ME/CFS Research: Herpes Autoimmune Spectrum Disorder

joshua.leisk · May 14, 2021

godlovesatrier · May 14, 2021

Hoosierfans said:
I am one of those that hasn’t responded to the Protocol (had some “immune response” but then that faded and went back to baseline...so no improvement) and am on gabapentin. Per @joshua.leisk’s hunch, I am going to try 75 mg EGCG for the next few days and then report back to see if that makes a difference.

I'm on day 5 now and I feel like this is happening to me too. Can't be completely sure yet. I've got a busy weekend planned hoping I can do more than usual because of the protocol plus my thaimine gains. If not then I'm not sure.

If I start getting super hungry but seeing no overall improvement from the resihi and lion's mane that's another sign in my experience that for me at least it probably isn't working. But still I need to wait another week or two yet.

Interesting about the egcg. Let us know how you get on.

godlovesatrier · May 14, 2021

Some fantastic products here as well in transdermal oil form. This site is buried somewhere in the PR forum, I can personally recommend the b12 transdermal oils, I take one shot and it has a very strong effect, I feel great but it gives me insomnia so I take it once a fortnight.

However it does also do transdermal b vitamins as well. Transdermal seems like a superior bioavailable route vs oral tablets. And easier than injections. Of course sublingual is also an option but it isnt for me:

https://b12oils.com/products.htm

I believe it ships from the states, so takes about 2-3 weeks to arrive in the UK.

https://b12oils.com/faq.htm

Elike · May 14, 2021

godlovesatrier said:
Also does anyone else's wee now stink of asparagus?

Supposedly that's related to sulfur. Haven't been able to figure out all the complex metabolomics re Josh's paper, so if anyone has any ideas I'm all for it.

Yes I have that too! Would love to understand whats behind it.

And I dont get, how strict has the diet to be? Meaning can I eat anything on top what joshua wrote or should it just be whats described in the dietary section?

godlovesatrier · May 14, 2021

Ah! I would too. I am really not sure what it is. I wondered if it was coming from the gelatin and veg capsules.

I think the diet is primarily to support everything else. Amongst other things.

themjay · May 14, 2021

Elike said:
Yes I have that too! Would love to understand whats behind it.

And I dont get, how strict has the diet to be? Meaning can I eat anything on top what joshua wrote or should it just be whats described in the dietary section?

Asparagus smelling urine is a common, harmless result of taking alpha lipoic acid.

Reading_Steiner · May 14, 2021

How important is it that we don't eat any sugar ? I think I've done well so far. Also did you ever have anyone you were experimenting on that only had a mild immune response each day but eventually recovered to normal health ? or does it require an intense fever / liver pain ?

joshua.leisk · May 14, 2021

godlovesatrier said:
I'm on day 5 now and I feel like this is happening to me too. Can't be completely sure yet. I've got a busy weekend planned hoping I can do more than usual because of the protocol plus my thaimine gains. If not then I'm not sure.

If I start getting super hungry but seeing no overall improvement from the resihi and lion's mane that's another sign in my experience that for me at least it probably isn't working. But still I need to wait another week or two yet.

Interesting about the egcg. Let us know how you get on.

The individual responses have varied a lot on the “mono phase”. I’ve seen some people first notice various “flare up” locations becoming inflamed first and then at some stage, “mono” happens. I think so far, I think the latest that was seen (without product mismatch issues) is about 8 days (best has been day 1).

So, based on my my experiences, as long as there is some tissue being remediated and you’re feeling drowsy / less than your usual self, I’d take that as a good early indication and wait for the real unpleasantness to begin.

The early headache for a few days is the other key telltale.

joshua.leisk · May 14, 2021

Reading_Steiner said:
How important is it that we don't eat any sugar ? I think I've done well so far. Also did you ever have anyone you were experimenting on that only had a mild immune response each day but eventually recovered to normal health ? or does it require an intense fever / liver pain ?

Important. It’s the serum glucose / insulin profile that may become an issue.

In the model, the high pancreatic GDH causes hyper-secretion of insulin. If the cells are already not using glycogen well and get force-fed glucose, it has to go somewhere, such as (eventually) the mitochondria, where it generates more ROS.

joshua.leisk · May 14, 2021

Elike said:
Yes I have that too! Would love to understand whats behind it.

