ME/CFS Research: Herpes Autoimmune Spectrum Disorder

[pamojja]

is that at all relating to Rudolf Steiner?

..my weakest subjects, mostly through lack of interest / trying.

I was mistaken too, by reading most of Steiner myself in my youth. Though soon after got distracted by the Pali texts, and ended up in a Burmese forest meditation monastery..

 

[joshua.leisk]

No, philosophy is one of my weakest subjects, mostly through lack of interest / trying.

Its a type of Engrish https://en.wikipedia.org/wiki/Wasei-eigo
There was a guy on here that knew what it meant but I haven't seen him posting lately, I think hes from the UK like I am.
Steins;Gate Opening HD 1080p Creditless


I have some other questions about the treatment strategy. 1) did any previous experiment subjects have Multiple Chemical Sensitivity and did it resolve after completing the treatment plan ? 2) how far into the treatment should people attempt to exceed their normal physical capabilities and try to emulate things a healthy person would do ? 3) can we eat penuts and potato crisps occasionally as those are quite convenient form of food ( and I'm getting bored of eating mostly cheese by itself and sometimes fish or kidney beans ).

With the increased immune response, I’ve seen one person have an increased allergic reaction (we assume) to an environmental allergen.

The general advice is that I wouldn’t start trying to be “normal” until after you’ve recovered from the 2 or so weeks laid up in bed feeling sick as a dog and cursing my name for having started. At that point, someone should feel quite energetic, their liver will not be feeling tender and they’ll “know” when it’s time to get up and go for “walkies” to test out their new / returned capabilities.

Trying to keep protein up during the immune response is sensible, as people are going to be replacing a lot of cells and this is going to demand a lot of energy and materials.

A small eg. 5mg dose of Forskolin, 3x a day, has been reported as being helpful for fatty acid oxidation, assuming NAC is being consumed per the plan.

Peanuts and occasional crisps in sensible portions should be okay, although not the healthiest foods to make a staple diet plan from.

 

[nerd]

https://kurkraft.com/collections/all/products/reishi doesn't contain triterpines and therefore isn't an option.

They don't declare triterpenes, but does this really mean there aren't any in this product?

I'm also considering an alcohol extract from Herb Pharma, but they also source it from China primarily. I guess there isn't any other option because the efficacy of the mushroom depends on where they grow.

Beside all those options, wouldn't a dedicated beta-glucan supplement do just as well?

For example, fresh Shiitake which are easier to source locally.

 

[pamojja]

They don't declare triterpenes, but does this really mean there aren't any in this product?

Since its standardized to a whooping 35% of polysaccarides, that means its water extract only. Because otherwise the additional alcohol extract would take away space from the total, and the standardized polysaccarides couldn't be as much as 35%.

For example the LEF extract also contains 6% triterpenes, leaving space for 13% polisaccarides only.

And one can be sure if any extract contains anything standardized, it always would be presented on the product page. Due to its higher cost and adding substancial value to the product.

 

[Reading_Steiner]

With the increased immune response, I’ve seen one person have an increased allergic reaction (we assume) to an environmental allergen.

The general advice is that I wouldn’t start trying to be “normal” until after you’ve recovered from the 2 or so weeks laid up in bed feeling sick as a dog and cursing my name for having started. At that point, someone should feel quite energetic, their liver will not be feeling tender and they’ll “know” when it’s time to get up and go for “walkies” to test out their new / returned capabilities.

Trying to keep protein up during the immune response is sensible, as people are going to be replacing a lot of cells and this is going to demand a lot of energy and materials.

A small eg. 5mg dose of Forskolin, 3x a day, has been reported as being helpful for fatty acid oxidation, assuming NAC is being consumed per the plan.

Peanuts and occasional crisps in sensible portions should be okay, although not the healthiest foods to make a staple diet plan from.

Its morning now and my fever has gone down, I was thinking about hoovering my room, took most of the drugs, no difference really in feeling, then drank the reishi last... now big change suddenly back to not feeling so good, headache coming back etc, does this mean that its the 'magic ingredient' in some ways or could it just be a reaction to the alcohol content ? it takes me quite a while to consume all the drugs by the way, up to an hour each time.

