Thiamine (Vitamin B1) - A common deficiency in disorders of energy metabolism, cardiovascular and nervous system dysfunction


FOTCM Member
I recently finished reading a book called "Thiamine Deficiency Disease, Dysautonomia, and High Calorie Malnutrition" by Dr Derrick Lonsdale and Chandler Marrs, PhD. It is a semi-academic text on the underlying biochemistry of thiamine metabolism, and how thiamine sufficiency is essential for all things related to intracellular energy production. Thiamine is an essential B vitamin, known as vitamin B1, and is involved as a cofactor for several enzyme complexes involved in the citric acid cycle, amino acid breakdown, and neurotransmitter synthesis. It lies at the top of the citric acid cycle, as a cofactor for the pyruvate dehydrogenase complex. If there is not enough B1, energy is shunted toward anaerobic (non-oxidative) metabolism. It is also critical for maintaining the function of the myelin sheath and proper signals in the nervous system.

The authors of this book elaborate on the "bioenergetic" theory of disease, which basically states that most, if not all diseases, are driven by a deficit of useable energy. When energy is low, ordinary maintenance and cellular function is disrupted and suboptimal back-up mechanisms are relied upon as mainstay.

End stage thiamine deficiency was commonly known to manifest as "beriberi", Wernicke's encephalopathy, and Korsakoff's psychosis:

[QUOTE author=Wikipedia]Symptoms of beriberi include weight loss, emotional disturbances, impaired sensory perception, weakness and pain in the limbs, and periods of irregular heart rate. Edema (swelling of bodily tissues) is common. It may increase the amount of lactic acid and pyruvic acid within the blood. In advanced cases, the disease may cause high-output cardiac failure and death.

Symptoms may occur concurrently with those of Wernicke's encephalopathy, a primarily neurological thiamine-deficiency related condition.

Beriberi is divided into four categories as follows. The first three are historical and the fourth, gastrointestinal beriberi, was recognized in 2004:
  • Dry beriberi specially affects the peripheral nervous system.
  • Wet beriberi specially affects the cardiovascular system and other bodily systems.
  • Infantile beriberi affects the babies of malnourished mothers.
  • Gastrointestinal beriberi affects the digestive system and other bodily systems.[/QUOTE]
Risk factors included chronic diarrhea, consumption of non-fortified refined grains such as white bread and white rice, alcoholism, and genetic transporter deficiencies. After fortification of food with extra thiamine began, the cases of clear thiamine deficiency were resolved. Now, thiamine deficiency is considered to be something of the past.

However, Dr Lonsdale's work at the Cleveland Clinic over the past 40 years demonstrated that thiamine deficiency was extremely common in a whole host of people who suffered from a wide variety of diseases. This was especially true for nervous system, cardiovascular, and gastrointestinal issues. The funny thing is, I was never taught that thiamine is so commonly deficient in people who are sick. This topic seems to be vastly under recognized.

The over-consumption of simple carbohydrates, sugars, and foods which contain thiamine-degrading enzymes (thiaminases - tea and coffee), rapidly depletes thiamine. An easy way to conceptualize this follows: For each molecule of glucose that is used to produce energy, the body needs to use thiamine. When excess glucose is consumed without the extra addition of thiamine, then the stores of thiamine are unable to match the requirement. This leads to dysfunctional metabolism of glucose, where glucose is converted into lactate in the cell fluid, rather than entering the mitochondria.

Based on my research over the past few months, there seems to be several factors which can potentially drive a thiamine deficiency (off of the top of my head):

- Excessive refined carbohydrate / sugar intake
- Gut dysbiosis/malabsorption/gut inflammation
- Excessive hydrogen sulfide gas production in the gut (smelly flatulence resembling rotten egg/sulfurous vegetable smell) - some animal research suggests that hydrogen sulfide degrades thiamine in the gut
- Some pharmaceutical medications (Metformin, oral contraceptive pill etc)
- Tea/coffee with meals
- Excessive oxalates in the diet/or endogenous production of oxalate

Thiamine can be used therapeutically in a wide range of conditions. Dr Lonsdale successfully treat many cases of nervous system disorder such as Postural Orthostatic Tachycardia Syndrome, dysautonomias, insomnia, depression, schizophrenia, along with cardiovascular disease, excessive vomiting, gut issues, and many more. There is research suggesting that thiamine can be used for diabetes (both type 1 and 2), fibromyalgia, and other conditions which I will lay out in another post below.

Below is a very good introduction to the topic by one of the authors of the book:

Beriberi, the Great Imitator
Because of some unusual clinical experiences as a pediatrician, I have published a number of articles in the medical press on thiamine, also known as vitamin B1. Deficiency of this vitamin is the primary cause of the disease called beriberi. It took many years before the simple explanation for this incredibly complex disease became known. A group of scientists from Japan called the “Vitamin B research committee of Japan” wrote and published the Review of Japanese Literature on Beriberi and Thiamine, in 1965. It was translated into English subsequently to pass the information about beriberi to people in the West who were considered to be ignorant of this disease. A book published in 1965 on a medical subject that few recall may be regarded in the modern world as being out of date and of historical interest only, however, it has been said that “Those who do not learn history are doomed to repeat it”. And repeat it, we are.

Beriberi is one of the nutritional diseases that is regarded as being conquered. It is rarely considered as a cause of disease in any well-developed country, including America. In what follows, are extractions from this book that are pertinent to many of today’s chronic health issues. It appears that thiamine deficiency is making a comeback but it is rarely considered as a possibility.

The History of Beriberi and Thiamine Deficiency
Beriberi has existed in Japan from antiquity and records can be found in documents as early as 808. Between 1603 and 1867, city inhabitants began to eat white rice (polished by a mill). The act of taking the rice to a mill reflected an improved affluence since white rice looked better on the table and people were demonstrating that they could afford the mill. Now we know that thiamine and the other B vitamins are found in the cusp around the rice grain. The grain consists of starch that is metabolized as glucose and the vitamins essential to the process are in the cusp. The number of cases of beriberi in Japan reached its peak in the 1920s, after which the declining incidence was remarkable. This is when the true cause of the disease was found. Epidemics of the disease broke out in the summer months, an important point to be noted later in this article.

Early Thiamine Research
Before I go on, I want to mention an extremely important experiment that was carried out in 1936. Sir Rudolf Peters showed that there was no difference in the metabolic responses of thiamine deficient pigeon brain cells, compared with cells that were thiamine sufficient, until glucose (sugar) was added. Peters called the failure of the thiamine deficient cells to respond to the input of glucose the catatorulin effect. The reason I mention this historical experiment is because we now know that the clinical effects of thiamine deficiency can be precipitated by ingesting sugar, although these effects are insidious, usually relatively minor in character and can remain on and off for months. The symptoms, as recorded in experimental thiamine deficiency in human subjects, are often diagnosed as psychosomatic. Treated purely symptomatically and the underlying dietary cause neglected, the clinical course gives rise to much more serious symptoms that are then diagnosed as various types of chronic brain disease.

  • Thiamine Deficiency Related Mortality. The mortality in beriberi is extremely low. In Japan the total number of deaths decreased from 26,797 in 1923 to only 447 in 1959 after the discovery of its true cause.
  • Thiamine Deficiency Related Morbidity. This is another story. It describes the number of people living and suffering with the disease. In spite of the newly acquired knowledge concerning its cause, during August and September 1951, of 375 patients attending a clinic in Tokyo, 29% had at least two of the major beriberi signs. The importance of the summer months will be mentioned later.
Are the Clinical Effects Relevant Today?
The book records a thiamine deficiency experiment in four healthy male adults. Note that this was an experiment, not a natural occurrence of beriberi. The two are different in detail. Deficiency of the other B vitamins is involved in beriberi but thiamine deficiency dominates the picture. In the second week of the experiment, the subjects described general malaise, and a “heavy feeling” in the legs. In the third week of the experiment they complained of palpitations of the heart. Examination revealed either a slow or fast heart rate, a high systolic and low diastolic blood pressure, and an increase in some of the white blood cells. In the fourth week there was a decrease in appetite, nausea, vomiting and weight loss. Symptoms were rapidly abolished with restoration of thiamine. These are common symptoms that confront the modern physician. It is most probable that they would be diagnosed as a simple infection such as a virus and of course, they could be.

Subjective Symptoms of Naturally Occurring Beriberi
The early symptoms include general malaise, loss of strength in knee joints, “pins and needles” in arms and legs, palpitation of the heart, a sense of tightness in the chest and a “full” feeling in the upper abdomen. These are complaints heard by doctors today and are often referred to as psychosomatic, particularly when the laboratory tests are normal. Nausea and vomiting are invariably ascribed to other causes.

General Objective Symptoms of Beriberi
The mental state is not affected in the early stages of beriberi. The patient may look relatively well. The disease in Japan was more likely in a robust manual laborer. Some edema or swelling of the tissues is present also in the early stages but may be only slight and found only on the shin. Tenderness in the calf muscles may be elicited by gripping the calf muscle, but such a test is probably unlikely in a modern clinic.

In later stages, fluid is found in the pleural cavity, surrounding the heart in the pericardium and in the abdomen. Fluid in body cavities is usually ascribed to other “more modern” causes and beriberi is not likely to be considered. There may be low grade fever, usually giving rise to a search for an infection. We are all aware that such symptoms come from other causes, but a diet history might suggest that beriberi is a possibility in the differential diagnosis.

Beriberi and the Cardiovascular System
In the early stages of beriberi the patient will have palpitations of the heart on physical or mental exertion. In later stages, palpitations and breathlessness will occur even at rest. X-ray examination shows the heart to be enlarged and changes in the electrocardiogram are those seen with other heart diseases. Findings like this in the modern world would almost certainly be diagnosed as “viral myocardiopathy”.

