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Messages - joshua.leisk

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General Discussion / Re: Where to start?
« on: April 25, 2022, 08:45:32 PM »
Apologies - rather embarrassing, however this post and some others from November 2021 - April 2022 weren't being actively monitored while a study was being conducted.

Most activity has been ramping up again on the discord server, however I'd be happy to assist here, if you're still after some help?

There's a new paper about to be released, also.

as above. could someone please help in understanding my results and potential treatments
Apologies - rather embarrassing, however this post and some others from November 2021 - April 2022 weren't being actively monitored while a study was being conducted.
Most activity has been ramping up again on the discord server, however I'd be happy to assist here, if you're still after some help?

Questions and Answers / Re: Food intake
« on: April 25, 2022, 08:38:03 PM »
Doesn't the body make glucogen by itself from fats?
Great question. You may find this useful reading -

Glucogen synthesis relies on a number of pathways which are often impaired with this metabolic cascade. 

Adrenergic signalling and precursors are often impaired, due to deficiencies of:
P5P or precursors ([Any form of B6, including P5P, minus the phosphate group] -> riboflavin / zinc / magnesium -> P5P),

These can be expected to be causal in many of the symptoms.

PS. Apologies for the delayed response. This forum has been quite inactive for a few months. The Discord server chatter is ramping up again.

Questions and Answers / Re: Starting Out and A Few questions
« on: April 25, 2022, 08:25:47 PM »
Also, where has everyone gone.  It seems this stopped being used in July.
The discord server has the daily chatter. I was also largely offline for 6 months with 2 studies. New paper incoming. 

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..]

Questions and Answers / Re: Berberine
« on: July 26, 2021, 02:23:01 AM »
Berberine upregulates CD36 ("Activation of AMPK by berberine induces hepatic lipid accumulation by upregulation of fatty acid translocase CD36 in mice") - that seems to be beneficial in Hepatitis C models, but not for Coxsackie (as discussed on Discord). Is Berberine something we want in the HHV model?

I'm asking because I would like to try it for its microbiome regulating properties.
I think there could be possible benefits, when pulsed. I noted some concerns in the first paper, also.

If I was experimenting with it, I'd probably test that as an evening dose.

Member Blogs / Re: BrightCandle's progress
« on: July 26, 2021, 02:14:43 AM »
The Coxsackie protocol in general is working out really badly. I can't sleep at all currently, fully wired and tired with really severe depression. I am going to have to bail on testing it as I can't continue to slip backwards like this. It doesn't work it just makes me worse.
Thanks for what you've done and appreciate you helping out with the coxsackie testing.

Did dropping the carbs back down change anything?

Member Blogs / Re: Calluna's journey
« on: July 10, 2021, 08:56:39 PM »
Diet could be a/the factor -- I've drifted back to my usual low-ish carb diet, which tends to be lower on the protein and higher on fats and carbs than example. Not super-high on the carbs, I'm still holding at <100g/day. Besides macros, which other parameters are super-important for me to keep an eye on when picking out meals?
I would aim for high protein. The funny thing about the term "protein" is that it really doesn't communicate all of the important amino acids. In the dietary guideline, I'd indicated around 1 : 1 : 1 ratios, as net carbs : fat : protein. Really, the protein intake would be as a minimum amount and significantly more can be included. Depending on the metabolic trap(s) in play, some people would be benefit from higher intakes of EAAs (includes BCAAs), tryptophan, lysine, as found in most proteins.

I personally eat around 160-240g of protein most days, although my needs are a little different to others here.

Member Blogs / Re: Calluna's journey
« on: July 10, 2021, 05:05:10 PM »
One thing that pops up with PEM blocking frequently is the dietary aspect. It’s a big player. 

How close to the example diet would you be eating lately?

Member Blogs / Re: Calluna's journey
« on: July 10, 2021, 05:48:25 AM »
Life Extension, 2 caps 3x/day working out to about 650mg actual EGCG per dose. When/how often for the BCAAs/NAC/water? I've already got them integrated per the protocol schedule.
That seems like a lot of EGCG?

