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Serotonin Syndrome and Thiamine: Is There a Connection?

Published on May 7, 2025

34.8K views

Serotonin syndrome is described as a drug-related condition and is commonly believed to be rare. Serotonin is a neurotransmitter, but its actions make it sound like a hormone. It is made in the central nervous system and the gastrointestinal nerve complex. The symptoms of serotonin syndrome arise as a result of an over-abundance of its release from the nervous system into the blood and can be mild to severe, depending on the amount of serotonin in circulation. For normal function, serotonin is stored in a tiny cavity at the end of a nerve, known as a synaptosome and is released by passing through the membrane that surrounds the synaptosome, into the brain. The syndrome is caused by medications, either alone or in combination that increase serotonin levels, e.g. antidepressants, migraine medications, opioid pain medications, or illegal drugs. It is treated by the withdrawal of the causative drugs. There are multiple symptoms arising from an excess of serotonin in the brain and there are also symptoms arising from a deficiency. It is perhaps the prime example of the importance of moderation in everything.

Too Much or Too Little Serotonin

Just as excess serotonin is linked with a variety of symptoms, including: shivering, diarrhea, irritability and/or restlessness, confusion, increased heart rate, high blood pressure, dilated pupils, twitching muscles, muscle rigidity, excessive sweating, headache, tremors, goose bumps, hallucinations, and in more severe cases, unresponsiveness, high fever, seizures, irregular heartbeat, unconsciousness or coma, too little serotonin may be linked to mood disturbances. Deficiency is associated with several psychological symptoms, such as anxiety, depressed mood, aggression, irritability, low energy and low self-esteem. It can cause carbohydrate craving, weight gain, fatigue and nausea, but also, digestive or gastrointestinal motility problems such as irritable bowel syndrome and constipation. It is also a key neurotransmitter in the sleep cycle and is an essential brain chemical.

Thiamine Deficiency and Serotonin

Since many of the posts on this website discuss the problem of symptoms that are frequently associated with deficiency of vitamin B1 (thiamine), I turned to the literature to see if there was any connection between this deficiency and the role of serotonin. I found two important studies that demonstrate the critical role of this vitamin and its association with serotonin. In the first study, researchers explored the role of thiamine deficiency in synaptic transmission, the high affinity uptake and release systems for neurotransmitters using synaptosomal preparations isolated from different parts of the brain in thiamine deficient rats. There was significant decrease in the uptake of serotonin by the synaptosomal preparations of the cerebellum. The administration of the vitamin in vivo resulted in a significant reversibility of the inhibition of serotonin uptake, coinciding with dramatic clinical improvement. The study supports the possibility of an important innervation of the cerebellum by serotonin and suggests a selective involvement of this system in the pathogenesis of some of the neurologic manifestations of thiamine deficiency.

The negative societal impacts associated with the increasing prevalence of violence and aggression needs to be understood. In the second study, researchers investigated the role thiamine using a mouse model of aggression. Ultrasound aggression in mice was induced and the molecular and cellular changes were studied. They found that the ultrasound-induced effects were ameliorated by treatment with thiamine and benfotiamine, both of which were able to reverse the ultrasound-induced molecular changes.

The clinical effects of both deficiency and excess of serotonin are all well described online. The deficiency symptoms described are exactly those associated with beriberi, the vitamin B1 deficiency disease. Serotonin cannot cross the blood brain barrier. Therefore, it must be produced separately in the brain and the gastrointestinal system. Its association with thiamine in the bowel amply reinforces the mystery of gastrointestinal beriberi.

The many posts on thiamine deficiency in Hormones Matter suggests that a mild deficiency of thiamine is responsible for the large number of the polysymptomatic illnesses reported. High calorie malnutrition is a common cause by its increase in the calorie/thiamine ratio. The relationship with drugs is another matter. Although the mechanism of an excess of circulating serotonin is described as the drug-related cause of this syndrome, I could not help but notice that I have seen some of these symptoms corrected by the use of megadose thiamine. For example, excessive sweating, dilated pupils, increased heart rate and “goose bumps” are all caused by increased activity in the sympathetic branch of the autonomic nervous system. Thiamine deficiency is a prime cause of imbalance in this system. Certain therapeutic drugs used in medical practice may trigger mitochondrial toxicity leading to a wide range of clinical symptoms and even a compromise of the patient’s life. Contemplating this made me wonder whether the vitamin might have an important bearing on maintaining serotonin in its median state of concentration, because of its vital role in energy metabolism.

Serotonin and COVID-19

Since it has been claimed that Americans consume a high calorie diet, it is important to stress the imbalance which is commonly high in carbohydrate and fat. Serotonin is synthesized from tryptophan, an amino acid that is found in first-class protein and is an essential component of the human diet. It plays a part in many metabolic functions including the synthesis of serotonin and melatonin. Supplementation of this amino acid is considered in the treatment of depression and sleep disorders. It is also used in helping to resolve cognitive disorders, anxiety, or even neurodegenerative diseases. Reduced secretion of serotonin is associated with autism spectrum disorder, obesity, anorexia and bulimia nervosa, as well as other diseases presenting with a variety of symptoms.

It has been hypothesized that aging occurs because of failure of the pineal gland to produce melatonin from serotonin. Evidence has been presented for a role of melatonin and serotonin in controlling the neuroendocrine and immune networks inhibiting the development of ischemic heart and Alzheimer’s disease, tumor formation and other degenerative processes associated with aging. However, a more modern concept for aging is that the production of intracellular reactive oxygen species is a major determinant of lifespan.

One important feature of Covid 19 pathophysiology is the activation of immune cells, with consequent massive production and release of inflammatory mediators that may cause impairment of several organ functions including the brain. In addition to its classical role as a neurotransmitter, serotonin has immunomodulatory properties, down regulating the inflammatory response by central and peripheral mechanisms. Although the interferon system is the first line of defense against viral infection in mammals, almost all viruses have evolved mechanisms to evade the interferon system by partially blocking their synthesis or action.

The Case for Thiamine Supplementation in COVID 19

Thiamine is an essential cofactor for four enzymes involved in the production of energy (ATP) and the synthesis of essential cellular molecules. The total body stores of the vitamin are relatively small and its deficiency can develop in patients secondary to inadequate nutrition, alcohol use disorders, increased urinary excretion and acute metabolic stress. Patients with sepsis are frequently thiamine deficient and patients undergoing surgical procedures can develop the deficiency. It can lead to congestive heart failure, peripheral neuropathy, Wernicke disease and gastrointestinal beriberi. It can result in the development of intensive care unit complications such as heart failure, delirium, critical care neuropathy, gastrointestinal dysfunction and unexplained lactic acidosis. Consequently clinicians need to consider thiamine deficiency in patients admitted to intensive care units and the development of this deficiency during the management of critically ill patients. Intravenous thiamine can correct lactic acidosis, improve cardiac function and treat delirium, without there being any possibility of toxicity. The many symptoms developed in Covid 19 patients are interpreted as a direct effect of the virus, whereas the evidence written in this post strongly suggests that deficiency or excess of serotonin are responsible and that intravenous thiamine could be given with impunity in the emergency room. The persistence of thiamine deficiency following the cessation of the acute phase of the disease would explain the long term symptoms that have been described, following what is generally accepted as recovery.

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More people than ever are reading Hormones Matter, a testament to the need for independent voices in health and medicine. We are not funded and accept limited advertising. Unlike many health sites, we don’t force you to purchase a subscription. We believe health information should be open to all. If you read Hormones Matter, like it, please help support it. Contribute now.

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This article was published originally on Jun 13, 2023.

Rest in peace Derrick Lonsdale, May 2024.

Blood Brain Barrier Integrity and Early Thiamine Deficiency

by Chandler Marrs, PhD

Published on May 5, 2025

6.8K views

In my quest to understand oxythiamine (oxythiamine is an anti-thiamine molecule that appears to be synthesized in individuals with kidney disease), I stumbled upon a study from the mid-nineties where researchers examined blood brain barrier (BBB) integrity in early and late thiamine deficiency. They found that BBB breakdown not only preceded the pathogenesis of the more commonly considered white matter lesions associated with severe and chronic thiamine deficiency, but that BBB disintegration drives the deficiency-induced brain damage. This makes sense of course, given thiamine’s role in energy metabolism and the fact that barrier function is energy intensive. If metabolic energy declines then the barrier’s ability to prevent noxious molecules from reaching the brain will decline, as will its ability to filter out endogenously created waste products and other toxins. The entire exchange process will be weakened and across time, brain damage will accumulate.

Insofar as the gut barrier and the brain barrier are intimately connected, might we surmise that if BBB disintegration precedes and drives much of the brain damage evoked by thiamine deficiency, then would not ‘leaky gut’ and the symptoms therewith come before the leaky brain? I believe so. This was not part of this experiment and in no way indicated directly, but there were some hints that point me in this direction and certainly research published over the last decade or so supports this.

In this particular study, the investigators were looking at the patterns of dysfunction that arose when thiamine deficiency was induced by different mechanisms. To explore these differences, they used four groups of mice:

Group 1: Mice fed a thiamine-free diet and given pyrithiamine, a thiamine antagonist that readily crosses the BBB.
Group 2: Mice fed a thiamine-free diet and given oxythiamine, a competitive thiamine antagonist that blocks the transketolase enzyme, but does not appear to cross the BBB.
Group 3: Mice fed a thiamine-free diet and given pyrithiamine for 10 days, and then fed a normal diet and given thiamine (20mg/kg) injections. This was to determine whether recovery was possible.
Group 4: The control group fed a normal diet.

Groups 1, 2, and 4 were sacrificed on days 8, 9, and 10, while group 3 was sacrificed on day 14.

I should note that estimates equating mouse lifespan with human lifespan propose that 9 days in the life of a mouse is equivalent to about one human year. In contrast, for rats, researchers estimate that 13.2 days equal one human year. Keep these numbers in mind when considering animal research. Other differences apply, of course, but lifespan differences are huge.

With that in mind, in this particular study where thiamine was completely abolished from diet and blocked using anti-thiamine molecules, neurological symptoms appeared after 10 days of thiamine deprivation in mice and if thiamine was not repleted, the animals died within 48 hours thereafter. In contrast, rodents can live up to 4-5 weeks before succumbing to the effects of thiamine deficiency.