Beriberi and the Nervous System
Polyneuritis and paralysis of nerves to the arms and legs occur in the early stages of beriberi and there are major changes in sensation including touch, pain and temperature perception. Loss of sensation in the index finger and thumb dominates the sensory loss and may easily be mistaken for carpal tunnel syndrome. “Pins and needles”, numbness or a burning sensation in the legs and toes may be experienced.

In the modern world, this would be studied by a test known as electromyography and probably attributed to other causes. A 39 year old woman is described in the book. She had lassitude (severe fatigue) and had difficulty in walking because of dizziness and shaking, common symptoms seen today by neurologists.

Beriberi and the Autonomic Nervous System
We have two nervous systems. One is called voluntary and is directed by the thinking brain that enables willpower. The autonomic system is controlled by the non-thinking lower part of the brain and is automatic. This part of the brain is peculiarly sensitive to thiamine deficiency, so dysautonomia (dys meaning abnormal and autonomia referring to the autonomic system) is the major presentation of beriberi in its early stages, interfering with our ability for continuous adaptation to the environment. Since it is automatic, body functions are normally carried out without our having to think about them.

There are two branches to the system: one is called sympathetic and the other one is called parasympathetic. The sympathetic branch is triggered by any form of physical or mental stress and prepares us for action to manage response to the stress. Sensing danger, this system activates the fight-or-flight reflex. The parasympathetic branch organizes the functions of the body at rest. As one branch is activated, the other is withdrawn, representing the Yin and Yang (extreme opposites) of adaptation.

Beriberi is characterized in its early stages by dysautonomia, appearing as postural orthostatic tachycardia syndrome(POTS). This well documented modern disease cannot be distinguished from beriberi except by appropriate laboratory testing for thiamine deficiency. Blood thiamine levels are usually normal in the mild to moderate deficiency state.

Examples of Dysfunction in Beriberi
The calf muscle often cramps with physical exercise. There is loss of the deep tendon reflexes in the legs. There is diminished visual acuity. Part of the eye is known as the papilla and pallor occurs in its lateral half. If this is detected by an eye doctor and the patient has neurological symptoms, a diagnosis of multiple sclerosis would certainly be entertained.

Optic neuritis is common in beriberi. Loss of sensation is greater on the front of the body, follows no specific nerve distribution and is indistinct, suggestive of “neurosis” in the modern world.

Foot and wrist drop, loss of sensation to vibration (commonly tested with a tuning fork) and stumbling on walking are all examples of symptoms that would be most likely ascribed to other causes.

Breathlessness with or without exertion would probably be ascribed to congestive heart failure of unknown cause or perhaps associated with high blood pressure, even though they might have a common cause that goes unrecognized.

The symptoms of this disease can be precipitated for the first time when some form of stress is applied to the body. This can be a simple infection such as a cold, a mild head injury, exposure to sunlight or even an inoculation, important points to consider when unexpected complications arise after a mild incident of this nature. Note the reference to sunlight and the outbreaks of beriberi in the summer months. We now know that ultraviolet light is stressful to the human body. Exposure to sunlight, even though it provides us with vitamin D as part of its beneficence, is for the fit individual. Tanning of the skin is a natural defense mechanism that exhibits the state of health.

Is Thiamine Deficiency Common in America?
My direct answer to this question is that it is indeed extremely common. There is good reason for it because sugar ingestion is so extreme and ubiquitous within the population as a whole. It is the reason that I mentioned the experiment of Rudolph Peters. Ingestion of sugar is causing widespread beriberi, masking as psychosomatic disease and dysautonomia. The symptoms and physical findings vary according to the stage of the disease. For example, a low or a high acid in the stomach can occur at different times as the effects of the disease advance. Both are associated with gastroesophageal reflux and heartburn, suggesting that the acid content is only part of the picture.
A low blood sugar can cause the symptoms of hypoglycemia, a relatively common condition. A high blood sugar can be mistaken for diabetes, both seen in varying stages of the disease.

It is extremely easy to detect thiamine deficiency by doing a test on red blood cells. Unfortunately this test is either incomplete or not performed at all by any laboratory known to me.

The lower part of the human brain that controls the autonomic nervous system is exquisitely sensitive to thiamine deficiency. It produces the same effect as a mild deprivation of oxygen. Because this is dangerous and life-threatening, the control mechanisms become much more reactive, often firing the fight-or-flight reflex that in the modern world is diagnosed as panic attacks. Oxidative stress (a deficiency or an excess of oxygen affecting cells, particularly those of the lower brain) is occurring in children and adults. It is responsible for many common conditions, including jaundice in the newborn, sudden infancy death, recurrent ear infections, tonsillitis, sinusitis, asthma, attention deficit disorder (ADD), hyperactivity, and even autism. Each of these conditions has been reported in the medical literature as related to oxidative stress. So many different diseases occurring from the same common cause is offensive to the present medical model. This model regards each of these phenomena as a separate disease entity with a specific cause for each.

Without the correct balance of glucose, oxygen and thiamine, the mitochondria (the engines of the cell) that are responsible for producing the energy of cellular function, cannot realize their potential. Because the lower brain computes our adaptation, it can be said that people with this kind of dysautonomia are maladapted to the environment. For example they cannot adjust to outside temperature, shivering and going blue when it is hot and sweating when it is cold.

So, yes, beriberi and thiamine deficiency have re-emerged. And yes, we have forgotten history and appear doomed to repeat it. When supplemental thiamine and magnesium can be so therapeutic, it is high time that the situation should be addressed more clearly by the medical profession.
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Here are another few articles which provide a rough overview of some of the functions of thiamine and clinical applications:

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

What is Thiamine to Energy Metabolism?

What is Energy?
Energy is an invisible force. The aggregate of energy in any physical system is a constant quantity, transformable in countless ways but never increased or diminished. In the human body, chemical energy is produced by the combination of oxygen with glucose. This reaction is known as oxidation. The chemical energy is transduced to electrical energy in the process of energy conservation. This might be thought of as the “engine” of the brain/body cells. We have to start thinking that it is electrical energy that drives the human body. The production of chemical energy is exactly the same in principle as the burning of any fuel but the details are quite different. The energy is captured and stored in an electronic form as a substance known as adenosine triphosphate (ATP) that acts as an energy currency. The chemical changes in food substances are induced by a series of enzymes, each of which combine together to form a chain of chemical reactions that might be thought of as preparing food for its ultimate breakdown and oxidation. Each of these enzymes requires a chemical “friend”, known as a cofactor. One of the most important enzymes, the one that actually enables the oxidation of glucose, requires thiamine and magnesium as its cofactors. Chemical energy cannot be produced without thiamine and magnesium, although it also requires other “colleagues”, since all vitamins are essential. A whole series of essential minerals are also necessary, so it is not too difficult to understand that all these ingredients must be obtained by nutrition. The body cannot make vitamins or essential minerals. There is also some evidence that thiamine may have a part to play in converting chemical energy to electrical energy. Thus, it may be the ultimate defining factor in the energy that drives function. If that is true, its deficiency would play a vital role in every disease.
Energy Consumption
Few people are aware that our lives depend on energy production and its efficient consumption. A car has to have an engine that produces the energy. This is passed through a transmission that enables the car to function. In a similar manner, we have discussed how energy is produced. It is consumed in a series of energy requiring chemical reactions, each of which requires an enzyme with its appropriate cofactor. This series of reactions can be likened to a transmission, enabling the human body to function. If energy is consumed faster than it can be synthesized, or energy cannot be produced fast enough to meet demand, it is not too difficult to see that it would produce a fundamental change in function. Lack of function in body organs affects our health. The symptoms are merely warning the affected individual that something is wrong. The underlying cause has to be ascertained in order to interpret how the symptoms are generated.
Why Focus on Thiamine?
We have already pointed out that thiamine does not work on its own. It operates in what might be regarded as a ”team relationship”. But it has also been determined as the defining cause of beriberi, a disease that has affected millions for thousands of years. Any team made up of humans requires a captain and although this is not a perfect analogy, we can regard thiamine as “captain” of an energy producing team. This is mainly due to its necessity for oxidation of glucose, by far and away the most important fuel for the brain, nervous system and heart. Thus, although beriberi is regarded as a disease of those organs, it can affect every cell in the body and the distribution of deficiency within that body can affect the presentation of the symptoms.
Thiamine exists only in naturally occurring foods and it is now easy to see that its deficiency, arising from an inadequate ingestion of those foods, results in slowing of energy production. Because the brain, nervous system and heart are the most energy requiring tissues in the body, beriberi produces a huge number of problems primarily affecting those organs. These changes in function generate what we call symptoms. Lack of energy affects the “transmission”, giving rise to symptoms arising from functional changes in the organs thus subserved. However, it must be pointed out that an enzyme/cofactor abnormality in the “transmission” can also interrupt normal function.
In fact, because of inefficient energy production, the symptoms caused by thiamine deficiency occur in so many human diseases that it can be regarded as the great imitator of all human disease. We now know that nutritional inadequacy is not the only way to develop beriberi. Genetic changes in the ability of thiamine to combine with its enzyme, or changes in the enzyme itself, produce the same symptoms as nutritional inadequacy. It has greatly enlarged our perspective towards the causes of human disease. Thiamine has a role in the processing of protein, fat and carbohydrate, the essential ingredients of food.
Generation of Symptoms
Here is the diagnostic problem. The earliest effects of thiamine deficiency are felt in the hindbrain that controls the automatic brain/body signaling mechanism known as the autonomic nervous system (ANS). The ANS also signals the glands in the endocrine system, each of which is able to release a cellular messenger. A hormone may not be produced in the gland because of energy failure, thus breaking down the essential governance of the body by the brain. Hypoxia (lack of oxygen) or pseudo-hypoxia (thiamine deficiency produces cellular changes like those from hypoxia) is a potentially dangerous situation affecting the brain and a fight-or-flight reflex may be generated. This, as most people know, is a protective reflex that prepares us for either killing the enemy or fleeing and it can be initiated by any form of perceived danger. Thus, thiamine deficiency may initiate this reflex repeatedly in someone that seeks medical advice for it. Not recognizing its underlying cause, it is diagnosed as “panic attacks”. Panic attacks are usually treated by psychologists and psychiatrists with some form of tranquilizer because of the anxiety expressed by the patient. It is easy to understand how it is seen as psychological, although the sensation of anxiety is initiated in the brain as part of the fight-or-flight reflex and will disappear with thiamine restoration. It may be worse than that: because the heart is affected by the autonomic nervous system, there may be a complaint of heart palpitations in association with the panic attacks and the heart might be considered the seat of the disease, to be treated by a cardiologist. The defining signal from the ANS is ignored or not recognized. Because it is purely a functional change, the routine laboratory tests are normal and the symptoms are therefore considered to be psychological, or psychosomatic. The irony is that when the physician tells the patient “it is all in your head”, he is completely correct but not recognizing that it is a biochemical functional change and that it has nothing to do with Freudian psychology.
A Sense of Pleasure
A friend of mine has become well aware that alcohol, in any form, or sugar, will automatically give him a migraine headache. He still will take ice cream and suffer the consequences. I have had patients tell me that they have given up this and that “but I can’t give up sugar: it is the only pleasure that I ever get”. They still came back to me to treat the symptoms. We have come to understand that we have no self-responsibility for our own health. If we get sick, it is just bad luck and the wonders of modern medicine can achieve a cure. The trouble is that a mild degree of thiamine deficiency might produce symptoms that will make it more difficult to make the necessary decisions for our own well-being. Let me give some examples of symptoms that are typically related to this and are not being recognized.