 

[godlovesatrier]

Reishi doesn't normally have much of an effect on me. If I take the 14:1 extract that I have I can go all day with tons of energy and then subsequently crash the next day as it's basically just lots of immune stimulation. I've since 2018 I've been taking immune modulators like reishi, astragalus, andrographis and others on and off, I think this is why overall my viral levels are lower. Even if for the last 6 months they've not been lower, which has made me feel significantly worse. Until I started taking the thiamine.

I've come to the conclusion if I don't fix the other pathways the thiamine on its own and other b vitamins are likely to just send me round in circles (symptomology wise).

So your startup reaction is good really. You would expect it to do that but probably not for 20 to 45 minutes after taking it. I would say an immediate reaction is the alcohol, but after that it should be the substance taken.

An hour is a very long time!! That sounds time consuming.

 

[pamojja]

it takes me quite a while to consume all the drugs by the way, up to an hour each time.

Wow, just 4 bulk powders, 6 different capsules and 1 tincture a whole hour to take each time? (https://forums.phoenixrising.me/thr...hua-leisk-and-aline-nocon.83881/#post-2337926)

I usually put my capsules/pills each dose separated in fish-tackle boxes for 3 weeks in advance. Which takes me half a day. Then taking them each time: one handful fasted, two handful with first meal (softgels and dry separated), one handful before the second meal, again two with the second and last meal, and one handful again before bed. Each dose takes just as long as it takes to gulp a handful with water down. Usually seconds. Additional a tablespoon of fish-oil with 5 drops of supplements in dropper form, also seconds.

Since I take multiple more powders, spices and herbs too, to mix those all in a glass of water does take me about 10 minutes each time trice a day, always taken with the capsules/pills on empty stomach. Since I only meassure by eye, once every 3 weeks I weigth all the powder-containers to know if I'm still in the range of doses choosen. Which takes an other half day, including having it calculated in a speadsheet.

So in total a whole day for 3 weeks preparation, additional 1/2 hour each day, makes in total 21 hours for about as many days and about 120 different powders and as many capsules or pills.

Which is probably at the extreme other end of how many supplement one is ever able to take. You still have a lot of time to optimize. ;-)

 

[joshua.leisk]

Its morning now and my fever has gone down, I was thinking about hoovering my room, took most of the drugs, no difference really in feeling, then drank the reishi last... now big change suddenly back to not feeling so good, headache coming back etc, does this mean that its the 'magic ingredient' in some ways or could it just be a reaction to the alcohol content ? it takes me quite a while to consume all the drugs by the way, up to an hour each time.

Sounds pretty similar to the messages I get frequently. Some more BCAAs and water may help with the headache, if sodium benzoate isn’t getting enough done.

 

[Reading_Steiner]

Some people are confused as to whether they need to preload the body with sodium benzoate for days before even starting on the antiviral stuff, my feeling was that the body likes to reach homeostasis so every time you took it, you'd go back to normal levels of metabolites within a few hours, was that the correct assumption, or is it possible to progressively lower your levels of bad stuff over the course of days ? I pretty much started it all simultaneously with a small build up for the sodium benzoate, which would have made it easier for me to identify any chemicals that I had a bad reaction to.

 

[joshua.leisk]

Some people are confused as to whether they need to preload the body with sodium benzoate for days before even starting on the antiviral stuff, my feeling was that the body likes to reach homeostasis so every time you took it, you'd go back to normal levels of metabolites within a few hours, was that the correct assumption, or is it possible to progressively lower your levels of bad stuff over the course of days ? I pretty much started it all simultaneously with a small build up for the sodium benzoate, which would have made it easier for me to identify any chemicals that I had a bad reaction to.

In the draft specification, the schedule is to start everything at once, however the yellow section (sodium benzoate) is only used for about 4 days (until the headaches stop).

During those 4 days.. and possibly a little longer, the carbohydrates are dramatically reduced to 50-85g of net carbs. We're trying to induce an energy deficit. This is done as part of an oxidative stress (ROS) reduction / reset process.

Once that reset process has completed and ROS levels normalised, a 'balanced' intake of carbohydrates, to maintain glycogen stores and energy usage is implemented and continued.

Ongoing, we also introduce specific microbes and prebiotics, food items to recolonise the gut microbiome.

 

[pamojja]

@joshua.leisk just in case you might have overseen my questions in this post from last page: https://forums.phoenixrising.me/thr...-spectrum-disorder.83371/page-11#post-2337918

If you don't know answers, also no problem.

