Long Covid: Dysfunction, Not Damage — Theory and Treatment Concepts

While Long Covid brings about a lot of bad news, the good news is that there is not a single type of organic damage found across all Long Covid sufferers which could explain even a fraction of the complex and evolving symptoms. This indicates Long Covid is due to dysfunction and not damage, making it easily treatable with the right understanding. While there is organic damage found, there is nothing causative and it only seems to be a side product of another process.

The Dysfunction, Not Damage Theory is that the acute phase of COVID19 causes a number of metabolic shifts, pushing the body into metabolic states which are stable but cause dysfunction. Combined with a small amount of (reversible) damage to the mitochondrial membranes, dysfunction of iron homeostasis and an unbalanced microbiome — this seems it can explain all of the complex and evolving symptoms of Long Covid.

Dysfunction, Not Damage Theory:

  • An acute oxidative event causes iron mobilization into the brain and other tissues, causing auto-oxidation, which produces massive oxidative stress and destroys cellular lipids, antioxidants and DNA. The bodies DNA repair system, PARP activates but due to oxidative conditions depletes NAD+and its building blocks, this triggers what I refer to as the “Niacin Sink Trap”.
  • At the same time, the production of vitamin B12 is interrupted, because the cobalamine building block is oxidized, triggering the “Methyl Trap”. Both the Niacin Sink Trap and Methyl Trap are stable metabolic dysfunction which cause a variety of evolving and complex symptoms.
  • The iron which was mobilized causes oxidative damage to cell membranes and DNA, since the body doesn’t have a mechanism to regulate extra iron well and is bound in the form of ferritin and possibly other compounds. These leak iron due to the bodies pro-inflammatory state and causes evolving and complex symptoms.
  • The mitochondrial membranes that got oxidized stick around as they get complexed with proteins, causing fatigue and lower bioenergetic functioning as they can not function properly.
  • The microbiome gets remodeled due to iron absorption, triggering microbial community changes, growth of more pathogenic microbes and disruption of gut/brain axis.
  • In some people, the oxidative stress/damage will reactivation dormant neurotrophic viruses like EBV and oxidized cell membranes will harbor any dormant Lyme disease pathogens. Parasites may overgrow due to the iron mobilization and oxidative stress as well as the microbiome remodeling.

Any one or more of these things happen together, many of them playing off each-other in feedback loops, with the resulting symptoms depending on the deficiencies in the vitamin co-factors and genetic predisposition at the time of oxidative assault, as well as any dormant infections.

Analysis based on symptom time progression research:

A recent study which surveyed thousands of participants all over the world regarding their disease progression and symptoms, then used statistical analysis and natural language processing found that there are three clusters of symptom progression over time which are highly correlated. This indicates that there are three main mechanisms in long covid and an analysis of the three graphs below indicates the mechanisms are coupled together.

Looking at the clusters below, it appears the three clusters correlate to:
Cluster 1 — Dysbiosis of the Microbiome
Cluster 2 — Niacin Sink Trap and Methyl Trap, Metabolic Dysfunction
Cluster 3 — Iron Mobilization and Dysfunction

This validates the “Dysfunction not Damage” theory of Long Covid and a further analysis of the symptoms and how they correlate to each of these mechanisms paints a very strong picture of the driving mechanisms behind Long Covid.

Analysis of Disease Mechanisms Based on Time Course of Symptoms:

Clusters of symptoms reported over time, from the paper, “Characterizing long COVID in an international cohort: 7 months of symptoms and their impact”

Cluster 1 — Dysbiosis of the Microbiome

Symptoms from the research paper:
Diarrhea, Loss of Appetite, Vomiting, Runny Nose, Sore Throat, Dry Cough, Rattling of Breath, Elevated temperature and Fever

Analysis:
The early peak and rapid drops in symptom prevalence over time in this cluster indicates it is due to an initial assault, this looks like microbiome disruption and bacterial mobilization and then re-balancing over time. The symptoms of GI and respiratory issues as well as fever are a strong indicator that is is microbial related. Iron mobilization will cause disruption of the microbiome, systematic mobilization of bacteria and a switch to pathogenic activity. This microbiome remodeling appears to be a compensation mechanism for the burst of free iron.

Lab Tests:
Microbiome analysis, organic acids panel

Cluster 2 — Niacin Sink and Methyl Trap

Symptoms from the research paper:
Fainting, Pain/Burning in Chest, Tachycardia, COVID toe, Abdominal Pain, Nausea, Bone Aches or Burning, Muscle Aches, Tightness in Chest, Acute/Sudden Confusion, Changes to Smell and Taste, Dizziness/Balance Issues, Hallucinations, Headaches, Insomnia, Other Sleeping Problems, Sleep Apnea, Slurring Words/Speech, Breathing Difficulty with Normal Oxygen Stats, Cough with Mucus Production, Coughing up Blood, Respiratory and Sinus Issues, Shortness of Breath, Sneezing, Chills/Flushing/Sweats, Fatigue, Low Temperature

Analysis:
The symptoms look like the combined symptoms of the two metabolic traps (niacin sink and methyl trap), showing a small peak on the front-end (most likely due to early pro-oxidative state) coupled to the other two charts, and then generally flat line activity indicative of a stable metabolic trap.

Drivers of Symptoms:
The Niacin Metabolic Trap will create symptoms of pellegra such as the well known “COVID Toe”, abdominal pain and others. This metabolic trap hijacks tryptophan to produce NAD+ and will prevent the production of circulatory serotonin and melatonin, cause issues with mood and sleeping/dreaming including inability to enter REM sleep and strange dreams. This will also cause release of neurotoxic quinoloic acid type compounds causing issues with mood, irritability, seizures and headaches. The core issue of NAD+ depletion will cause low energy, fatigue, post exercise malaise and many other issues. This state will lead to immune dysfunction as well as a lack of stimulation of bone marrow, leading in some cases to tooth loss, fragile bones and other issues.

The Methyl Metabolic Trap will create symptoms depending on the genetic makeup of the persons methylation system. Most common would be the symptoms of vitamin B12 deficiency including: anemia, “COVID tongue”, shortness of breath, feeling cold, neurological damage dizziness, irregular heartbeats, weight loss, numbness or tingling in your hands and feet, muscle weakness, personality changes, unsteady movements, mental confusion or forgetfulness.
Many people will have symptoms of hypohomocysteinemia as homocystein builds up due to the broken methyl cycle, these include: seizures, psychiatric issues, eye abnormalities, vascular issues. Many people will also have symptoms of glutathione deficiency including slowing down of physical reactions, speech (psychomotor retardation), intellectual disability and a loss of coordination (ataxia). The methyl trap will also cause issues with gene expression, epigenetic changes and demyelination of nerves.
The broken methylation cycle will present with histadelia symptoms (high histamine) such as: muscle pain, headaches, fatigue, insomnia, irritability, anxiety, paranoia, being suspicious, and hallucinations. This can also cause issues with sulfur metabolism, leading to the “COVID smell”.

