thiamine hypoxia

Depression, Anxiety, and the Chronically Hypoxic Brain

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I couldn’t help noticing the Wall Street Journal of Thursday, June 7, in which a column reported a completely unexpected suicide. The title of the column was “Kate Spade’s Family Recounts Her Battle With Depression”. It was reported that “Ms. Spade had suffered from depression and anxiety, and was being treated with medication and therapy. Depression and anxiety disorders occur simultaneously in about 25% of general practice patients. In the abstract, the author says “about 85% of patients with depression have anxiety and 90% of patients with anxiety have depression. Benzodiazepines may help alleviate insomnia and anxiety but not depression”. It must be obvious that the general impression is that these are two different expressions of psychological disarray that require different drugs to treat them. Evidently, Ms. Spade had left a suicide note indicating that she had been under mental stress from her marriage. There were other stresses reported. She had been living separately from her husband for 10 months and had been seeking help for the past five years.

The incongruity requires explanation. Here was a 55-year-old woman who was highly successful in the eyes of the world and her suicide appears to be completely incongruous, as indeed most suicides are. There should be a logical explanation for such an anachronism. The instinct for life is incredibly strong for us and indeed for all creatures in the animal kingdom. I offer my explanation here, based on the contention that the human brain is an electrochemical machine and that its functions are highly dependent on an adequate supply of energy. This does not take into account the concept of a soul that must remain one of the great mysteries of life.

Revisiting Freud: The Ego and the Id

According to Sigmund Freud, the id is the subconscious mind supervised by the ego and what he called the super-ego. All are built upon the presupposed existence of conscious and unconscious thoughts. Modern research has failed to find individual areas in the human brain dealing with the control of specific action. Its function is now regarded as an integrated organ, all parts of which share that action. However, much of this activity is entirely automatic and below conscious level. All brains in higher members of the animal kingdom are built on the same anatomical principle, presumably reflecting a “oneness” in design. If we are to accept evolution as the driving force, the brain of each animal has been developed to service that animal in its natural niche. The niche of Homo sapiens appears to be that of the dominant species and it has evolved from a more primitive state to a more sophisticated one, gradually introducing increased complexity. Brain action would be expected to become more and more sophisticated over time, perhaps making us more cooperative.

We have no idea what is in store for us with continued evolution, but it has long seemed to me that we are still relatively primitive at the philosophical level. Under stressful conditions, the actions of the human brain are much less predictable. However we consider the distribution of brain function, it is an electrochemical machine and a great deal of its activity is unconscious and purely automatic. Body organs signal the brain that then gives instructions to them via the autonomic and endocrine systems. It is therefore convenient to accept the ego and the id, each with its separate functions, however, they are controlled, by the conscious and unconscious mind. Some of the net behavior might be perceived as actions of the automatic component, governed and permitted by the conscious component. It has been suggested that human beings are built as “mean fighting machines equipped for self-interest”.

The Nervous System

Many posts on this website describe the difference between the so-called voluntary and the autonomic nervous systems. The term “voluntary” indicates that we can think and move at will and its actions are dictated by the conscious mind. The autonomic nervous system is almost completely automatic and governs many purely reflex actions, the fight-or-flight reflex being the best known. Hunger and thirst are self-preservatives. The sex drive preserves the continued existence of the species. Yes, these reflexes give us a sense of pleasure, which is the driving incentive and the brain provides us with sensory mechanisms that provide that pleasure. Everything is tied together by a complex code known as DNA, whose individual characteristics describe the physical profile and personality of each animal including humans. From a purely philosophical point of view, it calls into question whether we truly have free will or whether we are programmed by the environment in which we find ourselves. If all components fit together as designed, we can say that the “blueprint” for each person dictates the nature of the personality and reflects his/her mental and physical health. Our training to meet life starts in infancy and is in the hands of parents.

Of Stress and Stressors

Stress is a physical or mental event to which each of us has to adapt. As I have mentioned in other posts on this website, a Canadian researcher by the name of Hans Selye studied the effect of physical stress in animals for many years. He came to the conclusion that virtually any form of stress demanded an increase in the supply of cellular energy, much like the engine of a car climbing a hill. A stressed animal had to adapt to the injuries applied by Selye. He called it the “General Adaptation Syndrome”. He used many different methods to induce stress because he wondered whether there were different responses, depending on the nature of the stressor. He found that the stress response was uniformly identical across species and was able to divide the General Adaptation Syndrome into several predictable phases, each of which was repeatable in each experiment. Not surprisingly, his studies included an array of sequential biochemical changes in the body fluids. I found these changes to be similar to the laboratory changes seen in chronically sick patients. One of his students was able to produce the syndrome by first making the animal deficient in the vitamin thiamine, thus supporting the role of energy deficiency as the causative factor. Selye suggested that human health broke down as a result of energy failure, particularly in the brain, leading to what he called “the diseases of adaptation”. It is probably true that some form of life stress is absolutely necessary for a person to contemplate suicide. Therefore, it seems necessary to discuss the mechanisms by which the brain responds to stress.