And I dont get, how strict has the diet to be? Meaning can I eat anything on top what joshua wrote or should it just be whats described in the dietary section?

Prefacing everything I mention below as "specifically, in our disease model", "this is not medical advice", "YMMV", etc -

"For a moment, hypothetically forget everything you know about the immune response, or that we've heard the words 'triterpenes' or 'reishi'."
(I think I gave @Hoosierfans a mild heart-attack earlier, as I ineloquently gave her a preview of this post content and my casual phrasing may have given her the impression I was abandoning my research. lol.. Not a chance!)

Lets carefully look at the disease model again and at the ROOT CAUSE of the cascade.

Per paper 3: All non-autoimmunity issues (AKA lytic phase) are created by the ratio of activity between GDH and a-KGDH.

The carbohydrate intake profile therefore becomes a sensitive lever (or driving force) for creating ongoing or additional ROS and PEM, primarily because the concomitant hyper-secretion of insulin (caused by high GDH) is forcing energy into the mitochondrial reactions (think about kids getting "high" on sugar).
1) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3178282/
2) https://diabetes.diabetesjournals.org/content/51/3/712
3) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3136010/

Simultaneously, due to high GDH:
If the mitochondria have been getting force-fed mostly from "anaplerosis" via

a. glutaminolysis (->),
b. glutamate->a-KG (with high NAD+),
or
c. (once ROS becomes so high that the mitochondria "fragments", being very low / depleted a-KGDH), transamination at akg->glutamate + aspartate->oxaloacetate
d. excess urea->fumarate
e. excess B12+P5P->succinate (human intervention)

then there is already "sufficient" (or excess, rather) energy inside the mitochondrial reactions.

This means that due to "load sensing" vs "energy availability", glycolysis would be much less used and you'll likely see lactate later becoming higher than pyruvate.

Likewise, fatty acid oxidation will not be triggered as much... (which is probably helpful, considering that once the nitrogen excess has begun ramping up the disposal process via phenylacetylglutamine, acetyl-CoA is being rapidly depleted, impairing beta-oxidation - needed for burning fat, etc.)

Once acetyl-CoA starts being depleted, the cascade of messes start. (see post #74 for some of the many examples)

So, to CONTROL ALL OF THE METABOLIC ISSUES, it’s all about maintaining GDH vs a-KGDH, at the core of everything.

Once the ROS get too high, this becomes a runaway train and the symptoms snowball, because a-KGDH is ALWAYS going to be lower than GDH. "It's a trap!"

The ROS needs to be "reset" before you can climb out.

Accordingly, we can turn off PEM, burning, high glutamate / low GABA etc., without fixing the immune side, however this is "just" symptomatic remission.

The Balancing Act:

After we've cleared out -
1) The ammonia->urea issues, via eg. consuming additional water + (BCAAs, benzoate, B5, glycine, cysteine)
2) The energy overload crisis, high ROS has been arrested / reset (via induced carbohydrate, energy deficit)

The protocol aims to decrease and maintain all of the ROS-dysregulating factors to the barest minimum and normalise GDH.

The ROS is .. very highly catered for in the protocol (Vitamin C, E, R-ALA, liposomal glutathione, carb management and additional factors like eating broccoli / sulforaphane, etc.).

This therefore normalises a-KGDH.

The GDH elevation is treated by a combination of the triterpenes and EGCG. The dosing is based on a “natural model”, which includes one-or-more HHV infection(s) and no other drug interactions / pathogens / variables.

In many people (who don’t have any extra "unnatural" GDH altering factors), the suggested 25mg EGCG dose, every 4.5 hours is now quite balanced, when combined with the GDH "normalising" effect of the tripterpenes from reishi.

In others people, assuming the ROS/low a-KGDH issues are now resolved (no salicylates, arsenic, heavy metals, etc), GDH may still be too high, due to extra variables in play, or "bad reishi".

GDH / glutamate increasing factors:
Androgens (Endogenous: 5-AR metabolites, such as DHT. Exogenous: synthetic androgens that are either suitable DHT-derivatives or have an affinity for 5-AR and act as a suitable ligand to programatically alter GDH.)
Various drugs (we need to make a list of these), such as gabapentin, pregabalin (?)
Leucine (when above a serum threshold)
Sodium (when above a serum threshold)
Other infections:
C.diff

GDH / glutamate decreasing factors:
EGCG
Caffeine (however increases beta-oxidation efficiency and can create more ROS / increased energy availability)
.. others(?)

