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Topics - joshua.leisk

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Experimental Treatment Methodology / v3.43U (preview)
« on: April 09, 2022, 08:43:52 PM »

(PDF attached with clickable links, registration required)

A detailed description and a preprint to follow.


This enhanced fasting method targets selectively killing HHV / cancer / senescent cells using their metabolic differences as a selector, rather than requiring a functioning immune system for this function, as described from page 23/24 onwards in CFS/ME: A New Hope.

Materials needed:

NB. Supplements may NOT contain citrate, malate, fumarate or other mitochondrial energy source - check labels carefully.

Safety items -
1. Succinate (preferred) or Apple Cider Vinegar, as a source of succinic acid.
This is for rapidly exiting the fast, if needed.

Core items -
2. 3 x empty 1L bottles.

3. EGCG, as Green Tea Extract
Used to reduce the glutamate dehydrogenase (GDH) enzyme.

4. Sodium Chloride
Used to help maintain extracellular sodium levels. Use reagent grade or rock salt.)

Recommended Extras -
5. Potassium Chloride
(Reagent grade / high purity. NOT: Nu-Salt, Morton’s Salt Substitute.)
Used to help maintain intracellular potassium levels.

6. Magnesium Oxide
(Yes, really oxide. Yes, it's poorly absorbed and known to cause diarrhoea. That's the idea.)
Used to help maintain intracellular magnesium levels and also induce diarrhoea.

7. Resveratrol
Used to alter glycolysis and improve fatty acid oxidation.

8. Forskolin
Used to increase cAMP and fatty acid oxidation.

9. Hesperidin
Used to maintain increased cAMP and fatty acid oxidation.

10. Caffeine
Used to increased fatty acid oxidation.

Fasting Schedule:

Day 1 | Induction - lower doses of EGCG, Resveratrol
Add the capsule contents to EACH 1L bottle (and discard / recycle the empty capsules) -
EGCG 75-100mg (eg. 1/2 capsule)
Sodium Chloride 2g
Potassium Chloride 3g
Magnesium Oxide 250-500mg
Resveratrol 50-150mg (eg. 1/2 capsule)
Forskolin 10mg
Hesperidin 250-500mg
Caffeine (low dose - as desirable / tolerable)
Fill the rest of each 1L bottle with water. Shake well.

Day 2 | Full strength dosing, GI flush
Add the capsule contents to EACH 1L bottle (and discard / recycle the empty capsules) -
EGCG 500-600mg (eg. 3 capsules)
Sodium Chloride 2g
Potassium Chloride 3g
Magnesium Oxide 250-500mg
Resveratrol 300-500mg (eg. 2-3 capsules)
Forskolin 10mg
Hesperidin 250-500mg
Caffeine (low dose - as desirable / tolerable)
Fill the rest of each 1L bottle with water. Shake well.

Day 3+ | Full strength dosing, optional GI flush
Add the capsule contents to EACH 1L bottle (and discard / recycle the empty capsules) -
EGCG 500-600mg (eg. 3 capsules)
Sodium Chloride 2g
Potassium Chloride 3g
Magnesium Oxide 250-500mg (can remove if GI tract is now clear)
Resveratrol 300-500mg (eg. 2-3 capsules)
Forskolin 10mg
Hesperidin 250-500mg
Caffeine (low dose - as desirable / tolerable)
Fill the rest of each 1L bottle with water. Shake well.

NO food consumption for 6-8 hours after your last EGCG dose - food will HURT you by shutting off energy generation in your mitochondria.

According to expectations derived from the literature (and confirmed by a small number of reports from people who did not follow this advice), consuming any food during this 6-8 hour window will likely cause someone to be blacking in/out and convulsing in pain for the remaining hours, unless someone else places 100mg of succinate in this person's mouth, as they will likely be unable to
(This could easily be fatal, if you were eg. driving a motor vehicle or operating heavy machinery.)

Have succinate/succinic acid (or some high strength apple cider vinegar, which contains succinic acid) on hand in case you want to rapidly exit the fast, at 100mg. Otherwise, simply do not eat for 6-8 hours after your last dose of EGCG.

NO other supplements are to consumed.

Any medications which must be maintained due to tolerance or withdrawal symptoms should be continued. Antibiotics and antiviral can be combined with this fasting protocol.

Cannabis is allowed, where legal.
-THC may increase appetite, which could be problematic if not well-tolerated.
-CBD may decrease appetite and improve sleep.

You may freely drink additional plain water.

If the high dose EGCG flavour is intensely unpalatable, the capsules can be taken every 4-5 hours instead of mixed into the water.
Some optional flavouring could also be considered, however finding a compatible flavouring agent is problematic.

(Supplements may NOT contain citrate, malate, fumarate or other mitochondrial reaction source metabolite - check labels carefully.)

Be prepared to have loose stools. This may have benefits for SIBO, etc.
Be prepared to experience inflammation, unusual pains, rashes, etc., in any infected tissues.
This is a necessary physiological unpleasantness - there is currently no road back to health that avoids tissue remediation.

Creating a calm environment and set aside this fasting time away from work and other life pressures is highly recommended.

[This article is being regularly updated.]

Under normal human metabolism, blood pH is tightly regulated between 7.35-7.45.

Interstitial fluid pH (an extracellular fluid) also starts around 7.4 and for the general population, with intense physical activity, can often drop to 7.0 for brief periods, thanks to elevated activity by our muscle cells. In chronic disease the interstitial pH can shift towards acidosis. This can be accelerated and exacerbated by an impaired lymphatic system, which plays an important role in connecting our extracellular fluid compartment back to our circulatory system and modulating immune function. From there, blood transport efficiency, pulmonary respiration, hepatic and renal function are also critical.

