thiamine - Page 7

Energy Loss as a Cause of Disease

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I graduated from London University in 1948 and retired at the age of 88 years in 2012, so I have seen some remarkable changes in the practice of medicine. I have entered many reports on this website, detailing what should be a medical revolution. One of the best professional associations that I have ever made has been with Dr. Chandler Marrs, the editor of Hormones Matter. Both of us have tried hard for years now to explain the details of our experience, hoping to reach those many individuals who are being misdiagnosed and treated extremely badly. My recent experience has come from retiring in an excellent retirement home.

I am surrounded by people of my age, many of whom are taking numerous medications to treat their symptoms. The most recent example was in a gentleman who has been in and out of hospital several times with a set of symptoms whose origins are clearly due to cellular energy deficiency. When approaching him as a friend and asking him how he is faring, he told me that his list of symptoms remains as a medical mystery. In addition, two women, with whom I had become acquainted, had symptoms that were similar to his. One of them passed away without a diagnosis and the other one is presently being treated symptomatically. The reader might well ask the obvious question as to what happens if I should state an opinion. The answer is very simple; the offered explanation would fall on deaf ears. Unfortunately, this is eminently predictable and is the major reason why innovation that contradicts the medical standards of the day is regarded as heresy throughout history. Of course, “new” concepts must be backed by evidence to become accepted. We are trying to provide the evidence on this website for defective cellular energy as a major cause of disease.

Heresy in Medicine

I am pretty sure that I may have recorded the story of Dr. Semmelweiss on this website but it is a story so poignant that it is well worth repeating. It is a story that illustrates the difficulty of introducing innovation in medicine, or indeed anything new. Semmelweiss was a German Hungarian physician who lived before the discovery of microorganisms. He presided over an obstetrics ward in which there were perhaps 10 beds on one side of the room and 10 beds on the other. The physicians of the day would come in and deliver their patients without washing their hands or changing their clothes. It is difficult for some people to comprehend the total lack of any form of hygiene that doctors practiced before microorganisms were discovered. Semmelweiss observed that the physicians would often come into the ward directly from the morgue and concluded that they must be bringing something in on their hands that caused the patient to die from child-bed fever, as it was then called. From this observation, he organized the first controlled experiment in medicine. He directed the physicians on one side of the ward to wash their hands in chlorinated lime before they delivered the patient. The physicians operating on the other side of the ward carried on in the same old way.

The results were dramatic as we would expect today. Child-bed fever was reduced by 85% when the physicians washed their hands. The medical profession, including his colleagues, said that “because Semmelweiss could not explain what was on the hands of the physicians, his explanation was unscientific”.  It is important to note that they simply ignored the obvious benefit. He was discharged from his job and excluded from the hospital. He died as a pauper in a mental hospital.

The major point is that the concepts of the medical profession of the day were completely wrong,  He had clashed with the current medical model that was then accepted by mainstream medicine as “the truth”.  If we apply this lesson to today’s model of medicine, it is impossible not to wonder if the outstanding principle of the use of pharmaceutical drugs in medical practice is fundamentally wrong. Is treating symptoms without addressing their underlying cause scientifically justified? A glance at the Physicians’ Desk Reference that supplies information on the many prescription drugs available might put off the reader’s use of a prescription. For each drug there is a short description of its use, often with an admission that its action is only partly understood. Then follows a page or two describing its side effects. Does this not suggest that the use of pharmaceuticals to treat symptoms causes more problems than it solves? Are we approaching another Semmelweiss moment in medical history?

Envisioning an Alternative Approach

I envision the profession of medicine as like a traveler, hoping that the road leads to the best solution in the treatment of disease. For my analogy the traveler comes upon a fork in the road with a signpost. One sign says “Kill the Enemy“, (referring to the discovery of infecting microorganisms) and our traveler takes that road because the sign for the other fork is blank. “Kill the enemy” became the first paradigm (a model accepted by all) in medicine. We had to find means of killing bacteria, viruses, cancer cells or any other attacking agent and many years were spent in trying to find ways and means of doing this without killing the patient. The information was hard won and a lot of patients suffered untold hardship and even death until the discovery of penicillin. This in itself “proved that the correct fork in the road had been chosen”. As we know, this discovery led to the antibiotic era, but even these drugs are running into new problems.

To continue the analogy, our traveler goes back to the fork in the road and finds that the other sign has now been filled in. It reads “Assist the Defenses” and I believe that it should represent a new paradigm. Louis Pasteur and his colleagues discovered the disease producing microorganisms, but on his deathbed he is purported to have said “I was wrong, it is the terrain that matters”.  He meant that the terrain represented the defensive functions of the body that should be assisted.  Perhaps he formulated what I believe must be the second paradigm in medicine.

The Second Paradigm

How should we approach the introduction of this concept? It seems to me that the problem is that few people are aware of the basic principles of body function so I must provide another analogy that I have used before in Hormones Matter. The human body can be compared with a symphony orchestra in which part of the brain represents the conductor. The organs represent the banks of instrumentalists that make up the orchestra. Like the instrumentalists who, although they are experts in their own right, still have to obey the conductor, the cooperative function of all our cells must obey the automated signals from the brain to play the symphony of health. Each of us comes with a “blueprint” that is our inheritance and although we are all the same in principle, we are all uniquely different because of accidental or inherited variations in the “blueprint”. The autonomic (automatic) nervous system, controlled by the lower part of the brain, coordinates the function of organs in the body, behaving like a computer. It receives sensory information, enabling it to receive from and send signals to those organs, thus collectively playing the symphony. The endocrine system consists of a group of glands that produce hormones. Their function, also under the command of the brain, is to release the hormones that travel in the bloodstream to the organs and are thus signaling agents.

The voluntary nervous system, controlled by the upper part of the brain, gives us what we call willpower. The voluntary and autonomic systems are completely separate but have many connections, so some of the reflex activity conducted by the autonomic system can be influenced and overridden by an act of will. Perhaps the best example is the fight-or-flight reflex that is activated by a sense of danger but can be modified voluntarily. For example, the reflex response to an insult might result in violence if it is not modified by the voluntary system. Assuming that the blueprint provides all the machinery of survival, all it requires is energy.

The Production and Consumption of Energy

We cannot survive without food and water. There is, however, an overall tendency to ignore the appropriate nature of the food, in spite of the fact that it provides the fuel that gives us energy. Taste is the dominating influence, driving sales for the food industry without an appropriate consideration of calorie/micronutrient balance. It is clear that “vitamin enrichment” has hoodwinked us. Chemical energy is liberated from oxidation of fuel (food), but it must be transduced in the body to an electrical form of energy that enables us to function. The electrocardiogram and the electroencephalogram are both tools that identify the electrical nature of this function. The human body is well equipped with an enormously complex system of defense but its complexity requires energy that has to be increased when a person is under any form of physical (trauma, infection, severe weather etc) or mental (divorce, grief, business deadlines etc) stress. It is very important to think of stress as a “force” to which we have to adapt. The lower part of the brain, acting like a computer must automatically organize the complex defense machinery, including the immune system, so its energy requirement exceeds that required by the rest of the body and must be automatically increased to meet the required response to stress. What we call the “illness” (fever, swollen glands, inflammation, etc.) is evidence that the brain has gone into action to generate a defense. In fact, war is declared and the result is recovery, death, or prolonged chronicity where the attacker has not been completely defeated. A nutritionally deprived individual cannot muster the energy to initiate defensive action and may explain why stalemate or the stress of vaccination can be evidence of failure to adapt.

