thiamine Archives - Page 3 of 12

Health Shattered By Poor Diet and Conventional Medicine

Published on August 8, 2023

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My health has declined over the last few decades, to the point that I am totally disabled and haven’t driven in 10 years. I have severe POTS with high blood pressure while sitting and laying down. Previously, it was low. I am not able to stand up as my heart rate goes too high and I feel as though I’ll pass out. I have coat hanger pain, jaw tension, and headaches daily. I am very irritable and impatient. Emotional outbursts crying spells, depression. I feel like I am a completely different person. I am in survival mode. My body cannot shift out of sympathetic dominance. All of this has developed over the last 20 years; a progressive decline until everything hit the fan.

I thought I had a relatively healthy childhood and into my early 20s. I did have mono in 7th grade. Looking back though, I ate poorly growing up and did a lot of crazy starvation diets. I also consumed a lot of alcohol in my later teens through my early 20s. I stopped drinking in 1994. However in 2006, I started drinking on and off again and the night I had the severe vertigo attack, I had been drinking. Since then I haven’t touched alcohol.

My mom passed away when I was 22 and I had my first child at 23, which was a C-section. At 26, I developed rosacea. This was really my first health problem. At 27, I was divorced (1993). I remarried a year later and had another child at 30 years old. Three months later, I had my gallbladder removed. With all of this, I was still active and healthy with only rosacea that would come and go, but it would get really bad on occasions and was very distressing. This was until 2007, when life stressors, poor diet and illness caught up with me.

Unending Vertigo and the Protracted Decline of Health

I started working again in 2000 after we relocated to Arizona. I was a preschool teacher, a wife, and was raising my two sons. I had a very full schedule. I was always a high achiever. In 2004, I opened my own school with another teacher. Things got even more stressful. In January 2007, I had a very emotional falling out with my father and a couple weeks after that I was diagnosed with viral pharyngitis. Within a couple weeks of this diagnosis, I was thrown out of bed with the worst vertigo you can ever imagine. This went on for three days and I was unable to walk for over two weeks. As things were improving, the dizziness never did go away. I sought out multiple practitioners, including neurologists and audiologists, but none were able to help.

I went back to work but I was never the same, having to deal with constant dizziness and feeling of being off-balance. In October of 2007, I wound up in the ER with a resting heart rate of 160. This had come on out of nowhere over the day and by the evening I was very frightened. They gave me lorazepam and sent me on my way. I continued with the constant dizziness and then the anxiety and panic attacks started. My GP gave me a script for benzodiazepine and offered an anti-depressant. I tried the antidepressant and I had a bad reaction. I felt completely numb. I couldn’t laugh smile or have any sort of reaction. That was after just try half a tablet. I never tried that again.

In 2009, I had an ankle injury and was wearing a boot for most of that year. In October, of that year I ended up having a surgery on it. What was interesting is that I was not experiencing much of the dizziness for most of that year. It wasn’t until a couple months later when I had a sudden onset of the dizziness during my physical therapy session. So the dizziness had come back and the anxiety and panic attacks were getting worse. In September 2010, I basically collapsed at work. It was about four or five days later at home, I experienced a severe shift of my energy. I was severely fatigued and now was experiencing POTS.

Is it Lyme? Maybe. Maybe Not.

November 2010, I was diagnosed with Lyme, however, my test was not conclusive. The Lyme literate doctor said my immune system was so weak that it was hard to get a positive result. He diagnosed me clinically. This set me off on a seven year journey of protocols that included benzodiazepines, two IV chest ports, supplements, herbs, homeopathics, bio-hormones, coffee enemas, detoxification therapies, chelation, IV and oral antibiotics, Flagyl, anti-fungal drugs, and every diet imaginable. You name it I did it. We had spent our life savings and I was still disabled and incredibly ill.

I became addicted to the benzodiazepines that he prescribed. He never told me about how addictive they were. I was on them for three years and they made me so much worse! I tried to come off of them several times. They turned me into a 3 year old. I was so fearful I couldn’t leave my bedroom even to cross the hall into bathroom. Finally, in 2014 I was able to kick the addiction. It took me six months of liquid titration.

As If Things Weren’t Bad Enough: Cancer Too.

Also in 2014, I had a huge fibroid and had a procedure called UFE ( uterine fibroid embolization ) to cut off blood supply so it would shrink. I know now I had severe estrogen dominance.

In 2017, I hit menopause and stopped menstruating. I was using sublingual progesterone at the time. The doctor also had me on hydrocortisone for adrenals and a time-release thyroid supplement. These supplements never helped and only made me worse. I was in such bad shape. I wasn’t sleeping for 3 to 4 days at a time and then when I would sleep it was only couple hours. This sleep regime went on all year.

In May of that year, I woke up one morning and left breast had shrunk significantly overnight!! The doctor I was seeing, had me come in. He physically examined me and felt that it was not anything to worry about. He said that I needed to detoxify my breast because it was probably blocked lymph. He told me to do skin brushing on it. I was in such bad shape that I wanted to believe him but I was so frightened. In October, I saw a different doctor and she said I had to get a biopsy. It was cancer. I did not see an oncologist. I did not have any lymph nodes removed or chemo radiation. I just had a surgeon remove it. I left the rest up to God. At this point, I could not endure anything else mentally or physically. The pathology report indicated the cancer was 98% estrogen driven.

A Dysautonomia Specialist Prescribed More Antibiotics

In 2018, I tried one more doctor. He was an autonomic dysfunction doctor and his protocol was quite simple. It was focused on lowering inflammation in the brain and body and balancing gut bacteria. At this point, I had suffered from chronic constipation for at least 10 years, on top of POTS and all of the other health issues. I was put on fish oil, olive oil, Rifaxamin and Flagyl for the possible SIBO and a vagus nerve stimulator. He told me not to use any other supplements of any kind. He claimed that most all supplements were fraudulent and using them would interfere with progress. I could not finish the Flagyl. I was feeling severely agitated and I thought it was due to the drug. I took most of it though. He assured me that the Rifaxamin was very safe and that they actually have renamed this antibiotic as a eubiotic. I did see my rosacea clear up. I had read some research and trials were they used Rifaxamin for rosacea and had a very positive outcome. So over the last 2 1/2 years I’ve been faithful on this protocol. It seemed like I had periods of time where I was able to stand up longer and do more around my house but I always relapsed. I was using the Rifaxamin on and off as per his direction for 10 days at a time. This year he put me on it indefinitely to use daily. I’ve been on it now for 8 months straight, but in July I started to go downhill very fast. I was having a decent spell able and had been able walk around for a a bit, do some limited chores and even able to be out in the pool, but one night my heart just went crazy and began to race. The vertigo came back too. I have been bedridden again since.

Discovering Thiamine Deficiency

After going back to doing some research, I came upon Dr. Lonsdale and Dr. Marrs’ book Thiamine Deficiency Disease, Dysautonomia, and High Calorie Malnutrition. I am thinking thiamine deficiency could be a piece of my puzzle. After reading one of Dr. Lonsdale’s articles on high B12 correlating with thiamine deficiency, I remembered two of my B12 tests. One in 2014, where it was 2000 and one in 2017 was 1600. The max upper range is 946.

Although my ill health was progressive at first, over time, everything has just become unbearable. I have been bedridden now for 10 years. The POTS symptoms are severe and I think I have the hyperadrenergic POTS. My blood pressure is very high when both sitting and laying and when I stand up, both my blood pressure and heart rate climb. I feel as though I’ll pass out. As I mentioned previously, I also have coat hanger pain, jaw tension, and headaches daily. I am very irritable and impatient. Emotional outbursts crying spells, depression. I feel like I am a completely different person. I am in survival mode. My body cannot shift out of sympathetic dominance. I am hoping to get some direction and advice on using thiamine to possibly help my condition.

Supplements, Medications, and Diet

Upon learning about thiamine and mitochondria, I stopped taking the Rifaxamin about two weeks ago. Below is a list of supplements I currently take and some information about my diet.

Magnesium hydroxide, Magnesium glycinate, 100mg, magnesium citrate, 100mg and some magnesium oxide in an electrolyte drink, in some variation for the past 3 years
3000mg daily (6caps) DHA 500 by Now Foods for past 3 years
Liver capsules 4 daily past 3 months
Camu Camu powder, a natural Vitamin C, 100-300 mg just started about two weeks ago
Rice bran 1 tsp before bed started two weeks ago
Bee pollen 1/2 tsp daily, started 3 months ago
I follow gluten free diet. I eat beef, chicken, raw liver, raw dairy, raw kefir, cheese, bone broth, some fruit, oatmeal and some vegetables like tomatoes, green beans, onions.

Since learning about thiamine, I have begun using Thiamax but am having a rough time of it. I took my first half dose (50mg) of Thiamax on December 26, 2020 and continued that dose through December 31st. It seemed to increase my fatigue more than my normal, which is already pretty debilitating so I switched to 50mg thiamine HCL on January 1st. By January 3^rd, I had a big crash. Hoping to minimize these reactions, on January 4th I took 25 mg thiamine HCL with 12 mg Thiamax in two divided doses. The next evening, however, I rolled over at 2 AM and my heart rate went crazy. I was shaking and went into a panic attack. It took hours to settle down. I haven’t had anything like this in quite a few years and I can’t imagine this would be from the tiny doses of thiamine I’ve been taking. I also took 600mcg of biotin that night at around 6pm. This was for a longstanding fungal infection. The biotin may have contributed to my reaction, but I do not know. I skipped the thiamine and biotin the next day and was able to sleep. I have resumed the thiamine once again and so far, I am tolerating it. I understand that people with chronic health conditions have difficulty adjusting to thiamine and I am trying my best make it through to the other side, but these reactions are difficult to manage. Any input from others who have been through this would be appreciated. I desperately want to recover my health.

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This story was published originally on January 11, 2021.

Bactrim: An Anti-Folate, Anti-Thiamine, Potassium Altering Drug

by Chandler Marrs, PhD

Published on August 7, 2023

21591 views

A few weeks back we published a case story of young man who developed serious cardiac and neurological symptoms after beginning a course of two antibiotics, Bactrim and Keflex. His symptoms immediately reminded me of beriberi induced by an acute thiamine deficiency. After some digging, I found that at least one of the antibiotics, Bactrim, likely does indeed induce thiamine deficiency by potently blocking both thiamine transporters. This had been only recently and accidently discovered and is clearly not common knowledge. What is common knowledge, however, is that Bactrim is also an anti-folate. This was by design, as blocking bacterial folate metabolism makes for a potent antibacterial, which also just so happens, makes it a viable chemotherapeutic. While it is impossible to rule out the Keflex in his sudden illnesses, as this drug too carries potentially serious side effects, or the combination of the two drugs, I would like to focus on Bactrim for this post, and specifically, its anti-folate and anti-thiamine properties. I believe these aspects of the drug may underlie many its adverse reactions in addition to, and perhaps compounding, those associated with its propensity to induce hyperkalemia.

