ME/CFS Research: Herpes Autoimmune Spectrum Disorder

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joshua.leisk

Joshua Leisk (Researcher)
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I'm an anomaly. I'm a fully recovered CFS/ME sufferer (25 years free and clear) with a strong background in IT and and interest in bioinformatics. I "retired" at 38 and got bored. I like puzzles, pathways and systems. This was a puzzle that had bothered me for a few decades, so I thought it was worth helping people solve.

Here are our three most recent papers -

https://www.researchgate.net/publication/350043016_The_true_nature_of_an_autoimmune_disease

https://www.researchgate.net/publication/350399073_The_involvement_of_acetate_aspartate_butyrate_and_enzymatic_cofactors_in_the_HASD_CFSME_model

https://www.researchgate.net/publication/350956432_CFSME_A_New_Hope
(this paper is elaborated on here - https://forums.phoenixrising.me/thr...toimmune-spectrum-disorder.83371/post-2335821)

For CFS/ME, our primary research focus is the liver.

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 - the metabolic burden of the latent cell activities, hard-wired by GLS1 - KGA, GAC + GDH, etc., for protein-synthesis tasks, glutaminolysis and lactate production interfere by the behaviour of the neighbouring hepatic cells. eg Lactate cycle metabolism. Arresting the lytic phase does not solve CFS/ME, but it will reduce the antibodies.

Checking eg. EBV EBNA,VCA IgG counts for systemic latent infection and then inferring localised hepatic infection by performing the 'succinate challenge' I mentioned in the paper gives us an understanding of the pathophysiology. For other disorders and diseases, it's largely tissue specific.

We would happily perform more experiments ourselves, but we're a pair of researchers without a lab facility.

We would love to run a clinical trial based on some robust preliminary test results, however we are reliant on others for properly testing this hypothesis. We are currently engaging with some existing parties to make that happen, although are open to assistance from any other parties.

We're happy to work with others. In case we have misinterpreted any cited papers, we're open to any discussion and correction.

The background on this discovery is that in the course of my normal consulting, I had a cluster of 5 diet coaching clients over roughly one month presenting for a number of different goals, yet similar issues - with a common complaint of daytime fatigue.

Most had joint pains and involuntary muscle contractions. The male and female clients had endocrine, sleeping and neurological disorders, such as acute anxiety. The males and females exhibited signs of alopecia. All had extensive pathology data, spanning more than 10 years and a history of symptoms longer than 15 years. Only one client had ever been officially labeled as a "CFS/ME" patient.

I compiled and analyzed their pathology data and saw a common pattern of urea cycle abnormalities, cortisol / adrenal cortex dysregulation and mild leukopenia - specifically, borderline subclinical lymphocytes. ANA, CK, cRP, ESR, thyroid markers all unremarkable. Some minor liver enzyme elevations in some clients, which appeared to match their body composition and life choices. I thought the overall pattern was interesting, so I kept investigating.

Most clients had acute eating disorders. Ear/nose/throat infections were common. Environmental allergies were common. There was a history of GI issues and all had a specific pattern of food intolerances. Eggs and lecithin were consistently mentioned. I found that even more interesting.

I assessed their dietary habit using one of my favourite nutrition tracking tools, "Cronometer". The observed protein intake was very low - typically less than 40 grams per day, which did not match the unusual serum urea also being observed - BUN was typically high range, or in one client, very low range. This was interesting, because it suggested that either glutaminolysis was being used, and / or the urea cycle was impaired at different times.

3 of the clients had reported some benefits from ketogenic diets. 1 of them was currently employing a ketogenic diet. The others had not attempted this. This 1 client chose to discontinue their ketogenic diet and had an acute worsening of symptoms. This was interesting because it demonstrated a pattern of mitochondrial impairments.

All clients had a habitual lifestyle that obsessively revolved around dietary supplements. This was also interesting and it allowed me to ask them what supplements they took regularly and why.

Importantly, I also asked them what they didn't take and why - "what had they experienced negative reactions to?"