Of all the aspects of health maintenance, exercise, appropriate rest, socialization and fulfilling job assignment, perhaps nothing is more important than the nature of the food. Genetics, stress and nutrition are visualized as the “three circles of health“. I want to illustrate this relationship by retelling an incident that we reported in “Hormones Matter” a few years ago. The mother of an 18-year-old girl reported by email that her daughter had received the HPV vaccination (to increase immunity against the virus associated with cancer of the cervix) four years previously. Throughout the four years she had been more or less crippled by a condition known as postural orthostatic tachycardia syndrome (POTS). She had been seen by many physicians without any success. Her mother did her own research work and had come to the conclusion that her daughter had the vitamin B1 deficiency disease known as beriberi and she wished to prove it. A blood test clearly showed that she was correct. Because of this, several young people who had also suffered from POTS following the HPV vaccination were also found to be thiamine deficient. One young woman who had not received the vaccination also had POTS and was found to be thiamine deficient. One of the observations that had puzzled the parents of these young people was that, without exception, each of them had been recognized as an exceptionally good athlete and student before they had received the vaccine. We deduced from this that a superior brain was more likely to consume  more energy than someone less well endowed, thus increasing the risk of poor  nutrition and the ability to adapt to a potentially powerful stressor.

Although proof is not possible, we have accumulated a lot of evidence that has enabled us to hypothesize that the vaccination acted as a nonspecific form of stress in people who were marginally thiamine deficient, but asymptomatic before receiving the vaccine. For the youngster who had not received the vaccine, but who had succumbed to POTS, poor nutrition alone, with or without genetic risk, had to be blamed. Genetics, stress and nutrition are visualized as the “three circles of health“.

The Medical Revolution

We are proposing that energy loss is the major cause of disease and that it results commonly from a less than ideal diet or dysfunctional mitochondria. Failing in the balanced need of the caloric content and the  necessary non-caloric vitamins and minerals for efficient oxidation, the result of poor diet is energy deficiency. There is considerable evidence that thiamine plays a vital part in both the production of chemical energy (ATP) and its conversion to electrical energy for bodily function. We have concluded, also from evidence, that genes may or may not usually cause disease on their own. Either nutrition or overwhelming stress may be variable factors that create genetic risk. The prevailing addiction to sugar creates a variable degree of thiamine deficiency by the catatorulin effect. We further hypothesize that a mild to moderate thiamine deficiency leads to a gradual decay in the efficiency of the critical enzyme(s), insufficiently supported by the cofactor(s). Attributing the easily reversible symptoms to other causes and allowing them to continue, leads to chronic disease. This may or may not respond to pharmacological doses of cofactor, used to resuscitate the associated enzyme(s).

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

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This article was first published on July 1, 2019.    

Huntington’s Disease and Thiamine: New Research Finds Link

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Huntington’s disease (HD) is a genetically caused brain disease. The inheritance is an autosomal dominant gene, which means that only one individual, either male or female, can pass the gene to offspring. Albeit rare, it is a neurodegenerative condition, characterized by progressive motor, behavioral and cognitive decline, ending in death. The underlying genetic mutation for Huntington’s was discovered more than 20 years ago, nevertheless, traditional treatment remains focused on symptom management. Chorea (epitomized by an array of bodily twisting movements) is the most recognizable symptom and this does respond to one type of medication, but it is inadequate.

Neuropsychiatric symptoms may precede the classic motor symptoms of the full-blown disease by decades and this may well be extremely important in assessing a newly discovered linkage between Huntington’s disease and thiamine. In the publication, the authors discuss the prospect that megadose thiamine treatment may improve outcomes.  In the abstract, the authors provide a background. “Although promising gene silencing therapies are being tested for Huntington’s disease, no disease modifying treatments are available”. Thus, they turned to a study involving alternative molecular mechanisms that are highly technical and beyond this post. It involved the study of a great number of genes that had been damaged by this mechanism. One of the affected genes was a protein that is one of the essential factors that enable thiamine to enter cells. Because thiamine works inside body cells, its absorption requires a number of these proteins, depending on the part of the body where thiamine becomes essential to its function. They are known as transporters.

This damaged transporter gene, if genetically mutated, causes a biotin (another B vitamin) and thiamine dependent neurological disease (biotin/thiamine dependent basal ganglia [BTBG] disease). These investigators concluded that Huntington’s disease was really a BTBG-like thiamine deficiency and therefore had an easy to implement treatment. This is easier to accept, because of the dramatic publications of Costantini and his coauthors. Starting in June 2015, they published a report that they had found significant clinical Improvement in 50 cases of Parkinson’s disease with high dose thiamine. They have reported similar clinical benefits in Friedreich’s ataxia (another neurodegenerative disease), Multiple Sclerosis and Fibromyalgia, suggesting that each of these diseases, rather than having separate causes, are all energy dependent manifestations of disease.

In my own experience, I was confronted with a young woman who had been diagnosed with Multiple Sclerosis. I treated her successfully with high dose thiamine. She and her husband went to live in Italy for business purposes and she would call me annually for a resupply of nutrients.

I was impressed by the information that neuropsychiatric symptoms can appear in a person decades before the appearance of HD symptoms. It made me wonder whether, in some cases if not all, medical refusal to recognize vitamin deficiency symptoms had resulted in a gradual worsening that eventually became the symptoms of HD. There is no dispute over the genetic background of HD. What I am suggesting is that the abnormal gene requires another “stress” factor to become active like the genetic aspects of diabetes type 1 and possibly type 2.

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

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This article was published originally on November 8, 2021.

Sleep Requires Energy

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It is widely believed that almost no calories are used during sleep. That is incorrect: while the body rests during sleep and energy consumption is not high, it is a long way from zero. A convenient way to measure energy use is known as the “metabolic equivalent” (ME). This is defined as the rate of energy used by a person sitting and awake, the “resting metabolic rate”.  A person riding a bicycle may be using five MEs; a runner, nine or more. A sleeping person uses about 0.9 MEs, so we burn calories when we are asleep about 90% as fast as while sitting on the couch watching television.

Energy conservation is important in sleep, but it’s expenditure is still required. It has been proposed that sleep is a physiological adaptation to conserve energy but little research has examined this proposed function. In one study, the effects of sleep, sleep deprivation and recovery sleep on the whole-body, total daily energy expenditure was examined in seven healthy participants aged 22+/-5 years.  The findings provided support for the hypothesis that sleep conserves energy and that sleep deprivation increases total daily energy expenditure. I read somewhere that an enthusiastic young astronomer decided that sleep was unnecessary and used his telescope for 13 nights without sleeping during the day. He became extremely ill, thus showing the importance of sleep in survival. The recognition that sleep is one of the foundations of athletic performance is vital.

