ME/CFS Research: Herpes Autoimmune Spectrum Disorder

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YippeeKi YOW !!

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@Mariaba
Tagging you in because I think this is worth the effort of reading. Take it in little bites if you need do, but do give it a look ....

Here's a more user-friendly version that @joshua.leisk and Aline Nocon prepared especially for those of us who are more science-ly or brain fog impaired, or, if we're really firing on no cyclinders, both, simultaneously ....

Give it a leisurely browse whenever you're up to it....

CFS/ME: A New Hope
https://www.researchgate.net/publication/350956432_CFSME_A_New_Hope
 

joshua.leisk

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@Rebeccare , @Rufous McKinney , @Howard , @ljimbo423 , @Haley , @Blue Jay , @Rebecca under the papyrus , @Judee , @Art Vandelay , @Hip , @Hipsman , @IThinkImTurningJapanese .....

More tag-ins will follow as I try to drop-kick my brain, and the gopher wheel that currently runs it, into action ....

This is a staggering amount of information, both in scope, depth, width and breadth, and written and presented so lucidly and so beautifully that I’m speechless.

Ask anyone in these threads: that’s not my usual response :):) :xeyes::xeyes::xeyes:.

I’m equally impressed, perhaps even more so if that’s possible, by the character and nature of the presenter, @joshua.leisk and his unnamed life partner, whose contributions Joshua makes clear are invaluable.

The effort taken to make this depth of information accessible to almost anyone who can read, even in the small increments some of us have to apply to new input and information, and use the Google machine indicates someone whose interests lie a good distance from material gain or ego enrichment, but indicate instead a high intelligence and a genuinely questing mind and spirit, with the willingness and drive to put those gifts at the service of others. And to do so with grace and great wit, two other characteristics not usually in abundant display in the scientific and medical community.

DO START AT THE FIRST POST .... it's the woof/warp and weft for all that follows .... or, probably even better, here's a more user-friendly version that @joshua.leisk and Aline Nocon prepared especially for those of us who are more science-ly or brain fog impaired, or, if we're really firing on no cyclinders, both, simultaneously ....

Give it a browse ....

CFS/ME: A New Hope
https://www.researchgate.net/publication/350956432_CFSME_A_New_Hope
Thank you so much for the kind words and support! I’ve passed them onto Aline, also. :)

It’s been quite a journey so far. I’ve made a few fumbles along the way, but I’m always willing to learn and share.

If you have any questions, or need any help, please feel free to reach out via DM, or tag me - I’m trying my hardest to help people.
 

xebex

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i had a bizarre one-day remission last week after taking lions mane for 4 days. I took it for other reasons (part of my own uneducated guesswork into what could be going on) and hadn't seen this post then. I haven't been able to replicate the experience since - I presume it's because there are other pathways blocked.

So @joshua.leisk you are saying that all I need to do is drink 2 cups of green tea a day, take lions mane (as I already am) add in reishi and ALA? and I'll be better in a month? What do I do if I feel terrible?

Interestingly the lions mane did create an immune response and I went and took antihistamines for it! doh! should I stop my magnieusm malate and b6 supps?
 

nerd

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Thanks for opening this post and participating in a discussion. @joshua.leisk

3 of the clients had reported some benefits from ketogenic diets.
A common list of "problem" supplements for all clients was acetyl-l-carnitine

Acetyl-L-Carnitine seems to help many of us rather than cause problems. I personally get elevated cholesterol levels during the course of my keto diet when I stop taking it. The ketogenic diet helped me significantly, though not completely. I wrote a post about this here.

My existing research strongly suggests that it's a combination of the antibodies from the lytic phase, PLUS the primary issue of latent viral hepatitis

Learning the lessons from Myasthenia Gravis, my focus is the thymus. Except for seropositivity, Myasthenia Gravis manifests comparable immunological profiles as in CFS/ME and SLE. My hypothesis is that they all have the same EBV-induced immunological dysfunction and that SLE and MG are just an unfortunate reaction to the dysfunction.

Your focus is the liver. But by defining it a viral hepatitis, why do you assume a causally localized disease and not a systemic disease that manifests in the liver as well? The metabolic pathology you describe can only happen in the liver, regardless of localized causality. This means it is still possible that you could have a primary systemic immunological disease that just happens to have a greater influence on hepatic cells due to the nature of hepatic cells.