Lab Tests:
Niacin Sink Trap — Organic Acids Panel (tryptophan metabolites high)
Methyl Trap — Organic Acids Panel (methylmalonic acid high, uracil high), Low SAM/SAH ratio, Homocystein high, Histamine high, General Methylation Status Test

Cluster 3 — Iron Mobilization and Dysfunction

Symptoms from the research paper:
Bradycardia, Palpitations, Visibly Inflamed/Bulging Veins, Dermatographia, Other Skin and Allergy, Peeling Skin, Petechia, Skin Rashes, Constipation, Gastroesophageal Reflux, Hearing Loss, Other Ear/Hearing Symptoms, Tinnitus, Vision Symptoms, New Allergies, New Anaphylaxis Reaction, Joint Pain, Muscle Spasms, All Sensorimotor Symptoms, Brain Fog, Memory Issues, Nerve Pain, Speech/Language Issues, Tremors, Vibrating Sensations, All Menstrual/Period Issues, Bladder Control Issues, Other Temperature Issues, Post Exertional Malaise

Analysis:
If you overlap cluster 1 and cluster 3, they have a strong anti-correlation. Bacteria in the body will absorb excess iron, then they will mobilize and go out of balance and not be able to absorb it anymore as the microbiome is remodeled. This explains why cluster 3 (iron based) ramps up as cluster 1 (microbiome based) ramps down.

Drivers of Symptoms:
Iron mobilization and dysfunction will cause symptoms of hyperferritinemia/neuroferritinopathy such as: joint pain, abdominal pain, lack of sex drive, anti-phospholipid syndrome (sticky blood syndrome), auto-immune conditions such as lupus/rheumatoid arthritis, macrophage activation syndrome, eye damage, cardiac abnormalities, neurodegeneration, micro-clotting and vascular dysfunction, rhythmic shaking, internal tremors, involuntary muscle tensing, issues with swallowing or vocal cords, neurological symptoms which are only on one side of the body, general neuropathy. It will also cause symptoms which mimick dysautonomia. Iron is a driver of chronic diseases such as cardiac disease, cancer proliferation and secondary infections. This class of symptoms are MUCH more common in long haulers who got sick around March 2020, particularly those with internal tremors/vibrations.

Lab Tests:
Ferritin and full iron panel, research shows the ideal ferritin range is below 100. High ferritin puts you at risk but iron can mobilize and deposit even with low ferritin. Again, ferritin and other iron levels do not indicate the amount of iron stored in your nervous system or other tissues but can show if you have large amounts of stored iron that may be “leaking”, and can indicate if its safe to try and chelate iron.
8-OHdG, a DNA damage biomarker, may be most relevant and will be elevated if you have iron releasing from tissues causing oxidation.
High homocystein has been correlated to iron overload disorders although it is also expected to be elevated due to the methyl trap.
Serum copper and Ceruloplasmin enzyme levels can indicate if you have deficiencies in your iron transport system and would be important to understand and may have led to iron redistribution.
MRI with an educated technician can determine brain iron accumulation based on specific signal characteristics.
Observation of ferritin based Fleischer Rings in the eyes, in some visible under blacklight.
Transcranial sonography can be used to detect changes in some parts of the brain in brain iron accumulation disorders.

Other — Oxidative Damage to Membranes

Analysis:
There are other potential mechanisms which are not as pronounced such as oxidative damage to the mitochondria. There are very few long term tissue changes due to an intensive oxidative event, but this is one of them. secondary infections in terms of bacteria, neurotrophic viruses (EBV) and parasites. Specifically Lyme disease pathogens are known to thrive in an environment with oxidized cell membranes. These are secondary to the main metabolic traps and iron dysfunction and are also treatable/reversible.

Symptoms:
chronic fatigue, post exercise malaise and Lyme disease reactivation

Lab Tests:
Cellular respiration test

Other — Reactivation of Secondary Infections

Analysis:
Secondary infections in terms of bacteria, neurotrophic viruses (EBV) and parasites seem to be common in those suffering from Long Covid, as well as triggering of CIRS, or Chronic Inflammatory Response Syndrome in those that have historical exposure to biotoxins such as mold exposure. Specifically Lyme disease pathogens are known to thrive in an environment with oxidized cell membranes. These are secondary to the main metabolic traps and iron dysfunction and are also treatable/reversible. While Epstein-Bar virus is often reactivated in acute COVID19, anecdotally it does not seem to be a main driver of issues and blood brain crossing antivirals do not seem to be a magic bullet for long covid, EBV reactivation seems to be a consequence of an acute oxidative event and glutathione depletion.

Symptoms:
Diverse, complex and evolving

Lab Tests:
Testing for Lyme and associated pathogens is incredibly complex and misleading, its important to work with a doctor trained in Shoemaker or Klinghardt methods.
A lyme co-infection, Bartonella, often leaves visible “Bartonella Striae” which look similar to vertical parallel stretch marks, if those recently appeared it is a good indicator to get tested for Lyme disease.
A diagnosis of CIRS can be made from specific immune panels in the Shoemaker tradition.
Epstein-Bar and other viral re-activations can be detected using viral antibody tests.

Key Research Papers:

If I had to hand researchers a number of papers to connect the dots around “long covid”, I would pick:

Niacin Sink Trap:
- The COVID-19 Burden or Tryptophan Syndrome: Autoimmunity, Immunoparalysis and Tolerance in a Tumorigenic Environment
- The oxidative stress-induced niacin sink (OSINS) model for HIV pathogenesis

Methyl Trap:
- COVID-19: A methyl-group assault?

Iron redistribution:
- The Hyperferritinemic Syndrome: macrophage activation syndrome, Still’s disease, septic shock and catastrophic antiphospholipid syndrome

Detailed Mechanisms

Detailed Mechanism — Niacin Sink Metabolic Trap

The Niacin Sink Trap has been documented and well researched, initially during the study of HIV by Dr. Ethan Taylor and recently in the context of COVID19, the downstream effects on tryptophan and other systems has been researched in a groundbreaking paper regarding Long Covid. The Open Medicine Foundation, a leader in Chronic Fatigue Research, supports a number of research initiatives into this mechanism which they generally call the “Metabolic Trap Theory of CFS”. According to this theory, cofactors coupled to the oxidation/NAD+ cascade are critical to outcomes and this is seen in the observation that low selenium levels correlated to poor outcomes in China. Observations of high blood sugar being a predictor of death in COVID19 patients, regardless of diebetic status validate metabolic changes being a major risk factor of COVID19 according to NAD+ theory. Activation of the same kynurenine pathways predicted in NAD+ theory of COVID19 correlate to blood sugar deregulation. I wrote a dedicated blog post on the subject called “The Team of Doctors and Biohackers Who Seem to Be Successfully Treating “Long Covid””.

