ME/CFS Research: Herpes Autoimmune Spectrum Disorder

[Hoosierfans]

Have to go back and read this whole thread, but wanted to offer my N=1 experience with @joshua.leisk’s Protocol (most recent version) as I saw a few folks ask for others experience with the Protocol. He’s been working with me diligently for maybe 6 weeks now, and I very much appreciate his willingness to learn and help people out here — both with CFS and other maladies.

Quick caveats: while I have been diagnosed with CFS (viral origin), I do NOT meet the most recent criteria in that I don’t experience PEM (but have all the other symptoms). I also have some symptoms that don’t seem to be common — all over burning throughout my body (like a sunburn and electricity at the same time), severe dizziness and akathesia. Recent testing seems to show that there is a very strong autoimmune component to my illness.

So here is my N=1 experience.
1. I’ve been on the mushrooms for about 7 weeks now, and the EGCG for about 5. With those alone (and the ALA), I did not see the expected “immune response” or any change in symptoms.

2. When I added Valcyte (antiviral), things started to move — an initial improvement week 1, and significant worsening (“immune response”?) week 2 (this last week).

3. When I changed my diet to the recommended diet (similar to dirty keto), things have REALLY gotten worse — as he mentions, feeling like I have “mono” again — I can’t leave my bed. And it’s been like this for about a week. It feels like it is starting to lift a bit.

4. This could very well be the expected immune response, but I’m also cautioned that this could be the “keto flu” from drastically changing my diet. Interestingly, whether it’s keto flu or the expected immune response — both should last 1-2 weeks. And there should be increased energy afterwards. So, it’s going to be hard to tell whether this all has caused viruses to clear (“you don’t have CFS any longer!”) or whether it’s simply a function of diet / supps without any impact on the viruses. UNLESS (and heres my ultimate point)...any of us doing this are monitoring blood counts including IGG / PCR levels. So, for anyone doing this, and for @joshua.leisk to get really good data on whether this protocol / approach works, I would encourage you to get pre Protocol data, and then periodic blood work as you go.

5. I did blood work right at the time that the “immune response” was strong, and my white blood cell count had taken a significant dive (was down 50 percent!) and my absolute monocytes were down 80 percent. ). I am not immune deficient — my IGG subclasses are all fine, and my WBC is always on the higher end of the range. Thus, my body can and will mount an immune response. So, I am not sure that this was an “immune response” as is proposed in the paper / protocol as if that was the case you would expect to see higher WBC and other counts than my normal baseline.

6. I had significant increase in dizziness and burning from sodium benzoate; it was not beneficial for my symptoms / ammonia disposal. *We all have our own intolerances to be aware of**

7. For those with histamine / mast cell issues, please tread carefully with Lions Mane. It is a known mast cell degranulator. I developed hives from it.

Those are just my 2 (10!) cents. I’m planning on continuing with the EGCG, mushrooms, ALA, glutathione / NAC and diet for awhile...while on the Valcyte and working on some other issues (gut repair and pursuing IVIG).

 

[godlovesatrier]

I don't understand, does Reishi have to be alcohol tincture? Because only alcohol extract has Triterpenoids.

Yes it does need to be an alcohol tincture. Indigo herbs sell that too. Otherwise Bristol botanicals will create a 1:1 tincture for you if your prepared to wait a few weeks.

 

[xebex]

Yes it does need to be an alcohol tincture. Indigo herbs sell that too. Otherwise Bristol botanicals will create a 1:1 tincture for you if your prepared to wait a few weeks.