This was a strong suggestion that spironolactone has efficacy for arresting EBV, CMV lytic phase. Only expected side-effect being increased urination, requiring increased hydration and electrolytes.

I'm not sure about CMV, but I don't see why EBV PCR would prove the absence of lytic activity. Even with negative PCR, lytic signaling from transfected cells is possible. Have you considered that it isn't the viral antibodies but the viral proteins from transfected cells that keep circulating? EBI-2 would be such a protein, to name a common one.

Nevertheless, spironolactone might still show benefits even if it hasn't completely suppressed viral activity. Maybe it just doesn't reach sufficient efficacy given the dosage. A similar question is up for discussion regarding the use of Ivermectin for the same purpose.

The lytic phase is only partially responsible for CFS/ME.

I don't see this proven.
  1. PCRs show active or dead viral residue. They don't show viral signaling or quantify transfected cells.
  2. It's possible that the lytic activity happens localized. Maybe in the liver, maybe in the thymus. Localized viral signaling won't show up in the blood unless it becomes very severe. You also mention that you assume a localized pathology in the liver. There is no reason to believe that a blood PCR can show complete suppression of EBV residual activity.
What might be more helpful in this regard are biopsies of the respective hepatic or thymic tissues and a protein or gene analysis of viral signaling.
Alternatively, the course of EBV EA antibodies could also show when localized lytic activity happens. Check this post for more details and a discussion about the specificity and sensitivity of the different antibody types.

I prefer to learn things in my own way and explore topics in an organic way, where my brain absorbs them efficiently. I find structured education traditionally 'grinds my gears' by causing frustrations and inefficiencies, therefore I limit any formal education and certifications to the barest minimum required to permit me to work in any specific field.

I think this work style is really underrated. Elon Musk follows the same idea. Look where he got. The other stuff is just serving distraction and bureaucracy.

The current focus is getting this better balanced.. and also removing the a-KG buildup.

Your metabolic theory is partially consistent with the anecdotal success stories with high doses of thiamine. Here is a new post about this. While I think that their dosage might be too high, 100 - 200 mg might be fine to integrate into your protocol due to its synergistic effect on alpha-ketoglutarate to channel it away from the glutamate pathways to the KGDH, though you still need to fix the NAD+ dysbalance.

Regarding the NAD+ dysbalance, I'm not sure yet if I completely agree with the causal assumptions of your model. Not that I deny that this specific viral pathology can be one causality, but I think that there are many viral mechanisms from different viruses with the same effect on NAD+ balance and enzymatic activity that "drive off" the CAC. It's not just HHV. However, HHV could very well create a synergistic pathology with other viruses and also participate in synergistic signaling and reactivation cycles.

Nevertheless, I think you've modeled this subpathology of CFS/ME very well. I hope it will receive the recognition it deserves and that some other research teams (with laboratory access) can give liver pathology more attention.

I see you mention 10g of BCAA@'s 4x a day

In this forum, we've approached the topic of BCAA often and from many perspectives. I think most will agree when I say that the research suggests that only Leucine shows the desired benefits on the CAC and other metabolisms. Just yesterday, Murph created a post of a paper regarding this question. I could provide you more references if you are interested, all supporting either leucine or lysine.

In your protocol, you use sodium benzoate for nitrogen disposal. Consistent with the findings of Scheibenbogen et al. and other teams, intracellular sodium is usually too high. I personally avoid sodium all the way and take potassium to at least increase the availability of serum potassium and decrease the availability of serum sodium. CFS/ME seems to have multiple mechanisms that push off the intracellular electrolyte balance away from potassium and towards sodium and calcium. So I wonder - have you considered Glycerol Phenylbutyrate or Potassium Benzoate instead?

Lastly, I'd also strongly suggest adding Coenzyme Q10 to your protocol because it's an important cofactor for oxidative phosphorylation and oxidative phosphorylation is overstimulated in CFS/ME whilst necessary for NAD+ recycling.
 
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nerd

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My bad, I missed to recognize that there were three more pages.