The theory is that COVID19 causes NAD+ depletion, some people with vitamin deficiencies, existing NAD+ depletion or genetic deficits in energy metabolism have long term NAD+ dysfunction. The body tries to make up for low NAD+ by feeding in tryptophan, which is the precursor for serotonin and melatonin, causing poor mood and sleep. Serotonin is also a master regulator in circulation and having low levels causes a number of issues including with the gut/brain axis. Every time tryptophan is fed into the cycle, large amounts of neurotoxic Kynurenine metabolites are produced. Furthermore, energy disruptions are specific to high metabolically active tissues such as the heart and brain. A number of recent metabolomics papers have found massive disruptions in tryptophan and kynurenine markers.

Biochemical cascades in a vicious feedback cycle based on the original work of Dr. Taylor, “The oxidative stress-induced niacin sink (OSINS) model for HIV pathogenesis”

Unrelated to the core mechanism, a recent publication in the journal Nature, stated: “vitamin B3 (niacin or nicotinamide) is highly effective in preventing lung tissue damage. It might be a wise approach to supply this food supplement to the COVID-19 patients.” A recent bioinformatics analysis also indicated niacin should be studied as a treatment for COVID19. A forward looking pre-print indicates nicotinic acid may act as a one of a kind bioenergetic “pump” of inflammatory molecules out of cells, critical for COVID19. Niacin has been seen to easily cure systematic NAD+ deficiency in clinical research. An informal survey of over 200 long covid sufferers, showed a high correlation between niacin intake and improvement in a recent video by a patient advocate journalist. This same patient advocate journalist interviewed both myself and Dr. Ade Wentzel regarding biochemical aspects of this theory. In terms of doing the most good for the most number of people, repleating NAD+ using nicotinic acid/niacin is incredibly helpful in Long Covid.

Detailed Mechanism — Methyl Metabolic Trap

While it has been understood since the 1980’s, the methyl metabolic trap is very well explained in the context of COVID19 in the very important paper, “COVID-19: A methyl-group assault?”. One group of researchers points out the genetic complexities in this methyl trap in the context of COVID19, as well as the resulting homocystein overload that can be present.

One piece of clinical research points out that there is a link between biomarkers of NAD+, oxidative stress, methylation, folate and B12 — this is interesting as it bridges the gap between the two metabolic traps. In a pro-oxidative environment, the unstable cob(I)alamin gets oxidized to cob(II)alamin. The paper states, “MS inactivation occurs when free radicals oxidise cob(I)alamin to a cob(II)alamin species. Re-activation requires methyl group donation by SAM” Other than oxidative stress, another mechanistic bridge seems to be the enzyme “Cob(II)alamin_reductase”, which is an NAD+ dependent enzyme that converts cob(II)alamin back to cob(I)alamin. A third possibility is the direct disruption of methionone synthase or catalysis of homocystein production by iron . Whatever the mechanism, its clear the methylation/folate cycle is disrupted at the B12 dependant methionine synthase step. Research has found a link between B12, folate and iron disruption in the past although the mechanism is unclear.

Disruption of methionine synthase due to oxidative stress destroying cob(I)alamin

The Methyl Metabolic Trap will create symptoms depending on the genetic makeup of the persons methylation system. Most common would be the symptoms of vitamin B12 deficiency including: anemia, “COVID tongue”, shortness of breath, feeling cold, neurological damage dizziness, irregular heartbeats, weight loss, numbness or tingling in your hands and feet, muscle weakness, personality changes, unsteady movements, mental confusion or forgetfulness.
Many people will have symptoms of hypohomocysteinemia as homocystein builds up due to the broken methyl cycle, these include: seizures, psychiatric issues, eye abnormalities, vascular issues. Many people will also have symptoms of glutathione deficiency including slowing down of physical reactions, speech (psychomotor retardation), intellectual disability and a loss of coordination (ataxia). The methyl trap will also cause issues with gene expression, epigenetic changes and demyelination of nerves.
The broken methylation cycle can present with histadelia symptoms (high histamine) such as: muscle pain, headaches, fatigue, insomnia, irritability, anxiety, paranoia, being suspicious, and hallucinations. This can also cause issues with sulfur metabolism, leading to the “COVID smell”.

A mixture of hydroxycobalamine, folinic acid and TMG was used for treating functional methionine synthase deficiency which probably most mimicks the Methyl Trap in this case. In general, TMG also known as Betaine, is a successful treatment for the high homocystein levels expected in this situation.

The T2-Hyperintensities which are the most common issue found on MRI’s after COVID19 and the rarer cerebral atropy have been linked to vitamin B12 deficiency. Vitamin B12 is known to be correlated to leukoencephalopathy and ataxia and in combination with potential brain iron overload, explain the neurological findings in COVID19.

Detailed Mechanism — Iron Redistribution

Iron and COVID19:

There is strong indications of disruption of iron homo stasis in COVID19 — the paper “Iron: Innocent bystander or vicious culprit in COVID-19 pathogenesis?” reviews mechanisms and findings connected to iron in COVID19. Multiple papers have found that large amounts of free iron in the body are correlated to fatality, blood types with higher iron binding capacities correlate to fatality and iron dynamics are significantly interrupted in COVID19 patients. Iron is also a critical mechanism to mediate bacterial infections and forward looking research shows anomalous presence of bacterial DNA reads and biomarkers in COVID19 clinical data indicating attack of iron utilizing anaerobic Prevotella sp. bacteria on the blood.

COVID19 may most similarly mimic cadmium poisoning, where a catalytically active metal is causing systematic oxidative stress. It is relevant to note that in cadmium poisoning, the symptoms overlap perfectly with COVID19, including “cytokine storm”, anosmia and ground glass lung opacities. The cadmium poisoning mechanisms have been well studied and an analysis will show its close relationship. Combined with the many papers linking COVID19 and systematic oxidative stress, it paints a picture which looks more like a metal catalyzed oxidative disease than a respiratory illness. In fact, the whole “cytokine storm” concept in COVID19 seems to be pop-science, a recent paper indicates that the cytokine storm component of COVID19 is minimal, it appears to be an “oxidative storm”.

