Thiamine -key to energy metabolism

What Is Thiamine to Energy Metabolism?

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What Is Energy?

Energy is an invisible force. The aggregate of energy in any physical system is a constant quantity, transformable in countless ways but never increased or diminished. In the human body, chemical energy is produced by the combination of oxygen with glucose. This reaction is known as oxidation. The chemical energy is transduced to electrical energy in the process of energy conservation. This might be thought of as the “engine” of the brain/body cells. We have to start thinking that it is electrical energy that drives the human body.

The production of chemical energy is exactly the same in principle as the burning of any fuel but the details are quite different. The energy is captured and stored in an electronic form as a substance known as adenosine triphosphate (ATP) that acts as an energy currency. The chemical changes in food substances are induced by a series of enzymes, each of which combine together to form a chain of chemical reactions that might be thought of as preparing food for its ultimate breakdown and oxidation.

Each of these enzymes requires a chemical “friend”, known as a cofactor. One of the most important enzymes, the one that actually enables the oxidation of glucose, requires thiamine and magnesium as its cofactors. Chemical energy cannot be produced without thiamine and magnesium, although it also requires other “colleagues”, since all vitamins are essential. A whole series of essential minerals are also necessary, so it is not too difficult to understand that all these ingredients must be obtained by nutrition. The body cannot make vitamins or essential minerals. There is also some evidence that thiamine may have a part to play in converting chemical energy to electrical energy. Thus, it may be the ultimate defining factor in the energy that drives function. If that is true, its deficiency would play a vital role in every disease.

Energy Consumption

Few people are aware that our lives depend on energy production and its efficient consumption. A car has to have an engine that produces the energy. This is passed through a transmission that enables the car to function. In a similar manner, we have discussed how energy is produced. It is consumed in a series of energy requiring chemical reactions, each of which requires an enzyme with its appropriate cofactor[s]. This series of reactions can be likened to a transmission, consuming the energy provided from ATP and enabling the human body to function. If energy is consumed faster than it can be synthesized, or energy cannot be produced fast enough to meet demand, it is not too difficult to see that an insufficient supply of energy, a gap between supply and demand, would produce a fundamental change in function. This lack of function in the brain and body organs presents as a disease. The symptoms are merely warning the affected individual that something is wrong. The underlying cause of the energy deficiency has to be ascertained in order to interpret how the symptoms are generated.

Why Focus On Thiamine?

We have already pointed out that thiamine does not work on its own. It operates in what might be regarded as a “team relationship”. But it has also been determined as the defining cause of beriberi, a disease that has affected millions for thousands of years. Any team made up of humans requires a captain and although this is not a perfect analogy, we can regard thiamine as “captain” of an energy producing team. This is mainly due to its necessity for oxidation of glucose, by far and away the most important fuel for the brain, nervous system and heart. Thus, although beriberi is regarded as a disease of those organs, it can affect every cell in the body and the distribution of deficiency within that body can affect the presentation of the symptoms.

Thiamine exists only in naturally occurring foods and it is now easy to see that its deficiency, arising from an inadequate ingestion of those foods, results in slowing of energy production. Because the brain, nervous system and heart are the most energy requiring tissues in the body, beriberi produces a huge number of problems primarily affecting those organs. These changes in function generate what we call symptoms. Lack of energy affects the “transmission”, giving rise to symptoms arising from functional changes in the organs thus subserved. However, it must be pointed out that an enzyme/cofactor abnormality in the “transmission” can also interrupt normal function.

In fact, because of inefficient energy production, the symptoms caused by thiamine deficiency occur in so many human diseases that it can be regarded as the great imitator of all human disease. We now know that nutritional inadequacy is not the only way to develop beriberi. Genetic changes in the ability of thiamine to combine with its enzyme, or changes in the enzyme itself, produce the same symptoms as nutritional inadequacy. It has greatly enlarged our perspective towards the causes of human disease. Thiamine has a role in the processing of protein, fat and carbohydrate, the essential ingredients of food.

Generation Of Symptoms

Here is the diagnostic problem. The earliest effects of thiamine deficiency are felt in the hindbrain that controls the automatic brain/body signaling mechanism known as the autonomic nervous system (ANS). The ANS also signals the glands in the endocrine system, each of which is able to release a cellular messenger. A hormone may not be produced in the gland because of energy failure, thus breaking down the essential governance of the body by the brain. Hypoxia (lack of oxygen) or pseudo-hypoxia (thiamine deficiency produces cellular changes like those from hypoxia) is a potentially dangerous situation affecting the brain and a fight-or-flight reflex may be generated. This, as most people know, is a protective reflex that prepares us for either killing the enemy or fleeing and it can be initiated by any form of perceived danger. Thus, thiamine deficiency may initiate this reflex repeatedly in someone that seeks medical advice for it. Not recognizing its underlying cause, it is diagnosed as “panic attacks”. Panic attacks are usually treated by psychologists and psychiatrists with some form of tranquilizer because of the anxiety expressed by the patient.