 

[joshua.leisk]

I take this text from your paper to mean the beta-glucan content of lion's mane isn't known or too variable?

Barley flour seem to have 85% carbs, oat bran 61%. So about the same beta-glucan content per carbs. Would prefer barley though, since its available as traditional food, For example 'Tsampa', as it is used by Tibetans as their stable.

Interestingly, Sunday.de sells only Chaga extract standardized to 20% beta-glucans, all their other many different mushroom extracts including Lion's mane only standardized to 30% polysaccarides: https://www.sunday.de/vitalpilz/

While https://www.dynveo.fr/nos-produits/ sells 4 different mushroom extracts, except lion's mane, all standardized for 20% beta-glucan.

With all 20% for beta-glucan standardized mushroom extracts of chaga, maitake, reishi, shitake - but not lion's mane available on the european market - and plain reishi powder just as effective as its alcohol extracts, the question of course arises: Wouldn't really any of the other mushroom powders lent itself just as well for their natural beta-glucan content? Or right away simply upping the dose of the reishi powder for their additional triterpenes?

Beside all those options, wouldn't a dedicated beta-glucan supplement do just as well? (beside the Reishi) https://www.iherb.com/pr/California...e-Beta-Glucan-250-mg-90-Veggie-Capsules/99736

Sorry, no idea how I missed this!
Beta-glucans - there are different types and it’s not clear which ones are the most effective for stimulating the immune response. We’ve found the mix of beta-glucans from lions mane, reishi and oat bran to be highly potent / potentially overwhelming. It may be that eg. a straight beta-glucan supplement, which is usually derived from yeast, could be equally effective, however this is currently untested.

Serum D3 status is also important here.

The concern with large doses of reishi powder is that fungi draw toxins out of the environment. Someone may be getting a dose of eg. heavy metals with large amounts of raw reishi powder, which is why the organic powder and alcohol extracts are recommended.

I’m personally using 2-3g of organic reishi powder / day for maintenance (along with “very large” amounts of beta-glucans), however I haven’t tested it for heavy metals yet. My current presumption is that if it has passed certification standards in Australia, that I’m probably okay, however there’s no guarantee.

I tend to send in products for mass-spectrometry testing if they become a staple addition to my personal regimen. So far, I haven’t found any issues, however you hear the occasional story, hence the diligence.

 

[godlovesatrier]

Hey Josh,

Are you able to tell us the rest of your maintenance protocol and how long you've been taking it? I've heard you mention I think 10 or 25g of glycine a day too?

Thanks,

 

[Reading_Steiner]

I read the first paper again to try and get more insight and look for areas where I might be in error. I think I understand a little better but it gave me some simple questions.

1) you mention latent cells are hypothesized to be able to 'recruit' neighbouring cells, similar to something called a senescent cell ? how exactly does this work, does it mean that neighbouring cells also have PDH and a-KDGH deficiency and elevated level of ammonia production etc ? does this happen because the autoantibodies produced by herpes virus family spread out from the originating cell into neighbouring ones ?
wouldn't this mean that the treatment would also target those non infected yet affected cells ?

2) Do the latent infected cells not also produce energy by using ketones / ketogenesis ? in reference to the diet we are on.

3) what exactly causes these latent cells to 'unstealth' themselves and become detectable by the immune system in response to this treatment ? see question 1.

 

[joshua.leisk]

I read the first paper again to try and get more insight and look for areas where I might be in error. I think I understand a little better but it gave me some simple questions.

1) you mention latent cells are hypothesized to be able to 'recruit' neighbouring cells, similar to something called a senescent cell ? how exactly does this work, does it mean that neighbouring cells also have PDH and a-KDGH deficiency and elevated level of ammonia production etc ? does this happen because the autoantibodies produced by herpes virus family spread out from the originating cell into neighbouring ones ?
wouldn't this mean that the treatment would also target those non infected yet affected cells ?

2) Do the latent infected cells not also produce energy by using ketones / ketogenesis ? in reference to the diet we are on.

3) what exactly causes these latent cells to 'unstealth' themselves and become detectable by the immune system in response to this treatment ? see question 1.