A Medical Workhorse with a History of Adverse Events

Bactrim, a combination of two antibiotics, trimethoprim and sulfamethoxazole, was first approved in 1968 and 1973 in Canada and the US, respectively and has become a mainstay in pharmaceutical medicine. It is prescribed for everything from acne and UTIs to prophylactic treatments associated with HIV. On average, there have been between 6-7 million prescriptions of this drug written annually from 2007-2017, except for in 2015, where almost 12 million prescriptions were written.

It is one of those antibiotics, that because it has been around for so long, is considered safe and benign. In reality, however, there are a number of serious side effects associated with it including:

Aseptic meningitis – inflammation of the meninges (outer layer of the brain) absent bacterial involvement.
Hemolytic anemia – the destruction of red blood cells more quickly than they can be made particularly in folks with glucose-6-phosphate dehydrogenase (G6PD) deficiency. One study of hospitalized patients found 6 per 100,000 prescriptions resulted in hemolytic anemia.
Methemoglobinemia – decreased blood oxygen saturation via increase methemoglobin.
Delirium, gait disturbances and other CNS symptoms – owing to the ease in which it crosses the blood brain barrier. In one study of elderly patients, cerebral spinal fluid concentrations were ~50% of that in serum.
Stephens – Johnson Syndrome and toxic epidermal necrosis – a potentially life-threatening reaction where the lining of the skin and mucous membranes blisters and necrolyses.
Acute respiratory distress syndrome (ARDS), requiring mechanical ventilation, sometimes leading to organ transplant, often with poor outcomes, including death. This is particularly troubling, as it has been identified in children.
Renal disorders including: hyperkalemia and hyponatremia, and an acute interstitial nephritis, but also, hypertension and cardiac events, sometimes fatal. In immunocompromised patients, the rate of hyperkalemia with Bactrim hovers around 20%. Case studies suggest Bactrim induced hyperkalemia in non-immunocompromised patients as well, though its incidence is neither studied nor reported. In patients who also use spironolactone, a potassium sparing diuretic known for inducing hyperkalemia that is widely prescribed for hypertension, heart failure and for acne, but also as birth control (drospirenone is a spironolactone analog used in the oral contraceptive brands such as Yas, Yasmin and others), the risk of sudden death doubles. Although, the spironolactone + Bactrim > sudden death relationship is studied typically only in the elderly, both drugs are increasingly common in adolescents and young women and may account for a good percentage of the adverse events in these populations that are considered idiopathic. Similarly, the popular angiotensin enzyme inhibitors (ACE) and angiotensin II receptor blockers (ARB) used for hypertension, when combined with Bactrim carry 7-fold increased risk of potentially deadly interactions involving hyperkalemia.

A review published in 2011, identified 925 papers on the adverse effects of trimethoprim and sulfamethoxazole through 2011. Considering that the vast number of medication adverse reactions are rarely identified much less published, almost 1000 papers published suggests something is going on with this medication. While most of the adverse effects of this drug are attributed to its induction of hyperkalemia – high potassium levels via its blockage of the sodium channels in the kidneys, I think that is only part of the story. Another component, as I mentioned previously, involves its ability to block critical nutrients; first as an anti-folate, per its original design, and next quite incidentally, at least as far the published research is concerned, as a thiamine transporter antagonist. The blockade of the metabolism and uptake of these two critical nutrients is key to understanding the spectrum of adverse events associated with it, particularly those not directly induced by the sodium channel blockade that causes hyperkalemia. Although I would argue, deficiencies in these two nutrients would exacerbate Bactrim’s effects on sodium-potassium balance.

Bactrim Blocks Bacterial Folate Metabolism

Folate, or vitamin B9 is essential for DNA synthesis and repair. As such, it is critically important during reproduction for all organisms from bacteria to human. Folate deficiency during pregnancy is associated with serious neurodevelopment aberrations including neural tube defects like spina bifida and thus Bactrim should be strongly contraindicated for pregnant women, but at least one small study found that 3.2% of the pregnant women sampled were prescribed Bactrim.

Folate deficiency at any point across the lifespan may be equally problematic, though less frequently observed, as it provokes an array of symptoms that may attributable to any number of factors. Nevertheless, folate deficiency is linked to immune system dysfunction, dermatological issues, cardiovascular dysregulation, and neurologic problems, including sensory neuropathies with axonal damage. This is addition to a spectrum of neuropsychiatric manifestations from depression to dementia that are associated with this critical nutrient. Importantly, folate and folate products are linked to almost every other metabolic pathway through shared ATP, NAD, and NADP pools inasmuch as they both contribute to the production of NADPH and ATP, and are directly affected by the ratios of these molecules. Folate and vitamin B12 share a particularly close relationship, where deficiency in one, creates a functional deficiency in the other via alterations in methionine pathway leading to megaloblastic anemia. All told, folate is integral for healthy cell function and proliferation, mitochondrial respiration and epigenetic regulation.

Each of the two drugs that make up Bactrim block microbial folate synthesis precipitating complete folate deprivation in bacteria, capable of resulting in folate deficiency non-bacterial cells.

The trimethoprim component of Bactrim binds to a critical enzyme in the metabolism of folate, called dihydrofolate reductase (DFT). This inhibits the reduction of folate into cofactors necessary for DNA synthesis. By binding DHT, dihydrofolic acid (DHF) and then tetrahydrofolic acid (THF) are blocked. THF is essential in one carbon metabolism and the transfer of methyl, methylene, and formyl groups from one molecule to another during the production of nucleotides and amino acids e.g. DNA synthesis and repair.

Sulfamethoxazole also blocks folate metabolism, albeit at a different junction. It is a structural analog of the vitamin-like compound para-aminobenzoic acid (PABA) found in several foods and involved in the metabolism of folic acid. In bacteria, it is a required growth factor. As a structural analog to PABA, sulfamethoxazole binds to and blocks a key enzyme in the folate pathway (dihydropteroate synthetase) thereby inhibiting the conversion of PABA and downstream metabolites critical for folate synthesis and metabolism.

Neither trimethoprim nor sulfamethoxazole alone kill bacteria. They simply prevent bacterial replication. Taken together, however, the combination yields potent bactericidal effects. Bactericidal antibiotics, as a class of drugs and irrespective of specific mechanisms of action, fundamentally and sometimes irrevocably, damage mitochondria.

…it has been demonstrated that major classes of bactericidal antibiotics, irrespective of their drug-target interactions, induce a common oxidative damage cellular death pathway in bacteria, leading to the production of lethal reactive oxygen species (ROS) (4–12) via disruption of the tricarboxylic acid (TCA) cycle and electron transport chain
The overall importance of these observations relates to an expanded mechanism of action, whereby bactericidal antibiotics promote complex redox alterations that contribute to cellular damage and death, while also underlining a common evolutionary and developmental linkage between primordial bacteria and mitochondria (56,57).

Damaged mitochondria, in turn, imperil human health and no doubt, contribute to the vast array of post-antibiotic health issues that have become increasingly common and associated with a number of antibiotics.

Bactrim Blocks Thiamine Uptake

In addition to blocking folate metabolism, the trimethoprim component of Bactrim also blocks thiamine uptake. This was only recently discovered by accident. As part of a study on a cancer drug called Fedratinib, which is known to induce a severe form of thiamine deficiency called Wernicke’s encephalopathy, researchers tested the thiamine blocking capabilities of several drugs that were structurally analogous to Fedratinib. Trimethoprim was among the drugs tested and found to potently block both thiamine transporters. Absent the ability to transport thiamine from diet into the cells, deficiency ensues.

Like folate, thiamine or vitamin B1, is an essential cofactor for key enzymes involved in one carbon metabolism and energy production in all living cells. Thiamine acts as a catalyst and cofactor to all of the enzymatic reactions that participate in oxidative metabolism yielding ATP (see figure 1) and is absolutely critical for glucose metabolism. It also occurs twice in the pentose phosphate pathway (PPP), the alternative glucose oxidation pathway that provides nicotinamide adenine dinucleotide phosphate (NADPH) and ribose 5-phosphate (R5P) for glutathione, nucleic acid, and fatty acid synthesis and steroid hydroxylation, respectively, making thiamine necessary for not only ATP production, but required for duplication and detoxification processes. It is also involved at the alpha oxidation phase of fatty acids, at the HACL1 enzyme and is critical for the metabolism of the branched chain amino acids, leucine, isoleucine, and valine.

mitochondrial nutrients — Figure 1. Mitochondrial Nutrients from: Thiamine Deficiency Disease, Dysautonomia and High Calorie Malnutrition

Importantly, thiamine sits atop these processes, as a gatekeeper of sorts. Its absence or insufficiency thus, derails downstream functions associated the conversion of food into ATP in each of the substrate pathways, glucose, protein, and fats, creating a biological energy deficiency that imperils human health. Insofar as thiamine is only stored in the body for about 18 days, it must be consumed regularly to avoid insufficiency and outright deficiency. Insufficient consumption and/or ingestion of pharmaceutical compounds that block intestinal thiamine transporters responsible for bringing thiamine into the cells, pose a serious health risk that includes death. Mitochondrial ATP is requisite for cell functioning globally, as such decrements to ATP affect every organ and tissue in the body, but are most damaging where a consistent supply of ATP is requisite for survival – in the heart and the brain. That is why, the most serious conditions associated with thiamine deficiency are wet and dry beriberi and Wernicke’s encephalopathy, the condition for which Fedratinib contains a black box warning. More commonly, thiamine insufficiency is associated with a litany of dysautonomic syndromes, although it is not widely recognized as such.

The case story that compelled my investigation into Bactrim included clear symptoms of both wet and dry beriberi, marked by serious dysautonomic function. The bradycardia, chaotic heart rhythm and blood pressure changes were the most acutely dangerous for this individual, particularly if this was accompanied by disrupted sodium and potassium balance, as we can suspect was the case. Had he been older and/or carried additional comorbidities, he might not have survived. He did survive, however, but remains chronically symptomatic of thiamine deficiency 6 years later.

The question one must ask is how presumably healthy individuals develop thiamine insufficiency upon the usage of drugs like Bactrim. That is, how are Bactrim and other thiamine depleting drugs capable of provoking such a rapid decline into fulminant deficiency? Thiamine is, after all, in most enriched and fortified foods. A similar question, how then, even after cessation of the drug do these individuals develop unremitting health issues indicative of longstanding thiamine deficiency?

Absent outright thiamine starvation, most folks consume sufficient thiamine from food to avoid the more acute thiamine deficiencies, but not enough to prevent the more gradual and often chronic thiamine insufficiency syndromes that mark modern medicine and certainly not enough to offset the direct blockage of thiamine transporters from pharmaceuticals like Bactrim, the mitochondrial damage initiated by modern medications (here, here, here, here, and more), environmental chemical exposures and industrial food based toxicants to which we are all exposed. If one’s diet is high in sugars, supplemented with coffee or tea, and/or if alcohol is consumed regularly, the path to thiamine deficiency is expedited.