HHV seems straightforward now. I need to look at eg. coxsackie, parvo-b19 and a number of others. One of the annoying things I can already see ahead is that people with co-infections are going to start treating their HHV and still be left with issues from a secondary infection. I have a "no person left behind" approach here. We need better pathology data and ways to quantify the causal factors, to effectively help people.

I'm glad to see that you already recognized this. I think it will be very interesting to see what other disease models are consistent with this pathology. SARS-CoV-2 might be the most actual one to show. It has a very high ROS load.

6. ... other vectors I'm still exploring.

Speaking of heterogeneous localized pathology, the same is theorized by Ron Davis et al. to happen at the IDO enzymes. This would cause a depletion of Niacin in certain cells and hence a depletion of NAD buffer, making them even more susceptible to dehydrogenase stressors.

The writer in me LOVES this line "Is the symbiotic evolution of the herpesviridae family and their metabolic alterations directly responsible for the increased intelligence of homo sapiens as a species, while simultaneously shortening our lifespan via creating cancers and senescent cells? (Interestingly, HHV appears to function as a ubiquitous / highly transmissible viral equivalent of the “Apple from the Tree of Knowledge” described in Biblical texts. If someone wanted to deploy a resilient “software patch”, this is a really logical way to facilitate that.)"

I like this viewpoint. I try to keep up with ancient history and its research. The emerging understanding is that there have been more than just homo sapiens and neanderthals at some point and the homo sapiens acquired its immune system from another technologically and intellectually superior species. Maybe we didn't only get the immune system from them but also pathogens or resistance to pathogens that enabled us to or prevented us from becoming intelligent.

But the homo sapiens also mixed with the neanderthals to a greater extent than previously anticipated. Seems like they didn't fight each other so much but lived together mostly peacefully until, at some point, the neanderthals just vanished in a comparably short time, yet it took many centuries. History tells us that there have been many diseases in recent history that almost eradicated humanity or ethnic groups. I think it's possible that the neanderthals vanished due to a latent disease that was transmitted by homo sapiens or animals. And maybe the susceptible group of homo sapiens vanished together with them, so that mostly immune ones remained. After all, it's still neanderthal genes that make us susceptible to SARS and other viruses.
 
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YippeeKi YOW !!

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If you have any questions, or need any help, please feel free to reach out via DM, or tag me - I’m trying my hardest to help people.
@joshua.leisk
Am still working my way thru your incredibly accessible, beautifully explained easier version in small bites, due to floppy brain ....


It's a genuine work of art. Most science-y studies seem to do their best to be as inaccessible as possible to the general public. You've done the exact opposite :woot::woot: :thumbsup::thumbsup::thumbsup: !!!
 

YippeeKi YOW !!

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joshua.leisk

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i had a bizarre one-day remission last week after taking lions mane for 4 days. I took it for other reasons (part of my own uneducated guesswork into what could be going on) and hadn't seen this post then. I haven't been able to replicate the experience since - I presume it's because there are other pathways blocked.

So @joshua.leisk you are saying that all I need to do is drink 2 cups of green tea a day, take lions mane (as I already am) add in reishi and ALA? and I'll be better in a month? What do I do if I feel terrible?

Interestingly the lions mane did create an immune response and I went and took antihistamines for it! doh! should I stop my magnieusm malate and b6 supps?
Hi Xebex!

In our disease model:

The recovery process is likely to be ongoing for some months, unfortunately. Cleaning up the lytic phase alone will take 6-8 weeks once the infected B-cells are gone. This assumes someone just has HHV and no other infections. (I’m working on other pathogens at the moment.)

The fasting method is a rapid way to initiate recovery. Everyone - please heed the warnings about not eating within 8 hours of taking these supplements. I’ve had 2 people unfortunately discover the hard way why I put the large disclaimer in the 3rd paper. Lying in bed convulsing in agony for a couple of hours until the EGCG wears off is an unnecessary form of torture.

The immune response which follows, also during the management protocol is not pleasant, however can be sped up and slowed down in most cases.

Once the liver is the focus of the immune response, things will be reminiscent of an initial EBV infection - expect to be laid up in bed for a week or so, with flu-like symptoms and no energy. This can be patched around somewhat with supplements, however my advice is to let the body get on with the task at hand.

