Ron Davis Update

[Marylib]

if ammonia is high, the function medicine doctors know of a way to decrease it, namely with L-arginine alpha-ketoglutarate, no idea if it cross the BBB but it helped me to not pee anymore at night, i took 5-10 grams a day for a few weeks and the effect lasted for months. Also since NO is produced in the urea cycle, I got better erections and isn't that what's most important, haha.

The best stuff over the years always seems to come from body building websites. Good find, Max.

 

[Marylib]

If you think about it from an evolutionary point of view - people who don't get well after infections are meant to die off quicker than we do. We don't die immediately, and it seems that the fuel we can burn to sustain life is the kind that can be scarce except in times when the hunting or fishing is good - amino acids and proteins. Cheap fuel like sugar from fruit or grains doesn't work. Once our body fat is burned off, we starve to death and cease to be a problem for the rest of the tribe. It's that strange adaptation to sustain life in the absence of proper metabolic function that is so puzzling. I know what I say is nothing new, and maybe someday someone will figure out how shift that function. I wish I was more optimistic about when that accessible metabolic switch will be found. I'm grateful to OMF for keeping up that search. I'm pretty tired of the endless 'what's our biomarker' question. Who cares? If the symptoms can be reversed somehow - that is the goal.

 

[ruben]

Hello. Can anyone recommend a hair analysis lab here in UK. Thanks in advance.

 

[Violeta]

One has to remember that if a hair analysis shows that one is low in manganese or copper there may be different reasons for those results and it's possible that copper and/or manganese may be being precipitated in soft tissue somewhere in the body.

I believe this is very important and very possible because ME/CFS has many similarities to Parkinson's in which excess manganese in the brain is known to even be a cause.

I didn't realize copper metabolism is messed up in Parkinson's, too, but found this.

In Parkinson's disease, free copper is related to increased oxidative stress, alpha-synuclein oligomerization, and Lewy body formation.

So I hope someone researches beyond hair analysis in coming to conclusions about what to do about manganese and copper recommendations.

 

[Rufous McKinney]

If you think about it from an evolutionary point of view - people who don't get well after infections are meant to die off quicker than we do. We don't die immediately, and it seems that the fuel we can burn to sustain life is the kind that can be scarce except in times when the hunting or fishing is good - amino acids and proteins. Cheap fuel like sugar from fruit or grains doesn't work.

very interesting .....to ponder...further.

I think our disorder was extremely rare in a world made of of clean places, before chemicals, toxins, and so much metal was released in so many forms.

Somehow, genetics, viruses and pathogens which would have been less widespread in a low human population setting...people were far more isolated. Now they aren't. And if you think about multiple viral loads and reactivations.

Then, I might assert we had our 18-20% HSP within the general population. (different immune system, different wiring and reactivity.)

That group with this more "sensitive" wiring...is more vulnerable to the disorder.

Stress has always existed. But maybe we label it alot more now.

What we focus our eyes on, is what we notice.

 

[Oliver3]

If you think about it from an evolutionary point of view - people who don't get well after infections are meant to die off quicker than we do. We don't die immediately, and it seems that the fuel we can burn to sustain life is the kind that can be scarce except in times when the hunting or fishing is good - amino acids and proteins. Cheap fuel like sugar from fruit or grains doesn't work. Once our body fat is burned off, we starve to death and cease to be a problem for the rest of the tribe. It's that strange adaptation to sustain life in the absence of proper metabolic function that is so puzzling. I know what I say is nothing new, and maybe someday someone will figure out how shift that function. I wish I was more optimistic about when that accessible metabolic switch will be found. I'm grateful to OMF for keeping up that search. I'm pretty tired of the endless 'what's our biomarker' question. Who cares? If the symptoms can be reversed somehow - that is the goal.

Sometimes I think the evolutionary lens is overstated. Is going blind midlife or having a stroke or getting liver trouble an evolutionary problem or just the body messing up.
Not to argue for arguments sake but it just struck me when Ron was talking about the evolutionary basis of this, it could just be a damn fault!!
The evolutionary lens is still a lens. Maybe it doesn't matter

 

[bthompsonjr1993]

One has to remember that if a hair analysis shows that one is low in manganese or copper there may be different reasons for those results and it's possible that copper and/or manganese may be being precipitated in soft tissue somewhere in the body.

I believe this is very important and very possible because ME/CFS has many similarities to Parkinson's in which excess manganese in the brain is known to even be a cause.

I didn't realize copper metabolism is messed up in Parkinson's, too, but found this.

In Parkinson's disease, free copper is related to increased oxidative stress, alpha-synuclein oligomerization, and Lewy body formation.

So I hope someone researches beyond hair analysis in coming to conclusions about what to do about manganese and copper recommendations.

If you watched Ron's video on the Manganese grant, you would see that they are researching far beyond hair samples.

 

[Oliver3]

One has to remember that if a hair analysis shows that one is low in manganese or copper there may be different reasons for those results and it's possible that copper and/or manganese may be being precipitated in soft tissue somewhere in the body.

