mitochondrial stress and energy

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.

Derrick Lonsdale M.D., is a Fellow of the American College of Nutrition (FACN), Fellow of the American College for Advancement in Medicine (FACAM). Though now retired, Dr. Lonsdale was a practitioner in pediatrics at the Cleveland Clinic for 20 years and was Head of the Section of Biochemical Genetics at the Clinic. In 1982, Lonsdale joined the Preventive Medicine Group to specialize in nutrient-based therapy. Dr. Lonsdale has written over 100 published papers and the conclusions support the idea that healing comes from the body itself rather than from external medical interventions.


  1. I love your work thanks so much . A friend who also has has chronic fatigue syndrome has just been diagnosed with Thrombocytopenic Purpura- we are in the UK and haven’t got access to IV vitamins- would high dose oral or sublingual vitamins do instead obviously over longer period of time? Obviously Thiamine is a big player -what other vitamins would be useful – I’m aware you can’t give specific medical advice but any info or links or ideas would be amazing! Thanks

    • The major clue here is chronic fatigue syndrome, the hallmark of mitochondrial inefficiency. Since it is unlikely that a given person would have 2 diseases at the same time, we have to assume that thrombocytopenic purpura is another example of energy deficiency. Therefore it is represented in the bone marrow where the cells that produce platelets are for some reason lacking in that energy. I am becoming increasingly convinced that thiamin is the guardian of mitochondrial function. I would treat this friend with Lipothiamin (you can obtain this by calling Bonnie Fields in the United States at 1-800-275-3495. Also obtain magnesium and a well-rounded multivitamin). Dr. Marrs has found evidence that mitochondrial damage can occur during life as well as from a genetic influence and it appears to be extremely common in our toxic world.

      • Thanks so much for replying ! So it could literally mean that the bone marrow is lacking the energy to produce the platelets ? Really interesting. There is a lot of cancer in her family so maybe she has certain polymorphisms snps that are making her unable to detox in this increasingly toxic world causing mitochondrial dysfunction. I think she also has SIBO small intestinal bacterial overgrowth so no doubt the bacteria are depleting her of vital nutrients, and also giving off LPS lipopolysaccharides that can also cause mitochondrial dysfunction. I know that overgrowth of bacteria in small intestine steal iron and vitamin b12 – do you know if they also steal or deplete thiamine? Also just occurred to me that gut bacteria produce b vitamins and i’m assuming that there are bacteria that produce thiamine and therefore people with a robust microbiome will less likely be deficient even when they are not consuming thiamine rich foods as they are producing it endogenously – Can’t thank you enough for your info on thiamine- I also have chronic fatigue and SIBO ( no thrombocytopenic Purpura – yet!) and this thiamine aspect makes a lot of sense as various tests show and also going by how I feel show i’m not processing carbs well. I also got a lot worse after Flagyl which I know you have written about as it must have sent me from maybe mild deficiency into major deficiency – I’ve ordered Althiamine and am waiting for it to arrive. Will definitely pass this info onto my friend and to people in the fibromyalgia and chronic fatigue group I belong to. Thanks so much again !

        • I really don’t know what SIBO means. The microbiome consists of millions of bacteria that are essential to health and their place is not fully understood. Does SIBO mean that the bacteria are pathogenic in this individual? There are two enzymes that exist in the human bowel, synthesized by organisms that are common. One is called thiaminase I and the other one is thiaminase II. Depending on the pH of the reaction, these enzymes are capable of synthesizing or destroying thiamin and their place is still not fully understood. It is also important to know that thiamin is involved in some forms of cancer, so its ubiquitous nature in maintaining health may expand as our knowledge increases. The trouble is that very little of this research is being done in America. Most of the published manuscripts are coming from Eastern countries.

          • The thought is SIBO is bacteria(fungus too?) thats in the wrong place. It should be in the large intestine but thanks to a neuropathy in Ileocecal valve it ends up in the nutrient absorbing small intestine and causes body wide issues…the we dont know what you got disease called fibromyalgia perhaps? There seems to be a connection between SIBO and Fibro.There supposedly is now an accurate blood test for fibro (FM/a). A test that many doctors and makers of Lyrica dismiss or don’t know about. Investigate if your interested Christine. Im having it done next week. I have tested postive for methane SIBO, and told I have fibro. So this Ileocecal valve neuropathy is caused by thiamine deficiency perhaps….which could be coming from too many wrong/bad gut guys in your small intestine competing with you/your brain for thiamine? While your feeding/growing them with sugar I might add. Back to Hippocrates again right Doc?…all disease starts in the gut. Imagine a world if we all followed his ideas and not greed. Yoplait would be bigger than big pharma! 😉

