thiamine - Page 10

Migraine, Diet, and Thiamine

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In US population studies, the prevalence of migraine is approximately 18% in women and 6% in men. About 90% of sufferers have moderate or severe pain and 75% have a reduced ability to function during the headache attacks. One third require bed rest during an attack. A study at the Mayo Clinic showed the incidence in women increased 56% during the 1980s and 34% during the same period in men. Although the term “migraine” is often used to describe any severe headache, a migraine headache is the result of specific physiologic changes that occur within the brain leading to the characteristic pain and associated symptoms. They are usually accompanied by sensitivity to sound, light and odors and there may be nausea or vomiting. Typically, the headache involves only one side of the head but in some cases it may be bilateral. The pain is often described as throbbing, pounding and maybe made worse with physical exertion. Silent migraine is a variant where the patient may experience aura, nausea, vomiting and other nervous symptoms without headache.

Migraine headache is estimated to affect up to 28% of adolescents, most of whom are female. It has been associated with reduced quality of life and academic disruption due to missed school days. In 2014 the US Food and Drug Administration approved an existing medication called topiramate for prophylaxis in adolescents between the ages of 12 and 17 years. There are several possible adverse effects from this drug, some potentially serious. Prophylactic drugs are unpromising and unpredictable. A mild degree of prevention could be obtained from the use of acupuncture.

Migraine Precipitants

Of 171 patients who fully completed a survey, 49.7% reported alcohol as a precipitating factor of headache other than migraine. Only 8.2% reported aspartame and 2.3% reported carbohydrate. Patients with migraine were significantly more likely to report alcohol as a trigger. They also reported aspartame as a precipitant three times more often than those having other types of headache. Non-nutritive sweeteners, including aspartame, saccharin, sucralose, neotame, acesulfame-K and stevia have all been questioned as to their safety. Pregnant and lactating women, children, diabetics, migraine and epilepsy patients, represent the susceptible population. Although sucralose is not considered to be a migraine trigger, a patient was reported with attacks of migraine consistently triggered by this sweetener.

Hypoxia, Pseudo-hypoxia, and Migraine

Migraine with aura is prevalent in high-altitude populations, suggesting that hypoxia has a part to play in etiology. Of 15 patients with migraine headaches, artificially induced hypoxia triggered migraine attacks in eight patients.

Thiamine deficiency produces abnormal gene expression in brain exactly like that induced by true hypoxia. Migraine is a risk factor for thiamine deficiency and Wernicke encephalopathy (WE), the classic thiamine deficiency disease that affects the brain. Two female patients have been reported with chronic migraine. They also had clinical signs and laboratory support for WE. Both patients received intravenous thiamine supplementation, leading to improvement of both WE and the associated headache. The authors suggested that nausea and vomiting, occurring with migraine, may lead to the thiamine deficiency. However, headache, nausea, vomiting and loss of appetite are symptoms that occur in the early stages of WE, thus simulating migrainous features and the association is by no means clear. The authors suggest that thiamine supplementation might be a promising therapy in a subset of patients with chronic migraine.

Also, the range of pathologies associated with magnesium deficiency is staggering, including migraine, multiple sclerosis, glaucoma and many other disorders. It is important to emphasize once more that magnesium and thiamine work together in the cellular machinery that produces energy and deficiency of either is critical. Chronic recurrent nausea in childhood is a poorly described symptom and in a study of 45 affected children, 62% had migraine headaches. They also suffered from dizziness, anxiety, fatigue and sleep problems. The exact incidence of dizziness and vertigo during adolescence is not known. For those few adolescents who seek outpatient evaluation, the majority are diagnosed with migraine headaches and many suffer from postural orthostatic tachycardia syndrome (POTS), a condition that has been reportedly due to thiamine deficiency in some cases.

Autonomic Asymmetry

Normally there is a balance between the autonomic tone of the right and left half of the body. However, under stress or with hypothalamic instability this balance may be disrupted and result in the marked autonomic asymmetry seen in migraine. Abnormal regulation of the large cranial arteries appears to play a significant role in the mechanisms of migraine pain, also reflecting abnormal autonomic function.

Migraine and Diet

Attack frequency of migraine in children was associated with higher intake of high fat or sugar. The processing of both is dependent on thiamine. With these strong associations in the medical literature, it is impossible not to contemplate that the sweet sensory input from the tongue to the brain is an important trigger for migraine. There has been a steady increase in sugar consumption in America over the past few decades, suggesting the possibility that it represents the published increased incidence of migraine in the 1980s as mentioned above. It also suggests the possible implication of artificial sweeteners as migraine triggers.

The association of migraine with alcohol ingestion might be an important observation, since alcohol has long been known to be a cause of thiamine deficiency in the part of the brain that controls the autonomic nervous system. It has also long been known that beriberi, the classical thiamine deficiency disease, causes autonomic dysfunction in its early stages. One of the most important observations that I observed in practice was that a mild degree of this deficiency makes the brain extremely sensitive to many different input stimuli. It results in a high degree of sympathetic nervous system activity, hence so-called panic attacks that are really distorted fight-or-flight reflexes. Patients complain of constant anxiety, heart palpitations, unusual sweating, nausea, vomiting, dizziness and brief fainting attacks known as syncope. This collection of symptoms, thought by many physicians to be psychological in nature, is also referred to as postural orthostatic (positional) tachycardia (rapid heart) syndrome (POTS).

In a person who is in a marginal state of malnutrition, any mild stress such as a vaccination, a mild infection or some form of trauma may initiate POTS. A reader might conclude that this diversity of symptoms, that include the incidence of migraine, cannot be caused by a deficiency of a single nutritional element. In order to understand, it is necessary to be aware that a deficiency of energy in the brain resulting from a common form of malnutrition creates a multiplicity of cellular dysfunction according to the distribution of the deficiency. If this is the truth, it makes a mockery of the present medical model in which each described disease is thought to have a specific underlying cause. Hence, money is collected to find the cause of Alzheimer’s disease and is probably a pipe dream. It is well known a published association with thiamine metabolism strongly suggests that we should be looking for prevention rather than spending millions in trying to find a curative drug.