I'm not sure it HAS to be a tincture it just has to be extracted using alcohol, please point me to a source if I'm wrong. There's a couple of companys in Canada that dual extracts their reishi using both alcohol and hot water - then they mix the two batches together to create a powder/capsule form, with benefits of both methods.

freshcap
https://learn.freshcap.com/mushrooms/reishi/

and real mushrooms
https://shop.realmushrooms.com/products/reishi-mushroom-capsules

 

[Hoosierfans]

I'm not sure it HAS to be a tincture it just has to be extracted using alcohol, please point me to a source if I'm wrong. There's a couple of companys in Canada that dual extracts their reishi using both alcohol and hot water - then they mix the two batches together to create a powder/capsule form, with benefits of both methods.

freshcap
https://learn.freshcap.com/mushrooms/reishi/

and real mushrooms
https://shop.realmushrooms.com/products/reishi-mushroom-capsules

I have been using the Real Mushrooms brand the entire time I have been doing the Protocol, because they do a double extract. I use their Lions Mane, Reishi and Cordyceps.

 

[xebex]

I have been using the Real Mushrooms brand the entire time I have been doing the Protocol, because they do a double extract. I use their Lions Mane, Reishi and Cordyceps.

that's encouraging! i have been using their lions mane and will be getting the reishi soon!

what did you do about the hives caused by the lions mane? do you still take it?

 

[junkcrap50]

Very interesting thesis. I have to reread it. But I was wondering, for those who have had a Nutra-Eval / Mitochondrial/Metabolic testing, what would we look for in our test results to indicate this theory may apply to us or that we treatment may be helpful? What test results would confirm what is occurring according to the theory? Or are there other tests that could be done beforehand that would indicate this theory might apply to us?

Second question, can other supplements or medications be taken in addition to the ones listed in this theory? Or would that screw up the metabolism mechanics? What if someone is already on Valcyte? Already doing keto? Can they just add the fix for ammonia?

 

[joshua.leisk]

I don't understand, does Reishi have to be alcohol tincture? Because only alcohol extract has Triterpenoids.

Basically don’t use the water extract. 1:1 and alcohol extract only.

 

[joshua.leisk]

Thanks for the reply. I did btw look at figures- but after i read the papers rather than during. But I don't see those figures as novel to you at all. These are standard biochem pathways with well known connections between them. There are academic groups that show all these pathways at once in pictures so sort of just reinventing the wheel drawing your own- but some people out there seem to think this is new to you. (presumably folk not steeped in biochem)

When you say amost everything stems from Warberg or reverse, not sure if you mean your theory or just life in general- but as I noted, if you mean about your theroy, then still at the mechanistic level, i'm not seeing what's new about your claims. I will look though again at paper 3 to see the greater urea cycle details you mentioned are there and see if that part is anything new.

But sometimes, people can create succesful treatments even if they say nothing new in mechasism and even if their viral theory is wrong - I will hope that you are one of those. I know what you need to do to make this seriously publishable (and not in a journal where you pay them to publish) but presumably you'll get there eventually with the feedback eveyrone has been giving you.

Cheers - this is actually a key point:

I’m not presenting anything new - these articles are reviews. I’ve taken hundreds of citable breadcrumbs and connected them in a way that shows “intent” or “purpose” in a unified, mechanistic way that has been not well understood.

The model is robust and so far, all verifiable new data points / papers bolt straight into it, rather than reforming sections.

Hopefully people have enjoyed these three papers, as the next one in this series extends the model further as a unified theory around metabolism, endocrinology and energy / conversion.

 

[joshua.leisk]

Hard not to get excited, even if it is only for a clear treatment to try. Thanks for all the work. I just wish I could give this to my doctor and let him do the necessary tests + help me in sourcing the supplements. Even if I don't completely fit the profile I would still want to try it. I would welcome 1 week of agony, or a month, where my immune system is actually doing something.

When my CFS started EBV antibodies were high for at least a year. Years later my new doctor told me it was all negative. I'm not sure at which point I got 'cured'. I never completely believed it and theorized that my immune system was too weak to generate antibodies.

Still, I think my CFS started much earlier. I had a mycoplasma infection almost 15 years before the CFS. It is all very vague as it is so long ago, presumable related to a tick bite but I don't fit the lyme symptoms. Perhaps the tick transferred some other pathogens like HHV6, if that is even possible.

Have you seen MHV-68 or MHV-72?

Tick-borne version of EBV. Even detects as EBV Ig in labs.

