The Protocol

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General Mitochondrial & Wellness Protocol
(Technical Edition)


by
Joshua Leisk | (@joshual_tm on X/Twitter)
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What's new?

Here are the 10 most recent changes / updates:

For more detailed information, please see Changelog
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NB. Whilst efforts have been made to make this information accessible on mobile devices, it is best viewed on a computer.


Summary


This is an experimental protocol based on the disease model by Leisk et al., (preview here - https://bornfree.life/2024/the-disease-model/) which may be helpful for supporting the unique nutritional and wellness / lifestyle requirements of teenagers and adults with chronic illnesses that share various common features, including mitochrondrial dysfunction, hormone dysregulation, ferritin and other mineral deficiencies, microbiome dysbiosis, biofilms, neurotransmitter regulation and immune dysregulation, etc., such as:

Myalgic Encephalomyelitis / Chronic Fatigue Syndrome (ME/CFS) Long COVID, Post-Vaccine Syndrome Viral / Post-Viral Chronic Fatigue
Post-Exertional Malaise (PEM) “Floxed” Guillain-Barre syndrome (GBS)
Chronic Inflammatory Response Syndrome (CIRS) Breathlessness Hypoxia
Acidosis / Alkalosis / pH Dysregulation Dysregulated Cortisol Dyslipidemia
Post Finasteride Syndrome (PFS) Post SSRI Sexual Dysfunction (PSSD) Post Accutane Syndrome
Small Fibre Peripheral Neuropathy (SFPN) Mast Cell Activation Syndrome (MCAS) Diamine Oxidase (DAO) Deficiency
Stiff Person Syndrome Gut Fermentation Syndrome Glycogen Storage Disease (functional)
Histamine intolerance Brain Fog Sleep disorders
Anxiety Postural Orthostatic Tachycardia Syndrome (POTS) Autism Spectrum Disorders (ASD)
Fibromyalgia Dysautonomia Frequent Urination
GI Disorders “Small Intestinal Bowel Overgrowth” (SIBO) Vitamin B6 Toxicity
Vitamin A Toxicity Candidiasis Aspergillosis
Ehlers Danlos Syndrome (EDS) Joint Pain Connective Tissue Disorders
Tinnitus Polycystic Ovary Syndrome (PCOS) Erectile Dysfunction
Elevated Cholesterols / Fasting Glucose / D-Dimer Hashimotos Alopecia
Major and other types of Depression Cataracts Migraines

Contents


Warning:
This documentation contains a significant amount of information and it is expected that you will need multiple read-throughs and a number of hours to absorb and / or action the information.

How to Navigate This Information

There are multiple ways to approach this material:

  1. First Reading: We suggest that you read everything from start to finish in a linear fashion. This will help you become acquainted with all of the concepts.

  2. Guided Navigation: If you decide to act on the information, return here and use the visual navigation tool below to step through the protocol in a logical and structured manner.

  3. AI-supported (experimental): If you would like AI assistance in understanding the model and/or protocol, Google's NotebookLM is able to perform this function for free. A setup guide is available here - https://bornfree.life/2024/notebooklm-ai/ 


Title
Summary
Contents
Disclaimer
1 Introduction
2 The protocol
- (Optional) Pre-protocol support
2.1 Collect your data
- 2.1.1 Blood tests
- 2.1.2 Intracellular minerals
- 2.1.3 MosaicDX Organic Acids Test (OAT)
- 2.1.4 Cronometer
- 2.1.5 Microbiome testing
-- Fermenting species identification
2.2 Lifestyle changes
- 2.2.1 Diet
- 2.2.2 Lymphatic maintenance
- 2.2.3 Living without chronic dysbiosis
-- Nasopharynx
-- Gastrointestinal
-- Mammory glands, lactiferous ducts
-- Parasites
-- Interventions
-- Binders
-- Bacteriophages
-- DIY antiseptic
-- Biofilm breakers
-- Protective probiotics
-- Prebiotics
-- Herbal Anti-microbials
-- (Prescription-based interventions and other options)
-- Environment
- 2.2.4 The importance of pacing
- 2.2.5 Structural issues
- 2.2.6 Cortisol, limbic system, glycogen and IFN-γ
-- Anxiety, isolation, and phobia
- 2.2.7 Reproductive health, menstrual cycles, UTIs and PSSD
- 2.2.8 Sleep
- 2.2.9 PEM prevention and recovery
2.3 Daily Supplement Schedule
- Stage 1: Remineralisation, increasing collagen synthesis rates and performing a controlled initial “die-off”
- Stage 2: Increased GI / mucosal interventions
- Stage 3: Stimulate and support a strong immune response
- 2.3.1 Herxheimer / die-off / acetaldehyde support
- 2.3.2 Remineralisation
- 2.3.3 Blood-flow, hypoxia and fibrin-amyloid
- 2.3.4 Rapid withdrawal symptoms, hypo/hyper-metabolism
2.4 Optional follow-up
2.5 Ongoing preventative maintenance
3 Rationale for protocol inclusions and general notes
4 Calculating supplement doses
4.1 Electrolytes
4.2 Custom troches
4.3 DIY shake and DIY sipper
5 Ordering products
- Bacteriophage product selector
6 Frequently asked questions (FAQ)
Changelog

Disclaimer


Please read this entire document before taking any action based on its contents.

Important Notice:

While we strive to minimize adverse effects, you may experience some temporary symptoms when starting this protocol:

  • Paradoxical Effects: As deficiencies are corrected and neurotransmitter balance is restored, you might notice short-term increases in adrenaline and heart rate.
  • Copper Deficiency Correction: Addressing a severe copper deficiency may cause temporary kidney pain and nausea.
  • Immune Activity Increase: An initial boost in energy availability can heighten immune activity and symptom severity. This might be psychologically challenging and may cause hesitation in continuing the process.
  • Herxheimer Reactions: You may experience effects from microbial die-off, such as increased "burning" sensations and headaches.
  • Hormonal Changes: Temporary changes in libido or menstrual cycles can occur.
  • Inflammation and Flu-like Symptoms: Improvements in adaptive immune function might lead to brief periods of inflammation, fever, flu-like symptoms, nausea, and fatigue.

Support:

We host an online discussion and support group on Discord. Feel free to join us:

https://discord.gg/CAMXV78


Monitoring Recommendations:

In addition to the tests used in the protocol, we suggest regular blood tests to monitor:

  • D-dimer Levels
  • Vitamin B6 Levels
  • Cholesterol Levels
  • Fasting Glucose Levels

Medical Disclaimer:

This protocol is for research and educational purposes only. Always consult your doctor to determine if this information is appropriate for you, especially if you are taking medications like SNRIs/SSRIs, beta-blockers, MAO inhibitors, or drugs metabolized by CYP2D6 enzymes.


Overview of the Protocol

This protocol is based on a disease model that identifies a blind spot in the immune system as the root cause of certain syndromes. This gap allows harmful microorganisms to hide within biofilms located in mucosal and other tissues such as the nose, mouth, lungs, gut, sex organs, and even the bloodstream. These biofilms can begin forming in small quantities early in childhood. Under normal circumstances, they grow slowly over many years and are now being associated with aging processes. Various immunological events can rapidly accelerate biofilm growth.

Formation and Growth of Biofilms

The immune system typically halts biofilm growth by detecting and attacking microorganisms during their free-moving (planktonic) stage outside the biofilms. However, this defense can be compromised by factors such as infections, injections, drugs, trauma, malnutrition, and stress.

Toxins and Immune Response

A primary toxin produced by these bacteria is acetaldehyde, which is also a byproduct of alcohol metabolism, as seen in Gut Fermentation Syndrome. This toxin interferes with energy production and affects the immune system and gut lining. The disruption allows more microorganisms to breach bodily barriers, triggering an innate immune response involving interferon-gamma (IFN-γ) and reactive oxygen species to eliminate them. Other endotoxins and mycotoxins have relevance, also.

Challenges in Diagnosis and Treatment

Chronic inflammation can turn functional mineral deficiencies into long-term systemic issues. Measuring intracellular minerals during chronic inflammation is problematic due to altered transporter behavior in cell membranes, in different tissues. The cyclic nature of the disease and impaired absorption in the duodenum make it challenging to correct deficiencies through diet or oral supplements. Absorption and homeostasis of up to ten metals may be inhibited at different times, depending on inflammatory states and signaling.

Ongoing Research Insights

Our ongoing research has found that IFN-γ immune dysregulation and a persistent cyclic inflammatory process involving a peptide hormone called hepcidin disrupt homeostasis for at least 11 biologically active metals. These metals rely on common transporters: divalent metal transporter 1 (DMT-1) and ferroportin.

Additional mineral deficiencies have been observed. eg. Silicon may be excreted or depleted as a microorganism-produced Si-acetaldehyde compound. Dietary restrictions and toxins produced by bacteria or fungi can also alter zinc and other mineral homeostasis. Mineral deficiencies can create cascades of other issues; for example, lithium and rubidium deficiencies can worsen catecholamine metabolism and kidney function. Kidney problems may lead to electrolyte deficiencies, disrupting energy metabolism, neurotransmitter function, immune activity, and muscle contractions—including those of the heart and skeletal muscles.


Mineral Deficiencies and Dysregulation

Specific mineral deficiencies can disrupt your immune response, leading to further energy dysregulation and damage to nearby cells and tissues. This results in severe imbalances in the gut and other microbiomes, weakening the immune system.

Additional Dysregulations

This complex cascade affects neurotransmitters, cortisol levels, vitamin B6, cholesterol, histamine, hormones, kidney function, and body temperature regulation, among others.

Reversing the Trajectory
To reverse this progression, several key issues need to be addressed:

Fixing mineral and other deficiencies
is crucial, as it helps restore energy production, manage oxidative stress, and resolve issues with chronic human herpesviruses, among others.

Correcting imbalances in the microbiome, biofilms, and infections
by treating all mucosal surfaces and the bloodstream. This removes reservoirs of pathogens and endotoxins. Employing lifestyle changes which cultivate healthy microbiomes helps create ongoing resilience against future dysbiosis / infections.

Addressing structural problems
involving the lymphatic system and related structures can improve neural blood flow and reduce hypoxia.

Dealing with trauma and PTSD
is also essential for complete recovery, as it addresses limbic system influences affecting neurotransmitters, energy metabolism, and immune activity.


Current Findings and Research

Early testing shows that some individuals achieve long-term remission, while others significantly improve on their way to remission. Clinical trials are currently being organised.


Broader Implications

This metabolic cascade appears in many infections and chronic conditions. Associated dysfunctions include severe mitochondrial dysfunction, low intracellular oxygen levels, nervous system dysfunction, histamine dysregulation, collagen synthesis issues, and immune deficiency. This is not an exhaustive list.


Future Directions

Elemental deficiency patterns can predict various disease features and severity when linked to related enzyme impairments. Ongoing improvements are continuously reflected in protocol updates.



This protocol involves several steps that require multiple tests and a wide range of important supplements. While the expected results are unlikely to be realized without completing all these steps, efforts have been made to simplify them as much as possible. The steps are as follows:

  1. Collect Your Data
  2. Lifestyle Changes
  3. Stage 1: Remineralization, increasing collagen synthesis rates, and performing a controlled initial “die-off” (at least two weeks)
  4. Stage 2: Enhanced gastrointestinal and mucosal interventions (at least two weeks)
  5. Stage 3: Stimulate and support a strong immune response while breaking (circulating) biofilms (at least four weeks)
  6. Optional Follow-Up
  7. Ongoing Preventative Maintenance

We fully anticipate that individuals exploring this protocol may be highly sensitive to supplements. The reasons for this sensitivity are detailed in the disease model and have been accounted for within the protocol. The sensitivity to supplements and foods is expected to resolve as part of the protocol.

This protocol is designed to stimulate immune activity and may produce a “J-curve” trajectory, meaning you might feel progressively "quite sick" at the beginning of each stage. Increasing energy availability allows for heightened immune activity, which prioritizes energy metabolism toward these goals and can temporarily intensify symptoms. Carefully maintaining levels of electrolytes, copper, zinc, iron, manganese, selenium, glycogen, and B vitamins may help prevent severe symptoms and post-exertional malaise (PEM) or "crashing."


trajectory

Your individual experience may vary based on factors such as the pace of protocol implementation, the pathogens involved, your initial baseline condition, and the consistency and accuracy of your daily participation. Avoiding or delaying parts of the protocol can hinder progress and potentially lead to unnecessary discomfort. Support is available through our Discord discussion group.

Before beginning, assess your lymphatic system as described in the “2.2.2 Lymphatic Maintenance” section. Note any tissues that have been or continue to be sore, stiff, or inflamed—these areas are expected to flare during increased immune activity and may be adjacent to other infected tissues.

To help reduce expected symptoms when correcting deficiencies and experiencing Herxheimer reactions (fungal die-off effects) due to improved immune activity, a recommended starting sequence has been provided.

The "die-off effect" can cause a range of temporary but highly debilitating symptoms, including headaches, nausea, additional fatigue, dizziness, swollen glands, bloating, gas, constipation or diarrhea, joint or muscle pain, tachycardia, chills, cold hands or feet, itchiness, rashes, sweating, and fever resembling the "disulfiram effect."

A schedule of specific products is available, with vendor website links provided for different regions (see “5. Ordering Products”). These are not affiliate marketing links. With the exception of the Oxalobacter.com website (which was created out of necessity to address worldwide supply issues for "Oxalobacter formigenes" probiotics and is not intended as a for-profit endeavor), there are no financial incentives or benefits from providing links to products or tests. If you encounter supply shortages, please try to find the same product from another vendor or ask for help in the online Discord discussion group.

Deviating from the recommended starting order or substituting products may lead to avoidable and unpleasant symptoms or may simply be ineffective. You can space out the stages further if needed. Despite the extensive list of supplements—aside from one or two items included to make your experience more tolerable—all are necessary. Attempts to create a "lite" version of this protocol by swapping or omitting items have consistently resulted in failure.