The Biological Brain

Whether we like to recognize it or not, the brain is an electrochemical machine whose functions, like any machine, require energy. The fact that the brain requires 20% of the total oxygen inhaled is an absolute indication of its energy requirement. There is much evidence that even a mild reduction influences brain activity and this will be reflected in some kind of change in thought processes and the consequent behavior resulting from it. Nutrition affects mood. A deficiency of many vitamins is associated with psychological symptoms. In some elderly patients, folate deficiency is associated with depression. Iron deficiency is associated with apathy, depression, and rapid fatigue when exercising. In several studies, an improvement in thiamine status was associated with improved mood. One of the major manifestations of obstructive sleep apnea is profound and repeated (episodic) hypoxia (insufficient oxygen) during sleep. This increase in activity in the sympathetic nervous system affects blood pressure. Thiamine deficiency induces gene expression similar to that observed in hypoxia and has been referred to as causing pseudo-hypoxia. Magnesium and thiamine deficiency have both been implicated in depression.

Hypoxia and Pseudohypoxia in Depression and Anxiety

During many years of medical practice, I found that a mild degree of thiamine deficiency was responsible for symptoms that are often regarded as psychological. Chronic anxiety and depression were regularly alleviated by getting people to understand the importance of an appropriate diet, together with the administration of supplementary vitamins, the most important of which were thiamine and magnesium. I could never understand how a patient could be actually blamed for producing symptoms beyond the comprehension of the physician. Abnormal thoughts, emotions, and all forms of mental activity are produced by electrochemical reactions that are exaggerated by a mild degree of hypoxia or pseudo-hypoxia.

Anxiety and depression are perfectly normal emotional reactions but when they are sustained for absolutely no reason, it is because of this biochemically initiated exaggeration. In particular, the sympathetic branch of the autonomic nervous system is easily activated because any degree of oxygen lack is obviously dangerous to the organism and a fight-or-flight reflex reaction would be initiated by the perception of danger. This reflex, because of its nature, might give rise to aggressive behavior when a nursed a grievance explodes into violence. The widespread intake of empty calories, particularly in the form of sugary and fatty substances, is responsible for polysymptomatic disease in millions. Such individuals cannot handle the normal stresses of life and are much more easily imbued with a sense of hopelessness. Suicide seems to be the only option. The idea that dietary excesses might be responsible for depression and suicidal ideation is not a presently acceptable concept, but the biochemical results of alcohol and sugar ingestion are identical in the part of the brain that has to deal with these inbuilt vital reflexes.

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This article was published originally on June 20, 2018. 

New Developments in High-Dose Thiamine: The Legacy of Antonio Costantini

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In partnership with his colleagues, the Italian doctor Antonio Costantini pioneered the use of high-dose thiamine for treating a range of neurological and inflammatory conditions, including Parkinson’s disease (and here), multiple sclerosis, fibromyalgia, inflammatory bowel disease, and chronic cluster headaches.

Sadly, in 2020, Dr. Costantini contracted COVID-19 and died. While his work is finished, his legacy of exploring the therapeutic benefits of high-dose thiamine endures. In the past year, several important studies on high-dose thiamine have been released. This review briefly describes two of these studies and several related resources.

High-Dose Thiamine for IBD Fatigue

In the January 2021 issue of Alimentary Pharmacology & Therapeutics, Palle Bager and colleagues published a randomized controlled trial examining whether oral high-dose thiamine helped relieve fatigue in patients with quiescent inflammatory bowel disease (IBD) and severe chronic fatigue. Following a regimen adapted from Costantini’s earlier pilot study and other Costantini studies, the patients in Bager’s trial received 600 to 1,800 mg of oral thiamine hydrochloride daily, based on weight and gender. The 40 patients in the study were randomized to either receive high-dose thiamine or a placebo for four weeks. Following a four-week washout period, the control and treatment groups switched for another four weeks of treatment/placebo, so that everyone in the study received both high-dose thiamine and a placebo. The trial found that high-dose thiamine produced large reductions in self-reported fatigue on the validated IBD fatigue scale that were both clinically and statistically significant. No statistically significant relationship was observed between the impact of high-dose thiamine and patients’ baseline thiamine deficiency status.