This would seem to suggest that we, as humans, might survive the complete absence of thiamine from diet, plus anti-thiamine blockade via pyrithiamine, for up to a year. This is unlikely. However, experiments using extremely low doses of thiamine (.15-.45mg p/day) have shown survival, with severe neurological deficits and damage, but survival nevertheless, for up to 6 months. We also have reports of patients with significant, lab tested deficiency who, though quite ill, live for years.

In contrast to the experimental conditions though, with human thiamine deficiency, especially as it develops later in life (genetic defects that appear at birth are a different story), there is rarely a complete blockade of thiamine or absence of thiamine from diet. Dietary consumption and anti-thiamine factors vary considerably from day to day and year to year and so the trajectory from deficiency to illness in humans will be prolonged and non-linear. That being said, there are some things we can learn from experimental protocols such as this one. Namely, that the mechanism of deficiency matters as it will affect which body compartments are affect most prominently in the early stages.

The Compartmentalization of Thiamine Deficiency

In this study, we saw the effects of long term thiamine deficiency in different tissues generated by the different anti-thiamine molecules. Pyrithiamine affected the brain and nervous system, while the effects of oxythiamine were most prominent in the periphery, likely the GI system and in the heart, although these were not tested.

We also see the time course of symptomology, where early on symptoms are not as noticeable until a certain threshold of damage is met. For example, neither histological lesions nor symptoms were obvious prior to day 8 of thiamine deprivation in the pyrithiamine group. This is roughly equivalent to almost a year in human life span. The animals showed an initial weight gain followed by a sharp decline on day 9 and the onset severe neurological symptoms at day 10. According to the researchers:

The initial neurological signs of thiamine deficiency appeared acutely and precisely on day 10, consisting of loss of activity, hyperactivity on acoustic or tactile stimulation, and ataxia.

Commiserate with the neurological symptoms in the pyrithiamine group, disturbed BBB function, necrosis, and numerous brain lesions were observed. If thiamine was withheld, the animals died within 48 hours. If thiamine was repleted (this was done only with the pyrithiamine group), most, but not all, of the animals survived and neurological symptoms abated. This is promising, but suggests there are still unrecognized variables that influence recovery.

In contrast, there were no lesions within this timeframe for the oxythiamine group. With oxythiamine, the only observable symptoms were weight loss and decreased activity. In fact, the oxythiamine animals maintained normal weight and activity until day 6 and then on day 8, there was observable weight loss, anorexia and decreased activity. There were no behavioral signs of neurological damage. It is not clear at what point the oxythiamine animals would have died naturally or by what means, as they were sacrificed at day 10 regardless of state.

The Heart of the Matter

Another study using rodents, points to oxythiamine affecting the heart more prominently than pyrithiamine. Here, oxythiamine treated rats showed a similar pattern of weight loss beginning after the 7^th day, but also developed bradycardia and cardiac hypertrophy, which progressively worsened over the next few weeks. In contrast, the animals treated with pyrithiamine did not show heart-related changes until after developing the neurological symptoms. Moreover, the heart-related changes were not as prominent as those in the oxythiamine group. I will discuss this study more fully in a subsequent post, but it seems to suggest different mechanisms for what we call wet and dry beriberi. That is, oxythiamine results in peripheral metabolic symptoms perhaps related first to the GI system (weight loss and anorexia) and then to the heart, while blockade of thiamine via pyrithiamine results in brain and nervous system symptoms and damage. In both cases, I suspect there is disruption to gut barrier function. With pyrithiamine though barrier dysfunction seems to begin in the brain and nervous system and progress to the periphery, whereas with oxythiamine preferentially targets tissues in the periphery and only later reaches the BBB and the nervous system. Again though, this is not clear. As most of the studies I have read seem to investigate only one or the other.

Obviously, the mechanisms by which these two molecules deplete thiamine differs significantly, which then explains many of the differences observed in the animals, but what intrigues me is how closely the ‘symptoms’ align with human cases of thiamine deficiency where neither compound is administered. This begs many questions, not the least of which is whether and how we might produce these molecules endogenously or be exposed to them in everyday life. How could these patterns observed experimentally so closely align with the human experience (wet beriberi – oxythiamine, dry beriberi – pyrithiamine), where neither compound is provided. I do not know the answer. Yet. In the meantime, here is some more information on the mechanisms of oxythiamine and pyrithiamine and how we might be synthesizing them endogenously: Can We Synthesize Oxythiamine and Pyrithiamine Endogenously?

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More people than ever are reading Hormones Matter, a testament to the need for independent voices in health and medicine. We are not funded and accept limited advertising. Unlike many health sites, we don’t force you to purchase a subscription. We believe health information should be open to all. If you read Hormones Matter, and like it, please help support it. Contribute now.

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This article was published originally on September 7, 2023.

How Can Something As Simple as Thiamine Cause So Many Problems?

by Derrick Lonsdale MD, FACN, CNS

Published on April 29, 2025

167.9K views

I have read a criticism that thiamine deficiency is “too simple” to explain the devastating nature of the post Gardasil illnesses or the systemic adverse reactions to some medications. Sometimes, it is the simple and overlooked elements that are the most problematic.

Understanding Thiamine’s Role in Complex Adverse Reactions – The Limbic System

The lower part of the brain, called the brainstem, is a like computer, controlling the most basic aspects of survival, from breathing and heart rate, hunger and satiety, to fight or flight and reproduction. This computer-like function within the brainstem is called the autonomic system (ANS). The ANS together with the limbic system act in concert to regulate our most basic survival functions and behaviors. Both require thiamine to function.

Postural Orthostatic Tachycardia Syndrome or POTS , a type of dysautonomia (dysregulation of the autonomic system) seems to be the among the commonest manifestations of the Gardasil effect. Many cases have been diagnosed already, while others present all of the symptoms but have yet to receive a diagnosis. Dysautonomia and POTS have also been observed with adverse reactions to other medications, as well. Dysautonomia and POTS, at the most basic level, represent a chaotic state of the limbic-autonomic system. Let me explain.

Fragmented Fight or Flight

The brainstem autonomic system together with the limbic system enable us to adapt to our environment, presiding over a number of reflexes that allow us to survive. For example, fight-or-flight is a survival reflex, triggered by perception of a dangerous incident that helps us to kill the enemy or escape. This kind of “stress event” in our ancestors was different from that we experience today. Wild animal predators have been replaced by taxes/business deadlines/rush hour traffic etc. These are the sources of modern stress. The beneficial effect is that the entire brain/body is geared to physical and mental response. However, it is designed for short term action and consumes energy rapidly. Prolonged action is literally exhausting and results in the sensation of fatigue. In the world of today where dietary mayhem is widespread, this is commonly represented as Panic Attacks, usually treated as psychological. They are really fragmented fight-or-flight reflexes that are triggered too easily because of abnormal brain chemistry.

Thiamine and Oxidative Metabolism: The Missing Spark Plug

Our brain computers rely completely on oxidative metabolism represented simply thus:

Fuel + Oxygen + Catalyst = Energy

Each of our one hundred trillion body/brain cells is kept alive and functioning because of this reaction. It all takes place in micro “fireplaces” known as mitochondria. Oxygen combines with fuel (food) to cause burning or the combustion – think fuel combustion engine. We need fuel, or gasoline, to burn and spark plugs to ignite in order for the engines to run.

In our body/brain cells it is called oxidation. The catalysts are the naturally occurring chemicals we call vitamins (vital to life). Like a spark plug, they “ignite” the food (fuel). Absence of ANY of the three components spells death.

Antioxidants like vitamin C protect us from the predictable “sparks” (as a normal effect of combustion) known as “oxidative stress”. Vitamin B1, is the spark plug, the catalyst for these reactions. As vitamin B1, thiamine, or any other vitamin deficiency continues, more and more damage occurs in the limbic system because that is where oxygen consumption has the heaviest demand in the entire body. This part of the brain is extremely sensitive to thiamine deficiency.

Why Might Gardasil Lead to Thiamine Deficiency?

We do not know for sure how Gardasil or other vaccines or medications have elicited thiamine deficiency, but they have. We have two girls and one boy, tested and confirmed so far. More testing is underway. Thiamine deficiency in these cases may not be pure dietary deficiency. It is more likely to be damage to the utilization of thiamine from as yet an unknown mechanism, affecting the balance of the autonomic (automatic) nervous system. It is certainly able to explain POTS (one of the many conditions that produce abnormal ANS function) in two Gardasil affected girls. Beriberi, the classic B1 deficiency disease, is the prototype for ANS disease. Administration of thiamine will not necessarily bring about a cure, depending on time since onset of symptoms, but it may help.

Thiamine Deficiency Appetite and Eating Disorders

Using beriberi as a model, let us take appetite as an example of one of its many symptoms. When we put food into the stomach, it automatically sends a signal to a “satiety center” in the computer. As we fill the stomach, the signals crescendo and the satiety center ultimately tells us that we have eaten enough. Thiamine deficiency affects the satiety center, wrecking its normal action. Paradoxically it can cause anorexia (loss of appetite) or the very opposite, a voracious appetite that is never satisfied and may even go on to vomiting. It can also shift from anorexia to being voracious at different times within a given patient. That is why Anorexia Nervosa and Bulimia represent one disease, not two.

Thiamine Deficiency, Heart Rate and Breathing

The autonomic nervous system, responsible for fight or flight, regulates heart activity, accelerating or decelerating according to need. So heart palpitations are common in thiamine deficiency. Its most vital action is in control of automatic breathing and thiamine deficiency has long been known to cause infancy sudden death from failure of this center in brainstem.

Thiamine Deficiency and Sympathetic – Parasympathetic Regulation

The hypothalamus is in the center of the brain computer and it presides over the ANS, as well as the endocrine (hormone) system. The ANS has two channels of communication known as sympathetic (governs action) and parasympathetic (governs the body mechanisms that can be performed when we are in a safe environment: e.g. bowel activity, sleep, etc.). When the ANS system is damaged, sometimes by genetic influence, but more commonly by poor diet (fuel), our adaptive ability is impaired. A marginal energy situation might become full blown by a stress factor. In this light, we can view vaccines and medications as stress factors. From false signal interpretation, we may feel cold in a warm environment, exhibiting “goose bumps on the skin”, or we may feel hot in a cold environment and experience profuse sweating. The overriding fatigue is an exhibition of cellular energy failure in brain perception.