A common list of "problem" supplements for all clients was acetyl-l-carnitine, EGCG, choline, arginine, citrulline. Some of them reported that acetyl-l-carnitine caused acute edema and myopathy. I found that very interesting, also - suggesting influences to fatty acid oxidation / PDH, GDH, acetylcholine receptors, respectively.

All of the clients had exercise intolerance to even the mildest exertion levels, with suboptimal lactate threshold and oxygenation, even beyond my expectations for a sedentary lifestyle.

3 of the clients had prescriptions for salbutamol inhalers.

From this combined data, I saw more patterns forming. I analyzed other data they had captured, including HTMA tests, which excluded heavy metals, etc as a source of hypoxia.

At this point, I decided to take a personal interest in these cases and chose to work closely with 2 of these clients on a daily basis, exploring published literature and talking with them for typically 5-8 hours a day over many months, observing and analysing high levels of detail about their diet, daily activities, symptoms, influences / triggers / responses, while assembling connections between individual data points. This was a performed without any financial consideration. Being "retired" made this level of dedication and focus possible.

Dietary intervention of adding 2 eggs and some soy lecithin to every meal and 2 more before bed improved or resolved involuntary muscle spasms, with some not-unexpected discomforts. This was partially replaced by choline bitartate.

Pathology for Plasma Amino Acids found some common abnomalities with elevated glutamine, glutamic acid, low 1-methyl-histidine.

Exploring the literature and looking at the published CFS/ME metabolomics data, I saw many parallels between client data and published data. I explored this further, creating new connections along the way.

Serology markers showed high titre active EBV in both cases. There were differences in testing method availability, due to geographical location.

(Shared with full consent / expressed permissions.)

Client 1 -
EBV EBNA IgG++
EBV VCA IgG+++ (exceeded reporting thresholds)
EBV VCA IgM-
EBV EA was not provided
CMV IgG-
CMV IgM-
HSV-1++
HHV-6+
aPL-
AChR-MUSK-

Client 2 -
EBV EBNA was not provided
EBV VCA IgG++
EBV VCA IgM+
EBV EA was not provided
CMV IgG ++
CMV IgM -
aPL-
AChR-MUSK-

At this point, I considered that we had maybe progressed beyond "smoke", to "fire".

[QUESTION - "Perhaps the impact from lytic EBV infection or CMV was the source of the symptoms?"]

I reached out to those 2 clients' physicians and requested assistance. Under their care, off-label spironolactone (aldactone) was initiated at 25mg/day (Campo et al.) and client 1 increased to 2 x 25mg/day after 1 month. Client 2 also chose to self-administer nigella sativa for their CMV infection.

Over 3 months of close interactions, I observed many patterns in triggers / responses and durations, including associations between both clients' reported salbutamol usage vs timing of and cessation of upper-right abdominal pain, with increased energy levels.

The abdominal pain followed periods where they had been feeling better, with improved energy levels and decided to make use of them. Due to concomitant hypoxic symptoms, they self-administered salbutamol and this demonstrated a pattern of resolving their abdominal pain and also a reduction of the duration and intensity of post-exercise malaise. It also increased their energy levels. I found this very interesting.

The location of the pain and the relationship to the salbutamol dosage suggested strongly that beta-oxidation pathways were involved and the lactic acid cycle was impaired at hepatic gluconeogenesis. It didn't explain the cause of the high lactate, which I considered to be related to the impairments surrounding energy production.

Via close observation of client myopathy vs activity, I could see that unusual amounts of lactate were being generated, in addition to impairments in hepatic conversion back to glucose.

Combined with the noted urea cycle abnormalities and hypoxia, this was pointing strongly to a deficit in succinate and fumarate. The general lack of energy was suggesting an insufficient amount of ATP was being generated. This pointed to Complex V.

Gradually, over these months, I collected enough information from observations and literature searches to collectively create a hypothetical map.

Client 1 obtained a high result for EBV PCR roughly 1 month after starting spironolactone and flow cytometry, from the same sample showed low CD4. At 2 months, returned negative on PCR tests. WBC / flow cytometry all amazingly unremarkable.

Client 2 obtained negative results on both EBV and PCR test at roughly 6 weeks.