This study is significant for its use of a very rigorous evaluation method: a double-blind cross-over randomized controlled trial. Using this gold standard evaluation method, Bager and colleagues largely confirmed the findings of Costantini’s earlier pilot study. While the Bager study focused only on people with IBD, it provides reason to be optimistic that high-dose thiamine may be helpful for the other populations studied by Costantini and possibly for people with other neurological and inflammatory conditions.

Bager and colleagues suggest that the impact of thiamine in reducing fatigue among patients with IBD and chronic fatigue may be related to problems the patients experience with the active transport mechanism for thiamine:

While the effect of high-dose oral thiamine was highly significant in our study, its exact mechanisms still need to be explored and investigated. The theory of a dysfunction in thiamine transport from blood to mitochondria remains a plausible explanation. The participants in our study were exposed to high doses of thiamine which induces passive diffusion that will add thiamine to the cells and the mitochondria. Consequently, the carbohydrate metabolism can normalise, and a reduction of fatigue is likely to follow.

In a Letter to the Editor of Alimentary Pharmacology & Therapeutics, I urged consideration of an alternative hypothesis, grounded in thiamine’s property as a carbonic anhydrase inhibitor:

The inhibition of carbonic anhydrase isoenzymes by high-dose thiamine and the resulting production of carbon dioxide could lead to reductions in fatigue and other symptomatic improvement through one or more of four potential pathways: (a) by reducing intracranial hypertension and/or ventral brainstem compression; (b) by increasing blood flow to the brain; (c) by facilitating aerobic cellular respiration and lactate clearance through the Bohr effect; or (d) by dampening the pro-inflammatory Th-17 pathway, again through the Bohr effect, potentially mediated by reductions in hypoxia-inducible factor 1.

More background on my hypotheses on the potential mechanisms for the impact of high-dose thiamine, with full citations, may be found here. The authors’ thoughtful reply to my letter may be found here.

High-Dose Thiamine for COVID-19

Another important recent study on high-dose thiamine has been released on a preprint server and is currently under consideration at the journal Critical Care. The study found that administration of high-dose thiamine to 83 patients in Saudi Arabia who were critically ill with COVID-19 was associated with a 55% reduction in 30-day ICU mortality and a 51% reduction in in-hospital mortality, as well as a reduction of 81% in the incidence of thrombosis during their ICU stay. The patients received a median of 100 mg of thiamine (presumably intravenously) for a median of 7 days.

Unlike the Bager study, the COVID-19 study by Al Sulaiman and colleagues was a retrospective study using a case matching approach, rather than a prospective study using random assignment. The authors matched the patients treated with high-dose thiamine to other critically ill COVID-19 patients using propensity scores based on baseline characteristics and controlling for the use of systemic corticosteroids. Based on correspondence with the authors, I understand that the patients’ baseline thiamine levels were not measured and thus unavailable as a matching variable.

This study is significant for providing evidence of the potential of high-dose thiamine to help treat critically ill patients with COVID-19. As I noted in an earlier Hormones Matter blog post, a prior study had found that high-dose thiamine damped down the pro-inflammatory th-17 pathway associated with the COVID-19 cytokine storm, but that study did not involve the treatment of actual COVID-19 patients.  Outcome data from the Front Line COVID-19 Critical Care Alliance suggests that the combined use of Methylprednisolone, Ascorbic Acid (Vitamin C), Thiamine and Heparin  (the so-called MATH+ protocol) may be helpful for COVID-19, but those data do not isolate the impact of high-dose thiamine and do not compare outcomes for treated households to those of a comparison group.

A randomized controlled trial is needed to verify the results found by Al Sulaiman and colleagues and assess whether high-dose thiamine can reduce mortality from COVID-19 among critically ill patients. It would also be valuable to rigorously evaluate whether oral high-dose thiamine could help early stage COVID-19 outpatients avoid hospitalization by reducing the incidence of the COVID-19 cytokine storm. This could help reduce the burdens of hospitals in India, Brazil, and other countries with high COVID-19 caseloads.

Future Directions

I am hopeful that additional rigorous research will be conducted to assess the potential of high-dose thiamine to treat a range of neurological and inflammatory conditions. It is hard to imagine a better tribute to Costantini’s work than a series of additional randomized controlled trials evaluating whether the observations he made in his pilot and case studies hold up when tested with larger samples using rigorous methods.