Research in the general population has highlighted the importance of sleep on neurophysiology, cognitive function and mood. In a post on Hormones Matter, we reported several young people who had a post Gardasil vaccination crippling condition that turned out to be due to thiamine deficiency. All of them had been exceptional athletes and students before the vaccination. We concluded that the brain energy requirement for exceptional people put them at greater risk of succumbing to stress if their capacity for MEs was limited, either for genetic or nutritional reasons. We assumed that their thiamine deficiency before vaccination was marginal and either asymptomatic or producing trivial symptoms ascribed to other “medically more acceptable” causes.  The stress of the vaccination required an energy dependent adaptive response that precipitated fully symptomatic thiamine deficiency.  You might say that they were “weighed in the balance and found wanting” as the proverb says.

The Stages of Sleep

Sleep is a complicated process. The first sensation is known as “sleep latency” and registers the time taken from eye closure to falling asleep. The sleep cycle is then divided into five stages, each cycle lasting approximately 90-120 minutes. Stage one is known as light sleep. In stage 2 the brain is resting the parts used when awake. Stages 3 and 4 are deeply restorative. Stage V is known as rapid eye movement (REM) sleep and may be the most important part. Movement of the eyes behind closed lids is observed. The autonomic nervous system is activated for unknown reasons. It is in this stage when we dream and most sleep disorders occur.

Circadian Rhythm

The word circadian means “about 24 hours”. The circadian clock is a complex, highly specialized network in the brain that regulates its day/night metabolism and is a key for metabolic health. It is modulated by behavioral patterns, physical activity, food intake, sleep loss and sleep disorders. Disruption of this clock is associated with a variety of mental and physical illnesses and an increasing prevalence of obesity, thus illustrating that it is dependent on energy balance (production/consumption). Reduced sleep quality and duration lead to decreased glucose tolerance and insulin sensitivity, thus increasing the risk of developing type 2 diabetes. In other words there is a close link between circadian rhythm and available energy . I have seen patients who were unable to take the night shift at work because they were unable to adapt. The increase in obesity has been paralleled by a decline in sleep duration but the potential mechanisms linking energy balance and the sleep/wake cycle are not well understood. An experiment was reported in 12 healthy normal weight men. Caloric restriction significantly increased the duration of deep (stage 4) sleep, an effect that was entirely reversed upon free feeding.

Sleep Apnea

This condition is fairly common in the United States and is probably generally fairly well-known by most people. The patient stops breathing during sleep and may repeatedly awaken with a start. The disease was discovered because a woman reported that her husband kept waking up with a start because “he was affected by an evil spirit”. Fortunately, the physician took her seriously and it led to the studies that determined its cause. Many patients with, or at risk of, cardiovascular disease have sleep disordered breathing (SDB). These can be either obstructive because of intermittent collapse of the upper airway, or central because of episodic loss of respiratory drive. SDB is associated with sleep disturbance, hypoxemia, hemodynamic changes and sympathetic activation. Brainstem dysfunction combined with heart disease is the hallmark of the thiamine deficiency disease, beriberi.

What that means is that there are two types of sleep apnea. In the obstructive type, the tongue falls back into the pharynx and blocks the airway. In the one where there is loss of respiratory drive, the centers in the brain stem are compromised. It is these centers that completely take over the control of breathing when we are unconscious as in sleep. If their supervisory mechanisms fail, breathing ceases. Carbon dioxide concentration increases and stimulates the brain controls that restart breathing. Occasionally these mechanisms are so sick that breathing does not restart. Hence a form of  nocturnal sudden death follows. When we are awake we can override these centers and control our breathing voluntarily. Obesity and obstructive sleep apnea have a reciprocal relationship depending on the regulation of energy balance. When I was in practice I treated several patients with sleep apnea using large doses of thiamine. Because of this I hypothesized that the association of dysautonomia with so many different diagnoses is because of loss of oxidative efficiency and subsequent disorganization of controls that are mediated through the limbic system and brainstem. I came to the conclusion that energy deficiency in the brain was the core issue.

I recently had a letter from the parents of a then five-year-old child who came under my care 35 years ago. She has a genetically determined disorder that affects energy balance and I had treated her by dietary restriction and providing non-caloric nutrients. They informed me that she was doing very well. The condition is known as Prader Willi syndrome, a terminology that indicates that nothing was known about its cause when it was initially described. Today, 10 studies have provided evidence that total energy, resting energy,  sleep energy and activity energy expenditure are all lower in individuals with this syndrome. Dietary discipline and nutritional supplementation had paid off.

An Explanatory Analogy

You may think that comparing the human body with an automobile is manifestly absurd, but the principles that I will use in the analogy are simple.

Fuel

First of all, both use fuel: gasoline is the fuel for a car, but it must be calibrated to the design of the engine, giving rise to the gasoline choices at the pump. Although different forms of human food may be compared to gasoline choices, the primary fuel for our cells is glucose and this is particularly true for the brain. Glucose, a carbohydrate, can be synthesized in the body from other components in the diet and different diets are sometimes used therapeutically. Unlike the car, the human body must derive its “spark plug”  from the food and is the basic reason why organic, naturally occurring, food is a necessity. The food industry cannot imitate or replace it.

Engine

The engine in a car burns gasoline to create energy. It requires spark plugs to ignite the gasoline and waste gases are eliminated through an exhaust pipe.

Every cell in the human body has an “engine”. Without going into details this is known as the Krebs cycle (named after its discoverer). Its objective is to produce energy and glucose has to be “ignited” (oxidized). The oxidation process, while releasing energy, gives rise to carbon dioxide (the “ash”) that is eliminated in the breath. Energy is stored in an eletrochemical form known as adenosine triphosphate (ATP).The nearest parallel would be a battery. It releases an electrical form of energy that is then used for function. Whether we like to recognize it or not, we are electrochemical machines and the only way that we can preserve or retrieve health is by furnishing the complex of ingredients that enable food to be converted into energy.

To continue the analogy, when you put your car in the garage and turn off the ignition the car is technically “dead”. Obviously, we are unable to do that with the human body, but let us make a simple comparison. Supposing for some reason it was desirable to keep the car “alive” when it was in the garage. The engine would continue to run and it would be consuming fuel. Because the body requires energy to remain alive, the “engines” have to continue running, even when we are asleep. This does make sense for the consumption of energy when we are asleep———it keeps us alive !

Transmission

The energy developed from burning gasoline has to be transmitted to the wheels in order to produce the normal function of the car, which is the ability to move. The transmission is a series of levers that are interconnected.