Sometimes, it really is the simple, overlooked, elements that cause the most devastating consequences to human health. Thiamine deficiency is one of those elements.

To learn more about thiamine testing: Thiamine Deficiency Testing: Understanding the Labs.

We Need Your Help

More people than ever are reading Hormones Matter, a testament to the need for independent voices in health and medicine. We are not funded and accept limited advertising. Unlike many health sites, we don’t force you to purchase a subscription. We believe health information should be open to all. If you read Hormones Matter, like it, please help support it. Contribute now.

Yes, I would like to support Hormones Matter.

Photo by Robina Weermeijer on Unsplash.

This article was published originally in October 2013.

Rest in peace Derrick Lonsdale, May 2024.

Thiamine, Epigenetics, and the Tale of the Traveling Enzymes

by Chandler Marrs, PhD

Published on April 23, 2025

11.5K views

For some time now, we have been covering all the ways in which thiamine deficiency influences disease. The primary mechanisms are through the down regulation of mitochondrial enzymes critical for ATP production. The lack of thiamine impairs mitochondrial functioning significantly leading to complex, debilitating, chronic, and sometimes, deadly illnesses. With mitochondrial energy a requisite for cell functioning and survival it is easy to see how the diminishment of mitochondrial functioning would negatively impact health and how high-energy physiological systems like the nervous and cardiovascular systems might be particularly hard hit. More than just just derailing cell function, as if that wasn’t problematic enough, when mitochondrial energy production slows, the adaptive cascades that ensue include epigenetic modification, not only at the level of mitochondrial DNA (mtDNA), but also, at the level of gene expression from the cell nucleus or nDNA. This is a huge discovery with broad implications about health and disease. It means that all sorts of things considered innocuous, are directly influencing gene activation and deactivation by way of the mitochondria.

Epigenetics: How the Cells Adapt to the Environment

Epigenetic modification refers to the activation or deactivation of chromosomal gene expression absent mutation. These changes can be heritable and often are. Strictly speaking, epigenetics involves changes in methylation, histone modification and/or alterations in non-coding RNA that affect transcription. Epigenetics is the way our genome adapts to environmental circumstances and prepares our offspring to do the same. The majority of epigenetic work focuses on genomic changes. That is, those variables that affect gene expression from the cell nucleus or nDNA. There is a growing body of evidence, however, that mitochondrial DNA (mtDNA) are affected by epigenetic factors in much the same way as nDNA. In fact, given the mitochondria’s role in cell survival, one might suspect that mitochondria are more susceptible to environmental epigenetics, perhaps even the first responders and/or the initiators of chromosomal genetic changes.

Considering that nDNA accounts for over 90% of the proteins involved in mitochondrial functioning, how could damaged mitochondria, even functionally inefficient mitochondria, not affect gene expression in the cell’s nucleus? Though we tend to think of mitochondria as self-contained and discrete entities, black boxes of sorts, where stuff goes in and ATP magically comes out, this is not only not the case, it seems biologically illogical to think that way. So much of mitochondrial functioning is related to its environmental milieu. In fact, increasingly researchers are finding that the mitochondria are the center of the organismal universe, sensing and signaling danger, and effectively, regulating all adaptive responses, including epigenetic modification of the proteins encoded by the cell nucleus.

Beyond the strict definition of epigenetics, it seems to me that any factor that altered mitochondrial function, would eventually alter gene expression by any number of mechanisms, not just the direct ones. That is, because the mitochondria produce the energy required for cell survival, anything that derails their capacity to produce ATP, pharmaceutical and environmental chemicals, for example, should be considered, ipso facto, epigenetic modulators. Energy is a fundamental requirement for life. How could energy depletion not affect gene expression? It does, and now we know how.

Starve the Mitochondria, Alter the Genome

It turns out, when the mitochondria are starving and/or damaged the key enzyme complex that sits atop the entire energy production pathway and is critical for the production of the substrates involved directly (yes, I said directly) with gene expression, migrates from the mitochondria across the cell and into the cell’s nucleus where it then sets up shop and begins its work there. Sit with that for a minute. The entire enzyme complex decides that things are not working where it is, so it hitches a ride with some transporter proteins, several of them along the way, to find a more suitable home. The enzyme complex ‘knows’ that its functions are critical for survival and so it must move or die. What an incredible bit of adaptive capacity. A symbiosis, if you will.

To make matters even more interesting, the traveling enzyme complex just so happens to be the pyruvate dehydrogenase complex (PDC) and you guessed it, the PDC is highly, and I mean highly, thiamine dependent. But wait, there’s more. Several other enzymes involved in mitochondrial bioenergetics are also thiamine dependent. These include: alpha-ketoglutarate dehydrogenase (α- KGDH) in the tricarboxylic acid (TCA) or citric acid cycle, transketolase (TKT) within the pentose phosphate pathway (PPP), the branched chain alpha-keto acid dehydrogenase complex (BCKDC) involved in amino acid catabolism and, more recently, thiamine has be identified as a co-factor in fatty acid metabolism via an enzyme called 2-hydroxyacyl-CoA lyase (HACL1) in the peroxisomes (organelles that break down fatty acids before transporting them to the mitochondria). So thiamine deficiency is problematic. It not only causes dysfunction in the mitochondria, reducing bioenergetic capacity, but if severe enough and/or chronic, it alters the genome. And those changes are likely heritable. That is, your thiamine deficiency likely will affect your children’s ability to process thiamine.

Thiamine Deficiency and Gene Expression

Without sufficient thiamine, the PDC enzyme complex does not function well and because of its geographic position at the entry point into the citric acid cycle, when it is not working at capacity, everything below it eventually grinds to a halt resulting in severe neurological and neuromuscular deficits. Absent congenital PDC disorders, however, when it simply is inefficient or starved for its cofactors, metabolic disorders ensue because we cannot convert carbohydrates into ATP and the sugars that normally would be converted into energy, remain unmetabolized, floating around outside the cells and causing the whole cascade of effects that mark type 2 diabetes. When the PDC is inefficient, ATP levels wane and fatigue ensues. Systems that are highly energy dependent are hit the hardest. Think brain, heart, muscles, GI tract. When mitochondria are inefficient or damaged, reactive oxygen species (ROS) increase. Anti-oxidant capacity decreases and further damage to the PDC ensues. Inflammation increases, immune function decreases. Cell level hypoxia grows. Alternative energy pathways are activated, those that are endemic of cancer. Yes, cancer can be considered a metabolic disorder.

When the PDC is inefficient, mtDNA heteroplasmy, the balance between mutated mtDNA and healthy mtDNA grows with each mitogenic cycle. This, of course, further derails mitochondrial capacity (and increases the need for thiamine). Absent available resources, mitochondrial death cascades are initiated. And now, we know at some point in this disease and death spiral, when ATP diminishes and the litany of adaptive measures fail to maintain sufficient energy availability, the PDC up and leaves its mitochondrion and sets up shop in the cell nucleus, in what is presumably a last ditch effort to save its cell and the organism as a whole. What a remarkable bit of adaptive capacity.

The researchers, who discovered this, ruled out the possibility that the PDC enzyme complex was already in the cell nucleus. It wasn’t. It traveled by way of several transporter proteins. They also found that once in the nucleus, it began producing acetyl-coenzyme A (CoA). Acetyl-CoA is requisite for the acetylation and deacetylation of histones, post translational changes in DNA, but also lysine acetylation, which further affects metabolism – mitochondrial energy homeostasis. With insufficient acetyl-CoA and insufficient acetylation, DNA replication is aberrant. Moreover, without sufficient acetyl-CoA, acetylcholine synthesis, an incredibly important transmitter for nervous system functioning, diminishes.

A Constitutively Active Enzyme: What Could Possibly Go Wrong?

Even more interesting, the PDC in the cell nucleus appears to be constitutively active. Unlike in healthy mitochondria where checks and balances prevail, when the PDC travels to the nucleus it has no feedback control to temper its activity. The enzymes that normally shut down PDC production (pyruvate dehyrodgenase kinase) in the mitochondria, were not present in the cell nucleus, and thus, once the PDC was turned on, it stayed on. That means when the PDC translocates to the cell nucleus it operates independently much like a Warburg effect in cancer metabolism; one that fully supplants healthier metabolic pathways. Can you say tumorogenesis?

This research has enormous implications for everything from cancer to Alzheimer’s disease and everything in between that involves metabolic disturbances like diabetes and heart disease. Metabolism begins and ends with the mitochondria, at the PDC, and the PDC is highly dependent on thiamine. Every pharmaceutical and environmental chemical damages the mitochondria in some manner or another and that damage inevitably reduces ATP capacity. Some chemicals also deplete thiamine directly, thus downregulating the activity of the PDC and the other thiamine dependent enzymes. Even when these chemicals don’t deplete thiamine directly, the western diet is more often than not thiamine deficient, sometimes only marginally, others time quite significantly so with symptoms already expressed, but very rarely recognized. We have known that thiamine was critical for health and survival for some time. Now we have one more reason to tread carefully with lifestyles and exposures that deplete thiamine.

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More people than ever are reading Hormones Matter, a testament to the need for independent voices in health and medicine. We are not funded and accept limited advertising. Unlike many health sites, we don’t force you to purchase a subscription. We believe health information should be open to all. If you read Hormones Matter, like it, please help support it. Contribute now.

Yes, I would like to support Hormones Matter.

David Goodsell, CC BY 3.0, via Wikimedia Commons

This article was first published on April 25, 2017.