In addition to the conditions studied by Costantini, I would also encourage research into whether high-dose thiamine could be helpful for people with myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS) and the neurological complications of Ehlers-Danlos Syndrome (EDS) (such as those experienced by my daughter). In this Medium post (more technical discussion) and Health Rising post (less technical discussion), I explain why I think these populations could benefit from high-dose thiamine.

More recently, I documented the retrospective self-reported outcomes for 55 individuals with ME/CFS, EDS or Fibromyalgia who reported taking 200 mg of more daily of high-dose thiamine. Nearly two-thirds of the participants in this retrospective survey reported large benefits, most commonly in reducing fatigue, post-exertional malaise, and brain fog.  Interestingly, benefits were reported across a range of doses, including doses below those used by Costantini and Bager. Several study participants described high-dose thiamine as a game-changer that brought them substantial relief. The study has many limitations. For example, it was a small non-representative sample and based on self-reports only, but it is consistent with the potential of high-dose thiamine to provide large therapeutic benefits. I am hopeful it will help make the case for conducting more rigorous research in the future.

To the extent that Long COVID is similar to ME/CFS, I would also encourage the study of high-dose thiamine for people with this debilitating condition.

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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 June 10, 2021.

Why Do We Use Nasal Oxygen?

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I live in a retirement home and I see many residents who are receiving nasal oxygen, so I am going to try here to address the reason. They may have been diagnosed with either heart disease or lung disease and they have probably been observed clinically to be “short of breath”. Of course, I do not know the specific reason for a given individual receiving this treatment, but does the average patient understand why he or she has to tolerate this inconvenience? I strongly suspect that they have merely been told that they need oxygen administration without explaining the underlying reason. Generally speaking, most people take for granted that they are alive and have little interest in why or how, unless their health becomes threatened. Obviously, when nasty things start to occur, they ask a physician why it is happening to them and the physician tries to diagnose the affliction. It usually winds up by the patient being told that it is disease A or B and a superficial description of the disease is provided. Each disease is regarded as having a specific treatment and a specific cure that is usually being sought by a drug company. The most up-to-date drug is offered. Unfortunately, with the exception of bacterial infection, most drugs only treat the symptoms and do not address the underlying cause. Modern research focuses almost exclusively on genetics and for the most part little consideration is given to prevention other than making a diagnosis of early disease. So why are these people receiving nasal oxygen?

Why Do We Need Oxygen?

Of course, we all understand that our environment must supply us with oxygen, water and food, without any of which we die. Although I have written about oxygen utilization in many posts on this website, it bears repetition because of what I want to say about nasal oxygen administration as described above. First of all, it must be stated that the main three gases in air are nitrogen, oxygen and inert gases. Seventy-eight percent of air is made up of nitrogen, 21% is oxygen, just under 1% is argon and the remaining part is made up of other gases such as carbon dioxide and water vapor. In other words, our oxygen intake is dosed. Too much oxygen is as lethal as none at all, illustrating the wisdom that was propounded in ancient China called Yin and Yang, not too much and not too little. The thing that always amazes me is the concise nature of the natural world and how we should fit into it. The more I get to know about the human body the more I realize how little we know. However, we do know what we do with oxygen. It is called oxidation.

Understanding Oxidation

It is surprising to me that many people appear not to understand that when a fuel burns, it is because the fuel is combining with oxygen. The result is the production of energy in the form of heat, the simple physics that we learned in school. The word oxidation is defined as “cause to combine with oxygen”. But consider that a piece of newspaper will not burst into flame by itself. It has to be ignited. If we use a match, the heat generated from striking it on a rough surface is enough to make it burst into flame and that energy in the form of the flame is transferred to the newspaper. What we are looking at is simply the transfer of energy from one action to another. Even striking the match requires the energy of the individual who performs it. But there is another factor that comes into play here. The newspaper will produce what we call ash, representing the fact that the newspaper has not been completely consumed (oxidized). I am providing these simple principles to explain now that this is exactly what happens in the body. The principles are identical: the mechanisms are different.