 

[Strawberry]

Hi! The second protocol I discussed in the paper boils down to -

Start with the ammonia management.
First 4 days should have:
1g of sodium benzoate, 4x a day
1g of glycine, 4x a day
High dose P5P
Additional cysteine

Include and continue with (beyond the 4 days):
20-35mg EGCG, every 4.5h
500mg of reishi 1:1 (or equivalent alcohol extract), 3x a day
250mg of lions mane, 3x a day
200-300mg of R-ALA, 3x a day
Add 5-10g of creatine

If someone has lytic HHV, those antibodies will take 6-8 weeks to clear out, as a combination of time for infected b-cells to die and IgG to metabolise.

They can add more oat bran as your tolerance for immune response allows.

Expect them to have symptoms of a nasty case of flu for a while - gut issues, fever, inflammation, swollen lymph nodes, etc.

Edit: fixed typo - wrote pantothenic acid instead of P5P

Im sorry to say I don’t have the energy to read the paper yet, but at the moment I wouldn’t have the energy to follow “4 times per day” and remember how many days I’ve been on a protocol. I barely eat or drink on some days. And I’m better than many here. A caretaker sure would be nice through something like this!

Also, you say you have had people improve on your protocol, we’re they ill for a few years or a few decades? Sorry if you said that some where.

Im wishing you the best of luck, and thank you so much for your research.

 

[joshua.leisk]

Very interesting thesis. I have to reread it. But I was wondering, for those who have had a Nutra-Eval / Mitochondrial/Metabolic testing, what would we look for in our test results to indicate this theory may apply to us or that we treatment may be helpful? What test results would confirm what is occurring according to the theory? Or are there other tests that could be done beforehand that would indicate this theory might apply to us?

Second question, can other supplements or medications be taken in addition to the ones listed in this theory? Or would that screw up the metabolism mechanics? What if someone is already on Valcyte? Already doing keto? Can they just add the fix for ammonia?

The thing about GDX NutrEval / ION / Organix tests is that (using IT terminology) they are essentially a “memory dump” or “snapshot of the running environment” at a particular point in time.

This means that all inputs to that state need to be quantified, to obtain meaningful or actionable data.

In a perfect world, this includes all modifiers, such as drugs, supplements, dietary inputs, hormones, microbiome, water in/out, activity levels, genetic mutations and some surprising things that I’ll be talking about in my next paper.

As this is going to be quite difficult to achieve accurately, the bare minimum would be:

1. A (cronometer) diet log for the previous 4 days, including water.

2. Some biometric data from eg. Fitbit / Garmin which shows a reasonably good measure of calories burned, HR over time, sleep duration, steps, etc. (I previously tested this combination of 1+2 over a month to <5% error margin, using DEXA scans. Was very useful, but n=1, so..)

3. A full list of drugs, supplements and dose schedule for the previous 4 weeks, or longer, if any drugs have been recently discontinued which have longer metabolic half-lives.

4. (Preferred) List of SNPs.

5. (Preferred) Recent gut microbiome sample results.

6. (Preferred) Exhaustive list of serology markers. (We can also use the GDX report to infer families of infection.)

7. Pathology for full hormone profile, haematology and liver enzymes.


So looking at the GDX reports, the NutrEval report has the pretty pictures / diagrams and somewhat helpful hints as to what goes where. The other report types contain much the same data, without the pretty pictures.

From this data we can roughly see/infer a number of things:

1. Total energy, or “pressure” inside the cycle. We do this by summing all TCA metabolites, including nitrogen.

2. “Anaplerosis pressure” or enzymatic impairment at the next reaction step, by seeing “hot spots” and “cold spots”. The location of these can infer ROS levels, HIF activation, a-KGDH levels. They’ll also show the influence of eg. B vitamin supplements, etc., on creating additional pressure.