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.

Both clients had some tangible improvements to many symptoms, but were still showing all of the hallmark CFS/ME pattern of impairments I had personally experienced all those years ago.

[ANSWER - "The lytic phase is only partially responsible for CFS/ME. (n=2)"]

[QUESTION - "Wonderful, so what does this mean?"]

Looking at the pathway map I had created, three "hot-spots" were a-KGDH, PDH and selective beta-oxidation pathway insensitivity.

NutraEval reports are incredibly useful for identifying these abnormalities, however these need to be interpreted based on the level of activity prior to sampling, in much the same way that metabolomic studies need to be controlled against time of day and prior activity levels to provide any meaningful data.

Further to this, my research into the behaviour of HHV-infected cells revealed a metabolic preference for glutaminolysis (Krishna G et al), just like many cancer cells (Song Z et al.) and an ability to replicate via transcytosis (Hutt-Fletcher L et al.). This suggested a number of things, not the least of which was that these infected cells would be susceptible to the same metabolic influences as those cancer cells (Saunier E et al.). I considered that just like in certain types of cancer cells, the location and behaviour of the latent cells would have influence on the neighbouring cells. Where these are hepatic cells, this would unduly influence the hepatic function, in particular with regards to lactate metabolism / gluconeogenesis. In other tissues, many other disorders would be expected, where collagen synthesis and other tasks downstream of prolyl hydroxylase activities are degraded, leading to various states of inflammation and cortisol dysregulation.

As such, in my capacity as a diet and health coach, I educated Client 1 and Client 2 on the benefits of specific over-the-counter dietary supplements which are known for addressing these pathways, with advice to verify with their physician if contraindicated in their illnesses.

In the general population, like most dietary supplements in general, these specific dietary supplements would have little to no noticeable effects or benefits beyond those provided by a normal, balanced diet. They chose to purchase these from their local health food store or supplement vendor and self-administer them. They further chose to provide me with reports on their experiences with this self-experimentation.

Unlike the typical 'non-response' expected in the general population, the effects from these specific supplements were reported as both rapid and acute in both clients. Their energy levels returned to normal and they regained normal daily functionality and lifestyles. Due to their natural curiosity and a long history of experimentation with supplements, they also tried different combinations and dose schedules of these supplements and reported the effects. I analysed their reports and noticed a pattern, where failure to address any one of these "hot-spots" I had educated them on led to a consistently repeatable pattern of initial impairments and a resumption of full CFS/ME symptomology.

Using the combination of dietary supplments, viral EBNA IgG has been demonstrated to have decreased by 25% over 2 months, suggesting reduced systemic burden.

[ANSWER - "We are long past 'smoke', well past 'fire' and currently 'discussing the merits of different coloured fire extinguishers.'"]

[QUESTION - "This needs robust testing - how do I share this information with people who are in a better position to make use of it and without creating problems associated with communicating this around a demographic of patients who are desperate for early answers?"]

At this point, although having read perhaps 900 papers, I thought it would probably be best if I studied the literature further, wrote a review and shared it with the community. This presented some new difficulties, as although demonstrated by my recent manuscript, through personal interests my understanding of metabolism, rheumatology, cellular biology, immunology, endocrinology and biological pathways could be considered with some equivalencies to a PhD level education, due to my life choices and preference for self-education, usually by intense reading, I lack the credentials required to present these findings to a wider audience, in the format they would normally be inclined to appreciate and give due consideration.

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. This is also likely why I left school at 14 and "retired" at 38. Overall, I have lived an unusual life.

A self-taught "diet and health coach" traditionally does not write medical journal articles on complex metabolic disorders and virology. This is a significant anomaly, although my life to-date has been one long anomaly. Importantly, I also lacked a full understanding of the nuances and expectations of academia, with regards to publishing material for peer-review.