From this perspective, it is not inconceivable that a significant portion of the population is thiamine insufficient, if not outright deficient. Across different research projects, estimates suggest from 30-70% may have insufficient thiamine intake to meet the demands of daily living and given the corresponding rise in chronic health issues of metabolic e.g. mitochondrial origins, it is not surprising that many are just one medication away from full blown deficiency. To the extent that thiamine is connected to the synthesis of downstream metabolites like folate synthesis, it is not unexpected either, that a background insufficiency in both nutrients would be exacerbated and potentially become deadly with the addition of Bactrim to the mix. Moreover, absent nutrient repletion post antibiotic usage, it is entirely likely that the mitochondrial ill-effects imposed by this drug would become longstanding.

Of Bacteria and Men: A False Dichotomy

Although trimethoprim’s thiamine blocking capability was not known until 2017, had anyone bothered to look at the structure of the compound relative to that of thiamine, it would have been obvious. As far as I can tell, in the 50 years this drug has been on the market, its conformational similitude to thiamine was not considered. Nevertheless, it was well known that Bactrim blocked folate, that folate was critical to human health, and that its deficiency could wreak havoc on health. Why was its actions on folate metabolism not considered problematic? The answer to that question has to do in part to shoddy research and in part to an economically self-serving framework for understanding human physiology that has since become institutionalized into medical dogma. In other words, it was easier and more economically prudent not to question potential problems in the research or the assumptions driving said research than risk losing a useful and lucrative antibiotic.

When trimethoprim was originally discovered and yet still, medicine believed that bacteria were somehow entirely separate from the organism in which they resided. The otherness of potential drug targets holds true to this day.

Although trimethoprim inhibits dihydrofolate reductase in bacteria, it is estimated that an approximately 50,000 times increased concentration of the drug is required to inhibit the human form of this enzyme.”

This notion appears to be based upon a study in 1965, where uptake of the drug and subsequent DHT enzyme binding activity in lab grown bacteria (escherichia coli, staphylococcus aureus, proteus vulgaris), in other animal tissue, and in pulverized human liver cells post autopsy from one individual, were compared. The bacteria won. When trimethoprim was present, folate to DFT was not reduced, even when extra folic acid was added to the media. Remember, in order to get to usable folate – THF, we need the DFT enzyme to work. So, based upon the blockage of the DFT>THF pathway in bacteria, trimethoprim was deemed ‘strongly antibacterial’. Furthermore, it was deemed safe by its apparent inability to block folate in ‘human cells’. It should be noted that the stability of the enzymes from the animal and the human liver cells varied significantly from 25-60%, calling into question the very results upon which this medication was eventually developed and approved. No matter, a potential antibiotic was born and no one was the wiser.

The fallacies upon which trimethoprim safety was based were that bacteria are completely separate from the humans in and on which they reside, that they are solely responsible for illness, and that pharmaceuticals designed to attack said bacteria would affect only their intended targets. None of which are true. While it is true that some of the enzymes within the metabolic pathways in bacteria are different from those in other cells, they still share a degree of similarity, some 30% sequence homology, suggesting enzymes in these cells will also be affected, though perhaps not as strongly as those in the bacterial populations.

More importantly, however, and this speaks to the fallacy of separateness that medicine holds dear, at any given time, we carry with 3–6 pounds of commensal bacteria that are responsible for a myriad of functions, including “protective responses that prevent colonization and invasion by pathogens,” the inhibition of “growth of respiratory pathogens by producing antimicrobial products/signals and competing for nutrients and adhesion sites” and importantly, for our purposes, the synthesis and metabolism of vitamins to be used by the host; the very pathways blocked by these antibiotics.

Several intestinal bacteria in the colon, but also in the small intestine, are capable of biosynthesis of natural forms of folate as well as vitamin B12 and other B-vitamins (Camilo et al. 1996; Magnusdottir et al. 2015; Rossi et al. 2011). It has been shown that specific transporters in the colon actively absorb folate (Said 2013) and as such contribute to folate levels in peripheral tissues and the circulation (Aufreiter et al. 2009; Lakoff et al. 2014; Pompei et al. 2007b). These findings indicate that intestinal bacteria contribute to folate metabolism and that colonic contents represent a substantial and natural source of folate.

We are neither separate from our bacterial communities nor are our vitamin synthesis pathways sufficiently distinct from bacteria that we can target a pathway in one without affecting the other. We carry vast microbial ecosystems whose functions are critical to human survival; vitamin synthesis among them. Indeed, bacterial folate synthesis genes are ubiquitous across the gastrointestinal tract, 13% of which, contain all of the required for complete de novo folate synthesis and almost 40% have the genetic capacity to synthesize folates in the presence of PABA, the upstream intermediate blocked by the sulfamethoxazole component of Bactrim. Importantly, bacterial synthesis of folate and other B vitamins, represents a critical pathway not only for nutrient availability of the human host, but for managing the vast microbial ecosystems in a manner favorable to host survival. Disruption of these ecosystems involving nutrient depletion results in pathogenesis both of the infectious and oncogenic varieties.

Given the large number of gut bacteria in comparison to eukaryotic cells, which also contain evolutionary derived mitochondria (mitochondria are believed to originate from bacteria and as such share similar enzymes and metabolic pathways with them), it would seem that the blockade of these critical nutrient pathways while effectively antibacterial, may also, induce unintended harm. Materially,

…the summated populations of ‘simple’ organisms may in fact regulate the ultimate fate of our genetic material. In sum, it has become compellingly apparent that eukaryotic cells and complex organ systems cannot survive without the synergistic complex interactions of competent enteric bacteria and evolutionarily fashioned mitochondria…

but “go ahead and just cover him with some Bactrim. How can it hurt?”

Postscript

Bactrim is also sold under the names: Septra, Sulfatrim, Septrin, Apo-Sulfatrim, SMZ-TMP and cotrimoxazole.

Although I did not spend any time covering Keflex, the second drug prescribed to this individual, I would like to note that it too damages mitochondria, albeit by different mechanisms. Briefly, Keflex can cause a deficiency in leucine, an amino acid that regulates something called the mTOR receptor, which, when blocked or, in this case, absent its cognate ligand, would downregulate mTOR and deregulate mitochondrial function. The mTOR pathway regulates the balance between protein anabolism and catabolism critical for cell growth and division. Its down-regulation shifts towards catabolism resulting in muscle wasting.

If you experienced a negative reaction to Bactrim and would like to share your story, contact us.

We Need Your Help

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.

Yes, I would like to support Hormones Matter.

Photo by Haley Lawrence on Unsplash.

This article was published originally on October 20, 2020.

Is TTFD Toxic?

by Elliot Overton, DipCNM CFMP

Published on July 31, 2023

13358 views

I regularly receive correspondence from people asking whether thiamine tetrahydrofurfuryl disulfide (abbreviated TTFD), a thiamine (vitamin B1) derivative, is toxic or not. Most people following this line of inquiry base the assumptions of “toxicity” on statements previously made by the famous (and now deceased) Andrew Cutler, PhD. Cutler is most well-known for his work on mercury chelation and detoxification protocols and has amassed thousands of followers over the years. He was strongly opposed to the application of TTFD therapeutically and explicitly advised people against using this molecule as a nutritional supplement for thiamine repletion or heavy metal detoxification. Much of what he said on this topic was documented in the archives of the Onibasu website which can be found here. Cutler’s statements were speculative in nature, based on anecdotes, and to my knowledge, were never backed by any scientific evidence. In this article, I would like to address his claim that TTFD is toxic. I should note, based upon all of the available research, which is substantial, TTFD is not toxic, even at supra-physiological dosages. A version of this article was published on my website.

Is TTFD Toxic?

To understand whether TTFD or any compound may be considered toxic, it is important to recognize how toxicity is determined in pharmacology. Here toxicity is represented by something called a therapeutic index (TI). In animals, where much of the research is conducted initially, the TI is determined between by ratio of the lethal dose 50 (LD50), a dose at which 50% of the animals die, and the effective dose 50 (ED50), the dose at which a therapeutic response is noticed in 50% of the animals. This is represented as TI = LD50/ED50. In humans, instead of lethal dose, toxic dose is used (TD50). Here, the TD50 represents negative or adverse reactions in 50% of the population tested. The equation is basically the same, TI = TD50/ED50.

In both cases, higher therapeutic dosing windows relative to efficacy confers greater drug safety. Compounds where there is little wiggle room between the TD50 and LD50 – a small TI – are considered the most toxic. See Figure 1.

Therapeutic Index — Figure 1. Therapeutic index.

By way of example, alcohol/ethanol has a TI of 10, whereas LSD and cannabis have TI’s of greater than 1000. This means that one has to consume far less alcohol to achieve toxicity and lethality than either LSD or cannabis. Indeed, it is virtually impossible to overdose (OD) with LSD or marijuana compared to the ease at which one can OD on alcohol. Figure 2.

Lethal doses for common drugs — Figure 2. Lethal dose of common drugs.

Similarly, the TI for many common drugs is quite low. Figure 3. from a pharmacology lecture on SlideShare, shows the TI of common medications.

Figure 3. Therapeutic index of medications.

What Does Any of This Mean for TTFD?

In mice studies, the LD50 for TTFD has been calculated at 450mg/kg when given intravenously (IV) while the LD50 for an oral dose is 2200mg/kg. Since the conversion from mice to human dosage is not calculated directly based upon on weight, but accounts for interspecies differences in metabolism, an equivalent LD50 for a 70 kg (154 lb) human would be 2.5 grams of TTFD when administered via IV and 12.5 grams if taken orally. Whilst 2.5 (IV)-12.5 (oral) grams may seem low, no one realistically takes that amount of TTFD per day for therapeutic reasons. The highest oral doses I have observed are around ~1-2 grams per day. These are individuals with chronic thiamine deficiency, usually accompanied by underlying genetic issues. More commonly, observation and clinical research suggest between 100-300 mg/day is used for most treatment/research protocols (see the ‘What about Research in Humans’ section below).

Back to the math, the RDA for thiamine, not TTFD, but thiamine consumed from food naturally, from food fortification and/or via supplementation using the most common formulations of thiamine mononitrate or hydrochloride (HCL) is 1.1 and 1.2 mg per day for adult females and males respectively. Assuming that the RDA values represent an effective dose (there are no actual data on the ED50 for thiamine), and for simplicity, that TTFD is as effective as the other two formulations, when we calculate the TI for humans (TI= ED50/TD50) for humans, we get a huge range between effective dose and toxic or lethal dose. For IV administered TTFD the ratio would be ~2,500:1, while oral dosing, it would be ~12,500: 1. If we assume, based upon its bioactivity that TTFD is more potent than the other two formulations, the TI would increase even more.

Based just upon standard toxicology parameters, it is clear that TTFD is not toxic. An individual would have to take ~12,000 times the effective dose to approximate lethality. I say approximate, because there are no documented cases of TTFD overdose. Lethality, however, is just one component of toxicology. Adverse reactions are an important consideration. That is why, in human research, instead of LD50, TD50 is used. Here though, the work becomes a little murky, partly because animals are used and partly because the chemistry of TTFD metabolism is complicated.