ROS increasing / a-KGDH decreasing factors:
Low E
Low C
Low glutathione (depleted glycine, P5P, cysteine, B5), etc
Lots of mTOR (viral activity, tissues adaptations - resistance training, immune response)
Some radiant energy sources
Excess serum glucose (+ excess insulin)
Excess Succinate (or B12 + P5P)
Excess Fumarate (urea, etc)
..

So, if someone is still seeing PEM, etc and their a-KGDH / ROS management is being correctly handled, this only leaves the GDH variable.

The simple answer is that after being absolutely sure that a-KGDH isn't impaired (feeling hypoxic, or the succinate challenge may help here), we can keep increasing the EGCG dose amount until PEM / burning stops, while temporarily dosing extra water, BCAAs, benzoate, B5, glycine, cysteine. (If this dose gets too high, we may see elevated ALT in pathology markers, showing alanine is being used to make glutamate.)

However with drugs like gabapentin, BCAAs may not work well, because gabapentin disables one of the key cycles that the BCAAs influence here.

Normalising serum hormones, by increasing estrogen and/or decreasing DHT by increasing anti-androgens (DHEA / spironolactone) may also be helpful here.

godlovesatrier · May 15, 2021

Hmm I crashed badly in the night after exertion. So if I'm reading your post right something must be wrong with my dosing.

I think thought without an OAT test it's fairly impossible to know what to tweak. I'll be getting one of these in a week or so.

godlovesatrier · May 15, 2021

Strange and interesting fact. When my ME sore throat stopped 2 days ago, my astra zeneca jab site stopped hurting as well. What the hell that's all about I have no idea.

joshua.leisk · May 15, 2021

godlovesatrier said:
Hmm I crashed badly in the night after exertion. So if I'm reading your post right something must be wrong with my dosing.

I think thought without an OAT test it's fairly impossible to know what to tweak. I'll be getting one of these in a week or so.

godlovesatrier said:
Strange and interesting fact. When my ME sore throat stopped 2 days ago, my astra zeneca jab site stopped hurting as well. What the hell that's all about I have no idea.

What’s interesting is I’ve previously noticed a pattern where large numbers of people crash on the same day.. and that new people frequently tell me they do much better at night.

In the disease model of “excess energy / excess ROS”, this got me curious about a mechanism that could negatively influence ROS at a geographical scale, which apparently also involved day/night influence.

Interestingly enough, solar radiation supplies between 3-7.5kWh/m2/day, depending on location and season.

eg.
https://solcast.com/solar-radiation-map/world/#2021-05-14 (cool tool)

https://www.nrel.gov/gis/assets/images/solar-april-dni-2018-01.jpg

I know we clearly can’t photosynthesise efficiently like plants, however energy is never lost, only transformed, so suspect this may be something fun to study.

Low energy wifi can apparently alter glutamate metabolism - https://link.springer.com/referenceworkentry/10.1007/978-3-642-30018-9_210

Solar radiation appear to be an understudied potential influence, beyond the basics of “UV = ROS”:

https://pubmed.ncbi.nlm.nih.gov/27838483/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5928335/

godlovesatrier · May 15, 2021

I should have said that the sore throat only really went 2 days into the reishi and lion's mane having been added to the mix. And I still have an ulcer I can't get rid of. For me my mouth is always a sign of wether my body is struggling to do something. Hopefully this will clear up though as it makes talking difficult as it becomes very painful. It's always a little better after food. Which makes sense as the immune system is fuelled and more active after food intake. Hence why I believe that for me doing a low carb diet is a terrible idea as when I've done this in the past I've ended up with some very nasty infections and a long course of anti biotics.

Anyway interesting they crashed on the same day. All I can say is that the UK has zero sunshine where I live currently

that's global warming for you! Major contrast to last year's baking heat from March onwards.

godlovesatrier · May 15, 2021

I think some people do better at night because of the bio chemical processes that occur. The brain gets flushed out at night as does the spinal fluid. As shown in mouse models.