[ANSWER - "Fortunately, through fate and/or luck, my life-partner and co-author happens to be a brilliant scientist, holding a PhD in Neuroimmunology, with a Masters in Biochemistry. Keeping in line with my usual preference for organic learning, she helped me understand the normal requirements for publishing a paper, assisted and answered questions about lab methodology, where I found criticisms of papers I was reading, edited and helped proof the manuscript, along with many other key aspects of the journey towards where we are today. I'm always thankful for having her in my life." ]

In the process of continuing to map the pathophysiology, draw the diagrams and write the paper, my research connected the dots with a broader array of disorders and diseases. I realised that my research had significantly greater implications for many diseases and disorders. During the many weeks that was required to author the paper, I was was also contacted by some other clients and friends who had a number of different diseases / disorders - including bipolar disorder, schizophrenia, ehlers danlos syndrome, IBS, lupus and rheumatoid arthritis, which were already strongly hinted at having a common origin, by the growing manuscript and diagrams.

Consequently, I found the same signature of metabolic alterations and serology markers in those clients and they show an acute response to the same dietary supplement advice, although there are variations and further optimisations possible where hepatic impairment cannot be demonstrated or where lytic phase cannot be detected in serology. For each of these disease model sub-types, I have drafted early specifications that can be used for testing in clinical trial research around these disorders.

In v1, there were two small mitochondrial "leaks" to resolve regarding a-KG accumulation and ROS. They're now fixed in v2 and provide a treatment which allows normal daily life, however this can be further improved.
v2 is the "stable" tree, which will be refined with feedback.
"Unstable", or
v3 is already being conceived being used / tested.
A "Github" repository is possibly needed. :D

At this point, we have also filed a patent for the formula, to also aid later discussions with pharmaceutical companies. We are not selling any products. We are not selling any services. The treatment involves items that can be bought at vitamin stores and supermarkets. If people need help, I've been offering my time and assistance without any thought of financial gain. This is real and my aim is to help people.

However, this is also where WE need help in continuing this journey.

"Can you please assist us in making this a success for everyone?"

Here are the current draft specifications for a pilot study we are looking to conduct. Any input, criticism or other dialogue is welcomed and encouraged.

(edit: As the draft spec gets regular updates during the development lifecycle, I've now made a Bitly redirect that always points to the latest version, rather than a native redirect from my website. I'm trying to avoid any self-promotion.)

http://bit.ly/hasdcfslatest
 
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Pyrrhus

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For CFS/ME, our primary research focus is the liver.
I'm tagging @mariovitali here, who has also taken an interest in liver function in ME patients.

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
I'm also tagging @sometexan84 here, who has done a lot of research tying herpesviruses to auto-antibodies.

We would love to run a clinical trial based on some robust preliminary test results, however we are reliant on others for properly testing this hypothesis. We are currently engaging with some existing parties to make that happen, although are open to assistance from any other parties.
Yup, that's always the biggest obstacle to performing clinical trials- finding participants!

The observed protein intake was very low - typically less than 40 grams per day, which did not match the unusual serum urea also being observed
Interesting...

3 of the clients had reported some benefits from ketogenic diets.
Now I'm tagging @leokitten who also benefitted significantly from a ketogenic diet for a while.

Some of them reported that acetyl-l-carnitine caused acute edema and myopathy.
That's a new reaction to me!

EBV EBNA IgG++
EBV VCA IgG+++ (exceeded reporting thresholds)
EBV VCA IgM-
EBV EA was not provided
My understanding is that EBV Early Antigen (EA) is most consistently correlated with reactivations, so it's a pity you couldn't have data on that.

Further to this, my research into the behaviour of HHV-infected cells revealed a metabolic preference for glutaminolysis (Krishna G et al)
You may be interested in this paper, which implies that glutaminolysis is "activated" whenever pyruvate is lacking:

Glutamine oxidation maintains the TCA cycle and cell survival during impaired mitochondrial pyruvate transport
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4268166/
 

joshua.leisk

Joshua Leisk (Researcher)
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I'm tagging @mariovitali here, who has also taken an interest in liver function in ME patients.

My understanding is that EBV Early Antigen (EA) is most consistently correlated with reactivations, so it's a pity you couldn't have data on that.