3. Nitrogen load, as a sum of urea cycle metabolites, benzoic + hippuric metabolites and phenylacetylglutamine metabolites. The ratio between each of these will also infer levels of aspartate, Acetyl-CoA. (These can also be supported by a separate serum test for ALT, AST, drawn at the same time, along with the alanine marker.)

The nitrogen load will have a direct relationship to the total “pressure” in the TCA cycle metabolism, which is governed by specific dietary inputs (cronometer data), GABA agonism, hormone levels, activity levels (which we can confirm from the wearable tracker data). These be influenced by depletion of the mentioned metabolites, as also shown by higher activity in the phenylacetylglutamine pathway results.

In a more controlled environment, these GDX tests would be performed against a quantified standard set of (dietary, drug, supplement) inputs and activity level, with variations from “normal range” results noted.

—

Back to your other questions- valcyte should be fine. Keto should be fine.

 

[joshua.leisk]

Im sorry to say I don’t have the energy to read the paper yet, but at the moment I wouldn’t have the energy to follow “4 times per day” and remember how many days I’ve been on a protocol. I barely eat or drink on some days. And I’m better than many here. A caretaker sure would be nice through something like this!

Also, you say you have had people improve on your protocol, we’re they ill for a few years or a few decades? Sorry if you said that some where.

Im wishing you the best of luck, and thank you so much for your research.

Most people I’m working with have been sick for decades. I’m hoping to get the treatment to a “once-per-day” administration with timed release.

For severely impacted people, there’s a sequence we can follow to remove the current impact before jumping into the treatment. This involves treating the current nitrogen excess using eg. Ammonul and disabling the HIF factors. A clinical setting would be suggested.

 

[joshua.leisk]

I asked about the state of the cells I think because my image of the overall picture of whats going on is blurry still, probably due to the veil of fatigue that hangs over my mind constantly. I seem to think in a different way now thats more intuitive as a result. Anyway much of the research claims recently has been to do with signalling, Ron Davis' "something in the blood" that affects the cells impedance, and Prusty was talking about HHV-6 doing something that caused cells to fragment their mitochondrias en masse ( as clearly as I can remember the work ). I take it you are aware of these theories ?

My take on “something in the blood” is MiRNA.

The mitochondrial fragmentation is possibly what I’m showing as the a-KGDH deficiency and transamination.

 

[junkcrap50]

The thing about GDX NutrEval / ION / Organix tests is that (using IT terminology) they are essentially a “memory dump” or “snapshot of the running environment” at a particular point in time.

This means that all inputs to that state need to be quantified, to obtain meaningful or actionable data.

In a perfect world, this includes all modifiers, such as drugs, supplements, dietary inputs, hormones, microbiome, water in/out, activity levels, genetic mutations and some surprising things that I’ll be talking about in my next paper.

As this is going to be quite difficult to achieve accurately, the bare minimum would be:

1. A (cronometer) diet log for the previous 4 days, including water.

2. Some biometric data from eg. Fitbit / Garmin which shows a reasonably good measure of calories burned, HR over time, sleep duration, steps, etc. (I previously tested this combination of 1+2 over a month to <5% error margin, using DEXA scans. Was very useful, but n=1, so..)

3. A full list of drugs, supplements and dose schedule for the previous 4 weeks, or longer, if any drugs have been recently discontinued which have longer metabolic half-lives.

4. (Preferred) List of SNPs.

5. (Preferred) Recent gut microbiome sample results.

6. (Preferred) Exhaustive list of serology markers. (We can also use the GDX report to infer families of infection.)

7. Pathology for full hormone profile, haematology and liver enzymes.


So looking at the GDX reports, the NutrEval report has the pretty pictures / diagrams and somewhat helpful hints as to what goes where. The other report types contain much the same data, without the pretty pictures.

From this data we can roughly see/infer a number of things:

1. Total energy, or “pressure” inside the cycle. We do this by summing all TCA metabolites, including nitrogen.

2. “Anaplerosis pressure” or enzymatic impairment at the next reaction step, by seeing “hot spots” and “cold spots”. The location of these can infer ROS levels, HIF activation, a-KGDH levels. They’ll also show the influence of eg. B vitamin supplements, etc., on creating additional pressure.

