thiamine - Page 5

Thiamine Deficiency Causes Intracellular Potassium Wasting

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Whilst I always suspected a direct link between potassium and thiamine deficiency (outside of the context of refeeding syndrome), I had not come across any direct research elucidating the mechanisms – until NOW. In short, thiamine deficiency causes intracellular potassium wasting.

Animal research in rats showed that chronic thiamine deficiency increases sodium tissue content in heart, liver and skeletal muscle by 18-35%, while also decreasing potassium content by 18-25%. Interestingly, although tissue levels were altered, plasma levels of these electrolytes remained unaffected and stayed within the normal-high range (sodium at 141.6 and potassium at 4.8). This means that blood measurements did not reflect tissue content.

The thiamine deficient group also displayed remarkably lower levels of stored liver glycogen (0.3gm/100 vs 2.7gm/100 in controls). This inability to store glycogen is one factor which helps to explain the strong tendency towards hypoglycemia seen in many people with a thiamine deficiency.

Interestingly, the researchers showed a shift towards an increased level of extracellular water and reduced intracellular water. This finding, along with the shift in intracellular electrolyte concentrations, is 100% consistent with Ling’s Association-Induction hypothesis.

In short, the bioenergetic state of the cell governs its ability to retain potassium ions and structure water into a gel-like phase. A cell with plentiful ATP can maintain this ability, independent of the “sodium potassium pump”. On the other hand, cells lacking energy lose their capacity to retain potassium, intracellular water becomes “unstructured” and intracellular concentration of sodium ions increases and the electronic state of the cell is changed. This causes water to “leak” out of the cells into the extracellular space to produce a localised edema of sorts. Thiamine, playing a central role in energy metabolism, is partially responsible for maintaining healthy redox balance and a continuous supply of ATP. Hence, it is no wonder why a deficiency of this essential nutrient produces such drastic changes in the cellular electrolyte balance.

Thiamine, TTFD, Potassium, and Heart Function

The cells of the heart are particularly susceptible to a disturbance in electrolytes. One Japanese study on coronary insufficiency in dogs showed elevated sodium and reduced potassium content in the insufficient left ventricle. Intravenous administration 50mg thiamine, in the form of thiamine tetrahydrofurfuryl disulfide (TTFD), a derivative of thiamine with higher bioavailability and solubility than other formulations, restored electrolyte balance, likely through improving tissue energy metabolism.

Likewise, the same effect was also demonstrated in isolated Guinea pig atria kept in potassium-free medium. TTFD added to cells or administered as a pre-treatment prevented the loss of potassium and increase in sodium, which was shown to occur in controls. Importantly, this effect was not achieved by thiamine HCL or another derivative studied. TTFD also entered the atrial cells much more readily than other forms, demonstrating its superior absorbability and perhaps suggesting that this form would be useful for addressing cardiac thiamine insufficiency.

Low potassium is a known driver of cardiac arrhythmias, and TTFD possesses anti-arrhythmic properties and has historically been used to treat various types of arrhythmia in Japan.

Furthermore, thiamine TTFD was also been shown to be protective against the cardiac toxin Strophanthin-G, preventing the loss of potassium once again to preserve cardiac function. Likewise, atrial cell damage through exposure to the mitochondrial toxin N-ethylmaleimide was also prevented by high concentrations of TTFD in-vitro. This protective action was attributed to the prosthetic group specific to TTFD, and NOT the thiamine molecule itself.

So it would seem that thiamine, probably through its effects on energy metabolism inside cells, and perhaps due to an unknown “kosmotropic” property of TTFD, is extremely important for regulating cell ion concentrations. In thiamine deficiency, an underlying intracellular potassium deficiency may be going unnoticed due to unremarkable blood levels. In cases where potassium deficiency is suggested, thiamine deficiency may be indicated, and TTFD might used to more safely correct the electrolyte balance.

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This article was published originally on May 13, 2020. 

Thiamine and the Energy To Heal

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Over the last 8 years or so and since the publication of our book: Thiamine Deficiency Disease, Dysautonomia, and High Calorie Malnutrition, I have written dozens of articles and given countless interviews and talks on the importance of thiamine. Just last month, I was privileged to give a talk on thiamine at The Forum for Integrative Medicine. While the talk was recorded, it was available only to conference attendees, physicians, and other practitioners. So that others may have this information, I am including the PowerPoint below.

The talk was entitled: Thiamine and the energy to heal. In it, I outline why we ought to be looking at thiamine, why we are not, and why so many people are walking around with insufficient thiamine relative to the demands not only of modern living, but also, for their own genetic predisposition and unique constellation of environmental exposures. All of the benefits of modernity that we enjoy so readily, the fast and convenient foods with chemical preservatives that extend shelf life, the agricultural chemicals that promise to maximize production, the industrial chemicals that make transportation, heating and cooling, computer and cell phone technologies possible, and modern medications that override natural systems, all deplete thiamine and other nutrients. In other words, modern living demands more nutrition that we provide and that, I believe, is the root of all illness.

Sadly, conventional wisdom disagrees. We are taught that food availability, no matter its composition, equates with nutrient sufficiency. With a good portion of the population overweight or obese, the idea that we may be fundamentally malnourished seems comical. When speaking of nutrition, even prominent researchers and physicians use the term ‘over-nutrition’ to describe the health risks associated with being over-weight. Read just about any article on obesity and the term will likely be used. I won’t belabor the point, but I have to note, that how we define nutrient sufficiency determines whether or not we understand deficiency.

The title of the talk – thiamine and the energy to heal – points directly to the key concepts both Dr. Lonsdale and I have been pushing for years: that healing takes energy and energy takes thiamine. We know this intuitively. What do we do when ill? We rest to conserve energy. Over the last several decades, however, we have forgotten that in order to conserve energy, we have to be able to make energy. No amount of energy conservation will help if one cannot make energy efficiently in the first place.

