Ron Davis Update

BrightCandle

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Itaconate Pathway - Called a Shunt, Interrupts citric acid cycle bleeds it off into other uses so it doesn't get into ATP, its for infection fighting. Makes you tired and low energy. What if it doesn't turn off?

Issue is its not in all cells. Have to look at RNA signatures. Assay for that RNA.

Looking for a way with modelling to lock it on, why is it blocked on?

Its interesting because we know ME/CFS patients don't burn glucose and fat very well but they do burn amino acids. This pathway would explain why these don't work well but amino acids do, because Co enzyme A being used for fats and glucose.

Excited that this may be the underlying cause/initial event.

Can happen in the brain as well and if so you burn glutimate and glutimane and these are neurotransmitters, very bad thing! Likely brain fog cause.

The solution may involve inhibiting Interferon Alpha or the reason why is that being produced. Could be an systemic viral or otherwise infection.
 
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I"m quite taken with this hypothesis. I've been a doubter of Robert Phair's but it seems he didn't give up after the IDO1 metabolic trap and is now looking at this, so credit to him for continuing to work for us.

What's good about itaconate is it can really link the metabolic and immune aspects of the disease, which are both definitely present but are hard to grasp. Itaconate is famous for rewiring metabolism, as explained here.

https://portlandpress.com/biochemso...964/Itaconate-as-an-inflammatory-mediator-and

But that's not all. it can also give us a link to the blood flow aspects of the disease, because itaconate is able to affect nitric oxide production, and one of the important roles nitric oxide plays is regulating dilation nd contraction of blood vessels.

(of course, the body uses some systems and molecules for many things. mTorc is an exmaple, it seems to be involved in everything and it doesn't mean it is key to this disease, it's just a key part of the body. The fact itaconate is involved in several me/cfs disease processes could just mean it's one of those molecules that is up and involved in every process. i.e. it could be a red herring.)

Ron says at the end of the video that he thinks one cause of itaconate activation could be lingering infection. I've come around to the idea of lingering infection, and the possibility that it interacts with blood flow issues.

My idea is that possibly a virus has developed a survival strategy where it survives in peripheral tissues (e.g. muscle) and limits the ability of the immune system to detect it by physically reducing the amount of blood flow to the tissues where it sits. A strategy so simple as to be both unexpected and cunning!

Inflammation makes you red, that's your immune system dilating blood vessels to let things through. If in me/cfs dilation is impaired (perhaps the virus lingers in the endothelium, or can disrupt nictric oxide production via mitochondria, or is even in the parts of the nervous system that control vasodilation) then might immune function be imparied, not at a deep, clever, chemical way, but in a really simple mechanistic way where large immune cells can't get through to where the virus is hiding. Notably robert phair was in these pages no so long ago and when someone described how they don't go red, he said "There's also the question of how you can sweat without flushing since both are mediated, at least in part, by vasodilation. I'll look into that too. This feels like a productive line of investigation."

https://forums.phoenixrising.me/thr...nd-body-temperature.82073/page-3#post-2311336
 

BrightCandle

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I think Joshua Leisk's new protocol is attempting that re beta glucans
Could be why we feel better on the oat bran and lions mane. But reading this I am conflicted because its dampening down the immune system which is likely trying to fight a virus or bacteria. I am really unclear if the next thing to do is drop all the beta glucans or work out what the maximim I can take without hurting myself too much! I guess ramp it up and see what happens if I get a big infection outbreak I can stop and then maybe my body will notice the invader properly!
 

MonkeyMan

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I'm confused. Wasn't just a week or two ago that Ron seemed so dispirited in a video he made? Was that before this was discovered??
 

BrightCandle

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I'm confused. Wasn't just a week or two ago that Ron seemed so dispirited in a video he made? Was that before this was discovered??
We still haven't heard a word about the Tryptophan trap either. There doesn't seem to be a paper out on it being a failure and they ought to have tested all the drugs on their yeast by now. Just letting us know its not the route would be appreciated.
 