A paper titled, “COVID-19 gone bad: A new character in the spectrum of the hyper-ferritinemic syndrome?” goes into detailed and compares COVID19 biomarkers to hyper-ferritinimia biomarkers in the acute phase, but does not discuss the long term issues. Another paper links issues with the blood to ferritin biomarkers and states, “Strongly associated with the COVID-19 coagulopathies is the presence of hyperferritinemia”. Another paper discusses the role of iron chelators and COVID19 being a hyperferritinemic syndrome. A paper discussing iron nano-particle pollution and COVID19 mechanisms states, “altered iron balance favoring excess reactive or catalytic iron may be the single most important underlying pathological process predisposing to severe COVID”.

Some manifestations of Long Covid strongly mimic the unique symptoms of hyperferritinemia and other iron overload syndromes such as Neurodegeneration with Brain Iron Accumulation (NBIA): High glucose/glucose intolerance, joint pain, stomach pain, fatigue, cardiac abnormalities, changes in menstration are the common symptoms of NBIA.

Iron and oxidative stress:

Iron causes rampant oxidation in the body through energetic oxygen radical production, including via the extremely powerful Fenton reaction. Iron will oxidize any materials it comes into contact with, specifically cellular membrane lipids (such as the mitochondrial membrane) and DNA. Recently, a paper was published which reviewed biomarkers of oxidative DNA damage and found a strong correlation to COVID19 severity. Another paper which looked at Ascorbate levels which would be reduced during oxidative stress, states: “Our study revealed that vitamin C levels are undetectable in more than 90% of the patients included. The mechanisms of this significant reduction in vitamin C are uncertain.” A study of antioxidants as well as biomarkers of oxidative stress in COVID19 patients shows dramatic patterns of low antioxidants and high oxidative stress. Thiol levels, a common biological group very sensitive to oxidation is highly correlated to COVID19 disease progression in a recent paper. The serum thiol biomarker levels tested are considered a direct measure of redox status because of their rapid reaction with oxygen radicals.

A recent publication reviewed free DNA in the body and its correlation to disease state and found some astounding correlations, not only did COVID19 highly involve DNA fragments in circulation, but patients treated with experimental antivirals, experimental immunsupressives, hydroxychloroquine and/or the standard of care did not have changes in free DNA, as if the viral load was not correlated to free DNA. Its relevant to point out that free DNA itself can trigger cytokine storm and tissue damage.

Even more interesting was that a large percentage of this free DNA came from erythroblasts, the red blood cell precursors found in the bone marrow. This is a shocking discovery as damage this aggressive to the red blood cell precursors in the bone marrow can not be easily accounted for by any current viral mechanism. Interestingly, erythroblasts contain a large amount of iron (main site of iron utilization) and a structure that is not stable and resistant to auto-oxidation like mature red blood cells.

Iron and the Microbiome:

A detailed review of microbiome changes due to COVID19 show an increase in the abundance of four genera, Streptococcus, Clostridium, Lactobacillus, and Bifidobacterium with a decrease in Bacteroides, Roseburia, Faecalibacterium,
Coprococcus, and Parabacteroides. There was an increase in opportunistic pathogens Streptococcus, Rothia, Veillonella, and Actinomyces.

Iron release into the microbiome can disrupt biofilms and cause the mobilization of bacteria, it can also convert these bacteria to “pathobionts” or potentially harmful bacteria. In general, most pathogenic bacteria possess more efficient pathways to acquire free iron than beneficial bacteria as it is essential for virulence expression and replication.

Iron overload is known to alter the microbiome, particularly the tryptophan metabolism, which is already known to be causing issues in the niacin sink trap. This is another example of multiple mechanisms creating feedback loops and catalyzing each-other in Long Covid.

Interestingly, this is the exact mechanism proposed to contribute to Alzheimer’s Disease, known as the “Iron Dysregulation and Dormant Microbes (IDDM) hypothesis”. A recent paper states, “The simultaneous iron dysregulation and microbial aberrations affect the hematological system, promoting fibrin amylodiogenesis, and pathological clotting. Systemic inflammation and oxidative stress can contribute to blood brain barrier permeability and the ensuing neuro-inflammation, characteristic of Alzheimer’s type dementia's.”

Iron and the Brain:

Excess iron in the brain can cause a number of issues, including the micro-hemorrhaging seen on COVID19 MRI studies. This disease state is known as neuroferritinopathy or the general term, Neurodegeneration with Brain Iron Accumulation (NBIA). This could explain some of the strange symptoms of “long haulers” such as neurological changes on just one side of the body. Research around iron dysfunction in the brain and nervous system is one of the most exciting areas of medicine, with a recent paper stating: “A major feature of virtually all neurodegenerative diseases is the accumulation of excess iron.” In general, excess iron levels are associated with Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, Friedreich’s ataxia and other neurological disorders, cancer, Fanconi anemia, stroke, heart disease, diabetes and ageing. A fascinating video discussions how iron accumulation and dysregulation may be a core mechanism of aging and age related diseases.

Ferritin deposited in the brain will show up on MRI according to a review, “On brain MRI in neuroferritinopathy, iron deposits are observed as low-intensity areas on T2WI and as signal loss on T2(∗)WI. On T2WI, hyperintense abnormalities reflecting tissue edema and gliosis are also seen. Another characteristic finding is the presence of symmetrical cystic changes in the basal ganglia, which are seen in the advanced stages of this disorder. Atrophy is sometimes noted in the cerebellar and cerebral cortices.”.
T2 hyperintensities of white matter is one of the most common reported MRI findings in those that are suffering from long covid and a paper on iron storage disease states, “T2 hyperintensities in white matter have been reported in most NBIA (Neurodegeneration with Brain Iron Accumulation) subtypes”.

A number of long haulers are having vision degeneration, while changes in vision such as a loss of color or partial field of vision could be caused by the methyl trap, issues with the lens is a common manifestation of hyperferritinimia called Hyperferritinemia Cataract Syndrome. Ferritin accumulates in the eye causing a progressive distortion of the lens.

This seems to indicate why many people talk about “COVID eyes”, zombie/glassy looking eyes that seem to have been common in the acute phase in March 2020. Long haulers which have noticed changes in the color of their eyes or are having vision issues should ask their doctor to check for “Fleischer’s Ring”, an indication of ferritin in the eye that is easily seen. Interestingly, a number of long haulers with symptoms of vibrations and internal buzzing noticed that under a blacklight they had fluorescent Fleischer Rings (different than the copper containing Kayser-Fleischer Rings, even 18 months after infection.