Stage 1 focuses on delivering missing minerals and other nutrients to the body, sometimes via non-oral routes, to resolve measurable deficiencies caused by inhibited oral absorption of these micronutrients at levels typically found in foods. While this helps restore normal metabolism, these nutrients are also accessible to the microorganisms inhabiting your body. Therefore, an additional goal of selectivity is required, targeted by a combination of probiotics and antimicrobial interventions. Some of these interventions are included in Stage 1, while others are introduced in Stages 2 and 3.


It is not advisable to take the Stage 1 metabolic support supplements for an extended period without progressing to the parts of the protocol that address microbiome dysbiosis, such as dietary optimisation. Otherwise, you may feel increasingly better at first, but over time this may lead to amplification of existing microbiome issues. Nutrients that benefit your cells also benefit microorganisms that depend on you, and vice versa.


Fulvic Acid Usage
Fulvic acid is used in Stage 3 of the protocol. Due to its potent ability to "liberate" and recirculate metals sequestered during chronic inflammation; it is recommended to test your response to a single drop of Good State Ionic Man (fulvic acid multi-mineral) diluted in a glass of water during Stage 2. Increase the dosage slowly. Fulvic acid is also a potent biofilm breaker. If you experience any unpleasant effects, take a few days to gradually increase from a smaller dose—for example, place a drop in a bottle of water, mix it, and then transfer a drop from this first dilution into another glass of water—until you can consume a standard serving without adverse effects.


Nasal Inflammation Considerations

If you have nasal inflammation or notice any airway resistance or restriction when breathing, it may be appropriate to perform a nasal microbiome test. Unwanted microorganisms such as Candida, Aspergillus, Streptococcus, Staphylococcus, and Klebsiella species are sometimes found in the nasopharynx. These tests may also indicate the susceptibility of detected strains to interventions like fluconazole, itraconazole, voriconazole, or amoxicillin.

Aldehyde Metabolism Insufficiency
If your levels of magnesium, zinc, molybdenum, selenium, iron, iodine, or calcium are low, you may experience additional symptoms related to aldehyde metabolism insufficiency. These symptoms can be exacerbated by consuming excess alcohol, histamine, polyethylene glycol (PEG), vitamin A, or vitamin B6.

Issues with neurotransmitter metabolism, histamine regulation, and gut function are common and to be expected.


Correcting Deficiencies and Potential Effects

Correcting severe electrolyte deficiencies can temporarily create paradoxical effects, including increased metabolism rates and heart rate. Consuming certain minerals like copper or zinc on an empty stomach can easily induce nausea.


If taurine or magnesium affects your sleep or causes palpitations, tremors, or if you feel worse upon starting them, this may indicate a calcium deficiency. Adding 1–2 grams of elemental calcium per day, along with vitamin D3 and vitamin K2 MK-7, may help correct this. Be aware that addressing a calcium deficiency can initiate the process of oxalate dumping, which is necessary but may cause muscle pain. Low calcium levels may coincide with strontium and phosphorus deficiencies. The tests included in this protocol will help identify these issues. Low strontium levels in hair testing may serve as a proxy indication for calcium deficiency.


Correcting an iodine deficiency is likely to temporarily increase anti-thyroid peroxidase antibodies (anti-TPO) and Thyroid Stimulating Hormone (TSH), enhancing the activity of the sodium-iodide symporter (NIS) while improving levels of triiodothyronine (T3) and thyroxine (T4).


Simplifying Supplement Intake

We recognize that the extensive list of individual supplements required for this protocol presents a new challenge. We are collaborating with compounding pharmacies to simplify this process—transforming most of Stage 1 into two sublingual lozenges (troches) and a tub or bag of premixed powder. A DIY powder recipe is also included for those who prefer to mix their own.

Inositol and Glycogen Replenishment

Consuming mixed inositols will signal your cells to increase glucose uptake and glycogen synthesis, promoting glycolysis over other energy pathways. Inositol inhibits catalase, which may decrease your capacity to handle oxidative stress during immune activity, necessitating additional antioxidant support. If your liver and muscle glycogen stores are low—which is expected—you may initially feel extremely hungry or experience hypoglycemic symptoms such as dizziness, depression, and extreme fatigue. Consuming up to 500 grams of additional net carbohydrates and water over two to three days to replenish glycogen stores should help you feel significantly better. Glycogen binds with water at a 1:3 ratio, so your total body mass may increase by around 2 kilograms. Note that inositol can be problematic if you are following a ketogenic diet. D-chiro-inositol should be started at approximately 2.5 mg and very slowly increased as tolerated.

(Optional) Pre-protocol support


While getting started (ideally after sending off your baseline tests), you may help stabilise critical parts of the metabolism and help avoid unwanted MCAS + other symptoms by;
a) Consuming the suggested food items in 2.2.1 Diet.
b) Making a DIY "Sipper" of specific electrolytes and amino acids to put in a 500ml drink bottle and slowly sip between meals (see 4.1 Electrolytes and 4.3 DIY "shake" and "sipper"). You can start at 1/8 daily doses and increase. This can be combined with eg. green or other tea, lemon juice, lime juice, etc for flavour. (NB. Consuming too much at once may cause diarrhoea, headaches, nausea, water retention and/or rapid urination. Shake before each use, as dicalcium phosphate is largely insoluble.)
c) Taking [high dose Vitamin B1 as thiamine HCL, (sublingual) Vitamin B2 - FMN and (sublingual) Vitamin B3 - NMN] (or the compounded troches - see 4.2 Custom troches) at different times throughout the day.
d) Liberally applying the magnesium gel after showering, can be highly effective for magnesium absorption.
e) Working on your lymph flow - see
2.2.2 Lymphatic maintenance - this is especially important if addressing the electrolyte deficiencies allows immune activity to initially increase, which is more likely when these deficiencies are severe.

Product ordering links can be found in 5 Ordering products.


2.1 Collect your data


This protocol begins with a data collection process that helps you to identify specific deficiencies and microbial influences relevant to your metabolism.

There are multiple tests required to collect this data and the protocol is unlikely to succeed without them.

protocol-testing2

2.1.1 Blood tests


Testing blood is a helpful way to understand specific aspects of immune activity and metabolism. Minimally, it’s useful to have markers for blood group (needed for Oligoscan), red blood cell (RBC) and white blood cell (WBC) counts, comprehensive metabolic panel (CMP) and lipids, LDH isoenzymes, iron studies (iron, transferrin, transferrin saturation %, ferritin), vitamin B6 and vitamin D (inactive form). Your doctor is usually the best person to assist you with these, however private lab services are also available in many countries, should these be helpful.

USA


Australia


Lactate dehydrogenase (LDH) isoenzymes

Lactate dehydrogenase (LDH) is an enzyme primarily involved in converting pyruvate to lactate (and vice versa). It has five isoenzymes (LDH-1 to LDH-5), each consisting of different combinations of two subunits: H (heart) and M (muscle). Further, there are individual LDH isoforms - LDH-A/B/C which make up these isoenzymes. These isoforms have specific roles / functions. LDH is also a metalloenzyme, affected by zinc status and NAD+:NADH ratio. LDH isoenzymes are distributed across various tissues based on their metabolic needs.

The terms "H" (heart) and "M" (muscle) subunits were historically named based on the tissues where these subunits were first observed in high concentrations. The H (heart) subunit was first identified in cardiac tissue, which relies on aerobic metabolism. The M (muscle) subunit was discovered in skeletal muscle, which often utilizes anaerobic glycolysis, especially during high activity.

This test allows you to see if an elevation of a specific isoenzyme or pattern of elevations is present, further suggesting if a particular tissue is experiencing energy metabolism dysregulation, and/or upstream  influences affecting energy metabolism.

eg. If LDH-4 and LDH-5 (which contain more M subunits, characteristic of anaerobic glycolysis) are elevated, it can be indicative of reduced oxygen availability or prolyl hydroxylase inhibition for other reasons (oxidative stress, low Fe/Si, low Zn, low alpha-ketoglutarate, elevated succinate). These isoenzymes are more prevalent in tissues that rely on anaerobic metabolism, such as skeletal muscle and liver, and their elevation suggests a shift towards lactate production due to reduced oxygen, a common feature of hypoxic conditions and / or various issues which inhibit prolyl hydroxylase activity (see Figure 1).


2.1.2 Intracellular minerals / nutrients


Use at least one of the following two testing methods (hair mineral testing no longer supported for measuring most deficiencies due to unavoidable limitations in the methodology).

There are limitations to any testing methodology and potential ways for errors in sampling to occur. Some of these problems can be identified and avoided. Others can relate to eg. unpredictable sample transport delays.

To identify potential data errors, best practice is to triangulate and validate markers, deficiencies and issues from multiple data sources, eg. direct measurements of minerals and patterns in metabolites of enzymatic reactions which rely on these minerals.

White blood cells (WBC)


Currently, there are 3 competing laboratories which specialise in measuring the intracellular nutrient status inside WBCs - Cell Science Systems CMA (part of their CNA offering), SpectraCell Micronutrients and Vibrant America Micronutrients.

WBCs are used as a proxy to infer the nutrient status of other cell types, eg. brain, muscle, liver, etc. This data is very different to what is reported in serum (data sourced from outside the cells and any/all related mineral transporter function) or red blood cells, which lack mitochondria and therefore have very different metabolism. Vibrant America Micronutrients test does an excellent job of highlighting this issue in their report. It's frankly astonishing that serum testing is still considered the "gold standard" by public health systems, in light of these issues. However, this also highlights why chronic diseases have been difficult to research and solve.

Although all of these laboratories measure WBC nutrients, each of these tests has a different methodology and included array of markers. Therefore, the advantages and disadvantages for each have been carefully considered. Primarily due to the expansive array of markers more closely matching our requirements, Cell Science Systems CMA is used by this protocol. However, there are limitations to accommodate.

NB. Due to the preparation methodology used by the CMA assay, it's possible under certain circumstances for the report results to appear almost "normal" in the more severe patients with SEVERE deficiencies that affect how the cells behave, even when other deficient nutrients are added.
This can be identified by cross-referencing OAT metabolites and other data. Usually these are eg. phosphate and/or sulphur, however a severe enough deficiency of eg. B1 or magnesium can also limit cellular activity sufficiently to mask the effect of correcting other nutrient deficiencies.

By checking OAT results before ordering the CMA test, you can help identify if you're likely to have issues:
1. If you see elevated lactic acid (22), relative to pyruvic acid (23), elevated oxalic acid (21), and/or low phosphorus (76), this pattern is suggestive of excessive anaerobic glycolysis / lactic acid metabolism, metabolic acidemia and renal phosphate dumping.
2. A relative drop from citric acid (29) to aconitic acid (28), with similarly low 2-oxoglutaric acid (27) may indicate severe deficiency of magnesium.

The Pre-Protocol Support mentioned at the end of "2 The Protocol" may be helpful in bringing up the baseline metabolism enough to perform the test without issues. Alternatively, you could use the Oligoscan without this limitation.

However, if you receive a CMA report which is verifiably affected by this issue, you may be able to partially salvage the results by reinterpreting the markers as follows:
1. Any marker not all the way to the left, yet still green is re-interpreted as yellow.
2. Any marker that is yellow is re-interpreted as red.
3. Any marker that is red is re-interpreted as severely deficient.

Advantages:

1. Highly accurate and directly actionable data from an accredited laboratory.
2. Significant array of markers included.
3. Data is considered a snapshot of "current status", without any lag.
4. Blood sample can be collected at home, using a mobile phlebotomist.

Limitations:

1. 8–12 hours fasting is required.
2. Does not include fluorine, sulphur, silicon, various toxic metals, and some of the electrolytes – phosphorus, sodium and potassium
3. Does not indicate excess nutrient data, although this hasn't been a concern.
4. Transport of the sample needs to be rapid, to accommodate eg. cytokine half-life and nutrient transporter behaviour in the cellular membrane, otherwise report sensitivity can be lost. For non-US citizens, an express FedEx courier service is supplied by the laboratory (with an additional cost), along with any import/export clearance paperwork needed for getting blood samples through border security.
5. Sensitivity in the reporting appears to be significantly impacted by phosphate, sulphur and other deficiencies. I would suggest consuming eg. approximately 1.5g of dicalcium phosphate or monosodium phosphate, and 1g of taurine 3x/day for a week or more prior to testing. (Product links available in 5 Ordering products.)
6. Intracellular iron status does not capture systemic iron status data, as 75% of iron is circulating in RBC and serum. A separate test is required.

This comprehensive test is available internationally from a US laboratory. The test normally costs USD$239 - 264, plus express FedEx shipping (usually quoted / invoiced separately, shortly after purchase) and any phlebotomist costs.

1) https://www.dhalab.com/shop/cma-cellular-micronutrient-assay (USD$264)
or

2) https://previmedica.com/products/cellular-micronutrient-assay-cma-test  (US $239)



The reports track well with the other methodology, Oligoscan, where Oligoscan is interpreted using our upper and lower thresholds. CMA is more accurate and includes additional nutrients. However, as it also lacks some markers, some workarounds may apply:
Low iodine may be used to infer high fluorine.
Phosphorus data from the Organic Acids Test (OAT) can infer phosphorus status, although there are some differences, being urine / excretory data.
The protocol uses daily targets for electrolytes, however you won’t have an understanding of the baselines for these markers.
image-1


Skin

Research suggests that an Oligoscan, So/Check or Zell Check report can provide an approximation of your ACTUAL mineral status, using the skin of your hand as a data source. Note that “OligoLab” / “OligoHealth” / “Scantest” branded reports are currently not supported. This is normally an in-clinic test and a local practitioner will be required.

Your blood type, age, height and weight affect the sample calibration used to generate this report, so this information will be requested when you visit a clinic. Any inaccuracies can dramatically alter your results.

While not happy with the level of published evidence currently supporting this emerging methodology, our testing showed a clear pattern of deficiencies in ME/CFS, Long Covid and Covid19 vaccine injured people, with minor variability, which was not observed in controls.