According to our research, if/when your liver is fully healed and the lytic phase is also gone, someone shouldn’t have CFS/ME. We currently lack enough data to set expectations around a timeline for that, however this will improve over coming months. What I can say is that early participants have started seeing acute liver remediation and flu-like symptoms within weeks of starting. One of the people who no longer have CFS/ME symptoms is currently on the tail-end of a week in bed with flu-like symptoms, acute liver pressure and generally feeling pretty miserable. They're feeling a lot better now and getting out/about again. This is all really new, so I’ll keep everyone updated as we learn more about typical timelines.

Each person will have different sets of individual symptoms that will be addressed as the protocol is started. With help and input from community members, I’m creating a document that will assist with streamlining the transition / induction phase.

They’ll also have various medications, treatments and other supplements to monkey-branch from. It’s best that this is done under supervision, especially for people on complicated medications. eg. I *really hate* benzodiazepines - I understand their purpose and how helpful they are *initially* in managing the GABA depletion / synthesis issues, however their design, tolerance and concomitant withdrawal process is worse than CFS/ME. The benzodiazepine concept is a lazy and half-baked pharmaceutical solution to a problem that could have been better managed by stimulating the body to produce more endogenous GABA, in a dose-dependent manner, via additional aspartate and dopamine management. The GABA receptor agonism profile of benzodiazepines is a complete mess.

I’m working on solutions to the benzodiazepine withdrawal problem at the moment, with some early successes. I'll update people, as we have better data to share.

This is what the current management protocol looks like (taken from the v3.1 draft spec) [edit: this has been superseded - the dietary advice has been clarified in 3.2+]:
62EC62FB-0235-4426-8E52-5DC69EDEC80E.jpeg

I'd recommend reading the latest draft spec, as there are further notes.

I've also been considering the best ways to help people that are severely compromised - not just the 23.5-hours-a-day-in-bed people (these are already people I'm working with, daily). I'm referring to people with PICC lines and feeding tubes. People who are isolated by COVID from receiving medical care.

I think in these cases, once confirming that they meet the criteria (which requires serology plus a NutrEval report, with a full understanding of all drugs, supplements, nutritional inputs that contributed to the NutrEval result pattern), the best course of action would be to start on a high daily rate of IV hydration, installing a catheter (if not already in use), providing some pain management and then commencing a period of "Ammonul", along with a staged implementation of the management protocol. This also means changing the dietary macros, as detailed above. Someone would expect initial fatigue during adaptations to the different dietary macros.
 
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joshua.leisk

Joshua Leisk (Researcher)
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@joshua.leisk
Am still working my way thru your incredibly accessible, beautifully explained easier version in small bites, due to floppy brain ....


It's a genuine work of art. Most science-y studies seem to do their best to be as inaccessible as possible to the general public. You've done the exact opposite :woot::woot: :thumbsup::thumbsup::thumbsup:!!!
Thank you - I felt this was a necessity, although the format drew fire from some members of academia as being "disgraceful", due to the amount of "author's prerogative" displayed in engaging with the wider audience and communicating ideas / data.

It's a really complicated topic / disease model.. and while under normal circumstances (and in the fullness of time), dry scientific literature is normally translated into a human-readable format by someone more adept than me in both scientific writing and literary arts, I had some frustrations to workaround.

Given the delays we've already seen while trying to get the first 2 papers peer-reviewed and published, the potential timeline involved in waiting for this organic process to unfold wasn't acceptable to my innate desire to actually help people. 6-12(?) months of publishing delays and then cascading ripples through media is a lot of time lost - literally 6-12 months of unnecessary trauma for people who are suffering. (Unlike the necessary "natural trauma" of the inbuilt immune responses.)

The plan is to make some changes to the third paper and then submit a "dry version" for peer-review.

In retrospect, I could have written and submitted the dry version and made the more readable version available as a blog post. This is one of my "fumbles". :D
 

xebex

Senior Member
Messages
840
thanks so much for your speedy reply!

So much detail and really interesting that the supplements you list are where I'm starting to gravitate towards (I've tried pretty much all of them - but obviously not all together) It is very clear to me that I have liver issues, alongside positive tests for EBV, CMV and HSV (god knows what else i have!).