Cellular Oxidation

Starting with first principles, as we breathe, our lungs are taking in air and extracting oxygen from it. The oxygen is transferred into the bloodstream and picked up by combining with hemoglobin that coats red cells. This represents a transport system and the oxygen has to be delivered to each of the 70 to 100 trillion cells. This in itself is an amazing representation of the blood circulation. The deoxygenated blood is transferred to the venous circulation and transported back to be re-oxygenated. It is now that the process of oxidation takes place in the cells that have received the oxygen. To put it as simply as possible, glucose, the primary fuel, combines with oxygen to yield energy that drives the function of the cell in which the oxidation takes place. Just like the analogy of the newspaper, the combination of glucose with oxygen has to be “ignited”. Thiamine and other vitamins and minerals are the equivalent of a match. Carbon dioxide and water are the equivalent of ash from the newspaper. They have to be got rid of and so they are expired in the breath. Gasoline in a car engine has to be ignited so the explosion in a cylinder might be referred to as oxidation. The smoke in the exhaust pipe is the “ash”.

Nasal Oxygen and Hypoxia

It is my experience is that the use of nasal oxygen, although completely correct in itself, seems to be associated with ignorance of the fact that the sufferer is probably lacking the vitamins and minerals that enable the oxygen to be utilized in the body. Indeed, the lack of vitamins and minerals may be the main issue in the underlying cause of the disease, a fact that is flatly denied by the vast majority of physicians. The word for lack of oxygen in medical literature is hypoxia. The effects of thiamine deficiency, because it causes exactly the same symptoms, is referred to as pseudo-hypoxia (false lack of oxygen). In reality, the symptoms of the patient are caused by lack of oxidation, resulting in lack of cellular energy and consequently, their loss of function. Using the above analogy, it would be like holding a piece of newspaper and expecting it to burst into flame spontaneously. The most recent medical literature is full of manuscripts reporting the relationship of thiamine deficiency with chronic disease, even cancer, and various forms of traumatic surgery. It is not sufficiently recognized that the widespread ingestion of empty carbohydrate calories easily induces inefficient oxidation. This is but another reason why Dr. Marrs and I have written our book “Thiamine Deficiency Disease, Dysautonomia and High Calorie Malnutrition“, available at Amazon books. ‘

Conclusion

Why do so many individuals require nasal oxygen? With the present thought process, the patient is considered to have a condition that would benefit from its administration, perhaps heart or lung disease, operating on the present disease model. Physicians are not really thinking in terms of oxidative metabolism as the underlying mechanism. The point that we are trying to make here is that no amount of extraneously supplied oxygen will be effective unless the vitamins and minerals are present in sufficient quantity for the oxygen to be used in the creation of energy. Oxidation requires the presence of glucose, oxygen and the requisite vitamins and minerals and deficiency of any one of the three will be responsible for the symptoms.

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This article was published originally on April 5, 2018. 

Quick Thoughts: Thiamine, Hypoxia, and Bowel Function

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Insufficient thiamine intake creates a state of cell level hypoxia. Although it is called pseudo-hypoxia, because no obstruction is evident, deficiency-induced hypoxia elicits all of the same molecular changes one might expect with obstructive hypoxia. Most notably, the lack of thiamine stabilizes something called hypoxia-inducible factors or HIFs. There are multiple isoforms of this protein that perform slightly different functions in different regions of the body, but overall their job is to re-regulate the genes responsible for maintaining oxygen homeostasis in the face of low oxygen. To that end, HIFs control the transcription of hundreds of genes. Some of the functions managed by HIFs include erythropoiesis – the production of more red blood cells, angiogenesis to bring more blood and hence more oxygen to the region, and the switch to anaerobic metabolism so that energy production may be maintained, at least partially. Anaerobic metabolism is much less efficient than aerobic metabolism.

Where this gets interesting is once HIFs are stabilized, they turn around and block thiamine uptake. A recently published study found that in the epithelial cells that line the colon, and I would suspect elsewhere as well, HIF stabilization inhibits thiamine uptake by downregulating thiamine transporters. So the same proteins that are upregulated with insufficient thiamine, also downregulate the very nutrient required to resolve the hypoxia. In other words, low thiamine creates cell level hypoxia that stabilizes – turns on – the HIF cascades to bring more oxygen to the region. Simultaneously, stabilized HIF proteins limit thiamine uptake, causing a greater deficiency and larger hypoxic state. If extra thiamine is not consumed, which it rarely is, this would lead to a very destructive cycle.

In the intestines, this process alters, and ultimately limits, microbial synthesis, and uptake of thiamine. It also disrupts the microbial ecosystem itself, favoring more pathogenic organisms better equipped to maintain some semblance of thiamine sufficiency via what are called thiamine salvage pathways. The net result of these changes, is the downward spiral of gastrointestinal dysbiosis and dysmotility. Research like this points to gut dysfunction as one of the leading indicators of poor thiamine management.