There are also probably loads of immune functions and transactions that I'm convinced occur at night but to my knowledge these aren't documented.

joshua.leisk · May 15, 2021

godlovesatrier said:
I should have said that the sore throat only really went 2 days into the reishi and lion's mane having been added to the mix. And I still have an ulcer I can't get rid of. For me my mouth is always a sign of wether my body is struggling to do something. Hopefully this will clear up though as it makes talking difficult as it becomes very painful. It's always a little better after food. Which makes sense as the immune system is fuelled and more active after food intake. Hence why I believe that for me doing a low carb diet is a terrible idea as when I've done this in the past I've ended up with some very nasty infections and a long course of anti biotics.

Anyway interesting they crashed on the same day. All I can say is that the UK has zero sunshine where I live currently that's global warming for you! Major contrast to last year's baking heat from March onwards.

It’s maybe odd, but looks like your side of the pond still gets some reasonable UV, despite the lack of visible sunlight?

https://solcast.com/solar-radiation-map/united-kingdom/#2021-05-14

Elike · May 15, 2021

Uff thank

joshua.leisk said:
Prefacing everything I mention below as "specifically, in our disease model", "this is not medical advice", "YMMV", etc -

"For a moment, hypothetically forget everything you know about the immune response, or that we've heard the words 'triterpenes' or 'reishi'."
(I think I gave @Hoosierfans a mild heart-attack earlier, as I ineloquently gave her a preview of this post content and my casual phrasing may have given her the impression I was abandoning my research. lol.. Not a chance!)

Lets carefully look at the disease model again and at the ROOT CAUSE of the cascade.

Per paper 3: All non-autoimmunity issues (AKA lytic phase) are created by the ratio of activity between GDH and a-KGDH.

View attachment 42896

The carbohydrate intake profile therefore becomes a sensitive lever (or driving force) for creating ongoing or additional ROS and PEM, primarily because the concomitant hyper-secretion of insulin (caused by high GDH) is forcing energy into the mitochondrial reactions (think about kids getting "high" on sugar).
1) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3178282/
2) https://diabetes.diabetesjournals.org/content/51/3/712
3) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3136010/

Simultaneously, due to high GDH:
If the mitochondria have been getting force-fed mostly from "anaplerosis" via

a. glutaminolysis (->),
b. glutamate->a-KG (with high NAD+),
or
c. (once ROS becomes so high that the mitochondria "fragments", being very low / depleted a-KGDH), transamination at akg->glutamate + aspartate->oxaloacetate
d. excess urea->fumarate
e. excess B12+P5P->succinate (human intervention)

then there is already "sufficient" (or excess, rather) energy inside the mitochondrial reactions.

This means that due to "load sensing" vs "energy availability", glycolysis would be much less used and you'll likely see lactate later becoming higher than pyruvate.

Likewise, fatty acid oxidation will not be triggered as much... (which is probably helpful, considering that once the nitrogen excess has begun ramping up the disposal process via phenylacetylglutamine, acetyl-CoA is being rapidly depleted, impairing beta-oxidation - needed for burning fat, etc.)

Once acetyl-CoA starts being depleted, the cascade of messes start. (see post #74 for some of the many examples)

So, to CONTROL ALL OF THE METABOLIC ISSUES, it’s all about maintaining GDH vs a-KGDH, at the core of everything.

Once the ROS get too high, this becomes a runaway train and the symptoms snowball, because a-KGDH is ALWAYS going to be lower than GDH. "It's a trap!"

The ROS needs to be "reset" before you can climb out.

Accordingly, we can turn off PEM, burning, high glutamate / low GABA etc., without fixing the immune side, however this is "just" symptomatic remission.

The Balancing Act:

After we've cleared out -
1) The ammonia->urea issues, via eg. consuming additional water + (BCAAs, benzoate, B5, glycine, cysteine)
2) The energy overload crisis, high ROS has been arrested / reset (via induced carbohydrate, energy deficit)

The protocol aims to decrease and maintain all of the ROS-dysregulating factors to the barest minimum and normalise GDH.

The ROS is .. very highly catered for in the protocol (Vitamin C, E, R-ALA, liposomal glutathione, carb management and additional factors like eating broccoli / sulforaphane, etc.).

This therefore normalises a-KGDH.

