Thiamine Deficiency and Aberrant Fat Metabolism: Clues to Adverse Reactions

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Derrick Lonsdale, MD
Over the last several months, the writers and researchers at Hormones Matter have posted a number of articles about mitochondrial dysfunction and thiamine deficiency.  Thiamin, or thiamine as the internet search engines prefer, is critical to mitochondrial function. We’ve learned that thiamine deficiency can emerge gradually due to dietary inadequacies or more suddenly as a result of a medication, environmental or surgical insult. Regardless of the cause, deficits in thiamine evoke devastating health issues that can be treated easily if identified. More often than not, however, thiamine deficiency is not assessed and symptoms are left to escalate, mitochondrial damage increases, and patient suffering continues. Because thiamine deficiency is rarely considered in the modern scientific era, mild symptoms are ascribed to other causes such as “an allergy” or “it’s all in the patient’s head”. If, however, the cause is not revealed, the same old dietary habits will continue and can be guaranteed to produce much more severe and difficult to treat chronic disease.

Although there are a myriad reasons why mitochondria are damaged, medication or vaccine reactions paired with latent nutritional deficiencies seem to be common. Predicting who and how the mitochondrial dysfunction might appear, however, is more complicated. Quite often, athletes and individuals considered healthy are hit harder by a stress factor such as a vaccine than those whom we might not regard as particularly healthy. There are several potential reasons for this, some of which have been outlined previously. In this post, I would like to add one more reason why highly active, high performing individuals might be hit harder and more quickly than their less active counterparts with vaccine or medication reactions that induce thiamine deficiency.

Mitochondria are the Engines of the Cell

To use an analogy, the usefulness of a car obviously depends upon its engine. Mitochondria are the “engines” of each cell within our bodies, all 70 to 100 trillion cells that make up an adult body. They are known as organelles and are so small that their structure can only be seen with an electron microscope. But we can take this analogy further by comparing each cell to a different car model. A high powered car uses more gasoline than a low powered one and there are many models of each type of car. So some cells in the body require more energy than others, depending on the special function of the cell.  The most energy consuming cells are in the brain, the nervous system and the heart, followed by the gastrointestinal system and muscles. That is why those organs and tissues are most affected in the disease known as beriberi, the thiamine deficiency disease that we have discussed previously in other posts. The function of other organs is affected by the deficiency because of the changes in the control mechanisms originating in the brain through the autonomic (automatic) nervous system.

It has been pointed out that this disease in its early stages affects the autonomic nervous system by causing POTS. Beriberi and POTS, both being examples of dysautonomia (abnormal activity of the autonomic nervous system), can only be distinguished by finding evidence of thiamine or other nutrient deficiency as a cause. Thiamine is but one factor whose deficiency causes loss of cellular energy, resulting in defective brain metabolism and dysautonomia.  Although the relationship with vaccination is conjectural, some individuals with post Gardasil POTS were found to be thiamine deficient and had some relief of symptoms by taking supplementary fat soluble thiamine, an important derivative that occurs in garlic and has been synthesized. Not all of these thiamine deficient individuals have benefited to the same degree, suggesting that other deficiencies might also be involved. This post is to provide some information about more recent knowledge concerning the action of thiamine and the incredible, far-reaching effects of its deficiency, particularly in the brain. Experimental work in animals has shown that thiamine deficiency will damage mitochondria, a devastating effect for an acquired rather than a genetic cause. Far too much research has been devoted to genetic cause without sufficient attention to the way genes are influenced by diet and lifestyle.

The Importance of Enzymes to Mitochondrial Function

Before I provide this new information, let me remind the reader that enzymes, like cogwheels in a man-made machine, enable bodily function to occur. The importance of thiamine is that it is a cofactor to many of the enzymes that preside over energy metabolism. Without its cofactor an enzyme becomes inefficient. Perhaps it might be compared with missing teeth in a cog wheel. With missing teeth the cog wheel may still function but not nearly as well as it would with all of its component parts.