It is easy to understand how it is seen as psychological, although the sensation of anxiety is initiated in the brain as part of the fight-or-flight reflex and will disappear with thiamine restoration. It may be worse than that: because the heart is affected by the autonomic nervous system, there may be a complaint of heart palpitations in association with the panic attacks and the heart might be considered the seat of the disease, to be treated by a cardiologist. The defining signal from the ANS is ignored or not recognized. Because it is purely a functional change, the routine laboratory tests are normal and the symptoms are therefore considered to be psychological, or psychosomatic. The irony is that when the physician tells the patient “it is all in your head”, he is completely correct but not recognizing that it is a biochemical functional change and that it has nothing to do with Freudian psychology.

A Sense Of Pleasure

We have known for many years that dietary sugar precipitates thiamine deficiency. A friend of mine had become well aware that alcohol, in any form, or sugar, will automatically give him a migraine headache. He still will take ice cream and suffer the consequences. I have had patients tell me that they have given up this and that “but I can’t give up sugar: it is the only pleasure that I ever get”. They still came back to me to treat the symptoms. We have come to understand that we have no self-responsibility for our own health. If we get sick, it is just bad luck and the wonders of modern medicine can achieve a cure. The trouble is that a mild degree of thiamine deficiency might produce symptoms that will make it more difficult to make the necessary decisions for our own well-being. Let me give some examples of symptoms that are typically related to this and are not being recognized:

  • Occasional headache, heartburn or abdominal pain
  • Occasional diarrhea or constipation
  • Allergies
  • Fatigue
  • Emotional lability
  • Insomnia
  • Nightmares
  • Pins and needles
  • Hair loss
  • Palpitations of the heart
  • Persistent cough for no apparent reason
  • Voracious, or loss of appetite

The point is that thiamine governs the energy synthesis that is essential to our total function and it can affect virtually any group of cells in the body. However, the brain, heart and nervous system, particularly the autonomic (automatic) nervous system (ANS) are the most energy requiring organs and are likely to be most affected.

Since the brain sends signals to every organ in the body via the ANS, a distortion of the signaling mechanism can make it appear that the organ receiving the signal is at fault. For example, the heart may accelerate because of a signal from the brain, not because the heart itself is at fault. Hence heart palpitations are often treated as heart disease when a mild degree of thiamine deficiency in the brain is responsible.

We have known for many years that sugar in all its different forms can and will precipitate mild thiamine deficiency. It is probably the reason why sugar is considered to be a frequent cause of trouble. If thiamine deficiency is mild, any form of minor stress may precipitate a much more serious form of the deficiency. An attack by an infecting organism is a source of stress imposed on the affected person and requires a boost of energy consumption. Therefore the illness that follows can be regarded as a “war” between the attacking disease producing organism and the brain/body that has to mobilize a defense. Either death, recovery, or a “stalemate” might be the expected outcome. If this is the truth, then any disease will respond to the ingestion of nutrients, particularly thiamine. It strongly suggests that Holistic or Alternative medicine could add a huge benefit to health preservation or the treatment of disease.

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This article was published originally on August 25, 2020.

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. Hello,
    Thanks for your work. I am a little confused.
    Do I take the ideal dose for the rest of my life?

    That sounds expensive

    • Depends. If you eat the SAD then you will likely need to supplement but if you eat a Whole Foods (not the store), animal based diet, then you should be fine once you fix any deficiency since you’ll be getting most if not all needed nutrients from your diet. Also important to get proper sleep, limit stress, and avoid toxins.

  2. Jennifer, glad to see your daughter is well. I am having similar issues. Did your daughter adjust immediately or did you slowly increase folinic acid? I tried 400mcg folinic acid had a very strong mood reaction. Thank you.