I would be really interested in doing the protocol but not the fasting one - I've already been to ER after giving myself refeeding syndrome and don't want to go there again!

As for the list of supplements, i have major issues with b vitamins, and glycine triggers migraines, phosphatidylcholine causes severe irritability not sure if the bitartrate versions would be better so, is it possible to miss out some of the supps?

Do you think i could achieve any success JUST using the mushrooms, ECGC and ALA/NAC?
 

YippeeKi YOW !!

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I felt this was a necessity, although the format drew fire from some members of academia as being "disgraceful", due to the amount of "author's prerogative" displayed in engaging with the wider audience and communicating ideas / data.
Yeah, there's nothing that academia and the scientific and medical communities hate more than clear, comprehensible communication that might make the 'average' patient/reader think that they're smart enough to manage their own conditions and situations.

I don;t think it would have made much difference if you'd published the science-y one first, followed by a blog entry with the more accessible one. Their inherent loathing is for anything clear, concise, and easily understood that makes it seem like they're ..... what's the word I'm looking for here ..... hmmmm..... redundant? Unnecessary? De trop? (rebukes always sound better in French) .....
 

joshua.leisk

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thanks so much for your speedy reply!

So much detail and really interesting that the supplements you list are where I'm starting to gravitate towards (I've tried pretty much all of them - but obviously not all together) It is very clear to me that I have liver issues, alongside positive tests for EBV, CMV and HSV (god knows what else i have!).

I would be really interested in doing the protocol but not the fasting one - I've already been to ER after giving myself refeeding syndrome and don't want to go there again!

As for the list of supplements, i have major issues with b vitamins, and glycine triggers migraines, phosphatidylcholine causes severe irritability not sure if the bitartrate versions would be better so, is it possible to miss out some of the supps?

Do you think i could achieve any success JUST using the mushrooms, ECGC and ALA/NAC?
This is essentially the CFS/ME paradox I was describing in the third paper - the primary reason that taking any nutrients which are (measurably - see NutrEval FMV or other pathology) depleted can/will lead to headaches, PEM, etc., is all downstream from oxidative stress (ROS) and ammonia creation / metabolism.

By "filling any nutritional gap(s)" which were stalling any/all cellular activities, these cells with faulty metabolism are now able to "get back to work"... unfortunately now increasing the oxidative stress and further increasing the ammonia load which now has to get metabolised.

Mito-Build.png


This ammonia load starts a couple of excretion processes (which are also the origin of PEM, headaches, etc) which further drain key metabolites "creating all the gaps" again.. this becomes a vicious cycle. Those induced "nutritional / metabolite gaps" create all of the other neurological dysfunctions, thyroid issues, etc.

GABA and B vitamins, especially B12 can be readily converted into "succinate" in the TCA cycle (needs Vitamin B6 / P5P for this to work).

The urea cycle can also allow the TCA cycle to be fueled at "fumarate" .. which is a useful way to manage some of the ammonia being created.

This will reduce pathology markers for "urea" and reduce PEM.. briefly.. This also temporarily bypasses the mitochondrial limiter, allows normal respiration and corrects a number of issues around collagen synthesis, energy levels and hypoxia induced transcription factors, etc.. alleviating those symptoms..

However, the ongoing (faulty) mitochondrial activity continues, the ROS increases and the ammonia overload forces heavier use of the "expensive" ammonia excretion process - via "phenylacetylglutamine" (PAGN).

This is where it all starts to get ugly.

Mito-ComplexMap.png

With the ongoing metabolite depletions, including cysteine (via acetyl-CoA and CoA) and glycine, glutathione production and regeneration gets impaired. This means that oxidative stress (ROS) cannot be reduced / scavenged.. this leads to DNA transcription errors, cancers and... more ammonia to metabolise.. fortunately, the B vitamins get depleted, aspartate gets depleted and the whole thing shuts down and cools off...

.. creating issues with hypoxia, connective tissue disorders, neurological disorders, thyroid disorders, fatty acid oxidation issues, insulin resistance, etc..

