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Messages - joshua.leisk

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1
Questions and Answers / Re: Calculating mineral dosages?
« on: September 27, 2022, 02:10:53 AM »


Hi again,

There are some interesting markers in the report. As you've probably seen online, there are many different opinions on how to interpret HTMA reports and how to remediate them. 

My experiences have shown a pattern where electrolyte pairs are normally 'bound' and have relationships to other elements, except where additional modifiers are in play. These can sometimes be eg. calcium channel blocking drugs.

Your calcium is not bound to magnesium, suggesting a further calcium channel disturbance is in play. This needs to be quantified.

Sodium and potassium are exchanging pairs. Potassium deficiencies are associated with rubidium deficiencies. 
Calcium and magnesium are exchanging pairs. Calcium deficiencies are associated with strontium deficiencies. Magnesium deficiencies are associated with lithium deficiencies.

These all need to be remediated at the same time, although ideally not dosed at the same time of day due to competition for transporters. 

I'm curious why the iron levels are good, while other metals which use the same transporter are low. Likewise, the high levels of chromium. This could be indicative of another heavy metal accumulation which isn't tested by this particular report. There is a heavy metals specific HTMA from Doctors Data that might be useful in excluding this angle.

What does a week of eating and supplements look like for you, typically?

If this was my HTMA -

For the electrolytes, I'd follow the protocol intakes for calcium, magnesium, sodium and potassium, while adding 2mg/day of lithium and 500mg of strontium. I'd take the sodium and potassium with meals and sip on the calcium and magnesium separately, in between meals in my water bottle.

I'd also take 10 mg of manganese, 1 mg of vanadium, 150 mcg of germanium, 5 mg copper, 300 mcg iodine, 150 mcg molybdenum and a serving of the cobalt listed in the protocol. 

There's a supplement we've been testing which appears to increase absorption of certain metals. 
https://iherb.com/pr/morningstar-minerals-inner-vitality-fulvic-humic-minerals-32-oz-946-ml/61587
It's looking like it'll be a useful addition to the next protocol update. I'd happily include that.

For the elevated chromium and presumed untested heavy metal, 5g/day of Pectasol could also be worth exploring for 2-3 weeks.
https://iherb.com/pr/econugenics-pectasol-c-modified-citrus-pectin-5-29-oz-150-g/55234
I've seen some very impressive results in follow-up HTMAs.

Come join the chat on Discord, if you haven't already?

2
Understanding the Model / Updated disease model [WIP] v0.95b
« on: September 25, 2022, 03:08:47 PM »
This is a preview of the model being described in the upcoming paper. It may contain errors. An interactive version is being developed; however, you can right-click on the current image and save it for easier navigation -


3
Questions and Answers / Re: Calculating mineral dosages?
« on: August 03, 2022, 07:45:36 PM »
Hi All

I saw someone mention this protocol on Twitter and am very curious, particularly about the hair minerals since this ties in with Ron Davis' latest. I've ordered myself a hair test, but wondering if there is a particular formula we are supposed to be using for calculating the dose of the depleted minerals, based on those results? (as per 'Step 3', here)

I also note that there is a caution on manganese tolerance with Lyme, could anyone elaborate on this?
I have been chronically low to deficient in Mn over the years despite multiple rounds of 10mg/day and I never felt better for supplementing it. I've had positive Lyme IgM ELISAs in the past but it's my understanding that this can cross-react with Rheumatoid Factor. Both the follow up Blot testing done by my GP and Armin EliSpot and SeraSpot were negative. The only abnormality was a low CD57+ NK cells, but I can't find much in the literature to validate the significance of this. I'm fully expecting Mn to show low in this hair test but fairly confident I don't have Lyme ???
Thanks
Hi there,

What we've observed is that restoring manganese and certain other element levels back into 'normal' range can be quite challenging - this is especially true if iron is also low, as this indicates anaemia of inflammation and extra difficulties with remineralisation, while the inflammatory state is present. Aspects of the protocol target an array of influences towards that inflammatory state. You'll notice 20-40mg of manganese has been suggested in the protocol - even at these levels, it can take months to resolve a deficiency. Regular HTMAs are needed to monitor progress and prevent going into toxicity. The HTMA shows an 'average' of the elements across the time the hair follicle grew. eg. If taking supplements to increase levels, assuming a linear trajectory, a sample taken at 6 weeks would show the progress at approximately 3 weeks.

Given the different roles of these elements in energy and other metabolism, a balance between the 'aggressiveness' of remediating iron and elements involved with oxidative stress management. The bias needs to favour the latter. The means manganese, copper, zinc and selenium (where any are indicated deficient) need to be prioritised ahead of the iron.

Additionally, if there's an active bacterial or other infection, that should ideally be resolved before starting iron, as iron will benefit those pathogenic cells, plus your own metabolism.