The NAC / BCAAs / water can be a one-off dose if things slip up. alpha-GPC can also be helpful here. :D

Questions and Answers / Re: B vitamin support - B6 Paradox?
« on: July 09, 2021, 11:24:07 PM »
In theory, mishandled / deficient amounts of cofactors is a viable explanation for intracellular B6 vitamer dysfunction.

However, I really have a lot of trouble with the low Riboflavin claim. Perhaps there is an issue in maintaining both the di and mono forms of Riboflavin (FAD / FMN), but I myself have been B6 toxic on multi-vitamins that have sufficient amounts of Riboflavin. (and, regularly pulsed enough Riboflavin to cause strong yellow urine).

Maybe one of the versions of FAD/FMN is getting out of whack, or perhaps the behavior of PNPO / PL Kinase , etc. is further modified by metabolites that would be sourced from the Glutamine shunt? (e.g. "PNPO inhibitors", etc.)

Regardless, many fingers still point to the fasting mechanism for tamping down HHV infected cells as a better path then trying to do it while fed for anyone that has issues with B6 metabolism in the past.

Adding Riboflavin during the fast may have pros/cons to putting pressure on cells we want to die or start listening to apoptosis. Plus, the fact that it's not easy to find a relatively clean supplement of Riboflavin (most have rice flour and other crap in them) is a concern.
I'd probably run the fast "clean" (apart from maybe a sprinkle of forskolin, caffeine if the HR spikes up when glycogen runs out) and during post-fast replenishment, look to also focus on drip-feeding riboflavin all-day, over a few days to a week, to help with digestion / absorption bottlenecks. 

Member Blogs / Re: Calluna's journey
« on: July 09, 2021, 11:20:13 PM »
Day 16

Found the PEM 🙁 Today was pretty crappy; I threw up my empty-stomach pills this morning, slept an extra 5 hours after that, and the rest of the day's been a daze. I'm a bit discouraged right now, but also experiencing some noticeable mood symptoms, so that's certainly not helping anything. Hopefully I'll be mentally clearer tomorrow, and able to formulate questions tomorrow about how best to proceed; something something should I continue to bump up x, y, or z; something something am I letting something important slide by accident; something something should I go try enterovirus testing again, etc.

It's been a consistent worry in the back of my mind that the present improvements have been mostly or entirely placebo, and more a result of "I think I can do more" than "I think I need to do even less". This episode indicates to me that either that is true, or some alteration in my execution of the protocol has messed up something fundamental, or both. (Third option, it's been primarily placebo because of unknown enterovirus co-infection?)
Out of curiosity - which EGCG brand and dose are you using? 

You may find a 5g dose of BCAAs, 1g of NAC and 1L of water helps ameliorate PEM, if it's HHV-related.

Member Blogs / Re: BrightCandle's progress
« on: July 06, 2021, 04:56:19 AM »
Day ~47
Last week was good from an energy point of view but I had a lot of problems. Got super angry a couple of days in and seemed to have some pretty weird neurotransmitter/serotonin related issues on lower 5-HTP dose. Previously I have done that without much of anything happening but it was really dramatic on 3.31. This week I have gone for a hybrid with 3.2 except I have maintained the lower monohydrate, added the Forskolin, kept a higher EGCG and add some extra beta glucans all 3.31 like. I suspect the issue was Reishi but I am not taking a chance this week with further changing candesartan and 5-HTP is back up to full strength.

Other than the anger issues I was fairly energetic last week. I have been alternating exercise between resistance training one day and walking the next where resistance is up to about 12 sets a week and the walks are up to 40 minutes long. Walking speed is still quite slow, still getting higher heart rate than I would like but it came down last week and that is probably the reduction in Candesartan dose rather than a dramatic fitness gain as the drug worsens my POTS.

Headaches are about the same, mostly gone, definitely tolerable and not in the way very often. Still having low energy moments which go away if I add in some glucose based energy.
If you're seeing "hangry" moments, it sounds like your carbohydrates could need increasing to match increased activity levels. Your sleep may also be affected by higher cortisol, if you're running out of glycogen.

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