So how do we make energy? Biological energy or ATP is synthesized by deriving from the foods we eat essential macro (amino acids from protein, fatty acid from fats, and glucose from carbohydrates) and micro nutrients (vitamins, minerals, and metals) and funneling those substrates through a series reactions to make ATP. Those reactions take place in the cell, but mostly in the mitochondria, and all of them require ample nutrients to run. The manufactured ATP then drives everything else. It gives us the energy to live, to breathe, for the muscles to contract, the brain to function, the heart to beat, the immune system to fight illness, even the ability to die a peaceful death requires sufficient ATP. When we cannot make sufficient ATP to fuel the basic functions of living, to put it bluntly, sh%t goes wrong, and it goes wrong in some wildly bizarre and unique ways. Importantly, when we cannot make adequate ATP, no amount of rest will help. Indeed, some research suggests, extended periods of immobility may even degrade ATP synthesis. See here, here.

Why Thiamine?

Thiamine is key to making ATP. It serves as a rate-limiting nutrient to the entire process. If there is not enough thiamine relative to demand, ATP production suffers. Thiamine is the gatekeeper to mitochondrial production of ATP. It quite literally determines whether substrates of glucose can enter the mitochondria and produce up to 30 units of ATP per glucose molecule or if glucose has to be metabolized in the cell where we get only about 2 units of ATP per molecule. Thirty versus two is a huge difference in energy production. Imagine trying to function on such diminished energetic capacity. It just does not work.

That’s not all – thiamine is involved in fatty metabolism and fats can provide up to 100 units of ATP per molecule and it is involved in protein/amino acid metabolism where it determines the pattern of amino acids available for DNA/RNA and other functions. So thiamine is absolutely critical to health and we simply do not get enough from the modern diet both directly and relative to demand. Remember, modern living demands more thiamine than modern diets provide.

Returning back to having the energy to heal, if thiamine is instrumental in making energy, thiamine then is instrumental to healing. To the extent one is unable to heal or suffers with a chronic illness that will not resolve, it is very likely that thiamine intake is insufficient to the demands of the illness. Sure, there are other nutrients that are absolutely critical for health and healing and may also be deficient, but they are downstream of thiamine and require ATP to be managed effectively. That means when thiamine low, we are unable to utilize a whole bunch of other nutrients. It also means that many nutrient deficiencies may be relative to reduced ATP production from inadequate thiamine and not a reduction of the nutrient itself.

The bottom line is that thiamine is critical for health and healing and we ignore it at our own peril.

Thiamine and the energy to heal.

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Notes on Folate Carriers, Anti-Folate Medications, and Thiamine Deficiency

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A few years back, I wrote a paper about the anti-folate and anti-thiamine properties of a popular antibiotic called Bactrim. It is also sold under the trade names: Septra, Sulfatrim, Septrin, Apo-Sulfatrim, SMZ-TMP and cotrimoxazole. Bactrim is a formulation that combines two drugs, trimethoprim and sulfamethoxazole. Both drugs block folate, albeit via different mechanisms, but trimethoprim blocks thiamine too. The combination has a number of deleterious effects, not the least of which is the possibility for a drug-induced Wernicke’s encephalopathy.

Today, I would like take a closer look at the relationship between thiamine and folate status as it affects transporter activity. It turns out that there is a lot more to the story than simply the drug’s depletion of critical nutrients. There is an interaction at play that determines the potency of these drugs and the severity of the nutrient depletion. That is, the individual’s nutrient status before taking the drug, to a large extent, may determine its effects.

It makes sense, of course, that the individual’s nutrient status would affect drug response. Poor nutrient status in general would exacerbate any illness and increase the risk frank deficiency and drug-induced mitochondrial damage. Beyond these broad strokes, however, there wasn’t a clear mechanism that would account for why some people become so severely debilitated by certain drugs and while others do not.

With regard to anti-folate drugs, a study done over 20 years ago found that nutrient transporter trafficking and directionality may be related to thiamine status. A caveat, this was a cell culture study using murine cell lines, including leukemia cells, and extrapolation to vivo human, non-leukemia cells is necessary. More recent animal research involving the use of methotrexate in liver cancer demonstrates similar effects, although mechanisms are not discussed. High thiamine status reduces methotrexate uptake. Conversely, methotrexate induces thiamine and folate deficiency (here, here).

Returning to the cell study, thiamine concentrations before exposure to anti-folate drugs appears not only to determine how much of drug is taken up by the cell (low thiamine > more drug uptake) but also the degree to which folate and thiamine are depleted. In low thiamine states, the potency anti-folate drug like methotrexate, and I suspect other anti-folate drugs that were not tested, is magnitudes greater than with higher thiamine concentrations. What I found particularly interesting, was that this effect was mediated largely by changes in the folate transporter (RFC1), which controlled  not only the influx of folates and anti-folate drugs, but also, the efflux of thiamine pyrophosphate (TPP), the activated form of thiamine. The researchers found that when thiamine was low, more drug was taken up by the cell, while more TPP was spit out of the cell, essentially causing an intracellular deficiency of both folate and thiamine. Of note, a less active form of thiamine, thiamine monophosphate (TMP), appeared to be trafficked into the cell in exchange of the more active TPP.

Since a good portion of the population is likely low in thiamine, this means the potential damage by these drugs is significant and under-recognized. Might some of the adverse effects associated with these medications be related to either folate and/or thiamine deficiency? Possibly, which means supplementation with these nutrients may help.

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With Thiamine Paradox Symptoms Patience Is Key

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I wanted to share my experience going through thiamine paradox so that others may find hope as they navigate the process. In November of 2019, my life was completely flipped upside down. My full story is here, but briefly, I had taken an antibiotic called Tinidazole, the less popular but almost identical sister drug to Metronidazole. Within days of taking the antibiotic I began to experience frightening symptoms like loss of mobility in my hands, heart palpitations and intense feelings of depression and doom. Less than two weeks later, I went into surgery to get my wisdom teeth removed and was put on a course of penicillin for two weeks.