1) In the model, a tissue acts cohesively, as directed by the infected cells. This happens via traditional cell-cell communication methods - cytokines, lactate, etc

2) The low carb diet is initially “very low” to induce an energy deficit and may allow oxidative stress (ROS) to normalise. This is also needed due to hyper-insulin secretion from pancreatic cells with high GDH “forcing” blood glucose into already “full” cells. After this has taken place, carbohydrates are suggested to be increased to match glycogen usage.

3) The triterpenes in the reishi. They may fix the issues with NF-kB, which are downstream from CtBP.

 

[joshua.leisk]

Hey Josh,

Are you able to tell us the rest of your maintenance protocol and how long you've been taking it? I've heard you mention I think 10 or 25g of glycine a day too?

Thanks,

My personal regimen is normally based around my 3-4 hours of gym training a day. Lately.. I’ve sacrificed quite a lot to be able to focus on this to the level that has been required.

Sadly, that wasn’t fat being lost there (lol you can see the 3.5 day fast there mid-April).

Things are a bit better now, however in the fullness of time, I’ll prioritise getting that balance back.

 

[godlovesatrier]

Managed to get access to the GDX Europe OAT Test!! So I can get that ordered and sent off once I reach day 7.

 

[BrightCandle]

Can I drink coffee? What about decaf? I have some lovely beans from Ethiopia which sadly are decaying but I don't want to mess with the protocol unwittingly so I was avoiding it while fasting and early on as I am not sure what the interaction is likely to be.

 

[jump44]

Can I drink coffee? What about decaf? I have some lovely beans from Ethiopia which sadly are decaying but I don't want to mess with the protocol unwittingly so I was avoiding it while fasting and early on as I am not sure what the interaction is likely to be.

I asked this and was told coffee is ok for the non fasting version, although you may end up taking in a lot of caffeine if you’re drinking green tea for the ecg content. I’m pretty sure it’s no go for the fasting part, but Joshua would have to confirm that.

 

[joshua.leisk]

Can I drink coffee? What about decaf? I have some lovely beans from Ethiopia which sadly are decaying but I don't want to mess with the protocol unwittingly so I was avoiding it while fasting and early on as I am not sure what the interaction is likely to be.

I asked this and was told coffee is ok for the non fasting version, although you may end up taking in a lot of caffeine if you’re drinking green tea for the ecg content. I’m pretty sure it’s no go for the fasting part, but Joshua would have to confirm that.

Caffeine and coffee are a little complicated. From what I've been reading they influence GDH and related metabolism. If you were using full spectrum green tea, instead of EGCG, you'd be getting about 60mg of caffeine with each serving, to reach the desired GDH alterations. I think that this may be the reason that "full spectrum" green tea requires around double the amount of EGCG to achieve the same effect as EGCG in isolation. I've also read other studies showing caffeine decreasing GDH.. so it could be another compound in the tea. "More research is needed."

On a similar topic, I woke up with an "AHA!" moment, which I'm just exploring now.

Contrasting perhaps 27(?) people who have demonstrated positive results from the standard protocol, there have been 4 people that observed appropriate immune responses to v3.x protocol and/or minor / non-response for aspects of v2.x (although didn't implement the full protocol), despite having positive serology for one or more HHV.

This indicated more variable(s) in play that needed addressing.

My "AHA!" moment was waking up and realising that all 4 of them were on gabapentin.

Gabapentin (and likely pregabalin) appear to interfere with the same pathways being altered by the protocol (and the virus).

https://en.wikipedia.org/wiki/Gabapentin

Pharmacodynamics

Gabapentin is a ligand of the α2δ calcium channel subunit.[69][70] α2δ is an auxiliary protein connected to the main α1 subunit (the channel-forming protein) of high voltage activated voltage-dependent calcium channels (L-type, N-type, P/Q type, and R-type).[9] Gabapentin is not a direct channel blocker: it exerts its actions by disrupting the regulatory function of α2δ and its interactions with other proteins. Gabapentin prevents delivery of the calcium channels to the cell membrane, reduces the activation of the channels by the α2δ subunit, decreases signaling leading to neurotransmitters release, and disrupts interactions of α2δ with NMDA receptors, neurexins, and thrombospondins.[9][10][11] Out of the four known isoforms of α2δ protein, gabapentin binds with similar high affinity to two: α2δ-1 and α2δ-2.[70] Most of the pharmacological properties of gabapentin are explained by its binding to just one isoform - α2δ-1.[70][10]


