ME/CFS Research: Herpes Autoimmune Spectrum Disorder

[godlovesatrier]

My latest update here:

https://forums.phoenixrising.me/blog-articles/day-23-dose-2.2774/

I also found someone else (not sure who) commenting on an old blog of cort johnsons about the akgdh issue, but without any ideas on how it could be resolved. Rather interesting reading:

https://www.healthrising.org/blog/2...fatigue-syndrome-oxidative-stress-low-oxygen/

If you search the page for the following you'll find the comment which appears to discuss the same scientific pathways:

dejurgen on February 8, 2019 at 4:45 pm

 

[Marylib]

@joshua.leisk

Quite candidly, the situation on the homefront is becoming rather dire and the hour is drawing late. If I'm unable to experience some sort of renaissance over the next several months, my family and I could be facing utter financial ruination. Not wanting to burden loved ones with my continued collapse, it would feel prudent to remove myself from the narrative, thus freeing them from indignity, poverty, etc.

You're scaring me a little here @The Bard. I guess you can't send me a message? If you can please do.

 

[godlovesatrier]

@The Bard sorry I totally missed your post! How rude of me.

I can't message you either, it's a possibility that the feature is turned off, that or there's a fault with the site. @Jyoti any ideas?

Thanks,

 

[sb4]

If you search the page for the following you'll find the comment which appears to discuss the same scientific pathways:

dejurgen

Good find. Dejurgen has been posting interesting stuff in the comments for years. Shame he doesn't post here.

 

[godlovesatrier]

Interesting! Wonder who he is, agreed he seemed very switched on with a fantastic grasp of human bio metabolics. Most of which went right over my head.

 

[sb4]

Okay so I have read all 3 papers by @joshua.leisk . I am interested in the CAC stuff.

So please correct me if I am wrong and help me fill in the gaps.

Stealth virus causes increased ROS (as the cell tries to fight it) this ROS leads to alpha ketoglutarate dehydrogenase enzyme activity decreasing, as well as aconitase. Both these enzymes are key to the Citric Acid Cycle being a cycle so you get build up of substrate at certain points.

AKG and Citrate build up. The Citrate causes acetyl coa to get backed up lowering PDH and presumably diverting some pyruvate to lactate. The AKG can transform into oxaloacetate to keep the cycle going. The AKG can react with Hydrogen Peroxide (ROS) to form Succinate skipping a step in the CAC and producing more NADPH (antioxidant) instead of NADH (energy).

With PDH backed up, Glycolysis goes down the Pentose Phosphate Pathway instead, leading to more antioxidants to help clean up the excess ROS but at the expense of creating energy.

What happens to the Citrate?

If we block GDH we are further blocking energy to the cell, so how is this overcome?

I would like a barebones list of supplements and what they do. Like the minimum you would have to take to test this theory.

So far I have got:
Sodium Benzoate = Helps dispose of nitrogen.
Glycine ?
Cystein ?
Panthothenic Acid = Cofactor for transamination to oxaloacetate.
Reishi = Terpenes, help the stealth virus become visible. How does this work exactly?
R-ALA = ROS? PDH cofactor?
Lions Mane / Oat Bran = Beta Glucans which stimulate the immune system.
EGCG = Block GDH.
Bunch of Antioxidant type supplements.

 

[Martin aka paused||M.E.]

Just wanted to jump in and give an update. I'm now on day 11 and since yesterday my energy improves.
I'm one of the very skeptical members here but my situation is so bad that I told my partner to give it a try.

Now I can use my phone without Ativan for some hours again. Impossible in the last months.

No immune response yet.

Martin

 

[joshua.leisk]

Okay so I have read all 3 papers by @joshua.leisk . I am interested in the CAC stuff.

So please correct me if I am wrong and help me fill in the gaps.

Stealth virus causes increased ROS (as the cell tries to fight it) this ROS leads to alpha ketoglutarate dehydrogenase enzyme activity decreasing, as well as aconitase. Both these enzymes are key to the Citric Acid Cycle being a cycle so you get build up of substrate at certain points.

AKG and Citrate build up. The Citrate causes acetyl coa to get backed up lowering PDH and presumably diverting some pyruvate to lactate. The AKG can transform into oxaloacetate to keep the cycle going. The AKG can react with Hydrogen Peroxide (ROS) to form Succinate skipping a step in the CAC and producing more NADPH (antioxidant) instead of NADH (energy).

With PDH backed up, Glycolysis goes down the Pentose Phosphate Pathway instead, leading to more antioxidants to help clean up the excess ROS but at the expense of creating energy.

What happens to the Citrate?

If we block GDH we are further blocking energy to the cell, so how is this overcome?

I would like a barebones list of supplements and what they do. Like the minimum you would have to take to test this theory.