In previous posts we have discussed how thiamine deficiency can be caused by an excess of sugar in the diet. I have likened this to a “choked engine” in a car where an excess of gasoline, relative to insufficient oxygen concentration in the mixture, makes ignition of the gasoline extremely inefficient. Bad diet, one that is rich in sugary, carbohydrate laden foods may be one of the more common contributors to latent thiamine deficiencies. Excessive intake of processed fats and the concomitant changes to mitochondrial function and energy metabolism may be another important contributor.

Thiamine and Fat Metabolism

All the enzymes affected by thiamine deficiency have a vital part to play in obtaining cellular energy from food by the process of oxidation. Most of them have been known for many years but in the nineties a new enzyme was discovered. It has a very fancy name that has been simplified by calling it HACL1.  Only in recent years has it been found that HACL1 is dependent on thiamine as its cofactor. Although not reported, it may mean that it is also dependent on magnesium. This is exceedingly important because it introduces the fact that thiamine is involved in fat as well as carbohydrate metabolism, something brand new, even to biochemists.

Here I must digress again to describe another type of organelle called a peroxisome that occurs in our cells.  Like mitochondria, they are infinitesimally small. Their job is to break down fatty acids and they have a double purpose. One purpose is to synthesize very important substances that construct and maintain cells and their function: they are particularly important in the brain. The other purpose is what might be called fuel preparation. As the fatty acids, consisting of long carbon chains, are broken down, the resulting smaller fragments can be used by mitochondria as fuel to produce energy.  Failure to break down these fatty acids can result in the accumulation of natural components that may be toxic in the brain and nervous system or simply result in lack of one type of fuel. That is why feeding medium chain triglycerides by administration of coconut oil has been reported useful to treat early Alzheimer disease. They can be oxidized in mitochondria.

The Important Use of Fatty Acids in Mitochondrial Health

Here, I want to use another analogy. Imagine a lake that admits water to a river through a sluice gate that has to be opened and closed by a farmer who regulates the supply of water. If the gate is open the river will supply water to the surrounding fields. If however the gate is closed, the river will begin to dry up and the crops in the fields will suffer. Perhaps the farmer half closed the gate during a rainy period and has forgotten to open it when a dry period follows. High temperatures in the dry period results in insufficient water to meet the growth needs of the crops.

In this analogy, the lake represents food, the sluice gate is the HACL1 enzyme and the farmer who controls the gate represents thiamine. The water in the river represents the flow of fatty acids to the tissues for the double purpose of cellular construction and fuel for oxidation. The half open gate represents a minor thiamine deficiency, more or less sufficient for everyday life but not enough when there is greater demand. A high temperature that increases the water needs for crops represents Gardasil and many other medications as a stress factor, placing a greater demand on essential metabolic action.  The analogy also implicates the nature of the crops, some of which require more water than others. The crops, of course, represent body tissues and organs.

If we consider high performing individuals, whether academically or athletically, like high performance cars or crops that demand more nutrients, we can see how a previously unrecognized minor deficiency might trigger clinical disease by the stressful demands of a vaccine or medication. Some pharmaceuticals can attack thiamine directly, like Gardasil and the fluoroquinolones, while others attack different pathways within the mitochondria.

No matter the pathway, high performing individuals, with high energy needs not covered by diet, may be hit harder when a medication attacks mitochondrial energy.

The Outcome of Defective Fatty Acid Metabolism

Returning back to the HACL1 enzyme, we now know that HACL1 is the first thiamine dependent enzyme to be discovered in peroxisomes. It is research news of the highest importance, affecting us all. Its action is to oxidize a diet related fatty acid called phytanic acid and fatty acids with long carbon chains that cannot be used for fuel until they are broken down. Phytanic acid is obtained through consumption of dairy products, ruminant animal fats and some fish. People who consume meat have higher plasma phytanic acid concentrations than vegans. If the action of HACL1 is impaired because of thiamine deficiency the concentration of phytanic acid will be increased. The river in the analogy actually represents a series of enzymatic reactions that may be thought of as down-stream effects, whereas thiamine deficiency, being up-stream, affects all down-stream phenomena. One of the reasons thiamine deficiency is such an important contributor to illness is because its effects are broad.

