ME/CFS Research: Herpes Autoimmune Spectrum Disorder

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joshua.leisk

Joshua Leisk (Researcher)
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What's unique about the beta-glucans that helps with targeting the latent cells? (Apologies if I've missed this anywhere, lots of info to digest 🙂 )
Welcome! Best to start .. way back at the beginning.. I may take some of the key posts from here and put them into a quickly accessible place for people catching up.

The beta-glucans are to stimulate a strong immune response via macrophages, however it's the reishi triterpenes (and reduced mTOR) which first allow the latent cells to signal for apoptosis, first. That's the magic.

https://www.lifeextension.com/magazine/2009/12/the-immune-enhancing-benefits-of-beta-glucans
 
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Hey @joshua.leisk, I have finally made it to the forums! As always, thanks for all of your hard work putting this together. I have been reading this thread since I first found your protocol but I only started posting here as of now. I hope you don't mind a few questions/comments regarding what you said recently. Hopefully I am not missing something due to brain fog.

3-HSD metabolises DHT, allopregnanolone, alcohol and other metabolites. When it is low, the body cannot easily metabolise these things, which causes elevated serum levels.
I think it would be a bit clearer if you refer to 3-HSD as 3a-HSD since you are specifically referring to that isomer - that is the case right? Or are there also suspected issues with 3b-HSD?
More importantly, what makes you think that there are these issues at all (see my question at the end re: sources)?

I also don't quite follow where you are getting the idea that there will be increased allopregnanolone because of a low 3a-HSD level, as it is required for allopregnanolone synthesis:

Wikipedia: Allopregnanolone said:
The biosynthesis of allopregnanolone in the brain starts with the conversion of progesterone into 5α-dihydroprogesterone by 5α-reductase. After that, 3α-hydroxysteroid dehydrogenase converts this intermediate into allopregnanolone.
Many of us have found that supplementing with pregnenolone provides a clear benefit in terms of brain fog, sensory sensitivity, etc., and allopregnanolone (downstream from pregnenolone) has been shown to be a increased with pregnenolone supplementation (eg see this paper). I personally don't find that this effect can be replicated using DHEA or hydrocortisone, which suggests it is not an adrenally-driven phenomenon.


I also have found your claims regarding low LH and FSH to be a little strange - are you gathering all of these data from current patient cohorts, literature, or are you looking over mechanisms and proposing the issues purely theoretically?
I for one most recently had top of the range FSH and mid range LH, despite having severe ME/CFS etc.
 
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Hey @joshua.leisk, I have finally made it to the forums! As always, thanks for all of your hard work putting this together. I have been reading this thread since I first found your protocol but I only started posting here as of now. I hope you don't mind a few questions/comments regarding what you said recently. Hopefully I am not missing something due to brain fog.



I think it would be a bit clearer if you refer to 3-HSD as 3a-HSD since you are specifically referring to that isomer - that is the case right? Or are there also suspected issues with 3b-HSD?
More importantly, what makes you think that there are these issues at all (see my question at the end re: sources)?

I also don't quite follow where you are getting the idea that there will be increased allopregnanolone because of a low 3a-HSD level, as it is required for allopregnanolone synthesis:



Many of us have found that supplementing with pregnenolone provides a clear benefit in terms of brain fog, sensory sensitivity, etc., and allopregnanolone (downstream from pregnenolone) has been shown to be a increased with pregnenolone supplementation (eg see this paper). I personally don't find that this effect can be replicated using DHEA or hydrocortisone, which suggests it is not an adrenally-driven phenomenon.


I also have found your claims regarding low LH and FSH to be a little strange - are you gathering all of these data from current patient cohorts, literature, or are you looking over mechanisms and proposing the issues purely theoretically?
I for one most recently had top of the range FSH and mid range LH, despite having severe ME/CFS etc.
I just jump in because I'm talking about it rn with him... My LH is looooow...
 

joshua.leisk

Joshua Leisk (Researcher)
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Hey @joshua.leisk, I have finally made it to the forums! As always, thanks for all of your hard work putting this together. I have been reading this thread since I first found your protocol but I only started posting here as of now. I hope you don't mind a few questions/comments regarding what you said recently. Hopefully I am not missing something due to brain fog.