The same is true in the human body, but it is biochemical in nature. A series of energy consuming enzymes use the protein, fat and carbohydrate to build the diversity of tissues that make up the body. Throughout life, cells are destroyed and replaced, so this is a continuous process of energy consumption and repair. Every physical movement, every thought and emotion, consumes energy. Like the transmission in the car, the energy produced by the citric acid cycle engine is consumed in every movement of the body, every thought occurring in the brain and every emotion.

Chassis

The body of a car is just a container on wheels designed to carry around human beings. Its sole function is to move and until we have driverless cars a human being must be the driver.

In comparison, the body of a human being is merely a chassis that carries the brain around. It might be said that the brain can be compared with the car driver and every function of the body is under the command of the brain. Another analogy that I have used is an orchestra where the brain is the conductor and the organs are banks of instruments in which the cells come under the command of the conductor.

Putting It All Together

The 2019 Nobel prize has just been awarded to three scientists who have discovered how our body cells respond to low concentrations of oxygen (hypoxia). The reaction of medical scientists is very positive since this discovery will certainly be applied to the treatment of many diseases. Apparently scientists are already trying to find drugs that will influence this effect. For example, it has long been known that hypoxia will introduce inflammation. My forecast is that the use of nutrients will often correct the genetics by epigenetic mechanisms and this is already under way.

I found the Nobel prize extremely interesting because of a little-known phenomenon that was described by the early investigators of the vitamin B1 deficiency disease, beriberi. They had found in this disease that the arterial concentration of oxygen was low while the venous concentration was relatively high. Arterial blood carries oxygen from the lung to all the tissues of the body. It has to be unloaded into the cells that then use it to produce energy. The venous blood then returns to the lung to be loaded again with oxygen. A relatively low arterial oxygen reflects an inadequate loading at the lung tissues, while a relatively high venous oxygen indicates poor utilization by the cells to which it is delivered. This means that thiamine (vitamin B1) is an essential catalyst in the delivery of oxygen to the tissues. Its deficiency induces gene expression similar to that observed in hypoxia and has been referred to as a cause of pseudo-hypoxia (false hypoxia).

The heading of this article is that sleep requires energy, but I am making the case that being alive and well simply means that oxygen is being consumed efficiently, as long as the “blueprint” of DNA is healthy. It strongly suggests that hypoxia and/or pseudo -hypoxia are the underlying causes of disease and may explain why thiamine and its derivative are such important therapeutic agents.

We Need Your Help

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

Yes, I would like to support Hormones Matter. 

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This article was published originally on October 14, 2019. 

The Speed of Time in Health and Disease

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My father was an economist who came up with a formula for pricing derivatives called the Black-Scholes option-pricing model. He was interested in finance, but his background was physics, and his 1964 Harvard PhD thesis was about artificial intelligence. He instilled in me and my three younger sisters an abiding curiosity about the world, and a willingness to look at things in fresh ways. If I could describe him in two words, they’d be gentle irreverence.

Black-Scholes builds upon the work of others, including Louis de Broglie’s pilot-wave models, the idea of quantum equilibrium, and Brownian motion. De Broglie believed that all matter has wave properties. I am matter. Might I have wave properties, too?

In 2014, while living in a lake house in Dutchess County, New York that had a hidden mold problem, I developed a lot of issues with my health, but doctors couldn’t figure out what was wrong with me. I tried to figure out what was wrong myself, and in this essay, I will share some of what I learned with you.

Oxalate, Time, and Viral Infections

Oxalate is a crystal found in plants capable of photosynthesis. High-oxalate foods include rhubarb, tea, beets, and spinach. It can also be produced endogenously (internally). Both my parents were kidney-stone formers—most kidney stones are calcium-oxalate—and when I was sick, I seemed to do well with a low-oxalate diet.

I noticed it was when I most struggled with oxalate issues (joint inflammation, fatigue, crystals in my urine, pain at the site of old injuries) that I was most likely to experience the reactivation of old viruses. I had mononucleosis in my fourth year of college, and the Epstein-Barr virus (EBV) at times reactivates in me. Viral reactivation also occurs during spaceflight. Astronauts experience time differently than we do. Could the reason their viruses are re-activating have something to do with time?

Oxalate and time
Oxalate Crystal. Image: Facebook, Trying Low Oxalates

What is time? We don’t really have a solid answer at the moment, but it is a rich area of interest and research. Some physics equations that we use to describe the universe work best if we leave time out. But, intuitively—especially since we experience time on a daily basis—leaving it out of the equation does not feel quite right.

What if it is not that time is being left out so much as that it is being compensated for? When time speeds up—light slows down. When time slows down—light speeds up. When time is too fast or too slow, light has to be too slow or too fast, respectively. When light is too slow or too fast, it is not able to appear as itself. Instead of light qua light—light as light—it will appear as … oxalate crystal?

When the Cycle Spins Backwards

Thiamine has been studied extensively by Drs. Derrick Lonsdale and Chandler Marrs, whose book, Thiamine Deficiency Disease, Dysautonomia, and High Calorie Malnutrition, explores how thiamine deficiency alters the functioning of the brainstem and autonomic nervous system by way of metabolic changes at the level of the mitochondria.

I suffered from fatigue, gastrointestinal dysfunction, joint pain, and cognitive loss. The first time I tried high-dose thiamine (vitamin B1), I had a profound recovery. My body tightened, my pain vanished, and I felt clear-headed, strong, and happy.

But, after a few weeks, I hit a wall. Thiamine lost its potency, and I stopped.

A few months later, when I tried high-dose thiamine again, I experienced something odd: a slow-motion grinding in my gut that took my breath away. For lack of a better phrase, it felt as if time were slowing down for me.

Thiamine powers the Krebs (energy) cycle. When I took it the second time around, it felt as if I had eclipsed some limit, and was powering Krebs in reverse. Instead of using my energy cycle to make energy, I was using it to make matter.

The Speed of Reality

What is the nature of reality? I was raised Catholic, and continue to love my Catholic faith. I’m inclined to respect the old sayings, such as we are the light of the world. I respect the old ideas—while also probing and questioning them.

The holographic principle was first proposed by Nobel laureate Gerard ‘t Hooft in the 1990s. In 2017, a UK, Canadian, and Italian study provided substantial evidence that the universe is, indeed, holographic. But what would that mean? I know myself—and the world—as matter, not light.

What if light functions like a plasma? A plasma is something that possesses a dual character, such as a gel. In some ways, gels behave like a liquid; in other ways, like a solid. We see a similar indeterminate quality in stem cells. A plasma’s relationship with time is that of an open gate: not limited to one direction. Neither chicken nor egg, it is a kind of chickenegg.

Perhaps light functions similarly. It can display characteristics of matter, or characteristics of energy. When time (the background fabric) is slow, light can acquire speed, like matter. When time (the background fabric) is fast, light can acquire density, like energy. At the speed of light, the perception of the background fabric flips, from “slow,” to “fast.”

[O]ur observable universe is at the threshold of expanding faster than the speed of light.  ―physicist Lawrence M. Krauss

Er, “background fabric,” you say? What in the name of Michelson-Morley is that? We treat the background against which our observations are made as a vacuum—zero.