Follow up Oligoscan reports have also matched supplements taken and previous results. The array of elemental markers collected is almost the same as the Doctors Data HTMA reports, however it also includes silicon and usually fluorine. Unfortunately, it does not show rubidium or strontium markers.
image-2
Notes and limitations:
1. As over 75% of systemic iron is circulating, Oligoscan / skin data for iron will be an unreliable proxy for systemic levels – blood tests for serum iron studies (iron, transferrin, tsat% and ferritin) would be needed via your doctor or private lab testing.
Low manganese may also provide a hint for low iron, unless IV iron has recently been administered.
2. Calcium markers in skin data will be similarly unreliable – 99% of calcium is stored in skeletal tissue. This also makes serum calcium insensitive. As strontium and calcium can potentially substitute for each other in biological processes, using the “strontium” marker from the hair test as a proxy to indicate systemic calcium may be possible, but needs further study. Tremors and/or heart palpitations, especially in response to taurine or magnesium could indicate low calcium, also. Low phosphorus may indicate low calcium.
3. Copper and zinc appear to be over-estimated in some cases.
4. Due to an unusual quirk in methodology / reporting, highly elevated minerals need to be re-interpreted as highly deficient.
5. Highly elevated zinc in skin tissue may also indicate low protein / histidine intake and mask an actual zinc deficiency.

Oligoscan and CMA results are not known to be directly affected by the inflammatory cascade, meaning that these reports provide an actionable set of objective markers to use when choosing most mineral supplements to address deficiencies. (HTMA data can be referenced to help supplementation planning for rubidium and strontium, also inferring calcium).

For more information about the effects of specific mineral deficiencies, see the “Rationale for protocol inclusions and general notes” section. The Oligoscan and SO/Check reports include a number of vitamin markers, which appear to track relatively well with other data. A good general target for these is to exceed 55%.
Toxic metals are also reported. These are already targeted in the protocol. Any markers in the “High -/+” ranges should be monitored. Due to redistribution, heavy metals in skin often go up in the first stage of the protocol, then decline.
Unfortunately, a comprehensive list of providers is not yet available. If you have a good (or bad) experience with an Oligoscan practitioner, please share details with our community Discord group in the #oligoscan-providers channel. You can find local practitioners here: https://www.theoligoscan.com/nearest-provider

Hair minerals (deprecated / limited use)


Research suggests that a Hair Toxin Mineral Analysis (HTMA) may provide an approximation of your functional mineral status, averaged over the period of follicle growth, sampled adjacent to the transporter alterations from inflammation – where circulating minerals can be sequestered inside various brain, liver and kidney cells and consequently low in other cells. It cannot accurately report on the intracellular levels or systemic levels, as sequestered minerals are not shown in this data.

The results obtained from the HTMA data may be used to infer averaged intracellular mineral availability, downstream of any chronic inflammation, for the period of time in which the hair follicles grew, in a similar way to read HbA1C for glucose metabolism. This mechanism is largely relevant to the ten elements transported by DMT-1 and ferroportin.

A list of vendors offering a compatible list of markers and reference ranges is provided below. Doctors Data and other compatible laboratories
US https://www.walkinlab.com/products/view/dd-hair-elements-profile-doctors-data (not available in NY/ NYC and other areas.)
AU https://www.toxno.com.au/articles/heavy-metals/hair-tissue-mineral-analysis-hma-or-htma-in-australia/ (can manually add rubidium)
EU / UK https://regeneruslabs.com/products/hair-toxic-essential-elements-1
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/
PL https://analizawlosa.com.pl/produkt/analiza-wlosa/
UK / some EU https://www.lauristonlabs.co.uk/product/hair-elements-doctors-data/
Hair collection guide:
  1. 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. Use gloves.
  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 may occur. Collect at least two heaped tablespoons worth of hair, or approximately 250mg, or 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 resealable plastic bags as apparently hair “sweats” and the sample may be rejected, whereas Doctors Data supplies plastic bags in their kit.


2.1.3 Mosaic DX Organic Acids Test (OAT)


A Mosaic Diagnostics (Mosaic DX, formerly Great Plains) Organic Acids Test (OAT) is a comprehensive report on urine metabolites.
While there are various OAT vendors, eg. Genova Diagnostics, Vibrant, Nutripath, etc., the preferred vendor for this protocol is Mosaic DX, for reasons of reliability, results consistency and marker inclusion.

This test is available through local vendors, or  these websites:
International - https://mosaicdxinternational.com/products/mx-organic-acids-test-oat
US - https://www.integrativepsychiatry.net/shop/the-great-plains-laboratory/urine-organic-acids-test/
UK / EU - https://smartnutrition.co.uk/shop/great-plains-oat-organic-acids-test/

AU - via a RN Labs registered practitioner

Note: if there is a pattern of “left shift” or “suspiciously low” microbial markers on page 1 of the OAT results, it’s possible the sample has thawed in transit and the integrity compromised, AND/OR the concentration of the sample was out of range (hydration levels). You may need to repeat the test.

For best results a very short shipping time is needed and creatinine levels (marker 77) should ideally be between 80-180 mg/dL.

Mosiac DX automatically scale the report markers against the creatinine levels, which can induce a false LEFT-shift with very high concentrations and RIGHT-shift with very low-concentrations. Overall, it's something I think the lab could improve on.


In addition to allowing interpretation of metabolic impairment from the patterns observed in these markers, page 1 of the report shows various markers for microbial interference. The remaining pages show your metabolic impairments from infection and malnutrition. Elevation of yeast, bacterial and fungal metabolites in OAT results have been seen consistently in our collected data, with matching symptoms. A further MycoTOX test may provide further clarity on species and expected metabolic impairments, if required.

A clinician’s guide to interpreting OAT results is being drafted. Example interpretations of these reports can be found on our Discord online discussion group.

A basic OAT interpretation guide for the purposes of supplement selection can be found in 4 Calculating supplement doses.


2.1.4 Cronometer


Cronometer (https://cronometer.com) is a freemium online app which can visualise the performance of your current eating strategy / habits / restrictions and allow you to make positive changes. It has a mobile app for data collection and basic reporting. Using a desktop / laptop allows access to richer reporting options and diary view.

Logging at least two days of eating in Cronometer would be very helpful for identifying problems and also help you rebuild / restore your relationship with food, especially as any sensitivities are reduced / resolved over the duration of the protocol. (see “2.2.1 Diet”)

People usually find this process eye-opening.


When selecting food items to enter into the virtual diary, choosing NCCDB or USDA listed food items will provide more micronutrient data. CRDB (user-entered, moderated entries) only contain information displayed on the product labels rather than laboratory identified data.

An example day of eating, with nutritional report:

food_diary
scorecard
food_report

2.1.5 Microbiome testing


Dysbiosis and biofilms in the various microbiomes sits at the root of this disease model. Given the implications and progression described in the disease model, reviewing your medical history, from early childhood forward would be suggested. A common progression would be an early childhood infection / biofilm formation in the ears/nose/throat/sinuses that progresses to the gut (and sometimes lungs), before translocating to sex organs and urinary tract. Skin microbiome dysbiosis - eczema, acne, dandruff, fungal nails, etc is also common. 

Gut microbiome


Certain gut microbiome tests are useful in getting a rough understanding of the species present in your GI tract (with a focus on the large intestine), along with the metabolites they consume / produce and if any of these are toxic / relevant to your metabolic alterations. Currently there is no single "perfect" microbiome test available. There are a range of tests with strengths and weaknesses. For upper GI data, endoscopic biopsy / aspirate is currently the method-of-choice. Safer, easier and non-invasive methods for collecting upper GI data are desperately needed.

As the stool specimens are not homogenised, very different counts of species can be obtained from different parts of the same specimen. False negatives are common. This can create confusion for anyone who is used to interpreting various reports at face value. Any species counts need to be interpreted with low confidence.

However, the “overall trends” of species diversity and overgrowth can be useful in making decisions around changes to eating habits, supplements and other interventions, for example, consuming bismuth compounds and / or codonopsis / Dang Shen tea for inhibiting sulphur reducing bacteria and promoting bifidobacteria, or taking Akkermansia probiotics and/or pomegranate, if low or missing, along with a supportive diet.

Biomesight

For diversity / abundance testing and recommendations around dietary changes, Biomesight provide some useful reports and importantly, allows record-level data export to CSV for further detailed analysis, which can be used with the information here to make decisions around interventions. NB. fungal species are not reported.

A Biomesight data analysis tool is now available (beta), which will quickly interpret exported Biomesight CSV files against the disease model:
https://bornfree.life/2024/biomesight-tool/


Biomesight are offering a discounted test for people with Long COVID and you can also use the code "RemissionBiome" for any other Biomesight products, thanks to our ongoing collaboration with Remission Biome:
https://shop.biomesight.com/products/long-covid19-study-gut-microbiome-test

GI-MAP
For enhanced pathogen testing, also including parasites, along with reporting on GI related markers, a GI-MAP report provides more information, however the report lacks the detailed species diversity information provided by eg. Biomesight.
USA vendors:
https://www.dhalab.com/shop/gi-map-gi-microbial-assay-plus/

https://labtestshop.com/tests/gi-map-stool-test/
AU vendors:
https://healthandharmony.net.au/shop/gi-map-test-kit-gut-microbiome-stool-sample

https://elementalhealthandnutrition.com.au/product/gi-map-diagnostic-solutions/
UK, EU vendors:
https://smartnutrition.co.uk/shop/comprehensive-stool-test-gi-map-pathogen-plus-uk-and-europe-igimap/

https://www.ibsclinics.co.uk/product/gi-map/
https://ifu-wolfhagen.de/shop/stuhl-test/stuhl-und-verdauungsanalyse-pilze-gr-parasitologie-bakterien-bauchspeicheldruese-entzuendungsparameter/
IN vendors:
https://www.ithrive.shop/products/gi-map-stool-analysis-offered-by-diagnostic-solution-laboratory-us?variant=44135044612310

Other – sinuses, oral, lung, urinary tract and sex organ microbiome


If you have a known or suspected infection in any mucosal tissue, then combining qPCR and Next Generation Sequencing (NGS) 16S methodology can help identify the species present and help with decision-making processes around remediation. Reviewing your entire medical history since birth and highlighting / testing tissues with recurring issues would be highly appropriate.

They normally supply a "Level 1" report (targeted qPCR), followed by a "Level 2" report (NGS), a few days later. It's common that the Level 1 report results will be less than helpful.

MicrogenDX offer a range of different testing and reports, for different tissues. These are available to US and international customers.

https://microgendx.com/patients/microgendx-patient-test-service-dm-intl

Limitations:
1. Does not show Lyme species.

Circulating microorganisms - tick-borne, systemic infections


As anyone who has spent time around Lyme disease and tick-borne infections will tell you, getting good data on circulating and intracellular microorganisms is traditionally very, very difficult. Even if you have access to quality testing, the lifecycle of these species can make many of them difficult and expensive to quantify. However, Legionella and Rickettsia species frequently show up in Biomesight and other microbiome reports.

If you have a reason to suspect intracellular species are going to be included in your collection of pathogens
:
MicrogenDX
can provide "shotgun" metagenomic sequencing of samples to US customers for "research only" purposes and an extra fee, if your doctor contacts them.
ArminLabs EliSpot and TickPlex tests are able to detect a wide range of pathogenic species - https://arminlabs.com/en/tests/elispot
MDL
can provide comprehensive data via their OneSwab test - https://www.mdlab.com/testing/vector-borne/
Vibrant Wellness Tick-borne
test has a wide range of inclusions and uses multiple methodologies - https://shop.drjabanmoore.com/products/copy-of-vibrant-wellness-tickeborne-complete-1-0

Similarly, elimination of intracellular species has additional challenges to other microorganisms. Getting the immune system restored to normal functionality and ongoing use of circulating biofilm breakers is a key part of resolving these infections. Specific anti-microbials can be used to manage and accelerate this process.

Fermenting species identification


Once you have collected accurate microbiome data, you can use it to identify overgrowth of any species which produce alcohol and/or acetaldehyde using this table.

Notes and considerations:

1. Some species produce alcohol from
carbohydrates or lactic acid.
2. Other species produce acetaldehyde when provided with alcohol and may otherwise be harmless.
3. Some produce both.
4. Some probiotic species are also included for accuracy, however these are not considered problematic under normal circumstances.
5. Some species found outside the gut that only produce acetaldehyde may benefit from alcohol produced in the gut or from dietary intake. Therefore, you may have difficulties remediating overgrowth of these species in other tissues until moderate - severe fermentation by the gut microbiome is remediated.
6. This list is comprehensive, but not exhaustive. It will be added to as a comprehensive literature review is completed and GenBank entries processed.
7. It's a very interesting observation that all of the species known to be causal for common issues like acne and dandruff to various cancers are found in this list.



2.2.1 Diet


Planning and consuming an appropriate / strategic diet are complex topics for most people, even without a chronic disease.

For those with a chronic disease, it's significantly more complex. One common challenge is selectivity - trying to ensure that your cells are receiving these dietary nutrients, while avoiding feeding them to certain microorganisms residing in your GI tract - which then produce endotoxins / mycotoxins that poison your energy metabolism and neurotransmitter pathways. Acetaldehyde is one of the toxins discussed heavily in the disease model, as part of Gut Fermentation Syndrome (GFS).

Failure to adapt your diet around your personalised microbiome dysbiosis and chronic disease metabolism will invariably lead to "getting stuck" or even back-sliding. Unlike minerals deficiencies, which are normally slow to develop and slow to resolve, microbiome dysbiosis can rapidly shift during immune activity or by feeding the wrong microorganisms over a number of weeks. What you eat determines which microorganisms get promoted or inhibited.

Diet plays a pivotal role in chronic disease by influencing substrate availability for fermenting microbes and shaping the gut microbiota composition. High-carbohydrate diets provide ample fuel for microbial fermentation, exacerbating acetaldehyde production and metabolic disruptions. Conversely, low-carbohydrate diets can reduce substrate availability, potentially decreasing microbial fermentation and acetaldehyde levels, however these can also exacerbate glycogen storage issues and contribute to various symptoms like POTS, fatigue, depression and other neurological symptoms. This has been labelled by some as “low carb limbo”.


Depending on the functionality of different energy pathways, while first starting this protocol, you may also find you respond better to certain type of macronutrients, ie. carbohydrates, fats and proteins than others.