Conclusion

The clues that alcohol, sugar and artificial sweeteners are major triggers for producing migraine headaches are so strong, their avoidance would appear to be mandatory. However, it is almost certainly true that many sufferers know this, but make no attempt at avoidance, marking the taste of sweeteners as addictive. I became aware that there were millions of people in America suffering from symptoms that are constantly being unrecognized in medical clinics. Even if they are recognized as nutritional in nature, the doctor and patient are likely to ignore the appropriate prevention by adopting the consumption of an appropriate diet. Since most of the population is ingesting pills of one sort or another, perhaps advising the use of vitamin supplements as part of the dietary discretion might at least partially serve in the reversal of these common symptoms.

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Thiamine and Heart Function

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

Heart Disease and Beriberi: Case Stories

Heart disease has been central in beriberi, the classic thiamine deficiency disease, for centuries and the painstaking efforts that uncovered thiamine deficiency as the cause is unfortunately a little-known saga of human effort. Modern physicians have been completely convinced that no vitamin deficiencies exist in America, because of vitamin enrichment by the food industry. So is there any evidence that physicians are beginning to wonder whether thiamine plays a part in modern heart disease? This post is designed to show that there is indeed an awakening that could make a big difference to the role of cardiologists in treating heart disease.

Before I go to some medical literature, I want to describe a personal experience that occurred many years ago because it illustrates the incredible psychological resistance of the medical community to a vitamin deficiency. I was a pediatrician at Cleveland Clinic at the time. In the medical hierarchy, a pediatrician is regarded as being largely ignorant concerning disease in adults. A 67 year old anesthesiologist at a Columbus hospital reported to his colleagues with the symptoms of heart failure. He was subjected to heart catheterization and found to be perfectly normal in that respect.

His son was in medical school and studying his father’s case, he came to the conclusion that he had beriberi. For some reason unknown to me, the patient was referred to cardiologists at the Cleveland Clinic. Because my colleagues knew of my particular interest in thiamine, I was asked to see the patient. The story he gave me made the son’s diagnosis virtually a guarantee. Each day, as he went to get into his car in the morning, he would get the “dry heaves” in the garage. He would drive to the hospital where he gave anesthesia to as many as 10 patients. He would then go to the pediatric ward and cut himself a large piece of chocolate cake. When he got home he was too tired to eat dinner and would go to bed. I gave my reading of the case in the patient’s record and had no further contact. He was returned to the Columbus cardiologists and although I believe that he continued to receive thiamine, he died. I never received any information concerning his further care or whether the cardiologists really believed that this was beriberi. One can only conclude that the state of his heart was precarious and the history of thiamine treatment in beriberi had already showed us that there was a “tipping point” beyond which there was no response to thiamine treatment. Whether the cardiologists were aware of this or not is unknown. It is possible that his failure to respond may well have caused them to reject the diagnosis. What really impressed me was the extraordinary resistance to this diagnosis.

I am reminded of another case in my experience. There was a lady pathologist at Cleveland Clinic who was known to be brilliant. I visited her in the Department of Pathology for a reading on one of my patients. She told me that she was so utterly fatigued that a few days previously she had turned around on her way to work and gone home. I found to my amazement that she had a chocolate box in every room in her house and would take a chocolate at random as she went around her house. Without further advice I simply suggested to her to discontinue that practice and to take a supplement of thiamine, whereupon she recovered quickly. Fatigue is a symptom arising in the brain that notifies its owner of energy deficiency and undue fatigue is a logical result in beriberi.

Recognizing Vitamin Deficiencies in Disease

The problem with thiamine deficiency is that a physician has to change his attitude radically towards the cause of disease. This is because the underlying mechanism is derived from cellular lack of energy. If this is not perceived, a physician can be puzzled by a combination of heart and nervous system disease in a single patient. In the present medical model, he believes that he is confronted with two separate conditions.

Because of this resistance, in 1982 I joined a private practice specializing in nutrient-based medicine and began seeing adults as well as children. I joined a group that came to be known as the American College for Advancement in Medicine (ACAM). This relatively small group of physicians had all come to the same conclusion: nutrient-based therapy is, or should be, the methodology of the future. Many of these physicians were practicing alongside their orthodox colleagues in their local hospitals. One of my

ACAM friends told me the following story. He had a patient in the hospital with a pneumonia caused by antibiotic resistant infection. Together with the antibiotic treatment, he had given the patient intravenous vitamin C and she recovered. A patient in the next bed was under another physician with the same pneumonia and my friend approached him, suggesting that he tried the use of the same treatment. He was told to mind his own business and the patient subsequently died. I know of no better example of resistance and rejection of a principle that has yet to reach full acceptance in American medicine. As long as the psychological resistance to vitamin deficiency remains, it is seldom considered. I am happy to say that this resistance is beginning to break down as we shall see by looking at some of the recent medical literature. Not only that, the therapeutic use of vitamins in pharmacological doses it gradually being recognized for its therapeutic value.

Recent Reports of Thiamine’s Role in Clinical Care

Hear what a physician wrote as recently as 2015. The title of the paper is “Thiamine in Clinical Practice” and the author notes that the active form of the vitamin plays a role in nerve structure and function as well as brain and heart metabolism. Unexplained heart and kidney failure, alcoholism, starvation, vomiting in pregnancy or intestinal surgery “may increase the risk for thiamine deficiency”. Understanding the role of thiamine as a potential therapeutic agent for diabetes, some inborn errors of metabolism and neurodegenerative diseases all warrant further research. Surely, this is an indictment of our present approach by merely trying to control symptoms instead of addressing the primary cause.

A group of Canadian physicians stated that “the management of heart failure represents a significant challenge for both patients as well as the health care system in industrialized countries”. The abstract of their paper notes that thiamine is required in the energy-producing reactions that fuel heart contraction. Previous studies have reported a wide range in the prevalence of thiamine deficiency in patients with heart failure and the impact of its supplementation in patients is inconclusive. Of course, Dr. Marrs and I are appalled because such treatment is not only easy, it is completely non-toxic and therefore safe. If there is clinical evidence, why not use a non-toxic agent? However, the psychological restraints of being accused of being a charlatan are very real and can expose a physician to colleague ridicule.