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The Warburg Effect in Cancer

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In the 1930s Otto Warburg won a Nobel Prize for an observation that has since become known as “the Warburg effect” in oncology. He had reported that most cancer cells predominantly produce energy by a high rate of glycolysis (sugar metabolism) rather than the low rate in most normal cells. The energy in cancer cells, that typically have a glycolytic (sugar metabolism in action) rate up to 200 times higher than normal cells, is produced by fermentation. This form of energy production does not require oxygen and is known as anaerobic metabolism (without oxygen). Normal cells derive their energy from a chemical process that does require oxygen, hence the term oxidative, or aerobic (requiring oxygen), metabolism. The process of fermentation in cancer cells is much less efficient in producing energy than that in normal cells that derive energy from oxidative metabolism. Curiously, this anaerobic metabolism happens in cancer cells even when oxygen is plentiful. Although this has been much studied, its importance, either in cause or effect, remains unclear. Warburg had postulated that this change in metabolism is the fundamental cause of cancer, a claim now known as the Warburg hypothesis or Warburg effect. Today, mutations in oncogenes (genes associated with cancer) are thought to be responsible for malignant transformation and the Warburg effect is considered to be a result of these mutations rather than the cause. In other words, does the Warburg effect originate the cancer or is it an effect of the cancer? It is a typical “chicken and egg” question.

The Role of Thiamine in Cancer

The relationship between supplemental vitamins and various types of cancer has been the focus of recent investigation. Supplemental vitamins have been reported to modulate cancer rates and a significant association has been demonstrated between cancer and low levels of thiamine in the blood (1). This also gives rise to a “chicken and egg” question. Is the low level of thiamine a result of treatment using chemotherapy and radiation or does it have a causative relationship? Thiamine deficiency is increasingly recognized in medically ill patients. Its prevalence among cancer patients is unknown. However, thiamine deficiency was found in 119 (55.3%) of 217 patients with various types of cancer. Risk factors included effects of chemotherapy or undergoing active treatment (2). It is possible to induce a certain type of tumor in mice. Thiamine supplementation between 12.5 and 250 times the recommended dietary allowance (RDA for mice) stimulated the tumors. Doses 2500 times the RDA resulted in 10% inhibition of tumor growth (3). This inhibitory effect of exceedingly high doses of thiamine is unexplained and certainly merits further study.

Thiamine as a Drug

The definition of a drug is “a medicine or other substance which has a physiological effect when ingested or otherwise introduced into the body”. Therefore, if thiamine is taken as a supplement, it must be considered to be a drug. Conventional wisdom sees thiamine as a food-borne particle whose function, in a minute concentration, is to assist the enzymes to which it is attached. The daily dose is governed by the RDA and is stated as 1 to 1.5 mg/day. For this reason, if its deficiency as a cause of symptoms is recognized in a given patient, the treatment would be considered to be simply replacement value. Any increase in that dose would inevitably be considered completely unnecessary. This is in spite of the hard-won history that treating beriberi demanded as much as 100 mg of thiamine a day for months. Of course, as I have mentioned in these pages many times, conventional wisdom also denies that beriberi, or any other form of vitamin deficiency, exists in America or any other developed culture. There are now many reports in the medical literature of thiamine being used in megadoses to treat virtually any disease associated with or caused by a breakdown in energy metabolism. It is therefore worth considering the potential mechanism in the already established place of thiamine, or its derivatives, in cancer.

We used to think that our genes dominated our body functions in a fixed way throughout life. The relatively new science of epigenetics tells us that nutrition and lifestyle have a powerful influence on our genetically determined mechanisms. Research in cancer has been almost completely dominated by study of the influence of specialized genes, known as oncogenes. The question that should arise is what, if ever, is the influence of malnutrition on these genes. Could thiamine deficiency “turn on” or otherwise influence oncogenes through epigenetic mechanisms? Our book (Lonsdale D, Marrs C. Thiamine Deficiency Disease, Dysautonomia and High Calorie Malnutrition) emphasizes that widespread thiamine deficiency exists in America because of an inordinate ingestion of sugar in all its different forms. The book supplies evidence that an overload of glucose ingestion provides “empty calories” that overwhelms the capacity of thiamine metabolism in processing the glucose. In other words, the intake of thiamine in the diet might be sufficient for a normal calorie load but insufficient for the load of empty calories. This is referred to as “high calorie malnutrition”. Calibration of diet depends on a study of three meals a day. We suggest that it is the inordinate consumption of sugar associated with almost all social activities that may make the difference. We question whether there is a potential relationship with the increasing incidence of cancer. Is sugar our ultimate enemy? Is our hedonistic consumption of it a threat to our civilization? Although this sounds like a fictional idea for a novel, understanding the complex role of thiamine in glucose metabolism should make us pause to wonder whether the pleasure derived from taste is a potential cause of our undoing.