This pH shift can be caused by mitochondrial fragmention / HIF-1a alterations / Warburg metabolism seen in various infections / cancers / senescent cells. pH shift caused by various molds - notably many aspergillus and penicillium species. Mitochondrial fragmentation can also be caused by the spike protein seen in SARS-CoV-2 infections AND the current vaccines which produce analogues of this spike protein.. outcomes can benefit from preventing the pH shift.

A "somewhat normal" blood smear on a brightfield microscope may look something like this.
(Note the red blood cells are repelling each other and are maintaining a healthy round shape.)

When systemic pH is not tightly regulated, cellular metabolism is severely impaired.
Red blood cells no longer repel each other, clumping together and forming rouleaux.
These effects can be further impacted by the presence of biofilms, such as the ones visible in this next image.

When the red blood cells are extremely stressed, they display a "crowning effect", indicating membrane damage and impaired functionality.

These features can also be seen in the presence of pH-shifting molds, such as Aspergillus and Penicillium-

and have been observed in both COVID-19 infections and vaccinations, owing to induced mitchondrial fragmention and Warburg metabolism by both the wild-type and vaccine-induced spike proteins -

Ultimately, these features may lead to hypercapnia and/or hypoxia, while also preventing red blood cells travelling in single-file through tight places.

With haemoglobin's primary activity impaired, this places undue stress on bicarbonate levels to help maintain systemic pH.

Measuring blood pH has complications, however taking a first-morning sample of both saliva and urine with a high resolution digital pH meter or pH test strips may be beneficial in monitoring trends in pH over time and making adjustments. The morning sample should normally be the most alkaline sample of the day.

As these measurements do not show interstitial pH or blood pH, the data has limited uses. More research into practical ways to sample those fluids is being explored. Sweat may be a suitable inference for interstitial pH, however this has not been fully explored.

(A portable device used by athletes for measuring blood lactate may be an better option, however there may be some additional difficulties, also. L-lactate is produced by our metabolism and D-lactate is produced by microbial metabolism. Testing only L-lactate levels may show a false negative, if the source of the lactate problem is microbial D-Lactate. A solution could be to first perform a Genova Diagnostics Organix test or various others that sample both L and D lactate levels. If D-Lactate can be excluded, then L-Lactate may be a viable at-home marker to track, using a finger-prick test.) 

Depending on the level of pH, a pH imbalance can be labelled as -

Alkalosis (common types/causes):
- Nitrogen metabolite excess

Acidosis (common types/causes):
- Lactic acidosis
- Respiratory acidosis
- Renal tube acidosis
- Metabolic acidosis

The critical blood pH regulators are hemoglobin, bicarbonate, gas exchanges from respiration and normal renal function.

If hemoglobin count or morphology is unfavourable, this transfers considerable burden to bicarbonate to maintain homeostasis. If kidney function and alkaline blood flow is impaired, this can be catastrophic. If additional gas exchange from breathing is unable to maintain the balance, a poor outcome is expected.

Other pH influences are digestion end products, microbiome influence, mineral deficiencies including electrolytes, ferritin and related mineral metabolism substrates / cofactors.

Downstream effects of pH abnomalities include systemic ion channel disturbances and membrane inflammation. Most noticeably, these could be sodium/potassium related and rely on eg. Na+/K+/-ATPase for gradient regulation. Intracellular calcium accumulation may occur.

This could cause some of the symptoms relating to ME/CFS - post-exercise malaise, muscle contraction impairment and inflammation, dopamine transport / metabolism, major depression, pseudo-parkinsonism, encephalopathy, renal function abnormalities and calcium channel irregularities such as NMDA overexcitability.. and more.

This is very much a "tip of the iceberg" list, as this would be expected to create a catastrophic and familiar cascade of symptoms, and even prevent medication from working.

Identifying if someone may benefit from exploring this further would involve some testing.

Related biomarkers:
- Blood CO2 high / low, bicarb
- 24h urine electrolytes
- Anion gap, etc

Pulmonary function tests may be appropriate, including peak flow:

If either respiratory or renal functions are impaired, pH balance becomes problematic. If both functions are impaired, pH can become very problematic.

My suspicion is that dysautonomia and/or airway obstruction, including nasal inflammation may cause poor gas exchange and pH management. This could be further compounded by sleep-related breathing disorders.

Where the issue is CO2 accumulation / incomplete gas exchange, these effects could be transient over the day, or longer phases, with symptoms similar to hypercapnia. Increasing oxygen intake via an oxygen bottle is unfortunately not very helpful for removing carbon dioxide buildup.

(More details here -

As of v3+, the experimental protocol addresses pH shift from HHV-related mitochondrial impairment around ammonia metabolism, removal of some microbial nitrogen influences, as well as the lactic (acidosis) downstream from mitochondrial fragmentation / HIF-1a and impaired hepatic gluconeogenesis. Dietary inputs to metabolic acidosis are managed by vegetables and other foods in the example diet in v3.31, including the electrolyte intakes.