    • Occasional headache
    • Occasional heartburn or abdominal pain
    • Occasional diarrhea or constipation
    • Allergies
    • Fatigue
    • Emotional lability
    • Insomnia
    • Nightmares
    • Pins and needles
    • Hair falling out
    • Heart palpitations
    • Persistent cough for no apparent reason
    • Voracious or loss of appetite
The point is that thiamine governs the energy synthesis that is essential to our total function and it can affect virtually any group of cells in the body. However, the brain, heart and nervous system, particularly the autonomic (automatic) nervous system (ANS) are the most energy requiring organs and are likely to be most affected. Since the brain sends signals to every organ in the body via the ANS, a distortion of the signaling mechanism can make it appear that the organ receiving the signal is at fault. For example, the heart may accelerate because of a signal from the brain, not because the heart itself is at fault. Hence, heart palpitations are often treated as heart disease when a mild degree of thiamine deficiency in the brain is responsible. We have known for many years that sugar in all its different forms can and will precipitate mild thiamine deficiency. It is probably the reason why sugar is considered to be a frequent cause of trouble. If thiamine deficiency is mild, any form of minor stress may precipitate a much more serious form of the deficiency.

Thiamine, Fibromyalgia and Chronic Fatigue
Fibromyalgia affects roughly six million Americans, mostly women. Its symptoms include all-over muscle and tendon pain, increased pain sensitivity, chronic fatigue, sleep disturbances and brain fog. Fibromyalgia is often reported as feeling like a flu that never leaves. Similarly, symptoms of Chronic Fatigue Syndrome (CFS) overlap with many of those of fibromyalgia and the two conditions are often co-morbid. With chronic fatigue, however, the predominant symptom is a fatigue that never lets up versus all-over muscle and tendon pain.

Both fibromyalgia and chronic fatigue are co-diagnosed frequently in women with endometriosis, especially those who have had Lupron treatments. Similarly, we are finding a high incidence of chronic fatigue and fibromyalgia post Gardasil/Cervarix and post fluoroquinolone. All over muscle and tendon pain, coupled with never-ending tiredness seem to be common symptoms post medication or vaccine reaction. Could they be linked to a broader problem, specifically, thiamine deficiency?

What is Thiamine?
Thiamine or vitamin B1 is necessary for cellular energy. It is a required co-factor in several enzymatic processes, including glucose metabolism and interestingly enough, myelin production. We can get thiamine only from diet. Whendiet suffers, as in the case of chronic alcoholism where most of the research on this topic is focused, when nutritional uptake is impaired (leaky gut and other GI disturbances), or when other factors inhibit the enzymes necessary to carry out intracellular reactions, thiamine deficiency ensues. And thiamine deficiency can elicit a whole host of problems that are consistent with the current definitions of chronic fatigue and fibromyalgia.

Thiamine and Fibromyalgia – A Few Hints
A recent case study suggests that what is currently diagnosed as fibromyalgia and/or chronic fatigue may be attributable to thiamine deficiency. A very small case study (n =3) from Italian physicians found a significant reduction in fibromyalgia symptoms in patients given high dose thiamine. Researchers found:

    • Patient 1: 71.3% reduction in fatigue; 80% reduction in pain.
    • Patient 2: 37% reduction in fatigue; 50% reduction in pain.
    • Patient 3: 60.7% reduction in fatigue; 60% reduction in pain.
Thiamine and Chronic Fatigue
In a little bit larger study – 17 patients with Chronic Fatigue, researchers found a functional reduction of the enzymes involved in vitamin B metabolism (aspartate aminotransferase -pyridoxine, glutathione reductase and transketolase) compared to healthy controls, suggesting thiamine deficiency.

What This Means
It’s way too early to tell if thiamine deficiency is at root of fibromyalgia and/or chronic fatigue symptoms, or if adverse reactions to medications and vaccines can elicit the symptoms of fibromyalgia and chronic fatigue, but there are hints pointing in that direction. Much more research should be done. In the meantime, if you suffer from fibromylagia or chronic fatigue or undiagnosed neuromuscular pain, why not consider testing for thiamine. And while you’re at it, since many of these symptoms overlap with those of hypothyroidism, particularly of the autoimmune Hashimoto’s sort, why not get tested for that too. If you test positive for either of these, tell us about it, it will help other patients find solutions. To learn more about thiamine deficiency and other topics, search our growing library of research and patient stories here on Hormones Matter.
Thiamine in cardiovascular disease and diabetes:

Thiamine and Heart Function
Since there are many posts on this website about thiamine, it is entirely possible that some readers will regard it as being an obsession of the author’s. I can well imagine a reader believing that an explanation for so many different conditions is the fruit of such an obsession. I will counter this by stating that a paper in a prestigious medical journal reported 696 separate papers in which over 250 human diseases had been treated with this vitamin as long ago as 1962. I think that the explanation for recognizing the place of thiamine in human metabolism is a professional lifetime of clinical observation, resulting in the conclusion that disease is a representation of cellular energy deficiency. To use a simple analogy, spark plugs used in older cars were necessary to ignite the gasoline. Loss of a single plug made the engine run badly and if they were all affected, the car became completely useless. I have used the analogy frequently: thiamine deficiency is like an inefficient spark plug in the engine of a car.