Another paper reported that a total of 20 articles were reviewed and summarized. Recent evidence has indicated that supplementation with thiamine in heart failure patients has the potential to improve heart contractions. These authors recommend that this simple therapy should be tested in large-scale randomized clinical trials to further determine the effects of thiamine in heart failure patients. Diuretic treatment for heart failure may lead to an increased urinary thiamine excretion and in the long-term thiamine deficiency, further compromising heart function. Nine patients with diuretic treatment for chronic heart failure were studied with thiamine supplementation, producing beneficial effects on cardiac function. The authors state that subclinical thiamine deficiency is probably an underestimated issue in heart failure patients. It has even been shown that thiamine pyrophosphate, the active form of the vitamin, prevents the toxic heart injury caused by the cancer treating agent cisplatin. Dietary thiamine that has not been activated by the body did not prevent this.

It has been known for some time that thiamine in the diet has to be absorbed into the body by means of a protein known as a transporter of which there are quite a few. These transporters are under genetic control and absence of one or more of them will make it difficult for a given person to obtain an adequate amount of thiamine from diet into the part of the body where that thiamine transporter is active. A new thiamine transporter has been discovered whose genetic variants have an effect on blood pressure.

Although this post is about heart disease, I want to end by pointing out that vitamin treatment goes well beyond the consideration of just heart disease. Several years ago I received a letter from an aging physician who had specialized in OB/GYN. This letter was so poignant that I am repeating some of this letter:

I am writing to you, because I have found another mortal being who is particularly interested in the biological activities of thiamine. I had previously thought that I was nearly the lone believer in the benevolent effects of thiamine particularly for the treatment and prophylaxis of the toxemias of pregnancy and its many associated problems. I had even written to the chief of the Cleveland Clinic OB-GYN about the “miracles” I was performing and offered to work with him in further development of the concepts.

It was enclosed in a copy of a book by John B Irwin, M.D., the author of the letter.

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Mural que presenta un corazón en su forma anatómica sobre un fondo de rombos y triángulos blancos, negros y azules, a la altura del número 2 de la calle Alonso Benítez, barrio de Lagunillas, Málaga, España.

Thiamine, Epigenetics, and the Tale of the Traveling Enzymes

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

Epigenetics: How the Cells Adapt to the Environment

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

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

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

Starve the Mitochondria, Alter the Genome

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

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

Thiamine Deficiency and Gene Expression

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

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

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

A Constitutively Active Enzyme: What Could Possibly Go Wrong?

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

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

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

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David Goodsell, CC BY 3.0, via Wikimedia Commons

This article was first published on April 25, 2017. 

About TTFD: A Thiamine Derivative

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I recently received notification concerning a “review” posted on HerbCustomer, a commercial website that has been active since February 26, 2010. This so-called “review” was posted on January 16, 2018 by iHerbCustomer entitled “Dangerous allithiamine derivative with no thiamine activity”. The email was posted as well. This person made a potentially libelous statement by referring to me as lying about this thiamine derivative. Its commercial name is Lipothiamine. Its chemical name is thiamine tetrahydrofurfuryl disulfide (TTFD) and this post is to refute the accusations that are made public by this individual.

History of Thiamine Research

Thiamine is the chemical name for vitamin B1 and its deficiency in the diet has long been known as the cause of beriberi. This disease has been known for thousands of years but its underlying cause was only discovered in the closing years of the 19th century. Since beriberi was commonest in the rice consuming cultures, it is not surprising that the major research came from Japan. In the middle of the last century a group of university-based scientists was convened and they wrote a book (Review of the Japanese Literature on Beriberi and Thiamine). This was translated into English, ostensibly because these scientists wished to let people in the West know and understand the pernicious nature of disease resulting from thiamine deficiency. I was fortunate enough to receive a copy of this book from one of the scientists involved. The information in this post is derived from it. Because they were scientists and were well aware of the clinical effects of beriberi, their studies were very extensive. They knew that thiamine existed in garlic and much of their experimentation focused on studies of the garlic bulb. They discovered that there was a natural mechanism in garlic that created a derivative of thiamine and called it allithiamine. Note that this is a naturally occurring substance and the term should be entirely restricted to it.

On a number of occasions I have seen thiamine derivatives being called “The alithiamines” and one commercial product is called Allithiamine with a capital a. The name was given to this naturally occurring product because garlic is a member of the allium species of plants. It can be found in other members of the allium species. Because the Japanese scientists already knew a great deal about the clinical expressions caused by thiamine deficiency, they originally thought that this new derivative might have lost its vitamin dependent activity. They went on to test it in animal studies and found that it had a much greater biologic effect than the original thiamine from which it was derived. They found that it was extremely important that allithiamine was a thiamine disulfide derivative (disulfides are important in human physiology) and they synthesized many different types of thiamine disulfide as well as many non-disulfide derivatives, carefully testing each one for their biologic activity.

What is TTFD?

Without going into the biochemical details, what we now know is that thiamine tetrahydrofurfuryl disulfide (TTFD, Lipothiamine) is, for a number of reasons, the best of the bunch of synthetically produced derivatives and has exciting possibilities in therapy. For example, it has been shown from animal studies that Benfotiamine, a non-disulfide derivative, does not get into the brain whereas TTFD enables absorption of thiamine into the brain where it stimulates energy synthesis. When we take in thiamine, occurring only in our naturally formed food, it is biologically inert. It has to be “activated” within the body that possesses genetically determined mechanisms for its absorption and activation. To cut a technically difficult explanation, let me state that TTFD bypasses this process. It enables thiamine to split away from its disulfide attachment and enter the cells where its activity is required. The concentration achieved in the target cells is much greater than that achieved by the administration of the thiamine from which it was derived.

The Japanese scientists studied the effect of cyanide in mice and found that thiamine propyl disulfide (TPD), a forerunner of TTFD, gave significant protection from the lethal effect of this poison, an incredible discovery that alone should raise eyebrows. They studied this effect and were able to show its mechanism. They also found that it would protect animals from the effect of carbon tetrachloride, a poison that affects the liver. It is using its vitamin actions in a therapeutic manner.