You may be interested in this paper, which implies that glutaminolysis is "activated" whenever pyruvate is lacking:

Glutamine oxidation maintains the TCA cycle and cell survival during impaired mitochondrial pyruvate transport
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4268166/

Thank you! Ahh yes, some familiar faces. @mariovitali I've been getting to know quite well over the last few weeks. We've had some good discussions and there's some amazing synergies. I really, really like his software for crunching Pubmed data. Provides lovely breadcrumb trails to follow.

@sometexan84 and I have talked a little on Discord although I wasn't fully aware of his HHV research. I'm always interested in whatever people have to share.

Yes, fortunately the follow-up EBV real-time PCR tests were positive, which made that much easier. I've seen the EA data for many other people since that time. There are some patterns.

I've read that glutaminolysis get triggered by a number of states - high lactate, low glucose, low SIRT4, etc. I'm still exploring this angle now, with some acute interest.

Also, please note that the v2.x draft spec linked in my first post gets updated and revised with feedback almost weekly. It's far from perfect yet... but we're getting closer to getting the balance correct. There are so many variables. Dietary inputs and activity being a key part. Essentially, you'll see from the dietary component, we're trying to create a 'high protein diet' that is also low 'glutamate / low nitrogen', to accommodate and balance the behaviour of the cells. To do this, we have a low-moderate protein intake and then add EAAs / BCAAs.

While this is happening, as you'll see from the second paper, the gut microbiome is being remodeled to produce these organic acids directly, as they used to before CFS/ME.

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

The synopsis is (the technical details are mostly in the second paper, with reference to the first):

A. In CFS/ME, the mitochondrial efficiency is acutely impaired via aKGDH defciency - okay, so we can fix easily via anaplerosis at succinate..

(..so, we now have energy but the PDH issues cause lactate and the mitochondria are still broken at aKGDH, so we need to do something about that, as these now efficient mitochondria are increasing their outputs of unwanted metabolites..)

B. We added R-ALA and fix the PDH / lactate issues.. and in v1 initially increased beta-AR signalling efficiency by brute-forcing salbutamol.

(..great that seems simple enough, but may have longterm questions about metal chelation... and having high levels of adrenaline is unwanted..)

C. We looked at the accumulating glutamate and said..
"Well, there are perhaps 5 paths for this to get dealt with.."
1.To glutamine and PAGN, absorbing one ammonia (but you consume more acetate and butyrate, which need addressing)
2.To aKG and into the TCA, making one ammonia
3.To aKG and transamination, making one ammonia
4.To aKG and exported as an exosome, needing melatonin, making one ammonia (this works at night, during sleep)
5.To GABA, but this is only in specific neurons

(..so in the process of option 1, this normally consumes acetate and butyrate)
...
This means acetyl-CoA is depleted.
Which means acetyl-choline production gets impaired affecting brain and muscle activation.

Also meaning acetyl-l-carnitine production gets impaired affecting fatty acid oxidation and downstream needs
This means various neurological pathways get affected, eg. NAT8L. N-acetylserotonin etc.. this can give you depression

The upshot of this is that via a forced increase of aKG disposal, you're proportionally low on acetate, being disposed of to make PAGN. This now impairs the PAGN pathway, downregulates beta-oxidation via low acetyl-CoA (and decreases all the other acetyl-* synthesis), putting pressure on the other 4 nitrogen disposal pathways.
The additional acetate should come from the ACV in the treatment plan. A weakness in v2 is that I suspect we're currently not getting enough acetate from the ACV.
An option is to increase the acetate intake, eg. sodium acetate, magnesium acetate etc.
..or conversely, reduce the aKG in the first place - the latter being the more optimal way forward.
Perhaps a little of both being a sensible approach.

Once the gut microbiome gets healed, this becomes significantly easier, as the microbes produce these acids in vast quantities, once the microbiome is back to normal.
 
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Learner1

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The upshot of this is that via a forced increase of aKG disposal, you're proportionally low on acetate, being disposed of to make PAGN. This now impairs the PAGN pathway, downregulates beta-oxidation via low acetyl-CoA (and decreases all the other acetyl-* synthesis), putting pressure on the other 4 nitrogen disposal pathways.
How do you measure acetate?

What's PAGN?