Fleischer Rings fluorescing under blacklight in multiple long haulers with buzzing/vibrating feelings and electro-sensitivity

Its not clear which form iron is taking during COVID19 tissue accumulation as MRI research had found that iron exists in the form of the mineral magnetite in human brains and this may be contributing the brains electromagnetic interactions. In fact, a paper titled “Iron Oxides in the Human Brain” states “There is evidence for the formation of six of the recognized iron oxides in human brain tissue, namely, ferrihydrite, goethite, hematite, magnetite, maghemite, and wüstite”. It goes on to discuss the organic and other forms that are present in the brain, “Brain iron can be classified as heme or nonheme iron, where the latter takes many distinct forms within the human brain, including labile (unbound, ionic) iron and low molecular weight complexes and metalloproteins with one or more individual iron ion binding sites. Dense clusters of hundreds or thousands of iron ions can occur where iron is sequestered or deposited in iron storage proteins such as ferritin, in storage protein degradation products such as hemosiderin, or in pathological intra- and extracellular deposits and inclusions. In the pigment lipofuscin, iron is loosely bound along with a range of other metal elements . This contrasts with iron bound in the pigment neuromelanin and in ferritin and hemosiderin, where iron oxides or hydroxides (referred to collectively here as oxides) are formed with structures ranging from amorphous to highly organized crystalline structures.” Iron oxide compounds in the nervous system are known to create a feedback loop of oxidative stress, more iron accumulation and protein aggregation leading to neurodegeneration.

Iron dysfunction and the blood:

A recent paper discusses the unique aspects of iron induced fibrogen clots, they are not only remarkably resistant to degradation but they have an ability to “capture” red blood cells and cause further damage. The reason they are resistant to healthy degradation is due to the iron causing active oxidation to the enzymes trying to break them down. The study found tested multiple stabilization agents and found that sodium salicylate (aspirin) was effective against these very specific types of iron induced fibrogen clots while biologics were not able to break them down.

This strange decomposition resistant fibirin-amyloid type microclotting is the exact type seen in recent research from one of the worlds experts on spike protein and microclots and her research indicates that they are persistent after the acute COVID19 phase. Another study shows the connection between iron overload diseases and the strange blood clotting and red blood cell shape changes seen in COVID19.

Long haulers often suffer from “Sticky Blood Syndrome” where it is incredibly difficult to draw blood from them, this is a known effect of anti-phospholipid syndrome, an autoimmune disease commonly seen after COVDI19. While multiple studies show that COVID19 causes auto-antibodies targeting the blood, the root cause has not been identified. These exact same autoimmune diseases are seen in hyperferritinemia, triggered by free iron releasing in the blood. In fact, iron effecting the blood in this way can lead to “Catastrophic Anti-phospholipid Syndrome”, which one paper theorizes could be a mechanism of COVID19 fatality. A meta-analysis found almost half of patients hospitalized with COVID19 developed the same auto-antibodies that are known to be induced by iron. This same paper discusses iron causing macrophage activation syndrome. Its interesting to point out that in ferritin triggered macrophage activation syndrome, the general treatment is corticosteroids, the same treatment which is used in acute COVID19 cases and seems to prevent the manifestation of some long term side effects, but coming with its own issues.

This macrophage activation comes from their inability to process iron properly and get “fat with iron”, which some researcher believe is due to issues with copper/ceruloplasmin enzyme and a driver of auto-immune disease. A study correlates the lung damage seen in COVID19 with iron levels, indicating a mechanisms of lung damage similar to the ground glass opacities seen in cadmium toxicity- metal catalyzed auto-oxidation. Tissue analysis shows iron filled macrophages in lung tissue from COVID19 patients. Another tissue study shows a number of iron abnormalities, including iron laden macrophages and iron dysregulation in the bone marrow.

Iron storage issues:

Ferritin can “leak” iron in a number of situations, most often due to the modification of the ferritin enzyme structure by degredation, but also through reductive mobilization means. NAD+ dependent oxidoreductase enzymes have been speculated to be the mechanism where free iron is released from ferritin, linking NAD+ depletion to iron homeostasis. The pro-oxidative, pro-inflammatory environment in long covid with depleted NAD+ will dramatically lower the stability and iron holding abilities of ferritin, causing a feedback loop. Dysfunction in redox functioning may be the most likely cause of leaking ferritin, as the Methyl Trap will deplete glutathione and with NAD+ depleted, there is a very critical unbalancing of the redox chemistry in the body. Glutathinone is highly involved in redox state but also directly in iron trafficking. Another effect of the Methyl Trap is potentially causing changes which destabilize ferritin, as homocystein is highly correlated to iron release.

A paper reviewing methods of iron release from ferritin states the two main degradation mechanisms are “Lysosomal proteolysis following autophagy from the cytosol into lysosomes, and by the proteasome in the cytosol following tagging by ubiquitin.” Interestingly, Chloroquine (and Hydroxychloroquine) are known to prevent ferritin iron release by ferritin protein degradation in enterocyte, hepatocyte and reticulocyte cell culture models. There are other less understood mechanisms of iron release from ferritin including contact with lysosomes containing reducing agents.

Its not clear if the effects of long covid are due to over production of ferritin and normal leaking processes, or a targeted process that leaches iron from ferritin. As a side-note, a paper has recently been published which shows that there is a very interesting sequence similarity between hepcidin, the iron transport enzyme and the SARS-CoV-2 genetic sequence. This is relevant to research because as one paper states, genetic malfunctions affecting the hepcidin-ferroportin axis are a main cause of iron overload disorder.

Some researchers specializing in iron indicate that all iron lab tests do not represent iron deposited in the tissues and low iron is almost never due to lack of iron in the diet. In fact, there are many researchers who believe that the laws regulating that iron needs to be added to grains and other staple foods, are causing much more harm than good. They state there is evidence that iron is correlated to a number of modern disease states and combined with the environmental toxins like glyphosate disrupting iron homeostasis. This may be a case of pop-science driving public policy, as anemia seems to be caused by disruption of iron transport and not unavailability of iron in the diet. In fact, Morley Robbins states that the majority of people he sees in his nutritional practice with iron overload are actually vegetarians who eat more grains and other food artificially supplemented with iron. Groups like the Gates Foundation heavily promote iron supplementation in the developing world in an attempt to stamp out anemia, but on the population level they may be doing much more harm than good, particularly in the context of a disease like COVID19 which mobilizes and redistributes iron. It does seem that anemia is an issue with iron transport, not dietary iron, in fact the role of copper in anemia should be promoted instead of iron according to a study cited by researchers in this area.