Thiamine Deficiency and Dependency Syndromes: Case Reports

by Derrick Lonsdale MD, FACN, CNS

Published on April 14, 2025

40.9K views

I have been studying thiamine metabolism since 1969 when I published the first case of thiamine dependency: Intermittent cerebellar ataxia associated with hyperpyruvic acidemia, hyperalaninemia, and hyperalaninuria. The case involved a 6-year old boy experiencing recurrent episodes of cerebellar ataxia (a brain disease resulting in complete loss of a sense of balance). These episodes, occurring intermittently, were naturally self-limiting without any treatment and were triggered by inoculation, mild head trauma, or a simple infection such as a cold. In other words, his episodes of ataxia were repeatedly initiated by an environmental factor. I have called each of these variable factors a “stressor”. Our studies showed that one of these stressors would unmask the true underlying latent thiamine dependency, falsely giving the impression that the stressor was the primary cause. This may be the principle of post vaccination disease in some cases. It may also be too easy to explain symptoms arising from trauma or infection as primary cause. These recurrent ataxic episodes were prevented from occurring by giving him mega-doses of a thiamine supplement.

Cerebellar Ataxia of Metabolic Origins?

When ataxia, as in this child, or other symptoms, occur intermittently, as they did in many other patients whom I would treat across my career, it is difficult to identify the true cause. The studies performed by neurologists, neurosurgeons and others inevitably would be normal, causing diagnostic confusion. In other patients with less serious symptoms, they are considered to be somehow feigned or of psychological origin. Symptoms that appear and disappear in a seemingly random manner and are not supported by conventional laboratory data are often explained this way. Please be aware that ataxia should never be regarded as psychosomatic. The point is that less serious symptoms that cause deviant behavior may not be recognized as biochemical changes in the brain.

With the present medical model, it is difficult to understand and accept that a stress factor can initiate the symptoms of a metabolically caused disease that has been relatively innocuous or silent until the stress is imposed. Let me give you another example.

Loss of Consciousness, Edema, Joint Pain: Rheumatic Disease or Metabolic Disorder

Since I was working at a multi-specialty clinic I was sitting having lunch with an ear, nose, throat (ENT) surgeon who knew of my interest in sudden death in infants (Treatment of threatened SIDS with megadose thiamine hydrochloride). He had been called to put in a tracheostomy to a middle-aged woman who had suddenly stopped breathing. Unlikely as it sounds, he suggested that I should go and look at the situation unofficially.

In the hierarchy of specialization, a pediatrician is not supposed to know anything about adult conditions, so I was not welcome. Because the internists who were taking care of her were rheumatologists, it was considered to be some kind of rheumatic disease, because of aches and pains in joints and limbs. She had had periods of unconsciousness over many years and her body was profoundly swollen, the hallmark of beriberi. Without going into details I was able to prove that this was indeed beriberi.

When I approached the rheumatologist who was her primary physician, I could not convince her of what appeared to her as too bizarre to contemplate. Notwithstanding, I had the cooperation with the nurses who followed my directions. When the patient was given injections of thiamine, she recovered consciousness and the gross body edema disappeared.

So fixed in the mind of many physicians is the concept that a vitamin related emergency simply does not occur, it was called “spontaneous remission” by my colleagues and “had nothing to do with vitamin therapy”. When I asked the rheumatologist whether we could conference the patient, she ignored the request. Well, this was not the end of the story.

Resolving One Deficiency Often Unmasks Another

After she started the injections of thiamine, with recovery of the nervous system, she began to develop a progressive anemia. It was considered by the internists to be internal bleeding and a thorough search produced only negative results. So ingrained is the negative attitude to vitamin therapy, I was even in fear that I might be blamed for causing the anemia. In the meantime, I took a specimen of urine and found a substance in the urine that suggested a deficiency of folic acid. Readers will remember that folic acid is a member of the B group of vitamins, as is thiamine. A blood test proved that she was indeed deficient in folic acid. When this vitamin was given to her, the anemia rapidly disappeared. This, believe it or not, still did not interest my colleagues.

She was discharged from the hospital, receiving supplements of thiamine and folic acid and her nervous system gradually improved. Some months later she developed a rash of a type that had been reported a few months previously as due to vitamin B12 deficiency. She was given an injection of vitamin B12 and over the next few days suffered slight fever and variable joint pains. These were symptoms with which she was familiar and had been responsible for the diagnosis of rheumatic disease. This sometimes happens temporarily with vitamin therapy, but often enough that I refer to it as “paradox”, meaning that things seem to be worse before they get better. Note that this paradox is not the same as side effects from a drug. The symptoms that cause a patient to see a doctor are temporarily exacerbated. With our present model the patient concludes that this is side effects from the vitamin(s) being used. I had to learn that paradox was the best sign that improvement would follow with persistence. She then continued on the thiamine, folic acid and vitamin B12.

The Role of Lifestyle and Diet Disease Expression – Oft Ignored Stressors

The fact that this woman was a chronic beer drinker and smoker had been ignored. They were, if you will, the “stressors” that were the dominant cause, perhaps impacting on genetic risk factors. The relationship between alcohol and thiamine deficiency is well known and so she had induced her own disease. Since there was a profound ignorance concerning vitamin deficiency diseases, the beriberi had been referred to by her internists as “rheumatic” in nature. This is because joint and limb pain, usually not recognized for what the pains represent, are often associated with compromised oxidative metabolism, either in the limb itself or in the brain where the pain is interpreted.

Defective oxidative metabolism caused in this patient’s case by thiamine deficiency, causes exaggerated brain perception. The brain induced a pain that gave the false impression that the disease originated in the joints and other parts of the body. Even if the origin of the pain is truly from a joint or muscle, defective oxidative metabolism in the brain will exaggerate the sense of pain perceived by the patient. Although this “phantom” pain is known as “hyperalgesia”, the mechanism is not well known as being due to compromised oxidation in the pain perception brain centers. Thiamine deficiency was responsible for the hyperalgesia experienced by the case of a patient with eosinophilic esophagitis that was posted recently on this website.

Beyond Thiamine: Multi-Nutrient Deficiencies

What interested me in the woman with beriberi was that folic acid deficiency was not revealed until her metabolism had been accelerated by the pharmacological use of thiamine. The folic acid deficiency then became clinically expressed as her metabolism “woke up”. It had been well known for some time that folic acid produced anemia would have to be treated with both folic acid and vitamin B12.

In the case of folic acid deficient Pernicious Anemia, if vitamin B12 was not given at the same time, the patient would develop a disease known as subacute combined degeneration of the spinal cord. Because I had forgotten this fact, I had neglected to give her vitamin B12 until it was finally expressed clinically in the form of a rash. Associating a skin rash with a vitamin deficiency is certainly not commonly accepted as a possible indicator of an underlying cause by physicians.

Vitamin Deficiency Versus Dependency

Returning to the case of the 6-year old boy discussed above, we learned over time that his health was dependent on high doses of thiamine to function. Believe it or not, this child required 600 mg of thiamine a day in order to prevent his episodes of illness. If he began to notice the beginning of an infection he would double the dose. The recommended daily allowance for thiamine is between one and 1.5 mg a day. Here, and in many other cases, huge doses of the vitamin are required in order to accomplish the physiologic effect. This represents what I call vitamin dependency.

Thiamine and magnesium, like many other vitamins, are known as cofactors to enzymes. An enzyme without its cofactor works inefficiently if it works at all. The “magic” of evolution has “invented” this cooperative action which is in itself under genetic control. In technical terms, the vitamin has to “bond” with the enzyme. If this bonding mechanism is genetically compromised, the concentration of the corresponding cofactor has to be increased enormously by supplementation in order to prevent the inevitable symptoms. You can see that this requires a clinical perspective tied to unusual biochemical knowledge. This is in complete contrast to what is usually regarded as vitamin deficiency, arising from insufficient concentrations in the diet.

What is perhaps not known sufficiently is that prolonged vitamin deficiency appears to affect this bonding mechanism. For example, it has long been known that to cure chronic beriberi, megadoses of thiamine are required for months. I have concluded that the megadoses of thiamine given by supplementation to a patient with long term symptoms arising from unrecognized deficiency appears to re-activate the inefficient enzyme. It is as though the enzyme has to be repeatedly exposed to megadoses of its cofactor to stimulate it and restore its lost function.

This may mean that even if the bonding mechanism is normal in chronic deficiency, enzyme function has simply decayed from lack of stimulation. This may explain why genetically determined dependency and long term dietary deficiency will produce the same clinical effect. The dosing of vitamins, if the clinical effects of deficiency are recognized, is not well understood in traditional western medicine. When insufficient doses are given and the symptoms fail to abate, the practitioner views it as evidence that supplements do not work.

Biochemical Diagnoses are Complex

I want the general public to begin to understand the principles that underlie the complexity of biochemical diagnosis. Perhaps a reader might find that a case like this is a reminder of a loved one whose illness was never understood after seeing many different specialists, all of whom were like the blind men and the elephant. Each was confined to his specialist status but none of them could see the overall big picture.

Reading these cases, you might easily come to the conclusion that they represent a rarity. Chronically unrecognized thiamine deficiency is common. Dependency is not uncommon. It is not as rare as is presently thought. Believe me, cases like these are surprisingly common and are responsible for a great deal of diagnostic confusion.

Vitamins are essential to consumption of oxygen in all life processes. To go against the principles of diet dictated by Mother Nature is a risk to life and limb that is not worth the derived pleasure. When limb pain is experienced without an obvious trauma, it is difficult to accept that it is because of inefficient use of oxidation in the brain, but that is exactly what we found.

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Marginally Insufficient Thiamine Intake and Oxalates

by Chandler Marrs, PhD

Published on April 9, 2025

50.1K views

Over the last few years, it has become increasingly apparent how important thiamine is to overall health. Thiamine (thiamin) or vitamin B1, sits atop the mitochondria at multiple entry points involved in the metabolism of foods into cellular energy (ATP). It is also critical for several enzymatic reactions within the mitochondria. We have illustrated repeatedly how thiamine deficiency leads to mitochondrial dysfunction, which in turn leads to complex multi-organ system illnesses characterized by chronic inflammation, disturbed immune function, altered steroidogenesis. Each of these is related to deficient mitochondrial energetics. When serious or chronic, thiamine deficiency leads to erratic autonomic function, now called dysautonomia, and a set of disease processes called beriberi.