Being myself a consultant pediatrician in a prestigious medical institution, I was able to obtain an independent investigator license (IND) from the Federal Drug Administration, and obtained TTFD from Takeda Chemical Industries in Osaka, Japan, the makers of this product. TTFD is a prescription item in Japan, sold under the commercial name of Alinamin. I have read several publications, showing that it reverses fatigue in both animal and human studies. I was able to study the value of this incredible substance in literally hundreds, if not thousands of patients. Far from being toxic, as this person claims, I never saw a single item that suggested toxicity. Its therapeutic potential is largely untapped in America. This is because the current medical model does not recognize that defective energy metabolism, genetic errors and the nature of stress are the interrelated components whose variable effects in combination are the cause of disease. Do not mistake the use of the word stress, a word that is so commonly used inappropriately. An infection and any form of physical or mental trauma represent a form of stress. It is the ability or the inability to meet the required energy demand to resist that stress that matters in the preservation of health.

Clinical Benefits of TTFD

It is important to understand that the beneficial activity of TTFD is exactly the same as the thiamine from which it is derived. It is the mechanism of its introduction to cells, particularly those in the brain, that enable it to have such an effect on energy metabolism. Because of its strategic position in the cell, thiamine is of vast importance in oxidative metabolism in the complex mechanisms of energy production. There are at least two methods by which thiamine deficiency can be induced. The commonest one is an excess of sugar and fat that overwhelms the capacity of thiamine to conduct the mechanisms involved in energy synthesis. The discovery that thiamine has a part to play in fat metabolism is quite recent. The other one is because of genetic errors involving its biochemical action. However, we now know from a relatively new science called epigenetics that some mistakes in DNA can be overcome by the use of an appropriate nutritional substance like thiamine. The completely non-toxic use of TTFD depends merely on its ability to introduce thiamine into the cells of the body that require its magic. Under these circumstances, the big doses of thiamine are acting like a pharmaceutical by stimulating the missing action. We are not dealing with simple vitamin replacement. This should represent a new era in medicine when nutrient biochemistry takes its place in patient care.

Conclusion

The person that wrote this criticism fails to understand that TTFD and other thiamine derivatives represent a new basic principle of therapy. It recognizes that healing is a function of the body, not the activity of a so-called “healer”. All it requires is the foundation substances needed for repair and sufficient energy to use them. It demands a dramatic change in thinking about health and disease. If you understand the principles involved, it forces the conclusion that the word “cure” is a pipe dream. The only form of pharmaceutical drug that matters is one that safely kills an attacking microbe. Almost all the rest of them merely relieve symptoms and have no effect on the ultimate outcome.

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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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A Scientific Sermon on the Basis of Disease

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Why a sermon? The title was suggested from a breakfast discussion that I had with a resident in the retirement home in which I live, a retired minister of the United Christian Church. In the nearly 5 years that I have been living here, I have repeatedly sat and listened to my friends talking about their various handicaps and how they are being treated. I was a pediatrician at the Cleveland Clinic for 20 years and left it in 1982 to practice what has become known as “Alternative Complementary Medicine”. Because few people apparently understand the meaning of this, I am trying here to inject a little bit of science to explain it.

From the Unexplainable Comes Insight

In 1982, I began to see adults as well as children. I thought that there might be some interest in why my perspective changed and why I took early retirement from a prestigious orthodox medical institution. As a consultant pediatrician at the Clinic, I was exposed to the referral of children with strange diseases. There is a group of genetically determined rare conditions known as inborn errors of metabolism. The strange thing about them in common is that if they are not recognized at birth, some of these diseases cause the affected child to become mentally retarded. That is why there is a laboratory in each state capital that tests every newborn child for one of these inborn errors. It demands only a finger stick of blood on a strip of filter paper that can be mailed to the laboratory. Perhaps even stranger, many of them can be protected from mental retardation by starting them on a special diet that they have to maintain throughout life. It forced me to understand the necessary biochemistry, the nature of the special diet and why it prevented mental retardation.

One day, because of my studies in biochemistry, I was confronted with a 6-year old child with a weird story. I will refer to him as JV. He had suffered from infancy with intermittent episodes of a condition known as cerebellar ataxia (ataxia is a fancy word used to describe a lack of balance and coordinated movement). The cerebellum is part of the brain that deals with balance amongst many other responsibilities. Each one of these episodes lasted about 10 days, rose to a clinical climax and subsided automatically without treatment, just as though he had been drinking alcohol. Each episode left him a little bit more mentally affected. His clinical presentation was exactly like that of a drunk. He was unable to walk a straight line and his speech remained slurred as long as the attack lasted.

Alcohol has its major effect by inducing vitamin B1 deficiency in the cells that make up the cerebellum. He had been tested with every known method by neurologists and neurosurgeons, all of which produced no information.

To cut a long story short, I had to wait two years before he had one of these episodes when I admitted him to hospital for study. All I did was to collect urine that was subjected to biochemical testing. His urine was collected continuously for 12 hours during the night and separately for 12 hours during the day to see if it reflected differences in night/day metabolic processes. The ataxic episode lasted about 11 days, rose to a symptomatic climax at about the sixth day and gradually subsided without any treatment whatsoever. Of some interest, during the last few days the symptoms would be much less in the morning and gradually worsen as the day advanced. The abnormal chemical changes were reflected in the urine by being alternately high during the day and much lower during the night. Thus, the day/night rhythm of the brain known as circadian (circadian means about 24 hours) was affected. Yes, our brains are constructed to dovetail with the day/night seasonal rhythms of our world.

Without going into complex details I was able to show that he had vitamin B1 dependency. The chemical name for this vitamin is thiamine. Vitamin dependency means that a much greater amount of the vitamin is necessary for its normal action. Vitamins act as what are called cofactors to enzymes. The connection between the vitamin and its respective enzyme is under genetic control and it was this mechanism that was defective.

High Dose Nutrient Therapies to Compensate for Energetic Demands

From this case, I learned that this genetic defect might be overcome by using pharmacological doses of thiamine. It seemed as though the vitamin acted as a drug by stimulating the inefficient enzyme back to a more normal state of function. In a fanciful analogy, some man-made machines require cogwheels that transmit energy from the power source to the action. Enzymes in the body may be roughly compared with cogwheels. They transmit energy derived power to physical and mental action. To continue the analogy, cogwheels require oil and vitamins may be roughly (and I mean roughly) compared to oil given to a cogwheel. They are each essential components that engage with their respective enzymes. Without the appropriate vitamin, the corresponding enzyme gradually becomes dysfunctional.