Lyme spirochetes make use of manganese to defend against one of the body's defense mechanisms - superoxides. This means again that the process of supporting your own cells gives aid to the foreign cells. Ideally, the protocol would be combined with targeted anti-virals, anti-bacterials or anti-fungals, depending on the pathogenic landscape. Some of the protocol aims to inhibits specific classes of pathogens, at their energy sources, in ways that don't impair your own energy metabolism.

Hope that helps! Feel free to post your HTMA here or on the Discord for further discussion.

Regards,

Joshua

4
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.

5
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?

6
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 - https://www.ncbi.nlm.nih.gov/books/NBK279127/

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),
copper,
iron,
BH4.

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.

7
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. 

8
Experimental Treatment Methodology / v3.51U (preview)
« on: April 09, 2022, 08:43:52 PM »
General Mitochondrial and Wellness Protocol
(Author: Joshua Leisk, https://bornfree.life V3.51U - 31st December 2022)


This is a dietary supplement based protocol which may be helpful for supporting the unique nutritional requirements of people with:

Myalgic Encephalomyelitis / Chronic Fatigue Syndrome (ME/CFS).
Long COVID / Long Haulers, Viral / Post-Viral Chronic Fatigue.
Migraines.
Breathlessness, Hypoxia, Acidosis, Alkalosis / pH Dysregulation.
Dysregulated Cortisol, Dyslipidemia, Alopecia.
Small Fibre Peripheral Neuropathy (SFPN).
Mast Cell Activation Syndrome (MCAS).
Diamine Oxidase (DAO) Deficiency and Elevated Histamine.
Brain Fog. Sleep disorders.
Major and other types of Depression. Anxiety.
Postural Orthostatic Tachycardia Syndrome (POTS).
Chronic Inflammatory Response Syndrome (CIRS), Fibromyalgia.
Dysautonomia.
Frequent Urination.
GI Disorders, Small Intestinal Bowel Overgrowth (SIBO).
B6 Toxicity.
Ehlers Danlos Syndrome (EDS), Joint Pain, Connective Tissue Disorders, Tinnitus.
Polycystic Ovary Syndrome (PCOS).
Erectile Dysfunction.
Elevated Cholesterols / Fasting Glucose / D-Dimer.


NB. While all efforts are continuing to be made in eliminating them, some temporary paradoxical effects may be observed during protocol commencement. As certain deficiencies are corrected and neurotransmitter homeostasis is reset, paradoxical effects may include: temporary adrenaline and heart rate increases..


Existing "burning" sensations and headaches may also “flare”. Temporary alterations to libido may be expected. Resolving a severe copper deficiency may induce temporary kidney pain and nausea in some cases. Improvements to adaptive immune function are expected to occur during this protocol, which may result in some short periods of productive, yet otherwise unpleasant tissue inflammation and/or fever, flu-like symptoms, fatigue, etc.

Monitoring Lactate Dehydrogenase (LDH) - target 100-150 mmol/L, D-dimer, cholesterols and fasting glucose via blood tests would be suggested.


Disclaimer: Always consult with your doctor, especially if taking medications, eg. SNRI /SSRI, beta blockers, MAO inhibitors, etc.


INTRODUCTION
The human body contains a large number of elements. Many of these elements have been well-documented as having important biological activity in humans.





Our ongoing research has identified a persistent / cyclic inflammatory cascade, relating to immune dysfunction, which directly causes insufficiency of at least 9 important elements that use a common pair of transporters - Divalent Metal Transporter 1 and Ferroportin. Further deficiencies are created in the metabolic cascade being described.


However, some variability exists in the pattern of insufficiencies. This can be due to alterations in renal function and general homeostasis by complex relationships between the 9 affected elements and some seemingly unrelated heavy metals, along with additional trace elements. These complex relationships require further research.


The metabolic cascade appears in a surprising number of infections and chronic diseases. The model describes severe mitochondrial dysfunction, hypoxia, neurological alterations, collagen synthesis issues and immune deficiency. This is not an exhaustive list. The pattern of elemental deficiencies are also predictive of various disease features, when mapped to impairment of  related enzymatic reactions. A preview of the disease model and biochemistry pathways being described in our upcoming paper have been made available on the website and Discord server.

Correcting these nutritional deficiencies via diet and/or supplements can be extremely difficult due to the cyclic nature of the disease model and impaired absorption. Ongoing improvements to solving these deficiencies are reflected in protocol updates.



Complementary Therapies
(A short note on the general importance of maintaining a functioning lymphatic system.)

The lymphatic system is a network which spans the majority of the human body. Quite surprisingly, until very recently we were not aware that this also included the brain -
https://www.nih.gov/news-events/nih-research-matters/lymphatic-vessels-discovered-central-nervous-system
 
The lymphatic system has a number of important roles in immunity and circulation.

Lymphoid organs are the source of B and T lymphocytes. The system also collects extracellular fluid and metabolites from tissues, returning them via lymphatic vessels to the bloodstream, preventing lymphoedema or catastrophic fluid buildup and metabolic backlog.

