ME/CFS Research: Herpes Autoimmune Spectrum Disorder

Status
Not open for further replies.
Messages
12,038
Likes
26,959
Location
Second star to the right ...
Lost all my energy. No immune response. But Joshua is just great and does everything to find things out. Will continue.
Your absolute courage and determination are absolutely a beacon to us all.


Know that I'm not just aimlessly cheering for you, I'm deeply pulling for this protocol to produce a lasting improvement for you that can be further built on, hopefully, but that at least will pull you out of the disappointment of the post-Abilify downturn. Your fearlessness deserves nothing less :thumbsup::thumbsup: :hug::hug::hug:....

PS .... Hi to @Push Fwd ....
 
Last edited:

pamojja

Senior Member
Messages
2,286
Likes
3,306
Location
Austria
For me, reading through all this I do agree with the underlying thesis, however the approach of using so many supplements is going to lead to all kinds of interactions with people's secondary conditions. Why not take a more personalised approach if one is willing to do the research to understand effects?
  • For example; NAC according to supp.ai has 615 possible interactions between Acetylcysteine and the following drugs and supplements. If you react strongly enough to that alone you're unlikely to be able to continue with the protocol. I'm bringing up NAC specifically because thanks to this thread I decided to retry it as I'm in a state of improved health now but at two 50mg dosages throughout the day. Seemed to have a beneficial effect, I was flying around fighting aliens in my dreams in a good way. I'll continue to titrate up the dosage and unblock things but I can't imagine it would be wise for me to do all of this at once
Agree, we should remind us of the safe strategy to better start with lowest possible doses and increase them gradually over time. The few weeks or months maybe lost might not be as much as very severe reactions to some of the very high doses.

Right away 20 g of Glycine and 10 g of Creatine Monohydrate per day might cause gastrointestinal disstress in some. Up to 900 mg of R-ALA might cause a more consequental redistribution of mercury in at least a few. And with up to 3g NAC pulmonary hypertension might become a possibility for others susceptible already.

Lets not forget at this stage this is a completely experimental protocol. I would only increase very gradually to the full doses, and replace some of the incertain ingretients with safer alternatives. Like for example some Cystein for NAC.

  • If you are tracking your microbiome, you may be able to do better than the InnovixLabs Multi-Strain Probiotic 50 Billion probiotic although it does look to be a diverse one it may aggravate overgrowths if there is a lot of dysbiosis? Unsure on that one.
  • Why are we using the same dosages across people with a range of severity and weight etc?
  • Is the glycine/NAC + liposomal glutathione redundancy to ensure glutathione needs are sufficiently met.
Exactly. Why would I even need a probiotic since my ubiome showed more diversity than 93% of all tested?
Or high doses, while actually weighting 60kgs only?
Or such extensive glutathione supports, since my lab-test showed its already up?
 
Last edited:
Messages
45
Likes
144
Your absolute courage and determination are absolutely a beacon to us all.

Know that I'm not just aimlessly cheering for you, I'm deeply pulling for this protocol to produce a lasting improvement for you that can be further built on, hopefully, but that at least will pull you out of the disappointment of the post-Abilify downturn. Your fearlessness deserves nothing less :thumbsup::thumbsup: :hug::hug::hug:....

PS .... Hi to @Push Fwd ....
Thank you very much, we really appreciate that!
And indeed, Martin is very brave to do all this stuff. Hope he gets some improvement in exchange for that, at least a little bit.

Also I want to say that Joshua is very dedicated and supportive. That's absolutely not taken for granted. :thumbsup:
 

godlovesatrier

Senior Member
Messages
1,241
Likes
2,640
Location
United Kingdom
I don't even think you need to go that high on the dosings tbh.

I titrated glycine and nac for 3 weeks before I went to the higher dose. But even now I only do 600mg 3x a day. Initially 500mg knocked me on my ass for weeks.

Not sure I ever noticed any difference with glycine. But maybe.