The performance of your diet can be predicted in the Organic Acids Test (OAT) results, by looking at the relevant pathways for metabolites of each macronutrient, eg. glycolysis, fatty acids, amino acids. Some of the adjacent pathway markers, such as ketogenesis, lactic acid and oxalate metabolism are also helpful in identifying impaired pathways, indirectly.

Therefore, before we go into detailing specific foods and their attributes, it helps to understand a little more about the different energy pathways and how dietary macronutrients can be turned into energy:


Instant / burst energy (muscle tissue)

ATP-PC (Phosphocreatine) System

Where:
Not used in liver and adipose tissue.
Substrates:
Phosphocreatine (PC) stored in muscles.
Requirements:
Dietary creatine. Creatine produced from the urea cycle, using dietary protein. Dietary phosphorus intake. Promoted by sex and thyroid hormones.
Uses:
High-intensity, short-duration activities (e.g., sprinting, weightlifting).
Availability / Duration:
10-15 second bursts.
Trigger/Signaling:
Immediate energy demand; catecholamines increase utilization.

High intensity energy demands

Glycolysis

Where:
Not used in red blood cells (RBCs), as they rely entirely on anaerobic glycolysis, and white adipose tissue prefers fatty acid metabolism.
Substrates:
Glucose or glycogen.
Requirements:
Dietary carbohydrate intake or gluconeogenesis. Phosphorus. Biotin. Vitamin B3 (as NAD+). Zinc. Magnesium / Manganese. Potassium. Chromium. Vanadium. Thyroxine (calcium, iodine, selenium, heme, tyrosine). Vitamin B1 (as TPP). Lipoamide. Promoted by sex and thyroid hormones.
Uses: Brain activity. Moderate to high-intensity activities (eg., walking / running upstairs, thinking).
Availability / Duration:
Muscles - up to 2-3 minute bursts, subject to glycogen reserves.
Trigger/Signaling:
Increased ADP levels; catecholamines enhance glucose availability via cAMP-PKA signaling, inhibiting glycogen synthase and activating glycogen phosphorylase.

Glutaminolysis (anaplerosis)

Where:
Not used in red blood cells due to lack of mitochondria and adipose tissue due to limited metabolic flexibility.
Substrates:
Glutamine.
Requirements:
Dietary glutamine, or glutamine created from citric acid cycle activity. Vitamin B3 (as NAD+). Zinc. Magnesium / Manganese. Promoted by sex hormones.
Uses: Rapid cellular proliferation (eg., immune response) and intense brain activity.
Duration:
Continuous during demand.
Trigger/Signaling:
Stress-induced catecholamine elevation may indirectly upregulate this pathway.

Sustained energy demands

Fatty Acid Oxidation

Where:
Not used in brain cells due to fatty acids not crossing the blood-brain barrier, nor red blood cells due to lack of mitochondria.
Substrates:
Fatty acids
Requirements:
Dietary fats or lipolysis. Carnitine for the carnitine shuttle. Vitamin B2 (as FAD). Vitamin B5 + cysteine (as Coenzyme-A). Lymphatic system is used to transport dietary fats. 
Uses:
Basal daily metabolism. Low to moderate-intensity activities (eg., walking, endurance sports).
Duration:
Indefinite.
Trigger/Signaling:
Prolonged energy demand; catecholamines promote lipolysis, increasing free fatty acids for oxidation.

Branched Chain Amino Acid (BCAA) Catabolism

Where:
Low activity in the smooth muscle, brain and liver. Primarily used in skeletal muscle, heart, and kidney tissues.
Substrates:
Leucine, isoleucine, valine.
Requirements:
Dietary protein intake. Vitamin B2 (as FAD). Biotin. Vitamin B12 (as adenosylcobalamin). P5P.
Uses:
Prolonged exertion, especially with low glycogen.
Duration:
Sustained.
Trigger/Signaling:
Catecholamines promote protein breakdown, increasing BCAA availability.

Backup energy pathways for excessive load and various mitochondrial dysfunction

Anaerobic Glycolysis / Lactic Acid Metabolism

Where:
Not used in liver (under normal conditions) and heart (prefers aerobic metabolism). Promotes neurogenesis and myogenesis.
Substrates:
Glucose.
Requirements:
Dietary carbohydrate intake or gluconeogenesis. TBC.
Uses: High-intensity activities with limited oxygen.
Duration:
Short bursts, up to 2-3 minutes.
Trigger/Signaling:
High ADP/ATP ratio, catecholamines enhance lactate production through glycogenolysis.

Astrocyte-Neuron Lactate Shuttle (ANLS)

Where:
Found in the brain. Lactate can also circulate and participate in the Cori Cycle.
Substrates:
Glucose (astrocytes), lactate (neurons).
Requirements:
Dietary carbohydrate intake or gluconeogenesis.TBC.
Uses: Neural activity, intense cognitive tasks where glycolysis is insufficient.
Duration:
Continuous during brain function.
Trigger/Signaling:
IFN-gamma, others. Norepinephrine enhances glucose uptake in astrocytes, promoting lactate production for neurons, similar to an intra-brain Cori cycle.

Cori Cycle
/ Lactic Acid Cycle
Where:
Systemic  
Substrates:
Lactate (from muscles, brain).
Requirements:
Dietary carbohydrate intake or gluconeogenesis. TBC.
Uses: High-intensity exertion / mitochondrial dysfunction.
Duration:
Normally short-term, during recovery.
Trigger/Signaling:
Epinephrine increases lactate production, fueling the Cori cycle.

Ketogenesis + Ketosis

Where:
Ketones are generated in the liver, but not used by it. Red blood cells cannot use ketones due to lack of mitochondria.
Substrates:
Fatty acids.
Requirements:
Dietary fats and/or lipolysis. TBC.
Uses:
Prolonged fasting, low carbohydrate intake / impaired glycolysis, or low liver glycogen.
Duration:
Sustained during glycogen depletion.
Trigger/Signaling:
Catecholamines promote lipolysis, increasing fatty acids for ketone body production.

Examples of some less utilised pathways, which may be promoted / abused when primary pathways fail

Tyrosine Catabolism

Where:
Not used in red blood cells and adipose tissue due to limited enzymatic activity for this pathway.
Substrates:
Tyrosine.
Requirements:
Dietary intake of tyrosine and/or microbiome synthesis. P5P. Ferritin. Calcium. Magnesium.
Uses:
Various, including stress, mitochondrial dysfunction.
Duration:
Continuous, where tyrosine exists.
Trigger/Signaling:
Catecholamines do not directly regulate but are derived from tyrosine.

GABA Shunt

Where:
Not used in liver and skeletal muscle as they are not involved in neurotransmitter metabolism.
Substrates:
GABA via glutamate or polyamine metabolism.
Requirements:
P5P, magnesium.
Uses:
Neural activity, especially during TCA cycle impairment and oxidative stress.
Duration:
Continuous.
Trigger/Signaling:
Catecholamines influence neurotransmitter release but do not directly regulate GABA metabolism.

Urea Cycle (Argininosuccinate)
Where:
Not used in brain and muscle tissue since the urea cycle is primarily hepatic.
Substrates:
Amino acids (arginine).
Requirements:
Dietary protein intake. Aspartate.
Uses:
Ammonia elevation, protein metabolism / high protein intake.
Duration:
Continuous.
Trigger/Signaling:
Catecholamines indirectly increase ammonia load, requiring urea cycle activity.


Food Intolerances

You also may have already developed a number of food intolerances.

Some of these intolerances are "simply" endotoxins being produced by overgrowth of unwanted microbial species living in biofilms inside your GI tract, consequently being sustained by your intake of various dietary carbohydrates and/or other nutrients, such as sulfur-rich compounds These endotoxins can inhibit energy metabolism, neurotransmitter homeostasis, histamine degradation and various other pathways.

"Sometimes the easiest way to solve a problem is to stop participating in the problem." - Unknown
(In this context, "You cannot efficiently eliminate or reduce overgrown species while you're also feeding them.")

Standard Mixed Diets vs. Ketogenic Diets


Standard Mixed Diet

A standard mixed diet typically includes a balanced intake of carbohydrates, proteins, and fats. In the context of the disease model, this diet may inadvertently contribute to increased fermentation and unwanted biofilm development. The high carbohydrate content fuels microbial ethanol and acetaldehyde production, leading to continued impairment of energy pathways due to elevated acetaldehyde. Symptoms such as fatigue, cognitive impairment, and metabolic abnormalities may persist or worsen under this dietary regimen.

Depending on the species and locations of the biofilms containing these microbial species, you may have more success avoiding symptoms by consuming different types of carbohydrates.
eg.
a. Simple carbohydrates / sugars may feed any existing microbial overgrowth in the mouth / throat / oesophagus / stomach / small intestine. In the absence of dysbiosis in those tissues, simple carbohydrates can also be readily absorbed in the small intestine, before reaching any dysbiosis in the large intestine, should it exist.
b. Complex carbohydrates may not be broken down until further along the GI tract and may skip feeding some of the populations residing in biofilms in the small intestine.
c. Different types of dietary fibres and starches may selectively feed some species and not others. (see "2.2.3 -- Prebiotics"")
d. Gliadin in gluten may generate an immune response due to molecular mimicry of the protein in the "hook" of Candida's hyphae form. Gliadin is also used by a particular pathogenic strain of Streptococcus salivarus to produce an antigen that punches holes in enterocytes, leading to gut barrier degradation, immune response and inflammation. Giardia infections are also known to create gluten intolerance.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4368562/

https://pubmed.ncbi.nlm.nih.gov/22617359/

In some types of more severe dysbiosis (and where your B vitamin and mineral status also supports this), you may find swapping more carbohydrates for protein can be helpful in avoiding endotoxemia symptoms such as nausea, bloating, diarrhoea, histamine reactions, tachycardia, headaches, etc. These will resemble die-off symptoms, as the same toxins are involved (see: 2.3.1-Herxheimer / die-off / acetaldehyde-support).


Here is an example 2000kcal mixed-diet, visualised in Cronometer:

mixed_diet_example


Ketogenic Diet

The ketogenic diet, characterized by high fat, moderate protein, and very low carbohydrate intake, offers a contrasting approach to a standard mixed diet or a low carbohydrate diet.It also avoids "low carb limbo" by promoting generation of ketone bodies in the liver.

In extreme gut microbiome dysbiosis cases, changing to a ketogenic diet for a period of time can also be very helpful in reducing fermenting species, however will require commitment to endure an often unpleasant induction (1 week) and then adaptation phase (2 weeks). If your OAT results already show elevated ketone markers, this is much easier. Studies suggest the acute effects of a ketogenic diet on your gut microbiome will last around 12 weeks, before the microbiome adapts. Combining this window of opportunity with other interventions in this protocol can allow you to break the existing cycle with lasting results.

By significantly reducing carbohydrate consumption, this diet limits the substrates available for microbial fermentation. As a result, endogenous ethanol and acetaldehyde production may decrease significantly in response to food intake, alleviating some of the metabolic disruptions caused by GFS.

However, circulating acetaldehyde and other endotoxins will still be experienced, making the first 1-2 weeks of a ketogenic (the induction phase) more unpleasant than it would be for someone without GFS.

A key point of difference is that the ketogenic diet promotes fatty acid oxidation and ketone body production as alternative energy sources. Ketone bodies can cross the blood-brain barrier and provide energy to the brain (much more efficiently after weeks of being on a ketogenic diet), potentially improving cognitive function and reducing fatigue. Additionally, this diet may alter the gut microbiota significantly, reducing fermenting microbial populations and promoting a healthier balance.


Mechanisms of Ketogenic Diet's Impact on GFS


Carbohydrate Restriction

Limiting carbohydrate intake directly reduces the amount of glucose and other fermentable sugars in the gut. This reduction in substrates can lead to decreased microbial fermentation activity, resulting in lower ethanol and acetaldehyde production. With less acetaldehyde burden, the inhibitory effects on metabolic enzymes are alleviated, helping to restore the cellular redox balance and improve the function of gluconeogenesis and fatty acid oxidation pathways.


Fatty Acid Oxidation and Ketogenesis

The ketogenic diet's high-fat composition encourages the body to utilize fats as the primary energy source. This shift promotes the production of ketone bodies in the liver through a process called ketogenesis. Ketone bodies serve as an efficient alternative energy source for various tissues, including the brain and muscles. By providing a consistent energy supply, the diet addresses the energy deficits caused by acetaldehyde-induced metabolic disruptions. Additionally, relying less on impaired glucose production pathways reduces the risk of hypoglycaemia.


Benefits of a Ketogenic Diet in GFS

Implementing a ketogenic diet in GFS management offers several potential benefits. By reducing acetaldehyde levels, the diet can help restore normal metabolic functions, improving energy production and overall well-being. The provision of ketone bodies as an alternative energy source may alleviate symptoms such as fatigue and cognitive impairments. Furthermore, the reduction in carbohydrate intake may lead to favourable shifts in gut microbiota composition, decreasing the population of fermenting microbes responsible for excessive acetaldehyde production.

Potential Challenges

Despite its potential advantages, the ketogenic diet presents challenges that must be carefully considered. The restrictive nature of the diet can make long-term adherence difficult for some people. There is also a risk of nutrient deficiencies, particularly in electrolytes, fibre, vitamins, and minerals, if the diet is not properly managed. Monitoring thyroid function is also helpful, as very low carbohydrate intake can sometimes reduce T3 levels, potentially affecting metabolic rate. Additionally, high-fat diets can impact beneficial gut bacteria, necessitating careful planning to maintain gut health.

A manganese deficiency will significantly impact hepatic gluconeogenesis, as will zinc and magnesium deficiencies. These should be somewhat addressed before attempting keto induction.

NB. The reduction in glucose availability may affect cognitive function where neural hypoxia exists - due to eg. structural issues, coagulation and/or transport issues, severe iron deficiency, and also blocked lymph nodes in the neck and/or nasopharynx (usually relating to localised infection). The reduced glucose affects lactic acid metabolism involved in the Astrocyte-Neuron Lactate Shuttle and ultimately energy availability in neurons.