JES

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Yeah the tryptophan trap was supposedly proven to exist and was shown could be triggered in yeast cells. That's nice, but I reckon they still haven't been able to measure tryptophan or kynurenine levels in human cells. This supposedly required some expensive mass spectrometer, but I haven't heard any further news about that in a couple of years now.
 
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My idea is that possibly a virus has developed a survival strategy where it survives in peripheral tissues (e.g. muscle) and limits the ability of the immune system to detect it by physically reducing the amount of blood flow to the tissues where it sits. A strategy so simple as to be both unexpected and cunning!
Nice theory!
 

Oliver3

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I"m quite taken with this hypothesis. I've been a doubter of Robert Phair's but it seems he didn't give up after the IDO1 metabolic trap and is now looking at this, so credit to him for continuing to work for us.

What's good about itaconate is it can really link the metabolic and immune aspects of the disease, which are both definitely present but are hard to grasp. Itaconate is famous for rewiring metabolism, as explained here.

https://portlandpress.com/biochemso...964/Itaconate-as-an-inflammatory-mediator-and

But that's not all. it can also give us a link to the blood flow aspects of the disease, because itaconate is able to affect nitric oxide production, and one of the important roles nitric oxide plays is regulating dilation nd contraction of blood vessels.

(of course, the body uses some systems and molecules for many things. mTorc is an exmaple, it seems to be involved in everything and it doesn't mean it is key to this disease, it's just a key part of the body. The fact itaconate is involved in several me/cfs disease processes could just mean it's one of those molecules that is up and involved in every process. i.e. it could be a red herring.)

Ron says at the end of the video that he thinks one cause of itaconate activation could be lingering infection. I've come around to the idea of lingering infection, and the possibility that it interacts with blood flow issues.

My idea is that possibly a virus has developed a survival strategy where it survives in peripheral tissues (e.g. muscle) and limits the ability of the immune system to detect it by physically reducing the amount of blood flow to the tissues where it sits. A strategy so simple as to be both unexpected and cunning!

Inflammation makes you red, that's your immune system dilating blood vessels to let things through. If in me/cfs dilation is impaired (perhaps the virus lingers in the endothelium, or can disrupt nictric oxide production via mitochondria, or is even in the parts of the nervous system that control vasodilation) then might immune function be imparied, not at a deep, clever, chemical way, but in a really simple mechanistic way where large immune cells can't get through to where the virus is hiding. Notably robert phair was in these pages no so long ago and when someone described how they don't go red, he said "There's also the question of how you can sweat without flushing since both are mediated, at least in part, by vasodilation. I'll look into that too. This feels like a productive line of investigation."

https://forums.phoenixrising.me/thr...nd-body-temperature.82073/page-3#post-2311336
Is the metabolic trap dead in the water or is this a drilling down into further aspect s of the trap
 

LINE

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[QUOTE="Murph, post: 2402753, member: 28313"


But that's not all. it can also give us a link to the blood flow aspects of the disease, because itaconate is able to affect nitric oxide production, and one of the important roles nitric oxide plays is regulating dilation nd contraction of blood vessels.


https://forums.phoenixrising.me/thr...nd-body-temperature.82073/page-3#post-2311336[/QUOTE]

Nitric Oxide was a big issue for me. My blood pressure was soaring and not responding to commonly used hypertensive drugs such as ACE inhibitors or Beta Blockers. In fact, the ACE inhibitor sent me back into autoimmunity even at low doses. I found out that the ACE inhibitors work off the angiotensin-renin systems which unknown to most, regulates immunity. Even at very low doses, it was bad.

The doctor put me on a form of Nitroglycerin (Isosorbide Mononitrate) which controls Nitric Oxide. It brought the blood pressure down quickly. I can now see my veins in my hands which is a sign of vasodilation.

