A Metabolic Trap for ME/CFS?

[Cam Newton]

Listen to this video from 4:12 - 4:28, he gives some insight into the immune activation aspect of Robert Phair's theory.

https://www.facebook.com/OpenMedicineFoundation/videos/1524093601028389/

Isn’t clonal T-cell expansion a very specific immune activation? It seems like this would be at odds with the “overall immune activation” of the metabolic trap that Ron discussed.

Anyway, I have no idea what I’m talking about so let’s just wait a few more months

 

[Frenchguy]

OT @Janet Dafoe (Rose49) Have you ever tried Shilajit (Fulvic acid) for Whitney ? If not I would definitely suggest trying it. You can try Jarrow Formulas Shlajit Fulvic acid complex. Or you can buy the raw form from Amazon and use it. Ideally it works well with a glass of milk. If Whitney is not taking milk then he can take it immediately after breakfast. Ayurveda uses Shilajit for debility, emaciation, physical and mental exhaustion. It is worth a try. Take care.

Withney is tube feed, he don't drink milk... Try to learn about patient situation before suggesting things like that please...

 

[Sundancer]

removed

 

[pamojja]

Try to learn about patient situation before suggesting things like that please...

Please all be considerate of each others situation. He might even read the whole thread before, but due to brain-fog forgot. It definitely was well-intended.

 

[bthompsonjr1993]

Isn’t clonal T-cell expansion a very specific immune activation? It seems like this would be at odds with the “overall immune activation” of the metabolic trap that Ron discussed.

Anyway, I have no idea what I’m talking about so let’s just wait a few more months

I have no idea, but I asked Janet earlier in the tread if the metabolic trap theory is conpatible with the clonal T-Cell activation findings, and she said that Ron says it is. For for me that is that and I will not question it.

My uneducated opinion of what he means by the general activation is that tons of different types of T-cells are clonally activating.

 

[FMMM1]

I have no idea, but I asked Janet earlier in the tread if the metabolic trap theory is conpatible with the clonal T-Cell activation findings, and she said that Ron says it is. For for me that is that and I will not question it.

My uneducated opinion of what he means by the general activation is that tons of different types of T-cells are clonally activating.

Don't know much either.

Proposal (i.e. metabolic trap theory) is ME/CFS is a metabolic disease and a consequence is leaky gut (i.e.translocation of bacteria into bloodstream) and a shift in the microbiome to more pathogenic species - combined effect is immune activation (Unutmaz/Mark Davis). Reverse the metabolic trap and the leaky gut/shift in the microbiome/immune activation reverse. I.e. the observed T-cell activation/autoimmunity is a downstream consequence not the cause. As per comment above (Cam Newton) should be data/clarity in a few months.

 

[Learner1]

I just found this today. I hadn't seen in posted elsewhere and apologize if this is redundant. It is a nice overview of a lot of recent research.

Komaroff's conclusions indicate there are likely many causes for similar symptoms and many different illnesses underlying them.

As for the metabolic trap, it says this on the OMF websire. No T cells mentioned...

Phair’s metabolic trap hypothesis emerged from a synthesis of published enzyme kinetics using mechanistic computational modeling.

The new OMF-funded work will test this hypothesis using stable isotope metabolic tracer experiments on cells from ME/CFS patients and healthy controls (managed and carried out by a senior life science professional at Stanford, Julie Wilhelmy), and expert mass spectrometry at the Stanford Metabolic Chemistry Analysis Center headed by another collaborator, Curt R. Fischer, PhD. Everyone involved is already working hard on experimental tests.

 

[ljimbo423]

“Hot Areas in ME/CFS Research: 2018”- presented by Anthony L. Komaroff, MD, Simcox-Clifford-Higby Professor of Medicine at Harvard Medical School and Senior Physician at Brigham and Women’s Hospital.

At 45:13 in this video, originally posted above by @Learner1 he says this-

"I think that the recent suggestion that the gut microbiome maybe one trigger of this illness in some patients is also plausible."