3. Nitrogen load, as a sum of urea cycle metabolites, benzoic + hippuric metabolites and phenylacetylglutamine metabolites. The ratio between each of these will also infer levels of aspartate, Acetyl-CoA. (These can also be supported by a separate serum test for ALT, AST, drawn at the same time, along with the alanine marker.)

The nitrogen load will have a direct relationship to the total “pressure” in the TCA cycle metabolism, which is governed by specific dietary inputs (cronometer data), GABA agonism, hormone levels, activity levels (which we can confirm from the wearable tracker data). These be influenced by depletion of the mentioned metabolites, as also shown by higher activity in the phenylacetylglutamine pathway results.

In a more controlled environment, these GDX tests would be performed against a quantified standard set of (dietary, drug, supplement) inputs and activity level, with variations from “normal range” results noted.

—

Back to your other questions- valcyte should be fine. Keto should be fine.

Well I have/do 1-7 except for a recent #5. But it sounds like you have to analyze everyone on a case-by-case basis to see if our metabolism is inclined to your theory. Won't that be too much work? How would more people be able to consider your theory. Just try it and see what happens? What level would be a "high" nitrogen load?

 

[Reading_Steiner]

I didn't realize about the reishi requirements, that was the only thing I thought I already had, the indigo herb one does look good but it seems like it would be hard to measure out accurately and match to the weight in grams, also how long would the 100 ml bottle last ?

I see another one thats a powder made by Time " High Strength Reishi “Ganoderma lucidum” 50% Polysaccharides / 30% Beta 1,3/1,6 D Glucan - Dual Extracted "
and another one made by Mycowarriors, Red Reishi Dual Extract Powder 10:1 40% Polysaccharides

 

[joshua.leisk]

I didn't realize about the reishi requirements, that was the only thing I thought I already had, the indigo herb one does look good but it seems like it would be hard to measure out accurately and match to the weight in grams, also how long would the 100 ml bottle last ?

I see another one thats a powder made by Time " High Strength Reishi “Ganoderma lucidum” 50% Polysaccharides / 30% Beta 1,3/1,6 D Glucan - Dual Extracted "
and another one made by Mycowarriors, Red Reishi Dual Extract Powder 10:1 40% Polysaccharides

The Reishi product label needs to focus on the triterpene content. The ones that contain high beta-glucans appear to be water extracts, which are usually unsuitable. A dual-extract could be good, if they state the triterpene content.

 

[joshua.leisk]

Well I have/do 1-7 except for a recent #5. But it sounds like you have to analyze everyone on a case-by-case basis to see if our metabolism is inclined to your theory. Won't that be too much work? How would more people be able to consider your theory. Just try it and see what happens? What level would be a "high" nitrogen load?

It’s more that metabolic markers are not helpful without context.

A rather unpleasant, yet accurate way would be to perform the GDX test after a sufficient washout period from all supplements and then performing a fixed challenge of specific activity + diet.

I can’t see many CFS patients wanting to do this, so the softer route is to better understand all of the individual variables and then help educate clinicians on how to collect and interpret the data meaningfully.

 

[lint7]

My take on “something in the blood” is MiRNA.

Wouldn't they have easily found that by now?

 

[joshua.leisk]

I think people have said many similar things over the last few decades. In this case, these things are really, really tiny.

My approach has been -

“This has been exhaustively studied by a LOT of really smart people. Surely there must be enough data by now to try and solve it?”

I think I may end up studying the cascades for decades. There’s a lot to learn about our biology/programming by seeing what happens when things go wrong.

 

[Marylib]

@Hoosierfans - thanks for the report. I appreciated your letting us know that your symptoms are not post - exertional, unless I misunderstand you - PEM. I always thought that was the hallmark of ME, as opposed to MS, for instance - but maybe that's CFS. Or maybe that has changed over time for you. Whatever is happening, I hope this protocol works out really well for you.