Strategic Implementation

Successful implementation of a ketogenic diet for GFS requires proper planning to ensure safety and efficacy. A personalised nutritional plan tailored to individual needs and tolerances can enhance adherence and effectiveness. Cronometer is very helpful in planning and visualising a successful day. Setting expectations ahead of time will help allow you to "keep calm and keto on" during unpleasantness.

Supplementation with essential electrolytes, vitamins, minerals, and probiotics like the ones in this protocol may be necessary to address deficiencies and support gut health.

A gradual transition into the diet, by slowly reducing carbohydrate intake, prolongs keto adaptation and exacerbates energy crisis symptoms. It is not recommended.
 
A rapid transition normally creates temporary symptoms of "keto flu", which can be managed by using GoBHB exogenous ketone supplements and essential amino acids (EAAs) during the dietary transition.

Strictly restricting carbohydrate intake is paramount to the diet, which involves eliminating sugars and refined carbohydrates like sweets, sugary drinks, white bread, and pastries. Removing starchy foods such as potatoes, rice, pasta, and grains is also necessary. Instead, consuming non-starchy vegetables like broccoli, cauliflower, kale, and bell peppers (capsicum) provides essential nutrients with minimal carbohydrates. The target daily net carbohydrate (total carbohydrates, minus fibre) upper limit is 25g.

Increasing the intake of healthy fats supports the ketogenic approach. This includes consuming monounsaturated fats found in olive oil, avocados, and nuts, as well as omega-3 fatty acids from fatty fish such as salmon and mackerel. Saturated fats from sources like coconut oil and butter can be included. Butter is also a good source of butyrate, which may trigger rapid, beneficial changes to the microbiome, however, this will also trigger die-off symptoms and potentially induce rapid alcohol withdrawal symptoms.

Protein intake is important for essential amino acids and to allow the liver to perform hepatic gluconeogenesis for brain and other tissues. Balancing protein intake is important because excessive protein can be converted into glucose, potentially triggering an insulin response that inhibits keto induction / adaptation, while also fuelling microbial fermentation, depending on the location of the biofilms. The longer the protein take to digest, the further along the GI tract it will be before potentially feeding the microbiome.

Keto induction is easier with more fats than protein, initially. For example,

During keto induction, you could consume:

170g fat @ 1530 kcal +
100g protein @ 400 kcal
= 1930kcal

After keto induction, you can transition to consuming roughly 1:1 of fat:protein, on a per-gram basis:

150g fat x9 = 1350kcal
150g protein x4 = 600kcal.
= 1950kcal.

(Scale this by your calorific needs.)

High-quality protein sources such as lean meats, poultry, eggs (a great source of lecithin for phosphatidylcholine), and plant-based proteins like nuts (good mineral sources) and tofu (some people may have tolerance issues) are recommended.

Maintaining proper hydration and electrolyte balance is essential. Adequate water intake supports detoxification and metabolic processes, while sufficient electrolytes help prevent imbalances that will reliably occur during the initial stages of a ketogenic diet, as glycogen stores are intentionally depleted.


Here is an example 2000kcal ketogenic diet, visualised in Cronometer:

keto_example_diet


Inflammation and/or gut membrane permeability issues due to microbiome dysbiosis and related immune activity often leads to further histamine elevation and temporary IgG antibodies being produced. This is normal behaviour in response to complete foreign proteins getting through the barrier and triggering an immune response. In this state, foods which trigger mast cell activation and histamine release should be avoided for 6-8 weeks before reintroducing them, preferably after the barrier dysfunction has been sufficiently improved / resolved.

Due to metabolic impairments being described in this disease model, other food intolerance issues are entirely expected
. The disease model and collected data shows that aldehyde toxicity / impaired aldehyde metabolism leads to elevations of serum Vitamin B6, creates issues metabolising "inactive" forms of Vitamin A into the active forms, creates issues degrading histamine and separately, other issues promoting lactic acid metabolism also elevate endogenous biosynthesis of oxalate.

In this state, additional intakes of these nutrients / compounds may exacerbate existing symptoms. These issues are targeted in Stage 1 of the protocol and allows dietary intakes to become more flexible. Overall, foods need to be carefully managed and reintroduced as the related metabolic impairments and barrier function issues are resolved.

Meal composition and timing is also important when energy metabolism is impaired. Part of the metabolic cascade includes type-2 diabetes and metabolic syndrome, so the dietary strategies will look very similar.

In the context of the disease model including glucose uptake and glycogen storage issues, the BCAA content of dietary protein intake may be very helpful in refilling glycogen stores via an alternate route, depending on your manganese, zinc, magnesium, biotin, B1, B2, B3, P5P and B12 status. In addition to general energy availability improvements, the model shows this is helpful for preventing PEM and crashes, providing oxidative stress and coagulation is being managed.

A table of microbiome transforming foods is provided in 2.2.3 -- Prebiotics and should be considered a required part of the protocol and any strategic diet.

The concept of "roughage" and its role in helping to disrupt and remove mucous + biofilms, especially when combined with additional biofilm breaking food items / compounds is often underappreciated in meal planning.

Foods to generally consume as part of the protocol (as tolerance allows / increases):


Foods to consume cautiously (or in some cases, avoid) as your aldehyde metabolism, etc normalises (monitor serum cholesterols, B6, beta-carotene):


In the tables below, you'll find food items and their relevant attributes, which you can use to help you get started building meals.
These tables are best viewed on a computer or tablet. On mobile devices, some columns will be hidden to fit the screen.

The columns can be sorted and cautions or elevations of potentially inappropriate nutrients in foods items when getting started have been highlighted in red.
These tables are not intended to replace https://cronometer.com, which is incredibly helpful in visualising and planning your dietary strategy.

Protein sources:

Carbohydrate sources:

Micronutrient sources:


2.2.2 Lymphatic maintenance


The lymphatic system is a network which spans the majority of the human body. Until quite recently, it was not known that this also included the brain.

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 transports dietary fats and collects extracellular fluid and metabolites from tissues, returning them via lymphatic vessels to the bloodstream, preventing lymphoedema or catastrophic fluid build-up, pressure / pain 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. Calendula creams can also help move lymph.

In any disease where movement is being restricted, this creates additional difficulties for maintaining immune function, fat transport and metabolite circulation. The lymphatic system can become blocked. This may be observed as being stiff, or having sore swollen tissues that can feature enlarged lymph nodes, such as in the neck, groin and/or armpits, relative to adjacent infections. Failure to maintain the lymphatic system may create a serious roadblock to recovery.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5954877/

A session with a massage therapist who specialises in lymphatic drainage may help you assess and remediate any recurring lymphatic blockages. There are also some helpful videos online with comprehensive instructions.

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.
https://youtu.be/ccV24hCOe5A

https://youtu.be/dDrJajg2ZII

Localised pressure / oedema, numbness, hypoxia, impaired blood flow, "burning" sensations, pain and lactic acidemia can be expected when lymph nodes become blocked from nearby immune activity.

eg.

Intracranial pressure
is regulated by nasopharyngeal, occipital and cervical lymph nodes in the face and neck. If these lymph nodes become blocked, crippling head pressure can be experienced. This is especially noticeable if immune activity increases from eg. improved energy metabolism / resolving deficiencies. Intracranial pressure can be a blocking issue to making any forward progress, if left unresolved. Chronic intracranial pressure issues and nasal / sinus inflammation are commonly found where environmental mould issues are unresolved, see 2.2.3 Living without chronic dysbiosis.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10808075/

https://www.nih.gov/news-events/nih-research-matters/lymphatic-vessels-discovered-central-nervous-system

NB. The nasopharyngeal lymph nodes are largely inaccessible via manual manipulation, although a soft attachment and glancing angle with a vibrating massage tool on either side of the nose may help. Resolving infections in the nasopharynx reduce load on those lymphatic vessels. The occipital and cervical lymph nodes are much easier to access and clear.
https://bornfree.life/images/neck-lymphatic.mov

Face and sinuses
can become acutely painful if related lymph nodes are blocked. These nodes are usually very easy to access with your fingers or a vibrating massage tool.

Here is a diagram you can follow to help improve lymphatic flow, by dragging your fingers in the same locations and directions of the arrows. Areas with multiple arrows side by side may benefit from using multiple fingers:

face_lymph_sml


Hands and arms can be significantly affected by blocked lymph nodes in the neck and armpits. These nodes are usually very easy to access with your fingers or a vibrating massage tool.

Feet and legs
can be significantly affected by blocked lymph nodes either side of the groin and backs of the knees. These nodes are also easy to access with your fingers or vibrating massage tools.
NB.Most lymphatic drainage / massage specialists will skip the groin nodes due to being intimate areas, however these are commonly blocked, presumably from immune activity in the gut and/or sex organs.  

A strong paradoxical effect may be felt the first time a blockage is cleared.


2.2.3 Living without chronic dysbiosis


Yeasts, moulds and fungi are found everywhere in nature and have an important role. They decompose animals, plants and other organisms, recycling their elements and other nutrients, thereby continuing the circle of life.

Usually, these decomposing animals are not alive, however when an organism’s immune response is incapable of maintaining a defence against the normal daily background level of fungal challenge, the living organism will become food for yeast, mould and/or fungi. Various lifestyle influences contribute positively and negatively to maintaining this daily defence.

Lack of exposure to sunlight, lack of sufficient activity to maintain a specific immune function and/or lack of a balanced, protective microbiome can also contribute to an organism being more susceptible to mould. It has been previously said “we don’t grow old, we mould!”

Antibiotics are powerful tools in controlling bacterial infections, however they are also broadly indiscriminate in their effects and are overused in food production + minor infections, leading to a loss of microbiome diversity and also the development of drug-resistant strains. Acute use of them decreases systemic levels of both "good" and "bad" bacteria, creating opportunities for opportunistic fungal overgrowth. Without paying careful attention to diet, probiotics, prebiotics and host metabolism, using broadly destructive interventions against your microbiome can have deleterious effects on your health and happiness.

eg. If you pour weedkiller all over your garden, killing almost all of the flora and then don't replant and cultivate the garden again afterwards, you'll find that over a short time, the plant life now growing back is made up of the most hardy, versatile, adaptable species either left behind or reintroduced by natural processes. These are often the species of weeds you were trying to remove in the first place.


Growing a beautiful garden means making space for what you want to flourish, planting the seeds and then feeding the species you want to keep, so they can out-compete the others. Selective weeding is also helpful. Some fertilisers are selective for species, also. These will be discussed in the Probiotics and Prebiotics sections below.

garden_overgrown


Maintaining a protective gut microbiome in modern times has a number of challenges due to the germicidal effects of stomach acid, metabolic acidemia and chronic disconnection from our natural source of probiotics via our industrialised food chain / use of preservatives and general preference for cooked food.

image-15


The barrier function of the skin and mucosal layers play an important part in resilience against pathogens. Unfortunately, the human body has a number of tissues that are opportunistic for yeast / mould / fungal and bacterial infections to thrive with minimal interference from direct immune activity, thanks to their ability to form biofilms.
https://www.sciencedirect.com/science/article/pii/S0016508524050546


biofilms


Subgrouping for ME/CFS, PFS, PSSD and other patients may have a relationship with the locations of infected tissues. Localised pathogenic biofilm accumulation and chronic innate immune activation.

Nasopharnyx


One example for possible subgrouping relates to the nasopharynx
(and surrounding areas), which have a direct route to the central nervous system. Swollen / enlarged lymph nodes can often be found nearby infected tissues. If these blocked lymph nodes include the nasopharyngeal, occipital and cervical vessels in the neck and face, then crippling intracranial pressure can also be expected, as these nodes regulate intracranial pressure. This can cause debilitating pain, also creating a blocking issue / preventing remineralisation unless resolved beforehand. You can read more about this topic in 2.2.2 Lymphatic maintenance.




Do you have a history of cracked lips / ears / toes / feet / rectum, flaking skin, severe acne, dandruff, hair loss, red / inflamed skin patches / rashes, eczema, psoriasis,  nasal inflammation, tonsillitis, sleep breathing disorder, gut pain / issues, cystitis, prostatitis, mastitis, epididymitis, white or green/black film on tongue or discharge?

These are strong indicators for potentially invasive microbiome dysbiosis. The extent / severity of the invasiveness of these microbes has a direct correlation with the intensity and duration for activation of chronic innate immune response pathways. These alter energy metabolism towards specific immune functions and generate predictable symptoms, such as neurotransmitter and endocrine dysregulation, POTS, dysautonomia, elevated cholesterols, insomnia, frequent urination, etc., especially where coenzyme or mineral deficiencies are also present.

Orifices and tissues such as the nasopharynx, sinuses, throat, Eustachian tubes, ears, GI tract, rectum, vagina, feet, toes are areas which are not regularly exposed to direct sunlight. This list might well include all tissues, where someone is bed-bound or house-bound. These tissues provide “safe spaces” for any pathogenic microorganisms to colonise, create biofilms and thrive, without appropriate immune surveillance.

[source: https://commons.wikimedia.org/wiki/File:Paranasal_Sinuses_ant.jpg]

[source: https://commons.wikimedia.org/wiki/File:Paranasal_Sinuses_lat.jpg]


Gastrointestinal biofilms and pathogens


In the case of a GI tract infection
, this may also affect dietary absorption efficiency and cause endotoxemia, sometimes leading to gastroparesis, nausea / vomiting in response to food consumption, along with other potential systemic impairments.

The timing of symptoms onset, in relation to meals may be helpful in identifying the location of unhelpful biofilms / colonies and also which interventions may be the most appropriate. Generally, the shorter the duration between meals and symptom onset, the closer the biofilm / overgrowth is to the stomach.

Upper GI / small intestine dysbiosis / overgrowth may benefit from oral dosing of
specific biofilm breakers and related interventions, whereas lower GI / large intestine dysbiosis / overgrowth can be more easily targeted by administration of eg. robusta coffee enemas.

Similarly, upper GI microorganism colonies bloom in response to dietary intakes of simple sugars, BCAAs, etc., whereas colonies in the large intestine benefit more from more complex carbohydrates and proteins, which break down into simple sugars and BCAAs further along the digestion journey.

Different strategies are needed for different parts of the GI tract.