Heart Disease and Beriberi: Case Stories
Heart disease has been central in beriberi, the classic thiamine deficiency disease, for centuries and the painstaking efforts that uncovered thiamine deficiency as the cause is unfortunately a little-known saga of human effort. Modern physicians have been completely convinced that no vitamin deficiencies exist in America, because of vitamin enrichment by the food industry. So is there any evidence that physicians are beginning to wonder whether thiamine plays a part in modern heart disease? This post is designed to show that there is indeed an awakening that could make a big difference to the role of cardiologists in treating heart disease.
Before I go to some medical literature, I want to describe a personal experience that occurred many years ago because it illustrates the incredible psychological resistance of the medical community to a vitamin deficiency. I was a pediatrician at Cleveland Clinic at the time. In the medical hierarchy, a pediatrician is regarded as being largely ignorant concerning disease in adults. A 67 year old anesthesiologist at a Columbus hospital reported to his colleagues with the symptoms of heart failure. He was subjected to heart catheterization and found to be perfectly normal in that respect.
His son was in medical school and studying his father’s case, he came to the conclusion that he had beriberi. For some reason unknown to me, the patient was referred to cardiologists at the Cleveland Clinic. Because my colleagues knew of my particular interest in thiamine, I was asked to see the patient. The story he gave me made the son’s diagnosis virtually a guarantee. Each day, as he went to get into his car in the morning, he would get the “dry heaves” in the garage. He would drive to the hospital where he gave anesthesia to as many as 10 patients. He would then go to the pediatric ward and cut himself a large piece of chocolate cake. When he got home he was too tired to eat dinner and would go to bed. I gave my reading of the case in the patient’s record and had no further contact. He was returned to the Columbus cardiologists and although I believe that he continued to receive thiamine, he died. I never received any information concerning his further care or whether the cardiologists really believed that this was beriberi. One can only conclude that the state of his heart was precarious and the history of thiamine treatment in beriberi had already showed us that there was a “tipping point” beyond which there was no response to thiamine treatment. Whether the cardiologists were aware of this or not is unknown. It is possible that his failure to respond may well have caused them to reject the diagnosis. What really impressed me was the extraordinary resistance to this diagnosis.
I am reminded of another case in my experience. There was a lady pathologist at Cleveland Clinic who was known to be brilliant. I visited her in the Department of Pathology for a reading on one of my patients. She told me that she was so utterly fatigued that a few days previously she had turned around on her way to work and gone home. I found to my amazement that she had a chocolate box in every room in her house and would take a chocolate at random as she went around her house. Without further advice I simply suggested to her to discontinue that practice and to take a supplement of thiamine, whereupon she recovered quickly. Fatigue is a symptom arising in the brain that notifies its owner of energy deficiency and undue fatigue is a logical result in beriberi.
Recognizing Vitamin Deficiencies in Disease
The problem with thiamine deficiency is that a physician has to change his attitude radically towards the cause of disease. This is because the underlying mechanism is derived from cellular lack of energy. If this is not perceived, a physician can be puzzled by a combination of heart and nervous system disease in a single patient. In the present medical model, he believes that he is confronted with two separate conditions.
Because of this resistance, in 1982 I joined a private practice specializing in nutrient-based medicine and began seeing adults as well as children. I joined a group that came to be known as the American College for Advancement in Medicine (ACAM). This relatively small group of physicians had all come to the same conclusion: nutrient-based therapy is, or should be, the methodology of the future. Many of these physicians were practicing alongside their orthodox colleagues in their local hospitals. One of my
ACAM friends told me the following story. He had a patient in the hospital with a pneumonia caused by antibiotic resistant infection. Together with the antibiotic treatment, he had given the patient intravenous vitamin C and she recovered. A patient in the next bed was under another physician with the same pneumonia and my friend approached him, suggesting that he tried the use of the same treatment. He was told to mind his own business and the patient subsequently died. I know of no better example of resistance and rejection of a principle that has yet to reach full acceptance in American medicine. As long as the psychological resistance to vitamin deficiency remains, it is seldom considered. I am happy to say that this resistance is beginning to break down as we shall see by looking at some of the recent medical literature. Not only that, the therapeutic use of vitamins in pharmacological doses it gradually being recognized for its therapeutic value.
Recent Reports of Thiamine’s Role in Clinical Care
Hear what a physician wrote as recently as 2015. The title of the paper is “Thiamine in Clinical Practice” and the author notes that the active form of the vitamin plays a role in nerve structure and function as well as brain and heart metabolism. Unexplained heart and kidney failure, alcoholism, starvation, vomiting in pregnancy or intestinal surgery “may increase the risk for thiamine deficiency”. Understanding the role of thiamine as a potential therapeutic agent for diabetes, some inborn errors of metabolism and neurodegenerative diseases all warrant further research. Surely, this is an indictment of our present approach by merely trying to control symptoms instead of addressing the primary cause.
A group of Canadian physicians stated that “the management of heart failure represents a significant challenge for both patients as well as the health care system in industrialized countries”. The abstract of their paper notes that thiamine is required in the energy-producing reactions that fuel heart contraction. Previous studies have reported a wide range in the prevalence of thiamine deficiency in patients with heart failure and the impact of its supplementation in patients is inconclusive. Of course, Dr. Marrs and I are appalled because such treatment is not only easy, it is completely non-toxic and therefore safe. If there is clinical evidence, why not use a non-toxic agent? However, the psychological restraints of being accused of being a charlatan are very real and can expose a physician to colleague ridicule.
Another paper reported that a total of 20 articles were reviewed and summarized. Recent evidence has indicated that supplementation with thiamine in heart failure patients has the potential to improve heart contractions. These authors recommend that this simple therapy should be tested in large-scale randomized clinical trials to further determine the effects of thiamine in heart failure patients. Diuretic treatment for heart failure may lead to an increased urinary thiamine excretion and in the long-term thiamine deficiency, further compromising heart function. Nine patients with diuretic treatment for chronic heart failure were studied with thiamine supplementation, producing beneficial effects on cardiac function. The authors state that subclinical thiamine deficiency is probably an underestimated issue in heart failure patients. It has even been shown that thiamine pyrophosphate, the active form of the vitamin, prevents the toxic heart injury caused by the cancer treating agent cisplatin. Dietary thiamine that has not been activated by the body did not prevent this.
It has been known for some time that thiamine in the diet has to be absorbed into the body by means of a protein known as a transporter of which there are quite a few. These transporters are under genetic control and absence of one or more of them will make it difficult for a given person to obtain an adequate amount of thiamine from diet into the part of the body where that thiamine transporter is active. A new thiamine transporter has been discovered whose genetic variants have an effect on blood pressure.
Although this post is about heart disease, I want to end by pointing out that vitamin treatment goes well beyond the consideration of just heart disease. Several years ago I received a letter from an aging physician who had specialized in OB/GYN. This letter was so poignant that I am repeating some of this letter:
I am writing to you, because I have found another mortal being who is particularly interested in the biological activities of thiamine. I had previously thought that I was nearly the lone believer in the benevolent effects of thiamine particularly for the treatment and prophylaxis of the toxemias of pregnancy and its many associated problems. I had even written to the chief of the Cleveland Clinic OB-GYN about the “miracles” I was performing and offered to work with him in further development of the concepts.

Diabetes and Thiamine: A Novel Treatment Opportunity
Author: Chandler Marrs, PhD
Underlying all diabetic conditions is poor sugar control or hyperglycemia. Hyperglycemia can be due to a lack of insulin as in Type 1 diabetes or insulin resistance as in Type 2 diabetes. In either case, the corresponding diabetic complications that evolve over time in many diabetics, the cardiovascular disease, retinopathy, peripheral nerve and vascular damage, represent the effects of sustained hyperglycemia. Until recently, the mechanisms by which diabetic vascular damage developed eluded researchers. Although multiple, seemingly discrete biomarkers had been identified, no single, unifying mechanism was understood. It turns out that diabetics, both Type 1 and Type 2, are severely deficient in thiamine or vitamin B1 and that thiamine is required for glucose control at the cell level. Why is thiamine deficient in diabetics and how does thiamine manage glucose control? The answers to those questions highlight the importance of micronutrients in basic cellular functioning, particularly mitochondrial functioning, and the role of excessive sugar in disease.

Thiamine (thiamin) or vitamin B1 is an essential nutrient for all living organisms. The body cannot synthesize thiamine by itself and so it must be obtained from diet. Thiamine is present in yeast, pork, fish, various nuts, peas, asparagus, squash and grains (unprocessed) and because of the severity of the illnesses that thiamine deficiency evokes, many processed foods have been fortified with thiamine. Nevertheless, thiamine deficiencies thought resolved by modern nutritional technologies, are emerging once again. Modern thiamine deficits appear to be caused by diets of highly processed, carbohydrate and fat laden foods, exposures to thiamine blocking factors such as alcohol and those found in many medications (fluoroquinolones, possibly others) and vaccines (Gardasil, possibly others), environmental toxicants and some foods. Thiamine deficiency is also common after bariatric surgery and in disease processes like AIDS and cancer. Over the course of our research, thiamine deficiency has been observed in previously healthy, young, non-alcoholic patients, post medication or vaccine, along with symptoms of dysautonomia.
Thiamine Deficiency Symptoms
Thiamine deficiency at its worst is linked to severe decrements neurological functioning, like Wernicke’s Encephalopathy that include noticeable ataxic and gait disturbances (loss of voluntary control of muscle movements, balance and walking difficulties), aphasias (language comprehension and/or production difficulties), and if it persists, Korsakoff’s Syndrome (severe memory deficits, confabulations and psychosis). Early on though and as the deficiency is evolving, thiamine deficiency presents much like the mitochondrial disease that it is – with the myriad of seemingly unrelated symptoms, that are not typically attributed to thiamine deficiency, such as fatigue and excessive sleeping, hair loss, cardiac dysregulation, GI disturbances such as gastroparesis and others, autonomic instability, demyelinating syndromes and hormone irregularities, especially thyroid, but also reproductive hormones. In diabetics, thiamine deficiency may present as ketoacidosis, lactic acidosis, hyperglycemia and persistent encephalopathy. Thiamine deficiency attacks the mitochondria. Mitochondrial dysfunction presents diversely. In fact, with mitochondrial dysfunction, symptoms are as varied as the individuals who experience them. Diabetes, may be just one more phenotype of among many.
Thiamine Deficits in Diabetes
With diabetes, thiamine deficiencies are common, though likely under-recognized. Diabetics are susceptible to thiamine deficiencies mediated by diet and exposures like most of the Western world, but also have added risk factors associated with the disease itself. In diabetics, kidney function is altered which decreases thiamine reabsorption while increasing thiamine excretion. In some people, diabetic and non-diabetic alike, thiamine deficiency can be exacerbated even further by a mutation in the thiamine transporter protein that brings thiamine into the cells.
How thiamine deficient are diabetics? One study found that in comparison to non-diabetics, individuals with Type 1 and Type 2 diabetes had 75% and 64% less thiamine, respectively. Think about this for a moment. If diabetes predisposes individuals to thiamine deficiency without any other intervening factors, imagine what happens when diabetics are nutritionally thiamine deficient, exposed to the myriad of environmentally or medically thiamine-depleting substances currently on the market, or worse yet, carry the thiamine transporter mutation. Alone, but especially in combination, thiamine deficiency diseases, many of which align with diabetes-related complications, could be magnified exponentially. The remarkable thing about this new research is that treatment is easy, it requires only dietary changes and high dose thiamine therapy alongside normal diabetes interventions. (Although one suspects with Type 2 diabetes at least, dietary changes and thiamine supplements could replace other medications entirely). Backing up a bit though, let us look at the research and mechanisms by which thiamine moderates sugar exposure at the cell level and how thiamine modifies those processes.
The Hyperglycemic Cascades
Under normal conditions, with appropriate dietary nutrients and physiological concentrations glucose, dietary sugars are converted to ATP in the mitochondria. The byproduct of that reaction is the production of free radicals also known as oxidative stress or reactive oxygen species (ROS). ROS are neither good nor bad, but too much or too little ROS wreaks havoc on cellular functioning. The cells can clear the ROS and manage oxidative stress via activating antioxidizing pathways and shuttling the excess glucose to secondary, even tertiary processing paths. However, under conditions of chronic hyperglycemia, mediated by diet or diabetes, the conversion of glucose to ATP becomes dysregulated, the production of ROS become insurmountable and a cascade of ill-effects are set in motion.
Too much ROS causes the mitochondria to produce high concentrations of an enzyme called superoxide dismutase (SOD) in the endothelial cells of both the small and large blood vessels. SOD is a powerful antioxidant, however, like everything else, too much for too long causes problems. Superoxide then upregulates the five known chemical pathways that alone and together perturb vascular homeostasis and cause the diabetic injuries that have become commonplace. Technically speaking, hyperglycemia causes:
  1. Increased activation of the polyol pathway
  2. Increased intracellular formation of advanced glycation end products (AGEs)
  3. Increased AGE receptor expression and ligands
  4. Upregulated protein kinase C (PKC)
  5. Enhanced hexosamine pathway activity
In non-technical terms, elevated concentrations of circulating glucose increase the production of ROS and superoxide, but also, and as a compensatory survival reaction to maintain cellular health, secondary and tertiary glucose processing pathways come online. These backup pathways are not nearly as efficient and so produce additional, negative metabolic byproducts which can damage blood vessels if not cleared. The body is capable of clearing these byproducts, but only when the reactions are short term and the nutrient substrates feeding those reactions are present. If, however, the nutrients are deficient and/or the hyperglycemia is chronic, or both, those clearance mechanisms are insufficient to remove the toxins. The toxic byproducts build up and diabetic vascular diseases ensue.
High Dose Thiamine Therapy and Diabetes
Over the last decade or so, researchers have found that thiamine normalizes each of these five aberrant processes activated by sustained hyperglycemia and implicated in diabetic vascular complications. High dose thiamine (300mg/day) reduces the biochemical stress of hyperglycemia human subjects. Additionally, thiamine can prevent and/or offset incipient vascular damage in diabetic patients. Finally, in rodent models of Type 1 diabetes, thiamine transporters have been identified and emerging research shows that thiamine moderates pancreatic insulin secretion significantly. In rats fed a thiamine deficient diet, glycolosis (sugar processing and conversion to ATP by mitochondria) was inhibited by 41%, utilization of fatty acids (secondary energy processing pathway) declined by 61% in just 30 days and insulin production diminished by 14%. The connection between pancreatic downregulation of fatty acid utilization and thiamine is particularly interesting considering the recent discovery of a thiamine dependent enzyme in fatty acid regulation, the HACL1.
Diabetes and Modern Medicine
Diabetes and the destruction it causes affects every cell, tissue and organ system in the body. As such, some researchers have postulated that diabetes represents a model for the paradigm shift in modern medicine. If diabetes is the model for chronic, multi-system illness that marks modernity, then thiamine, and likely other nutrients, are the markers by which the new model of medicine must be drawn. Diabetes is, at its root a mitochondrial disorder. Whether diabetes is inherited, as in Type 1 or induced environmentally as in Type 2, diabetes exemplifies how we convert food to fuel to power cellular functions. When that food is deficient in vital nutrients, the power conversion processes adapt for survival. The compensatory actions have consequences, especially when sustained beyond their capacity to meet the needs of the body. Disease erupts, first gradually then explosively.
Consider the implications of thiamine deficiency, a single micronutrient available in food, on cellular health, and indeed, physical health. In addition its role in mitochondrial functioning, thiamine controls sugar metabolism through multiple pathways. Inefficient sugar metabolism leads to disease. Thiamine also regulates the metabolism of fatty acids and provides the necessary substrates for the neurotransmitters acetylcholine and GABA. Thiamine, much like other critical nutrients, is not only absent from the largely processed diets of modernity, but at every turn, can be depleted by medications and environmental toxicants. Against the backdrop of nutrient depleted and damaged mitochondria, accommodating medications, vaccines and environmental toxicants that also damage mitochondria, increase oxidative stress and further deplete critical nutrients, it is no wonder we are living sicker and dying younger than ever before. The depletion of critical nutrients is causing disease; diseases no medication can treat.
I was recently told about benfotiamine as an aid in overcoming things like diabetic neuropathy; have you heard of this or looked into it?
From one of Dr Lonsdale's papers titled "Thiamine"