Long before those symptoms emerge and absent severe deficiency, marginal thiamine status evokes subtle changes in metabolic function. Among these changes, enzymes that would normally metabolize certain foods fully and into useful substrates for other functions are downregulated, shifting the metabolic pathway towards more toxic end-products. The chemistry is complicated and we will go over it in a moment, but first I would like to propose a framework for understanding metabolism. For me, it is useful to imagine metabolism visually as giant maze of right and left turns; where wrong turns lead to dead ends and dead ends lead to the build up of endogenous toxins. Among the primary variables determining the route metabolism takes is enzyme nutrition.

Enzymes require nutrient cofactors to perform their metabolic tasks. When the appropriate nutrient co-factors are present in sufficient concentrations for the enzymes to operate fully, the food we eat is successfully metabolized into end-products that are useful for all manner of processes and cellular energy is produced. Even in the case of genetic aberrations that limit enzyme function endogenously, there is evidence that nutrient manipulation can overcome inadequate enzyme activity. When nutrient co-factors are in short-supply, however, resources are reallocated. Metabolism shifts directions, it takes a right turn when it should move left or vice versa. Different enzymes are activated and metabolism eventually reaches a dead end but not before potentially toxic, unused waste products build up. As these toxins build up, other systems become disrupted, inflammatory and immune responses are activated, demanding ever more energy to resolve. It is this energy spiral, I believe, that induces and maintains many of the illnesses we see today. This means that observing how one reacts to certain foods may point us to correctable nutrient deficiencies.

The Rise in Food Sensitivities

In recent years, I have become fascinated by the growing preponderance of food sensitivities and intolerances. It seems everyone has a problem with something. Given the current practices used in industrial food production, I suppose it is no wonder. We use a staggering number of chemicals to grow and process foods; chemicals that reduce the nutrient content of supposedly healthy foods, but also, present as toxicants that must be dealt with metabolically when ingested. The double hit of low nutrients/high toxicants is disastrous for metabolism. Throw in the generally high calorie content of the western diet and one has to wonder how our mitochondria function at all. And yet they do. Well, sort of. If we don’t count the exponential growth in chronic and seemingly intractable illnesses, but I digress. I believe that food, or lack of quality food, is top among the core contributors to modern illness and food sensitivities are among the key early warning signs of poor metabolism and by definition, faltering mitochondria.

Oxalate Problems

One of the more intriguing and troubling food intolerances that has become increasingly common is to the high oxalate foods. Oxalates are natural substances found in many healthy foods, especially dark leafy greens like spinach, that bind calcium and other minerals, and when left unmetabolized, can form crystals leading to kidney stones. Approximately 10% of men and 7% of women experience at least one episode of kidney stones across the lifetime. Beyond the kidney stone, oxalate intolerance is linked to wide range of chronic health conditions largely due to the build up oxalic acid which may or may not bind calcium, but causes problems nevertheless. Poor oxalate metabolism disrupts gut health, shifting the microbiome unfavorably causing dysbiosis, damages the mitochondria and induces system wide oxidative stress, inflammation and immune reactivity. Problems with oxalate metabolism have been found in individuals with autism, multiple sclerosis, arthritis, and fibromyalgia to name but a few. A common and usually somewhat successful remedy is to avoid the consumption of high oxalate foods. Below are some of the more common high oxalates.

Figure 1. High Oxalate Foods

Absent genetic aberrations leading to poor oxalate handling, I cannot help but wondering if the avoidance diet is the correct response, especially permanently. Certainly, it would help short term, and there may be foods that result in oxalate accumulation that could or should be avoided long term, but an across-the-board and permanent avoidance of most oxalate producing foods seems problematic nutritionally. If we consider that many who suffer from oxalate issues may also be sensitive to other foods, the avoidance approach could limit dietary options considerably. What if we are approaching this issue incorrectly? My gut tells me, and research seems to back it up, that barring genetic issues with oxalate metabolism, the dietary component is not simply one of excess oxalate consumption. It is a problem with inadequate nutrient consumption in the face of excessive non-nutrient foods – e.g. it is a problem with the modern western diet in its entirety.

Other Dietary Contributors to Oxalate Buildup: Processed Foods

If we dig into the oxalate issue a little more, we see that foods resulting in excess oxalate storage are not necessarily limited to whole foods listed above in Figure 1. A number of foods classified as high oxalate, are simply processed food products, high in carbohydrates, trans fats and low in nutrients. Below is a graph of some of the higher oxalate foods as compiled by the University of Chicago via Harvard’s School of Public Health. Notice, how processed foods make this list. Sure, their oxalate status is significantly lower than other foods, but consider what portion of the average western diet these products comprise. Click the links above to see a more complete listing foods that result in high oxalate accumulation. When you search through those lists (especially, the one from the University of Chicago), it becomes apparent that virtually all processed foods can result in oxalate problems.

Figure 2. Oxalate Content in Common Foods

food-oxalate-graph

One could argue that oxalate buildup involves shifts in the metabolic pathway that are directly related to nutrient deficiencies and those nutrient deficiencies emerge from the consumption of the modern diet. Processed carbohydrates, for example, in the presence of thiamine deficiency, are metabolized quite differently than when thiamine is present, with the former resulting in oxalate build up. Since a diet high in processed carbohydrates is one of the leading causes of thiamine deficiency in the first place, this begs the question, is the issue really oxalates or a sort of high calorie malnutrition resulting in thiamine deficiency, where oxalate accumulation is just a side-effect. Similarly, when thiamine is absent, fatty acid metabolism can go awry, making highly processed, high carbohydrate, high fat foods damaging on two fronts.

Finally, there are many other foods that can lead to high oxalate production in the presence of low thiamine including: beer, wine, tea, coffee, yogurt, bread, rice, soybean paste, soy sauce, and oil, along with foods that have been fermented, roasted, baked, or fried. And just like high carbohydrate diets can lead to thiamine deficiency, as nature would have it, all alcoholic drinks, coffee, and tea decrease thiamine uptake thereby both creating and exacerbating the thiamine deficiency that leads to oxalate accumulation. It could be that problems with oxalates is simply the early sign of thiamine deficiency and it may very well be a protective mechanism of sorts, a metabolic diversion, albeit an unhealthy one, to forestall the other issues associated with insufficient thiamine intake.

I should also mention that oxalate problems may not be solely related to diet. Inasmuch as all pharmaceuticals damage the mitochondria and either decrease thiamine directly or increase the demand for the need for thiamine indirectly, regular use of pharmaceuticals may also contribute to the problem. Similarly, a number of environmental exposures increase glyoxal (a precursor to oxalate build up in the face of low thiamine), including: cigarette smoke, smoke from residential log fires, vehicle exhaust, smog, fog, and some household cleaning products.

Is Thiamine Really the Problem?

It may be. The chemistry is complicated and detailed below, but basically, marginal thiamine status, prevents the proper metabolism of certain foods leading to the build up of toxins while simultaneously crippling the natural detox pathways. The combination of increased toxins and decreased detox ability leads to all sorts of damage and illness, high oxidative stress, and as illustrated by the graphic below, can lead to cancer (to be discussed in a subsequent article). Thiamine prevents this. A paper published in 2005, (from which Figure 3., is taken) details just how many mechanisms that lead to oxalate accumulation are initiated by low thiamine.

Figure 3. How Low Thiamine Leads to Elevated Glyoxal and Cancer

glyoxal pathways

The specifics involve a metabolic diversion that leads ‘food’ metabolites down what is called the glyoxal pathway, the pathway responsible for oxalates. Each of the red ‘X’s’ indicates an impaired thiamine dependent enzyme.

With Marginal Thiamine

Elevated glyoxal and methylglyoxal
- Diminished activity of thiamine dependent enzymes (transketolase, pyruvate dehydrogenase, branched chain ketoacid dehydrogenase, and a-ketoglutarate)
  - Low transketolase = low NADPH
  - Low NADPH = low glutathione (the primary detoxification agent in the body; glutathione also requires vitamin C)
    - Low glutathione = poor detoxification of glyoxal and methylglyoxal = increased carcinogenic protein adducts
- High Oxalate Foods
  - Glyoxal >glyoxalate > oxalates
Diminished pyridoxal kinase (PK) activity*
- *This is not discussed in the aforementioned paper, but should be included. PK is the enzyme that converts the inactive form of vitamin B6 (pyridoxine 5-phosphate) into its active form, pyridoxal 5-phosphate (P5P). Low P5P prevents glyoxalate from being converted back into glycine, leading to high oxalates. Many mistakenly assume that low vitamin B6 is responsible for high oxalates. While that is possible, it is also possible, and often more likely, that low thiamine is responsible.

With Sufficient Thiamine

Thiamine dependent enzymes work appropriately
- Sufficient transketolase activity = sufficient NADPH
Glyoxal and methylglyoxal are metabolized into other substrates and/or excess is detoxified
- Sufficient NADPH = sufficient glutathione
Glyoxalate is converted to a-hydroxy-b-ketoadipate or glycine and not oxalate
- Alanine glyoxylate amino transferase (AGT), the enzyme required to convert glyoxalate into to glycine instead of oxalate has sufficient activated vitamin B6.

This is not to say that there are not other vitamin and mineral deficiencies also associated with hyperoxaluria, there are. Research has shown that low magnesium (a requisite co-factor in many of same enzymes as thiamine), along with low vitamin A, in addition to the low vitamin B6, mentioned above play a role. Vitamin E may also be involved.

Take Home

The majority of modern illnesses are the result of poor diet and environmental exposures directly, cumulatively, and generationally. Over the span of a few short generations, we have forgotten that food is fuel and that good, clean, unprocessed food is required for health. The allure of processed foods and cheap agriculture through chemistry, has left much of the population starved of nutrients, while simultaneously bearing a high toxicant load. The result is all sorts of metabolic disturbances which may manifest as food insensitivities and intolerances. It is interesting to note that the metabolic changes involved in oxalate buildup do not require what we would consider a full-scale thiamine deficiency, but rather, a sort of thiamine insufficiency initiated by marginal thiamine intake, something that is likely common across populations.

A less complicated overview of the low thiamine > high oxalate connection can be viewed below.

Is Your Body Producing too much Oxalate?