The human digestive system


This protocol currently includes a number of staged interventions to address biofilms and pathogens in different locations inside the GI tract, such as Candex, Biofilm Phase 2 Advanced, NAC, spirulina, curcumin, fulvic acid, prebiotics, targeted probiotics, biofilm flushes, dietary interventions and water-fasting, with an aim of not unduly circulating endotoxins / acetaldehyde in the process of eliminating them, if at all possible. These strategies have been testing well and we are always exploring ways to improve on this process (please join the Discord online community to join the discussion).

Professional endoscopic biofilm removal is possible, however there appears to be a significant problem with general awareness of biofilm issues amongst gastoenterologists, so finding a willing clinician is currently challenging. A paper and video of removal here - https://x.com/joshual_tm/status/1825355958568304834

One of the key challenges is that invasive microorganisms which breach the (mucosal) barrier function can trigger an IFN-γ response, which causes collateral damage and inflammation to infected tissues in the process of oxidising pathogens, using reactive oxygen species.

If the rate of collateral oxidative damage + pathogenic damage exceeds the regenerative capacity of the tissue, this could further compromise the barrier function and dysregulate IFN-γ activity, leading to a “deadlocked” cycle / state. External indicators for insufficient collagen synthesis rates may include hEDS symptoms, poor skin texture, chronic cranial instability, slipped rib syndrome, thoracic outlet syndrome, etc.




A healthy microbiome appears to play a very important role in providing protection against invasive bacterial, yeast, mould and fungal infections.

Apart from generating gaseous toxins, ethanol and acetaldehyde – depleting silicon and other metals in compensation, many yeasts / mould / fungi and bacteria can cause dramatic metabolic alterations. They have an ability to break through our skin / epithelial tissue / mucosal barrier function from immune-evasive biofilms and cause recurring / chronic immune activation during the invasion. This immune activation inhibits specific mitochondrial metabolism and reconfigures a number of other metabolic pathways toward combating these pathogens. However, while ultimately beneficial, these alterations can be quite debilitating, under certain conditions.

Mammary glands and lactiferous ducts are present in both male and female anatomy. A less well-known fact is that males are also capable of lactating under unusual circumstances that involve low dopamine and elevated prolactin. These tissues are also another common area for microbial biofilm formation.When diagnosed with an infection, this is known as non-lactational mastitis.

Collecting any data on this microbiome is rather difficult when not lactating. It's possible that repurposing eg. MicroGenDX's WoundKEY panel could be useful, if a sample can be obtained.

For women, where biofilms in these microbiomes contain pathogenic species, it is expected that immune activity and inflammation in these (and any other infected) tissues will ramp up during oestradiol elevation, by allowing more IFN-gamma activity.

This immune activity elevation occurs as a short spike during pre-ovulation and for a range of days during the second half of the luteal phase, pre-menses. (see "2.2.7 Reproductive-health")

Sore and bumpy breasts during these times are common and inflammation may be observed in both the mammary glands and lactiferous ducts, with or without accompanying swollen inframammary, anterior axillary and parasternal lymph nodes.


While traditionally, many women have received advice about reducing oestradiol levels to prevent these symptoms, this logically leads to persistence of the infection.

Working with the body's natural signalling, while helping to manage the localised biofilm, oxidative stress and pathogens may help you break out of this unpleasant monthly cycle.

Topical use of 70% DMSO / 30% water (or 30% aloe vera gel), as a transport enhancer, combined with various biofilm breakers and anti-microbial interventions listed in this protocol may be an effective way to shorten this journey. This intervention can also be used with other tissues.

NB. DMSO is expected to create a localised histamine response when applied to skin, which will feel itchy for a short period. It's best applied with clean hands or gloves.


mammary_gland

Parasites


Co-infections of flesh-eating parasites such as worms, flukes, amoebas, etc., can temporarily induce severe ME/CFS symptoms by directly attacking the epithelial layer and allowing opportunistic invasion by any/all microbial species. Any of these can become systemic and create a chronic, recurring immune response in different tissues.

If you suspect you have a parasitic infection, over-the-counter and/or prescription pharmaceutical interventions such as ivermectin, fenbendazole, mebendazole, albendazole, methylene blue and pyrantel may be appropriate. Some of these anti-parasitics also have anti-fungal and other properties. These are commonly taken as either a single or multi-dose intervention by all inhabitants of a household, per your pharmacist’s or doctor’s advice.

For other species, such as amoebas, paromomycin and similar prescription drugs can be highly appropriate. Additionally, various herbal products based on black walnut, cloves and wormwood have also shown as highly effective, eg.
https://www.australianhealthfoods.com/product/ppc-herbs-herbal-tri-plex

The GI-Synergy product in Stage 2 already includes many of these ingredients.

Interventions


Whenever our efforts or immune system is successful in killing these microorganisms, their death can cause “dumping” and circulation of these toxins which contribute to a well-known “die-off effect” occurring. This die-off effect is responsible for a number of highly debilitating symptoms, such as headaches, nausea, additional fatigue, dizziness, swollen glands, bloating / gas, constipation or diarrhoea, joint or muscle pain, tachycardia, chills, cold hands / feet, itchiness, rashes, sweating and/or fever which resembles the “disulfiram effect”. Read more here: https://www.thecandidadiet.com/candida-die-off-symptoms/

This cascade can cause an ongoing / recurring cycle of extreme unpleasantness, if these infections and their original “safe spaces” (biofilms) are not fully resolved and a protective microbiome restored.

We have been actively researching a combination of some innovative and existing strategies to help kill these microorganisms and minimise the die-off symptoms (see 2.3.1 Herxheimer / die-off / acetaldehyde support). Some additional challenges relating to biofilms, which provide further protection against our immune activities are also targeted.

In addition to the metabolic supplement schedule included in this protocol, a more rapid clearance of any (somewhat) accessible microorganisms may be achieved by direct or topical interventions for these infected tissues. Commercial preparations are available with various levels of efficacy.

However, the quality of your data will determine the quality of your results.
Having known targets allows for precision interventions to be used, whereas having unknown targets leaves you no choice other than "throwing darts in a dark room, hoping one of more of them lands". With a competent immune system, targeting the biofilms allows the immune system to see the pathogens and throw precision "darts".


Binders


Area of effect: localised and systemic interventions exist.
Limitations:
somewhat selective interventions - matching products with toxins is important.
Risk profile:
"Final binders" are usually non-toxic, some binders can also bind to nutrients, such as minerals, causing deficiencies over a short time.

Silicol Gel, Enterosgel:
Both of these readily-available products are non-absorbing silica-based gels that act as “sponges” for endotoxins / LPS / acetaldehyde and salts of heavy metals, backed by clinical trials. These are consumed around mealtimes or interventions that induce die-off, to mitigate the Herxheimer effect symptoms.

Zeolite: Zeolite is a natural volcanic mineral with a high affinity for binding heavy metals, environmental toxins, and radioactive isotopes. It acts as a molecular sieve, trapping toxins within its cage-like structure. Zeolite is non-toxic and passes through the body without being absorbed, making it a popular detox aid. It is often used in detox protocols to support the elimination of lead, mercury, and other harmful substances.


Bentonite Clay:
Bentonite is a type of absorbent clay known for its ability to bind toxins, chemicals, and heavy metals. When hydrated, it swells and creates an electrical charge that attracts toxins like a magnet. It is often consumed mixed with water and is widely used for digestive issues, detoxification, and skin health. It can be especially useful after exposure to environmental toxins or as part of a regular detox regimen.

Diosmectite (Smecta):
Diosmectite is a natural clay-based binder with potent adsorption capabilities, specifically targeting bacterial toxins, viruses, and harmful substances in the gut. It forms a protective layer over the gut lining, reducing inflammation and aiding in the healing of gut mucosa. Diosmectite is commonly used for gastrointestinal issues like diarrhea and leaky gut and can be helpful in reducing symptoms of food poisoning and infections.

Activated Charcoal:
Activated charcoal is one of the most popular and widely available binders. It has a porous surface that traps toxins, chemicals, and gases, preventing their absorption into the bloodstream. Often used for acute poisoning or in situations involving gastrointestinal distress, it can also be part of regular detox protocols. It is taken in capsules or powder form and is effective in reducing bloating, gas, and Herxheimer reactions during detoxification.

Fulvic Acid:
Fulvic acid is a natural organic compound found in soil and water sources. It has strong binding properties and can help chelate heavy metals and toxins, making them more water-soluble and easier to eliminate through the kidneys. Fulvic acid is also known for its ability to enhance nutrient absorption and support cellular detoxification. It is often consumed in liquid form as a supplement for detox and overall health.

Humic Acid:
Humic acid is a large molecule that works alongside fulvic acid to bind heavy metals, glyphosate, mycotoxins, and other environmental toxins. Its complex structure allows it to act as a natural chelator, pulling toxins from the body and supporting liver and kidney detoxification. Humic acid is commonly used to help restore gut health and improve immune function.

Spirulina:
Spirulina is a blue-green algae rich in nutrients and known for its detoxifying properties. It is particularly effective at binding to heavy metals such as mercury, lead, and arsenic, promoting their elimination from the body. Spirulina is often used as part of heavy metal detox protocols and can be consumed in powder or tablet form.

Chlorella:
Chlorella, another algae, is renowned for its detoxifying capabilities, especially in binding heavy metals, pesticides, and other toxins. It contains a unique outer cell wall that traps and removes these substances from the body. Like spirulina, chlorella is used in detox protocols and is available in various forms, including tablets and powders.

Pectin:
Citrus pectin, especially in modified form, is a powerful binder that helps remove heavy metals and environmental toxins. It works by binding to these toxins in the bloodstream and digestive tract, preventing their reabsorption and facilitating their excretion through urine. Modified citrus pectin is often included in protocols for reducing toxic burden, particularly for lead and mercury.

Chitosan:
Derived from the shells of crustaceans, chitosan is a natural polymer that acts as a binder for fat-soluble toxins, heavy metals, and excess lipids. It has therapeutic effects against LPS. It is often used to support weight loss and detoxification by reducing the absorption of fats and toxins from the digestive system. Chitosan supplements are available in capsule form and can be helpful in detox protocols.

Cilantro (Coriander): Cilantro is a natural herb known for its ability to mobilize heavy metals, particularly mercury, from tissues. While it may not be as potent as synthetic chelators, cilantro is often used in combination with other binders like chlorella to promote the safe excretion of heavy metals. It is a common addition to natural detox protocols and is consumed as fresh leaves, tinctures, or supplements.

A number of these binders are already included in the protocol at different stages.



Bacteriophages


Area of effect:
localised, replicating and systemic (nebuliser, IV).
Limitations:
highly selective intervention - matching products with species and strain are important.
Risk profile:
Non-toxic, can create die-off symptoms.

A bacteriophage is a virus which doesn't infect human cells, however it does infect and kill bacteria with high specificity, unlike antibiotics. They've been studied for over a hundred years and Russia is well-established as the world-leader in this area.. which makes things a little tricky in 2024. 

Bacteriophages have been studied against gut microbiome dysbiosis in long COVID, with positive results.
https://www.mdpi.com/1999-4915/14/12/2614


A little-known fact about bacteriophages is that they can be found in seawater in concentrations of up to 107 mL−1, however this does not automatically mean that random doses of seawater will contain the relevant bacteriophages that eg. match your collections of pathogenic species.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7150976/


If you have data from a microbiome report that indicates particular species of pathogenic bacteria
, you may be able to use a bacteriophage product in that tissue to help eliminate them - very, very selectively.

However, on the basis of various species regularly appearing in different tissues, bacteriophage products are also available which target a range of common pathogenic species. It's possible you may need more than one product to target all of the species reported in your data.


A product selection table and various product instructions translated from Russian to English are provided in 5 Ordering products.

For GI related targets, oral + rectal administration is recommended by product manufacturers, presumably to avoid being degraded by stomach acid.
The same W302 nebuliser mentioned in the DIY antiseptic recipe section is also appropriate for bacteriophage delivery to lungs and circulating targets.
Luer slip syringes can be used for other tissues / orifices.

NB. Just like when using any other any other well-targeted anti-microbial, die-off is expected. The more potent the anti-microbial, the larger the wave of toxins you need to metabolise and/or excrete. Some support for this can be found in 2.3.1 Herxheimer / die-off / acetaldehyde support.

DIY antiseptic recipe: mucosal clean and flush, rinse, topical spray


Area of effect: localised, with some systemic absorption / effects in some cases, eg. black seed oil.
Limitations:
broad spectrum, can harm good and bad species. Requires follow-up probiotics.
Risk profile:
Negligible toxicity, can create significant initial inflammation and die-off symptoms. 

Popular antifungal soaps, shampoos and creams containing zinc pyrithione can be effective at inhibiting fungal overgrowth. However, these products are now banned in Europe due to concerns around causing DNA damage.

Part of a successful "untargeted" intervention for these tissues may also include first administering a solution to break up any protective biofilms, leaving this solution to incubate for 20–30 minutes before (where possible / appropriate) wiping the area clean and then administering a second solution to selectively inhibit these foreign cells. These two solutions can also be applied simultaneously. The process may be repeated daily for 1–2 weeks, or as necessary.

Getting started:

Ongoing testing and literature review has suggested that a simple solution of NAC and hypertonic sodium bicarbonate water solution can reliably break up many biofilms and lyase cells. Breaking biofilms exposes any remaining microbes to immune surveillance and any other interventions you may explore. Using this recipe in a Neilmed Sinugator, douche or other appropriate tool can be a gentler way to start clearing biofilms and remodelling microbiomes, such as the nasopharynx and sex organs.

Further research has also suggested that a solution containing diluted tea tree oil, clove oil and other oils, when applied with or immediately following NAC yields a tolerable, yet significant inhibitory effect on bacteria, yeasts, moulds and fungi which may rival or exceed existing pharmacological interventions and is appropriate for a range of applications.

Commercial preparations made from tea tree oil and clove oil, are also readily available as shampoos, vaginal douches, topical sprays, mouthwashes, creams and suppositories.

https://iherb.com/pr/tea-tree-therapy-suppositories-with-tea-tree-oil-for-vaginal-hygiene-6-suppositories/14691


Available from your local chemist, Neilmed make sinus washing products – such as “Sinugator” and “Sinus Rinse”, which can be highly effective at pre-rinsing these difficult-to-reach mucosal tissues, 20 minutes prior to application of any antiseptic products.

