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:
- Collect Your Data
- Lifestyle Changes
- Stage 1: Remineralisation, increasing collagen synthesis rates, and performing a controlled initial “die-off” (at least two weeks)
- Stage 2: Enhanced gastrointestinal and mucosal interventions (at least two weeks)
- Stage 3: Stimulate and support a strong immune response while breaking (circulating) biofilms (at least four weeks)
- Optional Follow-Up
- 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."
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 (microbial 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 recognise 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
Remineralisation Will Alter (Restore) Neurotransmitter Homeostasis or "Managing Transitional Neuropsychiatric Symptoms"
It's critical to note that most of the enzymes responsible for synthesising, degrading, or recycling neurotransmitters are B-vitamin dependent, and their active forms, such as FMN, FAD, TPP, P5P, and methylcobalamin, are functionally deficient in the data of people with chronic illness. This is not always due to dietary inadequacy, even relative to general population requirements. The applied data shows this is due to cofactor bottlenecks, impaired enzymatic activation, oxidative degradation, and zinc- / magnesium-dependent enzyme instability.
This is evident, for example, in the metabolism of vitamin B6. As shown in this detailed diagram of B6 metabolism, converting dietary B6 into its active form P5P involves a cascade of steps: alkaline phosphatase (ALP) activity outside the cell, membrane transport, and intracellular phosphorylation via pyridoxal kinase (PK). Each of these steps is dependent on magnesium and zinc, and many are redox-sensitive. Acetaldehyde, chronic inflammation, and low ATP all interfere. It's no surprise, then, that functional P5P levels are low, even when blood levels of pyridoxine or pyridoxal appear normal or highly elevated.
However, this problem isn’t limited to Vitamin B6.
eg. Riboflavin must be converted to FMN and FAD, a process impaired by low ATP, oxidative stress, zinc or magnesium loss. Thyroid synthesis and related minerals, substrates also influence this.
Thiamine must become TPP via thiamine pyrophosphokinase. B12 must be converted to methylcobalamin, a zinc- and glutathione-sensitive step. These are often affected by chronic acetaldehyde, either directly or indirectly.
Acetaldehyde burden affects not only ALDH directly, but also indirectly interferes with zinc-dependent enzymes, magnesium availability, and redox-sensitive pathways throughout this entire cascade. It also stimulates mast cell activation, promoting histamine release, while simultaneously impairing histamine degradation through inhibition of ALDH and depletion of cofactors like P5P and copper. This can disrupt the balance of neurotransmitters by overactivating histamine receptors, and indirectly suppressing dopamine synthesis via H₃-mediated inhibition of tyrosine hydroxylase. It acts as both a primary disruptor and a multiplier of vulnerability in neurotransmitter and cofactor systems.
The result is that small efforts to stimulate or correct neurotransmitter production can trigger paradoxical responses, including overshooting, agitation, anxiety, "brain on fire", insomnia, sedation, getting "stoned" / "high", or what many patients call a “weird” or “off” feeling.
The fix isn’t to push harder, it’s to intervene smarter - a staged approach works better. One example of a suggested optimal sequence:
1. Stabilise the redox and mineral terrain. This includes VERY SLOWLY introducing :
a) electrolytes, taken slowly over the day
b) NAD⁺ precursors (e.g. NMN or NR), taken sublingually
c) antioxidants (vitamin C, GSH donors like NAC), taken 2-3x/day. These may need tiny doses, to start.
d) (less slowly) L-carnitine / acetyl L-carnitine, creatine (for fatty acid transport and ATP-PC pathway)
e) mineral cofactors like zinc, copper, manganese, selenium, iodine, lithium, cobalt, boron, and molybdenum, etc. This helps balance the neurotransmitter synthesis pathway (and precursors), lowers the burden on ALDH and MAO pathways and reduces oxidative stress, allowing safer processing of neurotransmitter metabolites.
A schedule of products and dosing can be found below, in "Getting started (standard schedule)".
2. Introduce B1 and B2 in active or near-active forms, such as FMN and TTFD / TPP / cocarboxylase. These support mitochondrial redox balance, glycolysis, and the Pentose Phosphate Pathway. Depending on the severity of dysbiosis / acetaldehyde burden, the B1 dosing can range from 50-600mg of the active forms, eg. TTFD, cocarboxylase, starting from a low dose.
For severe cases / people with elevated susceptibility to (neuropsychiatric) symptoms from supplements, etc., a very gentle ramp up with tiny doses of B vitamins can be very helpful, before moving to the compounded multi-mineral products. Metabolics (UK) produce a range of liquid B vitamins which are ideal for these purposes, although they don't carry all products and some other vendors are required.