            Dr Mark Pimentel at Cedars-Sinai is Dr SIBO…he believes SIBO is caused by this Ileocecal valve neuropathy . He treats SIBO with a antibiotics combo of rifaximin and neomycin, but knows that doesn’t fix the neuropathy. So SIBO comes back in most cases. Dr Mahmoud Ghannoum at Case Western is Dr Fungus, yeast/fungus has a part in this is his assertion. Dr Derrick Lonsdale is Dr Thiamine..the spark that starts the engine. We need to get these three very smart Dr’s together and prevent the fall of Rome. ( a Little theatricalility for added effect 😉

            • Frankly, I am puzzled. Recent interest has been in the millions of “good” bacteria that live in the human intestine and are essential to our health. This is known as the microbiome, about which I recently wrote a post that has been published on Hormones Matter. From the literature that I have read, it is the full complement of the microbiome which contributes to health and it is its fragmentation from antibiotic use and other factors that are associated with disease. My clinical experience with IBS has been related to the autonomic neurological mechanism of peristalsis. If the ileocecal valve failed and the bacteria backed into the small intestine, it would be a (theoretical) transplant of “good” bacteria, possibly without any harm. I must emphasize however that the microbiome and its association with health is relatively new, under study and about which there is much ignorance.

              • OTOH, what if that neuropathy has the ileocecal valve frequently stuck in a closed position? My ICV has been chronically stuck shut for decades. This has made my upper gut a fermentation zone, where bacteria feast on my food before I can. This has left me with chronic thiamine deficiency. Imagine my surprise when I took Benfotiamine, then Allithiame, for the first time today, and my entire gut, including that ileocecal valve, sprang to life. Thank you so much for your work.

                • Brenda,

                  I have been dealing with illeocecal valve problems off and on for a few years now. It’s usually followed by a bout of interstitial cyctitis. I’ve recently been adding coconut oil to my coffee and cooking routine and am pleased to be quite pain free. I originally started adding coconut oil after reading on earth clinic.

          • Hi Christine, I just came across this great article and I was curious to find out if Althiamine has helped you and your friend. Thank you!

  2. Alas! It’s true. Disease potential now is miniscule compared with the future. We may read what is here and even accept it as the truth, but we won’t change!!

  3. Simple, profound and spot on for those people who still have difficulty around you are what you eat, you think how you eat, you feel how you eat, you move how you eat. Thanks to you, Derrick!.

    I feel like I have been an enlightened Hobbit for the past 46 years. I am 61 and started looking at diet when I was 15, in Arizona. Tons of wrestling, tons of losing weight quickly. I did a lot of swimming at night, and hiking. But part of my regimen included researching my vegetarianism, and I found researchers in Scandinavia (of all places, that meat-centric region) and other part of the world talking in detail about vitamins, enzymes, probiotics, herbs and more. I also had the chance to study some Native American (Papago) and native Mexican herbal and food routes to healing.

    Now, though, at 61, so much more is available. That Berberine, Quercetin, Turmeric, methyl folate, B-Complex, CO10 smile, for sure. It is a vast open medical landscape to delve into, and luckily, my D3 and St. John’s Wort, and all those Saw Palmetto blues are washed away.

    This is a heavy lift in a society that is generally polluted, from every angle, preconception, through gestation and through adolescence and then into adulthood.

    The explosion of hormone disrupters is something the average American cannot grasp. Better to take that General Anxiety Disorder and pull up an easy chair and chow down on Doritos, Buffalo wings, Reeses piece washed down by a Mountain Dew. If it were only those items on the menu. Everyday is Super bowl Sunday pig-out, unfortunately.

    The amount of skepticism in America is great – heck, 19 percent of Americans believe the Sun revolves around the earth, and 80 percent say they have a good angel protecting them. Yet. . . . I have argued till I was almost blue in the face about my vegetarianism – I have muscle mass, I used to bike 50 miles a day and run 8 miles a day, and still had power lifting abilities. I was a lacto-ovo vegetarian, but now, I have cut out casein, dairy, eggs for the most part, and amazingly, my fingers and wrists are pain-free. I have had every finger and both wrists broken at a young age, because of wrestling, judo and motocross racing. And the joint paid I always fought through. Starting at age 35.

    It works for me, that leafy greens diet, tons of legumes, and other high histamine foods at times.
    Nootropics like artichoke supplements, and, well, every so often, a wild salmon. Nuts, not as much gluten grains as I used to consume, but all those supplements. And thiamine and folate and other wonderful products.

    Added to this is traveling to other narrative contexts around health: I was lucky to travel in parts of the Jungle in Vietnam and Mexico and Central America. I understand the depth of legions of traditional healers. Maca root anyone?