What is not currently covered in v3 and may require individual assessment, remediation:
- Other pathogens - these may still benefit from antioxidants / glutathione precursors and HIF-1a modifiers, eg. very high dose [thiamine, benfotiamine, sulbutiamine, fursultiamine (thiamine tetrahydrofurfuryl disulfide) or allithiamine] / resveratrol / dichloroacetate to prevent lactic acid metabolism.
- Breathing sufficiency / efficiency. With chronic shallow breathing, it's possible that over time that a person could need to 'retrain' their breathing habits to restore normal gas exchange.
- Sleep breathing disorders.
- Kidney function (eGFR is not a comprehensive evaluation of renal sufficiency).
- Specific intracellular mineral deficiencies (such as magnesium, manganese, lithium, copper and zinc).
  Serum tests are not very helpful as they are also tightly regulated by the kidneys.
  White blood cells (SpectraCell tests) are a useful indicator for intracellular levels of vitamins, minerals and various metabolites.
  This may be combined with Hair Toxin Mineral Analysis (HTMA) reports and due to the nature of HTMA, need to be interpreted appropriately for obtaining actionable data. Trace elements often labelled as 'toxic' often have important function, but become toxic in excess. Rubidium, strontium and cobalt are good examples of these and may need resolving by diet and/or supplements, in balance.

Considerations and interventions:

In some circumstances, dietary interventions such as adding an appropriate amount of potassium bicarbonate to water, consumed between meals could be a useful way to temporarily alleviate or reduce symptoms of some pH imbalances.
Up to 1 grams / hour of potassium bicarbonate, dissolved in a glass of water, could be appropriate, with a daily limit of 3 grams.
Alternatively, up to 1 gram / hour of sodium bicarbonate, dissolved in a glass of water, could be appropriate, with a daily limit of 3 grams.

Controlled deep breathing exercises may be highly appropriate. Correcting a bicarbonate deficiency allows for improved pH buffering, however this is still dependent on respiration.

Medical devices for improving breathing efficiency during sleep, such as a bipap machine, can be discussed with an appropriate medical professional.

Some intracellular mineral deficiencies (and excesses), particularly electrolytes, can be problematic to remediate. According to widely available (anecdotal) evidence, it can often take many months for a chronic magnesium deficiency to be corrected. I suspect this can be improved on.

Additionally, creating serum spikes of an electrolyte by consuming supplements are known to cause rapid corrections via renal excretion, whereas taking small amounts over the day can prevent this. Studies have shown as little as 11% of supplemented magnesium is retained. For this reason, adding magnesium to your daily water intake is superior to taking a tablet.

Special forms of electrolyte supplements, such as acetylated electrolytes, including magnesium acetyltaurinate may also be very helpful in bypassing this issue.

Lithium has many important biological functions. A deficiency can cause renal magnesium wastage by altering the retention ratio. Unlike clinically relevant "therapeutic overdoses" of lithium (20mg-1800mg/day), 0.5-1mg has been suggested as a daily value for lithium / as an essential nutrient and is associated with longer lifespans and quality of life in the literature.

Some further complications are that due to compensations and altered homeostasis, increasing these depleted minerals could also cause paradoxically opposite effects, eg. supplementing or increasing magnesium may initially cause sleep disturbances and increased adrenergic signalling, until a new homeostasis is achieved.

Magnesium is directly involved in 300+ reactions and along with zinc, is a key cofactor for metabolising any/all dietary forms of Vitamin B6 into P5P. A deficiency of either can lead to B6 toxicity symptoms, such as small fiber peripheral neuropathy.

Dietary P5P supplements are less helpful than they appear, as digestion of any P5P supplements cleaves the phosphate group, thus requiring magnesium and zinc for later reassembly. P5P is responsible for 150+ reactions, including dopamine synthesis, so an intracellular magnesium deficiency can impair 450+ reactions.

Manganese is often overlooked and a deficiency can create issues with Vitamin B and C metabolism, along with creating further oxidative stress via decreased MnSOD.

Zinc also has important roles in Vitamin B6->P5P, neurotransmitter and catecholamine metabolism. Copper is also important and the intake of copper, zinc needs to be balanced. Excessive intake of either can also create symptoms of deficiency.

Magnesium and zinc are the primary inhibitors for NMDA receptors and the literature suggests their deficiency can cause excitotoxicity.

DBH and BH4

Our ongoing research strongly suggests that at a fundamental level, one of the key differences between mild, moderate and severe ME/CFS is dopamine metabolism.

Specifically, impaired dopamine beta hydroxylase (DBH) and Tetrahydrobiopterin (BH4) - the latter being a cofactor for tyrosine hydroxylase and L-DOPA synthesis, further acting to rate-limit dopamine synthesis. This may be an important feedback loop when dopamine synthesis exceeds release / metabolism, as mediated by a DBH insufficiency.

There are a multitude of ways that DBH can be impaired. It's expected that multiple influences may be exerted at the same time to create a 'perfect storm'.

For example, a number of Clostridia species are capable of creating "gaseous mycotoxins" which inhibit DBH, with catastrophic results. T.gondii is able to impair DBH. Excess agonism of alpha-adrenergic receptors can impair DBH. Polymorphisms for DBH related genes can impair DBH. Potassium and or magnesium deficiency can impair DBH. Low vitamin C and/or copper can impair DBH. Further, low manganese and/or excessive oxidative stress can cause intracellular vitamin C deficiencies.

Low fumarate, chloride and acetate can cause DBH abnormalities. This may be suggestive of problems with mitochondrial fragmentation with impaired methylation and/or impaired succinate dehydrogenase (SDH). SDH and methylation both rely heavily on a riboflavin metabolite - flavin adenine dinucleotide (FAD). SDH also requires ubiquinone as a cofactor. Impaired pulmonary respiration and/or hemoglobin transport function may also be causal for low fumarate.

Sustained neural and neuromuscular activity with mitochondrial fragmentation, impaired methylation and HIF-1a alterations could lead to interstitial lactic acidosis, which by nature means a low pH state. This can be further mediated by insufficient lymphatic clearance.