A friendly primer on the lymphatic system can be found here - https://www.britannica.com/science/lymphatic-system.

The lymphatic system relies on breathing and muscle contractions to maintain healthy circulation and waste excretion.

In any disease where movement is being restricted, this creates additional difficulties for maintaining immune functions and circulation.

Manual therapy may compensate for this.
A regular session with a massage therapist who specialises in lymphatic drainage may help you assess and remediate any recurring lymphatic blockages. These may also be observed as being stiff, sore swollen tissues that can feature enlarged lymph nodes, such as in the neck, groin or armpits. A strong paradoxical effect may be felt the first time a blockage is cleared.

A daily regimen to maintain any problematic areas by hand or vibrating massage gun (used on a glancing angle), may also assist unlocking functional gains and preventing pain in chronic illnesses / infections. Conversely, not maintaining the lymphatic system may create a roadblock.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5954877/


STEP 1 - COLLECT A HAIR SAMPLE


A baseline Hair Toxin Mineral Analysis (HTMA) is required to obtain an approximation of your mineral status and personalise mineral supplementation. For this purpose, a list of vendors offering a compatible list of markers and reference ranges is provided here:


Doctors Data and other compatible laboratories:
AU - https://www.toxno.com.au/articles/heavy-metals/hair-tissue-mineral-analysis-hma-or-htma-in-australia/ (can manually add rubidium)
EU - https://eneviahealth.com/en/tienda/mineralograma-de-pelo-doctors-data/ ($try UK site first)
EU - https://www.biocoherence.eu/en/shop/htma/ (doesn't include rubidium)
EU - https://www.lifelinediag.eu/en/product/eha-standard-en/#products (doesn't include rubidium)
NZ - https://www.houseofhealth.co.nz/product/hair-toxic-mineral-analysis/
UK, some EU - https://www.lauristonlabs.co.uk/product/hair-elements-doctors-data/
US - https://www.walkinlab.com/products/view/dd-hair-elements-profile-doctors-data (Not available in NY/ NYC and other areas.)


Online resellers for Trace Elements Inc (doesn’t include iodine, optional boron):
AU - https://interclinical.com.au/htma-pathology/
DE - https://www.verisana.de/shop/haarmineralanalyse/
FR - https://www.sante-detox.com/tests-et-analyses-minerales/1460-analyses-minerale-profil-1-avec-bore.html
NZ - https://www.garymoller.com/orderahtmatest
PL - https://analizawlosa.com.pl/produkt/analiza-wlosa/
SG - https://www.kimikimorganics.sg/products/adult-htma-hair-tissue-mineral-analysis-profile-1
UK - https://www.mineralstate.co.uk/hair-analysis-chart/
US & CAN - https://store.myersdetox.com/products/hair-mineral-analysis-with-no-consult-interpretation


Hair collection guide:
1. Please ignore any conflicting vendor-specific instructions.
2. The hair needs to be clean, well-rinsed, dry, untreated and uncoloured. Unwashed hair may provide false (elevated) data for sodium and potassium, from dried sweat.
3. Select suitable areas of sideburn, scalp and/or neck hair. If the hair is longer than 2.5cm / 1", first trim the sample area to this maximum length with clean stainless steel scissors. By using shorter hair, the report data relates to a more recent period of time.
4. Cut the (remaining) hair to be sampled as close to the skin as possible. Do not use clippers or an electric razor - metal contamination from tungsten blades, etc may occur. Collect at least 2 heaped tablespoons worth of hair, or approximately 250 mg. If the amount of hair provided is insufficient, the sample may be rejected.
5. Place the hair sample in the sample kit envelope provided, or in a clean, clearly labelled envelope or sachet. Whilst Trace Elements Inc says not to use ziplock bags as apparently hair “sweats” and the sample may be rejected, Doctors Data supplies ziplock bags in their kit.
6. Repeat the HTMA every eg. 6 weeks, using fresh regrowth from the same area, until an optimal mineral balance is achieved.


STEP 2 - ORDER YOUR SUPPLEMENTS


It will typically take 2-3 weeks to get your HTMA results and a potentially similar timeframe to order / receive supplements from any overseas vendors. Now would be an opportunistic time to order any/all supplements which do not require personalisation by HTMA results and presumptively, at least the 3 mineral supplements which are used early in the schedule. Expect 3+ months to remineralise from severe mineral deficiencies, although this is improving.