These enzymatic reactions, known technically as alpha oxidation, involve four separate stages. It has been known for some time that if another enzyme at stage two is missing because of a gene defect, the result will be damage to the neurological system known as Refsum’s disease. Symptoms include cerebellar ataxia (also reported after Gardasil vaccination), scaly skin eruptions, difficulty in hearing, cataracts and night blindness. Other genetic mutations in alpha oxidation, resulting in various biochemical effects, result in a whole variety of different diseases. This places thiamine deficiency as a potential cause for all the down-stream effects resulting from defective alpha oxidation, for it has been shown in mice that this vitally important chemistry is totally dependent on presence of thiamine. Since its complete absence would be lethal, we have to assume that it is mild to moderate deficiency, equivalent to a partial closure of the sluice gate in the analogy.

Sources of Phytanic Acid: How Diet Affects Thiamine

In ruminant animals, our source of beef, the gut fermentation of consumed plant materials liberates phytol, a constituent of chlorophyll, which is then converted to phytanic acid and stored in fat. The major source of phytol in our diet is, however, milk and dairy products.  It raises several important questions. If thiamine deficiency is capable of causing an increase in phytanic acid in blood and urine, it might be a means of depicting such a deficiency in a patient with confusing symptoms. It might also explain why some individuals who have been shown to have thiamine deficiency by means of an abnormal transketolase test have symptoms that are not traditionally accepted as those of such a deficiency, perhaps because of loss of efficiency in HACL1.

If an excess of sugar in the diet gives rise to a secondary (relative) thiamine deficiency, we are provided with an excellent view of the extraordinary danger of empty simple carbohydrate and fat calories, perhaps explaining much widespread illness in Western civilization. Interestingly, it would also suggest that something as benign as milk could give rise to abnormal brain action in the presence of thiamine deficiency, because of phytanic acid accumulation. Our problems with dairy products may go well beyond lactose intolerance and immune dysregulation.

In sum, the discovery of HCAL1 enzyme and its dependence upon thiamine suggests one more mechanism by which thiamine deficiency affects mitochondrial functioning. As emerging evidence indicates a myriad of environmental and pharmaceutical insults impair mitochondrial functioning, thiamine deficiency ought to be considered of prime importance. Deficits in thiamine evoke devastating health issues that can be treated easily if identified.  If, however, thiamine deficiency is not identified and the same old dietary habits continue, the latent thiamine deficiency can be guaranteed to produce a much more severe and difficult to treat chronic disease. Moreover, individuals with thiamine deficiency who do not respond sufficiently to thiamine replacement might also have aberrant fatty acid metabolism. This too should be investigated and dietary changes adopted.

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  1. I’ve just had a big realization regarding medications and Thiamine. My blood sugar was out of control so I doubled my metformin dose. I had a new episode of what I call dizzy and ditzy as a result. Can’t walk straight, difficulty comprehending speech, and my left eye won’t track right. I began to suspect thiamine was the problem because I had run out of my normal thiamine pyrophosphate sublingual and switched to a 500 mg Thiamine HCL while I waited on my reorder that was slow.

    While I was researching this as a possible explanation for the dizzy & ditzy episodes I’ve been having, I read an article about metformin and B1. Metformin uses the same transporters as thiamine. So my low doses of (13mg) thiamine pyrophosphate can’t compete against so my 2x 1000 g doses of metformin for uptake. I also read that Metformin promotes the excretion of thiamine by 20x. I got control of my blood sugar by taking multiple forms and doses of thiamine throughout the day and my other symptoms also decreased as well. I’m back to my 500mg 2x on Metformin and my glucose is almost under control. But I can’t seem to use fat/protein for energy. My vision won’t clear up til I take some carb.
    So beware metformin if you suspect problems with thiamine (I’m sensorineural hearing impaired as is my mother and daughter). Can’t get a doctor to run with that clue.