Within weeks, my health was in a total spiral. I began to experience constant bouts of tachycardia and panic, low blood sugar, dizziness, blurry vision and the inability to sleep. I went from somebody who sleeps 8 hours a night to sleeping for less than an hour on various nights. When sleep did come, I was jolted awake in a panic attack. At times, I was feeling symptoms that mimicked asthma…it was like I couldn’t breathe.

I had no idea what was going on. Multiple trips to the ER did nothing. I continued to get worse. It wasn’t until I traced back what drugs I had taken that I made my way to a Facebook group called “Metronidazole Toxicity Support Group.” It was in that group that I discovered that thousands of others were dealing with the same set of symptoms caused by this horrendously neurotoxic antibiotic. I had known for years that one should avoid fluoroquinolone antibiotics, but research has shown that metronidazole and others in its class present some of the same catastrophic side effects.

Through her own research and contact with Dr. Lonsdale and Dr. Marrs, the founder of the group discovered that metronidazole and other drugs in its class block thiamine in the body. The symptoms of the toxicity mimic those of Wernicke’s encephalopathy.

The solution? Take thiamine.

I thought it was going to be an easy fix. It wasn’t.

Like many posts on Hormones Matter, the topic of paradox frequently comes up, and I am the perfect case study.

In retrospect, I had longstanding symptoms of mild beriberi for a lot of my life. I was constantly dealing with low blood pressure and strange heart symptoms that date back to my teenage years. I grew up eating a typical American diet and started drinking large amounts of coffee in my teens. I loved sugar.

With longstanding thiamine deficiency, the human body changes its chemistry to adapt and survive. When thiamine is reintroduced and things get turned back, your body goes haywire until the chemistry can normalize.

For me, it took three attempts. Every time I would start even the tiniest dose of thiamine HCL, I would erupt in panic, tachycardia, feelings of “seizures” and doom and gloom, chest tightness and head pressure. It was akin to the feeling when somebody knows that they ingested way more marijuana than they should have. Sheer terror. When I took too much one time, I almost landed in the ER because I thought for sure that I was going into cardiac arrest.

My first attempt was in January 2020. I failed miserably and stopped because of the side effects. But I wasn’t getting better and my health continued to spiral. I tried again in March 2020 and made it for 2 weeks before dropping out again. I would crumble pills to get just a little thiamine HCL in my system and I would still feel like a total wreck.

Finally, on my third attempt in May 2020, I made it.

The solution is to start LOW and SLOW. I found a company in the UK that has a liquid form of thiamine HCL that allowed me to do this. I started with 10 mg per day and gradually increased by 10-20 mg over the course of many weeks. I also spread my dose out throughout the day. Dr. Lonsdale predicted the paradox will lift within a month, but for me, it took a bit longer. Within 8 weeks I began to notice that I could safely take a 100mg thiamine HCL pill without experiencing too many symptoms. It continued to get better with time.

Now, almost a year later, I’m taking 300-400mg of thiamine HCL a day and mixing in benfotiamine and allithiamine. In the last 6 months, my health has slowly started to trend upward. I’ve added in a B complex at times and I’m also working on my B12. The heart palpitations are significantly better, I’m less prone to panic attacks than I have been in years, and my brain fog has lifted. What I’m left with is some slight dizziness (though it is significantly better), blurry vision that waxes and wanes, and my blood sugar is still presenting some issues. Still, I feel like I’m trending in the right direction and that things continue to slowly improve.

My advice for those of you encountering paradox symptoms is this: BE PATIENT. It sucks. But the rewards on the other end are so worth it. I would also advise you to dramatically increase your potassium through food. This didn’t eliminate the paradox feelings entirely but it did help reduce them.

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This article was publish originally on January 26, 2021. 

Thiamine Deficiency: A Slow Road to Dementia

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‘Jo, you’ll be relieved to hear the tests are all normal.’

I’d heard this line so many times, and it wasn’t reassuring. Each time it became less likely that I had an illness that could be defined, diagnosed, and consequently cured, or even treated. If there was nothing wrong with me, why did I feel so awful? I had been gradually deteriorating over months, perhaps longer.

Fatigue and Other Seemingly Innocuous Symptoms

It’s difficult to say when I first felt unwell. One of the initial symptoms was terrific fatigue – struggling to find the energy to carry on each day at work. I was taking longer and more frequent tea breaks and relying on sugar to give me the buzz to carry on. Of course, it didn’t help that I didn’t sleep well. I would fall into a deep sleep early evening and then wake feeling strangely on edge with a racing heart, unable to sleep for most of the night. Even if I could sleep, it didn’t make me feel any better.

There were several other symptoms, which I could explain away, but one odd symptom was muscle twitches or fasciculations. These were worse when I was tired or had been more active. I also had dodgy guts – more about this later.

Even though I was exhausted I could continue working, being a mother to our four children – albeit a rather terrible one that repeatedly fell asleep in the middle of bedtime stories, until I developed brain fog. I felt like my thinking was occurring at less than half the usual speed. I struggled to hold a conversation, as this required listening, interpreting the other person’s words, formulating an answer, and talking. I would have to really concentrate to think about anything. I would forget things unless I wrote them down, which just meant I had unfinished lists scattered everywhere.

After falling on the ward where I had been working as a doctor, I finally acknowledged that I was sick, even if there was nothing apparently wrong with me. Once I stopped working, I deteriorated further, such that I was unable to recognize people and even places.

A Slow Road to Dementia

This was over 10 years ago. Clearly, I’ve improved since then. I’ve written a book to try to characterize my symptoms, explain what caused them, and why it was difficult to make a diagnosis. This seems even more pertinent since a lot of the symptoms I suffered with then resemble long Covid now.

My main concern was that I had developed dementia. I had many of the features: I struggled to remember recent events, I had problems following conversations, I was forgetting the names of friends and even commonly used objects, and I was repeating myself and having problems with thinking and reasoning. I also had difficulty recognizing where I was — this is visuospatial disorientation — a key marker of dementia.