As I have already noted, the connection between a vitamin and its respective enzyme is controlled by a genetically dependent mechanism. It is the breakdown of this mechanism that introduces dependency. Each of this child’s episodes of ataxia was triggered by a simple infection like a cold, a mild head injury or even an inoculation. I will refer to this as some form of stress. Several reports in the medical literature describe intermittent clinical episodes of their respective disease entity being exacerbated by an otherwise mild infection. This is important because sometimes a mild head injury or an infection is thought to be the cause of the generated symptoms on its own, whereas it may well be triggering the clinical situation in relationship to hitherto marginal energy availability.

The point that I am trying to make is that the injury, and indeed the defense against infection, automatically demands an energy-dependent response. That marginal energy availability may not be enough before the injury to cause symptoms, or perhaps mild symptoms in such an individual might be ascribed to other causes as conceived within our present medical model. For example, a given symptom may be “written off” as an allergy, thus confounding the situation even more. Energy is always required by the brain in order to respond to any form of mental or physical stress. Just as a car consumes more energy when climbing a hill, stress to us is like a hill to be climbed. This action takes place automatically when our capacity to synthesize energy is healthy.

If the increase in energy is not forthcoming, the affected cells do not function properly, giving rise to what we call symptoms. Symptoms are inevitably generated by sensory mechanisms in the brain, another factor which can be very confusing. For example, an injury in an elbow would result in a signal to the brain that generates the sensation called pain. The brain acknowledges the signal by announcing to its owner “I have a pain in my elbow”. The point is this; pain is a brain effect and can explain why there is such a phenomenon as psychological pain.

The Irony of Psychosomatization

I want to impress you however that psychology is always due to electro-chemical brain cell reactions because it has a scientifically plausible explanation. That means that so-called psychosomatic disease is not an invention by the patient. The symptoms are being generated by chemical disturbance in those brain cells and in today’s world, high calorie malnutrition is responsible for polysymptomatic diseases that haunt many physicians’ offices. They are often referred to as “problem patients” and the patient is sometimes told that it is “all in your head”. The irony is that this is the truth. It certainly is in the head but it has a real underlying cause that is being misinterpreted.

I recently read a column in the Wall Street Journal entitled “Is your teen depressed”? With direct quotes from this column “statistics show that teen depression is on the rise. In 2016 around 13% of US teenagers aged 12 to 17 had at least one major depression episode in the past year compared to almost 8% in 2006. The American Academy of pediatrics has recently recommended screening all those youngsters aged 12 and older annually for depression.  They define major depressive disorder as having five or more of the following symptoms present for two weeks: depressed mood most of the day, irritability, decreased interest or pleasure in most activities, significant change in weight or appetite, change in sleep, increased educational sluggishness, fatigue or loss of energy, feelings of guilt or worthlessness, changes in concentration and recurrent thoughts of death. They sometimes complain of stomachaches or headaches that don’t have an identifiable cause”. My explanation is the combination of three factors, represented as three interlocking circles of health, genetic risk/stress/nutrition.

Genes, Nutrition, and Energy

Let me explain genetic risk a little. We now know that our genes can be manipulated by nutritional elements and lifestyle. Many genetic diseases do not appear until late in life. If it was only the gene to blame, one would expect it to appear at birth and indeed some do. For example, type I diabetes has genetic determination but the symptoms may not appear until middle age and are often associated with some form of stress such as a cold, a mild injury or even a telegram giving bad news. Some recent research has shown that pharmacologic doses of thiamine might well protect diabetics from their well-known complications.

Thiamine is a vital naturally occurring chemical (the word vitamin was used to express its vital need for life when it was thought to be an amine. When it was synthesized and found not to be an amine the terminal e was dropped) that enables body cells to produce the energy they require for function and we have between 70 and 100 trillion cells that make up the human body, all of which require energy. Vitamins act as what are called cofactors to enzymes. JV actually had intermittent episodes of a classical disease known as beriberi, long known to be caused by deficiency of thiamine. However, because of genetic mechanisms that were at fault, he required huge doses of thiamine in order to prevent his intermittent episodes of beriberi, hence the use of the term dependency.

The RDA (recommended daily allowance) for thiamine is 1 to 2 mg a day and he required 600 mg a day. If he should succumb to a cold, experience a simple injury or some other form of physical stress, he found that he had to double the dose to 1200 mg a day. Contrast this with 1 to 2 mg a day as the RDA indicated for normal healthy people. On one occasion an episode occurred following an inoculation, so I had to assume that the inoculation represented some form of physical stress. Note that the needle stick sends a sensory message to the brain, notifying it of some form of attack. The signal causes the brain to formulate any necessary defensive action. Therefore, if somebody passes out following a needle stick, it is a temporary lack of energy mobilization in the brain.

I must emphasize again: the brain requires energy mobilization to meet any form of stress. Therefore, our energy consumption is in a constant state of flux on a day-to-day basis, much like climbing hills and descending into valleys on a journey For example, when this child was under treatment he was walking in a local park, tripped on a stone and suffered a relatively mild head injury. He became unconscious and was taken to a nearby emergency room. His mother called to notify me of the event. I called the physician in the emergency room and tried to explain to him that this child represented a special case and that he required an injection of thiamine. He thought that I was quite mad: such is the trust that leads to failure of communication between physicians.

Thiamine and Energy

This was such an intriguing experience that I began to perform clinical and library research on vitamins that have continued to the present. Glucose is the “gasoline” that is the major fuel of our cells and thiamine is the equivalent of the “spark plug”. The energy requirement for the brain and heart is enormous because both of them function 24 hours a day throughout life. That is why energy deficiency disease dominates the brain and heart with varying degrees of severity. Because I was a consultant pediatrician, I received referrals from private pediatricians in Ohio and even out-of-state. Some of my common referrals were children with attention deficit, hyperactivity, learning disability and other curious distortions of behavior. Of course I discovered that their diet was atrocious and using pharmacologic doses of thiamine brought them back to normal behavior. Not only that, I found that some of the strange diseases referred to the Clinic also responded to vitamin therapy, so I offer this explanation.