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More people than ever are reading Hormones Matter, a testament to the need for independent voices in health and medicine. We are not funded and accept limited advertising. Unlike many health sites, we don’t force you to purchase a subscription. We believe health information should be open to all. If you read Hormones Matter, like it, please help support it. Contribute now.

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Image: Scanning electron micrograph of the surface of a kidney stone showing tetragonal crystals of weddellite (calcium oxalate dihydrate) emerging from the amorphous central part of the stone; the horizontal length of the picture represents 0.5 mm of the figured original. Image credit: Kempf EK – Own work, CC BY-SA 3.0.

This article was published originally on August 15, 2019.

Introducing a New and Improved Thiamine Testing Platform

by Mahmood Bilal PhD, DABCC, FADLM, TS(ABB)

Published on March 20, 2025

7.1K views

Introduction

It is my great to pleasure to introduce a new thiamine testing platform, the Erythrocyte Transketolase Activity Coefficient (ETKAC), offered by the Clinical Immunology Laboratory, in North Chicago, IL. ETKAC is a functional enzymatic test designed to evaluate the activity of the thiamine-dependent enzyme, erythrocyte transketolase, both in its resting/uninfluenced and activated state. Compared to other available thiamine testing assays, the ETKAC provides functional assessment of in-cell activated thiamine and evaluates potential abnormalities in thiamine-dependent enzymes. The test is currently available via physician request, but we hope to provide more direct access in the future.

What Is Thiamine Deficiency and Why We Need Better Testing

Thiamine (vitamin B1) is the precursor to the coenzyme thiamine pyrophosphate (TPP), also termed thiamine diphosphate (TDP/ThDP). It is an essential B vitamin in humans that is required for carbohydrate, fatty acid, and even protein metabolism. As such, it is critical for health and plays an important role in nerve function.

TPP, the bioactive component of thiamine, drives enzymes found in multiple metabolic pathways that include the pentose phosphate pathway, citric acid cycle, and glycolysis. In this way, thiamine contributes to the structure of the nervous system by inducing energy production (ATP), and synthesis of vital compounds such as lipids and acetylcholine. Without thiamine, mitochondrial respiration is suppressed and ATP capacity wanes.

Frank or severe deficiencies in thiamine result in Beriberi and Wernicke-Korsakoff Syndrome. These syndromes are well understood and, in some cases, can be attributed to alcoholism and malnutrition. Despite being well understood, frank deficiency may be missed clinically, especially in non-alcoholic and presumably well-nourished populations, but also in the early stages of the deficiency when symptoms may be attributed to other common disease processes. Some of the patient populations with underlying thiamine deficiency who may benefit from thiamine testing include those diagnosed or suspected of chronic fatigue syndrome, fibromyalgia, individuals who are diabetic, or who are experiencing neurocognitive or neuromuscular symptoms. Pregnant women should also be tested for deficiency, especially when hyperemesis gravidarum or pre-eclampsia are present. More information on patient populations affected by insufficient thiamine can be found here.

Unfortunately, traditional testing may miss subclinical, functional, and genetically-induced thiamine deficiencies. Plasma testing, for example, is highly susceptible to dietary fluctuations in thiamine. If an individual has recently consumed thiamine-rich foods, the test may indicate thiamine sufficiency, when in reality, the individual is truly deficient. Likewise, if the individual is deficient in magnesium, which is required to activate thiamine (phosphorylate free thiamine into the bioactive thiamine pyrophosphate or TPP) and/or the individual has a genetic defect that diminishes the activity of any portion of the thiamine metabolic pathway, plasma thiamine tests will appear normal even though the individual is deficient. With magnesium deficiency, free thiamine may be sufficient, but bioactive thiamine will be deficient. Similarly, with thiamine-related genetic variants, free thiamine and perhaps even TPP will be within range, but the ability to use thiamine effectively will be impaired.

Whole blood TPP testing, although more accurate than plasma-based assessment and not susceptible to fluctuations in dietary intake, is still problematic in some cases. It is susceptible to supplemental intake [Tietz Textbook of Clinical Chemistry and Molecular Diagnostics, pg 661], which means that if the individual is supplementing with thiamine either alone or in a daily multi-vitamin, and/or is on a thiamine-repletion protocol due to a recognized deficiency, the testing may falsely indicate that he/she is no longer deficient, despite symptoms to the contrary. Since whole blood TPP assess the bioactive form of thiamine, TPP, it is more sensitive to some functional deficiencies. Unfortunately, it is not sensitive to whether or not the individual has the capacity to use that TPP because of genetic abnormalities or chronic health issues.

Measuring Enzyme Activity to Assess Nutrient Status

Rather than measure the nutrient in circulation, a more accurate form of testing involves the measurement of enzyme activity in erythrocytes or red blood cells. Since enzymes depend upon specific vitamins for functionality, when we measure the enzyme activity both in its basal state (resting/uninfluenced) and in response to the nutrient, we can reliably assess nutrient status. This will more accurately portray tissue concentrations than circulating concentrations. In that regard, enzyme activity tests are considered functional assessments of nutrient status.

Enzyme activity tests have been used for decades to assess a number vitamins and minerals. For example, glutathione reductase activity is used to measure riboflavin (vitamin B2) status. Similarly, the enzyme transaminase is used to measure vitamin B6 activity. Minerals like zinc and magnesium are best evaluated intracellularly instead of just measuring circulating levels.

To measure thiamine, the erythrocyte transketolase test is used. It was initially developed around 1962 and further improved and utilized through the 1970s. However, as time passed, the assay fell out of use in favor of the quicker and more cost effective, though less clinically sensitive, plasma and whole blood measures.

Recognizing the increased incidence of modern thiamine deficiency and a need for more sensitive testing, the scientists at the Nutritional Biomarker Laboratory (NBL), in the University of Cambridge, have developed an improved erythrocyte transketolase activity coefficient, or EKTAC, test. A slightly modified form of the NBL assay has been validated and applied at the lab in which I co-direct, Clinical Immunology Laboratory (CIL), in North Chicago, IL.

Evaluation of Thiamine via Erythrocyte Transketolase Activity

The transketolase enzyme is a TPP-dependent enzyme that can be found in the cytoplasm of a variety of tissues including blood cells and the liver. The Erythrocyte Transketolase Activity Coefficient (ETKAC) measures tissue level TPP as a function of transketolase ratio with and without the presence of exogenous TPP. That is, enzyme activity is assessed in its basal state and after TPP is added. If enzyme activity increases in the presence of TPP, it indicates deficiency. How much enzyme activity increases tells us how bad the deficiency is. Table 1. below shows the cutoff values between sufficiency and deficiency. The ETKAC range is well established in the literature and by the consensus of the clinical chemistry associations (AACC/ADLM).

Table 1. ETKAC reference ranges.

Thiamine Status	ETKAC
Sufficiency	<1.15 (less than 15% increase)
Insufficiency – Moderate Risk of Deficiency)	1.15-1.25 (15-25% increase)
High Risk of Deficiency	>1.25 (more than 25% increase)

When a Normal Transketolase Test May Not Be Normal

While the measurement of the transketolase activity in response to thiamine is among the most sensitive and specific tests of thiamine deficiency at the tissue level and its results tell us whether the individual is able to use circulating thiamine effectively, there are caveats. There are instances where transketolase activity in response to thiamine will appear normal or near normal (ETKAC values close to 1.0), but clinical symptoms and basal activity of the enzyme suggest problems with thiamine. This is because enzyme kinetics have been altered either genetically or environmentally. Some examples of conditions that alter enzyme kinetics include:

Genetic mutations: Some mutations in the transketolase enzyme cause a lower affinity of the enzyme to TPP. Here, the affected individual will show falsely normal ETKAC but low basal activity (i.e. without addition of exogenous TPP). In this case, the clinician can use this information to manage these individuals and potentially embark on genetic testing, when indicated by paying closer attention to enzyme basal activity.
Reduced transketolase levels. Individuals with chronic low levels of thiamine can undergo reduction of transketolase levels. This may show up as normal ETKAC but low basal activity. This effect seems to correct upon repletion of thiamine. In this case, an individual will have a normal ETKAC (close to 1.0) that eventually increases as transketolase enzyme levels increase; thus the deficiency is unmasked. This happens because of the increased expression of apoenzyme (non-thiamine bound enzyme) without concomitant increases of sufficient thiamine concentrations. After this, as the patient is more replete with thiamine, ETKAC corrects back to true normal levels near 1.0.
Increased ETKAC. Some patients with bronchial and breast carcinomas may have falsely elevated ETKAC. It is thought that this is likely due to conversion issues from thiamine to its TPP forms (active co-enzyme). Use of basal activity parameter in this case will assist in excluding the possibility of aberrant enzyme expression.
Additional nutrient deficiencies. Other nutrient deficiencies may affect total enzyme levels. For example, Vitamin D has been shown to increase the expression of transketolase by close to 4 fold (400%) in some in vitro studies. Similarly, if zinc or other gene expression factors are needed for transketolase transcription, then the same effect from the above point would occur until these factors are first addressed.
Clinical conditions and medications. There are known clinical conditions (e.g. liver disease, uremic neuropath, gastrointestinal dysfunction, polyneuritis, diabetes), and drugs that can reduce the levels of the apoenzyme.

It is for these conditions and potentially others, that assessing and reporting the basal activity of the enzyme, along with its activation quotient is useful.

How to Interpret Basal Activity Results

Although the cut-offs for basal activity are not as clearly understood as those for the ETKAC test, a value of 0.59 U/gHb or less has been shown to indicate thiamine deficiency across different patient populations. The Clinical Immunology Laboratory group has recently confirmed the lower limit of 0.59 U/gHb, and established an upper normal limit of 1.00 U/gHb.

Table 2. Proposed ranges for ETK basal activity tests.