Since the medical profession seemed to have no idea how to treat me I decided to try to work it out for myself. What choice did I have? Away from work, I had time to slowly read through medical papers, whilst I rested. I recognized that my symptoms improved after taking antibiotics for a gum infection. Any exertion made me markedly worse, but not immediately afterward, it would be the following day and last for several days. I improved if I rested. My other symptoms included pains in my hands and feet. I thought this was arthritis initially, but when I developed pins and needles and subsequently numbness, I realized this was a peripheral neuropathy – a problem with the sensory nerves in my extremities.

Some months earlier a close colleague had told me I was thiamine deficient, mainly because I had lost a lot of weight. I was taken aback, assuming he thought my diet was poor, or that I was drinking alcohol. I hadn’t drunk any alcohol for years as it made me feel rough after a few sips. I investigated thiamine deficiency and found that it causes loss of sensation as well as loss of balance; I already knew it affected memory from treating alcoholics under my care.

My friend kindly agreed to try high-dose intravenous thiamine on the ward. Neither of us really thought it would work, but it was worth a shot. I was astounded when after a few minutes of the infusion I started to be able to think clearer and even the pains in my hands and feet disappeared. I practically skipped off the ward to buy oral thiamine and dose up. Sadly, thiamine tablets didn’t work and two days later I was back on the unit begging for more shots. This thrice-weekly dosing of thiamine infusions continued for months.

The Gut Connection

I trained in Gastroenterology and General Medicine. They say doctors make the worst patients. For as long as I could remember I had suffered from intermittent severe central abdominal pains, which usually occurred after eating quickly on an empty stomach. According to my mother, I had been a colicky baby and had also returned to the hospital as a new baby with uncontrollable vomiting. Nothing abnormal was found.

In fact, not all the tests I had were normal. After several second opinions, I had a few abnormal tests. I had a CT scan of my abdomen, which showed that I had gut malrotation. The severe pains I had experienced throughout life were due to small bowel volvulus – twisting. I learned that if I stopped eating and lay down on my back the pain would gradually subside. Each time my guts twisted scar tissue formed adhesions, slowing down my gut movements.

My guts had been noticeably abnormal for many years. I had noisy guts and passed very loose, frequent motions. I don’t know many slim 20-year-olds who suffered from severe gastro-esophageal reflux as I did. As this progressed, I developed recurrent chest infections and required multiple courses of antibiotics. Eventually, I worked out that I was aspirating gut contents into my lungs each night, and I stopped eating in the evening and propped myself up with many pillows. All sorted – no more chest infections – no more antibiotics.

One of the other abnormal tests was an incredibly low vitamin D. Through late-night searches of anything vaguely relevant and my gastroenterology knowledge I worked out that a low vitamin D occurred in bacterial overgrowth. This made sense. I had developed bacterial overgrowth in my small intestines — the part of the gut responsible for the absorption of nutrients from food.

Small intestinal bacterial overgrowth or SIBO is due to an excess of bacteria in the small intestines. There are many risk factors including sluggish guts from adhesions, previous surgery, medications that slow the gut, but also multiple courses of antibiotics, poor immune system, and use of drugs that block acid production in the stomach, as well as pancreatitis. I’m sure that a diet high in sugar didn’t help.

I had another test specifically looking for bacterial overgrowth, which the nurse (a colleague I’d worked with many times) and I interpreted as abnormal. The consultant I saw thought the machine must have broken. This was frustrating; after so many normal tests to have a wildly abnormal test attributed to faulty equipment. I decided it was better to treat the patient (me) rather than a dubious test result. After starting antibiotics, I no longer needed the thiamine infusions. The diarrhea also improved.

I worked out that I had bacterial overgrowth from mal-rotated guts, obstructed from adhesions, which improved with antibiotics and were eventually treated with corrective surgery. I also had severe vitamin D deficiency, which was corrected with injections, and thiamine deficiency, which I subsequently managed with a fat-soluble thiamine analogue — benfotiamine. I found a paper online reporting thiamine deficiency in extremely obese patients who had undergone surgery on their small intestines to aid weight loss. Many of these patients had thiamine deficiency; they also had high folate, which was thought to be a marker of bacterial overgrowth. Oral thiamine had no effect on their thiamine levels, but after taking antibiotics the patients’ thiamine returned to normal. Interestingly, my folate was high.

What was less well known was that some bacteria produce an enzyme called thiaminase, which destroys thiamine. I can only assume that I had these kinds of bacteria in my gut. Interestingly these bacterial enzymes do not destroy benfotiamine.

I followed up on my theory of the underlying cause of dementia: that too many bacteria, producing a lot of thiaminase enzyme, destroy the thiamine in our food rendering us thiamine deficient. I found out that thiamine is essential for all living things, and it is necessary for the release of energy from food, particularly sugar or glucose. The brain only uses glucose as an energy supply. There are reports of low thiamine levels in the brain in patients who have died of dementia. Glucose metabolism in the brain is never normal in dementia. Benfotiamine has been shown to improve mild cognitive impairment. I speculated that this was the cause of my brain fog.

Thiamine Deficiency: The Missed Diagnosis

Why was it so difficult to make a diagnosis? I believe there are several reasons. Firstly, thiamine levels are rarely tested in the UK. Even though I had worked in the NHS for over 20 years I had never requested a thiamine test. Secondly, thiamine deficiency is known to present in widely differing ways. This is like many of the mysterious syndromes — a constellation of recognizable symptoms and signs with largely normal tests: irritable bowel syndrome, fibromyalgia, etc., and also long Covid. Thirdly, I wasn’t listened to. I’m not sure whether this is because I’m female, but I became extremely sick before anyone really tried to help, and even then I was reliant on friends I have in the medical profession.

I’m remarkably well now. I regained my memory and ability to think, although it probably took a couple of years. My guts still aren’t completely normal, but bacterial overgrowth is often a chronic condition. I still take supplements and I’m careful with my diet, avoiding sugar and alcohol. My diet is quite restrictive, but it’s worth it. I wouldn’t want to go back to how I was.