Every cell in the human body is a one-celled organism in its own right. Evolution has endowed each of them with special responsibilities in groups that make up the organs of the body. I think of the body as being somewhat like an orchestra where the groups of specialized cells represent the instrumentalists. The violins, as it were, are separated from the cellos, each representing a bank of instrumentalists. They all know what to do but require a conductor. The conductor in the body is of course that part of the brain that connects with all the organs through the nervous system known as autonomic. We have two types of nervous mechanisms: the voluntary system conveys will, thus allowing conscious control of body movement and thoughts. The autonomic nervous system is purely automatic. Its controls are in the lower part of the brain which is unusually sensitive to deficiency of thiamine. That is why alcohol addiction, heavily related to thiamine metabolism, results in a brain disease known as Wernicke encephalopathy that is well known to be caused by thiamine deficiency.

Signals from the brain to the body organs and from the organs to the brain enable us to adapt to all the vagaries of living in a hostile environment. This signaling system also requires a huge amount of energy and it is not surprising that the brain/body mechanisms deteriorate if there is insufficient energy.

I have come to the conclusion that thiamine is somewhat like the leader in an orchestra. Although the entire vitamin category represents the nutrient necessities of life and each has its own separate responsibility, they all work together. Because of its special place in energy metabolism it stands out with its clinical importance. Because energy metabolism is frequently inferior as the major cause of a disease, the diagnostic category, as we presently represent disease, ceases to matter. A reader might object by referring to genetically determined disease as a leading cause. However, the new science of epigenetics tells us that proper use of nutrients and adjustments of lifestyle can often correct the genetic mistake.

High Calorie Malnutrition: A Disease of Affluence

Now I would like to discuss what I mean by high calorie malnutrition because I believe it is an extraordinarily common cause of disease in our disorganized world. Malnutrition is usually thought of in relationship to starvation. The disease known as beriberi is a classic example of high calorie malnutrition. It was caused for centuries by the consumption of rice. Although the major effect has been in Eastern countries, it has appeared in many different parts of the world including America. The rice grain consists almost exclusively of starch that is broken down to glucose for use as fuel. The vitamins necessary for the metabolism of the glucose are in the cusp around the grain. When you remove the cusp you generate white rice and the Chinese peasants found that white rice looked nicer on the table. Therefore if and when they became more affluent they would take their rice to the rice mill for the removal of the cusps. The use of the rice mill was expensive, hence the association with affluence. They would place the white rice in silver bowls and invite their friends to dinner, not for culinary purposes but to demonstrate their new found affluence. Our constant deviation from the natural rules applied to health costs humanity dear. People with beriberi do not look starved. In fact they may be obese. Because they have bitter complaints and look relatively healthy they are often mistaken for neurotic complainers and treated indifferently. Not only that, if a physician might suspect his patient as having this disease and measure the level of thiamine in the blood he will probably find it to be normal. It is the ratio of calorie concentration to that of thiamine concentration, reminding me of what happens with too much gasoline in the cylinder of a car referred to as a choked engine.

I would like to give you a few examples. When I started my library research on thiamine, I discovered that a medical officer of health in England had been sent out to Hong Kong in the 1940s to investigate a form of sudden death that occurred in breast-fed infants of Chinese mothers. Hong Kong was then a British protectorate. She found that the rice consuming mothers gave their infants thiamine deficient breast milk. Although these infants were often considered to be the healthiest looking members of the family they suddenly died at the age of 3 to 4 months, exactly like sudden infant death syndrome that occurs today. Of historical interest, you may remember that the Japanese invaded Hong Kong and the Chinese people had their rice severely restricted. Although the breast feeding mothers were near to starving, the sudden infant death ceased to occur. When the Japanese were driven from the colony, the mothers had unrestricted rice and the sudden infant death began to reappear. This taught me the danger of empty calories.

At the Clinic, I kept seeing infants that had been classified as “threatened sudden infant death” and would place them on a breathing monitor that indicated when they had an episode of apnea (temporary cessation of automatic breathing) or slowing of the heart. When I gave them thiamine the monitors ceased to fire alarms. By special studies we found that the function of the brain stem in these infants was compromised, clearly indicating an electrochemical underlying mechanism. Although we published our work, it has been ignored. Advancing to my experience with adults after I had resigned from the Clinic a young woman came to see me from out-of-state. She had been diagnosed with a condition known as thrombocytopenic purpura, a disease in which platelets, one of the varieties of cells in the blood that have a function in clotting, were severely deficient. She had been receiving orthodox treatment for 10 years without success. I gave her a series of intravenously administered water soluble vitamins with complete resolution. I can provide lots more examples, but perhaps this has introduced to you the possibility of a different perspective in our constant search for what health really means and how it breaks down into disease. The bottom line, if you will, may come down to simple energy availability. If that is the case, then all disease processes, no matter their origins, would benefit from improving energy capacity.

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Semmelweiss Syndrome: Ignoring the Obvious to Save Face

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Who was Semmelweiss? Please read the post below to find out. We have an urgent message for both patient and physician. It isn’t really new because it started with Hippocrates in 400 BC “when he said ”let food be your medicine and medicine be your food”. He also said that no kind of treatment should ever be used that may do harm. All you have to do is to read the Physicians’ Desk Reference and read about almost any drug. It begins with a short sentence about what it must be used for. Then it very often states that nobody knows why the drug works. What follows is a lengthy discussion of side effects, pure evidence of its toxicity. The potential for harm is implicit. Hippocrates realized that healing was a natural process within the body itself and that any treatment method should assist this process. Today, we are well aware that this healing process requires a huge amount of energy that must be conserved and focused by resting body and mind. Modern  biochemistry provides us  with facts that show the wisdom of Hippocrates when he said “let food be your medicine”!