What other acetyl-* ?

What other nitrogen disposal pathways?

Sorry, these are new concepts. No one has discussed them around here before.... And trading through your experimental protocol, I thought of these questions.

First, is this the very same protocol for a 95lb 20 year old woman and a 230lb 60 year old man?

Seems like there's about 85-125g of extra aminos you're proposing, on top of diet? Many people typically eat 60-70g protein daily. Wouldn't that increase mTOR, which might have undesirable effects? Wouldn't too much protein eventually convert to glucose?

ALA and biotin oppose each other. Why so much ALA and no biotin?

ALA can pull out heavy metals sequestered in mitochondria. If they have nowhere to go, i.e. you don't have adequate glutathione and transsulfuration pathway, the metals can get redeposited somewhere else, which may not be a good idea... Why so much ALA without suspecting this problem?

Thorne Research makes great supplements, but their Basic B Complex is inadequate to support methylation. It's also very low in riboflavin, which can lead to high succinic acid. It has niacin, which reverses methylation. The amounts of folate and B13 are far too low for many of us. There's no zinc, magnesium or potassium, all needed for methylation.

Why choline bitartrate? What's the purpose? Why not lecithin or phospholipids, like phosphatidyl serine, phosphatidyl ethanolamine, phosphatidyl choline?

Why such a low dose of melatonin? Many of us are on 1, 3, 5, or 10mg...

Why 20g glycine? How does it mop up ROS? Why not glutathione or superoxide dismutase?

Why 2.4-4g NAC? Why not C to recycle glutathione? Why not no glutathione?

Why so much resveratrol? Resveratrol had a U shaped curve of effectiveness and can disrupt thyroid function. .

Why 40-80g of BCAAs? Isn't there a point of having too much?

Why that specific probiotic? It may not be tight for some patients' microbiomes.

FOS can get some patients into trouble :

"Inulin/FOS feeds only good bacteria, right?
Wrong. Manufacturers claim that Inulin/FOS specifically feeds only good bacteria. The reality of the situation is much different. If you examine the scientific literature about Inulin/FOS, you will find that this is untrue. The best example is concerning Klebsiella. Recent studies have shown that Inulin/FOS encourages the growth of Klebsiella, a bacterium implicated in Ankylosing Spondylitis and increased intestinal permeability. Inulin/FOS may indeed promote the growth of lactobacillus bacteria, but what other potentially harmful bacteria are we feeding as well? Furthermore, we have not even addressed the issue of yeast. Many different species of yeast are able to utilize Inulin/FOS for energy. Historically, microbes have demonstrated the innate ability to adapt to almost any condition and fuel source. If bacteria can adapt to break down industrial solvents in our soil and use them for energy, it would be irresponible to think that they will not adapt to utilize Inulin/FOS, a high energy carbohydrate. There are hundreds of different species of bacteria and several yeast strains living in our GI tracts. Studies have only looked at the effects of Inulin/FOS on a handful of these microbes."

What if someone is allergic to dairy? The dairy, probiotic, casein, and butter could cause problems...

What if someone is celiac?

What if someone has oxalates? The spinach, tofu, leeks, Jerusalem artichokes, asparagus, and potatoes would be problematic.

Why not use Valtrex, Valcyte or Famvir? Some studies have shown spirinolactone increased tumors. It also can increase thyroid antibodies and decrease testosterone. According to DrugBank, spirinolactone was originally only studied for its potassium sparing diuretic effect. Spironolactone competitively inhibits mineralocorticoid receptors in the distal convoluted tubule to promote sodium and water excretion and potassium retention. Inhibition of this receptor leads to increased renin and aldosterone levels.
Spironolactone is structurally similar to progesterone and as a result is associated with progestogenic and antiandrogenic effects.

Thank you for answering any of these you care to.
 
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Seems like excellent research although I can only loosely follow along the terms that i've picked up on this website. I find it particularly interesting because lately i've been suspecting I have strong viral activity interfering with my liver, reason being is my ALT level is 140. No liver pain or jaundice etc ... I got referred for an ultrasound but not being an expert i'm at the mercy of the NHS. Presumably if viral as in your subjects nothing can be detected by ultrasound.