That is right. We do. I am suggesting that we may be mistaken. I am suggesting that the background here—the Cosmic Microwave Background or CMB—is not a vacuum, but matter and energy, trading places.

And that matter and energy, trading places, is light.

Like Eugene Wigner, who famously noted the unreasonable effectiveness of mathematics in describing the natural world in 1960, I am fascinated by suspiciously ubiquitous symmetry. Moon’s size: 27.27% of earth’s size. Moon’s orbital period: 27.27 days. The sun is 400 times larger than the moon—and also 400 times farther away. Hmm. Kind of makes you scratch your head a little, doesn’t it?

The black hole at the center of our galaxy, Sagittarius A*, has the largest angular size in the sky, followed by M87. M87’s black hole is 1000 times bigger, but roughly 1000 times farther away. —Feryal Özel, Harvard University Black Hole Initiative

In the spirit of Plato and René Descartes in the old age, and Nick Bostrom and Donald Hoffman in the new one, this essay asks a fundamental question: Is what we perceive an image that’s being rendered? Perhaps reality is not static, like a painting; but it has speed, like a movie.

Does it have a “correct” speed? Yes and no. It has a correct speed, but the correct speed can be achieved in different ways. It can be achieved via (for example) the color green—or via yellow + blue.

We have assumed that time is like a river whose speed we are strapped to. What if it is more like a current in which we can swim backward or forward—or tread in place? Altering the pH of my brain (e.g. with a micro dose of “acid,” LSD) seems to affect how long I am able to remain in each discrete moment of time. The more acidic, the longer—up to a point.

In other words, if we think of time as being comprised of discrete units—the way an image is pixelated, the way a movie is comprised of frames—my speed need not match time’s speed, but if it veers too far afield, I can run into problems.

Homeostasis Against the Speed of Time

I am like a glass of water, pH7. I maintain homeostasis—balance. When I perceive a background force that is expanding (high manganese?), I contract, becoming more salty. But would we perceive too much salt in the glass if the fabric against which the glass was rendered were expanding?

When I perceive a background force that’s contracting (high iron?), I expand, becoming less salty. But would we perceive too little salt in the glass if the fabric against which the glass was rendered were condensing?

Here is how time seems to operate, in me.

To one side of the baseline, time is slower (dopamine). To the other side, time is faster (serotonin).

I can slow time down, using dopamine, up to a point. But if I start to have too much dopamine, I will compensate, by hyper-methylating.

I can speed time up, using serotonin, up to a point. But if I start to have too much serotonin, I will compensate, by hypo-methylating.

This creates problems with perception. For one thing, the feeling of hypo-methylating can mimic the feeling of dopamine. Is time slow—or am *I* slow? Similarly, the feeling of hyper-methylating can mimic the feeling of serotonin. Is time fast—or am *I* fast?

What if, in Parkinson’s disease, my metronome needle is stuck all the way to the time’s left (Alpha-shifted)? I am both dopamine-toxic—and hyper-methylating.

What if, in Amyotrophic lateral sclerosis (ALS), my metronome needle is stuck all the way to time’s right (Omega-shifted)? I am both serotonin-toxic—and hypo-methylating.

In both instances, I am trapped. If I am too fast (hyper-methylating), how can I slow down if the background is too slow? But if I am too fast, the background will look too slow. If I am too slow (hypo-methylating), how can I speed up if the background is too fast? But if I’m too slow, the background will look too fast.

With two parallel trains, it is difficult to judge speed in a meaningful way. Am I slow—or is the train beside me accelerating? Am I fast—or is the train beside me decelerating?

Of Tumors and Time

I am interested in looking at the cosmos as a whole, where what we perceive (a tumor, a planet) is not fundamentally separate from its environment. This is not balls of matter in a sea of air. It is light within a speed-of-light boundary (black hole?) that is both achieving the speed of light (“sun”) and precipitating out of solution (“moon”) simultaneously. The speed of light is the 2D tipping point about which time changes directions, from acceleration to deceleration.

The perception of the speed-of-light “speed limit” depends upon an observer, and varies.

The speed of light can function like a lens. When the image becomes too dense, to one side of the lens, it becomes too expanded, on the other.

With cancer, I am deranged on both sides of time—both sides of the speed of light lens. To one side, I am too salty, too bitter. To the other, I am not salty enough. Instead of the flower, I become the fruit and the seed.

Like the speed of time, the speed of light is not necessarily a simple number (“green”); it can be a compound number (“blue + yellow”). Light has a “net” speed that I am helping to create with my own speed.

Those brown sun-spots on my shoulder? It may look as if their metronome is keeping pace with the rest of me, but what if it’s a trick of the eye? I suspect they are both denser and wider than time. They require both more magnetism (iron)—and more electricity (copper). They present as “green.” But could they be “blue and yellow, superimposed,” behind the scenes?

Once my lens curves too little or too much, I am no longer “flat” (relatively speaking); I start to have more depth than my environment. Instead of space, I start to acquire time—a new axis that is perpendicular to space the way a quasar is perpendicular to a galaxy.

Quasar: Shutterstock.

What if, when I insert a new lens—a fresh perspective, “new light,” a stem cell—into an old environment, I run the risk of re-setting the metronome, and creating a new definition of so-called flatness—speed zero? Perhaps new light creates a new 2D plane from which light can expand and condense (energy)—or condense and expand (matter). It creates a “fresh green,” if you will, from which can be derived “fresh blue” and “fresh yellow.” New light is capable of operating at a different time signature—a different scale.

What does the basal cell carcinoma on my shoulder look like? A sinkpit. A small vortex. An actual indentation, like a tiny tornado. You can almost see light spinning so fast that it’s spinning backward—imploding, precipitating out of solution (rocky planets). If I use radiation or hypo-methylating agents to slow time down, I might swing too far to the other side, where light is spinning so slowly, it burns up (gas giants). Ideally, I want to be in the middle. I don’t want my metronome to be eclipsing the speed of light, to the right of time, and dipping beneath the speed of light, to the left of time, faster than the rest of my body, the rest of the universe. I want to be oscillating at the speed of light, along with the rest of the rendered world.

The Speed of Light Squared

Perhaps, in a holographic universe, the speed limit for a single universe is not the speed of light, but the speed of light squared. When we reach the speed of light squared, a new observer is created.

In this video clip, called “Microscope Imaging Station Cancer Cells behaving badly,” I believe we are witnessing cancer cells as they achieve the speed of light squared (“round up”) and become refractile. When we “round up,” we make duplicate copies of the same information (e.g. DNA). When we round up by a factor of two during embryogenesis, we produce twins. When we round up by a factor of three, we produce triplets.

We don’t create the new inside a vacuum. We make the new inside—or outside—the old.

I am interested in physicist Nikodem Poplawski’s theory that our universe is the interior of a black hole inside another universe. In fact, I wonder if we could be inside a black hole inside a black hole inside a black hole—etc.—where “black hole” is the 2D boundary known as the speed of light. Moving outward from brane to brane, scale increases. Moving inward from brane to brane, scale decreases.