The GDH elevation is treated by a combination of the triterpenes and EGCG. The dosing is based on a “natural model”, which includes one-or-more HHV infection(s) and no other drug interactions / pathogens / variables.

In many people (who don’t have any extra "unnatural" GDH altering factors), the suggested 25mg EGCG dose, every 4.5 hours is now quite balanced, when combined with the GDH "normalising" effect of the tripterpenes from reishi.

In others people, assuming the ROS/low a-KGDH issues are now resolved (no salicylates, arsenic, heavy metals, etc), GDH may still be too high, due to extra variables in play, or "bad reishi".

GDH / glutamate increasing factors:
Androgens (Endogenous: 5-AR metabolites, such as DHT. Exogenous: synthetic androgens that are either suitable DHT-derivatives or have an affinity for 5-AR and act as a suitable ligand to programatically alter GDH.)
Various drugs (we need to make a list of these), such as gabapentin, pregabalin (?)
Leucine (when above a serum threshold)
Sodium (when above a serum threshold)
Other infections:
C.diff

GDH / glutamate decreasing factors:
EGCG
Caffeine (however increases beta-oxidation efficiency and can create more ROS / increased energy availability)
.. others(?)

ROS increasing / a-KGDH decreasing factors:
Low E
Low C
Low glutathione (depleted glycine, P5P, cysteine, B5), etc
Lots of mTOR (viral activity, tissues adaptations - resistance training, immune response)
Some radiant energy sources
Excess serum glucose (+ excess insulin)
Excess Succinate (or B12 + P5P)
Excess Fumarate (urea, etc)
..

So, if someone is still seeing PEM, etc and their a-KGDH / ROS management is being correctly handled, this only leaves the GDH variable.

The simple answer is that after being absolutely sure that a-KGDH isn't impaired (feeling hypoxic, or the succinate challenge may help here), we can keep increasing the EGCG dose amount until PEM / burning stops, while temporarily dosing extra water, BCAAs, benzoate, B5, glycine, cysteine. (If this dose gets too high, we may see elevated ALT in pathology markers, showing alanine is being used to make glutamate.)

However with drugs like gabapentin, BCAAs may not work well, because gabapentin disables one of the key cycles that the BCAAs influence here.

View attachment 42895

Normalising serum hormones, by increasing estrogen and/or decreasing DHT by increasing anti-androgens (DHEA / spironolactone) may also be helpful here.

Thanks Joshua, with my heavy brainfog I feel so dumbed down, it will take some days to understand what you wrote here. Nevertheless thanks for your effort and time for trying to help us!!

godlovesatrier · May 15, 2021

Yes but its a known fact that cloud cover makes no difference. The uv light still penetrates. But my body does better in hotter climates. Dry ones. So I guess that's what I was angling at.

joshua.leisk · May 15, 2021

godlovesatrier said:
I think some people do better at night because of the bio chemical processes that occur. The brain gets flushed out at night as does the spinal fluid. As shown in mouse models.

There are also probably loads of immune functions and transactions that I'm convinced occur at night but to my knowledge these aren't documented.

There’s a lot going on there for sure. Melatonin and various other triggers for cleanup processes. Anyway, just some idle thoughts.

godlovesatrier · May 15, 2021

joshua.leisk said:
There’s a lot going on there for sure. Melatonin and various other triggers for cleanup processes. Anyway, just some idle thoughts.

The benefits of melatonin really are amazing. I had no idea ha! Probably why I now take it every night

ME/CFS Research: Herpes Autoimmune Spectrum Disorder

joshua.leisk

Joshua Leisk (Researcher)

godlovesatrier

Senior Member

godlovesatrier

Senior Member

Elike

godlovesatrier

Senior Member

themjay

Reading_Steiner

Senior Member

joshua.leisk

Joshua Leisk (Researcher)

joshua.leisk

Joshua Leisk (Researcher)

joshua.leisk

Joshua Leisk (Researcher)

godlovesatrier

Senior Member

godlovesatrier

Senior Member

joshua.leisk

Joshua Leisk (Researcher)

godlovesatrier

Senior Member

godlovesatrier

Senior Member

joshua.leisk

Joshua Leisk (Researcher)

Elike

godlovesatrier

Senior Member

joshua.leisk

Joshua Leisk (Researcher)

godlovesatrier

Senior Member