Thiamine occurs in at least four different forms in mammalian systems, the free or inactive molecule and three phosphorylated derivatives. There is also some evidence that there may be a methylated form necessary for the release of acetyl choline into the synaptosome.3 4 Its phosphorylation to mono, di(pyro), and triphosphate is similar to phosphorylation of adenosine and is importantly related to regulation of energy metabolism. Little information exists on the role of thiamine monophosphate (TMP) although it is undoubtedly present in many tissues.5 The pyrophosphate (TPP) is the best known since it is cofactor for at least 24 enzyme systems. Two important ones are pyruvic dehydrogenase, in which TPP is a catalyst in the synthesis of acetyl CoA, and a similar enzyme which dehydrogenates the branched chain keto acids derived from leucine, isoleucine and valine. It is also required by transketolase, an enzyme which occurs twice in the hexose monophosphate shunt.

Without discussing details of the biochemistry involved, it is well known that TPP is a vital link in the metabolism of glucose and its deficiency is a major disaster in energy metabolism. Thiamine triphosphate (TTP) is a form which is less well known or understood. It has a special role in the nervous system and its synthesis is catalyzed by a phosphotransferase which transfers a phosphate from ATP to TPP.5 The main concentration of TTP in the nervous system is in the brain stem and upper cord, and some cases of Leigh's disease6 have been found to be associated with a naturally occurring inhibitory substance which appears to block the formation of TTP in brain tissue.

The precise action of TTP is not completely understood, but it is found in excitable membranes and in an experimental situation it is known to leave the membrane and pass into the surrounding perfusate when an electrically stimulated impulse passes through the nerve.5 This suggests that it has an important bearing on phosphate exchanges which regulate energy metabolism in nerve tissue. It is also found in liver and heart, and of the four forms of the vitamin found in the nervous system, about 80 percent is TPP, 5 to 10 percent TTP, and the rest is present as TMP and free thiamine.5 Thiamine deficient animals may become more aggressive or irritable, 8 9 so the vitamin appears to have a direct effect on regulation of normal central nervous system function.

Clinical Deficiency Nutrition
Clinical deficiency of dietary thiamine, probably with other nutrient deficiency, causes beriberi, and a wealth of literature on the subject has recently been disregarded in well developed societies on the assumption that this is a pure starvation disease that has been eliminated. Even if the characteristic symptoms and signs should be recognized, it might be assumed that they would clear rapidly after a small dose of thiamine for a few days. If no rapid response occurred it would then be assumed that the cause of the symptoms was not due to such deficiency. Low dose thiamine replacement is not effective in a chronic deficiency state, for several reasons. First, the water soluble synthetic salts of thiamine are poorly absorbed and an active transport system is required. In long term dietary deficiency, with consequent loss of energy, there may be defective absorption so that the physiologic doses have to be increased drastically. Second, phosphorylation activates the vitamin, and this process would be expected to be inefficient or inactive due to the loss of energy from the original deficiency. This vicious cycle might be the explanation for the clinical observation that beriberi requires large doses of thiamine for months.10

Biologic effects are related to whether thiamine deficiency is "pure" or mixed. In practice it is more than likely to be mixed. The age of the patient and the rate of induction of the biochemical state are influencing factors. Infancy beriberi is a viciously lethal disease which occurs in several different forms, depending on its acuity. One form was studied in breast fed Chinese infants in Hong Kong.11 These infants received milk from their Bl avitaminotic mothers and revealed clinical characteristics which were surprisingly similar to those of Sudden Infant Death Syndrome (SIDS) as seen today in many countries. Sudden death occurred usually between two and five months, was rare under one month, or over one year, had a predilection for the apparently "healthiest" male infants, was more common in late winter, early spring, occurred usually at night while the infant was asleep and was associated frequently with a minor infection such as a cold. Autopsy findings were trivial as they are in modern SIDS. Fehily made a point of emphasizing that the acuity of this event appeared to be dependent upon the amount of milk ingested, thus underscoring the important fact that the nutritional demand for thiamine is closely related to caloric intake. If beriberi causes sudden infant death, then its epidemiology is identical to that of modern SIDS. Recently it was shown that some infants who die from SIDS have very high concentrations of thiamine in blood12 and the investigators have suggested that this represents thiamine toxicity. Perhaps the mechanism is a biochemical lesion in the activation of the vitamin resulting in accumulation of thiamine in its free unphosphorylated form. This explanation is supported by finding an occasional increase in serum
folate and B12 in the same infants.

Clinically, the effect would be the same as dietary deficiency. In an uncontrolled clinical study13 a group of 12 infants were reported to be relieved of their recurrent episodes of nocturnal apnea after administration of large doses of thiamine. Inactivation of cocar-boxylase was reported in experiments with dogs,14 induced by fractional bleeding. Hypotension occurred in thiamine deficient animals after losing less than 4 percent body weight, and copious intestinal hemorrhage occurred in 86 percent. In thiamine fortified dogs significant hypotension did not appear until after 5 percent loss of body weight, and there was no intestinal hemorrhage. Chronic infantile beriberi, characterized by vomiting, diarrhea, abdominal distension, neck stiffness, convulsions, dyspnea, cyanosis and tachycardia, is similar to the acute form of the disease seen in adults and called Shoshin by the Japanese. The more chronic varieties of the disease in adults are the "wet" or edematous form and the "dry" or polyneuritic type. Although the classic disease is rare in advanced societies today, the important question is whether it is seen in marginal expression and, if so, how common it is. The symptoms of the fully developed condition are so numerous that a review of this nature could not deal with them; nor should it, since older texts are plentiful and clinical and laboratory characteristics well described. There is much clinical evidence that marginal malnutrition is in virtually epidemic form today in the well developed countries, where prevailing attitude denies such a disaster.