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

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This article was published originally on June 30, 2022. 

Understanding Mitochondrial Energy, Health and Nutrition

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I live in a retirement community. In my everyday discussions with fellow residents, I find that the idea of energy metabolism as the “bottom line” of health is almost completely incomprehensible. Since my friends are all well-educated professional people, I came to the conclusion that few people really have an idea about energy. For example, we talk about people who indulge in physical sports being energetic, while people sitting behind a desk are classed as sedentary. What we fail to realize is that mental processes require even more energy than physical processes. Both physically and mentally active people consume energy, so it is obvious that some kind of attempt must be made to talk about energy as it applies to the human body.

Hans Selye and the Stress Response

I will begin by giving an outline of the work that was performed many years ago by a Canadian scientist by the name of Hans Selye. Originally he was a Hungarian medical student. Some of the teaching was done by presenting individual patients to the class of students. The professor would describe the details of the disease for each person. What interested Selye was that the facial expression of each patient appeared to him to be identical. He came to the conclusion that this was the facial expression of suffering, irrespective of the nature of the disease. He referred to this as the patient’s response to what he called “stress”. He decided to study the whole concept of stress. He immigrated to Canada and in Montréal he set up a research unit that came to be called “The Research Institute of Stress”.

Of course, Selye could not study human beings and his experiments were performed on literally thousands of rats. He subjected them to many forms of physical stress and detailed the laboratory and histological results. He found that each animal would begin by mustering the well-researched fight-or-flight reflex. If the stress was continued indefinitely, the metabolic resistance of the animal gradually decayed. He called this ability of the animal to resist stress the “General Adaptation Syndrome” and came to the conclusion that it was driven by some form of energy. If and when the supply of energy was exhausted, he found laboratory changes in blood and tissues that were listed carefully. Although extrapolating this information from animal studies, he ended up by saying that humans were suffering from “diseases of adaptation” and that they were the result of a failure to adapt to the effects of life stresses.

My addition to this is that it would have been better to describe them as “the diseases of maladaptation”, meaning that humans have to have some form of energy to meet life. If there is energy failure, disease will follow. The remarkable thing is that energy production in the human body was virtually unknown in Selye’s time, so his conclusion was a touch of genius. The mechanism by which energy is produced in the cells of the body is now well-known. We know that energy consumption is greatest in the lower part of the brain and the heart, organs that work 24 hours a day throughout life. The lower part of the brain that organizes and controls our adaptive capabilities is particularly energy consuming. So before we begin to think about energy as a driving force, let us consider what we mean by stress and how we adapt to it.

Human Stress: Surviving a Hostile Environment

We all live in an environment that is essentially hostile. We have to adapt to natural changes such as cold, hot, wet and dry. We are surrounded by enemies in the form of microorganisms and when they attack us, we have to set up a complex mechanism of defense. Add to this the possibility of trauma and the complexity of modern civilization, involving business and life decisions. We possess the machinery that enables us to meet these individual stresses, meaning that we are adapting. Health means that we adapt successfully and that is why “diseases of maladaptation” makes a lot of sense. Obviously, the key is that the machinery requires energy.

Energy Metabolism, Physics, and Chemistry

First of all, let us begin by trying to define energy. The dictionary describes it as “a force” and the only way in which we can appreciate its nature is by its effects. It is not a substance that we can see but the effects of light energy enable us to have vision. The old riddle might be mentioned; “Is there a sound in the forest when a tree falls?” The answer is of course that the only way that the resultant energy can be perceived is when it is felt by the human ear. Even that is not the end of the story, because the ear mechanism has to send a message to the brain where the sound is perceived. Thus, there is no sound in the forest when a tree falls. It is the perception of a form of energy, a force that impacts on the ear of any animal endowed with the ability to hear. Energy can be stored electrically in a battery or as heat energy in a hot water bottle, but the inevitable process is that the energy drains away. A hot cup of coffee cools. A battery gives up its stored energy and becomes just “another lump of matter”.

For example, if a stone is rolled up a hill, its natural tendency would be to roll down the hill again. Whatever force is being used to roll the stone up the hill is known as “potential energy”. In other words, there has to be a constant supply of energy as long as the stone is moving up a gradient against gravity. When it reaches the top, we say that the potential energy is being stored in the stone. It is the equivalent of electricity being stored in a battery. The “potential energy”, however, requires an electrical force to “electrify” the battery. The potential energy in the stone can be released by allowing it to roll down the hill and Newton called this kind of energy “kinetic” (the use of a force to produce movement). The force that is being used is of course the effect of gravity and the stone becomes stationary when it gets to the bottom of the hill. The use of gravity as the source of energy is simply wasted, but note that gravity has not changed. It is still available for use. Let us take a simple example of this energy being used for a purpose. Suppose that there is a wall at the bottom of the hill and a farmer wishes to create a gate. In a fanciful way he could use the stone to create a gap in the wall. The gap in the wall is the observable mark of the effect produced by consumption of kinetic energy.

The body consists of between 70 and 100 trillion cells, each of which has a special function. Each is a one-celled organism in its own right and in order to perform their function they need a constant supply of energy. This is developed by complex body chemistry. The “engines” in each cell are called mitochondria and one of their many different functions is to synthesize energy. The energy that is developed is stored in a chemical substance known as adenosine triphosphate (ATP) and in order to understand this a little more, perhaps we should think of the Newtonian analogy for comparison. The Newtonian hill is replaced by an electronic gradient and the stone by the chemical ATP

Of Mitochondria and ATP

Cellular energy is produced in the mitochondria by oxidative metabolism. This simply means that a fuel (glucose) combines with oxygen but, like any fuel, it has to be ignited. The best way to analogize that is to say that thiamine can be compared with a spark plug that ignites gasoline in a car. It “ignites” glucose. The resultant energy is used to add a phosphate molecule to adenosine three times to make ATP (the electronic gradient). We have “rolled an electronic stone up an electronic hill”. As the adenosine donates phosphate molecules, it becomes adenosine monophosphate (AMP) that must be “rolled uphill again”. As it is “rolling down the electronic hill”, it is transferring energy. Therefore, ATP can be thought of as an energy currency. Note that there must be a continuous supply of fuel (food) that must contain the equivalent of a spark plug (thiamine) in order to maintain an energy supply with maximum efficiency.