Low pH, impaired Na+/K+-ATPase and high intracellular calcium levels are able to completely impair DBH. In this way, exercise intolerance and the sterotypical ME/CFS "crashed" state can be reached by low levels of metabolic activity. Resting is required to partially revert this state.

Research is continuing towards quantifying all other known DBH influences.

DBH has multiple roles. Its key role is to metabolise dopamine into norepinephrine, thereby facilitating fatty acid oxidation and other adrenergic signalling. In presynaptic neurons, DBH also behaves as a critical membrane transporter for releasing noepinephrine outside the cell.

Dopamine circulates systemically and has many functions beyond activating post-synaptic neurons. A systemic dopamine deficiency, or insufficient D1 receptor agonism can easily create inflammation via increased NLRP-3.

NLRP-3 can cause anxiety, hypertension in a sodium-rich environment and catabolism of norepinephrine. Insufficient dopamine and/or norepinephrine can impair blood flow in key tissues, cause neurological disorders and is well-known for causing debilitating movement disorders / muscle paralysis, including gastrointestinal tissues.

Dopamine transport and binding events through cells membrane can also become catastrophically impaired when the cell is suffering from abnormally high/low extracellular pH and/or when electrolytes required to operate ion channels, transports and pumps are either low, or the gradient between the intracellular and extracellular pools are not being maintained by the ATP-dependent "pumps" or ATPases. This can directly affect systemic dopamine metabolism in a similar manner to DBH deficiency, only potentially much, much worse - as numerous other transporters, receptors and pathways will be similarly impaired by these abnormalities.

If presynaptic intracellular dopamine levels are excessively high due to low DBH and/or impaired dopamine transport, this may be rate-limited by biopterin recycling / low BH4. BH4 is responsible for synthesis of key neurotransmitters. Without BH4, tyrosine hydroxylase is impaired, reducing the conversion of tyrosine to L-DOPA and thus dopamine.

BH4 can be impaired by peroxynitrites, low ferritin, low riboflavin, low niacin and low 5-methyltetrahydrofolate (5-MTHF).

If excessive dopamine metabolism is combined with a DBH deficiency, the subjective experience could resemble the horrible "disulfiram effect" - custodially imposed on some cocaine users - any increase of dopamine and/or alcohol metabolism does not cause pleasure, instead causing anxiety, nausea, potential seizures and/or severe sensory-motor polyneuropathy.

An imbalanced GABA:glutamate ratio can lead to excessive dopamine metabolism, excitotoxicity and oxidative stress. This can sometimes be caused by insufficient NMDA inhibition (further relating to magnesium and/or zinc deficiency).

Another cause for GABA:glutamate imbalance may be P5P deficiency - further relating to a deficiency of magnesium and/or zinc and/or riboflavin - this is often caused as a downstream effect of high oxidative stress / mitochondrial fragmentation / Warburg metabolism, where P5P and methylation cofactors B9, B12 are ultimately converted into "mitochondrial fuel" as a backup pathway to maintaining Succinyl-CoA). Hormonal imbalances have also been previously discussed as causal. Damaged cell membranes and ion channels from pH imbalance are another possible cause. A less common cause may also include antibodies to glutamate decarboxylase.

This altered metabolism can be "somewhat patched" by benzodiapines and related pharmaceuticals, however this comes with an additional well-known set of problems and some benefits. 

A preferred approach (after confirming noradrenaline is low and/or vanillylmandelic acid is low on urine tests), is to normalise DBH, thereby correcting the downstream cascade. This would be best mediated by removing any/all "low-hanging fruit", such as:

1. Quantifying and remediating deficiencies of vitamin C, copper, manganese, magnesium, zinc, lithium, riboflavin and potassium. (PQQ may also be helpful.)
2. Quantifying and remediating interstitial and blood pH. Confirming by blood smear that red blood cell morphology is normal. Any clumping or rouleaux may act to limit other interventions.
3. Quantifying and remediating pulmonary respiration function.
4. Antagonising a2-adrenergic receptors, using a suitable intervention. (At this time, appropriate a2-antagonists may include small doses of yohimbe / yohimbine, rauwolscine and phenoxybenzamine. This is a WIP)
5. Further reducing NLRP-3 using eg. hesperidin.
6. Removing / remediating any detected pathogens that impair DBH - this can be a long process.
7. Investigating a BH4 deficiency - this is difficult to measure directly. This may appear as low levels of neurotransmitters, low ferritin, low intracellular riboflavin, low 5-MTHF / folinic acid, low citrulline.   

To summarise -

It appears that different pathogens affect specific energy metabolism pathways, often via neurotransmitters:
Low BH4 affects glycolysis, nitric oxide synthesis / blood volume, neurotransmitter synthesis / recycling and downstream of dopamine, adrenergic signalling and therefore fatty acid oxidation (FAO). It may also lead to low NAD+ and immunosuppression.
    Common BH4 insults may include lipopolysaccharides (LPS) and potentially low trace elements, such as rubidium.

Low DBH reduces norepinephrine synthesis, affects fatty acid oxidation and can cause obesity, malaise and impaired hepatic gluconeogenesis / lactic acidosis.
    Impaired DBH can also cause intense anxiety instead of pleasure when dopamine is increased.
    Common DBH insults may include: T.gondii, various clostridia species, low copper, low vitamin C, low potassium.

Low SAM-e will further impact FAO at conversion of norepinephrine to epinephrine, while also impacting serotonin metabolism.

Elevated glutamate dehydrogenase (GDH) upsets nitrogen metabolism, causing uremia and potentially hyperinsulinism, where GDH is high in pancreatic tissue.
    Hyperinsulinism, and/or insulin resistance cause by a low pH environment can readily impair glucose metabolism and glycogen storage.
    Common insults: The 9 HHV family members or tick-borne cousins, MHV-68 or MHV-72. HIV also increases GDH.