As for swapping cystiene for nac I can't see how cystiene would work in place of nac. I would just titrate up from tiny amounts of NAC. I started on 50mg - once a day.

I've never taken creatine. It's never made me feel great also makes me angry so just never took it.

I agree tho. Very important to titrate up from lower doses. Even with the egcg. I started at 25mg and gradually worked up to 200mg. I also didn't really notice any improvement on PEM until I hit about 100mg per day. I haven't taken any in the evening for about 9 days and it doesn't effect the PEM blocking activities at 200mg.

As for r-ala I've never taken more than 200mg for each dose. 3x a day.
 

hapl808

Senior Member
Messages
326
Likes
907
That's one of my issues with the protocol. I feel like there needs to be a stepwise approach, especially for those who are severe or have comorbid MCAS or issues with supplements. I can't see how it's possible to go from 0 to 12g glycine, 16 multi caps, 4 high dose R-ALA, 2400mg NAC, 10g creatine, 14 BCAA caps, sodium benzoate, etc. Just the digestive stress alone would keep me from that.

I'd love to see a way to ease into the program. I'm trying to start off with LOLA (instead of sodium benzoate), small amounts of BCAA and glycine, NAC 1-2 times per day, and a couple other items. But I'm unsure of the importance of each supplement, so I wish I had either a priority list or an explanation of the goals. I don't need to push through 'the 4 days' so quickly, unless that's an important part of the intervention?

And are different probiotics okay? Would eating yogurt suffice? Is ascorbic acid important? Is the type of multi important - or is a multi important at all? Is 20k IU of vitamin D for four days (in addition to presumably 2k IU or so in a multi) important? Are BCAAs important? Should BCAA, glycine, NAC, LOLA be taken at the same time, or will they compete? Should amino acids be taken on an empty stomach or full stomach?

I'm going to hopefully discuss more with Josh and then I can detail my own experiences.
 

BrightCandle

Senior Member
Messages
205
Likes
756
I am not sure but I think @BrightCandle might be female. However I agree with you @Marylib would be nice to know the balance as it does mainly seem to be men who've responded and gone into remission.

I know bright candle said her headaches have gone completely after years of not being able to get it sorted.
He/him, another pesky male in remission.

Today my back started to "resolve", it has felt fused and unforgiving for years but today I feel almost flexible, I can reach further to my toes having done nothing at all, my back just arches more. A lot of the pain went a week ago or so but now my back is feeling improved, this is one of the areas I would guess from the historical pain was/is infected.

Energy is good today, I am starting to jog up the stairs in my house just normally (I always used to jog around all over the place before I got sick) and I am moving with normal pace again without regard to energy. My broadband was broken this week and I had no issue spending 2 days testing routers and flashing firmwares and complex network setup as well as walking out to chat with the engineer who broke it.

Still having some coordination issues (dropped an egg for example) and fogginess mostly by the end of the day. I also spend most of my day now without headaches and the clarity is coming through at times. I haven't finished improving yet, still on 3.2 of the protocol I haven't moved across yet.

C19 Vaccine on monday, off the oats from now until some point next week as recommended and I hope that doesn't knock me on my arse, but since I was made worse by a C19 infection last year I am hoping for some of that sweet long hauler improvement from it in the end.
 

joshua.leisk

Joshua Leisk (Researcher)
Messages
232
Likes
634
Location
Sydney, Australia
I did not. I got fluish for the first couple of days on low carb, but I think that was the keto flu....as my blood draw that day actually showed a decrease vs increase in white blood cells.
I think the key aspect there was that you weren’t taking any beta-glucans. They control the immune response in the serum.

Reishi (NRF2, PIK3, AKT, etc.) + low energy in the mito (mTOR-) allows the cells to signal apoptosis.

Without the appropriate serum response, you may see the other mitochondrial/ metabolic alterations only.

This has been an approach used by VZV / shingles suffering people. Some have chosen to self-experiment with morning doses only of beta-glucans, or take days off them entirely to pace the immune response around sanity and pain management.
 