  3. Consider this!! An attack by ANY microorganism is a “declaration of war”. There are only 3 outcomes: the microorganism wins (death), you win (cure), or there is stalemate (chronic disease). The brain is responsible for organizing and controlling the defense. If its inherited construction is perfect, all it requires is energy. Probably a perfect DNA never occurs and many, if not all of us, have gene defects known as polymorphisms that are insufficient to cause disease on their own. For example, diabetes has a genetic background but does not appear until years later, often after the stress of a mild infection or a divorce. Epigenetics tells us that genes (say, polymorphisms) are influenced by nutrients. Any form of “stress” (a nasty divorce, a deadline, surgery, even an inoculation) demand a surge of energy to meet it. I suggest that “Longhaulers” after Covid-19 are suffering stalemate. Thiamine and magnesium together stimulate energy production, making the job of the brain more efficient to “win the war”. That is why thiamine deficiency has been reported in critical illness (stalemate) and after surgery. It strongly suggests that people who die from Covid-19 were experiencing high calorie malnutrition when they were assaulted by the virus. It also suggests that nutrition in America is inadequate to meet the stresses of modern life!!

  4. Dr Lonsdale, is it possible to make a video version of your article for own use? You will be cited as the source of course.

  5. Dr. Lonsdale,

    I have always dealt with anxiety, unstable performance/mood and insufficient energy levels, even though back then I was able to exercise consistently and study/work.
    I have always been pretty lean and used to eat whole foods for the most but I did allow myself to eat a fair amount of junk food a few times per week. And I was getting most of my calories from (decent sources of) carbs for most of my life.

    Funny thing is when I started incorporating longer fasts and low carb diets, even though my anxiety levels lowered and my performance stabilized, I started to experience this effect like my brain was on pilot/battery saving mode. My vision was blurry all the time, I could react easily to any stress situation or answer a question if someone asked me something, but I couldn’t do any complex thinking, or learn anything new anymore. My thoughts would disappear too soon like my mind was going blank, my short term memory went down. These symptoms persisted long after I adapted to low carb diets with proper electrolyte supplementation, even when I wasn’t even craving carbs anymore, and choosing protein and fats over carbs if I was given the choice. The symptoms progressed and now severely limit my work/study activities, at 28 years old. It quite literally feels like I am a previously intelligent individual locked in the mind of a very dumb one. Slightly raising carb intake only increased the side effects I used to experience before going low carb but still had no effect over my brain energy. Many supplements failed to improve symptoms. Magnesium supplements over the course of 2 months also had very little effects.

    I have only stumbled across your amazing work on thiamine and recently began supplementing 600-1800mg of T HCL, with great hopes of getting back the brain energy I used to have. I still don’t understand why I perform worse by going low carb, but can only hypothesize I got so thiamine (and magnesium) depleted during my life with a regular diet that I could not produce enough energy for optimal functioning when I reduced carb intake. And I suspect the higher carb intake was masking this lack of energy throughout my life by allowing some glucose to reach my brain somehow and allowing me to think clearly at least for some periods of the day. But that would still cause side effects when glucose levels were too high or too low, probably explaining the anxiety and mood instability.

    Would you think this is a valid hypothesis? How else could we explain me and a big portion of the population still being able to perform while on a high carb diet and probably deficient in many essential nutrients while I wasn’t able to perform at all on a lower carb nutrient rich diet? Could this really be all about thiamine or would you suspect of other issues? Would you recommend someone who’s on high dose thiamine therapy suspecting a deficiency to go really low carb at the beginning or stay on a moderate carb level until stores are replenished to avoid a higher drop in energy levels?

    • Well, consider this! Carbohydrates are “simple” (sugary things) and “complex” (plant carbs). Try a diet high in complex carbs and use increasing doses of thiamine. It is simple carbs that cause trouble.

  6. Dr’s. Lonsdale & Marrs,

    First, thank you so much for your long-needed knowledge and the “why” for so many maladies. I have read your book-which is an invaluable wealth of info-so much so I am reading it for a 2nd time, and surmise I will read it many times more.

    As an ex-nurse I have been on a hunt for the “cause” of the A-fib my husband first experienced 15 years ago, (notably, after a stressful incident) when he arrived home ashen, hypotensive & SOB (BP 60/40), hence off to the ER for (for overnight observation) & years later put on Metoprolol (to keep heart rate below 100 BPM). Fast forward to 2017 when we switched from an HMO to Stanford Health care, where he had a Maze Procedure (hybrid ablation) which put him in normal sinus rhythm for 2 years, then his symptoms worsened to include the following: Afib, PVC’s, Atrial flutter, tachycardia (203 BPM, possibly POTS), neuropathy both feet, restless leg syndrome, insomnia & vivid frightening dreams,

    Part of my research has been diet, as any stimulant, alcohol, sugar would set off an episode of Afib. Until I read your book I thought we were eating healthy & clean, however now realize any amount of sugar or junk food reverses the good effects of the many supplements we take, subsequently, we are in the throes of eliminating them all.