So far I have got:
Sodium Benzoate = Helps dispose of nitrogen.
Glycine ?
Cystein ?
Panthothenic Acid = Cofactor for transamination to oxaloacetate.
Reishi = Terpenes, help the stealth virus become visible. How does this work exactly?
R-ALA = ROS? PDH cofactor?
Lions Mane / Oat Bran = Beta Glucans which stimulate the immune system.
EGCG = Block GDH.
Bunch of Antioxidant type supplements.

(Obligatory "according to our model") -

That's a really great starting point. The cascade gets pretty unpleasant after that.

The key thing here is that we don't want to block GDH. It has an important function for energy homeostasis. We just want it normalised. The dose of reishi + EGCG targets a normal range. There will be a list of other influences coming soon.

GDH in the pancreas being high also causes hyper-secretion of insulin. This is why the glucose metabolism get further broken and creates ROS via being "forced" into the reaction cycle, once it can't be stored as glycogen.

The triterpenes in reishi correct pathways relating to NF-kB and apoptosis, however until mTOR is "not running", it appears that the cell won't signal for death. This relates to the total amount of energy in the reaction cycle and why there is a "ROS reset" period in the beginning of the protocol, followed by a strict diet that helps prevent ROS creation in this model.

The sodium benzoate is only used in the beginning to make hippurate, as when we correct the mito issues, the purine nucleotide cycle unloads an unpleasant backlog of ammonia. This is expected to cause an intense "crash" for typically 3-4 days.

Here's an early preview/draft of v3.3. The final version will be on RG, with more details included.
I don't suggest anyone self-experimenting deviates from the schedule as it's currently described (it does include some listed variables for individualisation.)

Cheers,
Josh

Edit: 3.3 preview updated and moved here - https://forums.phoenixrising.me/thr...toimmune-spectrum-disorder.83371/post-2344221

 

[cogent_thought]

Hi there @joshua.leisk ,

I'm interested in starting this protocol myself. I experienced herpes, HPV and EBV infections which triggered lasting fatigue symptoms. I don't believe I was particularly promiscuous! I keep myself upright on a battery of supplements/probiotics etc. but experience daily fatigue that stops me progressing in many areas of my life which is a tough fate to expect at the age of 32.

Questions for the protocol;

1. Prior to beginning the protocol, is it worth titrating up dosages for supplements especially antioxidants. Looking at NAC, r-ala and glutathione specifically if people have had poor reactions in the past?
2. Which tests are important for titres? EBV and HHV?
3. If one cannot find the titre tests is it even worth attempting the protocol? Are valacyclovir/spironolactone/tenofovir specific to infections or somewhat interchangeable? If there are no known high viral titres is it worth just moving into the fasting or startup phases?
4. The spironolactone are both antiandrogenic, a little concerning for a young male looking to hold onto virility!?

Thank you for your efforts and time. Sorry if you already answered these Qs, I have scoured the 32 page thread.

 

[godlovesatrier]

@cogent_thought I wasn't particularly promiscuous either, certainly has no baring on how we end up. I'm 35, got sick age 30, so understand how you feel.

I didn't have titer tests for hhv before starting, only ebv. But I found out the hard way that ebv was active by getting acute ebv in June last year - it was previously dormant.

Just wanted to wish you luck if you try the protocol.

 

[pamojja]

I’m personally using 2-3g of organic reishi powder / day for maintenance (along with “very large” amounts of beta-glucans),

1st day was on top of a small mountain of the existing reishi powder I had already been consuming.

Days 2,3+ were a single capsule of the LEF, 3x a day, plus a very large amount of oat bran, lions mane, etc

Thanks. So the triterpenes in 3 LEF capsules - almost 90mg from 3 caps - where actually much more stronger than the assumed 3x40=120mg triterpenes from 3x500mg plain Reishi powder daily. And plain Reishi powder therefore containing much less triterpenes than 80mg per gram. Maybe half of that

Missed the earlier quote of you actually taking even double the dose of plain reishi powder, just for maintainance. With the unique response to 3 LEF capsules, we must assume much lower triterpene content in plain reishi powder. Therefore even less down to a quarter, or only about 20mg of triterpene per gram of reishi powder.

 

[The Bard]

Apologies if the matter was previously addressed in this or an analogous thread, but I intend to tread the long dark roads of Moria, i.e. the fasting mechanism, in the coming days. However, I'm slightly vexed by whether the sodium benzoate is to be administered concurrently with the fast or during the three to four days prior to fasting. Intuitively, it seems that the concurrent route is more likely, but given the potentiality for mishaps when inducing this type of immune response, I'm erring on the side of atypical circumspection.