Thus the discerning and alert physician who knows the symptomatology of the classic nutritional deficiency diseases is recognizing them every day, and this includes minor expressions of beriberi. It is possible to use beriberi as a model from which we can understand how the body behaves under hypooxidative conditions. To summarize the effects of the disease, it can be stated that it represents a prototype for autonomic dysfunction.15 Autopsy findings clearly showed autonomic neuropathy15 and different stages during life were associated with parasympathetic or sympathetic dysfunction, according to the state of nutritional deprivation or its reversal after therapy began.16 Autonomic dysfunction may be seen in other nutritional deficiency states, arising perhaps because of inefficient use of oxygen in the nervous system. Experimental thiamine deficiency has been induced in human subjects.17 Depression, weakness, parasthesiae, dizziness, backache, hypotonic or painful musculature, cardiac palpitations, pericardial pain (pseudoangina) on exertion, insomnia, anorexia, nausea, vomiting, weight loss, hypotension, bradycardia at rest and tachycardia with sinus arrhythmia on exertion were all seen after severe deprivation for several weeks. Moderate, prolonged thiamine restriction without caloric deprivation resulted in emotional instability, irritability, mood changes, quarrelsome behavior, poor cooperation, fearfulness progressing to agitation and numerous somatic symptoms. The investigators noted that neither severe nor moderate deprivation of this one vitamin produced the classic syndrome seen in beriberi. Such symptoms as these are common in the U.S.A. today, particularly in children and adolescents, but are frequently considered to be the normal behavior of youth and excused as such. A vast industry has been built around the cult of sugar, and "soft" drinks are encouraged in excess in preference to "hard" alcohol. Society condones the huge intake of sugar as a source of "quick energy" and fails to recognize that it becomes a drug under these circumstances. It is apparent that an important cause of widespread lack of discipline and irrationally abnormal behavior can be traced to nutritional sources.

This 20th century paradox has been emphasized18 by showing that such behavior could be correlated in some youngsters with an abnormal red cell transketolase and that the response to dietary change could be monitored by this relatively simple laboratory test. The generic symptoms of beriberi may be considered in reference to increased naked calories, particularly from refined carbohydrate, which may be ingested easily in the form of fruit drinks, carbonated beverages, milk, and many other readily available and extremely alluring liquids, many of which are addictive. Thiamine requirement is dependent upon calories ingested, particularly those from carbohydrate. Hence thiamine analysis of diet may appear to be adequate unless this ratio is considered. This was illustrated in a report19 of a patient receiving intravenous fluids as the sole source of nutrition. Though the fluid included 24 mg of thiamine a day, Wernicke encephalopathy was found at autopsy, a disease which is known to be closely associated with thiamine deficiency. Two brothers were reported20 with nausea and vomiting after mild exertion. Calf tenderness, edema, pericardial effusion increased cardiac output, tachycardia, abdominal pain, loin pain, elevated pulse pressure and acidosis were all typical of acute beriberi. The conclusion was that this disease was a familial unknown form of cardiomyopathy. A nutritional history was not given and it is suggested that this illustrates the clinical myopia in considering the possibility of severe nutritional disease as a differential diagnosis in modern developed societies.
I was recently told about benfotiamine as an aid in overcoming things like diabetic neuropathy; have you heard of this or looked into it?
Yes, Benfotiamine is a useful source for diabetes blood sugar management and neuropathies.

However, for autonomic dysfunction and other brain-based pathology, lipid soluble thiamine is the only source which can pass the BBB and bathe the central nervous system.

The optimal form used was developed as a pharmaceutical in Japan, and is called tetrahydrofurfuryl disulfide (TTFD). It is also known as "Lipothiamine" or "Allithiamine", and is produced by a company called "Cardiovascular Research". This is the form used at high doses for long periods of time to restart thiamine metabolism.
Why low dose thiamine does NOT work in chronic deficiency states (from the same paper as the above post):

Because of its poor absorption and endogenous activation, physiologic doses of thiamine may be totally ineffective in chronic deficiency states. Japanese investigators have shown that 20 mg of thiamine hydrochloride will result in recovery of as much as 13 mg in the stool.50 There is no known storage mechanism for the vitamin in the body, so dietary sources must be continuously adequate to meet prevailing environmental circumstances. It is suggested that thiamine deficiency could result in a vicious cycle. Increasing failure of absorption would increase the deficiency, resulting in even worse absorption. Thiamine deficient animals excrete in urine an increased amount of creatine relative to creatinine,51 and this may be a reflection of membrane dysfunction, as already discussed. The dose of the vitamin for therapeutic purposes remains an open question, but there is ample reason to give very large doses with complete clinical safety, particularly when biochemical evidence of deficiency is present, or even where a theoretical reason exists. For example, it has been used successfully in treating a child reported to have defective activity of pyruvic carboxylase.52 The authors postulated that increased effectiveness of this biotin dependent enzyme resulted from positive stimulation of acetyl CoA from increased activity of thiamine stimulated pyruvic dehydrogenase. This then caused increased anaplerotic gluconeogenesis and relieved hypoglycemia in the patient. It is possible that stimulation of the carboxylase with biotin might have produced the same result, but this was not attempted in this case. A middle aged woman had complained for many years of symptoms considered to be neurotic in character. Tenderness in both gastrocnemius muscles, a physical sign seen in beriberi, suggested an underlying biochemical defect. Urine contained a large amount of TTP inhibitory substance7 and her symptoms were appreciably improved with megadoses of thiamine hydrochloride. One month later the urine test for inhibitor was negative (Lonsdale, D. Unpublished observations 1982). Perhaps other similar cases are common and detection of an underlying biochemical abnormality becomes a matter of considerable therapeutic importance.
Thiamine supplementation

Thiamine can be supplemented in various forms. The main form found in supplements is thiamine hydrochloride, which has fairly low bioavailability. Another form is benfotiamine, which is useful for certain purposes. However, the most superior (by far) is allithiamine/lipothiamine/tetrahydrofurfuryl disulfide. This can readily traverse cell membranes and enters the brain and central nervous system.

It should be noted that several of the enzymes which use thiamine also use magnesium and other B vitamins. Thiamine supplementation should be accompanied by magnesium, and likely the whole spectrum of other B vitamins.

One article written by Dr Lonsdale explains the nuances of supplemental forms:

Navigating Thiamine Supplements
Author: Derrick Lonsdale
Thiamin(e), vitamin B1, is spelled with and without an ‘e’. Originally thought to be an amine, the ‘e’ was dropped when the formula became known, but the spelling using the ‘e’ is still used in many texts and across the internet. We spell it with the ‘e’ on this site because of the enhanced search characteristics e.g. thiamine ranks higher than thiamin on search engines. In addition to the discrepancies in spelling, there is quite a bit of confusion surrounding this vitamin and its derivatives used in supplements. Even the most astute readers will find navigating the world of thiamine supplements confusing. For that reason, this post will address some of the more important issues concerning these supplements.

Thiamine Chemistry
In order to understand the writing that follows, I must try to show this formula.

Please excuse this presentation of the thiamine formula. It was made from the Apache Open Office Drawing file. Its representation is incomplete because it does not show the “double bonds”, but it illustrates that the atoms that bind together to form thiamine are in “two rings”. The 6-sided ring on the left is called a pyrimidine ring and the 5-sided one on the right is called a thiazole ring. The CH2 that joins them is called a methylene bridge. This is the naturally occurring thiamine that we must obtain from our diet. Its deficiency causes the classical disease known as beriberi. It is important to understand the atomic construction of thiamine in the discussion that follows concerning its derivatives.
The Vitamin B Research Committee of Japan, a group of university-based researchers, set out to study beriberi in detail, trying to find the best method of treatment for this disease which had been a scourge in Japan for thousands of years. Without covering the specific details, they found that thiamine was converted to a disulfide derivative by an enzyme found in garlic. Because this occurred in other members of the allium species of plants, they called it allithiamine. Thinking at first that thiamine had lost its biologic activity, when tested in animals the new compound was found to have a greater biologic activity than the original thiamine. It was found that the thiazole ring had been opened, creating a disulfide. They began a research program to synthesize a whole group of thiamine disulfides, two of which are shown below.

Although the arrangement of the atoms is different from the thiamine diagram, the important thing to notice is that the thiazole ring (right side) has been opened, creating a disulfide, including what is known as a prosthetic attachment (the part attached to the disulfide).

A disulfide is easily reduced (S-S becomes SH) when the molecule comes into contact with the cell membrane. The result is that the prosthetic group is removed and left outside the cell. The remainder of the molecule passes through the cell membrane into the cell. The thiazole ring closes to provide an intact thiamine molecule in the cell. It is inside the cell where thiamine has its activity and so this is an important method of delivering it to where it is needed. It is this ability to pass through the lipid barrier of the cell membrane that has caused allithiamine to be called fat-soluble. It only refers to this ability, however. It is soluble in water and can be given intravenously.

This “fat solubility” is extremely important because dietary thiamine has to be attached to a genetically determined protein, known as a transporter, to gain entry to cells. There are known to be diseases where the transporter is missing. Affected individuals have thiamine deficiency that does not respond to ordinary thiamine and are usually misdiagnosed. Therefore, a disulfide derivative that does not need the transporter is a method by which thiamine can be introduced to the cell when the transporter is missing. There is no difference between allithiamine and thiamine from a biological activity standpoint. It is this ability to pass the active vitamin through the cell membrane into the cell that provides the advantage.

I performed animal and clinical studies with thiamine tetrahydrofurfuryl (TTFD) for many years and found it to be an extremely valuable therapeutic nutrient. Any disease where energy deficiency is the underlying cause may respond to TTFD, unless permanent damage has accrued. Dr. Marrs and I believe that energy deficiency applies to any naturally occurring disease, even when a gene is at fault. For example, Japanese investigators found that TTFD protected mice from cyanide and carbon tetrachloride poisoning, an effect that was not shown by ordinary thiamine (Fujiwara, M. Absorption, excretion and fatal thiamine and its derivatives in the human body. In Shimazono, N, Katsura, E, eds. Beriberi and Thiamine. (pp 120-121) Tokyo, Igaku Shoin Ltd. 1965). They exposed a segment of dog’s intestine, disconnected it from its nerve supply and found that one of the disulfide derivatives stimulated peristalsis (the wavelike movement of the intestine). It is more than likely that TTFD could be used safely in patients with post operative paralysis of the intestine (paralytic ileus).
Other Derivatives
The Japanese investigators made many disulfide derivatives, testing them individually for their biologic activity. They found that thiamin propyl disulfide gave the best results, but unfortunately gave both treated animals and human subjects a pervasive body odor of garlic. They went on to create TTFD with a deliberate attempt to remove the garlic odor and the commercial product was named Alinamin F (odorless). This is by far the best of the disulfide derivatives. Besides the trade name of Alinamin, the Japanese product, TTFD is sold as Lipothiamine in the United States.