A holographic universe is one in which light can serve as background or foreground, canvas or painting—or canvas and painting. As lovely as this is—are we the light of the world, for reals?—it presents difficulties with perception. How can I know what type of light I am seeing? Is what I perceive light itself, the genuine article—or light playing the role of light? Or light playing the role of light playing the role of light playing the role of light?

How many iterations of light are in an E8 crystal?

Is the speed of light functioning as a boundary we can’t see beyond? And—perhaps more importantly—is there a degree of remove above or below which light is no longer light but something else entirely—matter or energy?

The Imprecision of Time

We don’t seem to have a solid grip on time. We need leap years—even leap seconds—to make our calendars work. But there is a “cosmological constant” when it comes to time. Was there a total solar eclipse on a certain date? Add or subtract 27,729 days, and see if there was also a total solar eclipse on that date (spoiler alert: there was).

eclipse to eclipse

27,729 days is ~76 years, about the length of a human life. It’s also roughly 70 times 360 plus 7 times 360 days. Could it be the number of days between branes of time—the distance above or below which light undergoes a state change?

I don’t know. But here’s something interesting. The Tunguska Event took place on June 30, 1908. The largest explosion the world has ever seen, it flattened 80 million trees. No one knows what caused it. But if you add 27,729 days to the date of Tunguska, you get another date—May 31, 1984. What happened on this date?: US performs nuclear test at Nevada Test Site.

Are we living inside a singularity? Beats me; I’m a short story writer. I barely understand what a singularity is. But I do know this. I was sixteen years old in 1986. When I was a teenager, I used to love Mary Chapin Carpenter, especially a song called When Halley Came to Jackson.

“It came from the east just as bright as a torch

She saw it in the sky from her daddy’s porch

As heavenly sent as it was back then”

Funny. Halley’s Comet “comes around” every ~76 years, almost like a nuclear reaction slicing backward through the branes of time. Almost like … Chernobyl.

Haley's Comet
On the Left: Haley’s Comet 1910, image Wikimedia Commons. On the right, Haley’s Comet 1986, image by Bob King.

What if, because of the act of rendering, light can exhibit characteristics of paradox? When it eclipses the speed of light, precipitating out of solution, it’s “too cold because it’s too fast.” When it dips beneath the speed of light, burning up, it’s “too hot because it’s too slow.”

Might this type of paradox—of metabolic cul-de-sac—have bearing on human illness? If I’m “too cold because I’m too fast,” how can I slow down? I’m already too cold! If I’m “too hot because I’m too slow,” how can I speed up? I’m already too hot! Time is a veil, and I am trapped to one side.

In these models, matter, light, and energy exist on a continuum. A spectrum. Matter or energy may behave as light, in locus light, as long as allowances are made. When light is denser than light (i.e. energy), it’s too hot, but it’s able to be too hot if time is too slow (Autism?). When light is faster than light (i.e. matter), it’s too cold, but it’s able to be too cold if time is too fast (ME/CFS, Chronic Fatigue Syndrome?).

So what’s the answer? I don’t know. I’m sorry; I wish I did. I’m better at asking questions than answering them. My hope is that others who understand biology, chemistry, and physics far better than I will join the conversation, and help us to decode our illnesses.

But I do know this. When I was at my sickest, my pineal gland and my eyes did not seem to be in agreement about the character of light they were observing. Was it going fast, like matter that has speed, in a 3D image where there’s foreground and background (blue + yellow)? Or was it innately fast (green), a 2D “mono” image, where the subject itself is high-energy? The pineal gland, a tiny crystal at the center of the brain, was dubbed “the seat of the soul” by René Descartes. It sets the circadian rhythm, communicates with the HPA axis, and is the font of the neuroendocrine cascade. If hormones matter, the pineal gland matters.

The lack of an objective, outside observer is a serious constraint. How can I gauge time if the instrument I am reading time with is part of time? I have to both read time (pH) and move around in it (core metabolic rate) using the same instrument: my brain.

A Metabolic Straitjacket

After my chronic fatigue had persisted for a while, I began to realize I was wearing a metabolic straitjacket. Whatever I ate or drank was not merely providing nutrients for my body; it was providing information for my brain. This “double duty” was a huge handicap. Sodium gave me the power to increase my metabolic rate—but not the permission. Potassium gave me the permission to increase my metabolic rate—but not the power. When I would attempt a metabolic increase in spite of an acidic terrain, I would get gout-like pain. This happened a month or two before my cancer.

My basal cell carcinoma is analogous to a local high-pressure system. A planet forming in the sea of me. The cells in my shoulder are “hoarding” my time, if you will. They are stealing my electricity and my magnetism—my copper and my iron. They’ll hoard my electrolytes, too. What can I do, other than try to have them removed? If I use vasodilating agents, like raw garlic extract or niacinamide, unless I inject them, my brain reads them and responds to them, too. It does not fix the asynchrony. If I use radiation or hypo-methylating agents, to slow down time, that might work for a while, but there is a tipping point—the speed of light—above which, to slow down is actually to speed up, and these cells reach that threshold sooner than the rest of me.

It’s not that they can’t dance. They’re just dancing to a different beat.

The best thing I ever did for my health was to eliminate all glyphosate, i.e. switch to a 100% organic diet. Glyphosate (“Roundup”) was giving my brain false information about light and time. Cosmetics, underwear, mattress, etc. I will not even chew a stick of gum if it isn’t organic. Nothing makes me sicker quicker than chemical fragrance in products such as Glade plug-ins, Bounce, Downy, Tide, etc. I use organic products that treat the universe as one coherent network, a communicating whole—a garden. Because it is.

Many Worlds

I am a fan of physicist Sean Carroll and his defense of the Many Worlds interpretation of quantum mechanics, first proposed by Hugh Everett in 1957. According to Many Worlds, the universe continually splits into new branches, to produce multiple versions of ourselves. Carroll thinks that, so far, Many Worlds is the simplest possible explanation of quantum mechanics.

Many Worlds may seem exotic at first, but it possesses a simple power, especially if we treat the speed of light as a lens. When viewed from beneath the speed of light lens, light will appear to be branching into many worlds. When viewed from above the speed of light lens, light will appear to be condensing into one. At the speed of light, light is light.

If my brain misunderstands the degree of curvature of the speed of light lens, and the way the speeds of light and time titrate, it can become metabolically trapped. In Chronic Fatigue Syndrome, I may be trapped above the speed of light. Many worlds are branching faster than I am able to move through them. In Autism, I may be trapped beneath the speed of light. Many worlds are condensing faster than I am able to move through them. In Autism, it is as if I am trapped in the future. In Chronic Fatigue Syndrome, it is as if I am trapped in the past.

Endnote: Before he met my mother, my father was engaged to a brilliant woman named Frances Marshall Watkins. Fran was diagnosed with Amyotrophic Lateral Sclerosis (ALS), and died before they could wed. I would like to dedicate this essay to her. Had she not died, I would never have lived.