ETK Basal Activity
Lower Cut-off	0.59 U/gHb
Upper Cut-off	1.00 U/gHb
Clinically Verified Cut-off for Thiamine Deficiency given Normal Enzyme Levels	<0.59 U/gHb

Conclusion

Thiamine, in its active form TPP, functions as a rate-limiting co-enzyme in multiple pathways related to carbohydrate and energy metabolism. Deficiency of thiamine results in a host of seemingly unconnected symptoms that range in severity depending on the degree and duration of deficiency. It is not uncommon for frank and subclinical thiamine deficiency to be missed due to the cluster of seemingly unconnected symptoms, but also because of unavailability of sensitive and accurate testing. The ETKAC assay has an advantage to other thiamine assays due to it being a functional enzymatic test that can detect transketolase abnormalities, as well as thiamine status, as discussed above. In contrast, directly measuring plasma thiamine or whole blood TPP can lead to false normal results or miss a functional deficiency, respectively.

The ETKAC and Basal Activity assays have not been readily available in the United States for clinical testing until now. The Clinical Immunology group in North Chicago, a high-complexity CLIA-approved laboratory, has recently validated an affordable, and easy to order ETKAC assay. The test currently requires ordering through a physician; however the laboratory is planning on providing a direct-to-consumer service in the near future. CIL’s ETKAC assay provides both quotient and Basal Activity parameters in order to give patients and doctors the results they need for appropriate treatment. More information about the test, the requisition and sample shipping instructions can be accessed through CIL’s webpage. CIL can be contacted for questions regarding ETKAC ordering and/or interpretation. More information about ETKAC can be found on the laboratory’s website.

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Breathing Easy With Thiamine Pyrophosphate

by John Rybicki

Published on March 19, 2025

13.7K views

This is a strange and somewhat disgusting story about how a few B vitamins have worked better than a wide range of antifungals for chronic diarrhea and a long list of other symptoms that developed over time. In addition to chronic diarrhea, air hunger/difficulty breathing, foot drop, other classic symptoms of thiamine deficiency were present but not recognized by physicians. I discovered and have begun correcting my thiamine deficiency on my own with some success. Hopefully, the reader will see some unique solutions in the account, as I’ve had very significant degrees of success with the various treatments in the attempt to overcome this condition. For anyone else who thinks there is a better way, I’m all ears in the comment section. I’m not recommending anyone try what I did, I’m just providing an account of my situation and what I regard as some success.

Raw Veganism and My Slide Into Poor Health

When I was in college I read a recommended book called “fit for life.” It recommended a radical shift to all raw veganism. It advocated dropping meat for cashews, addressing concerns for protein adequacy with quotes such as “and if (as a result) your fingernails fall out, they will grow back in even better.” I was extremely healthy, athletic, and had everything to lose, and I did lose everything following that advice. Mind you, I wasn’t doing it to spare the animals, I just thought I’d have some crazy edge on being healthy.

At some point while on this diet, I developed chronic diarrhea. Maybe some of those fantastic raw veggies were contaminated or maybe my immune system was compromised from other possible resulting nutrient deficiencies. Whatever the reason, I was stubborn and foolishly didn’t take the obvious net result of that lifestyle choice into consideration and I got used to living with severe diarrhea. By the time I had shifted gears and started getting things like salt, heme iron, complete protein, etc., I discovered that the symptoms remained.

At the height of my illness, I would have to run to the bathroom seven times a day. I’ve had plenty of jobs where that causes a lot of problems. I finally went to the doctor because it was so bad. My stools were bright yellow, so they were submitted for a stool pathogen test. It came up negative. He made an appointment for me to see a specialist in 6 months at the earliest. I was desperate, but I took the 6 months to wait and did not try and fix the problem myself. Maybe that was a mistake, but then again, I was never loaded up with antibiotics on a whim, so who knows maybe it was a blessing.

The Progression of Thiamine Deficiency Symptoms

Diarrhea and discolored stools began 20 years ago when I began the raw vegan diet. I was on this diet for a little over two years, before I changed course and began eating meat again. Since starting the raw vegan diet, and over the course of time, either more symptoms developed, or I just became more aware of them. The symptoms included breathing difficulty or air hunger, seemingly less sweat, and very frequent urination at times. In addition, I seemed to get cold easily despite having very high concentrations of the thyroid hormone triiodothyronine (T3) on lab tests. I also have bleeding gums, very sore soles of my feel (it is almost impossible to walk on a beach covered in seashells), significant loss of visual acuity in my left eye, a pronounced sense of difficulty keeping my eyes straight when tired, and an occasional sense that my feet are dragging. My foot would occasionally drag on the ground as if I had neglected to move it properly. I feel that I have a greater sense of the right side of my body over the left. During this time, I also noticed a reduction in earwax, particularly in my left ear, a reduction in fingernail growth, at least compared to when I was in college, and I sense a dullness where either my spleen, pancreas, or stomach is. My skin was dryer, and no longer oily. Often, I would have dandruff. For a long time, I could get dizzy upon standing. Also, I realized the constant body aches I felt were always present and not the result of delayed onset muscle soreness from my regular training. I was tired all the time. People would tell me it’s healthy to sleep if I was tired, but I found I felt just as bad sleeping 12 hours as I did after sleeping 4. I could sleep 17 hours, get up to eat, and go back to sleep. It was ridiculous, not to mention I had to economically survive, so instead of sleeping all day I began working 2 and 3 jobs at a time and resolved to spend the money experimenting on supplements.

Discovering Thiamine Deficiency

In addition to the stool test for pathogens that came up negative, I got a Spectracell test to assess my vitamin status. I was beginning to believe that nutrient deficiency was involved in my illness. After all, two years of a raw vegan diet, I lacked a number of critical B vitamins. I chose a Spectracell test, as opposed to a standard blood test because it is supposed to be more accurate. The makers of Spectracell argue that standard nutrient blood tests are inaccurate because they only show what’s in your blood at the moment, whereas the Spectracell method feeds nutrients to a culture of your white blood cells and extracts nutrients one at a time. If the culture dies too early from withdrawing a nutrient, they say that you need that nutrient. My test said I needed thiamine and vitamin B5. I don’t know if the usual vegetarian deficiencies were present at any time, because I had long since thrown supplements such as methyl folate, methylcobalamin, and Albion iron in a bid to resolve the problem, none of which had any effect after extended use. My testosterone, as of 2 years ago, was at 650 ng/dL. Every blood sugar test I take at the supermarket, says I’m in the normal range, but I exercise regularly. Supermarket blood pressure readings are never high, always in the low to normal range.

Successes, Failures, and Odd Results

If you managed to make it through the symptoms section, this part should be a relief as I’ve had a lot of success, some of which helped but had to be discontinued for one reason or another. That said, I’m not advocating anything I tried here, and people should discuss things with their open-minded health professionals before trying anything.

Antifungals and Herbs

Some herbal measures of note were undecanoic acid. This worked for the breathing but was intolerable to the GI tract. Tudca, and a particular standardized artichoke extract normalized stool color, helped tremendously with breathing, helped with energy but caused tremendously unbearable diarrhea. Turpentine mixed with olive oil taken with meals helped with breathing a little but reduced my energy and worsened diarrhea.

At one point, I took a black-market antifungal after I read how it acted on the cholesterol portion of a fungal infection and didn’t pose a threat to the healthy gut biome (if I had any left.) It helped a lot on the digestion, only as long as I took it. It didn’t help with the breathing but slowed the bowels. My stools were better formed, but for some reason, the last portion of them was still yellow. I took a meningitis dosage of fluconazole for 8 weeks and a few days after stopping it, the digestive symptoms totally returned. I tried another cycle some months later and stopped after a few weeks when it didn’t work anymore.

Probiotics

Mega-dosing probiotics helped a little. There is a site that sells powder with doses of 400 billion (compared to the 1-60 billion in stores). Acidophilus helped the most, but also aggravated the breathing problem severely. Other strains had no negative effect on my breathing. An example of a probiotic that had a semi-stabilizing effect on my digestion would be acidophilus at 1600 billion CFU’s/day. Unfortunately, it became extremely difficult to breathe when taking it. Not sure if it is the d-lactate content or the fact that some strains are histamine producers and others are histamine degraders. An example of a probiotic that didn’t cause breathing difficulty at any dose would be l-Plantarum. The manufacturer who sells these bulk probiotics describes acidophilus as a strain that produces d-lactate, and as I never developed air hunger from, say, a histamine-producing strain like thermophilus (although thermophilus never improved my digestion). I’m more inclined to think the issue is one of d-lactate and not about histamine. That said, below is an interesting chart from the book “Fix your Gut” by John W. Brisson.

histamine modulators — Histamine modulators and degraders from: Fix Your Gut by John W. Brisson.

Probiotics stopped me from running to the bathroom several times a day, even after discontinuing them, but they weren’t a fix. I don’t take them anymore.

Digestive Enzymes

One of the biggest things to help was the digestive enzymes that I took but it took some trial and error to figure out which ones worked best and at what dose. When I took too much or the wrong ones, it worsened my GI symptoms. I tried a very high-dose amylase pill (4 x 200mg per meal) and then incorporated the full dose of lipase from the same brand. I realized that there was definitely a lack of digestive enzymes, but that I reacted poorly to protease, which is included in most enzyme products. I can’t underemphasize how helpful taking enzymes in high doses without protease has been. I’ve tried to incorporate protease on several occasions. It is available in a 400k potency strength down to around a 50k potency. After reading the success of one reviewer on Amazon, I tried to power through the bad symptoms caused by several high potency proteases, because I believed it would be effective against infection and probably a premier defense against pathogens in the bowels, but it always resulted in diarrhea, lots of slime, and eventually, I would start to see specks of blood.

Strangely, at a lower dose of protease, the outer edge of my thumb and index finger would dry up. It’s a weird reaction considering all kinds of people can take a lot of proteases without any issues. For an extended period of time, I backed down to the one brand that has 50k potency, which I can tolerate somewhat, although it caused a rushed bowel sensation. Ironically, the one I’m happiest with is the strongest one I’ve taken, as it doesn’t seem to cause any of the side effects. The problem with tolerating a protease might be like what the protease-producing fungi were fed to produce protease in response to. I don’t believe trace elements of fungus are causing a problem in widely circulated brands in my case, as I can tolerate fungal lipase and amylase with no problems, but a probiotic protease cultured to digest wheat and milk proteins caused big problems for me. The high potency brand of protease I’m taking is tasteless, reduces bloating, and unlike the other proteases I’ve taken, it helps digestion, particularly with stool formation.