Last edited:

joshua.leisk

Joshua Leisk (Researcher)
Messages
232
Likes
634
Location
Sydney, Australia
@joshua.leisk are these the latest papers? I'm moderate/severe and prepare myself slowly to go for it. Did any severe patient follow your protocol? Thanks man!
Yes. “A new hope” is the latest one.

We have some severe people doing well and others on their way. One of the challenges I’ve been working on has been co-infections.

As @godlovesatrier mentioned, andrographis is something we’ve recently found reported as useful for 2 of the people who reported getting most of the benefits / response from the protocol, but retained head pressure, depression and insomnia. Seems to correlate to low FSH.

It has a potent effect on intracellular parasites like T.gondii and other pathogens. I suspect it’ll be useful for Lyme and mycotoxins, from the literature.

A small percentage of people have an acute allergic response to it. Needs a careful test dose, if someone was considering it.

People reported success with 400mg active extract (eg. 4000mg, 10%), 3x a day. Early days.

It also exerts benefits for NRF2, etc.
 
Last edited:

joshua.leisk

Joshua Leisk (Researcher)
Messages
232
Likes
634
Location
Sydney, Australia
yes briefly but it only lasted around 2 days.. Its never been as debilitating or painful as Joshua said we should expect. It seems to come and go but often its quite mild, the last one was a few days ago. I've been experimenting with different variables to try and figure out whats going on, it seems to often coincide with with a rise in EGCG ( green tea extract ), but if I maintain it at the higher level the fever doesn't persist. Tried raising vitamin D this week and I have a feeling it made me worse, but it could just be a normal crash caused by over exercise.

My general experience on the protocol is an overall reduction of negative symptoms e.g. aches and pains, headaches, brain fogs, needing to sleep multiple times per day, MCAS, stomach issues etc. I get up the stairs much easier and more recently I've noticed that in some more ... private areas of life my stamina increased in seemingly impossible ways. Downside is I haven't been able to study science properly since starting the protocol, my brain seems like it wants to stay switched off in some ways, but in other tasks and general feeling its similar or better. Also it seems that if I do crash and the negative symptoms come back, I can lessen it with 5g BCAA, Joshua says 10g but that would be an overdose according to the label. Succinnic acid also removes all the aches and feeling of lactic acid / low oxygen etc, but it doesn't seem to fully restore energy / fitness when you are in that super tired worn out state, whereas the first time I took it, it seemed to unlock my full potential.
One thing I’ll remind people is that the diet is a critical component of this model / method.

The EGCG (and friends) will reduce the GDH related energy excess and hyperinsulinism.

If the balance is not being met around GDH : a-KGDH, then a single high net carb meal can induce PEM. The profile of those carbs and how this relates to blood glucose is of high importance.

There are many other factors that increase GDH - spiking testosterone -> DHT from eg. resistance training, supplements are examples. The 5-AR reduction from reishi is helpful here in trying to normalise this.

Sulforaphane, in v3.3 increases 3-HSD, as does procyanidin. (3-HSD appears broken, around NADPH and retinoid metabolism and causes alcohol intolerance, high DHT, high allopregnanalone. This increases GDH and reduces LH.)

EGCG reduces GDH, in part, by partially blocking the androgen receptor.

Most of the GDH reducing components I’ve been looking into are found in post-menopausal plant extracts. An interesting pattern is that they’ll also have literature showing anti-EBV, anti-cancer and mitochondrial remediation benefits.

Spironolactone partially blocks the androgen receptor and reduces GDH also. It’s very good at that.
BCAAs are another. They’re simultaneously useful for other metabolism functions, so it’s a double-edged sword here. 😂

When looking at the infected cell behaviour, the energy in the mitochondrial reactions is what controls latent vs lytic states. GDH is something which controls mitochondrial energy. There are other inputs. eg. Arginine increases mitochondrial energy via fumarate (think arginine in HSV-1/2 flare ups). Stress increases adrenergic signalling and increases energy from fatty acid oxidation. Sunlight / UV exposure increases ETC and ROS. Exposure to other forms of radiation may do the same thing.