We Need Your Help

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

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What Is Thiamine to Energy Metabolism?

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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[s]. This series of reactions can be likened to a transmission, consuming the energy provided from ATP and 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 an insufficient supply of energy, a gap between supply and demand, would produce a fundamental change in function. This lack of function in the brain and body organs presents as a disease. The symptoms are merely warning the affected individual that something is wrong. The underlying cause of the energy deficiency 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

We have known for many years that dietary sugar precipitates thiamine deficiency. A friend of mine had 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, heartburn or abdominal pain
  • Occasional diarrhea or constipation
  • Allergies
  • Fatigue
  • Emotional lability
  • Insomnia
  • Nightmares
  • Pins and needles
  • Hair loss
  • Palpitations of the heart
  • 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. An attack by an infecting organism is a source of stress imposed on the affected person and requires a boost of energy consumption. Therefore the illness that follows can be regarded as a “war” between the attacking disease producing organism and the brain/body that has to mobilize a defense. Either death, recovery, or a “stalemate” might be the expected outcome. If this is the truth, then any disease will respond to the ingestion of nutrients, particularly thiamine. It strongly suggests that Holistic or Alternative medicine could add a huge benefit to health preservation or the treatment of disease.

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

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This article was published originally on August 25, 2020.

Paradoxical Reactions With TTFD: The Methylation Connection

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In a previous piece, I discussed some of the problems that could occur when supplementing with a particularly potent form of thiamine called tetrahydrofurfuryl disulfide or TTFD. Specifically, we examined how TTFD can temporarily deplete glutathione (GSH) and increase the recycling requirements (using activated riboflavin and NADPH). I also provided some recommendations for how one might improve this initial processing of TTFD in cells. Following on from that, we will now look at the next phase of TTFD processing to help pinpoint some of the reasons why some people suffer negative reactions when beginning supplementation. In short, the clearance of TTFD breakdown products requires adequate methylation capacity and many individuals who are thiamine deficient have insufficient methylation.

From Glutathione to Methylation

Once TTFD has been reduced (or “broken apart”) by glutathione (GSH), it is further bound or conjugated with more GSH, likely using the enzyme glutathione-s-transferase. This reaction produces a conjugate called glutathione tetrahydrofurfuryl disulfide (GTFD).

TTFD and methylation

The above diagram shows that this GTFD conjugate then needs to be methylated. Methylation is the process by which a methyl group is attached to its structure from a donor molecule (a “methyl donor”). The major methyl donor in cells is called S-adenosyl methionine, commonly known as SAM-e.

SAM-e is generated through a biochemical cycle called the methylation cycle. Dietary protein provides amino acids, one of which is methionine. Through combining with ATP, methionine can be “activated” to generate SAM-e. SAM-e possesses a methyl group, which it then donates to a variety of different molecules via methyltransferase enzymes. In simple terms, attaching a methyl group to a molecule serves to change its function in some way.

After having donated its methyl group, SAM-e becomes SAH (S-adenosyl homocysteine) and later homocysteine. Homocysteine can either be recycled back to methionine with the use of multiple nutrients (including folate and vitamin B12), or alternative can be drawn down through the transsulfuration pathway to generate cysteine.

The newly recycled methionine can further serve as the source of more SAM-e, which continues to be utilized in methylation reactions. This is ideally how the process should work.

Methylation is involved in DNA base synthesis, gene expression, detoxification, neurotransmitter production/clearance, and many other processes. As SAM-e is the major cellular methyl donor, cells must maintain a consistent level of SAM-e to fulfill those functions.

Since methylation is required for the synthesis and clearances of neurotransmitters and maintaining neurochemical balance in the brain, it is thought that changes in methylation status can be responsible for the underlying neurochemical abnormalities present in various psychiatric disorders. For the above reasons, SAM-e has been used effectively as a fast-acting anti-depressant medication and is also useful as an anxiolytic agent in specific cases.

In the context of longstanding deficiencies in the nutrients required to maintain a healthy methylation cycle, a relative inability to recycle homocysteine can yield elevated levels of homocysteine and consequentially less SAM-e. And because SAM-e is the primary methyl donor in the cell, methylation (and by definition, all of the many processes which require methylation) can become compromised.

TTFD and SAM-e

The above information is relevant to this topic because the breakdown of TTFD requires adequate levels of SAM-e. Through the enzyme thiol-s-methyltransferase, SAM-e donates a methyl group to GTFD to generate methyl tetrahydrofurfuryl disulfide (MTHFD). MTHFD is then later funneled through the sulfoxidation pathway in the liver to be cleared primarily through the urine.

The nuts and bolts of this: TTFD metabolism can deplete SAM-e. A lack of SAM-e could potentially help to explain some of the following side effects which are common with this therapy – including insomnia, anxiety, agitation, restlessness, flat mood, fatigue, and/or mild depression.

Oftentimes, it is assumed that these symptoms are caused by an inability to process the sulfur content of the molecule, or are simply a manifestation of the “paradoxical reaction”. Sometimes it subsides within a few days or weeks, whereas other times it doesn’t. The reason for this, in some people at least, might relate to changes in methylation status.

Furthermore, by using up SAM-e, TTFD could also theoretically increase the requirement for some of the other nutrients involved in the methylation cycle. These might include the B complex vitamins, particularly folate, riboflavin, and vitamin B12.

Clinical Experience Suggests A Relationship Between Methylation and TTFD Response

I recently had a client who explained that supplementing TTFD initially produced great increases in mental clarity, energy, and almost euphoria. However, within a few days, this shifted towards feelings of “depletion”, flatness, depression, and cognitive impairment. The individual described the symptoms as remarkably similar to those produced by other supplements which are referred to as “methyl buffers” – capable of affecting methylation capacity. For this same individual, the remedy was to supplement with extra methylfolate and methylcobalamin (vitamin B12) to increase methylation.

And so, might this be one of the mechanisms by which TTFD therapy can go on to “unmask” an underlying folate/B12 deficiency in some people? Dr. Lonsdale has documented cases of folate deficiency being “unmasked” in some people after undertaking thiamine therapy. I have also seen this on several occasions, and I suspect in some cases, it might be somewhat related.

Secondly, a lack of SAM-e can then theoretically produce neurochemical changes which are potentially responsible for sudden feelings of anxiety or depression that some people tend to experience.

This would especially apply to those people who already have compromised methylation, or tend towards lower levels of SAM-e, folate, B12, or a combination of all three.

To conclude, this highlights the importance of B complex therapy in conjunction with TTFD, as well as monitoring nutritional status at regular intervals if experiencing negative symptoms or side effects from this nutrient. If you are one of the people who experience depression or anxiety from taking the TTFD form of thiamine, then you might want to try investigating methylation status, or experiment with methylfolate, methyl B12, betaine, or SAM-e.

We Need Your Help

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

Yes, I would like to support Hormones Matter. 

Image by Michael Schwarzenberger from Pixabay.