I believe this is very important and very possible because ME/CFS has many similarities to Parkinson's in which excess manganese in the brain is known to even be a cause.

I didn't realize copper metabolism is messed up in Parkinson's, too, but found this.

In Parkinson's disease, free copper is related to increased oxidative stress, alpha-synuclein oligomerization, and Lewy body formation.

So I hope someone researches beyond hair analysis in coming to conclusions about what to do about manganese and copper recommendations.

I wonder if Ron et Al have heard of Morley Robbins and the magnesium advocacy group, as far s I understand it, he says magnesium dysregulation is at the heart of copper toxicity

 

[maybe some day]

@Janet Dafoe
Thank you for all your updates and time. Im sure your spread thin with the care of Whitney and other daily challenges. We sincerely appreciate you here on PR to help us all.

 

[Alvin2]

I started a thread on all this
https://forums.phoenixrising.me/threads/ron-davis-innate-immune-system-theory-treatment-ideas.88179/

 

[Violeta]

If you watched Ron's video on the Manganese grant, you would see that they are researching far beyond hair samples.

Would you be able to mention some of the research in this thread?

 

[bthompsonjr1993]

@Violeta Ron already shared it, I don't want to speak for him and risk incorrectly paraphrasing, it would be best to watch this video so you can hear exactly what he says about it:

 

[Violeta]

Thank you, @bctjr1993

 

[Oliver3]

very interesting .....to ponder...further.

I think our disorder was extremely rare in a world made of of clean places, before chemicals, toxins, and so much metal was released in so many forms.

Somehow, genetics, viruses and pathogens which would have been less widespread in a low human population setting...people were far more isolated. Now they aren't. And if you think about multiple viral loads and reactivations.

Then, I might assert we had our 18-20% HSP within the general population. (different immune system, different wiring and reactivity.)

That group with this more "sensitive" wiring...is more vulnerable to the disorder.

Stress has always existed. But maybe we label it alot more now.

What we focus our eyes on, is what we notice.

Just adding to that, is it fair to say that glyphosate leeches manganese?

 

[BrightCandle]

Another update - DNA/RNA tech and viruses with Peidong Shen

Summary
- Itaconate pathway has to be on for a long time and it comes on when you have an infection so could have a persistent infection and look for that
- Peidong has developed Tech to look for viruses, multiplexing, can test multiple viruses in a single tub and even ways to combine patients but they wont be doing that
- Looked for herpes viruses and RNA
- Run herpes test on 50 patients, only occasional activation and its similar in healthy patients so doesn't look like that is the answer.
- Enteroviruses conserved RNA sequences. Done 20 samples none found in the blood. Could be somewhere else still. Going to pull contents of Whitney's stomach to look for them there.
- Also looking for Parasites not ready for big analysis yet. This will include trypanosomes and working on a test for that. One patient with Nematodes working on sequencing it and to probe it in others.
- Long Covid looks like ME/CFS, OMF got funding to look for activation of herpes viruses from Sweden via Jonas Bergquist . 20 samples they found EBV activated in 18, 2 negative looking at those again and will do herpes viruses too.
- Tech allows them to amplify genes, they replicate it over and over and they can then use conventional methods.

- Looking also into the BH4 pathway could be mutations in the gene or the control region for the gene. Maybe a low level of enzyme or defective gene looking into if its responsible for low BH4. Assays to look for BH4 levels too and other products.
- Tech should allow them to look for messenger enzymes in the Itaconate pathway. Looking for them in a patients muscle sample which is quite invasive.
- Possible herpes is activated but not replicating. Could just turn on 1 RNA segment so the body perceives an infection and would trigger the Itaconate pathway. Would explain why we can't find it, idea from Prusty to look for this.
- This is exciting because its probing whether the pathway is on and detecting why its on.
- In the past couldn't find any DNA viruses, gone past just looking for RNA viruses and now looking for segments.
- They will be looking for more RNA viruses.
- If they do find something and its responsible for the Interferon Alpha and Itaconate Shunt being on then they should be able to shut it off and Rob Phair will be talking about that in the future.

There is also a complete transcript with the video in its description if you want to read it.

 

[BethRene']

Given the success of the Stellate ganglion block for some individuals, could cortisol and other hormones associated with dysautonomia play a role in keeping the Itaconate shunt turned on?

 

[Pyrrhus]

Enteroviruses conserved RNA sequences.