Navigating Nutrient Repletion

I became more interested in thiamine when I took a supplement called N02, which was a bodybuilding supplement consisting of a large dose of arginine that resulted in more vasodilation and more carbohydrates going toward glycogen. It provided a very pronounced benefit for me in terms of muscle-pump/glycogen storage, but the label said: “not for those who are thiamine deficient.” While I wanted to enjoy the benefits of the supplement, or now something I like better such as citrulline peptides or a 20-gram dose of beet powder, it made me unusually sleepier, and it caused extreme dryness on the left side of my neck every time. I wondered if I had this unusual reaction because I was low in thiamine. I now attribute the complications I noticed taking “pump” products to be the result of improved circulation causing an increase of infection into my bloodstream, as the problem is greatly reduced by the high potency protease I’m taking. I had tried thiamine several times, but in pill form at 100mg doses, which may not have been enough. I began looking for a good coenzyme thiamine powder, which I found. At that time, I also found acetyl coenzyme A powder at $2000/kilo -seriously. I bought them both.

I decided to only use coenzymated B vitamins – vitamins that are in their active form used by the enzyme – after reading this study on PubMed: The vitamin B6 paradox: Supplementation with high concentrations of pyridoxine leads to decreased vitamin B6 function – PubMed (nih.gov)

Vitamin B6 is a water-soluble vitamin that functions as a coenzyme in many reactions involved in amino acid, carbohydrates and lipid metabolism. Since 2014, >50 cases of sensory neuronal pain due to vitamin B6 supplementation were reported. Up to now, the mechanism of this toxicity is enigmatic and the contribution of the various B6 vitamers to this toxicity is largely unknown. In the present study, the neurotoxicity of the different forms of vitamin B6 is tested on SHSY5Y and CaCo-2 cells. Cells were exposed to pyridoxine, pyridoxamine, pyridoxal, pyridoxal-5-phosphate or pyridoxamine-5-phosphate for 24h, after which cell viability was measured using the MTT assay. The expression of Bax and caspase-8 was tested after the 24h exposure. The effect of the vitamers on two pyridoxal-5-phosphate dependent enzymes was also tested. Pyridoxine induced cell death in a concentration-dependent way in SHSY5Y cells. The other vitamers did not affect cell viability. Pyridoxine significantly increased the expression of Bax and caspase-8. Moreover, both pyridoxal-5-phosphate dependent enzymes were inhibited by pyridoxine. In conclusion, the present study indicates that the neuropathy observed after taking a relatively high dose of vitamin B6 supplements is due to pyridoxine. The inactive form pyridoxine competitively inhibits the active pyridoxal-5′-phosphate. Consequently, symptoms of vitamin B6 supplementation are similar to those of vitamin B6 deficiency.

I honestly don’t know if complications with non-coenzymated B6 occur similarly with other non-coenzymated b vitamins. With B1, I know that we do have extracellular coenzymated thiamine circulating in our blood. So-called coenzymated B complex supplements contain an unknown mix of coenzymated B’s with a majority of those same B vitamins in their non-coenzymated forms. Some B vitamins are never, or rarely, sold purely in their coenzymated forms, such as with thiamine and B5. Thiamine pyrophosphate bulk powder is hard to get. When someone writes about how they tried thiamine pyrophosphate and it didn’t help, I’m skeptical because it sells in tiny doses and I imagine people rarely give it a fair shake in large dosing protocols. Nobody sells coenzyme A, not even a brand ironically named “Coenzyme A Technologies” which just sells a precursor pantetheine in a very small amount.

Adding Acetyl-Coenzyme A, Thiamine, and Other B Vitamins

Initially, I worked with acetyl-coenzyme A. I ended up taking an estimated 600mg transdermally several times throughout the day with great success. To do this, I would splash some water on a thin-skinned area such as my shin or forearm and pour the powder onto the wet area before rubbing it in. There is a trick to make sure that there isn’t too much water being used and to also make sure the dose doesn’t splash everywhere. I would follow that with a DMSO cream. For those of you who don’t know, DMSO supposedly drives nutrients through your skin better. There are products that claim 99% absorption when DMSO is added, whereas without it the area would eventually lose the ability to keep absorbing a targeted nutrient after a few days, and it would just evaporate. DMSO smells horrible, so much so that this procedure isn’t possible unless you use the brand that has mixed it with a rose scent, which doesn’t smell bad at all. This basically resolved the exhaustion problem I have, particularly with regards to wakefulness/motivation.

Typically, I wake up more tired than when I went to sleep, but I have to work out at 7 am. I rub this into my skin and within 20 minutes I’m totally awake. It’s not a stimulant feeling, it’s just that suddenly sleep isn’t an option and attempting to sleep becomes annoying. I’ve also benefited from this during what may have been a thiamine paradox reaction, which in my case manifested as extreme tiredness and a definite drop in mood. It has taken 1-2 doses of acetyl coenzyme A about 1 hour apart to climb out of that, which otherwise could have easily lasted 4 hours. I can’t speak as to whether this overcomes normal tiredness, as again I have otherwise abnormally extreme tiredness. Unlike caffeine though, acetyl coenzyme A is a big part of the Krebs cycle, and niacin is too inflammatory for me; even niacinamide causes my nose to get very runny and I just don’t feel like inducing a histamine reaction is a good idea. Acetyl coenzyme A gets around that. Also, I remember a book called the Ultimate Healing Guide by Donald Lepore who was administering 9 grams of B5 a day in some cases, which always made me question how effective calcium pantothenate or pantethine is. That said, I can see why people don’t sell Acetyl coenzyme A. Long story short, it has to be sealed and at the very least refrigerated.

I also began using thiamine pyrophosphate powder. I take this transdermally as well. It has profoundly improved my breathing and given me a lot more oil or moisture to my skin. I’ve noticed sporadic increases in saliva, which I regard as healthy given that I produced a lot when I was a healthy kid. I’ve noticed my workouts have improved as well. I lift weights and my sets are a lot closer together now and I have more of a muscle-pump/glycogen storage during my workout which buffers the unpleasantry of moving all that heavyweight around. I’m taking approximately 600mg 4 times a day following meals and protein shakes. I don’t take it on an empty stomach. I believe a higher dose would further improve saliva production and breathing and I am presently taking it slow getting to that higher dose.

I noticed I don’t have improved breathing if I stop taking the high potency protease and interestingly, my breathing is terrible if I take the protease without the thiamine. I’m speculating that the protease is having a huge antipathogenic effect, which may reduce hydrogen sulfide gas and possibly compromise the thiamine I’m taking. Another possibility I’ve considered is that the protease causes enough of a reduction in the pathogens that the thiamine effects can be observed and are otherwise drowned out by an overwhelming amount of histamine or whatever is causing the breathing shortage. I’ve noticed also that any drowsiness or drops in mood seemingly caused by high doses of thiamine pyrophosphate (perhaps due to improvements in circulation and which an infection is also able to take advantage of) are negated when I take the high potency protease. Thus, I would attribute those symptoms to the infection I likely have.

I’m also taking p5p, which has a kind of nerve stimulation benefit to it for me. I take 20mg sublingually every three hours. At one point early on, I couldn’t tolerate 40mg without feeling like the contents of my bowels were sliding through me (followed by diarrhea), 20 mg wasn’t a problem though. I feel the p5p is synergistic with the acetyl-coenzyme A.

I also take R5P at 50mg 4x a day with meals. Not sure it helps, but I read it helps with the coenzymation of the other B vitamins.

In total, these four B vitamins have reduced my bleeding gums to less than 2-percent of what it was. They have reduced the soreness in the bottoms of my feet, drastically improved my energy and motivation, drastically improved my breathing, and improved my athletic endurance/muscle glycogen. I noticed a pronounced reduction in the frequency of urination, earwax production has increased, particularly in the left ear where it was reduced.

Theories

I have listed some theories below with my own observations notating them. I’d like to hear other opinions. Disagreements are definitely welcomed.

Was my problem a result of too much flora lost from chronic diarrhea, which led to fungal overgrowth, which led to hydrogen sulfide, which then continuously degraded my thiamine?
- There is a book online Fix Your Gut by an author I felt has some insight that says fungal infections reduce both thiamine and b5. My Spectracell test showed I wasn’t low in anything else but those two nutrients.
Was the paradoxical effect from thiamine that resulted in exhaustion and a drop in mood from the improved circulation generated by an increase in nitric oxide or other means? Did this then allow the already-present fungal infection to enter the blood and cause mood problems and exhaustion?
- I would support this theory by mentioning how taking nitric oxide supplements (i.e., citrulline peptides, beet powder standardized for nitrates) also resulted in this exhaustion as well, where it becomes difficult to keep my eyes straight. I would also support this saying that the high-potency protease I take, which I regard as a strong anti-fungal, negates that complication.
Is the acetyl-coenzyme A is only helping because it is circulating pathogens or their chemical excretions from my blood? I’ve been doing it for many months, and it isn’t like I’m needing less of a dose or less frequency, which I would imagine someone would see if they were addressing a deficiency. I suppose it is possible the extra amount is needed due to possible ongoing fungal problems.
Was the lack of enzymes caused by an infection in this case and not by a lack of vagus nerve stimulation? Ultimately, I’d like to be producing my own enzymes and I feel being able to do so gets me closer to the cause of all this. I suspect a fungal infection can somehow offset the necessary stimulation nerves normally receive, and ultimately compromised my pancreas if it wasn’t compromised in other ways by an infection. I don’t have any sharp pains consistent with severe pancreatitis, just a reoccurring dullness in the area. I’ve tried a number of nutrients to increase nerve stimulation with no effect and imagine if there is an issue here with the vagus nerve, it is more directly caused by complications from an infection.

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Photo by LOGAN WEAVER on Unsplash.

This story was posted originally on March 28, 2022.

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Figure 1. High Oxalate Foods

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Raw Veganism and My Slide Into Poor Health

The Progression of Thiamine Deficiency Symptoms

Discovering Thiamine Deficiency

Successes, Failures, and Odd Results

Antifungals and Herbs

Probiotics

Digestive Enzymes

Navigating Nutrient Repletion

Adding Acetyl-Coenzyme A, Thiamine, and Other B Vitamins

Theories

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