This statement is in alignment with ME/CFS researchers Chris Armstrong and Derya Unutmaz.

I think it's the altered gut microbiome and increased intestinal permeability from that, that leads to the metabolic trap or mitochondrial dysfunction.

Jim

 

[wigglethemouse]

Here is a July 2018 review article on mitochondrial activity in T cells. It may interest folks in this thread who are asking about T-Cells and impaired energy production and how it affects immune dysfunction

- T cells rely on mitochondria during all stages of adaptive immune responses
- ATP and Calcium buffering are essential during migration and proliferation.
- mROS signaling contribute to the proliferation phase.
- Fusion and fission mitochondrial events are important during memory phase.
- Mitochondrial metabolism dictates T cell differentiation program
- And in summary "possibly triggering chronic inflammation or autoimmune diseases"

Link:
https://www.sciencedirect.com/science/article/pii/S1567724917301927

The concept that mitochondria are simply the power plant of the cell has become obsolete. Nowadays, mitochondria are considered as bioenergetic, biosynthetic and signaling centers, controlling a plethora of processes in the cell. T cells rely on a fine-tuned response of mitochondria during their migration, activation, proliferation, differentiation, memory phase, and exhaustion (Fig. 1). Without a tight control of mitochondrial behavior, immune responses are compromised, leading to ineffective protection against infection or tumor cells, or to imbalances in effector T cell populations, possibly triggering chronic inflammation or autoimmune diseases (Sukumar et al., 2016).

 

[Tuha]

Maybe a stupid question but What is the next step to understand all this better?

 

[FMMM1]

Maybe a stupid question but What is the next step to understand all this better?

Haven't seen Komaroff's video but I'm planning to look at it.

Look at Chris Armstrong's 2016 webinar and search on this site for his response to questions etc [(https://forums.phoenixrising.me/index.php)?threads/exercise-induced-relapse-autoimmune-theory.52708/)].

Unutmaz is due to do a webinar (on 19th July?).

Check out Cort Johnson; search for something like [molecular trap Pair] - no quotation marks on my keyboard!

Good luck.

 

[FMMM1]

I just found this today. I hadn't seen in posted elsewhere and apologize if this is redundant. It is a nice overview of a lot of recent research.

Komaroff's conclusions indicate there are likely many causes for similar symptoms and many different illnesses underlying them.

As for the metabolic trap, it says this on the OMF websire. No T cells mentioned...

Around 38.25 minutes he gives a good summary of leaky gut; referring to tight junction proteins or something similar. He refers to bacteria/bacterial toxins crossing the gut lining into the bloodstream. He doesn't refer to T-cells e.g. Unutmaz (activation of MAIT T-cells in gut lining) or Mark Davis's work on T-cell activation. He's been asked to summarise and speak to 80% lay people; possibly this may be why he doesn't go into these specific research findings or the fact that these are preliminary findings (larger studies haven't been carried out, published etc).

Around 40.17 he reviews the metabolic research; he doesn't use "metabolic trap" but neither did Chris Armstrong. I wouldn't get hung up on the language.

He also highlights the HPA axis (from memory) based on genetic screening. I wonder if this is a steroid hormone and if it's one of the hormones Bergquist OMF/Uppsala is currently looking at.

Did a Google search and Cort Johnson describes him as a class act [https://www.healthrising.org/forums...e-cfs-research-in-smci-webinar-tomorrow.5957/].

 

[nryanh94]

If it is indeed multiple diseases, is the theory that each disease is leading to this “metabolic trap” and thus fixing the metabolic trap would fix each underlying disease?

 

[Learner1]

If it is indeed multiple diseases, is the theory that each disease is leading to this “metabolic trap” and thus fixing the metabolic trap would fix each underlying disease?

That is an excellent question.

 

[nryanh94]

That is an excellent question.

Basically (this is my hope so that everyone can be treated/cured), there are several small roads (diseases) to get to a certain location (ME/CFS), but all of those roads are one way and everyone can take the interstate (cure for metabolic trap) to get back home (pre illness self).