2g boric acid and 5–10mg of liquid iodine can also be added to the Neilmed solution, for additional potency, however this may not be appropriate for daily use. A temporary smell of iodine and some burning / stinging would also be expected where infected tissues exist.

Note: Due to the die-off effect when killing fungi, using this antiseptic recipe while not using the other supplements from Stage 1 may be unnecessarily unpleasant and exacerbate symptoms.

Recipe 1: A potent essential oil-based solution
Part 1: Mix 500mg of NAC powder (preferably not from a capsule, as these usually have fillers, although these could also be filtered / strained after stirring), 500mg of sodium bicarbonate (baking soda), 1g of xylitol and >5 ml of water.

Part 2: Separately, mix essential oils –  20 drops of tea tree oil, 80 drops of black seed oil, 6 drops of oregano oil, 6 drops of clove oil, 1 capsule of Biofilm Phase 2 Advanced (BP2A). (You can add more black seed oil if you find this too strong.)

Mix both parts together to form your final solution – allow a 2 week shelf life. Store in an empty glass bottle with a dropper for convenient dosing. Shake well before use.


To test this as a nasal antiseptic: while laying on your back, with your head tilted back and breathing through your mouth, drip about 6 drops of the solution into each nostril.

Let the solution run into the nasopharynx and incubate for a minute or so, while you suffer through some shockingly unpleasant burning for a few minutes (the first time), assuming you have infected tissue. (See the experiences reported in the Discord server for more information.)

Healthy tissues won’t be irritated at this concentration, so if it "burns" – repeat this process every 1-3 days until irritation / inflammation is not observed. It will get progressively much easier.

Rotating your head slowly to each side and gently “equalising” (like pinching your nose, gently exhaling through the nose against the close nostrils and "popping your ears", like on an aeroplane) with fluid in the nasopharynx may allow the solution to access the Eustachian tubes. (Performing the same in reverse and inhaling against closed nostril can evacuate the tubes, also.)  After some time, blow / purge your nose, leaving some residue behind. A follow-up nasal probiotic may be very helpful after eg. 5-7 days of this, assuming there is no significant inflammation in response to the antiseptic.

To test this as a topical antiseptic: simply clean the area and then spray / apply the solution. A cotton tip could assist application to the ear canal or rectum (don’t use this in enemas).

To test this as a dental pre-rinse: apply a few drops to your tongue, teeth and gums, or more to gargle and spit. Wait a few minutes, then brush / floss as usual. Note: unpleasant flavour. Note: as an antiseptic, small amounts reaching your throat isn’t likely to cause toxicity, whereas drinking it intentionally could be harmful.

Sensitive tissues

Recipe 2:

For these and more sensitive infected tissues, e.g. ocular and vaginal infections, a pH balanced “gentle” rinse / douche can also be effective.

Combine a “squirt” of Johnson & Johnson Baby Shampoo (it contains a gentle detergent and EDTA as a biofilm breaker. NB. We are currently exploring organic alternatives) ,
plus;
1 x "Neilmed hypertonic sodium sachet" (or a teaspoon of sodium bicarbonate / baking soda), for osmolality,
in 240mL of clean water.
This recipe makes a gentle, yet potent, biofilm breaking intervention that can be used in a Neilmed Sinugator/Sinus Rinse tool, vaginal douche, Waterpik, etc.


Alternatively, you can also make another DIY rinse recipe

Recipe 3:

Per 500mL of boiled / cooled water -

Mix 5g of sodium bicarbonate (baking soda) with 5g NAC. This allows an acid:base reaction (and gas release) to occur, which helps create a pH balanced solution.

This can then be combined with ¼ teaspoon of boric acid (making a 1½–2% solution) and 10 drops of the 5% Lugol’s iodine or 25 drops of 2% Lugol’s iodine.

https://tinyurl.com/borates2023


To administer recipe 2 or 3:

  • Eyebath: Use 30mL of the solution to bathe each eyeball, also cleaning the eyelids, lashes.
  • Urethra: Administer 5–30mL of the solution via a large (needleless, Luer slip) syringe to the opening.
  • Vagina: Administer 50-120mL, using a suitable douche tool or syringe and keep your hips and legs elevated for 30 mins.
  • Lungs: (Use "Recipe 3" only) Administer 1-3mL via a drop-feed ultrasonic nebuliser, such as a "W302", found in most online marketplaces
  • Sinuses, Eustachian tubes: This recipe can also be added to the Neilmed Sinugator reservoir.


The colostrum from Stage 2 can also be successfully used in mucosal tissues to neutralise unwanted species, antigens, etc.

Rotating between the “potent” recipe and the “gentle” recipes for 1–2 days is recommended if intense inflammation for more than 30 minutes is experienced. Continue with the nasal probiotics from the next section once an inflammatory response can’t be provoked by the normal antiseptic recipe.

Regardless of the recipe used, strong die-off effects can be expected the first time and should only be implemented after metabolic and detox support supplements are added in Stage 1 of the protocol.

Links to ingredients and tools mentioned can be found in the "5 Ordering products" section.


Biofilm breakers


Area of effect: some are localised, others are systemic.
Limitations:
does not directly kill microorganisms - requires immune activity, probiotic species and/or other interventions to eliminate the species inside. Different biofilm compositions respond to different biofilm breakers - more than one may be required in chronic diseases with more than one pathogen indicated.
Risk profile:
usually broad effects on biofilms for both good and bad species. Can trigger elevated immune activity and redistribution of microorganisms. If misused or overused, can damage microbiome diversity and abundance profiles.

Biofilm Phase 2 Advanced (BP2A):
a localised bismuth-thiol biofilm breaker. Doesn't absorb. Included in Stage 2 and DIY antiseptic recipe.

NAC:
a systemic biofilm breaker, particularly at higher doses.

Glutathione:
a systemic biofilm breaker, particularly at higher doses.

Fulvic acid / humic acid
: a systemic biofilm breaker, even at lower doses.

R-Alpha lipoic acid
: a systemic biofilm breaker and metal chelator, particularly at higher doses.

Soap / detergent
: a localised biofilm breaker, when used externally.

Ethylene Diamine Tetraacetic Acid (EDTA):
a localised biofilm breaker and metal chelator, usually supplied bound to an electrolyte or mineral. Doesn't absorb well, orally - 5%. Can be used IV for circulating biofilms.

Dimercaptosuccinic acid (DMSA)
: a systemic biofilm breaker and metal chelator. Doesn't absorb well, orally - 25-30%. Can be used IV for circulating biofilms.

Dimercaptopropane-1-sulfonic acid (DMPS):
a systemic biofilm breaker and metal chelator. Can be used orally or IV.

Microdacyn / hypochlorous acid
: a localised biofilm breaker. Some absorption.

Ethyl acetate:
a systemic biofilm breaker, even at very low doses. Found in robusta coffee and various acetone-free nail polish remover products.

Silver:
a systemic biofilm breaker, even at very low doses.

Compounds found in foods:
Allicin (Garlic), Curcumin (Turmeric), Epigallocatechin gallate (Green tea), Quercetin (Onions, Apples), Resveratrol (Grapes, Red wine), Eugenol (Cloves), Cinnamonaldehyde (Cinnamon), Sulforaphane (Broccoli, Brussels sprouts), Apigenin (Parsley, Celery, Chamomile), Berberine (Goldenseal, Barberry), Thymol (Thyme, Oregano), Carvacrol (Oregano, Marjoram), Fisetin (Strawberries, Apples), Linalool (Coriander, Lavender), Gallic acid (Blueberries, Pomegranates), Cinnamic acid (Honey, Cinnamon), Citric acid (Citrus fruits), Naringenin (Citrus fruits), Rosmarinic acid (Rosemary, Basil), Catechin (Cocoa, Dark chocolate), Ellagic acid (Pomegranates, Raspberries), Diallyl disulfide (Garlic), Capsaicin (Chili peppers), Piperine (Black pepper), Hydroxytyrosol (Olive oil), Xylitol (Berries, Plums), Isothiocyanates (Kale, Mustard greens), Ferulic acid (Rice bran, Oats), Kaempferol (Spinach, Kale), Pterostilbene (Blueberries), Saponins (Beans, Legumes), Chlorogenic acid (Coffee, Potatoes), Luteolin (Peppers, Carrots)
Probiotics:
many of the probiotic species included in the protocol have potent functions as biofilm degraders and inhibitors. (see "Protective probiotics").

A number of these biofilm breakers are already included in the protocol. Overall, biofilm breakers should be considered an integral part of any microbiome dysbiosis or infection intervention and food sources should be included in any dietary strategy.


There are some additional strategies being tested which may feature in future updates, for example:

Upper GI biofilm flush, bind and purge recipe (advanced):
This a 3 step process, with similarities to a colonoscopy prep or gallbladder flush procedure. This is not intended to ever be used a daily routine, as this intervention is significantly broad spectrum and is highly destructive to the entire microbiome in the upper GI. It would be used in limited circumstances only.

Step 1
contains a potent mix of biofilm breakers and anti-microbials, plus some starch and warm water. Some of these items are not normally consumed, however they are successfully used for pre-faecal microbiome transplant (FMT) procedures. The mixture of anti-biofilm and anti-microbial interventions is adapted from Dr Thomas Borody’s excellent pre-FMT biofilm flush protocol and uses 2g biocompatible detergent (baby shampoo), 4mL of 1% iodine and 50mL Microdacyn).

The biofilm flush recipe adaptation includes some additional items - an extra biofilm degrader (ethyl acetate, from 2 shots of ground robusta coffee), 1 spoonful of diatomaceous earth as a bulking agent and binder, along with an optional (opened) capsule of cascara to irritate / stimulate the bowels and increase GI motility.  All of these items are added to an empty glass and half a glass of hot water is stirred in.

3 large spoonfuls of sifted potato starch (to prevent clumping) slowly stirred in to make a rubbery mass that helps dislodge and drag / sweep along the broken biofilms. Fill the remaining part of the glass with cool water.

(This delightful concoction needs to be consumed quickly, or it'll polymerise in the glass.)


Step 2
, 20 mins later - binders to help absorb toxins instead of allowing them to circulate, which was a concern with the original pre-FMT protocol. This next step includes a generous mix of binders, being 1/2 tablespoon of charcoal, 1/2 tablespoon of zeolite, 1/2 tablespoon of pectin and 1/2 tablespoon ofslippery elm powder, mixed into a glass of water.

Step 3
, 20 mins later - this functions just like a colonoscopy prep or gallbladder flush recipe. A large amount of electrolytes (Epsom salts / magnesium sulphate) and lots of water are consumed. The large volume of magnesium sulphate draws water into the bowel and purges the contents in a predictably dramatic fashion.

Add 1 teaspoon of Epsom salts (magnesium sulphate) to a glass of water. Stir until dissolved and consume.
Repeat this step 2 more times - 60 and 120 minutes later.

Overall, this allows the original biofilm breaking concoction from Step 1 around 40 minutes of travel throughout the GI tract, before being chased and diluted by the flush, reducing the impact of the biofilm breakers on the remaining length of bowel. It can potentially be adapted around the timing of peak gas output during a SIBO breath test, or reactivity timing to food.

Expect some unpleasant die-off symptoms / herxheimer-style reactions, diarrhoea, nausea shortly afterwards. Exclusive bathroom access would be advisable for the next 12-18 hours.


Step 4
, 12-24 hours later - consume S.boulardii, Bifidobacteria and Lactobacillus probiotics + prebiotics, related foods.

This flush could be performed 1-3 times, if severe upper GI overgrowth exists, as evidenced by reactions to food in under 1 hour. Excessive use of this recipe would NOT be recommended.


Protective probiotics


Area of effect: localised, however can translocate to other tissues.
Limitations:
probiotics may not provide a comprehensive solution in isolation.
Risk profile:
Non-toxic, can create significant die-off symptoms. The literature suggests some species can be opportunistic pathogens in highly immunocompromised people.

Following on from any efforts in clearing unwanted biofilms and microbial species overgrowth in the eyes, sinuses, nasopharynx, mouth, throat, oesophagus, lungs, GI tract, vagina, urethra and other mucosal tissues, further restorative efforts are usually needed in repopulating these tissues with helpful species to promote and maintain a healthy microbiome. (Links to these products can be found in the “5 Ordering products” section.)

These helpful species assist in inhibiting unwanted species, degrading biofilms and preventing opportunistic growth. They can also provide helpful functions, such as metabolism of oxalates, acetaldehyde, histamine, plus production of short chain fatty acids and other compounds beneficial to humans. Please note inclusion of these probiotics are based on an observed pattern of diversity loss and are included for specific functions, to generally promote a healthier balance in the microbiome, when combined with remineralisation and dietary changes.

They are not intended to replace MARCoNS, vaginal swabs, “GI-MAP” or Biomesight gut microbiome tests.

Many of these species were traditionally found in the Bacillus, Lactobacillus and Bifidobacterium genus, although recent taxonomy changes have relabeled / reclassified some of them, providing some minor confusion when researching species.

Bacillus subtilis:
Key Mechanism:
Produces enzymes and antimicrobial compounds that degrade biofilms.
Notable Features:
Spore-forming bacterium, resilient and able to survive harsh conditions, which allows it to act more potently against biofilms.
Effective Against:
Both Gram-positive and Gram-negative bacteria.
Additional Benefits:
Supports overall gut health and resilience against environmental stressors.

Lactobacillus fermentum ME-3:

Key Mechanism:
Produces glutathione (antioxidant), disrupts pathogenic biofilms, reduces oxidative stress.
Notable Features:
Dual-action as a biofilm breaker and antioxidant producer. Glutathione production sets it apart from many other probiotics, as it supports cellular detoxification.
Effective Against:
Harmful gut pathogens and biofilm-forming bacteria, also including H. pylori..
Additional Benefits:
Supports immune function, reduces inflammation, and has cardioprotective effects.

