stress response

Understanding Mitochondrial Energy, Health and Nutrition

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

Hans Selye and the Stress Response

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

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

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

Human Stress: Surviving a Hostile Environment

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

Energy Metabolism, Physics, and Chemistry

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

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

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

Of Mitochondria and ATP

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

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

Health and Disease in the Context of Energy

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

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

Why Thiamine

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

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

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This article was published originally on February 14, 2018.

What is Stress?

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Do We Really Understand Stress?

Sometimes, we use a relatively meaningless phrase when we say that a given person “is all stressed out”. I came to the conclusion that the word “stress”, as used in medicine, needed to have some discussion and explanation, even though I have addressed the subject previously. I turned to the 1946 work of Hans Selye. Selye was a medical student in Hungary who described how he got the idea of studying the impact of stress on the human body. As is common in medical education, the professor would bring patients into the classroom. Each patient had a known diagnosis, such as Rheumatoid Arthritis, or Parkinson’s disease, for example. The patient’s clinical course, including the symptoms, the physical findings observed by a physician and the response to treatment, would be discussed by the professor. However, Selye was not listening to the professor and not paying much attention to how the diagnosis was derived. He was looking at the demeanor of each patient. He decided that they all looked more or less the same. The facial expression was that of long-suffering and he concluded that each was expressing the “stress” from the impact of the disease, no matter what cause could be attached. This must surely make us think what this means for our present concepts of human disease. Does the present paradigm model totally answer the basic underlying reason for our loss of health? Is the everlasting search of the pharmaceutical industry for the right treatment of each and every disease the right track for medicine or not?

Selye’s Answer

After graduation, Selye immigrated to Canada and set up an Institute in Montréal that ultimately became known as the Stress Institute. He chose the rat as the subject of his studies and over many years, they were detailed and meticulous. Stress was imposed on each of his animal subjects by the performance of cruel trauma or by forced exercise to exhaustion. Many different laboratory studies were repeatedly performed as each animal became sicker from the imposed continued stress. Note that “stress” is used as the application of an attack that the animal has to survive (adapt to) or perish from exhaustion. He came to the conclusion that there was a set of predictable pathophysiologic changes as the stress continued. These consecutive changes in the blood and tissues defined the state of health (the ability to resist or adapt) in the experimental animal that he then called the General Adaptation Syndrome (GAS). It had three stages; the state of alarm, was the recognition of an attack (the stress); the state of resistance was how the animal defended itself against the attack and the state of exhaustion precluded death.

The remarkable thing about the conclusions of Selye was that the first two stages were dependent on the mobilization of the chemically produced cellular energy required to meet resistance and the third stage was dependent on failure to produce the required energy. At that time, little was known concerning the synthesis of energy in the human body. Now we know how energy is produced, the GAS makes perfect sense in determining how we perceive health and disease. Our lives are spent in a hostile environment where our preservation is of no interest to Mother Nature. Earthquakes, tsunamis, other natural events and our own physical actions, injure us if they do not kill. We are surrounded by a multitude of potentially lethal microorganisms. Our brains also require huge amounts of energy to meet the mental stresses of modern civilization.

Selye’s experiments were designed to attack the constitution of his experimental animals to see how they resisted or adapted. The laboratory studies of blood and tissues became the markers of the adaptive resistance. One of his students was able to reproduce the GAS by causing the experimental animal to become deficient in vitamin B1 (thiamine), thus demonstrating the role of energy in the first two stages and its deficiency in the third. He formulated the idea that human disease represented what he called “the diseases of adaptation”.

I was fortunate to be able to visit Dr. Selye and I discovered that he was confident in predicting that his work would be at the center of 21st-century medicine. Although I found that it is mentioned online, it certainly is not at the center of our medical approaches today. I concluded that his work did not gain sufficient attraction because of the cruelty of his experiments. Perhaps we should consider that the experimental animals sacrificed their lives to our well-being, because I believe that the GAS provides reasonable answers to so many of the mysteries that remain in modern medicine. The trouble is that it trashes the medical model that proclaims each and every disease as a separate and unique entity with its own particular cause and symptom treatment. Obviously, if the GAS represents the truth, it should eventually become acceptable as a prescription for addressing the reality of health and disease.

Of Energy and Oxidation

As repeated in many posts on this website, oxidation is the key to energy production. The energy is consumed by the complex mechanisms of defense with which the human body is equipped and it is carefully regulated. Too little oxidation is as bad as too much, since these extremes emphasize oxidation inefficiency. As in all things, moderation is optimum. These extremes are called oxidative stress. The balance is maintained by vitamins that are known as oxidants (they enable oxygen to be consumed) and antioxidants (they keep the oxidation from getting out of control). For example, without the scientific details, thiamine acts always as both an oxidant and an antioxidant whereas vitamin C acts as an antioxidant at its usual, natural dose and an oxidant at another. Though circulating antioxidant capacity in the blood is regulated automatically, a study found that antioxidant capacity varied according to the site of the injury. This means, of course, that the damage of trauma is highly dependent on the functional capacity of healthy oxidation in the healing process. We now know that the brain controls the defensive mechanisms that are mobilized in response to infection. Stress must initiate the appropriate physical and mental actions for survival. The physician has to become consciously aware of the extraordinary genius of the human bodies that he/she has the responsibility and privilege to examine and advise.