Hypoxia, Thiamine and Cancer

Hypoxia is one of the hallmarks of the tumor microenvironment (referring to the local concentration of oxygen that exists around cells that become cancerous). It is the result of insufficient blood supply to support growing tumor cells (4). This would result in lack of oxygen, but also would restrict the supply of vitamins, including thiamine. It is interesting that thiamine deficiency results in a metabolic disturbance that induces a state similar to deficiency of oxygen and is known as pseudo-hypoxia (pseudo-, meaning false)(5).

The term vitamin was derived from the finding that each one of these chemical substances found in naturally occurring food is “vital” to life. Thiamine’s role is to turn chemical food substances into energy. Therefore, it must be recognized as having the same life-giving effect in the body as oxygen. Granted that it is not the only vitamin required for this, however, it appears to have a degree of importance that makes it the dominant factor. Early studies of the relationship of thiamine deficiency as the cause of beriberi showed that, as the disease progressed, there were different metabolic patterns marking the degree of deficiency. For example, patients with a normal blood sugar responded to thiamine easily. Those with a high blood sugar were slower to respond and those with a low blood sugar often didn’t respond at all. The far-reaching consequences of the increasing effect of thiamine deficiency as the disease progressed need to be understood better.

It is known that the part of the brain that enables us to adapt to and thrive in our hostile environment, is particularly susceptible to thiamine deficiency. Therefore, its deficiency provides effects that are exactly similar to partial deprivation of oxygen. Is it possible that thiamine deficiency, resulting as it does in loss of efficient oxidative metabolism, is the underlying factor that initiates the cancer by an epigenetic mechanism? The low dose/high dose administration of thiamine in producing the opposite effects may be a mystery of thiamine metabolism requiring further research. Perhaps thiamine deficiency activates the genetic mechanisms that are known to be involved in the transition of the normal cell into a cancerous one. It may be that some cancers (and a lot of other diseases) could be prevented by a rational approach to a diet that spares us from metabolic stress induced by this highly artificial “high calorie malnutrition”.

Although this article is written for general readership, references are included to show that the statements made within the article are supported by publication in the medical literature.

References

  1. Lu’o’ng KV, Nguyen LT. The role of thiamine in cancer: possible genetic and cellular signaling mechanisms. Cancer Genomics Proteomics, 2013, 10 (4): 169-85.
  2. Isenberg-Grzeda, E., Shen, M. J., Alici, Y., Wills, J., Nelson, C., & Breitbart, W. High rate of thiamine deficiency among inpatients with cancer referred for psychiatric consultation: results of a single site prevalence study. Psychooncology 2016. May 26. doi. 10. 1002/pon. 4155. [Epub ahead of print]
  3. Comin-Anduix B, Boren J, Martinez S, et al. The effect of thiamine supplementation on tumor proliferation. A metabolic control analysis study Eur J Biochem, 2001, 268 (15): 4177-82.
  4. Kumar V, Gabrilovich DI. Hypoxia-inducible factors in regulation of immune responses in tumor microenvironment. Immunology, 2014, 143 (4): 512-9.
  5. Sweet RL, Zastre JA. HIF1-α-mediated gene expression induced by vitamin B1 deficiency. Int J Vitam Nutr Res 2013, 823 (3): 188-97.

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Thiamine Deficiency and Sugar in Diabetes

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Thiamine is one of the B vitamins and I need to explain its action. To put it as simply as possible, it regulates sugar metabolism in every cell within the body and has a special importance in the brain. About four years ago a researcher in England reported that there was a mild deficiency of thiamine (vitamin B1) in diabetic patients, a disease that affects sugar metabolism. He said that all diabetics should have a supplement of thiamine because he had anticipated that it will prevent complications in this devastating disease. If that is not enough to make a diabetic sit up and take notice I would be very surprised.  I will try to explain this a little further.

A program on PBS television called “The Quiet Revolution” reported that there were 29 million patients in the United States with type two diabetes and as many as 70 million with pre-diabetes, meaning that they were on their way  to contract the disease. If we had 29 million cases of “flu” it would be called a pandemic. Most people with type 2 diabetes have no idea that their health before the onset of the disease is within their own responsibility. Our culture says “go ahead, do what you like, eat what you like, drink what you like; if you get sick, it is just bad luck and you go to one of those clever characters called Dr. who will produce the magic bullet that “cures” you because of the wonders of modern scientific medicine.