The loss of any one of a huge number of components in food that work in a team relationship with thiamine, lowers the energy maximum. That is why thiamine deficiency has been earmarked as the major cause of a disease called beriberi that has haunted mankind for thousands of years. Its deficiency particularly affects the lower part of the brain and the heart because of their huge energy demand. Since the lower brain contains the control mechanisms that enable us to adapt to the environment, as depicted above, it is easy to see that we would be maladapted if there is energy deficiency, just as Selye predicted. In fact, one of his students was able to produce a failure of the General Adaptation Syndrome by making his experimental animals thiamine deficient. It also suggests that a lot of heart and brain disease is really nothing more than energy deficiency that could be easily treated in its early stages. If the energy deficiency is allowed to continue indefinitely because of our failure to recognize the implications, it would not be surprising that changes in structure would develop and produce organic disease.

Health and Disease in the Context of Energy

With this concept in view, the present disease model looks antiquated. There are only three factors to be considered. The first one is obviously our genetic inheritance. If it is perfect, all it requires is energy to drive it. However, DNA is probably never perfect in its formation. It may not be imperfect enough to cause disease in its own right, but a slight imperfection would constitute what I call “genetic risk”, causing disease in association with a stressor such as an otherwise mild infection or trauma.

Suppose that a given patient died from an infection (think of the 2018 flu).The present medical model would place the blame on the pathogenic virulence of the virus without considering whether malnutrition played a part by failing to produce sufficient energy for the complex immune response. Therefore, the second factor to be considered is the perfection of the fuel supply and that obviously comes from the quality of nutrition. Stress (the viral attack or non-lethal trauma) becomes the third consideration, since we have shown that an adequate energy supply is required for adapting on a day-to-day basis. There is even a new science called epigenetics in which it has been shown that nutrient components can be used to upgrade genetic mistakes in DNA. A fanciful interpretation of these three factors, genetics, nutrition and stress can be portrayed by the use of Boolean algebra. This is a mathematical representation as interlocking circles. The area of each circle can be easily assessed, marking their relative importance. The interlocking area between any two of the three circles and that of the three circles together completes the picture. It becomes easy to perceive how a prolonged period of stress can impact health. The present flu epidemic may be an example of the Three Circles of Health in operation, explaining why some people have only a mild illness while others die. Could the appalling nutrition in America play a part?

Why Thiamine

The pain produced by a heart attack has always been a mystery in explaining why and how it occurs. The answer of course is that pain is always felt by sensory apparatus in the brain. The brain is able to identify the source of the signal as coming from the heart but cannot interpret the reason. I am suggesting that in some cases, the heart is having difficulties from energy deficiency and notifying the brain. A coronary thrombosis would introduce local energy deficiency, but other methods of producing energy deficiency would apply. It is logical to assume also that brain disease is a manifestation of cellular energy deficiency. That is why I had found that so many children referred to me for various mental conditions responded to megadoses of thiamine. It is also why I had found that so much emotional disease was related to diet and not to poor parenthood.

I recently came across a patient that I had seen many years ago when he was a child. He had a diagnosis of Tourette’s syndrome, made elsewhere. I treated him with megadoses of thiamine and his symptoms resolved completely. Medical skepticism would answer this by calling it a placebo effect, but since this effect is well-known, it must have a mechanism. For many years I have believed that therapeutic nutrition “turns on” this effect by enhancing cellular energy. A small group of physicians known as “Alternative Medicine Practitioners” use water-soluble vitamins, given intravenously, irrespective of the acceptable clinical diagnosis. For example, I remember a young woman who came to see me with a diagnosis of “Thrombocytopenic Purpura”. This disease is a loss of cellular elements known as platelets and it had resisted orthodox treatment for years. I gave her a series of intravenous injections of water soluble vitamins with complete resolution of the problem. I must end by stating that healing is a function of the body. The only way that a healer can be justifiably recognized is by supplying the body with the ingredients that it requires to carry out the healing process. Perhaps spontaneous healing, as for example initiated by religious belief, is an ability to muster those ingredients that are present, but hitherto unused.

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This article was published originally on February 14, 2018.

Healing From Lupron and Endometriosis With Thiamine

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I was diagnosed with stage 4 endometriosis in 1996. In 2017, I was ready for a hysterectomy. I had two children and was finished with childbirth. I was having a lot of pain on my left side where my ovary was located. My Veterans Administration GYN refused to do a hysterectomy without first giving me Lupron shots assuming that my pain was due to the endometriosis. I was trying to hold down a very demanding government job and missing a lot of work from the pain. I had two laparoscopic surgeries in 1996 and 2001, respectively. Both were to excise the endometriosis. At the time, I was required to take Lupron in order to have a hysterectomy, I was 46 years old. I was denied a hysterectomy after my son was born in 2000 because I was considered too young at 30 years old to have a hysterectomy.

Endometriosis in the Colon and Lupron

After the injections of Lupron, a colonoscopy confirmed a diverticula pocket in that spot that was painful and others on my large intestine. The laparoscopy and excision in 1996 confirmed that my endometriosis extended to my large intestine. The colonoscopy found that I have so many pockets of diverticulosis, a resection surgery was not possible. Basically, if I were to become septic due to an endometriosis/diverticulosis flare, they would need to remove all of my large intestine. My options were very limited. My GYN wouldn’t perform a hysterectomy and laparoscopy under the assumption that the pain I was having was due to endometriosis. He convinced me to start the shots to see if they would help the pain because he assumed the pain was due to endo. I didn’t research the Lupron injections much prior to receiving them. I fully trusted my GYN. He mentioned hot flashes and suppression of symptoms with estradiol.