    Thankfully due to you and Dr. Marr’s book I started us both on Lipothiamine, my husband for all the above symptoms, me for arthritis & occasional Diverticulitis. I started with 50mg/per day & titrated up 50 mg every 10-14 days to the current dose of 300 mg TID (three times a day) & I am happy to report that my husband’s having less episodes of A-fib & tachycardia, plus the neuropathy “pins & needles” of both feet are almost non-existent!

    At this juncture my question is, should we continue with the current 300 mg dose to see if the symptoms continue to subside or continue to titrate up? Is there a protocol for when to take this amount of thiamine, as well as should we take Mag taurate, B, Multi-vitamins with each dose, or is once a day OK for these?

    Last, if I might suggest there be a place on HM’s site for a list of naturopathic doctors (who have read & understand Thiamine Deficiency Disease, Dysautonomia, and High Calorie Malnutrition), or functional med docs or PA’s that administer IV Thiamine, etc…to help us navigate, rather than doing it all by the seat of our pants?

    Kindest regards, Midge

    • That is a good idea. I will try to find out how many physicians have read the book and use it in practice.

  7. I am wondering if Beclotiamine is similar, different or just another name for benfotiamine.
    What kind of use has beclotiamine had besides research in chickens with coccidiosis ?

  8. Folate and B 12 are energy dependent and are often not activated without boosting energy, so add thiamine

  9. Hi Dr. Lonsdale,

    In your experience, have you seen cases of thiamine deficiency presenting mainly with full-body painful neuropathy? I seem to have developed nerve pain all over my body almost overnight after a few months of dealing with an odd set of health issues (restless sleep, stomach discomfort, shortness of breath, joint pain, tingling feet), and have been suffering with it for two months now. I have been suspecting a combination of undiagnosed celiac, increased consumption of junk food, and high coffee/tea/alcohol intake for several years as contributors to a thiamine deficiency that is causing my neuropathy.

    I began taking 300mg of Allithiamine about a month ago, and have honestly never felt worse in terms of the nerve pain. Can paradox last this long? Alternatively, I have also read that symptoms of neuropathy in thiamine deficiency are frequently the slowest to resolve. Is that true?


    • Have you stopped the junk food? The symptoms of TD are nonspecific because they are a result of energy deficiency and paradox can last as long as 1 + month. For TD you need B complex and magnesium

    • In case B returns, I must emphasize the necessity of starting with low dose thiamine and wait for paradox to subside. Anyone looking for help should survey the many posts on this website dealing with a complex issue arising from unrecognized, prolonged thiamine deficiency. Few physicians are aware of this common cause of debilitating disease and this website deals with the facts in many posts.

  10. Dr. Lonsdale, I have a friend who has an autistic kid. The doctor of this kid recommended methylfolate and methylcobalamin but the kid had a bad reaction to them. Can it be because the kid needs the Thiamine to have them used by his body, or this forms of b9 and b12 don’t need the B1 to be absorved?

    • If I can make a guess – maybe the child is not MTHFR deficient. Could a person be MTHR over expressed ? In G6PD – people can be deficient, normal or over-expressed.

    • All the B-vitamins are synergistic together. You need all of them together for the best results.
      It would be best to check for polymorphisms related to methylation, these include MTHFR, MTR, MTRR, BHMT and CBS.

      Alternatively you can also check for homocysteine and any level outside the normal range will indicate poor methylation.

      To process homocysteine you require B6 and zinc a co-factor for the conversion. It may be that he needs more B6 and more zinc, but no more than 40mg. Be careful with that as high-doses can be detrimental. Always check for upper-limit and toxicity.

      You need B1 as part of the first step for energy metabolism so that the cell can do the rest of the work needed in every other step of metabolism. B1 is an absolute necessity and it cannot hurt to include more especially since there is no upper-limit for toxicity. To be more thorough, slowly increase the dose incrementally and see how the person responds. DEFINITELY expect a possible paradoxical response that will improve within a couple days to a week or more.

    • I am just trying to figure things out, but I have read recently that many autistic kids have MTHFR and a homozygous or slow COMT… and giving the person methylated vitamins will cause overmethylation. My daughter has this issue and is not autistic. We have to use non-methylated forms of B12 and folate for her to not mania that goes into psychosis. If she is on folinic acid (not folic) and adenosylcobalamin B12, she is stable and functioning well.

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