Some products are not available domestically in all regions and will need to be imported from the US. As such, the “master list” is based around US suppliers. However, a list of local vendors / supplements for regions has been provided for some products. It is expected that local lists will expand over time. (PRODUCTS RECENTLY UPDATED are marked in GREEN)


[USA / Master List 1/2 - most products ship internationally]
Standard supplements, regardless of HTMA:
Liposomal Riboflavin* - https://www.solacenutrition.com/product/cyto-b2/
(*This is a unique product - do not substitute. If you buy 2, a cheaper shipping option appears and the total order price doesn’t change. Digestion and absorption / transport bottlenecks exist for riboflavin. Multiple alternate forms have been tested without success. This microencapsulated product bypasses these issues.)
Liposomal or sublingual NAD+ precursor (standard oral NAD+ precursors don’t absorb well) - https://renuebyscience.com/product/pure-nad-nasal-spray-10-grams-pure-nicotinamide-adenine-dinucleotide-nad-new/
NAC - https://nootropicsdepot.com/n-acetyl-l-cysteine-500mg-capsules/
Vitamin C + D-Ribose - https://www.pureformulas.com/vitality-c-200g-by-american-nutriceuticals.html
[iHerb Quicklist for this section -  https://iherb.co/Z96YEtb ]
ALCAR - https://iherb.com/pr/now-foods-acetyl-l-carnitine-500-mg-200-veg-capsules/15271
Berberine - https://iherb.com/pr/natural-factors-wellbetx-berberine-500-mg-120-vegetarian-capsules/85657
PQQ + CoQ10 - https://iherb.com/pr/natural-factors-pqq-10-pqq-20-mg-coq10-200-mg-30-softgels/105659
Thorne Basic B Complex* - https://iherb.com/pr/thorne-research-basic-b-complex-60-capsules/18791
(*Do not substitute. This B complex product has been carefully selected to contain sufficient amounts of the required forms of each coenzyme, minus inappropriate amounts of pyridoxine, yet adequate P5P.)
Folinic Acid (not folic acid) - https://iherb.com/pr/source-naturals-megafolinic-800-mcg-120-tablets/7735
Vitamin D3 - https://iherb.com/pr/now-foods-vitamin-d-3-125-mcg-5-000-iu-240-softgels/22335
Vitamin A - https://iherb.com/pr/21st-century-vitamin-a-3-000-mcg-10-000-iu-110-softgels/43717
DHA - https://iherb.com/pr/source-naturals-vegan-omega-3s-non-fish-epa-dha-300-mg-60-vegan-softgels/46882
EGCG - https://iherb.com/pr/now-foods-egcg-green-tea-extract-400-mg-180-veg-capsules/11598
A-GPC Choline - https://iherb.com/pr/now-foods-alpha-gpc-300-mg-60-veg-capsules/12803
Forskolin - https://iherb.com/pr/life-extension-forskolin-10-mg-60-vegetarian-capsules/49696
Artichoke / Luteolin - https://iherb.com/pr/jarrow-formulas-artichoke-180-veggie-caps/177
R-ALA - https://iherb.com/pr/allmax-r-ala-60-capsules/67927
TTFD - https://iherb.com/pr/ecological-formulas-allithiamine-vitamin-b1-50-mg-250-capsules/61109
ACV - https://iherb.com/pr/swanson-apple-cider-vinegar-625-mg-180-capsules/109045
Apigenin - https://iherb.com/pr/codeage-liposomal-apigenin-non-gmo-vegan-90-capsules/114120
Reishi* - https://iherb.com/pr/life-extension-reishi-extract-mushroom-complex-60-vegetarian-capsules/46279
(*PRODUCT DOES NOT SHIP TO EU - use EU source. Do not substitute. A USP study found approximately 75% of reishi products are fake. This product passed our HPLC + LCMS mass spectrometer testing. Most did not. Further, different metabolites are extracted from different parts of the fungi, eg. fruiting body, spores and mycelium. Beta-glucans require hot water extracts, triterpenes require alcohol extracts.)
Lions Mane + Ergothioneine* - https://iherb.com/pr/real-mushrooms-ergo-l-ergothioneine-60-capsules/113975
(*PRODUCT MAY NOT SHIP TO EU - if so, use EU source.)
Taurine - https://iherb.com/pr/now-foods-double-strength-taurine-1-000-mg-250-veg-capsules/39933

“Standard” Elemental Supplements:
(For any Naturitas products, there is a mobile app available. You can also use https://www.naturitas.com or these links to redirect to your local region):

Fulvic acid “complexed” ionic multi-mineral (Boron, Chromium, Iodine, Lithium, Magnesium, Manganese, Molybdenum, Potassium, Rubidium, Selenium, Strontium, Zinc, others) - https://goodstate.com/collections/man/products/ionic-man-mans-liquid-ionic-multi-mineral
Silicon (not tested by these HTMA reports, however a key elemental deficiency frequently observed) -
https://www.naturitas.com/#/dffullscreen/query=FNature%20Organic%20Silica
Calcium Phosphate (Marine) - https://iherb.com/pr/veglife-red-marine-calcium-90-tablets/70153
Magnesium (oral) - https://iherb.com/pr/now-foods-magnesium-citrate-180-softgels/22552
* AND * (transdermal) - https://iherb.com/pr/life-flo-magnesium-oil-sport-spray-8-fl-oz-237-ml/49247
(Transdermal absorption route appears to be significantly more effective in some people. This magnesium product has eucalyptus and menthol, providing additional benefits for energy metabolism and immune support.)