High levels of oxidative stress or mitochondrial fragmentation will further exacerbate nitrogen metabolism, while altering hypoxia inducible factors and triggering lactic acid metabolism / pH shift down, blood clotting / rouleaux, hypoxia / hypercapnia, while rapidly depleting B12, folate (impacting BH4), B6->(magnesium, zinc, riboflavin/FAD)->P5P.
    This may also prevent collagen synthesis, leading to tissue degradation and ageing (see CFS/ME: A New Hope, figure 6.).
    Common insults: NMDA over-excitability, rampant viral protein synthesis, SARS-cov-2, all known COVID-19 vaccines and a long list of pathogens that trigger Warburg metabolism. Low trace elements such as manganese. Low dietary antioxidants. Gut microbiome dysbiosis. Heavy metal toxicity. Poisoning.

Low magnesium and zinc may lead to NMDA over-excitability, further altered by acidosis and intracellular calcium accumulation. This can overdrive dopamine synthesis, creating a very unpleasant situation, if DBH is low. This may be limited if/when this or low riboflavin causes P5P to run low, or if BH4 runs low.

Low riboflavin/FAD may lead to impaired succinate dehydrogenase and other mitochondrial reactions, elevated succinate and low fumarate, especially if combined with poor hemoglobin function / respiration.

Low P5P metabolism caused by the previous 3 points can readily cause toxic B6 accumulation and peripheral neuropathy.

When glucose, glycolysis and fatty acid metabolism are all impaired, with low pH and/or insulin resistance, this forces these cells to survive via HIF-1a and lactic acid metabolism, contributing to systemic load and can be fairly catastrophic, if lymphatic, hepatic, blood transport or renal function are insufficient.
    This may also lead to high levels of cortisol being generated in an attempt to trigger gluconeogenesis and recover. Edema response to androgens and estrogens may become apparent.
    NB. Rapidly disabling HIF-1a / Warburg metabolism in this state will cause acute energy loss to these cells and this may be observed by an intolerance to NAC, R-ALA, resveratrol and/or any other antioxidants. Conversely, increasing oxidative stress via eg. opiate use may be reported as beneficial.

Low pH and acidosis is expected during these conditions, further impairing all cell membranes, ligand binding, ion channels, electrolytes.

Any other cause for lymphatic, renal or hepatic impairment can also lead to this state.

[To be continued..]

We've all had an exceedingly frustrating time making sense of Reishi (ganoderma lucidum) product variability.

This has been a puzzle in itself, so I reached out to a specialist lab here in Sydney to help solve it.

After a thorough tour of their amazing facility and a very pleasant morning with erudite managing director, Dr. Ernest Lacey and his equally fantastic team, some clarity has been achieved.


4 products were tested and a PDF report is attached to this post with further details.

The product identifiers are:

SM10.2_1 Kudzu Root Extract - a reishi broken spore powder, shipped from China and labelled as "kudzu root extract", claimed at 20% triterpene content and sold through resellers worldwide under different labels. Unopened, as shipped by the vendor.

SM10.2_2 Ganderma (Sistema) - a raw ganoderma powder, also originating from China and sold locally in Australia as Austral Herbs Reishi. Presumably sold in many places. Packaged in a Sistema brand container and borrowed from my kitchen. Possibility of mild contamination.

SM10.2_3 Reisho Spore Oil - a reishi spore oil, shipped from China and labelled as "essential oil", claimed at 28.8% triterpene content and sold through resellers worldwide under different labels. Unopened, as shipped by the vendor.

SM10.2_4 Complex capsule - Life Extension Reishi Complex, containing an alcohol extract of the fruiting body (claimed at 6% triterpenes) and broken spore extract. An unopened bottle, as shipped by the vendor.

A cover letter was attached, explaining the reports:

Dear Joshua,

Attached please find a PDF containing the results of the 4 extracts we analysed. The first analysis is a HPLC run using a C18 reverse phase column with DAD UV detection. The data was analysed using our internal software, Comet and shows the comparative abundance of the ganoderic acids eluting at 4 to 6 min for each of the products. The capsules were clearly the most abundant.  Then I have included the NovaC LCMS analysis (the eluting conditions were similar over a longer time frame. The traces of the Sistema and Kudzu root are shown, these traces are normalised to show all the peaks. For the capsules I have given you the data for each of the major peaks. The NovaC program predicts molecular weights based on the MS adduct ion patterns, for quite a few peaks there are multiple MWts suggests the peaks are mixtures but more likely than not there are multiple ions that fit the expected adduct patterns thus predicting a number of tentative MWts. Without standards it is not straightforward to identify one ganoderic acid from another. An interesting longer term puzzle.

Sorry about the delay, it has been difficult to cobble together the time to mull over the data. I hope your investigations with Ganoderma go well and I wish good fortune with your studies.

Regards, Ern

Here are the HPLC results, with the 4 products overlaid:

We can see that the Life Extension product displays the most abundant level of ganoderic acids, followed by the raw reishi powder. The two spore products did not display significant amounts of all desired active ingredients. Let's take a look at these results individually, using the LCMS (numbered peaks are further detailed in the attached PDF):

SM10.2_1 Kudzu Root Extract - a reishi broken spore powder, shipped from China and labelled as "kudzu root extract", claimed at 20% triterpene content.
- we can see 2 peaks, only (17,21)

SM10.2_2 Ganderma (Sistema) - a raw ganoderma powder, also originating from China and sold locally in Australia.
- this looks like raw ganoderma lucidum and some spore content.