S-acyl derivatives
The Japanese investigators synthesized a whole series of thiamine derivatives where the prosthetic group was attached to the carbon atom (bottom right C on the thiazole ring). They are all so-called open ring derivatives but the prosthetic group has to be separated by an enzyme in the body for the thiazole ring to close. The best known of these is known as Benfotiamine and several papers have been published concerning its benefits in the treatment of neuropathy. It has also been published that it does not cross into the brain, whereas TTFD does and this seems to be the major difference between Benfotiamine and Lipothiamine. Benfotiamine, a synthetic S-acyl thiamine derivative, has different mechanisms of action and a different pharmacological profile than lipid-soluble thiamine disulfide derivatives. It is predictable that TTFD would be the best choice since it has beneficial effects both inside and outside the brain and it certainly needs to be explored and researched further as a very valuable therapeutic agent.

Thiamine Salts
Thiamine is found in health food stores as thiamine hydrochloride and thiamine mononitrate. These are known as “salts” of thiamine. Like dietary thiamine, they require a protein transporter to get the vitamin into the cell. Their absorption used to be thought to be extremely limited, but megadoses are effective in some situations. The absorption of salts is therefore inferior to that of the thiamine derivatives discussed above. They are all so-called “open ring (thiazole)” forms of thiamine and represent the most useful way of getting big doses of thiamine into the cell. The reader should be aware that when we talk about big doses of a vitamin, it is being used as a drug. Although they can be used for simple vitamin deficiency, their medical use goes far beyond that because they can be effective sometimes when thiamine absorption is genetically compromised.
Thiamine Testing - Why I would NOT recommend or trust average blood/urine measurements of thiamine status

Unfortunately, testing for thiamine is complex. Simple blood or urine measurements are measuring the inactive forms of thiamine which are present at basal levels, and do not give us any indication of whether thiamine is being used biochemically inside the cells. The various transporters for thiamine, along with the enzyme complexes which use it, can become "sluggish" after long-term insufficiency.

Dr Lonsdale found that when someone is chronically low, the proteins which use thiamine become less active, less sensitive, and perhaps lower in number. This makes sense, since if you are not using much of a protein, then why would the body choose to invest energy to produce lots of it?

Interestingly, he found that only by megadosing thiamine could you re-sensitise the enzyme complexes and transporters to begin working efficiently. Sort of like sending a message of nutrient abundance to the system - so that everything can become upregulated and start working properly again. Of course, this can take some time.

Historically, the test used to measure functional thiamine status was a combination of the erythrocyte transketolase activity (TKA) coupled with the thiamine pyrophosphate effect (TPPE). The EKA test measures to activity of transketolase, which is an enzyme which uses thiamine as a cofactor. Theoretically, low TKA would indicate poor thiamine usage. However, TKA can be ordinary in some individuals who still are low in thiamine. The TPPE measures how much thiamine is taken up by cells for use. A low TPPE after a loading dose indicates that the cells are sufficiently full of thiamine, and do not require any more. A high TPPE means that cells readily take up thiamine and indicates deficiency.

Together, these tests provide functional information on how much cells need thiamine, and also how well they can utilise them.

Unfortunately, the lab which used to run both tests has shut down. Now, there are only one or two which measure TKA, without running the TPPE simultaneously. This means that solely relying on TKA can give false information of thiamine adequacy.

Instead, liquid chromatography/tandem mass spectrometry can be used to measure thiamine inside the cell of a whole blood sample with high accuracy. Although this is not perfect, I believe it can give a good measurement. The one lab that I know if who performs this test is called "LabCorp" and they are based in the US. The sample requires 1ml of frozen blood, which is fairly simple to collect.

Here is a link for the test: _121186: Vitamin B1, Whole Blood | LabCorp
Low carbohydrate diets & ketogenic diets use half as much thiamine

Due to the biochemistry, ketogenic diets use around half the amount of thiamine than ordinary carbohydrate diets. This means that low carbohydrates spare thiamine. Aside from the clear benefits of ketones in many people, might the reason why some people benefit so much from lowering carbohydrates be due to thiamine deficiency, and an inability to process carbohydrates because of that? This would make sense, at least in some situations.

A brief overview follows:

1. Thiamine is a cofactor for Pyruvate dehydrogenase, which converts pyruvate (from glucose) into acetyl coA. This is the entry point into the citric acid cycle and only occurs with glucose. This makes thiamine essential for the metabolism of glucose.

2. Thiamine is also a cofactor for alphaketoglutarate dehydrogenase, which is involved in the processing of both glucose AND fat (in the form of acetyl coA). This also makes thiamine essential for fat metabolism

When on a ketogenic diet, energy is processed slightly differently. Instead of producing pyruvate from glucose to make acetyl coA, the majority of acetyl coA is coming from the breakdown of fatty acids via beta oxidation.

In essence, this simply means that ketogenic diets probably use around half of the thiamine when compared to carbohydrate rich diets. Hence, if there is underlying thiamine deficiency, this may render ketogenic diets more beneficial.

Chris masterjohn made a video about this very topic. He mentions mold toxicity, thiaminases in foods, and also touches upon the sulfur issue pointing out that excess sulfite is a potential issue. Anyone with problems metabolizing sulfur in the gut (to produce hydrogen sulfide, or sulfite) should think about thiamine. For anyone who didn't catch up with the H&W show with Stephanie Seneff, make sure to listen to it here. We spoke about how glyphosate, the common herbicide, can screw with someone ability to process sulfur. This can lead to excess sulfite, hydrogen sulfide, and low molybdenum, which could theoretically also contribute to the thiamine issue.

I have attached Chris Masterjohn's video below for anyone who wants the details:


Dr. Berg talks about vitamin B1 (Thiamine). It is one of the nutrients that is most depleted by consuming carbohydrates and a cofactor of 5 key enzymes in the mitochondria. Vitamin B1 deficiency is called Beriberi. He also discussed about the several functions of vitamin B1.
B1 Functions: 1. Makes myelin and helps maintain energy
2. Protects the cell (mitochondria esp.) from the damage of high sugar
3. Considered a nerve vitamin
4. Rids lactic acid (Reduces lactic acidosis)
5. Help factor in turning food into energy (Controls 4 mitochondrial enzymes)
6. Prevents damage to mitochondria

Btw, I started taking B1 since last week - this
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Wanted to say thanks for this thread. I have a whole bunch of the symptoms described. The cramping in the calves (especially after exercise, or after eating too much sugar) is especially interesting, and has been ongoing on and off for years (potassium is the only thing that fixes it regularly).
I had taken benfotiamine in the past, but it caused issues. Reading that it needs magnesium I took the two together (low dose mag) for a month or so and my physical energy has been fantastic. Without the magnesium it would give me migraines.
I've found I need the occasional dose of vitamin C with this too, as I noticed my gums where receding a bit a week or two in to taking it.
If I remember correctly smoking also decreases B1 status, so is probably important if you are a smoker.

The lower part of the human brain that controls the autonomic nervous system is exquisitely sensitive to thiamine deficiency. It produces the same effect as a mild deprivation of oxygen. Because this is dangerous and life-threatening, the control mechanisms become much more reactive, often firing the fight-or-flight reflex that in the modern world is diagnosed as panic attacks. Oxidative stress (a deficiency or an excess of oxygen affecting cells, particularly those of the lower brain) is occurring in children and adults. It is responsible for many common conditions, including jaundice in the newborn, sudden infancy death, recurrent ear infections, tonsillitis, sinusitis, asthma, attention deficit disorder (ADD), hyperactivity, and even autism. Each of these conditions has been reported in the medical literature as related to oxidative stress. So many different diseases occurring from the same common cause is offensive to the present medical model. This model regards each of these phenomena as a separate disease entity with a specific cause for each.
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.

I found the following to go with the above:
The Impact of Thiamine Treatment on Generalized Anxiety Disorder
ABSTRACT Objective: Patients with generalized anxiety disorder (GAD) are fearful. They constantly worried about minor matters, and they anticipate the worst. The GAD is diagnosed when a patient experiences excessive anxiety and worry for at least 6 months. The cause of GAD is unknown. In the present paper, we discuss patients with GAD who have low levels of thiamine in their bloods. We also discuss the role of thiamine in the pathogenesis and treatment of GAD. Methods:We examined 9 patients (6 males and 3 females) who met the DSM-IV-TR diagnostic criteria for GAD. These patients had no history of alcoholism. Their ages ranged from 57 to 83 years old (mean age –72.8 ± 2.9 years). All of the pa-tients had low blood thiamine levels (mean –25.1 nmol/L ± 6.0 nmol/L; normal level—70 nmol/L - 180 nmol/L). Par-ticipants completed the Hamilton Anxiety Rating Scale (HARS) for anxiety before and after thiamine treatments. All of the patients received daily thiamine 100 mg intramuscularly. Results: Thiamine supplementation significantly improved HARS scores, increased both appetite and general well-being, and reduced fatigue in patients with GAD. Interestingly,these patients were able to discontinue taking anxiolytic and β-blocker medications. Conclusion: Parental thiamine significantly affects patients with GAD.
Thiamine deficiency is characterized by a selec-tive loss of neurons in the hypothalamus, midbrain, brainstem and cerebellum of humans and animals [16,17]. Encephalopathy due to thiamine deficiency may involve impairment of the function of cholinergic neurotransmit-ters. Thiamine is a coenzyme that is required for the synthesis of acetylcholine (ACh). The synthesis of ACh is impaired in the brains of thiamine deficient rats [18], which leads to a significant reduction of neural ACh lev-els [19]. Using biochemical analyses, Mair et al. [20] demonstrated that the concentration of norepinephrine was significantly reduced in the brain of rats’ (at both the cortex-hippocampus boundary and in the olfactory bulbs). Furthermore, this reduction in norepinephrine was accompanied by a concomitant decrease in learning and memory in the thiamine-deficient rats. Animal studies have suggested that thiamine is involved in the presynaptic release of ACh. Thiamine binds to nicotinic receptors and may exhibit anticholinesterase activity [21]. More-over, thiamine deficiency induces an early central mus-carinic cholinergic lesion [22]. The muscarinic cholinergic synaptic receptor densities were reduced by 30% in the homogenates of the hippocampus and by 40% in the homogenates of the temporal cortex of alcoholics [23,24]. Patients with GAD had fewer α2-adrenergic receptors than did control subjects [25]. A blunted growth hormone response to clonidine in patients with GAD indicated that these patients exhibit decreased postsynaptic α2-adrener-gic receptor sensitivity [26].