Treatment Theory*

*Talk to your doctor before any changes in supplementation or lifestyle, this is research analysis and not medical advice.

Treating iron dysfunction:

The paradoxical thing is that some long haulers have low iron/ferritin but seem to also have symptoms of iron buildup in their nervous system and other tissues, other have very high levels of ferritin — dependating on transporter issues. It seems like those with long covid never have ferritin in a healthy 20–100 range. Supplementing with iron makes sense if ferritin is low, but must be done under medical supervision and discontinued if it causes issues. Ferritin between 20–100 is the range researchers have discussed as healthy, although the reference range on the lab tests and average range of the population is higher.

Its very important to note that ferritin is an iron storage enzyme and it is measured in circulating serum for lab tests, but its possible that ferritin or other iron forms and complexes could accumulate in organs/tissues and not be accurately represented by the serum ferritin test. Particularly ferritin in the brain and central nervous system. Iron can also collect in skeletal muscle, connective tissues and weight gain is common when the body tries to create fats to dilute and counteract the iron and its oxidation. Iron can be problematically deposited in tissues without high iron biomarkers and the most relevant test may be 8-OHdG, a DNA damage biomarker, or other oxidative stress based tests. High homocystein has been correlated to iron overload and can also correlate with the methyl trap, indicating that a urinary organic acids test can open some windows into understanding the metabolic disruption.

While MRI can be used with a skilled technician to analyze the iron present in the brain, not all types of iron can be properly visualized. According to research on brain iron oxides, “An alternative clinical technique for the detection of brain iron is transcranial ultrasound or transcranial sonography (TCS). TCS has been developed as a cost-effective and portable method to detect changes in certain brain regions exhibiting iron accumulation”.

In terms of treating iron in the nervous system, there are a number of approaches, including new classes of compounds mainly investigated for Alzheimer's. A drug called Defiriprone is on the market for iron overload disorders and trialed for Alzheimers patients, while it has its own issues and side effects it does seem to be effective at removing unwanted iron from the brain and nervous system.

What I consider one of the greatest advances in preventing disease in my lifetime is the compound NMBI, developed as a method for safely removing mercury and other metals from the brain and other organs. It binds free metals in the body, without binding metals that are being used in biological functions and unlike other chelators for removing heavy metals, it binds them irreversibly and does not cause redistribution. The inventor points out that it is also one of the strongest anti-oxidants and enormous amounts have been given to animals in studies with no side effects. Amazingly, animals given NMBI can handle injections of toxic amounts of mercury that would be fatal under any other conditions.

NMBI was sold as a supplement under the label OSR in the early 2000’s, but the FDA simultaneously changed their supplement laws and shut down OSR. This was due to the fact that OSR is essentially a synthetic combination of two natural compounds. It currently has orphan drug status and the inventor is working through clinical trials via the company EmeraMed. The effectiveness of NMBI for mercury and other metal toxicity is so profound and painless that people are successfully coordinating on Facebook groups to order the powdered raw material from custom synthesis labs, have it tested and work together to dose themselves with their own protocols.

There are naturalistic ways to get rid of excess iron. Compounds like green tea extract, curcumin and IP-6 are used by functional medicine practitioners, with IP-6 being the most aggressive. Donating blood is also used in some cases of genetic iron overload and can drop ferritin levels as much as 20 points in one donation. In the case of COVID19 recovery, its very important to have a full blood panel done as well as copper and ceruloplasmin enzyme to determine if you need to supplement copper/iron. There does not seem to be any test for showing iron accumulated in the nervous system and other tissues but the general DNA oxidation marker 8-OHdG can shed a light on if you have a source of metal catalyzed auto-oxidation in the body. High homocystein, also a product of the metabolic trap, is a marker of iron overload according to one study and is found on the common urinary organic acids panel. Certain methods using MRI can indicate levels of iron, but require a trained and dynamic MRI technition to understand the complexities of visualizing iron deposits. A paper explains the patterns in iron integration with the brain in neuro-degenerative disease and may be relevant for signs of COVID19 iron integration with the nervous system and brain.

Its important to make sure to not only bind iron, but support the iron transporting mechanisms by having enough copper, magnesium and other co-factors. Copper is highly involved in proper iron transport. Zinc, Copper and Selenium deficiencies can lead to iron accumulation, which is interesting as these particularly metals correlate to COVID19 outcomes. A paper found that higher levels of copper and the important iron shuttling copper based enzyme ceruloplasmin, was correlated with better outcomes in acute COVID19 cases. Issues with ceruoplasmin have been known to lead to iron accumulation in the retina, liver, pancreas and brain. Ceruoplasmin is one of the most complex enzymes in our body, with many functions and can be easily disrupted, particularly through environmental toxicity, one of the strongest disruptors being the industrial pesticide, Glyphosate.

Morley Robbins, author of the Root Cause protocol, has dedicated his life to understanding iron dysfunction points out that anemia is often not a dietary deficiency of iron, but an issue with Ceruoplasmin or other iron transporters and just pumping in more iron is not the solution. He states that we need more bioavaliable copper, more magnesium and less iron to regulate copper more efficiently. Vitamin A is also another compound involved in Ceruplasmin that contributes to copper regulating iron homeostasis.

One company has made a product which is copper bound to nicotinic acid, for bio-available delivery, while expensive, it may be an important part of recovering from iron dysregulation in the nervous system. The MitoSynergy product line is one of the more expensive supplements, but seems to be a very new and unique approach for supporting proper iron homeostasis.

Another method is to trigger autophagy, which is the bodies cellular clearing mechanism. Usually it is done through intermittant fasting supplements such as high dose nicotinic acid will also trigger it. A group on facebook with over 6000 long haulers is having success in dramatically lowering their symptoms by triggering autophagy on the weekend. Through trial and error the group has developed a protocol for diet and supplementation which supports autophagy. While it does take a number of weeks, the results from the patient surveys speak for themselves — in my opinion this validates the theory that iron is driving most of the issues with long covid as autophagy will lower stored iron even in areas such as the brain and CNS.

Research shows that iron overload impairs normal autophagy which may be a general problem with long haulers. There is a phenomenon of ferritinophagy and iron triggered cell death which makes sense why the long haulers triggering autophagy can “feel” autophagy starting which is normally not possible. They feel aches and pains in different places on their body, indicating free iron may being released during the cleanup process and causing inflammation and oxidative stress.