SM10.2_3 Reisho Spore Oil - a reishi spore oil, shipped from China and labelled as "essential oil", claimed at 28.8% triterpene content.
-This sample performed so poorly on the HPLC, that a follow-up LCMS was not deemed worthy of further machine time.

SM10.2_4 Complex capsule - Life Extension Reishi Complex
-Confirming what has been observed and reported by people self-experimenting with various reishi products, this sample shows marked peaks where expected.

To summarise:
A recent study carried out in partnership with USP showed that 74% of reishi products were mislabeled.

From our limited testing, we could suggest that where products actually contain reishi, different parts of the fungi contain different metabolites.
"Spore" products contain only 2 major peaks and are missing all of the (presumed) ganoderic acids A-T observed in other samples between 4-6 minutes.

Additionally, it would appear that the reishi spore oil based product sample that Ern and team very kindly analysed contained only trace amounts of the peaks observed in the reishi spore powder sample from the same vendor.

Based on this data, the best profile of ganoderic acids may be obtained from an alcohol extract of the fruiting body, combined with reishi spore powder.

Alternatively, you may infer that approximately 3-5g of genuine raw reishi powder could equate to 1 capsule of Life Extension Reishi Complex.

Thanks again to Ern and team for all their efforts!


In this post, I'm going to attempt to break down and elaborate on the CFS/ME paradox I was describing in the second paper.

Why is it that consuming specific supplements "hurts" us?

As this is already a large amount of information to digest, a breakdown the specific viral alterations will be described in the next post.

The primary reason that consuming any nutrients which are measurably depleted will predictably lead to headaches, PEM, etc. - is all downstream from "runaway" oxidative stress (ROS) and ammonia generation / metabolism / excretion processes.

The metabolites being depleted are common co-factors for many metabolic pathways and some depletions can cause a bottleneck for energy production in the mitochondrial reactions.

By "refilling any nutritional gap(s)" which were stalling cellular activities, these infected cells with "faulty metabolism" are now able to "get back to work" (they're programmed to build viral proteins, etc., using any/all available resources and lack programming for a "quiescent state", if resources are dwindling)... unfortunately this never-ending workload is constantly creating / increasing oxidative stress and further reducing the primary rate-limiting enzyme for the mitochondria - alpha-ketoglutarate dehydrogenase (a-KGDH).

This naturally increases the oxidative stress and ammonia load - which is quickly metabolised to a group of various other metabolites and collectively referred to as "nitrogen". This becomes an escalating problem.
This growing ammonia load (metabolites of which are also the origin of PEM, headaches, etc) triggers an increase of systemic "nitrogen excretion processes".

One of these disposal processes further drains key metabolites, creating an "energy crisis".. again.. and this becomes a vicious cycle, every time we eat, as we continue escalating this vicious cycle.

However, these induced "nutritional / metabolite gaps" also create a cascade of neurological dysfunctions, brain fog, thyroid issues, oxalate production, etc., along with muscle activation issues.

Now this becomes significantly worse, once the ROS increases to a state where a-KGDH is COMPLETELY impaired.

Normally, this should be a temporary event, allowing the mitochondria to briefly "slow down" and let the ROS scavenging processes (glutathione, antioxidants like vitamin E, C and alpha lipoic acid) catch up, cooling things down.

Now, in the event that the mitochondria is "fragmented" at a-KGDH, how is the mitochondria supposed to keep the cell alive? 

"Don't worry", this is biology - there are always a number of redundant pathways for every pathway / process.

The first thing that happens is a "transamination", where a tricky enzymatic reaction bypasses the impaired enzyme at a-KGDH and performs a "dual-metabolism" reaction, where two things happen at once: as a-Ketoglutarate goes through a reaction to make glutamate, aspartate is simultaneously converted into oxaloacetate, bridging through the middle of the cycle and restarting it at the top of the cycle (see the cyan pathway in Figure 5, above.)

Okay.. but what about all of the other cycle reactions after a-KGDH? How are these supposed to be maintained?

Two of these redundant pathways needed to heal the second half of the citric acid cycle are at "succinate" :
GABA + P5P (P5P is active form of Vitamin B6 - needs magnesium, zinc, riboflavin to be created) can be converted into succinate.
B12 + Folate + P5P (riboflavin, magnesium, zinc), can be readily converted into Succinate, via Succinyl-CoA, also (not shown in the diagram below).
(there are a few more)

However using these key metabolites as "backup fuel" too often leads to new problems, as you'll soon run out of them, too.

1. Methylation issues are observed and you'll expect to see the MCV in haematology reports significantly increase.
2. Without sufficient P5P, you'll see .. many.. issues, however a prominent one is tyrosine synthesis to dopamine is impaired, causing issues for mental health and motor functions.
3. If GABA is now being consumed for fuel, this creates further issues for maintaining a balance between "excitory" signalling (glutamate) and "inhibitory" signalling (GABA).

Now if dopamine is already low, aspartate is supposed to create more GABA in specific cells, such as retinae, as a backup pathway.. (unless aspartate is already low, because..)

The urea cycle can also allow the citric acid cycle to be fueled at "fumarate" .. which is a useful "low cost" way to recycle some of the ammonia being created - until either aspartate or argininosuccinate is depleted. It can also be used to create 5-HTP->L-DOPA->Dopamine.

This will reduce pathology markers for "urea" and reduce PEM.. briefly..

This also temporarily bypasses the "mitochondrial rate-limiter" (a-KGDH), allowing normal respiration and potentially correcting a number of issues around collagen synthesis, energy levels and hypoxia induced transcription factors (HIF-1a), etc.. alleviating those symptoms.