Do any of your study subjects present with high ALT ? I was healthy then had sudden viral onset like many others, me/cfs severity reasonably stable since 2017, so seemingly inconsistent with some sort of well documented progressive liver disease.
 

Learner1

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leokitten

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@joshua.leisk if your theory for ME is correct then I’m a textbook case.

EBV VCA IgG +++ (beyond reporting threshold)
EBV EBNA IgG +++ (beyond reporting threshold)
EBV EA-D IgG +++ (beyond reporting threshold)

CMV IgG +++
HHV-6 +++

Chronically above normal liver enzymes (not very high but above normal range)
Evidence of liver enlargement, even though I’m thin normal weight, eat healthy, etc

Only treatment that ever had any effect, other than Abilify, was ketogenic diet which worked for a few months, but then slowly stopped working and I started having chronic extreme hunger (likely from overexertion)

What supplements do you recommend I take to try and battle whatever might be happening in my liver that might be driving my ME?
 
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Learner1

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@joshua.leisk if your theory for ME is correct then I’m a textbook case.

EBV VCA IgG +++ (beyond reporting threshold)
EBV EBNA IgG +++ (beyond reporting threshold)
EBV EA-D IgG +++ (beyond reporting threshold)

CMV IgG +++
HHV-6 +++

Chronically above normal liver enzymes (not very high but above normal range)
Evidence of liver enlargement, even though I’m thin normal weight, eat healthy, etc

Only treatment that ever had any effect, other than Abilify, was ketogenic diet which worked for a few months, but then slowly stopped working and I started having chronic extreme hunger (likely from overexertion)

What supplements do you recommend I take to try and battle whatever might be happening in my liver that might be driving my ME?
You'd need to have more labwork, like plasma amino acids, organic acids, etc.

And have you tried Valcyte?
 

joshua.leisk

Joshua Leisk (Researcher)
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Hi All, sorry for the absence!

I thought I had notifications set up, but clearly that wasn't happening.

I've been rather busy researching / writing and we're about to release a 3rd paper in the next few days.
The language is aimed at a wider audience and answers many of these questions, or will likely replace them with new questions.

Based on the new paper, the solution presented will almost completely replace the current protocol by going a layer deeper and instead targeting the entire cascade of issues at the source, removing the need for the long laundry list of interventions to manage the issues mentioned in the first two papers. It' doesn't require prescription medication.
 
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Really interesting research paper. Most of what you've got on here aligns with what I've noticed, in that some souped up nutritionals, like multi vits etc just cause insomnia and don't seem to address the issues. D-ribose never helped me for example, I just crash if I take that every day. Also you've not got q10 - which while useful seems to not owrk for long.

Also I've tried magnesium supplementation and vitamin d, but these both deplete other nutrients which just leads to different types of fatigue. I'm just about to try some new things to treat my ME, I think your guide in the above post will be really helpful, so thanks!
 
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I see you mention 10g of BCAA@'s 4x a day? I get insomnia if I take about 5-8 grams in the am, for me it takes about 3-4 hours for it fully kick in. If I add a 14:1 reishi extract into the mix 800mg then I definitely have trouble sleeping. Yet I see you've only recommended melatonin of 600mcg, this on its own probably wouldn't be enough to get an over stimulated patient off to sleep. I just read Learner above and he's right most are on 1 to 10mg, I take 1 to 3mg depending on severity of physical over stimulation.

Have you seen any patients (I assume not based on the above write up re 2 patient case study) have bad insomnia from your proposed full protocol? As it seems like you've got a ton of stimulants (by way of there biological effects not the fact that they are stimulants) in the protocol.

I've recently had some luck changing my microbiome, albiet a small amount and it's got me intrigued to try to see how far I can take it.