For others, Nitric Oxide is a powerful chemical that not only dilates the blood vessels which lowers blood pressure and allows for more blood flow through the body, it is involved in the immune response*, it is also involved in the inflammatory response. It has been vigorously studied and is considered one of the most important molecules in the body. Other roles of NO include help with diabetes, muscle soreness, vitality and sexual dysfunction (ED drugs such as Viagra work by modifying NO).

*Here is a PubMed article on NO and immunity.
Nitric oxide and immune response - PubMed (nih.gov)

Nitric oxide (NO), initially described as a physiological mediator of endothelial cell relaxation plays an important role in hypotension. It is an intercellular messenger and has been recognized as one of the most versatile players in the immune system.

Cells of the innate immune system--macrophages, neutrophils and natural killer (NK) cells use pattern recognition receptors to recognize molecular patterns associated with pathogens. Activated macrophages then inhibit pathogen replication by releasing a variety of effector molecules, including NO. In addition to macrophages, a large number of other immune system cells produce and respond to NO. Thus, NO is important as a toxic defense molecule against infectious organisms.

It also regulates the functional activity, growth and death of many immune and inflammatory cell types including macrophages, T lymphocytes, antigen-presenting cells, mast cells, neutrophils and NK cells. However, the role of NO in non-specific and specific immunity in vivo and in immunologically mediated diseases and inflammation is poorly understood. This review discusses the role of NO in immune response and inflammation and its mechanisms of action in these processes.
 
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Oliver3

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[QUOTE="Murph, post: 2402753, member: 28313"


But that's not all. it can also give us a link to the blood flow aspects of the disease, because itaconate is able to affect nitric oxide production, and one of the important roles nitric oxide plays is regulating dilation nd contraction of blood vessels.


https://forums.phoenixrising.me/thr...nd-body-temperature.82073/page-3#post-2311336
Nitric Oxide was a big issue for me. My blood pressure was soaring and not responding to commonly used hypertensive drugs such as ACE inhibitors or Beta Blockers. In fact, the ACE inhibitor sent me back into autoimmunity even at low doses. I found out that the ACE inhibitors work off the angiotensin-renin systems which unknown to most, regulates immunity. Even at very low doses, it was bad.

The doctor put me on a form of Nitroglycerin (Isosorbide Mononitrate) which controls Nitric Oxide. It brought the blood pressure down quickly. I can now see my veins in my hands which is a sign of vasodilation.

For others, Nitric Oxide is a powerful chemical that not only dilates the blood vessels which lowers blood pressure and allows for more blood flow through the body, it is involved in the immune response*, it is also involved in the inflammatory response. It has been vigorously studied and is considered one of the most important molecules in the body. Other roles of NO include help with diabetes, muscle soreness, vitality and sexual dysfunction (ED drugs such as Viagra work by modifying NO).

*Here is a PubMed article on NO and immunity.
Nitric oxide and immune response - PubMed (nih.gov)

Nitric oxide (NO), initially described as a physiological mediator of endothelial cell relaxation plays an important role in hypotension. It is an intercellular messenger and has been recognized as one of the most versatile players in the immune system.

Cells of the innate immune system--macrophages, neutrophils and natural killer (NK) cells use pattern recognition receptors to recognize molecular patterns associated with pathogens. Activated macrophages then inhibit pathogen replication by releasing a variety of effector molecules, including NO. In addition to macrophages, a large number of other immune system cells produce and respond to NO. Thus, NO is important as a toxic defense molecule against infectious organisms.

It also regulates the functional activity, growth and death of many immune and inflammatory cell types including macrophages, T lymphocytes, antigen-presenting cells, mast cells, neutrophils and NK cells. However, the role of NO in non-specific and specific immunity in vivo and in immunologically mediated diseases and inflammation is poorly understood. This review discusses the role of NO in immune response and inflammation and its mechanisms of action in these processes.[/QUOTE]
Did the increase in NO significantly increase your energy levels ?