This is pretty savage.. as we all have experienced.. people are left between a choice of:
A) a body crippled with a personal selection of every disease we have named in the papers..
B) headaches, PEM, being incredibly overstimulated / overpowered by their environment to the point of being shutdown or placed on benzodiazapines.
C) an ongoing mix of both, every time we eat... often leading to a snowball effect where you can't eat... which is a slippery slope to hell*.

*NB. The thing about (C) is.. if someone didn't eat *anything* for say 5 days, while keeping water and electrolytes up.. they'd later see a vast reduction in symptoms, by having killed off many of the infected cells (perhaps 1-2 weeks after the fast). The catch-22 is, 5 days of fasting is likely going to consume 2-2.5kg of body fat. If someone is already in a fragile state, this option may not be available to them, initially.

Adding an ongoing high dose of EGCG (and resveratrol) to the fasting process speeds this up dramatically, by removing the other large source of stored energy available to the cell (from glutamine->glutamate-aKG). It also completely disables the transamination I described in the papers - this is why the first day has "low dose" EGCG - giving time for the ROS to drop and transamination to "turn off".

This should mean that 3 days of EGCG fasting could be equivalent to 5-7 days of traditional water fasting. You're diving into the "pointy end of the fast" earlier.

So, circling back.. when implementing the treatment protocol, the expectation is that the first 3-4 days is going to generate a LARGE amount of ammonia, as various pathways start working again. For this reason, we have been using sodium benzoate + glycine (and b5, NAC) to create an outlet for this initial surge. Even with that, someone could expect a stunning headache for 3-4 days. "Ammonul", if they have deep pockets and a friendly doctor, would be an ideal adjunct to include at this time.

After that, thanks to the alterations provided by the reishi, EGCG and ROS scavengers (ALA / glutathione / NAC / Vitamin C / Vitamin E), someone would expect to be able to consume normal amounts of B vitamins and not create headaches, PEM, or other symptoms... providing they're NOT creating additional "pressure" inside the mitochondrial reactions by overloading the cell with glucose (hence the dietary aspects). Excessive doses of B vitamins will still be expected to create mitochondrial pressure and ROS, also.

At this point, things our model suggests things may start improving.. although they'll still have lytic phase "autoimmunity" to wade through for the next 6-8 weeks, unless they've previously been using eg. spironolactone / tenofovir, etc.

However, while all of these life improvements are happening... they're going to get tested. Their ongoing immune response is going to cause flare-ups of every single tissue they've historically had issues with. It may be quite acute, at times.

Having trust that this is both necessary and one of the last times someone would have to experience these symptoms requires personal satisfaction that they're doing the right thing. Having exhaustive pathology markers to refer to during this process may help their resolve. EBV VCA IgG should be decreasing, with a 6-8 week lag (if titres are within the maximum lab ranges... most people's are not..)

If someone has other infections, IVIg may be an absolute panacea.. however this is going to prevent them from tracking their own serology markers / IgG. If someone doesn't need IVIg, they'll have better reporting.
 
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joshua.leisk

Joshua Leisk (Researcher)
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Thanks for opening this post and participating in a discussion. @joshua.leisk

I'm not sure about CMV, but I don't see why EBV PCR would prove the absence of lytic activity. Even with negative PCR, lytic signaling from transfected cells is possible. Have you considered that it isn't the viral antibodies but the viral proteins from transfected cells that keep circulating? EBI-2 would be such a protein, to name a common one.

Nevertheless, spironolactone might still show benefits even if it hasn't completely suppressed viral activity. Maybe it just doesn't reach sufficient efficacy given the dosage. A similar question is up for discussion regarding the use of Ivermectin for the same purpose.



I don't see this proven.
  1. PCRs show active or dead viral residue. They don't show viral signaling or quantify transfected cells.
  2. It's possible that the lytic activity happens localized. Maybe in the liver, maybe in the thymus. Localized viral signaling won't show up in the blood unless it becomes very severe. You also mention that you assume a localized pathology in the liver. There is no reason to believe that a blood PCR can show complete suppression of EBV residual activity.
What might be more helpful in this regard are biopsies of the respective hepatic or thymic tissues and a protein or gene analysis of viral signaling.
Alternatively, the course of EBV EA antibodies could also show when localized lytic activity happens. Check this post for more details and a discussion about the specificity and sensitivity of the different antibody types.