Latent phase is the mitochondrial low-energy mode and is primarily for undetected replication of one or more cells in a tissue / organ, slowly becoming a “raft” and quietly taking over that tissue. It’s never dormant.

Lytic phase is the mitochondrial high-energy mode and is used for infecting other tissues / organs at a high rate, hijacking the immune system. This “seeds” infected cells into other tissues, which then can create rafts of infected cells, via latent replication.

From the serum, the immune system can detect and kill lytic cells. This is when we “notice” an infection - because it hurts when the immune system attacks the cells / tissues.

The immune system can’t easily see inside cells and requires the cell to signal for apoptosis when it detects that the “running code” is different to the “stored code”. This is mediated by NF-kB.

Problem is, the apoptosis signalling is disrupted by the viral infection.

Adding further complication is that the cell appears to prioritise mTOR / protein synthesis over apoptosis. (“I cannot die until my work is done.”) The viral protein synthesis tasks drive mTOR up, by default.

Until you bring the energy in the mitochondrial reactions down and pull down mTOR, it appears that even if you’ve “fixed” NF-kB, the cell won’t signal for death / replacement.

It may also be that the cell doesn’t even need much help on NF-kB and will simply signal for death if you pull down the energy/mTOR alone.
 
Last edited:

joshua.leisk

Joshua Leisk (Researcher)
Messages
232
Likes
634
Location
Sydney, Australia
That's one of my issues with the protocol. I feel like there needs to be a stepwise approach, especially for those who are severe or have comorbid MCAS or issues with supplements. I can't see how it's possible to go from 0 to 12g glycine, 16 multi caps, 4 high dose R-ALA, 2400mg NAC, 10g creatine, 14 BCAA caps, sodium benzoate, etc. Just the digestive stress alone would keep me from that.

I'd love to see a way to ease into the program. I'm trying to start off with LOLA (instead of sodium benzoate), small amounts of BCAA and glycine, NAC 1-2 times per day, and a couple other items. But I'm unsure of the importance of each supplement, so I wish I had either a priority list or an explanation of the goals. I don't need to push through 'the 4 days' so quickly, unless that's an important part of the intervention?

And are different probiotics okay? Would eating yogurt suffice? Is ascorbic acid important? Is the type of multi important - or is a multi important at all? Is 20k IU of vitamin D for four days (in addition to presumably 2k IU or so in a multi) important? Are BCAAs important? Should BCAA, glycine, NAC, LOLA be taken at the same time, or will they compete? Should amino acids be taken on an empty stomach or full stomach?

I'm going to hopefully discuss more with Josh and then I can detail my own experiences.
I think one conceptual aspect around this is that the protocol is designed to cause an intense immune response and attack every problematic tissue in your body.

It’s going to be unpleasant, by design.

For this reason, my logic suggests there’s little benefit in trying to “ease into unpleasantness”.

Likewise, when the purine nucleotide cycle restarts, very early on, you’re expected to be hit by a wave of backlogged ammonia, which will cause temporary (reportedly 3-4 days) PEM / headaches, etc. and this is why the sodium benzoate (or L-ornithine L-aspartate) is included.

When the immune response commences, people (myself included) report being dizzy, fatigued, wiped out and then flu symptoms - aches, pains. This isn’t enjoyable either.

The best advice for anyone considering self-experimenting is to follow the published method accurately. Don’t expect it to be at all pleasant in the beginning. You have to “do the work”. The gut microbiome and gall bladder alterations are going to be uncomfortable for a period.

You may be able to take holidays from “the work” by removing beta-glucans, butter/butyrates from your diet for a period of time. This could be a gentler way to start the protocol, as mentioned in the early preview of v3.3.