Toxicity Studies Using High Dose TTFD

Consistently, the animal data show that excessive doses for extended periods of time, even during pregnancy and across multiple generations, TTFD is not toxic.

Research performed on the reproductive effects of TTFD in monkeys showed that massive doses of 500mg/kg, close to supposed LD50 for that species, found no deaths. To put this in context, it would be the human equivalent of taking 10-11 grams per day for MONTHS.
That same study also looked at massive doses in rabbits and found no significant increase in incidence of fetal malformations in either group was observed, even in groups treated with high doses and no significant teratogenic effects or developmental abnormalities in pregnancy occurred.
As referenced in this document, Takeda’s research by Mizutani demonstrated that administration of 100, 300 and 500mg/kg in rats for two generations from the time of maturation to the time of reproduction showed no abnormalities. The average human equivalent (70Kg) of these doses would be 570mg, 1.7 grams and 2.8 grams per day for life.
The results of another study showed that long-term oral administration of 30-300mg/kg to pregnant animals failed to produce any significant developmental abnormality. Intraperitoneal administration of 1000mg/kg also showed no sign of chromosome aberration, damage to sex organs or spermatogenesis.

TTFD Metabolism

If TTFD is not toxic via the traditional measures, is there something about the molecule itself that may be problematic and cause unwanted effects? Cutler speculated that the mercaptan part of TTFD was responsible for toxicity, and that this primarily affected the liver. The word “mercaptan” refers to the thiol group that breaks away from thiamine after its absorption into the cell. This mercaptan group essentially accounts for the “TFD” of the abbreviation TTFD. After TTFD is absorbed, it gets “broken apart” (the disulfide bond is chemically reduced) by glutathione, cysteine, or hemoglobin to release the free thiamine molecule, which will become trapped inside the cell and ultimately used by the body.

mercaptan metabolism — Figure 4. Mercaptan metabolism phase 1.

In more technical terms, the prosthetic mercaptan is released and then rapidly metabolized by the liver through methylation and later sulfoxidation by liver mono-oxygenase enzymes into breakdown products which are then excreted in urine. Is mercaptan toxic as Cutler suggested? The original series of studies on the enzymatic breakdown of TTFD and mercaptan show that it is not toxic and is rapidly excreted from urine.

If mercaptan itself is not toxic, perhaps it metabolizes into something else and one of its by-products are problematic. From Figure 5., we see that mercaptan is metabolized into a sulfate that is then eliminated via urinary excretion and a few other compounds that are processed by the liver first before being eliminated via urinary excretion as well. The breakdown products are shown below in Figure 5.

TTFD - mercaptan metabolism — Figure 5. TTFD – Mercaptan metabolism.

A study titled “Pharmacological study of S-alkyl side chain metabolites of thiamine alkyl disulfides” sought to determine the acute and sub-acute toxicity levels of each metabolite. They concluded that toxicity of these breakdown products was low. Remember the LD50, the dose that causes death in 50% of the study animals, research shows that the LD50 each of these breakdown products is enormous, far more than would be clinical relevant in humans. The results of this study showed:

Inorganic sulfate: non-toxic
Delta-methylsulfonyl-gamma-valerolactone: also non-toxic.
- Intravenously, the LD50 in mice was in excess of 5 grams/kg body weight. For comparison, the LD50 estimate for a 70KG human: 5 grams intravenously.
- Orally the LD50 in mice was 6 grams/kg body weight, which, for a 70 kg human would translate to approximately.
4-Hydroxy-5-(methylsulfonyl) valeric acid
- Intravenous LD50 in mice: 1.5 grams/kg body weight
- LD50 estimate for a 70KG human: 3 grams intravenously

Once again, it appears that none of these compounds is toxic. In humans, approximately 82-90% of these metabolites are excreted within 24hrs and 100% are excreted within 48hrs. What this tells us is that by themselves, these metabolites are not toxic except in supra-physiologic doses, which are not relevant from a clinical perspective.

What About Liver Damage?

Cutler speculated that metabolism of TTFD resulted in liver damage. To quote Cutler:

My guess is the tetrahydrofurfuryl mercaptan part kills your liver.

Here too, however, the data suggest otherwise. In animals with artificially induced liver damage by carbon tetrachloride and/or hepatic dysfunction due to choline deficiency, the breakdown products of TTFD were assessed. They showed that the quantity of excreted metabolites in the hepatotoxic group were equal to the control, and in choline deficiency the quantity of excreted metabolites was only slightly reduced. In the hepatotoxic group, a qualitative difference was found with a lower proportion of methyl metabolites (MTHFSO, MTHFS02). This suggests, even in with pre-existing or induced hepatotoxicity, TTFD can be excreted albeit slightly differently.

A peer-reviewed study published in 2018 entitled “The Effects of Thiamine Tetrahydrofurfuryl Disulfide on Physiological Adaption and Exercise Performance Improvement” studied the effects of different doses of TTFD in 30 animals for a period of 6 weeks. The highest oral dose used was 500mg/kg in 10 test subjects, which is the human equivalent to 40mg/kg which, in a 70KG human, is 2.8 GRAMS per day for 6 weeks. Remarkably, they showed that this highest dose produced significant improvement in endurance capacity and lactate homeostasis.

More importantly, this study also performed comprehensive measures of sub-acute toxicity with the aim of evaluating the safety of high doses in humans. Even at the highest dose taken for 6 whole weeks, no changes in behavior, diet, growth curve, or organ weight (liver, kidney, muscle, heart, lung etc.) was observed. Furthermore, to assess liver function, they performed comprehensive metabolic analysis including liver enzymes (ALT, AST), creatine, uric acid, total cholesterol, triglycerides, albumin, total protein, ammonia, creatine kinase, and total protein. The only significant changes were a slight reduction in total cholesterol and significant reduction in lactate, creatine kinase and blood urea nitrogen (all of which are considered positive changes). Every other liver marker was perfectly in range. To gain further insight into the liver function and the health of other tissues, they performed histopathological analysis of the tissue under microscope and showed that massive doses caused no pathological changes in any tissue whatsoever. The authors conclude:

In the current study, we proposed that the higher thiamine derivative, TTFD, could significantly improve physical activities and physiological adaption with evidence-based safety validation. For practical application, we recommend that athletes should consume a daily intake of 40 mg/kg TTFD (equivalently converted from mouse 500 mg/kg dose based on body surface area between mice and humans by formula from the US Food and Drug Administration [36]) to improve energy regulation for higher performance in a combined nutritional strategy, including carbohydrate loading for efficient energy demand during extended exercise.

They were so convinced of the supplement’s safety that they recommended athletes take the equivalent of 2.8 GRAMS per day LONG-TERM to improve athletic performance.

What About Research in Humans?

To those who complain that these are “animal studies”, the comparative metabolic studies have found that the metabolism of TTFD is essentially the same in animals and humans. This means that humans are likely to respond similarly. As one of the first medical doctors to use TTFD as a clinical intervention in the Western world, Dr. Derrick Lonsdale obtained a special license from the FDA to import this molecule and studied its effects in his pediatric patients. In his own words:

I was able to study the value of this incredible substance in literally hundreds, if not thousands of patients. Far from being toxic, as this person claims, I never saw a single item that suggested toxicity.

Some reports published by Lonsdale and other authors include:

22 children with Down’s Syndrome, 12 of which were administered TTFD for 12 months and 12 of which were administered TTFD for 6 months. No serious adverse events noted.
Brainstem dysfunction – three infants saw symptomatic improvement with thiamine disulfide treatment.
Abnormal brainstem auditory evoked potentials, one infant was administered intravenous TTFD and displayed normalization of brainstem function
21 patients subacute necrotizing encephalomyelopathy treated with thiamine derivatives TPD/TTFD 10 Children – no serious adverse events – 1 experienced worsening of behavior/symptoms, 2 with rash
44 polyneuropathy patients treated with 50mg TTFD injection, no adverse effects reported.
Prosultiamine (TPD) at 300mg per day for 12 weeks (TPD, a very similar molecule to TTFD) used to treat spinal cord injury in human T lymphotropic virus type I-associated myelopathy/tropical spastic paraparesis (2013). Significant improvement in motor functions and bladder control, as well as reducing viral numbers in blood. Only adverse symptom was mild epigastric discomfort. No safety concerns.

For a comprehensive look at thiamine research, refer to Drs. Lonsdale and Marrs’ book: Thiamine Deficiency Disease, Dysautonomia and High Calorie Malnutrition

TTFD Used in Other Countries

It is worth noting that TTFD is not well known in Western medicine. The regions of the world in which it is used extensively include Japan, China, and other countries in the Far East.

Japanese Cases

Unfortunately, much of the Japanese literature is not published in English, so it can be difficult to find. I use a translator application called DeepL to read these articles. Furthermore, TTFD is so regularly prescribed for treating thiamine deficiency that much of the literature refers to TTFD simply as “thiamine” or “vitamin B1”, using the terms interchangeably. This means that finding research papers without TTFD in the actual title is very difficult. Below are 33 case reports from the Japanese literature, including some in children, which document the benefits of TTFD clinically. In all of the papers I have read, I have not once seen mention of safety concerns using this. In several reports, hundreds of milligrams are maintained indefinitely with no apparent issues.