    1. I am concerned because “a little knowledge is a dangerous thing”, a very old and important proverb.Susan does not tell us why she had blood sugar out of control. I presume that it is diabetes type 2 because she is using Metformin. However, few people, even diabetics, are unaware that both types 1 and 2 are associated with a severe degree of thiamine deficiency and that Metformin could probably be dispensed with. She says “I can’t use fat/protein for energy” suggesting that she has a defective HAC L1 enzyme as explained above. If I were her physician, I would want to look for evidence of urinary phytanic acid (see above) and If I found it I would order order a supplement of thiamine pyrophosphate because that is the cofactor for this enzyme. It is very troubling to me to see so much evidence of medical ignorance. I am discussing facts that are written in the medical literature. The trouble is that medicine is running on the dictates of the pharmaceutical industry and has not yet come to the realization that a new form of medicine is slowly but surely developing.

      1. They probably wouldn’t find any because I’m allergic to 44 different foods including Milk, eggs, wheat, barley, oats etc. However I have noticed that I don’t seem to get much energy from fish and none of the omega-3 oils I tried for my meal replacement shake worked as well as canola oil. I also have malabsorption problems (pancreatic exocrine insufficiency).

        I was taking 13 mg sublingual TPP daily since the food allergy diagnosis so I didn’t think I could possibly be thiamine deficient. I thought the symptoms were brought on by my allergies, but when I had a bad dizzy & ditzy episode during a reaction to my allergy desensitizing shots, my allergist assured me the allergy was not the cause. So I went looking for other answers. That’s how I found the transporter issue with metformin. Metformin was blocking thiamine uptake. 1000 mg beats 13 mg every time. Benfotiamine doesn’t seem to help, but sulbutiamine does help with memory when the dizzy episodes are active. It took months for me to recover from the allergy shots episode. Then I had to increase my metformin dose and was off again.

        I suspect I have a problem with thiamine, possibly mitochondrial because my mother, myself, and I all have sensorineural deafness. I also have homozygous mutations in MTHFR & MTRR. I think the diabetes is partly due to some rare mutations I have in TCF7L2 which results in reduced insulin secretion. My current primary wanted me on a high fat/high protein diet and it didn’t work.

        It is nice to have explanations. My primary referred me to a nutritionist who specializes in nutrigenomics can help me sort out the various risks I have and reconcile it with the all my food allergies. If anyone knows of a clinic or doctor treating adults with undiagnosed metabolic genetic diseases please share. (my gene results are from 23 and me and a lot of researching on my part)

        I’m thinking of trying Vanderbilt at Nashville, it’s about 4 hours from here. My last primary NP said I was just over her head. The local endocrinology group doesn’t take uninsured patients.

        1. PS. I read a lot of your papers in 2012. I had digestive problems and something I called Frankenstein Foot where my calf was stiff and my ankle didn’t bend easily. I take magnesium glycinate as well as various sublingual B’s. The normal B12 and Folic acid are not good for me and I knew that before I got diagnosed. Your body will tell you if you listen but don’t expect a doctor to know symptoms.
          If you are overweight the medical community does not listen when you tell them you’re too tired to get out of your chair, even if that is very abnormal for you. It is pretty much expected to be a couch potato if you are diabetic. I had diagnosis of GERD before they figured out the food allergies, so I suffered a long time because the GI didn’t care to follow up on the cause of the GERD or the Pancreatic exocrine insufficiency which is still unknown cause.