However, the ongoing (faulty) mitochondrial activity continues, the ROS increases, starts damaging the cell, DNA, and this ongoing ammonia overload forces heavier use of the "expensive" ammonia excretion process - via "phenylacetylglutamine" (PAGN).

This is where it all starts to get very unpleasant.

This is because acetyl-CoA (one of the most critical metabolites in the cell), glutamine and upstream metabolites are being constantly dumped from the cells, converted into urinary metabolites and excreted. 

With the ongoing metabolite depletions, including cysteine (via acetyl-CoA + CoA) and glycine, glutathione production and regeneration gets impaired.

This means that oxidative stress (ROS) cannot be reduced / scavenged.. leading to DNA transcription errors that can't be corrected if acetyl-CoA is impaired, cancers and... yet more ammonia to metabolise.. fortunately, as the B vitamins get depleted and/or aspartate gets depleted, half the cycle shuts down and the mitochondria cools off...

.. meanwhile creating issues with hypoxia, connective tissue disorders like (h)EDS, neurological disorders, thyroid disorders, fatty acid oxidation issues, insulin resistance, POTS / dysautonomia / orthostatic intolerance, etc..

Without sufficient acetyl-CoA, our cells are unable to make "acetylated" metabolites, such as:

Acetylcholine - required for cognitive function and muscle activation


n-Acetylserotonin (which also mean low melatonin, required to trigger nightly cellular metabolite cleanup processes and give refreshing sleep),

Without acetyl-CoA, this also :

Reduces energy flow into the mitochondrial reactions from pyruvate (glycogen, glucose metabolism) - leading to insulin resistance

Impairs beta-oxidation of fatty acids, further reducing energy availability and causing us to store fat, but not be able to use it efficiently.

As this is tissue specific, the systemic imbalance may lead to excessive epinephrine production, as a form of compensation - leading to POTS / dysautonomia / orthostatic intolerance. (This can be further exacerbated by a dopamine beta hydroxylase deficiency, caused by many factors, including other pathogens such as clostridia-derived mycotoxins and t.gondii, which will be covered in a separate article.)

(Some organs are now receiving too much adrenergic signalling, to allow the impaired tissues to get 'enough' to maintain energy production.)

This also leads to cortisol and further anxiety issues.

This is highly debilitating.. people are left between a choice of:
A) a body crippled with a personal selection of every disease we have named in the papers..
B) headaches, PEM, being incredibly overstimulated / overpowered by their environment to the point of being shutdown or placed on benzodiazapines.
C) an ongoing mix of both, every time we eat... often leading to a snowball effect where you can't eat... which is a slippery slope to hell*.

*NB. The thing about (C) is.. if someone didn't eat *anything* for say 5 days, as may happen in hunter-gatherer day, while perhaps keeping water and electrolytes up.. after going through a few days of their own personal hell, they'd later see a vast reduction in symptoms (perhaps 1-2 weeks after the fast), by having killed off many of the infected cells, simply by using their altered metabolic behavior.

This also bypasses any immune system deficiencies.

The catch-22 is, 5 days of fasting is likely going to consume 2-2.5kg of body fat. If someone is already in a fragile state, this option may not be available to them, initially.

Adding an ongoing high dose of EGCG (and resveratrol) to the fasting process speeds this up dramatically, by removing the other large source of stored energy available to the cell (from glutamine->glutamate-aKG). It also completely disables the transamination I described in the papers - this is why the first day of fasting has "low dose" of EGCG - giving time for the ROS to drop and transamination to "turn off".

This should mean that 3 days of EGCG fasting could be equivalent to 5-7 days of traditional water fasting. You're diving into the "pointy end of the fast", much earlier.

As an alternative to fasting, we have proposed an experimental treatment protocol.

However, implementing the proposed treatment protocol, the expectation is that the first 3-4 days is going to temporarily generate a LARGE amount of ammonia, as various pathways start working again, including the purine nucleotide cycle.

This will induce a (currently unavoidable) "crashed" state for those 3-4 days.

For this reason, we have selected sodium benzoate + glycine (and B5, NAC) to create an outlet for this initial surge.
Even with that adjunct, someone could expect a stunning headache for 3-4 days and extreme PEM.
"Ammonul", if they have deep pockets and a friendly doctor, would be an ideal adjunct to include at this time.
L-ornithine l-aspartate is another option which may be appropriate.

After that, thanks to the metabolic alterations provided by the reishi triterpenes, EGCG and various ROS scavengers (R-ALA / glutathione / NAC / Vitamin C / Vitamin E), someone would expect to be able to consume normal amounts of B vitamins and not create headaches, PEM, or other symptoms... providing they're NOT creating additional "pressure" inside the mitochondrial reactions by overloading the cell with glucose (hence the dietary modifications).

Excessive doses of B vitamins will still be expected to create mitochondrial pressure and ROS, also, by anaplerosis at succinate, as described above.

At this point, things our model suggests things may start improving.. although they'd still be expected to have artefacts of lytic phase "autoimmunity" to wade through for the next 6-8 weeks, unless they've previously been using eg. spironolactone / tenofovir, etc., for a similar period.

However, while all of these life improvements are happening... people are going to get tested.

Their ongoing immune response is going to cause flare-ups and inflammation of every single tissue they've historically had issues with.
It may be very unpleasant, at times.

Having trust that this is both necessary and one of the last times someone would have to experience these symptoms requires personal satisfaction that they're doing the right thing. Having exhaustive pathology markers to refer to during this process may help their resolve. eg. EBV VCA IgG should be decreasing, with a 6-8 week lag (if titres are within the maximum lab ranges... most people's are not..)