An Obvious Fallacy in Modern Medicine

Healing is a natural process from within the body that operates best when it is focused. The modern hospital, with its constant clatter and its complete failure to give the patient the rest and tranquility required for energy conservation, works against the healing process. The question that we must ask, is how we should proceed in order to assist healing. The answer must be obvious: help to supply the means by which energy is produced and conserved in the body. Health is a balance between the attack of environment (the enemy) and the constant mobilization of adaptive function that requires energy to maintain functional efficiency (the defense)

Alternative Medicine

This is the philosophy that has given rise to the development of a small group of physicians that use nutrient-based medicine. The point is this: modern medicine attempts always to kill the enemy. Kill the bacteria, the virus, the cancer cell, without killing the patient. Alternative medicine respects this only if it does no harm to the patient. The main approach of these physicians is to anticipate the body’s requirements in all its different ways in attempting to heal itself, the philosophy that was put forward by Hippocrates. These physicians often find that they are excluded from the conventional medical hierarchy, spurned by their former colleagues and despised. When they have a brilliant success with a patient, it is invariably labeled as “spontaneous remission” and we have wondered why this seems to be so inevitable in human affairs.

The Story of Semmelweis

The apocryphal story is that of Ignaz Semmelweiss who was a European physician who practiced before microorganisms had been discovered. He observed that doctors came in from the morgue and delivered their patients without washing their hands or changing clothes. The puerperal fever (childbed fever) rate was excessively high, of course. Semmelweiss concluded that the doctors must be bringing something in on their hands. He divided the ward into two sections and directed that doctors attending patients on one side should wash their hands in chlorinated lime before they performed a delivery, whereas the doctors on the other side should continue in the same old way. It did not need a statistician to see the difference in the incidence of infection. But what happened to Semmelweiss was just as predictable. He had done something new that disagreed with the medical establishment of the day. He was accused of being unscientific by suggesting that an unknown substance on the hands of the doctors was the cause of the problem. He was fired from the hospital and eventually died in a mental institution. He was right and they were wrong. The truly amazing thing is that the medical establishment never bothered to look at the results and times have not changed.

Nutrients Matter: It’s That Simple

People who have to admit their loved ones to hospital as an emergency, knowing and understanding the dramatic effect of nutrient-based treatment, are almost always completely powerless to get the attending physician even to listen to them. A physician of my acquaintance had a patient in hospital with pneumonia due to a resistant bacterial organism. He gave the patient nutritional IVs with water soluble vitamins. The patient recovered. In the next bed was a patient with exactly the same pneumonia who was under the care of another physician. My acquaintance approached what should have been his colleague and suggested that he do the same treatment, using the vitamin therapy. He was told flatly to mind his own business. The patient died. You would think that the second physician would want to discuss the reasoning and the scientific evidence to support the action. Was the belief in his own competence (ego) more important than the life of his patient? This is happening today in the world of medicine. We have come to accept it as the great “Bonanza” of scientific advance. Readers should be aware that the leadership for change will not come from the medical profession. It will come from those most interested in solving those personal health problems that have defied solution, sometimes for years. This website can spread the good news that there are often alternatives to be sought.

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

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Image: An injection against croup at the Hôpital Trousseau, Paris. Photogravure by Bruun Clement, 1899, after P.A.A. Brouillet, 1893. Wellcome Collection. Public Domain Mark. Source: Wellcome Collection.

A New Model for Medicine

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What is a Medical Model?

 In the Oxford English dictionary the word model is defined as “design to be followed, style of structure”. Then it follows that there must be a model to distinguish health from disease, that differentiates the two states of being. No disease can be treated without knowing exactly what caused it. Let us go back to Hippocrates, 400 BCE, who said “let food be your medicine and your medicine be your food”. What Hippocrates was saying was essentially that nutrition was the core issue in the maintenance of health. At this time and throughout the Middle Ages there was no model for the cause of disease. Consequently, treatment was extremely primitive and almost purely empirical. In the time of ancient Egypt it was believed that mental illness was caused by the presence of evil spirits in a person’s head. They bored holes in the skull to let the evil spirits out. If you think about that, perhaps it relieved the occasional headache because of increased pressure in the skull caused by a brain tumor. Hence, a few successes might have caused it to be retained as beneficial. During the Middle Ages, the only treatment that seems to have been used is bloodletting. It might have been temporarily useful in people with high blood pressure. A few successes yielded the conclusion that it was beneficial for all disease.

The First Controlled Experiment

Semmelweis was a 19 th century Hungarian physician. In those days, the incidence of puerperal disease (childbed fever) was absurdly high. Semmelweis made the observation that doctors, delivering their patients, entered the delivery room and went directly to their patients without changing their garments or washing. He came to the simple conclusion that the doctors were bringing something in with their hands that caused the problem. The obstetric ward consisted of a number of beds on each side of the room and Semmelweis directed that doctors delivering their patients on one side should wash their hands in chlorinated lime, while doctors on the other side of the room would continue in the old way. Of course, the incidence of childbed fever was so different that it did not need a statistician to document the difference. Semmelweis’s observations conflicted with the established scientific and medical opinions of the time, particularly as he was unable to explain what was on the hands of the doctors. Some doctors were even offended at the suggestion that they should wash their hands. It is truly an amazing vision of human behavior. Innovation carries with it loss of reputation for the innovator, no matter how successful the innovation. Well, of course everyone today knows that it was microorganisms on the hands of the doctors that caused the disease, but they had not yet been discovered. Poor Semmelweis wound up in a lunatic asylum and died in his 40s after a beating by attendants. Today, he is regarded as the first person to introduce antiseptic medicine.

The First Paradigm in Medicine: Microscopic Organisms

Most people are aware that the invention of the microscope, and the work of historical figures like Louis Pasteur, led to the discovery of organisms, that could only be seen with the microscope, caused what we now call infection. We are all familiar with the fact that a tremendous number of diseases are due to infection by bacteria, viruses or fungi. It was a perfectly logical conclusion that the development of treatment should be aimed at killing these organisms. This was the first paradigm in medicine, meaning that it was accepted by all. A glance at history will tell us that the search for medication that would kill these organisms was hard won. It was difficult to find something that would kill the germs without killing the patient and many patients lost their lives as a result of this search. The discovery of penicillin represented a dramatic change in perspective as it gave birth to the antibiotic age. Millions of lives have been saved. However, we are now entering an era where the development of antibiotic resistance is becoming an increasing problem. More and more potentially damaging antibiotics have been synthesized that present their own problems in therapy.