The endogenous α-amino acids L-leucine and L-isoleucine, which resemble gabapentin in chemical structure, bind α2δ with similar affinity to gabapentin and are present in human cerebrospinal fluid at micromolar concentrations.[71] They may be the endogenous ligands of the α2δ subunit, and they competitively antagonize the effects of gabapentin.[71][72] Accordingly, while gabapentin has nanomolar affinity for the α2δ subunit, its potency in vivo is in the low micromolar range, and competition for binding by endogenous L-amino acids is likely to be responsible for this discrepancy.[10]
Gabapentin is a potent activator of voltage-gated potassium channels KCNQ3 and KCNQ5, even at low nanomolar concentrations. However, this activation is unlikely to be the dominant mechanism of gabapentin's therapeutic effects.[73]
Despite the fact that gabapentin is a structural GABA analogue, and in spite of its name, it does not bind to the GABA receptors, does not convert into GABA or another GABA receptor agonist in vivo, and does not modulate GABA transport or metabolism.[69]
Pharmacokinetics

Gabapentin is absorbed from the intestines by an active transport process mediated via an amino acid transporter, presumably, LAT2.[74] As a result, the pharmacokinetics of gabapentin is dose-dependent, with diminished bioavailability and delayed peak levels at higher doses.[70]
The oral bioavailability of gabapentin is approximately 80% at 100 mg administered three times daily once every 8 hours, but decreases to 60% at 300 mg, 47% at 400 mg, 34% at 800 mg, 33% at 1,200 mg, and 27% at 1,600 mg, all with the same dosing schedule.[5][75] Drugs that increase the transit time of gabapentin in the small intestine can increase its oral bioavailability; when gabapentin was co-administered with oral morphine, the oral bioavailability of a 600 mg dose of gabapentin increased by 50%.[75]
Gabapentin at a low dose of 100 mg has a Tmax (time to peak levels) of approximately 1.7 hours, while the Tmax increases to 3 to 4 hours at higher doses.[70] Food does not significantly affect the Tmax of gabapentin and increases the Cmax and area-under-curve levels of gabapentin by approximately 10%.[75]
Gabapentin can cross the blood–brain barrier and enter the central nervous system.[69] Gabapentin concentration in cerebrospinal fluid is approximately 9-14% of its blood plasma concentration.[75] Due to its low lipophilicity,[75] gabapentin requires active transport across the blood–brain barrier.[76][69][77][78] The LAT1 is highly expressed at the blood–brain barrier[79] and transports gabapentin across into the brain.[76][69][77][78] As with intestinal absorption mediated by an amino acid transporter, the transport of gabapentin across the blood–brain barrier by LAT1 is saturable.[76] Gabapentin does not bind to other drug transporters such as P-glycoprotein (ABCB1) or OCTN2 (SLC22A5).[76] It is not significantly bound to plasma proteins (<1%).[75]
Gabapentin undergoes little or no metabolism.[70][75]
Gabapentin is eliminated renally in the urine.[75] It has a relatively short elimination half-life, with the reported average value of 5 to 7 hours.[75] This value changes with increasing doses, from 5.4 hours for a 200 mg single dose, to 8.3 hours for a 1,400 mg dose.[80] Because of its short elimination half-life, gabapentin must be administered 3 to 4 times per day to maintain therapeutic levels.[81] Gabapentin XR (brand name Gralise) is taken once a day.[82]

Animals:
https://pubmed.ncbi.nlm.nih.gov/9599007/
https://pubmed.ncbi.nlm.nih.gov/8565962/

Later stuff, in humans:
Appears to be tissue specific differences and a rebound effect
Interesting- benzo-like effects without the BZ binding issues..
https://www.frontiersin.org/articles/10.3389/fpsyt.2018.00078/full https://www.nature.com/articles/npp2012142

Interaction with BCAAs:
https://academic.oup.com/jn/article/131/3/846S/4687143
https://www.seizure-journal.com/article/S1059-1311(02)00295-9

So it looks like gabapentin increases GDH and then shunts more glutamate to GABA..
Hypothetically, a higher dose of EGCG could possibly counter the undesirable parts. I'd (completely) guess at 60-75mg of EGCG, instead of 25mg, if there’s a way to normalise this without reducing / removing gabapentin.