I think it would be a bit clearer if you refer to 3-HSD as 3a-HSD since you are specifically referring to that isomer - that is the case right? Or are there also suspected issues with 3b-HSD?
More importantly, what makes you think that there are these issues at all (see my question at the end re: sources)?

I also don't quite follow where you are getting the idea that there will be increased allopregnanolone because of a low 3a-HSD level, as it is required for allopregnanolone synthesis:



Many of us have found that supplementing with pregnenolone provides a clear benefit in terms of brain fog, sensory sensitivity, etc., and allopregnanolone (downstream from pregnenolone) has been shown to be a increased with pregnenolone supplementation (eg see this paper). I personally don't find that this effect can be replicated using DHEA or hydrocortisone, which suggests it is not an adrenally-driven phenomenon.


I also have found your claims regarding low LH and FSH to be a little strange - are you gathering all of these data from current patient cohorts, literature, or are you looking over mechanisms and proposing the issues purely theoretically?
I for one most recently had top of the range FSH and mid range LH, despite having severe ME/CFS etc.
Welcome. :D
Correct, 3a-HSD. (I should have been more specific, however in my defense - I'd just woken up and decided to fat-thumb a response before I'd had some coffee, or got out of bed..)

https://en.m.wikipedia.org/wiki/3α-Hydroxysteroid_dehydrogenase
https://en.m.wikipedia.org/wiki/Aldo-keto_reductase
https://platform.opentargets.org/target/ENSG00000198610
https://pubmed.ncbi.nlm.nih.gov/17526768/

My suspicion for 3a-HSD being abnormal lies around the alcohol intolerance, which gets reported a lot and I remember from my own CFS/ME days. There was also a gradual increase of PEM threshold noticed with about a 2 week delay from a stable dose being reported. They reported this needed an increased EGCG dose and hinted that as LH->T increased, the DHT had increased to previous levels, suggesting 3a-HSD was low. This would also explain a glutamate:GABA balance that leans towards excess excitatory behaviour.

(This needs more research - I'm still looking into it, just speaking openly ahead of the next paper.)

Allopreg - whoops, thank you for pointing that out - I've definitely made an error in my post above (I'll go correct this). What I was talking about earlier with increasing allopreg was in reference for low preg, LH (under 3IU/L). It's the preg->[...]->allopreg intermediary metabolite that will be high.

Preg is metabolised by 5-AR to 5a-dihydroprogesteron and this would be high.
3a-HSD metabolises that to allopreg, so if 3a-HSD is low, allopreg would be low. Sulforaphane and procyanidin B2 are known to increase 3a-HSD.

Allopreg seems to be difficult to test, although I believe DUTCH tests will capture it.

The low LH, high DHT I've seen as a common trend in both privately collected data and in the published literature. I made mention of it in the first paper, also when discussing hCG as a possible therapeutic tool.

2383E2C1-EC7E-4D44-87A8-6908455E890E.jpeg

and spironolactone-

4F950FB5-3B17-4FB5-91C6-9DB4144998A1.jpeg


LH and hCG are identical and hCG is given to some males on HRT to maintain intratesticular testosterone levels, in the same way that LH does.

LH and hCG appear to have an understudied function in regenerating neuronal and other tissue, so I see having low LH as something that is detrimental to healing and health.
https://tahomaclinic.com/2014/01/hcg-neuronal-regeneration/
 

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Allopreg - whoops, thank you for pointing that out - I've definitely made an error in my post above (I'll go correct this). What I was talking about earlier with increasing allopreg was in reference for low preg, LH (under 3IU/L). It's the preg->[...]->allopreg intermediary metabolite that will be high.

Preg is metabolised by 5-AR to 5a-dihydroprogesteron and this would be high.

3a-HSD metabolises that to allopreg, so if 3a-HSD is low, allopreg would be low. Sulforaphane and procyanidin B2 are known to increase 3a-HSD.
Happy to help :D. How are you sure that pregnenolone levels themselves aren't suppressed vs the issue stemming from 3a-HSD? Is it based on the low LH high DHT you saw in some patients? I feel as though I definitely have issues with low pregnenolone (or downstream metabolites) but my LH has never tested low.