The Second Paradigm in Medicine: Immunity

It has been said that Louis Pasteur made the statement on his deathbed, “I was wrong: it is the defenses of the body that matter”. I believe that this may well become the second paradigm in medicine. So what are we talking about? Everyone recognizes that we have immunity but the average person has only the vaguest idea of what this really means. In fact, body defenses against infection are exquisitely complex and incredibly efficient when the immune system is healthy. The primary mechanism for health maintenance is exactly what Hippocrates said, not only the quantity but the quality of nutrition. By recognizing this, the concept is offered that preventive medicine, the use of nutrients based on a knowledge of the biochemical machinery that give our cells function, is the second paradigm.

Presently, we stimulate our immunity by the use of vaccines. However, each vaccine gives a protection to a specific microorganism, perhaps the best example being the flu. Most of us are aware that there are many strains of the flu virus and it may not be possible to predict the particular strain responsible for the “next epidemic”. Natural immune defense mechanisms recognize most invaders as “enemies”. Those whose adaptive/immune mechanisms cannot respond will succumb to the infection. Assisting the immunity mechanisms by making energy synthesis as efficient as possible and killing the “enemy” with maximum safety to the patient might just be the way of the future.

How the Body Responds to Environmental Stressors  

Each one of us comes with a “blueprint” derived from our parents in the form of genes that carry a code called DNA. This code is unique for each person and provides the structure that makes up a living person. The body is composed of 70 to 100 trillion cells, all of which have to cooperate to produce what we call function. I think of it being like an orchestra where all the organs are made up of cells, each one of which has a specific specialty to provide its contribution. Like instrumentalists in an orchestra, the cells within each body organ have to work together. This requires a conductor, a function that is performed by the subconscious brain. Coordination is administered through an automatic (autonomic) nervous system and a bunch of glands known as the endocrine system that produce messengers called hormones.

Consider what happens when a person is attacked by a pathogenic Streptococcus, for example. The throat becomes sore, the marker of inflammation. Controlled and executed through the brain, it increases local blood supply, bringing white blood cells into the area and is part of a defensive process. Glands in the neck become enlarged and this is also a defensive process, designed to catch and destroy the germs beginning to spread. Body temperature becomes elevated because disease producing bacteria are most virulent at normal body temperature and their efficiency is reduced at a higher body temperature. A standard procedure in medicine for many years has been to reduce the fever and it has always seemed to me to be a disadvantage, based on this explanation. We sweat when the environmental temperature is high and evaporation from the skin results in cooling. When the environmental temperature is low, we shiver and the muscular activity produces heat to maintain body temperature. These are examples of how we are able to adapt to changes in our environment that threaten our well-being. All of this is purely automatic and the only thing to complete the picture is how our food (fuel) is used to create energy. Maximum efficiency of brain metabolism is mandatory. Assist and protect the “conductor”.

How We Create Energy: Enter the Mitochondria

Because any form of burning is the union of oxygen with the fuel, in the body it is termed oxidation. The process is complex and many vitamins and minerals are involved, besides calories. It has long been known that thiamine (vitamin B1) deficiency is the cause of beriberi, the disease that had plagued humanity for thousands of years. Because this deficiency affects every cell in the body, it can degrade the efficiency of virtually any organ. But because different tissues have their own rate of metabolism and the brain and heart are the two tissues that require fast and efficient oxidation, it is the cells in those tissues that are most affected. Therefore, thiamine deficiency has its major effect in the brain and heart, but they are not exclusive.

Glucose is the main fuel, but like any other fuel used to produce energy, it has to be ignited. Thiamine, much like a spark plug in a car, processes this ignition. All simple sugars taken in the diet are broken down to glucose.  But before this happens in the body, dietary sugars have two effects. The first is a signal from the tongue to the pleasure zones of the brain. It is this sweet taste that makes sugar addictive. The second is that this excess of sugar overwhelms the capacity of thiamine to oxidize glucose to create energy. A person may have a perfectly normal thiamine level in the blood that is inadequate to meet the demand. It is the ratio of “empty carbohydrate calories” to the concentration of available thiamine that counts. I have called this “high calorie malnutrition” that seems to be an oxymoron since malnutrition is generally considered to be on the way to starvation. The patients with this form of malnutrition may be obese, remain relatively active, do not look ill and multiple symptoms are regarded by their physicians as “psychologic, or psychosomatic”. There appears to be no reason to seek laboratory evidence of malnutrition and the patient is written off as a “problem patient”. It is hardly surprising that the patient leaves the doctor’s office angry and tells friends that “the doctor told me that it was all in my head”.

The irony is that it IS in the patient’s head, but because of electro-chemical changes in brain metabolism. It has always seemed odd to me that physicians often consider that “psychological issues” are somehow “invented” by patients without thinking that every thought, every action, has a mechanism produced in a chemical “machine” called a brain. Distortions are the result of a combination of cellular energy deficiency (malnutrition), coupled with a potential genetic risk and perhaps a stress factor such as an otherwise mild infection/injury, or an inoculation. Any one of the three factors may dominate the clinical presentation, but in most cases the other two are involved.

A New Model: Genetics, Nutrition, and Stress

Throughout life each of us depends on our ability to survive in an essentially hostile environment. The first thing that it depends upon is our genetic inheritance that I have called “the blueprint”. But we also know that the “engines” of our cells, known as mitochondria, have their own genes in which the DNA is more susceptible to damage than our cellular genes. A new model must consider the fact that any stress requires energy in an adaptive response to any form of environmental attack resulting from a mental or physical problem or infection. The only way that we can protect the structural components of our bodies is by the use of the natural ingredients of nutrition, the ancient teaching of Hippocrates. The new science of epigenetics finds evidence that nutrition and lifestyle can make changes to our genes that might be beneficial or not, according to the circumstances. If a person has become sick from an excess of empty calories and refuses to change, the only way to treat that person would be by increasing the concentration of the missing nutritional ingredient in the form of a supplement. It is of paramount interest that in 1962 a paper was written in a prestigious medical journal. The author had found 696 medical journal manuscripts that reported 250 different diseases that had been treated with supplementary thiamine, with varying degrees of success. This suggests the possibility that health is produced by a combination of genetic influence, how we meet the daily impacts of stress and the quality of our nutrition. Disease results from, either genetic failure (cellular or mitochondrial), failure to meet stress because of energy deficiency, malnutrition, or combinations of the three elements.

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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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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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