Thiamine deficiency activates hypoxia inducible factor-1α to facilitate pro-apoptotic responses in mouse primary astrocytes

Thiamine is an essential enzyme cofactor required for proper metabolic function and maintenance of metabolism and energy production in the brain. In developed countries, thiamine deficiency (TD) is most often manifested following chronic alcohol consumption leading to impaired mitochondrial function, oxidative stress, inflammation and excitotoxicity. These biochemical lesions result in apoptotic cell death in both neurons and astrocytes. Comparable histological injuries in patients with hypoxia/ischemia and TD have been described in the thalamus and mammillary bodies, suggesting a congruency between the cellular responses to these stresses. Consistent with hypoxia/ischemia, TD stabilizes and activates Hypoxia Inducible Factor-1α (HIF-1α) under physiological oxygen levels. However, the role of TD-induced HIF-1α in neurological injury is currently unknown. Using Western blot analysis and RT-PCR, we have demonstrated that TD induces HIF-1α expression and activity in primary mouse astrocytes. We observed a time-dependent increase in mRNA and protein expression of the pro-apoptotic and pro-inflammatory HIF-1α target genes MCP1, BNIP3, Nix and Noxa during TD. We also observed apoptotic cell death in TD as demonstrated by PI/Annexin V staining, TUNEL assay, and Cell Death ELISA. Pharmacological inhibition of HIF-1α activity using YC1 and thiamine repletion both reduced expression of pro-apoptotic HIF-1α target genes and apoptotic cell death in TD. These results demonstrate that induction of HIF-1α mediated transcriptional up-regulation of pro-apoptotic/inflammatory signaling contributes to astrocyte cell death during thiamine deficiency.

So what if B1 levels in the brain are low enough to register as 'hypoxia' in the brain, would that not cause generalised anxiety and chronic activation of fight/flight? A constant unknown fear/fearfulness?
I've been taking Allithiamine for several weeks now, and this seems to be the case for me. I'm more able to move forward without anxiety, my neuroticism (in the form of over thinking) has dropped to next to nothing, and I seem to be left with just the learned patterns of behaviour that developed around this (the difference being I seem to be able to move past them now).
Adding in a low daily dose of B2 after the post in the MTHFR thread (MTHFR mutations) has also helped a lot (and incidentally brought up unresolved issues around anger and moving forward).

If anyone decides to try these, watch out for detox symptoms, unbalancing of other B vitamins and lack of magnesium/vitamin c. And if deep healing is occurring, watch out for lack of potassium.

An additional thought I had while writing this reply, what role does lack of B1 play in cancer? If I am remembering correctly, cancer is partly due to the cells inability to produce energy and devolving into 'cancer' in order to survive. Could B1 be a missing ingredient here? Do cancer patients have low B1?

I was recently told about benfotiamine as an aid in overcoming things like diabetic neuropathy; have you heard of this or looked into it?

I'm not sure if this would help, but Dibencozide can be good at helping peripheral nerves to regenerate. Watch out for worsening of symptoms before they get better (it's part of the healing unfortunately). See this post: MTHFR mutations
Well, I got a bottle of it and have been taking it faithfully and I think I have to agree: a definite improvement in my energy and my legs feel lighter, too. I already take magnesium nearly every night anyway, and 5 grams of vit C with glycine in the morning with breakfast every day.
Thanks for sharing, Keyhole! I've noted that I have some of the symptoms associated with Thiamine deficiency, and more recently some hair loss on my legs that started last year that I couldn't make sense of, and a 'shakiness' in my nervous system that's been really bothering me as of late. I've always struggled with adapting to the cold or fluctuations in temperature and thought maybe it was the cold baths even though I feel great afterwards, or somehow my testosterone levels were dropping due to stress in the last few months, not to mention the horrific weather here in Canada this past while with very little sunlight and grounding, but I eat a lot of meat and fat and try and lift heavy weights at least once, sometimes twice a week. So I just ordered two bottles of the Allithiamine and will megadose it until I finish the bottles and see if there are any changes.
Hi RedFox,

I'm glad to hear that you have experienced benefits with thiamine. I will attempt to "flesh out" your questions a little bit with some details.

So what if B1 levels in the brain are low enough to register as 'hypoxia' in the brain, would that not cause generalised anxiety and chronic activation of fight/flight? A constant unknown fear/fearfulness?
I spoke about this briefly in that health and wellness video we made, but I will explain a bit further. In short, the answer to your question seems to be a solid YES.

Here is an excerpt from an article I wrote on this:
Thiamine's vital role in glucose metabolism renders certain parts of the brain uniquely sensitive to thiamine deficiency. The brain utilizes a large portion of the total pool of body glucose for its metabolic requirements, both in the synthesis of ATP and also as substrate for the formation of various neurotransmitters, including acetylcholine.

Thiamine is needed for glutamate dehydrogenase, an enzyme which breaks down the excitatory neurotransmitter glutamate. Thiamine deficiency has been shown to reduce acetylcholine synthesis in the brain and induce excessive glutamate release, effectively paving the way for neuronal excitotoxicity and dysfunction.

Thiamine also appears to be required for the activation of other vitamins. The activation of vitamin B6 to Pyridoxal-5-Phosphate is achieved by the enzyme pyridoxal kinase, and this enzyme may be downregulated in thiamine deficiency. Low levels of activated B6 disrupt the enzymatic breakdown of tryptophan in the brain and may contribute to accumulation of neurotoxic compounds such as quinollinic acid, further contributing to the brain burden. Thiamine is also likely involved in nerve conduction, although the mechanisms are not well elucidated at this point.

The essential roles played by thiamine in the brain and nervous system mean that insufficient amounts can have drastic consequences for practically every other system in the body. The autonomic nervous system is a branch of the central nervous system responsible for maintaining homeostatic control and coordinating involuntary physiological processes such as heart rate, body temperature, and digestion (among many other processes). Through shifting the balance between sympathetic and parasympathetic activation, this system allows the body to adapt to varied environmental stimuli and effectively stay alive.


The control centers for autonomic regulation are located within lower regions of the brain, the brain stem and the limbic system. These areas are particularly sensitive to thiamine deficiency because of their high rate of oxygen consumption. Defective energy metabolism in these regions can result in autonomic dysfunction, or "dysautonomia", characterized by sympathetic or parasympathetic dominance and faulty homeostatic control. The early stages of thiamine deficiency can produce dysautonomic symptoms. Dysautonomias can manifest in a variety of ways, with symptoms ranging from resting tachycardia, cardiac arrhythmias, bowel dysmotility, irregular sweating, gastroparesis, and orthostatic hypotension. Postural Orthostatic Tachycardia Syndrome, a prime example of dysautonomia, can be caused by thiamine deficiency.
Aside from the symptoms/manifestations mentioned above, one of the earliest signs of defective energy metabolism in the brain is anxiety and fearfulness.

An additional thought I had while writing this reply, what role does lack of B1 play in cancer? If I am remembering correctly, cancer is partly due to the cells inability to produce energy and devolving into 'cancer' in order to survive. Could B1 be a missing ingredient here? Do cancer patients have low B1?
This topic is understudied. There is a very strong theoretical role in cancer, although not many studies. There are some which show low dose thiamine can be detrimental, whereas high dose is inhibitory for cancer cells. Here is an article by Dr Lonsdale on that: A Role for Thiamine Deficiency in Cancer - Hormones Matter

From what I understand, there have been cases of thiamine deficiency reported in cancer. However, thiamine is usually not tested for, and if they do actually test it, they usually run the wrong kinds of tests anyway. Blood B1 testing is quite inaccurate, and the best test is a red blood cell transketolase coupled with a thiamine pyrophosphate effect - run on the same sample. Unfortunately, this test is not even offered by any lab anymore, and I doubt hospitals will be running this test.

However, looking at the compound called Dichloroacetate (DCA) - which is very effective in some cases of cancer... it operates based on a similar mechanism as thiamine. In fact, the suppliers of DCA actually recommend taking thiamine alongside the compound.

If you look at cancer metabolism (in a very simplified manner) there is a problem with converting glucose (pyruvate) into the next step in oxidative metabolism (called acetyl coA). If glucose is not converted into this metabolite, then it is shunted toward producing lactate. The "block" is on the enzyme pyruvate dehydrogenase.


The enzyme which takes pyruvate and converts into acetyl Co A is call pyruvate dehydrogenase (PDH).

The main cofactor for this enzyme is Thiamine, but dichloracetate is also a potent pyruvate dehydrogenase activator. Stimulating this enzyme allows the cells to begin using oxygen and producing much higher levels of ATP to start functioning once again as they should.

So with that in mind, I think that thiamine is potentially implicated in cancer, if only as a contributing factor, at least in some cases!
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