Data analysis of over 1000 patient surveys, using autophagy according to the “Recover from Long Covid” facebook group method

While the mechanism is not clear, anecdotally, high dose nicotinic acid (500mg+) seems to have a purging effect on iron materials accumulated in the body (and will trigger autophagy if pulsed on and off during the week), potentially through rebalancing low level redox chemistry in the cells which may have lead to iron “leaking” in the first place. There are strange reports of long haulers having small black balls emerge from their skin after this protocol and finding those balls are magnetic, indicating they contain an iron compound. In the context of redox balancing it would make sense to supplement proper forms of copper and magnesium to support this mechanism.

There are methods of detoxification that were promoted in the past, such as the famous niacin/sauna protocol. One clinic promotes the use of high dose nicotinic acid and sauna for detoxing heavy metals, with a famous case being a cohort of 9/11 firefighters with metal overload/neurodegeneration from suspected magnesium metal contamination. In the photo below you can see the heavy metals that were removed from the body and collected on his towel during a series of sessions. This is something to explore as metals in the nervous system will lead to horrible neurodegeneration in the long run.

Stains from suspected magnesium salts collected on a towel after a series of niacin/sauna detox

Treating Niacin Sink Metabolic Trap:

The Niacin Sink Trap was identified early on in the pandemic by a number of patient-centric researchers and is one of the easier aspects to deal with. In November, I had written the blog post, The Team of Doctors and Biohackers Who Seem to Be Successfully Treating “Long Covid” about a group in South Africa who were able to treat Long Covid based on an understanding of the Niacin Sink Trap. While I had hundreds of people reach out and say it helped them get their lives back, and it did the most good for the most number of people with no adverse issues, it was not the full story for everyone.

Based on my anecdotal observations, taking nicotinic acid or niacin (vitamin B3) at high doses works miracles for long covid. There does seem to be a dose-response curve and some people only get benefits at the level of 500mg+ a day, which is much larger than the daily recommended allowance and causes a “niacin flush” effect until tolerance builds. The niacin flush is similar to feeling like you have sunburn and tingling on your skin for an hour or so. I would suggest to take 100mg of instant release niacin to calibrate your response. The average person will have a flushing reaction visible on their skin. If you are an under-methylator, you may not have a flush at all, this can also happen if the butyrate producing bacteria in your gut are not doing their job ( very common after COVID19) and you may need to take a butyrate supplement for a few days before. Some people can have a very disruptive flushing effect at this amount that makes them feel anxious, this is an indication that you are part of the 9% or so of the population who is an over-methylator.

It seems ideal to work your way up to 500mg of nicotinic acid, matched with 500mg of nicotinamide, the other form of vitamin B3. While this seems excessive, these vitamins are water soluble and doses well beyond 3000mg are often given for lipid metabolism issues. In fact there is an entire field of health called Orthomolecular medicine which advocates for very large, multigram daily doses of niacin and vitamin C. This seems best if matched with NAC, around 1500mg a day, which will replenish glutathione and the cellular stores of cystein. There are a number of other important co-factors such as zinc, vitamin C, selenium, quercetin and vitamin D. This metabolic trap should be dealt with before anything else as it will support the body in handling oxidative stress.

Using an organic acids panel test will give you the best insight into your metabolic situation and should be used by your doctor before any changes in diet or supplementation. In the case of the Niacin Sink Trap, you would expect to see tryptophan metabolites high, there are multiple of these on the organic acids panel and this would be a good indicator.

Interview with Dr. Dmitry Kats:

I did a quick interview with Dr. Dmitry Kats, a researcher involved in COVID19 research and a giant proponent of niacin.

Nikita Alexandrov: In your experience promoting niacin, what do you recommend for long haulers:

Dr. Dmitry Kats: Start between 50–100mg to see how you respond, depending on your response, if you respond normally, 500mg is a good daily dose to achieve as tolerance builds. Some people will require as much as double that but most people much less. This should be matched with equal amounts of nicotinamide. NAC should be included, 1500mg a day. Vitamin C, TMG, methyl B vitamins, zinc, magnesium and butyrate are other important co-factors.

Nikita Alexandrov: Some researchers say that you should avoid other forms of B3 such as nicotinamide due to its effects on sirtuins, what do you think?

Dr. Dmitry Kats: From observations it seems to be beneficial and I recommend it be used in equal amounts of nicotinic acid. We are treating bio-energetic balance in the body, this is new territory and its still mysterious but it has its own pathways and benefits and seems to work in synergy. For example nictonic acid acts in cellular organelles while nicotinamide seems to act in the cytoplasm. I added this to the protocols because I noticed that some people did not get the results they wanted with nicotinic acid improved with addition of nicotinamide.

Nikita Alexandrov: How many people have you talked to that used these methods and what kind of results have you seen?

Dr. Dmitry Kats: I have heard from around 10,000–15,000 people since March 2020 on the use of niacin for COVID19 and the protocol helps across the board, but there seems to be a population of around 10% of long haulers who are more resistant to treatment, this is attributed to iron deposited in the nervous system, secondary infections and metabolic/nutrient inbalances — this is something I am working on. Chelating iron compounds needs to happen in a targeted way. My goal is 100% curative therapy for long haulers and if you really understand the disease state, it is an achievable goal.

Treating Methyl Metabolic Trap:

The methyl metabolic trap is complex because there are many different types of genetic pre-dispositions to an altered methylation status and it involves a number of feedback loops. Therefore, its best to consult a functional medicine doctor who is confident in testing methylation status. For the average person the best way to push out of the methyl metabolic trap is to supplement with methyl folate and a methyl donor such as TMG for a few days, and then start taking vitamin B12 at high dose. If you only take vitamin B12, for example, by injection and are in the methyl trap, it can make you feel worse due to a buildup of homocystein, you need to support the methylation cycle first. B6 supplementation may be important as this is coupled to the same system but should come in the later stages. Using an organic acids panel test will give you the best insight into your metabolic situation and should be used by your doctor before any changes in diet or supplementation. methylmalonic acid and uracil would be expected to be high on an organic acids panel, often methylmalonic acid is used as a proxy for vitmain B12 and many doctors have told their patients their B12 is through the roof when it is infact a proxy indicator. Another issues is that due to the methyl trap, B12 building blocks can be oxidized and trigger false positives on a proper B12 test. Homocystein and histamine are two other panels that may be expected to be high due to the methyl trap. Experts on the methylation cycle use a low SAM/SAH ratio to determine methylation dysfunction.