Immediately I noticed a difference. I don’t take prescription drugs of any kind unless I am really sick. I had nothing for any preexisting conditions. I could not tolerate the injections and function at work. I had severe hot flashes every few seconds 24/7 for three months even with add back estradiol. Worse, the estradiol made my migraines flare and so I was a hot mess. After stopping estradiol, my migraines continued to flare and still do without supplementation. I was also having diverticulosis flares every month sometimes twice a month. I had terrible gas and severe IBS symptoms. My work leave, FMLA and advanced sick leave were dwindling from all the visits to the various doctors. Within three months of my last Lupron injection, I was forced to retire or be fired for not being able to work. I never fully recovered from the Lupron.

Finally, a Hysterectomy

My GYN finally agreed to the hysterectomy in 2018 where they found my left ovary and left fallopian tube in one mass of adhesion scarring with my large intestine. The GYN removed the left polycystic ovary, left and right fallopian tubes along with my uterus, which had fibroids, and cervix leaving me with just my right ovary. Prior to the hysterectomy, I began noticing some numbness and cramping or burning in my feet at work that was much worse at night. I had the same kind of cramping and burning in my lower back too. I would later learn that these are symptoms of thiamine deficiency. Trying to keep it together at work with all of this was a nightmare.

Around this time, I also began having severe nausea and pain in my stomach. The GI doctors did an upper GI scope to confirm duodenal ulcers. The digestive issues, especially the diverticulosis should disqualify anyone from having Lupron as Lupron causes major digestive upset according to the FDA fact sheet. My digestive tract was inflamed from mouth to anus post Lupron. I had an inflamed esophagus and ulcers, diverticulosis flares, IBS with constipation and diarrhea and hemorrhoids that I couldn’t heal with meds. The low FODMAP diet helped though.

No More Pharmaceuticals

In 2019, I finally stopped taking all pharmaceuticals. No pharmaceutical made me feel better. Every medication I took for GI issues and neuropathy made me worse. I only took one for one or two weeks at a time to log all my side effects from each so I could have them added to my growing list of allergic reactions. I did have some sensitivity issues with prescription drugs prior to Lupron, just not as bad. I have the MC1R redhead gene. Redheads are more sensitive to pharmaceuticals and have more adverse reactions. I struggle with topical solutions as well. I couldn’t use estradiol patches because I’m allergic to the adhesive. Thankfully, my primary care physician also has endometriosis and suggested herbal supplements and remedies. All of this ,surprisingly, is from the veteran’s hospital. I was ordered by her to stop working. This was a final attempt to heal my ulcers, as they would eventually kill me if I could not find relief.

How I Healed Myself With Thiamine and Diet

I decided to try high dose thiamine after researching it via Drs. Lonsdale and Marrs and Elliot Overton. I started with 100mg daily for 6 months. Then 500mg for 3 months and currently 1000mg (500mg 2x daily). The thiamine works as well as the acupuncture with EMS. I also take Alpha Lipoic Acid and Dandelion root daily. The increases in thiamine are proving to be a significant factor in recovery. If I miss one day of supplements I’m sick for several days so I’m convinced that it is working.

To help myself heal, I no longer work a 9 to 5 job. I follow a low FODMAP diet with modification for diverticulosis and supplement with elderberry or dandelion for inflammation and immunity, turmeric, prebiotic + probiotics, magnesium for bone loss, palpations, anxiety, alpha lipoic acid for neuropathy, high dose thiamine for neuropathy, fatigue anxiety and brain fog, b vitamins and D3+K2 for b1 uptake regulation and delta 8 CBD for fibromyalgia pain and fatigue. I have regular chiropractor adjustments of my neck and lower back. Acupuncture and light therapy on my feet helped with the burning and cramping.

Where I Am Now

Currently, I have no endometriosis pain, only some lingering PMDD. I have no ovarian cysts and the migraines are not as frequent. Now only a couple a month versus weekly. I still have some burning and cramping in my legs and feet, but it is tolerable. Before thiamine, I was bedridden. The back and neck pain I had previously has improved with thiamine along with physical therapy/yoga and regular chiropractic care. I no longer experience diverticulosis flares with the new diet and supplements for inflammation like dandelion root, turmeric, and elderberry. I switch out the dandelion and elderberry because they work about the same. Depends on what is on sale.

I am able to stand for longer periods of time. My anxiety is significantly reduced, my palpations are gone, I can remember things, and my ADHD flare ups are minimal. In 2022, I only had two mild diverticulosis flares. Prior to the diet changes and supplements, I was having them once a month. I went from being bedridden completely to cooking (I still need to sit some), cleaning with short breaks, gardening with a sit on garden cart, and walking about a half mile every few days. I still have numbness in both feet. I am hopeful that lowering my A1C will resolve this. It may be permanent. Only time will tell. I’m going to the VA this week for a checkup and requesting more PT to see if it will help. They did an EMP on both legs with normal results. That was pretty painful but I felt nothing in my 3 little toes on both feet. Overall, I am doing much better with the higher dose thiamine and have much more energy.

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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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Charcot Marie Tooth Disease and Thiamine: A New Genetic Connection

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It is very probable that a non-medical reader, coming across this title, would not be further interested. Charcot was a famous neurologist in France, Marie one of his students, and Tooth was an English neurologist. They were the first physicians to observe a disease pattern that reappeared from time to time in their experience. Because the cause was unknown, their names were used to document the disease in medical texts. This post is being written to describe its complex genetic mechanisms that are coupled with thiamine metabolism and the fact that it is the most common inherited neuromuscular disorder.

Symptoms of Charcot Marie Tooth Disease

Symptoms commonly begin in childhood or early adulthood, although they may appear much later. Muscle degeneration in hands and legs appears together with a burning sensation in feet and hands. There is decreased sensation in the feet and hands and an awkward gait that is observed in the patient. Abnormal curvature of the spine, known as scoliosis appears and there is increased clumsiness and tripping.