“It gets worse before it gets better.” ☺️
 
Last edited:

joshua.leisk

Joshua Leisk (Researcher)
Messages
232
Likes
634
Location
Sydney, Australia
@joshua.leisk i’ve been thinking about this a lot, and as far as I can see, physically pushing myself causes an immune response which my body then freaks out about and starts to shut down. So why would we need to take something to cause the immune response, couldn’t we just do something that would normally aggravate it?
Thanks
Can you describe this more? What sequence / symptoms are you noticing?

Cheers
 

joshua.leisk

Joshua Leisk (Researcher)
Messages
232
Likes
634
Location
Sydney, Australia
Agree, we should remind us of the safe strategy to better start with lowest possible doses and increase them gradually over time. The few weeks or months maybe lost might not be as much as very severe reactions to some of the very high doses.

Right away 20 g of Glycine and 10 g of Creatine Monohydrate per day might cause gastrointestinal disstress in some. Up to 900 mg of R-ALA might cause a more consequental redistribution of mercury in at least a few. And with up to 3g NAC pulmonary hypertension might become a possibility for others susceptible already.

Lets not forget at this stage this is a completely experimental protocol. I would only increase very gradually to the full doses, and replace some of the incertain ingretients with safer alternatives. Like for example some Cystein for NAC.



Exactly. Why would I even need a probiotic since my ubiome showed more diversity than 93% of all tested?
Or high doses, while actually weighting 60kgs only?
Or such extensive glutathione supports, since my lab-test showed its already up?
One thing about the protocol design is that it’s aimed to cover a wide range of circumstances, rather than individual circumstances. It works on the assumption of “worst case scenario”, in that respect.

eg. If someone has data showing a functional gut microbiome, they may not need a probiotic. However for a “one size fits all” protocol, I need to allow for these things in the method, generally. ☺️🙏🏻
 

xebex

Senior Member
Messages
644
Likes
1,232
Can you describe this more? What sequence / symptoms are you noticing?

Cheers
when I crash I will usually get very sleepy and have to go to bed and usually lie there for several hours in a semi-conscious state, sometimes in a silent migraine state too with neuro issues, then when I wake up the next day I will experience flu-like symptoms - the feeling of a head cold coming on, aching muscles, sometimes POTs symptoms and an overall weakened resilience to activity so everything is much harder to do than my usual baseline, it's the malaise feeling you get at the start of flu, plus autonomic symptoms and other weird stuff. Is that not the immune response? I always thought it was my immune system kicking in, isn't that what PEM is?
 

joshua.leisk

Joshua Leisk (Researcher)
Messages
232
Likes
634
Location
Sydney, Australia
when I crash I will usually get very sleepy and have to go to bed and usually lie there for several hours in a semi-conscious state, sometimes in a silent migraine state too with neuro issues, then when I wake up the next day I will experience flu-like symptoms - the feeling of a head cold coming on, aching muscles, sometimes POTs symptoms and an overall weakened resilience to activity so everything is much harder to do than my usual baseline, it's the malaise feeling you get at the start of flu, plus autonomic symptoms and other weird stuff. Is that not the immune response? I always thought it was my immune system kicking in, isn't that what PEM is?
My observations and experiences suggest this is the usual ammonia and cascade. Many of the things you mention are described in the model as downstream of Acetyl-CoA depletion and therefore related to impaired beta-oxidation pathway.

In the model, replenishing Acetyl-CoA, via eg. NAC, BCAAs may be helpful here, along with a lot of water to excrete the urea, etc.
 

jump44

Senior Member
Messages
122
Likes
164
Definitely have been hit hard with mono/flu symptoms. Also probably made worse by mowing the lawn the other day. But it’s been interspersed with clarity/energy , which I never get with classic PEM. As a male however I admit I’m a bit concerned with the emphasis on androgen blocking and 5ar inhibiting- these things can cause issues that don’t just go away for some unlucky men.. however I am willing to take the chance if it ultimately helps the cfs but I do admit I find it somewhat concerning. I trust the other “pathways” will balance all this out.
 
Status
Not open for further replies.