This article was published originally on January 7, 2021. 

Why Thiamine Supplementation Requires Magnesium

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In this article, we will briefly examine some of the reasons why supplementing with the mineral magnesium is often essential when repleting thiamine, and also when using higher doses to support health conditions. In a minority of people, intolerance of magnesium supplements might be resolved when using thiamine simultaneously.

First of all, thiamine and magnesium are closely paired biochemically speaking. Magnesium is either directly or indirectly involved in the activity of numerous thiamine-dependent enzymes. Importantly, the activation of thiamine inside the cell greatly depends upon sufficient magnesium stores.

Thiamine Activation Requires Magnesium

thiamine activation by magnesiumAfter absorption, dietary forms of thiamine gain entry into the cell through transport proteins. Once inside, free thiamine must be converted (or “activated”) into thiamine pyrophosphate (TPP), the biochemically active coenzyme form. This is achieved by an enzyme called thiamine pyrophosphokinase, which removes a phosphate from adenosine triphosphate (ATP) and attaches it to thiamine to make TPP. This enzymatic reaction has been shown to require a divalent cation, which in most cases is magnesium.

This is especially important when using supplements with the aim of rapidly increasing intracellular thiamine levels, because the above “activation” process will increase the requirement for magnesium. Without enough magnesium to meet this demand, it is at least theoretically plausible that there will be less active TPP which can be utilized.

The Transketolase Enzyme

Likewise, the transketolase enzyme located within the pentose phosphate pathway also requires magnesium to undertake its activities. Research has shown that both magnesium and thiamine alone are capable of increasing transketolase activity.
thiamine transketolase pentose phosphate pathway

Alpha-ketoglutarate Dehydrogenase and Pyruvate Dehydrogenase

Magnesium ions were shown to directly increase the activity of the thiamine-dependent rate-limiting alpha-ketoglutarate dehydrogenase complex (KGDH), an enzyme unit involved in the Krebs cycle (part of the larger process of generating cellular energy). Research indicates that KGDH requires both TPP and magnesium for maximal activity.

 

Furthermore, a similar thiamine-dependent enzyme complex positioned at the interface between glycolysis and the Krebs cycle called the pyruvate dehydrogenase complex (PDHC) also requires magnesium, but indirectly. The PDHC is essential for carbohydrate metabolism. Although magnesium ions do not directly interact with the PHDC, they do exert significant influence on a related regulatory enzyme called pyruvate dehydrogenase phosphate phosphatase (PDHP). Magnesium activates PDHP, and PDHP is responsible activation of the PDHC. Hence, thiamine directly increases PDHC activity, and magnesium indirectly increase it as well.

Thiamine and Magnesium Should Be Supplemented Together

With the numerous interrelated roles of these two nutrients taken into consideration, is it any wonder that research has demonstrated negative consequences of supplementing one without the other?

One animal study showed that thiamine supplementation in magnesium-deficiency (and/or sulfate deficiency) resulted in reduced thiamine concentrations in liver and elevated triglycerides, suggesting a role for magnesium in liver retention of thiamine. Another study looking at thiamine supplementation in magnesium deficient animals found that the addition of thiamine results in a significant decrease in blood and bone concentrations of magnesium, which indicates an increased demand for magnesium and depletion of the stored mineral. The same study showed a lower levels of thiamine in nerve, liver, and kidney of magnesium deficient animal, providing further support for magnesium’s role in thiamine retention. Additionally, they showed that thiamine could not increase transketolase activity in the presence of magnesium deficiency.

Correcting Wernicke Encephalopathy, the end stage neurological consequence of severe thiamine deficiency with thiamine alone was found to be ineffective in one case report, and only after correcting hypomagnesaemia (addressing magnesium deficiency) did the patient’s transketolase normalize and symptoms resolve. A more recent report showed the same results.

So to conclude, it is clear that magnesium is absolutely essential for normal thiamine activity in the body, and one should take great care to ensure sufficient intake when addressing underlying thiamine issues. This is especially important when consistently using high doses.

Magnesium and Thiamine

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This article was published originally on October 25, 2021. 

Thiamine Deficiency Gaining Recognition: New Book

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In the 5 years since Dr. Lonsdale and I published our book: Thiamine Deficiency Disease, Dysautonomia, and High Calorie Malnutrition (and 50 years since Dr. Lonsdale first began working with thiamine) recognition of the role of thiamine in health and disease have increased steadily year over year. Sales of the book double each year. Admittedly, the numbers were low and remain low in comparison to other popular topics, but the increase in awareness is heartening. Unfortunately, much of this awareness has not reached the medical profession. We regularly see reports in the medical literature boasting recognition of ‘rare’ cases of thiamine deficiency diseases like beriberi and Wernicke’s. If only physicians knew how common these conditions were and that they are only rare because we are not looking. Insufficient thiamine is Hiding in Plain Sight.

A New Book

In 2020, a UK physician by the name of Jo Dixon published a new book on thiamine deficiency, a personal account of her declining health, her discovery of thiamine, and her efforts to get treatment and spread the word. The book, called The Missing Link in Dementia, A Memoir, documents her journey. Unfortunately, she neither mentions thiamine in the title, the description, or even in the text until halfway through. One would not know the book is about thiamine until one reads it or unless it is recommended, so I will recommend it here. This would be a great starter book for someone beginning their health journey.

She has a second book listed on Amazon, Swimming in Circles that I have not read, but I suspect it details thiamine deficiency in fish in other animal populations.

While I would have preferred her to mention thiamine deficiency in the title or introduction, I found the book quite telling of the lengths one has to go to uncover this deficiency, even as a physician. Her case, unfortunately, is highly typical of what we see in patients everywhere. She had longstanding bowel dysfunction, which limited her ability to eat and maintain nutritional status. She led a busy life as a physician and mother of four children, which put pressure on thiamine stability. Even so, she functioned quite well for a long time. It wasn’t until her health took a severe turn for the worse that thiamine deficiency was recognized. Like others who develop issues with thiamine, she was forced to diagnose herself. No other physician, and she saw many, could provide any answers to her declining health. She had to figure it out herself. She was also forced to treat herself. Fortunately for her, she convinced a physician friend to provide IV thiamine, a protocol that was not accepted by her hospital and one she could not readily provide to other patients when she identified their deficiencies.

All of this is typical. We believe that thiamine deficiency was solved and thus any cases that do appear must be rare (to a tee, most case reports include ‘rare’ in the title or introduction). In reality, they are only rare because we do not look for them. We believe falsely that thiamine deficiency emerges acutely, and while it does in some cases, mostly it sits in the background, quietly and insidiously destroying one’s health. We have cases of high functioning individuals whose health begins to decline and whose thiamine levels are tested as low and should merit treatment but ignored for years as not being pertinent. And those are the lucky ones. Most physicians refuse to test for thiamine.

Thiamine deficiency is easily treatable if recognized early. It becomes more complicated as the years pass, and it is impossible if we never bother to look.

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

Yes, I would like to support Hormones Matter. 

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