Prevalence data from the general population is lacking. At present 47 hereditary neuropathy genes are known to be involved and it has been estimated that 30-50 genes are yet to be identified. However, in 2018, it was shown that deficiency of a single gene (DHTKD1) in mice caused them to develop the symptoms of the disease.

DHTKD1 and Thiamine

Maintaining the functional integrity of mitochondria, the energy producing organelles in cells, is crucial for cell function. Mitochondrial dysfunctions may alter energy metabolism and in many cases are associated with neurological disease. Although the function of DHTKD1 in the mitochondria remains unknown, it has been reported that there is a strong correlation with ATP production, the currency of energy metabolism. Genetically determined suppression of DHTKD1 leads to Impaired mitochondrial biogenesis and increased reactive oxygen species. In simple language, energy production is impaired.

What interested me was that the structure of the DHTKD1 gene is reported to be associated with thiamine. Mutations have been associated with certain metabolites in urine (2-amino adipic and 2- oxoadipic acids), Charcot Marie Tooth disease, and eosinophilic esophagitis (EoE). The pathophysiology of these two clinically distinct disorders remains elusive. It suggests that named diseases, each with its alleged distinctive laboratory studies, could all be the variable result of cellular energy deficit. It calls to mind the energy dependent General Adaptation Syndrome that gave rise to the conclusions of Hans Selye who described human diseases as “The Diseases of Adaptation”.

An experiment in rats investigated the long-term changes in brain metabolism after a single injection of 400mg/Kg thiamine. Protocols were established for discrimination of the activities of the two dehydrogenase complexes that constitute the enzymes derived from the DHTKD1 gene. The thiamine induced changes depended on brain-region-specific expression of the thiamine dependent dehydrogenases. In the cerebral cortex, the “thinking” part of the brain, both were relatively high and did not increase with thiamine administration. In the cerebellum, part of the automatic brain function, the original levels of both were relatively low and the activities of both were upregulated by the injection.

Energy Deficiency

The well-known effect of thiamine deficiency (TD) is the disease called beriberi. Because the brainstem, limbic system and cerebellum are peculiarly sensitive to thiamine deficiency, the autonomic nervous system becomes dysregulated, giving rise to symptoms of dysautonomia. Many case reports are to be found in the medical literature where a given disease has been found to be associated with dysautonomia, where the association observed is considered to be a mystery.

A case report of a single patient with eosinophilic esophagitis (EoE) was reported to have TD as the underlying cause of the associated dysautonomia. Since it is well known that sugar easily induces TD, the publication asks whether EoE is a sugar sensitive disease. Thiamine is a necessity for the metabolism of the vagus nerve, part of the autonomic nervous that is now known to control the mechanisms of inflammation, an essentially defense mechanism that occurs in many disease conditions.

Beriberi is variably polysymptomatic. None of the symptoms are exclusive to the disease. The reason seems to be adequately explained by the fact that it is the most obvious energy deficiency condition known. Potentially affecting every cell in the body, it would be expected to have its major effects in the most metabolically active tissues. It is well known that the brain, nervous system and heart are the organs that answer to that criterion. I have always been interested in seeing a written report of a neurological disease in which heart disease is seen as an unexpected complication. The observer usually believes that this represents the appearance of a second disease instead of looking for energy deficiency as the cause of both.

Protein Folding and Thiamine

Enzymes are proteins and are constructed from long chains of amino acids bound together, possibly by electro-magnetic attraction. When not in use, the chain has to be folded, presumably for storage. When required for use as an enzyme it has to be unfolded. The folding/unfolding details of these chains are exquisitely complex and repetitive but the mechanism remains unknown. Every polypeptide has the capacity to misfold and form a non-functional protein.

A normal protein called the prion protein exists in the body. Its functions are largely unknown. It is also the key molecule involved in the family of neurodegenerative disorders, also known as prion diseases. Several forms of disease result from an accumulation of a variably misfolded isoform of this protein. Of profound interest, it has been reported from animal studies that the prion protein binds thiamine, leading to the hypothesis that thiamine metabolism might supply the energy required for protein folding and unfolding.

Genetics Versus Epigenetics in Charcot Marie Tooth Disease

The relatively recent discovery that nutrients can have an effect on genes has led to the science of epigenetics. It seems to be apparent that, although genes can cause a disease on their own, many genetically determined mechanisms may be insufficient to cause a disease by themselves. Perhaps the symptoms of a well-established, genetically determined disease such as Charcot Marie Tooth disease might respond clinically and biochemically to an epigenetic trial of a nutrient associated with its structure and consequent function. The symptoms of Charcot Marie Tooth disease are those that could be expected from a deficiency of energy affecting the genetically determined associated cellular defects.

Parkinson’s, Alzheimer’s, Huntington’s diseases and prion disease, as well as a variety of other disorders, are regarded as examples of an anomalous aggregation of proteins and all associated with thiamine. Also, Costantini and his group have shown that Parkinson’s disease responds clinically to high dose thiamine. This group had already reported that high dose thiamine had relieved the fatigue associated with ulcerative colitis and Crohn ‘s disease, implicating that energy deficiency was the cause of fatigue. The question arising from all of this – is energy deficiency the cause of disease, represented in a massive conglomerate of different manifestations ?

Conclusion

Charcot Marie Tooth is now an old-fashioned way of describing a disease, particularly because a single gene defect has been implicated to be responsible for this disease as well as EoE, two entirely different conditions. It is suggested here that the genetic changes lead to energy deficiency in the affected cells. Evidence is accumulating that Selye’s explanation of human diseases as the “diseases of adaptation” may be correct. Perhaps it may lead to general acceptance of Orthomolecular Medicine as proposed by the late Linus Pauling.

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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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Benefros at English Wikipedia, CC BY-SA 3.0 <http://creativecommons.org/licenses/by-sa/3.0/>, via Wikimedia Commons.

This article was published originally on July 14, 2021. 

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