Additional elements, as indicated by HTMA:

Fulvic acid “complexed” Copper - https://goodstate.com/collections/ionic-copper/products/good-state-liquid-ionic-copper-96-servings-at-2mg-each-plus-2-mg-fulvic-acid-8-fl-oz
Fulvic acid “complexed” Iron - https://goodstate.com/collections/ionic-iron/products/good-state-liquid-ionic-iron-48-servings-at-10mg-plus-2-mg-fulvic-acid-8-fl-oz
Sulphur - https://www.naturitas.com/#/dffullscreen/query=msm%20%20salud
Vanadium - https://www.naturitas.com/#/dffullscreen/query=ifigen%20vanadium
Cobalt - https://www.naturitas.com/#/dffullscreen/query=ifigen%20cobalt
Bismuth - https://www.naturitas.com/#/dffullscreen/query=ifigen%20bismuth
Germanium GE-132 - https://www.nutricology.com/organo-germanium-50-vegetarian-capsules


Foods, salts (use local sources):

Sodium Chloride  - https://www.amazon.com/Amazon-Brand-Happy-Ground-Ounces/dp/B07QW1G8MW/
Potassium Chloride - https://www.amazon.com/No-Salt-Substitute-11/dp/B00KPX1YPM/
Ginger (ground) - https://www.amazon.com/Organic-Ground-Anthonys-Gluten-Free-Non-GMO/dp/B019ZW9XBA/
Oat Bran - https://www.amazon.com/Bundle-Two-16oz-Packages-BELLATAVO-Certified/dp/B09MCPY86H




[EU / Europe - alternate / domestic sources for some products]
Standard supplements, regardless of HTMA:

NAC - https://www.amazon.de/dp/B07X58JBY8
Reishi - https://www.lifeextensioneurope.de/reishi-extract-mushroom-complex
Lions Mane - https://www.amazon.de/dp/B07W668CZF
PQQ + CoQ10 - https://www.sunday.de/en/polyphenol-21-komplex.html

Additional elements, as needed:

Calcium + Phosphorus - https://www.sunday.de/en/natural-calcium-400mg-high-dose-capsules-set.html
Potassium - https://www.amazon.de/-/en/Potassium-Tablets-Vegan-Additives-Dosage/dp/B08VRPR39L/

Foods, salts:

Sodium Chloride - https://www.amazon.de/-/en/dp/B07PBJG722
Potassium Chloride - https://www.amazon.de/-/en/No-Salt-Sodium-Free-Alternative/dp/B000H185N6/
Oat Bran - https://www.amazon.de/-/en/764087/dp/B06WVLBX5P
Ginger - https://www.amazon.de/Ginger-Powder-120-Additives-Laboratory/dp/B09B2GRNG7



[AU / Australia - alternate / domestic sources for some products]
Standard supplements, regardless of HTMA:

Taurine - https://www.aminoz.com.au/amino-z-taurine.html
TTFD - https://revivifyhealth.com.au/products/objective-nutrients-thiamax
NAC - https://www.ebay.com.au/itm/223966754293
PQQ + CoQ10 - https://return2health.com.au/jarrow-qh-pqq-ubiquinol-pyrroloquinoline-quinone

Additional elements, as needed:

Magnesium (transdermal) - https://www.chemistwarehouse.com.au/buy/84838/bioglan-active-magnesium-cream-100g

Foods, salts:

Sodium Chloride - https://www.woolworths.com.au/shop/productdetails/320992/mckenzie-s-natural-salt-sea
Potassium Chloride - https://ozdingo.com.au/products/pure-potassium-chloride-powder
Oat Bran - https://www.woolworths.com.au/shop/productdetails/203867/woolworths-oat-bran
Gingerhttps://www.woolworths.com.au/shop/productdetails/680510/woolworths-crushed-ginger



[Supplements currently in testing for future updates, known benefits]
Rosemary Extract - glucose uptake, catecholamines, ACh, muscle preservation, anti-inflammatory, increases catecholamines
Boswellia - anti-inflammatory
PEA - anti-inflammatory
Bitter Melon - anti-inflammatory, increased acyl-coa dehydrogenases, SOD promotion
Fulvic “Trace Elements” - potential replacement for the additional elemental supplements


STEP 3 - CALCULATE SUPPLEMENTS / DOSES


Except for electrolytes, adjust / remove / replace mineral supplements using your HTMA report as an approximate guide. These reports are unable to show eg. tissue-specific deficiencies.


