic sepsis then presumably the outcome of a relatively common infection may (in some susceptible individuals) be ME/CFS; i.e. owing to their genetic susceptibility [Cort Johnson*]. I.e. you can predict susceptibility to ME/CFS from the version of HLA/KIR genes which the person carries [recent NIH grant to Ron Davis]. On the plus side research into sepsis is well funded; therefore, some research has already been carried out/further research is likely to be funded. Also, some of those working on ME/CFS have worked on sepsis [Wenzhong Xiao, Tompkins, (& Ron Davis?). I'm guessing that HLA type may also be related to severity of ME/CFS.

Check out Cort Johnson* for accessible/understandable reviews.
https://www.healthrising.org/blog/2...me-cfs-research-center-fulfills-crucial-need/
 
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W

Wally

Senior Member
Messages
1,167
@JES and @FMMM1 - I wanted to say thank you for your responses to my question. My science knowledge is limited and I wanted to be sure I understood what was meant by a metabolic block and how a person’s individual genes could play into that issue. Your response(s) really helped me to put this together in my (cognitively challenged) brain in a very straightforward and concise way.
 
F

FMMM1

Senior Member
Messages
513
Wally said:
@JES and @FMMM1 - I wanted to say thank you for your responses to my question. My science knowledge is limited and I wanted to be sure I understood what was meant by a metabolic block and how a person’s individual genes could play into that issue. Your response(s) really helped me to put this together in my (cognitively challenged) brain in a very straightforward and concise way.
Click to expand...

I was winging it. I left my basic level (technician) science behind a long time ago.

OMF will presumably explain further at some point i.e. once the research has concluded (at the end of the summer).

Many of us are hoping for some significant progress as soon as possible. All the best.
 
K

keepontruckin

Senior Member
Messages
213
I am wondering what kind of testing a person should seek about their mitochondrial problems, so that whenever any potential treatment might become available they already have some idea of their problems. Then the question will become what kind of queue and expert to see. In Canada the waiting times for specialist can be lengthy but honestly we would be ready to queue up anywhere in North America if there were a place to go. It has been 30 years since mono hit and each decade is getting worse.
 
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FMMM1

Senior Member
Messages
513
If you're interested in this metabolic block/trap----, and you can get hold of the Invest in ME Research International ME 2018 Conference DVD, then check out Professor Karl Johan Tronstad presentation. Karl worked with Fluge and Mella and was one of the authors on the paper showing problems with PDH enzyme. Google something like - Tronstad Fluge and Mella PDH enzyme - and you should find some stuff.
 
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