Although both types one and two have different causative factors, I want to emphasize very strongly that both types are not purely genetically determined. The genetic risk in type 1 is much greater than in type 2 and is certainly the major component as the underlying cause. Type 2 is much more clearly initiated by dietary indiscretion in a person who might be, shall we say, at genetic risk. Much of our diet today involves the consumption of man-made foods developed by the food industry. Of course, the main drive of this industry is to sell their products and so it appeals to our palatability, a sensory phenomenon that has nothing to do with good nutrition. We all know what pleasure we get from tasting anything that is sweet. Since sweetness sells, it explains why so many man-made foods are laced with sugar, so long thought to be harmless and even good for you by supplying quick energy.

Sweet and Dangerous: Sugar and Thiamine Deficiency

In 1973, John Yudkin, a professor of nutrition in a large London Hospital wrote a book with the title “Sweet and Dangerous”, the result of his many years of research into the dangers of sugar.  He reported that many diseases, including heart disease, were related to its ingestion. As so often happens, this terribly important book was ignored and cholesterol became the demon for the cause of heart disease. Now, 40 years later, many people know that the cholesterol story has been debunked. Because sugar requires vitamin B 1 to metabolize it, in much the same way as gasoline requires a spark plug to burn it, taking sugar on its own in the form of empty calories easily overwhelms the power of thiamine to carry out its function.

That means that you have an imbalance between the calories and the vitamin or a relative deficiency of thiamine. Your daily intake of thiamine may be sufficient for a good diet but not enough to take care of the overload of sugar represented as the bad diet which is so common.  It may easily be accomplished by the consumption of the stuff that we consume in our social activities.  Yes, there is no doubt that it makes the mouth water and the sweetness underlies the joy of the social event but if it is causing widespread disease, I ask you, is it worth it?

The lower part of the human brain is particularly sensitive to thiamine deficiency and because this part of the brain organizes the entire body in its performance of adapting to the environment in which we find ourselves, we easily become maladapted. For example, we may feel cold when it is hot or hot when it is cold, a mistake in sensory input and brain interpretation. The nervous system involved in this reaction is known as the autonomic nervous system and is entirely automatic.  The message from the brain to the heart causes it to accelerate when it is a necessary adaptive need as, for example, running for a bus.  But when this happens spontaneously for no apparent reason at all, we might take this to a physician and tell him that “I have palpitations of my heart”.  Unfortunately the medical focus would be on the heart not on the nervous system that caused the acceleration. For this reason one of the complications in diabetes is called “autonomic neuropathy”, meaning that the autonomic nervous system is disorganized. Thiamine protects diabetics from complications because it improves the ability of our cells to produce adequate energy for function by “burning sugar as brain fuel”.  Think of it as a change of inefficient spark plugs in a car engine.

Thiamine deficiency is sometimes referred to as pseudo (or false) hypoxia because it results in exactly the same symptoms as those from a mild to moderate deprivation of oxygen. Its effect on the lower part of the brain is to make it more reactive to all input signals. When you read a telegram giving you bad news, your eyes send a signal to the brain that has to interpret the meaning of the signal. I refer to the input signals, whether they are physical or mental, as “stress”. Your response to the stress is organized by the lower brain with “advice and consent” from the higher brain. Freud referred to the lower brain as the “id”. It reacts automatically to anything perceived as danger or self indulgence and the upper brain as the “ego” because it either permits or prevents the ensuing action. It is our moral censor.

I have studied the effects of this kind of “high calorie malnutrition” and it is responsible for a huge amount of mental illness and unpredictable bad behavior. It makes the “id” irritable and weakens the “ego” making a person much more likely to act in response to a whim or a nursed grievance.  There is much evidence that it can even affect criminal behavior.  This kind of malnutrition is widespread in America, but I have never seen it discussed in relation to whether the behavior exhibited at inexplicable school shootings is a potential factor. A recent exhibition of “road rage” projected on TV news might just be comprehensible because it was otherwise well beyond civilized behavior. Although this may sound too far-fetched, we have an epidemic of Attention Deficit Disorder, with or without hyperactivity, learning disability and obesity in our children that defies a genetically determined cause. Nature does not make that kind of mistake in so many individuals. Their young brains are irritable and disorganized because of dietary indulgence.

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