I just researched the probiotics you mention as potential recommendations, I know other probiotics exist! I currently use biokult but I haven't a clue if that's any good, although it does actualy make me feel better in my case. But only alongside Lauricidin for bacterial cleardown.
The probiotic you mention "InnovixLabs Multi-Strain Probiotic " has some pretty bad reviews on amazon, the reviews mainly point towards incorrect bacterial species being listed on the website vs the box that is actually delivered, which makes it a tad dubious to figure out what's in it: https://www.amazon.co.uk/InnovixLabs-Innovix-Multi-Strain-Probiotic/dp/B07TH9DQTW the american website reviews seem a lot better, but that does make me wonder why the UK website reviews are so much worse.

You also mention eggs, dairy and such. I've been allergic to eggs and fruit since I was about 14, the former gives me headaches, nausea and mild weakness, the latter anaphalytic like reactions and internal hives + stomach bloating, loose stools, etc. Wheat just gives me muscle fatigue as opposed to making me feel sleepy as it would in a healthy person. So I avoid these like the plague. But you do mention in the protocol which got me a bit confused?
 
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leokitten

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Thanks @joshua.leisk for all your hard work. I forgot to add to my relevant ME caused issues that seem to make me a textbook case for your hypothesis, ME caused me to have a rapid change to my skin and hair. My hair started falling out (not male pattern) like alopecia and total change in texture, my skin started getting a rapid increase in flat mole or small dark spot creation even in places that have never seen the sun in my life so it’s not sun related. All REALLY weird symptoms caused by ME.
 
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lenora

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I don't know if you want to hear from me or not. I'm a 74 yr. old female who has had ME for 35++ years (forget), have Syringomyelia (SM) and Arnold-Chiari Malformation. I've had surgery for both many years ago and this is some of my input.

Prior to the SM & ACM being discovered, I was also diagnosed and treated for a pituitary tumor. I was on bromocriptine for years and I really had no overt symptoms. I am always being tested for thyroid problems, but nothing ever seems to show up. That's fine...I'm not looking for other trouble.

I never had an eating disorder until I had Shingles which left me with anorexia. It took a long time to return to semi-good health b/c I had 3 attacks one after the other. This made 4 attacks in total, the first was when I was 30.

Since your research included people with eating disorders, isn't it possible their hair fell out b/c of it?

I've never had problems taking acetyl-choline.

No, I don't like milk of any kind (well, almond milk, but that's it). Eggs, no but I will eat a fried egg sandwich.

My protein level is probably lower than it should be, but I do have one really nutritious meal/day. I still don't eat much, but have gained weight due to meds b/c of multiple hospitalizations over the past 18 mos. or so.

I have severe allergies and immune problems that never end. I've had a mild heart attack & have 6 stents and high BP and cholesterol (don't know how!) My father died at age 40 of a myocardial infarct.

I take medication for anxiety/panic disorders and have depression if I'm not on medication.

May I ask what led you to the conclusion (?) that the liver is involved? I did read your research, but I'm getting a bit too old to be reading involved research. (And my mind won't let me remember everything.)

I'm from a large family. When I was a child one of my sisters had hepatitis. I can't give you more info because it was during childhood, my mother and just about all of my brothers and sisters have passed away. I did ask that sister if she knew what type of hepatitis it was, but she didn't. She was younger than I was at the time.
She also had an illness known as Stiff People Syndrome...nasty business.

I have autoimmune encephalitis which has impaired my thinking. Used to have a great memory, but even though I've tried very hard, I can't get it back to what it was before the encephalitis. This is a new Illness.

I was also diagnosed with epilepsy...and indeed I have had blackouts. I broke my wrist during one but didn't realize the cause until I spent time and effort trying to figure out everything that had occurred. I'll be on medication for the remainder of my life. Epilepsy is also a fairly new Illness.

About 2 years ago, I heard about a form of celiac disease that does not present in the normal manner. The new form destroys the neurological system and seems to begin late in life. Thus far, there have been approx. 4 known cases of this illness. Even though patients are treated with chemo drugs, all have died. You may find research at Columbia. No pain is associated with this illness, but it looks like ALS.

I'm giving you this information b/c not too many people of my age are involved and we're a hard group to reach. I thought you may find it of some interest...if not, that's fine.

Thanks for trying to help us. I'm glad that you recovered...enjoy it. Yours, Lenora.
 
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