If someone is suffering from co-infections, these may require additional remediation. Research is ongoing into co-infections, with some success. HHV is not the only input to this disease model - there are a number of potential causes.

The protocol is being expanded to allow for any additional 'metabolic traps' or impaired pathways identified by further research.

We've since identified the roles of excess DHT, insufficient Vitamin D3, Vitamin A in this disease model.
Further work into the roles of neurotransmitters and metabolites of them is being investigated.

For this reason, we also subsequently discovered that people using spironolactone, as discussed in the 3rd paper, benefited from it performing the same functions as EGCG.

Therefore, without using spironolactone, this has necessitated significantly increasing the doses of EGCG and/or using other plant extracts, which provide the same benefits.

This will be discussed in more detail in other posts.

Understanding the Model / The origin of this discovery
« on: June 14, 2021, 04:46:25 AM »
(This backstory was first shared at S4ME and then Phoenix Rising, in early 2021. Minor edits/updates have been made.)

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, currently in preprint -

For CFS/ME, our primary research focus is the liver (and now also the brain).

My original research strongly suggested 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, where hypoxia is present. 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 here in Australia, 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 VCA IgG+++ (exceeded reporting thresholds)
EBV EA was not provided

Client 2 -
EBV EBNA was not provided
EBV EA was not provided
CMV IgG ++

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. This has implications for Ehlers Danlos Syndrome and others.

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 was demonstrated in small numbers to provide symptomatic remission, with gradual improvements to latent cell burden, if combined with a prescription for eg. spironolactone.
v3 is being actively tested.

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?"

Experimental Treatment Methodology / v3.31AU (DEPRECATED)
« on: June 14, 2021, 04:18:40 AM »
v3.31 is now on RG -

Attached is a draft for v3.31AU, with region-specific vendor links, for convenience.

(You must be logged in to access files.)




2021-07-16 UPDATE: A "WIP" towards a "Coxsackie B-inclusive" protocol for the next update is in testing.

The earlier V3.2 protocol may be more appropriate for anyone suspected as seropositive for Coxsackie B. Clarifying one aspect of v3.2, where beta-glucans are listed, this referred to the beta-glucans content of those items, rather than the total amount of each. eg. 15g of oat bran = approximately 1000mg of beta-glucans.

L-ornithine L-aspartate (LOLA) has been added back in as an option during the induction phase, while the purine nucleotide cycle restarts. (Separate L-ornithine and L-aspartate products are acceptable, if supply issues continue.)

We were exploring LOLA in v2. It may provide a more pleasant experience while processes the initial backlog of ammonia during the induction phase.

The EGCG dose was significantly increased to allow sufficient reduction / balance of GDH without simultaneous use of spironolactone. The 4th dose was reduced to allow for a stable serum profile / steady-state. There are appears to be large variability between EGCG content of different brands / products / batches, despite labelling. Adjustments may be needed around sleep / PEM blocking.

Sulforaphane, retinoic acid, boron and Vitamin D3’s role in stabilising hormonal influences of GDH included.

Forskolin added for improved cAMP and beta-oxidation, also helping to normalise catecholamines, GDH.

I lab-tested various reishi products. Currently “Life Extension Reishi Complex” is the only compatible product. There will be a post on this when I have received an email with the HPLC and LCMS reports. The reishi dose was increased to further decrease (normalise) 5-AR with a longer metabolic half-life than EGCG, allowing for more stable GDH levels throughout the day, with potential enhancements for viral apoptosis.

This version of the schedule contains food items needed for feeding tube scenarios and a link to an example diet which meets the baseline requirements for less severe people.

The baseline parameters are roughly [1g net carbs: 1g fat : 1g] protein for people who are fairly sedentary / immobile, after the initial induction phase, where we aim to deplete some stored glycogen, total energy intake and decrease oxidative stress, which is required to move forward. More protein is encouraged.

Once people are able to be more active, the carbohydrates will need to be increased to match glycogen usage, however still maintaining lower GI carbs and a pseudo-diabetic approach to avoid blood glucose spikes.

(These blood glucose spikes may be problematic if pancreatic GDH is still high, as hyperinsulinism is then expected, adding to the excess energy issues described in the mitochondria for other cells.)

Overall, "grazing" is suggested, rather than big, heavy meals.

Here's an image / link to the example diet.

Adjustments for tolerances / preferences can be made. eg. coffee / dairy aren't mandatory, just demonstrating that they're acceptable.

Bell peppers are included for hesperidin content, which works with the forskolin to improve cAMP levels. This assists normalise beta-oxidation of fatty acids, improving energy levels and cognition while also decreasing neural GDH via cAMP modulating TrKB, BDNF.

Broccoli is included to assist with sulforphane intake and would be best consumed with radishes and / or mustardseed for myrosinase, which helps improve the sulforaphane content derived from that meal.

Sulforaphane is also included in the Life Extension Mix multi in v3,3. It's included to assist with increasing 3a-HSD, along with other ingredients.
Normalising 3a-HSD helps reduce DHT -> GDH and increase allopregnanolone.

Announcements / Welcome (..again!)
« on: June 13, 2021, 11:22:18 PM »
This community forum was founded on 9th-June-2021 as a new home for open discussion around the research and methodology described currently in preprints, while providing updates, Q&A and home for people seeking to learn more information around the proposed Herpesviridae Autoimmune Spectrum Disorder.

After some days of wrestling with buggy forum software, on 14th-June-2021 we concluded it wasn't a suitable platform to build a community on and made the decision to switch to SMF, which has been quite a contrast.

Unfortunately, this means all members will need to reset their passwords.

All historical information can be found here:

Key information from these previous discussions will also be transferred into a new structure here.

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