267 cases of sudden-onset deafness was treated with 150mg TTFD orally, with most therapeutic effect seen after 2-3 months of treatment
20 cases of perceptive deafness, 20 cases of laryngeal disease, 7 cases of facial nerve palsy and 3 cases of anosmia injected with TTFD 50mg once per day for 5-20 days. 60% effective and no side effects.
24 subjects without nutritional deficiency, 20 cases of alcoholism, and 48 cases of alcoholism with signs of deficiency and/or liver disease were given either TTFD, Thiamine propyldisulfide (a similar disulfide derivative), or thiamine HCL. They showed no toxic effects at 3-6 months in any group, and demonstrated that oral TTFD/TPD increased whole blood, erythrocyte, and cerebrospinal fluid thiamine levels at an equivalent level to intravenous thiamine HCL.
Beriberi treated with 150mg IV one week, followed by 100mg oral long-term (2014)
Cardiac failure 100mg IV (1987)
Heart and circulatory failure (2008)
TTFD administered to 15 year old boy to treat beriberi, remained on the therapy long-term
18 patients with non-diabetic peripheral neuropathy 1-3 months, no serious side effects
Wernicke encephalopathy in hemodialysis – 100mg/iv, later oral continued for 2 months until improvement (2009)
Diabetic lactic acidosis – 100mg/day IV for 7 days resolution in symptoms, followed by 75mg indefinitely (2008)
Beriberi w/ pulmonary hypotension – 50mg long-term (2019)
E/beriberi after intestinal resection – 150mg IV three days, 75mg long-term (2018):
E/Shoshin beriberi – 150mg/IV, 75mg oral long-term (2013)
A case of Wernicke’s encephalopathy with severe cardiac sympathetic dysfunction – 100mg (2012)
Marked anasarca with impaired consciousness, which was thought to be caused by shoshin beriberi due to impaired vitamin B1 utilization. – TTFD 40mg +400mg HCL, followed by 2 months+ TTFD 100mg (2015)
Beriberi neuropathy and shoshin beriberi that developed 6 years after gastrectomy on the cardia side – 100mg TTFD long term (2013)
Chemotherapy induced W.E – IV thiamine HCL followed by TTFD 75mg long-term (2008)
Postoperative W.E treated with 100mg IV TTFD (1998)
Cardiomyopathy associated with mitochondrial disease that developed heart failure, treated with 100mg long-term (2017)
Mitochondria rescue formula recommended for acute encephalopathy: including TTFD 100mg (2019)
Pediatric acute encephalopathy neuroprotection protocol – cocktail including 200mg TTFD in 15 children (2013)
200mg TTFD x 31 children childhood acute encephalopathy (part of protocol) (2014)
Lactic acidosis caused by low-dose metformin: Thiamine HCL 100mg followed by 75mg TTFD long-term, normalization of all liver values (2014)
Beriberi mimicking Guillain-Barré syndrome – IV TTFD 100mg resolved this
Shoshin beriberi – IV TTFD 150mg for 11 days, indefinite oral dose 150mg TTFD long-term
6 infants (0-1 yrs old) treated with TTFD for childhood congenital lactic acidosis. Doses included 35mg/KG – 50mg/KG. Some cases were unresponsive to thiamine HCL, where TTFD ONLY could reduce lactate significantly “Fursulthiamine hydrochloride was significantly superior to thiamine hydrochloride in reducing lactate.” Only the cases which used TTFD survived. Children were kept on high doses permanently with no adverse effects.
75mg TTFD improved cerebral blood flow in deficiency
75mg TTFD used in mitochondrial myopathy long-term
50mg TTFD used to treat edema and weight gain and marginal thiamine deficiency – authors recommend TTFD instead of thiamine HCL (2021)
Biguanide-induced lactic acidosis treated with 100mg, then 300mg TTFD (2017)
100mg used to treat encephalopathy w/ hyperammonemia (2003)
Subacute spinal degeneration caused by B12 deficiency treated with B12 and 75mg TTFD long-term (2020)
Statement by a Japanese physician: recommendation to use TTFD instead of thiamine HCL due to superior qualities.

Chinese Cases

Like the Japanese research, most (if not all) of the Chinese studies using TTFD are not published in English. However, it is clear that the Chinese medical system uses TTFD frequently and has done so for several decades. Most of the studies below were reported within the last 20-30 years. Once again, I could not find any concern regarding the safety of this molecule and it was demonstrated as remarkably effective for a variety of conditions. Interestingly, the Chinese not only use it for deficiency, but also for non-deficient conditions where it is often injected directly into acupoints (acupuncture meridians) either alone, or in combination with other nutrients/medications. They still use these methods to this day. Here are 32 more articles regarding the safety and efficacy of TTFD from the Chinese literature.

194 cases of infantile beriberi cured with IM/IV thiamine and TTFD (1987)
50 infants treated with TTFD for cardiac beriberi (1997)
70 children with infantile beriberi cured with intravenous TTFD (1990)
48 cases of infantile cerebral beriberi (0-3 years old) treated with TTFD (1997)
35 cases of infantile beriberi cured TTFD (2010)
10 cases of infantile cerebral beriberi cured with B1 HCL and TTFD
10 cases of cerebral beriberi and basal ganglia damage treated with TTFD injections (2003)
125 children with pneumonia treated using TTFD as primary treatment (10mg IM <3 months old, 20mg IM <6 months, 20mg twice per day >6 months old)
283 out of 285 children with rectal prolapse cured by TTFD injection into “changqiang” acupoint (1988)
89 cases of rectal prolapse also treated with TTFD acupoint injection (1998)
50 cases of cerebral hypoplasia improved with acupoint injection of acetyl glutamine and TTFD (1983)
35 patients treated for hyperthyroidism with TTFD as adjunctive treatment (1999)
50 cases of costochondritis cured with Analgin + TTFD injection (1993)
13 children with ocular nerve palsy cured with TTFD (2010)
50 cases of urinary incontinence treated with acupoint injection of combination of acetyl glutamine, TTFD and/or r-aminobutyric acid (1990)
26 cases of delayed peripheral neuropathy due to organophosphate poisoning treated with acupuncture and TTFD injection (2001)
47 cases of lumbar disc protrusion treated with acupoint injection, B12 and TTFD (1994)
38 cases of facial neuritis treated with acupuncture and vitamins including TTFD injection (1999)
60 cases of migraine treated with Chinese medicine, flunarizine, and TTFD (2004)
24 cases of migraine treated with TTFD acupoint injection (1990)
40 patients with cerebrovascular disease addressed using acetyl glutamine and TTFD scalp acupoint injections (2001)
30 cases diabetic neuropathy, 75mg TTFD used as a control in– 60% effective (2002)
69 cases of Bell’s Palsy, TTFD used with acyclovir (1999)
120 cases of Bell’s Palsy treated with oral TTFD, methylb12, and/or electroacupuncture and facial muscle exercise (2019)
65 cases of Meniere’s Diseases treated with TCM, vitamins including TTFD injections
118 cases of herpes zoster treated with TTFD in conjunction with acyclovir and traditional Chinese medicine (2013).
100 cases of senile deafness treated with cocktail including TTFD (2000)
36 cases of cervical spondylotic radiculopathy treated with control of TTFD and naproxen – 75% effective (2009)
60 cases of postherpetic neuralgia treated with cocktail including TTFD
1 case of polerarteritis nodosa w/peripheral neuritis treated with cocktail including TTFD
1 case of central paralytic dysphagia (tuberculosis meningitis) unresponsive to conventional treatment cured by injection of TTFD at meridian acupoint (1974)
1 case of drug-induced diplopia treated with methyl B12 and TTFD

TTFD Is Not Toxic

At this point, it should be clear that TTFD is not toxic at either therapeutic or even supraphyisiological doses. This is supported by in vitro, animal, and human studies. One would have to use ~12,000 times the therapeutic dose to approximate toxicity and even then it is not clear that there would be the problems that Cutler suggested. That is not to say that everyone who takes this supplement responds favorably. Clinically, there are individuals for whom other formulations of thiamine work better. This is generally related to a lack of the necessary nutrient cofactors involved with the detox enzyme glutathione. I have written about that previously here. That perceived intolerance, however, is not the same as toxicity. The toxicity data are clear. TTFD is safe. The clinical data are also clear. TTFD is effective. The molecule has been in use for over half a century and is used extensively in medical practice in Eastern countries. No safety concerns or claims of toxicity have been raised, apart from those made by Cutler.

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This articles was published originally in February 2022.

Thiamine Deficiency, Fatigue, and Erectile Dysfunction

by Kash

Published on July 27, 2023

3998 views

Thiamine deficiency and erectile dysfunction

Hello, I am a 33 year old male who has been experiencing a vast range of symptoms over four years including progressively worsening fatigue, brain fog, muscle weakness, body pain and erectile dysfunction. Only a few months ago, I discovered that there could be a relevance of thiamine in all of my issues. All of my health problems worsened at the age of 29 years old. More context can be found below.

Childhood Problems

I had problems with:

Concentration and focus
Emotionally down
Prone to common cold (infection)
- Unfortunately I was put on antibiotics more often every few months as a kid (amoxicillin)
Brain fog
- My brain is slow at processing things, there is always a latency associated with me to perceive things.

Health Journey

My health journey is complex. In the sections below I have tried my best to capture the sequence of events and diagnostic data we have so far. I began developing fatigue, not feeling refreshed even after sleep in my early 20’s but I continued pushing myself – not knowing how to address this. Irrespective of these limitations, I was an active adult – I was working out regularly, lean and athletic. My food habits were clean i.e., no processed foods, no alcohol, but majority of my calories were from carbs. My macro mix was approximately 50% carbs, 25% fat, 25% protein. Being a South Asian, white rice is part of my staple diet.

Things started to go really bad around 29 years of age when my fatigue, brain fog, muscle weakness, body pain worsened and nocturnal erections started to degrade. I was not able to obtain erection without Viagra. I started my health journey to fix my erectile issues. Because of my appearance (lean and athletic) all the doctors refused to even work with me, saying the issues were psychological. I found an alternative doctor who ordered blood work and we found few biomarkers that were off.

Very low Vitamin-D3 – 12.8
Low Platelets – 60,000 – 80,000 x10E3/uL
Subclinical Hypothyroidism (Elevated TSH – 9.5 uIU/mL and Reverse T3 – 33.8 ng/dl)
Testosterone was low for my age but not below reference range – 525 ng/dl

Unfortunately, this is the first time I had a comprehensive health checkup, so I don’t have any previous data to compare against. Since I was in the Pacific Northwest area where there is not much sun, I was living with low D3 for years. I worked with a hematologist to ensure low platelets were not as a result of any major illness. I started addressing my thyroid using levothyroxine and low vitamin-D3 with a vitamin-D3 supplement.

Subclinical Hypothyroid and Low D3

We developed a plan to address vitamin-D3 deficiency via supplements and also thyroid via levothyroxine. We started with 50 mcg of levothyroxine, which improved some of my symptoms slightly. The fatigue, brain fog and erectile issues improved somewhat. Unfortunately this was short lived and after ~4-6 weeks, my health started deteriorating again. Since I saw initial progress with thyroid, the doctors assumed my health issues were related to thyroid and started treating me with different thyroid formulations, different forms etc., to improve thyroid function.

After looking at my thyroid labs, doctors always mention that my thyroid hormones – FreeT3, FreeT4 were good but my reverseT3 and TSH were always elevated.

Neuropathy and Disc Herniation

In the end of 2020, I began developing burning pain in my lower back, which eventually started flowing to both my feet. MRI confirmed that disc herniation in my L5-S1 layer impacted S1 nerve root. I also took EMG that confirmed there is mild impact on S1 nerve root. The burning pain coincided with worsening erectile dysfunction. I was no longer responding to Viagra and I was in immense burning pain. After a few months of intense pain, the pain has begun to recede, but I am still experiencing a constant burning sensation, except when I sleep.

Disc herniation or burning pain was not as a result of any incident. It seemed to develop gradually, like everything else. A straight leg test or no movement worsened it immediately. One neurologist had an alternate theory that burning pain was not coming from disc herniation but because my D3 was low for a long time my microbiome was affected. Since gut bacteria synthesize B vitamins, she suspected that I was deficient. Her theory was I was deficient in vitamin-B5, which was resulting in burning pain and sleep issues. It is also possible that burning pain is caused by thiamine deficiency. I talk about this in the thiamine supplementation section below.

Neurological Issues

During this time period when I developed burning pain, I was also struggling with temperature regulation issues. When I moved from outside ~90f to inside ~70f, I would get chills. I was feeling cold most of the time, cold hands and feet, and sweating profusely. I used to get pins and needles randomly when out in the sun or while walking.