Grateful for your insights and for all those who have been beyond welcoming in my first few days as an active forum participant!

 

[godlovesatrier]

I'll message you @The Bard I've got the answers.

 

[mattie]

Sorry if this has already been answered somewhere, but I could not find it answered in this thread when @JoeS asked the same thing:

Sodium benzoate + vit. c = benzene.

How can ingesting 1000 mg sodium benzoate / day be safe? By avoiding all sources of vit. C ??

@joshua.leisk

https://www.researchgate.net/public...bonated_soft_drinks_Exposure_and_health_risks

There is a serious concern about the use of sodium benzoate in non-alcoholic carbonated (soft) drinks because of its mechanistic ability to convert to benzene, a classified carcinogen. It is this concern that drove this study to determine consumer exposures to sodium benzoate and possible health risks from intake of such soft drinks. A survey was conducted during which Google Forms were used to collect drink consumption data from 113 consumers including males and females. During this same period, 38 varieties of non-alcoholic carbonated (soft) drinks were collected from two major markets in Ghana. These drink samples were subsequently subjected to extraction protocols and the levels of sodium benzoate quantified using HPLC. Information from the Google Forms together with the quantification of sodium benzoate formed the basis of the determination of exposure of sodium benzoate according to the USEPA protocols. Using the Palisade @Risk software, elements of exposure of sodium benzoate (mg/mL ingested, volume-mL of non-alcoholic carbonated (soft) drink consumed, and body weight-kg of consumers) were integrated and iterated (at 10⁵) to estimate the simulated chronic exposures. Simulated risks (hazard quotient, HQ, margin of exposure, MoE, and cancer risk, LTCR) were determined using thresholds obtained from regulatory bodies. High levels of sodium benzoate, above the acceptable limit of 150 mg/L based on USEPA recommendations, were detected in 6 (16%) of the 38 non-alcoholic carbonated (soft) drinks sampled. The results of the study showed that the concentrations of sodium benzoate ranged from a minimum of 51.0 mg/L to a maximum of 277.0 mg/L. It was clear that the consumption patterns of males created relatively high exposures leading to unsurprisingly higher risks compared to female consumers. The high-risk indices determined in this study, relative to regulatory thresholds (HQ>1, MoE<10⁴ and LTCR >10⁻⁶) are all serious indicators of grave public health concerns. These observations emphasize potential benzenes in our food chains and a call for a more forceful monitoring of product quality and safety to ensure adherence to standards.

 

[joshua.leisk]

Sorry if this has already been answered somewhere, but I could not find it answered in this thread when @JoeS asked the same thing:

Sodium benzoate + vit. c = benzene.

How can ingesting 1000 mg sodium benzoate / day be safe? By avoiding all sources of vit. C ??

@joshua.leisk

https://www.researchgate.net/public...bonated_soft_drinks_Exposure_and_health_risks

Your body produces a level of benzoate / benzoaic acid daily. This is secreted from both your gut microbiome and the benzoic acid you consume in both fruits and preserved foods.

Sodium benzoate is used clinically at up to 5g per day and in special cases is considered safe at 250mg/kg - https://ojrd.biomedcentral.com/articles/10.1186/s13023-016-0513-0

In this protocol, it's used for the induction only, as when you first fix the mitochondrial fragmentation, the purine nucleotide cycle dumps ammonia into the serum. You are expected to crash and it won't be enjoyable.

You could certainly begin the protocol without it. You may regret doing so, however.

 

[joshua.leisk]

Apologies if the matter was previously addressed in this or an analogous thread, but I intend to tread the long dark roads of Moria, i.e. the fasting mechanism, in the coming days. However, I'm slightly vexed by whether the sodium benzoate is to be administered concurrently with the fast or during the three to four days prior to fasting. Intuitively, it seems that the concurrent route is more likely, but given the potentiality for mishaps when inducing this type of immune response, I'm erring on the side of atypical circumspection.

Grateful for your insights and for all those who have been beyond welcoming in my first few days as an active forum participant!

It's been reported as useful whenever someone is in a crashed state, when used at around 250mg/hr, consumed with a glass of water. There's nothing preventing someone for using it during the fast and then continuing it when starting the management protocol, until the initial crash / PEM has lifted.

 

[joshua.leisk]

Missed the earlier quote of you actually taking even double the dose of plain reishi powder, just for maintainance. With the unique response to 3 LEF capsules, we must assume much lower triterpene content in plain reishi powder. Therefore even less down to a quarter, or only about 20mg of triterpene per gram of reishi powder.

Lately, I've been doing my best to provoke any kind of immune response.
Breakfast is getting weird at my place.

Since those couple of days I had immune symptoms, I haven't noticed anything intense. Seeing what appears to be ongoing skin and other benefits.