Treating Oxidized Mitochondrial Membranes:

This may be the last step in recovering from Long Covid, many find that after other protocols they feel well but still get exhausted easily and in general have fatigue. A solution to this is called “Lipid Replacement Therapy” where phospholipids are taken to replace the burned membrane lipids. NTFactor is a purpose made supplement for this purpose and has a number of clinical trials showing impressive results for diseases involving fatigue such as Chronic Fatigue Syndrome. Otherwise, Soy Lecithin is a great source and taking somewhere around 5 grams a day will accomplish the same thing over time, butyrate will help burn off the existing membranes and compounds like acetyl-carnitine and ALA will help shuttle the lipids and burned protein/lipid rafts. This process can take many months but in the clinical trials there were signifigant improvements in fatigue using this method. This will also lower the potential for Lyme disease and associated pathogens to thrive by feeding on the oxidized membranes. Triggering autophagy will not only assist with removing iron based materials but also help repair oxidized mitochondrial membranes.

Treating Microbial Remodeling:

In terms of repairing the microbiome, as long as your diet is healthy, it will remodel and repair itself when the other issues have been taken care of. If you have high ferritin values or symptoms of iron accumulation in your body it would make sense to deal with that first. An organic acids panel test would also give insight into the amount of microbiome disruption, as well as a window into the methyl and niacin sink metabolic traps. Microbiome tests exist that can tell you the makeup of your microbiome, and while interesting and a powerful tool, can not contribute much past showing a dysbiosis.

A common type of bacteria to become scarce after COVID19 is butyrate producing bacteria, while there are no commercial probiotics that contain this species, research shows that taking butyrate supplements actually increase the butyrate producing bacteria. Butyrate supplementation is known to rebalance the microbiome through other mechanisms also. Butyrate is also a co-factor for a receptor (GPR109A) that nicotinic acid acts on and is required for some of its therapeutic action, as well as having a positive effect on the lipid replacement therapy process. It would also be important to take fiber also as butyrate is responsible for fiber metabolism. Taking probiotics and pre-biotics would be important as well as biotoxin binders such as zeolite, activated charcoal, chlorella and bentonite.

Other Treatments:

There are other groups and methodology for treating long covid but none of them seem to work as well nicotinic acid and other naturalistic methods. One group is IncelDX, run by Dr. Bruce Patterson. They developed the first biomarker system which showed long covid inflammatory dysfunction. Using their existing biotechnology platform, they identified fragments of of non-replication competent viral material were found in monocytes and state that all long covid symptoms are a result of over-activation of monocytes.

They treat long covid with a mix and match Ivermectin, Statins, SSRI’s and steroids and seem to have a reduction in brain fog and inflammation, but in my observation nobody I know has made a full recovery using their methods. Ivermectin may have benefit for acute COVID19 but it does not seem to be a magic bullet for long covid, with a high potential for neurotoxicity in people who have a disrupted blood/brain barrier. While there can be a normalization of inflammatory biomarkers using these methods, I have talked to some patients who had a normalization of biomarkers but no change in symptoms during treatment, while others did not have treatment and had normalization of biomarkers. Interestingly they promote the use of niacin in some of their webinars. While I commend them for focusing on long covid, they should be more patient centric and more responsive to symptoms, they have their hands full with running a biotechnology company and with multiple self-promotional appearances on Dr. Drew. They are not rushing to understand why many of their patients arent getting better regardless of using their treatments and biomarkers stabilizing. In a recent webinar, Dr. Patterson blamed “de-conditioning” for the lack of his patients fully recovering. I would challenge IncelDX to compare their treatments with even a simple nicotinic acid/NAC/IP-6 stack.

Dr. Adrian Wentzel, Robert Miller and Guy Richards saw an association with COVID19 outcomes and bioenergetic functioning at an early stage in the pandemic and have done a large amount of high quality patient-centric work. I wrote about this group in a previous article and their niacin based stack has helped tens if not hundreds of thousands of people get their lives back.

Dr. Tina Peers promotes anti-histamines on-top of a similar stack but from my observations anti-histamines only work in the short run before they become ineffective and these methods do not address methylation issues or iron dysfunction properly. Anti-histamines may in fact be a good way of determining if you have a histamine issues/methylation issues, specifically if they lower brain fog and other systematic issues.

Leronlimab, is a monoclonal antibody by CytoDyn which has just released preliminary results and will most likely be the FDA approved drug for Long Covid in the future. It is injection only, incredibly expensive and the clinical trial patients flocking to Facebook groups state that while it did make them feel better, the effects seemed to wear off after a few weeks. Regardless, as usual in the pharmaceutical approach, it has hit the carefully designed clinical trial endpoints, has a long patent life and investor interest to push it through the FDA process, so it will most likely be “the solution” in the future.

The pharmaceutical treatments like Leronlimab and the ones promoted by Dr. Bruce Patterson seem to only “turn off the fire alarms” but not “put out the fire” and seem to be the usual manifestation of a scientific/medical system that does not really understand the human body and is disconnected from human needs.

Example Long Covid Treatment Protocol*:

*Talk to your doctor before any changes in supplementation or lifestyle, this is research analysis and not medical advice.

Before starting:
Nicotinic acid “challenge”, 100mg flush niacin on an empty stomach before moving on to higher doses, should cause a temporary feeling like sunburn but no inflammatory or cardiac reactions.

Tests:
Full Iron Panel
Urinary Organic Acids Panel
Ceruloplasmin/Copper Levels
Histamine
8-OHdG

Supplementation:
Oxidative stress support:
500mg NAC 3x day
500mg Vitamin C 3x a day

Niacin trap:
100mg nicotinic acid 3x a day (moving to 200mg week 2 and 300mg week 3) matched with equal amounts of nicotinamide

Methyl trap:
Methyl Folate 500mcg 3x a day
B12 (hydroxycobalamin) 1000mcg sublingual 1x a day
Betaine/TMG 1000mg 3x a day

Microbiome:
1000mg psyllium fiber 3x a day
2000mg sodium butyrate 3x a day
Probiotic tablet
2 tbsp zeolite before bed

Cofactors:
Zinc 15mg 1x a day
Selenium 200mcg 1x a day
Mitosynergy copper tablet 1x a day
Magnesium biglycidate 200mg
B vitamin complex 1x a day

Iron chelation:
500mg curcumin 3x a day
500mg green tea extract 3x a day
500mg inositol hexaphosphate 3x a day
*must be done with iron panel testing/medical monitoring, iron bisglycinate 18mg a day if highly deficient

Lipid replacement therapy:
1000mg sunflower lechitin 3x a day

*Talk to your doctor before any changes in supplementation or lifestyle, this is research analysis and not medical advice.

“To change something, build a new model that makes the existing model obsolete.” — Buckminster Fuller.

Nikita K. Alexandrov, Chem, MBA
7/23/21

Contact for collaboration/consultation:
NKA369@protonmail.ch
https://twitter.com/N1K1TAKA

Elegant solutions for complex problems.