The general expectation is that deficiencies for iron, manganese (and copper, typically where lead, mercury or uranium are measured low) will exist, along with various others. These may take some months to restore. Special forms of some elements may be required for efficient remineralisation. Recheck your HTMA every 4-6 weeks and adjust as needed. At 6 weeks, averaged results will approximate 3 weeks progress, assuming linear progress.


If your HTMA profile shows elevated levels of heavy metals (eg. lead, mercury or uranium), taking a final binder (eg. 5g of activated charcoal, micronised zeolite or bentonite clay) or 5g of Pectasol-C could be appropriate before bed and far away from meals. Join us online for help.


Where a HTMA profile shows low potassium and similarly low rubidium, the rubidium deficiency will need correcting or else potassium levels may be difficult to restore. Similarly calcium with strontium and magnesium with lithium. High zinc can indicate low histidine / insufficient protein.


NB. Consuming higher than recommended daily intakes of minerals where a deficiency is not present could create additional health problems and should be generally avoided. Consuming certain minerals on an empty stomach will quite likely induce nausea.


Foods to generally consume as part of this protocol, per HTMA results:
Brazil and other nuts (silicon, rubidium, strontium, cobalt, warning - high selenium)
Liver, organ meats (very nutrient dense, not every day)
Broccoli + radish / mustard seed (additional sulforaphane, trace elements)
Cabbage (zirconium, rubidium), Carrots (Vitamin A), Green beans (silicon),
Eggs (Iron, iodine, choline, lecithin, biotin, etc),
Beetroot (nitrates for blood volume, nitric oxide and dopamine synthesis),
Ginger 2.5-5g/day (gut microbiome dysbiosis and itaconate / isocitrate lyase inhibition),
Oat bran (40 g+ /day for beta glucans, silicon - immunity, itaconate pathway),
Pineapple (100-200 g for silicon, bromelain - fibrin clots). Generally avoid fructose.
High protein diet (essential amino acids, often good phosphate sources) >1.5g/kg/day
Low-GI carbs 1.5-2g/kg/day, unless employing a ketogenic diet.


Hydration:
2.5-3L of water / day to help prevent dehydration and red blood cell rouleaux formation. 


Other electrolytes (potassium, sodium, calcium, magnesium, phosphate, bicarbonate):
Maintaining electrolytes can be challenging, due to expected renal dysfunction. Electrolytes are required for ion channels / transporters and signalling pathways. Where deficient, neurological symptoms, muscle spasms and pain/inflammation may occur. Nutrient absorption may be impaired. Electrolytes should be consumed slowly over the day and typically with carbohydrates / food. Consult your doctor, if suffering from any pre-existing kidney disease.
Total daily (elemental) targets -
Sodium: 2-2.5 g, eg. 5 g (teaspoon) of table salt.
Potassium: >5 g, eg. 900g / 3 large potatoes, or eg.10g of potassium chloride (Nu-Salt).
Magnesium: >750 mg. 1.5-2 g, where deficient.
Calcium: >750 mg. 1.5-2 g, where deficient
Phosphate: 1 g for maintenance, higher where deficient. eg. Meat, dairy, red lentils, sunflower seeds, potatoes. Supplements which combine phosphate with various electrolytes, eg. calcium phosphate may be available in some regions.


Elemental weights, by compound, for calculating servings of various electrolytes:
Sodium Phosphate Dibasic | 32% sodium, 22% phosphorus
eg. 7.8 g = 2.5 g sodium, 1.7 g phosphorus
Trisodium Phosphate | 42% sodium, 19% phosphorus
eg. 6 g = 2.5 g sodium, 1.1 g phosphorus
Sodium Chloride | 39% sodium, 61 % chloride
eg. 6.4 g = 2.5 g sodium, 3.9 g chloride
Sodium Bicarbonate (Baking Soda) | 27% sodium (best not consumed near meals)
eg. 9.3 g = 2.5 g sodium + bicarbonate overdose (diarrhoea, in a single dose)
Potassium Phosphate | 55% potassium, 15% phosphorus
eg. 9 g = 5 g potassium, 1.4 g phosphorus
Potassium Chloride | 52% potassium, 48% chloride
eg. 9.6 g = 5 g potassium, 4.6 g chloride
Magnesium Monophosphate | 28% magnesium, 23% phosphorus
eg. 2.7 g = 750 mg magnesium, 600 mg phosphorus
Calcium Phosphate | 39% calcium, 20% phosphorus
eg. 3.8 g = 1500 mg calcium, 770 mg phosphorus


STEP 4 - START THE PROTOCOL


It is fully expected that people exploring this protocol are highly sensitive to supplements.
To help avoid paradoxical symptoms that aren’t relating to improved immune activity, a starting order has been provided. Deviations from this starting order may induce avoidable and unpleasant symptoms, however you can space out the stages further, if needed.


BEFORE YOU START

1) First assess, remediate and maintain your lymphatic system. Take note of any tissues which have been or continue to be sore / stiff / inflamed - these will be expected to flare during immune activity.