        2. OOps. I mean me, my mother, and my daughter. Also possibly my maternal grandmother. Something fishy mitochondrial.

  2. I’m a 67 year old male with treatment resistant rapid cycling/mixed state bipolar, poor sleep and physical health issues(increasing weight gain since 2016, metabolic sydnrome, fatigue, ‘brain fog’, inability to handle stress, sensory overload). One of the most upsetting is the loss of libido/erectile function. I was diagnosed with low testosterone in 2013 and have been on injections, compounded cream and Testopel implantation. Though my labs have reflected high total T and high free T, it’s almost as if I’m resistant to testosterone, though I don’t think that’s possible. Thyroid medication didn’t help either. Could thiamine deficiency be a factor ? Thank you.

    1. All the symptoms you describe are those of defective energy metabolism and thiamin certainly could be a huge factor. It always concerns me that physicians give people testosterone without thinking why a patient is not making his own testosterone. I would suggest supplementation with thiamin, magnesium and a well-rounded multivitamin. Although thiamin is extremely important, it does not work on its own. It is the “captain of a team”.

  3. This is an amazing article! I have suffered from a lifetime of brain fog, years back I used to randomly try supplements and thiamine made me feel like I came back to life! I had never felt anything like it, my memory came back I was personable, I was all of a sudden good with directions, I wasn’t depressed. But the effects slowly wore off and I had to keep upping the dosage until one day it did nothing for me. Now years later after trying literally probably 50 times megadosing it has no effect on me and I’m desperate to get that feeling back. If you have any idea what could be going on I’d appreciate the advice. (Huperzine a and Acytel l carnitine also had the same A fax but also wore off after a couple weeks. No other vitamin has ever affected me really, just those three)

    1. It is important to be aware of how thiamin (and any other vitamin for that matter) functions. It is a cofactor to many vitally important enzymes in the body that preside over energy metabolism. Magnesium, however is also a cofactor for the same enzymes. I have never given thiamin on its own to anyone. It should be accompanied by magnesium, B complex and a well-rounded multivitamin. I suspect that thiamin without magnesium produced an imbalance that eventually made itself known

  4. Wow, this is interesting. Chandler, is it the estrogen in oral contraceptives that promote thiaminase? I am wondering if bioidentical estrogen (estrogen and estriol) and ovestin (estriol) also promote thiaminase and whether it matters whether it is topical or oral. Any ideas? I’m deficient in both thiamine and estrogen. Not sure how to get both working properly 😉

    1. As far as I know, estrogen and estriol have nothing to do with thiaminases 1 and 2. Both are enzymes that occur in some bacteria that are found commonly in human intestine, fish guts and some plants. Both attack the methylene bridge between the pyrydinium and thiazolium rings of thiamin. Perhaps surprisingly, these enzymes can also reverse the reaction and synthesize thiamin from the independently occurring rings, although the equilibrium of the reaction depends on the pH of the environment and is favored towards breakage rather than synthesis. We do not have any research on whether thiamin synthesis is a viable reaction in the human intestine.

  5. Dr. Lonsdale,
    My daughter had multiple emotional and physical problems post gardasil vaccine. I am quite desperate to speak with you regarding your research. I have an appointment with an integrative doctor and would like to get my thoughts organized so that we can come up with an appropriate treatment plan. If you are able to contact me by email, I would appreciate your help.

  6. The simple answer is that we do not know. On the other hand, we can speculate. Thiamin is the essential factor in the conversion of glucose to cellular energy. The drug acts as a stress factor, initiating energy requiring cellular defense mechanisms, turning a minor deficiency into a more major one. Now that we know that thiamin has a place in fatty acid metabolism, the downstream effects would be enormous, including the construction of cell membranes.

  7. Thank you for the excellent article, Dr. Lonsdale! Can you tell me how pharmaceuticals like Gardasil and/or fluoroquinolones deplete thiamine from cells? I suspect that the magnesium depletion caused by fluoroquinolones is due to lipid and membrane disturbances induced by the FQs. Do you think thatthiamine depletion comes about from membrane and lipid disturbances? Thank you!

    1. Both promote thiaminase although via different mechanisms. Thiaminase is an enzyme that blocks/disables thiamine. Oral contraceptives also promote thiaminase.

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