I really hope they are not using PCR primers from the first ~40 nucleotides of the 5' end of the viral genome. Those first ~40 nucleotides are lost from the genome in the persistent phase of the infection:
https://forums.phoenixrising.me/thr...-interviews-diane-griffin.88181/#post-2406465

Looking also into the BH4 pathway

Due to the highly reactive nature of BH4, it might be particularly susceptible to oxidative stress, and one might therefore expect to find pockets of BH4 depletion in any inflamed tissue:
https://forums.phoenixrising.me/thr...on-cycle-trap-or-blockage.83459/#post-2331704

 

[Breagjam]

Another update - DNA/RNA tech and viruses with Peidong Shen

Summary
- Itaconate pathway has to be on for a long time and it comes on when you have an infection so could have a persistent infection and look for that
- Peidong has developed Tech to look for viruses, multiplexing, can test multiple viruses in a single tub and even ways to combine patients but they wont be doing that
- Looked for herpes viruses and RNA
- Run herpes test on 50 patients, only occasional activation and its similar in healthy patients so doesn't look like that is the answer.
- Enteroviruses conserved RNA sequences. Done 20 samples none found in the blood. Could be somewhere else still. Going to pull contents of Whitney's stomach to look for them there.
- Also looking for Parasites not ready for big analysis yet. This will include trypanosomes and working on a test for that. One patient with Nematodes working on sequencing it and to probe it in others.
- Long Covid looks like ME/CFS, OMF got funding to look for activation of herpes viruses from Sweden via Jonas Bergquist . 20 samples they found EBV activated in 18, 2 negative looking at those again and will do herpes viruses too.
- Tech allows them to amplify genes, they replicate it over and over and they can then use conventional methods.

- Looking also into the BH4 pathway could be mutations in the gene or the control region for the gene. Maybe a low level of enzyme or defective gene looking into if its responsible for low BH4. Assays to look for BH4 levels too and other products.
- Tech should allow them to look for messenger enzymes in the Itaconate pathway. Looking for them in a patients muscle sample which is quite invasive.
- Possible herpes is activated but not replicating. Could just turn on 1 RNA segment so the body perceives an infection and would trigger the Itaconate pathway. Would explain why we can't find it, idea from Prusty to look for this.
- This is exciting because its probing whether the pathway is on and detecting why its on.
- In the past couldn't find any DNA viruses, gone past just looking for RNA viruses and now looking for segments.
- They will be looking for more RNA viruses.
- If they do find something and its responsible for the Interferon Alpha and Itaconate Shunt being on then they should be able to shut it off and Rob Phair will be talking about that in the future.

There is also a complete transcript with the video in its description if you want to read it.

Thanks so much for this summary!! I‘m thankful to Ron & Janet for doing these videos.

Testing in blood for enterovirus needs to be done via the neutralization method, as done at ARUP labs for coxsackie B and echovirus. I’m hoping they used this method….

 

[Pyrrhus]

Testing in blood for enterovirus needs to be done via the neutralization method, as done at ARUP labs for coxsackie B and echovirus. I’m hoping they used this method….

I believe you're referring to enterovirus antibody testing, not to enterovirus RNA testing.

Enterovirus RNA is not expected to be found in the blood, as was suggested by (Bouquet et al., 2019):

Whole blood human transcriptome and virome analysis of ME/CFS patients experiencing PEM following CPET (Bouquet et al., 2019)
https://forums.phoenixrising.me/thr...-pem-following-cpet-bouquet-et-al-2019.84824/
(in this study, the only enterovirus RNA found in blood belonged to a control sample)


Nonetheless, there have been two researchers who claimed to find enterovirus RNA in the blood:

1. Dr. Antonio Toniolo co-cultured whole blood from post-polio patients with cells "permissive" for enterovirus. After co-culturing the cells, he detected enterovirus RNA. There are no reports that anyone has tried to replicate Toniolo's findings, but it is rumored that Dr. Maureen Hanson has tried.
2. Dr. John K. Chia, who is a clinician who also dabbles in research, used a cutting-edge RNA stabilizing agent - added to the patient's blood immediately at time of collection - and found evidence of enterovirus in the blood of ME patients.

 

[Breagjam]

I believe you're referring to enterovirus antibody testing, not to enterovirus RNA testing.

Enterovirus RNA is not expected to be found in the blood, as was confirmed by (Bouquet et al., 2019):

Whole blood human transcriptome and virome analysis of ME/CFS patients experiencing PEM following CPET (Bouquet et al., 2019)
https://forums.phoenixrising.me/thr...-pem-following-cpet-bouquet-et-al-2019.84824/
(in this study, the only enterovirus RNA found in blood belonged to a control sample)


Nonetheless, there have been two researchers who claimed to find enterovirus RNA in the blood:

1. Italian researcher Toniolo co-cultured whole blood from post-polio patients with cells "permissive" for enterovirus. After co-culturing the cells, he detected enterovirus RNA from the blood of post-polio patients. There are no reports that anyone has tried to replicate Toniolo's findings, but it is rumored that Maureen Hanson has tried.
2. Clinician Dr. John K. Chia, who is primarily a clinician who also dabbles in research, used a cutting-edge RNA stabilizing agent - added to the patient's blood immediately at time of collection - and found evidence of enterovirus in the blood of ME patients.

Gotcha. That makes sense, glad there is an answer. Thanks for the info.