2) Due to fulvic acid’s potent and desired ability to “liberate” and recirculate metals that are being sequestered during chronic inflammation, it is suggested that you test your response to a single drop of the the Good State Fulvic Ionic Man (multi-mineral) in a glass of water before starting the protocol. If you experience any unpleasant effects, take a few days to titrate up from a smaller dose (eg. place a drop in a bottle of water, mix and then transfer a drop from this first dilution into another glass of water) until you can consume a standard serving without observing these effects.


3) If you test a nasal application of the NAD+ spray and experience a temporary burning sensation in your nose / throat / ears, you may have a localised infection in those tissues. Performing a MARCoNS test through your health practitioner could be appropriate. Candida, Aspergillus, Staphylococcus and Klebsiella species are unwanted microorganisms sometimes found in these tissues. NAD+, Berberine and NAC may provide additional benefits against these pathogens, by inhibiting their energy availability, breaking down biofilms and other mechanisms..

NB. An unpleasant “herxheimer-like” effect would be expected during any increased immune response activity.


4) If your intracellular magnesium levels are low, you may experience “B6 toxicity” symptoms which would be enhanced by consuming additional B6 in any form. Gut motility issues are also commonly experienced.

You may help avoid unwanted symptoms by first consuming electrolytes to reach the suggested total daily intakes for 7 - 10 days, along with the Good State Ionic Man multi-mineral, before commencing the standard protocol. Liberally applying the magnesium gel 2+ times / day covering armpits to elbows, stomach, etc. can be highly effective.

NB. Correcting severe electrolyte deficiencies can create temporary paradoxical effects and increased rates of metabolism.


5) Where described below, “x 3” means “3 times per day” and not “3 doses all at once”.


Days 1-3+
Start (or continue) consuming / absorbing the foods and various electrolytes discussed in Step 3, plus:
Liposomal Riboflavin 200-250 mg, 2 x 2 large scoops, or 1 large scoop, x4. (This will reduce over time, as manganese / copper / selenium levels increase.
Liposomal NAD+ intranasal 2 sprays x 2-3
PQQ 20mg, CoQ10 200 mg x 1-3
Acetyl L-Carnitine 500-1000 mg x 2
Vitamin D3 5000 IU - 8000 IU x 1
Vitamin A 3000 mcg x 1 (or eat carrots)
DHA 300-500 mg x 1
Silica x 1 serving (or eat cooked green beans)
Berberine 500-1000mg x 3 (15-30 mins before / after meals)


Morning, after food -
Good State Fulvic Ionic Multi Mineral x 1 serving (Days 1,2,3+)
Taurine - 500mg - 3000mg (caution if using beta-blockers - reduces epinephrine release)
Lunchtime, after food  -
Good State Fulvic Ionic Multi Mineral x 1 serving (Days 2,3+)
Good State Fulvic Ionic Copper x eg. 2-4 servings as one dose
Taurine - 500mg - 3000mg (caution if using beta-blockers - reduces epinephrine release)
Evening, after food -
Good State Fulvic Ionic Multi Mineral x 1 serving (Days 3+)
Taurine - 500mg - 3000mg (caution if using beta-blockers - reduces epinephrine release)
+ Vanadium, Cobalt, Bismuth, Germanium, Sulphur (where indicated by your HTMA)


Days 4-6+
Continue taking the items in all previous days and add:
Thorne Basic B Complex 1 cap x 1-3 (Can expect to reduce this over time as key minerals are restored. Excess can cause peripheral neuropathy, via B6 / P5P.)
Folinic Acid (NOT Folic) 800-1200 mcg x 1
Vitamin C + D-Ribose x 1
EGCG 100-200 mg x 2-3
A-GPC Choline >250 mg x 2 (If muscle stiffness or headache occurs, reduce or pause dosing.)


Before bed, with food  -
Good State Fulvic Ionic Multi Mineral x 1 serving (total of 4+ doses/day)



Days 7+
Continue taking the items in all previous days and add:
R-ALA  (First 3 weeks at 100 mg x 3, then reduce to 100 mg x 1.)
NAC (Thrombolytic, biofilm breaker and mineral chelator - first 3 weeks at 1000 mg x 3, then reduce to < 500 mg x 1 until selenium is in range.)

Forskolin 10 mg x 1-2 (Temporary adrenergic increase, reduced histamine.)
Artichoke (Luteolin) 25 mg x 1 (Temporary adrenergic increase, reduced histamine.)


TTFD 50mg x 1 (Increase dose from 1/10th capsule, temporary neuro symptoms expected.)
ACV 2-3 caps x 3 (may cause temporary GI upset, histamine increase.)


Days 10+
Continue taking the items in all previous days and add:
Life Extension Reishi Complex* x 2
*A 1-3 day initial headache is possible when starting reishi.
Lions Mane (beta glucans) >250mg x1 AM (may increase histamine / insomnia, low dose.)
Apigenin eg. 50mg x 1 AM (p38 MAPK inhibitor and NADase inhibitor, start at ¼ dose and increase. Upper threshold for effective dose may be 400mg/day.)