 

[joshua.leisk]

Hi there @joshua.leisk ,

I'm interested in starting this protocol myself. I experienced herpes, HPV and EBV infections which triggered lasting fatigue symptoms. I don't believe I was particularly promiscuous! I keep myself upright on a battery of supplements/probiotics etc. but experience daily fatigue that stops me progressing in many areas of my life which is a tough fate to expect at the age of 32.

Questions for the protocol;

1. Prior to beginning the protocol, is it worth titrating up dosages for supplements especially antioxidants. Looking at NAC, r-ala and glutathione specifically if people have had poor reactions in the past?
2. Which tests are important for titres? EBV and HHV?
3. If one cannot find the titre tests is it even worth attempting the protocol? Are valacyclovir/spironolactone/tenofovir specific to infections or somewhat interchangeable? If there are no known high viral titres is it worth just moving into the fasting or startup phases?
4. The spironolactone are both antiandrogenic, a little concerning for a young male looking to hold onto virility!?

Thank you for your efforts and time. Sorry if you already answered these Qs, I have scoured the 32 page thread.

(Obligatory "if it was me, this is not medical advice, etc") -
I'd personally dive in with the expectations from reading this thread that the beginning is going to be a bit rough and knock me around.. and that it's going to get "worse" before it gets better, once the immune response starts.

People are expected to end up in bed, with the worst case of flu they've possibly had since "mono".

I'd follow the v3.3 preview PDF I shared above accurately.

Someone can delay/pause the majority of the immune response by leaving out beta-glucans sources.

EBV is one of the human herpesvirus (HHV) family members (HSV-1, HSV-2, VZV, EBV, CMV, HHV-6, HHV-7, HHV-8). To do things properly, you'd need to exhaustively know which of the 8 (and cousins) you may have and identify co-infections for all the usual pathogens (parvo-b19, coxsackie, T.gondii, HPV etc). This may take private labs, or a friendly doctor.

Not sure if you've read the latest protocol, but we're not using other antivirals at this stage. Valacyclovir is... not amazing at all.. spironolactone works nicely at the LYTIC phase only, as does tenofovir. Neither doesn't anything impressive about the latent infection.

In v3.2, the EGCG dose was based from observations surrounding concurrent use of spironolactone.
In v3.3 it's been increased to accommodate removing spironolactone, along with individual variables.

The role of androgens in this disease model I'll be talking a lot about shortly... However, at the moment, I'll simply mention that in this model, your androgen levels are already too high and a large part of the problem.

Testosterone is converted into DHT. DHT is the "real" androgenic hormone.

If you check your DHT levels, you'll likely find they're >700 pmol/L, even though your free testosterone levels are surprisingly low. This high level of DHT is acting as the HPG feedback input and reducing the testosterone production, via producing less LH. This has an effect of reducing your oestrogen / oestradiol.

Overall the unbalanced DHT : oestradiol has a detrimental effect in this disease model.

Interestingly enough, virility / libido is often related to neurosteroids. One of those neurosteroids is allopregnanolone. Like DHT, it's also a 5-AR metabolite. In this way, reducing 5-AR too much can reduce libido, however this is temporary.

Part of the diet plan example I listed partially addresses the reason the DHT : oestradiol ratio is so unbalanced. This will be further improved when I finish writing the v3.3 document and may allow for less EGCG usage.

I'm currently taking the same anti-androgenic compounds and I assure you, I'm feeling no less male.

 

[Reading_Steiner]

Sorry if this has already been answered somewhere, but I could not find it answered in this thread when @JoeS asked the same thing:

Sodium benzoate + vit. c = benzene.

How can ingesting 1000 mg sodium benzoate / day be safe? By avoiding all sources of vit. C ??

@joshua.leisk

https://www.researchgate.net/public...bonated_soft_drinks_Exposure_and_health_risks

avoid stuff with vit C except at night. he said in the chart to take the vitamin c at night. I didn't take it often though because its not nice, taking it more now, but i've been off the sodium b for 2 weeks or so. Its really good in my opinion. I made a mistake though and took BCAAs that have vitamin C in, have to be careful ! I think green tea might have it in too though, its hard to completely avoid.

 

[Boba]

EBV is one of the human herpesvirus (HHV) family members (HSV-1, HSV-2, VZV, EBV, CMV, HHV-6, HHV-7, HHV-8). To do things properly, you'd need to exhaustively know which of the 8 (and cousins) you may have and identify co-infections for all the usual pathogens (parvo-b19, coxsackie, T.gondii, HPV etc). This may take private labs, or a friendly docto

In which way does knowing about the viruses influence the protocol? I'm sure I have HSV 1&2 + HPV, but don't know about other viruses. Thanks Joshua!!