Gastrointestinal Issues

When I developed burning pain, I also started experiencing bad constipation. I was not able to empty my bowel at all. I had to take herbal laxatives every day for my bowel movement. I have also been experiencing bloating, seeing undigested foods in stool, chronic bad breath – potentially from SIBO. In the last three years, I have lost more than 20 pounds. I look more lean and weak at this point.

Sleep Issues

It has been years since I woke up feeling refreshed. I rarely dream. I have noticed that I am able to easily fall asleep and stay asleep most of the time but my sleep quality is bad, especially the later half of the sleep where REM sleep occurs.

Erectile Dysfunction

I have no nocturnal erections at this point and have not had any over the last several years. I still rely on Viagra and am now taking more than 100 mg, which is the max dosage of Viagra. On some days I don’t respond to Viagra as well. All other obvious issues associated with erectile dysfunction were ruled out including hypertension, heart issues, and hormonal issues. Essentially, I am a ‘healthy’ individual suffering from erectile dysfunction. With all of the other issues, am I really healthy? I don’t think so, but the doctors do.

Toxins and Micronutrient Deficiencies

One of the theories of a doctor who evaluated me was that I was exposed to some toxins. Testing revealed that I had high levels of ochratoxin A, a mycotoxin, which is usually from aspergillus but may be impacted by glyphosate exposures. Based on my blood and urine markers, they confirmed that my detox pathways were impaired and in need of more B-vitamins. I also did a Spectracell testing, which looks at the vitamins and minerals in the cell level, and it did show a deficiency in vitamin-B5, and borderline deficiencies in few other vitamins, which supplementing with a multi-vitamin didn’t appear help.

Thiamine (Benfotiamine) Supplementation

I began supplementing with Life Extension – 250mg of Benfotiamine and many things happened.

My sleep quality improved and I felt slightly refreshed the next morning.
I started getting partial nocturnal erections.
I started responding to the same dosage of Viagra much better than before taking Benfotiamine.
Better energy and mood.
Burning pain in my feet reduced greatly.

The problem, from second day onwards my sleep quality fell apart. I was easily able to fall asleep but was not able to sleep for more than ~5-6 hours and my REM + Deep sleep was less than 90 minutes.

I increased electrolytes

Potassium
- Add 1 litre of coconut water
- Added 1 teaspoon of cream of tartar
Magnesium
- Increased from 250 mg to 375 mg – I am taking Magnesium Malate

This improved my sleep quality slightly, but I still struggled. I couldn’t sustain taking Benfotiamine at the same dosage for a long time. So I had to stop.

Current State

Supplements I take currently:

Vitamin B12 – 1000 mcg
Vitamin D3 – 10,000 IU
Magnesium Malate – 375 mg
Creatine (~3 grams)
Athletic Greens (Multi Vitamins)

I am still suffering with all the issues mentioned above and struggling to incorporate thiamine. How should I proceed here?

Should I try small dosages of TTFD and proceed from there? What cofactors to incorporate?
Should I work with doctors and take thiamine injections or incorporate IV?
Should I try Myer’s IV – which contains below formula once a week for few weeks to see if I can experience any improvement to validate this theory
- 5 mL of magnesium chloride hexahydrate (20%)
- 3 mL of calcium gluconate (10%)
- 1 mL of hydroxocobalamin (1,000 μ/mL)
- 1 mL of pyridoxine hydrochloride (100 mg/mL)
- 1 mL of dexpanthenol (250 mg/mL)
- 5 mL of vitamin C (500 mg/mL)
- 20 mL of sterile water
- 1 mL of B-complex 100 containing:
  - 100 mg of thiamine HCl
  - 2 mg of riboflavin
  - 2 mg of pyridoxine HCl
  - 2 mg of panthenol
  - 100 mg of niacinamide
  - 2% benzyl alcohol

I have been very determined to get myself out of these conditions. Any help or guidance here will be much appreciated?

We Need Your Help

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, and like it, please help support it. Contribute now.

Yes, I would like to support Hormones Matter.

Mitochondria Need Nutrients

by Chandler Marrs, PhD

Published on July 20, 2023

17107 views

One of the more common questions I get asked is which nutrients do the mitochondria need to function well? This is really two questions. The first involves which nutrients are involved in the enzymatic processes that allow the mitochondria to convert food to ATP and to manage all of the other tasks that they are responsible for like inflammation, immune function, and steroidogenesis. The second question applies specifically to the individual. It is a question of what he/she needs to be healthy. The answers to both are entirely different. While it is true that there are a set of nutrient co-factors involved in the mitochondrial machinery and these are necessary for mitochondrial function for everyone, which ones and how much of each an individual may need to support his or her health varies significantly. Moreover, although there are baseline minimum nutrient requirements that tell us where insufficiency diseases are likely to develop, what determines an individual’s health or disease is entirely dependent upon genetics, exposures, diet and lifestyle, and even day to day stress. Here, there is no one-size-fits all prescription for nutrient replacement and supplementation or even diet and exercise. This frustrates folks to no end and I think it is one of the reasons both patients and physicians are so reticent to look toward nutrient supplementation seriously as a therapeutic option.

Both the current model of medicine, and to a large degree, the way we approach nutritional therapies, relies very heavily on the silver bullet approach to health. If we’re honest with ourselves, so too do we. It is so much simpler to believe that if we just take X drug or vitamin in Y dose, all of our health issues will disappear and they will disappear at set rate that is linear and predictable. Unfortunately, this is not how the body works. While there is an internal chemistry that requires certain nutrients to function appropriately, that chemistry varies ever so slightly by genetics and is endlessly modified by life itself. There is no one-size-fit-all. There are no magic supplements. There is just your chemistry and your needs.

Since I have written repeatedly on the mitochondria and the reasons why nutrients are required for health, this post will not tackle those topics. Articles on those topics can be found on Hormones Matter with any number of search terms. This information can also be found in the book, Thiamine Deficiency Disease, Dysautonomia, and High Calorie Malnutrition, that I co-authored with Dr. Lonsdale. Here, since many have requested it, I just would like to present a graphic illustrating mitochondrial nutrient requirements. This is from Chapter 3 of our book. Use this as template to understanding your health.

Figure 1. Nutrient requirements for healthy mitochondria.

mitochondrial nutrients A few things should be pointed out. First, while these nutrients are required by everyone for proper mitochondrial functioning, not everyone needs to supplement with each one, or even sometimes any of them, although that is becoming increasingly rare with modern dietary patterns. Secondly, notice how many times and where vitamin B1 (thiamine) appears in this chart. It is at the entry points of the entire system and at various junctures throughout. This suggests that among all of the nutrients required for healthy mitochondria, thiamine is particularly important. Unfortunately, it is the one nutrient that is so often ignored or missed in testing. Indeed, that is why we wrote the book. Thirdly, notice how many vitamins are required to process the food we eat into ATP. Contrary to popular opinion, we need more than simply empty calories. For the foods we eat to be converted into ATP, there are multitude of vitamins and minerals required that may or may not be included in sufficient density with the macronutrients we consume daily. Finally, not discussed in this chart, but discussed in great detail in the book, synthetic chemicals, whether in form of pharmaceuticals, industrial, environmental, or food production, damage the mitochondria. Some deplete nutrients directly, while others damage aspects of mitochondrial functioning that necessitate increased nutrient density for the enzyme machinery to work. Of course, underlying all of this, are the genetic variables that each of us brings to the table. These influence how well or poorly we metabolize any of these nutrients from the get-go. All of this combines to make nutrient therapies complicated.

What is not complicated, however, is that we need nutrients to function and so, no matter what else we do to improve health, if we do not address nutrient concentrations, we can never be well. Mitochondrial functioning demands nutrients, and thus, health demands the same. Nutrient deficiencies are not something we can override with a pharmaceutical. That being said, addressing nutrient deficiencies holds great promise for those seeking health. If you or someone you love experiences chronic and complicated illnesses that have been treatment refractory, consider healing the mitochondria by tackling nutrient deficiencies. You might be surprised at well this works.

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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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This article was originally published on November 11, 2019.

SIBO, IBS, and Constipation: Unrecognized Thiamine Deficiency?

by Elliot Overton, DipCNM CFMP

Published on July 12, 2023

112442 views

In many of my clients, chronic upper constipation and gastroesophageal reflux disease (GERD) are misdiagnosed as bacterial overgrowth. Unfortunately, they are often non-responsive to antimicrobial treatments. Yet, sometimes the issues are fixed within a few days of vitamin B1 repletion. This has shown me that often times, the small intestinal bacterial overgrowth (SIBO) is simply a symptom of an underlying vitamin B1 or thiamine deficiency.

GI Motility and Thiamine

The gastrointestinal (GI) tract is one of the main systems affected by a deficiency of thiamine. Clinically, a severe deficiency in this nutrient can produce a condition called “Gastrointestinal Beriberi”, which in my experience is massively underdiagnosed and often mistaken for SIBO or irritable bowel syndrome with constipation (IBS-C). The symptoms may include GERD, gastroparesis, slow or paralysed GI motility, inability to digest foods, extreme abdominal pain, bloating and gas. People with this condition often experience negligible benefits from gut-focused protocols, probiotics or antimicrobial treatments. They also have a reliance on betaine HCL, digestive enzymes, and prokinetics or laxatives.

To understand how thiamine impacts gut function we have to understand the GI tract. The GI tract possesses its own individual enteric nervous system (ENS), often referred to as the second brain. Although the ENS can perform its job somewhat autonomously, inputs from both the sympathetic and parasympathetic branches of the autonomic nervous system serve to modulate gastrointestinal functions. The upper digestive organs are mainly innervated by the vagus nerve, which exerts a stimulatory effect on digestive secretions, motility, and other functions. Vagal innervation is necessary for dampening inflammatory responses in the gut and maintaining gut barrier integrity.

The lower regions of the brain responsible for coordinating the autonomic nervous system are particularly vulnerable to a deficiency of thiamine. Consequently, the metabolic derangement in these brain regions caused by deficiency produces dysfunctional autonomic outputs and misfiring, which goes on to exert detrimental effects on every bodily system – including the gastrointestinal organs.

However, the severe gut dysfunction in this context is not only caused by faulty central mechanisms in the brain, but also by tissue specific changes which occur when cells lack thiamine. The primary neurotransmitter utilized by the vagus nerve is acetylcholine. Enteric neurons also use acetylcholine to initiate peristaltic contractions necessary for proper gut motility. Thiamine is necessary for the synthesis of acetylcholine and low levels produce an acetylcholine deficit, which leads to reduced vagal tone and impaired motility in the stomach and small intestine.

In the stomach, thiamine deficiency inhibits the release of hydrochloric acid from gastric cells and leads to hypochlorydria (low stomach acid). The rate of gastric motility and emptying also grinds down to a halt, producing delayed emptying, upper GI bloating, GERD/reflux and nausea. This also reduces one’s ability to digest proteins. Due to its low pH, gastric acid is also a potent antimicrobial agent against acid-sensitive microorganisms. Hypochlorydria is considered a key risk factor for the development of bacterial overgrowth.