Evening, with food (elemental amounts, only where indicated by your HTMA results) -
Good State Fulvic Ionic Iron x 2-4 servings


With "anaemia of inflammation", iron, manganese, copper and other mineral absorption is blocked in the GI tract and other cells at DMT1 and ferroportin. Alternate mineral forms / sources which do not use these transporters are needed. An IV infusion may be appropriate, where indicated by your healthcare professional. Any rapid ferritin increase can cause or accelerate hypophosphatemia. Care should be taken to consume optimal levels of phosphates, especially where already deficient. If an active eg. bacterial / fungal infection is present, these are best resolved before starting iron supplementation.



STEP 5 - OPTIONAL FOLLOW UP


When the element levels reported by your HTMA are optimal, a 3 day “water fast” may provide additional benefits. This is NOT advisable with severe mineral deficiencies.


If this is your first water fast, it is generally advisable to have someone monitoring you during this time. Avoid driving vehicles, stress and excessive exertion.


Fasting protocol requirements (per day):
No food or other supplements.
3L water.
5g (teaspoon) of sodium chloride (table salt = 2.5g sodium elemental)
1g of baking soda (110 mg of sodium)


(Optional add-ons)
500mg EGCG x 3*
Resveratrol 120mg x 3
Hesperidin 500mg x 2


(*NB. Important safety consideration: To break a water fast “early”, use 2 or more Apple Cider Vinegar doses - without capsules - as a succinate source.
This is only a requirement if EGCG has been dosed in the previous 6 hours.

Failure to observe this safety consideration may result in rapid cyclical blackouts and convulsions until the EGCG is fully metabolised or until someone else administers Apple Cider Vinegar.
This could easily be fatal if eg. operating a motor vehicle. YOU HAVE BEEN WARNED.)


9
Purpose:

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.
https://www.amazon.com/Gluten-Free-Remedies-Succinic-Acid-250mg/dp/B00IFJC4GG/

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

3. EGCG, as Green Tea Extract
Used to reduce the glutamate dehydrogenase (GDH) enzyme.
https://www.amazon.com/NOW-Supplements-Green-Extract-Capsules/dp/B001DNV5CA/

4. Sodium Chloride
Used to help maintain extracellular sodium levels. Use reagent grade or rock salt.)
https://www.amazon.com/dp/B000SWVKAE/

Recommended Extras -
5. Potassium Chloride
(Reagent grade / high purity. NOT: Nu-Salt, Morton’s Salt Substitute.)
Used to help maintain intracellular potassium levels.
https://www.amazon.com/NOW-Potassium-Chloride-Powder-8-Ounces/dp/B00028M02Q/

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.
https://www.amazon.com/dp/B06VW5YP1Z/

7. Resveratrol
Used to alter glycolysis and improve fatty acid oxidation.
https://www.amazon.com/Ultra-Purity-Resveratrol-Capsules-Trans-Resveratrol/dp/B07R634S5D/

8. Forskolin
Used to increase cAMP and fatty acid oxidation.
https://www.amazon.com/Life-Extension-Forskolin-Vegetarian-Capsules/dp/B000LVG7J6/

9. Hesperidin
Used to maintain increased cAMP and fatty acid oxidation.
https://amazon.com/Hesperidin-Capsules-aurantium-Metabolic-Cardiovascular/dp/B0896VYQ9Y/

10. Caffeine
Used to increased fatty acid oxidation.
https://www.amazon.com/Bulksupplements-Caffeine-Capsules-gelatin-capsules/dp/B01IA8YFAE/

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.

Strictly:
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.

Guidance:
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.
https://www.amazon.com/SweetLeaf-Sweet-Liquid-Stevia-Sweetener/dp/B00B7V6YHY/
(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.

10
[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:
https://en.wikipedia.org/wiki/Pulmonary_function_testing
https://www.amazon.com/peak-flow-meter/s?k=peak+flow+meter

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 -
https://www.urmc.rochester.edu/encyclopedia/content.aspx?contenttypeid=167&contentid=carbon_dioxide_blood
https://www.verywellhealth.com/hypercapnia-symptoms-treatment-914862
https://labblog.uofmhealth.org/lab-notes/chronic-high-carbon-dioxide-levels-blood-associated-more-hospitalizations-and-death)

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.
https://www.amazon.com/s?k=potassium+bicarbonate

Controlled deep breathing exercises may be highly appropriate. Correcting a bicarbonate deficiency allows for improved pH buffering, however this is still dependent on respiration.
https://www.healthline.com/health/copd/breathing-exercises#3-deep-breathing
https://www.wimhofmethod.com/breathing-exercises

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..]

11
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.

12
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?

13
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.

14
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?

15
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

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