In your protocol, you use sodium benzoate for nitrogen disposal. Consistent with the findings of Scheibenbogen et al. and other teams, intracellular sodium is usually too high. I personally avoid sodium all the way and take potassium to at least increase the availability of serum potassium and decrease the availability of serum sodium. CFS/ME seems to have multiple mechanisms that push off the intracellular electrolyte balance away from potassium and towards sodium and calcium. So I wonder - have you considered Glycerol Phenylbutyrate or Potassium Benzoate instead?

Lastly, I'd also strongly suggest adding Coenzyme Q10 to your protocol because it's an important cofactor for oxidative phosphorylation and oxidative phosphorylation is overstimulated in CFS/ME whilst necessary for NAD+ recycling.
Great comments and I just saw your follow up. :D

In my mind, the latent phase, which uses transcytosis is the silent / overlooked problem. It appears to be the main cause of CFS/ME symptoms. The EBV VCA IgG marker appears to be the marker that infers latent cell burden. This is confounded by other factors, so needs to be interpreted with a grain of salt. EBNA may be a suitable marker, also.

Spironolactone + sodium benzoate (HDAC inhibitor) performed reasonably well in this regard (commenced January 2021) -

October 2020:
oct20.png

March 2021:
mar12.png


However, from my understanding of the viral alterations downstream of C-terminal Binding Protein, addressing this is/was the key - the triterpenes in Reishi appear to switch this altered cascade off (also silencing lytic and latent) while allowing apoptosis. (CtBP->SIRT4->NF-KB. p53 also normalised.)

I've started looking deeper into how these triterpenoids are derived in the fungi and they appear to have a relationship to the trees the fungi grows on - there are similarities to betulinic acid, etc. Likewise, the beta-glucans in Lion's Mane appear to be partially derived from the host plant - wheat bran and oat bran often gets used to grow them, commercially.

Sodium - yes.. we found this issue also. Spironolactone being a potassium sparing diuretic balances this somewhat, however we've been including diet management as part of the protocol.

4-PBA, combined with NAC would be another useful nitrogen management tool. My biggest problem around nitrogen disposal has been the restriction on accessing useful compounds such phenylacetate, as they are precursors for making "meth".

CoQ10 is very useful - in the v3.x protocol, I haven't used it, as we've removed the problems further upstream. I'm possibly over-engineering the ROS management in 3.1, however it seemed sensible to allow for additional ROS from immune response, etc.

Once ROS gets too high, the whole process snowballs. On paper, it shouldn't happen with reishi, egcg, etc, however for now I'd prefer a more consistent, stable approach. It's something I may look at reducing in the future.

--

What I'd currently like is a wider array of pathology data for ALT before / after low-dose EGCG implementation, so I can better gauge the EGCG dosing schedule. That's a WIP.

Based on early participant feedback, we seem to be covering this effectively, however like everything else, this will continue to be refined with more clinical data and feedback.
 

godlovesatrier

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Brilliant thank you.

I'm going to qoute the non-fasting protocol here as per the study, if it breaks any rules please delete this post @Mary @Sushi

The study discusses a protocol for fasting and non-fasting load in periods, non-fasting is quoted below:

(2) NON-FASTING: Administering 750-1000mg of the food preservative sodium
benzoate, 1000-2000mg of glycine, plus sufficient pantothenic acid and cysteine, 4x a day for
the first 3-4 days

The study then refers to the protocol study v3.1 (which Joshua has already quoted above from his 3.1 paper):

1619682553377.png


I just thought it might be easier if I quoted it all in one place for people to read and digest.
 
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joshua.leisk

Joshua Leisk (Researcher)
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Brilliant thank you.

I'm going to qoute the non-fasting protocol here as per the study, if it breaks any rules please delete this post @Mary @Sushi

The study discusses a protocol for fasting and non-fasting load in periods, non-fasting is quoted below:



The study then refers to the protocol study v3.1 (which Joshua has already quoted above from his 3.1 paper):

View attachment 42641

I just thought it might be easier if I quoted it all in one place for people to read and digest.

little error of mine there - it’s pantothenic acid, rather than P5P. 👍🏻
 
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