Reconsidering Selye’s General Adaptation Syndrome

The State of Alarm

The normal human response to any form of danger is the fight-or-flight reflex, something with which most people are quite familiar. It is initiated automatically through activation of the sympathetic branch of the autonomic nervous system as it prepares an individual to meet the foe. It does not define the nature of the stress that may be physical (trauma, infection) or mental (divorce, business deadlines etc.). Part of the reflex, all of which depends on healthy metabolism, is anxiety or fear (a sense of alarm). However, hypoxia or pseudo-hypoxia (a lack of oxygen or oxidation) is dangerous to the organism and will trigger the fight-or-flight reflex. This would, for example, enable the affected person to escape from a physical cause such as a bedroom gradually filling with an odorless poison gas. However, pseudo-hypoxia, caused by deficiency of thiamine, like hypoxia, will also trigger the fight-or-flight reflex. Because the affected individual does not know that thiamine deficiency is the underlying cause, there is no visual or tactile perception of the source of danger. Thus the sensations of the reflex are called symptoms and are considered to be due to an illness. This is referred to as a “panic attack” or “panic disorder”. It also explains why these attacks are associated with many other symptoms such as the heart racing, faster breathing or unusual sweating, all part of the fight-or-flight reflex.

It is easy to understand how this misperception of both doctor and patient becomes a “bone of contention”. The doctor sees it as a patient’s state of unnecessary worry, leading to the erroneous diagnosis of “psychological”. No consideration is given to the fact that psychological perceptions are produced by electrochemical brain reactions that consume energy. The patient is often somehow considered to be responsible by “giving in” to self pity, an absurdity that is hard to swallow. The same thing happens sometimes when, in the presence of thiamine deficiency, a trivial injury to a limb may give rise to persistence of unexpectedly severe pain. This used to be known as “sympathetic dystrophy” and is now known as “complex regional pain syndrome”. The pseudo-hypoxia is causing a state of alarm to persist by extending the sympathetically driven reflex to the affected limb. The pain is a result of highly abnormal signals sent from the hypoxic (pseudo-hypoxic) limb to the sensory system in the brain. It explains why an injection of B complex might relieve an otherwise totally inexplicable limb pain caused by pseudo-hypoxia.

The State of Resistance

By extrapolating the observations and laboratory data from the stressed animal to the human, the GAS might be thought of as “the illness”. It might also be thought of as the actions of defense against the attacking agent. I would like to provide a personal example. When I was a boy, before the antibiotic age, a splinter in my foot gave rise to ascending infection in the leg that could have led to general septicemia and ultimately death. My mother was instructed by a homeopathic doctor to wrap my whole leg in strips of blankets that had been boiled and allowed to cool enough to apply. I became delirious with a temperature of 104 or 105 but the ascending infection was conquered by improving my state of resistance. My immune system had been stimulated in its fight against the foe (the attacking bacteria) probably because of the high body temperature.

Fever is an important part of body defense because bacteria are programmed to be at their most virulent at normal body temperature. The high body temperature renders the action of the attacking bacteria less efficient. The state of resistance can be triggered falsely. For example, two children have been described in the medical literature whose attacks of “febrile lymphadenopathy” (swollen neck glands from inflamed throat) were caused by their indulgence with sweets, causing thiamine deficiency pseudo-hypoxia. The pseudo-hypoxia from thiamine deficiency caused a continued state of stress and kept triggering a false state of resistance at intervals, a perspective that appeared to be a genuine response to an attacking microorganism. On the other hand, it could have been a grossly exaggerated defense against a microorganism that would not have otherwise attacked.

The State of Exhaustion

What Selye concluded was that the stressed organism had consumed huge amounts of energy during the state of resistance and could no longer supply it. If energy metabolism is the center of health and its failure the center of disease, this work by Selye makes perfect sense. Perhaps the state of exhaustion might be what we now call “shock”, a phenomenon which has resisted explanation. It also explains why thiamine deficiency is frequently found in critically ill patients in the emergency room.

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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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Cortisol: The Stress Hormone

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Cortisol is a steroid hormone produced in the cortex of adrenal gland. It belongs to a class of hormones called glucocorticoids and plays an important role in regulating cardiovascular function, blood pressure, glucose metabolism, sugar maintenance, and inflammatory response. Cortisol is best known as the stress hormone. It is released in response to stress, and is part of the fight or flight system.

Under normal conditions the body regulates cortisol levels which are usually high in the morning and low at night. But under stressful conditions more cortisol is secreted. Small increases in cortisol produce positive effects such as increased sustained energy, diminished pain sensitivity or memory enhancement. But a prolonged cortisol increase during chronic stress results in negative side effects: increased blood pressure, sugar imbalance in blood, decreased bone density, cognitive problems, and reduced thyroid function. It also slows down healing processes and suppresses the immune system, perhaps the reason we are more apt to get sick when we are stressed.

Continuously, stress-induced elevated cortisol levels lead to an increase in the level of other hormones (testosterone, estradiol, insulin).  High cortisol levels are often linked to insulin resistance (Type 2 Diabetes), weight gain and general inflammatory conditions. High cortisol is toxic to the brain and can cause memory loss and contribute to Alzheimer’s disease or senile dementia. Elevated cortisol levels and lack of diurnal variation have been identified with Cushing’s disease. Low cortisol levels are found in primary adrenal insufficiency (e.g. adrenal hypoplasia, Addison’s disease).

Cortisol and progesterone bind to common receptors in cells. Cortisol blocks progesterone activity, and some suggest, that high levels of cortisol, initiated by chronic stress, dispose one to a condition called estrogen dominance.  Estrogen dominance is condition where women cease to ovulate regularly and progesterone concentrations are lower than necessary during the second half of the menstrual cycle. Many suspect estrogen dominance underlies PMS and other cycle related symptoms.