My suspicion for 3a-HSD being abnormal lies around the alcohol intolerance, which gets reported a lot and I remember from my own CFS/ME days. There was also a gradual increase of PEM threshold noticed with about a 2 week delay from a stable dose being reported. They reported this needed an increased EGCG dose and hinted that as LH->T increased, the DHT had increased to previous levels, suggesting 3a-HSD was low. This would also explain a glutamate:GABA balance that leans towards excess excitatory behaviour.
Yes, I definitely have had alcohol intolerance even from when I first caught my triggering virus and was still virtually "normal" just tired - it's one of the first symptoms I noticed.

What do you mean by "from a stable dose reported"? Do you mean once someone found an EGCG dose that they responded favourably to? Here you are saying DHT increased to previous levels - do you mean the abnormally high levels (observed in your low LH high DHT patients) or to a normal level (from a low level)?


Allopreg seems to be difficult to test, although I believe DUTCH tests will capture it.

The low LH, high DHT I've seen as a common trend in both privately collected data and in the published literature. I made mention of it in the first paper, when discussing hCG as a possible therapeutic tool.

LH and hCG are identical and hCG is given to some males on HRT to maintain intratesticular testosterone levels, in the same way that LH does.

LH and hCG appear to have an understudied function in regenerating neuronal and other tissue, so I see having low LH as something that is detrimental to healing and health.
https://tahomaclinic.com/2014/01/hcg-neuronal-regeneration/
I'm sceptical about the utility of measuring urinary levels of neurosteroids without seeing data supporting their direct correlation with levels in their active tissues (ie brain etc).

This reminds me of something you said earlier about testing serum GDH levels - in your planned trial perhaps? I think you should try and keep in mind that serum (or urinary) concentrations can oftentimes have a very limited correlation with active/cellular (or in this case, mitochondrial?) levels of specific compounds. This is the case with eg fT3. If this isn't an established method (apologies if it is - I didn't look into it), you would potentially need to do some reasonably detailed characterisation and method development prior to relying on such metrics clinically.

Very interesting to hear about the neuronal regeneration aspects of HCG, I hadn't heard that before.
 

joshua.leisk

Joshua Leisk (Researcher)
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Quite an impressive increase in triterpenes. From originally 1.5g of plain Reishi powder with variable, maybe ~30mg of triterpenes per day.
So my logic here is to increase the reishi dosing for 2 improvements -
More stable GDH throughout the day, meaning less adjustments with EGCG.
More latent cell remediation.

12 LEF Mix capsules at €2.19 per day for conviniently replacing the Green Tea extract, the B-Vitamin Complex and Vitamin E is therefore not really a reasonable option:
My logic here is that relevant to the model, in addition to B,C,E vitamins, it also has -
Suforaphane, proanthocyanidin (for 3a-HSD)
Silymarin, quercetin (GDH)
Hesperedin (which synergises with the forskolin for increasing cAMP)
TMG (NAD+ regen)
Apigenin (https://www.spandidos-publications.com/10.3892/ijo.2015.3243)
Wild blueberry anthocyanin (ammonia->hippurate)
Boron (normalises SHBG, altering ratio of free androgens : free estrogens)
Inositol (albeit a tiny amount, this may be increased separately - I'll be talking about this soon.)
...
If it helps people, a little birdy mentioned iHerb give you 20% off with "SHOPAPP" code, which may still be active.
This works out to be EUR1.32 / day for the Life Extension Mix.
https://de.iherb.com/pr/Life-Extension-Mix-Capsules-360-Capsules/86458

(You will still need additional EGCG and I'm including additional vitamin C as a separate supplement.)

I suppose another factor about this protocol is that the monthly cost is not considered to be a life-long expense. The intention is that once remediation is complete, normal life resumes.

In between, as things improve, it's possible that some of the more expensive items like glutathione may be discontinued.
 
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BrightCandle

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I should put a summary thread together really if we can't get it added to @Hip 's thread - but I assumed it's a bit too soon to compile a list yet.?
I agree it is too early. The response from my body so far is nothing short of miraculous so far but I have had clear days even weeks before and crashed back spectacularly, sustainable trajectory of remission is what I am not sure about.
 

godlovesatrier

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I think remission means your back to your old self. Not just that you no longer have PEM. My sleep is pretty crap on this protocol. I'm still trying to decide if 7 hours sleep is healthy? Seems to get between 7 and 8 but I feel like I could do with more. I've removed the b vitamins as of yest to see if this helps at all. As it's been the culprit in the past.