B1 / TPP - https://www.metabolics.com/products/vitamin-b1-thiamine-pyrophosphate
B2 / FMN - https://www.metabolics.com/products/riboflavin-5-phosphate
B3 / NMN - https://renuebyscience.com/products/pure-powder-100-grams (already in the main supplements section)
B6 / P5P - https://www.metabolics.com/products/vitamin-b6-pyridoxal-5-phosphate
B9 / Folinic Acid - https://mandimart.eu/en-nl/products/folinic-acid-30mls-alcohol-free-by-california-gold-nutrition
B12 - https://www.metabolics.com/products/vitamin-b12-hydroxocobalamin
3. Layer in B6 (as P5P), B9 and B12 (as methylcobalamin or hydroxocobalamin) only after upstream redox stress is under control. In the context of unresolved aldehyde or monoamine overload, these can be disruptive if introduced too early.
4. Use non-oral routes to bypass known bottlenecks. Transdermal, sublingual, or parenteral delivery helps sidestep transporter saturation, liver metabolism, or dysregulated GI environments. Dissolving nutrients in DMSO is another useful strategy.
5. P5P in DMSO is one example of an advanced strategy. Dissolving P5P in a DMSO solution bypasses multiple upstream steps: it does not rely on ALP, avoids compromised membrane transporters, and skips over pyridoxal kinase activation. This makes it ideal in states where P5P is known to be low despite B6 repletion. It may also enter intracellular compartments more efficiently, including mitochondria. (A new section on DMSO will be added soon, as will a significant upgrade to the current mineral troches.)
In this context, neurotransmitter restoration is about more than just quantity - it's about kinetics, cofactor availability, and redox context. A patient may be taking all the right nutrients, but if those nutrients are stuck upstream, degraded by peroxynitrite, or unable to bind to their target enzymes due to low zinc, the net effect is failure. Worse, poorly timed repletion can destabilise the system further.
The half-life of each vitamin is frequently overlooked. Dosing vitamins 2-4 times per day is often necessary to achieve sufficient benefit.
eg. Vitamins B1, B2, B3, B5, B6, B7/H, B8, B9, B12 and C are taken 2-3x/day, often sublingually.
In the context of restoring severe deficiencies, strategic sequencing matters. B vitamins are powerful, especially in active forms, however they also act as signals in a complex control system. If introduced out of order or in isolation, they may trigger compensatory reactions that mimic toxicity, when in fact they are just unmasking hidden dysfunction.
Many of these mechanisms may also help explain why certain neuropsychiatric conditions appear during chronic illness and how they can act as precursor states to systemic collapse.
ADHD, for instance, is often characterised by signs of noradrenaline and dopamine dysregulation, impaired impulse control, and chronic restlessness, traits which may reflect an early-stage compensation for failing neurotransmitter recycling or low-grade redox and metabolic dysfunction. If these compensations begin to fail, especially under stress, infection, or prolonged nutritional depletion, the system may tip into a more energy-conserving, downregulated state, as observed in ME/CFS, long COVID, post vaccination syndrome, etc.
Bipolar disorder may reflect a different kind of instability, one in which neurotransmitter tone swings between overcompensation and collapse, and this too may be compounded by aldehyde load, especially acetaldehyde, which inhibits ALDH enzymes responsible for clearing dopamine breakdown products like DOPAL.
Dietary contributions to acetaldehyde burden, such as excessive intake of alcohol, sugar, or fermentable carbohydrates, can further amplify this inhibition by fuelling microbial overgrowth and endogenous ethanol production in the gut. When ALDH function is compromised, neurotoxic intermediates accumulate, further impairing redox balance and downstream dopamine synthesis. Over time, this may shift the system toward an oscillatory or collapsing state, where any attempt to stabilise mood or energy is undermined by bottlenecks in detoxification and neurotransmitter recycling These cycles could, in part, emerge from fluctuating availability of critical cofactors like P5P, B2, or SAMe, or episodic redox crashes that disrupt normal mood-regulating feedback.
Getting started (standard schedule)
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. The troches are potent and starting at eg. 1/8th troche per day, may be helpful to soften / slow the metabolic shift when restoring severe deficiencies.
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.)
f) Testing for and and addressing blood-flow / hypoxia issues. (see 2.3.3 Blood-flow, hypoxia and fibrin-amyloid).
Product ordering links can be found in 5 Ordering products.