The pancreas is one of the richest stores of thiamine in the human body, and the metabolic derangement induced by thiamine deficiency causes a major decrease in digestive enzyme secretion. This is one of the reasons why those affected often see undigested food in stools. Another reason likely due to a lack of brush border enzymes located on the intestinal wall, which are responsible for further breaking down food pre-absorption. These enzymes include sucrase, lactase, maltase, leucine aminopeptidase and alkaline phosphatase. Thiamine deficiency was shown to reduce the activity of each of these enzymes by 42-66%.

Understand that intestinal alkaline phosphatase enzymes are responsible for cleaving phosphate from the active forms of vitamins found in foods, which is a necessary step in absorption. Without these enzymes, certain forms of vitamins including B6 (PLP), B2 (R5P), and B1 (TPP) CANNOT be absorbed and will remain in the gut. Another component of the intestinal brush border are microvilli proteins, also necessary for nutrient absorption, were reduced by 20% in the same study. Gallbladder dyskinesia, a motility disorder of the gallbladder which reduces the rate of bile flow, has also been found in thiamine deficiency.

Malnutrition Induced Malnutrition

Together, these factors no doubt contribute to the phenomena of “malnutrition induced malnutrition”, a term coined by researchers to describe how thiamine deficiency can lead to all other nutrient deficiencies across the board. In other words, a chronic thiamine deficiency can indirectly produce an inability to digest and absorb foods, and therefore produce a deficiency in most of the other vitamins and minerals. In fact, this is indeed something I see frequently. And sadly, as thiamine is notoriously difficult to identify through ordinary testing methods, it is mostly missed by doctors and nutritionists. To summarize, B1 is necessary in the gut for:

Stomach acid secretion and gastric emptying
Pancreatic digestive enzyme secretion
Intestinal brush border enzymes
Intestinal contractions and motility
Vagal nerve function

Based on the above, is it any wonder why thiamine repletion can radically transform digestion? I have seen many cases where thiamine restores gut motility. Individuals who have been diagnosed with SIBO and/or IBS and are unable to pass a bowel movement for weeks at a time, begin having regular bowel movements and no longer require digestive aids after addressing their thiamine deficiency. In fact, the ability of thiamine to address these issues has been known for a long time in Japan.

TTFD and Gut Motility

While there are many formulations of thiamine for supplementation, the form of thiamine shown to be superior in several studies is called thiamine tetrahydrofurfuryl disulfide or TTFD for short. One study investigated the effect of TTFD on the jejunal loop of non-anesthetized and anesthetized dogs. They showed that intravenous administration induced a slight increase in tone and a “remarkable increase” in the amplitude of rhythmic contractions for twenty minutes. Furthermore, TTFD applied topically inside lumen of the intestine also elicited excitation.

Another study performed on isolated guinea pig intestines provided similar results, where the authors concluded that the action of TTFD was specifically through acting on the enteric neurons rather than smooth muscle cells. Along with TTFD, other derivatives have also been shown to influence gut motility. One study in rats showed an increase in intestinal contractions for all forms of thiamine including thiamine hydrochloride (thiamine HCL), S-Benzoyl thiamine disulphide (BTDS -a formulation that is somewhat similar to benfotiamine), TTFD, and thiamine diphosphate (TPD). A separate study in white rats also found most thiamine derivatives to be effective within minutes.

Most interestingly, in another study, this time using mice, the effects of thiamine derivatives on artificially induced constipation by atropine and papaverine was analyzed. The researchers tested whether several thiamine derivatives could counteract the constipation including thiamine pyrophosphate (TPP), in addition to the HCL, TTFD and BTDS forms. Of all the forms of thiamine tested, TTFD was the ONLY one which could increase gut motility. Furthermore, they ALSO showed that TTFD did not increase motility in the non-treatment group (non-poisoned with atropine). This indicated that TTFD did not increase motility indiscriminately, but only when motility was dysfunctional. Finally, severe constipation and gastroparesis identified in patients with post-gastrectomy thiamine deficiency, was alleviated within a few weeks after a treatment that included three days of IV TTFD at 100mg followed by a daily dose of 75mg oral TTFD. Other symptoms also improved, including lower limb polyneuropathy.

To learn more about how thiamine affects gut health:

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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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This article was first published on HM on June 1, 2020.

From Mother to Daughter: The Legacy of Undiagnosed Vitamin Deficiencies

by B. Figueroa

Published on July 10, 2023

14113 views

This is a story of a mother with undiagnosed vitamin B deficiencies who gave birth to a daughter who was also born with undiagnosed vitamin B deficiencies. In the eyes of conventional doctors and labs, there was not much wrong with us, but we knew that life was harder than it should be. We lived managing debilitating dizziness, daily migraines, fibromyalgia pain, chronic fatigue, allergies, hormonal changes, anxiety, and depression. Until we discovered that we were both hypermobile with histamine issues, hypoglycemic, and had many vitamin B deficiencies. The biggest challenge was for my daughter to start taking thiamine (vitamin B1). Her heart rate was all over the place and she had such a bad paradoxical reaction to thiamine that we believe she had been living with undiagnosed beriberi along with POTS.

Mom’s Health Marked by Asthma, Anxiety, Migraines, and a Difficult Pregnancy

All I remember as a child is being afraid to talk in school even if I knew the answer to a question. I had allergies and could not exercise due to asthma. During college, I had to read over and over the same thing because I could not concentrate. I worked extremely hard because the fear of failure was too much to bear. I started to have hormonal imbalances and missing periods. I successfully finished college and moved away to another state. That is when migraines started. Later, I became pregnant with my first child and started having blood clots. Anxiety and depression would come and go with hormonal changes.

When I was pregnant with my second child, my daughter, I was sick every morning with nausea. After 6 months of pregnancy, I had gained only 6 pounds. Ultrasounds showed that the baby was growing normally, but I was losing weight. At that point, I also could see blood clots on my leg. I was placed on bed rest. By the 8^th month, my water broke and my daughter was born. She was jaundiced and placed under UV light for a week. I also stayed in the hospital for a week dehydrated, with blood clots, and with the “baby blues”. We left the hospital after a week, and she had a “normal” development. However, you could see that she was a baby that would not go with anyone, not even the people close to us, indicating some anxiety.

Daughter’s Early Health Issues: Selective Mutism, Asthma, Concentration Issues

When my daughter turned four years old, we moved out of state and that is when she stopped talking outside the house. I later found out that it is called selective mutism, a form of severe social anxiety. She started seeing a school counselor to try to help with her anxiety and self-esteem issues. I brought a girl scout group to my house so that she could start having friends and talk to others in her area of comfort. She also developed asthma and needed nebulizer/albuterol treatments frequently and daily QVAR for prevention. She was given Singulair, but it made her very depressed. Her grades in all classes were all over, from A to D. She would spend the whole time after school trying to complete homework, but she couldn’t. Her teacher told me that she really did not have that much homework. I would ask her to watch the dog eating and to take her outside as soon as the dog finished but she would be wandering around the kitchen and could not pay attention to the dog. Her neurologist gave her Strattera and that helped a little. Her EGG also showed some abnormal activity. The doctor recommended anti-seizure medicine and said that she was probably having mal-petit seizures. I refused medication based on how she reacted to Singulair and because the doctors were using words like “probably” and “just in case”. I kept an eye on her and noticed when she ate ice cream and got asthma. I had her stop sugars and dairy. Soon after that, a teacher called me, excited to tell me that my daughter was talking at school. She also was able to stop all asthma medication except for 2 weeks every year when seasonal allergies would hit. At this point, it had been already four years since she stopped talking outside our house. She started excelling in all classes and we were able to stop Strattera. However, the continuous anxiety remained.

The Teenage Years: Continuous Migraine, More Medications, and No Answers

At 16 years old, she got a cold that turned into asthma with a continuous headache that just would not go away. She started waking up every day with a migraine, depressed with no energy. We had to wait three months to see a pediatric neurologist. Meanwhile, I would take her to my chiropractor early in the morning, give her an Excedrin, and she would go to school whenever she felt better. She began drinking at least 2 cups of coffee every day to help with the pain. Sometimes she would go to school at 11am, sometimes at 1pm. Even if there was just one class left, she would go to school. At this point, she felt that she wouldn’t have a future.

When we finally went to the neurologist, he recommended amitriptyline. I had been on amitriptyline and woke up one day not knowing which year or season was, but I was told that the issue was the high dose given to me (125mg), after decades of it increasing it every year. I agreed as long as it was a low dose. Amitriptyline lessened the continuous headache, but it was not really gone, and she still needed some Excedrin. She started daily aspirin as well. She was just getting by day to day trying to manage her pain and mood and trying to have a normal teenage life.

Increasing Weakness When Outdoors: Untangling Root Causes

She became very weak whenever we would go to the beach or to a park. We would have to drag her indoors and give her water. On some occasions, she would say that she could not see. Somehow, she successfully managed to graduate from high school. We started seeing functional doctors. We found that she had some variants related to mitochondria dysfunction, but we really didn’t know how to address this. We also found out that she had Hashimoto’s and antibodies against intrinsic factors, which was indicative of pernicious anemia. We knew right there, that she had issues that conventional doctors had missed.

We also did a Dutch test and found that all of her hormones were high. The functional doctors suggested sublingual B12, folinic acid, and a B complex. She said the vitamins made her feel awake for the first time. However, chronic fatigue was still a major struggle for her. Eventually, she had to stop folinic acid because it made her depressed and unmotivated. Meanwhile, she managed her anxiety with herbs, but it was a real struggle. She also continued to have asthma requiring albuterol every fall season. She chose a very challenging career in cell biology with biochemistry. She went through college with many cups of coffee just to control migraines, have energy, and be alert.

Discovering Her POTS Symptoms

The summer of 2019, before her senior year of college, the nurse checked her vitals as part of her new summer internship. The nurse thought the pulse monitor was broken because her heart rate was 120 sitting down. After a few minutes, it went down to 99, so the nurse dismissed it. When she told me that, I started paying attention to her heart rate. We went to her physician and neurologist and in both instances, her heart rate was 100, just sitting down waiting for the doctor. I asked if it was normal, and they said that it was in the upper range but not a concern. I was still concerned and made an appointment with a cardiologist but also bought her an iwatch. She noticed right away how her standing heart rate would be over 100, and by only taking a few steps, her heart rate would go even higher and she would become fatigued and even dizzy. From the heart rate monitor on her iwatch, we could see how quickly her heart rate would climb upon standing and then slow a bit when sitting.

That is when I remember that I have read about POTS and hypermobile people. I remember that when she was a child, the neurologist had said that she was hypermobile, but never said that it could be a problem for her. It just seemed like a fun thing to have. I started asking in health groups and someone mentioned that her medications could also cause high heart rate. I searched and amitriptyline did have that side effect. That is when my daughter showed me that her resting heart rate was in the 90s and it would fluctuate from 29 to 205 without exercising. When we went to the cardiologist and explained all of this, he said that he did not even know how to diagnose POTS because it is rare. He did testing and said that the heart was fine but there was some inefficiency due to some valve leaking but that it usually does not cause symptoms. I asked about amitriptyline and he confirmed that it could raise heart rate. At that point, she stopped amitriptyline and her maximum heart rate was 180 instead of 205.