Lactobacillus reuteri:

Key Mechanism:
Produces reuterin, a powerful antimicrobial compound that breaks down biofilms.
Notable Features:
Strong antimicrobial activity, especially effective in the oral cavity and gut.
Effective Against:
Pathogens like E. coli, H. pylori, and oral biofilm formers.
Additional Benefits:
Promotes oral and gut health, reduces inflammation.

Lactobacillus rhamnosus:

Key Mechanism:
Produces bacteriocins and SCFAs, which inhibit biofilm formation.
Notable Features:
Excellent at inhibiting gut biofilms and maintaining gut balance.
Effective Against:
E. coli, Pseudomonas aeruginosa, and other biofilm-producing pathogens.
Additional Benefits:
Supports immune system, often used in combating gastrointestinal infections.

Lactobacillus plantarum:

Key Mechanism:
Produces hydrogen peroxide and antimicrobial peptides that break down biofilms.
Notable Features:
Broad-spectrum biofilm inhibition, active in the gut and oral cavity.
Effective Against:
Gut and oral pathogens, including Candida and Staphylococcus aureus.
Additional Benefits:
Improves digestive health, supports immune system function.

Lactobacillus casei:

Key Mechanism:
Disrupts biofilms through production of bacteriocins and lactic acid.
Notable Features:
Particularly effective against Helicobacter pylori biofilms in the gut.
Effective Against:
H. pylori and other gut pathogens.
Additional Benefits:
Supports digestive health, beneficial in addressing stomach ulcers.

Bifidobacterium bifidum:

Key Mechanism:
Produces SCFAs like acetate, which create an acidic environment that disrupts biofilms.
Notable Features:
Prevents biofilm formation by pathogenic bacteria in the gut.
Effective Against:
Pathogens like Clostridium difficile and other harmful gut bacteria.
Additional Benefits:
Supports overall gut health, improves digestion and immune system.

Bifidobacterium longum:

Key Mechanism:
Like B. bifidum, B. longum produces SCFAs that lower the pH in the gut, which can inhibit biofilm formation. It also promotes the production of antimicrobial peptides and enzymes that disrupt pathogenic biofilms.
Notable Features:
One of the most common Bifidobacterium species in the human gut, B. longum is well-adapted to the gut environment and plays a crucial role in maintaining microbial balance. It is especially good at outcompeting pathogenic bacteria.
Effective Against: 
Effective against a range of harmful bacteria, reducing biofilm formation in the gut.
Additional Benefits:
Enhances immune function and promotes gut health, further protecting against biofilm-related infections.

Bifidobacterium lactis:

Key Mechanism: 
B. lactis can modulate immune responses, leading to the production of compounds that degrade biofilms or prevent their formation. It also produces lactic acid and acetic acid, which inhibit the growth of biofilm-forming pathogens.
Notable Features:
Known for its resilience in the gastrointestinal tract, B. lactis is widely used in probiotic supplements due to its strong ability to survive stomach acid and bile. It's particularly effective at adhering to the gut lining, enhancing its biofilm prevention capabilities.
Effective Against:
  Has shown effectiveness in reducing biofilm formation by Escherichia coli and other gut pathogens.
Additional Benefits:
Improves gut barrier function and promotes overall digestive health.

Bifidobacterium breve:

Key Mechanism:
  B. breve produces metabolites that interfere with pathogen adhesion and biofilm formation. It can inhibit the colonization of harmful bacteria by promoting a balanced gut microbiome and maintaining a lower gut pH through lactic acid and acetate production.
Notable Features:
B. breve is one of the earliest colonizers of the human gut in infancy, making it especially important in the development of a healthy microbiome. It plays a significant role in maintaining gut integrity and has strong antimicrobial activity against pathogens.
Effective Against:
  Effective against Clostridium difficile and other gut pathogens that form biofilms.
Additional Benefits:
Helps alleviate symptoms of gut dysbiosis, supports digestion, and reduces inflammation in the gut.

Bifidobacterium adolescentis:

Key Mechanism:
  Produces SCFAs and antimicrobial peptides that help prevent pathogenic biofilm formation. B. adolescentis can also enhance gut mucosal immunity, providing an additional layer of protection against biofilm-forming bacteria.
Notable Features:
B. adolescentis is prevalent in the adult gut and plays a crucial role in breaking down complex carbohydrates, contributing to overall digestive health. Its ability to stimulate immune cells makes it particularly effective in preventing gut infections.
Effective Against:
Reduces biofilm formation by pathogens in the gut, such as Salmonella and Escherichia coli.
Additional Benefits:
Supports the immune system, promotes gut health, and reduces inflammation.

Saccharomyces boulardii:

Key Mechanism:
Inhibits biofilms and outcompetes pathogens in the gut.
Notable Features:
Effective against Candida and Clostridium difficile biofilms. Not susceptible to antibiotic influence.
Effective Against:
Fungal pathogens and gut pathogens, particularly in cases of infection or dysbiosis.
Additional Benefits:
Supports gut health, reduces diarrhea and inflammation, commonly used in traveler's diarrhea prevention.


Also potentially helpful is Oxalobacter formigenes, as an oxalate degrading species. When present in the small intestine, it also signals the host to secrete oxalates into the gut, instead excreting them via the kidneys. However, acidemia will override this.

Bifidobacterium are largely pH sensitive. You will have difficulties in restoring diversity and abundance while lactic acid metabolism is overused and zinc is low (hypoxia, impaired glycolysis, low minerals, anxiety disorders). Your OAT results should help indicate if lactic acid (+ oxalates) markers are elevated or the lactic acid : pyruvic acid ratio is elevated.

Studies and dosing information for these microorganisms in different mucosal tissues can be found on the Discord online discussion group and/or the literature. This protocol currently includes a number of key probiotics relating to these studies and their described functions / benefits:

  • Life Extension Florassist: (Oral microbiome)
    Probiotics - BLIS M18 S. salivarius M18, L. plantarum L-137

  • DrFormulas Nexabiotic for Women: (Acid resistant capsule)
    PaCran®SP (Cranberry fruit 50:1 extract), D-Mannose,
    Probiotics - Saccharomyces boulardii, Lactobacillus helveticus, Lactobacillus delbrueckii LE, Enterococcus faecium, Bifidobacterium bifidum, Bifidobacterium longum, Bacillus coagulans, Lactobacillus rhamnosus LB3, Lactobacillus plantarum LM, Lactobacillus acidophilus, Lactobacillus rhamnosus, Bifidobacterium animalis lactis (formerly named Bifidobacterium infantis), Lactobacillus fermentum, Lactobacillus gasseri, DE111® (Bacillus subtilis), Lactococcus lactis, Lactobacillus casei, Lactobacillus salivarius, Lactobacillus brevis, Lactobacillus reuteri, Streptococcus thermophilus, Bifidobacterium lactis, Low moisture rice dextrin, delayed release capsule (hydroxypropyl methylcellulose, pectin, and water), silica. Allergen warning: Contains milk.

  • DrOhhira RegActiv Essential ME-3: (Survives stomach acid.)
    Probiotics - Lactobacillus fermentum ME-3®, maltodextrin, magnesium salts of fatty acids (anti-caking agent). Vegetable capsule (hydroxypropylmethylcellulose).

  • CFUful 300 Billion CFU: (Acid resistant capsule)
    Probiotics - Bifidobacterium longum BB536, Bifidobacterium longum HRVD90b, Bifidobacterium breve BR3, Bifidobacterium breve HRVD521, Lactiplantibacillus plantarum LP1, Lacticaseibacillus rhamnosus LR6, Lacticaseibacillus rhamnosus HRVD113, Lacticaseibacillus rhamnosus GG, Bifidobacterium infantis M63, Bifidobacterium lactis BS5, Bifidobacterium lactis HRVD524, Bifidobacterium lactis SD150, Lactobacillus crispatus LCR01, Lacticaseibacillus casei HRVD300, Limosilactobacillus fermentum LF8, Lactobacillus reuteri RD830, Lactobacillus acidophilus, Ligilactobacillus salivarius LS1, Bifidobacterium longum CECT7347, Lactobacillus casei CECT9104, Bifidobacterium bifidum, Lactiplantibacillus plantarum LPLDL, Bifidobacterium lactis MB2409.

    Prebiotics - Fructooligosaccharides (FOS), Organic Barley Grass Powder, Organic Wheat Grass Powder, Organic Alfalfa Grass Powder, Organic Oat Grass Powder, Organic Beet Juice Powder, Organic Spinach Powder, Organic Suma Root Powder, Organic Licorice Root Powder, Organic Dandelion Root Powder, Organic Astragalus Root Powder, Organic Milk Thistle Seed Extract, Organic Ginkgo Leaf Extract, Organic Bilberry Extract, Organic Ginger Root Powder
     
  • General Biotics Equilibrium Boost MegaDose Probiotic: (2 x acid resistant capsules per container.)
    Probiotics - 115 strains, which have their own page, here - https://www.generalbiotics.com/equilibrium/strains/

  • Ochek: (Only needed if indicated as missing in gut microbiome data. Promoted by dietary oxalates.)
    Probiotics - O. formigenes, L. acidophilus, L. rhamnosus, B. lactis
    Prebiotics - FOS

  • Pendulum Akkermansia: (Only needed if indicated as missing in gut microbiome data. Promoted by pomegranate.) 
    Probiotics - Akkermansia muciniphila

  • (Various sources, Kimchi) - L. sakei: (Anti-microbial. Also used in food production to prevent spoilage, etc.)
    Probiotics: Lactobacillus Sakei


NB. DrFormulas Nexabiotic for Women, L. sakei and DrOhhira RegActiv Essential ME-3 can be directly administered to mucosal tissues, using appropriate methods - generally mixing a suitable amount of the probiotic (remove capsule where appropriate) with a small amount of clean water and then administering it where needed.

For example:
Nostrils:
cotton tip / fingertip and apply inside the nostrils. Eustachian tubes: place drops of liquid into the nose and use the “equalisation” technique.
Mouth / throat / oesophagus / upper GI:
gargle and swallow.
Lungs: nebuliser, 1-2 mL.
Vagina: add to a 5ml vaginal douche and elevate hips/legs for 15 minutes, while laying down, or place recently moistened, unopened capsule deep into fornix and allow it to dissolve.
Lower GI tract: use a probiotic rectal syringe (no tip)  with <50mL of water, then “down dog” yoga pose for 15 mins to bypass stomach acid. Achieves a similar colonisation rate to FMT.
Eyes: place drops of liquid into the corners of the eyes and / or under the eyelids.

Prebiotics


Area of effect: localised, with systemic benefits.
Limitations:
can be highly selective for promoting helpful species, if well-selected.
Risk profile:
Non-toxic, can create die-off symptoms. Can promote unwanted species, if poorly selected.

You cannot solve dysbiosis by probiotics alone. Strategically feeding your microbiome and correcting symbiotic host metabolism, via remineralisation, etc. is the best way to make any lasting transformations. If you've ever made yoghurt, you'll have a good understanding of just how rapidly 2L of milk can turn into a (probiotic) fermentation product. 8 - 12 hours can turn eg. 2L of milk into 2L of yoghurt with just a spoonful of starter culture / microorganisms.

Your GI tract is no different, in this respect. Your choice of foods (substrates) allows you to achieve some selectivity in the species being fed and promoted. What you eat matters.


Inulin + fructooligosaccharides (FOS) are types of soluble fiber found in a variety of plants. Some common food sources include:
Chicory root (one of the richest sources), Jerusalem artichokes, Garlic, Onions, Leeks, Asparagus, Bananas, Dandelion greens, Wheat

Galacto-oligosaccharides (GOS) is often added to foods as a prebiotic fiber, but it is also found in trace amounts naturally in certain foods. Some food sources include:

Human breast milk (high content of GOS), Cow's milk, Lentils, Chickpeas, Green peas, Soybeans

Resistant starch is a type of starch that resists digestion and feeds beneficial gut bacteria. Common sources include:

Green (unripe) bananas, Cooked and cooled potatoes (cooking and cooling increases resistant starch), Cooked and cooled rice, Oats, Legumes (lentils, chickpeas, beans), Barley, Corn

Polyphenols are compounds found in many fruits, vegetables, and beverages. Some common polyphenol-rich foods include:

Berries (blueberries, strawberries, raspberries), Pomegranates, Cranberries, Dark chocolate (high in cocoa content), Green tea (especially rich in EGCG), Red wine, Olive oil, Nuts (walnuts, almonds), Herbs and spices (turmeric, cloves, oregano)

These should be considered as high priority food items to introduce when planning your diet. However, they'd be expected to create some die-off reactions, gas and digestive discomfort at first. (see "2.2.1 Diet" for information on food items which also includes prebiotics)


Herbal Anti-microbials


Area of effect: localised and systemic
Limitations:
may have broader effects on metabolism.
Risk profile:
over-the-counter, generally regarded as safe. Can create significant initial die-off symptoms. Can alter drug metabolism.

There are a number of very effective and highly selective, plant-based anti-microbial products / foods.
Some of these interventions can simultaneously promote good species at the same time as inhibiting unwanted species. These would ideally be introduced in Stage 2 and will relate to your microbiome report data.

Notes:

Vanillin
is often used at 2g, 2x per day and has been shown to kill sulphur-reducing and other unwanted species, however these species can be producing metabolites which have an antidepressant-like effect. Removing these species can create antidepressant-like 'rapid withdrawal' symptoms for up to 2 weeks.

Resveratrol
has broadly beneficial effects at 300-600mg, 3x per day, but can inhibit aldehyde dehydrogenase activity, especially in larger doses.

Short-chain fatty acids (SCFAs) such as butyrate
can have highly positive effects on the microbiome and epithelium, however can create significant alterations which induce multi-day long die-off. Starting slowly is advisable.

Quercetin
has many beneficial effects, but can inhibit aldehyde dehydrogenase activity, especially in larger doses.

Berberine
has potent effects against Clostridia, but has similarly potent effects on enhancing fatty acid transport at CD36 and inhibiting mitochondrial complex 1. May not be well tolerated by some people, especially before Stage 2.

Here is a table of direct and indirect promoters and inhibitors, by genus / species
(sorry, this table is too large for mobile and tablet screens):