    This concept of humans under stress 24/7 is acceptable, and hence, the trillions we spend in traditional industrial western medicine. Amazingly, we accept a world of planned and perceived obsolescence, 60 percent of all food thrown away, complete blasphemy around toxins in air, water, soil, food, and on and on about the disposable generations of modern society.

    But, again, why do zebras not have ulcers? That scientist, Robert Sapolsky, explains in his work.

    Quoting Sapolsky:

    Let me give you an example: a human ritual. Two humans sit at a table. They are silent. They do not
    move. They do not make eye contact. They do nothing more physically taxing than every now and then
    one of them lifts an arm and moves a piece of wood on the table. And if these are two chess
    grandmasters in the middle of a tournament, they are maintaining the blood pressure for hours of
    marathon runners and they are doing it just with thought. And that is the amazing thing with us. We sit
    around and we activate the same physiological systems. I mean you sit there and you get stressed over
    something psychological and you are secreting the same hormones that fish and reptiles and birds do
    when they are stressed. And what are we doing? We are thinking about ozone layers or something
    completely abstract. We turn on the same stress response. With us, we have the same old physiological
    wiring as every other mammal out there and then we use it for utterly bizarre circumstances, as we will

    Finally, third domain. There are circumstances of human behavior where there is simply no animal
    precedent. Now, let me give you an example here—shocking example. You have a couple; they come
    home from work at the end of the day; they talk; they have dinner; they talk; they go to bed; they have
    sex; they talk; they fall asleep. The next day, they do the same exact thing. They come home from
    work; they talk; they eat; they talk; they go to bed; they have sex; they talk; they fall asleep. They do
    the same thing every night for 30 days in a row. Hippos would be repulsed by this. Hardly any other
    species have non-reproductive sex and nobody else talks about it afterward. And at that regard, we are totally unprecedented. In those domains, if you want to make sense of us as a species, there is simply
    no animal equivalent. –end quote–

    Yet, stress is what Capitalism eats off of, like a virus gone rampant. I see stress in the PK12 students I have taught, the college students I have engaged with (and taught), the homeless-substance abusers-reentry-traumatized clients as a social worker. My old days taking care of adults living with developmental disabilities put me face to face with broken systems as these great men and women ate themselves into anxiety, depression, brain fog, lethargy, and physical decay. These are clients from a social worker’s POV, many of whom had that “IQ” below 70, and others on the autism spectrum and many damaged as fetal alcohol sufferers.

    Daily, what is the connection to environmental decay and pollution to the ailments now plaguing Western Cultures? It’s huge.

    Pretty much all commercial plastic leaches synthetic estrogen. So, hmm, when grandma hit puberty, that average age was 17; today, it’s 12 today (and getting younger by the decade – 10 is not uncommon for first menstruation). And, men have lost 50 percent of sperm numbers since 1950, and on average, the average penis is 2 cm shorter than our grandfather’s.

    From a great piece on the garbage gyres in our oceans,

    quote: Read The Feminization of Nature, by Deborah Cadbury, for a comprehensive look at endocrine disrupting and estrogen mimicking chemicals. Whether diphenyls and bispherol, virtually all commercially available plastics leach synthetic estrogens, and may be contributing to a host of health problems. Indeed, it’s already happening. One’s grandfather’s penis was, on average, two centimeters longer; our grandmothers hit puberty at age 17; their granddaughters at age 12: Estrogen-saturated parody adults. A final joke before extinction. Sperm counts are down 50 percent since the 1950s. “In another 50 years we may not be able to reproduce,” Ebbesmeyer said.

    In the endgame, we’ll be a race of sexed-up tweener girls and sterile dudes with little dicks wandering baffled through a rubbish-filled world. Then those poor mismatched souls will grow old and die. End of story.

    Gyres: The terrifying true story of the garbage that could kill the whole human race by Bucky McMahon

    So, do hormones matter? Does the website, Hormones Matter, matter? Come on – the answer is yes-yes-yes.

    So, plastics industry is $375 billion a year business. Plastics end up in the food web, in terms of marine species and what humans like to eat. But what about the plastics in those cans of tomato soup? The plastics in all the items we crave as consumers?

    Just the plastic garbage in the Pacific, well, a Greenpeace study surmises that it would take 68 ships trawling 24 hours a day an entire year to cover 1 percent of the Pacific. They would burn up a tremendous amount of fuel and do more harm than good.

    That’s just PLASTIC. Imagine all those glyphosate compounds in all those Cheetos and burger buns? All the other chemicals in our human quagmire of interlocking and intertwined chemicals we’re exposed to?

    This little corner of the web-sphere, Hormones Matter, gives voice to those outliers, innovators and leading edge thinkers and hands on researchers. Keep on truckin’

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