So even though my PEM has disappeared for the last 6 days apart from the light fatigue from the covid jab which I'm not counting. I think it depends on your definition of remission.

Mentally I'm also agitated but I reckon that until 3 months into the resihi and lion's mane assault my mood won't return to normal.

Also if I consider I've had energy production issues since age 12 and depression with food allergies and what not. All of which could easily be attributable to herpes veridai based on the currently proposed new thinking around viruses by Naivaux and others. Then I might end up in a better place after those 3 months than I did before I really started to feel shitty.

Also feeling a bit aggressive and unpleasantly stimulated today. Although that could quite easily be the covid jab. But it's not enjoyable!
 
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I think remission means your back to your old self. Not just that you no longer have PEM. My sleep is pretty crap on this protocol. I'm still trying to decide if 7 hours sleep is healthy? Seems to get between 7 and 8 but I feel like I could do with more. I've removed the b vitamins as of yest to see if this helps at all. As it's been the culprit in the past.

So even though my PEM has disappeared for the last 6 days apart from the light fatigue from the covid jab which I'm not counting. I think it depends on your definition of remission.

Mentally I'm also agitated but I reckon that until 3 months into the resihi and lion's mane assault my mood won't return to normal.

Also if I consider I've had energy production issues since age 12 and depression with food allergies and what not. All of which could easily be attributable to herpes veridai based on the currently proposed new thinking around viruses by Naivaux and others. Then I might end up in a better place after those 3 months than I did before I really started to feel shitty.

Also feeling a bit aggressive and unpleasantly stimulated today. Although that could quite easily be the covid jab. But it's not enjoyable!
@joshua.leisk told me that he was referring to old posts and he now doesn’t get PEM anymore. So that’s a remission ...
if you still meet the CCC (PEM) then you’re better but not in remission
 

godlovesatrier

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For me I think no PEM and the ability to tolerate excercise with no PEM is remission. I'm hoping to achieve that within the next month. And then sustain it. So be interesting to see if I achieve it.

But as I've managed it 3 times in the last 6 to 9 days I reckon it should be possible.

We've discussed this a lot on the recovery thread and elsewhere. Lots of people can define remission differently. Which can be problematic. Even if it sounds semantic and a tad anal.
 
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For me I think no PEM and the ability to tolerate excercise with no PEM is remission. I'm hoping to achieve that within the next month. And then sustain it. So be interesting to see if I achieve it.

But as I've managed it 3 times in the last 6 to 9 days I reckon it should be possible.

We've discussed this a lot on the recovery thread and elsewhere. Lots of people can define remission differently. Which can be problematic. Even if it sounds semantic and a tad anal.
I lay my health in Joshuas hands now. If he cures me he is the biggest fucking genius in the world. If not, he did a looooot of effort no doctor ever did. And I will go on... or lie on...
 

perrier

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First noticed improvements around 10 days in, substantial improvement 20 days. I have a variety of posts in this topic with the day number in them explaining my symptoms and improvements at the time.
Dear Brightcandle, you may have responded to this before, but in this bombarded world we live in, I do not recall if you were severe or mild ME. Also, there is a progress thread here. I am unable to find it. Would someone be so kind as to indicate it. Maybe it needs a name change: Progress of Joshua Leisk Protocol, or something. Thanks in advance.
 

godlovesatrier

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Here we go:

Bright Candles last background update: page 33 of this thread.

Yes.
On the Hummingbird scale
Worst last year = 3%,
before doing this protocol = 5%,
currently = > 50% maybe more, I haven't tested my body beyond it but I am pushing bands again, jogging about etc it is a stark difference even at my lowest.

In usual ME speak that is Moderate/Severe -> Mild/Moderate or a 1.0 point improvement. I suspect today is PEM but the capacity and limit is much pushed back. I may have crashed but I am cooking my own dinner rather than eating through a straw so even a crashed day is vastly different levels of fatigue.

Doing a proper test tomorrow getting my vaccine, will probably walk about 1.5 miles, furthest I will have attempted to go in 2 years.
 
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