 

[FMMM1]

If it is indeed multiple diseases, is the theory that each disease is leading to this “metabolic trap” and thus fixing the metabolic trap would fix each underlying disease?

I assume that the proposal is that the metabolic effect (outcome) is common and the immune activation (Unutmaz/Mark Davis etc) will be reversed once the metabolism is corrected.

Check out Komaroff's video (27 minutes ish). It appears that human cells/some viruses can produce dUTPase; which activates the innate immune system (T-cells). High levels of dUTPase appear to trigger fatigue. [Not sure I understand this; never heard of dUTPase's before]

So if you can reverse the metabolic effect then you don't get the fatigue.

Should know more by the end of the summer.

 

[perrier]

Thanks Learner for posting this video by Dr Komaroff. Very useful summary. I can't help but wonder what Dr Davis concluded after looking at the paper that was sent to him from Victoria Bohne. Komaroff mentioned the enzyme problem (pyruvate...) and Victoria Bohne's very special diet sees to address this.

It's a hard road for the very sick, though.

 

[mariovitali]

A bit of a dissapointment from the video i saw. Things are moving forward very quickly, however i did not hear anything about enterohepatic circulation (=Gut and the Liver).

I see that a lot is being said about leaky gut. I begin to understand its potential importance myself although i have been trying to point the attention of Researchers to the Liver.

Note below that Liver function is inherently related to Gut Dysbiosis (through dysregulation of Bile Acids) and also Gut Permeability :

Liver products primarily influence the gut microbiota composition and gut barrier integrity, whereas intestinal factors regulate bile acid synthesis, glucose and lipid metabolism in the liver.

Alcoholic and nonalcoholic fatty liver diseases share key characteristics, such as intestinal dysbiosis, gut permeability and shifts in levels of bile acids, ethanol and choline metabolites.

Bile Acids (BAs) and the gut microbiota closely interact and modulate each other; BAs exert direct control on the intestinal microbiota. By binding to FXR, they induce production of antimicrobial peptides (AMPs) such as angiogenin 1 and RNase family member 4, which are directly involved in inhibiting gut microbial overgrowth and subsequent gut barrier dysfunction

Intestinal permeability is characterized by compromised tight junctions between enterocytes and is consistently seen across the spectrum of liver diseases 66,67. Liver damage is associated with small intes- tinal bacterial overgrowth (SIBO) and dysbiosis of the lower gastrointestinal tract 68.

All experimental models of liver fibrosis result in gut microbial dysbiosis and increased intestinal permeability, and treatment of the gastrointestinal tract with nonabsorbable antibiotics (such as rifax- imin and neomycin) improved survival by immuno-modulation, reducing translocation and incidence of infection159. Mice with genetic ablations of the receptors for bacterial product ligands (TLR2, TLR4, TLR9 and NLP3) are protected from experimental liver fibrosis

I would like to see how the Metabolic Trap relates to the Liver Theory.

Link : https://www.nature.com/articles/s41575-018-0011-z

 

[Learner1]

And toxicity?

 

[FMMM1]

A bit of a dissapointment from the video i saw. Things are moving forward very quickly, however i did not hear anything about enterohepatic circulation (=Gut and the Liver).

I see that a lot is being said about leaky gut. I begin to understand its potential importance myself although i have been trying to point the attention of Researchers to the Liver.

Note below that Liver function is inherently related to Gut Dysbiosis (through dysregulation of Bile Acids) and also Gut Permeability :

Chris Armstrong Melbourne/OMF describes role of bile acids and possible effect of impaired energy production in this [https://www.melbournebioanalytics.org/metabolism-chris-armstrong-written-transcription/]. Search for bile in the transcript. Phair and Chris are both members of OMF so I assume that they will be looking at this.

I would like to see how the Metabolic Trap relates to the Liver Theory.

Link : https://www.nature.com/articles/s41575-018-0011-z