She went back to her last year of college when Covid hit. She came back home and we could see the lack of energy and how much doing any little thing or stress would crash her for days. Since I needed glutathione for chemical sensitivities, I decided to see if it would help her. Glutathione with co-factors helped her recover, instead of crashing for days, she would recover the next day. That is when she told me that every time she walked to school, she felt that she would pass out. When she gets up in the morning, she ends up lying on the floor because of dizziness. Despite her dizziness, daily muscle pain, daily migraines, and chronic fatigue, she had big dreams. She just kept pushing through day by day, with coffee, herbs, and whatever it took, but she knew that something had to change. She successfully graduated in May, Magna Cum Laude, and she had a couple of months to deal with her health before she would leave to start her graduate studies and research job. That is when I found people that knew about Dr. Marrs’ work and thiamine, and her life finally changed.

Introducing Thiamine and Other Micronutrients: Navigating the Paradox

A functional doctor recommended magnesium and niacin for her migraines and they significantly helped. This gave the functional doctor the idea to try tocotrienols. High doses of tocotrienols worked better for reducing her migraine pain than amitriptyline and aspirin combined. Then she started taking high doses of B6. This helped her muscle pain and improved her mobility. Despite being hypermobile, easy stretches gave her intense muscle cramps prior to starting B6. Guided by very knowledgeable researchers belonging to Dr. Marrs’ Facebook group, Understanding Mitochondrial Nutrients, we started Allithiamine. The first thing she said was “wait, the sun does not hurt?”. I asked her what she meant. She explained that all her life, being in the sun gave her pain in her eyes and forehead and that she couldn’t understand why people wanted to be outside. No wonder she never wanted to go outside. She also said her migraines were gone. We have waited 4 years to hear that!

After just a couple of days, she started having a lot of nausea and lower-intensity migraines returned. The researchers knew right away that she needed more potassium. She started to eat apricots, coconut water, or orange juice every time she had nausea and it helped. However, it was happening every hour so we decided to try a different Thiamine. We tried half Lipothiamine and Benfotiamine but she didn’t feel as much benefit and still gave her issues. We went back to 1/10 of Allithiamine. Chatting with the researchers, one asked if she also experienced blinding episodes. Yes! Finally, someone that knew about that! They recommended B2 and we started it. That’s when we discovered that her pain in the sun and dizziness were caused by a B2 deficiency. She continued waking up with crashes needing potassium every hour. She did not sleep that week. The researchers suggested taking cofactors including the rest of the B vitamins, phosphate salts, phospholipids, and beef organs. Beef organs and phospholipids helped with energy and bloating, phosphate salts helped with nausea and irritability.

Then researchers suggested that she needed to stabilize sugars and have more meat. That is when we realized that she had some type of hypoglycemia. We had noticed that she would get very tired and got shaky hands if she didn’t eat. Functional doctors had mentioned that she may have reactive hypoglycemia since she had a fasting glucose of 70. She started having more meat to stabilize her sugars and removed all packaged foods, sugars, grains, and starches. She started having just fresh meat, veggies, rice, beans, nuts, and berries. She felt that she was so much better with beef that she started using it for potassium between meals and bedtime.

She was able to increase allithiamine little by little. She would mix a little bit with orange juice since it tasted so awful. Little by little, she started having fewer crashes and feeling better. It took a month for her to be able to tolerate one capsule of Allithiamine. She was sleeping more but not the whole night. That is when our functional doctor suggested supporting adrenals. That really helped but then she began having stomach pain and nausea after eating beef and developed frequent diarrhea. Chicken always increased her hunger and reduced her energy compared to beef and but now she was afraid of having beef. She stopped all sources of beef and phospholipids.

We consulted a very good functional doctor. She did Nutraeval and confirmed that all her B vitamins were low or deficient and recommended TUDCA and Calcium D Glucarate along with trying lamb and bison first. Both helped in reducing bloating/nausea and she was able to start eating lamb and bison along with reintroducing a minimal amount of carbs. Soon after, she was eating beef again with no pain. After starting TUDCA, her bilirubin levels were normal for the first time in her life. We continued to work with the functional doctor to fix other deficiencies.

Recovery from Multiple Nutrient Deficiencies and the Prospect of a Normal Life

After Allithiamine and vitamin B2, we worked with our functional doctor to balance the remaining B vitamins. She is now able to go out in the sun without bothering her eyes and without passing out. She gained weight after starting the B vitamins and began looking healthier, compared to how skinny and underdeveloped she looked before. She also learned how to manage electrolytes. She sometimes needs more sodium, but other times needs more potassium. She feels sick when electrolytes get out of balance. Although she still had some continuous pressure in her head, she no longer needs any amitriptyline, aspirin, or Excedrin for pain. One thing that remained problematic was folate deficiency. She still became depressed with folinic acid, so she tried methylfolate instead. She felt so unmotivated that preferred not to have it, but she realized that it was key to something that she struggled with all her life: anxiety. She figured that she could have methylfolate every other day, so that she could have less anxiety.

Now, for the first time, she began to have a normal life. She can now exercise daily without dizziness and her heart rate skyrocketing. Her heart rate in general is more normal, doesn’t go down to 29 or up to 205. She had not had any asthma requiring albuterol. She started driving without having to deal with anxiety and panic attacks. She was able to walk to her office without fainting. She now can now live alone dealing with the stress of having a full-time job, graduate classes, cooking her food, and exercise every day! She is not cured completely but for a person that once thought she couldn’t have a future, she is doing pretty darned good!

We Need Your Help

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, and like it, please help support it. Contribute now.

Yes, I would like to support Hormones Matter.

This article was published originally on July 22, 2021.

Health Requires Energy. Energy Requires Nutrients.

by Derrick Lonsdale MD, FACN, CNS

Published on June 27, 2023

11374 views

A Fundamental Issue

I was horrified to watch the “60 Minutes” program Sunday, April 12th, 2020 on television that dealt with the colossal number of Americans suffering from obesity, chronic fatigue and diabetes, both types I and II. About half of the program dealt with the essential consumption of natural food, reminding us that Hippocrates, 400 BCE said “let food be your medicine and let medicine be your food”. This must have been said thousands of times but everything in our modern civilization is totally destructive to the whole idea. I have seen so many hundreds, if not thousands, of people whose illness was caused by themselves. It was treatable by making sure that each individual understood the fundamental issue. So before I illustrate a typical illness situation within my experience, I will try to state what I mean by describing what I consider to be the “fundamental issue”.

“We behave according to what we eat”.

I have stated this so many times but unfortunately the American medical profession is the major inhibitor to its clinical success. When a suffering patient with many symptoms arising from what I call “dietary mayhem”, goes to his or her physician, they simply do not recognize the clinical expression of the popular high calorie malnutrition. The many symptoms are usually referred to as psychosomatic and the unfortunate patient is told that “it is all in your head”. I have witnessed this so many times; I cannot understand why the physicians don’t pay a little more attention to what the patient is trying to tell them. Often the patient has discovered the real cause of the problem but find that her words are considered to be the voice of ignorance and delusion.

Food and Energy

Our food consists of fuel that must be burned (oxidized) to liberate energy. In any text this element of the food is described as “calories”. The energy quality of our food intake is measured in kilocalories and a single one is defined as “the energy needed to raise the temperature of 1 kg of water through 1°C”. Notice the use of the word energy, the result of oxidation. Now, as everyone knows, vitamins and minerals, known as non-caloric nutrients, are vital to the release of energy from the caloric elements. To understand how this combination of chemicals works, there must be a ratio of calories to the noncaloric elements. That is why high calorie foods without vitamins or minerals are known as empty calories. It is the consumption of empty calories across America that has given rise to the idea of high calorie malnutrition. I have actually seen a written statement that this is an oxymoron. “How can excess of calories be considered a form of malnutrition?” It seems that few people understand this vital ratio and they seem to think that as long as you are consuming calories, you will flourish. Also, the food industry fills the grocery store with cartons of temptation and seems to have no regard for the well-being of its consumers. They keep using the term “all natural” so much, it becomes meaningless.

A Typical Case of Energy Deficiency

I was a pediatrician at Cleveland Clinic and one of my interests was sudden infant death (SIDS). So one day I was having lunch with one of the surgeons who practised ear nose and throat surgery. He told me that he had been called to the medical ICU because a woman had stopped breathing and he had performed a tracheostomy. He was intrigued by the reason for this disaster and, knowing my interest, he suggested that I should take a look. Pediatricians are assumed to be familiar with diseases of children but ignorant of adult disease and I knew that I was not welcome. I found a 50-year-old woman who was grossly edematous and unconscious. Without considering the technical details, I proved that she had the vitamin B1 deficiency disease beriberi. With injections of thiamine she became conscious and the edema disappeared. During her recovery she developed a progressive anemia, thought to be evidence of internal bleeding, but all the tests were negative. I took some urine from her and subjected it to a special type of test. It showed that she was deficient in folate, another B vitamin. It is important to note that she did not develop folate deficiency until she began her recovery from thiamine, it was masked by cellular energy deficiency. When she began to receive folate there was an immediate recovery from the anemia but she had been given at least one injection of thiamine by then.

She was discharged from hospital, wheelchair bound, taking both thiamine and folate. When she returned as an outpatient, I found that she had a skin rash and that her legs were, if anything, weaker. It had long been known that anemia would develop from either folate or B12 deficiency, but the folate deficient variety required B12 supplementation as well as folate. If B12 was not provided, the patient would develop paralysis of the legs and I had forgotten this. Also, it is not well-known that vitamin B12 deficiency can cause a skin rash. I gave her an injection of B12 and the rash disappeared. However, for a few days she had muscle aches and fever that I did not understand at that time. Looking back I would now assume that this was what we call “paradox” on Hormones Matter. To those that may not have read about this it is the temporary worsening effect by introducing an essential nutrient to someone who has long been deficient in that nutrient. One of the things that had probably been a serious indictment on self cause was that she was a chronic cigarette smoker, a well-known habit that damages oxidation.

Energy Metabolism

Can we extrapolate from this case any general ideas about how medical treatment should advance? Perhaps the general opinion would be that this is a rare and unusual case, an outlier from the “usual and customary diagnosis”. But if we consider the facts; long-term cigarette smoking, dietary indiscretion and genetic risks appear to be quite common. I treated a 12-year old girl with a conventional diagnosis of Juvenile Rheumatoid Arthritis, using a nutritional supplement. Without discussing the technicalities of laboratory evidence, it was clear that defective energy metabolism was the underlying cause. The combination of genetic risk, failure to adapt to any form of stress (infection, trauma, chronic useless brain activity etc) and inadequate energy metabolism are the three factors that either collectively or singly lead to breakdown of health. As Selye predicted, energy for adaptation is the essential ingredient.

We Need Your Help

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.

Yes, I would like to support Hormones Matter.

Image by Inns-Web from Pixabay.

This article was published originally on April 22, 2020.

thiamine - Page 3

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